FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Elias, AF Bono, JL Carroll, JA Stewart, P Tilly, K Rosa, P AF Elias, AF Bono, JL Carroll, JA Stewart, P Tilly, K Rosa, P TI Altered stationary-phase response in a Borrelia burgdorferi ropS mutant SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; OUTER SURFACE-PROTEIN; POLYMERASE CHAIN-REACTION; INDUCED CROSS PROTECTION; SIGMA-FACTOR SIGMA(S); HEAT-SHOCK RESPONSE; ESCHERICHIA-COLI; RPOS GENE; IN-VITRO; ENZYMATIC AMPLIFICATION AB The homolog of the chromosomally encoded stationary-phase sigma factor RpoS in Borrelia burgdorferi was inactivated using gyrB(r) as a selectable marker. Two-dimensional nonequilibrium pH gradient electrophoresis of stationary-phase cell lysates identified at least 11 differences between the protein profiles of the rpoS mutant and wild-type organisms. Wild-type B. burgdorferi had a growth phase-dependent resistance to 1 N NaCl, similar to the stationary-phase response reported for other bacteria. The B. burgdorferi rpoS mutant strain was less resistant to osmotic stress in stationary phase than the isogenic rpoS wild-type organism. The results indicate that the B. burgdorferi rpoS homolog influences protein composition and participates in stationary-phase-dependent osmotic resistance. This rpoS mutant will be useful for studying regulation of gene expression in response to changing environmental conditions. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Microscopy Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Elias, AF (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 60 TC 53 Z9 54 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2000 VL 182 IS 10 BP 2909 EP 2918 DI 10.1128/JB.182.10.2909-2918.2000 PG 10 WC Microbiology SC Microbiology GA 309JE UT WOS:000086764100031 PM 10781562 ER PT J AU Su, TP AF Su, TP TI Delta opioid peptide [D-Ala(2),D-Leu5]enkephalin promotes cell survival SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Neuroscience CY OCT 23-28, 1999 CL MIAMI BEACH, FLORIDA SP Soc Neurosci DE opioid; enkephalin; DADLE; transplantation; hibernation; apoptosis; methamphetamine; dopamine; ischemia; reperfusion; PC12 cells; neuroprotection ID HIBERNATION INDUCTION TRIGGERS; METHAMPHETAMINE; PRESERVATION; ENKEPHALIN; BLOCKS; TIME AB By studying the hibernation in ground squirrels, a protein factor termed hibernation induction trigger (HIT) was found to induce hibernation in summer-active ground squirrels. Further purification of HIT yielded an 88-kD peptide that is enriched in winter hibernator, Partial sequence of the 88-kD protein indicates that it may be related to the inhibitor of metalloproteinase. Delta opioid [DAla(2),D-Leu(5)]enkephalin (DADLE) also induced hibernation. HIT and DADLE were found to prolong survival of peripheral organs preserved en bloc or as a single preparation. These organs include the lung, the heart, liver a nd kidney. DADLE also promotes survival of neurons in the central nervous system. Methamphetamine (METH) is known to cause destruction of dopaminergic (:DA) terminals in the brain, DADLE blocked and reversed the DA terminal damage induced by METH, DADLE acted against this effect of METH at least in part by attenuating the mRNA expressions of a tumor necrosis factor p53 and an immediate early gene c-fos, DADLE also blocked the neuronal damage induced by ischemia-reperfusion following a transient middle cerebral artery occlusion. In PC12 cells, DADLE blocked the cell death caused by serum deprivation in a naltrexone-sensitive manner. Thus, DADLE, and by extension the endogenous delta opioid peptides and delta opioid receptors, may play an important role in organ and neuronal survival. Here, critical developments concerning these fascinating cell protective properties of DADLE are reviewed. Copyright (C) 2000 National Science Council, ROC and S. Karger Ag, Basel. C1 NIDA, Mol Neuropsychiat Sect IRP,Cellular Pathobiol Unit, Cellular Neurobiol Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Su, TP (reprint author), NIDA, Mol Neuropsychiat Sect IRP,Cellular Pathobiol Unit, Cellular Neurobiol Res Branch, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 25 TC 49 Z9 54 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD MAY-JUN PY 2000 VL 7 IS 3 BP 195 EP 199 DI 10.1007/BF02255466 PG 5 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 312DB UT WOS:000086927000003 PM 10810237 ER PT J AU Kong, LY Jeohn, GH Hudson, PM Du, L Liu, B Hong, JS AF Kong, LY Jeohn, GH Hudson, PM Du, L Liu, B Hong, JS TI Reduction of lipopolysaccharide-induced neurotoxicity in mouse mixed cortical neuron/glia cultures by ultralow concentrations of dynorphins SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-for-Neuroscience CY OCT 23-28, 1999 CL MIAMI BEACH, FL SP Soc Neurosci DE dynorphin; cortical neurons; nitric oxide; glia, mixed; lipopolysaccharide ID OPIOID PEPTIDE DYNORPHIN; NMDA RECEPTOR CHANNELS; NEURONAL CELL INJURY; NITRIC-OXIDE; GLUTAMATE NEUROTOXICITY; PERITONEAL-MACROPHAGES; ENDOGENOUS OPIOIDS; RESPIRATORY BURST; IMMUNE-SYSTEM; FACTOR-ALPHA AB Previously we reported that ultralow concentrations of dynorphins (10(-16) to 10(-12) M) inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and proinflammatory cytokines in mouse glia without the participation of kappa-opioid receptors. In the current study using mouse cortical neuron-glia cocultures, we examined the possibility that inhibition of glia inflammatory response by dynorphins might be neuroprotective for neurons. LPS, in a concentration-dependent manner, markedly increased the release of lactate dehydrogenase (LDH), an indicator of cellular injury, Ultralow concentrations (10(-14) to 10(-12) M) of dynorphin (dyn) A-(1-8) significantly prevented the LPS-induced release of LDH, loss of neurons, and changes in cell morphology, in addition to inhibition of LPS-induced nitrite production. Meanwhile, ultralow concentrations (10(-15) to 10(-13) M) Of des-[Tyr(1)]-dyn A-(2-17), a nonopioid peptide which does not bind to kappa-opiod receptors exhibited the same inhibitory effect as dyn A-(1-17). These results suggest that dynorphins at ultralow concentrations are capable of reducing LPS-induced neuronal injury and these neuroprotective effects of dynorphins are not mediated by classical opioid receptors, Copyright (C) 2000 National Science Council, ROC and S. Karger AG. Basel. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, MD F1-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM hong3@niehs.nih.gov RI liu, Bin/A-7695-2009 NR 48 TC 14 Z9 14 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD MAY-JUN PY 2000 VL 7 IS 3 BP 241 EP 247 PG 7 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 312DB UT WOS:000086927000009 PM 10810243 ER PT J AU Orsulic, S Kemler, R AF Orsulic, S Kemler, R TI Expression of Eph receptors and ephrins is differentially regulated by E-cadherin SO JOURNAL OF CELL SCIENCE LA English DT Article DE cadherin/catenin complex; cell adhesion; epithelial-mesenchymal transition; mRNA differential display; Eph; ephrin ID VASCULAR-ENDOTHELIAL-CADHERIN; ADHESION MOLECULE UVOMORULIN; PROTEIN-TYROSINE KINASE; CELL-CELL-ADHESION; RHOMBOMERE-SPECIFIC EXPRESSION; TRANSCRIPTION FACTOR LEF-1; NEURAL CREST MIGRATION; CYTOPLASMIC DOMAIN; MOUSE EMBRYOS; BETA-CATENIN AB E-cadherin is the main cell adhesion molecule of early embryonic and adult epithelial cells. Downregulation of E-cadherin is associated with epithelial-mesenchymal transition during embryonic mesoderm formation and tumor progression. To identify genes whose expression is affected by the loss of E-cadherin, we compared mRNA expression patterns between wild-type and E-cadherin null mutant embryonic stem (ES) cells. We found that expression of several Eph receptors and ephrins is dependent on E-cadherin. Rescue of E-cadherin null ES cells with E-cadherin cDNA restores the wild-type expression pattern of Eph family members. Rescue of E-cadherin null ES cells with N-cadherin cDNA does not restore the wild-type expression pattern, indicating that the regulation of differential expression of Eph family members is specific to E-cadherin, Constitutive ectopic expression of E-cadherin in non-epithelial NIH3T3 cells results in the production of the EphA2 receptor. In epithelial cells, E-cadherin is required for EphA2 receptor localization at cell-cell contacts; in the absence of functional E-cadherin, EphA2 localizes to the perinuclear region. Our results indicate that E-cadherin mag be directly or indirectly required for the membrane localization of Eph receptors and their membrane-bound ligands. C1 Max Planck Inst Immunbiol, D-79108 Freiburg, Germany. RP Orsulic, S (reprint author), NIH, Bldg 49-4A56,49 Convent Dr, Bethesda, MD 20892 USA. NR 87 TC 88 Z9 94 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY PY 2000 VL 113 IS 10 BP 1793 EP 1802 PG 10 WC Cell Biology SC Cell Biology GA 321FV UT WOS:000087446200015 PM 10769210 ER PT J AU Rapoport, JL Inoff-Germain, G AF Rapoport, JL Inoff-Germain, G TI Practitioner review: Treatment of obsessive-compulsive disorder in children and adolescents SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES LA English DT Review DE obsessive-compulsive disorder; anxiety; behavior therapy; children; adolescents; immune disorders; neuropsychiatry; pharmacology ID COGNITIVE-BEHAVIORAL TREATMENT; SEROTONIN REUPTAKE INHIBITORS; AUTOIMMUNE NEUROPSYCHIATRIC DISORDERS; TRANSCRANIAL MAGNETIC STIMULATION; DOUBLE-BLIND; LONG-TERM; INTRAVENOUS CLOMIPRAMINE; FOLLOW-UP; RISPERIDONE AUGMENTATION; STREPTOCOCCAL INFECTIONS AB This paper reviews the treatment of obsessive-compulsive disorder (OCD) in children and adolescents. Focusing on clinical features of the disorder and its treatment particular to pediatric onset, diagnosis, assessment, and behavioral, pharmacological, as well as new investigative treatments are covered. Adaptation of cognitive-behavioral therapy for children and adolescents, use of augmenting agents in drug treatment, and subtyping of OCD cases are developments relevant for current practice. C1 NIMH, Bethesda, MD 20892 USA. RP Rapoport, JL (reprint author), NIMH, Room 3N202,10 Ctr Dr,MSC 1600, Bethesda, MD 20892 USA. NR 143 TC 30 Z9 32 U1 9 U2 14 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry Allied Discip. PD MAY PY 2000 VL 41 IS 4 BP 419 EP 431 DI 10.1017/S0021963000005588 PG 13 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 315VV UT WOS:000087134400003 PM 10836672 ER PT J AU Hribal, ML Federici, M Porzio, O Lauro, D Borboni, P Accili, D Lauro, R Sesti, G AF Hribal, ML Federici, M Porzio, O Lauro, D Borboni, P Accili, D Lauro, R Sesti, G TI The Gly -> Arg(972) amino acid polymorphism in insulin receptor substrate-1 affects glucose metabolism in skeletal muscle cells SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DEPENDENT DIABETES-MELLITUS; PROTEIN-KINASE-B; PHOSPHATIDYLINOSITOL 3-KINASE; GLYCOGEN-SYNTHESIS; IRS-1 GENE; TRANSPORT; MICE; ACTIVATION; AKT; TRANSLOCATION AB Molecular scanning of insulin receptor substrate-1 (IRS-1) revealed several amino acid substitutions. The most common IRS-1 variant, a Gly to Arg(972) change, is more prevalent among type 2 diabetic patients. In this study we overexpressed wild-type and Arg(972)IRS-1 variant in L6 skeletal muscle cells and examined the functional consequences of this polymorphism on insulin metabolic signaling. L6 cells expressing Arg(972)-IRS-1 (L6-Arg(972)) showed a decrease in insulin-stimulated IRS-l-associated phosphatidylinositol 3-binase (PI 3-kinase) activity compared with L6 cells expressing wild-type IRS-1(L6-WT) as a consequence of decreased binding of p85 subunit of PI S-kinase to IRS-1. L6-Ar-972 exhibited a decrease in both basal and insulin-stimulated glucose transport due to a reduction in the amount of both GLUT1 and GLUT4 translocated to the plasma membrane. Both basal and insulin-stimulated Akt phosphorylations were decreased in L6-Arg(972) compared with L6-WT. Basal glycogen synthase kinase-3 (GSK-3) activity was increased in L6-Arg(972) compared with L6-WT, and insulin-induced inactivation of GSK-3 was also reduced in L6-Arg(972). This change was associated with a significant decrease in insulin-stimulated glucose incorporation into glycogen and glycogen synthase activity in L6-Arg(972) compared with L6-WT. These results indicate that the Arg(972)-IRS-1 polymorphism impairs the ability of insulin to stimulate glucose transport, glucose transporter translocation, and glycogen synthesis by affecting the PI 3-kinase/Akt/GSK-3 signaling pathway. The present data indicate that the polymorphism at codon 972 of IRS-1 may contribute to the in vivo insulin resistance observed in carriers of this variant. C1 Univ Roma Tor Vergata, Dept Internal Med, Mol Med Lab, I-00173 Rome, Italy. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Med, New York, NY 10027 USA. RP Sesti, G (reprint author), Univ Roma Tor Vergata, Dept Internal Med, Mol Med Lab, Via Orazio Raimondo, I-00173 Rome, Italy. EM sesti@uniroma2.it RI Sesti, Giorgio/B-1509-2012; Federici, Massimo/G-9940-2012; OI Federici, Massimo/0000-0003-4989-5194; Lauro, Davide/0000-0002-8597-4415; Sesti, Giorgio/0000-0002-1618-7688 FU Telethon [E.0695] NR 45 TC 68 Z9 77 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2000 VL 85 IS 5 BP 2004 EP 2013 DI 10.1210/jc.85.5.2004 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WZ UT WOS:000088387300046 PM 10843189 ER PT J AU DeClue, JE Heffelfinger, S Benvenuto, G Ling, B Li, SW Rui, W Vass, WC Viskochil, D Ratner, N AF DeClue, JE Heffelfinger, S Benvenuto, G Ling, B Li, SW Rui, W Vass, WC Viskochil, D Ratner, N TI Epidermal growth factor receptor expression in. neurofibromatosis type 1-related tumors and NF1 animal models SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN CARCINOMA-CELLS; SCHWANN-CELLS; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; BENIGN NEUROFIBROMAS; GENE; RAS; MUTATIONS; DELETIONS; IDENTIFICATION; PROLIFERATION AB We have found that EGF-R expression is associated with the development of the Schwann cell-derived rumors characteristic of neurofibromatosis type 1 (NF1) and in animal models of this disease. This is surprising, because Schwann cells normally lack EGF-R and respond to ligands other than EGF. Nevertheless, immunoblotting, Northern analysis, and immunohistochemistry revealed that each of 3 malignant peripheral nerve sheath tumor (MPNST) cell lines from NF1 patients expressed the EGFR, as did 7 of 7 other primary MPNSTs, a non-NF 1 MPNST cell line, and the S100(+) cells from each of 9 benign neurofibromas. Furthermore, transformed derivatives of Schwann cells from NF1 (-/-) mouse embryos also expressed the EGF-R. All of the cells or cell lines expressing EGF-R responded to EGF by activation of downstream signaling pathways. Thus, EGF-R expression may play an important role in NF1 tumorigenesis and Schwann cell transformation. Consistent with this hypothesis, growth of NF1 MPNST lines and the transformed NF1 (-/-) mouse embryo Schwann cells was greatly stimulated by EGF in vitro and could be blocked by agents that antagonize EGF-R function. C1 NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Dept Cell Biol Neurobiol & Anat, Cincinnati, OH USA. Univ Utah, Dept Genet, Salt Lake City, UT USA. RP DeClue, JE (reprint author), NCI, Cellular Oncol Lab, Bldg 36,Room 1D-32, Bethesda, MD 20892 USA. FU NINDS NIH HHS [NS28840, R01 NS028840] NR 46 TC 104 Z9 106 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2000 VL 105 IS 9 BP 1233 EP 1241 DI 10.1172/JCI7610 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 311UR UT WOS:000086904500012 PM 10791998 ER PT J AU Lindsey, KR Rosenberg, SA Sherry, RM AF Lindsey, KR Rosenberg, SA Sherry, RM TI Impact of the number of treatment courses on the clinical response of patients who receive high-dose bolus interleukin-2 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; 199 CONSECUTIVE PATIENTS; ACTIVATED KILLER CELLS; RECOMBINANT INTERLEUKIN-2; METASTATIC MELANOMA; CANCER-PATIENTS; IMMUNOTHERAPY; TOXICITY; THERAPY AB Purpose: to determine the impact of treatment with successive courses of high-dose bolus interleukin-2 (IL-2) on the incidence of clinical responses in patients with metastatic melanoma or renal cell cancer. Patients and Methods: A consecutive series of 350 patients with either metastatic melanoma or renal cell cancer who were treated with high-dose bolus IL-2 in the Surgery Branch, National Cancer institute, between September 1985 and November 1996 was analyzed, with a median potential follow-up of 7.1 years. All patients were treated with 720,000 IU/kg of IL-2 administered by a 15-minute intravenous infusion every 8 hours for vp to 5 days, as clinically tolerated per cycle. Patients were retreated according to clinical response and tolerance ta the IL-2 therapy. Results: Of the 149 patients with melanoma, 10 achieved complete responses (CRs) and 13 partial responses (PRs), for an overall response rate of 15.4%. Of the 201 patients with renal cell cancer, 18 achieved CRs and 20 PRs, for an overall response rate of 19.0%, Among responding patients, 21 of 23 with melanoma and 34 of 38 with renal cell cancer developed at least PRs after the first course of IL-2, Conclusion: Mast patients with metastatic melanoma and renal cell cancer who achieved PRs or CRs to intravenous high-dose bolus IL-2 were identified after the first course of therapy, Those who demonstrated no response after two treatment courses failed to respond to additional IL-2 therapy. Based on this retrospective analysis, we recommend that patients who exhibit objective responses to treatment with high-dose bolus IL-2 receive additional treatment courses until either CR or IL-2 intolerance develops. Patients who do not achieve objective responses after two courses of IL-2 should receive no further treatment with this regimen. (C) 2000 by American Society of Clinical Oncology. C1 NCI, Div Clin Sci, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Lindsey, KR (reprint author), NCI, Div Clin Sci, Surg Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 2B 51, Bethesda, MD 20892 USA. NR 19 TC 27 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 2000 VL 18 IS 9 BP 1954 EP 1959 PG 6 WC Oncology SC Oncology GA 311FK UT WOS:000086873900018 PM 10784637 ER PT J AU Cheson, BD AF Cheson, BD TI The curious case of the baffling biological SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID NON-HODGKINS-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; RECOMBINANT LEUKOCYTE; MONOCLONAL-ANTIBODY; CLINICAL-TRIAL; INTERFERON; THERAPY; MAINTENANCE; MULTICENTER; DOXORUBICIN C1 NCI, Bethesda, MD 20892 USA. RP Cheson, BD (reprint author), NCI, Bethesda, MD 20892 USA. NR 34 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 2000 VL 18 IS 10 BP 2007 EP 2009 PG 3 WC Oncology SC Oncology GA 315YE UT WOS:000087139900001 PM 10811663 ER PT J AU Wexler, LH Meyer, WH Parham, DM Tsokos, M AF Wexler, LH Meyer, WH Parham, DM Tsokos, M TI Neural differentiation and prognosis in peripheral primitive neuroectodermal tumor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID EWINGS-SARCOMA C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. NCI, Bethesda, MD 20892 USA. RP Wexler, LH (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. NR 7 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 2000 VL 18 IS 10 BP 2187 EP 2188 PG 2 WC Oncology SC Oncology GA 315YE UT WOS:000087139900028 PM 10811686 ER PT J AU Moody, SL Wise, SP AF Moody, SL Wise, SP TI A model that accounts for activity prior to sensory inputs and responses during matching-to-sample tasks SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID PREDICTABLE ENVIRONMENTAL EVENTS; SELECTIVE VISUAL-ATTENTION; PRIMATE PREFRONTAL CORTEX; SHORT-TERM-MEMORY; NEURONAL-ACTIVITY; PREMOTOR CORTEX; FRONTAL-CORTEX; UNIT-ACTIVITY; NEURAL MECHANISMS; SINGLE NEURONS AB Neural network models were examined during delayed matching-to-sample tasks (DMS), and neurons in a monkey's prefrontal cortex were studied during the performance of comparable tasks. In DMS, various input stimuli follow a sample stimulus, and an output should occur whenever the sample reappears. Our previous models have been restricted to certain kinds of inputs, outputs, and temporal patterns. Here, Rie generalized the models by training them on both spatial and nonspatial inputs, spatial and nonspatial outputs, and both fixed and variable interstimulus intervals. Two versions of DMS were presented to both the model and the monkey, both involving nonspatial samples: (1) Two stimuli simultaneously appeared at a variable interval after the sample; and (2) A series of single stimuli appeared at fixed intervals after the sample. Both versions required identical spatial responses, reflecting the direction (left or right) of the matching stimulus relative to a central origin. Thus, these two versions of DMS involved the same samples, memory, and responses, but established different response contexts. Our analysis focused on unit activity prior to stimuli, as well as that prior to responses, termed anticipatory and response-related activity, respectively. In both the model and the monkey, anticipatory activity occurred only for fixed interstimulus intervals. In the model, we could determine that anticipatory activity acted either like a filter to suppress inappropriate responses or it served to enhance the network's general readiness to respond. As for response-related activity, units in both the model and the monkey showed directional selectivity and had a strong dependence on response context. In the model, we could show that this activity contributed both to the suppression of inappropriate responses and to the generation of correct ones. None of the model's hidden units contributed exclusively to computing the direction of match output. Instead, their response-related activity contributed to the computation of both the match decision and the correct response direction. C1 NIMH, LSN, NIH, Bethesda, MD 20892 USA. RP Wise, SP (reprint author), NIMH, LSN, NIH, 49 Convent Dr,Bldg 49,Room B1EE17,MSC 4401, Bethesda, MD 20892 USA. NR 37 TC 10 Z9 10 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAY PY 2000 VL 12 IS 3 BP 429 EP 448 DI 10.1162/089892900562255 PG 20 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 324XJ UT WOS:000087646900007 PM 10931770 ER PT J AU Baum, BJ AF Baum, BJ TI Transferring genes to salivary glands: a powerful way to probe biology and a potentially useful clinical tool. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 2000 VL 79 IS 5 BP 1257 EP 1257 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 325QJ UT WOS:000087687601720 ER PT J AU Yim, PJ Mullick, R Choyke, PL AF Yim, PJ Mullick, R Choyke, PL TI Vesselize: A system for analysis and visualization of magnetic resonance angiography SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT 17th Symposium for Computer Applications in Radiology held at the Annual Meeting of the Society-for-Computer-Applications-in-Radiology (SCAR 2000) CY JUN 03-06, 2000 CL PHILADELPHIA, PENNSYLVANIA SP Soc Comp Applicat Radiol C1 NIH, Dept Diagnost Radiol, NIH Canc Ctr, Warren G Magnuson Clin Ctr,Imaging Sci Program, Bethesda, MD 20892 USA. RP Yim, PJ (reprint author), NIH, Dept Diagnost Radiol, NIH Canc Ctr, Warren G Magnuson Clin Ctr,Imaging Sci Program, Bldg 10,Room 1C660, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD MAY PY 2000 VL 13 IS 2 SU 1 BP 219 EP 220 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 319KA UT WOS:000087339000060 PM 10847409 ER PT J AU Zieler, H Garon, CF Fischer, ER Shahabuddin, M AF Zieler, H Garon, CF Fischer, ER Shahabuddin, M TI A tubular network associated with the brush-border surface of the Aedes aegypti midgut: Implications for pathogen transmission by mosquitoes SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE malaria; Plasmodium gallinaceum; adhesion; basement membrane; vector; insect; pathogen transmission; mosquito; Aedes aegypti ID WHEAT-GERM-AGGLUTININ; NIGRA L BARK; PLASMODIUM-GALLINACEUM; M-CELLS; ULTRASTRUCTURAL-CHANGES; SOYBEAN AGGLUTININ; ENDOCRINE-CELLS; SIALIC-ACID; L INSECTA; MALARIA AB The mosquito Aedes aegypti is capable of transmitting a variety of pathogens to man and to other vertebrates. The midgut of this insect has been well-studied both as the tissue where the first contact occurs between ingested pathogens and the insect host, and as a model system for blood meal digestion in blood-sucking insects. To understand better the nature of the midgut surface encountered by parasites or viruses, we used scanning electron microscopy to identify the most prominent structures and cell morphologies on the luminal midgut surface. The luminal side of the midgut is a complex and layered set of structures. The microvilli that are found on most, but not all, cells are covered by a network of fine strands that we have termed the microvilli-associated network (MN), The MN strands are membranous, as shown by a membrane bilayer visible in cross sections of MN strands at high magnification in transmission electron micrographs. The MN is found in blood-fed as well as unfed mosquitoes and is not affected by chitinase treatment, suggesting that it is not related to the chitinous peritrophic membrane that is formed only after blood feeding. The cells in the midgut epithelium have two distinct morphologies: the predominant cell type is densely covered with microvilli, while cells with fewer microvilli are found interspersed throughout the midgut, We used lectins to probe for the presence of carbohydrates on the midgut surface. A large number of lectins bind to the luminal midgut surface, suggesting that a variety of sugar linkages are present on the structures visualized by electron microscopy, Some of these lectins partially block attachment of malaria ookinetes to the midgut surface in vitro, Thus, the mosquito midgut epithelium, like the lining of mammalian intestines, is complex, composed of a variety of cell types and extensively covered with surface carbohydrate that may play a role in pathogen attachment. C1 NIAID, Parasit Dis Lab, Med Entomol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Rocky Mt Labs, Microscopy Branch, NIH, Hamilton, MT 59840 USA. RP Shahabuddin, M (reprint author), NIAID, Parasit Dis Lab, Med Entomol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 62 TC 48 Z9 51 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD MAY PY 2000 VL 203 IS 10 BP 1599 EP 1611 PG 13 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 321BD UT WOS:000087434300009 PM 10769222 ER PT J AU He, JP Gurunathan, S Iwasaki, A Ash-Shaheed, B Kelsall, BL AF He, JP Gurunathan, S Iwasaki, A Ash-Shaheed, B Kelsall, BL TI Primary role for Gi protein signaling in the regulation of interleukin 12 production and the induction of T helper cell type 1 responses SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE G protein; interleukin 12; T helper cell type 1; pertussis toxin; leishmaniasis ID LEISHMANIA-MAJOR; DENDRITIC CELLS; CUTANEOUS LEISHMANIASIS; PROTECTIVE IMMUNITY; INTERFERON-GAMMA; PERTUSSIS TOXIN; TH1 CELLS; IN-VIVO; MICE; EXPRESSION AB We explored the role of Gi protein signaling in the regulation of interleukin (IL)-12 production and T helper cell type 1 (Th1) T cell differentiation. In initial studies, we showed that treatment of normal mice with pertussis toxin (PT), which inhibits Gi protein signaling, enhanced the capacity of splenocytes to produce IL-12 in response to both microbial and nonmicrobial stimuli. In addition, PT treatment increased the production of tumor necrosis factor (TNF)-alpha and IL-10 by stimulated cells. These findings were corroborated by the fact that untreated Gi2 alpha(-/-) mice exhibited enhanced production of IL-12 and TNF-alpha by splenocytes, and of IL-12 p40 by purified spleen CD8 alpha(+) lymphoid dendritic cells. Finally, we showed that while normal BALB/c mice infected with Leishmania major exhibited a nonhealing phenotype, those treated with PT when infection was initiated exhibited a healing phenotype along with an enhancement of leishmania-specific Th1 responses in draining lymph nodes. Further, healing was prevented by coadministration of anti-IL-12 and PT. These data demonstrate that endogenous Gi protein signaling has a primary role in the regulation of IL-12 production and the induction of Th1 responses in vivo. C1 NIAID, Immune Cell Interact Unit, Mucosal Immun Sect, Lab Clin Invest,NIH, Bethesda, MD 20892 USA. NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Kelsall, BL (reprint author), NIAID, Immune Cell Interact Unit, Mucosal Immun Sect, Lab Clin Invest,NIH, Bldg 10,Rm 11N238,10 Ctr Dr, Bethesda, MD 20892 USA. NR 30 TC 79 Z9 80 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 2000 VL 191 IS 9 BP 1605 EP 1610 DI 10.1084/jem.191.9.1605 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 311LC UT WOS:000086884900016 PM 10790434 ER PT J AU Duncan, MD Tihan, T Donovan, DM Phung, QH Rowley, DL Harmon, JW Gearhart, PJ Duncan, KLK AF Duncan, MD Tihan, T Donovan, DM Phung, QH Rowley, DL Harmon, JW Gearhart, PJ Duncan, KLK TI Esophagogastric adenocarcinoma in an E1A/E1B transgenic model involves p53 disruption SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 16-19, 1999 CL ORLANDO, FLORIDA SP Soc Surg Alimentary Tract DE esophageal cancer; transgenic; p53 ID BARRETTS-ESOPHAGUS; CARCINOMA; PROTEIN; CANCER; EXPRESSION; EPITHELIUM; METAPLASIA; DYSPLASIA; JUNCTION AB We studied tumorigenesis and p53 immunostaining in a murine transgenic model introducing E1A/E1B under the control of the mouse mammary tumor virus-long terminal repeat (MMTV-LTR) promoter in which adenocarcinoma occurs at the squamocolumnar junction in the foregut, predominantly in males, and at no other site. Mutations of p53 are frequent in human esophageal adenocarcinoma and the E1B gene product interferes with p53-mediated apoptosis, inhibiting turner suppression at the G(1)/S checkpoint. Transgenic animals were generated utilizing a purified linear 6.7 kb fragment of plasmid DNA containing MMTV-LTR/E1A/E1B and were confirmed by dot blot hybridization of tail DNA to P-32-labeled E1A/E1B probe and polymerase chain reaction (PCR) amplification of E1A. Transgenic and control animals were observed for morbidity and weight changes. Eleven of 45 animals were transgenic (24% efficiency) with an estimated 5 to 57 copies of the gene per genome. Profound weight loss (>20%) led to sacrifice or death of one of five females (at 12 weeks) and four of six males (at 16 to 17 weeks). Grossly visible tumors (2 to 10 mm) were noted in the forestomach at the visible margin between the: proximal (squamous-lined) stomach and the distal glandular stomach. Histologic sections confirmed adenocarcinoma arising in each case at the squamocolumnar junction with glandular formation, pleomorphism, and frequent mitotic figures. Immunostaining was positive for p53 indicating accumulation of mutated or altered p53 protein. E1A/E1B transgenic animals developed macroscopic and microscopic adenocarcinoma at the squamocolumnar junction, which corresponds to adenocarcinoma at the human esophagogastric junction. Disruption of p53 was present in the transgenic model as in the human cancer. C1 Johns Hopkins Bayview Med Ctr, Sect Surg Sci, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. NIA, Transgen & Knockout Facil, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. RP Duncan, MD (reprint author), Johns Hopkins Bayview Med Ctr, Sect Surg Sci, A-563,4940 Eastern Ave, Baltimore, MD 21224 USA. RI Duncan, Kimberly /C-3655-2013 NR 27 TC 8 Z9 8 U1 0 U2 0 PU QUALITY MEDICAL PUBLISHING INC PI ST LOUIS PA 11970 BORMAN DR, STE 222, ST LOUIS, MO 63146 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY-JUN PY 2000 VL 4 IS 3 BP 290 EP 297 DI 10.1016/S1091-255X(00)80078-5 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 315XT UT WOS:000087138800015 PM 10769092 ER PT J AU Canto, MT Shankar, S AF Canto, MT Shankar, S TI Utilization of routine medical services among immigrants from El Salvador SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article ID HEALTH-CARE; BEHAVIORAL-MODEL; ACCESS; ACCULTURATION; HISPANICS C1 Natl Inst Dent & Craniofacial Res, Off Sci Policy & Anal, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. RP Canto, MT (reprint author), Natl Inst Dent & Craniofacial Res, Off Sci Policy & Anal, 45 Ctr Dr MSC 6401,Natcher Bldg,Room 3AN44, Bethesda, MD 20892 USA. NR 21 TC 4 Z9 4 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD MAY PY 2000 VL 11 IS 2 BP 125 EP 134 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 306HZ UT WOS:000086592400001 PM 10793509 ER PT J AU Culver, M Johnson, WE Pecon-Slattery, J O'Brien, SJ AF Culver, M Johnson, WE Pecon-Slattery, J O'Brien, SJ TI Genomic ancestry of the American puma (Puma concolor) SO JOURNAL OF HEREDITY LA English DT Article; Proceedings Paper CT Symposium on Genetic Diversity and Evolution CY JUN 12-13, 1999 CL PENN ST UNIV, UNIVERSITY PK, PA SP Penn St Univ HO PENN ST UNIV ID CAT FELIS-CATUS; MITOCHONDRIAL-DNA; POPULATION BOTTLENECKS; NUCLEOTIDE-SEQUENCES; FLORIDA PANTHER; HIGH-RESOLUTION; EVOLUTION; MICROSATELLITES; POLYMORPHISMS; INTERCHANGE AB Puma concolor, a large American cat species, occupies the most extensive range of any New World terrestrial mammal, spanning 110 degrees of latitude from the Canadian Yukon to the Straits of Magellan, Until the recent Holocene, pumas coexisted with a diverse array of carnivores including the American lion (Panthera atrox), the North American cheetah (Miracynonyx trumani), and the saber toothed tiger (Smilodon fafalis), Genomic DNA specimens from 315 pumas of specified geographic origin (261 contemporary and 54 museum specimens) were collected for molecular genetic and phylogenetic analyses of three mitochondrial gene sequences (16S rRNA, ATPase-8, and NADH-5) plus composite microsatellite genotypes (10 feline loci). Six phylogeographic groupings or subspecies were resolved, and the entire North American population (186 individuals from 15 previously named subspecies) was genetically homogeneous in overall variation relative to central and South American populations. The marked uniformity of mtDNA and a reduction in microsatellite allele size expansion indicates that North American pumas derive from a recent (late Pleistocene circa 10,000 years ago) replacement and recolonization by a small number of founders who themselves originated from a centrum of puma genetic diversity in eastern South America 200,000-300,000 years ago. The recolonization of North American pumas was coincident with a massive late Pleistocene extinction event that eliminated 80% of large vertebrates in North America and may have extirpated pumas from that continent as well. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers & Dev Ctr, Frederick, MD 21702 USA. RP O'Brien, SJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers & Dev Ctr, Frederick, MD 21702 USA. RI Johnson, Warren/D-4149-2016 OI Johnson, Warren/0000-0002-5954-186X NR 74 TC 139 Z9 146 U1 6 U2 58 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 EI 1465-7333 J9 J HERED JI J. Hered. PD MAY-JUN PY 2000 VL 91 IS 3 BP 186 EP 197 DI 10.1093/jhered/91.3.186 PG 12 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 316WK UT WOS:000087190900002 PM 10833043 ER PT J AU Griffin, MD Hong, DK Holman, PO Lee, KM Whitters, MJ O'Herrin, SM Fallarino, F Collins, M Segal, DM Gajewski, TF Kranz, DM Bluestone, JA AF Griffin, MD Hong, DK Holman, PO Lee, KM Whitters, MJ O'Herrin, SM Fallarino, F Collins, M Segal, DM Gajewski, TF Kranz, DM Bluestone, JA TI Blockade of T cell activation using a surface-linked single-chain antibody to CTLA-4 (CD152) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTE ANTIGEN-4; IN-VIVO; NEGATIVE REGULATOR; MAMMALIAN-CELLS; B-CELLS; CD28; RECEPTOR; EXPRESSION; ENGAGEMENT; INDUCTION AB CTLA-4 (CD152) engagement can down-regulate T cell activation and promote the induction of immune tolerance. However, the strategy of attenuating T cell activation by engaging CTLA-4 has been limited by sharing of its natural ligands with the costimulatory protein CD28, In the present study, a CTLA-4-specific single-chain Ab (scFv) was developed and expressed on the cell surface to promote selective engagement of this regulatory molecule. Transfectants expressing anti-CTLA-4 scFv at their surface bound soluble CTLA-4 but not soluble CD28, Coexpression of anti-CTLA-4 scFv with anti-CD3 epsilon and anti-CD28 scFvs on artificial APCs reduced the proliferation and IL-2 production by resting and preactivated bulk T cells as well as CD4(+) and CD8(+) T cell subsets. Importantly, expression of anti-CTLA-4 scFv on the same cell surface as the TCR ligand,vas essential for the inhibitory effects of CTLA-4-specific ligation, CTLA-4-mediated inhibition of tyrosine phosphorylation of components of the proximal TCR signaling apparatus was similarly dependent on coexpression of TCR and CTLA-4 ligands on the same surface. These findings support a predominant role for CTLA-4 function in the modification of the proximal TCR signal. Using T cells from DO11.10 and 2C TCR transgenic mice, negative regulatory effects of selective CTLA-4 ligation were also demonstrated during the stimulation of Ag-specific CD4(+) and CD8(+) T cells by MHC/peptide complexes. Together these studies demonstrate that selective ligation of CTLA-4 using a membrane-bound scFv results in attenuated T cell responses only when coengaged with the TCR during T cell/APC interaction and define an approach to harnessing the immunomodulatory potential of CTLA-4-specific ligation. C1 Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Univ Chicago, Comm Immunol, Chicago, IL 60637 USA. Mayo Clin & Mayo Fdn, Dept Internal Med, Div Nephrol, Rochester, MN 55905 USA. Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. Genet Inst, Cambridge, MA 02140 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Bluestone, JA (reprint author), Univ Chicago, Ben May Inst Canc Res, 5842 S Maryland Ave,MC1089, Chicago, IL 60637 USA. RI Griffin, Matthew/A-1688-2009; Fallarino, Francesca/O-3358-2013 OI Griffin, Matthew/0000-0002-8701-8056; Fallarino, Francesca/0000-0002-8501-2136 FU NIAID NIH HHS [AI35294, AI35990] NR 69 TC 52 Z9 53 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 MAY 1 PY 2000 VL 164 IS 9 BP 4433 EP 4442 PG 10 WC Immunology SC Immunology GA 306XQ UT WOS:000086624300002 PM 10779742 ER PT J AU Bosco, MC Curiel, RE Zea, AH Malabarba, MG Ortaldo, JR Espinoza-Delgado, I AF Bosco, MC Curiel, RE Zea, AH Malabarba, MG Ortaldo, JR Espinoza-Delgado, I TI IL-2 signaling in human monocytes involves the phosphorylation and activation of p59(hck) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; PERIPHERAL-BLOOD MONOCYTES; FACTOR-ALPHA PRODUCTION; RECEPTOR BETA-CHAIN; JAK-3 JANUS KINASE; HUMAN B-CELLS; INTERLEUKIN-2 RECEPTOR; INTERFERON-GAMMA; GENE-EXPRESSION; HERBIMYCIN-A AB The activating properties of IL-2 and the structure of the IL-2R on human monocytes are web characterized. However, relatively little is known about the biochemical mechanisms involved in IL-2 signal transduction in these cells. We investigated the role of protein tyrosine kinases (PTKs) in the activation of monocytes by IL-2. Incubation of monocytes with the PTK inhibitor herbimycin A (HA) resulted in the dose-dependent suppression of IL-2-induced monocyte tumoricidal activity. This inhibition was rather potent, as a concentration of HA as low as 0.5 mu M caused a complete abrogation of cytolytic activity. Furthermore, HA markedly suppressed the ability of IL-2 to induce IL-1 beta, TNF-alpha, IL-6, and IL-8 mRNA expression and protein secretion by monocytes. Anti-phosphotyrosine immunoblotting demonstrated that IL-2 induced a rapid and time-dependent increase in tyrosine phosphorylation of several cellular proteins of molecular masses ranging from 35 to 180 kDa. Interestingly, IL-2 caused a significant up-regulation of the constitutive levels of hck PTK mRNA and protein relative to medium-treated cells as well as an increase in p59(hck) tyrosine phosphorylation. Finally, we demonstrated by in vitro kinase assay that the specific activity of p59(hck) PTK was also induced by IL-2 in monocytes. Thus, these data show that the activation of PTKs is required for the triggering of monocyte effector and secretory functions by IL-2 and strongly suggest that p59(hck) is a key participant in IL-2 signaling ih human monocytes. The Journal of Immunology, 2000, 164: 4575-4585. C1 Louisiana State Univ, Med Ctr, Dept Med, New Orleans, LA 70112 USA. Louisiana State Univ, Med Ctr, Dept Microbiol, New Orleans, LA 70112 USA. Louisiana State Univ, Med Ctr, Stanley S Scott Canc Ctr, New Orleans, LA 70112 USA. Ist Giannina Gaslini, Mol Biol Lab, I-16148 Genoa, Italy. NCI, Frederick Canc Res & Dev Ctr, Cytokines Mol Mech Sect, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Espinoza-Delgado, I (reprint author), Louisiana State Univ, Med Ctr, Dept Med, 1542 Tulane Ave,Suite 604K, New Orleans, LA 70112 USA. RI Malabarba, Maria Grazia/L-4805-2015; Bosco, Maria Carla/J-7928-2016 OI Malabarba, Maria Grazia/0000-0002-9457-2047; Bosco, Maria Carla/0000-0003-1857-7193 NR 62 TC 11 Z9 12 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 MAY 1 PY 2000 VL 164 IS 9 BP 4575 EP 4585 PG 11 WC Immunology SC Immunology GA 306XQ UT WOS:000086624300020 PM 10779760 ER PT J AU de Vos, AF Fukushima, A Lobanoff, MC Vistica, BP Lai, JC Grivel, JC Wawrousek, EF Whitcup, SM Gery, I AF de Vos, AF Fukushima, A Lobanoff, MC Vistica, BP Lai, JC Grivel, JC Wawrousek, EF Whitcup, SM Gery, I TI Breakdown of tolerance to a neo-self antigen in double transgenic mice in which B cells present the antigen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REACTIVE LYMPHOCYTES-B; T-CELLS; IMMUNE PRIVILEGE; TISSUES; IMMUNODOMINANT; DETERMINANTS; AUTOANTIGEN; CRYSTALLIN; INDUCTION; MEMBRANE AB Transgenic (Tg) mice expressing a foreign Ag, hen egg lysozyme (HEL), under control of the alpha A-crystallin promoter ("HEL-Tg" mice) develop immunotolerance to HEL attributed to the expression of HEL in their thymus, In this paper we analyzed the immune response in double (Dbl)-Tg mice generated by mating the HEL-Tg mice with Tg mice that express HEL Abs on their B cells ("Ig-Tg" mice). The B cell compartment of the Dbl-Tg mice was unaffected by the HEL presence and was essentially identical to that of the Ig-Tg mice, A partial breakdown of tolerance was seen in the T cell response to HEL of the Dbl-Tg mice, i.e., their lymphocyte proliferative response against HEL was remarkably higher than that of the HEL-Tg mice. T-lymphocytes of both Dbl-Tg and Ig-Tg mice responded to HEL at concentrations drastically lower than those found stimulatory to lymphocytes of the wild-type controls. Cell mixing experiments demonstrated that 1) the lymphocyte response against low concentrations of HEL is due to the exceedingly efficient Ag presenting capacity of the Ab expressing B cells and 2) breakdown of tolerance in Dbl-Tg mice can also be attributed to the APC capacity of B cells, that sensitize in vivo and stimulate in vitro populations of T cells with low affinity toward HEL, assumed to be escapees of thymic deletion. These results thus indicate that T cell tolerance can be partially overcome by the highly potent Ag presenting capacity of Ab expressing B cells. C1 NEI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIH Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD 20814 USA. RP Gery, I (reprint author), NEI, NIH, Bldg 10,Room 10N112, Bethesda, MD 20892 USA. RI Wawrousek, Eric/A-4547-2008 NR 38 TC 15 Z9 15 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 MAY 1 PY 2000 VL 164 IS 9 BP 4594 EP 4600 PG 7 WC Immunology SC Immunology GA 306XQ UT WOS:000086624300022 PM 10779762 ER PT J AU Frucht, DM Aringer, M Galon, J Danning, C Brown, M Fan, S Centola, M Wu, CY Yamada, N El Gabalawy, H O'Shea, JJ AF Frucht, DM Aringer, M Galon, J Danning, C Brown, M Fan, S Centola, M Wu, CY Yamada, N El Gabalawy, H O'Shea, JJ TI Stat4 is expressed in activated peripheral blood monocytes, dendritic cells, and macrophages at sites of Th1-mediated inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TYROSINE PHOSPHORYLATION; INTERFERON-GAMMA; TH2 CELLS; IL-12; RESPONSES; DIFFERENTIATION; TRANSCRIPTION; ARTHRITIS; ALPHA AB Stat4 is a key transcription factor involved in promoting cell-mediated immunity, whose expression in mature cells has been reported to be restricted to T and NK cells. We demonstrate here, however, that Stat4 expression is not restricted to lymphoid cells. In their basal state, monocytes do not express Stat4, Upon activation, however, IFN-gamma- and LPS-treated monocytes and dendritic cells express high levels of Stat4, Monocyte-expressed Stat4 in humans is phosphorylated in response to IFN-alpha, but not IL-12. In contrast, the Th2 cytokines, IL-4 and IL-10, specifically down-regulate Stat4 expression in activated monocytes, while having little effect on Stat6 expression. Moreover, macrophages in synovial tissue obtained from patients with rheumatoid arthritis express Stat4 in vivo, suggesting a potential role in a prototypical Th1-mediated human disease. IFN-alpha -induced Stat4 activation in human monocytes represents a previously unrecognized signaling pathway at sites of Th1 inflammation. C1 NIAMSD, Lymphocyte Cell Biol Sect, Bethesda, MD 20892 USA. NIAMSD, Clin Res Grp, Bethesda, MD 20892 USA. NIAMSD, Genet Sect, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. RP Frucht, DM (reprint author), Bldg 10,Room 9N262,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 22 TC 114 Z9 118 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2000 VL 164 IS 9 BP 4659 EP 4664 PG 6 WC Immunology SC Immunology GA 306XQ UT WOS:000086624300030 PM 10779770 ER PT J AU Ahmad, F Cong, LN Holst, LS Wang, LM Landstrom, TR Pierce, JH Quon, MJ Degerman, E Manganiello, VC AF Ahmad, F Cong, LN Holst, LS Wang, LM Landstrom, TR Pierce, JH Quon, MJ Degerman, E Manganiello, VC TI Cyclic nucleotide phosphodiesterase 3B is a downstream target of protein kinase B and may be involved in regulation of effects of protein kinase B on thymidine incorporation in FDCP2 cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; INSULIN-INDUCED PHOSPHORYLATION; DEPENDENT HEMATOPOIETIC-CELLS; RAT ADIPOSE-CELLS; GROWTH FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; ADENOSINE-MONOPHOSPHATE; AMP PHOSPHODIESTERASE; TRANSCRIPTION FACTOR AB Wild-type (F/B), constitutively active (F/B*), and three kinase-inactive (F/Ba-, F/Bb(-), F/Bc(-)) forms of Akt/protein kinase B (PKB) were permanently overexpressed in FDCP2 cells. In the absence of insulin-like growth factor-1 (IGF-1), activities of PRE, cyclic nucleotide phosphodiesterase 3B (PDE3B), and PDE4 were similar in nontransfected FDCP2 cells, mock-transfected (FN) cells, and F/B and F/B- cells. In FN cells, IGF-1 increased PKB, PDE3B, and PDE4 activities similar to 2-fold. In F/B cells, IGF-1, in a wortmannin-sensitive manner, increased PKB activity similar to 10-fold and PDE3B phosphorylation and activity (similar to 4-fold), but increased PDE4 to the same extent as in FN cells. In F/B* cells, in the absence of IGF-1, PKB activity was markedly increased (similar to 10-fold) and PDE3B was phosphorylated and activated (3- to 4-fold); wortmannin inhibited these effects, In F/B* cells, IGF-1 had little further effect on PKB and activation/phosphorylation of PDE3B, In F/B- cells, IGF-1 activated PDE4, not PDE3B, suggesting that kinase-inactive PKB behaved as a dominant negative with respect to PDESB activation. Thymidine incorporation was greater in F/B* cells than in FN cells and was inhibited to a greater extent by PDE3 inhibitors than by rolipram, a PDE4 inhibitor. In F/B cells, IGF-1-induced phosphorylation of the apoptotic protein BAD was inhibited by the PDE3 inhibitor cilostamide, Activated PKB phosphorylated and activated rPDE3B in vitro. These results suggest that PDE3B, not PDE4, is a target of PKB and that activated PDE3B may regulate cAMP pools that modulate effects of PKB on thymidine incorporation and BAD phosphorylation in FDCP2 cells. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Lund, Dept Cell & Mol Biol, Sect Mol Signaling, Lund, Sweden. RP Ahmad, F (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room 5N-307,10 Ctr Dr,MSC 1434, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 85 TC 46 Z9 50 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 MAY 1 PY 2000 VL 164 IS 9 BP 4678 EP 4688 PG 11 WC Immunology SC Immunology GA 306XQ UT WOS:000086624300033 PM 10779773 ER PT J AU Bergmann-Leitner, ES Abrams, SI AF Bergmann-Leitner, ES Abrams, SI TI Differential role of Fas/Fas ligand interactions in cytolysis of primary and metastatic colon carcinoma cell lines by human antigen-specific CD8(+) CTL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FAS-MEDIATED CYTOTOXICITY; IN-VITRO; DEATH RECEPTORS; TUMOR-CELLS; APOPTOSIS; LYMPHOCYTES; EXPRESSION; RESPONSES; CANCER; CD95 AB We have previously identified mutated ras peptides reflecting the glycine to valine substitution at position 12 as HLA-A2-restricted, CD8(+) CTL neo-epitopes. CTL lines produced against these peptide epitopes lysed the HLA-A2(+) Ag-bearing SW480 primary colon adenocarcinoma cell line, although IFN-gamma. treatment of the targets was necessary to achieve efficient cytotoxicity. Here, we compared the lytic phenotype of the SW480 cell line to its metastatic derivative, SW620, as an in vitro paradigm to further characterize the nature of a HLA class I-restricted, Ag-specific CTL response against neoplastic cell lines of primary and metastatic origin. Although both colon carcinoma cell lines were lysed by these Ag-specific CTL following IFN-gamma pretreatment, the mechanisms of lysis were distinct, which reflected differential levels of sensitivity to the Fas pathway. Whereas IFN-gamma pretreatment rendered SW480 cells sensitive to both Fas-dependent and -independent (perforin) pathways, SW620 cells displayed lytic susceptibility to Fas-independent mechanisms only, Moreover, pretreatment of SW480 cells with the anti-colon cancer agent, 5-fluorouracil (5-FU), led to enhanced Fas and ICAM-1 expression and triggered Ag-specific CTL-mediated lysis via Fas- and perforin-based pathways. In contrast, these phenotypic and functional responses were not observed with SW620 cells. Overall, these data suggested that 1) IFN-gamma, and 5-FU may enhance the lytic sensitivity of responsive colon carcinoma cells to immune effector mechanisms, including Fas-induced lysis; 2) the malignant phenotype may associate with resistance to Fas-mediated lysis in response to Ag-specific T cell attack; and 3) if Ag-specific CTL possess diverse lytic capabilities, this may overcome, to some extent, the potential "escape" of Fas-resistant carcinoma cells. C1 NCI, Tumor Immunol & Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Abrams, SI (reprint author), NCI, Tumor Immunol & Biol Lab, Div Basic Sci, NIH, Bldg 10,Room 5B46,10 Ctr Dr, Bethesda, MD 20892 USA. RI Bergmann-Leitner, Elke/B-3548-2011 OI Bergmann-Leitner, Elke/0000-0002-8571-8956 NR 46 TC 35 Z9 37 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 MAY 1 PY 2000 VL 164 IS 9 BP 4941 EP 4954 PG 14 WC Immunology SC Immunology GA 306XQ UT WOS:000086624300065 PM 10779805 ER PT J AU Allen, TM Vogel, TU Fuller, DH Mothe, BR Steffen, S Boyson, JE Shipley, T Fuller, J Hanke, T Sette, A Altman, JD Moss, B McMichael, AJ Watkins, DI AF Allen, TM Vogel, TU Fuller, DH Mothe, BR Steffen, S Boyson, JE Shipley, T Fuller, J Hanke, T Sette, A Altman, JD Moss, B McMichael, AJ Watkins, DI TI Induction of AIDS virus-specific CTL activity in fresh, unstimulated peripheral blood lymphocytes from rhesus macaques vaccinated with a DNA prime/modified vaccinia virus Ankara boost regimen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CYTOTOXIC T-LYMPHOCYTES; HEPATITIS-B VIRUS; HIV IMMUNE-RESPONSES; PROTECTIVE EFFICACY; NONHUMAN-PRIMATES; PRIMARY INFECTION; FOREIGN EPITOPES; INFLUENZA-VIRUS; VIRAL-INFECTION AB The observed role of CTL in the containment of AIDS virus replication suggests that an effective HIV vaccine will be required to generate strong CTL responses, Because epitope-based vaccines offer several potential advantages for inducing strong, multispecific CTL responses, we tested the ability of an epitope-based DNA prime/modified vaccinia virus Ankara (MVA) boost vaccine to induce CTL responses against a single SIVgag CTL epitope. As assessed using both Cr-51 release assays and tetramer staining of in vitro stimulated PBMC, DNA vaccinations administered to the skin with the gene am induced and progressively increased p11C, C-->M (CTPYDINQM)-specific CD8(+) T lymphocyte responses in six of six Mamu-A*01(+) rhesus macaques. Tetramer staining of fresh, unstimulated PBMC from two of the DNA-vaccinated animals indicated that as much as 0.4% of all CD3(+)/ CD8 alpha(+) T lymphocytes were specific for the SIVgag CTL epitope, Administration of MVA expressing the SIVgag CTL epitope further boosted these responses, such that 0.8-20.0% of CD3(+)/CD8 alpha(+) T lymphocytes in fresh, unstimulated PBMC were now Ag specific. Enzyme-linked immunospot assays confirmed this high frequency of Ag-specific cells, and intracellular IFN-gamma staining demonstrated that the majority of these cells produced IFN-gamma after peptide stimulation. Moreover, direct ex vivo SIV-specific cytotoxic activity could be detected in PBMC from five of the six DNA/MVA-vaccinated animals, indicating that this epitope-based DNA prime/MVA boost regimen represents a potent method for inducing high levels of functionally active, Ag-specific CD8(+) T lymphocytes in non-human primates. C1 Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53715 USA. Powderject Inc, Madison, WI 53711 USA. Univ Oxford, Inst Mol Med, Oxford, England. Epimmune Inc, San Diego, CA 92121 USA. Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Allen, TM (reprint author), Univ Wisconsin, Wisconsin Reg Primate Res Ctr, 1223 Capitol Court, Madison, WI 53715 USA. RI Allen, Todd/F-5473-2011 FU NCRR NIH HHS [RR0167]; NIAID NIH HHS [R01AI40913] NR 74 TC 224 Z9 228 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 MAY 1 PY 2000 VL 164 IS 9 BP 4968 EP 4978 PG 11 WC Immunology SC Immunology GA 306XQ UT WOS:000086624300068 PM 10779808 ER PT J AU Bedrosian, I Roros, JG Xu, SW Nguyen, HQ Engels, F Faries, MB Koski, GK Cohen, PA Czerniecki, BJ AF Bedrosian, I Roros, JG Xu, SW Nguyen, HQ Engels, F Faries, MB Koski, GK Cohen, PA Czerniecki, BJ TI Granulocyte-macrophage colony-stimulating factor, interleukin-2, and interleukin-12 synergize with calcium ionophore to enhance dendritic cell function SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE immature dendritic cells; cytokines; calcium ionophore; calcineurin; melanoma peptides ID PERIPHERAL-BLOOD MONOCYTES; ANTIGEN-PRESENTING CELLS; ANTITUMOR IMMUNITY; T-LYMPHOCYTES; IN-VITRO; MELANOMA PATIENTS; LANGERHANS CELLS; VACCINATION; COSTIMULATION; PEPTIDE AB The authors previously showed that monocytes treated with calcium ionophore (CI) acquire characteristics of mature dendritic cells (DC) in part through a calcineurin-dependent pathway. In this study, the authors evaluated the ability of granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-2 (IL-2), and interleukin-12 (IL-12) alone or in combination with CI to induce DC characteristics in peripheral blood monocytes. Monocytes obtained by leukapheresis and countercurrent centrifugal elutriation were cultured with calcium, cytokines, or both, profiled by flow cytometry, and assessed for antigen uptake and sensitization of autologous CD8(+) T cells to antigen. Monocytes treated with the combination of GM-CSF, IL-2, and IL-12 resulted in immunophenotypic and antigen uptake profiles typical of immature DC, including loss of surface CD14 expression, de novo low-level expression of B7.1, negligible CD83 expression, marked enhancement of CD40 and ICAM-1, and high major histocompatibility complex class I and II levels. A high level of antigen uptake by macropinocytosis was observed. In contrast, CI treatment significantly upregulates B7.1, B7.2, CD40, CD54, and CD83 and substantially downregulates CD14 and macropinocytosis, a profile consistent with mature DC. Many CI-induced modulations, but none resulting from cytokine treatment alone, were inhibited by the calcineurin phosphatase inhibitor cyclosporin A. Compared with monocytes treated with CI alone, combined treatment of monocytes with GM-CSF, IL-2, IL-12, and CI augmented B7.1 and CD83 expression and enhanced sensitization of autologous CD8(+) T cells to melanoma-antigen-derived peptides. These results suggest that several independent pathways of DC activation can cooperatively enhance the function of monocyte-derived DC. C1 Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RP Czerniecki, BJ (reprint author), Cleveland Clin Fdn, Dept Surg, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 32 TC 8 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2000 VL 23 IS 3 BP 311 EP 320 DI 10.1097/00002371-200005000-00004 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 316DW UT WOS:000087153200004 PM 10838660 ER PT J AU Marroquin, CE White, DE Steinberg, SM Rosenberg, SA Schwartzentruber, DJ AF Marroquin, CE White, DE Steinberg, SM Rosenberg, SA Schwartzentruber, DJ TI Decreased tolerance to interleukin-2 with repeated courses of therapy in patients with metastatic melanoma or renal cell cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE biologic response modifiers; immunotherapy; interleukin-2; melanoma; renal cell cancer; renal insufficiency; toxicity ID HIGH-DOSE INTERLEUKIN-2; ACTIVATED KILLER-CELLS; 199 CONSECUTIVE PATIENTS; RECOMBINANT INTERLEUKIN-2; CONTRAST-MEDIA; TOXICITY; CARCINOMA; IMMUNOTHERAPY; RELEASE AB High-dose interleukin-2 (IL-2) therapy has a response rate of approximately 20% in patients with metastatic melanoma and renal cell cancer. Animal models have shown that the anti-rumor effects of IL-2 are dose and schedule dependent, and one report has shown that patients with melanoma who responded to IL-2 therapy received more doses of IL-2 than did those who did not respond. The current study evaluated patients' tolerance to IL-2 over multiple courses of therapy and the factors that affected the number of doses delivered. Patients with metastatic melanoma or renal cell cancer who received at least two consecutive courses of high-dose intravenous IL-2 alone from October 1, 1985 through December 31, 1996 were evaluated. Patients served as their own controls in paired analyses. The number of doses tolerated from one course to the next and the reasons for stopping therapy were analyzed. One hundred fifty-nine patients received two or more courses of therapy during the study. The median number of doses of high-dose IL-2 decreased from course 1 (15 doses) to course 2 (12 doses) (p2 = 0.0001). Pretreatment factors were not found to significantly influence the decrease in the number of doses delivered. Only 2 of 33 separate toxic effects resulting in discontinuation of IL-2 dosing were found to be significantly different between courses. After adjusting for multiple tests of statistical significance, serum aspartate aminotransferase elevations were more likely to stop course 1 (p2 = 0.0033) and creatinine elevations were more Likely to stop course 2 (p2 = 0.00007). The influence of renal toxicity was further assessed by comparing the median creatinine value at the time IL-2 dosing was discontinued. This difference was found to be significant when cycle 1 of course 1 (1.5 mg/dL) was compared with cycle 1 of course 2 (1.8 mg/dL; p2 = 0.0001). When pretreatment factors were analyzed, male sex (p2 = 0.006), a diagnosis of renal cell cancer (p2 = 0.008), previous nephrectomy (p2 = 0.001), and older age (p2 = 0.0055) were significantly associated with the development of renal toxicity that resulted in discontinuation of IL-2 therapy. Furthermore, the same four patient subsets had higher baseline creatinine values in individual univariate analyses. This study identified subsets of patients who tolerated less IL-2 with repeated courses. The decreasing tolerance to IL-2 was associated primarily with elevations in creatinine. Finding ways to ameliorate the renal toxicity seen during IL-2 therapy in this patient population may allow an increase in the number of IL-2 doses administered and potentially an increase in clinical response. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Schwartzentruber, DJ (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B-04,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2000 VL 23 IS 3 BP 387 EP 392 DI 10.1097/00002371-200005000-00012 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 316DW UT WOS:000087153200012 PM 10838668 ER PT J AU Biggar, RJ Whitby, D Marshall, V Linhares, AC Black, F AF Biggar, RJ Whitby, D Marshall, V Linhares, AC Black, F TI Human herpesvirus 8 in Brazilian Amerindians: A hyperendemic population with a new subtype SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; HTLV TYPE-II; KAPOSIS-SARCOMA; DNA-SEQUENCES; SEXUAL TRANSMISSION; SEROLOGIC EVIDENCE; PERIPHERAL-BLOOD; KAYAPO INDIANS; HUMAN-HERPESVIRUS-8; INFECTION AB Human herpesvirus 8 (HHV-8) epidemiology in Brazilian Amerindians was studied. Use of an immunofluorescence (IFA) test for latent antibody demonstrated that the prevalence of HHV-8 in 781 Amerindians of diverse tribes (overall, 53% prevalence) was not related to language group or sex but rather increased gradually from 41% in children <10 years of age to 65% in adults greater than or equal to 30 years of age. In IFA-positive subjects, HHV-8 DNA was detected in 3 (16%) of 19 mononuclear cell samples from peripheral blood and in 1 of 16 saliva samples, The sequences of conserved ORF22 and K6 genes were typical of HHV-8, but the variable KI gene sequences were only 70%-75% identical to other known HHV-8 strains. Thus, a new HHV-8 subtype, E, is hyperendemic in Brazilian Amerindians, although Kaposi's sarcoma has not been reported. Transmission is probably oral rather than sexual. The limited genetic pool in isolated groups may permit more frequent transmission of a virus with a low prevalence in heterogeneous populations. C1 NCI, Viral Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Viral Epidemiol Sect, AIDS Vaccine Program,Sci Applicat Int Corp, Frederick, MD USA. Fdn Nacl Saude, Inst Evandro Chagas, Belem, Para, Brazil. Yale Univ, Sch Publ Hlth, Dept Epidemiol, New Haven, CT USA. RP Biggar, RJ (reprint author), EPS 8014,6120 Execut Blvd, Rockville, MD 20852 USA. FU NCI NIH HHS [N01CO56000] NR 41 TC 120 Z9 128 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 2000 VL 181 IS 5 BP 1562 EP 1568 DI 10.1086/315456 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 319QV UT WOS:000087353700006 PM 10823754 ER PT J AU Chougnet, C Kovacs, A Baker, R Mueller, BU Luban, NLC Liewehr, DJ Steinberg, SM Thomas, EK Shearer, GM AF Chougnet, C Kovacs, A Baker, R Mueller, BU Luban, NLC Liewehr, DJ Steinberg, SM Thomas, EK Shearer, GM TI Influence of human immunodeficiency virus-infected maternal environment on development of infant interleukin-12 production SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 13th European Immunology Meeting CY JUN 22-25, 1997 CL AMSTERDAM, NETHERLANDS ID BLOOD MONONUCLEAR-CELLS; PERINATAL HIV-INFECTION; NEONATAL T-CELLS; CD40 LIGAND; CORD-BLOOD; IFN-GAMMA; SUCCESSFUL PREGNANCY; CYTOKINE PRODUCTION; VACCINE ANTIGENS; IL-12 PRODUCTION AB Monocyte-derived cytokine production by cord blood mononuclear cells (CBMC) from infants born to human immunodeficiency virus (HIV)-positive and -negative women was measured to determine whether monocyte dysfunction could contribute to the accelerated HIV disease of pediatric patients. Production of interleukin (IL)-12, but not that of tumor necrosis factor-alpha and IL-10, was reduced, compared with adult peripheral blood mononuclear cells (PBMC). This deficiency was more pronounced in infants of HIV-positive women, whose IL-12 production was also deficient, CBMC IL-12 levels were increased by interferon-gamma and CD40 ligand but remained deficient, compared with PBMC, IL-12 production was undetectable in 7 of 8 HIV-positive infants, in contrast to 21 of 26 uninfected infants. Uninfected infants of infected women exhibited an intermediate profile. These findings suggest that the maternal environment and/or exposure in utero to HIV products influence the newborn's immune response and that the differences between infants born to HIV-positive and -negative women may persist. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Univ So Calif, Comprehens Maternal Child HIV Management & Res Ct, Sch Med, Los Angeles, CA USA. INOVA Fairfax Hosp Children, Dept Neonatol, Falls Church, VA USA. Childrens Natl Med Ctr, Dept Med, Washington, DC 20010 USA. Immunex Res & Dev Corp, Seattle, WA 98101 USA. RP Shearer, GM (reprint author), NCI, Expt Immunol Branch, NIH, 9000 Rockville Pike,Bldg 10,Rm 4B36, Bethesda, MD 20892 USA. NR 45 TC 58 Z9 58 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 2000 VL 181 IS 5 BP 1590 EP 1597 DI 10.1086/315458 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 319QV UT WOS:000087353700010 PM 10823758 ER PT J AU Losso, MH Belloso, WH Emery, S Benetucci, JA Cahn, PE Lasala, MC Lopardo, G Salomon, H Saracco, M Nelson, E Law, MG Davey, RT Allende, MC Lane, HC AF Losso, MH Belloso, WH Emery, S Benetucci, JA Cahn, PE Lasala, MC Lopardo, G Salomon, H Saracco, M Nelson, E Law, MG Davey, RT Allende, MC Lane, HC CA Vanguard Study Grp TI A randomized, controlled, phase II trial comparing escalating doses of subcutaneous interleukin-2 plus antiretrovirals versus antiretrovirals alone in human immunodeficiency virus-infected patients with CD4(+) cell counts >= 350/mm(3) SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INTRAVENOUS INTERLEUKIN-2; PROTEASE INHIBITOR; HIV-1 INFECTION; THERAPY; SUPPRESSION; RITONAVIR AB A total of 73 patients with baseline CD4(+) cell counts greater than or equal to 350 cells/mm(3) who were receiving combination antiretroviral therapy (ART) were randomized to receive subcutaneous interleukin-2 (IL-2; n = 36) in addition to ART or to continue ART alone (n = 37), Subcutaneous IL-2 was delivered at 1 of 3 doses (1.5 million international units [MIU], 4.5 MIU, and 7.5 MIU per dose) by twice-daily injection for 5 consecutive days every 8 weeks. After 24 weeks, the time-weighted mean change from baseline CD4(+) cell count was 210 cells/mm(3) for recipients of subcutaneous IL-2, compared with 29 cells/mm(3) for recipients of ART alone (P < .001). There were no significant differences between treatment groups for measures of plasma human immunodeficiency virus RNA (P = .851). Subcutaneous IL-2 delivered at doses of 4.5 MIU and 7.5 MIU resulted in significant increases in CD4(+) cell count (P = .006 and P < .001, respectively), compared with that seen in control patients. These changes were not significant in the 1.5 MIU dose group compared with that in the control patients (P = .105). Side effects that occurred from subcutaneous IL-2 administration were generally low grade, of short duration, and readily managed in an outpatient environment. C1 Hosp JM Ramos Mejia, Serv Immunocomprometidos, Dept Med, RA-1221 Buenos Aires, DF, Argentina. Hosp Italiano, Infect Dis Sect, Buenos Aires, DF, Argentina. Hosp FJ Muniz, Unit 17, Buenos Aires, DF, Argentina. Hosp JA Fernandez, Infect Dis Sect, Buenos Aires, DF, Argentina. Hosp Clin Buenos Aires, Div Infect Dis, Buenos Aires, DF, Argentina. Fdn Ctr Estudios Infectol, Buenos Aires, DF, Argentina. Univ Buenos Aires, Natl AIDS Reference Ctr, Buenos Aires, DF, Argentina. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. Univ Minnesota, Coordinat Ctr Biomet Res, Minneapolis, MN USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Hosp JM Ramos Mejia, HIV Team, RA-1221 Buenos Aires, DF, Argentina. Univ Buenos Aires, Div Immunol, Buenos Aires, DF, Argentina. Minist Hlth, Natl AIDS Program, La Plata, Argentina. Univ Buenos Aires, Dept Pharmacol, Buenos Aires, DF, Argentina. Tecnofarma SA, Buenos Aires, DF, Argentina. Univ Minnesota, Ctr Biometr Res, Minneapolis, MN 55455 USA. RP Losso, MH (reprint author), Hosp JM Ramos Mejia, Serv Immunocomprometidos, Dept Med, Urquiza 609,Pabellon Clin 2 Piso, RA-1221 Buenos Aires, DF, Argentina. NR 15 TC 58 Z9 58 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 2000 VL 181 IS 5 BP 1614 EP 1621 DI 10.1086/315430 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 319QV UT WOS:000087353700013 PM 10823761 ER PT J AU Lima, AAM Moore, SR Barboza, MS Soares, AM Schleupner, MA Newman, RD Sears, CL Nataro, JP Fedorko, DP Wuhib, T Schorling, JB Guerrant, RL AF Lima, AAM Moore, SR Barboza, MS Soares, AM Schleupner, MA Newman, RD Sears, CL Nataro, JP Fedorko, DP Wuhib, T Schorling, JB Guerrant, RL TI Persistent diarrhea signals a critical period of increased diarrhea burdens and nutritional shortfalls: A prospective cohort study among children in northeastern Brazil SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the International-Centers-for-Tropical-Disease-Research CY APR 26-28, 1999 CL NIH, BETHESDA, MARYLAND SP Int Ctr Trop Dis Res HO NIH ID ENTEROAGGREGATIVE ESCHERICHIA-COLI; CRYPTOSPORIDIUM-PARVUM INFECTION; CATCH-UP GROWTH; RISK-FACTORS; RURAL BANGLADESH; YOUNG-CHILDREN; PERUVIAN CHILDREN; PHYSICAL GROWTH; URBAN-COMMUNITY; EARLY-CHILDHOOD AB Persistent diarrhea (PD; duration greater than or equal to 14 days) is a growing part of the global burden of diarrheal diseases. A 45-month prospective cohort study (with illness, nutritional, and microbiologic surveillance) was conducted in a shantytown in northeastern Brazil, to elucidate the epidemiology, nutritional impact, and causes of PD in early childhood (0-3 years of age). A nested case-control design was used to examine children's diarrhea burden and nutritional status before and after a first PD illness. PD illnesses accounted for 8% of episodes and 34% of days of diarrhea, First PD illnesses were preceded by a doubling of acute diarrhea burdens, were followed by further 2.6-3.5-fold increased diarrhea burdens for 18 months, and were associated with acute weight shortfalls. Exclusively breast-fed children had 8-fold lower diarrhea rates than did weaned children. PD-associated etiologic agents included Cryptosporidium, Giardia, enteric adenoviruses, and enterotoxigenic Escherichia coli, PD signals growth shortfalls and increased diarrhea burdens; children with PD merit extended support, and the illness warrants further study to elucidate its prevention, treatment, and impact. C1 Fed Univ Ceara, Hosp Walter Condidio, Dept Physiol & Pharmacol, Fac Med,Clin Res Unit, BR-60436160 Fortaleza, Ceara, Brazil. Univ Virginia, Sch Med, Dept Med, Div Geograph & Int Med, Charlottesville, VA 22908 USA. Univ Washington, Sch Med, Dept Pediat, Div Gen Pediat, Seattle, WA 98195 USA. Hlth Alliance Int, Seattle, WA USA. Johns Hopkins Univ, Sch Med, Div Infect Dis & Gastroenterol, Dept Med, Baltimore, MD 21205 USA. Univ Maryland, Ctr Vaccine Dev, Baltimore, MD 21201 USA. NIH, Dept Clin Pathol, Microbiol Serv, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div HIV AIDS, Atlanta, GA USA. RP Lima, AAM (reprint author), Fed Univ Ceara, Hosp Walter Condidio, Dept Physiol & Pharmacol, Fac Med,Clin Res Unit, Av Jose Bastos,3390 Sala 90,Porangabussu, BR-60436160 Fortaleza, Ceara, Brazil. FU NIAID NIH HHS [U01AI26512, AI33096] NR 64 TC 118 Z9 127 U1 1 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 2000 VL 181 IS 5 BP 1643 EP 1651 DI 10.1086/315423 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 319QV UT WOS:000087353700017 PM 10823764 ER PT J AU Branch, OH Oloo, AJ Nahlen, BL Kaslow, D Lal, AA AF Branch, OH Oloo, AJ Nahlen, BL Kaslow, D Lal, AA TI Anti-merozoite surface protein-1 19-kDa IgG in mother-infant pairs naturally exposed to Plasmodium falciparum: Subclass analysis with age, exposure to asexual parasitemia, and protection against malaria. V. The Asembo Bay Cohort Project SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID C-TERMINAL FRAGMENT; B-CELL EPITOPES; 19-KILODALTON DOMAIN; SERUM ANTIBODIES; IMMUNE-RESPONSE; IN-VITRO; INHIBIT; GROWTH; BLOOD; MSP1 AB The anti-merozoite surface protein-1 19-kDa IgG (anti-MSP1(19KD)) IgG responses of 33 parasitemic infants, aged 6-14 months, were compared with those of their mothers at the time of the infant's delivery and at the time the infants were sampled; the antimalaria protection associated with these responses was also compared. IgG1 and IgG3 were the predominant subclasses. Infants <300 days old and pregnant mothers had the lowest cytophilic-to-noncytophilic IgG ratio. By 300 days of age, the infants had IgG subclass compositions and levels similar to those of their mothers at the same date. Among infants, older infants with only 1 or 2 detected asexual parasitemias had the highest cytophilic-to-noncytophilic IgG ratio and IgG1 levels. IgG1 level was negatively correlated with protection. The findings suggest that the MSP1(19KD) antibody response develops with age, not with multiple experiences with parasitemia, and, thus, that an antimalaria vaccine strategy for pregnant mothers could delay infants' first parasitemias until they are more capable of mounting a favorable anti-MSP1(19KD) response. C1 Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA USA. Emory Univ, Atlanta, GA 30322 USA. Kenya Med Res Inst, Vector Biol & Control Res Ctr, Kisumu, Kenya. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Lal, AA (reprint author), Ctr Dis Control & Prevent, Mail Stop F12,4770 Buford Hwy, Chamblee, GA 30341 USA. NR 30 TC 36 Z9 36 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 2000 VL 181 IS 5 BP 1746 EP 1752 DI 10.1086/315424 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 319QV UT WOS:000087353700030 PM 10823777 ER PT J AU King, JC Borkowsky, W Mahidhara, N Madore, D Shapiro, ED Rutstein, RM Tan, TQ Farley, JJ Dankner, WM Nachman, S Simoes, E Flynn, PM Clemens, J Hamilton, RG AF King, JC Borkowsky, W Mahidhara, N Madore, D Shapiro, ED Rutstein, RM Tan, TQ Farley, JJ Dankner, WM Nachman, S Simoes, E Flynn, PM Clemens, J Hamilton, RG TI Group-specific antibody levels surrounding invasive pneumococcal illness in children infected with human immunodeficiency virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the Society-for-Pediatric-Research CY MAY 02-06, 1997 CL WASHINGTON, D.C. SP Soc Pediat Res ID CONJUGATE VACCINE; ACTIVATION; DISEASE; SERUM AB Pneumococcal antibody levels surrounding systemic pneumococcal illness (SPI) were measured in children infected with human immunodeficiency virus (HIV). Archived serum samples were collected from 28 HIV-infected children who had 34 cases of SPI, caused by pneumococcal groups 4, 6, 9, 14, 19, and 23. Serum samples collected within 23 weeks before and 13 weeks after the SPI were assayed by ELISA for antipneumococcal polysaccharide (PnPs) IgG antibody to 6 representative pneumococcal serotypes, There was a wide range (0.16-30.80 mu g/mL) of pre-SPI anti-PnPs antibody levels to the presumed infecting serotypes, with a geometric mean level of 0.83 mu g/mL (n = 34), Seventy-six percent of the antibody values were <2.0 mu g/mL and 95% were <5.0 mu g/mL. Homologous seroresponses (greater than or equal to 4-fold rise in anti-PnPs antibody) were detected in only 4 (27%) of 15 paired serum samples. Heterologous, noninfecting group seroresponses were detected frequently (72%) in the paired serum samples from these 4 homologous group seroresponders. C1 Univ Maryland, Sch Med, Dept Pediat, Med Syst, Baltimore, MD 21201 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NICHHD, NIH, Bethesda, MD 20892 USA. NYU Med Ctr, New York, NY 10016 USA. Wyeth Lederle Vaccines & Pediat, W Henrietta, NY USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Yale Univ, Sch Med, New Haven, CT USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Northwestern Univ, Sch Med, Chicago, IL USA. Childrens Hosp, Denver, CO 80218 USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP King, JC (reprint author), Univ Maryland, Sch Med, Dept Pediat, Med Syst, 700 W Lombard St, Baltimore, MD 21201 USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 2000 VL 181 IS 5 BP 1817 EP 1821 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 319QV UT WOS:000087353700046 PM 10823792 ER PT J AU Green, KY Ando, T Balayan, MS Berke, T Clarke, IN Estes, MK Matson, DO Nakata, S Neill, JD Studdert, MJ Thiel, HJ AF Green, KY Ando, T Balayan, MS Berke, T Clarke, IN Estes, MK Matson, DO Nakata, S Neill, JD Studdert, MJ Thiel, HJ TI Taxonomy of the caliciviruses SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Workshop on Human Caliciviruses CY MAR 29-31, 1999 CL ATLANTA, GEORGIA SP Ctr Dis Control & Prevent, US EPA, US FDA, Natl Inst Infect Dis Japan, Natl Inst Publ Hlth & Environm Protect, NIAID, Publ Hlth Lab Serv, Task Force Child Survival & Dev, USA Med Res & Mat Command, WHO, Merck Res Labs, SmithKline Beecham Biol, Wyeth Lederle Vaccines & Pediat, Natl Ctr Infect Dis ID RABBIT HEMORRHAGIC-DISEASE; HUMAN ENTERIC CALICIVIRUSES; ROUND-STRUCTURED VIRUSES; BROWN HARE SYNDROME; NORWALK-LIKE VIRUS; FELINE CALICIVIRUS; MOLECULAR CHARACTERIZATION; ANIMAL CALICIVIRUSES; INFECTED-CELLS; SEQUENCE AB The International Committee on Taxonomy of Viruses (ICTV) has recently approved several proposals submitted by the present Caliciviridae Study Group. These proposals include the division of the family into 4 new genera designated Lagovirus, Vesivirus, "Norwalk-like viruses" (NLVs), and "Sapporo-like viruses" (SLVs); the latter 2 genera were assigned temporary names until acceptable names can be determined by the scientific community. The genera have been further divided into the following species: Feline calicivirus and Vesicular exanthema of swine virus(genus Vesivirus), Rabbit hemorrhagic disease virus and European brown have syndrome virus (genus Lagovirus), Norwalk virus (genus NLV), and Sapporo virus (genus SLV). In addition, the ICTV approved a proposal to remove the hepatitis E virus from the Caliciviridae into an "unassigned" classification status. C1 NIH, Bethesda, MD 20832 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Russian Acad Med Sci, Inst Poliomyelitis & Viral Encephalitis, Moscow 142782, Russia. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Univ Southampton, Southampton, Hants, England. Baylor Coll Med, Houston, TX 77030 USA. Sapporo Med Univ, Sch Med, Sapporo, Hokkaido, Japan. USDA, Ames, IA 50010 USA. Univ Melbourne, Parkville, Vic 3052, Australia. Univ Giessen, Inst Virol, D-6300 Giessen, Germany. RP Green, KY (reprint author), NIH, 9000 Rockville Pike,Bldg 7,Room 137, Bethesda, MD 20832 USA. NR 57 TC 218 Z9 236 U1 2 U2 27 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 2000 VL 181 SU 2 BP S322 EP S330 DI 10.1086/315591 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 321DH UT WOS:000087439400014 PM 10804145 ER PT J AU Jiang, X Wilton, N Zhong, WM Farkas, T Huang, PW Barrett, E Guerrero, M Ruiz-Palacios, G Green, KY Green, J Hale, AD Estes, MK Pickering, LK Matson, DO AF Jiang, X Wilton, N Zhong, WM Farkas, T Huang, PW Barrett, E Guerrero, M Ruiz-Palacios, G Green, KY Green, J Hale, AD Estes, MK Pickering, LK Matson, DO TI Diagnosis of human caliciviruses by use of enzyme immunoassays SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Workshop on Human Caliciviruses CY MAR 29-31, 1999 CL ATLANTA, GEORGIA SP Ctr Dis Control & Prevent, US EPA, US FDA, Natl Inst Infect Dis Japan, Natl Inst Publ Hlth & Environm Protect, NIAID, Publ Hlth Lab Serv, Task Force Child Survival & Dev, USA Med Res & Mat Command, WHO, Merck Res Labs, SmithKline Beecham Biol, Wyeth Lederle Vaccines & Pediat, Natl Ctr Infect Dis ID ROUND-STRUCTURED VIRUSES; NORWALK-LIKE VIRUS; IMMUNE ELECTRON-MICROSCOPY; SNOW MOUNTAIN AGENT; LINKED IMMUNOSORBENT ASSAYS; CAPSID PROTEIN; MEXICO VIRUS; MOLECULAR CHARACTERIZATION; IMMUNOGLOBULIN-M; UNITED-KINGDOM AB The application of molecular technologies, such as the expression of viral proteins in baculovirus, has provided a powerful approach to the diagnosis of human calicivirus (HuCV) infections, The baculovirus-expressed HuCV capsid protein self-assembles into virus-like particles, providing excellent reagents for immunologic assays, such as enzyme immunoassays (EIAs), Following the expression of the capsid protein of Norwalk virus, the capsid proteins of 8 other HuCV strains have been expressed in baculovirus. The unlimited supply of baculovirus-produced reagents for HuCVs allows these EIAs to be applied in large-scale clinical and epidemiological studies. Both the antigen and antibody-detection EIAs are highly sensitive. The antigen-detection EIAs are highly specific, but the antibody-detection EIAs are more broadly reactive. This article reviews baculovirus expression techniques used to produce HuCV capsid antigens, development of EIAs using these antigens, and application of these EIAs in studies of HuCV infection and illness. C1 Eastern Virginia Med Sch, Childrens Hosp Kings Daughters, Ctr Pediat Res, Norfolk, VA 23510 USA. Dept Hlth, Richmond, VA USA. Inst Nutr, Dept Infect Dis, Mexico City, DF, Mexico. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Div Virol, Houston, TX USA. Cent Publ Hlth Lab, Virus Reference Lab, London NW9 5HT, England. RP Jiang, X (reprint author), Eastern Virginia Med Sch, Childrens Hosp Kings Daughters, Ctr Pediat Res, 855 W Brambleton Ave, Norfolk, VA 23510 USA. NR 83 TC 71 Z9 74 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 2000 VL 181 SU 2 BP S349 EP S359 DI 10.1086/315577 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 321DH UT WOS:000087439400017 PM 10804148 ER PT J AU Kapikian, AZ AF Kapikian, AZ TI The discovery of the 27-nm Norwalk virus: An historic perspective SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Workshop on Human Caliciviruses CY MAR 29-31, 1999 CL ATLANTA, GEORGIA SP Ctr Dis Control & Prevent, US EPA, US FDA, Natl Inst Infect Dis Japan, Natl Inst Publ Hlth & Environm Protect, NIAID, Publ Hlth Lab Serv, Task Force Child Survival & Dev, USA Med Res & Mat Command, WHO, Merck Res Labs, SmithKline Beecham Biol, Wyeth Lederle Vaccines & Pediat, Natl Ctr Infect Dis ID IMMUNE ELECTRON-MICROSCOPY; INFECTIOUS NONBACTERIAL GASTROENTERITIS; VIRAL GASTROENTERITIS; VOLUNTEERS; PARTICLES; AGENT AB In 1972, a 27-nm virus-like particle was discovered by use of immune electron microscopy (IEM) in an infectious stool filtrate derived from an outbreak of gastroenteritis in an elementary school in Norwalk, Ohio, IEM enabled the direct visualization of antigen-antibody interaction, as the particles were aggregated and coated by specific antibodies, This allowed the recognition and identification of a 27-nm virus-like particle that did not have a distinctive morphology, was low-titered, and was among the smallest viruses known, Serum antibody responses to the 27-nm particle were demonstrated in key individuals infected under natural or experimental conditions; this and other evidence suggested that this virus-like particle was the etiologic agent of the Norwalk gastroenteritis outbreak. The fastidious 27-nm Norwalk virus is now considered to be the prototype strain of a group of noncultivatable viruses that are important etiologic agents of epidemic gastroenteritis in adults and older children. C1 NIAID, Infect Dis Lab, Epidemiol Sect, NIH, Bethesda, MD 20892 USA. RP Kapikian, AZ (reprint author), NIAID, Infect Dis Lab, Epidemiol Sect, NIH, Bldg 7,Room 103,7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. NR 39 TC 42 Z9 44 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 2000 VL 181 SU 2 BP S295 EP S302 DI 10.1086/315584 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 321DH UT WOS:000087439400010 PM 10804141 ER PT J AU Dimon-Gadal, S Gerbaud, P Therond, P Guibourdenche, J Anderson, WB Evain-Brion, D Raynaud, F AF Dimon-Gadal, S Gerbaud, P Therond, P Guibourdenche, J Anderson, WB Evain-Brion, D Raynaud, F TI Increased oxidative damage to fibroblasts in skin with and without lesions in psoriasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE dinitrophenylhydrazine; fibroblasts; oxidative modification; protein carbonyls; psoriasis; skin ID TUMOR NECROSIS FACTOR; PROTEIN OXIDATION; PATHOLOGY; RADICALS; GENETICS; ENZYMES; CELLS AB Differences in oxidative damage, as measured by an increase in the carbonylation of macromolecules, were determined in situ with skin biopsies from psoriatic patients and controls. High levels of carbonyl residues were consistently detected in the dermis and never in the epidermis of sections of these skin biopsy samples. The dermis of psoriatic skin without lesions had a higher level of carbonylation than the dermis of normal skin. In this study, we found that there was more oxidative damage in cultured fibroblasts prepared from skin with and without lesions from psoriasis patients than in normal fibroblasts from the skin of age-matched controls. The extent of protein carbonylation in cell extracts was determined by immunoblotting, using an antidinitrophenylhydrazone antibody, and in intact cells was determined by immunocytochemical analysis with the same antibody. The higher level of carbonylation detected was used here as a measure of oxidative stress, and showed that some oxidative damage occurred before the appearance of typical psoriatic plaques. These results suggest that fibroblasts are affected before the onset of psoriasis and that this damage is independent of any inflammatory infiltrate. C1 Univ Paris 05, Fac Sci Pharmaceut & Biol, INSERM, U427, F-75270 Paris 06, France. Hop Bicetre, Serv Biochim, Le Kremlin Bicetre, France. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Raynaud, F (reprint author), Univ Paris 05, Fac Sci Pharmaceut & Biol, INSERM, U427, 4 Ave Observ, F-75270 Paris 06, France. NR 41 TC 26 Z9 31 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2000 VL 114 IS 5 BP 984 EP 989 DI 10.1046/j.1523-1747.2000.00962.x PG 6 WC Dermatology SC Dermatology GA 313CC UT WOS:000086981100013 PM 10771481 ER PT J AU Vellutino, FR Scanlon, DM Lyon, GR AF Vellutino, FR Scanlon, DM Lyon, GR TI Differentiating between difficult-to-remediate and readily remediated poor readers - More evidence against the IQ-achievement discrepancy definition of reading disability SO JOURNAL OF LEARNING DISABILITIES LA English DT Article ID LEARNING-DISABILITIES; RETARDATION; IRRELEVANT; CHILDREN AB In this article we discuss research bearing on the traditional use of the IQ-achievement discrepancy to define specific reading disability. We initially review the evidence presented by Rutter and Yule (1975) in support of this practice, and then discuss results from subsequent studies that have questioned the reliability of their findings. We also discuss results from more recent studies demonstrating that the IQ-achievement discrepancy does not reliably distinguish poor from normal readers, whereas language-based measures do reliably distinguish these groups. We highlight results from a study we recently completed, in which it was found that IQ scores did not differentiate between poor readers who were found to be readily remediated and poor readers who were difficult to remediate. In view of the convergent evidence against the use of IQ scores to define specific reading disability, we suggest that the IQ-achievement discrepancy definition of this disorder be discarded. C1 SUNY Albany, Dept Psychol, Albany, NY 12222 USA. SUNY Albany, Dept Educ & Counseling Psychol, Albany, NY 12222 USA. SUNY Albany, Child Res & Study Ctr, Albany, NY 12222 USA. NICHHD, Child Dev & Behav Branch, NIH, Bethesda, MD 20892 USA. RP Vellutino, FR (reprint author), SUNY Albany, Child Res & Study Ctr, Husted Hall,135 Western Ave, Albany, NY 12222 USA. FU NICHD NIH HHS [P50HD25806] NR 38 TC 171 Z9 173 U1 1 U2 13 PU PRO-ED INC PI AUSTIN PA 8700 SHOAL CREEK BLVD, AUSTIN, TX 78757-6897 USA SN 0022-2194 J9 J LEARN DISABIL-US JI J. Learn. Disabil. PD MAY-JUN PY 2000 VL 33 IS 3 BP 223 EP 238 DI 10.1177/002221940003300302 PG 16 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 313DX UT WOS:000086986000004 PM 15505962 ER PT J AU Dyer, KD Rosenberg, HF AF Dyer, KD Rosenberg, HF TI Shared features of transcription: mutational analysis of the eosinophil/basophil Charcot-Leyden crystal protein gene promoter SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE hematopoiesis ID FETAL LIVER HEMATOPOIESIS; INTRONIC ENHANCER; BINDING PROTEINS; NEUROTOXIN RNS2; FACTOR GATA-1; LYSOPHOSPHOLIPASE; EXPRESSION; CELLS; BETA; AML1 AB The lineage-specific Charcot-Leyden crystal (CLC) protein is found in human eosinophils and basophils where it comprises 7-10% of the cellular protein content, Previous work from our laboratory has identified the motif GGAGA[A/G] as a powerful enhancer of gene transcription in two eosinophil ribonuclease genes. To evaluate a potentially larger role for this motif in the transcriptional regulation of eosinophil genes, we have isolated 1504 nucleotides 5' to the transcriptional start site of the gene encoding CLC protein and identified a functionally active promoter that includes three distinct copies of the GGAGAA motif. Destruction of only one of the three motifs by site-directed mutagenesis resulted in loss of promoter activity (73 +/- 6% reduction), suggesting that this core motif is necessary but not sufficient to support enhanced transcriptional activity. Sequence comparisons and site-specific mutagenesis has permitted further delineation of this enhancer element which, as a result of this work, is now defined as GGAGA[A/G]NNNA. Electromobility shift assays demonstrated specific binding of nuclear protein(s) from an eosinophilic clone-15 nuclear extract to this extended motif, Similar analysis of a GATA-1 binding site demonstrated enhancer activity, with mutagenesis resulting in a 94 +/- 1.4% reduction in activity, whereas the AML1 site functioned as a gene silencer. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Physiol & Biophys, Washington, DC USA. RP Rosenberg, HF (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N104,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 12 Z9 12 U1 0 U2 0 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 MAY PY 2000 VL 67 IS 5 BP 691 EP 698 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 330ME UT WOS:000087965200014 PM 10811010 ER PT J AU Kennedy, J Vicari, AP Saylor, V Zurawski, SM Copeland, NG Gilbert, DJ Jenkins, NA Zlotnik, A AF Kennedy, J Vicari, AP Saylor, V Zurawski, SM Copeland, NG Gilbert, DJ Jenkins, NA Zlotnik, A TI A molecular analysis of NKT cells: identification of a class-I restricted T cell-associated molecule (CRTAM) SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE human; mouse; T lymphocytes; cell-surface molecules ID PROMPTLY PRODUCE INTERLEUKIN-4; ALPHA-BETA; CYTOKINE PRODUCTION; GENE-EXPRESSION; THYMOCYTES; RECEPTOR; MOUSE; FAMILY; SUBSET; LYMPHOCYTES AB cDNA library subtraction techniques were used to identify transcripts expressed by activated mouse alpha beta TCR+ CD4(-)CD8(-) (double-negative; DN) T cells, a subset of natural killer T (NKT) cells. The most frequent cDNAs identified included the chemokines TCA3, macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and lymphotactin (LPTN), the cytokines interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), and a granzyme, We also identified a new member of the immunoglobulin superfamily (Ig-SF), This molecule was designated class I-restricted T cell-associated molecule (CRTAM) as a result of its restricted expression pattern in T cells. Human CRTAM was also identified, and shares the same expression pattern as the mouse molecule. LPTN and CRTAM exhibit the same expression pattern in T cells, suggesting the existence of a gene expression program common to class I-MHC-restricted T cells. C1 DNAX Res Inst Mol & Cellular Biol Inc, Dept Immunol, Palo Alto, CA 94304 USA. DNAX Res Inst Mol & Cellular Biol Inc, Dept Mol Biol, Palo Alto, CA 94304 USA. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Zlotnik, A (reprint author), DNAX Res Inst Mol & Cellular Biol Inc, Dept Immunobiol, 901 Calif Ave, Palo Alto, CA 94304 USA. RI Zlotnik, Albert/C-3791-2011 FU NCI NIH HHS [N01-CO-46000] NR 53 TC 56 Z9 59 U1 0 U2 3 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 MAY PY 2000 VL 67 IS 5 BP 725 EP 734 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 330ME UT WOS:000087965200018 PM 10811014 ER PT J AU Lambert, G Amar, MJA Martin, P Fruchart-Najib, J Foger, B Shamburek, RD Brewer, HB Santamarina-Fojo, S AF Lambert, G Amar, MJA Martin, P Fruchart-Najib, J Foger, B Shamburek, RD Brewer, HB Santamarina-Fojo, S TI Hepatic lipase deficiency decreases the selective uptake of HDL-cholesteryl esters in vivo SO JOURNAL OF LIPID RESEARCH LA English DT Article DE reverse cholesterol transport; apoA-I; apoA-II; SR-BI ID HIGH-DENSITY-LIPOPROTEIN; TRANSGENIC MICE; RAT-LIVER; TRIGLYCERIDE LIPASE; IN-VIVO; SR-BI; METABOLISM; RECEPTOR; ATHEROSCLEROSIS; CELLS AB Recent in vitro studies have provided evidence that hepatic lipase (HL) facilitates the selective uptake of HDL cholesteryl esters (CE), but the in vivo physiological relevance of this process has not been demonstrated, To evaluate the role that HL plays in facilitating the selective uptake of HDL-CE in vivo, we studied the metabolism of [H-3]CEt, I-125-labeled apolipoprotein (apo) A-I, and I-131- labeled apoA-II-labeled HDL in HL-deficient mice. Kinetic analysis revealed similar catabolism of I-125-labeled apoA-I (as well as I-131-labeled apoA-II) in C57BL controls and HL deficient mice, with fractional catabolic rates (FCR) of 2.17 +/- 0.15 and 2.16 +/- 0.11 d(-1) (2.59 +/- 0.14 and 2.67 +/- 0.13 d(-1), respectively). In contrast, despite similar hepatic scavenger receptor BI expression, HL-deficient mice had delayed clearance of [H-3]CEt compared to controls (FCR = 3.66 +/- 0.29 and 4.41 +/- 0.18 d(-1), P < 0,05), The hepatic accumulation of [H-3]CEt in HL-deficient mice (62.3 +/- 2.1% of total) was significantly less than in controls (72.7 +/- 3.0%), while the [H-3]CEt remaining in the plasma compartment increased (20.7 +/- 1.8% and 12.6 +/- 0.5%) (P < 0,05, all). In summary, HL deficiency does not alter the catabolism of apoA-I and apoA-II but decreases the hepatic uptake and the plasma clearance of HDL-CE, These data establish for the first time an important role for HL in facilitating the selective uptake of HDL-CE in vivo.Hepatic lipase deficiency decreases the selective uptake of HDL- cholesteryl esters in vivo. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Inst Pasteur, INSERM, U325, Dept Atherosclerose, F-59019 Lille, France. RP Lambert, G (reprint author), NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. OI Martin, Pascal/0000-0002-4271-658X NR 26 TC 45 Z9 46 U1 0 U2 5 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAY PY 2000 VL 41 IS 5 BP 667 EP 672 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 314KD UT WOS:000087054200001 PM 10787427 ER PT J AU Pan, DA Mater, MK Thelen, AP Peters, JM Gonzalez, FJ Jump, DB AF Pan, DA Mater, MK Thelen, AP Peters, JM Gonzalez, FJ Jump, DB TI Evidence against the peroxisome proliferator-activated receptor alpha (PPAR alpha) as the mediator for polyunsaturated fatty acid suppression of hepatic L-pyruvate kinase gene transcription SO JOURNAL OF LIPID RESEARCH LA English DT Article DE hepatic nuclear factor-4 (HNF4); peroxisome proliferators; cytochrome P450 4A; glycolysis; lipogenesis ID ELEMENT-BINDING PROTEIN-1; RESPONSE ELEMENT; CARBOHYDRATE REGULATION; MOUSE-LIVER; EXPRESSION; RAT; MECHANISM; GLUCOSE; BIOSYNTHESIS; METABOLISM AB The glycolytic enzyme, L-pyruvate kinase (L-PK), plays an important role in hepatic glucose metabolism. Insulin and glucose induce L-PK gene expression, while glucagon and polyunsaturated fatty acids (PUFA) inhibit L-PK gene expression. We have been interested in defining the PUFA regulation of L-PK. The cis-regulatory target for PUFA action includes an imperfect direct repeat (DR1) that binds HNF-4, HNF4 plays an ancillary role in the insulin/glucose-mediated transactivation of the L-PK gene, Because the fatty acid-activated nuclear receptor, peroxisome proliferator-activated receptor (PPAR alpha), binds DR1-like elements and has been reported to interfere with HNF4 action, we examined the role PPARa plays in the regulation of L-PK gene transcription. Feeding rats either fish oil or the potent PPAR alpha activator, WY14,643, suppressed rat hepatic L-PK mRNA and gene transcription. The PPAB alpha-null mouse was used to evaluate the role of the PPAR alpha in hepatic transcriptional control of L-PK. While WY14,643 control of L-PK gene expression required the PPAR alpha, PUFA regulation of L-PK gene expression was independent of the PPAR alpha,. Transfection studies in cultured primary hepatocytes localized the cis-regulatory target for WY14,643/PPAR alpha action to the L-PK HNF4 binding site. However, PPAR alpha/RXR alpha heterodimers did not bind this region. Although both WY14,643 and PUFA suppress L-PK gene transcription through the same element, PUFA regulation of L-PK does not require the PPARa and PPAR alpha/RXR alpha does not bind the L-PK promoter. These studies suggest that other intermediary factors are involved in both the PUFA and PPAR alpha regulation of L-PK gene transcription. Evidence against the peroxisome proliferator-activated receptor alpha (PPAR alpha) as the mediator for polyunsaturated fatty acid suppression of hepatic L-pyruvate kinase gene transcription. C1 Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA. Michigan State Univ, Dept Biochem, E Lansing, MI 48824 USA. Michigan State Univ, Dept Bot, E Lansing, MI 48824 USA. Michigan State Univ, Dept Plant Pathol, E Lansing, MI 48824 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Jump, DB (reprint author), Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA. RI Peters, Jeffrey/D-8847-2011 FU NIDDK NIH HHS [DK-43220, R01 DK043220] NR 42 TC 48 Z9 49 U1 0 U2 3 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAY PY 2000 VL 41 IS 5 BP 742 EP 751 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 314KD UT WOS:000087054200009 PM 10787435 ER PT J AU Murphy, EJ Stiles, T Schroeder, F AF Murphy, EJ Stiles, T Schroeder, F TI Sterol carrier protein-2 expression alters phospholipid content and fatty acyl composition in L-cell fibroblasts SO JOURNAL OF LIPID RESEARCH LA English DT Article DE sterol carrier protein-2; phospholipids; plasmalogens; fatty acids; L-cells; fibroblasts ID LIPID-TRANSFER PROTEIN; DIHYDROXYACETONE PHOSPHATE ACYLTRANSFERASE; PERFORMANCE LIQUID-CHROMATOGRAPHY; RAT-LIVER; COENZYME-A; SUBCELLULAR-LOCALIZATION; CHOLINE PLASMALOGENS; MAMMALIAN-TISSUES; BINDING PROTEIN; ACID AB The effects sterol carrier protein-2 (SCP-2) expression on L-cell. phospholipid levels and fatty acyl composition was assessed using L-cells transfected with the murine cDNA encoding for either the 15 kDa proSCP-2 or 13.2 kDa SCP-2, Expression of these proteins reduced total phospholipid mass (nmol/mg protein) by 24% and reduced the cholesterol to phospholipid ratio 60 and 28%, respectively. In 15 kDa proSCP-2 expressing cells, individual phospholipid class masses, excluding sphingomyelin (CerPCho), were reduced as follows: phosphatidylinositol (PtdIns) and phosphatidylserine (PtdSer) >> ethanolamine glycerophospholipid (EtnGp1)> choline glycerophospholipid (ChoGp1), Furthermore, ethanolamine plasmalogen mass was decreased 25%, while choline plasmalogen mass was elevated 30% in 15 kDa proSCP-2 expressing cells. In 13.2 kDa SCP-2 expressing cells, phospholipid class mass was decreased as follows: PtdIns and PtdSer >> ChoGpl, These changes in phospholipid mass resulted in altered cellular phospholipid composition. Expression of either protein differentially altered the type of fatty acid esterified onto the phospholipids. These effects included a greater proportion of polyunsaturated fatty acids and a reduction in saturated fatty acids, although 15 kDa proSCP-2 expression had a more robust effect on these parameters than did 13.2 kDa SCP-2 expression. In summary, expression of SCP-2 reduced individual phospholipid class mass, except for CerPCho, and altered the fatty acid composition of each phospholipid class examined. These results clearly demonstrate that SCP-2 expression altered basal phospholipid levels, suggesting that SCP-2 can alter the function of endoplasmic reticulum phospholipid synthetic enzymes. Sterol carrier protein-2 expression alters phospholipid content and fatty acyl composition in L-cell fibroblasts. C1 Texas A&M Univ, Dept Pharmacol & Physiol, TVMC, College Stn, TX 77843 USA. RP Murphy, EJ (reprint author), NIA, Sect Brain Physiol & Metab, Bldg 10,Room 6C103, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK41402] NR 62 TC 22 Z9 22 U1 1 U2 2 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAY PY 2000 VL 41 IS 5 BP 788 EP 796 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 314KD UT WOS:000087054200013 PM 10787439 ER PT J AU Hunt, MC Lindquist, PJG Peters, JM Gonzalez, FJ Diczfalusy, U Alexson, SEH AF Hunt, MC Lindquist, PJG Peters, JM Gonzalez, FJ Diczfalusy, U Alexson, SEH TI Involvement of the peroxisome proliferator-activated receptor alpha in regulating long-chain acyl-CoA thioesterases SO JOURNAL OF LIPID RESEARCH LA English DT Article DE acyl-CoA thioesterases; acyl-CoA; fasting; peroxisome proliferator-activated receptor; lipid metabolism; fat free diet; clofibrate ID ACID N-ACYLTRANSFERASE; RAT-LIVER; FATTY-ACIDS; MOLECULAR-CLONING; BINDING-PROTEIN; ADAPTIVE RESPONSE; GENE-EXPRESSION; CLOFIBRIC ACID; PPAR-ALPHA; INDUCTION AB Long-chain acyl-CoA thioesterases catalyze the hydrolysis of acyl-CoAs to the corresponding free fatty acid and CoA, We recently cloned four members of a novel multigene family of peroxisome proliferator-induced genes encoding cytosolic (CTE-I), mitochondrial (MTE-I), and peroxisomal (PTE-Ia and PTE-Ib) acyl-CoA thioesterases (Hunt ct al. 1999, J. Biol. Chem. 274: 34317-34326), As the peroxisome proliferator-activated receptor alpha (PPAR alpha) plays a central role in regulating genes involved in lipid metabolism, we examined the involvement of this receptor in regulation of the thioesterases, particularly CTE-I and MTE-I. Northern blot analysis shows that the induction of these thioesterases by clofibrate is mediated through a strictly PPAR alpha-dependent mechanism. All four acyl-CoA thioesterases are induced at mRNA level by fasting and using PPAR alpha-null mice, it is evident that the increase in CTEI due to fasting is mainly independent of the PPAR alpha in liver and heart. The CTEI gene responds rapidly to fasting, with induction of mRNA and protein evident after 6 h. This: fasting effect is rapidly reversible, with CTE-I mRNA returning almost to control levels after 3 h refeeding, and being further repressed to 20% of control after 9 h refeeding. Although CTEI mRNA shows a low basal expression in liver, it can be suppressed 90% by feeding a fat-free diet. These data demonstrate that the nutritional regulation of the thioesterases involves the PPAR alpha and other signaling pathways responsible for activation and repression, Putative physiological functions for the acyl-CoA thioesterases are discussed. Involvement of the peroxisome proliferator-activated receptor alpha in regulating long-chain acyl-CoA thioesterases. C1 Huddinge Univ Hosp, Karolinska Inst, Dept Med Lab Sci & Technol, Div Clin Chem, S-14186 Huddinge, Sweden. NIH, Met Lab, Bethesda, MD 20892 USA. RP Alexson, SEH (reprint author), Huddinge Univ Hosp, Karolinska Inst, Dept Med Lab Sci & Technol, Div Clin Chem, S-14186 Huddinge, Sweden. RI Diczfalusy, Ulf/A-5336-2008; Peters, Jeffrey/D-8847-2011 NR 42 TC 44 Z9 44 U1 1 U2 3 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAY PY 2000 VL 41 IS 5 BP 814 EP 823 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 314KD UT WOS:000087054200016 PM 10787442 ER PT J AU Worrall, TA Lin, SH Cotter, RJ Woods, AS AF Worrall, TA Lin, SH Cotter, RJ Woods, AS TI On-probe sample purification of lipids for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry SO JOURNAL OF MASS SPECTROMETRY LA English DT Letter ID HAEMOPHILUS-INFLUENZAE; ENDOTOXIN PREPARATIONS; DESORPTION; MEMBRANES; LIPOOLIGOSACCHARIDES; LIPOPOLYSACCHARIDES; SPHAEROIDES; RECOGNITION; PEPTIDES; PROTEINS C1 Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mol Sci, Baltimore, MD 21205 USA. RP Woods, AS (reprint author), NIDA, Intramural Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIGMS NIH HHS [GM54882] NR 25 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD MAY PY 2000 VL 35 IS 5 BP 647 EP 650 DI 10.1002/(SICI)1096-9888(200005)35:5<647::AID-JMS973>3.3.CO;2-5 PG 4 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 310RJ UT WOS:000086840900009 PM 10800055 ER PT J AU Dincer, P Akcoren, Z Demir, E Richard, I Sancak, O Kale, G Ozme, S Karaduman, A Tan, E Urtizberea, JA Beckmann, JS Topaloglu, H AF Dincer, P Akcoren, Z Demir, E Richard, I Sancak, O Kale, G Ozme, S Karaduman, A Tan, E Urtizberea, JA Beckmann, JS Topaloglu, H TI A cross section of autosomal recessive limb-girdle muscular dystrophies in 38 families SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE limb-girdle muscular dystrophy; genetic linkage analysis; sarcolemmal complex proteins ID GAMMA-SARCOGLYCAN; BETA-SARCOGLYCAN; CHROMOSOME 2P; GENE; MUTATIONS; MAPS; DEFICIENCY; GLYCOPROTEIN; LINKAGE; COMPLEX AB Limb-girdle muscular dystrophies constitute a broad range of clinical and genetic entities. We have evaluated 38 autosomal recessive limb-girdle muscular dystrophy (LGMD2) families by linkage analysis for the known loci of LGMD2A-F and protein studies using immunofluorescence and western blotting of the sarcoglycan complex. One index case in each family was investigated thoroughly. The age of onset and the current ages were between 1 1/2 and 15 years and 6 and 36 years, respectively. The classification of families was as follows: calpainopathy 7, dysferlinopathy 3, alpha sarcoglycan deficiency 2, beta sarcoglycan deficiency 7, gamma sarcoglycan deficiency 5, delta sarcoglycan deficiency 1, and merosinopathy 2. There were two families showing an Emery-Dreifuss phenotype and nine showing no linkage to the LGMD2A-F loci, and they had preserved sarcoglycans. gamma sarcoglycan deficiency seems to be the most severe group as a whole, whereas dysferlinopathy is the mildest. Interfamilial variation was not uncommon. Cardiomyopathy was not present in any of the families. In sarcoglycan deficiencies, sarcoglycans other than the primary ones may also be considerably reduced; however, this may not be reflected in the phenotype. Many cases of primary gamma sarcoglycan deficiency showed normal or only mildly abnormal delta sarcoglycan staining. C1 Hacettepe Univ, Sch Med, Dept Med Biol, TR-06100 Ankara, Turkey. Hacettepe Univ, Sch Med, Dept Paediat Neurol, TR-06100 Ankara, Turkey. Hacettepe Univ, Sch Med, Dept Paediat Pathol, TR-06100 Ankara, Turkey. Genethon, F-91002 Evry, France. Hacettepe Univ, Sch Med, Dept Paediat Cardiol, TR-06100 Ankara, Turkey. Hacettepe Univ, Sch Med, Dept Neurol, TR-06100 Ankara, Turkey. Grp Hosp Pitie Salpetriere, Inst Myol AFM7, F-75651 Paris, France. RP Topaloglu, H (reprint author), NINDS, NIH, DMNB, Bldg 10,Room 3D 03,10 Ctr Dr, Bethesda, MD 20892 USA. RI Beckmann, Jacques S /A-9772-2008; Richard, isabelle/J-8298-2013 OI Beckmann, Jacques S /0000-0002-9741-1900; NR 53 TC 13 Z9 13 U1 1 U2 1 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 MAY PY 2000 VL 37 IS 5 BP 361 EP 367 DI 10.1136/jmg.37.5.361 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 315WR UT WOS:000087136400006 PM 10807695 ER PT J AU Kovbasnjuk, ON Bungay, PM Spring, KR AF Kovbasnjuk, ON Bungay, PM Spring, KR TI Diffusion of small solutes in the lateral intercellular spaces of MDCK cell epithelium grown on permeable supports SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE caged compound; HEPES; dextran; fluid transport; caged protons; neuraminidase ID PH; BUFFERS AB The diffusion coefficients of four solutes ranging in molecular weight from 238 to 10,000 in the lateral intercellular spaces (LIS) of cultured kidney cells (MDCK) grown on permeable supports were determined from the spread of fluorescence produced after the release of caged compounds by a pulse from a UV laser. Two types of experiments were performed: measurement of the rate of change of fluorescence after releasing a caged fluorophore, and measurement of the change in fluorescence of a relatively static fluorescent dye produced by the diffusion of an uncaged ligand for the dye. Fluorescence intensity was determined by photon-counting the outputs of a multichannel photomultiplier tube. Diffusion coefficients were determined in free solution as well as in the LIS of MDCK cells grown on permeable supports and the hindrance factor, theta, determined from the ratio of the free solution diffusivity to that in the LIS. The hindrance factors for 3000-MW dextran, 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS, MW 524) and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES, MW 338) were not significantly different from 1. The diffusion of 10,000-MW dextran was substantially reduced in the LIS with a theta of 5.6 +/- 0.3. Enzymatic digestion by neuraminidase of the sialic acid residues of the glycosylation groups in the LIS increased the diffusivity of the 10,000-MW dextran 1.8-fold indicating hindrance by the glycocalyx. We conclude that small solutes, such as Na+ and Cl-, would not be significantly restricted in their diffusion in the LIS and that solute concentration gradients could not develop along the LIS under physiologic conditions. C1 NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. NHLBI, Bioengn & Phys Sci Program, Off Res Serv, Bethesda, MD 20892 USA. RP Spring, KR (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. NR 14 TC 6 Z9 6 U1 0 U2 3 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 MAY 1 PY 2000 VL 175 IS 1 BP 9 EP 16 DI 10.1007/s002320001050 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 312NN UT WOS:000086949500002 PM 10811963 ER PT J AU Hansen, MC Palmer, RJ White, DC AF Hansen, MC Palmer, RJ White, DC TI Flowcell culture of Porphyromonas gingivalis biofilms under anaerobic conditions SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE biofilm; anaerobic; laser confocal microscopy; Porphyromonas gingivalis; plaque; periodontal disease AB We have developed an anaerobic biofilm culture system. The system is inexpensive, simple to use and, unlike an anaerobic glovebox, requires no dedicated space. As a test of the system, Porphyromonas gingivalis was cultured under low oxygen (1-2 ppm) and under anaerobic conditions (less than or equal to 0.1 ppm O-2). In the presence of small amounts of oxygen, the organism attached and formed an initial biofilm over the course of 4 h, but the biofilm was unable to maintain its growth and had lost biomass after Is h. Also, ambiguous results were obtained when the biofilm was stained with a viability stain. Under anaerobic conditions, the biofilm was able to continue growth - biomass was greater after 18 h than after 4 h, and the anaerobic biofilm had a less ambiguous staining pattern than did the low-O-2-grown biofilm. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 Univ Tennessee, Ctr Environm Biotechnol, Knoxville, TN 37932 USA. Tech Univ Denmark, Dept Microbiol, DK-2800 Lyngby, Denmark. Oak Ridge Natl Lab, Div Environm Sci, Oak Ridge, TN USA. RP Palmer, RJ (reprint author), NIDCR, NIH, Bldg 30,Room 308,30 Convent Dr, Bethesda, MD 20892 USA. NR 13 TC 22 Z9 22 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD MAY PY 2000 VL 40 IS 3 BP 233 EP 239 DI 10.1016/S0167-7012(00)00126-3 PG 7 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 318HZ UT WOS:000087279000006 PM 10802140 ER PT J AU Emmert-Buck, MR Strausberg, RL Krizman, DB Bonaldo, MF Bonner, RF Bostwick, DG Brown, MR Buetow, KH Chuaqui, RF Cole, KA Duray, PH Englert, CR Gillespie, JW Greenhut, S Grouse, L Hillier, LW Katz, KS Klausner, RD Kuznetzov, V Lash, AE Lennon, G Linehan, WM Liotta, LA Marra, MA Munson, PJ Ornstein, DK Prabhu, VV Prange, C Schuler, GD Soares, MB Tolstoshev, CM Vocke, CD Waterston, RH AF Emmert-Buck, MR Strausberg, RL Krizman, DB Bonaldo, MF Bonner, RF Bostwick, DG Brown, MR Buetow, KH Chuaqui, RF Cole, KA Duray, PH Englert, CR Gillespie, JW Greenhut, S Grouse, L Hillier, LW Katz, KS Klausner, RD Kuznetzov, V Lash, AE Lennon, G Linehan, WM Liotta, LA Marra, MA Munson, PJ Ornstein, DK Prabhu, VV Prange, C Schuler, GD Soares, MB Tolstoshev, CM Vocke, CD Waterston, RH TI Molecular profiling of clinical tissue specimens - Feasibility and applications SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Reprint ID LASER CAPTURE MICRODISSECTION; PROSTATIC INTRAEPITHELIAL NEOPLASIA; GENE-EXPRESSION PATTERNS; MEN1 GENE; SUSCEPTIBILITY LOCUS; DNA MICROARRAYS; SEQUENCE TAGS; ALLELIC LOSS; HUMAN BRAIN; CANCER C1 NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Canc Genome Anat Project, Off Director, Bethesda, MD 20892 USA. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. Univ Iowa, Dept Physiol & Biophys, Iowa City, IA 52242 USA. NICHD, Lab Integrat & Med Biophys, Bethesda, MD USA. Bostwick Labs, Richmond, VA USA. NCI, Lab Populat Genet, Bethesda, MD 20892 USA. Washington Univ, Genome Sequencing Ctr, St Louis, MO USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Univ Calif Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Integrated Mol Anal Genomes & Their Express Conso, Livermore, CA USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. British Columbia Canc Res Ctr, Genome Sequence Ctr, Vancouver, BC V5Z 1L3, Canada. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, NIH, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Bonner, Robert/C-6783-2015; Marra, Marco/B-5987-2008; Cole, Kristina/M-3922-2015 NR 52 TC 48 Z9 49 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAY PY 2000 VL 2 IS 2 BP 60 EP 66 DI 10.1016/S1525-1578(10)60617-4 PG 7 WC Pathology SC Pathology GA 365EH UT WOS:000089935100002 PM 11272889 ER PT J AU Beutler, JA McCall, KL Herbert, K Herald, DL Pettit, GR Johnson, T Shoemaker, RH Boyd, MR AF Beutler, JA McCall, KL Herbert, K Herald, DL Pettit, GR Johnson, T Shoemaker, RH Boyd, MR TI Novel cytotoxic diterpenes from Casearia arborea SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID SYLVESTRIS SW FLACOURTIACEAE; CLERODANE DITERPENES; ANTITUMOR PRINCIPLES; ZUELANIA-GUIDONIA; STEM BARK; CORYMBOSA; LEAVES AB Cytotoxicity-guided fractionation of the dichloromethane-methanol extract of the roots of Casearia arborea yielded five novel clerodane diterpenes, casearborins A-E (1-5), as well as cucurbitacin B. The presence of cucurbitacins glycosides was also detected. The absolute configuration of casearborin E was determined by X-ray crystallography. C1 NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Lab Drug Discovery Res & De, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Lab Drug Discovery Res & De, Bldg 1052,Rm 121, Frederick, MD 21702 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU NCI NIH HHS [N01 CO 56000] NR 21 TC 57 Z9 62 U1 0 U2 6 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 MAY PY 2000 VL 63 IS 5 BP 657 EP 661 DI 10.1021/np990553r PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 318CT UT WOS:000087266900017 PM 10843580 ER PT J AU Murphy, DD Andrews, SB AF Murphy, DD Andrews, SB TI Culture models for the study of estradiol-induced synaptic plasticity SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID DENDRITIC SPINE DENSITY; LONG-TERM POTENTIATION; HIPPOCAMPAL-NEURONS; ESTROUS-CYCLE; PERFORATED SYNAPSES; MAMMALIAN BRAIN; RAT NEOCORTEX; SYNAPTOGENESIS; INCREASES; CELLS AB Estrogen, which classically affects areas of the brain related to reproduction, has also been found to affect brain regions important in learning and memory. Additionally, it has been suggested that estrogen exerts protective effects against neurodegenerative diseases such as Alzheimer's disease. Important mechanisms by which estrogen may confer protection are through the maintenance or modulation of existing synapses, or by the production of new ones. It has now been demonstrated that estrogen can increase synaptogenesis and spine production in the hippocampus, both in vivo as well as in primary hippocampal neurons in culture. The latter model system is the primary focus of this review. Synaptogenesis and spine production have been well characterized in developing and adult animals, and parallels between the synaptic morphology reflecting these processes can be readily observed in high-density primary hippocampal cultures. Moreover, in culture, estrogen induces a variety of ultra structural modifications, many of which occur in vivo, that have been linked to various in vivo models of learning and memory. For these reasons, high-density hippocampal culture systems should be regarded as valuable tools with which to predict in vivo physiology, and may well be particularly useful for studies of the neuroprotective effects of estrogen. C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Murphy, DD (reprint author), NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 38 TC 8 Z9 8 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD MAY-JUN PY 2000 VL 29 IS 5-6 BP 411 EP 417 DI 10.1023/A:1007121525399 PG 7 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 405NH UT WOS:000167165500011 PM 11424957 ER PT J AU Makino, S Baker, RA Smith, MA Gold, PW AF Makino, S Baker, RA Smith, MA Gold, PW TI Differential regulation of neuropeptide Y mRNA expression in the arcuate nucleus and locus coeruleus by stress and antidepressants SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE neuropeptide Y; stress; insulin; corticosterone; arcuate nucleus; locus coeruleus ID CORTICOTROPIN-RELEASING HORMONE; MESSENGER-RNA LEVELS; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; REPEATED IMMOBILIZATION STRESS; GENE-EXPRESSION; RAT-BRAIN; TYROSINE-HYDROXYLASE; THERAPEUTIC IMPLICATIONS; RIBONUCLEIC-ACID; DIABETIC RATS AB In rats, circulating corticosterone and insulin are involved in regulation of the hypothalamic neuropeptide Y (NPY) system, which in turn, is involved in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Since the HPA axis and stress responsivity is altered in diseases such as depression, we investigated interactions between the effects of stress and antidepressant drug treatment on arcuate nucleus and locus coeruleus NPY mRNA expressions using in-situ hybridization histochemistry. After acute (2 h) and repeated immobilization (2 h daily, for 14 days), plasma concentrations of corticosterone increased, and those of insulin decreased. The expression of NPY mRNA was significantly increased in the arcuate nucleus, but was unchanged in the locus coeruleus following acute and repeated immobilization. Adrenalectomized rats with systemic corticosterone replacement (ADX + CORT), whose corticosterone concentration was maintained at approximate to 50-100 ng/ml during repeated stress, showed a decrease in plasma insulin and an increase in arcuate nucleus NPY mRNA similar to that observed in sham rats, suggesting that changes in NPY mRNA levels are more closely tied to circulating insulin than to circulating corticosterone. In contrast, locus coeruleus NPY mRNA expressions in ADX+CORT rats were significantly higher than those in sham rats after repeated stress. Desmethylimipramine (DMI) treatment for 24 days did not affect basal plasma concentrations of corticosterone or insulin, or arcuate nucleus NPY mRNA expressions, but significantly decreased basal levels of locus coeruleus NPY mRNA compared to saline-treated rats. After repeated immobilization (2 h daily, for 4 days), DMI significantly reduced the stress-induced rise in locus coeruleus NPY mRNA levels, but potentiated the stress-induced rise in arcuate nucleus NPY mRNA expression. These results demonstrate that: (1) the increase in arcuate nucleus NPY mRNA expressions in stressed rats closely follows the decrease in plasma concentrations of insulin; (2) increases in NPY mRNA expressions occur in the absence of changes in plasma corticosterone; and (3) desipramine treatment potentiated the effect of stress on arcuate nucleus NPY mRNA expressions, but blocked the repeated stress-induced increase in locus coeruleus NPY mRNA expressions. Thus, NPY mRNA expression in the arcuate nucleus and the locus coeruleus is sensitive to the effects of stress and to the antidepressant drug desipramine, but the arcuate nucleus NPY system is regulated by different mechanisms than the locus coeruleus NPY system. The results provide further evidence for the importance of circulating insulin in the regulation of the arcuate nucleus NPY system. C1 NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Makino, S (reprint author), NIMH, Clin Neuroendocrinol Branch, Bldg 10,Room 2D-46,10 Ctr Dr,MSC-1284, Bethesda, MD 20892 USA. NR 47 TC 61 Z9 61 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD MAY PY 2000 VL 12 IS 5 BP 387 EP 395 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 308GP UT WOS:000086702400003 PM 10792576 ER PT J AU Rabadan-Diehl, C Lolait, S Aguilera, G AF Rabadan-Diehl, C Lolait, S Aguilera, G TI Isolation and characterization of the promoter region of the rat vasopressin V-1b receptor gene SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE vasopressin; V1b receptor gene; promoter; transcription start points ID PROTEIN-KINASE-C; CHROMOSOMAL LOCALIZATION; CHRONIC STRESS; PITUITARY; TRANSCRIPTION; EXPRESSION; INTRON; CELLS; SEQUENCE; ENHANCER AB Regulation of pituitary vasopressin V-1b receptors plays a critical role in regulating pituitary adrenocorticotropic hormone (ACTH) secretion during adaptation to stress. The objective of this study was to isolate the promoter regulatory region of the V-1b receptor gene to better understand the molecular mechanisms involved in V-1b receptor regulation. Screening of a rat genomic library using probes directed to the coding region and to the 5'UTR of the rat V-1b receptor resulted in the isolation of several clones containing the 5'upstream regions of the V-1b receptor cDNA. Sequencing of an 11.2 Kb fragment revealed 8.2 Kb upsteam of the reported cDNA sequence, which contains a putative promoter regulatory region. The 3' end of the clone contained 1472 base pairs corresponding to the recognized cDNA sequence, followed by 1506 bp of unknown sequence located at the end of the sixth transmembrane domain, probably corresponding to an intron, characteristic of these family of receptors. An additional 161 bp intron was found in the 5'UTR, similar to that described in the rat oxytocin receptor gene. 5'RACE and RNase protection analysis mapped two major putative transcription start points at -830 and -861 bp from the starting methionine. Analysis of the putative promoter region showed no indication of a proximal TATA box, but the presence of a CACA box, a GAGA box, several AP-1 and AP-2 sites and a cluster of Sp1 sites upstream of the AP-2 sites. A luciferase construct containing a 2.1-kb of putative promoter, and part of the 5'UTR including the first intron, showed promoter activity when transfected into COS-7, CHO and PC12 cell lines but not in AtT-20 cells. A similar construct without the intron and distal 5'UTR sequence has no promoter activity in the same cell lines. In summary, the V-1b receptor gene contains at least 3 exons and 2 introns. The 5'flanking sequence contains several potential sites for transcriptional regulation, and induced luciferace activity only in constructs containing intron 1, suggesting that the latter is important for receptor gene activation. The data provide bases for future analysis of the regulatory elements controlling V-1b receptor transcription. C1 NIMH, Sect Endocrine Physiol, Dev Endocrinol Branch, NICHHD,NIH, Bethesda, MD 20892 USA. NIMH, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rabadan-Diehl, C (reprint author), NIMH, Sect Endocrine Physiol, Dev Endocrinol Branch, NICHHD,NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. NR 35 TC 16 Z9 16 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD MAY PY 2000 VL 12 IS 5 BP 437 EP 444 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 308GP UT WOS:000086702400010 PM 10792583 ER PT J AU Sakic, B Maric, I Koeberle, PD Millward, JM Szechtman, H Maric, D Denburg, JA AF Sakic, B Maric, I Koeberle, PD Millward, JM Szechtman, H Maric, D Denburg, JA TI Increased TUNEL staining in brains of autoimmune Fas-deficient mice SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE autoimmunity; brain; lupus; choroid plexus; hippocampus; TUNEL assay; immunohistochemistry; confocal microscopy; apoptosis; T-lymphocytes; MRL mice ID CENTRAL-NERVOUS-SYSTEM; PROGRAMMED CELL-DEATH; MRL-LPR MICE; MOUSE-BRAIN; IN-VIVO; APOPTOSIS; DISEASE; EXPRESSION; BEHAVIOR; INTERLEUKIN-6 AB Profound changes in brain morphology and behavior coincide with the spontaneous development of systemic autoimmune/inflammatory disease in Fas-deficient MRL-lpr mice. The dendrites atrophy, the density of hippocampal and cortical neurons decreases, and an anxious/depressive-like behavior emerges while lymphoid cells infiltrate into the choroid plexus of MRL-lpr mice. We hypothesized that the inherited lack of the Fas-dependent anti-inflammatory mechanism would lead to unsuppressed immune activity, characterized by reduced apoptosis in the MRL-lpr brain. Using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeled (TUNEL) method as an indicator of apoptosis, a surprisingly high incidence of TUNEL-positive cells was observed in the hippocampus, choroid plexus and periventricular regions of MRL-lpr mice, 5-10-fold higher than that found in the MRL +/+ control brain. Immunostaining with anti-CD3, CD4 and CD8 monoclonal antibodies showed limited overlap between CD-positive and TUNEL-positive cells, suggesting that the dying cells are for the most part (similar to 70%) not T-lymphocytes. Although further characterization of the phenotype of the dying cells and the mechanism of cell death are required, the present results suggest the involvement of a Fas-independent apoptotic process in neurodegeneration induced by systemic autoimmune disease. (C) 2000 Elsevier Science B.V. All rights reserved. C1 McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON L8N 3Z5, Canada. McMaster Univ, Dept Med, Hamilton, ON, Canada. McMaster Univ, Dept Pathol, Hamilton, ON, Canada. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Sakic, B (reprint author), McMaster Univ, Dept Psychiat & Behav Neurosci, HSC 4N77A,1200 Main St, Hamilton, ON L8N 3Z5, Canada. RI Szechtman, Henry/A-4706-2009 OI Szechtman, Henry/0000-0003-3986-4482 NR 50 TC 35 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAY 1 PY 2000 VL 104 IS 2 BP 147 EP 154 DI 10.1016/S0165-5728(99)00277-5 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 297FL UT WOS:000086071200007 PM 10713354 ER PT J AU Chima, SC Lach, B Ryschkewitsch, CF Ressetar, HG Stoner, GL AF Chima, SC Lach, B Ryschkewitsch, CF Ressetar, HG Stoner, GL TI Primary progressive multifocal leukoencephalopathy (PML) due to JC virus Type 1 in a schizophrenic patient. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. Ottawa Civic Hosp, Ottawa, ON K1Y 4E9, Canada. Mt Sinai Med Ctr, Div Neuropathol, New York, NY 10029 USA. RI Chima, Sylvester Chidi/N-5564-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2000 VL 59 IS 5 MA 69 BP 436 EP 436 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 311EE UT WOS:000086871100079 ER PT J AU Wong, K Topaloglu, H Tresser, N Schiffmann, R AF Wong, K Topaloglu, H Tresser, N Schiffmann, R TI Dementia with Lewy bodies and Parkinson's disease in a type 1 Gaucher disease patient. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2000 VL 59 IS 5 MA 141 BP 454 EP 454 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 311EE UT WOS:000086871100151 ER PT J AU Monuki, ES Ji, B Porter, FD Walsh, C AF Monuki, ES Ji, B Porter, FD Walsh, C TI Loss of cerebral cortex and expansion of choroid plexus in mice lacking Lhx2. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2000 VL 59 IS 5 MA 153 BP 457 EP 457 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 311EE UT WOS:000086871100163 ER PT J AU Li, CY AF Li, CY TI Novel mechanism of inhibition by the P2 receptor antagonist PPADS of ATP-activated current in dorsal root ganglion neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID BULLFROG SENSORY NEURONS; SYNAPTIC TRANSMISSION; HIPPOCAMPAL-NEURONS; P-2X PURINOCEPTORS; ION CHANNELS; RAT; SURAMIN; REACTIVE-BLUE-2; RESPONSES; BLOCK AB The antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) has been proposed to selectively antagonize the actions of ATP at P2X receptors. Whole cell patch-clamp recording techniques therefore were used to characterize PPADS inhibition of ATP-activated current in bullfrog dorsal root ganglion (DRG) neurons. PPADS, 0.5-10 mu M, inhibited ATP-activated current in a concentration-dependent manner with an IC50 of 2.5 +/- 0.03 mu M. PPADS produced a gradual decline of ATP-activated current to a steady state, but this was not an indication of use dependence as the gradual declining component could be eliminated by exposure to PPADS before ATP application. In addition, ATP-activated current recovered completely from inhibition by PPADS in the absence of agonist. The slow onset of inhibition by PPADS was not apparently due to an action at an intracellular site as inclusion of 10 eta M PPADS in the recording pipette neither affected the ATP response nor did it alter inhibition of the ATP response when 2.5 mu M PPADS was applied externally. PPADS, 2.5 mu M, decreased the maximal response to ATP by 51% without changing its EC50. PPADS inhibition of ATP-activated current was independent of membrane potential between -80 and +40 mV and did not involve a shift in the reversal potential of the current. The magnitude of PPADS inhibition of ATP-activated current was dependent on the duration of the prior exposure to PPADS. The time constants of both onset and offset of PPADS inhibition of ATP-activated current did not differ significantly with changes in ATP concentration from 1 to 5 mu M. Recovery of ATP-activated current from PPADS inhibition also exhibited a slow phase that was not accelerated by the presence of agonist and was dependent on the concentration of PPADS. The apparent dissociation rate of PPADS from unliganded ATP-gated ion channels was much greater than the rate of the slow phase of recovery of ATP-activated current from PPADS inhibition. The results suggest that PPADS can inhibit P2X receptor function in a complex noncompetitive manner. PPADS produces a long-lasting inhibition that does not appear to result from open channel block but rather from an action at an allosteric site apparently accessible from the extracellular environment that involves a greatly reduced rate of dissociation from liganded versus unliganded ATP-gated ion channels. C1 NIAID, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Li, CY (reprint author), AstraZeneca, Dept Lead Discovery, R&D Boston, 3 Biotech,1 Innovat Dr, Worcester, MA 01605 USA. NR 39 TC 19 Z9 20 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2000 VL 83 IS 5 BP 2533 EP 2541 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 312AX UT WOS:000086921400008 PM 10805655 ER PT J AU Diamond, JS Jahr, CE AF Diamond, JS Jahr, CE TI Synaptically released glutamate does not overwhelm transporters on hippocampal astrocytes during high-frequency stimulation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LONG-TERM POTENTIATION; RAT-BRAIN; TIME-COURSE; LASTING POTENTIATION; CHLORIDE CHANNEL; PYRAMIDAL CELLS; SILENT SYNAPSES; CLIMBING FIBER; TRANSMISSION; LTP AB In addition to maintaining the extracellular glutamate concentration at low ambient levels, high-affinity glutamate transporters play a direct role in synaptic transmission by speeding the clearance of glutamate from the synaptic cleft and limiting the extent to which transmitter spills over between synapses. Transporters are expressed in both neurons and glia, but glial transporters are likely to play the major role in removing synaptically released glutamate from the extracellular space. The role of transporters in synaptic transmission has been studied directly by measuring synaptically activated, transporter-mediated currents (STCs) in neurons and astrocytes. Here we record from astrocytes in the CA1 region of hippocampal slices and elicit STCs with high-frequency (100 Hz) stimulus trains of varying length to determine whether transporters are overwhelmed by stimuli that induce long-term potentiation. We show that, at near-physiological temperatures (34 degrees C), high-frequency stimulation (HFS) does not affect the rate at which transporters clear glutamate from the extrasynaptic space. Thus, although spillover between synapses during "normal" stimulation may compromise the absolute synapse specificity of fast excitatory synaptic transmission, spillover is not exacerbated during HFS. Transporter capacity is diminished somewhat at room temperature (24 degrees C), although transmitter released during brief, "theta burst" stimulation is still cleared as quickly as following a single stimulus, even when transport capacity is partially diminished by pharmacological means. C1 Oregon Hlth Sci Univ, Vollum Inst, Portland, OR 97201 USA. RP Diamond, JS (reprint author), NINDS, NIH, Synapt Physiol Unit, Bldg 36,Rm 2C09,36 Convent Dr, Bethesda, MD 20892 USA. RI Diamond, Jeffrey/C-1835-2015 OI Diamond, Jeffrey/0000-0002-1770-2629 FU NINDS NIH HHS [NS-10041, NS-21419] NR 58 TC 95 Z9 96 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2000 VL 83 IS 5 BP 2835 EP 2843 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 312AX UT WOS:000086921400034 PM 10805681 ER PT J AU Dosemeci, A Reese, TS Petersen, J Cheng, JHT AF Dosemeci, A Reese, TS Petersen, J Cheng, JHT TI A novel particulate form of Ca2+/CaMKII-dependent protein kinase II in neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Ca2+/calmodulin-dependent protein kinase II; CaMKII; hippocampal cultures; postsynaptic density; energy depletion; translocation ID TRANSIENT CEREBRAL-ISCHEMIA; RAT-BRAIN; POSTSYNAPTIC DENSITIES; INTRACEREBRAL MICRODIALYSIS; HIPPOCAMPAL-NEURONS; CA1 REGION; CALMODULIN; TRANSLOCATION; PHOSPHORYLATION; LOCALIZATION AB Cytoskeletal and postsynaptic density (PSD) fractions from forebrain contain discrete spherical structures that are immunopositive for Ca2+/calmodulin-dependent protein kinase II (CaMKII). Spherical structures viewed by rotary shadow electron microscopy have an average diameter of similar to 100 nm and, in distinction to postsynaptic densities, do not immunolabel for PSD-95. These structures were purified to near homogeneity by extraction with the detergent N-lauryl sarcosinate. Biochemical analysis revealed that CaMKII accounts for virtually all of the protein in the purified preparation, suggesting that spherical structures are clusters of self-associated CaMKII. Exposure of cultured hippocampal neurons to a mitochondrial uncoupler in glucose-free medium promotes the formation of numerous CaMKII-immunopositive structures identical in size and shape to the CaMKII clusters observed in subcellular fractions. Clustering of CaMKII would reduce its kinase function by preventing its access to fixed substrates. On the other hand, clustering would not affect the ability of the large cellular pool of CaMKII to act as a calmodulin sink, as demonstrated by the Ca2+-dependent binding of gold-conjugated calmodulin to CaMKII clusters. We propose that the observed clustering of CaMKII into spherical structures is a protective mechanism preventing excessive protein phosphorylation upon loss of Ca2+ homeostasis, without compromising calmodulin regulation. C1 NINCDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Dosemeci, A (reprint author), Marine Biol Lab, 7 MBL St, Woods Hole, MA 02543 USA. OI Petersen, Jennifer/0000-0003-1107-8535 NR 28 TC 72 Z9 72 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 2000 VL 20 IS 9 BP 3076 EP 3084 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 309RL UT WOS:000086783000005 PM 10777771 ER PT J AU Granholm, AC Reyland, M Albeck, D Sanders, L Gerhardt, G Hoernig, G Shen, LY Westphal, H Hoffer, B AF Granholm, AC Reyland, M Albeck, D Sanders, L Gerhardt, G Hoernig, G Shen, LY Westphal, H Hoffer, B TI Glial cell line-derived neurotrophic factor is essential for postnatal survival of midbrain dopamine neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE trophic factors; GDNF; neurodegeneration; transplantation; neural development; substantia nigra; DA neurons ID MICE LACKING GDNF; VENTRAL MESENCEPHALIC GRAFTS; SUBSTANTIA-NIGRA; PARKINSONS-DISEASE; IMPROVES SURVIVAL; IN-VIVO; REDUCES APOPTOSIS; NERVOUS-SYSTEM; MESSENGER-RNA; RAT AB Glial cell line-derived neurotrophic factor (GDNF) is one of the most potent trophic factors that have been identified for midbrain dopamine (DA) neurons. Null mutations for trophic factor genes have been used frequently for studies of the role of these important proteins in brain development. One problem with these studies has been that often only prenatal development can be studied because many of the knockout strains, such as those with GDNF null mutations, will die shortly after birth. In this study, we looked at the continued fate of specific neuronal phenotypes from trophic factor knockout mice beyond the time that these animals die. By transplanting fetal neural tissues from GDNF -/-, GDNF +/-, and wild-type (WT) mice into the brain of adult wild-type mice, we demonstrate that the continued postnatal development of ventral midbrain dopamine neurons is severely disturbed as a result of the GDNF null mutation. Ventral midbrain grafts from -/- fetuses have markedly reduced DA neuron numbers and fiber outgrowth. Moreover, DA neurons in such transplants can be "rescued" by immersion in GDNF before grafting. These findings suggest that postnatal survival and/or phenotypic expression of ventral mesencephalic DA neurons is dependent on GDNF. In addition, we present here a strategy for studies of maturation and even aging of tissues from trophic factor and other knockout animals that do not survive past birth. C1 Univ Colorado, Hlth Sci Ctr, Dept Basic Sci, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Neurosci Training Program, Denver, CO 80262 USA. NICHHD, LMGD, NIH, Bethesda, MD 20892 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Granholm, AC (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Basic Sci, Box C286, Denver, CO 80262 USA. FU NIA NIH HHS [AG04418, AG12122, AG15239] NR 46 TC 99 Z9 101 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 2000 VL 20 IS 9 BP 3182 EP 3190 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 309RL UT WOS:000086783000016 PM 10777782 ER PT J AU Agostini, HT Ryschkewitsch, CF Baumhefner, RW Tourtellotte, WW Singer, EJ Komoly, S Stoner, GL AF Agostini, HT Ryschkewitsch, CF Baumhefner, RW Tourtellotte, WW Singer, EJ Komoly, S Stoner, GL TI Influence of TC virus coding region genotype on risk of multiple sclerosis and progressive multifocal leukoencephalopathy SO JOURNAL OF NEUROVIROLOGY LA English DT Article; Proceedings Paper CT Symposium on An Update on Multiple Sclerosis Research and Care CY MAY 03-05, 1999 CL MILAN, ITALY SP Dompe Biotec, Farmades s p a, Serono Pharma, Teva Pharm, Beckman Coulter, Int Lab, Celbio, Space Inport Export, Dasit, PBI Int DE polyomavirus; genotype; demyelination; nuclear factor-1 site ID POLYOMAVIRUS JC-VIRUS; BRAIN-TISSUE; CEREBROSPINAL-FLUID; REGULATORY REGIONS; TRANSGENIC MICE; SEQUENCES; DNA; INFECTION; PROTEIN; URINE AB Two features of the biology of JC virus make it a particularly suitable candidate for an agent in MS-like disease: its neurotropic capability targeting glial cells as evidenced in progressive multifocal leukoencephalopathy lesions, and its capacity for latency and persistence as illustrated by its behaviour in the kidney. TC virus is chronically or intermittently excreted in the urine by some 40% of the population. The existence of TC virus in multiple coding-region genotypes provides a unique approach to the study of JC virus-induced neurological disease. We have previously shown that a genotype originating in Asia but also present in Europe and the US, called Type 2B, is more frequently found in PML brain than expected based on its prevalence in urine samples from a control population. In contrast, we find that the excretion of JCV in MS patients is similar in both genotype and frequency to that of control individuals, and appears to be regulated by factors unrelated to those that control CNS disease activity. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. W Los Angeles Vet Affairs Med Ctr, Serv Neurol, Los Angeles, CA 90073 USA. John Ferenc Del Pesti Teaching Hosp, Budapest, Hungary. RP Stoner, GL (reprint author), NINDS, Neurotoxicol Sect, NIH, Bldg 36,Room 4A-27,MSC-4126, Bethesda, MD 20892 USA. NR 41 TC 14 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD MAY PY 2000 VL 6 SU 2 BP S101 EP S108 PG 8 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 326RN UT WOS:000087748700023 PM 10871796 ER PT J AU Berti, R Soldan, SS Akhyani, N McFarland, HF Jacobson, S AF Berti, R Soldan, SS Akhyani, N McFarland, HF Jacobson, S TI Extended observations on the association of HHV-6 and multiple sclerosis SO JOURNAL OF NEUROVIROLOGY LA English DT Article; Proceedings Paper CT Symposium on An Update on Multiple Sclerosis Research and Care CY MAY 03-05, 1999 CL MILAN, ITALY SP Dompe Biotec, Farmades s p a, Serono Pharma, Teva Pharm, Beckman Coulter, Int Lab, Celbio, Space Inport Export, Dasit, PBI Int DE HHV-6; multiple sclerosis ID POLYMERASE CHAIN-REACTION; HUMAN HERPESVIRUS-6; INFECTION; CHILDREN AB Throughout the years, a long list of viruses has been associated with multiple sclerosis (MS), however no virus to date has been definitively identified as the etiologic agent of this disease. Recently, human herpesvirus 6 (HHV-6), a newly described herpesvirus, has been suggested to play a role in MS based on: immunohistochemical demonstration of HHV-6 in MS plaques, increased antibodies response to HHV-6 in sera and CSF of MS patients, and the demonstration of HHV-6 DNA in the serum of MS patients but not in normal individuals. To extend these observations we have focused our research in multiple directions. We have increased the number of MS patients tested for HHV-6 serum DNA providing confirmation of our previous study. Additionally we have investigated a possible correlation between HHV-6 viremia and clinical activity. Finally to provide insight into the pathogenesis of this disease, we have begun to characterize the cellular immune response of MS patients to HHV-6. Collectively these studies will help to define the role that HHV-6 may play in the pathogenesis of MS. C1 NIH, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. George Washington Univ, Inst Biomed Sci, Washington, DC 20052 USA. George Washington Univ, Dept Genet, Washington, DC 20052 USA. RP Jacobson, S (reprint author), NINDS, NIB, NIH, Bldg 10,Room 5B16,10 Ctr Dr, Bethesda, MD 20892 USA. NR 17 TC 18 Z9 18 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD MAY PY 2000 VL 6 SU 2 BP S85 EP S87 PG 3 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 326RN UT WOS:000087748700019 PM 10871792 ER PT J AU Hou, J Major, EO AF Hou, J Major, EO TI Progressive multifocal leukoencephalopathy: JC virus induced demyelination in the immune compromised host SO JOURNAL OF NEUROVIROLOGY LA English DT Article; Proceedings Paper CT Symposium on An Update on Multiple Sclerosis Research and Care CY MAY 03-05, 1999 CL MILAN, ITALY SP Dompe Biotec, Farmades s p a, Serono Pharma, Teva Pharm, Beckman Coulter, Int Lab, Celbio, Space Inport Export, Dasit, PBI Int DE demyelination; JC virus; transcription regulation; immune cells ID MOLECULAR-BIOLOGY; PATHOGENESIS; PROGNOSIS; INFECTION; IMPROVES; THERAPY; DISEASE; BRAIN; AIDS; DNA AB Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system that predominantly affects immunocompromised individuals. The etiologic agent, JCV, is a widespread polyomavirus with a very specific target, the myelin-producing oligodendrocytes of the brain, During periods of immune suppression, the virus can be reactivated from lymphoid tissues and kidney, causing targeted myelin destruction and corresponding neurological deficits. The incidence of PML has increased in recent years, due in large part to the advent of AIDS and the growing number of immunodeficient individuals. Furthermore, previous serological studies have shown that greater than 80% of the human population has antibodies to JCV in circulation. When combined, these statistics highlight an increasing need to establish effective treatment regimens for infected individuals as well as strategies to identify those at risk for developing PML. C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bldg 36,Room 5-W21,36 Convent Dr,MSC4164, Bethesda, MD 20892 USA. NR 16 TC 40 Z9 41 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD MAY PY 2000 VL 6 SU 2 BP S98 EP S100 PG 3 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 326RN UT WOS:000087748700022 PM 10871795 ER PT J AU Messam, CA Major, EO AF Messam, CA Major, EO TI Stages of restricted HIV-1 infection in astrocyte cultures derived from human fetal brain tissue SO JOURNAL OF NEUROVIROLOGY LA English DT Article; Proceedings Paper CT Symposium on HIV and Nervous System: Emerging Issues CY APR 14-16, 1999 CL BETHESDA, MARYLAND SP Natl Inst Mental Hlth, Natl Inst Neurol DE HIV-1; astrocytes; cell culture; latency ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; GLIAL-CELLS; JC-VIRUS; GENE-EXPRESSION; POTENTIAL ROLE; AIDS PATIENTS; NEF; PROTEIN; TAT AB The predominant cell types infected by HIV-1 in AIDS associated ensephalopathy are cells of the macrophage/microglial lineage. There has been consistent evidence, however, that astrocytes also become infected although not at the same frequency or level of multiplication as microglial cells. HIV-1 antigens and/or nucleic acid have been identified in astrocytes in brain autopsy tissue from both adult and pediatric AIDS cases. In cell cultures, HIV-1 infection of astrocytes results in an initial productive but non-cytopathogenic infection that diminishes to a viral persistence or latent state. Understanding the nature of HIV-1 infection of astrocytes, which represents the largest population of cells in the brain, will contribute to the understanding of AIDS encephalopathy and the dementia that occurs in nearly one-quarter of all AIDS patients. C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 27 TC 40 Z9 42 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD MAY PY 2000 VL 6 SU 1 BP S90 EP S94 PG 5 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 326RM UT WOS:000087748600013 PM 10871771 ER PT J AU Rausch, D Kerza-Kwiatecki, A AF Rausch, D Kerza-Kwiatecki, A TI Symposium - HIV and the nervous system: Emerging issues SO JOURNAL OF NEUROVIROLOGY LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; AIDS DEMENTIA COMPLEX; CHEMOKINE RECEPTORS; INFECTION; IMPAIRMENT C1 NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. RP Rausch, D (reprint author), NIMH, Ctr Mental Hlth Res AIDS, 6001 Execut Blvd,Room 6212,MSC 9623, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD MAY PY 2000 VL 6 SU 1 BP S1 EP S4 PG 4 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 326RM UT WOS:000087748600001 ER PT J AU Wu, DT Woodman, SE Weiss, JM McManus, CM D'Aversa, TG Hesselgesser, J Major, EO Nath, A Berman, JW AF Wu, DT Woodman, SE Weiss, JM McManus, CM D'Aversa, TG Hesselgesser, J Major, EO Nath, A Berman, JW TI Mechanisms of leukocyte trafficking into the CNS SO JOURNAL OF NEUROVIROLOGY LA English DT Article; Proceedings Paper CT Symposium on HIV and Nervous System: Emerging Issues CY APR 14-16, 1999 CL BETHESDA, MARYLAND SP Natl Inst Mental Hlth, Natl Inst Neurol DE blood-brain barrier; leukocyte transmigration; tat; adhesion molecules; chemokines; CXCR4 ID BLOOD-BRAIN-BARRIER; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CENTRAL-NERVOUS-SYSTEM; MONOCYTE-CHEMOATTRACTANT PROTEIN-1; ENDOTHELIAL-CELLS; HIV-1 INFECTION; AIDS DEMENTIA; MESSENGER-RNA; EXPRESSION; ASTROCYTES AB HIV-1 encephalitis occurs in up to one-third of HIV-1-infected individuals. The mechanisms through which this pathology develops are thought to involve viral passage across the blood-brain barrier (BBB), as well as entry of HIV-infected and/or uninfected inflammatory cells into the central nervous system (CNS), Viral proteins and cytokines may also contribute to the pathogenesis of encephalitis. We show that the chemokines SDF-1 and MCP-1 induce transmigration of uninfected human lymphocytes and monocytes across our model of the EBB, a co-culture of human fetal astrocytes and endothelial cells, We also demonstrate that the HIV-1 protein Tat induces adhesion molecule expression and chemokine production by human fetal astrocytes and microglia, which could further contribute to leukocyte entry into the CNS. Finally, our data indicate that inflammatory cytokines modulate the expression of CXCR4, a co-receptor for HIV-1, on human fetal astrocytes, suggesting that these cytokines may potentially modulate the infectability of astrocytes by HIV-1. These findings support the hypothesis that there may be several different mechanisms that contribute to the development and progression of HIV-1 encephalitis. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Berlex Biosci, Dept Immunol, Richmond, CA 94806 USA. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. Univ Kentucky, Med Ctr, Kentucky Clin, Dept Neurol, Lexington, KY 40536 USA. Univ Kentucky, Med Ctr, Kentucky Clin, Dept Immunol, Lexington, KY 40536 USA. Univ Kentucky, Med Ctr, Kentucky Clin, Dept Microbiol, Lexington, KY 40536 USA. RP Berman, JW (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. NR 22 TC 70 Z9 72 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD MAY PY 2000 VL 6 SU 1 BP S82 EP S85 PG 4 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 326RM UT WOS:000087748600011 PM 10871769 ER PT J AU Mansour, PM Smith, MF Dilsizian, V Bacharach, SL AF Mansour, PM Smith, MF Dilsizian, V Bacharach, SL TI Regional left ventricular function and perfusion from gated spect (201)T1 scans: A 4D model using spherical harmonics. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 69 BP 18P EP 18P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400070 ER PT J AU Lee, IJ Vaquero, JJ Barbosa, FJ Seidel, J Green, MV AF Lee, IJ Vaquero, JJ Barbosa, FJ Seidel, J Green, MV TI A high performance phoswich detector module for small animal PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. Thomas Jefferson Natl Lab, Newport News, VA USA. RI Vaquero, Juan Jose/D-3033-2009 OI Vaquero, Juan Jose/0000-0001-9200-361X NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 74 BP 19P EP 20P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400075 ER PT J AU Raedler, TJ Knable, MB Jones, DW Gorey, JG Lee, KS Sunderland, T Weinberger, DR AF Raedler, TJ Knable, MB Jones, DW Gorey, JG Lee, KS Sunderland, T Weinberger, DR TI Age-related chances in central muscarinic receptor availability in vivo. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ Hamburg, Hamburg, Germany. Stanley Fdn Res Programs, Rockville, MD USA. NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 92 BP 24P EP 24P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400093 ER PT J AU Jones, DW Raedler, TJ Crook, JM Knable, MB Gorey, JG Lee, KS Hyde, TM Weinberger, DR AF Jones, DW Raedler, TJ Crook, JM Knable, MB Gorey, JG Lee, KS Hyde, TM Weinberger, DR TI In vivo and in vitro evidence of induced muscarinic receptor availability in schizophrenia in patients. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Stanley Fdn, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 99 BP 26P EP 26P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400100 ER PT J AU Raedler, TJ Jones, DW Knable, MB Urbina, RA Gorey, JG Lee, KS Egan, MF Weinberger, DR AF Raedler, TJ Jones, DW Knable, MB Urbina, RA Gorey, JG Lee, KS Egan, MF Weinberger, DR TI Comparison of the in vivo muscarinic cholinergic receptor availability in patients treated with olanzapine and clozapine. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ Hamburg, Hamburg, Germany. NIMH, NIH, Bethesda, MD 20892 USA. Stanley Fdn Res Programs, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 100 BP 26P EP 26P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400101 ER PT J AU McDevitt, MR Miederer, M Ma, D Curcio, MJ Lai, LT Pellegrini, V Brechbiel, MW Scheinberg, DA AF McDevitt, MR Miederer, M Ma, D Curcio, MJ Lai, LT Pellegrini, V Brechbiel, MW Scheinberg, DA TI A novel alpha particle emitting Ac-225 labeled anti-CD33 antibody construct: Synthesis and in vitro evaluation of biochemistry, potency, specificity and mechanism of cell death. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Tech Univ Munich, D-8000 Munich, Germany. NCI, Bethesda, MD 20892 USA. RI Miederer, Matthias/C-4405-2014 NR 0 TC 1 Z9 1 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 116 BP 30P EP 30P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400117 ER PT J AU Lang, LL Ma, Y Jagoda, E Eckelman, WC AF Lang, LL Ma, Y Jagoda, E Eckelman, WC TI F-18 labeled 4-cis and -trans FCWAY and 3-cis and -trans FCWAY. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 153 BP 39P EP 40P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400154 ER PT J AU Ma, Y Lang, L Jagoda, E Eckelman, WC AF Ma, Y Lang, L Jagoda, E Eckelman, WC TI Metabolism of fluorinated WAY100635 derivatives with varying affinity constants. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 154 BP 40P EP 40P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400155 ER PT J AU Silverman, DH Small, GW de Aburto, MAK Hoffman, JM Salmon, E de Leon, MJ Mielke, R Jagust, WJ Pietrini, P Alexander, G Czernin, J Phelps, ME AF Silverman, DH Small, GW de Aburto, MAK Hoffman, JM Salmon, E de Leon, MJ Mielke, R Jagust, WJ Pietrini, P Alexander, G Czernin, J Phelps, ME TI Diagnostic accuracy of FDG-PET in evaluation of dementia: International multicenter pooled brain scan and autopsy data. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. NCI, Bethesda, MD 20892 USA. Univ Liege, Liege, Belgium. NYU, New York, NY USA. Max Planck Inst, Cologne, Germany. Univ Calif Davis, Sacramento, CA 95817 USA. Univ Pisa, Pisa, Italy. Arizona State Univ, Tempe, AZ USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 247 BP 63P EP 63P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400248 ER PT J AU Wong, DF Bauer, W Yokoi, F Cantilena, L Elkashef, A Dogan, S Stephane, M Gjedde, A AF Wong, DF Bauer, W Yokoi, F Cantilena, L Elkashef, A Dogan, S Stephane, M Gjedde, A TI Comparison of measures of in vivo human dopamine transporter occupancy of GBR12, 909. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDA, Bethesda, MD 20892 USA. Univ Aarhus, Aarhus, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 262 BP 67P EP 67P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400263 ER PT J AU Herscovitch, P Szajek, L Plascjak, P Carson, RE Eckelman, WC AF Herscovitch, P Szajek, L Plascjak, P Carson, RE Eckelman, WC TI Biodistribution and radiation dose estimates for (TC)-T-94m sestamibi for PET imaging. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 334 BP 85P EP 85P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400335 ER PT J AU Bencherif, B Madar, I Gorelick, D Musachio, JL Ravert, HT Mathews, WB Nelson, RA Dannals, RF Frost, JJ AF Bencherif, B Madar, I Gorelick, D Musachio, JL Ravert, HT Mathews, WB Nelson, RA Dannals, RF Frost, JJ TI Voxel by voxel atrophy correction of brain MU opioid receptor binding in chronic cocaine users. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. NIDA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 417 BP 105P EP 106P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400418 ER PT J AU Orchard, KH Cooper, MS Wijdenes, J Borchardt, P Quadri, SM Buscombe, JR Hilson, AJ Mehta, A Prentice, HG AF Orchard, KH Cooper, MS Wijdenes, J Borchardt, P Quadri, SM Buscombe, JR Hilson, AJ Mehta, A Prentice, HG TI Pre-clinical evaluation of candidate antibodies for targeted radiotherapy for patients with multiple myeloma. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 UCL Royal Free & Univ Coll, Sch Med, London, England. Diaclone, Besancon, France. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NIH, Bethesda, MD 20892 USA. UCL Royal Free Hosp, London NW3 2QG, England. RI Hilson, Andrew/C-8554-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 463 BP 117P EP 118P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400464 ER PT J AU Wilbur, DS Chyan, MK Hamlin, DK Brechbiel, MW AF Wilbur, DS Chyan, MK Hamlin, DK Brechbiel, MW TI Synthesis and radiolabeling of a new biotin-CHX-A" derivative for use with In-111, Y-90 or Bi-213 in tumor pretargeting. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 474 BP 120P EP 120P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400475 ER PT J AU Ma, Y Kiesewetter, DO Jagoda, E Eckelman, WC AF Ma, Y Kiesewetter, DO Jagoda, E Eckelman, WC TI Metabolism of F-18 FP-TZTP in rat and human hepatocytes and in vivo. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 479 BP 122P EP 122P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400480 ER PT J AU Riddell, C Carrasquillo, JA Libutti, SK Bacharach, SL AF Riddell, C Carrasquillo, JA Libutti, SK Bacharach, SL TI Class-dependent gaussian filtering of short transmission scans for unbiased PET attenuation correction. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 532 BP 135P EP 135P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400533 ER PT J AU Heinz, A Jones, DW Hommer, D Linnoila, M Weinberger, DR AF Heinz, A Jones, DW Hommer, D Linnoila, M Weinberger, DR TI Reduction in raphe serotonin transporters in alcoholism is associated with plasma cortisol concentrations. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Cent Inst Mental Hlth, D-6800 Mannheim, Germany. NIMH, Bethesda, MD 20892 USA. NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 537 BP 136P EP 136P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400538 ER PT J AU Buvat, I Bacharach, SL Kitsiou, AN Dilsizian, V Benali, H Di Paola, R AF Buvat, I Bacharach, SL Kitsiou, AN Dilsizian, V Benali, H Di Paola, R TI Fused images for combined assessment of myocardial perfusion and function. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 U494 INSERM, Paris, France. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 729 BP 157P EP 158P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400623 ER PT J AU Ferrand, SK Carson, JM Bacharach, SL Smith, MF Davis, CM Dilsizian, V AF Ferrand, SK Carson, JM Bacharach, SL Smith, MF Davis, CM Dilsizian, V TI Changes in regional metabolic utilization of fluorodeoxyglucose in congestive heart failure patients are associated with opposite shifts in palmitic acid kinetics. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 757 BP 164P EP 164P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400651 ER PT J AU Smith, MF Brown, BP Driver, DR Dilsizian, V Schraml, FV Carson, JM Bacharach, SL AF Smith, MF Brown, BP Driver, DR Dilsizian, V Schraml, FV Carson, JM Bacharach, SL TI Cardiac imaging with gamma camera coincidence (hybrid) PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 811 BP 178P EP 178P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400705 ER PT J AU Lodge, MA Mansour, PM Carrasquillo, JA Whatley, M Libutti, SK Bacharach, SL AF Lodge, MA Mansour, PM Carrasquillo, JA Whatley, M Libutti, SK Bacharach, SL TI Non-invisible estimation of the arterial input function for measurement of tumor blood now using sequential PET acquisitions. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Mt Vernon Hosp, Northwood HA6 2RN, Middx, England. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 826 BP 182P EP 182P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400720 ER PT J AU Kurdziel, KA Kalen, JD Olsson, CL King, LD AF Kurdziel, KA Kalen, JD Olsson, CL King, LD TI Optimal imaging time for lung tumors on hybrid PET systems. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. NIH, Midlothian, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 831 BP 183P EP 183P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400725 ER PT J AU Heinz, A Williams, W Kerich, H Linnoila, M Hommer, D AF Heinz, A Williams, W Kerich, H Linnoila, M Hommer, D TI FDG-PET shows orbitofrontal activation in alcoholics with low serotonin turnover. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Cent Inst Mental Hlth, D-6800 Mannheim, Germany. NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 918 BP 204P EP 204P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400812 ER PT J AU Carson, RE Channing, MA Sanchez-Pernaute, R Harvey-White, J Der, MG Herscovitch, P Bankiewicz, KS Eckelman, WC AF Carson, RE Channing, MA Sanchez-Pernaute, R Harvey-White, J Der, MG Herscovitch, P Bankiewicz, KS Eckelman, WC TI Kinetic evaluation of 6-[F-18]Fluoro-L-M-Tyrosine: Comparison of input function and reference region methods. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 944 BP 210P EP 210P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400838 ER PT J AU John, CS Cole, CE Kiesewetter, DO Eckelman, WC AF John, CS Cole, CE Kiesewetter, DO Eckelman, WC TI Synthesis, characterization, in-vitro cell binding, and biodistribution of radioiodinated [I-125]paclitaxel, [I-125]PAC. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1020 BP 229P EP 229P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400914 ER PT J AU Jeong, HJ Yao, ZS Park, CW Wong, KJ Park, LS Kao, CHK Mallet, RW Fritzberg, AR Axworthy, DB Pastan, I Carrasquillo, JA Paik, CH AF Jeong, HJ Yao, ZS Park, CW Wong, KJ Park, LS Kao, CHK Mallet, RW Fritzberg, AR Axworthy, DB Pastan, I Carrasquillo, JA Paik, CH TI Use of polylysine (PL) as a carrier of biotin and radionuclide for tumor targeting. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD USA. NEORX Corp, Seattle, WA 98119 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1033 BP 233P EP 233P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400927 ER PT J AU Lee, KS Zhang, L Schieck, C Jones, DW Eckelman, WC Gorey, JG Adams, HR Glennon, RA Weinberger, DR AF Lee, KS Zhang, L Schieck, C Jones, DW Eckelman, WC Gorey, JG Adams, HR Glennon, RA Weinberger, DR TI Autoradiography of R(-)-[Br-76]DOB, a potent 5-HT-2A/2C serotonin receptor agonist, in rat brain. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1069 BP 242P EP 242P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400963 ER PT J AU Sato, N Kobayashi, H Saga, T Nakamoto, Y Ishimori, T Brechbiel, MW Konishi, J AF Sato, N Kobayashi, H Saga, T Nakamoto, Y Ishimori, T Brechbiel, MW Konishi, J TI Intraperitoneal tumor targeting of DNA complexed with polyamidoamine dendrimers or avidin and its imaging in mice. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Kyoto Univ, Grad Sch Med, Kyoto, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1144 BP 260P EP 260P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401038 ER PT J AU Yao, ZS Wong, KJ Park, LS Dadachova, K Garmestani, K Brechbiel, MW Waldmann, TA Eckelman, WC Paik, CH Carrasquillo, JA AF Yao, ZS Wong, KJ Park, LS Dadachova, K Garmestani, K Brechbiel, MW Waldmann, TA Eckelman, WC Paik, CH Carrasquillo, JA TI Comparative cellular catabolism and retention of astatine, bismuth and lead radiolabeled internalizing monoclonal antibody. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1149 BP 261P EP 262P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401043 ER PT J AU Yao, ZS Zhang, ML Drumm-Giuseppe, DL Wong, KJ Park, CW Garmestani, K Waldmann, TA Axworthy, DB Mallett, RW Fritzberg, AR Pastan, I Brechbiel, MW AF Yao, ZS Zhang, ML Drumm-Giuseppe, DL Wong, KJ Park, CW Garmestani, K Waldmann, TA Axworthy, DB Mallett, RW Fritzberg, AR Pastan, I Brechbiel, MW TI Biodistribution and dosimetry of Yttrium/indium labeled biotin in A431 xenografted mice pretargeted with B3-streptavidin conjugate. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NeoRx Corp, Seattle, WA USA. NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1148 BP 261P EP 261P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401042 ER PT J AU Yao, ZS Zhang, ML Garmestani, K Brechbiel, MW Axworthy, DB Mallett, RW Fritzberg, AR Eckelman, WC Waldmann, TA Pastan, I Carrasquillo, JA AF Yao, ZS Zhang, ML Garmestani, K Brechbiel, MW Axworthy, DB Mallett, RW Fritzberg, AR Eckelman, WC Waldmann, TA Pastan, I Carrasquillo, JA TI Pre-targeting biodistribution of B3-streptavidin antibody (B3-SA) conjugate and bismuth radiolabeled biotin. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NeoRx Corp, Seattle, WA USA. NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1150 BP 262P EP 262P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401044 ER PT J AU Zhang, ML Yao, ZS Axworthy, DB Mallett, RW Fritzberg, AR Garmestani, K Goldman, CK Wong, KJ Paik, CH Brechbiel, MW Carrasquillo, JA Waldmann, TA AF Zhang, ML Yao, ZS Axworthy, DB Mallett, RW Fritzberg, AR Garmestani, K Goldman, CK Wong, KJ Paik, CH Brechbiel, MW Carrasquillo, JA Waldmann, TA TI Internalization of HAT-streptavidin conjugate in leukemia cells. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NeoRx Corp, Seattle, WA USA. NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1152 BP 262P EP 262P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401046 ER PT J AU Ma, D McDevitt, MR Barendswaard, E Lai, L Curcio, MJ Pellegrini, V Brechbiel, MW Finn, RD Scheinberg, DA AF Ma, D McDevitt, MR Barendswaard, E Lai, L Curcio, MJ Pellegrini, V Brechbiel, MW Finn, RD Scheinberg, DA TI Two novel alpha particle emitting constructs for radioimmunotherapy of lymphoma. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1175 BP 268P EP 268P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401069 ER PT J AU Miederer, M Nikula, T Brandes, K Handschuh, G Adam, C Schuhmacher, C Apostolidis, C Brechbiel, MW Schmid, E Senekowitsch-Schmidtke, R AF Miederer, M Nikula, T Brandes, K Handschuh, G Adam, C Schuhmacher, C Apostolidis, C Brechbiel, MW Schmid, E Senekowitsch-Schmidtke, R TI Cytotoxicity of the alpha emitter Bi-213 coupled to a specific antibody. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 GSF, Inst Strahlenbiol, Munich, Germany. NCI, Bethesda, MD 20892 USA. Tech Univ Munich, Chirurg Klin, D-8000 Munich, Germany. Univ Munich, Inst Pathol, D-8000 Munich, Germany. Inst Transuranium, Karlsruhe, Germany. Tech Univ Munich, Nukl Med Klin, D-8000 Munich, Germany. RI Miederer, Matthias/C-4405-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1177 BP 268P EP 268P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401071 ER PT J AU Park, JB Levine, M AF Park, JB Levine, M TI Intracellular accumulation of ascorbic acid is inhibited by flavonoids via blocking of dehydroascorbic acid and ascorbic acid uptakes in HL-60, U937 and Jurkat cells SO JOURNAL OF NUTRITION LA English DT Article DE ascorbic acid; dehydroascorbic acid; U937; HL-60; and Jurkat; flavonoids; glucose transporters (GLUT 1 and GLUT 3) ID GLUCOSE-TRANSPORTER; GLUT1; QUERCETIN; TRANSFORMATION; FAMILY AB In HL-60, U937 and Jurkat cells, the intracellular accumulation of ascorbic acid occurred via uptakes of both dehydroascorbic acid (an oxidized metabolite of ascorbic acid) and ascorbic acid (vitamin G). Dehydroascorbic acid and ascorbic acid were transported into cells by sodium-independent glucose transporters (GLUT 1 and GLUT 3) and sodium-dependent ascorbic acid transporters, respectively. Flavonoids inhibited the intracellular accumulation of ascorbic acid by blocking dehydroascorbic acid and ascorbic acid uptakes in the transformed cells. At flavonoid concentrations of 10-70 mu mol/L, similar to 50% of dehydroascorbic acid uptake was inhibited in the cells. In Jurkat cells, two potent flavonoids (myricetin and quercetin) competitively inhibited dehydroascorbic acid uptake, and K-i values were similar to 14 and 15 mu mol/L, respectively. Because GLUT 1 and GLUT 3 transport dehydroascorbic acid, the inhibition of dehydroascorbic acid uptake by flavonoids was investigated by using Chinese hamster ovary cells overexpressing rat GLUT 1 or human GLUT 3. Myricetin at concentrations of 22 and 18 mu mol/L, respectively, inhibited half of dehydroascorbic acid uptake in the cells overexpressing GLUT 1 and GLUT 3. Myricetin also inhibited ascorbic acid uptake; inhibition was noncompetitive with K-i = 14 mu mol/L in jurkat cells. These data indicate that flavonoids inhibit both ascorbic acid and dehydroascorbic acid uptake but do so by different mechanisms. These data may contribute to new understanding of the biological effect of flavonoids on the intracellular accumulation of ascorbic acid in human cells. C1 USDA, ARS, BHNRC, Phytonutrients Lab, Beltsville, MD 20705 USA. NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Park, JB (reprint author), USDA, ARS, BHNRC, Phytonutrients Lab, Beltsville, MD 20705 USA. NR 30 TC 47 Z9 48 U1 0 U2 4 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2000 VL 130 IS 5 BP 1297 EP 1302 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 311FC UT WOS:000086873200035 PM 10801933 ER PT J AU Hambidge, M Cousins, RJ Costello, RB AF Hambidge, M Cousins, RJ Costello, RB TI Zinc and health: Current status and future directions - Introduction SO JOURNAL OF NUTRITION LA English DT Editorial Material C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Florida, Gainesville, FL 32611 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Hambidge, M (reprint author), Univ Colorado, Hlth Sci Ctr, 4200 E 9th Ave, Denver, CO USA. NR 0 TC 13 Z9 13 U1 3 U2 9 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2000 VL 130 IS 5 SU S BP 1341S EP 1343S PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 311ZP UT WOS:000086917400001 ER PT J AU Sharma-Wagner, S Chokkalingam, AP Malker, HSR Stone, BJ McLaughlin, JK Hsing, AW AF Sharma-Wagner, S Chokkalingam, AP Malker, HSR Stone, BJ McLaughlin, JK Hsing, AW TI Occupation and prostate cancer risk in Sweden SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID PHYSICAL-ACTIVITY; PESTICIDE APPLICATORS; UNITED-STATES; FOLLOW-UP; WORKERS; MORTALITY; COHORT; FARMERS; INDUSTRY; DEATH AB To provide new lends regarding occupational prostate cancer risk factors, we linked 36,269 prostate cancer cases reported to the Swedish National Cancer Registry during 1961 to 1979 with employment information from the 1960 National Census. Standardized incidence ratios for prostate cancer, within major (1-digit) general (2-digit) and specific (3-digit) industries and occupations, were calculated, Significant excess risks were seen for agriculture-related industries, soap and perfume manufacture, and leather processing industries. Significantly elevated standardized incidence ratios were also seen for the following occupations:farmers, leather workers, and white-collar occupations. Our results suggest that farmers; certain occupations and industries with exposures to cadmium, herbicides, and fertilizers; and men with low occupational physical activity levels have elevated prostate cancer risks. Further research is needed to confirm these findings and identify specific exposures related to excess msk in these occupations and industries. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. George Washington Univ, Sch Med & Hlth Sci, Publ Hlth Program Epidemiol, Washington, DC 20052 USA. Natl Board Occupat Safety & Hlth, Solna, Sweden. Int Epidemiol Inst, Rockville, MD USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 7058,MSC 7234,6120 Execut Blvd, Bethesda, MD 20892 USA. NR 57 TC 46 Z9 47 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAY PY 2000 VL 42 IS 5 BP 517 EP 525 DI 10.1097/00043764-200005000-00010 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 313PC UT WOS:000087007200008 PM 10824305 ER PT J AU Stratakis, CA Ball, DW AF Stratakis, CA Ball, DW TI A concise genetic and clinical guide to multiple endocrine neoplasias and related syndromes SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Review DE Carney complex; multiple endocrine neoplasia syndromes; lentiginosis; Peutz-Jeghers syndrome; Cowden disease; hamartomatoses ID RET PROTOONCOGENE MUTATIONS; SPOTTY SKIN PIGMENTATION; PEUTZ-JEGHERS-SYNDROME; VON-HIPPEL-LINDAU; CARNEY-COMPLEX; HIRSCHSPRUNG-DISEASE; GERMLINE MUTATIONS; COWDEN-DISEASE; MYXOMAS; OVERACTIVITY AB Several familial neoplastic syndromes are associated with endocrine gland oncogenesis, The main ones are: multiple endocrine neoplasia type 1 (MEN 1), which affects primarily the pituitary, pancreas, and parathyroid glands; MEN 2A and MEN 2B, which involve mainly the thyroid and parathyroid glands and the adrenal medulla; familial medullary thyroid carcinoma (FMTC), which affects only the thyroid gland; and, finally, Carney complex, which affects the adrenal cortex, pituitary, thyroid gland, and the gonads. Carney complex is also associated with pigmentation abnormalities and myxoid and other neoplasms of mesenchymal origin. Thus, this syndrome also belongs to another group of genetic disorders, those associated with pigmentation defects and multiple tumors, including tumors of the endocrine glands. Peutz-Jeghers syndrome and Cowden disease are just two of these disorders that have recently been elucidated at the molecular level, von Hippel-Lindau disease is another condition that affects the pancreas and adrenal medulla and its gene is also known. The inheritance of the MENs, Carney complex, and related syndromes is autosomal dominant. Clinical recognition of these syndromes at a young age improves clinical outcome and prognosis of the various tumors and decreases associated morbidity and mortality. This review considers a wider, more inclusive view of the MEN syndromes, summarizes their clinical features and presents the newest information on their molecular elucidation. C1 NICHD, Unit Genet & Endocrinol, DEB, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Surg, Baltimore, MD USA. RP Stratakis, CA (reprint author), NICHD, Unit Genet & Endocrinol, DEB, NIH, Bldg 10,Rm 10N262,10 Ctr Dr,MSC1862, Bethesda, MD 20892 USA. NR 37 TC 24 Z9 26 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD MAY PY 2000 VL 13 IS 5 BP 457 EP 465 PG 9 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 309UJ UT WOS:000086787400001 PM 10803862 ER PT J AU Finer, NN Vohr, BR Robertson, CMT Ehrenkranz, RA Verter, J Wright, LL Hoffman, HJ Walsh-Sukys, MC Dusick, AM Fleisher, BE Steichen, J Laadt, G Yolton, K Delaney-Black, V Vohr, BR Whitfield, MF Blayney, MP Sauve, RS Casiro, OG Saigal, S Riley, SP Robertson, CMT Sankaran, K Gosselin, R Reynolds, A Stork, E Gorjanc, E Verter, J Powers, T Sokol, GM Appel, D Wright, LL Van Meurs, K Rhine, W Ball, B Brilli, R Moles, L Crowley, M Backstrom, C Crouse, D Hudson, T Konduri, GG Bara, R Kleinman, M Hensmann, A Rothstein, RW Ehrenkranz, RA Solimano, A Germain, F Walker, R Ramirez, AM Singhal, N Bourcier, L Fajardo, C Cook, V Kirpalani, H Monkman, S Johnston, A Mullahoo, K Finer, NN Peliowski, A Etches, P Kamstra, B Sankaran, K Riehl, A Blanchard, P Gouin, R Wearden, ME Gomez, MR Moon, YS Avery, GB D'Alton, ME Bracken, MB Catz, C Gleason, CA Maguire, M Redmond, CK Sinclair, JC Verter, J AF Finer, NN Vohr, BR Robertson, CMT Ehrenkranz, RA Verter, J Wright, LL Hoffman, HJ Walsh-Sukys, MC Dusick, AM Fleisher, BE Steichen, J Laadt, G Yolton, K Delaney-Black, V Vohr, BR Whitfield, MF Blayney, MP Sauve, RS Casiro, OG Saigal, S Riley, SP Robertson, CMT Sankaran, K Gosselin, R Reynolds, A Stork, E Gorjanc, E Verter, J Powers, T Sokol, GM Appel, D Wright, LL Van Meurs, K Rhine, W Ball, B Brilli, R Moles, L Crowley, M Backstrom, C Crouse, D Hudson, T Konduri, GG Bara, R Kleinman, M Hensmann, A Rothstein, RW Ehrenkranz, RA Solimano, A Germain, F Walker, R Ramirez, AM Singhal, N Bourcier, L Fajardo, C Cook, V Kirpalani, H Monkman, S Johnston, A Mullahoo, K Finer, NN Peliowski, A Etches, P Kamstra, B Sankaran, K Riehl, A Blanchard, P Gouin, R Wearden, ME Gomez, MR Moon, YS Avery, GB D'Alton, ME Bracken, MB Catz, C Gleason, CA Maguire, M Redmond, CK Sinclair, JC Verter, J CA Neonatal Inhaled Nitric Oxide Stud TI Inhaled nitric oxide in term and near-term infants: Neurodevelopmental follow-up of The Neonatal Inhaled Nitric Oxide Study Group (NINOS) SO JOURNAL OF PEDIATRICS LA English DT Article ID PERSISTENT PULMONARY-HYPERTENSION; EXTRACORPOREAL MEMBRANE-OXYGENATION; SENSORINEURAL HEARING-LOSS; RESPIRATORY-FAILURE; NEWBORN; SURVIVORS; VENTILATION; MULTICENTER AB Background: Inhaled nitric oxide (INO) improved oxygenation and reduced the occurrence of death or extracorporeal membrane oxygenation in term and near-term hypoxic neonates. We report the results of neurodevelopmental follow-up of infants enrolled in the NINOS trial. Methods: Hypoxic infants greater than or equal to 34 weeks' gestation and <14 days of age were randomized to 20 ppm INO or 100% oxygen as control. Comprehensive neurodevelopmental assessment of survivors occurred at 18 to 24 months of age. Results: A total of 235 infants were enrolled in the original trial. There were 36 deaths, 20 of 121 infants in the control group and 16 of 114 infants in the INO-treated group. Of the 199 surviving infants, 173 (86.9%) were seen for follow-up (88 members of the control group and 85 members of the INO-treated group), and 135 infants were normal (69 [79.3%] members of the control group and 66 [77.6%] members of the INO-treated group). Twenty-two infants had sensorineural hearing loss (12 members of the control group and 10 members of the INO-treated group). Moderate to severe cerebral palsy occurred in 13 infants (7 infants in the control group and 6 infants in the INO-treated group). Mental developmental index scores (87 +/- 18.7 in the control group vs 85 +/- 21.7 in the INO-treated group) and psychomotor developmental index scores (93.6 +/- 17.5 in the control group vs 85.7 +/- 21.2 in the INO-treated group) were not different. A total of 29.6% of the control group compared with 34.5% of the INO-treated group had at least one disability. Infants with congenital diaphragmatic hernia, enrolled in a separate but parallel trial, had similar outcomes with a higher incidence of sensorineural hearing loss. Conclusion: Inhaled nitric oxide is not associated with an increase in neurodevelopmental, behavioral, or medical abnormalities at 2 years of age. C1 Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Indiana Univ, Indianapolis, IN 46204 USA. NICHD, Bethesda, MD USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Cincinnati, Cincinnati, OH USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ Tennessee, Memphis, TN USA. Wayne State Univ, Detroit, MI USA. Women & Infants Hosp, Providence, RI USA. Yale Univ, New Haven, CT USA. British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada. Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. Foothills Hosp, Calgary, AB T2N 2T9, Canada. Hlth Sci Ctr, Winnipeg, MB, Canada. McMaster Univ, Hamilton, ON, Canada. Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. Royal Alexandra Hosp, Edmonton, AB, Canada. Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada. Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada. Texas Childrens Hosp, Houston, TX 77030 USA. NIDCD, Bethesda, MD USA. Natl Childrens Hosp, Med Ctr, Washington, DC USA. New England Med Ctr, Boston, MA 02111 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Finer, NN (reprint author), Univ Calif San Diego, Med Ctr, 200 W Arbor Dr,8774, San Diego, CA 92103 USA. NR 24 TC 53 Z9 57 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 2000 VL 136 IS 5 BP 611 EP 617 PG 7 WC Pediatrics SC Pediatrics GA 313DW UT WOS:000086985900011 ER PT J AU Wojda, U Miller, JL AF Wojda, U Miller, JL TI Targeted transfer of polyethylenimine-avidin-DNA bioconjugates to hematopoietic cells using biotinylated monoclonal antibodies SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article; Proceedings Paper CT Conference on Macromolecular Drug Delivery CY JUL 14-17, 1999 CL BRENCKENRIDGE, COLORADO SP Alza, Bayer, Adv Inhalat Res, Wyeth Lederle Vaccines, Valentis ID IN-VIVO; GENE-TRANSFER; SURFACE RECEPTORS; CROSS-LINKING; K562 CELLS; DELIVERY; ENDOCYTOSIS; VITRO; VECTORS; BRAIN AB Here we examine whether attachment of biotinylated antibodies to proteins on the cell surface increases the transfection efficiency of polyethylenimine-avidin-DNA bioconjugate gene transfer. Preliminary experiments were performed to compare avidin endocytosis into cells incubated with biotinylated antibodies. Antibody biotinylation resulted in the endocytosis of avidin-FITC into nearly 100% of cells compared with no detectable binding or entry into unbiotinylated cells. Gene transfer was accomplished with avidin conjugated to polyethylenimine (PEI) at a molar ratio of 4:1 (PA4). Plasmid DNA encoding the green fluorescent protein (GFP) gene was condensed on the PA4, and transfection efficiencies were measured by flow cytometry as the percentage of cells that fluoresced at levels greater than two standard deviations above the negative control. Gene transfer efficiencies were compared among K562, HEL, and Jurkat leukemia cell lines. Control transfections with DNA alone or untargeted PEI-DNA resulted in less than or equal to 2% GFP positive cells. Targeting PEI-avidin-DNA to antibody biotinylated cells increased transfection efficiency several fold over untargeted PEI. For each cell type, the increase in transfection efficiency was not significantly different among four biotinylated antibodies tested (antiCD55, antiCD59, antiCD71, and antiCD98). These data suggest biotinylated antibodies may be useful for targeting polyethylenimine-avidin mediated gene transfer. (C) 2000 Wiley-Liss, Inc. C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Miller, JL (reprint author), NIDDKD, Biol Chem Lab, NIH, 9000 Rockville Pk, Bethesda, MD 20892 USA. RI Wojda, Urszula/M-6079-2015 OI Wojda, Urszula/0000-0002-4525-2004 NR 32 TC 12 Z9 13 U1 0 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD MAY PY 2000 VL 89 IS 5 BP 674 EP 681 DI 10.1002/(SICI)1520-6017(200005)89:5<674::AID-JPS13>3.3.CO;2-V PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 312CN UT WOS:000086925800013 PM 10756333 ER PT J AU Ventura, ALM Sibley, DR AF Ventura, ALM Sibley, DR TI Altered regulation of the D-1 dopamine receptor in mutant Chinese hamster ovary cells deficient in cyclic AMP-dependent protein kinase activity SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID AGONIST-INDUCED DESENSITIZATION; OPOSSUM KIDNEY-CELLS; BETA(2)-ADRENERGIC RECEPTOR; HOMOLOGOUS DESENSITIZATION; ADENYLYL-CYCLASE; MESSENGER-RNA; BETA-2-ADRENERGIC RECEPTOR; PHOSPHORYLATION SITES; NEUROBLASTOMA-CELLS; DISTINCT PATHWAYS AB To investigate the role of the cAMP-dependent protein kinase (PKA) in the desensitization and down-regulation of the D-1 dopamine receptor, we stably expressed the rat cDNA for this receptor in mutant Chinese hamster ovary (CHO) cell lines deficient in PKA activity. The 10260 mutant CHO cell line has been characterized as expressing less than 10% of type I and type II PKA activities relative to the parental 10001 CHO cell line. The 10248 mutant CHO line lacks type II PKA activity and expresses a defective type I PKA. The transfected parental and mutant cell lines were found to express similar to 1 pmol/mg D-1 receptor binding activity (B-max) as determined using [H-3]SCH-23390 binding assays. All three cell lines demonstrated similar levels of dopamine-stimulated adenylyl cyclase activity. Pretreatment of all three CHO cells with dopamine resulted in desensitization of the adenylyl cyclase response, although the maximum desensitization was attenuated by 20 and 40% in the 10260 and 10248 cell lines, respectively. Dopamine also promoted, in a time- and dose-dependent fashion, a >90% down-regulation of D-1 receptors in the parental cell line but only a 50 and 30% decrease in the 10260 and 10248 cells, respectively. Similarly, treatment of the cells with the membrane-permeable cAMP analog 8-(4-chlorophenylthio)-cAMP induced functional desensitization and down-regulation of the D-1 receptor, although it was not as great as that observed with agonist pretreatment. As with the agonist pretreatments, the 8-(4-chlorophenylthio) induced responses were attenuated in the mutant cells with the 10248 line exhibiting the least desensitization/down-regulation. Our results suggest that PKA significantly contributes to the desensitization and down-regulation of D-1 receptors in CHO cells and that type II PKA may be the more relevant isoform with respect to regulating D-1 receptor function. C1 NINDS, Mol Neuropharmacol Branch, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Sibley, DR (reprint author), NINDS, Mol Neuropharmacol Branch, Expt Therapeut Branch, NIH, Bldg 10,Rm 5C108,10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. NR 30 TC 12 Z9 12 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 MAY PY 2000 VL 293 IS 2 BP 426 EP 434 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 309HY UT WOS:000086763500016 PM 10773012 ER PT J AU Liu, B Du, LN Hong, JS AF Liu, B Du, LN Hong, JS TI Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NECROSIS-FACTOR-ALPHA; IMMUNODEFICIENCY-VIRUS TYPE-1; NITRIC-OXIDE; INDUCED HYPERACTIVITY; ALZHEIMERS-DISEASE; CELL-DEATH; CULTURES; NEUROTOXICITY; BRAIN; EXPRESSION AB Degeneration of dopaminergicrgic neurons in the substantia nigra of the brain is a hallmark of Parkinson's disease and inflammation and oxidative stress are closely associated with the pathogenesis of degenerative neurological disorders. Treatment of rat mesencephalic mixed neuron-glia cultures with lipopolysaccharide (LPS)-activated microglia, resident immune cells of the brain, to release proinflammatory and neurotoxic factors tumor necrosis factor-alpha, interleukin-1 beta, nitric oxide, and superoxide and subsequently caused damage to midbrain neurons, including dopaminergic neurons. The LPS-induced degeneration of the midbrain neurons was significantly reduced by cotreatment with naloxone, an opioid receptor antagonist. This study focused on understanding the mechanism of action for the protective effect of naloxone on dopaminergic neurons because of relevance to Parkinson's disease. Both naloxone and its opioid receptor inactive stereoisomer (+)-naloxone protected the dopaminergic neurons with equal potency. Naloxone inhibited LPS-induced activation of microglia and release of proinflammatory factors, and inhibition of microglia generation of superoxide free radical best correlated with the neuroprotective effect of naloxone isomers. To further delineate the site of action, naloxone was found to partially inhibit the binding of [H-3]LPS to cell membranes, whereas it failed to prevent damage to dopaminergic neurons by peroxynitrite, a product of nitric oxide and superoxide. These results suggest that naloxone at least in part interferes with the binding of LPS to cell membranes to inhibit microglia activation and protect dopaminergic neurons as well as other neurons in the midbrain cultures from inflammatory damage. C1 NIEHS, Lab Pharmacol & Chem, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. RP Liu, B (reprint author), NIEHS, Lab Pharmacol & Chem, Neuropharmacol Sect, MD F1-01,POB 12233, Res Triangle Pk, NC 27709 USA. RI liu, Bin/A-7695-2009 NR 45 TC 252 Z9 279 U1 1 U2 11 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 MAY PY 2000 VL 293 IS 2 BP 607 EP 617 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 309HY UT WOS:000086763500039 PM 10773035 ER PT J AU Gu, YJ Chen, WY Xia, ZX AF Gu, YJ Chen, WY Xia, ZX TI Molecular modeling of the interactions of trichosanthin with four substrate analogs SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE trichosanthin; substrate analogues; molecular dynamics; simulated annealing; interaction energy ID RIBOSOME-INACTIVATING PROTEINS; RICIN-A-CHAIN; ANGSTROM RESOLUTION; 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURE; ACTIVE-SITE; COMPLEX; MOMORCHARIN; MECHANISM; DYNAMICS AB Trichosanthin (TCS) is a ribosome-inactivating protein (RIP) that possesses N-glycosidase activity. It inactivates ribosomes and arrests protein synthesis by removing a specific adenine from 28S rRNA. A molecular dynamics simulated annealing method was applied to study the binding modes of TCS with substrate analogs, three oligonucleotides GAG, GAGA, and CGAGAG, based on the crystal structures of the stable complexes of TCS with NADPH and with the reaction product adenine. A water molecule proposed-to be responsible for hydrolyzing the N-glycosidic bond was included in the model. All the oligoribonucleotides can dock into the active cleft of TCS without unfavorable contacts. The interaction energies between TCS and the three oligonucleotides were calculated. The interactions of TCS with NADH were also studied by a molecular dynamics simulated annealing method. The interaction energy between NADH and TCS was compared with that between NADPH and TCS, showing that the lack of 2'-phosphate group leads to an energy rise of 20 kcal/mol. C1 Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Bioorgan & Nat Prod Chem, Shanghai 200032, Peoples R China. RP Xia, ZX (reprint author), NCI, Frederick Canc Res & Dev Ctr, Biomol Struct Grp, Frederick, MD 21702 USA. RI Gu, Yijun/B-6017-2012 NR 37 TC 2 Z9 2 U1 1 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD MAY PY 2000 VL 19 IS 4 BP 291 EP 297 DI 10.1023/A:1007047413373 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 358VU UT WOS:000089578500006 PM 11043934 ER PT J AU Sher, L AF Sher, L TI Neuroimaging, auditory hallucinations, and the bicameral mind SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Editorial Material DE auditory cortex; brain; consciousness; hallucinations; magnetic resonance imaging C1 NIMH, Bethesda, MD 20892 USA. RP Sher, L (reprint author), NIMH, Bldg 10,Room 35-231,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 7 Z9 7 U1 1 U2 2 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 1180-4882 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD MAY PY 2000 VL 25 IS 3 BP 239 EP 240 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 317RQ UT WOS:000087241100002 PM 10863883 ER PT J AU Nagao, E Kaneko, O Dvorak, JA AF Nagao, E Kaneko, O Dvorak, JA TI Plasmodium falciparum-infected erythrocytes: Qualitative and quantitative analyses of parasite-induced knobs by atomic force microscopy SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE atomic force microscopy; tapping mode; erythrocyte; knob; malaria; Plasmodium falciparum ID HUMAN CEREBRAL MALARIA; MEMBRANE; SURFACE; CELLS; PROTEIN AB We used the combination of an atomic force microscope and a light microscope equipped with epifluorescence to serially image Plasmodium falciparum-infected erythrocytes. This procedure allowed us to determine unambiguously the presence and developmental stage of the malaria parasite as well as the number and size of knobs in singly, doubly, and triply infected erythrocytes, Knobs are not present during the ring stage of a malaria infection but a lesion resulting from invasion by a merozoite is clearly visible on the erythrocyte surface. This lesion is visible into the late trophozoite stage of infection. Knobs begin to form during the early trophozoite stage of infection and have a single-unit structure. Our data suggest the possibility that a two-unit structure of knobs, which was reported by Aikawa et al. (1996, Exp. Parasitol. 84, 339-343) using atomic force microscopy, appears to be a double-tipped image. The number of knobs per unit of host cell surface area is directly proportional to parasite number in both early and late trophozoite stages. These results indicate that knob formation by one parasite. does not influence knob formation by other parasites in a multiply infected erythrocyte. In addition, knob volume is not influenced by either parasite stage or number at the late trophozoite stage, indicating that the number of component molecules per knob is constant throughout the parasite maturation process. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Nagao, E (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 22 TC 53 Z9 56 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD MAY PY 2000 VL 130 IS 1 BP 34 EP 44 DI 10.1006/jsbi.2000.4236 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 317HC UT WOS:000087219100004 PM 10806089 ER PT J AU Iwasa, KH AF Iwasa, KH TI Effect of membrane motor on the axial stiffness of the cochlear outer hair cell SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID ACTIVE FORCE GENERATION; MOTILITY; SHAPE AB Voltage-dependent motility of the cell body of the cochlear outer hair cell has been successfully explained by an "area motor" model, which is based on tight coupling between charge transfer across the membrane and changes in the membrane area. The model might appear to contradict a recent report that the axial stiffness of the outer hair cell is dependent on the membrane potential. Here, it is shown that the area motor model indeed predicts a considerable voltage dependence of the axial stiffness of the outer hair cell. The predicted changes resemble those observed experimentally, although the predicted changes are smaller at the two extremes of the membrane potential. [S0001-4966(00)04805-0]. C1 Natl Inst Deafness & Other Commun Disorders, Biophys Sect, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. RP Iwasa, KH (reprint author), Natl Inst Deafness & Other Commun Disorders, Biophys Sect, Lab Cellular Biol, NIH, 9 Ctr Dr, Bethesda, MD 20892 USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 12 TC 13 Z9 14 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2000 VL 107 IS 5 BP 2764 EP 2766 DI 10.1121/1.428663 PN 1 PG 3 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 312WX UT WOS:000086967900048 PM 10830400 ER PT J AU Castellanos, FX Marvasti, FF Ducharme, JL Walter, JM Israel, ME Krain, A Pavlovsky, C Hommer, DW AF Castellanos, FX Marvasti, FF Ducharme, JL Walter, JM Israel, ME Krain, A Pavlovsky, C Hommer, DW TI Executive function oculomotor tasks in girls with ADHD SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; executive function; oculomotor tasks; go-no go; delayed response tasks ID DEFICIT HYPERACTIVITY DISORDER; PURSUIT EYE-MOVEMENTS; FAMILIAL TRANSMISSION; MAGNETIC-RESONANCE; ATTENTION; CHILDREN; SCHIZOPHRENIA; AGE; PSYCHOLOGY; SACCADES AB Objective: To assess executive function in girls with attention-deficit/hyperactivity disorder (ADHD) using oculomotor tasks as possible trait markers for neurobiological studies. Method: Thirty-two girls aged 6 to 13 years with DSM-IV ADHD and 20 age-matched, normal control girls were tested on a variety of oculomotor tasks requiring attention, working memory, and response inhibition, which included smooth pursuit, delayed response, and go-no go tasks. Results: Girls with ADHD performed the delayed response task correctly an 32% of trials as measured by number of memory-guided saccades, in contrast to 62% of trials for control subjects (p = .0009). Patients made twice as many commission errors to no go stimuli (p = .0001) and 3 times as many intrusion errors (saccades in the absence of go or no go stimuli; p = .004) during the go-no go task compared with controls. Smooth pursuit performance was statistically equivalent across subject groups. Repeated testing in a subgroup of 15 patients revealed substantial practice effects on go-no go performance. Conclusions: The data confirm that girls with ADHD exhibit impairments in executive function, as has been reported in boys, implying a similar pathophysiology of ADHD in both sexes. However, practice effects may limit the utility of the oculomotor go-no go task far some neurobiological studies. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Arizona State Univ, Tempe, AZ USA. Univ Penn, Philadelphia, PA 19104 USA. NIAAA, Brain Electrophysiol & Imaging Sect, Bethesda, MD USA. Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. Univ Salvador, Buenos Aires, DF, Argentina. RP Castellanos, FX (reprint author), Bldg 10 Room 3B-19,10 Ctr Dr, Bethesda, MD 20892 USA. RI Roy, Amy/J-7613-2013; OI Castellanos, Francisco/0000-0001-9192-9437 NR 36 TC 74 Z9 75 U1 1 U2 9 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 MAY PY 2000 VL 39 IS 5 BP 644 EP 650 DI 10.1097/00004583-200005000-00019 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 308DC UT WOS:000086694400019 PM 10802983 ER PT J AU Gottdiener, JS Arnold, AM Aurigemma, GP Polak, JF Tracy, RP Kitzman, DW Gardin, JM Rutledge, JE Boineau, RC AF Gottdiener, JS Arnold, AM Aurigemma, GP Polak, JF Tracy, RP Kitzman, DW Gardin, JM Rutledge, JE Boineau, RC TI Predictors of congestive heart failure in the elderly: The cardiovascular health study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR MASS; ISOLATED SYSTOLIC HYPERTENSION; 6 ANTIHYPERTENSIVE AGENTS; TO-MODERATE HYPERTENSION; SINGLE-DRUG THERAPY; VITAL CAPACITY; SERIAL CHANGES; UNITED-STATES; OLDER ADULTS; DISEASE AB OBJECTIVES We sought to characterize the predictors of incident congestive heart failure (CHF), as determined by central adjudication, in a community-based elderly population. BACKGROUND The elderly constitute a growing proportion of patients admitted to the hospital with CHF, and CHF is a leading source of morbidity and mortality in this group. Elderly patients differ from younger individuals diagnosed with CHF in terms of biologic characteristics. METHODS We analyzed data from the Cardiovascular Health Study, a prospective population-based study of 5,888 elderly people >65 years old (average 73 +/- 5, range 65 to 100) at four locations. Multiple laboratory measures of cardiovascular structure and function, blood chemistries and functional assessments were obtained. RESULTS During an average follow-up of 5.5 years (median 6.3), 597 participants developed incident CHF (rate 19.3/1,000 person-years). The incidence of CHF increased progressively across age groups and was greater in men than in women. On multivariate analysis, other independent predictors included prevalent coronary heart disease, stroke or transient ischemic attack at baseline, diabetes, systolic blood pressure (BP), forced expiratory volume 1 s, creatinine >1.4 mg/dl, C-reactive protein, ankle-arm index <0.9, atrial fibriuation, electrocardiographic (ECG) left ventricular (LV) mass, ECG ST-T segment abnormality, internal carotid artery wall thickness and decreased LV systolic function. Population-attributable risk, determined from predictors of risk and prevalence, was relatively high for prevalent coronary heart disease (13.1%), systolic BP greater than or equal to 140 mm Hg (12.8%) and a high level of C-reactive protein (9.7%), but was low for subnormal LV function (4.1%) and atrial fibrillation (2.2%). CONCLUSIONS The incidence of CHF is high in the elderly and is related mainly to age, gender, clinical and subclinical coronary heart disease, systolic BP and inflammation. Despite the high relative risk of subnormal systolic LV function and atrial fibrillation, the actual population risk of these for CHF is small because of their relatively low prevalence in community-dwelling elderly people. (C) 2000 by the American College of Cardiology. C1 St Francis Hosp, Roslyn, NY 11576 USA. Georgetown Univ Hosp, Div Cardiol, Washington, DC 20007 USA. Washington Univ, Dept Biostat, Seattle, WA USA. Univ Massachusetts, Med Ctr, Div Cardiol, Worcester, MA USA. Tufts New England Med Ctr, Dept Radiol, Boston, MA USA. Univ Vermont, Colchester Res Facil, Colchester, VT USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Calif Irvine, Irvine, CA USA. Univ Calif Davis, Div Cardiovasc Med, Davis, CA 95616 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Gottdiener, JS (reprint author), St Francis Hosp, 100 Port Washington Blvd, Roslyn, NY 11576 USA. FU NHLBI NIH HHS [N01-HC-15103, N01-HC-85079-85086] NR 61 TC 472 Z9 481 U1 4 U2 17 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 MAY PY 2000 VL 35 IS 6 BP 1628 EP 1637 DI 10.1016/S0735-1097(00)00582-9 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 310LB UT WOS:000086828700032 PM 10807470 ER PT J AU Yellowitz, JA Horowitz, AM Drury, TF Goodman, HS AF Yellowitz, JA Horowitz, AM Drury, TF Goodman, HS TI Survey of US dentists' knowledge and opinions about oral pharyngeal cancer SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article AB Background, Oral pharyngeal cancer constitutes the most life-threatening of all dental and craniofacial conditions. The U.S. five-year survival rate of 52 percent for these cancers is one of the lowest and has not changed in decades. Methods. The authors mailed a pretested survey to 7,000 randomly selected general dentists; They obtained information on 3,200 dentists' levels of knowledge about oral pharyngeal cancer risks and diagnostic procedures for providing an oral cancer examination, as well as about related opinions and interest in continuing education, or CE, courses on the topic. The authors carried out analyses using unweighted data; they used both bivariate and logistic analytical techniques and evaluated at a significance level of P less than or equal to .01. Results. Based on responses to 14 questions, the average knowledge of oral cancer risks score was 8.4. About one-half of dentists surveyed knew the two most common sites of intraoral cancer and that most oral cancers are diagnosed at a late stage. Conclusions. The reported knowledge of these dentists regarding oral cancer suggests that they are not as knowledgeable as they could be about cancer prevention and early detection and that they recognize these deficiencies. Most of the dentists were interested in oral cancer CE. Clinical Implications. Dentists need to know where in the mouth to look and what types of lesions to look for to provide a comprehensive oral cancer examination. C1 NIDCR, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Dent, Dept Oral Hlth Care Delivery, Baltimore, MD 21201 USA. Maryland Dept Hlth & Mental Hyg, Off Oral Hlth, Baltimore, MD USA. RP Horowitz, AM (reprint author), NIDCR, NIH, Bldg 45,Room 3AN 44B, Bethesda, MD 20892 USA. NR 15 TC 69 Z9 70 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 MAY PY 2000 VL 131 IS 5 BP 653 EP 661 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 313YW UT WOS:000087028200022 PM 10832259 ER PT J AU Slavkin, HC AF Slavkin, HC TI Obesity, brain and gonadal functions, ano osteoporosis SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID POSTMENOPAUSAL WOMEN; BONE LOSS; LEPTIN; BURDEN C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), Natl Inst Dent & Craniofacial Res, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 22 TC 1 Z9 2 U1 0 U2 0 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 MAY PY 2000 VL 131 IS 5 BP 673 EP 677 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 313YW UT WOS:000087028200026 PM 10832263 ER PT J AU Luoto, R Manolio, T Meilahn, E Bhadelia, R Furberg, C Cooper, L Kraut, M AF Luoto, R Manolio, T Meilahn, E Bhadelia, R Furberg, C Cooper, L Kraut, M TI Estrogen replacement therapy and MRI-demonstrated cerebral infarcts, white matter changes, and brain atrophy in older women: The Cardiovascular Health Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE estrogen; magnetic resonance imaging; population study; MMSE; hormone replacement therapy ID RISK-FACTORS; POSTMENOPAUSAL WOMEN; COGNITIVE FUNCTION; ALZHEIMERS-DISEASE; LESIONS; ATHEROSCLEROSIS; ABNORMALITIES; PREVALENCE; ROTTERDAM; GENDER AB OBJECTIVE: We studied the relationship between the use of estrogen replacement therapy (ERT) and cerebral magnetic resonance imaging (MRI) abnormalities among older women. DESIGN: A population-based prospective study (Cardiovascular Health Study). SETTING: Four regions in the United States. PARTICIPANTS: A total of 2133 (62.9% of the eligible) women aged 65 to 95 years (mean age 74.8), on whom MRI was performed in 1992-1994. MEASUREMENTS: Presence of global brain atrophy, white matter changes, small infarct-like lesion (ILL) (<3 mm), MRI infarcts (greater than or equal to 3 mm, mostly small and asymptomatic), and cognitive function as measured by Mini-Mental State Exam (MMSE), and by ERT use (current/past/never), adjusted for a number of socioeconomic, lifestyle, and reproductive covariates. RESULTS: Current use of ERT was reported by 15% and past use by another 23% of participants; 35% of all women had MRI infarcts. The prevalence of MRI infarcts did not differ in current or past users from those who had never used ERT (nonusers). Bifrontal distance, the largest distance between frontal horns, and the size of ventricles were larger among current ERT users compared to past users or nonusers (P (trend) =.01), adjusted for all other covariates, but no dose-response relationship to current or past ERT use was found. Duration of estrogen use was not associated with any atrophy measure. Cortical atrophy measure, sulcal widening, or white matter disease did not differ significantly by ERT use or duration of use. Central measures of atrophy, bifrontal distance, and ventricular size were significantly associated with cognition as measured by MMSE. CONCLUSIONS: Current ERT users had much more clinically significant central atrophy than nonusers, but the implications remained unclear. J Am Geriatr Soc 48:467-472, 2000. C1 Natl Publ Hlth Inst, Dept Hlth & Disabil, FIN-00300 Helsinki, Finland. NHLBI, NIH, Bethesda, MD USA. London Sch Hyg & Trop Med, Dept Epidemiol & Publ Hlth, London WC1, England. Tufts New England Med Ctr, Ultrasound Reading Ctr, Boston, MA USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Johns Hopkins Radiol, Baltimore, MD USA. RP Luoto, R (reprint author), Natl Publ Hlth Inst, Dept Hlth & Disabil, Mannerheimintie 166, FIN-00300 Helsinki, Finland. NR 29 TC 26 Z9 28 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2000 VL 48 IS 5 BP 467 EP 472 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 312AW UT WOS:000086921200001 PM 10811537 ER PT J AU Masys, DR Brennan, PF Ozbolt, JG Corn, M Shortliffe, EH AF Masys, DR Brennan, PF Ozbolt, JG Corn, M Shortliffe, EH TI Are medical informatics and nursing informatics distinct disciplines? The 1999 ACMI debate SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article AB The 1999 debate of the American College of Medical Informatics focused on the proposition that medical informatics and nursing informatics are distinctive disciplines that require their own core curricula, training programs, and professional identities. Proponents of this position emphasized that informatics training, technology applications, and professional identities are closely tied to the activities of the health professionals they serve and that, as nursing and medicine differ, so do the corresponding efforts in information science and technology. Opponents of the proposition asserted that informatics is built on a re-usable and widely applicable set of methods that are common to all health science disciplines, and that "medical informatics" continues to be a useful name for a composite core discipline that should be studied by all students, regardless of their health profession orientation. C1 Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. Univ Wisconsin, Madison, WI USA. Vanderbilt Univ, Nashville, TN USA. Natl Lib Med, Bethesda, MD USA. Stanford Univ, Stanford, CA 94305 USA. RP Masys, DR (reprint author), Univ Calif San Diego, Sch Med, 9500 Gilman Dr,BSB Room 1317, La Jolla, CA 92093 USA. NR 4 TC 12 Z9 12 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY-JUN PY 2000 VL 7 IS 3 BP 304 EP 312 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 314KV UT WOS:000087055700012 PM 10833168 ER PT J AU McCray, AT Ide, NC AF McCray, AT Ide, NC TI Design and implementation of a national clinical trials registry SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID REPRESENTATION; ELIGIBILITY; SYSTEM AB The authors have developed a Web-based system that provides summary information about clinical trials being conducted throughout the United States. The first version of the system, publicly available in February 2000, contains more than 4,000 records representing primarily trials sponsored by the National Institutes of Health. The impetus for this system has come from the Food and Drug Administration (FDA) Modernization Act of 1997, which mandated a registry of both federally and privately funded clinical trials "of experimental treatments for serious or life-threatening diseases or conditions." The system design and implementation have been guided by several principles. First, all stages of system development were guided by the needs of the primary intended audience, patients and other members of the public. Second, broad agreement on a common set of data elements was obtained. Third, the system was designed in a modular and extensible way, and search methods that take extensive advantage of the National Library of Medicine's Unified Medical Language System (UMLS) were developed. Finally, since this will be a long-term effort involving many individuals and organizations, the project is being implemented in several phases. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP McCray, AT (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM mccray@nlm.nih.gov NR 26 TC 50 Z9 50 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY-JUN PY 2000 VL 7 IS 3 BP 313 EP 323 PG 11 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 314KV UT WOS:000087055700013 PM 10833169 ER PT J AU Eitner, F Cui, Y Hudkins, KL Stokes, MB Segerer, S Mack, M Lewis, PL Abraham, AA Schlondorff, D Gallo, G Kimmel, PL Alpers, CE AF Eitner, F Cui, Y Hudkins, KL Stokes, MB Segerer, S Mack, M Lewis, PL Abraham, AA Schlondorff, D Gallo, G Kimmel, PL Alpers, CE TI Chemokine receptor CCR5 and CXCR4 expression in HIV-associated kidney disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNOHISTOCHEMICAL DETECTION; INSITU HYBRIDIZATION; GENETIC RESTRICTION; MOLECULAR-CLONING; LYMPH-NODES; INFECTION; NEPHROPATHY; TISSUE; AIDS AB The chemokine receptors CCR5 and CXCR4 have been identified as essential coreceptors for entry of HIV-1 strains into susceptible cells. Direct infection of renal parenchymal cells has been implicated in the pathogenesis of HIV-associated renal disease, although data are conflicting. The localization of CCR5 and CXCR4 in kidneys with HIV-associated renal disease is unknown. Formalin-fixed, paraffin-embedded renal biopsies from patients with HIV-associated nephropathy (HIVAN) (n = 13), HIV-associated immune complex glomerulonephritis (n = 3), HIV-associated thrombotic microangiopathy (n = 1), and HIV-negative patients with collapsing glomerulopathy (n = 8) were analyzed in this study. Cellular sites of expression of CCR5 and CXCR4 were identified by immunohistochemistry and by in situ hybridization. The presence of HIV-1 was detected by immunohistochemistry and by in situ hybridization. Expression of both chemokine receptors CCR5 and CXCR4 was undetectable in intrinsic glomerular, tubular, and renovascular cells in all analyzed cases. In the presence of tubulointerstitial inflammation, CCR5 and CXCR4 expression was localized to infiltrating mononuclear leukocytes. HIV-1 protein was undetectable by immunohistochemistry in ail cases of HIV-associated renal disease. HIV-1 RNA was identified in one case of HIVAN but was restricted to infiltrating leukocytes. HIV-1 RNA was not detected in intrinsic renal cells in all analyzed cases. Identifying the cellular expression of HIV-coreceptors CCR5 and CXCR4 may help to clarify which tissues are permissive for direct HIV infection. These data do not support a role of productive HIV-1 infection of renal parenchymal cells in the pathogenesis of HIV-associated renal disease. C1 Univ Washington, Dept Pathol, Seattle, WA 98195 USA. LMU, Klinikum Innenstadt, Med Poliklin, Munich, Germany. Oregon Hlth Sci Univ, Div Pediat Infect Dis, Portland, OR 97201 USA. George Washington Univ, Med Ctr, Dept Pathol & Med, Washington, DC 20037 USA. NYU, Dept Pathol, New York, NY 10016 USA. NIH, Bethesda, MD 20892 USA. RP Alpers, CE (reprint author), Univ Washington, Dept Pathol, Box 356100,1959 NE Pacific St, Seattle, WA 98195 USA. RI Eitner, Frank/B-8712-2008 FU NHLBI NIH HHS [HL63652]; NIDDK NIH HHS [DK47659, DK49514] NR 54 TC 51 Z9 53 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2000 VL 11 IS 5 BP 856 EP 867 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 309JG UT WOS:000086764300006 PM 10770963 ER PT J AU Walther, MM Shawker, TH Libutti, SK Lubensky, I Choyke, PL Venzon, D Linehan, WM AF Walther, MM Shawker, TH Libutti, SK Lubensky, I Choyke, PL Venzon, D Linehan, WM TI A phase 2 study of radio frequency interstitial tissue ablation of localized renal tumors SO JOURNAL OF UROLOGY LA English DT Article DE kidney; carcinoma, renal cell; hyperthermia, induced ID NEPHRON SPARING SURGERY; CELL CARCINOMA; THERMAL ABLATION; FOLLOW-UP; EXPERIENCE; CANCER; PROSTATE; ADENOMA; DISEASE AB Purpose: Small renal tumors are frequently detected during the screening of patients with a hereditary type of renal cancer. The development of nonsurgical treatment modalities would greatly improve quality of life in these patients. We present our experience with radio frequency interstitial tissue ablation, a heating device approved by the Food and Drug Administration for treating soft tissue tumors. Materials and Methods: Patients underwent radio frequency interstitial tissue ablation of small renal tumors just before surgical excision. Pathological examination of the renal tumors was done to evaluate the treatment effect. Computerized tomography and renal function testing were performed before and after therapy to evaluate toxicity. Results: Four patients underwent treatment of a total of 14 tumors with the radio frequency interstitial tissue ablation device just before surgical removal of the tumors.. All lesions were brown after ablation, in contrast to the normal pink appearance of untreated lesions that were resected. On color Doppler ultrasound blood flow to each tumor evident before was not visualized after treatment. The Wilcoxon rank sum test demonstrated no difference preoperatively and postoperatively in blood urea nitrogen, serum creatinine, creatinine clearance or differential renal function. We identified no toxicity associated with radio frequency interstitial tissue ablation. Of the excised tumors 11 were renal cell carcinoma and 3 fibrotic hemorrhagic cysts. For renal cell carcinoma the treatment effect involved the loss of nuclear detail and nonvisualization of nucleoli. These changes were not observed in any tumors resected without radio frequency interstitial tissue ablation. The treatment effect was noted in 10 of the 11 lesions, and in 1 case the treatment effect involved 35% of the tumor. Conclusions: No toxicity was associated with radio frequency interstitial tissue ablation, Percutaneous treatment of renal tumors is planned to evaluate the treatment effect better and further evaluate toxicity. C1 NCI, Urol Oncol Branch, Dept Radiol, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Walther, MM (reprint author), NCI, Urol Oncol Branch, Dept Radiol, NIH, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 26 TC 57 Z9 62 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2000 VL 163 IS 5 BP 1424 EP 1427 DI 10.1016/S0022-5347(05)67634-3 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 303HN UT WOS:000086416600005 PM 10751849 ER PT J AU Propert, KJ Schaeffer, AJ Brensinger, CM Kusek, JW Nyberg, LM Landis, JR AF Propert, KJ Schaeffer, AJ Brensinger, CM Kusek, JW Nyberg, LM Landis, JR CA Interstitial Cystitis Data Base St TI A prospective study of interstitial, cystitis: Results of longitudinal followup of the interstitial cystitis data base cohort SO JOURNAL OF UROLOGY LA English DT Article DE bladder; cystitis, interstitial; cohort study; pain; urination disorders ID CATS; REGRESSION AB Purpose: We present baseline characteristics and longitudinal profiles of symptoms in the Interstitial Cystitis Data Base study, a prospective cohort study of patients with interstitial cystitis. Materials and Methods: A total of 637 eligible patients were entered into the study and followed for symptoms of pain, urgency and urinary frequency. Median followup was 31 months. Results: More than 90% of patients were white women with a median age of 43 years. Using the overall pain-urgency-frequency score 7% of participants presented with mild, 44% with moderate and 49% with severe symptoms. Severe urgency in 41% of cases and severe 24-hour frequency in 41% were more common than severe pain in 29%, Of the patients 51% reported nighttime frequency of 2 or more voids. Median duration of interstitial cystitis symptoms was 8 years and 68% of participants were previously diagnosed with the condition. The 36% of patients who withdrew from study or were lost to followup were more likely to have had more severe symptoms at baseline. Patterns of change with time suggest initial symptom improvement due to regression to the mean, and an intervention effect associated with the increased followup and care of cohort participants. Although all symptoms fluctuated, there was no evidence of significant long-term change in overall disease severity. Conclusions: Our observations support the clinical observation that interstitial cystitis is a chronic disease and no current treatments have a significant impact on symptoms with time. These results provide a foundation for the design and performance of future clinical trials in interstitial cystitis using these end points in a similar patient population. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Northwestern Univ, Chicago, IL 60611 USA. NIDDKD, Bethesda, MD 20892 USA. RP Propert, KJ (reprint author), Univ Penn, Sch Med, Blockley Hall,6th Floor,423 Guardian Dr, Philadelphia, PA 19104 USA. RI Landis, J. Richard/A-9330-2010 FU NIDDK NIH HHS [U01-DK-45859, U01-DK-45013, U01-DK-54127] NR 21 TC 105 Z9 108 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2000 VL 163 IS 5 BP 1434 EP 1439 DI 10.1016/S0022-5347(05)67637-9 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 303HN UT WOS:000086416600009 PM 10751852 ER PT J AU Odegrip, R Schoen, S Haggard-Ljungquist, E Park, K Chattoraj, DK AF Odegrip, R Schoen, S Haggard-Ljungquist, E Park, K Chattoraj, DK TI The interaction of bacteriophage P2 B protein with Escherichia coli DnaB helicase SO JOURNAL OF VIROLOGY LA English DT Article ID LAMBDA-REPLICATION ORIGIN; O-PROTEIN; NUCLEOPROTEIN STRUCTURES; INITIATION; GENE; BINDING; COMPLEX; COLIPHAGE-186; SPECIFICITY; MUTANTS AB Bacteriophage P2 requires several host proteins for lytic replication, including helicase DnaB but not the helicase loader, DnaC, Some genetic studies have suggested that the loading is done by a phage-encoded protein, P2 B, However, a P2 minichromosome containing only the P2 initiator gene A and a marker gene can be established as a plasmid without requiring the P2 B gene, Here we demonstrate that P2 B associates with DnaB, This was done by using the yeast two-hybrid system in vivo and was confirmed in vitro, where S-35-labeled P2 B bound specifically to DnaB adsorbed to Q Sepharose beads and monoclonal antibodies directed against the His-tagged P2 B protein were shown to coprecipitate the DnaB protein. Finally, P2 B was shown to stabilize the opening of a reporter origin, a reaction that is facilitated by the inactivation of DnaB, In this respect, P2 Il was comparable to lambda P protein, which is known to be capable of binding and inactivating the helicase while acting as a helicase loader. Even though P2 B has little similarity to other known or predicted helicase loaders, we suggest that P2 B is required for efficient loading of DnaB and that this role, although dispensable for P2 plasmid replication, becomes essential for P2 lytic replication. C1 Stockholm Univ, Dept Genet, S-10691 Stockholm, Sweden. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Haggard-Ljungquist, E (reprint author), Stockholm Univ, Dept Genet, S-10691 Stockholm, Sweden. NR 56 TC 19 Z9 19 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 MAY PY 2000 VL 74 IS 9 BP 4057 EP 4063 DI 10.1128/JVI.74.9.4057-4063.2000 PG 7 WC Virology SC Virology GA 302KV UT WOS:000086365000014 PM 10756017 ER PT J AU Betakova, T Wolffe, EJ Moss, B AF Betakova, T Wolffe, EJ Moss, B TI The vaccinia virus A14.5L gene encodes a hydrophobic 53-amino-acid virion membrane protein that enhances virulence in mice and is conserved among vertebrate poxviruses SO JOURNAL OF VIROLOGY LA English DT Article ID STRUCTURAL PROTEINS; RNA-POLYMERASE; ENVELOPE; IDENTIFICATION; SEQUENCE; GENOME; EXPRESSION; PREDICTION; COMPONENT; CLEAVAGE AB A short sequence, located between the A14L and A15L open reading frames (ORFs) of vaccinia virus, was predicted to encode a hydrophobic protein of 53 amino acids that is conserved in orthopoxviruses, leporipoxviruses, yatapoxiruses, and molluscipoxviruses, We constructed a recombinant vaccinia virus with a 10-codon epitope tag appended to the C terminus of the A14.5L ORF, Synthesis of the tagged protein occurred at late times and was blocked by an inhibitor of DNA replication, consistent with regulation by a predicted late promoter just upstream of the A14.5L ORF, Hydrophobicity of the protein was demonstrated by extraction into the detergent phase of Triton X-114. The protein was associated with purified vaccinia virus particles and with membranes of immature and mature virions that were visualized by electron microscopy of infected cells. Efficient release of the protein from purified virions occurred after treatment with a nonionic detergent and reducing agent. A mutant virus, in which the A14.5L ORF was largely deleted, produced normal-size plaques in several cell lines, and the yields of infectious intra- and extracellular viruses were similar to those of the parent. In contrast, with a mouse model, mutant viruses with the A14.5L ORF largely deleted were attenuated relative to that of the parental virus or a mutant virus with a restored A14.5L gene. 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 31 TC 38 Z9 39 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 MAY PY 2000 VL 74 IS 9 BP 4085 EP 4092 DI 10.1128/JVI.74.9.4085-4092.2000 PG 8 WC Virology SC Virology GA 302KV UT WOS:000086365000017 PM 10756020 ER PT J AU Stittelaar, KJ Wyatt, LS de Swart, RL Vos, HW Groen, J van Amerongen, G van Binnendijk, RS Rozenblatt, S Moss, B Osterhaus, ADME AF Stittelaar, KJ Wyatt, LS de Swart, RL Vos, HW Groen, J van Amerongen, G van Binnendijk, RS Rozenblatt, S Moss, B Osterhaus, ADME TI Protective immunity in macaques vaccinated with a modified vaccinia virus Ankara-based measles virus vaccine in the presence of passively acquired antibodies SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL REPLICATION; RECOMBINANT; GENES; EXPRESSION; INDUCTION; INFECTION; PROTEIN AB Recombinant modified vaccinia virus Ankara (MVA), encoding the measles virus (MV) fusion (F) and hemagglutinin (H) (MVA-FH) glycoproteins, was evaluated in an MV vaccination-challenge model with macaques, Animals were vaccinated twice in the absence or presence of passively transferred MV-neutralizing macaque antibodies and challenged 1 year later intratracheally with wild-type MV. After the second vaccination with MVA-FH, all the animals developed MV-neutralizing antibodies and MV-specific T-cell responses. Although MVA-FH was slightly less effective in inducing MV-neutralizing antibodies in the absence of passively transferred antibodies than the currently used live attenuated vaccine, it proved to be more effective in the presence of such antibodies. All vaccinated animals were effectively protected from the challenge infection. These data suggest that MVA-FH should be further tested as an alternative to the current vaccine for infants with maternally acquired MV-neutralizing antibodies and for adults with waning vaccine-induced immunity. C1 Erasmus Univ, Inst Virol, NL-3000 DR Rotterdam, Netherlands. Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Osterhaus, ADME (reprint author), Erasmus Univ, Inst Virol, POB 1738, NL-3000 DR Rotterdam, Netherlands. RI De Swart, Rik/E-6508-2011 OI De Swart, Rik/0000-0003-3599-8969 FU NIAID NIH HHS [AI-93-06, AI-35144] NR 28 TC 91 Z9 96 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 MAY PY 2000 VL 74 IS 9 BP 4236 EP 4243 DI 10.1128/JVI.74.9.4236-4243.2000 PG 8 WC Virology SC Virology GA 302KV UT WOS:000086365000034 PM 10756037 ER PT J AU Alexander, L Weiskopf, E Greenough, TC Gaddis, NC Auerbach, MR Malim, MH O'Brien, SJ Walker, BD Sullivan, JL Desrosiers, RC AF Alexander, L Weiskopf, E Greenough, TC Gaddis, NC Auerbach, MR Malim, MH O'Brien, SJ Walker, BD Sullivan, JL Desrosiers, RC TI Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection SO JOURNAL OF VIROLOGY LA English DT Article ID LIMITING DILUTION ANALYSIS; CYTOTOXIC LYMPHOCYTES-T; LONG-TERM SURVIVOR; HIV-1 INFECTION; DISEASE PROGRESSION; REVERSE-TRANSCRIPTASE; GENETIC RESTRICTION; VIRAL REPLICATION; MOLECULAR CLONE; RHESUS-MONKEYS AB Factors accounting for long-term nonprogression may include infection with an attenuated strain of human immunodeficiency virus type 1 (HIV-1), genetic polymorphisms in the host, and virus-specific immune responses. In this study, we examined eight individuals with nonprogressing or slowly progressing HIV-1 infection, none of whom were homozygous for host-specific polymorphisms (CCR5-Delta 32, CCR2-64I, and SDF-1-3'A) which have been associated with slower disease progression. HTV-1 was recovered from seven of the eight, and recovered virus was used for sequencing the full-length HTV-1 genome; full-length HIV-1 genome sequences from the eighth were determined following amplification of viral sequences directly from peripheral blood mononuclear cells (PBMC), Longitudinal studies of one individual with HIV-1 that consistently exhibited a slow/low growth phenotype revealed a single amino acid deletion in a conserved region of the gp41 transmembrane protein that was not seen in any of 131 envelope sequences in the Los Alamos HIV-1 sequence database. Genetic analysis also revealed that five of the eight individuals harbored HIV-1 with unusual 1- or 2-amino-acid deletions in the Gag sequence compared to subgroup B Gag consensus sequences. These deletions in Gag have either never been observed previously or are extremely rare in the database. Three individuals had deletions in Nef, and one had a 4-amino-acid insertion in Vpu, The unusual polymorphisms in Gag, Env, and Nef described here were also found in stored PBMC samples taken 3 to 11 years prior to, or in one case 4 years subsequent to, the time of sampling for the original sequencing. In all, seven of the eight individuals exhibited one or more unusual polymorphisms; a total of 13 unusual polymorphisms were documented in these seven individuals. These polymorphisms may have been present from the time of initial infection or may have appeared in response to immune surveillance or other selective pressures. Our results indicate that unusual, difficult-to-revert polymorphisms in HIV-1 can be found associated with slow progression or nonprogression in a majority of such cases. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. Univ Massachusetts, Sch Med, Dept Pediat, Program Mol Med, Worcester, MA 01605 USA. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. NCI, Lab Genet Divers, Frederick, MD 21702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Boston, MA 02114 USA. RP Desrosiers, RC (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, 1 Pine Hill Dr, Southborough, MA 01772 USA. OI Malim, Michael/0000-0002-7699-2064 FU NCRR NIH HHS [K26 RR000168, P51 RR000168]; NIAID NIH HHS [AI25328, AI28568, AI38559, R01 AI025328, R01 AI028568, R37 AI025328, R37 AI028568] NR 59 TC 120 Z9 120 U1 0 U2 4 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 MAY PY 2000 VL 74 IS 9 BP 4361 EP 4376 DI 10.1128/JVI.74.9.4361-4376.2000 PG 16 WC Virology SC Virology GA 302KV UT WOS:000086365000048 PM 10756051 ER PT J AU Chabot, DJ Chen, H Dimitrov, DS Broder, CC AF Chabot, DJ Chen, H Dimitrov, DS Broder, CC TI N-linked glycosylation of CXCR4 masks coreceptor function for CCR5-dependent human immunodeficiency virus type 1 isolates SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTIOUS MOLECULAR CLONE; T-CELL LINES; HIV-1 ENTRY; CHEMOKINE RECEPTORS; VACCINIA VIRUS; MONONUCLEAR PHAGOCYTES; EXTRACELLULAR DOMAINS; ENVELOPE GLYCOPROTEIN; DISEASE PROGRESSION; MONOCLONAL-ANTIBODY AB chemokine receptors CXCR4 and CCR5 are the principal coreceptors for infection of X4 and R5 human immunodeficiency virus type 1 (HIV-1) isolates, respectively. Here we report on the unexpected observation that the removal of the N-linked glycosylation sites in CXCR4 potentially allows the protein to serve as a universal coreceptor for both X4 and R5 laboratory-adapted and primary HIV-1 strains. We hypothesize that this alteration unmasks existing common extracellular structures reflecting a conserved three-dimensional similarity of important elements of CXCR4 and CCR5 that are involved in HIV envelope glycoprotein (Env) interaction. These results may have far-reaching implications for the differential recognition of cell type-dependent glycosylated CXCR4 by HIV-1 isolates and their evolution in vivo. They also suggest a possible explanation for the various observations of restricted virus entry in some cell types and further our understanding of the framework of elements that represent the Env-coreceptor contact sites. C1 Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. RP Broder, CC (reprint author), Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. FU NIAID NIH HHS [R01 AI043885, R01AI43885, R29AI414110] NR 90 TC 82 Z9 84 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 MAY PY 2000 VL 74 IS 9 BP 4404 EP 4413 DI 10.1128/JVI.74.9.4404-4413.2000 PG 10 WC Virology SC Virology GA 302KV UT WOS:000086365000052 PM 10756055 ER PT J AU Center, RJ Earl, PL Lebowitz, J Schuck, P Moss, B AF Center, RJ Earl, PL Lebowitz, J Schuck, P Moss, B TI The human immunodeficiency virus type 1 gp120 V2 domain mediates gp41-independent intersubunit contacts SO JOURNAL OF VIROLOGY LA English DT Article ID GP41 TRANSMEMBRANE GLYCOPROTEIN; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; OLIGOMERIC STRUCTURE; RECEPTOR-BINDING; EPITOPE EXPOSURE; DISULFIDE BONDS; HIV-1 GP41; NEUTRALIZATION; COMPLEX AB The envelope protein of human immunodeficiency virus type 1 HIV-1 undergoes proteolytic cleavage in the Golgi complex to produce subunits designated gp120 and gp41, which remain noncovalently associated. While gp41 has a well-characterized oligomeric structure, the maintenance of gp41-independent gp120 intersubunit contacts remains a contentious issue. Using recombinant vaccinia virus to achieve high-level expression of gp120 in mammalian cells combined with gel filtration analysis, we were able to isolate a discrete oligomeric form of gp120. Oligomerization of gp120 occurred intracellularly between 30 and 120 min after synthesis. Analysis by sedimentation equilibrium unequivocally identified the oligomeric species as a dimer. In order to identify the domains involved in the intersubunit contact, we expressed a series of gp120 proteins lacking various domains and assessed the effects of mutation on oligomeric structure. Deletion of the V1 or V3 loops had little effect on the relative amounts of monomer and dimer in comparison to wild-type gp120. in contrast, deletion of either all or part of the V2 loop drastically reduced dimer formation, indicating that this domain is required for intersubunit contact formation. Consistent with this, the V2 loop of the dimer was less accessible than that of the monomer to a specific monoclonal antibody, Previous studies have shown that while the V2 loop is not an absolute requirement for viral entry, the absence of this domain reduces viral resistance to neutralization by monoclonal antibodies or sera. We propose that the quaternary structure of gp120 may contribute to resistance to neutralization by limiting the exposure of conserved epitopes. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIH, Mol Interact Resource Bioengn & Phys Sci Program, Off Res Serv, Bethesda, MD 20892 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Rm 229,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Schuck, Peter/0000-0002-8859-6966 NR 53 TC 48 Z9 48 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2000 VL 74 IS 10 BP 4448 EP 4455 DI 10.1128/JVI.74.10.4448-4455.2000 PG 8 WC Virology SC Virology GA 306ZV UT WOS:000086629400002 PM 10775580 ER PT J AU Pinto, LA Blazevic, V Patterson, BK Mac Trubey, C Dolan, MJ Shearer, GM AF Pinto, LA Blazevic, V Patterson, BK Mac Trubey, C Dolan, MJ Shearer, GM TI Inhibition of human immunodeficiency virus type 1 replication prior to reverse transcription by influenza virus stimulation SO JOURNAL OF VIROLOGY LA English DT Article ID CD8(+) T-CELLS; ALPHA-INTERFERON; HIV-1-INFECTED INDIVIDUALS; INFECTED INDIVIDUALS; DISEASE PROGRESSION; PERIPHERAL-BLOOD; HIV-INFECTION; VACCINATION; MIP-1-BETA; RANTES AB It is now recognized that, in addition to drug-mediated therapies against human immunodeficiency virus type 1 (HIV-1), the immune system can exert antiviral effects via CD8(+) T-cell-generated anti-HIV factors. This study demonstrates that (i) supernatants from peripheral blood mononuclear cells (PBMC) stimulated with influenza A virus inhibit replication of CCR5- and CXCR4-tropic HIV-1 isolates prior to reverse transcription; (ii) the HIV-suppressive supernatants can be generated by CD4- or CD8-depleted PBMC; (iii) this anti-HIV activity is partially due to alpha interferon (IFN-alpha), but not to IFN-gamma, IFN-beta, the beta-chemokines MIP-1 alpha, MIP-1 beta, and RANTES, or interleukin-16; (iv) the anti-HIV activity is generated equally well by PBMC cultured with either infectious or UV-inactivated influenza A virus; and (v) the antiviral activity can be generated by influenza A-stimulated PBMC from HN-infected individuals. These findings represent a novel mechanism for inhibition of HIV-1 replication that differs from the previously described CD8 anti-HIV factors (MIP-la, MIP-1 beta, RANTES, and CD8 antiviral factor). C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, FCRDC, SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. Northwestern Univ, Sch Med, Lab Viral Pathogenesis, Chicago, IL 60611 USA. Wilford Hall USAF Med Ctr, Lackland AFB, TX 78236 USA. RP Shearer, GM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Rm 4B36, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 41 TC 32 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2000 VL 74 IS 10 BP 4505 EP 4511 DI 10.1128/JVI.74.10.4505-4511.2000 PG 7 WC Virology SC Virology GA 306ZV UT WOS:000086629400008 PM 10775586 ER PT J AU Dey, B Lerner, DL Lusso, P Boyd, MR Elder, JH Berger, EA AF Dey, B Lerner, DL Lusso, P Boyd, MR Elder, JH Berger, EA TI Multiple antiviral activities of cyanovirin-N: Blocking of human immunodeficiency virus type 1 gp120 interaction with CD4 and coreceptor and inhibition of diverse enveloped viruses SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-INACTIVATING PROTEIN; BACTERIOPHAGE-T7 RNA-POLYMERASE; RECOMBINANT VACCINIA VIRUS; T-CELL LINES; PRIMARY MACROPHAGES; FUSION; FELINE; GLYCOPROTEIN; RECEPTOR; EXPRESSION AB Cyanovirin-N (CV-N) is a cyanobacterial protein with potent neutralizing activity against human immuno-deficiency virus (HIV). CV-N has been shown to bind HIV type 1 (HIV-1) gp120 with high affinity; moreover, it blocks the envelope glycoprotein-mediated membrane fusion reaction associated with HIV-1 entry. However, the inhibitory mechanism(s) remains unclear. In this study, we show that CV-N blocked binding of gp120 to cell-associated CD4. Consistent with this, pretreatment of gp120 with CV-N inhibited soluble CD4 (sCD4)-dependent binding of gp120 to cell-associated CCR5. To investigate possible effects of CV-N at post-CD4 binding steps, we used an assay that measures sCD4 activation of the HIV-1 envelope glycoprotein for fusion with CCR5-expressing cells, CV-N displayed equivalently potent inhibitory effects when added before or after sCD4 activation, suggesting that (CV-N also has blocking action at the level of gp120 interaction with coreceptor, This effect was shown not to be due to CV-N-induced coreceptor down-modulation after the CD4 binding step. The multiple activities against the HIV-1 envelope glycoprotein prompted us to examine other enveloped viruses. CV-N potently blocked infection by feline immunodeficiency virus, which utilizes the chemokine receptor CXCR4 as an entry receptor but is CD 1 independent. CV-N also inhibited fusion and/or infection by human herpesvirus 6 and measles virus but not by vaccinia virus, Thus, CV-N has broad-spectrum antiviral activity, both for multiple steps in the HIV entry mechanism and for diverse enveloped viruses. This broad specificity has implications for potential clinical utility of CV-N. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. San Raffaele Sci Inst, Dept Biol & Technol Res, Unit Human Virol, I-20132 Milan, Italy. NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diagno, Frederick, MD USA. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 237, Bethesda, MD 20892 USA. NR 34 TC 129 Z9 139 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2000 VL 74 IS 10 BP 4562 EP 4569 DI 10.1128/JVI.74.10.4562-4569.2000 PG 8 WC Virology SC Virology GA 306ZV UT WOS:000086629400014 PM 10775592 ER PT J AU Sei, S Yang, QE O'Neill, D Yoshimura, K Nagashima, K Mitsuya, H AF Sei, S Yang, QE O'Neill, D Yoshimura, K Nagashima, K Mitsuya, H TI Identification of a key target sequence to block human immunodeficiency virus type 1 replication within the gag-pol transframe domain SO JOURNAL OF VIROLOGY LA English DT Review ID PEPTIDE NUCLEIC-ACIDS; POLYMERASE CHAIN-REACTION; HIV PROTEASE INHIBITORS; ACTIVE ANTIRETROVIRAL THERAPY; CHRONICALLY INFECTED-CELLS; SMALL-MOLECULE INHIBITOR; BLOOD MONONUCLEAR-CELLS; MAMMARY-TUMOR VIRUS; AUG INITIATOR CODON; CD4(+) T-CELLS AB Although the full sequence of the human immunodeficiency virus type 1 (HIV-1) genome has been known for more than a decade, effective genetic antivirals have Set to be developed. Here we show that, of 22 regions examined, one highly conserved sequence (ACTCTTTGGCAACGA) near the 3' end of the HIV-1 gag-pol transframe region, encoding viral protease residues 4 to 8 and a C-terminal Vpr-binding motif of p6(Gag) protein in two different reading frames, can be successfully targeted by an antisense peptide nucleic acid oligomer named PNA(PR2). A disrupted translation of gag-pol mRNA induced at the PNA(PR2)-annealing site resulted in a decreased synthesis of pr160(Gag-Pol) polyprotein, hence the viral protease, a predominant expression of pr55(Gag) devoid of a fully functional p6(Gag) protein, and the excessive intracellular cleavage of Gag precursor proteins, hindering the processes of virion assembly. Treatment with PNA(PR2) abolished virion production by up to 99% in chronically HIV-l-infected H9 cells and in peripheral blood mononuclear cells infected with clinical HIV-1 isolates with the multidrug-resistant phenotype. This particular segment of the gag-pol transframe gene appears to offer a distinctive advantage over other regions in invading viral structural genes and restraining HIV-1 replication in infected cells and may potentially be exploited as a novel antiviral genetic target. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, HIV Clin Interface Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Lab Cell & Mol Struct, Frederick, MD 21702 USA. NCI, Expt Retrovirol Sect, Bethesda, MD 20892 USA. Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 860, Japan. RP Sei, S (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, HIV Clin Interface Lab, Bldg 322,Rm 27B,POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 154 TC 37 Z9 39 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2000 VL 74 IS 10 BP 4621 EP 4633 DI 10.1128/JVI.74.10.4621-4633.2000 PG 13 WC Virology SC Virology GA 306ZV UT WOS:000086629400020 PM 10775598 ER PT J AU Doh-Ura, K Iwaki, T Caughey, B AF Doh-Ura, K Iwaki, T Caughey, B TI Lysosomotropic agents and cysteine protease inhibitors inhibit scrapie-associated prion protein accumulation SO JOURNAL OF VIROLOGY LA English DT Article ID CULTURED-CELLS; CONGO RED; INCUBATION PERIOD; PRP ACCUMULATION; DEXTRAN SULFATE; MOUSE SCRAPIE; INFECTION; PROLONGATION; REPLICATION; PATHOLOGY AB We report that lysosomotropic agents and cysteine protease inhibitors inhibited protease resistant prion protein accumulation in scrapie-infected neuroblastoma cells. The inhibition occurred without either apparent effects on normal prion protein biosynthesis or turnover or direct interactions with prion protein molecules. The findings introduce two new classes of inhibitors of the formation of protease-resistant prion protein. C1 Kyushu Univ, Dept Neuropathol, Inst Neurol, Grad Sch Med Sci,Higashi Ku, Fukuoka 8128582, Japan. NIAID, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Doh-Ura, K (reprint author), Kyushu Univ, Dept Neuropathol, Inst Neurol, Grad Sch Med Sci,Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. RI U-ID, Kyushu/C-5291-2016 NR 33 TC 222 Z9 236 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2000 VL 74 IS 10 BP 4894 EP 4897 DI 10.1128/JVI.74.10.4894-4897.2000 PG 4 WC Virology SC Virology GA 306ZV UT WOS:000086629400053 PM 10775631 ER PT J AU Adler, SG Feld, S Striker, L Striker, G LaPage, J Esposito, C Aboulhosn, J Barba, L Cha, DR Nast, CC AF Adler, SG Feld, S Striker, L Striker, G LaPage, J Esposito, C Aboulhosn, J Barba, L Cha, DR Nast, CC TI Glomerular type IV collagen in patients with diabetic nephropathy with and without additional glomerular disease SO KIDNEY INTERNATIONAL LA English DT Article DE diabetic nephropathy; type IV collagen; glomerulonephritis; collagen alpha 2(IV) mRNA ID EXTRACELLULAR-MATRIX COMPONENTS; NONDIABETIC RENAL-DISEASE; BASEMENT-MEMBRANE; MESSENGER-RNA; PROGRESSIVE GLOMERULOSCLEROSIS; DIFFERENTIAL EXPRESSION; SUBTOTAL NEPHRECTOMY; MOLECULAR ANALYSIS; GENE-EXPRESSION; MESANGIAL CELLS AB Background. Type IV collagen is a constituent of mesangial matrix and is increased in amount in many forms of glomerular injury. Methods. We performed renal biopsies in patients who (1) were donating a kidney to a relative (LRD, N = 6), (2) had diabetic glomerulopathy with or without nephrosclerosis (DM, N = 6), or (3) had diabetic glomerulopathy with a superimposed glomerular lesion (DM+, N = 5). Glomerular collagen alpha 2(IV) and control glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNAs were measured, and the former correlated with clinical and morphological data to assess its usefulness in reflecting glomerular injury. Results. Collagen alpha 2(IV) mRNA levels were lowest in LRD (2.9 +/- 0.6 attomol/glomerulus), higher in DM (5.9 +/- 1.6, P = 0.05), and highest in DM+ (12.7 +/- 2.8 attm/glomerulus, P < 0.05 vs. LRD and vs. DM). Control GAPDH mRNA levels were not significantly different (P > 0.05). Levels of proteinuria, serum creatinine, and glomerular size did not correlate with collagen alpha 2(IV) mRNA levels. The fractional mesangial area and the fractional mesangial area occupied by type IV collagen were higher in both diabetic groups than in LRD (P < 10(-6)), but the intensity of type IV collagen staining in the diabetic patients was significantly less than that seen in the LRD (P < 0.01). In DM+ patients, extramesangial type IV collagen was present. Fractional mesangial area and glomerular collagen alpha 2(IV) mRNA levels correlated (r = 0.45, P < 0.05). Conclusion. These data are consistent with a view of diabetic nephropathy as a lesion of increased alpha 2 type IV collagen transcription, increased total amount of collagen present, but decreased mesangial density relative to other matrix molecules. These data further demonstrate that glomerular injury superimposed on diabetic nephropathy contributes to additional structural damage by inducing increased synthesis of type IV collagen at extramesangial sites. C1 Harbor UCLA Med Ctr, Harbor UCLA Res & Educ Inst, Div Nephrol & Hypertens, Torrance, CA 90509 USA. NIH, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Adler, SG (reprint author), Harbor UCLA Med Ctr, Harbor UCLA Res & Educ Inst, Div Nephrol & Hypertens, 1000 W Carson St,Box 406, Torrance, CA 90509 USA. FU NCRR NIH HHS [MO1 RR00425] NR 54 TC 32 Z9 33 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 MAY PY 2000 VL 57 IS 5 BP 2084 EP 2092 DI 10.1046/j.1523-1755.2000.00058.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 310WL UT WOS:000086852000029 PM 10792628 ER PT J AU Potkay, S AF Potkay, S TI OLAW's compliance oversight: Noncompliance with PHS policy SO LAB ANIMAL LA English DT Article C1 NIH, Off Lab Anim Welf, Compliance Oversight Div, Bethesda, MD USA. RP Potkay, S (reprint author), NIH, Off Lab Anim Welf, Compliance Oversight Div, 6705 Rockledge Dr,Rockledge 1,Suite 1050,MSC 7982, Bethesda, MD USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD MAY PY 2000 VL 29 IS 5 BP 32 EP 37 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 310HF UT WOS:000086819900005 ER PT J AU Hampshire, V Davis, J McNickle, C AF Hampshire, V Davis, J McNickle, C TI Red carpet rodent care: Making the most of dollars and sense in the animal facility SO LAB ANIMAL LA English DT Article AB Cutting-edge biomedical research programs have entered an era in which phenotypic characterizations for genetically altered rodents can facilitate appropriate care. The veterinary care requirements necessary to support such animal models can include the procedures already adapted as standard practice in companion animal hospitals, and can decrease data variability while increasing survival rates. C1 Adv Vet Applicat, Bethesda, MD 20817 USA. NIH, Anim Care Sect, Div Intramural Res, Bethesda, MD 20892 USA. RP Hampshire, V (reprint author), Adv Vet Applicat, 7307 Nevis Rd, Bethesda, MD 20817 USA. NR 8 TC 13 Z9 13 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD MAY PY 2000 VL 29 IS 5 BP 40 EP 46 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 310HF UT WOS:000086819900006 ER PT J AU Kovalchuk, AL Mushinski, EB Janz, S AF Kovalchuk, AL Mushinski, EB Janz, S TI Clonal diversification of primary BALB/c plasmacytomas harboring T(12;15) chromosomal translocations SO LEUKEMIA LA English DT Article DE illegitimate genetic recombination; Igh/c-myc junctions; clonal evolution; abnormal isotype switching ID IMMUNOGLOBULIN HEAVY-CHAIN; ENDOGENOUS IGH LOCUS; C-MYC RECOMBINATIONS; SWITCH REGION; GENOMIC INSTABILITY; MOUSE PLASMACYTOMAS; BREAKSITE REGIONS; GENE-EXPRESSION; HYBRIDOMA CELLS; B-CELLS AB DNA sequence analysis of PCR amplified lgh/c-myc junction fragments of T(12;15) chromosome translocations and immunohistochemical determination of immunoglobulin isotype production were employed to study the clonal diversification of neoplastic translocated plasma cells that resided in peritoneal inflammatory granulomas of BALB/c mice harboring primary plasmacytomas. The diversity of plasma cells was found to take two major forms when the fine structure of the T(12;15) translocation was used as the clonotypic marker. First, mosaics of clones containing translocations that were apparently unrelated to each other were detected in nine out of 17 (53%) mice. Second, subclones derived from common T(12;15)(+) progenitors by either secondary deletions in translocation breakpoint regions or aberrant isotype switching near translocation breaksites were found in five of 17 (29.5%) mice. When Ig expression was utilized as the clonotypic marker, clonal mosaics were shown to occur in all mice. This was demonstrated by the finding that the prevalent IgA- or IgG-producing plasmacytoma clone was invariably accompanied by smaller clones of IgG- or IgA-expressing neoplastic plasma cells, respectively. These results provided new insights into the clonal diversification at the terminal stage of plasmacytomagenesis. In addition, they suggested that BALB/c plasmacytomas may be uniquely useful for studying clonal diversity during B cell oncogenesis, since clonal evolution can be evaluated in a pool of tumor and tumor precursor cells that is clearly defined by the T(12;15) chromosomal translocation and the production of monoclonal immunoglobulin. C1 NCI, Genet Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Janz, S (reprint author), NCI, Genet Lab, Div Basic Sci, 37 Ctr Dr, Bethesda, MD 20892 USA. NR 38 TC 15 Z9 15 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2000 VL 14 IS 5 BP 909 EP 921 DI 10.1038/sj.leu.2401676 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA 310HA UT WOS:000086819400022 PM 10803525 ER PT J AU London, SJ Smart, J Daly, AK AF London, SJ Smart, J Daly, AK TI Lung cancer risk in relation to genetic polymorphisms of microsomal epoxide hydrolase among African-Americans and Caucasians in Los Angeles County SO LUNG CANCER LA English DT Article DE ephx; MEH; susceptibility; variant introduction ID S-TRANSFERASE M1; SUSCEPTIBILITY; ASSOCIATION; EXPRESSION AB Microsomal epoxide hydrolase participates in the metabolism of benzo[a]pyrene, an important carcinogen in tobacco smoke. Two relatively common polymorphisms of the microsomal epoxide hydrolase gene that influence enzyme activity have been described. An association between genetic variation in microsomal epoxide hydrolase and lung cancel. risk has been reported in one of two studies of Caucasians. We examined the relation between these two polymorphisms and lung cancer risk among 337 incident cases and 700 population controls of African-American and Caucasian ethnicity enrolled in a case-control study in Los Angeles County. African-Americans, homozygous for the exon 3 variant allele conferring reduced activity, were at decreased risk of lung cancer (odds ratio (OR) = 0.08, 95% CI 0.01-0.62). When data from both the exon 3 and exon 4 polymorphisms were combined into indices of predicted microsomal epoxide hydrolase activity, a decreased risk was seen among African-American subjects with very low predicted activity OR = 0.10 (95%, CI 0.01-0.83). No comparable association was seen among Caucasians. Although the three published results for Caucasians are somewhat variable, the association among African-Americans in these data provides some support for the hypothesis that genetically reduced microsomal epoxide hydrolase activity may be protective against lung cancer. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ Newcastle Upon Tyne, Sch Med, Dept Pharmacol Sci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. RP London, SJ (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. RI Daly, Ann/H-3144-2011 OI London, Stephanie/0000-0003-4911-5290; Daly, Ann/0000-0002-7321-0629 FU NCI NIH HHS [N01-CN-25403] NR 15 TC 54 Z9 55 U1 0 U2 18 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 MAY PY 2000 VL 28 IS 2 BP 147 EP 155 DI 10.1016/S0169-5002(99)00130-0 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 312RV UT WOS:000086957500007 PM 10717332 ER PT J AU Corn, M AF Corn, M TI The granting game: Part I, a guide to NLM funding for informatics research SO M D COMPUTING LA English DT Article C1 Natl Lib Med, Bethesda, MD USA. RP Corn, M (reprint author), Natl Lib Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-6811 J9 M D COMPUT JI M D Comput. PD MAY-JUN PY 2000 VL 17 IS 3 BP 29 EP 32 PG 4 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 316ZE UT WOS:000087197700014 PM 10842980 ER PT J AU Aletras, AH Tsoref, L Navon, G AF Aletras, AH Tsoref, L Navon, G TI In vivo H-1 double quantum filtered MRI of the human wrist and ankle SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE H-1; proton; DQF MRI; human; wrist; ankle; tendons ID NMR-SPECTROSCOPY; TISSUES; TENDON; WATER AB Proton double quantum filtered (DQF) NMR imaging was applied in vivo to the human wrist and ankle with a clinical 1.5 T MR scanner. Water molecules having anisotropic motion were detected from tendons and ligaments. Images of Achilles tendon were obtained for a voxel size of 1.25 x 1.25 x 20 mm with three values of TR = 1.0, 0.5, and 0.2 sec, resulting in total acquisitions time of 17, 8.5, and 3.4 mins, respectively. Some degradation of the signal-to-noise ratio was observed at the shortest TR value and the contrast was significantly reduced due to SQ coherence leakage. The in vivo DQF images showed structure within the tendon that is otherwise not visible by conventional gradient-recalled echo (GRE) methods. Magn Reson Med 43:640-644, 2000. Published 2000 Wiley-Liss, Inc. C1 Tel Aviv Univ, Sch Chem, IL-69978 Tel Aviv, Israel. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sch Phys, IL-69978 Tel Aviv, Israel. RP Navon, G (reprint author), Tel Aviv Univ, Sch Chem, IL-69978 Tel Aviv, Israel. OI Aletras, Anthony/0000-0002-3786-3817 NR 13 TC 6 Z9 6 U1 1 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 MAY PY 2000 VL 43 IS 5 BP 640 EP 644 DI 10.1002/(SICI)1522-2594(200005)43:5<640::AID-MRM4>3.0.CO;2-W PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 309VQ UT WOS:000086790300004 PM 10800027 ER PT J AU Matsuo-Takasaki, M Lim, JH Beanan, MJ Sato, SM Sargent, TD AF Matsuo-Takasaki, M Lim, JH Beanan, MJ Sato, SM Sargent, TD TI Cloning and expression of a novel zinc finger gene, Fez, transcribed in the forebrain of Xenopus and mouse embryos SO MECHANISMS OF DEVELOPMENT LA English DT Article DE forebrain; neural induction; neurogenesis; zinc-finger genes; Xenopus laevis; mouse embryos; neural genes ID NEURAL INDUCTION; LAEVIS; PLATE AB We have identified and cloned a novel zinc finger gene, Fez (forebrain embryonic zinc-finger), as a potential downstream determinant of anterior neural plate formation in Xenopus. Fez was isolated as one of several neural-specific genes that was induced by the neuralizing factor, noggin (Smith and Harland, 1992. Cell 70, 829-840), in uncommitted ectoderm. Fez has an open reading frame comprising 466 amino acids, and contains six C2H2 type zinc finger domains, which are highly conserved among Drosophila, zebrafish, mouse, and human. In Xenopus, the expression of Fez begins at stage 12 in the rostral end of the neural plate, and by stage 45, it is localized to several telencephalic regions, including the olfactory bulbs, nervus terminalis, and ventricular zone. The mouse homologue of Fez is similarly expressed in the mouse forebrain by embryonic day 11. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Sargent, TD (reprint author), NICHHD, Mol Genet Lab, NIH, Bldg 6B,Room 412,MSC 2790,6 Ctr Dr, Bethesda, MD 20892 USA. NR 12 TC 38 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD MAY PY 2000 VL 93 IS 1-2 BP 201 EP 204 DI 10.1016/S0925-4773(00)00264-1 PG 4 WC Developmental Biology SC Developmental Biology GA 314HL UT WOS:000087050300023 PM 10781957 ER PT J AU Santos, AD Padlan, EA AF Santos, AD Padlan, EA TI Does mRNA translation starting from an alternative initiation site contribute to the pathology of Huntington's disease? SO MEDICAL HYPOTHESES LA English DT Article ID MUTATIONS AB Huntington's disease is associated with an expanded and unstable trinucleotide repeat (GAG)(n). Various possibilities have been suggested to explain the significance of poly-(CAG) length in HD, including changes in the structure of the product (huntingtin) which result in the protein acquiring deleterious properties. We have looked at the nucleotide sequence coding for huntingtin and find that another possibility may exist for the correlation between the occurrence of HD and poly-GAG length. We have noted an alternative reading frame that includes the trinucleotide repeat, now read as (GGA)(n). Upon close examination of this alternative gene product, we observe features that suggest it can likewise have deleterious properties. (C) 2000 Harcourt Publishers Ltd. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Philippines, Coll Sci, Quezon 1101, Philippines. RP Padlan, EA (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD MAY PY 2000 VL 54 IS 5 BP 689 EP 690 DI 10.1054/mehy.1998.0815 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 322AE UT WOS:000087487100002 PM 10859666 ER PT J AU Winkelstein, JA Marino, MC Johnston, RB Boyle, J Curnutte, J Gallin, JI Malech, HL Holland, SM Ochs, H Quie, P Buckley, RH Foster, CB Chanock, SJ Dickler, H AF Winkelstein, JA Marino, MC Johnston, RB Boyle, J Curnutte, J Gallin, JI Malech, HL Holland, SM Ochs, H Quie, P Buckley, RH Foster, CB Chanock, SJ Dickler, H TI Chronic granulomatous disease - Report on a national registry of 368 patients SO MEDICINE LA English DT Article ID PRIMARY IMMUNODEFICIENCY DISORDERS; LUPUS-ERYTHEMATOSUS; CHILDHOOD; CHILDREN; LESIONS; MANAGEMENT; MANIFESTATIONS; COLITIS; SWEDEN C1 Immune Deficiency Fdn, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Yale Univ, Sch Med, New Haven, CT USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Seattle, WA USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Duke Univ, Sch Med, Durham, NC USA. RP Winkelstein, JA (reprint author), Johns Hopkins Hosp, Dept Pediat, CMSC 1102,600 N Wolfe St, Baltimore, MD 21287 USA. FU NIAID NIH HHS [AI-25153] NR 53 TC 761 Z9 806 U1 1 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAY PY 2000 VL 79 IS 3 BP 155 EP 169 DI 10.1097/00005792-200005000-00003 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 316GM UT WOS:000087159300003 PM 10844935 ER PT J AU Segal, BH Leto, TL Gallin, JI Malech, HL Holland, SM AF Segal, BH Leto, TL Gallin, JI Malech, HL Holland, SM TI Genetic, biochemical, and clinical features of chronic granulomatous disease SO MEDICINE LA English DT Review ID RESPIRATORY-BURST OXIDASE; PHAGOCYTE NADPH OXIDASE; CELL-FREE SYSTEM; DISCOID LUPUS-ERYTHEMATOSUS; PROTEIN-KINASE-C; ADENINE-DINUCLEOTIDE PHOSPHATE; NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; RECOMBINANT INTERFERON-GAMMA; BONE-MARROW TRANSPLANTATION C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Host Def Lab, NIH, 10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. NR 441 TC 511 Z9 540 U1 1 U2 27 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAY PY 2000 VL 79 IS 3 BP 170 EP 200 DI 10.1097/00005792-200005000-00004 PG 31 WC Medicine, General & Internal SC General & Internal Medicine GA 316GM UT WOS:000087159300004 PM 10844936 ER PT J AU Slayden, RA Barry, CE AF Slayden, RA Barry, CE TI The genetics and biochemistry of isoniazid resistance in Mycobacterium tuberculosis SO MICROBES AND INFECTION LA English DT Review DE isoniazid; KatG; catalase; tuberculosis; pro-drug ID CATALASE-PEROXIDASE GENE; SITE-DIRECTED MUTAGENESIS; OXIDATIVE-STRESS; KATG GENE; ENOYL REDUCTASE; DRUG-RESISTANCE; MYCOLIC ACIDS; ENZYMATIC CHARACTERIZATION; MOLECULAR MECHANISMS; REGULATORY GENE AB Although the primary targets of activated isoniazid (INH) are proteins involved in the biosynthesis of cell wall mycolic acids, clinical resistance is dominated by specific point mutations in katG. Mutations associated with target mutations contribute to, but still cannot completely explain, resistance ro INH. Despite the wealth of genetic information currently available, the molecular mechanism of cell death induced by INH remains elusive. (C) 2000 Editions scientifiques et medicales Elsevier SAS. C1 NIAID, TB Res Sect, Host Def Lab, NIH, Rockville, MD 20852 USA. RP Slayden, RA (reprint author), NIAID, TB Res Sect, Host Def Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. RI Barry, III, Clifton/H-3839-2012; Slayden, Richard/O-8626-2016 OI Slayden, Richard/0000-0001-6857-7277 FU Intramural NIH HHS [Z01 AI000783-11] NR 109 TC 137 Z9 150 U1 1 U2 14 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD MAY PY 2000 VL 2 IS 6 BP 659 EP 669 DI 10.1016/S1286-4579(00)00359-2 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 327LB UT WOS:000087794400011 PM 10884617 ER PT J AU Katoh, R Kawaoi, A Miyagi, E Suzuki, K Nakamura, Y Kakudo, K AF Katoh, R Kawaoi, A Miyagi, E Suzuki, K Nakamura, Y Kakudo, K TI Thyroid transcription factor-1 in normal, hyperplastic, and neoplastic follicular thyroid cells examined by immunohistochemistry and nonradioactive in situ hybridization SO MODERN PATHOLOGY LA English DT Article DE immunohistochemistry; in situ hybridization; reverse transcription-polymerase chain reaction; thyroid neoplasms; thyroid transcription factor-1 ID THYROTROPIN RECEPTOR GENE; FACTOR-I TTF-1; EXPRESSION; THYROGLOBULIN; PROMOTER; PROTEIN; AUTOREGULATION; HOMEODOMAIN; UPSTREAM; PAX-8 AB Thyroid transcription factor-1 (TTF-1) has been known to regulate the transcriptional activity of thyroid-specific genes. We examined the expression of TTF-1 in non-neoplastic and neoplastic thyroid tissues. By immunohistochemistry, the nuclei of normal and hyperplastic follicular cells strongly reacted with the antibody against TTF-1. Immunohistochemistry also revealed a distinctive nuclear positivity of TTF-1 in all 33 differentiated follicular cell tumors, including 15 follicular adenomas, 5 follicular carcinomas, and 13 papillary carcinomas. No immunoreactions were observed in three of four undifferentiated carcinomas, whereas an isolated and weak nuclear positivity was obtained in one, in normal and hyperplastic tissues, the distribution of TTF-1 was fairly related to that of thyroid-specific proteins thyroglobulin and thyroperoxidase. However, discrepancies in the distribution were observed in tumor tissues. By irt situ hybridization, the riboprobe hybridized distinctively with the cytoplasm of neoplastic cells as well as normal follicular cells. Papillary carcinoma cells expressed TTF-1 mRNA in all but two cases, and Its expression was also demonstrated ha one of four undifferentiated carcinomas. Reverse transcription-polymerase chain reaction confirmed the presence of TTF-1 mRNA in two human undifferentiated carcinoma cell lines, TTA-1 and TTA-2. in conclusion, the investigation of TTF-1 provides useful information on the functional activities and/or differentiation of thyroid tumors and may lead to an increase in our understanding of the biologic nature of thyroid tumors. C1 Yamanashi Med Univ, Dept Pathol, Sch Med, Tamaho, Yamanashi 40938, Japan. NIDDKD, Metab Dis Branch, Cell Regulat Sect, NIH, Bethesda, MD 20892 USA. Wakayama Med Coll, Dept Pathol, Wakayama 640, Japan. RP Katoh, R (reprint author), Yamanashi Med Univ, Dept Pathol, Sch Med, 1110 Shimokato, Tamaho, Yamanashi 40938, Japan. RI Nakamura, Yasushi/J-5143-2014 NR 25 TC 50 Z9 54 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 2000 VL 13 IS 5 BP 570 EP 576 DI 10.1038/modpathol.3880098 PG 7 WC Pathology SC Pathology GA 316KU UT WOS:000087166800014 PM 10824930 ER PT J AU Rathore, D McCutchan, TF AF Rathore, D McCutchan, TF TI Heparin can regulate the binding of Plasmodium falciparum circumsporozoite protein SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE heparin; binding; Plasmodium falciparum; circumsporozoite protein ID SULFATE PROTEOGLYCANS; REGION-II; SPOROZOITES; MEMBRANE; MOTIF C1 NIAID, Parasit Dis Lab, Growth & Dev Sect, NIH, Bethesda, MD 20892 USA. RP McCutchan, TF (reprint author), NIAID, Parasit Dis Lab, Growth & Dev Sect, NIH, Room 126,Bldg 4,4 Ctr Dr MSC 0425,9000 Rockville, Bethesda, MD 20892 USA. NR 9 TC 5 Z9 6 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 MAY PY 2000 VL 108 IS 2 BP 253 EP 256 DI 10.1016/S0166-6851(00)00214-0 PG 4 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 321ZV UT WOS:000087486000009 PM 10838228 ER PT J AU Nakamura, T Yamazaki, Y Saiki, Y Moriyama, M Largaespada, DA Jenkins, NA Copeland, NG AF Nakamura, T Yamazaki, Y Saiki, Y Moriyama, M Largaespada, DA Jenkins, NA Copeland, NG TI Evi9 encodes a novel zinc finger protein that physically interacts with BCL6, a known human B-Cell proto-oncogene product SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; PLZF-RAR-ALPHA; POZ DOMAIN; IN-VIVO; NUCLEAR; REPRESSION; GENE; COREPRESSOR; LYMPHOMA; SMRT AB Evi9 is a common site of retroviral integration in BXH2 murine myeloid leukemias. Here we show that Evi9 encodes a novel zinc finger protein with three tissue-specific isoform;: Evi9a (773 amino acids [aa]) contains two C2H2-type zinc finger motifs, a proline-rich region, and an acidic domain; Evi9b (486 aa) lacks the first zinc finger motif and part of the proline-rich region; Evi9c (239 aa) lacks all but the first zinc linger motif, Proviral integration sites are located in the first intron of the gene and lead to increased gene expression. Evi9a and Evi9c, but not Evi9b? show transforming activity for NIH 3T3 cells, suggesting that Evi9 is a dominantly acting proto-oncogene, Immunolocalization studies show that Evi9c is restricted to the cytoplasm whereas Evi9a and Evi9b are located in the nucleus, where they form a speckled localization pattern identical to that observed for BCL6, a human B-cell proto-oncogene product, Coimmunoprecipitation and glutathione S-transferase pull-down experiments show that Evi9a and Evi9b, but not Evi9c, physically interact with BCL6, while deletion mutagenesis localized the interaction domains in or near the second zinc finger and POZ domains of Evi9 and BCL6, respectively, These results suggest that Evi9 is a leukemia disease gene that functions, in part, through its interaction with BCL6. C1 Japanese Fdn Canc Res, Inst Canc, Toshima Ku, Tokyo 1708455, Japan. Japan Sci & Technol Corp, PRESTO, Toshima Ku, Tokyo 1708455, Japan. Tottori Univ, Sch Med, Dept Mol Biol, Tottori 6830826, Japan. Univ Minnesota, Ctr Canc, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. NCI, Mammalian Genet Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Nakamura, T (reprint author), Japanese Fdn Canc Res, Inst Canc, Toshima Ku, 1-37-1 Kami Ikebukuor, Tokyo 1708455, Japan. RI Largaespada, David/C-9832-2014 NR 41 TC 60 Z9 65 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2000 VL 20 IS 9 BP 3178 EP 3186 DI 10.1128/MCB.20.9.3178-3186.2000 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 303LB UT WOS:000086422400023 PM 10757802 ER PT J AU Ashcroft, M Taya, Y Vousden, KH AF Ashcroft, M Taya, Y Vousden, KH TI Stress signals utilize multiple pathways to stabilize p53 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR P53; DNA-DAMAGE; NUCLEAR-LOCALIZATION; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; FEEDBACK LOOP; MDM2; PHOSPHORYLATION; P19(ARF); PROTEIN AB The p53 tumor suppressor is activated by many diverse stress signals through mechanisms that result in stabilization and accumulation of the p53 protein. p53 is normally degraded through the proteasome following interaction with MDM2, which both functions as a ubiquitin ligase for p53 and shuttles to the cytoplasm, where p53 degradation occurs. Stabilization of p53 in response to stress is associated with inhibition of MDM2-mediated degradation, which has been associated with phosphorylation of p53 in response to DNA damage or activation of ARF. In this study we show distinct responses, as measured by phosphorylation, transcriptional activity, and subcellular localization, of p53 stabilized by different activating signals. Although normal cells and wild-type p53-expressing tumor tells showed similar responses to actinomycin D and camptothecin treatment, the transcriptional activity of stabilized p53 induced by deferoxamine mesylate, which mimics hypoxia, in normal cells was lost in all three tumor cell lines tested. Our results show that multiple pathways exist to stabilize p53 in response to different forms of stress, and they may involve down-regulation of MDM2 expression or regulation of the subcellular localization of p53 or MDM2. Loss of any one of these pathways may predispose cells to malignant transformation, although reactivation of p53 might be achieved through alternative pathways that remain functional in these tumor cells. C1 NCI, Regulat Cell Growth Lab, Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Natl Canc Ctr, Res Inst, Chuo Ku, Tokyo 104, Japan. RP Vousden, KH (reprint author), NCI, Regulat Cell Growth Lab, Basic Res Program, Frederick Canc Res & Dev Ctr, Bldg 560,Room 22-96,W 7th St, Frederick, MD 21702 USA. NR 59 TC 283 Z9 288 U1 2 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2000 VL 20 IS 9 BP 3224 EP 3233 DI 10.1128/MCB.20.9.3224-3233.2000 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 303LB UT WOS:000086422400027 PM 10757806 ER PT J AU Piras, G El Kharroubi, A Kozlov, S Escalante-Alcalde, D Hernandez, L Copeland, NG Gilbert, DJ Jenkins, NA Stewart, CL AF Piras, G El Kharroubi, A Kozlov, S Escalante-Alcalde, D Hernandez, L Copeland, NG Gilbert, DJ Jenkins, NA Stewart, CL TI Zac1 (Lot1), a potential tumor suppressor gene, and the gene for epsilon-sarcoglycan are maternally imprinted genes: Identification by a subtractive screen of novel uniparental fibroblast lines SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; SILVER-RUSSELL-SYNDROME; MUSCULAR-DYSTROPHY 2D; ZINC-FINGER PROTEIN; RETROVIRAL VECTORS; BREAST-CANCER; LINKAGE MAP; LONG ARM; MOUSE; EXPRESSION AB Imprinted genes are expressed from one allele according to their parent of origin, and many are essential to mammalian embryogenesis. sere we show that the epsilon-sarcoglycan gene (Sgce) and Zac1 (Loll) are both paternally expressed imprinted genes. They were identified in a subtractive screen for imprinted genes using a cDNA library made from novel parthenogenetic and wild-type fibroblast lines. Sgce is a component of the dystrophin-sarcoglycan complex, Zac1 is a nuclear protein inducing growth arrest and/or apoptosis, and Zac1 is a potential tumor suppressor gene. Sgce and Zac1 are expressed predominantly from their paternal alleles in ail adult mouse tissues, except that Zac1 is biallelic in the liver and Sgce is weakly expressed from the maternal allele in the brain. Sgce and Zac1 are broadly expressed in embryos, with Zac1 being highly expressed in the liver primordium, the umbilical region, and the neural tube. Sgce, however, is strongly expressed in the allantoic region on day 9.5 but becomes more widely expressed throughout the embryo by day 11.5, Sgce is located at the proximal end of mouse chromosome 6 and is a candidate gene for embryonic lethality associated dth uniparental maternal inheritance of this region. Zac1 maps to the proximal region of chromosome 10, identifying a new imprinted locus in the mouse, homologous with human chromosome 6q24-q25. In humans. unipaternal disomy for this region is associated with fetal growth retardation and transient neonatal diabetes mellitus. In addition, loss of expression of ZAC has been described for a number of breast and ovarian carcinomas, suggesting that ZAC is a potential tumor suppressor gene. C1 NCI, Lab Canc & Dev Biol, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Stewart, CL (reprint author), NCI, Lab Canc & Dev Biol, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. NR 49 TC 149 Z9 150 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2000 VL 20 IS 9 BP 3308 EP 3315 DI 10.1128/MCB.20.9.3308-3315.2000 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 303LB UT WOS:000086422400035 PM 10757814 ER PT J AU Pise-Masison, CA Mahieux, R Jiang, H Ashcroft, M Radonovich, M Duvall, J Guillerm, C Brady, JN AF Pise-Masison, CA Mahieux, R Jiang, H Ashcroft, M Radonovich, M Duvall, J Guillerm, C Brady, JN TI Inactivation of p53 by human T-cell lymphotropic virus type 1 tax requires activation of the NF-kappa B pathway and is dependent on p53 phosphorylation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSFORMS RAT FIBROBLASTS; CYCLE CHECKPOINT PATHWAY; TUMOR-SUPPRESSOR PROTEIN; CREB-BINDING-PROTEIN; LEUKEMIA-VIRUS; DNA-DAMAGE; I TAX; TRANSCRIPTIONAL ACTIVATION; ATAXIA-TELANGIECTASIA; GENE AMPLIFICATION AB p53 plays a key role in guarding cells against DNA damage and transformation. We previously demonstrated that the human T-cell lymphotropic virus type 1 (HTLV-1) Tax can inactivate p53 transactivation function in lymphocytes. The present study demonstrates that in T cells, Tax-induced p53 inactivation is dependent upon NF-kappa B activation. Analysis of Tax mutants demonstrated that Tan inactivation of p53 function correlates with the ability of Tax to induce NF-kappa B but not p300 binding or CREB transactivation. The Tax-induced p53 inactivation can be overcome by overexpression of a dominant I kappa B mutant. Tax-NF-kappa B-induced p53 inactivation is not due to p300 squelching since overexpression of p300 does not recover p53 activity in the presence of Tax. Further, using wild-type and p65 knockout mouse embryo fibroblasts (MEFs), we demonstrate that the p65 subunit of NF-kappa B is critical for Tax-induced p53 inactivation. While Tax can inactivate endogenous p53 function in wild-type MEFs, it fails to inactivate p53 function in p65 knockout MEFs. Importantly, Tax-induced p53 inactivation can be restored by expression of p65 in the knockout MEFs. Finally, we present evidence that phosphorylation of serines 15 and 392 correlates with inactivation of p53 by Tax in T cells. This study provides evidence that the divergent NF-kappa B proliferative and p53 cell cycle arrest pathways may be cross-regulated at several levels, including posttranslational modification of p53. C1 NCI, Lab Receptor Biol & Gene Express, Virus Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. NCI, ABL, Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Pise-Masison, CA (reprint author), NCI, Lab Receptor Biol & Gene Express, Virus Tumor Biol Sect, NIH, Bldg 41 B303, Bethesda, MD 20892 USA. NR 87 TC 101 Z9 103 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 MAY PY 2000 VL 20 IS 10 BP 3377 EP 3386 DI 10.1128/MCB.20.10.3377-3386.2000 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 308ET UT WOS:000086698100005 PM 10779327 ER PT J AU Smith, ML Ford, JM Hollander, MC Bortnick, RA Amundson, SA Seo, YR Deng, CX Hanawalt, PC Fornace, AJ AF Smith, ML Ford, JM Hollander, MC Bortnick, RA Amundson, SA Seo, YR Deng, CX Hanawalt, PC Fornace, AJ TI p53-mediated DNA repair responses to UV radiation: Studies of mouse cells lacking p53, p21, and/or gadd45 genes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEOTIDE-EXCISION-REPAIR; IRRADIATED HUMAN FIBROBLASTS; PIGMENTOSUM VARIANT CELLS; INDUCED G(1) ARREST; ASSEMBLY FACTOR-I; WILD-TYPE P53; ANTICANCER AGENTS; PROTEIN; EXPRESSION; CHROMATIN AB Human cells lacking functional p53 exhibit a partial deficiency in nucleotide excision repair (NER), the pathway for repair of UV-induced DNA damage. The global genomic repair (GGR) subpathway of NER, but not transcription-coupled repair (TCR), is mainly affected by p53 loss or inactivation. We have utilized mouse embryo fibroblasts (MEFs) lacking p53 genes or downstream effector genes of the p53 pathway, gadd45 (Gadd45a) or p21 (Cdkn1a), as well as MEFs lacking both gadd45 and p21 genes to address the potential contribution of these downstream effecters to p53-associated DNA repair. Loss of p53 or gadd45 had a pronounced effect on GGR, while p21 loss had only a marginal effect, determined by measurements of repair synthesis (unscheduled DNA synthesis), by immunoassays to detect removal of UV photoproducts from genomic DNA, and by assays determining strand-specific removal of CPDs from the mouse dhfr gene. Taken together, the evidence suggests a role for Gadd45, but relatively little role for p21, in DNA repair responses to UV radiation. Recent evidence suggests that Gadd45 hinds to UV-damaged chromatin and may affect lesion accessibility. MEFs lacking p53 or gadd45 genes exhibited decreased colony-forming ability after UV radiation and cisplatin compared to wildtype MEFs, indicating their sensitivity to DNA damage. We provide evidence that Gadd45 affects chromatin remodelling of templates concurrent with DNA repair, thus indicating that Gadd45 may participate in the coupling between chromatin assembly and DNA repair. C1 Indiana Univ, Sch Med, Ctr Canc, Dept Microbiol, Indianapolis, IN 46202 USA. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. Indiana Univ, Sch Med, Ctr Canc, Walther Oncol Ctr, Indianapolis, IN 46202 USA. RP Smith, ML (reprint author), Indiana Univ, Sch Med, Ctr Canc, Dept Microbiol, R4-155, Indianapolis, IN 46202 USA. RI Fornace, Albert/A-7407-2008; deng, chuxia/N-6713-2016 OI Fornace, Albert/0000-0001-9695-085X; FU NCI NIH HHS [CA44349, KO8-CA64330] NR 51 TC 319 Z9 326 U1 0 U2 8 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 MAY PY 2000 VL 20 IS 10 BP 3705 EP 3714 DI 10.1128/MCB.20.10.3705-3714.2000 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 308ET UT WOS:000086698100038 PM 10779360 ER PT J AU Slattery, JP Murphy, WJ O'Brien, S AF Slattery, JP Murphy, WJ O'Brien, S TI Patterns of diversity among SINE elements isolated from three Y-chromosome genes in carnivores SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Letter DE retroposon; SINE; carnivore; Y chromosome; evolution ID RNA-DERIVED RETROPOSONS; PHYLOGENETIC RECONSTRUCTION; RIBOSOMAL-RNA; CYTOCHROME-B; X-CHROMOSOME; SEQUENCES; EVOLUTION; FELIDAE; DNA; DIVERGENCE C1 NCI, Lab Genom Divers, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Slattery, JP (reprint author), NCI, Lab Genom Divers, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 40 TC 20 Z9 20 U1 0 U2 3 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 USA SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD MAY PY 2000 VL 17 IS 5 BP 825 EP 829 PG 5 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 311GA UT WOS:000086875300016 PM 10779543 ER PT J AU Kenworthy, AK Petranova, N Edidin, M AF Kenworthy, AK Petranova, N Edidin, M TI High-resolution FRET microscopy of cholera toxin B-subunit and GPI-anchored proteins in cell plasma membranes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; POLARIZED EPITHELIAL-CELLS; RESONANCE ENERGY-TRANSFER; SIGNAL-TRANSDUCTION; LIPID MICRODOMAINS; CROSS-LINKING; LIVING CELLS; MDCK CELLS; CAVEOLAE MEMBRANE; FOLATE RECEPTORS AB "Lipid rafts" enriched in glyeosphingolipids (GSL), GPI-anchored proteins, and cholesterol have been proposed as functional microdomains in cell membranes. However, evidence supporting their existence has been indirect and controversial. In the past year, hive studies used fluorescence resonance energy transfer (FRET) microscopy to probe for the presence of Lipid rafts; rafts here would be defined as membrane domains containing clustered GPI-anchored proteins at the cell surface. The results of these studies, each based on a single protein, gave conflicting views of rafts. To address the source of this discrepancy, we have now used FRET to study three different GPI-anchored proteins and a GSL endogenous to several different cell types. FRET was detected between molecules of the GSI, GM1 labeled with cholera toxin B-subunit and between antibody-labeled GPI-anchored proteins, showing these raft markers are in submicrometer proximity in the plasma membrane. However, in most cases FRET correlated with the surface density of the lipid raft marker, a result inconsistent with significant clustering in microdomains. We conclude that in the plasma membrane, lipid rafts either exist only as transiently stabilized structures or, if stable, comprise at most a minor fraction of the cell surface. C1 Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Acad Sci Czech Republ, Inst Mol Genet, Lab Leucocytes Antigens, CR-14220 Prague, Czech Republic. RP Kenworthy, AK (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18 T,Room 101, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [5PO1DK44375] NR 64 TC 335 Z9 340 U1 3 U2 27 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 2000 VL 11 IS 5 BP 1645 EP 1655 PG 11 WC Cell Biology SC Cell Biology GA 314HE UT WOS:000087049700012 PM 10793141 ER PT J AU Carlisle, AJ Prabhu, VV Elkahloun, A Hudson, J Trent, JM Linehan, WM Williams, ED Emmert-Buck, MR Liotta, LA Munson, PJ Krizman, DB AF Carlisle, AJ Prabhu, VV Elkahloun, A Hudson, J Trent, JM Linehan, WM Williams, ED Emmert-Buck, MR Liotta, LA Munson, PJ Krizman, DB TI Development of a prostate cDNA microarray and statistical gene expression analysis package SO MOLECULAR CARCINOGENESIS LA English DT Article DE bioinformatics; nylon filter array; radionucleotide detection and analysis; image processing ID INTERMEDIATE FILAMENTS; CONSTRUCTION; DISCOVERY; PATTERNS; CANCER; CELLS AB A cDNA microarray comprising 5184 different cDNAs spotted onto nylon membrane filters was developed for prostate gene expression studies. The clones used for arraying were identified by cluster analysis of > 35 000 prostate cDNA library-derived expressed sequence tags (ESTs) present in the dbEST database maintained by the National Center for Biotechnology information. Total RNA from two cell lines, prostate line 8.4 and melanoma line UACC903, was used to make radiolabeled probe for filter hybridizations. The absolute intensity of each individual cDNA spot was determined by phosphorimager scanning and evaluated by a bioinformatics package developed specifically for analysis of cDNA microarray experimentation. Results indicated 89% of the genes showed intensity levels above background in prostate cells compared with only 28% in melanoma cells. Replicate probe preparations yielded results with correlation values ranging from r = 0.90 to 0.93 and coefficient of variation ranging from 16 to 28%. Findings indicate that among others, the keratin 5 and vimentin genes were differentially expressed between these two divergent cell lines. Follow-up northern blot analysis verified these two expression changes, thereby demonstrating the reliability of this system. We report the development of a cDNA microarray system that is sensitive and reliable, demonstrates a low degree of variability, and is capable of determining verifiable gene expression differences between two distinct human cell lines. This system will prove useful for differential gene expression analysis in prostate-derived cells and tissue. Mel. Carcinog. 28: 12-22, 2000. (C) 2000 Wiley-Liss, Inc. C1 NCI, Pathol Lab, Rockville, MD USA. NCI, Canc Genome Anat Project, Rockville, MD USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Res Genet Inc, Huntsville, AL 35801 USA. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Krizman, DB (reprint author), Adv Technol Ctr 134F, 8717 Grovement Circle, Gaithersburg, MD 20877 USA. RI Williams, Elizabeth/B-1538-2008 OI Williams, Elizabeth/0000-0002-3364-6655 NR 18 TC 66 Z9 69 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 MAY PY 2000 VL 28 IS 1 BP 12 EP 22 DI 10.1002/(SICI)1098-2744(200005)28:1<12::AID-MC3>3.0.CO;2-Q PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 311VX UT WOS:000086907500003 PM 10820484 ER PT J AU Stephan, DA Chen, YD Jiang, Y Malechek, L Gu, JZ Robbins, CM Bittner, ML Morris, JA Carstea, E Meltzer, PS Adler, K Garlick, R Trent, JM Ashlock, MA AF Stephan, DA Chen, YD Jiang, Y Malechek, L Gu, JZ Robbins, CM Bittner, ML Morris, JA Carstea, E Meltzer, PS Adler, K Garlick, R Trent, JM Ashlock, MA TI Positional cloning utilizing genomic DNA microarrays: The Niemann-Pick type C gene as a model system SO MOLECULAR GENETICS AND METABOLISM LA English DT Article ID DIRECT SELECTION; SURVEILLANCE COMPLEX; EXPRESSION PATTERNS; MESSENGER-RNAS; SEQUENCES; AMPLIFICATION; TRANSLATION; PROTEIN; CELLS AB A major obstacle in positional cloning is identifying the specific mutated gene from within a large physical contig, Here we describe the application of DNA microarray technology to a defined genomic region (:physical map) to identify: ii) exons without a priori sequence data and (ii) the disease gene based on differential gene expression in a recessive disorder. The feasibility was tested using resources from the positional cloning of the Neimann-Pick Type C: (NP-C) disease gene, NPC1. To identify NPC1 exons and optimize the technology, an array was generated from genomic fragments of the 110-kb bacterial artificial chromosome, 108N2, which encodes NPC1, First, as a test case fur blindly identifying exons, fluorescently labeled NPC1 cDNA identified 108N2 fragments that contained NPC1 exons, many of which also contained intronic sequences and could be used to determine part of the NPC1 genomic structure, Second, to demonstrate that the NPC1 disease gene could be identified based upon differential gene expression, subarrays of 108N2 fragments were hybridized with fluorescently labeled cDNA probes generated from total RNA from hamster cell lines differentially expressing NPC1, A probe derived from the NP-C cell line CT60 did not detect NPC1 exons or other genomic fragments from 108N2. In contrast, several NPC1 exons were detected by a probe generated from the non-NP-C cell Line 911D5A13, which was derived from CT60, and expressed NPC1 as a consequence of stable transduction with a YAC that contains N1DC1 and encompasses 108N2, Thus, the array technology identified NPC1 as a candidate gene based on a physical contig and differential NPC1 expression between NP-C and non-NP-C cells, This technique should facilitate gene identification when a physical contig exists For a region of interest and mutations result in changes in the mRNA level of the disease gene or portions thereof. (C) 2000 Academic Press. C1 Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NEN Life Sci Prod Inc, Boston, MA 02119 USA. RP Stephan, DA (reprint author), Childrens Natl Med Ctr, Med Genet Res Ctr, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 25 TC 8 Z9 9 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAY PY 2000 VL 70 IS 1 BP 10 EP 18 DI 10.1006/mgme.2000.2989 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 327MH UT WOS:000087797300002 PM 10833327 ER PT J AU Pratley, RE Ren, K Milner, MR Sell, SM AF Pratley, RE Ren, K Milner, MR Sell, SM TI Insulin increases leptin mRNA expression in abdominal subcutaneous adipose tissue in humans SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE leptin mRNA; insulin; adipose tissue; glucose clamp ID OB GENE-EXPRESSION; MESSENGER-RNA EXPRESSION; PLASMA LEPTIN; PIMA-INDIANS; RAT ADIPOCYTES; OBESE SUBJECTS; FOOD-INTAKE; IN-VITRO; HYPERINSULINEMIA; WEIGHT AB Insulin regulates expression and production of leptin in rodents but whether this is also true in humans remains unclear. To test the effects of acute hyperinsulinemia on expression of leptin mRNA in humans, percutaneous needle biopsies of abdominal subcutaneous adipose tissue were performed at baseline and immediately following a 200-min two-step hyperinsulinemic-euglycemic glucose clamp in 16 Pima Indians (8M/8F). Leptin mRNA was quantified by reverse transcription, PCR amplification and expressed relative to actin mRNA. Leptin mRNA levels were higher in women than men (25.6 +/- 1.7 v 16.9 +/- 2.1 relative units, P = 0.003) at baseline. Baseline levels were directly related to percentage body fat (r = 0.54, P = 0.03) and fasting plasma glucose concentrations (r = 0.57, P = 0.02) and were negatively correlated to glucose disposal at physiologic insulin concentrations (750 +/- 40 pmol/L) during the clamp (r = -0.51, P = 0.04). Acute hyperinsulinemia (final insulin concentration 11560 +/- 950 pmol/L) increased leptin mRNA levels in 13 of 16 individuals an average of 13% (21.3 +/- 1.7 to 24.2 +/- 1.2 relative units, P = 0.01). Changes in leptin mRNA were directly related to glucose disposal rates during physiologic hyperinsulinemia (r = 0.54, P < 0.04). These results suggest that the expression of leptin mRNA is regulated by insulin in humans, as it is in rodents, (C) 2000 Academic Press. C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. RP Pratley, RE (reprint author), NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. NR 47 TC 18 Z9 19 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAY PY 2000 VL 70 IS 1 BP 19 EP 26 DI 10.1006/mgme.2000.2995 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 327MH UT WOS:000087797300003 PM 10833328 ER PT J AU Schultze-Mosgau, A Katzur, AC Arora, KK Stojilkovic, SS Diedrich, K Ortmann, O AF Schultze-Mosgau, A Katzur, AC Arora, KK Stojilkovic, SS Diedrich, K Ortmann, O TI Characterization of calcium-mobilizing, purinergic P2Y(2) receptors in human ovarian cancer cells SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE ATP receptors; calcium; cell proliferation; phospholipase C ID GROWTH-FACTOR; EXTRACELLULAR ATP; MESSENGER-RNA; INTRACELLULAR CALCIUM; EPITHELIAL-CELLS; GRANULOSA-CELLS; APOPTOSIS; PROLIFERATION; EXPRESSION; DIFFERENTIATION AB In human ovarian EFO-21 and EFO-27 carcinoma cells, extracellular ATP induced a concentration-dependent rise in intracellular calcium concentration ([Ca2+](i)). suggesting the expression of a purinoreceptor. ATP and UTP were equipotent in generating [Ca2+](i) signals, followed by ATP-gamma-S and ADP, whereas beta,gamma-ATP, 2 methyl 1 thio-ATP, 3'-o-(4-benzoyl) benzoyl-ATP, AMP, and adenosine were ineffective. This pharmacological profile suggested the presence of the P2Y(2) subtype in both cell types, and this was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) analysis using P2Y(2) primers. ATP-induced [Ca2+](i) signals were composed of two phases: an early and extracellular calcium-independent phase, followed by a sustained plateau phase that was dependent on capacitative calcium influx. In addition to the rise in the [Ca2+](i), a time- and concentration-dependent increase in phosphatidylethanol accumulation was observed in ATP-stimulated cells, indicating an increase in phospholipase D activity. RT-PCR analysis identified the expression of a transcript for the phospholipase D-1 subtype of this enzyme. Activation of these receptors by a slowly degradable analogue, ATP-gamma-S, attenuated basal and fetal calf serum-induced cell proliferation in a time- and concentration-dependent manner. These results indicate that ATP may act as an extracellular messenger in controlling the ovarian epithelial cell cycle through P2Y(2) receptors. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Univ Lubeck, Dept Obstet & Gynecol, D-23538 Lubeck, Germany. RP Stojilkovic, SS (reprint author), NICHD, Sect Cellular Signaling, ERRB, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. NR 35 TC 25 Z9 26 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD MAY PY 2000 VL 6 IS 5 BP 435 EP 442 DI 10.1093/molehr/6.5.435 PG 8 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 310KC UT WOS:000086824200009 PM 10775647 ER PT J AU Imada, K Leonard, WJ AF Imada, K Leonard, WJ TI The Jak-STAT pathway (vol 37, pg 1, 2000) SO MOLECULAR IMMUNOLOGY LA English DT Correction C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 5 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAY PY 2000 VL 37 IS 7 BP 403 EP 403 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 372XU UT WOS:000165260000007 ER PT J AU Magoun, L Zuckert, WR Robbins, D Parveen, N Alugupalli, KR Schwan, TG Barbour, AG Leong, JM AF Magoun, L Zuckert, WR Robbins, D Parveen, N Alugupalli, KR Schwan, TG Barbour, AG Leong, JM TI Variable small protein (Vsp)-dependent and Vsp-independent pathways for glycosaminoglycan recognition by relapsing fever spirochaetes SO MOLECULAR MICROBIOLOGY LA English DT Article ID BORRELIA-BURGDORFERI; LYME-DISEASE; ANTIGENIC VARIATION; MAJOR PROTEINS; MOUSE MODEL; HOST-CELLS; HERMSII; SPIROCHETE; PROTEOGLYCANS; TURICATAE AB Tick-borne relapsing fever, caused by pathogenic Borrelia such as B. hermsii and B. turicatae, features recurrent episodes of bacteraemia, each of which is caused by a population of spirochaetes that expresses a different variable major protein. Relapsing fever is also associated with the infection of a variety of tissues, such as the central nervous system. In this study, we show that glycosaminoglycans (GAGs) mediate the attachment of relapsing fever spirochaetes to mammalian cells. B. hermsii strain DAH bound to immobilized heparin, and heparin and dermatan sulphate blocked bacterial binding to host cells. Bacterial binding was diminished by inhibition of host cell GAG synthesis or sulphation, or by the enzymatic removal of GAGs. GAGs mediated the attachment of relapsing fever spirochaetes to potentially relevant target cells, such as endothelial and glial cells. B. hermsii was able to attach to GAGs independently of variable major proteins, because strains expressing the variable major proteins Vsp33,,Vlp7 or no variable major protein at all each recognized GAGs. Nevertheless, we found that a variable major protein of B. turicatae directly promoted GAG binding by this relapsing fever spirochaete. B. turicatae strain Oz1 serotype B, which expresses the variable major protein VspB, bound to GAGs more efficiently than did B. turicatae Oz1 serotype A, which expresses VspA, Recombinant VspB, but not VspA, bound to heparin and dermatan sulphate. Previous studies have shown that strain Oz1 serotype B grows to higher concentrations in the blood than does Oz1 serotype A. Thus, relapsing fever spirochaetes have the potential to express Vsp-dependent and Vsp-independent GAG-binding activities and, for one pair of highly related B. turicatae strains, differences in GAG binding correlate with differences in tissue tropism. C1 Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92697 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. RP Leong, JM (reprint author), Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, 55 Lake Ave N, Worcester, MA 01655 USA. RI Barbour, Alan/B-3160-2009 OI Barbour, Alan/0000-0002-0719-5248 FU NIAID NIH HHS [R01-AI 24424, R01-AI 37601] NR 57 TC 28 Z9 28 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2000 VL 36 IS 4 BP 886 EP 897 DI 10.1046/j.1365-2958.2000.01906.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 324XK UT WOS:000087647000011 PM 10844676 ER PT J AU Lorenzo, PS Beheshti, M Pettit, GR Stone, JC Blumberg, PM AF Lorenzo, PS Beheshti, M Pettit, GR Stone, JC Blumberg, PM TI The guanine nucleotide exchange factor RasGRP is a high-affinity target for diacylglycerol and phorbol esters SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-KINASE-C; CYSTEINE-RICH REGION; N-CHIMAERIN; BINDING; ACTIVATION; DOMAINS; TRANSFORMATION; SPECIFICITY; RECEPTOR; ISOZYMES AB RasGRP is a recently described guanine nucleotide exchange factor (GEF) that possesses a single C1 domain homologous to that of protein kinase C (PKC). The phorbol ester [(3)H]phorbol 12,13-dibutyrate ([(3)H]PDBu) bound to this C1 domain (C1-RasGRP) with a dissociation constant of 0.58 +/- 0.08 nM, similar to that observed previously for PKC. Likewise, the potent PKC activator bryostatin 1, a compound currently in clinical trials, showed high affinity binding for C1-RasGRP. Structure activity analysis using several phorbol ester analogs showed both similarities and differences in ligand selectivity compared with PKC; the differences were comparable in magnitude to those between different PKC isoforms. Similarly, the potency of the PKC inhibitor calphostin C to inhibit [(3)H]PDBu binding to C1-RasGRP was similar to that observed for PKC. In contrast to the relative similarities in ligand recognition, the lipid cofactor requirements differed between RasGRP and PKC. The C1 domain plus the EF-hand motif of RasGRP (C1EF-RasGRP) was markedly less dependent on acidic phospholipids than was PKC alpha. The differences in lipid requirements were reflected in differential ligand selectivity under conditions of limiting lipid. Despite the presence of twin EF-hand like motifs, calcium did not affect the binding of [(3)H]PDBu to C1EF-RasGRP. We conclude that RasGRP is a high affinity receptor for phorbol esters and diacylglycerol. RasGRP thus provides a direct link between diacylglycerol generation or phorbol ester/bryostatin treatment and Ras activation. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. Univ Alberta, Dept Biochem, Edmonton, AB, Canada. Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. RP Blumberg, PM (reprint author), 37 Convent Dr,MSC 4255,Bldg 37,Room 3A0a, Bethesda, MD 20892 USA. EM blumberp@dc37a.nci.nih.gov NR 37 TC 100 Z9 103 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 2000 VL 57 IS 5 BP 840 EP 846 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 309HH UT WOS:000086762100002 PM 10779365 ER PT J AU Lee, SH Chang, MY Lee, KH Park, BS Lee, YS Chin, HR Lee, YS AF Lee, SH Chang, MY Lee, KH Park, BS Lee, YS Chin, HR Lee, YS TI Importance of valine at position 152 for the substrate transport and 2 beta-carbomethoxy-3 beta-(4-fluorophenyl) tropane binding of dopamine transporter SO MOLECULAR PHARMACOLOGY LA English DT Article ID AMINOBUTYRIC-ACID TRANSPORTER; PROTEIN-COUPLED RECEPTORS; TRANSMEMBRANE DOMAIN; SEROTONIN TRANSPORTER; COCAINE BINDING; NEUROTRANSMITTER TRANSPORTERS; NOREPINEPHRINE TRANSPORTERS; STRUCTURAL DOMAINS; RECOGNITION; EXPRESSION AB Human and bovine dopamine transporters (DAT) demonstrate discrete functional differences in dopamine (DA), 1-methyl-4-phenylpyridium (MPP+) transport, and cocaine analog binding. In a previous study, the functional analyses on the chimeras of human and bovine DAT have revealed that the region from residues 133 through 186 (encompassing the third transmembrane domain) is responsible for the substrate transport and cocaine analog binding. The present study has been carried out to determine the specific amino acid(s) conferring DAT functions by interchanging the amino acid residues in the corresponding region between human and bovine DAT. As described previously, the DA, MPP+ transport, and 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (CFT) binding almost disappeared in chimera hb3 in which the region from residues 133 through 186 of bovine DAT was substituted into human DAT. Replacement of isoleucine, residue 152 of chimera hb3 (bovine DAT sequence), with valine, the human DAT residue at the identical position, remarkably restored the substrate transport and CFT binding to 76% to 98% of the human DAT values. Similarly, substitution of isoleucine for valine at position 152 in the human DAT reduced the substrate transport and CFT binding by 57% to 97%. Among other amino acids tested at position 152 of the chimera hb3, only alanine resulted in small but significant increases in the DAT functions ranging from 16 to 34%. Thus, valine at position 152 plays a crucial role for molecular mechanisms underlying the interactions of DA, MPP+, and CFT with human DAT. C1 Hanyang Univ, Mental Hlth Res Inst, Seoul, South Korea. NIMH, Div Basic & Clin Neurosci Res, Bethesda, MD USA. RP Lee, YS (reprint author), Hanyang Univ, Coll Med, Dept Biochem, 17 Haengdang Dong,Sungdong Ku, Seoul 133791, South Korea. NR 34 TC 42 Z9 42 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 MAY PY 2000 VL 57 IS 5 BP 883 EP 889 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 309HH UT WOS:000086762100007 PM 10779370 ER PT J AU Yu, ZG Huse, LM Adler, P Graham, L Ma, JX Zeldin, DC Krotez, DL AF Yu, ZG Huse, LM Adler, P Graham, L Ma, JX Zeldin, DC Krotez, DL TI Increased CYP2J expression and epoxyeicosatrienoic acid formation in spontaneously hypertensive rat kidney SO MOLECULAR PHARMACOLOGY LA English DT Article ID NA-K-ATPASE; ARACHIDONIC-ACID; MOLECULAR-CLONING; ENZYMATIC CHARACTERIZATION; CYTOCHROME-P450; EPOXYGENASE; METABOLISM; EICOSANOIDS; INHIBITORS; HEART AB Epoxyeicosatrienoic acids (EETs) are major products of cytochrome P450 (CYP)-catalyzed metabolism of arachidonic acid in the kidney. The potent effect of EETs on renal vascular tone and tubular ion and water transport implicates their role in the regulation of renal function and blood pressure. The present study was designed to test the hypothesis that CYP-catalyzed EET formation was altered in the spontaneously hypertensive rat (SHR) kidney. The formation of 14,15- and 11,12-EET was similar to 2-fold higher in incubations of arachidonic acid with SHR renal cortical microsomes relative to microsomes from normotensive Wistar-Kyoto (WKY) rats. This was consistent with increased expression of a CYP2J2 immunoreactive protein in the SHR cortex and outer medulla. In contrast, there was no significant difference in the levels of the CYP2E and CYP2C epoxygenases in SHR and WKY kidneys. Protein and RNA analysis suggests that the CYP2J2 immunoreactive protein that is overexpressed in the SHR kidney is distinct from the known rat CYP2J isoforms. EET formation also was documented in vivo from measurements of urinary EET excretion. Importantly, the excretion rates of 14,15-, and 11,12-EETs were 2.5- and 1.8-fold higher, respectively, in SHR than WKY kidney. These studies provide both in vitro and in vivo evidence for increased EET formation in the SHR kidney and identify a novel CYP2J2 immunoreactive protein that is differentially expressed in the hypertensive kidney. In light of the known biological properties of the EETs, these findings may be important in elucidating the mechanisms that control renal vascular tone and tubular ion transport in the SHR. C1 Univ Calif San Francisco, Sch Pharm, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA. RP Univ Calif San Francisco, Sch Pharm, Dept Biopharmaceut Sci, 513 Parnassus,Box 0446, San Francisco, CA 94143 USA. EM deanna@itsa.ucsf.edu FU NHLBI NIH HHS [HL53994] NR 40 TC 64 Z9 68 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 2000 VL 57 IS 5 BP 1011 EP 1020 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 309HH UT WOS:000086762100023 PM 10779386 ER PT J AU Elizondo, G Fernandez-Salguero, P Sheikh, MS Kim, GY Fornace, AJ Lee, KS Gonzalez, FJ AF Elizondo, G Fernandez-Salguero, P Sheikh, MS Kim, GY Fornace, AJ Lee, KS Gonzalez, FJ TI Altered cell cycle control at the G(2)/M phases in aryl hydrocarbon receptor-null embryo fibroblast SO MOLECULAR PHARMACOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; EPITHELIAL-CELLS; PROTEIN-KINASE; APOPTOSIS; DIOXIN; PROLIFERATION; ACTIVATION; EXPRESSION; MICE; INDUCTION AB The aryl hydrocarbon receptor (AHR) is known to mediate the toxic and carcinogenic effects of polycyclic aromatic hydrocarbons and dioxins. High-affinity AHR ligands, such as 2,3,7,8-tetrachlorodibenzeno-p-dioxin, have been shown to modify cell proliferation and differentiation. However, the mechanisms by which AHR affects cell proliferation and differentiation are not fully understood. To investigate the role of AHR in cell proliferation, mouse embryonic fibroblasts (MEFs) derived from AHR-null mice were obtained and characterized. Compared with wild-type MEFs, AHR-null cells exhibited a lower proliferation rate with an accumulation of 4N DNA content and increased apoptosis. The expression levels of Cdc2 and Plk, two kinases important for G(2)/M phase of cell cycle, were down-regulated in AHR-null MEFs. In contrast, transforming growth factor-beta (TGF-beta), a proliferation inhibitor in several cell lines, was present at high levels in conditioned medium from AHR-null MEFs. Concomitant with G(2)/M cell accumulation, treatment of wild-type MEFs with TGF-beta 3 also resulted in down-regulation of both Cdc2 and Plk. Thus, overproduction of TGF-beta in AHR-deficient cells appears to be the primary factor that causes low proliferation rates and increased apoptosis. Taken together, these results suggest that AHR influences TGF-beta production, leading to an alteration in cell cycle control. C1 NCI, Lab Metab, Div Basic Sci, Bethesda, MD 20892 USA. NCI, Gene Response Sect, Div Basic Sci, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Div Basic Sci, Bldg 37,Room 3E24, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008; OI Fornace, Albert/0000-0001-9695-085X; Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 40 TC 118 Z9 120 U1 0 U2 4 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 MAY PY 2000 VL 57 IS 5 BP 1056 EP 1063 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 309HH UT WOS:000086762100029 PM 10779392 ER PT J AU Vandenbergh, DJ Thompson, MD Cook, EH Bendahhou, E Nguyen, T Krasowski, MD Zarrabian, D Comings, D Sellers, EM Tyndale, RF George, SR O'Dowd, BF Uhl, GR AF Vandenbergh, DJ Thompson, MD Cook, EH Bendahhou, E Nguyen, T Krasowski, MD Zarrabian, D Comings, D Sellers, EM Tyndale, RF George, SR O'Dowd, BF Uhl, GR TI Human dopamine transporter gene: coding region conservation among normal, Tourette's disorder, alcohol dependence and attention-deficit hyperactivity disorder populations SO MOLECULAR PSYCHIATRY LA English DT Article DE polymorphism; chromosome 5p15.3; sequence; transmission disequilibrium test; psychiatric disorder ID PARKINSONS-DISEASE; NEUROTRANSMITTER TRANSPORTERS; LINKAGE DISEQUILIBRIUM; RECEPTOR GENE; MICE LACKING; IN-VIVO; POLYMORPHISM; ASSOCIATION; COCAINE; ORGANIZATION AB The dopamine transporter (DAT) provides major regulation of the synaptic levels of dopamine and is a principal target of psychostimulant drugs. Associations between DAT gene polymorphisms and human disorders with possible links to dopaminergic neurotransmission, including attention-deficit/hyperactivity disorder (ADHD) and consequences of cocaine and alcohol administration, have been reported. We now report approximately 60 000 bp of genomic sequence containing the entire DAT gene. This sequence was used to amplify each of the 15 DAT gene exons and several introns and analyze these amplification products by single-stranded sequence conformation (SSCP) and/or direct sequencing. These results define silent allelic single nucleotide sequence variants in DAT gene exons 2, 6, 9 and 15. Rare conservative mutations are identified in amino acids encoded by DAT exons 2 and 8, Analyses of the common nucleotide variants and the previously reported VNTR in the non-coding region of exon 15 define the pattern of linkage disequilibrium across the DAT locus. These comprehensive analyses, however, fail to identify any common protein coding DAT sequence variant in more than 150 unrelated individuals free of neuropsychiatric disease, 109 individuals meeting City of Hope criteria for Tourette's syndrome, 64 individuals with DSM-IV diagnoses of ethanol dependence, or 15 individuals with ADHD. These data are consistent with substantial evolutionary conservation of the DAT protein sequence. They suggest that gene variants that alter levels of DAT expression provide the best current candidate mechanism for reported associations between DAT gene markers, ADHD and other more tentatively associated neuropsychiatric disorders. C1 NIDA, IRP, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. Univ Toronto, Dept Pharmacol, Toronto, ON M5S 2S1, Canada. Univ Chicago, Lab Dev Neurosci, Dept Psychiat, Chicago, IL 60637 USA. City Hope Med Ctr, Dept Med Genet, Duarte, CA USA. Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON M4X 1K9, Canada. Univ Toronto, Dept Pharmacol, Toronto, ON M4X 1K9, Canada. Univ Toronto, Dept Psychiat & Med, Toronto, ON M4X 1K9, Canada. Univ Toronto, Sunnybrook & Womens Coll Hlth Sci Ctr, Toronto, ON M4X 1K9, Canada. RP Uhl, GR (reprint author), NIDA, IRP, Mol Neurobiol Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Krasowski, Matthew/0000-0003-0856-8402 NR 46 TC 105 Z9 108 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 2000 VL 5 IS 3 BP 283 EP 292 DI 10.1038/sj.mp.4000701 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 325DL UT WOS:000087661000012 PM 10889531 ER PT J AU Iwata, N Virkkunen, M Goldman, D AF Iwata, N Virkkunen, M Goldman, D TI Identification of a naturally occurring Pro385-Ser385 substitution in the GABA(A) receptor alpha 6 subunit gene in alcoholics and healthy volunteers SO MOLECULAR PSYCHIATRY LA English DT Article DE GABA receptor; alcoholism; single-stranded conformational polymorphism (SSCP); polymorphism; genetic variation; amino acid substitution ID GAMMA-AMINOBUTYRIC-ACID; MOLECULAR-BIOLOGY; A RECEPTORS; ETHANOL; SENSITIVITY; PHOSPHORYLATION; PHARMACOLOGY; MECHANISM; DNA AB In the rat, variation in alcohol and benzodiazepine sensitivity has been correlated with an inherited variant of the GABA(A)alpha 6 receptor. Our goal was to identify polymorphisms in the human GABA(A)alpha 6 receptor gene and determine whether a variant of the receptor is associated with alcoholism. The GABA(A)alpha 6 receptor gene coding region was screened in 80 unrelated patients with alcoholism using single strand conformational polymorphism analysis. For rapid genotyping, a Polymerase Chain Reaction-Restriction Fragment Length polymorphism (PCR-RFLP) assay was developed. A relatively abundant amino acid substitution and three synonymous DNA substitutions were detected. The synonymous variants, 35A > G, 665A > G, and 1031 > G > C had rare-allele frequencies of 0,25, 0,02, and 0,47, respectively. The Pro38-5Ser substitution is located in the second intracellular domain of the receptor adjacent to a putative phosphorylation site. Pro385Ser has rarer allele frequencies of 3.3% and 4.8% in 196 Finnish alcoholic patients and 189 controls, respectively (P = NS). A naturally occurring non-conservative Pro385Ser was detected in the GABA(A)alpha 6 receptor. The variant is not associated with alcoholism. C1 NIAAA, DICBR, Neurogenet Lab, Bethesda, MD 20892 USA. Univ Helsinki, Dept Psychiat, Helsinki 00810, Finland. RP Iwata, N (reprint author), NIAAA, DICBR, Neurogenet Lab, 12420 Parklawn Dr,Pk 5-451,MSC8110, Bethesda, MD 20892 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 27 TC 12 Z9 12 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 2000 VL 5 IS 3 BP 316 EP 319 DI 10.1038/sj.mp.4000706 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 325DL UT WOS:000087661000016 PM 10889535 ER PT J AU Hallett, M Litvan, I AF Hallett, M Litvan, I CA Task Force Surg Parkinson's Dis Am TI Scientific position paper of the movement disorder society evaluation of surgery for Parkinson's disease SO MOVEMENT DISORDERS LA English DT Editorial Material ID UNILATERAL PALLIDAL STIMULATION; DEEP BRAIN-STIMULATION; PALLIDOTOMY; NUCLEUS; TRANSPLANTATION RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. OI Litvan, Irene/0000-0002-3485-3445 NR 17 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 2000 VL 15 IS 3 BP 436 EP 438 DI 10.1002/1531-8257(200005)15:3<436::AID-MDS1003>3.0.CO;2-L PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 315XH UT WOS:000087137900003 PM 10830406 ER PT J AU Nehls, S Snapp, EL Cole, NB Zaal, KJM Kenworthy, AK Roberts, TH Ellenberg, J Presley, JF Siggia, E Lippincott-Schwartz, J AF Nehls, S Snapp, EL Cole, NB Zaal, KJM Kenworthy, AK Roberts, TH Ellenberg, J Presley, JF Siggia, E Lippincott-Schwartz, J TI Dynamics and retention of misfolded proteins in native ER membranes SO NATURE CELL BIOLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; ENDOPLASMIC-RETICULUM; LIVING CELLS; INTERMEDIATE COMPARTMENT; INTRACELLULAR-TRANSPORT; LATERAL DIFFUSION; GOLGI-APPARATUS; QUALITY-CONTROL; GLYCOPROTEIN; OLIGOMERIZATION AB When co-translationally inserted into endoplasmic reticulum (ER) membranes, newly synthesized proteins encounter the lumenal environment of the ER, which contains chaperone proteins that facilitate the folding reactions necessary for protein oligomerization, maturation and export from the ER. Here we show, using a temperature-sensitive variant of vesicular stomatitis virus G protein tagged with green fluorescent protein (VSVG-GFP), and fluorescence recovery after photobleaching (FRAP), the dynamics of association of folded and misfolded VSVG complexes with ER chaperones. We also investigate the potential mechanisms underlying protein retention in the ER. Misfolded VSVG-GFP complexes at 40 degrees C are highly mobile in ER membranes and do not reside in post-ER compartments, indicating that they are not retained in the ER by immobilization or retrieval mechanisms. These complexes are immobilized in ATP-depleted or tunicamycin-treated cells, in which VSVG-chaperone interactions are no longer dynamic, These results provide insight into the mechanisms of protein retention in the ER and the dynamics of protein-folding complexes in native ER membranes. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. European Mol Biol Lab, Gene Express & Cell Biol Program, Heidelberg, Germany. Rockefeller Univ, Ctr Studies Phys & Biol, New York, NY 10021 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T, Bethesda, MD 20892 USA. EM jlippin@helix.nih.gov RI Ward, Theresa/E-9650-2013 OI Ward, Theresa/0000-0002-9881-8649 FU NIGMS NIH HHS [R0I GM59018-01] NR 39 TC 188 Z9 190 U1 2 U2 13 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY PY 2000 VL 2 IS 5 BP 288 EP 295 PG 8 WC Cell Biology SC Cell Biology GA 313FX UT WOS:000086990600018 PM 10806480 ER PT J AU Fukuhara, S Gutkind, JS AF Fukuhara, S Gutkind, JS TI A new twist for the tumour suppressor hamartin SO NATURE CELL BIOLOGY LA English DT Article ID SMALL G-PROTEIN; TUBEROUS-SCLEROSIS; ERM PROTEINS; RHO; GENE; ASSOCIATION; ACTIVATION; RADIXIN; MOESIN; FAMILY AB Ezrin/radixin/moesin (ERM) proteins form crosslinks between cortical actin filaments and the plasma membrane. New findings indicate that they may also bind to the tumour-suppressor protein hamartin, thereby regulating Rho GTPases, the actin-based skeleton and cell adhesion. Loss of hamartin function disrupts cell adhesion, which may contribute to the formation of tumours in individuals carrying hamartin mutations. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Fukuhara, S (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bldg 30,30 Convent Dr, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 22 TC 2 Z9 2 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY PY 2000 VL 2 IS 5 BP E76 EP E78 PG 3 WC Cell Biology SC Cell Biology GA 313FX UT WOS:000086990600006 PM 10806489 ER PT J AU Marin, MC Jost, CA Brooks, LA Irwin, MS O'Nions, J Tidy, JA James, N McGregor, JM Harwood, CA Yulug, IG Vousden, KH Allday, MJ Gusterson, B Ikawa, S Hinds, PW Crook, T Kaelin, WG AF Marin, MC Jost, CA Brooks, LA Irwin, MS O'Nions, J Tidy, JA James, N McGregor, JM Harwood, CA Yulug, IG Vousden, KH Allday, MJ Gusterson, B Ikawa, S Hinds, PW Crook, T Kaelin, WG TI A common polymorphism acts as an intragenic modifier of mutant p53 behaviour SO NATURE GENETICS LA English DT Article ID HUMAN LUNG-CANCER; CERVICAL-CANCER; CELL-LINES; WILD-TYPE; GENE; MUTATIONS; P73; SUPPRESSION; GROWTH; RISK AB The p73 protein, a homologue of the tumour-suppressor protein p53, can activate p53-responsive promoters and induce apoptosis in p53-deficient cells. Here we report that some tumour-derived p53 mutants can bind to and inactivate p73. The binding of such mutants is influenced by whether TP53 (encoding p53) codon 72, by virtue of a common polymorphism in the human population, encodes Arg or Pro. The ability of mutant p53 to bind p73, neutralize p73-induced apoptosis and transform cells in cooperation with EJ-Ras was enhanced when codon 72 encoded Arg. We found that the Arg-containing allele was preferentially mutated and retained in squamous cell tumours arising in Arg/Pro germline heterozygotes. Thus, inactivation of p53 family members may contribute to the biological properties of a subset of p53 mutants, and a polymorphic residue within p53 affects mutant behaviour. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. London Sch Hyg & Trop Med, London WC1, England. Inst Canc Res, Sect Cell Biol & Expt Pathol, London SW3 6JB, England. Univ Sheffield, No Gen Hosp, Dept Gynecol Oncol, Sheffield S5 7AU, S Yorkshire, England. Univ Birmingham, CRC, Inst Canc Studies, Birmingham, W Midlands, England. Ctr Cutaneous Res, London, England. NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. St Marys Hosp, Imperial Coll Sci Technol & Med, Ludwig Inst Canc Res, London, England. Tohoku Univ, Inst Dev Aging & Canc, Dept Cell Biol, Sendai, Miyagi 980, Japan. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI gusterson, barry/D-3752-2009; Marin Vieira, Maria del Carmen/B-8108-2015; 井川, 俊太郎/L-5911-2015 OI Marin Vieira, Maria del Carmen/0000-0002-7149-287X; NR 49 TC 396 Z9 405 U1 1 U2 6 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 MAY PY 2000 VL 25 IS 1 BP 47 EP 54 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 311KU UT WOS:000086884000015 PM 10802655 ER PT J AU Grimm, C Wenzel, A Hafezi, F Yu, S Redmond, TM Reme, CE AF Grimm, C Wenzel, A Hafezi, F Yu, S Redmond, TM Reme, CE TI Protection of Rpe65-deficient mice identifies rhodopsin as a mediator of light-induced retinal degeneration SO NATURE GENETICS LA English DT Article ID APOPTOTIC CELL-DEATH; PHOTORECEPTOR DEGENERATION; MACULAR DEGENERATION; PIGMENT EPITHELIUM; DIFFUSIBLE FACTOR; MUTANT RHODOPSIN; TRANSGENIC MICE; BLUE-LIGHT; C-FOS; SURVIVAL AB Light-induced apoptosis of photoreceptors represents an animal model for retinal degeneration(1). Major human diseases that affect vision, such as age-related macular degeneration (AMD) and some forms of retinitis pigmentosa (RP), may be promoted by light(2-7). The receptor mediating light damage, however, has not yet been conclusively identified; candidate molecules include prostaglandin synthase(8), cytochrome oxidase(9), rhodopsin(10), and opsins of the cones and the retinal pigment epithelium(11) (PE). We exposed to bright light two groups of genetically altered mice that lack the visual pigment rhodopsin (Rpe65(-/-) and Rho(-/-)). The gene Rpe65 is specifically expressed in the PE and essential for the re-isomerization of all-trans retinol in the visual cycle and thus for the regeneration of rhodopsin after bleaching(12). Rho(-/-) mice do not express the apoprotein opsin in photoreceptors, which, consequently, do not contain rhodopsin(13). We show that photoreceptors lacking rhodopsin in these mice are completely protected against light-induced apoptosis. The transcription factor AP-1, a central element in the apoptotic response to light(14,15), is not activated in the absence of rhodopsin, indicating that rhodopsin is essential for the generation or transduction of the intracellular death signal induced by light. C1 Univ Zurich Hosp, Dept Ophthalmol, Lab Retinal Cell Biol, CH-8091 Zurich, Switzerland. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Grimm, C (reprint author), Univ Zurich Hosp, Dept Ophthalmol, Lab Retinal Cell Biol, CH-8091 Zurich, Switzerland. RI Hafezi, Farhad/A-1446-2010; OI Hafezi, Farhad/0000-0001-8935-4558; Redmond, T. Michael/0000-0002-1813-5291 NR 29 TC 170 Z9 176 U1 2 U2 11 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 MAY PY 2000 VL 25 IS 1 BP 63 EP 66 DI 10.1038/75614 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 311KU UT WOS:000086884000018 PM 10802658 ER PT J AU Stone, DL Slavotinek, R Bouffard, GG Banerjee-Basu, S Baxevanis, AD Barr, M Biesecker, LG AF Stone, DL Slavotinek, R Bouffard, GG Banerjee-Basu, S Baxevanis, AD Barr, M Biesecker, LG TI Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome SO NATURE GENETICS LA English DT Article ID CCT AB McKusick-Kaufman syndrome (MKKS, MIM 236700) is a human developmental anomaly syndrome comprising hydrometrocolpos (HMC), postaxial polydactyly (PAP) and congenital heart disease(1,2) (CHD). MKKS has been mapped in the Old Order Amish population to 20p12, between D20S162 and D20S894 (ref. 3). Here we describe the identification of a gene mutated in MKKS. We analysed the approximately 450-kb candidate region by sample sequencing, which revealed the presence of several known genes and EST clusters. We evaluated candidate transcripts by northern-blot analysis of adult and fetal tissues. We selected one transcript with widespread expression, MKKS, for analysis in a patient from the Amish pedigree and a sporadic, non-Amish case. The Old Order Amish patient was found to be homozygous for an allele that had two missense substitutions and the non-Amish patient was a compound heterozygote for a frameshift mutation predicting premature protein truncation and a distinct missense mutation. The MKKS predicted protein shows amino acid similarity to the chaperonin family of proteins, suggesting a role for protein processing in limb, cardiac and reproductive system development. We believe that this is the first description of a human disorder caused by mutations affecting a putative chaperonin molecule. C1 Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD USA. NIH Intramural Sequencing Ctr, Gaithersburg, MD USA. Univ Michigan, Med Ctr, NIH,NHGRI, Genome Technol Branch, Ann Arbor, MI USA. Univ Michigan, Med Ctr, Dept Pediat, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Obstet, Ann Arbor, MI 48109 USA. RP Biesecker, LG (reprint author), Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD USA. NR 20 TC 133 Z9 138 U1 1 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2000 VL 25 IS 1 BP 79 EP 82 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 311KU UT WOS:000086884000021 PM 10802661 ER PT J AU Restifo, NP AF Restifo, NP TI Not so Fas: Re-evaluating the mechanisms of immune privilege and tumor escape SO NATURE MEDICINE LA English DT Editorial Material ID LIGAND EXPRESSION; CD95 LIGAND; ALLOGRAFT-REJECTION; GRAFT-REJECTION; MELANOMA-CELLS; T-LYMPHOCYTES; INHIBITION; APOPTOSIS; MYOBLASTS; ISLETS AB Based on early studies, it was hypothesized that expression of Fas ligand (FasL) by tumor cells enabled them to counterattack the immune system, and that transplant rejection could be prevented by expressing FasL on transplanted organs. More recent studies have indicated that the notion of FasL as a mediator of immune privilege needed to be reconsidered, and taught a valuable lesson about making broad conclusions based on small amounts of data. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, NIH, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 31 TC 196 Z9 217 U1 0 U2 3 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 MAY PY 2000 VL 6 IS 5 BP 493 EP 495 DI 10.1038/74955 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 309YB UT WOS:000086796200018 PM 10802692 ER PT J AU Takaki, A Wiese, M Maertens, G Depla, E Seifert, U Liebetrau, A Miller, JL Manns, MP Rehermann, B AF Takaki, A Wiese, M Maertens, G Depla, E Seifert, U Liebetrau, A Miller, JL Manns, MP Rehermann, B TI Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C SO NATURE MEDICINE LA English DT Article ID T-LYMPHOCYTE RESPONSE; VIRUS-INFECTION; NONSTRUCTURAL PROTEIN-3; CELLS; CLEARANCE; MICE AB As acute hepatitis C virus (HCV) infection is clinically inapparent in most cases, the immunologic correlates of recovery are not well defined. The cellular immune response is thought to contribute to the elimination of HCV-infected cells(1) and a strong HCV-specific T-helper-cell (Th) response is associated with recovery from acute hepatitis C (ref. 2). However, diagnosis of resolved hepatitis C is based at present on the detection of HCV-specific antibodies and the absence of detectable HCV RNA, and detailed comparison of the humoral and cellular immune response has been hampered by the fact that patient cohorts as well as HCV strains are usually heterogeneous and that clinical data from acute-phase and long-term follow-up after infection generally are not available. We studied a cohort of women accidentally exposed to the same HCV strain of known sequence(3) and found that circulating HCV-specific antibodies were undetectable in many patients 18-20 years after recovery, whereas HCV-specific helper and cytotoxic T-cell responses with an interferon (IFN)-gamma-producing (Tc1) phenotype persisted. The data indicate these HCV-specific CD4(+) and CD8(+) T cells are biomarkers for a prior HCV exposure and recovery. Because of undetectable antibodies against HCV, the incidence of self-limited HCV infections and recovery may be underestimated in the general population. C1 Med Hsch Hannover, Dept Gastroenterol & Hepatol, D-30625 Hannover, Germany. Stadt Klinikum St Georg, Klin Innere Med 2, D-04129 Leipzig, Germany. Hepatitits Program, B-9052 Ghent, Belgium. NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), Med Hsch Hannover, Dept Gastroenterol & Hepatol, Carl Neuberg Str 1, D-30625 Hannover, Germany. NR 19 TC 543 Z9 555 U1 1 U2 13 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 MAY PY 2000 VL 6 IS 5 BP 578 EP 582 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 309YB UT WOS:000086796200044 PM 10802716 ER PT J AU Mize, RR Talamo, BR Schoenfeld, RI Huffman, LK Fellows, RE AF Mize, RR Talamo, BR Schoenfeld, RI Huffman, LK Fellows, RE TI Neuroscience training at the turn of the century: a summary report of the third annual ANDP survey SO NATURE NEUROSCIENCE LA English DT Editorial Material ID SCIENCE AB The claim that there are too many life sciences graduate students has generated much debate, including a recent editorial in Nature Neuroscience. A 1998 survey suggests that these concerns ave misplaced, and that career prospects for neuroscience graduates remain bright. C1 Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Cell Biol & Anat, New Orleans, LA USA. NIMH, Off Sci Policy, Bethesda, MD 20892 USA. Univ Iowa, Dept Physiol, Iowa City, IA 52242 USA. RP Talamo, BR (reprint author), Tufts Univ, Sch Med, Dept Neurosci, 136 Harrison Ave, Boston, MA 02111 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2000 VL 3 IS 5 BP 433 EP 435 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 309DG UT WOS:000086752000010 PM 10769381 ER PT J AU Tsujishita, Y Hurley, JH AF Tsujishita, Y Hurley, JH TI Structure and lipid transport mechanism of a StAR-related domain SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID ACUTE REGULATORY PROTEIN; LIPOID ADRENAL-HYPERPLASIA; LIGAND-BINDING; X-RAY; STEROIDOGENESIS; EXPRESSION; CELLS; GENE; IDENTIFICATION; PURIFICATION AB The steroidogenic acute regulatory protein (StAR) regulates acute steroidogenesis in the adrenal cortex and gonads by promoting the translocation of cholesterol to the mitochondrial inner membrane where the first step in steriod biosynthesis is catalyzed. StAR-related lipid transfer (START) domains occur in proteins involved in lipid transport and metabolism, signal transduction. and transcriptional regulation. The 2.2 Angstrom resolution crystal structure of the START domain of human MLN64 reported here reveals an alpha/beta fold built around a U-shaped incomplete beta-barrel. The interior of the protein encompasses a 26 x 12 x 11 A hydrophobic tunnel that is large enough to bind a single cholesterol molecule. The StAR and MLN64 START domains bind 1 mole of C-14 cholesterol per mole of protein in vitro. Based on the START domain structure and cholesterol binding stoichiometry, it is proposed that StAR acts by shuttling cholesterol molecules one at a time through the intermembrane space of the mitochondrion. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 43 TC 335 Z9 345 U1 1 U2 14 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAY PY 2000 VL 7 IS 5 BP 408 EP 414 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 311WH UT WOS:000086908800018 PM 10802740 ER PT J AU Pickeral, OK Li, JZ Barrow, I Boguski, MS Makalowski, W Zhang, J AF Pickeral, OK Li, JZ Barrow, I Boguski, MS Makalowski, W Zhang, J TI Classical oncogenes and tumor suppressor genes: A comparative genomics perspective SO NEOPLASIA LA English DT Article DE bioinformatics; comparative genomics; functional genomics; proteomics; Human Genome Project ID EXPRESSED SEQUENCE TAGS; SIMIAN SARCOMA-VIRUS; GROWTH-FACTOR; DATABASE; HOMOLOG; CANCER; MAP AB We have curated a reference set of cancer-related genes and reanalyzed their sequences in the light of molecular information and resources that have become available since they were first cloned, Homology studies were carried out for human oncogenes and tumor suppressors, compared with the complete proteome of the nematode, Caenorhabditis elegans, and partial proteomes of mouse and rat and the fruit fly, Drosophila melanogaster. Our results demonstrate that simple, semi-automated bioinformatics approaches to identifying putative functionally equivalent gene products in different organisms may often be misleading. An electronic supplement to this article(1) provides an Integrated view of our comparative genomics analysis as well as mapping data, physical cDNA resources and links to published literature and reviews, thus creating a "window" into the genomes of humans and other organisms for cancer biology. C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD USA. NIH, Genome Technol Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM boguski@ncbi.nim.nih.gov RI Makalowski, Wojciech/I-2843-2016 NR 23 TC 8 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1476-5586 J9 NEOPLASIA JI Neoplasia PD MAY-JUN PY 2000 VL 2 IS 3 BP 280 EP 286 PG 7 WC Oncology SC Oncology GA 320KZ UT WOS:000087401500011 PM 10935514 ER PT J AU Haxby, JV Petit, L Ungerleider, LG Courtney, SM AF Haxby, JV Petit, L Ungerleider, LG Courtney, SM TI Distinguishing the functional roles of multiple regions in distributed neural systems for visual working memory SO NEUROIMAGE LA English DT Reprint ID POSITRON EMISSION TOMOGRAPHY; PRIMATE PREFRONTAL CORTEX; SUSTAINED ACTIVITY; FRONTAL-CORTEX; MEDIAL WALL; OBJECT; PET; ACTIVATION; LOCATION; HUMANS AB We have investigated the human neural systems for visual working memory using functional magnetic resonance imaging to distinguish sustained activity during memory delays from transient responses related to perceptual and motor operations. These studies have identified six distinct frontal regions that demonstrate sustained activity during memory delays. These regions could be distinguished from brain regions in extrastriate cortex that participate more in perception and from brain regions in medial and lateral frontal cortex that participate more in motor control. Moreover, the working memory regions could be distinguished from each other based on the relative strength of their participation in spatial and face working memory and on the relative strength of sustained activity during memory delays versus transient activity related to stimulus presentation. These results demonstrate that visual working memory performance involves the concerted activity of multiple regions in a widely distributed system. Distinctions between functions, such as perception versus memory maintenance, or spatial versus face working memory, are a matter of the degree of participation of different regions, not the discrete parcellation of different functions to different modules. (C) 2000 Academic Press. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Psychol, Baltimore, MD 21218 USA. Grp Imagerie Neurofonctionnelle, F-14074 Caen, France. RP Haxby, JV (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RI GINSPAN, All/B-8714-2008; Petit, Laurent/D-6583-2011 OI Petit, Laurent/0000-0003-2499-5367 NR 35 TC 142 Z9 145 U1 1 U2 13 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 2000 VL 11 IS 5 BP 380 EP 391 DI 10.1006/nimg.2000.0592 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 318EG UT WOS:000087270500005 PM 10806025 ER PT J AU Sadato, N Ibanez, V Deiber, MP Hallett, M AF Sadato, N Ibanez, V Deiber, MP Hallett, M TI Gender difference in premotor activity during active tactile discrimination SO NEUROIMAGE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; SEX-DIFFERENCES; WORKING-MEMORY; HUMAN-BRAIN; CORTICOSPINAL PROJECTIONS; GONADAL-HORMONES; MACAQUE MONKEYS; FRONTAL-LOBE; MOTOR AREAS; PET IMAGES AB To investigate possible gender differences in tactile discrimination tasks, we measured cerebral blood flow of seven men and seven women using positron emission tomography and O-15 water during tactile tasks performed with the right index finger. A nondiscrimination, somatosensory control task activated the left primary sensorimotor cortex and the left parietal operculum extending to the posterior insula without any gender difference. Compared with the control task, discrimination tasks activated the superior and inferior parietal lobules bilaterally, right dorsal premotor cortex, and dorsolateral prefrontal cortex in both genders, consistent with the motion of right hemisphere involvement during exploratory attentional movements. In both genders, symmetric activation of the superior and inferior parietal lobules and asymmetric activation of the right dorsolateral prefrontal cortex were confirmed. The former is consistent with the spatial representation of the tactile input and the latter with the spatial working memory. However, activation of the dorsal premotor cortex was asymmetric in men, whereas it was symmetric in women, the gender difference being statistically significant. This may suggest gender differences in motor programs for exploration in manipulospatial tasks such as tactile discrimination with active touch, possibly by greater interhemispheric interaction through the dorsal premotor cortices in women than in men. (C) 2000 Academic Press. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20892 USA. Fukui Med Univ, Biomed Imaging Res Ctr, Fukui, Japan. Natl Inst Physiol Sci, Dept Cerebral Res, Okazaki, Aichi 444, Japan. Univ Hosp Bel Air, Geneva, Switzerland. Univ Geneva, Fac Psychol & Sci Educ, Geneva, Switzerland. RP Sadato, N (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RI Deiber, Marie-Pierre/M-5949-2014 NR 61 TC 29 Z9 30 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 2000 VL 11 IS 5 BP 532 EP 540 DI 10.1006/nimg.2000.0566 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 318EG UT WOS:000087270500018 PM 10806038 ER PT J AU DeGraba, TJ Pettigrew, LC AF DeGraba, TJ Pettigrew, LC TI Why do neuroprotective drugs work in animals but not humans? SO NEUROLOGIC CLINICS LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; CALCIUM-CALMODULIN BINDING; NIH STROKE SCALE; MAGNETIC-RESONANCE; NEOCORTICAL INFARCTION; RANDOMIZED TRIAL; ARTERY OCCLUSION; NEURONAL DAMAGE; BRAIN ISCHEMIA; HUMAN-DISEASE AB Many neuroprotective agents that seemed promising in animal studies of ischemic brain injury prove to have no effect when tested in clinical trials, suggesting that fundamental elements of translational research require better definition. A number of modifications have led to improvements in preclinical and human studies since the earliest controlled trials failed to confirm hypotheses suggested by animal data. Continued re-evaluation and sharing of information derived from the laboratory bench or the patient's bedside should eventually lead to effective neuroprotection in acute stroke. Experimental data should be carefully studied to improve the quality of agents coming to clinical trials and to design trial phasing that effectively determines drug safety and efficacy. This article will examine preclinical modeling and its translation to prospective studies of acute stroke therapy and will focus on some potential solutions directed at clinical trial design. C1 Univ Kentucky, Sanders Brown Ctr Aging, Stroke Program, Coll Med, Lexington, KY 40536 USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Univ Kentucky, Sanders Brown Ctr Aging, Stroke Program, Coll Med, 101 Sanders Brown Bldg, Lexington, KY 40536 USA. EM cpettigrew@aging.coa.uky.edu NR 86 TC 70 Z9 79 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8619 EI 1557-9875 J9 NEUROL CLIN JI Neurol. Clin. PD MAY PY 2000 VL 18 IS 2 BP 475 EP + DI 10.1016/S0733-8619(05)70203-6 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 317WR UT WOS:000087250400013 PM 10757837 ER PT J AU Grimm, JW See, RE AF Grimm, JW See, RE TI Dissociation of primary and secondary reward-relevant limbic nuclei in an animal model of relapse SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE basolateral amygdala; cocaine; nucleus accumbens; relapse; reward; self-administration ID COCAINE-SEEKING BEHAVIOR; CONDITIONED PLACE PREFERENCE; SELF-ADMINISTERED COCAINE; BASOLATERAL AMYGDALA; FUNCTIONAL ABLATION; EXCITOTOXIC LESIONS; 2ND-ORDER SCHEDULE; PREFRONTAL CORTEX; CAUDATE-NUCLEUS; D-AMPHETAMINE AB The neural substrates underlying relapse to drug-seeking behavior after chronic drug abuse may differ from those underlying immediate drug-taking behavior. In a model of relapse to drug-seeking behavior following chronic cocaine self-administration and prolonged extinction, we have previously shown that rats will significantly reinstate lever responding for either primary reward (cocaine) or secondary reward (tone + light stimulus previously paired with cocaine). In the present study, we utilized reversible inactivation of discrete brain nuclei with tetrodotoxin (TTX) in order to examine the neural substrates mediating primary and secondary cocaine reward in rats allowed two weeks of cocaine self-administration. After one week of daily extinction sessions, bilateral inactivation of the basolateral amygdala resulted in significant attenuation of lever pressing for a cocaine-conditioned reward (tone + light). Following three more days of extinction, bilateral TTX inactivation of the basolateral amygdala had no effect on the reinstatement of cocaine self-administration. In contrast, TTX inactivation of the nucleus accumbens produced the exact opposite effects, with significant blockade of primary reward (cocaine alone), but not secondary reward (tone + light). Thus, cocaine-conditioned reward is neuroanatomically dissociated from primary cocaine reward. Published by Elsevier Science Inc. C1 Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP See, RE (reprint author), Med Univ S Carolina, Dept Physiol & Neurosci, 167 Ashley Ave,Suite 614, Charleston, SC 29425 USA. FU NIDA NIH HHS [DA-10462] NR 43 TC 158 Z9 161 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2000 VL 22 IS 5 BP 473 EP 479 DI 10.1016/S0893-133X(99)00157-8 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 298FZ UT WOS:000086129800003 PM 10731622 ER PT J AU Adler, CM Elman, I Weisenfeld, N Kestler, L Pickar, D Breier, A AF Adler, CM Elman, I Weisenfeld, N Kestler, L Pickar, D Breier, A TI Effects of acute metabolic stress on striatal dopamine release in healthy volunteers SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE 2-deoxyglucose; glucoprivation; striatum; dopamine; raclopride; PET ID CEREBRAL BLOOD-FLOW; PLASMA HOMOVANILLIC-ACID; C-11 RACLOPRIDE BINDING; EXCITATORY AMINO-ACIDS; PREFRONTAL CORTEX; AXIS ACTIVATION; MENTAL STRESS; LIFE EVENTS; SCHIZOPHRENIA; HYPOGLYCEMIA AB Several lines of evidence indicate that a variety of metabolic stressors, including acute glucose deprivation are associated with dopamine release. Pharmacologic doses of the glucose analogue, 2-deoxyglucose (2DG) cause acute glucoprivation and are associated with enhanced dopamine turnover in preclinical studies. In this study, we utilized [C-11]raclopride PET to examine 2DG-induced striatal dopamine release in healthy volunteers. Six healthy volunteers underwent PET scans involving assessment of 2DG-induced (40 mg/kg) decrements in striatal binding of the D-2/D-3 receptor radioligand [C-11]raclopride. Decreases in [C-11]raclopride specific binding reflect 2DG-induced changes in synaptic dopamine. Specific binding significantly decreased following 2DG administration, reflecting enhanced synaptic dopamine concentrations (p = .02). The administration of 2DG is associated with significant striatal dopamine release in healthy volunteers. Implications of these data for investigations of the role of stress in psychiatric disorders are discussed. Published by Elsevier Science Inc. C1 NIMH, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Lilly Res Labs, Indianapolis, IN USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46204 USA. RP Adler, CM (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, 231 Bethesda Ave, Cincinnati, OH 45267 USA. NR 44 TC 52 Z9 52 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2000 VL 22 IS 5 BP 545 EP 550 DI 10.1016/S0893-133X(99)00153-0 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 298FZ UT WOS:000086129800011 PM 10731630 ER PT J AU Adams, GP Shaller, CC Chappell, LL Wu, C Horak, EM Simmons, HH Litwin, S Marks, JD Weiner, LM Brechbiel, MW AF Adams, GP Shaller, CC Chappell, LL Wu, C Horak, EM Simmons, HH Litwin, S Marks, JD Weiner, LM Brechbiel, MW TI Delivery of the alpha-emitting radioisotope bismuth-213 to solid tumors via single-chain Fv and diabody molecules SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE alpha particles; single-chain Fv; diabody; radioimmunotherapy; solid tumors ID B-CELL LYMPHOMA; MONOCLONAL-ANTIBODY; IN-VIVO; RADIOIMMUNOTHERAPY; THERAPY; FRAGMENTS; PROTEIN; LYSINE; BI-213; MICE AB Intravenously administered anti-tumor single-chain Fv (scFv) and diabody molecules exhibit rapid clearance kinetics and accumulation in tumors that express their cognate antigen. In an attempt to fit the rate of isotope decay to the timing of delivery and duration of tumor retention, anti-HER2/neu CHX-A" DTPA-C6.5K-A scFv and diabody conjugates were labeled with the alpha-particle emitter Bi-213 (t(1/2) = 47 min). Radioimmunotherapy studies employing 0.64, 0.35, or 0.15 mu Ci of Bi-213-labeled C6.5K-A diabody or 1.1, 0.6, or 0.3 mu Ci of Bi-213-labeled C6.5K-A scFv were performed in nude mice bearing early, established SK-OV-3 rumors. Only the 0.3 mu Ci dose of Bi-213-labeled C6.5K-A scFv resulted in both acceptable toxicity and a reduction in tumor growth rate. The specificity of the anti-tumor effects was determined by comparing the efficacy of treatment with 0.3 and 0.15 mu Ci doses of Bi-213-labeled C6.5K-A scFv and Bi-213-labeled NM3E2 (an irrelevant scFv) in nude mice bearing large established tumors. The 0.3 mu Ci dose of Bi-213 On both the C6.5K-A and NM3E2 scFvs resulted in similar anti-tumor effects (p = 0.46) indicating that antigen-specific targeting was not a factor. This suggests that the physical half-life of Bi-213 may be too brief to be effectively paired with systemically-administered diabody or scFv molecules. NUCL MED BIOL 27;4: 339-346, 2000. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Anesthesiol & Pharmaceut Chem, San Francisco, CA 94143 USA. RP Adams, GP (reprint author), Fox Chase Canc Ctr, Dept Med Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. FU NCI NIH HHS [CA65559] NR 38 TC 63 Z9 65 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 2000 VL 27 IS 4 BP 339 EP 346 DI 10.1016/S0969-8051(00)00103-7 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 345PG UT WOS:000088823900003 PM 10938467 ER PT J AU Kaludov, NK Wolffe, AP AF Kaludov, NK Wolffe, AP TI MeCP2 driven transcriptional repression in vitro: selectivity for methylated DNA, action at a distance and contacts with the basal transcription machinery SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HISTONE DEACETYLASE COMPLEX; BINDING-PROTEIN MECP2; CHROMATIN STRUCTURE; COOPERATIVE BINDING; CPG METHYLATION; RNA GENE; DOMAIN; COREPRESSOR; INVITRO; TFIIB AB The pathways for selective transcriptional repression of methylated DNA templates by the methyl-CpG-binding protein MeCP2 have been investigated using a purified in vitro transcription system that does not assemble chromatin. MeCP2 selectively inhibits transcription complex assembly on methylated DNA but does not destabilize a pre-assembled transcription complex. MeCP2 functions to repress transcription at a distance of >500 bp from the transcription start site. The transcription repression domain (TRD) of MeCP2 will repress transcription in vitro when fused to a heterologous Gal4 DNA-binding domain. The TRD associates with TFIIB, Exogenous TFIIB does not relieve transcriptional repression established by either intact MeCP2 or a Gal4-TRD fusion protein under these in vitro conditions, nor does the addition of histone deacetylase inhibitors. We find that the transcriptional repression established by both MeCP2 and the Gal4-TRD fusion protein in vitro also correlates with selective assembly of large nucleoprotein complexes. The formation of such complexes reflects a local concentration of DNA-bound transcriptional repressor that may stabilize a state of repression even in the presence of exogenous transcriptional machinery. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. NR 43 TC 92 Z9 97 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 MAY 1 PY 2000 VL 28 IS 9 BP 1921 EP 1928 DI 10.1093/nar/28.9.1921 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 310RY UT WOS:000086842200011 PM 10756192 ER PT J AU Grady, PA AF Grady, PA TI News from NINR SO NURSING OUTLOOK LA English DT News Item C1 NINR, NIH, Bethesda, MD 20892 USA. RP Grady, PA (reprint author), NINR, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD MAY-JUN PY 2000 VL 48 IS 3 BP 127 EP 127 PG 1 WC Nursing SC Nursing GA 330YU UT WOS:000087989900009 ER PT J AU Filozof, CM Murua, C Sanchez, MP Brailovsky, C Perman, M Gonzalez, CD Ravussin, E AF Filozof, CM Murua, C Sanchez, MP Brailovsky, C Perman, M Gonzalez, CD Ravussin, E TI Low plasma leptin concentration and low rates of fat oxidation in weight-stable post-obese subjects SO OBESITY RESEARCH LA English DT Article DE post-obese; resting metabolic rate; fat oxidation; leptin; risk factors for body weight gain ID ENERGY-EXPENDITURE; PHYSICAL-ACTIVITY; SERUM LEPTIN; OB/OB MICE; HUMANS; GAIN; METABOLISM; CHILDREN; WOMEN; GENE AB Objective: A low resting metabolic rate for a given body size and composition, a low rate of fat oxidation, low levels of physical activity, and low plasma leptin concentrations are all risk factors for body weight gain. The aim of the present investigation was to compare resting metabolic rate (RMR), respiratory quotient (RQ), levels of physical activity, and plasma leptin concentrations in eight post-obese adults (2 males and 6 females; 48.9 +/- 12.2 years; body mass index [BMI]: 24.5 +/- 1.0 kg/m(2); body fat 33 +/- 5%; mean +/- SD) who lost 27.1 +/- 21.3 kg (16 to 79 kg) and had maintained this weight loss for greater than or equal to 2 months (2 to 9 months) to eight age- and BMI-matched control never-obese subjects (1 male and 7 females; 49.1 +/- 5.2 years; BMI 24.4 +/- 1.0 kg/m2; body fat 33 +/- 7%). Research Methods and Procedures: Following 3 days of weight maintenance diet (50% carbohydrate and 30% fat), RMR and RQ were measured after a 10-hour fast using indirect calorimetry and plasma leptin concentrations were measured using radioimmunoassay. Levels of physical activity were estimated using an accelerometer over a 48-hour period in free living conditions. Results: After adjustment for fat mass and fat-free mass, post-obese subjects had, compared with controls, similar levels of physical activity (4185 +/- 205 vs. 4295 +/- 204 counts) and similar RMR (1383 +/- 268 vs. 1430 +/- 104 kcal/day) but higher RQ (0.86 +/- 0.04 vs. 0.81 +/- 0.03, p < 0.05). Leptin concentration correlated positively with percent body fat (r = 0.57, p < 0.05) and, after adjusting for fat mass and fat-free mass, was lower in post-obese than in control subjects (4.5 +/- 2.1 vs. 11.6 +/- 7.9 ng/mL, p < 0.05). Discussion: The low fat oxidation and low plasma leptin concentrations observed in post-obese individuals may, in part, explain their propensity to relapse. C1 Hosp Italiano Buenos Aires, Cardiol Unit, Buenos Aires, DF, Argentina. Ctr Nutr Enfermedades Metab, Buenos Aires, DF, Argentina. Univ Buenos Aires, Dept Pharmacol, Buenos Aires, DF, Argentina. NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Filozof, CM (reprint author), Ciudad de la Paz 1461,PB 1, RA-1426 Buenos Aires, DF, Argentina. NR 42 TC 44 Z9 46 U1 1 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD MAY PY 2000 VL 8 IS 3 BP 205 EP 210 DI 10.1038/oby.2000.23 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 315WC UT WOS:000087135100001 PM 10832762 ER PT J AU Elkas, J Armstrong, A Pohl, J Cuttitta, F Martinez, A Gray, K AF Elkas, J Armstrong, A Pohl, J Cuttitta, F Martinez, A Gray, K TI Modulation of endometrial steroid receptors and growth regulatory genes by tamoxifen SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; REPRODUCTIVE-TRACT; ADRENOMEDULLIN; EXPRESSION; PROTEIN AB Objective: We investigated tamoxifen's effects on the expression of growth regulatory genes in the endometrium to identify the mechanism by which tamoxifen induces proliferation. Methods: Using immunohistochemical techniques, we analyzed 39 endometrial specimens for expression of Ki-67, lactoferrin, transforming growth factor-alpha, tumor necrosis factor receptor-II, adrenomedullin, estrogen receptors, and progesterone receptors. Twenty specimens were obtained from postmenopausal breast cancer patients treated with tamoxifen (20 mg/day) for at least 6 months to include two endometrial adenocarcinoma specimens. Five secretory phase, three proliferative phase, and seven atrophic endometrial specimens were used as controls. In addition, four endometrial adenocarcinoma specimens were reviewed from patients not treated with tamoxifen. Intensity of immunostaining was quantified using digitized imaging techniques. Results: Overexpression of both estrogen receptors and progesterone receptors, and an elevated proliferative index were the most consistent effects observed in benign endometrial specimens from tamoxifen-treated patients compared with atrophic controls (P <.003). This staining pattern was also evident in adenocarcinomas from patients who received tamoxifen. Benign endometrium from tamoxifen-treated patients also expressed transforming growth factor-alpha, tumor necrosis factor receptor-II, lactoferrin, and adrenomedullin at levels comparable with those found in proliferative endometrial specimens. Conclusion: These data provide further documentation that the uterotropic effects of tamoxifen may be due, at least in part, to the induction of estrogen receptors and progesterone receptors, as well as other genes associated with the proliferative phase. Furthermore, analysis of estrogen receptors, progesterone receptors, and Ki-67 may be useful in identifying postmenopausal individuals on tamoxifen, who are at increased risk for developing endometrial cancer. (Obstet Gynecol 2000;95:697-703.). C1 Natl Naval Med Ctr, Dept Obstet & Gynecol, Bethesda, MD USA. Walter Reed Army Med Ctr, Dept Obstet & Gynecol, Washington, DC 20307 USA. NCI, Dept Cell & Canc Biol, NIH, Rockville, MD USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. RP Elkas, J (reprint author), 817 10th St,Unit 103, Santa Monica, CA 90403 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 11 TC 27 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2000 VL 95 IS 5 BP 697 EP 703 DI 10.1016/S0029-7844(99)00660-2 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 307HW UT WOS:000086648700013 PM 10775732 ER PT J AU Monaghan, SC Little, RE Hulchiy, O Strassner, H Gladen, BC AF Monaghan, SC Little, RE Hulchiy, O Strassner, H Gladen, BC TI Preterm birth in two urban areas of Ukraine SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID DELIVERY AB Objective: To determine whether the preterm birth rate was elevated in two urban areas of Ukraine, a former eastern bloc country that experienced serious economic, social, and health problems during its transition from a socialist republic. Methods: We identified every pregnancy in a defined period in two urban sites where a separate study of pregnancy and childhood was being conducted. We obtained gestational age and vital status at delivery for each. Information about onset of labor and conduct of delivery was available for the subgroup enrolled in the collaborating study. Results: Among 17,137 pregnancies, all but 6774 were terminated voluntarily. Among the continuing pregnancies, the preterm birth rate was 6.6% for live-born singletons of 20 or more weeks' gestation. Only 12% of preterm births involved medical, intervention, the rest were idiopathic. The preterm birth rate was higher than in Europe (4.0% to 5.4%) and Canada (5.9%) but lower than for whites in the United States (8.4%). Conclusion: Live-born preterm birth rates are influenced by whether infants survive to be included in calculations. The high fetal mortality rate in Ukraine causes many preterm births to be excluded, thus lowering the rate. Frequent pregnancy termination and lack of ultrasound dating in Ukraine also might cause the preterm birth rate to be lower. Preterm birth rates, especially among live-born infants, are difficult to interpret and treacherous to compare across nations. Survival of the fetus and its health and development at birth are better indicators of reproductive outcome. (C) 2000 by The American College of Obstetricians and Gynecologists. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Illinois, Sch Publ Hlth, Chicago, IL USA. Natl Med Univ, Kyiv, Ukraine. Rush Med Ctr, Chicago, IL USA. RP Little, RE (reprint author), NIEHS, A3-05,Box 12233, Res Triangle Pk, NC 27709 USA. NR 15 TC 11 Z9 11 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2000 VL 95 IS 5 BP 752 EP 755 DI 10.1016/S0029-7844(99)00630-4 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 307HW UT WOS:000086648700023 PM 10775742 ER PT J AU Berrigan, D AF Berrigan, D TI Correlations between measures of thermal stress resistance within and between species SO OIKOS LA English DT Article ID DROSOPHILA-MELANOGASTER; HEAT; SELECTION; TEMPERATURES AB Resistance to an environmental stress such as elevated temperature can almost always be measured in several different ways. A number of recent studies in Drosophila show that lethal and non-lethal measures of resistance to heat stress are genetically independent. In contrast, data reported here suggest that there are interspecific correlations between measures of thermal stress resistance. Together, these results show that studies of intraspecific variation in stress resistance must demonstrate the ecological relevance of the measures of stress resistance chosen for study. In contrast, interspecific comparisons could be based on any of several measures of resistance. It would he interesting to determine if this pattern holds for resistance to other major environmental stresses. C1 Univ Washington, Dept Zool, Seattle, WA 98195 USA. RP Berrigan, D (reprint author), NCI, 6120 Execut Blvd MSC 7105, Bethesda, MD 20892 USA. NR 17 TC 25 Z9 25 U1 3 U2 9 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0030-1299 J9 OIKOS JI Oikos PD MAY PY 2000 VL 89 IS 2 BP 301 EP 304 DI 10.1034/j.1600-0706.2000.890211.x PG 4 WC Ecology SC Environmental Sciences & Ecology GA 312ZH UT WOS:000086973500011 ER PT J AU Walsh, TJ Wayne, AS AF Walsh, TJ Wayne, AS TI Management of infections in patients with acute leukemia - The article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID ALLOGENEIC BONE-MARROW; RISK-FACTORS; DONOR; QUINUPRISTIN/DALFOPRISTIN; TRANSPLANTATION; VANCOMYCIN; RECIPIENTS C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 2000 VL 14 IS 5 BP 676 EP 677 PG 2 WC Oncology SC Oncology GA 368QN UT WOS:000090129200014 ER PT J AU Coleman, CN AF Coleman, CN TI Biological basis of radiation sensitivity Part 2: Cellular and molecular determinants of radiosensitivity - Reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 NCI, Sci Program, NIH, Bethesda, MD 20892 USA. RP Coleman, CN (reprint author), NCI, Sci Program, NIH, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 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 MAY PY 2000 VL 14 IS 5 BP 757 EP + PG 3 WC Oncology SC Oncology GA 368QN UT WOS:000090129200024 ER PT J AU Carlsson, J Neuzner, J Rosenberg, YD AF Carlsson, J Neuzner, J Rosenberg, YD TI Therapy of atrial fibrillation: Rhythm control versus rate control SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Review ID RADIOFREQUENCY CATHETER MODIFICATION; LEFT-VENTRICULAR FUNCTION; IDIOPATHIC DILATED CARDIOMYOPATHY; CURRENT ELECTRICAL CARDIOVERSION; ANTIARRHYTHMIC DRUG-THERAPY; ADVANCED HEART-FAILURE; QUALITY-OF-LIFE; SINUS RHYTHM; ATRIOVENTRICULAR JUNCTION; PHARMACOLOGICAL THERAPY C1 Kerckhoff Klin GmbH, Dept Cardiol, D-61231 Bad Nauheim, Germany. NHLBI, Bethesda, MD 20892 USA. RP Carlsson, J (reprint author), Kerckhoff Klin GmbH, Dept Cardiol, Benekestr 2-8, D-61231 Bad Nauheim, Germany. NR 108 TC 14 Z9 15 U1 0 U2 1 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD MAY PY 2000 VL 23 IS 5 BP 891 EP 903 DI 10.1111/j.1540-8159.2000.tb00861.x PG 13 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 316KH UT WOS:000087165700015 PM 10833712 ER PT J AU Lawrence, N Stowers, A Mann, V Taylor, D Saul, A AF Lawrence, N Stowers, A Mann, V Taylor, D Saul, A TI Recombinant chimeric proteins generated from conserved regions of Plasmodium falciparum merozoite surface protein 2 generate antiparasite humoral responses in mice SO PARASITE IMMUNOLOGY LA English DT Article DE Plasmodium falciparum; merozoite surface proteins; recombinant chimeric proteins; epitope mapping; T-helper epitopes ID MONOCLONAL-ANTIBODIES; ANTIGEN MSA2; MALARIA; GLYCOPROTEIN; EPITOPE AB The merozoite surface protein 2 of P. falciparum is highly polymorphic in nature, but has regions of almost complete conservation at its N- and C-termini. We produced a chimeric recombinant protein comprising these regions only (hereafter termed NC). Mice immunized with the NC antigen produce antibodies at levels comparable to those immunized with 1624, a full-length recombinant protein representing MSP2 from P. falciparum. Antisera raised against NC recognized P. falciparum schizonts by IFA and a P. falciparum protein of M-r 45 kDa by Western blot. However, antibody specificities were observed to differ between anti-NC and anti-1624 sera, and this resulted in differences in parasite recognition, despite similar levels of antibodies having been produced. The response to the NC antigen was also shown to be restricted in some mice (H2-d), but this was overcome by including appropriate T-cell help, which was accomplished by creating recombinant protein chimeras that contained NC and T-helper epitopes from Tetanus toxoid, or MSP1(19) from P. berghei. C1 Queensland Inst Med Res, Australian Ctr Int & Trop Hlth & Nutr, Brisbane, Qld 4029, Australia. Univ Queensland, PO Royal Brisbane Hosp, Brisbane, Qld 4029, Australia. Queensland Inst Med Res, CRC Vaccine Technol, Brisbane, Qld 4029, Australia. QIAGEN Pty Ltd, Clifton Hill, Vic 3068, Australia. NIAID, Malaria Vaccines Sect, LPD, NIH, Bethesda, MD 20892 USA. Tulane Univ, Med Ctr, Dept Trop Med, New Orleans, LA 70112 USA. RP Lawrence, N (reprint author), Queensland Inst Med Res, Australian Ctr Int & Trop Hlth & Nutr, PO Royal Brisbane Hosp, Brisbane, Qld 4029, Australia. RI Saul, Allan/I-6968-2013; Lawrence, Nicole/A-5573-2017 OI Saul, Allan/0000-0003-0665-4091; Lawrence, Nicole/0000-0002-9013-1770 NR 23 TC 10 Z9 10 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD MAY PY 2000 VL 22 IS 5 BP 211 EP 221 DI 10.1046/j.1365-3024.2000.00293.x PG 11 WC Immunology; Parasitology SC Immunology; Parasitology GA 313CJ UT WOS:000086981700001 PM 10792760 ER PT J AU Hanson, JW Thomson, EJ AF Hanson, JW Thomson, EJ TI Genetic testing in children: Ethical and social points to consider SO PEDIATRIC ANNALS LA English DT Article ID HUMAN-GENOME-PROJECT; FOLLOW-UP CARE; INHERITED PREDISPOSITION; INFORMED CONSENT; CANCER; RECOMMENDATIONS; DISCRIMINATION; INDIVIDUALS; DISCOVERY AB Recent advances in human genetics have raised a new set of issues for health care professionals to consider. The authors review the differences between diagnostic and screening genetic tests and other medical procedures and discuss the ethical and social concerns surrounding genetic testing in children. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Hanson, JW (reprint author), Clin & Genet Epidemiol Res Branch, Epidemiol & Genet Res Program, Execut Plaza S,Room 214,6120 Execut Blvd, Bethesda, MD 20892 USA. NR 32 TC 11 Z9 11 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD MAY PY 2000 VL 29 IS 5 BP 285 EP + PG 8 WC Pediatrics SC Pediatrics GA 313JR UT WOS:000086997000008 PM 10826323 ER PT J AU Izevbigie, EB Gutkind, JS Ray, PE AF Izevbigie, EB Gutkind, JS Ray, PE TI Angiotensin II and basic fibroblast growth factor mitogenic pathways in human fetal mesangial cells SO PEDIATRIC RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Pediatric-Society/Society-for-Pediatric-Research CY MAY 01-04, 1999 CL SAN FRANCISCO, CALIFORNIA SP Amer Pediat Soc, Soc Pediat Res ID SMOOTH-MUSCLE CELLS; ACTIVATED PROTEIN-KINASE; CYCLIC ADENOSINE-MONOPHOSPHATE; ADRENERGIC-RECEPTORS; HYPERTENSIVE RATS; CAMP; INHIBITION; PROLIFERATION; EXPRESSION; CASCADE AB Angiotensin II (Ang II) and basic fibroblast growth factor (bFGF/FGF-2) play relevant roles in renal development. Since the signaling pathways modulating the mitogenic effects of Ang LI and bFGF in human fetal mesangial cells (HFMc) are not clearly defined, we carried out experiments to determine whether they would exert their mitogenic effects by modulating the activity of the mitogen-activated protein kinases (MAPK) [extracellular signal-regulated kinase-2 (ERK-2)] and cAMP signaling pathways. In confluent HFMc, bFGF (20 ng/mL) induced a significant 4-fold increase in ERK-2 activity and [H-3]-thymidine incorporation (6-fold). In contrast, under similar tissue culture conditions, Ang II (10(-6) M) induced a more modest increase in ERK-2 activity (2-fold) and [H-3]-thymidine incorporation (35 +/- 4%). The mitogen-activated protein kinase kinase-l (MEK-1) inhibitor PD098059 (25 mu M) almost completely abolished the bFGF-induced proliferation in HFMc but did not significantly affect Ang II proliferative effects, In the presence of the cAMP elevating agent isoproterenol, Ang II and bFGF induced opposite changes in cAMP accumulation and cell growth. Isoproterenol inhibited the basal and bFGF-induced proliferation of HFMc through a MEK-1/2-independent pathway that included the accumulation of cAMP, In contrast, isoproterenol increased Ang II mitogenic effects in correlation with a reduction in cAMP accumulation. We conclude that Ang II and bFGF modulate the proliferation of HFMc through the stimulation of different MEK-1/2-dependent and independent signaling pathways. Activation of MEK-1/2 is required but not sufficient fur mitogenesis in HFMc. The accumulation of cAMP in HFMc counteracts the mitogenic effects of bFGF by a MEK-1/1-independent pathway. C1 Childrens Res Inst, Childrens Natl Med Ctr, Ctr Mol Physiol Res, Washington, DC 20010 USA. NIDR, Oral & Pharyngeal Canc Brach Program, NIH, Bethesda, MD 20892 USA. RP Ray, PE (reprint author), Childrens Res Inst, Childrens Natl Med Ctr, Ctr Mol Physiol Res, Room R-211,111 Michigan Ave NW, Washington, DC 20010 USA. RI Gutkind, J. Silvio/A-1053-2009 FU NHLBI NIH HHS [R0-1HL 55605]; NIDDK NIH HHS [DK49419-S1, R0-1DK 4919] NR 52 TC 16 Z9 16 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 2000 VL 47 IS 5 BP 614 EP 621 DI 10.1203/00006450-200005000-00010 PG 8 WC Pediatrics SC Pediatrics GA 310CA UT WOS:000086807900010 PM 10813586 ER PT J AU Casibang, M Moody, TW AF Casibang, M Moody, TW TI (Tyr(0),Bpa(4))bombesin is a GRP receptor agonist SO PEPTIDES LA English DT Article DE receptor binding; GRP receptor; cytosolic calcium; c-fos mRNA ID CELL LUNG-CANCER; GASTRIN-RELEASING PEPTIDE; BOMBESIN-LIKE PEPTIDES; SWISS 3T3 CELLS; P NK-1 RECEPTOR; SUBSTANCE-P; GROWTH-FACTORS; CROSS-LINKING; NEUROMEDIN-B; IDENTIFICATION AB (Tyr(0),Bpa(4))bombesin, (YB)BB was synthesized and its biologic activity evaluated using T47D breast cancer cells. (I-125-Tyr(0),Bpa(4))BB bound with high affinity (K-d = 5 nM) to T47D cells. Specific (I-125-Tyr(0),Bpa(4))BB binding was inhibited with high affinity by BB, BW2258U89, GRP, GRP(14-27) and NMB (IC50 values of 10, 2, 15, 20, and 150 nM)but not GRP(1-16) (IC50 value of > 1000 nM). (I-125-Tyr(0),Bpa(4))BB bound to the surface of T47D cells at 4 degrees C but was internalized at 37 degrees C. After binding at 4 degrees C followed by irradiation using ultraviolet light, (I-125-Tyr(0),Bpa(4))BB labeled a 75 kDa protein using T47D cells. (Tyr(0),Bpa(4))BB, 10 nM, elevated cytosolic calcium using T47D cells within 10 s. Also (Tyr(0),Bpa(4))BB, 10 nM, elevated c-fos mRNA after 45 min. These results indicate that (Tyr(0),Bpa(4))BB is an agonist for GRP receptors. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NCI, Cell & Canc Biol Dept, Med Branch, Rockville, MD 20850 USA. RP Casibang, M (reprint author), NCI, Cell & Canc Biol Dept, Med Branch, Bldg KWC,Rm 300,9610 Med Ctr Dr, Rockville, MD 20850 USA. NR 30 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD MAY PY 2000 VL 21 IS 5 BP 649 EP 653 DI 10.1016/S0196-9781(00)00198-4 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 330AW UT WOS:000087941500007 PM 10876047 ER PT J AU Hope, PJ Turnbull, H Farr, S Morley, JE Rice, KC Chrousos, GP Torpy, DJ Wittert, GA AF Hope, PJ Turnbull, H Farr, S Morley, JE Rice, KC Chrousos, GP Torpy, DJ Wittert, GA TI Peripheral administration of CRF and urocortin: effects on food intake and the HPA axis in the marsupial Sminthopsis crassicaudata SO PEPTIDES LA English DT Article DE urocortin; corticotrophin-releasing factor; antalarmin; marsupial; Sminthopsis crassicaudata; cortisol; CRF receptor ID CORTICOTROPIN-RELEASING-FACTOR; FACTOR-RECEPTOR; UROTENSIN-I; FUNCTIONAL EXPRESSION; NERVOUS-SYSTEM; HIGH-AFFINITY; RAT-BRAIN; HORMONE; ANTAGONIST; MICE AB The hypothalamic peptides corticotrophin releasing factor (CRF) and urocortin (UCN) decrease food intake and increase energy expenditure when administered either centrally or peripherally to rodents. The effects of CRF and UCN on food intake in other mammals (for example marsupials), however, are not known. Peripherally administered CRF induced cortisol release in the marsupial Sminthopsis crassicaudata via the CRF1 receptor, and central CRF administration potently decreased food intake, as in rodents. When peripherally administered, both CRF and UCN decreased food intake in S. crassicaudata, but UCN was considerably more potent (similar to 50 fold) in this regard. The anorectic effects of CRF and UCN were not blocked by the CRF1 receptor antagonist antalarmin, suggesting that the peripheral effects of CRF and UCN on food intake are mediated primarily by the CRF2 receptor. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Adelaide, Royal Adelaide Hosp, Dept Med, Adelaide, SA 5000, Australia. St Louis Univ, Div Geriatr Med, St Louis, MO 63104 USA. St Louis Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, St Louis, MO 63104 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Greenslopes Private Hosp, Neuroendocrine Res Unit, Brisbane, Qld 4120, Australia. RP Wittert, GA (reprint author), Univ Adelaide, Royal Adelaide Hosp, Dept Med, Adelaide, SA 5000, Australia. RI morley, john/F-9177-2011 OI morley, john/0000-0001-6444-2965 NR 49 TC 32 Z9 32 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD MAY PY 2000 VL 21 IS 5 BP 669 EP 677 DI 10.1016/S0196-9781(00)00196-0 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 330AW UT WOS:000087941500009 PM 10876049 ER PT J AU Tanda, G Goldberg, SR AF Tanda, G Goldberg, SR TI Alteration of the behavioral effects of nicotine by chronic caffeine exposure SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article; Proceedings Paper CT 4th International Pharmacology Biochemistry and Behavior CY JAN 10-10, 2000 CL MORZINE, FRANCE DE caffeine; nicotine; schedule-controlled behavior; drug self-administration; drug discrimination; dopamine microdialysis; nucleus accumbens; tobacco; coffee; drug abuse; cigarettes ID DISCRIMINATIVE STIMULUS PROPERTIES; ADENOSINE DOPAMINE INTERACTIONS; CIGARETTE-SMOKING BEHAVIOR; NON-PSYCHOSTIMULANT DRUGS; MEDIAL PREFRONTAL CORTEX; COCAINE-TAKING BEHAVIOR; CENTRAL-NERVOUS-SYSTEM; LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; COFFEE-DRINKING AB The prevalence of tobacco smoking and coffee drinking place nicotine and caffeine among the most used licit drugs in many societies and their consumption is often characterised by concurrent use. The pharmacological basis for any putative interaction between these drugs remains unclear. Some epidemiological reports support anecdotal evidence, which suggests that smokers consume caffeine to enhance the effects of nicotine. This paper reviews various aspects of the pharmacology of caffeine and nicotine, in humans and experimental animals, important for the understanding of the interactions between these drugs. In particular, recent experiments are reviewed in which chronic exposure to caffeine in the drinking water of rats facilitated acquisition of self-adminstration behavior, enhanced nicotine-induced increases in dopamine levels in the shelf of the nucleus accumbens and altered the dopaminergic component of a nicotine discrimination. These studies provide evidence that the rewarding and subjective properties of nicotine can be changed by chronic caffeine exposure and indicate that caffeine exposure may be an important environmental factor in shaping and maintaining tobacco smoking. (C) 2000 Elsevier Science Inc. C1 NIDA, NIH, Intramural Res Program, Preclin Pharmacol Sect, Baltimore, MD 21224 USA. Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20007 USA. RP NIDA, NIH, Intramural Res Program, Preclin Pharmacol Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sgoldber@intra.nida.nih.gov RI Tanda, Gianluigi/B-3318-2009 OI Tanda, Gianluigi/0000-0001-9526-9878 NR 235 TC 46 Z9 46 U1 5 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 2000 VL 66 IS 1 BP 47 EP 64 DI 10.1016/S0091-3057(00)00234-3 PG 18 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 319CN UT WOS:000087322500007 PM 10837843 ER PT J AU Piscitelli, SC Kress, DR Bertz, RJ Pau, A Davey, R AF Piscitelli, SC Kress, DR Bertz, RJ Pau, A Davey, R TI The effect of ritonavir on the pharmacokinetics of meperidine and normeperidine SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Clinical-Pharmacy CY OCT 25, 1999 CL KANSAS CITY, MISSOURI SP Amer Coll Clin Pharm ID PROTEASE INHIBITORS AB Study Objective. To determine the effects of ritonavir on the pharmacokinetics of meperidine and normeperidine. Design. Open-label, crossover, pharmacokinetic study. Setting. United States government research hospital. Subjects. Eight healthy volunteers who tested negative for the human immunodeficiency virus. Intervention. Subjects received oral meperidine 50 mg and had serial blood samples collected for 48 hours. They then received ritonavir 500 mg twice/day for 10 days, followed by administration of a second 50-mg meperidine dose and collection of serial samples. Measurements and Main Results. Plasma samples were assayed for meperidine, normeperidine, and ritonavir. Meperidine's area under the curve (AUC) decreased in all subjects by a mean of 67 +/- 4% in the presence of ritonavir (p<0.005). Mean +/- SD maximum concentration was decreased from 126 +/- 47 to 51 +/- 21 ng/ml. Normeperidine's mean AUC was increased 47%, suggesting induction of hepatic metabolism. Conclusion. Meperidine's AUC is significantly reduced, not increased, by concomitant ritonavir. Based on these findings, the risk of narcotic-related adverse effects from this combination appears to be minimal. However, increased concentrations of normeperidine suggest a potential for toxicity with increased dosages or long-term therapy. C1 NIAID, Ctr Clin, Dept Pharm, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Abbott Labs, Abbott Pk, IL 60064 USA. RP Piscitelli, SC (reprint author), NIAID, Ctr Clin, Dept Pharm, NIH, Bldg 10,Room 1N257, Bethesda, MD 20892 USA. NR 15 TC 23 Z9 23 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAY PY 2000 VL 20 IS 5 BP 549 EP 553 DI 10.1592/phco.20.6.549.35162 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 311HF UT WOS:000086878100005 PM 10809341 ER PT J AU Burstein, AH Fisher, KM McPherson, ML Roby, CA AF Burstein, AH Fisher, KM McPherson, ML Roby, CA TI Absorption of phenytoin from rectal suppositories formulated with a polyethylene glycol base SO PHARMACOTHERAPY LA English DT Article ID ADMINISTERED PHENYTOIN AB Study Objective. To compare phenytoin pharmacokinetics following administration of an oral suspension and a rectal suppository formulated with a polyethylene glycol base. Design. Unblinded, single-dose, randomized, crossover trial. Setting. University-affiliated pharmacokinetics and biopharmaceutics laboratory Subjects. Six healthy subjects. Intervention. Subjects were given a single 200-mg dose of phenytoin as an oral suspension and a rectal suppository separated by a 1-week washout. Measurements and Main Results. Blood for plasma phenytoin concentrations was obtained at baseline and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration. Plasma was analyzed by high-performance liquid chromatography (coefficient of variation < 6%) for total phenytoin concentration. Phenytoin maximum concentration (C-max), time to C-max (T-max), time to first measurable concentration (T-lag), and area under the curve from time zero to time of last measurable concentration (AUC(last)) were estimated for oral and rectal administration by WinNonlin (v 1.1) and compared using Wilcoxon's signed rank test (p<0.05 for statistical significance). Two subjects did not have detectable plasma phenytoin concentrations after rectal administration. For the other four subjects, median rectal C-max was significantly lower than oral C-max (0.4 vs 1.9 mu g/ml, p=0.028), median rectal T-max did not differ from oral T-max (11.9 vs 8.0 hrs, p=0.465), and median rectal AUC(last), although highly variable, was significantly lower than oral AUC(last) (5.4 vs 36.2 mu g.hr/ml, p=0.046). No Tlag was seen after oral administration, but with rectal administration the median T-lag was 2 hours. The estimated relative bioavailability of rectal phenytoin suppositories based on AUC(0-24) was 4.7%, with individual values ranging from 0-58.3%. Conclusion. It appears that absorption of phenytoin from polyethylene glycol rectal suppositories in healthy subjects is highly variable and unpredictable. Thus this formulation is not recommended. C1 Univ Maryland, Dept Pharm Practice & Sci, Pharmacokinet & Biopharmaceut Lab, Baltimore, MD 21201 USA. RP Burstein, AH (reprint author), NIH, Ctr Clin, Dept Pharm, Bldg 10,Room 1N257, Bethesda, MD 20892 USA. NR 6 TC 9 Z9 9 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAY PY 2000 VL 20 IS 5 BP 562 EP 567 DI 10.1592/phco.20.6.562.35157 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 311HF UT WOS:000086878100007 PM 10809343 ER PT J AU Bassett, CL Nickerson, ML Cohen, RA Rajeevan, MS AF Bassett, CL Nickerson, ML Cohen, RA Rajeevan, MS TI Alternative transcript initiation and novel post-transcriptional processing of a leucine-rich repeat receptor-like protein kinase gene that responds to short-day photoperiodic floral induction in morning glory (Ipomoea nil) SO PLANT MOLECULAR BIOLOGY LA English DT Article DE cryptic intron; flowering; Ipomoea; multiple transcripts; RNA processing; signal transduction ID MESSENGER-RNA ACCUMULATION; FLOWERING-TIME; PHARBITIS-NIL; ABSCISIC-ACID; ARABIDOPSIS; ENCODES; PLANTS; MAIZE; TRANSLATION; ELEMENTS AB A gene (inrpk1) encoding a putative receptor-like protein kinase was isolated from the Japanese morning glory, Ipomoea (Pharbitis) nil Roth. cv. Violet. The receptor-like portion of the largest derived polypeptide contains 26 direct leucine-rich repeats (LRRs) in a single block, and the catalytic portion has all the conserved amino acid residues characteristic of Ser/Thr protein kinases. RNA blot analysis detected multiple transcripts in cotyledons. The largest (4.4 kb) transcript encodes the predicted full length polypeptide (INRPK1), whereas a 1.6 kb transcript apparently originates from a secondary transcription initiation site within the gene and potentially encodes a protein kinase identical to INRPK1, but lacking most of the LRRs. Two transcripts (ca. 2.7 and 2.6 kb) are created by alternative 3'-splicing of a large (ca. 1.4-1.5 kb) cryptic intron in the LRR region, creating one transcript (2.6 kb) potentially encoding a small, secretable polypeptide. The larger transcript encoding a polypeptide identical to INRPK1, but lacking 21 LRRs, predominates in vegetative roots. Competitive PCR indicates that inrpk1 mRNA increases 20-fold in cotyledons in response to a previously given single floral-inducing short-day (SD). No differences of this magnitude were detected in any other organs examined from plants similarly treated. This pattern of expression and differential processing suggests a role for inrpk1 in some aspect of SD photoperiodic-induced flowering in morning glory. C1 ARS, USDA, Appalachian Fruit Res Stn, Kearneysville, WV 25430 USA. NCI, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Primedica Inc, Rockville, MD 20850 USA. Ctr Dis Control, Atlanta, GA 30322 USA. RP Bassett, CL (reprint author), ARS, USDA, Appalachian Fruit Res Stn, 45 Wiltshire Rd, Kearneysville, WV 25430 USA. NR 64 TC 14 Z9 16 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-4412 J9 PLANT MOL BIOL JI Plant Mol.Biol. PD MAY PY 2000 VL 43 IS 1 BP 43 EP 58 DI 10.1023/A:1006408011873 PG 16 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 332QQ UT WOS:000088085300005 PM 10949373 ER PT J AU Ackerman, MJ AF Ackerman, MJ TI Electronics and health care revisited: Thirty-eight years later SO PROCEEDINGS OF THE IEEE LA English DT Article C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Ackerman, MJ (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9219 J9 P IEEE JI Proc. IEEE PD MAY PY 2000 VL 88 IS 5 BP 706 EP 707 DI 10.1109/5.849172 PG 2 WC Engineering, Electrical & Electronic SC Engineering GA 333XE UT WOS:000088155400010 ER PT J AU Kundu, SD Kim, IY Yang, T Doglio, L Lang, S Zhang, XJ Buttyan, R Kim, SJ Chang, J Cai, XY Wang, Z Lee, C AF Kundu, SD Kim, IY Yang, T Doglio, L Lang, S Zhang, XJ Buttyan, R Kim, SJ Chang, J Cai, XY Wang, Z Lee, C TI Absence of proximal duct apoptosis in the ventral prostate of transgenic mice carrying the C3(I)-TGF-beta type II dominant negative receptor SO PROSTATE LA English DT Article DE TGF-beta; apoptosis; C3 promoter; TGF-beta dominant negative receptor ID PROGRAMMED CELL-DEATH; BETA; PROLIFERATION; CASTRATION; ACTIVATION AB BACKGROUND. Prostatic epithelial cells are sensitive to the inhibitory effects of TGF-beta. However, TGF-beta signaling in the prostate is dependent on androgenic status. Under the in vivo conditions, it is difficult to dissociate the effect of TGF-beta from that of androgen on the prostate. METHODS, The objective of the present study was to create and verify a transgenic mouse system in which epithelial cells of the ventral prostate are insensitive to the actions of TGF-beta. By using a modified prostate-specific promoter, C3(1), the TGF-beta dominant negative receptor is only expressed in the epithelial cells of the ventral prostate, and these cells are resistant to TGF-beta. Morphology of transgenic animal prostates was compared to wild-typo animal prostates by immunohistochemistry and microscopy. RESULTS. The prostate of transgenic mice exhibited an abnormal morphology with multiple layers of epithelial cells lining the proximal ducts, in contrast to the simple cuboidal monolayer of cells seen in the normal prostate. This observation was accompanied by a loss of apoptosis in this region, as seen by TUNEL assay. There was no significant difference in serum levels of testosterone between the wild-type and transgenic animals. CONCLUSIONS. These results demonstrated that a loss of sensitivity to TGF-beta results in the accumulation of multiple lavers of epithelial cells in the proximal region of the ventral prostate. This abnormal growth Illustrates that TGF-beta plays an important role in regulating prostate growth. The current transgenic system can be used as an experimental model to study the functional role of TGF-beta in prostatic growth and function. (C) 2000 Wiley-Liss, Inc. C1 Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA. Baylor Coll Med, Dept Urol, Houston, TX 77030 USA. Childrens Mem Inst Educ & Res, Chicago, IL USA. Columbia Univ, Coll Phys & Surg, Dept Urol, New York, NY USA. NCI, Chemoprevent Lab, Bethesda, MD 20892 USA. RP Lee, C (reprint author), Northwestern Univ, Sch Med, Dept Urol, 300 E Chicago Ave, Chicago, IL 60611 USA. FU NIDDK NIH HHS [DK43541, DK47561] NR 9 TC 31 Z9 34 U1 3 U2 11 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAY 1 PY 2000 VL 43 IS 2 BP 118 EP 124 PG 7 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 304VN UT WOS:000086505000006 PM 10754527 ER PT J AU Panlilio, LV Schindler, CW AF Panlilio, LV Schindler, CW TI Self-administration of remifentanil, an ultra-short acting opioid, under continuous and progressive-ratio schedules of reinforcement in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE self-administration; progressive ratio; pharmacokinetic; remifentanil; heroin; rat ID COCAINE; INFUSION; PARADIGM; DELIVERY AB Rationale: Remifentanil is a mu-opioid agonist with an exceptionally short duration of action. Evaluating remifentanil's effects within the self-administration model of drug abuse may provide insight into the relationship between a drug's duration of action and its effectiveness as a reinforcer. Objectives: This study was conducted to establish a dose-effect function for intravenous remifentanil self-administration in rats and to assess the drug's ability to maintain responding under intermittent schedules of reinforcement. Methods: Inter-infusion intervals were recorded under two continuous-reinforcement schedules of remifentanil self-administration. In the fixed-dose schedule, the unit dose (0.25-32 mu g/kg) was held constant within sessions but varied across sessions. In the variable-dose schedule, four different doses were self-administered in random order within each session. For comparison, heroin (6.25-125 mu g/kg) was studied with the variable-dose schedule. Remifentanil and heroin were also compared under a progressive-ratio schedule of reinforcement in which the response requirements increased exponentially with each successive infusion until responding ceased within each session. Results: Under the continuous-reinforcement schedules, inter-infusion intervals for both drugs increased monotonically as a function of dose, with the remifentanil curve being considerably flatter. Under the progressive-ratio schedule, breaking points varied as an inverted-U shaped function, and the highest breaking points maintained by remifentanil and heroin were similar. At the doses that maintained the highest breaking points under the progressive-ratio schedule, post-infusion pauses under the continuous-reinforcement schedule were about three times shorter with remifentanil than with heroin. Conclusions: Although rates of self-administration are clearly influenced by a drug's duration of action, the ability to maintain responding under intermittent schedules of reinforcement may be independent of duration of action. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Panlilio, LV (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 27 TC 43 Z9 44 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2000 VL 150 IS 1 BP 61 EP 66 DI 10.1007/s002130000415 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 329AX UT WOS:000087884900008 PM 10867977 ER PT J AU Thayer, JF Friedman, BH Borkovec, TD Johnsen, BH Molina, S AF Thayer, JF Friedman, BH Borkovec, TD Johnsen, BH Molina, S TI Phasic heart period reactions to cued threat and nonthreat stimuli in generalized anxiety disorder SO PSYCHOPHYSIOLOGY LA English DT Article; Proceedings Paper CT World Congress of Behavioural and Cognitive Therapies CY JUL 10-16, 1995 CL COPENHAGEN, DENMARK DE generalized anxiety disorder; hypervigilance; cardiac orienting; heart period ID RATE-VARIABILITY; VAGAL TONE; AUTONOMIC CHARACTERISTICS; INFORMATION; WORRY AB The hallmark of generalized anxiety disorder (GAD) is chronic uncontrollable worry. A preattentive bias toward threat cues and hypervigilance may support this ongoing state of apprehension. A study was conducted to bridge the attentional and physiological underpinnings of GAD by examining phasic heart period (HP) responses to cued threat and nonthreat stimuli. Thirty-three GAD clients and 33 nonanxious control participants engaged in an S1-S2 procedure that employed cued threat and nonthreat word stimuli, during which phasic HP reactions were recorded. As compared with the control group, the GAD group showed (1) smaller cardiac orienting responses and impaired habituation of cardiac orienting to neutral words, (2) KR acceleration in response to threat words, and (3) a conditioned anticipatory HR deceleration to threat words over repeated trials. The cardiac-autonomic underpinnings of GAD appear to rigidly maintain precognitive defensive responses against threat. This portrayal is discussed in the context of an integrative model that depicts diminished global adaptive variability in GAD. C1 Univ Missouri, Dept Psychol, Columbia, MO USA. Virginia Polytech Inst & State Univ, Dept Psychol, Blacksburg, VA 24061 USA. Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. Univ Bergen, Dept Clin Psychol, Bergen, Norway. RP Thayer, JF (reprint author), NIA, GRC, LPC, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM thayer@lpc.grc.nia.nih.gov FU NIMH NIH HHS [MH-39172] NR 49 TC 88 Z9 89 U1 2 U2 21 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAY PY 2000 VL 37 IS 3 BP 361 EP 368 DI 10.1017/S0048577200982192 PG 8 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 321WG UT WOS:000087477200010 PM 10860413 ER PT J AU Boorman, GA McCormick, DL Ward, JM Haseman, JK Sills, RC AF Boorman, GA McCormick, DL Ward, JM Haseman, JK Sills, RC TI Magnetic fields and mammary cancer in rodents: A critical review and evaluation of published literature SO RADIATION RESEARCH LA English DT Review ID SPRAGUE-DAWLEY RATS; MALE BREAST-CANCER; TOXICITY ONCOGENICITY EVALUATION; FEMALE ELECTRICAL WORKERS; ELECTROMAGNETIC-FIELDS; OCCUPATIONAL EXPOSURE; UNITED-STATES; DIETARY-FAT; DMBA; CARCINOGENESIS AB Epidemiological data suggesting a possible increase in breast cancer risk in male electricians have raised concerns about the relationship between exposure to power-frequency magnetic fields and breast cancer, In this paper, we review the results of animal studies that are relevant to identifying possible increases in breast cancer risk resulting from exposure to 50 or 60 Hz magnetic fields. Three large-scale chronic bioassays of carcinogenesis in rats or mice exposed to magnetic fields for 2 years demonstrated no increases in the incidence of mammary cancer it is generally accepted that power-frequency magnetic fields have little or no activity as a complete carcinogen in the rodent mammary gland. Findings from one laboratory, though inconsistent, suggest that magnetic fields may stimulate mammary neoplasia in rats treated with a chemical carcinogen, However, studies conducted in two other laboratories failed to confirm these findings; rats exposed to magnetic fields demonstrated patterns of tumor incidence, multiplicity, size and latency that were generally similar to those in sham-exposed controls. Where differences were seen, the groups exposed to magnetic fields generally had fewer mammary tumors than did sham-exposed controls. On this basis, evaluations of the activity of 50 or 60 Hz magnetic fields in models of multistage mammary cancer in rodents have generally been negative; positive findings have been reported from only one laboratory. The totality of rodent data does not support the hypothesis that power-frequency magnetic-field exposure enhances mammary cancer in rodents, nor does it provide experimental support for possible epidemiological associations between magnetic-field exposure and increased breast cancer risk. (C) 2000 by Radiation Research Society. C1 NIEHS, Res Triangle Pk, NC 27709 USA. IIT, Res Inst, Chicago, IL 60616 USA. NCI, Frederick, MD 21702 USA. RP Boorman, GA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. RI huang, hongqi/N-1473-2014 NR 54 TC 15 Z9 16 U1 0 U2 4 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 2000 VL 153 IS 5 BP 617 EP 626 DI 10.1667/0033-7587(2000)153[0617:MFAMCI]2.0.CO;2 PN 2 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 317BL UT WOS:000087204400002 PM 10790284 ER PT J AU Boorman, GA Rafferty, CN Ward, JM Sills, RC AF Boorman, GA Rafferty, CN Ward, JM Sills, RC TI Leukemia and lymphoma incidence in rodents exposed to low-frequency magnetic fields SO RADIATION RESEARCH LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TOXICITY ONCOGENICITY EVALUATION; E-MU-PIM1 TRANSGENIC MICE; ELECTROMAGNETIC-FIELDS; CHILDHOOD LEUKEMIA; OCCUPATIONAL EXPOSURE; F344 RATS; RESIDENTIAL EXPOSURE; CLINICAL PROGRESSION; LYMPHOCYTIC-LEUKEMIA AB A weak association between residential or occupational exposure to electric and magnetic fields (50/60 Hz fields) and an increased incidence of leukemia has been reported, Numerous animal studies have evaluated the potential association between magnetic-field exposure and leukemia. These include long-term (up to 2% years);bioassays, initiation/promotion studies, investigations in transgenic models, and tumor growth studies, Exposure to 60 Nz circularly polarized magnetic fields at 1,400 mu T for 28 months did not affect lymphoma incidence in mice, The study included over 2000 C57BL/6J mice. In another study, 1000 B6C3F(1), mice exposed to 60 Hz magnetic fields up to 1000 mu T for 2 years showed no increase in lymphomas, Approximately 400 transgenic E mu-Pim1 mice exposed to 50 Hz fields up to 1000 mu T for up to 18 months had no increased incidence of leukemia. Similarly, Tup53(+/-) mice and Pim1 transgenic mice exposed to 60 Hz magnetic fields for 23 weeks showed no increased incidence of lymphoma. Three studies in F344 rats exposed to 50 or 60 Hz magnetic fields up to 5 mT showed no increased incidence of leukemia, The combined animal bioassay results are nearly uniformly negative for magnetic-field exposures enhancing leukemia and weaken the possible epidemiological association between magnetic-field exposures and leukemia in humans as suggested by epidemiological data, (C) 2000 by Radiation Research Society. C1 NIEHS, Res Triangle Pk, NC 27709 USA. EPRI, Palo Alto, CA 94304 USA. NCI, Frederick, MD 21702 USA. RP Boorman, GA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. RI huang, hongqi/N-1473-2014 NR 69 TC 32 Z9 34 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 2000 VL 153 IS 5 BP 627 EP 636 DI 10.1667/0033-7587(2000)153[0627:LALIIR]2.0.CO;2 PN 2 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 317BL UT WOS:000087204400003 PM 10790285 ER PT J AU Harry, GJ Bartenbach, M Haines, W Bruccoleri, A AF Harry, GJ Bartenbach, M Haines, W Bruccoleri, A TI Developmental profiles of growth-associated protein (Gap43), Ngfb, Bndf and Ntf4 mRNA levels in the rat forebrain after exposure to 60 Hz magnetic fields SO RADIATION RESEARCH LA English DT Article ID NERVOUS-SYSTEM; ELECTRIC-FIELD; LEAD-EXPOSURE; GAP-43; BRAIN; CELLS; EXPRESSION; COMPONENT; EARTH; CONES AB Fischer 344 rats were exposed to 60 Hz magnetic fields (EMFs) during gestation and lactation. Rats received continuous exposure to 2-, 200- or 1000-mu T magnetic fields for 18.5 h per day, 7 days a week, or sham exposure (sham controls). During postnatal development, on postnatal days 1, 3, 6, 9, 15 and 20, forebrain tissue from male pups was examined for alterations in mRNA level for developmentally regulated central nervous system-specific proteins. Alterations in these factors during critical periods of development could result in alterations in the final neural network. Gap43 (growth-associated protein 43) mRNA was measured by Northern hybridization as a developmental indicator of axonal growth during the development of the neuron. Between postnatal days 1 and 9, detectable levels of Gap43 mRNA displayed a similar pattern across all sham control and exposure groups. In addition to Gap43, mRNA levels for the nervous system-specific growth factors ciliary neurotrophic factor (Cntf), brain-derived neurotrophic factor (Bdnf), beta nerve growth factor (Ngfb), neurotrophin-3 (Ntf3), and neurotrophin-4 (Ntf4) were examined by RNase protection assay. While there is public concern for developmental neurotoxicity associated with exposure to EMFs, these data, generated from animals exposed to 2-, 200 or 1000-mu T magnetic fields during both gestational and lactational periods of development, suggest that under these conditions no significant alterations in these critical factors for brain development occur. (C) 2000 by Radiation Research Society. C1 NIEHS, Neurotoxicol Grp, Res Triangle Pk, NC 27709 USA. RP Harry, GJ (reprint author), NIEHS, Neurotoxicol Grp, POB 12233,MD C1-04, Res Triangle Pk, NC 27709 USA. NR 30 TC 7 Z9 8 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 2000 VL 153 IS 5 BP 642 EP 647 PN 2 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 317BL UT WOS:000087204400005 PM 10790287 ER PT J AU Boorman, GA Owen, RD Lotz, WG Galvin, MJ AF Boorman, GA Owen, RD Lotz, WG Galvin, MJ TI Evaluation of in vitro effects of 50 and 60 Hz magnetic fields in regional EMF exposure facilities SO RADIATION RESEARCH LA English DT Article ID ANCHORAGE-INDEPENDENT GROWTH; INTRACELLULAR CALCIUM OSCILLATIONS; ORNITHINE DECARBOXYLASE ACTIVITY; T-CELL LINE; ELECTROMAGNETIC-FIELDS; TRANSCRIPT LEVELS; CHILDHOOD-CANCER; FLUX DENSITIES; JB6; ENHANCEMENT AB A weak association between magnetic-field exposure and increased incidences of cancer has been reported, While alterations in cellular processes after in vitro magnetic-field exposures have also been reported to provide plausibility for this association, other laboratories have been unable to repeat the findings. As part of an accelerated electric- and magnetic-field (EMF) research program, the National Institute of Environmental Health Sciences with the Department of Energy identified the replication of the published positive effects as a priority. Regional EMF exposure facilities were established to investigate major in vitro effects from the literature. These included effects on gene expression, intracellular calcium, colony growth in soft agar, and ornithine decarboxylase activity. The laboratories that first reported these effects provided experimental protocols, cell lines, and other relevant experiment details. Regional facility studies included sham/sham exposures (no applied field in either chamber) and were done in a blinded fashion to minimize investigator bias. In nearly all experiments, no effects of magnetic-field exposure were found. The effort provided insight into dealing with the difficulty of replication of subtle effects in complex biological systems. Experimental techniques provided some clues for the differences in experimental results between the regional facility and the original investigator. Studies of subtle effects require extraordinary efforts to confirm that the effect can be attributed to the applied exposure. (C) 2000 by Radiation Research Society. C1 NIEHS, Off Special Programs, Res Triangle Pk, NC 27709 USA. US FDA, Ctr Device & Radiol Hlth, Rockville, MD 20850 USA. NIOSH, Div Biomed & Behav Sci, Cincinnati, OH 45226 USA. NIOSH, Off Extramural Programs, Atlanta, GA USA. RP Boorman, GA (reprint author), NIEHS, Off Special Programs, POB 12233,MD B3-08, Res Triangle Pk, NC 27709 USA. NR 36 TC 17 Z9 18 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 2000 VL 153 IS 5 BP 648 EP 657 DI 10.1667/0033-7587(2000)153[0648:EOIVEO]2.0.CO;2 PN 2 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 317BL UT WOS:000087204400006 PM 10790288 ER PT J AU Rankin, T Dean, J AF Rankin, T Dean, J TI The zona pellucida: using molecular genetics to study the mammalian egg coat SO REVIEWS OF REPRODUCTION LA English DT Review ID SPERM RECEPTOR ACTIVITY; O-LINKED OLIGOSACCHARIDES; CDNA CLONING; TRICHOSURUS-VULPECULA; BRUSHTAIL POSSUM; ORYZIAS-LATIPES; XENOPUS-LAEVIS; NUCLEOTIDE-SEQUENCE; STRUCTURAL-ANALYSIS; VITELLINE ENVELOPE AB An extracellular matrix that mediates critical steps in fertilization and early development surrounds all vertebrate eggs. In mice and humans, this matrix is known as the zona pellucida and comprises three glycoproteins: ZP1, ZP2 and ZP3. Homologues of these proteins isolated from other vertebrates have conserved protein motifs that may be important for establishing a common fibrillar structure. However, specific but contradictory biological roles have been assigned to individual egg coat proteins based on assays in vitro in a wide range of species. Mouse lines lacking either ZP1 or ZP3 have been established with abnormal or absent zona matrices and varying degrees of infertility to examine zona structure and function in vivo. By crossing mouse lines lacking individual zona proteins with those expressing human homologues, the structural integrity of the zona matrix can be restored. Because mouse and human spermatozoa exhibit order-specific binding to the zona pellucida, mice with 'humanized' chimaeric zonae may provide an experimental system to elucidate the molecular basis of sperm-zona interaction. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rankin, T (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 67 TC 50 Z9 54 U1 0 U2 5 PU JOURNALS OF REPRODUCTION FERTILITY LTD PI CAMBRIDGE PA 22 NEWMARKET RD, CAMBRIDGE CB5 8DT, ENGLAND SN 1359-6004 J9 REV REPROD JI Rev. Reprod. PD MAY PY 2000 VL 5 IS 2 BP 114 EP 121 DI 10.1530/ror.0.0050114 PG 8 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 319NJ UT WOS:000087347800008 PM 10864856 ER PT J AU Ortmann, RA Klippel, JH AF Ortmann, RA Klippel, JH TI Update on cyclophosphamide for systemic lupus erythematosus SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID DOSE INTRAVENOUS CYCLOPHOSPHAMIDE; STEM-CELL TRANSPLANTATION; INTERSTITIAL LUNG-DISEASE; PULSE CYCLOPHOSPHAMIDE; CONTROLLED TRIAL; IMMUNOSUPPRESSIVE TREATMENT; TRANSVERSE MYELOPATHY; CLINICAL PRESENTATION; AUTOIMMUNE-DISEASE; CYTOTOXIC THERAPY AB Over the past decade cyclophosphamide has come to assume an increasingly prominent role in the management of severe, life-threatening manifestations of SLE. Intermittent, intravenous pulse cyclophosphamide has become the standard of treatment of diffuse proliferative lupus nephritis (WHO Class IV), and there is now substantial clinical literature to suggest an indication for intermittent cyclophosphamide therapy in most other forms of serious lupus affecting major organ systems, in particular lupus vasculitis and acute central nervous system manifestations. This update reviews the use of cyclophosphamide in the management of lupus nephritis, expands on its role in other manifestations of SLE, and discusses potential complications of the drug. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Ortmann, RA (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9S 205, Bethesda, MD 20892 USA. NR 78 TC 29 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD MAY PY 2000 VL 26 IS 2 BP 363 EP + DI 10.1016/S0889-857X(05)70143-5 PG 14 WC Rheumatology SC Rheumatology GA 302JL UT WOS:000086361900010 PM 10768217 ER PT J AU Austin, HA Balow, JE AF Austin, HA Balow, JE TI Treatment of lupus nephritis SO SEMINARS IN NEPHROLOGY LA English DT Review ID INTRAVENOUS PULSE CYCLOPHOSPHAMIDE; ACUTE NONLYMPHOCYTIC LEUKEMIA; STEM-CELL TRANSPLANTATION; SOLUBLE CD40 LIGAND; CONTROLLED TRIAL; MEMBRANOUS NEPHROPATHY; AUTOIMMUNE-DISEASE; IMMUNOSUPPRESSIVE AGENTS; CYCLOSPORINE TREATMENT; PROGNOSTIC FACTORS C1 NIDDKD, NIH, Kidney Dis Sect, Bethesda, MD 20892 USA. RP Austin, HA (reprint author), NIDDKD, NIH, Kidney Dis Sect, Bldg 10,Room 3N112, Bethesda, MD 20892 USA. NR 88 TC 21 Z9 27 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 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAY PY 2000 VL 20 IS 3 BP 265 EP 276 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 315AM UT WOS:000087090500005 PM 10855936 ER PT J AU Simon, R Bryant, J Day, R Lee, SJ Zelen, M AF Simon, R Bryant, J Day, R Lee, SJ Zelen, M TI Clinical trials and sample size considerations: Another perspective - Comment SO STATISTICAL SCIENCE LA English DT Article C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, Bldg EPN,Room 739, Bethesda, MD 20892 USA. NR 9 TC 7 Z9 7 U1 1 U2 3 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 7, 3401 INVESTMENT BLVD, HAYWARD, CA 94545 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD MAY PY 2000 VL 15 IS 2 BP 103 EP 110 PG 8 WC Statistics & Probability SC Mathematics GA 348CT UT WOS:000088967700002 ER PT J AU Chaves, CJ Silver, B Schlaug, G Dashe, J Caplan, LR Warach, S AF Chaves, CJ Silver, B Schlaug, G Dashe, J Caplan, LR Warach, S TI Diffusion- and perfusion-weighted MRI patterns in borderzone infarcts SO STROKE LA English DT Article DE cerebral infarction; magnetic resonance imaging, diffusion-weighted; magnetic resonance imaging, perfusion-weighted ID ACUTE CEREBRAL-ISCHEMIA; ACUTE HUMAN STROKE; WATERSHED INFARCTS; BLOOD-FLOW; BRAIN; PATHOGENESIS; BYPASS AB Background and Purpose-The pathophysiology of borderzone infarcts: is not well understood. We investigated whether combined diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) could identify pathophysiologically meaningful categories of borderzone infarcts. Methods-Seventeen patients with borderzone infarcts were identified from the Beth Israel Deaconess Medical Center Stroke Database. All patients had DWI and PWI, the majority of them within the first 24 hours of symptom onset. Results-Three patterns of perfusion abnormalities were associated with the diffusion lesions: 1, normal perfusion (5 patients); 2, localized perfusion deficits matching the area of restricted diffusion (5 patients); and 3, extensive perfusion deficits involving 1 or more vascular territories (7 patients). All but 1 patient with pattern I had transient peri-infarct hypotension as the presumed stroke mechanism. Two patients with pattern 2 had cardiac or aortic embolic sources; none had large-artery disease or arterial hypotension. Reperfusion was detected in all patients with this pattern who submitted to a follow-up study. All patients with pattern 3 had severe stenosis or occlusion of a large artery: the internal carotid, anterior cerebral, or middle cerebral. Conclusion-We postulate that the perfusion abnormality varies according to the mechanism of the borderzone infarction. Transient perfusion deficits occurring with hypotension in the absence of significant large-artery disease may not be revealed by PWI. Embolism may cause some cases of small borderzone perfusion deficits, Critical large-artery disease may cause large territorial perfusion deficits and predispose to borderzone infarction. C1 Beth Israel Deaconess Med Ctr, Dept Neurol, Stroke Div, Boston, MA 02115 USA. Tufts Univ, New England Med Ctr Hosp, Dept Neurol, Stroke Div, Boston, MA 02111 USA. London Hlth Sci Ctr, Dept Clin Neurol Sci, London, ON, Canada. NINDS, Stroke Branch, Bethesda, MD 20892 USA. RP Chaves, CJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Stroke Div, Dana 710,330 Brookline Ave, Boston, MA 02115 USA. NR 36 TC 47 Z9 54 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2000 VL 31 IS 5 BP 1090 EP 1096 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 310HN UT WOS:000086820600012 PM 10797170 ER PT J AU Velez, G de Smet, MD Whitcup, SM Robinson, M Nussenblatt, RB Chan, CC AF Velez, G de Smet, MD Whitcup, SM Robinson, M Nussenblatt, RB Chan, CC TI Iris involvement in primary intraocular lymphoma: Report of two cases and review of the literature SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE iris; large B-cell lymphoma; lymphoma; non-Hodgkin's lymphoma ID RETICULUM-CELL SARCOMA; CENTRAL-NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; MALIGNANT-LYMPHOMA; OCULAR LYMPHOMA; GENE REARRANGEMENT; OPTIC NEUROPATHY; DIAGNOSIS; BIOPSY; CHEMOTHERAPY AB Non-Hodgkin's lymphoma involves ocular tissues either as a primary tumor or as secondary metastasis from systemic disease. Diagnosis is based on the identification of malignant cells in the eye by biopsy. Although primary intraocular lymphoma cells have been identified in the optic nerve, ciliary body, and iris of a small number of patients by histopathology, these sites of infiltration have rarely been observed on clinical examination. We studied clinical and histopathological findings of two patients with iris infiltration by primary intraocular lymphoma and reviewed the findings of 163 cases reported in the literature. (Surv Ophthalmol 44:518-526, 2000. (C) 2000 by Elsevier Science Inc. All rights reserved.). C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands. RP Velez, G (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10S219,10 Ctr Dr, Bethesda, MD 20892 USA. OI de Smet, Marc/0000-0002-9217-5603 NR 60 TC 34 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAY-JUN PY 2000 VL 44 IS 6 BP 518 EP 526 DI 10.1016/S0039-6257(00)00118-1 PG 9 WC Ophthalmology SC Ophthalmology GA 329YK UT WOS:000087935900005 PM 10906383 ER PT J AU Baumann, MH Ayestas, MA Dersch, CM Brockington, A Rice, KC Rothman, RB AF Baumann, MH Ayestas, MA Dersch, CM Brockington, A Rice, KC Rothman, RB TI Effects of phentermine and fenfluramine on extracellular dopamine and serotonin in rat nucleus accumbens: Therapeutic implications SO SYNAPSE LA English DT Article DE in vivo microdialysis; anorectics; dopamine transporter; serotonin transporter; obesity; drug dependence; addiction ID MONOAMINE-OXIDASE INHIBITORS; INVIVO MICRODIALYSIS; MESOLIMBIC DOPAMINE; COCAINE WITHDRAWAL; I-125 RTI-55; H-3 DOPAMINE; RELEASE; BRAIN; TRANSPORTERS; AMPHETAMINE AB Combined administration of the amphetamine analogs phentermine and fenfluramine (PHEN/FEN) has been used in the treatment of obesity. While these medications are thought to modulate monoamine transmission, the precise neurochemical effects of the PHEN/FEN mixture have not been extensively studied. To assess the mechanism of PHEN/FEN action, in vivo microdialysis studies were performed in the nucleus accumbens of conscious freely moving rats. A series of amphetamine derivatives including phentermine, chlorphentermine, fenfluramine, and PHEN/FEN (1:1 ratio), were infused locally into the accumbens via reverse-dialysis (1, 10, 100 mu M) or injected systemically (1 mg/kg, ip). Dialysate samples were assayed for dopamine (DA) and serotonin (5-HT) by high-performance Liquid chromatography with electrochemical detection. When infused locally, phentermine preferentially increased extracellular DA, whereas fenfluramine selectively increased extracellular 5-HT. Local administration of chlorphentermine or the PHEN/FEN mixture caused parallel elevations of both transmitters. Analogous results were obtained when the drugs were injected systemically. Phentermine stimulated robust locomotor activity in mice, whereas chlorphentermine and fenfluramine did not. PHEN/FEN caused modest locomotor stimulation after a low dose, but had no effect at the highest dose. Accumulating evidence suggests that chronic drug and alcohol abuse is associated with deficits in both DA and 5-HT neuronal function. Thus, dual activation of DA and 5-HT neurotransmission with monoamine releasing agents may be an effective treatment strategy for substance use disorders, as well as for obesity. Published 2000 Wiley-Liss, Inc. C1 NIDA, Clin Psychopharmacol Sect, IRP, NIH, Baltimore, MD 21224 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Baumann, MH (reprint author), NIDA, Clin Psychopharmacol Sect, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 56 TC 64 Z9 65 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD MAY PY 2000 VL 36 IS 2 BP 102 EP 113 DI 10.1002/(SICI)1098-2396(200005)36:2<102::AID-SYN3>3.0.CO;2-# PG 12 WC Neurosciences SC Neurosciences & Neurology GA 301BE UT WOS:000086287600003 PM 10767057 ER PT J AU Slikker, W Olivero, OA Patterson, TA Poirier, MC AF Slikker, W Olivero, OA Patterson, TA Poirier, MC TI Potential toxicities of HIV therapeutics in the developing infant SO TERATOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ZIDOVUDINE; MICE; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE; PHARMACOKINETICS; TRANSMISSION C1 US FDA, Neurotox Div, NCTR, Jefferson, AR 72079 USA. NCI, Div Basic Sci, Bethesda, MD 20892 USA. RP Slikker, W (reprint author), US FDA, Neurotox Div, NCTR, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 9 TC 3 Z9 3 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 0040-3709 J9 TERATOLOGY JI Teratology PD MAY PY 2000 VL 61 IS 5 BP 397 EP 398 DI 10.1002/(SICI)1096-9926(200005)61:5<397::AID-TERA16>3.0.CO;2-8 PG 2 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 310FM UT WOS:000086815900015 PM 10777839 ER PT J AU del Zoppo, GJ Hallenbeck, JM AF del Zoppo, GJ Hallenbeck, JM TI Advances in the vascular pathophysiology of ischemic stroke SO THROMBOSIS RESEARCH LA English DT Article DE microvessel; stroke; cerebral ischemia; inflammation; endothelial cell; astrocyte ID MIDDLE CEREBRAL-ARTERY; TISSUE PLASMINOGEN-ACTIVATOR; FOCAL BRAIN ISCHEMIA; BASAL LAMINA; RAT-BRAIN; HEMORRHAGIC TRANSFORMATION; MATRIX METALLOPROTEINASES; ENDOTHELIAL-CELLS; TERRITORY STROKE; NITRIC-OXIDE AB The cerebral vascular supply is constructed to protect the cerebral hemispheres and brainstem from the consequences of blood flow cessation. Reversal of blood flow around local obstructions is a feature of the microvascular beds of the striatum and cerebral cortex. Cerebral capillaries of these beds consist of endothelial cells, basal lamina, and astrocyte end-feet that sit in close apposition. The interaction of astrocytes with neurons indicates the close relationship, of microvessels to neurons, These relationships are altered when blood flow ceases in the supplying artery. Increased endothelial cell permeability and endocytoses load to edema formation, and matrix degradation is associated with hemorrhage, Autoregulation is lost, Ischemia initiates leukocyte adhesion receptor expression, which is promoted by cytokine generation from the neuropil and activated monocytes. "Preactivation" may further augment the inflammatory responses to ischemia, The activation of cerebral microvessels by ischemia is heterogeneous, involving alterations in integrin-matrix interactions, leukocyte-endothelial cell adhesion, permeability changes, and the "no-reflow'' phenomenon due to platelet activation, fibrin formation, and leukocyte adhesion. Ischemia produces swelling of the microvascular endothelium, and rapid detachment and swelling of the astrocyte end-feet. Ischemic injury targets the microvasculature, where the inflammatory responses are initiated and contribute to tissue injury. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP del Zoppo, GJ (reprint author), Scripps Res Inst, Dept Mol & Expt Med, 10550 N Torrey Pines Rd,MEM 132, La Jolla, CA 92037 USA. NR 67 TC 34 Z9 34 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD MAY 1 PY 2000 VL 98 IS 3 SI V3 BP V73 EP V81 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 316JB UT WOS:000087162900001 ER PT J AU Moats, LC AF Moats, LC TI What is the role of the speech-language pathologist in assessing and facilitating spelling skills? SO TOPICS IN LANGUAGE DISORDERS LA English DT Editorial Material C1 NICHD, Early Intervent Project, Washington, DC USA. RP Moats, LC (reprint author), NICHD, Early Intervent Project, Washington, DC USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21704 USA SN 0271-8294 J9 TOP LANG DISORD JI Top. Lang. Disord. PD MAY PY 2000 VL 20 IS 3 BP 85 EP 87 PG 3 WC Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA 309VU UT WOS:000086790600011 ER PT J AU Mahler, JF AF Mahler, JF TI The use of genetically altered animals in toxicology SO TOXICOLOGIC PATHOLOGY LA English DT Article DE genetically altered animals; animal modeling; altered genes; nontumor endpoints; carcinogenesis ID TRANSGENIC MICE; DEFICIENT MICE; OXIDATIVE STRESS; RECEPTOR; TOXICITY; NEUROTOXICITY; REGENERATION; METABOLISM; DISRUPTION; RESISTANT C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Mahler, JF (reprint author), NIEHS, Lab Expt Pathol, POB 12233, Res Triangle Pk, NC 27709 USA. NR 22 TC 6 Z9 6 U1 0 U2 1 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 2000 VL 28 IS 3 BP 447 EP 449 DI 10.1177/019262330002800315 PG 3 WC Pathology; Toxicology SC Pathology; Toxicology GA 321KT UT WOS:000087455200014 PM 10862564 ER PT J AU Maronpot, RR AF Maronpot, RR TI The use of genetically modified animals in carcinogenicity bioassays SO TOXICOLOGIC PATHOLOGY LA English DT Article DE carcinogenicity bioassays; harmonization of testing requirements; genetically modified mice; genetically altered models C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Maronpot, RR (reprint author), NIEHS, Lab Expt Pathol, POB 12233, Res Triangle Pk, NC 27709 USA. NR 4 TC 8 Z9 8 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 2000 VL 28 IS 3 BP 450 EP 453 DI 10.1177/019262330002800316 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 321KT UT WOS:000087455200015 PM 10862565 ER PT J AU Huff, J Chan, P Nyska, A AF Huff, J Chan, P Nyska, A TI Is the human carcinogen arsenic carcinogenic to laboratory animals? SO TOXICOLOGICAL SCIENCES LA English DT Article ID CLINICALLY ACHIEVABLE CONCENTRATIONS; INDUCED CELL-TRANSFORMATION; DIMETHYLARSINIC ACID; CHEMICAL CARCINOGENESIS; BLADDER CARCINOGENESIS; MALIGNANT LYMPHOCYTES; CHRONIC STIMULATION; GROWTH-INHIBITION; SKIN NEOPLASIA; RATS C1 NIEHS, Div Intramural Res Program, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), NIEHS, Div Intramural Res Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM huff1@niehs.nih.gov NR 54 TC 53 Z9 55 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2000 VL 55 IS 1 BP 17 EP 23 DI 10.1093/toxsci/55.1.17 PG 7 WC Toxicology SC Toxicology GA 310FH UT WOS:000086815500003 PM 10788555 ER PT J AU van Birgelen, APJM Chou, BJ Renne, RA Grumbein, SL Roycroft, JH Hailey, JR Bucher, JR AF van Birgelen, APJM Chou, BJ Renne, RA Grumbein, SL Roycroft, JH Hailey, JR Bucher, JR TI Effects of glutaraldehyde in a 2-year inhalation study in rats and mice SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Society-for-Toxicology CY MAR 14-18, 1999 CL NEW ORLEANS, LOUISIANA SP Soc Toxicol DE glutaraldehyde; toxicity; carcinogenicity; nose ID ZERO DOSE CONTROL; BODY-WEIGHT; RESPIRATORY-TRACT; B6C3F(1) MICE; LONG-TERM; FORMALDEHYDE; TOXICITY; CARCINOGENICITY; ACETALDEHYDE; ALDEHYDES AB Whole-body inhalation toxicology and carcinogenicity studies were performed with the widely used fixative and cold-sterilant glutaraldehyde. Groups of 50 male and female F344/N rats and B6C3F(1) mice were exposed to glutaraldehyde (rats: 0, 250, 500, or 750 ppb; mice: 0, 62.5, 125, or 250 ppb)6 h/day, 5 days/week, for 104 weeks. Survival of 500- and 750-ppb female rats was less than that of controls. Mean body weights of all exposed groups of male rats, 500- and 750-ppb female rats, and 250-ppb female mice were generally less than those of controls. No exposure-related neoplastic lesions were observed in either rats or mice. Non-neoplastic lesions were limited primarily to the most anterior region of the nasal cavity. In rats, hyperplasia and inflammation of the squamous epithelium; hyperplasia, goblet cell hyperplasia, inflammation, and squamous metaplasia of the respiratory epithelium; and hyaline degeneration of the olfactory epithelium were observed. In mice, the nasal lesions were qualitatively similar to those in rats. Squamous metaplasia of the respiratory epithelium was observed in both sexes of mice while female mice also had inflammation and hyaline degeneration of the respiratory epithelium. In contrast to the nasal carcinogen formaldehyde, no neoplastic lesions were observed after inhalation exposure to glutaraldehyde. However, exposure to glutaraldehyde resulted in considerable non-neoplastic lesions in the noses of rats and mice. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Battelle Pacific NW, Richland, WA USA. RP van Birgelen, APJM (reprint author), Hoffmann La Roche Inc, Bldg 100,340 Kingsland St, Nutley, NJ 07110 USA. NR 55 TC 11 Z9 11 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 MAY PY 2000 VL 55 IS 1 BP 195 EP 205 DI 10.1093/toxsci/55.1.195 PG 11 WC Toxicology SC Toxicology GA 310FH UT WOS:000086815500022 PM 10788574 ER PT J AU Achanzar, WE Achanzar, KB Lewis, JG Webber, MM Waalkes, MP AF Achanzar, WE Achanzar, KB Lewis, JG Webber, MM Waalkes, MP TI Cadmium induces c-myc, p53, and c-jun expression in normal human prostate epithelial cells as a prelude to apoptosis SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE cadmium; prostate; apoptosis; cytotoxicity; human ID WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE ANALYSIS; TUMOR-INDUCTION; INJECTION SITE; L6 MYOBLASTS; CYCLE ARREST; ORAL CADMIUM; IN-VIVO; CARCINOGENESIS; CANCER AB Cadmium is a suspected human prostatic carcinogen shown to induce prostatic tumors and proliferative lesions in rats. The carcinogenic mechanism of cadmium is unknown, but its poor mutagenicity points toward an epigenetic mechanism. Here we studied the effect of cadmium on genes involved in growth regulation of prostate epithelial cell using the human prostate epithelial cell line RWPE-1, which is immortalized but not transformed and is androgen-responsive. Treatment with 10 mu M cadmium resulted in transient increases in c-myc and p53 mRNA levels that peaked at 2-fold and 1.4-fold, respectively, compared to control after 2 h. In contrast, c-jun mRNA levels were increased >3-fold after 2, 4, and 6 h and 20-fold after 24 h, DNA synthesis decreased after 24 h of cadmium exposure. Further study revealed a significant increase in apoptosis after 48 h of cadmium exposure. However, approximately 358 of the cells were still viable and appeared normal, indicating this subpopulation was more resistant to cadmium. Furthermore, these resistant cells had 2.5-fold more metallothionein than untreated control cells. This suggests that cadmium could act to select for apoptotic-defective cells in vivo, thereby increasing the likelihood of tumor formation. This work represents the first description of cadmium affecting oncogene expression in a human cell model of a potential in vivo target site of cadmium carcinogenesis. (C) 2000 Academic Press. C1 NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27706 USA. Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA. Michigan State Univ, Dept Med, E Lansing, MI 48824 USA. RP Waalkes, MP (reprint author), MD F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 50 TC 83 Z9 94 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY 1 PY 2000 VL 164 IS 3 BP 291 EP 300 DI 10.1006/taap.1999.8907 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 313UP UT WOS:000087017900006 PM 10799339 ER PT J AU Yuan, C Kadiiska, M Achanzar, WE Mason, RP Waalkes, MP AF Yuan, C Kadiiska, M Achanzar, WE Mason, RP Waalkes, MP TI Possible role of caspase-3 inhibition in cadmium-induced blockage of apoptosis SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE cadmium; chromium; apoptosis ID CULTURED-MAMMALIAN-CELLS; DNA-DAMAGE; GLUTATHIONE-REDUCTASE; PARAMAGNETIC CHROMIUM; METAL CARCINOGENESIS; GENE-EXPRESSION; LIVER-CELLS; IN-VITRO; GENOTOXICITY; INDUCTION AB Cadmium (Cd) and chromium (Cr) are human carcinogens. Cr(VI) is taken up into cells and reduced by cellular reductants to the potential DNA damaging species Cr(V), (TV), and (III). Reactive oxygen species and carbon-based radicals may also be produced during Cr reduction. We previously found that Cd blocks Cr-induced apoptosis, which could allow a larger proportion of genetically damaged cells to escape and become transformed. This study helped define the mechanisms of Cd-induced suppression of apoptosis. Chinese hamster ovary (CHO K1-BH4) cells were treated with either Cd (5-20 mu M), Cr(VI) (350 mu M), or Cd (5-20 mu M) plus Cr(VI) (350 mu M) for 3 h and then cultured in metal-free media for an additional 48 h at which time DNA was extracted or nuclei were examined to determine apoptosis. Cd markedly reduced Cr-induced DNA fragmentation and reduced the number of Cr-induced apoptotic cell nuclei to control levels. Additional study investigated the biokinetics and cellular metabolism of Cr. Cd did not alter the cellular Cr accumulation and there were no differences in the levels of reduced glutathione, a compound possibly important in Cr reduction and reflective of the cellular reducing environment. The antiapoptotic effect of Cd was not due to diminished cellular reduction of Cr(VI) as assessed by electron-spin resonance determination of the Levels of Cr(V). Thus, Cd suppression of Cr-induced apoptosis is not based on altered Cr toxicokinetics or metabolism. In addition to Cr, Cd also inhibited apoptosis induced by hygromycin B and actinomycin D. Cd was a very effective inhibitor of caspase-3 activity, a central mediator of apoptosis, with nontoxic levels of Cd resulting in up to similar to 60% inhibition. These results indicate that Cd may have a generalized inhibitory effect on apoptosis, possibly by inhibiting caspase-3. Inhibition of apoptosis by Cd may allow a greater portion of genetically damaged cells to survive, or give selective growth advantages, and has implications as a potential nongenotoxic mechanism of Cd carcinogenesis. C1 NIEHS, NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Waalkes, MP (reprint author), NIEHS, NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, POB 12233,111 Alexander Dr,MD F0-09, Res Triangle Pk, NC 27709 USA. NR 49 TC 69 Z9 75 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY 1 PY 2000 VL 164 IS 3 BP 321 EP 329 DI 10.1006/taap.2000.8921 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 313UP UT WOS:000087017900010 PM 10799343 ER PT J AU Smith, JD Leitman, SF AF Smith, JD Leitman, SF TI Filtration of RBC units: effect of storage time and temperature on filter performance SO TRANSFUSION LA English DT Article ID WHITE CELL-REDUCTION; RED-CELLS; LEUKOCYTE DEPLETION; BACTERIAL-INFECTION; TRANSFUSION; PREVENTION; REMOVAL AB BACKGROUND: The influence of time, temperature, and rate of filtration on the efficacy of WBC reduction of RBC units was studied in a controlled, paired-donor format. STUDY DESIGN AND METHODS: Ten donors underwent whole-blood phlebotomy on two to four occasions each. Units were filtered (RCXL-1, Pall Biomedical) under laboratory conditions and gravity flow as follows. 1) after 0 to 2 hours of storage at 22 degrees C, 2) after 7 to 8 hours at 22 degrees C, 3) after 14 days of storage at 4 degrees C, and 4) under mock bedside conditions after 14 days of storage at 4 degrees C. Prefiltration and postfiltration cell counts and prefiltration WBC CD11a expression were assessed on Days 0 and 14. RESULTS: WBC content before filtration was 2.20 and 2.34 x 10(9) (p>0.05) for units stored for 2 and 8 hours (Groups 1 and 2) and declined to 52.8 and 7.57 x 10(4) (p<0.01) after filtration. The efficacy of WBC reduction in units stored for 14 days was similar to that in units stored for 8 hours, but absolute postfiltration WBC counts were significantly lower because of a 0.6 log reduction in the starting WBC count after 14 days of storage (postfiltration WBC content of 1.02 and 2.31 x 104 for units filtered under laboratory vs, bedside conditions (p>0.051). Filtration under bedside conditions was associated with a greater degree of variation in residual WBC counts than laboratory filtration. WBC reduction by filtration was significantly greater in units stored for at least 8 hours (Groups 2, 3, and 4) than in those stored for less than 2 hours (4.59 log vs. 3.83 log reduction in WBC content, p<0.05). Surface expression of leukocyte function antigen 1 as measured by CD11a was similar in all groups. CONCLUSION: WBC reduction of RBC units by filtration was least effective when performed within 2 hours of collection. Efficacy of WBC reduction increased significantly after the units were stored for 8 hours to 14 days, without significant differences between these storage intervals. Laboratory filtration yielded more consistent results than did mock bedside filtration. Temperature and filtration rate had no effect on the efficacy of WBC reduction by filtration. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Smith, JD (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bldg 10,Room 1C-711, Bethesda, MD 20892 USA. NR 21 TC 11 Z9 14 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2000 VL 40 IS 5 BP 521 EP 526 DI 10.1046/j.1537-2995.2000.40050521.x PG 6 WC Hematology SC Hematology GA 316BK UT WOS:000087147300005 PM 10827253 ER PT J AU Koonin, EV Aravind, L AF Koonin, EV Aravind, L TI The NACHT family - a new group of predicted NTPases implicated in apoptosis and MHC transcription activation SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Letter ID FUNGUS PODOSPORA-ANSERINA; GTP-BINDING; VEGETATIVE INCOMPATIBILITY; PROTEIN; DOMAIN; DEATH 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, Bethesda, MD 20894 USA. NR 9 TC 177 Z9 182 U1 1 U2 8 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 MAY PY 2000 VL 25 IS 5 BP 223 EP 224 DI 10.1016/S0968-0004(00)01577-2 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 314NH UT WOS:000087061800006 PM 10782090 ER PT J AU Lohrum, MAE Vousden, KH AF Lohrum, MAE Vousden, KH TI Regulation and function of the p53-related proteins: same family, different rules SO TRENDS IN CELL BIOLOGY LA English DT Review ID P53; MDM2; DEGRADATION; APOPTOSIS; CANCER; DOMAIN; GENE; E2F AB The tumour-suppressor protein p53 has recently been shown to belong to a family that includes two structurally related proteins, p63 and p73. Although all three proteins share similar transcriptional functions and the ability to induce apoptosis, each of them appears to play a distinct role in development and tumour suppression, In order for cell division to occur, the antiproliferative activities of these proteins must be tightly controlled, and exciting advances have been mane in our understanding of the pathways involved in regulating p53 activity. C1 NCI, Regulat Cell Growth Lab, FCRDC, Frederick, MD 21702 USA. RP Lohrum, MAE (reprint author), NCI, Regulat Cell Growth Lab, FCRDC, Bldg 560,Room 22-96,W 7th St, Frederick, MD 21702 USA. NR 60 TC 94 Z9 98 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD MAY PY 2000 VL 10 IS 5 BP 197 EP 202 DI 10.1016/S0962-8924(00)01736-0 PG 6 WC Cell Biology SC Cell Biology GA 307KL UT WOS:000086652400006 PM 10754563 ER PT J AU Barry, CE Schroeder, BG AF Barry, CE Schroeder, BG TI DNA microarrays: translational tools for understanding the biology of Mycobacterium tuberculosis SO TRENDS IN MICROBIOLOGY LA English DT Editorial Material ID GENE-EXPRESSION; BCG C1 NIAID, TB Res Sect, Host Def Lab, NIH, Rockville, MD 20852 USA. RP Barry, CE (reprint author), NIAID, TB Res Sect, Host Def Lab, NIH, Twinbrook II,Room 239,12441 Parklawn Dr, Rockville, MD 20852 USA. RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11] NR 11 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD MAY PY 2000 VL 8 IS 5 BP 209 EP 210 DI 10.1016/S0966-842X(00)01740-6 PG 2 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 314CF UT WOS:000087036100009 PM 10785636 ER PT J AU Mattson, MP LaFerla, FM Chan, SL Leissring, MA Shepel, PN Geiger, JD AF Mattson, MP LaFerla, FM Chan, SL Leissring, MA Shepel, PN Geiger, JD TI Calcium signaling in the ER: its role in neuronal plasticity and neurodegenerative disorders SO TRENDS IN NEUROSCIENCES LA English DT Review ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; AMYLOID BETA-PEPTIDE; SMOOTH ENDOPLASMIC-RETICULUM; CULTURED HIPPOCAMPAL-NEURONS; CEREBELLAR PURKINJE-CELLS; RYANODINE BINDING-SITES; LONG-TERM DEPRESSION; KNOCK-IN MICE; CA2+ RELEASE; OXIDATIVE STRESS AB Endoplasmic reticulum (ER) is a multifaceted organelle that regulates protein synthesis and trafficking, cellular responses to stress. and intracellular Ca2+ levels. In neurons, it is distributed, between the cellular compartments that regulate plasticity and survival, which include axons, dendrites, growth cones and synaptic terminals. Intriguing communication networks between ER, mitochondria and plasma membrane are being revealed that provide mechanisms for the precise regulation of temporal and spatial aspects of Ca2+ signaling. Alterations in Ca2+ homeostasis in ER contribute to neuronal apoptosis and excitotoxicity, and are being linked to the pathogenesis of several different neurodegenerative disorders, including Alzheimer's disease and stroke. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Calif Irvine, Lab Mol Neuropathogenesis, Dept Neurobiol & Behav, Irvine, CA 92697 USA. Univ Manitoba, Fac Med, Dept Pharmacol & Therapeut, Winnipeg, MB R3E 0W3, Canada. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 85 TC 330 Z9 339 U1 6 U2 27 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAY PY 2000 VL 23 IS 5 BP 222 EP 229 DI 10.1016/S0166-2236(00)01548-4 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 309DK UT WOS:000086752300010 PM 10782128 ER PT J AU Sdrobolini, A Contu, A Massidda, B Gasperoni, S Recchia, F Iannelli, A Tomao, S Romiti, A Raffaele, M Ortu, S Campisi, C Gebbia, V Olmeo, N Ionta, MT Angiona, S Di Costanzo, F AF Sdrobolini, A Contu, A Massidda, B Gasperoni, S Recchia, F Iannelli, A Tomao, S Romiti, A Raffaele, M Ortu, S Campisi, C Gebbia, V Olmeo, N Ionta, MT Angiona, S Di Costanzo, F TI 5-fluorouracil plus folinic acid with or without ifosfamide in advanced colorectal cancer: A phase II randomized trial SO TUMORI LA English DT Article DE advanced colorectal cancer; 5-fluorouracil; folinic acid; ifosfamide ID SUPPORTIVE CARE; ISOPHOSPHAMIDE; FLUOROURACIL; TUMORS; MESNA AB Aim: This phase II trial evaluated the biomodulation of 5-fluorouracil (5-FU) plus folinic acid (FA) with or without ifosfamide (IFO) in chemotherapy-naive patients with colorectal cancer. Patients and methods: Forty-eight patients were randomized to receive: FA (25 mg/m(2) iv bolus days 1 to 3), followed by 5-FU (750 mg/m(2) iv bolus days 1 to 3), arm A; or FA (25 mg/m(2) iv bolus days 1 to 3), followed by 5-FU (750 mg/m(2) iv bolus days 1 to 3) plus IFO (2,000 mg/m(2) in 1000 mt 5% dextrose in a 2-hr infusion, days 1 to 3), arm B. Mesna was added during and after IFO to prevent hemorrhagic cystitis. Treatment was repeated every 21 days in both arms. Results: Forty-five patients were assessable for response: in arm A, 5 patients achieved a partial response (overall response, 25%), and in arm B, 2 patients achieved a complete and 1 a partial response (overall response, 12%). Time to failure was 3.5 months (range, 1-38) in patients treated with 5-FU plus FA, and 3 months (range, 1-21) in patients treated with the IFO combination. The median survival time was 13.5 months (range, 1-49 months) in arm A and 16 months (range, 1-43 months) in arm B, Diarrhea, stomatitis and vomiting were the most common nonhematologic toxicities in both arms. The most notable hematologic toxicity was leukopenia; 15% and 20% of patients experienced grade 4 in arm A and arm B, respectively. Conclusions: IFO does not increase the activity of the 5-FU plus FA combination in advanced colorectal cancer. C1 Hosp Santa Maria, Dept Med & Med Oncol, Terni, Italy. Hosp Sassari, Dept Med Oncol, Sassari, Italy. Businco Hosp, Dept Surg & Med Oncol, Cagliari, Italy. Hosp Avezzano, Dept Med Oncol, Avezzano, Italy. Hosp Siderno, Dept Med Oncol, Siderno, Italy. Natl Canc Inst, Genoa, Italy. Hosp Olbia, Dept Med Oncol, Olbia, Italy. CNR, Inst Biomed Technol, Rome, Italy. La Maddalena Hosp, Palermo, Italy. RP Di Costanzo, F (reprint author), Azienda Osped Santa Maria, Dipartimento Med & Oncol, Day Hosp, Modulo Dipartiemtale Oncol, Terni, Italy. OI Gebbia, Vittorio/0000-0001-8848-5951 NR 13 TC 0 Z9 0 U1 0 U2 0 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD MAY-JUN PY 2000 VL 86 IS 3 BP 211 EP 214 PG 4 WC Oncology SC Oncology GA 347JU UT WOS:000088926500007 PM 10939601 ER PT J AU Spencer, BA Wood, BJ Dretler, SP AF Spencer, BA Wood, BJ Dretler, SP TI Helical CT and ureteral colic SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE FLANK PAIN; SPIRAL COMPUTERIZED-TOMOGRAPHY; TISSUE RIM SIGN; URINARY CALCULI; FILLING DEFECTS; CHEMICAL-COMPOSITION; EXCRETORY UROGRAPHY; PLAIN RADIOGRAPHY; DIAGNOSIS; NUMBERS AB Helical CT has many advantages over intravenous urography and ultrasound, making it the gold standard for the evaluation of flank pain that is suspicious for ureteral colic. Technological advances, important radiographic diagnostic methods, and a review of the literature supporting the use of helical CT are presented. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol,Wang Ambulatory Care Ctr 486, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Georgetown Univ, Med Ctr, Dept Radiol, Washington, DC 20007 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Dretler, SP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol,Wang Ambulatory Care Ctr 486, Boston, MA 02114 USA. NR 41 TC 20 Z9 20 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 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD MAY PY 2000 VL 27 IS 2 BP 231 EP + DI 10.1016/S0094-0143(05)70253-6 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 302PC UT WOS:000086373200005 PM 10778466 ER PT J AU Koch, RM Roche, NS Parks, WT Ashcroft, GS Letterio, JJ Roberts, AB AF Koch, RM Roche, NS Parks, WT Ashcroft, GS Letterio, JJ Roberts, AB TI Incisional wound healing in transforming growth factor-beta 1 null mice SO WOUND REPAIR AND REGENERATION LA English DT Article ID FACTOR-BETA; TGF-BETA; INFLAMMATORY RESPONSE; NEUTRALIZING ANTIBODY; TARGETED DISRUPTION; IMPAIRED WOUNDS; TISSUE-REPAIR; EXPRESSION; DISEASE; LOCALIZATION AB Expression of endogenous transforming growth factor-beta 1 is reduced in many animal models of impaired wound healing, and addition of exogenous transforming growth factor-beta has been shown to improve healing. To test the hypothesis that endogenous transforming growth factor-beta 1 is essential for normal wound repair, we have studied wound healing in mice in which the transforming growth factor-beta 1 gene has been deleted by homologous recombination. No perceptible differences were observed in wounds made in 3-10-day-old neonatal transforming growth factor-beta 1 null mice compared to wild-type littermates. To preclude interference from maternally transferred transforming growth factor-beta 1, cutaneous wounds were also made on the backs of 30-day-old transforming growth factor-beta 1 null and littermate control mice treated with rapamycin, which extends their lifetime and suppresses the inflammatory response characteristic of the transforming growth factor-beta 1 null mice. Again, no impairment in healing was seen in transforming growth factor-beta 1 null mice. Instead these wounds showed an overall reduction in the amount of granulation tissue and an increased rate of epithelialization compared to littermate controls. Our data suggest that release of transforming growth factor-beta 1 from degranulating platelets or secretion by infiltrating macrophages and fibroblasts is not critical to initiation or progression of tissue repair and that endogenous transforming growth factor-beta 1 may actually function to increase inflammation and retard wound closure. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. NR 52 TC 56 Z9 60 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAY-JUN PY 2000 VL 8 IS 3 BP 179 EP 191 DI 10.1046/j.1524-475x.2000.00179.x PG 13 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 328GQ UT WOS:000087841600005 PM 10886809 ER PT J AU Rocchi, E Khodjakov, A Volk, EL Yang, CH Litman, T Bates, SE Schneider, E AF Rocchi, E Khodjakov, A Volk, EL Yang, CH Litman, T Bates, SE Schneider, E TI The product of the ABC half-transporter gene ABCG2 (BCRP/MXR/ABCP) is expressed in the plasma membrane SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BREAST-CANCER CELLS; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; DRUG ACCUMULATION; OVEREXPRESSION; PROTEIN; MITOXANTRONE; LINE; MRP AB The products of the ABC gene family can be generally classified as either full-transporters of half-transporters. Full-transporters are expressed in the plasma membrane, whereas half-transporters are usually found in intracellular membranes. Recently, an ABC half-transporter, the ABCG2 gene product Breast Cancer/Mitoxantrone Resistance Protein (BCRP/ MXR), has been shown to cause mitoxantrone and topotecan resistance. The purpose of this study was to determine the expression and the intracellular localization of this protein in various drug-resistant cell lines. BCRP/MXR expression was determined by Western blot and immunohistochemistry. This protein is highly overexpressed in several drug-resistant cell lines and localizes predominantly to the plasma membrane, instead of to intracellular membranes as seen with all Other known half-transporters. Therefore, BCRP/MXR is unique among the ABC half-transporters by being localized to the plasma membrane. (C) 2000 Academic Press. C1 New York State Dept Hlth, Wadsworth Ctr Labs & Res, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Rensselaer, NY 12144 USA. Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan. Natl Taiwan Univ, Coll Med, Grad Inst Med, Taipei 10018, Taiwan. Univ Copenhagen, Panum Inst, DK-2200 Copenhagen, Denmark. NCI, Med Branch, Bethesda, MD 20892 USA. RP Schneider, E (reprint author), New York State Dept Hlth, Wadsworth Ctr Labs & Res, Empire State Plaza, Albany, NY 12201 USA. FU NCI NIH HHS [CA72455]; NIGMS NIH HHS [R01 GM059363, R01 GM059363-02] NR 27 TC 127 Z9 143 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 29 PY 2000 VL 271 IS 1 BP 42 EP 46 DI 10.1006/bbrc.2000.2590 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 310ZX UT WOS:000086860600007 PM 10777678 ER PT J AU Liu, X Ito, K Lee, RJ Uyeda, TQP AF Liu, X Ito, K Lee, RJ Uyeda, TQP TI Involvement of tail domains in regulation of Dictyostelium myosin II SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE myosin; regulatory light chain; regulation; phosphorylation; Dictyostelium ID HEAVY-CHAIN PHOSPHORYLATION; SMOOTH-MUSCLE MYOSIN; RABBIT SKELETAL-MUSCLE; DEPENDENT REGULATION; ATPASE ACTIVITY; MONOCLONAL-ANTIBODIES; 2 HEADS; ACTIN; DISCOIDEUM; SITE AB The actin-dependent ATPase activity of Dictyostelium myosin II filaments is regulated by phosphorylation of the regulatory light chain. Four deletion mutant myosins which lack different parts of subfragment 2 (S2) showed phosphorylation-independent elevations in their activities. Phosphorylation-independent elevation in the activity was also achieved by a double point mutation to replace conserved Glu932 and Glu933 in S2 with Lys. These results suggested that inhibitory interactions involving the head and S2 are required for efficient regulation. Regulation of wild-type myosin was not affected by copolymerization with a S2 deletion mutant myosin in the same filaments. Furthermore, the activity linearly correlated with the fraction of phosphorylated molecules in wild-type filaments. These latter two results suggest that the inhibitory head-tail interactions are primarily intramolecular, (C) 2000 Academic Press. C1 Natl Inst Adv Interdisciplinary Res, Biomol Res Grp, Tsukuba, Ibaraki 3058562, Japan. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. RP NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL43821] NR 36 TC 21 Z9 21 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 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 29 PY 2000 VL 271 IS 1 BP 75 EP 81 DI 10.1006/bbrc.2000.2582 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 310ZX UT WOS:000086860600013 PM 10777684 ER PT J AU Gladwin, MT Rodgers, GP AF Gladwin, MT Rodgers, GP TI Pathogenesis and treatment of acute chest syndrome of sickle-cell anaemia SO LANCET LA English DT Editorial Material ID INHALED NITRIC-OXIDE; RISK-FACTORS; DISEASE; HYDROXYUREA; ANEMIA; TRANSFUSION; HEMOGLOBIN; BLOOD C1 NIDDK, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. NIDDK, Crit Hematol Branch, NIH, Bethesda, MD USA. RP Rodgers, GP (reprint author), NIDDK, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. NR 17 TC 28 Z9 29 U1 0 U2 3 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 29 PY 2000 VL 355 IS 9214 BP 1476 EP 1478 DI 10.1016/S0140-6736(00)02157-7 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 310LR UT WOS:000086830100004 PM 10801164 ER PT J AU Pratley, RE AF Pratley, RE TI A shocking case of diabetic neuropathy SO LANCET LA English DT Letter C1 Natl Inst Hlth, Diabet & Metab Unit, Clin Diabet & Nutr Sect, Phoenix, AZ 85016 USA. RP Pratley, RE (reprint author), Natl Inst Hlth, Diabet & Metab Unit, Clin Diabet & Nutr Sect, Phoenix, AZ 85016 USA. NR 0 TC 1 Z9 1 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 APR 29 PY 2000 VL 355 IS 9214 BP 1560 EP 1560 DI 10.1016/S0140-6736(05)74618-3 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 310LR UT WOS:000086830100066 PM 10801209 ER PT J AU Kennedy, AK Haniford, DB Mizuuchi, K AF Kennedy, AK Haniford, DB Mizuuchi, K TI Single active site catalysis of the successive phosphoryl transfer steps by DNA transposases: Insights from phosphorothioate stereoselectivity SO CELL LA English DT Article ID V(D)J RECOMBINATION; ESCHERICHIA-COLI; HIV-1 INTEGRASE; STRAND TRANSFER; RAG2 PROTEINS; POLYMERASE-I; TARGET SITE; RETROVIRAL INTEGRATION; TN10 TRANSPOSITION; SYNAPTIC COMPLEX AB The transposase family of proteins mediate DNA transposition or retroviral DNA integration via multistep phosphoryl transfer reactions. For Tn10 and phage Mu a single active site of one transposase protomer catalyzes the successive transposition reaction steps. We examined phosphorothioate stereoselectivity at the scissile position for all four reaction steps catalyzed by the Tn10 transposase. The results suggest that the first three steps required for double-strand cutting at the transposon end proceed as a succession of pseudo-reverse reaction steps while the 3' end of the transposon remains bound to the same side of the active site. However, the mode of substrate binding to the active site changes for the cut transposon 3' end to target DNA strand joining. The phosphorothioate stereoselectivity of the corresponding steps of phage Mu transposition and HIV DNA integration matches that of Tn10 reaction, indicating a common mode of substrate-active site interactions for this class of DNA transposition reactions. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Western Ontario, Dept Biochem, London, ON N6A 5C1, Canada. RP Mizuuchi, K (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 40 TC 64 Z9 66 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 28 PY 2000 VL 101 IS 3 BP 295 EP 305 DI 10.1016/S0092-8674(00)80839-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 308ZC UT WOS:000086741900009 PM 10847684 ER PT J AU Nakayama, J Klar, AJS Grewal, SIS AF Nakayama, J Klar, AJS Grewal, SIS TI A chromodomain protein, Swi6, performs imprinting functions in fission yeast during mitosis and meiosis SO CELL LA English DT Article ID MATING-TYPE LOCI; EPIGENETIC INHERITANCE; SCHIZOSACCHAROMYCES-POMBE; DNA METHYLATION; CHROMOSOME SEGREGATION; HETEROCHROMATIN; CHROMATIN; DROSOPHILA; REPRESSION; DOMAINS AB Inheritance of stable states of gene expression is essential for cellular differentiation. In fission yeast, an epigenetic imprint marking the mating-type (mat2/3) region contributes to inheritance of the silenced state, but the nature of the imprint is not known. We show that a chromodomain-containing Swi6 protein is a dosage-critical component involved in imprinting the mat locus. Transient overexpression of Swi6 alters the epigenetic imprint at the mat2/3 region and heritably converts the expressed state to the silenced state. The establishment and maintenance of the imprint are tightly coupled to the recruitment and the persistence of Swi6 at the mat2/3 region during mitosis as well as meiosis. Remarkably, Swi6 remains bound to the mat2/3 interval throughout the cell cycle and itself seems to be a component of the imprint. Our analyses suggest that the unit of inheritance at the mat2/3 locus comprises the DNA plus the associated Swi6 protein complex. C1 Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. NCI, Frederick, MD 21702 USA. RP Grewal, SIS (reprint author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA. RI Nakayama, Jun-ichi/C-6003-2011 FU NIGMS NIH HHS [R01 GM59772-01A1] NR 43 TC 129 Z9 131 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 28 PY 2000 VL 101 IS 3 BP 307 EP 317 DI 10.1016/S0092-8674(00)80840-5 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 308ZC UT WOS:000086741900010 PM 10847685 ER PT J AU Bellahcene, A Bonjean, K Fohr, B Fedarko, NS Robey, FA Young, MF Fisher, LW Castronovo, V AF Bellahcene, A Bonjean, K Fohr, B Fedarko, NS Robey, FA Young, MF Fisher, LW Castronovo, V TI Bone sialoprotein mediates human endothelial cell attachment and migration and promotes angiogenesis SO CIRCULATION RESEARCH LA English DT Article DE bone sialoprotein; angiogenesis; integrins ID HUMAN BREAST-CANCER; INTEGRIN ALPHA(V)BETA(3); MATRIX PROTEINS; BLOOD-VESSELS; IN-VITRO; ADHESION; EXPRESSION; OSTEOPONTIN; RGD; ALPHA-V-BETA-3 AB Bone sialoprotein (BSP) is a secreted glycoprotein primarily found in sites of biomineralization. Recently, we demonstrated that BSP is strongly upregulated in osteotropic cancers and particularly those that exhibit microcalcifications, BSP contains an Arg-Gly-Asp (RGD) motif found in other adhesive molecules that interact with cellular integrins, In bone, BSP has been shown to mediate the attachment of osteoblasts and osteoclasts via alpha(v)beta(3) integrin receptors. Ligands for alpha(v)beta(3) integrin are considered to play a central role during angiogenesis. Therefore, we used human umbilical vein endothelial cells (HUVECs) to study the potential role of BSP in angiogenesis. We found that purified eukaryotic recombinant human BSP (rhBSP) is able to promote both adhesion and chemotactic migration of HUVECs in a dose-dependent manner. These interactions involve HUVEC alpha(v)beta(3) integrin receptors and the RGD domain of BSP. Indeed, HUVECs attach to a recombinant BSP fragment containing the RGD domain, whereas this response is not observed with the same fragment in which RGD has been mutated to Lys-Ala-Glu (KAE), A cyclic RGD BSP peptide inhibits both adhesion and migration of HUVECs to rhBSP, Moreover, anti-alpha(v)beta(3) but not anti-alpha(v)beta(5) monoclonal antibodies also prevent BSP-mediated adhesion and migration of HUVECs. We observed that both rhBSP and the RGD BSP recombinant fragment stimulated ongoing angiogenesis on the chorioallantoic chick membrane assay. BSP angiogenic activity was inhibited by anti-alpha(v)beta(3) antibody, and the KAE BSP fragment was inactive. Our findings represent the first report implicating BSP in angiogenesis. BSP could play a critical role in angiogenesis associated with bone formation and with tumor growth and metastatic dissemination. C1 Univ Liege, Metastasis Res Lab, B-4000 Liege, Belgium. Natl Inst Dental & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Castronovo, V (reprint author), Univ Liege, Metastasis Res Lab, Tour Pathol,B23, B-4000 Liege, Belgium. NR 44 TC 80 Z9 95 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 28 PY 2000 VL 86 IS 8 BP 885 EP 891 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 311TY UT WOS:000086902800012 PM 10785511 ER PT J AU Francischetti, IMB Ribeiro, JMC Champagne, D Andersen, J AF Francischetti, IMB Ribeiro, JMC Champagne, D Andersen, J TI Purification, cloning, expression, and mechanism of action of a novel platelet aggregation inhibitor from the salivary gland of the blood-sucking bug, Rhodnius prolixus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TICK ORNITHODOROS-MOUBATA; NITRIC-OXIDE; SHAPE CHANGE; TYROSINE PHOSPHORYLATION; ADENOSINE-DIPHOSPHATE; STIMULATED PLATELETS; CALCIUM MOBILIZATION; BLOODSUCKING INSECT; ADENYLATE-CYCLASE; COLLAGEN RECEPTOR AB Rhodnius prolixus aggregation inhibitor 1 (RPAI-1), a 19-kDa protein isolated from the salivary gland of R. prolixus was purified by strong cation exchange and reverse-phase high performance liquid chromatographies. Based on 49 amino-terminal amino acid sequences of RPAI-1, primers were produced to generate probes to screen an R. prolixus salivary gland cDNA library. A phage containing the full-length clone of RPAI-1 codes for a mature protein of 155 amino acids. RPAI-1 shows sequence homology to triabin and pallidipin, lipocalins from Triatoma pallidipennis. The cDNA sequence was cloned in Petl17B Escherichia coli expression vector, producing an active peptide. RPAI-1 inhibits human platelet-rich plasma aggregation triggered by low concentrations of ADP, collagen, arachidonic acid, thromboxane A(2) mimetics (U46619), and very low doses of thrombin and convulxin. Here we show that ADP is the target of RPAI-1 since (i) RPAI-1 inhibits ADP-dependent large aggregation formation and secretion triggered by U46619, without affecting Ca2+ increase and shape change; (ii) ADP restored the inhibition of U46619-induced platelet aggregation by RPAI-1, (iii) PGE(1)-induced increase of cAMP (which is antagonized by U46619 in an ADP-dependent manner) was restored by RPAI-1, (iv) RPAI-1 inhibits low concentrations of ADP-mediated responses of indomethacin-treated platelets, and (v) RPAI-1 binds to ADP, as assessed by large zone chromatography. RPAI-1 affects neither integrin alpha(2)beta(1)- nor glycoprotein VI-mediated platelet responses. We conclude that RPAI-1 is the first lipocalin described that inhibits platelet aggregation by a novel mechanism, binding to ADP. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Georgia, Dept Entomol, Athens, GA 30602 USA. Univ Arizona, Dept Biochem, Tucson, AZ 85721 USA. RP Ribeiro, JMC (reprint author), Bldg 4,Rm 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. OI Ribeiro, Jose/0000-0002-9107-0818 NR 87 TC 80 Z9 83 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 28 PY 2000 VL 275 IS 17 BP 12639 EP 12650 DI 10.1074/jbc.275.17.12639 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309HK UT WOS:000086762300040 PM 10777556 ER PT J AU Ma, Q Renzelli, AJ Baldwin, KT Antonini, JM AF Ma, Q Renzelli, AJ Baldwin, KT Antonini, JM TI Superinduction of CYP1A1 gene expression - Regulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced degradation of Ah receptor by cycloheximide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ARYL-HYDROCARBON RECEPTOR; PROTEIN-DNA INTERACTIONS; MOUSE HEPATOMA-CELLS; TRANSCRIPTIONAL ENHANCER; AROMATIC-HYDROCARBONS; NUCLEAR TRANSLOCATOR; CYTOCHROME P4501A1; DIOXIN RECEPTOR; MICE LACKING; 1C1C7 CELLS AB Cycloheximide superinduces the transcription of CYP1A1 in the presence of an agonist for the Ah receptor (AhR). To investigate the molecular target for "superinduction," we analyzed the agonist-induced degradation of AhR. Whereas 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent agonist of AhR, induces a rapid reduction of the AhR protein, cycloheximide blocks the downregulation of steady state AhR. Analyses of the turnover of AhR reveal that cycloheximide blocks the shortening of the half-life of AhR by TCDD, Blocking of the TCDD-induced AhR degradation requires inhibition of protein synthesis, because (a) cycloheximide inhibits protein synthesis at the concentration at which it causes superinduction and inhibition of AhR degradation; and (b) puromycin, an inhibitor of protein synthesis by mimicking aminoacyl-tRNA, also blocks the TCDD-induced AhR degradation. The blocking of the TCDD-induced AhR degradation correlates with the superinduction of CYP1A1 gene expression in a time- and dose-dependent manner. Furthermore, cycloheximide is shown to increase the accumulation of the TCDD-activated AhR and the functional AhR Amt complex in nucleus. Collectively, our results reveal a mechanism of superinduction by cycloheximide by enhancing the stability of agonist-activated AhR, The finding that inhibition of protein synthesis blocks the TCDD-induced AhR turnover implicates a cycloheximide-sensitive, labile factor (designated as (A) under bar hR (d) under bar egradation (p) under bar romoting (f) under bar actor, or ADPF) in controlling the removal of agonist-activated AhR in nucleus. C1 Ctr Dis Control & Prevent, NIOSH, Pathol & Physiol Res Branch,Hlth Effects Lab Div,, NIH, Morgantown, WV 26505 USA. Ctr Dis Control & Prevent, NIOSH, Mol Toxicol lab,Toxicol & Mol Biol Branch, NIH, Morgantown, WV 26505 USA. RP Ma, Q (reprint author), Ctr Dis Control & Prevent, NIOSH, Pathol & Physiol Res Branch,Hlth Effects Lab Div,, NIH, Mailstop 3014,1095 Willowdale Rd, Morgantown, WV 26505 USA. NR 53 TC 75 Z9 76 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 APR 28 PY 2000 VL 275 IS 17 BP 12676 EP 12683 DI 10.1074/jbc.275.17.12676 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309HK UT WOS:000086762300045 PM 10777561 ER PT J AU Liu, Y Li, HC Tanaka, K Tsumaki, N Yamada, Y AF Liu, Y Li, HC Tanaka, K Tsumaki, N Yamada, Y TI Identification of an enhancer sequence within the first intron required for cartilage-specific transcription of the alpha 2(XI) collagen gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHONDROCYTE-SPECIFIC ENHANCER; SRY-RELATED GENE; AUTOSOMAL SEX REVERSAL; II COLLAGEN; CAMPOMELIC DYSPLASIA; RAT CHONDROSARCOMA; FIBRILLAR COLLAGEN; MOUSE EMBRYOS; XI COLLAGEN; CELL-LINE AB Type XI collagen, a heterotrimer composed of alpha 1(XI), alpha 2(XI) and alpha 3(XI), is primarily synthesized by chondrocytes in cartilage and is also present in some other tissues. Type XI collagen plays a critical role in collagen fibril formation and skeletal morphogenesis. We investigated a tissue-specific transcriptional enhancer in the first intron of the alpha 2(XI) collagen gene (Col11a2). Transient transfection assays using reporter gene constructs revealed that a 60-base pair (bp) segment within intron 1 increased promoter activity of Col11a2 in rat chondro-sarcoma cells but not in either BalB/3T3 cells or undifferentiated ATDC5 cells, suggesting that it contained cell tape-specific enhancer activity. In transgenic mice, this 60-bp fragment was also able to target beta-galactosidase expression to cartilage including the limbs and axial skeleton, with similar localization specificity as the full-length intron 1 fragment. Competition experiments in gel shift assays using mutated oligonucleotides showed that recombinant Sox9 bound to a 7-bp sequence, CT-CAAAG, within the 60-bp segment. Anti-Sox9 antibodies supershifted the complex of the 60-bp segment with recombinant Sox9 or with rat chondrosarcoma cell extracts, confirming the binding of Sox9 to the enhancer. Moreover, a site-specific mutation within the 7-bp segment resulted in essentially complete loss of the enhancer activity in chondrosarcoma cells and transgenic mice. These results suggest that the 7-bp sequence within intron 1 plays a critical role in the cartilage-specific enhancer activity of Col11a2 through Sox9-mediated transcriptional activation. C1 NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Yamada, Y (reprint author), NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Rm 405, Bethesda, MD 20892 USA. NR 35 TC 72 Z9 75 U1 0 U2 3 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 APR 28 PY 2000 VL 275 IS 17 BP 12712 EP 12718 DI 10.1074/jbc.275.17.12712 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309HK UT WOS:000086762300049 PM 10777565 ER PT J AU Caffrey, JJ Safrany, ST Yang, XN Shears, SB AF Caffrey, JJ Safrany, ST Yang, XN Shears, SB TI Discovery of molecular and catalytic diversity among human diphosphoinositol-polyphosphate phosphohydrolases - An expanding Nudt family SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INOSITOL HEXAKISPHOSPHATE KINASE; DIADENOSINE POLYPHOSPHATES; SACCHAROMYCES-CEREVISIAE; PROTEIN; PENTAKISPHOSPHATE; TETRAKISPHOSPHATE; TURNOVER; SITE; HYDROLASES; MUTATIONS AB The turnover of the "high energy" diphosphoinositol polyphosphates by Ca2+- and cyclic nucleotide-modulated enzymes is considered a regulatory, molecular switching activity. Target processes may include intracellular trafficking. Following our earlier identification of a prototype human (d) under bar iphospho (i) under bar nositol-(p) under bar olyphosphate phosphohydrolase (hDIPP1), we now describe new 21-kDa human isoforms, hDIPP2 alpha and hDIPP2 beta, distinguished from each other solely by hDIPP2 beta possessing one additional amino acid (Gln(86)). Candidate DIPP2 alpha and DIPP2 beta homologues in rat and mouse were also identified. The rank order for catalytic activity is hDIPP1 > hDIPP2 alpha > hDIPP2 beta. Differential expression of hDIPP isoforms may provide flexibility in response times of the molecular switches. The 76% identity between hDIPP1 and the hDIPP2s includes conservation of an emerging signature sequence, namely, a Nudt (MutT) motif with a GX(2)GX(6)G carboxy extension. Northern and Western analyses indicate expression of hDIPP2s is broad but atypically controlled; these proteins are translated from multiple mRNAs that differ in the length of the 3'-untranslated region because of utilization of an array of alternative (canonical and noncanonical) polyadenylation signals. Thus, cells can recruit sophisticated molecular processes to regulate diphosphoinositol polyphosphate turnover. RP Caffrey, JJ (reprint author), NIEHS, Inositide Signaling Grp, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 32 TC 49 Z9 53 U1 0 U2 3 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 APR 28 PY 2000 VL 275 IS 17 BP 12730 EP 12736 DI 10.1074/jbc.275.17.12730 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309HK UT WOS:000086762300052 PM 10777568 ER PT J AU Herrera, JE Schiltz, RL Bustin, M AF Herrera, JE Schiltz, RL Bustin, M TI The accessibility of histone H3 tails in chromatin modulates their acetylation by P300/CBP-associated factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SCANNING FORCE MICROSCOPY; NUCLEOSOMAL ARRAYS; ACETYLTRANSFERASE ACTIVITY; LINKER HISTONES; IN-VIVO; TRANSCRIPTION; PCAF; DEACETYLATION; DOMAINS; FIBERS AB P300/CBP-associated factor (PCAF) is a transcriptional coactivator with intrinsic histone acetylase activity. Reversible acetylation of the core histone tails in chromatin has been linked to transcriptional regulation. Here we investigate the mechanism whereby PCAF acetylates its target in chromatin. We demonstrate that recombinant PACF preferentially acetylates the H3 tail in oligonucleosomes, as compared with nucleosome core particles. The rate of acetylation is directly related to the length of the oligonucleosomal substrate. Using a trypsin accessibility assay, we demonstrate that the rate of acetylation is also related to the accessibility of the H3 tail in uncondensed oligonucleosomes. We suggest that PCAF, and perhaps other histone acetyltransferases, acetylate chromatin templates more efficiently than core particle subunits and that this preference arises from an increased accessibility of the H3 tail in either condensed or uncondensed oligonucleosomes. Acetylation of the H3 tails by the native PCAF complex is not affected by the length of the oligonucleosomal substrate. Our results suggest that the accessibility of the H3 tail in chromatin is a major factor affecting their rate of acetylation and that component(s) in the native PCAF complex function to modify the organization of these tails in chromatin thereby enhancing their accessibility to PCAF. C1 NCI, Div Basic Sci, Lab Metab, Prot Sect,NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Herrera, JE (reprint author), NCI, Div Basic Sci, Lab Metab, Prot Sect,NIH, Bldg 37 Room 3D20, Bethesda, MD 20892 USA. RI Bustin, Michael/G-6155-2015 NR 32 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 APR 28 PY 2000 VL 275 IS 17 BP 12994 EP 12999 DI 10.1074/jbc.275.17.12994 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309HK UT WOS:000086762300085 PM 10777601 ER PT J AU Arteca, GA Luo, X AF Arteca, GA Luo, X TI Structural complexity and population analysis of hydrogen-bonded networks in proteins SO JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM LA English DT Article DE hydrogen bonds; network complexity; connectivity; protein surfaces; water-protein interaction; molecular shape ID MOLECULAR-DYNAMICS SIMULATION; LIQUID WATER; DIFFERENT TEMPERATURES; NEUTRON-SCATTERING; SUPERCOOLED WATER; SOLVENT STRUCTURE; HYDRATION SHELL; RIBONUCLEASE-A; AMINO-ACID; BEHAVIOR AB We discuss an approach to characterize the structural organization of hydrogen-bonded networks formed by proteins. Emphasis is made on global descriptors, deriving inspiration from percolation theory, which convey size and connectivity. Our goal is to test whether there is a pattern of network features shared by hydrated proteins. To this end, we have compared a number of experimental structures where detailed information on hydrogen bond geometry is available. For the selected proteins, we have studied the following population properties associated with network topology: (a) the number of hydrogen atoms embedded in water-only, protein-only, and water-protein networks; (b) the total number and size distribution of the maximum-connected components of these networks. Using these properties, we compute two order parameters of network complexity. These parameters allow one to compare the hydrogen-bonding patterns in hydrated (or dry) proteins with those of bulk water. Our results suggest a general relation between these order parameters in proteins, as well as "avoided" regions with molecular shape features that may not be reachable in actual hydration-shell networks. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Laurentian Univ, Dept Chim & Biochim, Sudbury, ON P3E 2C6, Canada. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Laurentian Univ, Dept Chim & Biochim, Ramsey Lake Rd, Sudbury, ON P3E 2C6, Canada. NR 60 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 J MOL STRUC-THEOCHEM JI Theochem-J. Mol. Struct. PD APR 28 PY 2000 VL 501 BP 479 EP 493 DI 10.1016/S0166-1280(99)00462-5 PG 15 WC Chemistry, Physical SC Chemistry GA 322ZY UT WOS:000087541100053 ER PT J AU Miller, MA Flanders, WD AF Miller, MA Flanders, WD TI A model to estimate the probability of hepatitis B- and Haemophilus influenzae type b-vaccine uptake into national vaccination programs SO VACCINE LA English DT Article DE hepatitis B; Haemophilus influenzae type b; vaccines; economics AB Most countries have been slow to adopt new vaccines into national vaccination schedules, despite recommendations from global multi-lateral agencies. Characteristics of countries that have adopted hepatitis B (HB) vaccine were analysed and used to formulate a logistic regression model. The model was applied to country-specific data to predict HB and Haemophilus influenzae type b (Hib) vaccine uptake. The greatest predictors of HB uptake were coverage rates of other vaccines, vaccine cost relative to the economy, and perceived disease burden. The logistic regression model's probability estimate of vaccine uptake agreed well with observed data for HB and Hib, (c-statistic 85 and 82%, respectively). Application of this model to other antigens may aid in predicting potential national markets to better plan new vaccine supply and demand. (C) 2000 Published by Elsevier Science Ltd. All rights reserved. C1 WHO, CH-1211 Geneva, Switzerland. Emory Univ, Atlanta, GA 30322 USA. RP Miller, MA (reprint author), Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. NR 11 TC 10 Z9 10 U1 3 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 28 PY 2000 VL 18 IS 21 BP 2223 EP 2230 DI 10.1016/S0264-410X(99)00563-0 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 307ZE UT WOS:000086683400007 PM 10717341 ER PT J AU Berezhkovskii, AM Szabo, A Weiss, GH AF Berezhkovskii, AM Szabo, A Weiss, GH TI Theory of the fluorescence of single molecules undergoing multistate conformational dynamics SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID FLUCTUATIONS AB The fluorescence decay of an N-state system observed in certain single-molecule experiments is multiexponential with random amplitudes when the duration of the experiment, T, is finite. We derive the probability density for these amplitudes. When Tis sufficiently large, the probability density for a given amplitude is shown to be a Gaussian centered at the equilibrium probability of the corresponding state, The width of the Gaussian is determined by the correlation time describing equilibrium fluctuations of the population of this state. To get an expression applicable at moderately large T we approximately map the N-state problem to a two-state problem. This allows us to make use of an analytical expression for the probability density of the two-state system derived previously. Illustrative calculations for a three-state system are given which compare the exact. Gaussian, and the equivalent two-state results. C1 LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. NICHHD, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Berezhkovskii, AM (reprint author), NICHHD, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012 NR 12 TC 27 Z9 27 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD APR 27 PY 2000 VL 104 IS 16 BP 3776 EP 3780 DI 10.1021/jp993067I PG 5 WC Chemistry, Physical SC Chemistry GA 329GY UT WOS:000087900200003 ER PT J AU Matsuda, T Bebenek, K Masutani, C Hanaoka, F Kunkel, TA AF Matsuda, T Bebenek, K Masutani, C Hanaoka, F Kunkel, TA TI Low fidelity DNA synthesis by human DNA polymerase-eta SO NATURE LA English DT Article ID PIGMENTOSUM VARIANT CELLS; ESCHERICHIA-COLI; HYPERMUTABILITY; PHOTOPRODUCTS; MUTAGENESIS; REPLICATION; MUTATION AB A superfamily of DNA polymerases that bypass lesions in DNA has been described(1-4). Some family members are described as error-prone because mutations that inactivate the polymerase reduce damage-induced mutagenesis. In contrast, mutations in the skin cancer susceptibility gene XPV5,6, which encodes DNA polymerase (pol)-eta, lead to increased ultraviolet-induced mutagenesis(7-11). This, and the fact that pol-eta primarily inserts adenines during efficient bypass of thymine-thymine dimers in vitro(8,12,13), has led to the description of pol-eta as error-free. However, here we show that human pol-eta copies undamaged DNA with much lower fidelity than any other template-dependent DNA polymerase studied. Pol-eta lacks an intrinsic proofreading exonuclease activity and, depending on the mismatch, makes one base substitution error for every 18 to 380 nucleotides synthesized. This very low fidelity indicates a relaxed requirement for correct base pairing geometry and indicates that the function of pol-eta may be tightly controlled to prevent potentially mutagenic DNA synthesis. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Osaka Univ, Inst Mol & Cellular Biol, Suita, Osaka 5650871, Japan. Japan Sci & Technol Corp, CREST, Suita, Osaka 5650871, Japan. RIKEN, Wako, Saitama 3510198, Japan. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RI Masutani, Chikahide/I-6160-2014 NR 28 TC 276 Z9 287 U1 0 U2 4 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 27 PY 2000 VL 404 IS 6781 BP 1011 EP 1013 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 309HG UT WOS:000086762000060 PM 10801132 ER PT J AU Tang, MJ Pham, P Shen, X Taylor, JS O'Donnell, M Woodgate, R Goodman, MF AF Tang, MJ Pham, P Shen, X Taylor, JS O'Donnell, M Woodgate, R Goodman, MF TI Roles of E-coli DNA polymerases IV and V in lesion-targeted and untargeted SOS mutagenesis SO NATURE LA English DT Article ID SINGLE-STRANDED VECTOR; ESCHERICHIA-COLI; RECA PROTEIN; CIS-SYN; ULTRAVIOLET-LIGHT; MOUSE HOMOLOGS; REPLICATION; MUTATION; BYPASS; PHOTOPRODUCTS AB The expression of the Escherichia coli DNA polymerases pol V (UmuD'(2) C complex)(1,2) and pol IV (DinB)(3) increases in response to DNA damage(4). The induction of pol V is accompanied by a substantial increase in mutations targeted at DNA template lesions in a process called SOS-induced error-prone repair(4). Here we show that the common DNA template lesions, TT (6-4) photoproducts, TT cis-syn photodimers and abasic sites, are efficiently bypassed within 30 seconds by pol V in the presence of activated RecA protein (RecA*), single-stranded binding protein (SSB) and pol III's processivity beta,gamma-complex. There is no detectable bypass by either pol IV or pol III on this time scale. A mutagenic 'signature' for pol V is its incorporation of guanine opposite the 3'-thymine of a TT (6-4) photoproduct, in agreement with mutational spectra. In contrast, pol III and pol IV incorporate adenine almost exclusively. When copying undamaged DNA, pol V exhibits low fidelity with error rates of around 10(-3) to 10(-4), with pol IV being 5- to 10-fold more accurate. The effects of RecA protein on pol V, and beta,gamma-complex on pol IV, cause a 15,000- and 3,000-fold increase in DNA synthesis efficiency, respectively. However, both polymerases exhibit low processivity, adding 6 to 8 nucleotides before dissociating. Lesion bypass by pol V does not require beta,gamma-complex in the presence of non-hydrolysable ATP gamma S, indicating that an intact RecA filament may be required for translesion synthesis. C1 Univ So Calif, Dept Biol Sci & Chem, Los Angeles, CA 90089 USA. Washington Univ, Dept Chem, St Louis, MO 63130 USA. Rockefeller Univ, New York, NY 10021 USA. Howard Hughes Med Inst, New York, NY 10021 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Goodman, MF (reprint author), Univ So Calif, Dept Biol Sci & Chem, Univ Pk, Los Angeles, CA 90089 USA. NR 30 TC 320 Z9 327 U1 3 U2 11 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 27 PY 2000 VL 404 IS 6781 BP 1014 EP 1018 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 309HG UT WOS:000086762000061 PM 10801133 ER PT J AU Abbott, KC Oliver, JD Ko, CW Kirk, AD Agodoa, LY AF Abbott, KC Oliver, JD Ko, CW Kirk, AD Agodoa, LY TI Aseptic necrosis after cadaveric renal transplantation: Data from the UNOS/USRDS database. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDCD, Epidemiol Stat & Data Syst Branch, NIH, Bethesda, MD USA. NIH, Organ Transplant Serv, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 813 BP S323 EP S323 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800811 ER PT J AU Abbott, KC Oliver, JD Ko, CW Kirk, AD Agodoa, Y AF Abbott, KC Oliver, JD Ko, CW Kirk, AD Agodoa, Y TI Fractures after cadaveric renal transplantation: Data from the UNOS/USRDS database. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Serv Nephrol, Bethesda, MD USA. Natl Inst Deafness & Other Commun Disorders, Epidemiol Stat & Data Syst Branch, NIH, Bethesda, MD USA. NIH, Organ Transplant Serv, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 678 BP S288 EP S288 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800676 ER PT J AU Abbott, KC Oliver, JD Ko, CW Kirk, AD Polly, SM Jones, CA Agodoa, LY AF Abbott, KC Oliver, JD Ko, CW Kirk, AD Polly, SM Jones, CA Agodoa, LY TI Patient and renal allograft survival in patients seropositive for human immunodeficiency virus infection at transplantation: Data from the UNOS/USRDS database. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Washington, DC USA. NIDCD, Epidemiol Stat & Data Syst Branch, NIH, Bethesda, MD USA. NIH, Organ Transplant Serv, Bethesda, MD USA. Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20307 USA. NIDDK, NIH, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 400 BP S217 EP S217 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800398 ER PT J AU Batty, DS Swanson, SJ Polly, SM Oliver, JD Oliver, DK Ko, CW Kirk, AD Agodoa, LY Abbott, KC AF Batty, DS Swanson, SJ Polly, SM Oliver, JD Oliver, DK Ko, CW Kirk, AD Agodoa, LY Abbott, KC TI Impact of recipient and donor hepatitis C virus infection status on outcomes after renal transplantation: Data from the UNOS/USRDS database. SO TRANSPLANTATION LA English DT Meeting Abstract C1 NIH, Organ Transplant Serv, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Serv Nephrol, Bethesda, MD USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Serv Nephrol, Washington, DC 20307 USA. NIDCD, Epidemiol Stat & Data Syst Branch, NIH, Bethesda, MD USA. NIDDK, NIH, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Washington, DC USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RI Kirk, Allan/B-6905-2012 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 90 BP S135 EP S135 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800091 ER PT J AU Eckhoff, DE Contreras, JL Lobashevsky, AL Hubbard, WJ Moore, J Cook, WJ Zinn, K Thomas, FT Neville, D Thomas, JM AF Eckhoff, DE Contreras, JL Lobashevsky, AL Hubbard, WJ Moore, J Cook, WJ Zinn, K Thomas, FT Neville, D Thomas, JM TI A preclinical paradigm of tolerance without chronic allograft nephropathy (CAN) following peritransplant T cell ablation (TCA) with dendritic cell maturation arrest (DCMA). SO TRANSPLANTATION LA English DT Meeting Abstract C1 UAB, Transplant Ctr, Birmingham, AL USA. NIH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 132 BP S147 EP S147 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800133 ER PT J AU Elster, EA Xu, H Burkly, LC Berning, JD Baumgartner, RE Kampen, RL Patterson, NB Tadaki, DK Harlan, DM Kirk, AD AF Elster, EA Xu, H Burkly, LC Berning, JD Baumgartner, RE Kampen, RL Patterson, NB Tadaki, DK Harlan, DM Kirk, AD TI Primary skin allograft acceptance with anti-CD154 in a non-human primate model. SO TRANSPLANTATION LA English DT Meeting Abstract C1 NIH, Transplantat & Autoimmun Branch, Bethesda, MD 20892 USA. USN, Med Res Ctr, Bethesda, MD 20084 USA. Biogen Inc, Cambridge, MA 02142 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 493 BP S239 EP S239 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800491 ER PT J AU Hubbard, WJ Smyth, CA Moore, JK Contreras, JL Nagata, K Neville, DM Thomas, JM AF Hubbard, WJ Smyth, CA Moore, JK Contreras, JL Nagata, K Neville, DM Thomas, JM TI Immunological profiles of long-term tolerized rhesus macaques induced with IT and DSG. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. BioMed Labs Inc, R&D Ctr, Tokyo, Japan. NIMH, Mol Biol Lab, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 502 BP S242 EP S242 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800500 ER PT J AU Kirk, AD Tadaki, DK Xu, H Elster, EA Burkley, LC Celniker, A Batty, DS Baumgartner, RE Berning, JD Fechner, JH Kampen, RL Knechtle, SJ Patterson, NB Swanson, SJ Harlan, DM AF Kirk, AD Tadaki, DK Xu, H Elster, EA Burkley, LC Celniker, A Batty, DS Baumgartner, RE Berning, JD Fechner, JH Kampen, RL Knechtle, SJ Patterson, NB Swanson, SJ Harlan, DM TI Primate allotransplantation using costimulation blockade. SO TRANSPLANTATION LA English DT Meeting Abstract C1 NIH, Transplantat & Autoimmun Branch, USN, Med Res Ctr, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI USA. Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20307 USA. Biogen Inc, Cambridge, MA 02142 USA. Genet Inst, Cambridge, MA 02140 USA. RI Kirk, Allan/B-6905-2012; Fechner, John/C-5962-2016 OI Fechner, John/0000-0002-8220-7237 NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 1156 BP S414 EP S414 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911801154 ER PT J AU Ma, S Jiang, XL Stavrov, S Thomas, FT Neville, DM Thomas, JM AF Ma, S Jiang, XL Stavrov, S Thomas, FT Neville, DM Thomas, JM TI Analysis of anti-CD3 it on activation of T lymphocyte and cytokine expression in vitro. SO TRANSPLANTATION LA English DT Meeting Abstract C1 UAB, Birmingham, AL USA. NIMH, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 1000 BP S372 EP S372 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800998 ER PT J AU Ojo, AO Kaplan, B Hanson, JA Meier-Kriesche, HU Leichtman, AB Magee, JC Cibrik, DM Wolfe, RA Port, FK Agodoa, LYC Kaufman, DB AF Ojo, AO Kaplan, B Hanson, JA Meier-Kriesche, HU Leichtman, AB Magee, JC Cibrik, DM Wolfe, RA Port, FK Agodoa, LYC Kaufman, DB TI Impact of transplant types on long-term mortality in type 1 diabetics with end-stage nephropathy. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIDDK, Bethesda, MD USA. Northwestern Univ, Evanston, IL 60208 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 612 BP S270 EP S270 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800610 ER PT J AU Swanson, SJ Abbott, KC Oliver, JD Ko, CW Kirk, AD Agodoa, LY AF Swanson, SJ Abbott, KC Oliver, JD Ko, CW Kirk, AD Agodoa, LY TI Impact of donor and recipient factors on graft survival after cadaveric renal transplantation: Data from the UNOS/USRDS database. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. NIDCD, Epidemiol Stat & Data Syst Branch, NIH, Bethesda, MD USA. NIH, Organ Tissue Transplant Res Ctr, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 584 BP S262 EP S263 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800582 ER PT J AU Thomas, JM Ma, S Contreras, JL Hubbard, WJ Smyth, CA Thomas, FT Neville, DM AF Thomas, JM Ma, S Contreras, JL Hubbard, WJ Smyth, CA Thomas, FT Neville, DM TI Contrasting in vitro and in vivo activity of F(Ab)(2) and IgG anti-CD3 immunotoxin (IT) in tolerance induction. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. NIMH, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 50 BP S124 EP S124 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800051 ER PT J AU Valujskikh, A Lantz, O Matzinger, P Heeger, PS AF Valujskikh, A Lantz, O Matzinger, P Heeger, PS TI Indirect allorecognition by CD8 T cells is relevant to minor antigen disparate skin graft rejection. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Stokes VAMC, Cleveland, OH USA. Unite Inserm, Paris, France. NIH, Bethesda, MD 20892 USA. RI Lantz, Olivier/J-4960-2012 OI Lantz, Olivier/0000-0003-3161-7719 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 1006 BP S374 EP S374 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911801004 ER PT J AU Xu, H Arnaud, F Tadaki, DK Burkly, LC Harlan, DM Kirk, AD AF Xu, H Arnaud, F Tadaki, DK Burkly, LC Harlan, DM Kirk, AD TI Human platelets activate porcine endothelial cells through a CD154 dependent mechanism. SO TRANSPLANTATION LA English DT Meeting Abstract C1 USN, Med Res Ctr, Transplantat & Autoimmun Branch, NIH, Bethesda, MD 20084 USA. Biogen Inc, Cambridge, MA 02142 USA. RI Kirk, Allan/B-6905-2012 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 1045 BP S384 EP S384 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911801043 ER PT J AU Xu, H Tadaki, DK Blair, PJ Harlan, DM Kirk, AD AF Xu, H Tadaki, DK Blair, PJ Harlan, DM Kirk, AD TI Porcine endothelium costimulates human T cells in the absence of human antigen presenting cells (APCs). SO TRANSPLANTATION LA English DT Meeting Abstract C1 NIH, Transplantat & Autoimmun Branch, Bethesda, MD 20892 USA. USN, Med Res Ctr, Bethesda, MD 20084 USA. RI Kirk, Allan/B-6905-2012 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 566 BP S258 EP S258 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800564 ER PT J AU Kant, AK Schatzkin, A Graubard, BI Schairer, C AF Kant, AK Schatzkin, A Graubard, BI Schairer, C TI A prospective study of diet quality and mortality in women SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NATIONAL-HEALTH; RISK; QUESTIONNAIRE; MEN; DIVERSITY AB Context Most studies of diet and health care have focused on the role of single nutrients, foods, or food groups in disease prevention or promotion. Few studies have addressed the health effects of dietary patterns, which include complex mixtures of foods containing multiple nutrients and nonnutrients. Objective To examine the association of mortality with a multifactorial diet quality index. Design and Setting Data from phase 2 (1987-1989) of a prospective cohort study of breast cancer screening, the Breast Cancer Detection Demonstration Project, with a median follow-up of 5.6 years. Participants A total of 42 254 women (mean age, 61.1 years) who completed the food frequency questionnaire portion of the survey. Main Outcome Measure All-cause mortality by quartile of Recommended Food Score (RFS; the sum of the number of foods recommended by current dietary guidelines [fruits, vegetables, whole grains, low-fat dairy, and lean meats and poultry] that were reported on the questionnaire to be consumed at least once a week, for a maximum score of 23). Results There were 2065 deaths due to all causes in the cohort. The RFS was inversely associated with all-cause mortality. Compared with those in the lowest quartile, subjects in the upper quartiles of the RFS had relative risks for all-cause mortality of 0.82 (95% confidence interval [CI], 0.73-0.92) for quartile 2, 0.71 (95% CI, 0.62-0.81) for quartile 3, and 0.69 (95% CI, 0.61-0.78) for quartile 4 adjusted for education, ethnicity, age, body mass index, smoking status, alcohol use, level of physical activity, menopausal hormone use, and history of disease (chi(1)(2) for trend = 35.64, P<.001 for trend). Conclusions These data suggest that a dietary pattern characterized by consumption of foods recommended in current dietary guidelines is associated with decreased risk of mortality in women. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Schatzkin, A (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7032, Bethesda, MD 20892 USA. RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 NR 27 TC 318 Z9 329 U1 1 U2 20 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 APR 26 PY 2000 VL 283 IS 16 BP 2109 EP 2115 DI 10.1001/jama.283.16.2109 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 305MA UT WOS:000086542800026 PM 10791502 ER PT J AU Willinger, M Ko, CW Hoffman, HJ Kessler, RC Corwin, MJ AF Willinger, M Ko, CW Hoffman, HJ Kessler, RC Corwin, MJ TI Factors associated with caregivers' choice of infant sleep position, 1994-1998 - The National Infant Sleep Position Study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DEATH-SYNDROME; RECEPTOR-BINDING; ARCUATE NUCLEUS; RISK; PREVALENCE; ENVIRONMENT; DECLINE AB Context The success and simplicity of the 1994 national "Back to Sleep" campaign to reduce sudden infant death syndrome provides an opportunity to study which elements determine whether a behavior will change in the desired direction in response to a public health intervention. Objective To examine sociodemographic characteristics, motivation, and message exposure to ascertain which factors influenced a caregiver's choice of infant sleep position after implementation of the campaign. Design Annual nationally representative telephone surveys conducted between 1994 and 1998. Setting The 48 contiguous United States. Participants Nighttime caregivers of infants born within the 7 months prior to interview between 1994 and 1998. Approximately 1000 interviews were conducted each year. Main Outcome Measures The position the infant was usually placed in for sleep, sleep position recommendations received from specific sources, and reasons reported for position choice. Results Between 1994 and 1998, prone placement declined from 44% to 17% among white infants and from 53% to 32% among black infants. Supine placement increased from 27% to 58% among white infants and from 17% to 31% among black infants. During this period, reports of supine recommendations from at least 1 source doubled from 38% to 79%. From 1995 to 1998, 86% of caregivers who placed the infant prone reported receiving only nonprone recommendations. Infant comfort was given as a reason for prone placement by 82% of these caregivers. In multivariate analysis, physician recommendation of "supine not prone" had the strongest influence and was associated with decreased prone placement (odds ratio [OR], 0.25 [95% confidence interval {CI}, 0.16-0.39]) and increased supine placement (OR, 3.37 [95% CI, 2.38-4.76]). Recommendations from all 4 sources (the physician, neonatal nurse, reading materials, and radio/television) further increased the probability of supine placement (OR, 6.01 [95% CI, 4.57-7.90]). Other factors independently associated with increased prone and decreased supine placement included maternal black race, parity of more than 1, and living in a southern or mid-Atlantic state. Conclusions According to our study, as of 1998, approximately one fifth of infants were still placed prone, and only half were placed supine. Recommendations of supine placement during infancy by physicians at well-baby checks and by neonatal nursery staff and print and broadcast media have increased the proportion of infants placed supine. Caregiver beliefs regarding perceived advantages of prone sleeping should be addressed to attain further reduction in prone placement. C1 NICHHD, Ctr Res Mothers & Children, Pregnancy & Perinatol Branch, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Epidemiol Stat & Data Syst Branch, Bethesda, MD USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston Med Ctr, Dept Pediat, Boston, MA 02118 USA. RP Willinger, M (reprint author), NICHHD, Ctr Res Mothers & Children, Pregnancy & Perinatol Branch, Execut Bldg,Room 4B03,6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD-2-9067] NR 32 TC 125 Z9 125 U1 0 U2 6 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 APR 26 PY 2000 VL 283 IS 16 BP 2135 EP 2142 DI 10.1001/jama.283.16.2135 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 305MA UT WOS:000086542800030 PM 10791506 ER PT J AU Yau, WM Gawrisch, K AF Yau, WM Gawrisch, K TI Lateral lipid diffusion dominates NOESY cross-relaxation in membranes SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 12420 Parklawn Dr,Room 158, Rockville, MD 20852 USA. NR 7 TC 27 Z9 27 U1 2 U2 7 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 APR 26 PY 2000 VL 122 IS 16 BP 3971 EP 3972 DI 10.1021/ja9944756 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 309KC UT WOS:000086766200024 ER PT J AU Cho, HC Tsushima, RG Nguyen, TTT Guy, HR Backx, PH AF Cho, HC Tsushima, RG Nguyen, TTT Guy, HR Backx, PH TI Two critical cysteine residues implicated in disulfide bond formation and proper folding of Kir2.1 SO BIOCHEMISTRY LA English DT Article ID RECTIFYING POTASSIUM CHANNEL; K+ CHANNEL; PROTEIN STABILITY; SUBUNIT STOICHIOMETRY; RECTIFICATION; PURIFICATION; SELECTIVITY; MODELS; SITE AB Inwardly rectifying potassium channels are important in cellular repolarization of many excitable tissues. Amino acid sequence alignment of different mammalian inward rectifier K+ channels revealed two absolutely conserved cysteine residues in the putative extracellular face, suggesting a possible disulfide bond. Replacement of these cysteine residues in the Kir2.1 channel (i.e., C122 and C154) with either alanine or serine abolished current in Xenopus laevis oocytes although Western blotting established that the channels were fully expressed. The digestion pattern of channels treated with Vs protease combined with Western blotting under reducing and nonreducing conditions confirmed intrasubunit cross-linking of C122 and C154. Whole-cell and single channel current recordings of oocytes expressing tandem tetrameric constructs with one or two of the mutant subunits suggested that insertion of one mutant subunit is sufficient to eliminate channel function. Coexpression studies confirmed that the cysteine mutant channels eliminate wild-type Kir2,1 currents in a dominant-negative manner. Despite these results, sulfhydryl reduction did not alter the functional properties of Kir2.1 currents. Molecular modeling of Kir2.1 with the two cysteines cross-linked predicted that the extracellular loop between the first transmembrane domain and the pore helix contains a beta-hairpin structure. Distinct from the KcsA structure, the disulfide bond together with the beta-hairpin structure is expected to constrain and stabilize the P-loop and selectivity filter. Taken together, these results suggest that intramolecular disulfide bond exists between C122 and C154 of Kir3.1 channel and this cross-link might be required for proper channel folding. C1 Univ Toronto, Dept Physiol, Toronto, ON M5G 2C4, Canada. Univ Toronto, Dept Med, Toronto, ON M5G 2C4, Canada. Univ Hlth Network, Toronto, ON M5G 2C4, Canada. NCI, Math Biol Lab, DCBDC, NIH, Bethesda, MD 20892 USA. RP Backx, PH (reprint author), Univ Toronto, Dept Physiol, 100 Coll St, Toronto, ON M5G 2C4, Canada. NR 30 TC 38 Z9 38 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 25 PY 2000 VL 39 IS 16 BP 4649 EP 4657 DI 10.1021/bi992469g PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308XG UT WOS:000086737700010 PM 10769120 ER PT J AU Fan, YX McPhie, P Miles, EW AF Fan, YX McPhie, P Miles, EW TI Regulation of tryptophan synthase by temperature, monovalent cations, and an allosteric ligand. Evidence from arrhenius plots, absorption spectra, and primary kinetic isotope effects SO BIOCHEMISTRY LA English DT Article ID ULTRAVIOLET VISIBLE SPECTROSCOPY; ALPHA(2)BETA(2) COMPLEX REVEALS; INDUCED CONFORMATIONAL-CHANGES; SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; BIENZYME COMPLEX; INTERSUBUNIT COMMUNICATION; ALPHA-SUBUNIT; BETA-SUBUNIT; CATALYTIC MECHANISM AB To investigate the linkage between enzyme conformation and catalysis, we have determined the effects of temperature on catalytic properties of the tryptophan synthase alpha(2)beta(2) complex and beta(2) subunit in the absence or presence of different monovalent cations (Cs+, Na+, and CuH+) and of an allosteric ligand, alpha-glycerol 3-phosphate. Arrhenius plots of the activity data between 5 and 50 degrees C are nonlinear in the presence of certain ligands but not others. The conditions that yield nonlinear Arrhenius plots also yield temperature-dependent changes in the equilibrium distribution of enzyme-substrate intermediates and in primary kinetic isotope effects. The results provide evidence that the nonlinear Arrhenius plots are caused by a temperature-dependent conformational change that precedes the rate-limiting step in catalysis. Thermodynamic analysis of the data associated with the conformational change shows that the activation energies are much higher at low temperatures than at high temperatures. We correlate the results with a model in which the enzyme is converted by increased temperature under certain conditions from a low-activity "open" conformation to a high-activity "closed" conformation. The allosteric Ligand and different monovalent cations, including GuH(+), which also acts as a chaotropic agent, affect the equilibrium between the open and closed forms. The large positive entropy changes in the conformational conversion suggest that the closed conformation results from tightened hydrophobic interactions that exclude water from the active site of the beta subunit. C1 NIDDKD, Sect Enzyme Struct & Funct, Lab Biochem & Genet, Bethesda, MD 20892 USA. RP Miles, EW (reprint author), NIDDKD, Sect Enzyme Struct & Funct, Lab Biochem & Genet, Bldg 8,Room 225,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. EM EdithM@intra.niddk.nih.gov NR 64 TC 43 Z9 44 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 25 PY 2000 VL 39 IS 16 BP 4692 EP 4703 DI 10.1021/bi9921586 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308XG UT WOS:000086737700015 PM 10769125 ER PT J AU Lee, YN Park, YG Choi, YH Cho, YS Cho-Chung, YS AF Lee, YN Park, YG Choi, YH Cho, YS Cho-Chung, YS TI CRE-Transcription factor decoy oligonucleotide inhibition of MCF-7 breast cancer cells: Cross-talk with p53 signaling pathway SO BIOCHEMISTRY LA English DT Article ID AMP RESPONSE ELEMENT; CYCLIC-AMP; GENE-TRANSCRIPTION; SOMATOSTATIN GENE; DEPENDENT KINASES; GRANULOSA-CELLS; NUCLEAR-PROTEIN; DNA-DAMAGE; GROWTH; BINDING AB The CRE, 5'-TGACGTCA-3', has been described as the consensus sequence for the cis-element that directs cAMP-regulated gene expression Many transcription factors bind to this element and regulate the expression of a wide variety of cellular and viral genes. We have shown that CRE-transcription factor decoy oligonucleotide restrains the growth of cancer cells in vitro and in vivo [Park, Y. G., Nesterova, M., Agrawal, S., and Cho-Chung, Y. S. (1999) J. Biol. Chem. 274, 1573-1580]. The growth inhibition was accompanied by changes in cell morphology and apoptosis. To elucidate the molecular mechanism (s) of the growth inhibition by the CRE-decoy oligonucleotide, we investigated the p53 signaling pathway. Herein, we report that CRE-decoy oligonucleotide treatment results in an increase in the p53 protein level in MCF-7 human breast cancer cells that express wild-type p53. The p21WAF1/Cip1 protein levels were also increased in the CRE-decoy oligonucleotide treated cells accompanying a reduction in Cdk2- and cyclin E-dependent kinase activity and pRb phosphorylation. Pulse-chase experiments reveal that the p53 upregulation was due to increased stability of the protein. The decoy oligonucleotide treatment also enhanced the p53 promotor-directed transcription in vivo along with the increase in p53-CBP (CREB-binding protein) complex formation. Thus, the stabilization and activation of p53 may have contributed to the growth inhibition induced by CRE-transcription factor decoy oligonucleotide in MCF-7 breast cancer cells. This decoy oligonucleotide approach offers great promise as a tool for defining cellular regulatory processes and treating cancer and other diseases. C1 NCI, Cellular Biochem Sect, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Lab Tumor Immunol & Biol, Bldg 10,Room 480-8587, Bethesda, MD 20892 USA. NR 37 TC 34 Z9 34 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 25 PY 2000 VL 39 IS 16 BP 4863 EP 4868 DI 10.1021/bi992272o PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308XG UT WOS:000086737700034 PM 10769144 ER PT J AU Sood, R Makalowska, I Carpten, JD Robbins, CM Stephan, DA Connors, TD Morgenbesser, SD Su, K Pinkett, HW Graham, CL Quesenberry, MI Baxevanis, AD Klinger, KW Trent, JM Bonner, TI AF Sood, R Makalowska, I Carpten, JD Robbins, CM Stephan, DA Connors, TD Morgenbesser, SD Su, K Pinkett, HW Graham, CL Quesenberry, MI Baxevanis, AD Klinger, KW Trent, JM Bonner, TI TI The human RGL (RalGDS-like) gene: cloning, expression analysis and genomic organization SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE RGL; prostate cancer; gene structure; expression ID NUCLEOTIDE DISSOCIATION STIMULATOR; RAS; CANCER AB Ral GDP dissociation stimulator (RalGDS) and its family members RGL, RLF and RGL2 are involved in Ras and Ral signaling pathways as downstream effector proteins. Here we report the precise localization and cloning of two forms of human RGL gene differing at the amino terminus. Transcript A, cloned from liver cDNA libraries has the same amino terminus as the mouse RGL, whereas transcript B cloned from brain has a substitution of 45 amino acids for the first nine amino acids. At the genomic level, exon 1 of transcript A is replaced by two alternative exons (1B1 and 1B2) in transcript B. Both forms share exons 2 through is. The human RGL protein shares 94% amino acid identity with the mouse protein. Northern blot analysis shows that human RGL is expressed in a wide variety of tissues with strong expression being seen in the heart, brain, kidney, spleen and testis. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Genzyme Genet Corp, Framingham, MA USA. NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Sood, R (reprint author), Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bldg 36,Room 3D05,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Pinkett, Heather/M-9235-2014 NR 12 TC 9 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD APR 25 PY 2000 VL 1491 IS 1-3 BP 285 EP 288 DI 10.1016/S0167-4781(00)00031-2 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 307PD UT WOS:000086661000030 PM 10760592 ER PT J AU Parker, R Liu, M Eyre, HJ Copeland, NG Gilbert, DJ Crawford, J Sutherland, GR Jenkins, NA Herzog, H AF Parker, R Liu, M Eyre, HJ Copeland, NG Gilbert, DJ Crawford, J Sutherland, GR Jenkins, NA Herzog, H TI Y-receptor-like genes GPR72 and GPR73: molecular cloning, genomic organisation and assignment to human chromosome 11q21.1 and 2p14 and mouse chromosome 9 and 6 SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE G-protein coupled receptor; neuropeptide Y; ligand binding; cell-surface expression ID LINKAGE MAP; RAT-BRAIN; ORGANIZATION; EXPRESSION; PROTEINS; LOCI AB Two novel G-protein-coupled receptors, one from human, GPR72, and one from mouse, GPR73 have been isolated, sequenced and their genomic organisation determined. Non-isotopic in situ hybridisation and radiation hybrid mapping have identified GPR72 to be localised on human chromosome 11q21.1, and GPR73 on human chromosome 2p14. Interspecific mouse backcross mapping has localised the genes to mouse chromosomes 9 and 6, respectively. Northern analysis reveals GPR72 mRNA expression only in brain tissue. However, GPR73 mRNA can be found in heart, skeletal muscle and pancreas. Both receptors are closely related with 36 and 33% overall amino acid identity, respectively, to the Y-receptor family. However, although successful cell surface expression in a heterologous expression system can be achieved no specific binding to this ligand family can be detected, indicating that perhaps additional factors are required for binding. (C) 2000 Elsevier Science B.V. All rights reserved. C1 St Vincents Hosp, Garvan Inst Med Res, Neurobiol Program, Sydney, NSW 2010, Australia. Womens & Childrens Hosp, Dept Cytogenet & Mol Genet, Ctr Med Genet, Adelaide, SA 5006, Australia. Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL Basic Res Program, Frederick, MD 21702 USA. RP Herzog, H (reprint author), Garvan Inst Med Res, 384 Victoria St, Sydney, NSW 2010, Australia. RI Sutherland, Grant/D-2606-2012; Crawford, Joanna /F-9135-2013 OI Crawford, Joanna /0000-0003-0786-6889 NR 18 TC 22 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD APR 25 PY 2000 VL 1491 IS 1-3 BP 369 EP 375 DI 10.1016/S0167-4781(00)00023-3 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 307PD UT WOS:000086661000043 PM 10760605 ER PT J AU Zeng, HW Plisov, SY Simons, SS AF Zeng, HW Plisov, SY Simons, SS TI Ability of the glucocorticoid modulatory element to modify glucocorticoid receptor transactivation indicates parallel pathways for the expression of glucocorticoid modulatory element and glucocorticoid response element activities SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE glucocorticoid modulatory element; GME; glucocorticoid receptor; transactivation ID TYROSINE AMINOTRANSFERASE GENE; TISSUE-CULTURE CELLS; TRANSCRIPTIONAL ACTIVATION; HORMONE RECEPTORS; NUCLEAR RECEPTORS; AGONIST ACTIVITY; DEPENDENT TRANSCRIPTION; BIOLOGICAL-ACTIVITY; BINDING-FACTOR; CO-REPRESSOR AB The glucocorticoid modulatory element (GME) of the rat tyrosine aminotransferase gene is located at - 3.6 kb and 1 kb upstream of the glucorticoid response elements (GREs). The GME has the unique transcriptional properties of modulating both the dose-response curve of agonists bound to the glucocorticoid receptor (GR) and the residual agonist activity of GR-bound antisteroids. The expression of GME activity involves the binding of two novel proteins (GMEB-1 and GMEB-2) that we have recently cloned. However, the mechanistic details are limited. The DNA sequence requirements for GME activity (CGTC) also remain poorly defined, which restricts efforts to identify other GME modulated genes. To help understand the mechanism for the unusual activities of the GME and to identify permissive gene environments for GME activity, we compared the changes in GME activity and GRE action (i.e, the fold induction by GR) caused by modifying several parameters. Phasing between the GME and downstream tandem GREs was unimportant, in contrast to other cis-acting elements like the GRE, while GME activity decreased rapidly when placed at increasingly larger distances 3' to a tandem GRE. A minimal promoter was less effective in supporting GME than GRE activity. Although CREB binds to the GME, overexpression of CREB reduced GRE, but not GME, activity and a CRE was inactive when substituted for the GME. No effect of the GME was observed on the binding of GRs to a single GRE. However, the GME upstream of a single GRE was also unable to produce a left shift in the Dex dose-response curve under conditions where the GME was active with two GREs. In the absence of any GREs, the GME displayed intrinsic activity by elevating basal level expression. Collectively, these results indicate that an optimal position for a functional GME is within 250 bp upstream of a tandem GRE driving a complex promoter. Furthermore, as the changes in GME activity did not correlate with those for fold induction from the GRE, the mechanisms for expression of GME and GRE activities appear to utilize parallel, as opposed to common pathways. Published by Elsevier Science Ireland Ltd. C1 NIDDK, LMCB, NIH, Steroid Hormones Sect, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDK, LMCB, NIH, Steroid Hormones Sect, Bldg 8,Room B2A-07, Bethesda, MD 20892 USA. NR 59 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD APR 25 PY 2000 VL 162 IS 1-2 BP 221 EP 234 DI 10.1016/S0303-7207(99)00208-7 PG 14 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 324VW UT WOS:000087642900024 PM 10854715 ER PT J AU Hacke, W Warach, S AF Hacke, W Warach, S TI Diffusion-weighted MRI as an evolving standard of care in acute stroke SO NEUROLOGY LA English DT Editorial Material C1 Univ Heidelberg, Dept Neurol, D-96120 Heidelberg, Germany. NINDS, Bethesda, MD 20892 USA. RP Hacke, W (reprint author), Univ Heidelberg, Dept Neurol, Neuenheimer Feld 400, D-96120 Heidelberg, Germany. NR 10 TC 44 Z9 44 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 APR 25 PY 2000 VL 54 IS 8 BP 1548 EP 1549 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 307FD UT WOS:000086642000001 PM 10762488 ER PT J AU Konitsiotis, S Blanchet, PJ Verhagen, L Lamers, E Chase, TN AF Konitsiotis, S Blanchet, PJ Verhagen, L Lamers, E Chase, TN TI AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys SO NEUROLOGY LA English DT Article DE PD; dyskinesia; levodopa; MPTP; basal ganglia; nonhuman primates; animal models ID MOTOR RESPONSE COMPLICATIONS; MONOAMINE-DEPLETED RATS; PROTEIN-KINASE-A; PARKINSONS-DISEASE; L-DOPA; GLUTAMATE RECEPTORS; ANTAGONIST NBQX; BASAL GANGLIA; TYROSINE PHOSPHORYLATION; NMDA ANTAGONISTS AB Objective: To evaluate the contribution of amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) glutamate receptors to the pathogenesis of parkinsonian signs and levodopa-induced dyskinesias. Background: Motor fluctuations and dyskinesias reflect, in part, altered function of glutamate receptors of the NMDA subtype. The possible role of AMPA receptors, however, has not yet been examined. Methods: The authors compared the ability of an AMPA agonist (CX516) and a noncompetitive AMPA antagonist (LY300164) to alter parkinsonian symptoms and levodopa-induced dyskinesia in MPTP-lesioned monkeys. Eight levodopa-treated parkinsonian monkeys received rising doses of each drug, first in monotherapy and then in combination with low-, medium-, and high-dose levodopa. Results: CX516 alone, as well as when combined with low-dose levodopa, did not affect motor activity but induced dyskinesia. Moreover, following injection of the higher doses of levodopa, it increased levodopa-induced dyskinesia by up to 52% (p < 0.05). LY300164 potentiated the motor activating effects of low-dose levodopa, increasing motor activity by as much as 86% (p < 0.05), and that of medium-dose levodopa as much as 54% (p < 0.05). At the same time, LY300164 decreased levodopa-induced dyskinesia by up to 40% (p < 0.05). Conclusions: AMPA receptor upregulation may contribute to the expression of levodopa-induced dyskinesia. Conceivably, noncompetitive AMPA receptor antagonists could be useful, alone or in combination with NMDA antagonists, in the treatment of PD, by enhancing the antiparkinsonian effects of levodopa without increasing and possibly even decreasing levodopa-induced dyskinesia. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Rm 5C103, Bethesda, MD 20892 USA. NR 49 TC 145 Z9 150 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 25 PY 2000 VL 54 IS 8 BP 1589 EP 1595 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 307FD UT WOS:000086642000011 PM 10762498 ER PT J AU Bara-Jimenez, W Aksu, M Graham, B Sato, S Hallett, M AF Bara-Jimenez, W Aksu, M Graham, B Sato, S Hallett, M TI Periodic limb movements in sleep - State-dependent excitability of the spinal flexor reflex SO NEUROLOGY LA English DT Article DE periodic limb movement disorder; periodic leg movements during sleep; periodic limb movements; sleep; physiology; restless legs syndrome; spinal cord; flexor reflex ID RESTLESS LEGS SYNDROME; NOCTURNAL MYOCLONUS; CORD LESION AB Objective: To test the hypothesis that periodic limb movements (PLMs) are related to spinal flexor reflexes (FRs), the authors compared the state-dependent changes in FR excitability in 10 patients with restless legs syndrome (RLS) and PLMs with those from matched controls. Background: PLM is a disorder of motor control during sleep, frequently occurring in RLS. Clinically, PLMs resemble spinal FRs. Methods: FRs were obtained by electrically stimulating the medial plantar nerve and recording from antagonist leg and thigh muscles bilaterally. Results: Compared with controls, patients had significantly increased spinal cord excitability, as indicated by lower threshold and greater spatial spread of the FR, which was more prominent during sleep. Multiple late responses were seen during sleep in all patients and in some controls at higher threshold. The most prominent of these responses had a very long duration and a latency range of 250 to 800 msec, and because of its close temporal relationship to the FR stimulus, the authors considered it was a late, high-threshold component of the FR (FR3). The authors also found a similarity between the pattern of muscle recruitment and spatial spread of late components of the FR and those of spontaneous PLMs. Conclusions: The results support the hypothesis that PLMs in RLS and FRs share common spinal mechanisms and suggest that PLMs may result from enhanced spinal cord excitability in RLS patients. Because dopaminergic mechanisms are involved in spinal FR control, the results are consistent with the current view that RLS is a disorder of dopaminergic function. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. NR 37 TC 162 Z9 166 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 25 PY 2000 VL 54 IS 8 BP 1609 EP 1615 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 307FD UT WOS:000086642000014 PM 10762502 ER PT J AU Li, M Dalakas, MC AF Li, M Dalakas, MC TI The muscle mitogen-activated protein kinase is altered in sporadic inclusion body myositis SO NEUROLOGY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the American-Academy-of-Neurology CY APR 17-24, 1999 CL TORONTO, CANADA SP Amer Acad Neurol DE muscle mitogen-activated protein kinase; sporadic inclusion body myositis ID SKELETAL-MUSCLE; MYOPATHY; PHOSPHORYLATION; EXPRESSION; MUTATIONS; CELLS; TAU AB Objective: To examine the origin of hyperphosphorylated proteins within the vacuolated myofibers in sporadic inclusion body myositis (s-IBM) and search for dysregulated intracellular protein phosphorylation. Background: s-IBM is morphologically characterized by primary endomysial inflammation and vacuolated myofibers containing tubulofilaments that originate from cytoskeletal proteins. Mitogen-activated protein kinases (MAPKs) play a role in regulating phosphorylation and maintaining the stability of the cytoskeletal architecture. Methods: Muscle biopsies from seven patients with s-IBM and 15 controls were examined for the expression of the active components of the various MAPKs, including p44/42MAPK, p38MAPK, p46JNK1, p54JNK2, and p54JNK3, using immunocytochemistry and Western blot analysis. The expression of selected phosphorylated components was also examined in the same specimens. Results: In a-IBM, but not the disease controls, the vacuolated muscle fibers express active p42MAPK but not JNK or p38MAPK. Western blots of cell lysates confirmed the hyperexpression of p42MAPK and demonstrated a novel 35 kD phosphoprotein. Antibodies against phosphoepitopes of the 55 kD protein preferentially immunostained antigens within the vacuolated muscle fibers of s-IBM but not disease controls. Conclusion: In s-IBM, there is increased p42MAPK activation and abnormal intracellular protein phosphorylation with selective accumulation of a 35 kD phosphoprotein within the vacuolated fibers. Although the hyperexpression of 35kD protein may represent cytoskeletal by-products due to heightened p42MAPK activation, its abundant expression only in s-IBM implies that hyperphosphorylated myofibrillar proteins may be involved in the primary disease process. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Rm 4N248,10 Ctr Dr,MSC 1382, Bethesda, MD 20892 USA. NR 29 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 25 PY 2000 VL 54 IS 8 BP 1665 EP 1669 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 307FD UT WOS:000086642000023 PM 10762511 ER PT J AU Zhang, JZ Dyer, KD Rosenberg, HF AF Zhang, JZ Dyer, KD Rosenberg, HF TI Evolution of the rodent eosinophil-associated RNase gene family by rapid gene sorting and positive selection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VARIABLE-REGION GENES; RESPIRATORY SYNCYTIAL VIRUS; RIBONUCLEASE-A SUPERFAMILY; VERTEBRATE IMMUNE-SYSTEM; CLASS-I LOCI; DARWINIAN SELECTION; CATIONIC PROTEIN; MOLECULAR EVOLUTION; SPERM PROTEIN; NEUROTOXIN AB The mammalian RNase A superfamily comprises a diverse array of ribonucleolytic proteins that have a variety of biochemical activities and physiological functions. Two rapidly evolving RNases of higher primates are of particular interest as they are major secretory proteins of eosinophilic leukocytes and have been found to possess anti-pathogen activities in vitro. To understand how these RNases acquired this function during evolution and to develop animal models for the study of their functions in vivo, it is necessary to investigate these genes in many species. Here, we report the sequences of 38 functional genes and 23 pseudogenes of the eosinophil-associated RNase (EAR) family from 5 rodent species. Our phylogenetic analysis of these genes showed a clear pattern of evolution by a rapid birth-and-death process and gene sorting, a process characterized by rapid gene duplication and deactivation occurring differentially among lineages. This process ultimately generates distinct or only partially overlapping inventories of the genes, even in closely related species. Positive Darwinian selection also contributed to the diversification of these EAR genes. The striking similarity between the evolutionary patterns of the EAR genes and those of the major histocompatibility complex, immunoglobulin, and T cell receptor genes stands in strong support of the hypothesis that host-defense and generation of diversity are among the primary physiological function of the rodent EARs. The discovery of a large number of divergent EARs suggests the intriguing possibility that these proteins have been specifically tailored to fight against distinct rodent pathogens. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 55 TC 107 Z9 110 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 APR 25 PY 2000 VL 97 IS 9 BP 4701 EP 4706 DI 10.1073/pnas.080071397 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 308GW UT WOS:000086703000057 PM 10758160 ER PT J AU Geiman, TM Muegge, K AF Geiman, TM Muegge, K TI Lsh, an SNF2/helicase family member, is required for proliferation of mature T lymphocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENE REARRANGEMENT; CELL DEVELOPMENT; DNA METHYLATION; RECEPTOR; EXPRESSION; PROTEINS; COMPLEX; MICE; TRANSCRIPTION; ACTIVATION AB Lsh (Hells) is closely related to SNF2/helicase family members that remodel chromatin and thus regulate gene transcription. In the adult mouse Lsh is expressed primarily in lymphoid tissue, showing the highest level in thymocytes, Lsh gene expression can be induced in thymic pro-T cells by pre-T cell receptor crosslinking and in mature T cells by T cell receptor crosslinking together with costimulation via CD28, The time course of Lsh gene and protein expression correlated closely with the onset of S phase of the cell cycle. To explore the function of Lsh during lymphoid development or activation, we deleted the Lsh gene by homologous recombination in ES cells. Fetal liver cells from Lsh(-/-) were used as a source of hematopoietic precursors to reconstitute lymphoid development in Rag2(-/-) mice. Lsh-/- (compared to Lsh+/+ or +/-) chimeras showed a modest reduction in thymocyte numbers due to a partial arrest at the transition from the CD4(-)CD8(-) stage to the CD4(+)CD8(+) stage of T cell development. Mature peripheral lymphocytes were reduced in number to approximate to 60% for T cells and 40% for B cells; however, V(D)J recombination of the immune receptor genes was normal. Although polyclonal activation of Lsh-/- T cells induced normal levels of cytokines, cell proliferation was severely suppressed and cells underwent apoptosis, Several genes involved in the regulation of apoptosis were expressed normally with the exception of Bcl-2 that was actually elevated. These findings demonstrate that Lsh is not obligatory for normal lymphoid development but is essential for normal proliferation of peripheral T lymphocytes. C1 NCI, Mol Immunoregulat Lab, Intramural Res Support Program, Sci Applicat Int Corp,Frederick Canc Res & Dev Ct, Frederick, MD 21702 USA. RP Muegge, K (reprint author), NCI, Mol Immunoregulat Lab, Intramural Res Support Program, Sci Applicat Int Corp,Frederick Canc Res & Dev Ct, Frederick, MD 21702 USA. FU PHS HHS [N01-C0-56000] NR 28 TC 53 Z9 54 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 25 PY 2000 VL 97 IS 9 BP 4772 EP 4777 DI 10.1073/pnas.97.9.4772 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 308GW UT WOS:000086703000069 PM 10781083 ER PT J AU McCraith, S Holtzman, T Moss, B Fields, S AF McCraith, S Holtzman, T Moss, B Fields, S TI Genome-wide analysis of vaccinia virus protein-protein interactions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID URACIL-DNA GLYCOSYLASE; SINGLE-STRANDED-DNA; CORE PROTEIN; BINDING-PROTEIN; GENE-PRODUCT; ESCHERICHIA-COLI; RNA-POLYMERASE; E3L GENE; IDENTIFICATION; TRANSCRIPTION AB To detect interactions between proteins of vaccinia virus, we carried out a comprehensive two-hybrid analysis to assay every pairwise combination. We constructed an array of yeast transformants that contained each of the 266 predicted viral ORFs as Gal4 activation domain hybrid proteins. The array was individually mated to transformants containing each ORF as a Gal4-DNA-binding domain hybrid, and diploids expressing the two-hybrid reporter gene were identified. Of the approximate to 70,000 combinations, we found 37 protein-protein interactions, including 28 that were previously unknown. In some cases, e.g., late transcription factors, both proteins were known to have related roles although there was no prior evidence of physical associations. For some other interactions, neither protein had a known role. In the majority of cases, however, one of the interacting proteins was known to be involved in DNA replication. transcription, virion structure, or host evasion, thereby providing a clue to the role of the other uncharacterized protein in a specific process. C1 Univ Washington, Dept Genet, Howard Hughes Med Inst, Seattle, WA 98195 USA. Univ Washington, Dept Med, Howard Hughes Med Inst, Seattle, WA 98195 USA. Univ Washington, Locke Comp Ctr, Seattle, WA 98195 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Univ Washington, Dept Genet, Howard Hughes Med Inst, Box 357360, Seattle, WA 98195 USA. EM fields@u.washington.edu FU NIGMS NIH HHS [GM54415] NR 60 TC 204 Z9 210 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 APR 25 PY 2000 VL 97 IS 9 BP 4879 EP 4884 DI 10.1073/pnas.080078197 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 308GW UT WOS:000086703000087 PM 10781095 ER PT J AU Mothet, JP Parent, AT Wolosker, H Brady, RO Linden, DJ Ferris, CD Rogawski, MA Snyder, SH AF Mothet, JP Parent, AT Wolosker, H Brady, RO Linden, DJ Ferris, CD Rogawski, MA Snyder, SH TI D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CULTURED HIPPOCAMPAL-NEURONS; AMINO-ACID OXIDASE; NMDA-RECEPTORS; RAT-BRAIN; EXTRACELLULAR CONCENTRATION; GLUTAMATE RECEPTORS; MAMMALIAN BRAIN; BINDING-SITE; NR1 SUBUNIT; ASTROCYTES AB Functional activity of N-methyl-D-aspartate (NMDA) receptors requires both glutamate binding and the binding of an endogenous coagonist that has been presumed to be glycine, although D-serine is a more potent agonist, Localizations of D-serine and it biosynthetic enzyme serine racemase approximate the distribution of NMDA receptors more closely than glycine, We now show that selective degradation of D-serine with D-amino acid oxidase greatly attenuates NMDA receptor-mediated neurotransmission as assessed by using whole-cell patch-clamp recordings or indirectly by using biochemical assays of the sequelae of NMDA receptor-mediated calcium flux. The inhibitory effects of the enzyme are fully reversed by exogenously applied D-serine, which by itself did not potentiate NMDA receptor-mediated synaptic responses. Thus, D-serine is an endogenous modulator of the glycine site of NMDA receptors and fully occupies this site at some functional synapses. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. NINDS, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RP Snyder, SH (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, 725 N Wolfe St, Baltimore, MD 21205 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU NIDA NIH HHS [K05 DA000074, DA00074]; NIMH NIH HHS [MH-18501, R01 MH018501, R37 MH018501] NR 41 TC 633 Z9 645 U1 2 U2 30 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 APR 25 PY 2000 VL 97 IS 9 BP 4926 EP 4931 DI 10.1073/pnas.97.9.4926 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 308GW UT WOS:000086703000095 PM 10781100 ER PT J AU Bastien, N McBride, AA AF Bastien, N McBride, AA TI Interaction of the papillomavirus E2 protein with mitotic chromosomes SO VIROLOGY LA English DT Article ID BOVINE PAPILLOMAVIRUS; DNA-BINDING; HISTONE H3; TRANSCRIPTIONAL REPRESSOR; TRANSACTIVATION DOMAIN; FUNCTIONAL INTERACTION; METAPHASE CHROMOSOMES; TRANSIENT REPLICATION; EPISOMAL MAINTENANCE; TERMINAL DOMAIN AB The bovine papillomavirus E2 transactivator protein is a multifunctional protein that activates viral transcription, cooperates in initiation of viral DNA replication, and is required for long-term episomal maintenance of viral genomes. We have shown previously that the E2 transactivator protein and bovine papillomavirus type 1 genomes are associated with mitotic chromosomes and have proposed that E2 links the genomes to cellular chromosomes to ensure segregation to daughter nuclei. In this study, we show that E2 is associated with cellular chromosomes at all stages of mitosis. We also further map the regions of E2 that are required for this association. The transactivation domain of E2 is necessary and sufficient to mediate the interaction with mitotic chromosomes; the DNA binding domain, and the flexible hinge region that separates the two domains, is not required. Furthermore, mutation of previously identified phosphorylation sites (serine residues 235, 298, and 301) has no effect on the ability of the E2 protein to bind mitotic chromosomes. (C) 2000 Academic Press. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 137,4 Ctr Dr,MSC 0455, Bethesda, MD 20892 USA. OI McBride, Alison/0000-0001-5607-5157 NR 49 TC 83 Z9 86 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 25 PY 2000 VL 270 IS 1 BP 124 EP 134 DI 10.1006/viro.2000.0265 PG 11 WC Virology SC Virology GA 311NG UT WOS:000086889900013 PM 10772985 ER PT J AU Khattar, SK Yunus, AS Collins, PL Samal, SK AF Khattar, SK Yunus, AS Collins, PL Samal, SK TI Mutational analysis of the bovine respiratory syncytial virus nucleocapsid protein using a minigenome system: Mutations that affect encapsidation, RNA synthesis, and interaction with the phosphoprotein SO VIROLOGY LA English DT Article ID MESSENGER-RNA; N-PROTEIN; P-PROTEIN; TEMPLATE FUNCTION; SEQUENCE-ANALYSIS; TERMINAL DOMAIN; MAMMALIAN-CELLS; REPLICATION; TRANSCRIPTION; BINDING AB The nucleocapsid (N) protein of bovine respiratory syncytial virus (BRSV) is a multifunctional protein that plays a central role in transcription and replication of viral genomic RNA. To investigate the domains and specific residues involved in different N activities, we generated a total of 27 deletion and 12 point mutants of the N protein. These mutants were characterized using an intracellular BRSV-CAT minigenome replication system for the ability to (1) direct minigenome RNA synthesis, (2) direct minigenome encapsidation, and (3) form a complex with the phosphoprotein (P). The mutations tested were defective in synthesis of RNA from the BRSV-CAT minigenome template with the exception of the following: a deletion involving the first N-terminal amino acid and mutations involving conservative substitution at the second amino acid and at certain internal cysteine residues. Micrococcal nuclease enzyme protection assays showed that mutations involving amino acids 1-364 of the 391-amino-acid N protein prevented minigenome encapsidation. Thus the BRSV N protein has a C-terminal, 27-amino-acid tail that is not required for encapsidation. Interestingly, two of the mutations that ablated encapsidation did not greatly affect RNA synthesis; the mutant involving deletion of the N-terminal amino acid and the mutant involving a substitution at position 2. This finding indicates that the formation of a nucleocapsid sufficient to protect the RNA from nuclease is not required for template function. Coimmunoprecipitation of N and P using N- or P-specific antiserum revealed two regions of the N protein that are important for association with the P protein: a central portion of 244-290 amino acids and a C-terminal portion of 338-364 amino acids. (C) 2000 Academic Press. C1 Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. NR 33 TC 19 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 25 PY 2000 VL 270 IS 1 BP 215 EP 228 DI 10.1006/viro.2000.0264 PG 14 WC Virology SC Virology GA 311NG UT WOS:000086889900022 PM 10772994 ER PT J AU Wigley, FM Wise, R Haythornthwaite, J Rand, C Smith, EA Maricq, HR Middaugh, S Silver, RM Valter, I Allenback, G Arnold, J Steedman, S Risinger, A King, A Bielory, L Attanasio, V Tarantola, J Centeno, L Jacob, RG Medsger, T Jennings, R Scheier, M Vaughan, C Wasko, MC Steen, VD Dunbar-Jacob, J Tamres, L Freedman, RR Mayes, MD Brejnak, C Tindall, C Bielory, L Thompson, B Frederick, M Canner, M Canner, J Canner, P Shaffer, TR Hill, DR Kaufmann, PG Czajkowski, S Geller, N Hunsberger, S Jennings, C Stevens, WM Hess, EV Corson, JA Jobe, JB Smith, H Tilley, B AF Wigley, FM Wise, R Haythornthwaite, J Rand, C Smith, EA Maricq, HR Middaugh, S Silver, RM Valter, I Allenback, G Arnold, J Steedman, S Risinger, A King, A Bielory, L Attanasio, V Tarantola, J Centeno, L Jacob, RG Medsger, T Jennings, R Scheier, M Vaughan, C Wasko, MC Steen, VD Dunbar-Jacob, J Tamres, L Freedman, RR Mayes, MD Brejnak, C Tindall, C Bielory, L Thompson, B Frederick, M Canner, M Canner, J Canner, P Shaffer, TR Hill, DR Kaufmann, PG Czajkowski, S Geller, N Hunsberger, S Jennings, C Stevens, WM Hess, EV Corson, JA Jobe, JB Smith, H Tilley, B CA Raynauds Treatment Study Investiga TI Comparison of sustained-release nifedipine and temperature biofeedback for treatment of primary Raynaud phenomenon - Results from a randomized clinical trial with 1-year follow-up SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DOUBLE-BLIND TRIAL; BEHAVIORAL TREATMENTS; GEOGRAPHIC-VARIATION; DISEASE; PREVALENCE; STRESS; TERM AB Background: The efficacy and safety of sustained-release nifedipine for the treatment of primary Raynaud phenomenon (RP) has not previously been demonstrated by a randomized, controlled trial. Temperature biofeedback has been studied in patients with primary RP but not in a large multicenter controlled trial or compared with nifedipine therapy. Objective: To evaluate and compare the effectiveness of sustained-release nifedipine and temperature biofeedback for the treatment of primary RP. Participants and Methods: This is a randomized, controlled clinical trial, double-masked for drug and placebo but not masked for temperature and control biofeedback. It included 313 persons with primary RP as defined by medical history, physical examination findings, normal nailfold capillaries, and a history of 2 or more attacks per day during the previous cold season. Participants were randomized to 1 of 4 treatment groups: (1) sustained-release nifedipine, (2) pill placebo, (3) temperature biofeedback, or (4) control (electromyographic) self-reported, color chart-verified RP attacks during 1 winter month approximately 1 year after initiation of treatment. Secondary outcome measures included verified attacks at 2 months, all attacks at 2 months and 1 year, and quality of life. Results: Nifedipine-treated participants showed a 66% reduction in verified attacks compared with placebo recipients (P<.001); temperature biofeedback training did not reduce attacks significantly compared with control biofeedback (P = .37). Comparison of nifedipine and temperature biofeedback treatments favored nifedipine use (P = .08); similar results were obtained for the secondary end points. Adverse effects resulted in discontinuation of nifedipine treatment in 15% of participants. Conclusions: Temperature biofeedback is not better than its control treatment and is inferior to sustained-release nifedipine for treating primary RP, whereas sustained-release nifedipine is a safe and effective treatment for this disease. C1 Johns Hopkins Univ, Med Ctr, Baltimore, MD 21218 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Wayne State Univ, Detroit, MI 48202 USA. Clin Trials & Surveys Corp, Baltimore, MD 21210 USA. US Dept HHS, Publ Hlth Serv, Indian Hlth Serv, Supply Ctr, Perry Point, MD USA. NHLBI, Div Epidemiol & Clin Applicat, Behav Med Sci Res Grp, Project Off, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NHLBI, Div Extramural Affairs, Bethesda, MD 20892 USA. Univ Cincinnati, Div Immunol, Cincinnati, OH 45221 USA. Dartmouth Med Sch, Dept Psychiat, Hanover, NH USA. NIA, Bethesda, MD 20892 USA. Duke Univ, Sch Divin, Durham, NC 27706 USA. Henry Ford Hosp, Div Biostat & Res Epidemiol, Detroit, MI 48202 USA. RP Thompson, B (reprint author), Clin Trials & Surveys Corp, 350 W Quadrangle,Village Cross Keys, Baltimore, MD 21210 USA. NR 49 TC 41 Z9 41 U1 0 U2 4 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 APR 24 PY 2000 VL 160 IS 8 BP 1101 EP 1108 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 306FL UT WOS:000086586600005 ER PT J AU Francischetti, IMB Chiang, TM Guimaraes, JA Bon, C AF Francischetti, IMB Chiang, TM Guimaraes, JA Bon, C TI Role of the recombinant non-integrin platelet collagen receptor P65 on platelet activation induced by convulxin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CROTALUS-DURISSUS-TERRIFICUS; GLYCOPROTEIN-VI; MOLECULAR-BASIS; VENOM; AGGREGATION; ADHESION; PROTEIN AB Convulxin (Cvx) isolated from Crotalus durissus terrificus venom selectively binds with a high affinity to platelets and induces platelet aggregation by a mechanism that resembles that induced by collagen. Taking advantage that P65 has been recently cloned and expressed as a recombinant soluble protein (rec-P65), we examined the role of this non-integrin collagen receptor in platelet activation induced by Cvx. Rec-P65 blocked platelet adhesion to collagen-coated surfaces and inhibited platelet aggregation and ATP secretion induced by type I collagen. On the other hand, rec-P65 did not inhibit platelet aggregation and ATP secretion induced by Cvx, and it did not affect platelet adhesion to Cvx. In addition, ligand-blotting indicated that the Cvx binding to the collagen receptor GPVI was preserved in the presence of rec-P65. These observations indicate that P65 does not play a significant role in platelet activation by Cvx; in contrast, platelet response to collagen involves multiple receptors, (C) 2000 Academic Press. C1 Inst Pasteur, Unite Venins, F-75724 Paris, France. Univ Fed Rio de Janeiro, Dept Bioquim Med, ICB, CCS, BR-21941590 Rio De Janeiro, Brazil. Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Biochem, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Memphis VA Med Ctr, Memphis, TN 38163 USA. Univ Fed Rio Grande Sul, Ctr Biotecnol, BR-91509900 Porto Alegre, RS, Brazil. RP Francischetti, IMB (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. OI Guimaraes, Jorge A./0000-0001-6354-6789 NR 24 TC 3 Z9 5 U1 0 U2 0 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 APR 21 PY 2000 VL 270 IS 3 BP 932 EP 935 DI 10.1006/bbrc.2000.2529 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 309WX UT WOS:000086793200046 PM 10772928 ER PT J AU Kirschner, LS Stratakis, CA AF Kirschner, LS Stratakis, CA TI Structure of the human ubiquitin fusion gene Uba80 (RPS27a) and one of its pseudogenes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE genomic structure; genomic mapping; ribosomal proteins; ubiquitin ID RIBOSOMAL-PROTEIN GENES; HONEYCOMB RETINAL DYSTROPHY; OXIDE SYNTHASE GENE; PROCESSED PSEUDOGENE; NUCLEOTIDE-SEQUENCE; PROMOTER REGION; LOCALIZATION; ORGANIZATION; EXPRESSION; CHROMOSOME AB Ubiquitin is a highly conserved 76 amino acid protein that is generated in the cell by proteolysis of larger proteins containing either polyubiquitin chains or ubiquitin fused to carboxyl extension proteins (CEPs). In humans, the two human ubiquitin-CEP genes are Uba80 and Uba52, which code for ubiquitin fused to ribosomal protein S27a and L40, respectively, Working from a recently generated physical map of human chromosome 2p16, we determined the genetic and physical location and the genomic structure of the Uba80 gene in its entirety. A comparison of Uba80 to Uba52 revealed that the two genes share a conserved 5'-end structure, but that the structure of the ubiquitin coding regions was not conserved. Analysis of 400 bp of the promoter of Uba80 revealed strong similarity not only to the Uba52 promoter, but also to the other known human ribosomal gene promoters that have been identified to date. Homology searches also detected the presence of a pseudogene for Uba80, and the structure of this sequence feature is also reported. (C) 2000 Academic Press. C1 NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Kirschner, LS (reprint author), NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC1862, Bethesda, MD 20892 USA. NR 34 TC 18 Z9 21 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 APR 21 PY 2000 VL 270 IS 3 BP 1106 EP 1110 DI 10.1006/bbrc.2000.2568 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 309WX UT WOS:000086793200076 PM 10772958 ER PT J AU Dekel, I Russek, N Jones, T Mortin, MA Katzav, S AF Dekel, I Russek, N Jones, T Mortin, MA Katzav, S TI Identification of the Drosophila melanogaster homologue of the mammalian signal transducer protein, Vav SO FEBS LETTERS LA English DT Article DE Vav; signal transducer; DroVav ID TYROSINE KINASE-ACTIVITY; T-CELL RECEPTOR; SH2 DOMAIN; PROTOONCOGENE PRODUCT; EGF RECEPTOR; GENE; BINDING; EXCHANGE; PATHWAY; FAMILY AB Mammalian Vav signal transducer protein couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation. We have isolated and characterized the DroVav gene, the homologue of hVav in Drosophila melanogaster. DroVav encodes a protein (793 residues) whose similarity with hVav is 47% and with hVav2 and hVav3 is 45%. DroVav preserves the unique, complex structure of hVav proteins, including the 'calponin homology', dbl homology, pleckstrin homology; SH2 and SH3 domains in addition to regions that are acidic rich, proline rich and cysteine rich. DroVav is located on the X chromosome in polytene interval 18A5;18B and is expressed in all stages of development and in all tissues, In mammalian cells, DroVav is tyrosine-phosphorylated in response to epidermal growth factor receptor (EGFR) induction; in vitro, the DroVav SH2 region is associated with tyrosine-phosphorylated EGFR, Thus, DroVav probably plays a pivotal role as a signal transducer protein during fruit fly development. (C) 2000 Federation of European Biochemical Societies. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Hubert H Humphrey Ctr Expt Med & Canc Res, IL-91120 Jerusalem, Israel. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Katzav, S (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Hubert H Humphrey Ctr Expt Med & Canc Res, IL-91120 Jerusalem, Israel. RI Mortin, Mark/B-4251-2008 NR 43 TC 19 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 21 PY 2000 VL 472 IS 1 BP 99 EP 104 DI 10.1016/S0014-5793(00)01413-7 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 308UL UT WOS:000086731200021 PM 10781813 ER PT J AU Jhee, KH McPhie, P Miles, EW AF Jhee, KH McPhie, P Miles, EW TI Yeast cystathionine beta-synthase is a pyridoxal phosphate enzyme but, unlike the human enzyme, is not a heme protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 4th Meeting on PQQ and Quinoproteins CY OCT 31-NOV 05, 1999 CL SANTA FE, NEW MEXICO ID O-ACETYLSERINE SULFHYDRYLASE; TRYPTOPHAN SYNTHASE; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; SALMONELLA-TYPHIMURIUM; L-SERINE; 3-DIMENSIONAL STRUCTURE; MECHANISM; IDENTIFICATION; PURIFICATION AB Our studies of cystathionine beta-synthase from Saccharomyces cerevisiae (yeast) are aimed at (1) clarifying the cofactor dependence and catalytic mechanism and (2) obtaining a system for future investigations of the effects of mutations that cause human disease (homocystinuria or coronary heart disease). We report methods that yielded high expression of the yeast gene in Escherichia coli and of purified yeast cystathionine beta-synthase. The absorption and circular dichroism spectra of the homogeneous enzyme were characteristic of a pyridoxal phosphate enzyme and showed the absence of heme, which is found in human and rat cystathionine beta-synthase. The absence of heme in the yeast enzyme facilitates spectroscopic studies to probe the catalytic mechanism. The reaction of the enzyme with L-serine in the absence of L-homocysteine produced the aldimine of aminoacrylate, which absorbed at 460 nm and had a strong negative circular dichroism band at 460 nm. The formation of this intermediate from the product, L-cystathionine, demonstrates the partial reversibility of the reaction. Our results establish the overall catalytic mechanism of yeast cystathionine beta-synthase and provide a useful system for future studies of structure and function. The absence of heme in the functional yeast enzyme suggests that heme does not play an essential catalytic role in the rat and human enzymes. The results are consistent with the absence of heme in the closely related enzymes O-acetylserine sulfhydrylase, threonine deaminase, and tryptophan synthase. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Miles, EW (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Rm 225,MSC 0830,8 Ctr Dr, Bethesda, MD 20892 USA. NR 41 TC 59 Z9 61 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 APR 21 PY 2000 VL 275 IS 16 BP 11541 EP 11544 DI 10.1074/jbc.C000056200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308DP UT WOS:000086695500002 PM 10766767 ER PT J AU Rivas, G Lopez, A Mingorance, J Ferrandiz, MJ Zorrilla, S Minton, AP Vicente, M Andreu, JM AF Rivas, G Lopez, A Mingorance, J Ferrandiz, MJ Zorrilla, S Minton, AP Vicente, M Andreu, JM TI Magnesium-induced linear self-association of the FtsZ bacterial cell division protein monomer - The primary steps for FtsZ assembly SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUANINE-NUCLEOTIDE-BINDING; TUBULIN DOUBLE RINGS; CALF BRAIN TUBULIN; ESCHERICHIA-COLI; GTP HYDROLYSIS; GDP-TUBULIN; ACTIN POLYMERIZATION; INORGANIC-PHOSPHATE; CIRCULAR-DICHROISM; GENOME SEQUENCE AB The bacterial cell division protein FtsZ from Escherichia coli has been purified with a new calcium precipitation method. The protein contains one GDP and one Mg2+ bound, it shows GTPase activity, and requires GTP and Mg2+ to polymerize into long thin filaments at pH 6.5. FtsZ, with moderate ionic strength and low Mg2+ concentrations, at pH 7.5, is a compact and globular monomer, Mg2+ induces FtsZ self-association into oligomers, which has been studied by sedimentation equilibrium over a wide range of Mg2+ and FtsZ concentrations, The oligomer formation mechanism is best described as an indefinite self-association, with binding of an additional Mg2+ for each FtsZ monomer added to the growing oligomer, and a slight gradual decrease of the affinity of addition of a protomer with increasing oligomer size. The sedimentation velocity of FtsZ oligomer populations is compatible with a linear single-stranded arrangement of FtsZ monomers and a spacing of 4 nm. It is proposed that these FtsZ oligomers and the polymers formed under assembly conditions share a similar axial interaction between monomers (like in the case of tubulin, the eukaryotic homolog of FtsZ). Similar mechanisms may apply to FtsZ assembly in vivo, but additional factors, such as macromolecular crowding, nucleoid occlusion, or specific interactions with other cellular components active in septation have to be invoked to explain FtsZ assembly into a division ring. C1 CSIC, Ctr Invest Biol, E-28006 Madrid, Spain. CSIC, Ctr Nacl Biotecnol, E-28006 Madrid, Spain. NIDDKD, NIH, Bethesda, MD 20892 USA. RP CSIC, Ctr Invest Biol, Velazquez 144, E-28006 Madrid, Spain. EM grivas@cib.csic.es RI Mingorance, Jesus/B-7562-2009; Zorrilla, Silvia/J-9771-2014; Ferrandiz, Maria-Jose/K-2820-2014; OI Mingorance, Jesus/0000-0001-6173-5711; Zorrilla, Silvia/0000-0002-6309-9058; Ferrandiz, Maria-Jose/0000-0003-1428-9506; Andreu, Jose M/0000-0001-8064-6933; Rivas, German/0000-0003-3450-7478 NR 92 TC 117 Z9 118 U1 0 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 21 PY 2000 VL 275 IS 16 BP 11740 EP 11749 DI 10.1074/jbc.275.16.11740 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308DP UT WOS:000086695500031 PM 10766796 ER PT J AU Dianov, GL Thybo, T Dianova, II Lipinski, LJ Bohr, VA AF Dianov, GL Thybo, T Dianova, II Lipinski, LJ Bohr, VA TI Single nucleotide patch base excision repair is the major pathway for removal of thymine glycol from DNA in human cell extracts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLI ENDONUCLEASE-III; COCKAYNE-SYNDROME PATIENTS; ESCHERICHIA-COLI; OXIDATIVE DAMAGE; MAMMALIAN-CELLS; HUMAN HOMOLOG; TRANSCRIPTION; INVITRO; RESIDUES; RECONSTITUTION AB The repair pathways involved in the removal of thymine glycol (TG) from DNA by human cell extracts have been examined. Closed circular DNA constructs containing a single TG at a defined site were used as substrates to determine the patch size generated after in vitro repair by cell extracts. Restriction analysis of the repair incorporation in the vicinity of the lesion indicated that the majority of TG was repaired through the base excision repair (BER) pathways. Repair incorporation 5' to the lesion, characteristic for the nucleotide excision repair pathway, was not found. More than 80% of the TG repair was accomplished by the single-nucleotide repair mechanism, and the remaining TGs were removed by the long patch BER pathway. We also analyzed the role of the xeroderma pigmentosum, complementation group G (XPG) protein in the excision step of BER. Cell extracts deficient in XPG protein had an average 25% reduction in TG incision. These data show that BER is the primary pathway for repair of TG in DNA and that XPG protein may be involved in repair of TG as an accessory factor. C1 NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. Univ Aarhus, Dept Biol Mol & Struct, DK-8000 Aarhus C, Denmark. RP Dianov, GL (reprint author), NIA, Genet Mol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 36 TC 65 Z9 67 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 APR 21 PY 2000 VL 275 IS 16 BP 11809 EP 11813 DI 10.1074/jbc.275.16.11809 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308DP UT WOS:000086695500040 PM 10766805 ER PT J AU Harrod, R Kuo, YL Tang, Y Yao, Y Vassilev, A Nakatani, Y Giam, CZ AF Harrod, R Kuo, YL Tang, Y Yao, Y Vassilev, A Nakatani, Y Giam, CZ TI p300 and p300/cAMP-responsive element-binding protein associated factor interact with human T-cell lymphotropic virus type-1 Tax in a multi-histone acetyltransferase/activator-enhancer complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; HTLV-I TAX; TRANSCRIPTIONAL ACTIVATOR TAX; ADENOVIRAL ONCOPROTEIN E1A; SERUM RESPONSE FACTOR; CREB-BINDING; TRANSACTIVATOR TAX; 21-BASE-PAIR REPEATS; COACTIVATOR CBP; LEUKEMIA AB The human T-cell lymphotropic virus, type (HTLV)-1 trans-activator, Tax, coordinates with cAMP-responsive element-binding protein (CREB) and the transcriptional co-activators p300/CBP on three 21-base pair repeat elements in the proviral long terminal repeat (LTR) to promote viral mRNA transcription. Recruitment of p300/CBP to the activator-enhancer complex, however, is insufficient to support Tax-dependent LTR trans-activation. Here, we report that the p300/CBP-associated factor (P/CAF) is a critical and integral component of the functional HTLV-1 activator-enhancer complex. The HTLV-1 Tax protein directly binds P/CAF in vitro and co-immunoprecipitates with this co-activator in vivo. The Tax mutants (K88A and V89A) defective for p300/CBP-binding and LTR trans-activation, retained their abilities to interact with P/CAF. The M47 mutant (L319R, L320S) protein, which has previously been shown to interact with p300/CBP, by contrast, failed to form complexes with P/CAF and is impaired in LTR trans-activation. Furthermore, LTR trans-activation by Tax is competitively inhibited by the adenoviral E1A 12S gene product, which displaces P/CAF from p300/CBP and inhibits the histone acetyltransferase activities of both P/CAF and p300/CBP. This inhibition is partially reversed by exogenously added P/CAF. These results imply that simultaneous recruitment of two distinct coactivators (p300/CBP and P/CAF) by Tax is essential for the assembly of a trans-activation competent, nucleoprotein complex. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Giam, CZ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. FU NCI NIH HHS [R01 CA/GM 75688, R01 CA48709] NR 69 TC 93 Z9 96 U1 1 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 APR 21 PY 2000 VL 275 IS 16 BP 11852 EP 11857 DI 10.1074/jbc.275.16.11852 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308DP UT WOS:000086695500046 PM 10766811 ER PT J AU Lockwich, TP Liu, XB Singh, BB Jadlowiec, J Weiland, S Ambudkar, IS AF Lockwich, TP Liu, XB Singh, BB Jadlowiec, J Weiland, S Ambudkar, IS TI Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; CAPACITATIVE CALCIUM-ENTRY; OPERATED HTRP3 CHANNELS; MEMBRANE DOMAINS; PLASMA-MEMBRANE; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; PROTEIN; LOCALIZATION; CHOLESTEROL AB Trp1 has been proposed as a component of the store-operated Ca2+ entry (SOC) channel. However, neither the molecular mechanism of SOC nor the role of Trp in this process is yet understood. We have examined possible molecular interactions involved in the regulation of SOC and Trp1 and report here for the first time that Trp1 is assembled in signaling complex associated with caveolin-scaffolding lipid raft domains. Endogenous hTrp1 and caveolin-1 were present in low density fractions of Triton X-100-extracted human submandibular gland cell. membranes. Depletion of plasma membrane cholesterol increased Triton X-100 solubility of Trp1 and inhibited carbachol-stimulated Ca2+ signaling. Importantly, thapsigargn stimulated Ca2+ influx, but not internal Ca2+ release, and inositol 1,4,5-triphosphate (IP3)-stimulated I-soc were also attenuated. Furthermore, both anti-Trp1 and anti-caveolin-1 antibodies co-immunoprecipitated hTrp1, caveolin-1, G alpha(q/11), and IP3 receptor-type 3 (IP3R3). These results demonstrate that caveolar microdomains provide a scaffold for (i) assembly of key Ca2+ signaling proteins into a complex and (ii) coordination of the molecular interactions leading to the activation of SOC. importantly, we have shown that Trp1 is also localized in this microdomain where it interacts with one or more components of this complex, including IP3R3. This finding is potentially important in elucidating the physiological function of Trp. C1 NIDCR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), Bldg 10,Rm IN-113, Bethesda, MD 20892 USA. OI Singh, Brij/0000-0003-0535-5997 NR 40 TC 295 Z9 303 U1 0 U2 3 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 APR 21 PY 2000 VL 275 IS 16 BP 11934 EP 11942 DI 10.1074/jbc.275.16.11934 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308DP UT WOS:000086695500057 PM 10766822 ER PT J AU Tong, HY Chen, WN London, RE Murphy, E Steenbergen, C AF Tong, HY Chen, WN London, RE Murphy, E Steenbergen, C TI Preconditioning enhanced glucose uptake is mediated by p38 MAP kinase not by phosphatidylinositol 3-kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT SKELETAL-MUSCLE; 3T3-L1 ADIPOCYTES; GLUT4 TRANSLOCATION; NITRIC-OXIDE; GLUCOSE-TRANSPORTER-4 TRANSLOCATION; TRANSPORTER TRANSLOCATION; INSULIN ACTION; PROTEIN; STIMULATION; ACTIVATION AB Ischemia is reported to stimulate glucose uptake, but the signaling pathways involved are poorly understood. Modulation of glucose transport could be important for the cardioprotective effects of brief intermittent periods of ischemia and reperfusion, termed ischemic preconditioning, Previous work indicates that preconditioning reduces production of acid and lactate during subsequent sustained ischemia, consistent with decreased glucose utilization, However, there are also data that preconditioning enhances glucose uptake. The present study examines whether preconditioning alters glucose transport and whether this is mediated by either phosphatidylinositol 3-kinase (PI3K) or p38 MAP kinase, Langendorff-perfused rat hearts were preconditioned with 4 cycles of 5 min of ischemia and 5 min of reperfusion, with glucose as substrate. During the last reflow, glucose was replaced with 5 mM acetate and 5 mM 2-deoxyglucose (2DG), and hexose transport was measured from the rate of production of 2-deoxyglucose 6-phosphate (2DG6P), using P-31 nuclear magnetic resonance. Preconditioning stimulated 2DG uptake; after 15 min of perfusion with 2DG, 2DG6P levels were 165% of initial ATP in preconditioned hearts compared with 96% in control hearts (p < 0.05). Wortmannin, an inhibitor of PI3K, did not block the preconditioning induced stimulation of 2DG6P production, but perfusion with SB202190, an inhibitor of p38 MAP kinase, did attenuate 2DG6P accumulation (111% of initial ATP, p < 0.05 compared with preconditioned hearts), SB202190 had no effect on 2DG6P accumulation in nonpreconditioned hearts. Preconditioning stimulation of translocation of GLUT I: to the plasma membrane was not inhibited by wortmannin, The data demonstrate that ischemic preconditioning increases hexose transport and that this is mediated by p38 MAP kinase and is PI3K-independent. C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Steenbergen, C (reprint author), Duke Univ, Med Ctr, Dept Pathol, Box 3712, Durham, NC 27710 USA. FU NHLBI NIH HHS [R01 HL039752] NR 53 TC 64 Z9 66 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 APR 21 PY 2000 VL 275 IS 16 BP 11981 EP 11986 DI 10.1074/jbc.275.16.11981 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308DP UT WOS:000086695500063 PM 10766828 ER PT J AU Murga, C Fukuhara, S Gutkind, JS AF Murga, C Fukuhara, S Gutkind, JS TI A novel role for phosphatidylinositol 3-kinase beta in signaling from G protein-coupled receptors to Akt SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING PROTEINS; PHOSPHOINOSITIDE 3-KINASE; GAMMA-SUBUNITS; KINASE-B; DEPENDENT ACTIVATION; JUN KINASE; PATHWAY; P85; INSULIN; CLONING AB The protein kinase Akt plays a central role in a number of key biological functions including protein synthesis, glucose homeostasis, and the regulation of cell survival or death, The mechanism by which tyrosine kinase growth factor receptors stimulate Akt has been recently defined. In contrast, the mechanism of activation of Akt by other cell surface receptors is much less understood. For G protein-coupled receptors (GPCRs), conflicting data suggest that these receptors stimulate Akt in a cell type-specific manner by a set to be fully elucidated mechanism. Here, we took advantage of the availability of cells, where Akt activity could not be enhanced by agonists acting on this large family of cell surface receptors, such as NIH 3T3 cells, to investigate the pathway linking GPCRs to Akt. We present evidence that expression of phosphatidylinositol 3-kinase (PI3K) beta is necessary and sufficient to transmit signals from G proteins to Akt in these murine fibroblasts and that the activation of PI3K beta may represent the most likely mechanism whereby GPCRs stimulate Akt, as the vast majority of cells do not express PI3K gamma, a known G protein-sensitive PI3K isoform. Furthermore, available evidence indicates that GPCRs activate Akt by a pathway distinct from that utilized by growth factor receptors, as it involves the tyrosine phosphorylation-independent activation of PI3K beta by G protein beta gamma dimers. C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, 9000 Rockville Pike,Bldg 30,Rm 211, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; Murga, Cristina/E-1965-2014 OI Murga, Cristina/0000-0002-8964-4077 NR 38 TC 158 Z9 159 U1 1 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 APR 21 PY 2000 VL 275 IS 16 BP 12069 EP 12073 DI 10.1074/jbc.275.16.12069 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308DP UT WOS:000086695500074 PM 10766839 ER PT J AU Wan, QJ Fang, TW Fenick, D Garfield, S Bienfait, B Marquez, VE Blumberg, PM AF Wan, QJ Fang, TW Fenick, D Garfield, S Bienfait, B Marquez, VE Blumberg, PM TI The lipophilicity of phorbol esters as a critical factor in determining the pattern of translocation of protein kinase C delta fused to green fluorescent protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE KERATINOCYTES; 12-MYRISTATE 13-ACETATE; DIFFERENTIAL REGULATION; TUMOR PROMOTERS; LIVING CELLS; BINDING; ACTIVATION; ISOZYMES; ALPHA; BRYOSTATIN-1 AB Our previous study showed differential subcellular localization of protein kinase C (PKC) delta by phorbol esters and related ligands, using a green fluorescent protein-tagged construct in living cells. Here we compared the abilities of a series of symmetrically substituted phorbol 12,13-diesters to translocate PKC delta. In vitro, the derivatives bound to PBC with similar potencies but differed in rate of equilibration. In vivo, the phorbol diesters with short, intermediate, and long chain fatty acids induced distinct patterns of translocation. Phorbol 12,13-dioctanoate and phorbol 12,13-nonanoate, the intermediate derivatives and most potent tumor promoters, showed patterns of translocation typical of phorbol 12-myristate 13-acetate, with plasma membrane and subsequent nuclear membrane translocation. The more hydrophilic compounds (phorbol 12,13-dibutyrate and phorbol 12,13-dihexanoate) induced a patchy distribution in the cytoplasm, more prominent nuclear membrane translocation, and little plasma membrane localization at all concentrations examined (100 nM to 10 mu M). The highly lipophilic derivatives, phorbol 12,13-didecanoate and phorbol 12,13-diundecanoate, at 1 mu M caused either plasma membrane translocation only or no translocation at incubation times up to 60 min. Our results indicate that Lipophilicity of phorbol esters is a critical factor contributing to differential PKC delta localization and thereby potentially to their different biological activities. C1 NCI, Mol Mechanisms Tumor Promot Sect, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Blumberg, PM (reprint author), NCI, Mol Mechanisms Tumor Promot Sect, Cellular Carcinogenesis & Tumor Promot Lab, NIH, 37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 35 TC 1 Z9 1 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 APR 21 PY 2000 VL 275 IS 16 BP 12136 EP 12146 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308DP UT WOS:000086695500084 ER PT J AU Gao, BN Sekido, Y Maximov, A Saad, M Forgacs, E Latif, F Wei, MH Lerman, M Lee, JH Perez-Reyes, E Bezprozvanny, I Minna, JD AF Gao, BN Sekido, Y Maximov, A Saad, M Forgacs, E Latif, F Wei, MH Lerman, M Lee, JH Perez-Reyes, E Bezprozvanny, I Minna, JD TI Functional properties of a new voltage-dependent calcium channel alpha(2)delta auxiliary subunit gene (CACNA2D2) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EATON-MYASTHENIC-SYNDROME; TUMOR-SUPPRESSOR GENE; BETA-SUBUNIT; MOLECULAR DIVERSITY; DNA METHYLATION; SKELETAL-MUSCLE; GAMMA-SUBUNIT; CA2+ CHANNELS; LUNG-CANCER; N-TYPE AB We have positionally cloned and characterized a new calcium channel auxiliary subunit, alpha(2)delta-2 (CACNA2D2), which shares 56% amino acid identity with the known alpha(2)delta-1 subunit. The gene maps to the critical human tumor suppressor gene region in chromosome 3p21.3, showing very frequent allele loss and occasional homozygous deletions in lung, breast, and other cancers. The tissue distribution of alpha(2)delta-2 expression is different from alpha(2)delta-1, and alpha(2)delta-2 mRNA is most abundantly expressed in lung and testis and well expressed in brain, heart, and pancreas. In contrast, alpha(2)delta-1 is expressed predominantly in brain, heart, and skeletal muscle. When co-expressed (via cRNA injections) with alpha(1B) and beta(3) subunits in Xenopus oocytes, alpha(2)delta-2 increased peak size of the N-type Ca2+ currents 9-fold, and when co-expressed with alpha(1C) or alpha(1G) subunits in Xenopus oocytes increased peak size of L-type channels 2-fold and T-type channels 1.8-fold, respectively. Anti-peptide antibodies detect the expression of a 129-kDa alpha(2)delta-2 polypeptide in some but not all lung tumor cells, We conclude that the alpha(2)delta-2 gene encodes a functional auxiliary subunit of voltage-gated Ca2+ channels. Because of its chromosomal location and expression patterns, CACNA2D2 needs to be explored as a potential tumor suppressor gene linking Ca2+ signaling and lung, breast, and other cancer pathogenesis. The homologous location on mouse chromosome 9 is also the site of the mouse neurologic mutant ducky (du), and thus, CACNA2D2 is also a candidate gene for this inherited idiopathic generalized epilepsy syndrome. C1 Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dept Internal Med, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75390 USA. Univ Birmingham, Birmingham B15 2TT, W Midlands, England. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA. RP Minna, JD (reprint author), Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dept Internal Med, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. RI Sekido, Yoshitaka/P-9756-2015 FU NCI NIH HHS [CA71618, P50 CA070907, P50-CA70907, R01 CA071618]; NINDS NIH HHS [NS38691, R01 NS038691] NR 59 TC 107 Z9 114 U1 1 U2 13 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 APR 21 PY 2000 VL 275 IS 16 BP 12237 EP 12242 DI 10.1074/jbc.275.16.12237 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308DP UT WOS:000086695500096 PM 10766861 ER PT J AU Kenan, Y Murata, T Shakur, Y Degerman, E Manganiello, VC AF Kenan, Y Murata, T Shakur, Y Degerman, E Manganiello, VC TI Functions of the N-terminal region of cyclic nucleotide phosphodiesterase 3 (PDE 3) isoforms SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INHIBITED CAMP-PHOSPHODIESTERASE; INSULIN-SENSITIVE PHOSPHODIESTERASE; CATALYTIC DOMAIN; HUMAN-PLATELETS; GUINEA-PIG; AMP PHOSPHODIESTERASE; MOLECULAR-CLONING; FAT-CELLS; EXPRESSION; LOCALIZATION AB The N-terminal portion of phosphodiesterase (PDE) 3 was arbitrarily divided into region 1 (amino acids 1-300), which contains a large hydrophobic domain with six predicted transmembrane helices, and region 2 (amino acids 301-500), with a smaller hydrophobic domain (similar to 50 residues). To analyze these regions, full-length human (H)PDE3A and mouse (M)PDE3B and a series of N-terminal truncated mutants were synthesized in Sf9 cells. Activities of HPDE3A, H3A-Delta 189, MPDE3B, and M3B-Delta 196, which retained all or part of the hydrophobic domain in region 1, were recovered almost entirely in particulate fractions. H3A-Delta 321 and M3B-Delta 302, containing region 2, were recovered essentially equally in particulate and cytosolic fractions. H3A-Delta 397 and H3A-Delta 457, lacking both hydrophobic domains, were predominantly cytosolic. H3A-Delta 510 and M3B-Delta 604, lacking both regions 1 and 2, were virtually completely cytosolic. M3B-Delta 196 eluted as a large aggregated complex during gel filtration. With removal of greater amounts of N-terminal sequence, aggregation of PDE3 decreased, and H3A-Delta 607, H3A-Delta 721, and M3B-Delta 604 eluted as dimers. Truncated HPDE3A proteins were more sensitive than full-length HPDE3A to inhibition by lixazinone. These results suggest that the hydrophobic domains in regions 1 and 2 contain structural determinants important for association of PDE3 with intracellular membranes, as well for self-association or aggregation during gel filtration and sensitivity to a specific inhibitor. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Univ Lund, Dept Cell & Mol Biol, Sect Mol Signalling, S-22100 Lund, Sweden. RP Manganiello, VC (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Rm 5N-307,Bldg 10, Bethesda, MD 20892 USA. NR 43 TC 45 Z9 47 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 APR 21 PY 2000 VL 275 IS 16 BP 12331 EP 12338 DI 10.1074/jbc.275.16.12331 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308DP UT WOS:000086695500109 PM 10766874 ER PT J AU Ma, BY Kumar, S Tsai, CJ Hu, ZJ Nussinov, R AF Ma, BY Kumar, S Tsai, CJ Hu, ZJ Nussinov, R TI Transition-state ensemble in enzyme catalysis: Possibility, reality, or necessity? SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article ID YEAST CHORISMATE MUTASE; LANDSCAPE PERSPECTIVE; ANTIBODY CATALYSIS; ELECTRON TRANSFERS; ENERGY LANDSCAPE; BINDING-ENERGY; GROUND-STATE; MECHANISMS; PROTEINS; FUNNELS AB Proteins are not rigid structures; they are dynamic entities, with numerous conformational isomers (substates). The dynamic nature of protein structures amplifies the structural variation of the transition state for chemical reactions performed by proteins. This suggests that utilizing a transition state ensemble to describe chemical reactions involving proteins may be a useful representation. Here we re-examine the nature of the transition state of protein chemical reactions (enzyme catalysis), considering both recent developments in chemical reaction theory (Marcus theory for SN2 reactions), and protein dynamics effects. The classical theory of chemical reactions relies on the assumption that a reaction must pass through an obligatory transition-state structure. The widely accepted view of enzymatic catalysis holds that there is tight binding of the substrate to the transition-state structure, lowering the activation energy. This picture, may, however, be oversimplified. The real meaning of a transition state is a surface, not a single saddle point on the potential energy surface. In a reaction with a "loose" transition-state structure, the entire transition-state region, rather than a single saddle point, contributes to reaction kinetics. Consequently, here we explore the validity of such a model, namely, the enzymatic modulation of the transition-state surface. We examine its utility in explaining enzyme catalysis. We analyse the possibility that instead of optimizing binding to a well-defined transition-state structure, enzymes are optimized by evolution to bind efficiently with a transition-state ensemble, with a broad range of activated conformations. For enzyme catalysis, the key issue is still transition state (ensemble) stabilization. The source of the catalytic power is the modulation of the transition state. However, our definition of the transition state is the entire transition-state surface rather just than a single well-defined structure. This view of the transition-state ensemble is consistent with the nature of the protein molecule, as embodied and depicted in the protein energy landscape of folding, and binding, funnels. (C) 2000 Academic Press. C1 NCI, Intramural Res Support Program SAIC, Lab Expt & Computat Biol, FCRDC, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Intramural Res Support Program SAIC, Lab Expt & Computat Biol, FCRDC, Bldg 469,Rm 151, Frederick, MD 21702 USA. RI Ma, Buyong/F-9491-2011; OI Ma, Buyong/0000-0002-7383-719X; Kumar, Sandeep/0000-0003-2840-6398 FU NCI NIH HHS [N01CO56000] NR 63 TC 31 Z9 32 U1 0 U2 7 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD APR 21 PY 2000 VL 203 IS 4 BP 383 EP 397 DI 10.1006/jtbi.2000.1097 PG 15 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 304DT UT WOS:000086468100005 PM 10736215 ER PT J AU Major, EO Rausch, D Marra, C Clifford, D AF Major, EO Rausch, D Marra, C Clifford, D TI HIV-associated dementia SO SCIENCE LA English DT Letter ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA; TYPE-1 INFECTION; BRAIN; AUTOPSY; RNA C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. Ctr Mental Hlth Res AIDS, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Neurol & Med, Seattle, WA 98195 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 20 TC 33 Z9 35 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 21 PY 2000 VL 288 IS 5465 BP 440 EP 441 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 306YJ UT WOS:000086626000019 PM 10798979 ER PT J AU Abe, K Tumanoy, AV Ito, D Shakhov, AN Nedospasov, SA AF Abe, K Tumanoy, AV Ito, D Shakhov, AN Nedospasov, SA TI Impaired development of dendritic cells from bone marrow progenitors in mice with single and combined TNF/LT deficiencies SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, DBS,Lab Mol Immunoregulat, Frederick, MD 21701 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21701 USA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1051 EP A1051 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100822 ER PT J AU Aliberti, J Wells, T Huffnagle, G Sher, A AF Aliberti, J Wells, T Huffnagle, G Sher, A TI CCR5 ligation is a signal for IL-12 production in CD8 alpha(+) dendritic cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. ARES, SERONO, Res Inst, Geneva, Switzerland. NIAID, Immunobiol Sect, LPD, NIH, Bethesda, MD 20892 USA. RI Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1028 EP A1028 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100687 ER PT J AU Anderson, CC Carrol, JM Gallucci, S Cheever, AW Matzinger, P AF Anderson, CC Carrol, JM Gallucci, S Cheever, AW Matzinger, P TI On the tolerogenicity/adjuvanticity of grafts SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Ghost Lab, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. Genet Inst, Andover, MA 01810 USA. Biomed Res Inst, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1215 EP A1215 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101785 ER PT J AU Anderson, HA Roche, PA AF Anderson, HA Roche, PA TI A role for membrane rafts in antigen presentation by MHC class II molecules SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1195 EP A1195 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101665 ER PT J AU Arudchandran, R Saitoh, S Manetz, TS Zhang, W Sommer, CL Love, PE Samelson, LE Rivera, J AF Arudchandran, R Saitoh, S Manetz, TS Zhang, W Sommer, CL Love, PE Samelson, LE Rivera, J TI LAT is essential to Fc epsilon RI-mediated mast cell responses. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1246 EP A1246 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101966 ER PT J AU Ashcroft, GS Lei, K Jin, W Wahl, SM AF Ashcroft, GS Lei, K Jin, W Wahl, SM TI Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, NIDCR, OIIB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1150 EP A1150 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101399 ER PT J AU Basta, M Baranyi, L Savay, S Bodo, M Alving, CR Szebeni, J AF Basta, M Baranyi, L Savay, S Bodo, M Alving, CR Szebeni, J TI Intravenous immunoglobulin inhibits liposome-induced,complement-mediated hemodynamic changes in pigs and rats SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A957 EP A957 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100264 ER PT J AU Bergmann-Leitner, ES Abrams, SI AF Bergmann-Leitner, ES Abrams, SI TI Characterization of an anti-ras oncogene-specific CD4(+) T cell response in tumor immune reactions. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RI Bergmann-Leitner, Elke/B-3548-2011 OI Bergmann-Leitner, Elke/0000-0002-8571-8956 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1016 EP A1016 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100612 ER PT J AU Bettinotti, MP Wang, E Monsurro, V Hadzikadic, L Marincola, FM AF Bettinotti, MP Wang, E Monsurro, V Hadzikadic, L Marincola, FM TI Lack of correlation between Flu/HLA-A*0201 or A*0205 tetrameric complexes staining and immunogenicity of Flu-M1 (58-66) in HLA-A*0201 and A*0205 bearing individuals SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1056 EP A1056 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100851 ER PT J AU Bleesing, JJH Straus, SE Fleisher, TA AF Bleesing, JJH Straus, SE Fleisher, TA TI alpha/beta(+) CD4(-) CD8(-) T cells (alpha/beta-DNT cells) in humans with the Autoimmune Lymphoproliferative Syndrome (ALPS) express the CD45 isoform B220 characteristic of murine LPR and GLD alpha/beta-DNT cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1213 EP A1213 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101769 ER PT J AU Bleesing, JJH Brown, MR Dale, JK Straus, SE AF Bleesing, JJH Brown, MR Dale, JK Straus, SE TI Reduced CD27 positive B cells in the peripheral blood of patients with autoimmune lymphoproliferative syndrome (ALPS) SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Inst Hlth, Bethesda, MD USA. NIAID, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1122 EP A1122 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101239 ER PT J AU Brutkiewicz, RR Spence, PM Yewdell, JW Bennink, JR Bacik, I Roberts, TJ AF Brutkiewicz, RR Spence, PM Yewdell, JW Bennink, JR Bacik, I Roberts, TJ TI Processing of endogenous antigens presented by mouse CD1 molecules to NK T cells occurs in an endocytic compartment SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Walther Oncol Ctr, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1196 EP A1196 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101672 ER PT J AU Candotti, F Frucht, DM Nelson, J Kaminski, E Melia, P Schumacher, RF Muul, L Fleisher, TA Notarangelo, LD O'Shea, JJ AF Candotti, F Frucht, DM Nelson, J Kaminski, E Melia, P Schumacher, RF Muul, L Fleisher, TA Notarangelo, LD O'Shea, JJ TI An adult patient with JAK3 deficiency, T cell development and unusually mild immunodeficiency SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Derriford Hosp, Plymouth PL6 8DH, Devon, England. Univ Brescia, I-25121 Brescia, Italy. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A931 EP A931 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100111 ER PT J AU Cao, WX Verma, M Germain, RN AF Cao, WX Verma, M Germain, RN TI Novel genes involved in thymic development SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A919 EP A919 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100042 ER PT J AU Caspi, RR Sun, SH David, CS Hargrave, PA McDowell, H Wiggert, B Chan, CC Pennesi, IG AF Caspi, RR Sun, SH David, CS Hargrave, PA McDowell, H Wiggert, B Chan, CC Pennesi, IG TI A humanized model of experimental autoimmune uveitis in HLA-transgenic mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A998 EP A998 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100511 ER PT J AU Chegini, S Hagaman, D Holland, S AF Chegini, S Hagaman, D Holland, S TI Linezolid hypersensitivity: An intravenous (IV) desensitization protocol SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1244 EP A1244 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101955 ER PT J AU Chen, WJ Frank, ME Jin, WW Wahl, SM AF Chen, WJ Frank, ME Jin, WW Wahl, SM TI Release of transforming growth factor-beta (TGF-beta) by apoptotic T cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDCR, Cellular Immunol Sect, OIIB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1225 EP A1225 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101845 ER PT J AU Chen, ZE Gramaglia, I Panoskaltis-Mortari, A Murphy, WJ Zeller, J Roncarolo, M Boussiotis, VA Blazar, BR AF Chen, ZE Gramaglia, I Panoskaltis-Mortari, A Murphy, WJ Zeller, J Roncarolo, M Boussiotis, VA Blazar, BR TI Alloreactive CD4+T cells can be renderd anergic by a combination of IL-10+TGF beta due to a failure of cell cycle progression SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Minnesota, Minneapolis, MN 55455 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Hosp San Raffaele, TIGET, I-20132 Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1089 EP A1089 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101044 ER PT J AU Chiang, YJ Kole, HK Brown, K Shevach, E Gu, H AF Chiang, YJ Kole, HK Brown, K Shevach, E Gu, H TI T cell hyperproliferation and IL-2 hyperproduction lead development of autoimmune disease in Cbl-b deficient mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1176 EP A1176 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101554 ER PT J AU Chiaramonte, MG Cheever, AW Donaldson, DD Wynn, TA AF Chiaramonte, MG Cheever, AW Donaldson, DD Wynn, TA TI Reversal of hepatic pathology in chronic murine schistosomiasis by IL-13 blockade SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. Genet Inst, Andover, MA 01810 USA. BRI, Rockville, MD 20852 USA. RI Wynn, Thomas/C-2797-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A952 EP A952 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100236 ER PT J AU Chiodetti, LM Barber, DL Schwartz, RH AF Chiodetti, LM Barber, DL Schwartz, RH TI Biallelic expression of the interleukin-2 locus under optimal stimulation conditions SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1167 EP A1167 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101502 ER PT J AU Choi, Y Simon-Stoos, KL Puck, JM AF Choi, Y Simon-Stoos, KL Puck, JM TI Abnormal activation and apoptosis of T cells from autoimmune MRL mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 Kangnung Natl Univ, Kangnung, South Korea. NHGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A995 EP A995 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100493 ER PT J AU Chu, CC Chua, K Strober, W Tian, W AF Chu, CC Chua, K Strober, W Tian, W TI Genes expressed in human B cells during class switching: Pitfalls to avoid. SO FASEB JOURNAL LA English DT Meeting Abstract C1 N Shore Univ Hosp, Manhasset, NY 11030 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1046 EP A1046 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100790 ER PT J AU Chung, DH Natarajan, K Tormo, J Mariuzza, RA Yokoyama, WM Margulies, DH AF Chung, DH Natarajan, K Tormo, J Mariuzza, RA Yokoyama, WM Margulies, DH TI Mapping the ligand of the NK inhibitory receptor Ly49A on living cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, MBS, NIH, Bethesda, MD 20892 USA. Univ Maryland, Inst Biotechnol, CARB, Rockville, MD USA. Washington Univ, Sch Med, HHMI, Div Rheumatol, St Louis, MO USA. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1019 EP A1019 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100633 ER PT J AU Collazo, CM Yap, GS Taylor, GA Sher, A AF Collazo, CM Yap, GS Taylor, GA Sher, A TI The IFN-gamma-inducible GTPase (IGTP) is required for in vivo control of Toxoplasma gondii infection in both hematopoeitic and non-hematopoeitic host cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, LPD, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A955 EP A955 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100252 ER PT J AU d'Hellencourt, CL Harry, GJ AF d'Hellencourt, CL Harry, GJ TI Cytokine receptor expression in hippocampal injury: alterations induced by trimethyltin. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Toxicol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1251 EP A1251 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101993 ER PT J AU Dasso, JF Lee, J Mage, RG AF Dasso, JF Lee, J Mage, RG TI Quantification of human immunoglobulins: Comparison of a multiplexed flow cytometric assay with ELISA. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1237 EP A1237 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101913 ER PT J AU Davies, AH Margulies, DH Soloski, MJ AF Davies, AH Margulies, DH Soloski, MJ TI Studying the function of the class Ib molecule Qa-1 using a transgenic single chain beta-2 microglobulin-Qa-1 molecule. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1056 EP A1056 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100852 ER PT J AU Dawson, HD Collins, G Nadal, C Pyle, RS Taub, DD AF Dawson, HD Collins, G Nadal, C Pyle, RS Taub, DD TI Mechanisms involved in retinoid-induced TH2 polarization of activated T cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, GRC, NIH, Baltimore, MD 21224 USA. Barry Univ, Miami Shores, FL 33161 USA. RI Dawson, Harry/H-8242-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A987 EP A987 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100446 ER PT J AU Diaw, L Siwarski, D Jones, G Huppi, K AF Diaw, L Siwarski, D Jones, G Huppi, K TI Dual expression of kappa and lambda light chain genes defines a subset of B cells in mouse plasmacytomas SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1043 EP A1043 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100772 ER PT J AU Difilippantonio, MJ Zhu, J Chen, HT Meffre, E Nussenzweig, MC Max, E Ried, T Nussenzweig, A AF Difilippantonio, MJ Zhu, J Chen, HT Meffre, E Nussenzweig, MC Max, E Ried, T Nussenzweig, A TI Ku80 is essential for maintaining genomic stability. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NIH, FDA, Bethesda, MD 20892 USA. Rockefeller Inst, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1047 EP A1047 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100799 ER PT J AU Dols, AM Meijer, SL Wood, JG Doran, T Justice, L Alvord, G Smith, JW Urba, WJ Fox, BA AF Dols, AM Meijer, SL Wood, JG Doran, T Justice, L Alvord, G Smith, JW Urba, WJ Fox, BA TI Identification of breast tumor-specific T cells in patients following hormonal or chemotherapy SO FASEB JOURNAL LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Ctr Canc,Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Can Res Ctr, Portland, OR 97201 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1015 EP A1015 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100608 ER PT J AU Farr, A Rubin, J LaRochelle, W Erickson, M AF Farr, A Rubin, J LaRochelle, W Erickson, M TI Thymocyte-derived KGF: a paracrine regulator of thymic epithelium SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A916 EP A916 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100025 ER PT J AU Finkelman, FD Schopf, L Jankovic, D Morris, SC Urban, JF AF Finkelman, FD Schopf, L Jankovic, D Morris, SC Urban, JF TI IgE contributes to accelerated worm expulsion during a second Trichinella spiralis infection. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Cincinnati, Coll Med, Cincinnati, OH USA. VAMC, Cincinnati, OH USA. USDA, Beltsville, MD 20705 USA. NIAID, LPD, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A952 EP A952 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100235 ER PT J AU Franco, JL Rosenzweig, S Montoya, CJ Grimbacher, B Holland, SM Patino, PJ Zelazko, M Puck, JP AF Franco, JL Rosenzweig, S Montoya, CJ Grimbacher, B Holland, SM Patino, PJ Zelazko, M Puck, JP TI Multisystem findings and cytokine studies of immune disfunction in hyper IgE syndrome SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. Univ Antioquia, Medellin, Colombia. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A932 EP A932 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100119 ER PT J AU Freitag, C Schito, M Near, KA Chougnet, C Langhorne, J Sher, A AF Freitag, C Schito, M Near, KA Chougnet, C Langhorne, J Sher, A TI Infection with murine malaria induces increased viral expression in HIV-1 transgenic mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, LPD, NIH, Bethesda, MD 20892 USA. NCI, EIB, NIH, Bethesda, MD 20892 USA. NIMR, London, England. NIH, HHMI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A939 EP A939 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100158 ER PT J AU Gadina, M Sudarshan, C Visconti, R Gu, H Neel, BG O'Shea, JJ AF Gadina, M Sudarshan, C Visconti, R Gu, H Neel, BG O'Shea, JJ TI The adapter molecule Gab2 is induced by lymphocyte activation and is involved in signaling by IL-2 and IL-15 but not other common gamma chain-using cytokines. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAMS, LCBS, ARB, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RI Gu, Haihua/G-6364-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1084 EP A1084 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101014 ER PT J AU Gallegos, S Lam, A Malkovska, I Fowler, DH Gress, RE Hakim, FT AF Gallegos, S Lam, A Malkovska, I Fowler, DH Gress, RE Hakim, FT TI Lymphocyte reinfusion enhances post transplant CD4 recovery. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1078 EP A1078 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100978 ER PT J AU Gonsky, R Deem, RL Young, HA Targan, SR AF Gonsky, R Deem, RL Young, HA Targan, SR TI CD2-mediated activation of STAT: Transactivation of the IFN-gamma intronic STAT cis-element is unique for LPMC and independent of IL-12. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Los Angeles, CA 90048 USA. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1083 EP A1083 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101006 ER PT J AU Grammer, AC Haudek, SB Shii, D Vale, T Lipsky, PE AF Grammer, AC Haudek, SB Shii, D Vale, T Lipsky, PE TI CD40-induced NF-kB activation in human B cells is mediated by TRAF-dependent and independent signaling pathways SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAMS, NIH, Autoimmun Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A970 EP A970 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100341 ER PT J AU Gran, B Zhao, Y Pinilla, C Hemmer, B Markovic-Plese, S Martin, R Simon, R AF Gran, B Zhao, Y Pinilla, C Hemmer, B Markovic-Plese, S Martin, R Simon, R TI A new strategy for the quantitative analysis of T-Cell receptor degeneracy and the identification of potential target epitopes SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. Torrey Pines Inst Mol Studies, San Diego, CA USA. Univ Marburg, Dept Neurol, D-35032 Marburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1165 EP A1165 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101487 ER PT J AU Greenwell-Wild, T Orenstein, JM Wahl, SM AF Greenwell-Wild, T Orenstein, JM Wahl, SM TI Differential cellular gene expression during HIV-1 infection of macrophages. SO FASEB JOURNAL LA English DT Meeting Abstract C1 GWU, Washington, DC USA. NIDCR, OIIB, NIH, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1033 EP A1033 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100715 ER PT J AU Hakim, FT Cepeda, R Jones, E Chow, C Gress, R AF Hakim, FT Cepeda, R Jones, E Chow, C Gress, R TI Long term recovery of CD4 T cells in adults correlates with recovery of CD45RA CD4 cells and increased thymic size. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1078 EP A1078 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100981 ER PT J AU Hanson, EM Gupta, N Keegan, AD AF Hanson, EM Gupta, N Keegan, AD TI Role of SHP-1 in IL-4-induced STAT6 activation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Amer Red Cross, Holland Lab, Dept Immunol, Rockville, MD USA. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1087 EP A1087 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101030 ER PT J AU He, J Gurunathan, S Iwasaki, A Kelsal, BL AF He, J Gurunathan, S Iwasaki, A Kelsal, BL TI Primary role of Gi-protein signaling in the regulation of IL-12 production and the induction of a Th1 response to Leishmania major SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immune Cell Interact Unit, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1081 EP A1081 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100998 ER PT J AU He, R Tan, L Browning, DD Wang, JM Ye, RD AF He, R Tan, L Browning, DD Wang, JM Ye, RD TI The synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met is a potent chemotactic agonist for mouse formyl peptide receptor SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Illinois, Dept Pharmacol, Chicago, IL 60612 USA. Frederick Canc Res Dev Ctr, Natl Canc Inst, Div Basic Sci, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1095 EP A1095 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101076 ER PT J AU Herndon, TM Shan, X Tsokos, GC Wange, RL AF Herndon, TM Shan, X Tsokos, GC Wange, RL TI Expression of ZAP-70 and SLP-76 is required for NF-kappa B activation in Jurkat T cells following engagement of CD3 and CD28 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1177 EP A1177 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101564 ER PT J AU Hilburger, ME Abrams, SI AF Hilburger, ME Abrams, SI TI Wild-type p53 as a model for analysis of mechanisms of CTL-mediated antitumor activity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1006 EP A1006 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100557 ER PT J AU Hook, S Prout, M Camberis, M Konig, M Zimmer, A Van Heeke, G Le Gros, G AF Hook, S Prout, M Camberis, M Konig, M Zimmer, A Van Heeke, G Le Gros, G TI Th2 dependent airway eosinophilia is regulated by preproenkephalin SO FASEB JOURNAL LA English DT Meeting Abstract C1 Novartis Horsham Res Ctr, Horsham, W Sussex, England. NIMH, Dev Biol Unit, Cell Biol Lab, Bethesda, MD 20892 USA. Wellington Sch Med, Malaghan Inst Med Res, Wellington, New Zealand. RI Le Gros, Graham/C-6725-2011; Zimmer, Andreas/B-8357-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A925 EP A925 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100078 ER PT J AU Horner, AA Takabayashi, K Belyakov, I Cininan, N Nguyen, MD Richman, DD Raz, E AF Horner, AA Takabayashi, K Belyakov, I Cininan, N Nguyen, MD Richman, DD Raz, E TI Induction of systemic and mucosal T and B cell immunity by mucosal vaccination with immunostimulatory DNA and gp120 SO FASEB JOURNAL LA English DT Meeting Abstract C1 UCSD, Sch Med, La Jolla, CA USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A941 EP A941 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100169 ER PT J AU Howard, GMZ Dong, HF Subleski, J Strobl, S Shirakawa, AK Nelson, EL Oppenheim, JJ AF Howard, GMZ Dong, HF Subleski, J Strobl, S Shirakawa, AK Nelson, EL Oppenheim, JJ TI CCR8 is a receptor for 1309, TARC and LEC on myeloid cells and is antagonized by an ureido analog of distamycin SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, IRSP, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, CSP SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1094 EP A1094 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101072 ER PT J AU Hu-Li, J Pannetier, C Gu, H Watson, C Lohning, M Radbruch, A Paul, WE AF Hu-Li, J Pannetier, C Gu, H Watson, C Lohning, M Radbruch, A Paul, WE TI Regulation of expression of IL-4 alleles. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, Bethesda, MD 20892 USA. DRFZ, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1087 EP A1087 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101032 ER PT J AU Iwashiro, M Peterson, K Chesebro, B Hasenkrug, K AF Iwashiro, M Peterson, K Chesebro, B Hasenkrug, K TI Long term immunosuppression by CD4+cells with Friend virus persistence. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A929 EP A929 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100099 ER PT J AU Jankovic, D Kullberg, M Caspar, P Hieny, S Yap, G Sher, A AF Jankovic, D Kullberg, M Caspar, P Hieny, S Yap, G Sher, A TI During infection with Toxoplasma gondii or Schistosoma mansoni polarized Th1/Th2 cells arise in the absence of instruction by IL-12 OR IL-4. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, LPD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A952 EP A952 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100237 ER PT J AU Jeevan, A Yoshimura, T McMurray, DN AF Jeevan, A Yoshimura, T McMurray, DN TI Inhibition of IFN-gamma mRNA expression in guinea pig cells treated with virulent Mycobacterium tuberculosis SO FASEB JOURNAL LA English DT Meeting Abstract C1 Texas A&M Hlth Sci Ctr, College Stn, TX 77843 USA. NCI, FCRDC, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1058 EP A1058 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100863 ER PT J AU Kaminski, DA Martin, F Letterio, JJ Burrows, PD AF Kaminski, DA Martin, F Letterio, JJ Burrows, PD TI Abnormal B cell development in TGF-beta 1(-/-) mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Alabama, Dept Microbiol, Birmingham, AL USA. NCI, Chemoprevent Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1183 EP A1183 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101595 ER PT J AU Karp, CL Ma, X Cuomo, P Wahl, L Trinchieri, G de Almeida, A AF Karp, CL Ma, X Cuomo, P Wahl, L Trinchieri, G de Almeida, A TI Type I interferons and IL-12: Convergence and cross regulation among mediators of cellular immunity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. NIDR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1181 EP A1181 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101585 ER PT J AU Khaled, A Kim, K Muegge, K Durum, SK AF Khaled, A Kim, K Muegge, K Durum, SK TI IL-7 withdrawal induces a rise in intracellular pH through the NHE causing Bax translocation and a transient mitochondrial hyperpolarization. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Canc Inst, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1090 EP A1090 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101051 ER PT J AU Koh, CY Raziuddin, A Welniak, LA Blazar, BR Bennett, M Murphy, WJ AF Koh, CY Raziuddin, A Welniak, LA Blazar, BR Bennett, M Murphy, WJ TI The effects of NK inhibitory receptor blockade on normal and transformed hematopoietic cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, LLB, DBS,SAIC Frederick, Frederick, MD 21702 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. RI Koh, Crystal/D-9986-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1138 EP A1138 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101328 ER PT J AU Koski, G Lyakh, L Cohen, P Rice, N AF Koski, G Lyakh, L Cohen, P Rice, N TI Activation of nuclear NF-kappa B is common to dendritic cell differentiation programs induced in serum-free culture by bacterial LPS, TNF-alpha and calcium ionophore SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Frederick, MD 21701 USA. Cleveland Clin Fdn, Surg Res Ctr, Cleveland, OH 44195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1047 EP A1047 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100797 ER PT J AU Kurlander, RJ Chao, F Fields, J AF Kurlander, RJ Chao, F Fields, J TI A hydrophobic transmembrane region protects adjacent immunogenic epitopes from extracellular protease degradation and promotes their presentation by APC to CD8 cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Ctr Clin, Dept Clin Pathol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1056 EP A1056 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100848 ER PT J AU Lally, K Nielsen, MB Ohnmacht, G Bettinotti, MP Marincola, FM AF Lally, K Nielsen, MB Ohnmacht, G Bettinotti, MP Marincola, FM TI Unmasking cryptic epitopes after loss of immunodominant tumor antigen expression SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1005 EP A1005 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100551 ER PT J AU Le, Y Gong, W Li, B Dunlop, NM Shen, W Su, SB Ye, RD Oppenheim, JJ Wang, JM AF Le, Y Gong, W Li, B Dunlop, NM Shen, W Su, SB Ye, RD Oppenheim, JJ Wang, JM TI Utilization of FPRL1 and FPR by the synthetic peptide WKYMVm for human phagocyte activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, DBS, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. Univ Illinois, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1095 EP A1095 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101079 ER PT J AU Leitner, WW Ying, H Driver, DA Dubensky, TW Restifo, NP AF Leitner, WW Ying, H Driver, DA Dubensky, TW Restifo, NP TI Enhancement of DNA plasmids with alphaviral replicase: The next generation of DNA vaccines? SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Chiron Corp, Ctr Gene Therapy, Emeryville, CA 94608 USA. RI Restifo, Nicholas/A-5713-2008; Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1002 EP A1002 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100532 ER PT J AU Liao, F Shirakawa, A Rabin, RL Farber, JM AF Liao, F Shirakawa, A Rabin, RL Farber, JM TI CCR6 is expressed on both resting and activated B cells, but signals effectively only on activated cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1093 EP A1093 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101066 ER PT J AU Lillard, JW Boyaka, PN Taub, DD McGhee, JR AF Lillard, JW Boyaka, PN Taub, DD McGhee, JR TI RANTES potentiates acquired mucosal immunity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Morehouse Sch Med, Atlanta, GA 30310 USA. Univ Alabama, Birmingham, AL 35294 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1204 EP A1204 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101717 ER PT J AU Liu, K Hodes, RJ Weng, NP AF Liu, K Hodes, RJ Weng, NP TI Dissociation between telomerase reverse transcriptase (hTERT) expression and telomerase activity in human lymphocytes SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. NIA, NIH, Bethesda, MD USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1170 EP A1170 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101518 ER PT J AU Lucas, PJ Kim, SJ Melby, S Gress, RE AF Lucas, PJ Kim, SJ Melby, S Gress, RE TI Disruption of T cell subset homeostasis in mice expressing a T cell specific dominant negative TGF-beta II receptor SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1225 EP A1225 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101843 ER PT J AU Mackey, MF Eichelberg, K Germain, RN AF Mackey, MF Eichelberg, K Germain, RN TI Structure-function studies of the CD40 receptor in primacy murine dendritic cells using retroviral gene transduction SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1086 EP A1086 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101025 ER PT J AU Massey, B Matzinger, P AF Massey, B Matzinger, P TI TUMOR INFLAMMATION: Immune stimulating treatment for cancer SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Ghost Lab, LCMI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1137 EP A1137 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101325 ER PT J AU Maul, LM Tuschong, L Soenen, S Blaese, RM AF Maul, LM Tuschong, L Soenen, S Blaese, RM TI Immune response to fetal calf serum (FCS) in adenosine deaminase (ADA) deficient gene therapy patients SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHGRI, Clin Gene Therapy Branch, NIH, Newtown, PA USA. Kimeragen, Newtown, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A932 EP A932 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100120 ER PT J AU Mazzoni, A Bronte, V Apolloni, E Zanovello, P Visintin, A Spitzer, JH Titus, JA Segal, DM AF Mazzoni, A Bronte, V Apolloni, E Zanovello, P Visintin, A Spitzer, JH Titus, JA Segal, DM TI Nitric oxide dependent inhibition of immune responses by immortalized myeloid suppressor cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Padua, Dept Oncol & Surg Sci, Padua, Italy. RI Bronte, Vincenzo/K-7902-2016 OI Bronte, Vincenzo/0000-0002-3741-5141 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1011 EP A1011 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100586 ER PT J AU McCartney-Francis, N Mizel, D Wahl, S AF McCartney-Francis, N Mizel, D Wahl, S TI Aberrant expression of transcription factor NF-kappa B in TGF-beta 1 null mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDCR, OIIB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1156 EP A1156 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101435 ER PT J AU McDowell, MA Marovich, MA Sacks, DL AF McDowell, MA Marovich, MA Sacks, DL TI IL-12p70 production in human dendritic cells by Leishmania spp. is species and strain dependent. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A952 EP A952 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100239 ER PT J AU McHugh, RS Natarajan, K Margulies, DH Shevach, EM AF McHugh, RS Natarajan, K Margulies, DH Shevach, EM TI A TCR transgenic model of severe spontaneous organ-specific autoimmunity SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A993 EP A993 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100482 ER PT J AU McIntyre, TM Strober, W AF McIntyre, TM Strober, W TI Ig-receptor crosslinking confers a survival advantage to B cells in the presence of high concentrations of TGF-beta needed for high-rate IgA switching. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Walter Reed Army Inst Res, Silver Spring, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1201 EP A1201 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101702 ER PT J AU McKean, DJ Huntoon, CJ Bell, MP Tai, X Sharrow, S Hedin, KE Conley, A Singer, A AF McKean, DJ Huntoon, CJ Bell, MP Tai, X Sharrow, S Hedin, KE Conley, A Singer, A TI CD28 signal intensity regulates positive vs negative selection of CD4 CD8 thymocytes SO FASEB JOURNAL LA English DT Meeting Abstract C1 Mayo Clin & Mayo Grad Sch Med, Dept Immunol, Rochester, MN 55901 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A918 EP A918 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100037 ER PT J AU McNeil, AC Shupert, WL Mican, JA Connors, M AF McNeil, AC Shupert, WL Mican, JA Connors, M TI Antigen-specific proliferation is suppressed during HIV-1 viremia despite maintenance of antigen specific CD4+T-cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A937 EP A937 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100149 ER PT J AU Mehta, IK Smith, HRC Wang, J Margulies, DH Yokoyama, WM AF Mehta, IK Smith, HRC Wang, J Margulies, DH Yokoyama, WM TI A chimeric C57L-derived Ly49 inhibitory receptor resembling the Ly49D activation receptor. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Washington Univ, Sch Med, Div Rheumatol, HHMI, St Louis, MO 63110 USA. NIAID, Immunol Lab, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1019 EP A1019 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100635 ER PT J AU Memon, S Gress, RE Hakim, FT AF Memon, S Gress, RE Hakim, FT TI Recovery of T cell receptor CDR3 diversity post transplant is associated with recovery of naive CD45RA+CD4 T cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. RI Memon, Sarfraz/E-1198-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1078 EP A1078 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100979 ER PT J AU Mongini, P Inman, J AF Mongini, P Inman, J TI BCR activation phenomena exhibit differing dependencies upon BCR co-ligation with the CD21 : CD19 : CD81 co-stimulatory complex. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Immunol Lab, Bethesda, MD 20892 USA. NYU Med Ctr, Hosp Joint Dis, Dept Rheumatol, New York, NY 10016 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A962 EP A962 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100295 ER PT J AU Monsurro, V Nielson, MB Lee, KH Wang, E Marincola, FM AF Monsurro, V Nielson, MB Lee, KH Wang, E Marincola, FM TI Modulation of vaccine-specific T-cell frequency and TCR repertoire during epitope-based vaccination. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Inst Hlth, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1139 EP A1139 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101335 ER PT J AU Moratz, C Hayman, R Gu, H Kehrl, J AF Moratz, C Hayman, R Gu, H Kehrl, J TI Alterations in B cell migration and signal transduction in RGS1 deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1149 EP A1149 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101393 ER PT J AU Morrow, MR Bleesing, JJH Fleisher, TA AF Morrow, MR Bleesing, JJH Fleisher, TA TI Proliferating human T-cells increasingly express the murine-like CD45 isoform B220 after stimulation with staphylococcal enterotoxin B (SEB) SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1167 EP A1167 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101503 ER PT J AU Noben-Trauth, N Hu-Li, J Paul, WE AF Noben-Trauth, N Hu-Li, J Paul, WE TI Conventional CD4+T cells provide an initial source of IL-4 during Th2 differentiation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A924 EP A924 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100070 ER PT J AU Obiakor, H Sehgal, D Dasso, J Malekafzali, A Bonner, R Mage, RG AF Obiakor, H Sehgal, D Dasso, J Malekafzali, A Bonner, R Mage, RG TI Comparison of three methods for collection of single lymphocytes from tissue sections for high fidelity PCR and Ig gene sequencing SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, LI, NIH, Bethesda, MD 20892 USA. NICHD, LIMB, NIH, Bethesda, MD 20892 USA. RI Bonner, Robert/C-6783-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1044 EP A1044 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100781 ER PT J AU Ortaldo, JR Winkler-Pickett, RT Wiegand, G AF Ortaldo, JR Winkler-Pickett, RT Wiegand, G TI Activating Ly-49 NK receptors: Ontogeny of function and their repertoire SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, DBS, Expt Immunol Lab, Frederick, MD 21701 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1020 EP A1020 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100639 ER PT J AU Ouyang, YL Virasch, N Aubrey, MT Mukerjee, N Bierer, BE Freed, BM AF Ouyang, YL Virasch, N Aubrey, MT Mukerjee, N Bierer, BE Freed, BM TI Suppression of human IL-1 beta, IL-2, IFN-gamma and TNF-alpha production by cigarette smoke extracts. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1113 EP A1113 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101184 ER PT J AU Panoskaltsis-Mortari, A Strieter, RM Hermanson, JR Fegeding, K Murphy, WJ Farrell, CL Lacey, DL Blazar, BR AF Panoskaltsis-Mortari, A Strieter, RM Hermanson, JR Fegeding, K Murphy, WJ Farrell, CL Lacey, DL Blazar, BR TI Preferential induction of CC chemokines in the lung during the generation of idiopathic pneumonia syndrome (IPS) following allogeneic murine bone marrow transplantation (BMT). SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Minnesota, Minneapolis, MN 55455 USA. Univ Michigan, Ann Arbor, MI 48109 USA. WRAI, Washington, DC USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Amgen, Thousand Oaks, CA 91320 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1077 EP A1077 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100975 ER PT J AU Patterson, RM Stachlewitz, R Germolec, D AF Patterson, RM Stachlewitz, R Germolec, D TI Induction of apoptosis in TCDD-induced endotoxin hypersensitivity SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Inotek Inc, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1088 EP A1088 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101036 ER PT J AU Perez-Diez, A Ohnmacht, GA Restifo, NP Marincola, FM AF Perez-Diez, A Ohnmacht, GA Restifo, NP Marincola, FM TI Comparing viral versus peptide vaccine in a mouse model by real time quantitative PCR (qRT-PCR). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1012 EP A1012 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100588 ER PT J AU Peterson, K Chesebro, B AF Peterson, K Chesebro, B TI Interferon-gamma production by friend retrovirus-specific CD4+T cells is influenced by MHC genotype at both the class I and class II loci. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1040 EP A1040 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100753 ER PT J AU Phalen, SW Yamashiro, S Yoshimura, T McMurray, DN AF Phalen, SW Yamashiro, S Yoshimura, T McMurray, DN TI In situ detection of IL-8 and MCP-1 in cells from tuberculous pleural effusions in the guinea pig SO FASEB JOURNAL LA English DT Meeting Abstract C1 Texas A&M Univ, Dept Med Microbiol & Immunol, Syst Hlth Sci Ctr, College Stn, TX 77843 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1091 EP A1091 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101055 ER PT J AU Pinilla, C Houghten, RA Wilson, D Gran, B Martin, R AF Pinilla, C Houghten, RA Wilson, D Gran, B Martin, R TI Identification and optimization of antigens for T cells clones of clinical relevance SO FASEB JOURNAL LA English DT Meeting Abstract C1 Torrey Pines Inst Mol Studies, San Diego, CA USA. Mixture Sci Inc, San Diego, CA USA. NINDS, Neuroimmunol Branch, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A982 EP A982 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100412 ER PT J AU Poussin, MA Fuller, CL Goluszko, E Braciale, VL Christadoss, P AF Poussin, MA Fuller, CL Goluszko, E Braciale, VL Christadoss, P TI Mechanisms of bm12 mice resistance to experimental autoimmune myasthenia gravis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Dept Microbiol Immunol, Galveston, TX 77555 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A998 EP A998 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100509 ER PT J AU Rabin, RL Farber, JM AF Rabin, RL Farber, JM TI Dual roles for CXCR3 in T cell activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1096 EP A1096 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101085 ER PT J AU Sada, K Zhang, J Siraganian, RP AF Sada, K Zhang, J Siraganian, RP TI The SH2 domain-mediated targeting, but not localization of Syk in the plasma membrane is critical for Fc epsilon RI signalling pathway. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A960 EP A960 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100284 ER PT J AU Schito, M Kennedy, P Berger, E Sher, A AF Schito, M Kennedy, P Berger, E Sher, A TI Immunopharmacological interventions that block microbial induced HIV-1 expression in a murine transgenic model. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A938 EP A938 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100152 ER PT J AU Sehgal, D Schiaffella, E Anderson, AO Mage, RG AF Sehgal, D Schiaffella, E Anderson, AO Mage, RG TI Different B-CELL clonal lineages in rabbit splenic germinal centers utilize a diverse set of kappa light chain genes, gene conversion, receptor revision and hypermutation to generate heterogeneous high affinity anti-DNP antibodies SO FASEB JOURNAL LA English DT Meeting Abstract C1 USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1043 EP A1043 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100775 ER PT J AU Seiter, S Nielson, MB Monsurro, V Marincola, FM AF Seiter, S Nielson, MB Monsurro, V Marincola, FM TI Evolution of a tumor infiltrating lymphocyte culture followed by HLA/epitpop tetrameric complexes (tHLA) SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1011 EP A1011 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100583 ER PT J AU Seki, N Brooks, AD Lee, JK Mason, AT Wiltrout, RH Yagita, H Sayers, TJ AF Seki, N Brooks, AD Lee, JK Mason, AT Wiltrout, RH Yagita, H Sayers, TJ TI Cytokines enhance lysis of a murine renal cancer by T cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Lab Exper Immunol, DBS, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD USA. Juntendo Univ, Sch Med, Tokyo 113, Japan. RI Sayers, Thomas/G-4859-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1009 EP A1009 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100573 ER PT J AU Semnani, RT Sabzevari, H Nutman, TB AF Semnani, RT Sabzevari, H Nutman, TB TI Alteration of dendritic cell maturation by antigen derived from filarial parasite SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A947 EP A947 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100210 ER PT J AU Shaw, SG Dorman, SE Uzel, G Holland, SM Buckley, RH AF Shaw, SG Dorman, SE Uzel, G Holland, SM Buckley, RH TI Correction of complete IFNGR2 deficiency with transplantation of bone marrow from a parent SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A933 EP A933 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100124 ER PT J AU Smith, DA Dixon, D Germolec, DR AF Smith, DA Dixon, D Germolec, DR TI Exacerbation of systemic lupus erythematosis (SLE)-like disease in male and female autoimmune-prone MRL/lpr mice by prenatal exposure to dioxin SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Lab Toxicol Environm Immunol, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1210 EP A1210 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101752 ER PT J AU Son, N Murray, S Yanovski, J Hodes, RJ Weng, N AF Son, N Murray, S Yanovski, J Hodes, RJ Weng, N TI Lineage specific telomere shortening and unaltered capacity for telomerase expression in human T and B lymphocytes with age SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. NICHD, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1227 EP A1227 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101857 ER PT J AU Standifer, NE Lenardo, MJ Infante, AJ AF Standifer, NE Lenardo, MJ Infante, AJ TI Covalent MHC/peptides as probes of T cell specificity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Micro & Pedi, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1213 EP A1213 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101772 ER PT J AU Stewart, DM Tian, L Nelson, DL AF Stewart, DM Tian, L Nelson, DL TI Cdc42-interacting protein 4 (CIP4) mediates binding of the Wiskott-Aldrich syndrome protein (WASP) to microtubules SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A927 EP A927 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100090 ER PT J AU Su, SB Silver, PB Zhang, MF Chan, CC Caspi, RR AF Su, SB Silver, PB Zhang, MF Chan, CC Caspi, RR TI Pertussis toxin aborts induction of experimental autoimmune uveitis by blocking chemokine-dependent cell migration SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A994 EP A994 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100485 ER PT J AU Sun, B Sun, SH Chan, CC Caspi, RR AF Sun, B Sun, SH Chan, CC Caspi, RR TI An inhibitory role of IL-10 in experimental autoimmune uveitis-resistant rat? SO FASEB JOURNAL LA English DT Meeting Abstract C1 Chinese Acad Sci, Shanghai Inst Cell Biol, Shanghai 200021, Peoples R China. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A996 EP A996 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100497 ER PT J AU Tatari, Z Gress, R Hakim, FT AF Tatari, Z Gress, R Hakim, FT TI IL-15 supports the differentiation and expansion of human atypical CD28-CD57+CD8 subpopulations. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A987 EP A987 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100443 ER PT J AU Taylor, ML Dastych, J Sehgal, D Mage, RG Nilsson, G Sundstrom, M Akin, C Metcalfe, DD AF Taylor, ML Dastych, J Sehgal, D Mage, RG Nilsson, G Sundstrom, M Akin, C Metcalfe, DD TI The activating mutation D816V of the c-kit receptor enhances stem cell factor-dependent cell migration. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1128 EP A1128 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101274 ER PT J AU Tkaczyk, C Metcalfe, DD Gilfillan, AM AF Tkaczyk, C Metcalfe, DD Gilfillan, AM TI Fc epsilon RI-dependent tyrosine phosphorylation in human mast cells: Comparative effects of tyrosine kinase and tyrosine phosphatase inhibitors. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1245 EP A1245 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101960 ER PT J AU Tumanov, AV Kuprash, DV Lagarkova, MA Stewart, CL Nedospasov, SA AF Tumanov, AV Kuprash, DV Lagarkova, MA Stewart, CL Nedospasov, SA TI Tissue-specific inactivation of LT-beta gene in B cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 SAIC Frederick, IRSP, Frederick, MD USA. DBS, LMI, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Canc & Dev Biol Lab, Frederick, MD 21701 USA. RAS, Engelhardt Inst Mol Biol, Moscow 117901, Russia. MSU, Belozersky Inst Phys Chem Biol, Moscow, Russia. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1149 EP A1149 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101394 ER PT J AU Uzel, G Kleiner, DE Holland, SM AF Uzel, G Kleiner, DE Holland, SM TI Leukocyte adhesion deficiency and colitis SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1153 EP A1153 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101417 ER PT J AU Visconti, R Gadina, M Chiariello, M Chen, EH Stancato, LF Gutkind, JS O'Shea, JJ AF Visconti, R Gadina, M Chiariello, M Chen, EH Stancato, LF Gutkind, JS O'Shea, JJ TI Importance of the MKK6-p38 pathway for IL-12-induced Stat4 serine phosphorylation and transcriptional activity SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1084 EP A1084 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101017 ER PT J AU Visintin, A Mazzoni, A Spitzer, JH Wyllie, DH Dower, SK Segal, DM AF Visintin, A Mazzoni, A Spitzer, JH Wyllie, DH Dower, SK Segal, DM TI Differential expression of toll like receptors during dendritic cell maturation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. Univ Sheffield, Div Med & Mol Genet, Sheffield S10 2JF, S Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1031 EP A1031 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100705 ER PT J AU Wang, JM Li, B Wetzel, MA Rogers, TJ Henderson, EE Su, SB Gong, W Le, Y Sargeant, R Dimitrov, DS Oppenheim, JJ Shen, W AF Wang, JM Li, B Wetzel, MA Rogers, TJ Henderson, EE Su, SB Gong, W Le, Y Sargeant, R Dimitrov, DS Oppenheim, JJ Shen, W TI Down-regulation of the chemokine receptor CCR5 by activation of chemotactic formyl peptide receptor in human monocytes SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, LECB, DBS, Frederick, MD 21702 USA. Millennium Biotechnol, Ramona, CA 92065 USA. NCI, Frederick Canc Res & Dev Ctr, IRSP, SAIC Frederick, Frederick, MD 21702 USA. Temple Univ, Sch Med, Philadelphia, PA 19140 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1095 EP A1095 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101081 ER PT J AU Wu, CY Wang, X Presky, DH Magram, J AF Wu, CY Wang, X Presky, DH Magram, J TI IL-12 receptor beta 2 (IL-12Rb2)-deficient mice bind IL-12 but are defective in IL-12-mediated responses SO FASEB JOURNAL LA English DT Meeting Abstract C1 Hoffmann La Roche Inc, Nutley, NJ 07110 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1182 EP A1182 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101591 ER PT J AU Wyllie, DH Kiss-Toth, E Visintin, A Segal, D Duff, GW Dower, SK AF Wyllie, DH Kiss-Toth, E Visintin, A Segal, D Duff, GW Dower, SK TI Evidence for an accessory protein function for the Toll-like receptor TLR1 in lipopolysaccharide responses SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Sheffield, Div Med & Mol Genet, Funct Genomics Grp, Sheffield, S Yorkshire, England. RI Kiss-Toth, Endre/A-8596-2014 OI Kiss-Toth, Endre/0000-0003-4406-4017 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1032 EP A1032 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100710 ER PT J AU Wynn, TA Chiaramonte, MG Cheever, AW Hoffmann, KF AF Wynn, TA Chiaramonte, MG Cheever, AW Hoffmann, KF TI Indespensable roles for IL-10 and IL-13 in the generation and maintenance of a Th2-dependent immune response in vivo SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1086 EP A1086 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101026 ER PT J AU Xie, ZH Zhang, J Siraganian, RP AF Xie, ZH Zhang, J Siraganian, RP TI Positive regulation of JNK and TNF-alpha production but not histamine release by SHP-1 in RBL-2H3 mast cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDCR, OIIB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1245 EP A1245 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101958 ER PT J AU Yang, D Chen, O Chertov, O Oppenheim, JJ AF Yang, D Chen, O Chertov, O Oppenheim, JJ TI Human neutrophil defensins are selective chemoattractants for different subsets of human T and dendritic cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, NIH, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, DBS,NIH, Frederick, MD 21702 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1115 EP A1115 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101197 ER PT J AU Yu, CR Peden, KWC Zaitseva, MB Golding, H Farber, JM AF Yu, CR Peden, KWC Zaitseva, MB Golding, H Farber, JM TI CCR9 is a receptor for CCL25 with two forms that show differing sensitivities to ligand and that has SIV go-receptor. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. US FDA, CBER, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1166 EP A1166 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101495 ER PT J AU Zhao, ZS Graf, MM Pohl, LR AF Zhao, ZS Graf, MM Pohl, LR TI Apoptosis of intrahepatic gamma delta T cells in drug-induced hepatotoxicity: Possible role of heat shock protein (HSP) 25 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1219 EP A1219 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101808 ER PT J AU Zhou, JH Tang, Q Broussard, SR Shen, WH VanHoy, RW Kelley, KW AF Zhou, JH Tang, Q Broussard, SR Shen, WH VanHoy, RW Kelley, KW TI IL-12 protects T cells from FAS mediated apoptosis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Mucosal Immun Sect, Clin Invest Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1090 EP A1090 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101050 ER PT J AU Zhou, P Freidag, B Seder, R AF Zhou, P Freidag, B Seder, R TI IL12p35 but not IL12-p40deficient mice have functional Th1 responses to primary and secondary infection with Histoplasma Capsulatum SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A980 EP A980 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100402 ER PT J AU Zhu, J Stonehouse, T Guo, L Watson, C Huang, H Paul, WE AF Zhu, J Stonehouse, T Guo, L Watson, C Huang, H Paul, WE TI Transient inhibition of IL-4 signaling by TCR engagement. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Immunol Lab, Bethesda, MD 20892 USA. Loyola Univ, Dept Cell Biol, Maywood, IL 60153 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 2000 VL 14 IS 6 SU S BP A1086 EP A1086 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101024 ER PT J AU Lu, SF Herbert, B Haufe, G Laue, KW Padgett, WL Oshunleti, O Daly, JW Kirk, KL AF Lu, SF Herbert, B Haufe, G Laue, KW Padgett, WL Oshunleti, O Daly, JW Kirk, KL TI Syntheses of (R)- and (S)-2- and 6-fluoronorepinephrine and (R)- and (S)-2- and 6-fluoroepinephrine: Effect of stereochemistry on fluorine-induced adrenergic selectivities SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SUBSTITUTION; RECEPTORS; CHEMISTRY AB Several routes to the enantiomers of fluoronorepinephrines (1) and fluoroepinephrines (2) were explored. A catalytic enantioselective oxazaborolidine reduction and a chiral (salen)Ti-IV catalyzed asymmetric synthesis of silyl cyanohydrins proved efficacious in the key stereo-defining steps of two respective routes. Binding studies of the catecholamines with alpha(1)-, alpha(2)-, beta(1)-, and beta(2)-adrenergic receptors were examined. The assays confirmed that fluorine substitution had marked effects on the affinity of (R)-norepinephrine and (R)-epinephrine for adrenergic receptors, depending on the position of substitution. Thus, a fluoro substituent at the 2-position of (R)-norepinephrine and (R)-epinephrine reduced activity at both alpha(1)- and alpha(2)-receptors and enhanced activity at beta(1)- and beta(2)-receptors, while fluorination at the 6-position reduced activity at the beta(1)- and beta(2)-receptors. The effects of fluorine substitution on the S-isomers were less predictable. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20893 USA. Univ Munster, Inst Organ Chem, D-48149 Munster, Germany. RP Kirk, KL (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20893 USA. NR 20 TC 33 Z9 37 U1 0 U2 4 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 APR 20 PY 2000 VL 43 IS 8 BP 1611 EP 1619 DI 10.1021/jm990599h PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 308DL UT WOS:000086695200020 PM 10780918 ER PT J AU Hu, JG Goldman, S Gray, CG Guy, HR AF Hu, JG Goldman, S Gray, CG Guy, HR TI Calculation of the conductance and selectivity of an ion-selective potassium channel (IRK1) from simulation of atomic scale models SO MOLECULAR PHYSICS LA English DT Article ID MOLECULAR-DYNAMICS; K+ CHANNEL; GRAMICIDIN-A; WATER; RECTIFICATION; TRANSPORT AB We present the equations and methodology for the theoretical prediction of the conductance, permeability and selectivity of a K+ channel on the basis of atomic scale models for it. The methodology involves the use of Langevin dynamics and activated trajectories in order to obtain translocation free energies, rate constants and transmission coefficients for an ion going through the channel. The models are for the Inward Rectifier K+ channel (IRK1) which is a member of a family of ion-selective K+ channels. The IRK1 channel is biologically important because of its role in cardiac pacemaker function. The models we use for the IRK1 channel are developed from a model of the Shaker voltage-gated K+ channel. We find that the theoretically predicted conductance is too low by three orders of magnitude. We attribute this underestimate to a specific structural defect in the model used. Perhaps our most significant result is that the computed conductance is tremendously sensitive to the structural details of the so-called 'P-loop' that lines the outer half of the permeation pathway of the channel. This sensitivity may be useful in future studies on ion channel proteins for which the structure is not known from X-ray crystallography. In addition, this sensitivity may help determine whether X-ray structures of these proteins correspond to open or closed conformations. C1 Univ Guelph, Guelph Waterloo Program Grad Work Phys, Guelph, ON N1G 2W1, Canada. Univ Guelph, Guelph Waterloo Ctr Grad Work Chem, Guelph, ON N1G 2W1, Canada. NCI, Math Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Univ Guelph, Guelph Waterloo Program Grad Work Phys, Guelph, ON N1G 2W1, Canada. EM goldman@chembio.uoguelph.ca NR 36 TC 14 Z9 14 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0026-8976 EI 1362-3028 J9 MOL PHYS JI Mol. Phys. PD APR 20 PY 2000 VL 98 IS 8 BP 535 EP 547 PG 13 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 308EU UT WOS:000086698200008 ER PT J AU Roth, DB Gellert, M AF Roth, DB Gellert, M TI Cancer - New guardians of the genome SO NATURE LA English DT Editorial Material ID V(D)J RECOMBINATION; KU86-DEFICIENT; GENES C1 Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Roth, DB (reprint author), Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA. NR 15 TC 31 Z9 31 U1 1 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 20 PY 2000 VL 404 IS 6780 BP 823 EP 825 DI 10.1038/35009180 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 306XY UT WOS:000086625000027 PM 10786775 ER PT J AU Ryan, KM Ernst, MK Rice, NR Vousden, KH AF Ryan, KM Ernst, MK Rice, NR Vousden, KH TI Role of NF-kappa B in p53-mediated programmed cell death SO NATURE LA English DT Article ID RIBOSOMAL S6 KINASE; P53-DEPENDENT APOPTOSIS; DNA-DAMAGE; P53; ALPHA; INDUCTION; DEGRADATION; MUTANTS AB The tumour suppressor p53 inhibits cell growth through activation of cell-cycle arrest and apoptosis(1), and most cancers have either mutation within the p53 gene or defects in the ability to induce p53. Activation or re-introduction of p53 induces apoptosis in many tumour cells and may provide effective cancer therapy 2. One of the key proteins that modulates the apoptotic response is NF-kappa B, a transcription factor that can protect or contribute to apoptosis(3). Here we show that induction of p53 causes an activation of NF-kappa B that correlates with the ability of p53 to induce apoptosis. Inhibition or loss of NF-kappa B activity abrogated p53-induced apoptosis, indicating that NF-kappa B is essential in p53-mediated cell death. Activation of NF-kappa B by p53 was distinct from that mediated by tumour-necrosis factor-alpha and involved MEK1 and the activation of pp90(rsk). Inhibition of MEK1 blocked activation of NF-kappa B by p53 and completely abrogated p53-induced cell death. We conclude that inhibition of NF-kappa B in tumours that retain wild-type p53 may diminish, rather than augment, a therapeutic response. C1 NCI, Frederick Canc Res & Dev Ctr, Regulat Cell Growth Lab, Frederick, MD 21702 USA. RP Vousden, KH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Regulat Cell Growth Lab, Bldg 560,Room 22-96,W 7th St, Frederick, MD 21702 USA. NR 30 TC 548 Z9 578 U1 1 U2 17 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 20 PY 2000 VL 404 IS 6780 BP 892 EP 897 DI 10.1038/35009130 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 306XY UT WOS:000086625000050 PM 10786798 ER PT J AU Schatzkin, A Lanza, E Corle, D Lance, P Iber, F Caan, B Shike, M Weissfeld, J Burt, R Cooper, MR Kikendall, JW Cahill, J Freedman, L Marshall, J Schoen, RE Slattery, M AF Schatzkin, A Lanza, E Corle, D Lance, P Iber, F Caan, B Shike, M Weissfeld, J Burt, R Cooper, MR Kikendall, JW Cahill, J Freedman, L Marshall, J Schoen, RE Slattery, M CA Polyp Prevention Trial Study Grp TI Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED TRIAL; COLON-CANCER; ANTIOXIDANT VITAMINS; CLINICAL-TRIAL; NURSES HEALTH; LARGE-BOWEL; PREVENTION; RISK; WOMEN; EPIDEMIOLOGY AB Background: We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas, which are precursors of most large-bowel cancers. Methods: We randomly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before randomization to one of two groups: an intervention group given intensive counseling and assigned to follow a diet that was low in fat (20 percent of total calories) and high in fiber (18 g of dietary fiber per 1000 kcal) and fruits and vegetables (3.5 servings per 1000 kcal), and a control group given a standard brochure on healthy eating and assigned to follow their usual diet. Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps; they remained in the study for approximately four years, undergoing colonoscopy one and four years after randomization. Results: A total of 1905 of the randomized subjects (91.6 percent) completed the study. Of the 958 subjects in the intervention group and the 947 in the control group who completed the study, 39.7 percent and 39.5 percent, respectively, had at least one recurrent adenoma; the unadjusted risk ratio was 1.00 (95 percent confidence interval, 0.90 to 1.12). Among subjects with recurrent adenomas, the mean (+/-SE) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group. The rate of recurrence of large adenomas (with a maximal diameter of at least 1 cm) and advanced adenomas (defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high-grade dysplasia, including carcinoma) did not differ significantly between the two groups. Conclusions: Adopting a diet that is low in fat and high in fiber, fruits, and vegetables does not influence the risk of recurrence of colorectal adenomas. (N Engl J Med 2000;342:1149-55.) (C) 2000, Massachusetts Medical Society. C1 NCI, Bethesda, MD 20892 USA. SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. Vet Affairs Edward Hines Jr Hosp, Vet Affairs Med Ctr, Hines, IL USA. Kaiser Fdn Res Inst, Oakland, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Utah, Salt Lake City, UT USA. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. WESTAT Corp, Rockville, MD 20850 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Arizona, Tucson, AZ USA. RP Schatzkin, A (reprint author), NCI, Bethesda, MD 20892 USA. NR 37 TC 604 Z9 625 U1 5 U2 29 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 20 PY 2000 VL 342 IS 16 BP 1149 EP 1155 DI 10.1056/NEJM200004203421601 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 305DG UT WOS:000086523700001 PM 10770979 ER PT J AU Morens, DM AF Morens, DM TI Death of a president - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 20 PY 2000 VL 342 IS 16 BP 1222 EP 1222 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 305DG UT WOS:000086523700028 ER PT J AU Tian, EM Sawyer, JR Largaespada, DA Jenkins, NA Copeland, NG Shaughnessy, JD AF Tian, EM Sawyer, JR Largaespada, DA Jenkins, NA Copeland, NG Shaughnessy, JD TI Evi27 encodes a novel membrane protein with homology to the IL17 receptor SO ONCOGENE LA English DT Article DE insertional mutagenesis; novel cytokine receptor; IL-17R related gene; myeloid leukemia ID MYELOPROLIFERATIVE LEUKEMIA-VIRUS; MYELOID-LEUKEMIA; CHROMOSOME-TRANSLOCATION; CYTOKINE RECEPTOR; INTEGRATION SITE; CELL-LINES; T-CELL; GENE; MOUSE; EXPRESSION AB Evi27 is a common site of retroviral integration in BXH2 murine myeloid leukemias. Here me show that integration at Evi27 occurs in a CpG island similar to 6 kb upstream from a novel gene (designated Evi27) with homology to the IL17 receptor (Il17r) and that proviral integrations result in increased expression of the Evi27 protein on the cell surface. The human EVI27 homology was also cloned and mapped to chromosome 3p21, Multiple Evi27 isoforms were detected at the RNA and protein level in both human and mouse, indicating that Evi27 expression is complex. Some of the isoforms are shown to likely represent secreted soluble forms of the protein produced by intron incorporation or by proteolytic cleavage. In the mouse, highest Evi27 expression occurs in liver and testes with lower expression in kidney and lung, In humans, EVI27 is expressed at high levels in the kidney, with moderate levels in the liver, brain, and testes. Within hematopoietic cells, Evi27 expression is restricted. Northern and Western analysis showed that Evi27 is expressed in selected T-cell B-cell and myeloid cell lines. These results suggest that Evi27 expression is tightly regulated during hematopoietic differentiation. Collectively, these studies identify a nea member of the cytokine receptor family whose increased and uncoordinated expression may lead to myeloid leukemia by altering Evi27's normal ability to control the growth and/or differentiation of hematopoietic cells. C1 Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Univ Minnesota, Dept Genet Cell Biol & Dev, Ctr Canc, Minneapolis, MN 55455 USA. NCI, Frederick Canc Res & Dev Ctr, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Shaughnessy, JD (reprint author), Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. RI Largaespada, David/C-9832-2014 NR 45 TC 49 Z9 56 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 20 PY 2000 VL 19 IS 17 BP 2098 EP 2109 DI 10.1038/sj.onc.1203577 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 308TB UT WOS:000086728000003 PM 10815801 ER PT J AU Nicot, C Mahieux, R Opavsky, R Cereseto, A Wolff, L Brady, JN Franchini, G AF Nicot, C Mahieux, R Opavsky, R Cereseto, A Wolff, L Brady, JN Franchini, G TI HTLV-I Tax transrepresses the human c-Myb promoter independently of its interaction with CBP or p300 SO ONCOGENE LA English DT Article DE tax; c-Myb; transrepression; CBP/p300 ID T-CELL LEUKEMIA; VIRUS TYPE-1 TAX; CREB BINDING-PROTEIN; INDUCED TRANSCRIPTION ACTIVATION; NEGATIVE REGULATORY DOMAIN; NF-KAPPA-B; MESSENGER-RNA; V-MYB; PHOSPHORYLATION SITE; ABERRANT EXPRESSION AB The c-Myb proto-oncogene is preferentially expressed in hematopoietic lineages, and highly expressed in several leukemia types. The Human T-cell Leukemia Virus Type I (HTLV-I) is the etiological agent of Adult T-cell Leukemia/Lymphoma (ATLL), A previous report suggested that Tax, the viral transactivator, is able to suppress the transactivation potential of c-Myb protein by competing for recruitment of CBP, We tested whether such a competition could affect transcription from the c-Myb promoter in Tax expressing T-cells, Using several c-Myb promoter reporter constructs carrying mutations in various regions, we demonstrate that Tax suppression of c-Myb transactivation results in transrepression of the c-Myb promoter through the Myb responsive elements in Jurkat T-cells, The ability of Tax mutants M22, M47 and V89A to interact with the full-length CBP and p300 proteins in vitro, and their ability to repress the c-Myb promoter, was then evaluated. Although both M47 and M22 bind to CBP and p300 to a similar extent, only M47 was able to repress the c-Myb promoter, suggesting that competition for CBP/p300 binding was not the mechanism underlying Tax's effect. This concept was further supported by the fact that the Tax mutant V89A transrepresses the c-Myb promoter efficiently in spite of an impaired binding to CBP and p300, Therefore, Tax-mediated repression of the c-Myb promoter appears to be independent from a direct competition between c-Myb and Tax for recruitment of CBP/p300, Interestingly, a decreased transcription from the endogenous c-Myb promoter was observed in several HTLV-I transformed T-cell lines. Finally, the ability of Tax to directly repress the endogenous c-Myb promoter was demonstrated in a Jurkat cell line stably transfected with a tax gene driven by a cadmium-inducible promoter. C1 NCI, Div Basic Sci, Basic Res Lab, Bethesda, MD 20814 USA. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20814 USA. NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Nicot, C (reprint author), NCI, Div Basic Sci, Basic Res Lab, 9000 Rockville Pike,Bldg 41,Room C303, Bethesda, MD 20814 USA. NR 71 TC 32 Z9 33 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 20 PY 2000 VL 19 IS 17 BP 2155 EP 2164 DI 10.1038/sj.onc.1203536 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 308TB UT WOS:000086728000009 PM 10815807 ER PT J AU Zweckstetter, M Bax, A AF Zweckstetter, M Bax, A TI Prediction of sterically induced alignment in a dilute liquid crystalline phase: Aid to protein structure determination by NMR SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID HIV-INACTIVATING PROTEIN; DIPOLAR COUPLINGS; CYANOVIRIN-N; MACROMOLECULES; RELAXATION C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 15 TC 522 Z9 525 U1 0 U2 23 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 APR 19 PY 2000 VL 122 IS 15 BP 3791 EP 3792 DI 10.1021/ja0000908 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 308TT UT WOS:000086729500035 ER PT J AU Vandier, D Calvez, V Massade, L Gouyette, A Mickley, L Fojo, T Rixe, O AF Vandier, D Calvez, V Massade, L Gouyette, A Mickley, L Fojo, T Rixe, O TI Transactivation of the metallothionein promoter in cisplatin-resistant cancer cells: a specific gene therapy strategy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID THYMIDINE KINASE GENE; CIS-DIAMMINEDICHLOROPLATINUM(II) RESISTANCE; OVARIAN-CANCER; EXPRESSION; LINES; CARCINOMA; DNA; GANCICLOVIR; MECHANISM; DELIVERY AB Background: Cisplatin (cis-diammine-dichloroplatinum) is one of the most active agents against a broad range of malignancies, including ovarian cancer. Cisplatin resistance appears to be associated with several molecular alterations, including overexpression of metallothionein, a metal-binding protein. In the present study, we attempted to take advantage of metallothionein overexpression to overcome cisplatin resistance. Methods: Using a virus-free system (liposomes), we sought to express the suicide gene, thymidine kinase (TK), driven by the promoter of the human metallothionein IIa (hMTIIa) gene using the pMT-TK plasmid, We used cisplatin-resistant human ovarian carcinoma cells as a model. Results: Ne first analyzed metallothionein expression using a ribonuclease protection assay, In comparison to parental cells, the cisplatin-resistant cells were found to have increased expression of metallothionein messenger RNA (mRNA). Metallothionein overexpression in these cells was not associated with an increased copy number of the hMTIIa gene or with different transfection efficiencies. Furthermore, we showed by reverse transcription-polymerase chain reaction analysis that transfection of the pMT-TK plasmid results in a 56-fold higher expression of thymidine kinase mRNA in cisplatin-resistant cells compared with parental cells, consistent with increased metallothionein promoter-mediated transactivation in the cisplatin-resistant cells, Transfection of resistant cells with pMT-TK; or a control plasmid (pCD3-TK) resulted in a marked sensitization to ganciclovir, wth a 50% cell growth-inhibitory concentration (IC50) of 20 mu g/mL and 9 mu g/mL, respectively. Transfections of the cisplatin-sensitive cells resulted in no sensitization to ganciclovir with pMT-TK; (IC50 200 mu g/ mL) and a high sensitization with pCD3-TK( (IC50 = 6 mu g/mL). Conclusion: These studies suggest that pMT-TK gene therapy may provide an alternative treatment for cisplatin-refractory ovarian tumors. C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Hop La Pitie Salpetriere, Serv Virol, Paris, France. INSERM, U490, Mol Toxicol Lab, Paris, France. Inst Gustave Roussy, Lab Pharmacotoxicol & Pharmacogenet, CNRS, UMR 8532, Villejuif, France. Clin Claude Bernard, Dept Oncol, Metz, France. RP Fojo, T (reprint author), NCI, Med Branch, Div Clin Sci, NIH, Bldg 10,Rm 12C428, Bethesda, MD 20892 USA. NR 34 TC 19 Z9 23 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 19 PY 2000 VL 92 IS 8 BP 642 EP 647 DI 10.1093/jnci/92.8.642 PG 6 WC Oncology SC Oncology GA 306HL UT WOS:000086591200014 PM 10772682 ER PT J AU Fisher, B AF Fisher, B TI Tamoxifen prevention of breast cancer: an instance of the fingerpost - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. RP Fisher, B (reprint author), Natl Surg Adjuvant Breast & Bowel Project, 4 Allegheny Ctr,Suite 602, Pittsburgh, PA 15212 USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 19 PY 2000 VL 92 IS 8 BP 659 EP 660 DI 10.1093/jnci/92.8.659 PG 2 WC Oncology SC Oncology GA 306HL UT WOS:000086591200022 PM 10772691 ER PT J AU Chen, YR Deterding, LJ Tomer, KB Mason, RP AF Chen, YR Deterding, LJ Tomer, KB Mason, RP TI Nature of the inhibition of horseradish peroxidase and mitochondrial cytochrome c oxidase by cyanyl radical SO BIOCHEMISTRY LA English DT Article ID 2.8 ANGSTROM; INACTIVATION; CYANIDE; H2O2; OXIDATION AB Previous studies established that the cyanyl radical (.CN), detected as 5,5-dimethyl-1-pyrroline N-oxide (DMPO)/.CN by the electron spin resonance (ESR) spin-trapping technique, can be generated by horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2) and by mitochondrial cytochrome c oxidase (CcO) in the absence of H2O2 TO investigate the mechanism of inhibition by cyanyl radical, we isolated and characterized the iron protoporphyrin IX and heme a from the reactions of CN- with HRP and CcO, respectively. The purified heme from the reaction mixture of HRP/H2O2/KCN was unambiguously identified as cyanoheme by the observation of the protonated molecule, (M + H)(+), of m/z = 642.9 in the matrix-assisted laser desorption/ionization (MALDI) mass spectrum. The proton NMR spectrum of the bipyridyl ferrous cyanoheme complex revealed that one of the four meso protons was missing and had been replaced with a cyanyl group, indicating that the single, heme-derived product was meso-cyanoheme. The holoenzyme of HRP from the reconstitution of meso-cyanoheme with the apoenzyme of HRP (apoHRP) showed no detectable catalytic activity. The Soret peak of cyanoheme-reconstituted apoHRP was shifted to 411 nm from the 403 nm peak of native HRP. In contrast, the heme a isolated from partially or fully inhibited CcO did not show any change in the structure of the protoporphyrin IX as indicated by its MALDI mass spectrum, which showed an (M + H)(+) of m/z = 853.6, and by its pyridine hemochromogen spectrum. However, a protein-centered radical on the CcO can be detected in the reaction of CcO with cyanide and was identified as the thiyl radical(s) based on inhibition of its formation by N-ethylmaleimide pretreatment, suggesting that the protein matrix rather than protoporphyrin IX was attacked by the cyanyl radical. In addition to the difference in heme structures between HRP and CcO, the available crystallographic data also suggested that the distinct heme environments may contribute to the different inhibition mechanisms of HRP and CcO by cyanyl radical. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Chen, YR (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 27 TC 33 Z9 34 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 18 PY 2000 VL 39 IS 15 BP 4415 EP 4422 DI 10.1021/bi992652+ PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304LB UT WOS:000086484200025 PM 10757991 ER PT J AU Vaidyanathan, VV Roche, PA AF Vaidyanathan, VV Roche, PA TI Structure and chromosomal localization of the mouse SNAP-23 gene SO GENE LA English DT Article DE mouse chromosome 2; SNAP-23 gene ID SYNAPSE PROTEIN SNAP-25; MEMBRANE-FUSION; SNARE COMPLEX; TRANSCRIPTION FACTOR; CELL-SURFACE; CDNA CLONES; IDENTIFICATION; EXOCYTOSIS; ISOFORMS; SYNTAXIN AB SNAP-23 plays an important role in the regulation of vesicle trafficking in mammalian cells, In this report, we have determined the exon/intron organization of the mouse SNAP-23 gene. The SNAP-23 gene spans 31 kb of the mouse genome and consists of eight exons interrupted by seven introns. The exon organization of the mouse SNAP-23 gene is identical to that of the related SNAP-25 gene in both chicken and Drosophila, suggesting that SNAP-23 arose by duplication of the SNAP-25 gene. Primer extension analysis revealed a major transcription start site approximately 112 bp upstream of the translation start site. Like many ubiquitously expressed housekeeping genes, the proximal promoter region for the mouse SNAP-23 gene lacks consensus TATA and CAAT boxes. The SNAP-23 gene was localized to mouse chromosome 2 at band 2E5 using both fluorescence in-situ hybridization and radiation hybrid panel mapping studies. The identification of the structure of the mouse SNAP-23 gene reveals that the overall exon organization of SNAP-25 family members is conserved throughout evolution. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 42 TC 6 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 18 PY 2000 VL 247 IS 1-2 BP 181 EP 189 DI 10.1016/S0378-1119(00)00100-1 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 308BR UT WOS:000086689100019 PM 10773458 ER PT J AU Hsin, LW Webster, EL Chrousos, GP Gold, PW Eckelman, WC Contoreggi, C Rice, KC AF Hsin, LW Webster, EL Chrousos, GP Gold, PW Eckelman, WC Contoreggi, C Rice, KC TI Synthesis and biological activity of fluoro-substituted pyrrolo[2,3-d]pyrimidines: The development of potential positron emission tomography imaging agents for the corticotropin-releasing hormone type 1 receptor SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID RAT-BRAIN; IN-VIVO; ANTAGONIST; PITUITARY; INFLAMMATION; CP-154,526; PEPTIDE; CRF AB A series of fluoro-substituted 4-(dialkylamino)pyrrolo[2,3-n]pyrimidines was synthesized and their binding affinity for corticotropin-releasing hormone type 1 receptor (CRHR1) was investigated. Compounds 11a and 11b possessed very high CRHR1 affinity (K-i = 3.5, 0.91 nM, respectively). They are promising candidates for the development of F-18-containing nonpeptide PLT radioligands for CRHR1. Published by Elsevier Science Ltd. C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, Ctr Clin, NIH, Bethesda, MD 20892 USA. NICHD, Pediat Endocrinol Sect, PREB, Clin Ctr,NIH, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. NIDA, Brain Imaging Unit, Baltimore, MD 21224 USA. RP Rice, KC (reprint author), NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. OI HSIN, LING-WEI/0000-0001-5018-4491 NR 19 TC 19 Z9 19 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 17 PY 2000 VL 10 IS 8 BP 707 EP 710 DI 10.1016/S0960-894X(00)00071-8 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 304JP UT WOS:000086480300006 PM 10782669 ER PT J AU Saavedra, JE Mooradian, DL Mowery, KA Schoenfisch, MH Citro, ML Davies, KM Meyerhoff, ME Keefer, LK AF Saavedra, JE Mooradian, DL Mowery, KA Schoenfisch, MH Citro, ML Davies, KM Meyerhoff, ME Keefer, LK TI Conversion of a polysaccharide to nitric oxide-releasing form. Dual-mechanism anticoagulant activity of diazeniumdiolated heparin SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PLATELET AB We describe heparin/diazeniumdiolate conjugates that generate nitric oxide (NO) at physiological pH. Like the heparin from which they were prepared, they inhibit thrombin-induced blood coagulation. Unlike heparin, they can also inhibit and reverse ADP-induced platelet aggregation (as expected for an NO-releasing agent), suggesting potential utility as dual-action antithrombotics. Published by Elsevier Science Ltd. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. Univ Minnesota, Dept Biomed Engn, Blood & Biocompatibil Res Lab, Minneapolis, MN 55455 USA. Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. George Mason Univ, Dept Chem, Fairfax, VA 22030 USA. RP Keefer, LK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-56000]; NIGMS NIH HHS [GM-56991] NR 9 TC 18 Z9 19 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 17 PY 2000 VL 10 IS 8 BP 751 EP 753 DI 10.1016/S0960-894X(00)00086-X PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 304JP UT WOS:000086480300015 PM 10782678 ER PT J AU Verheijen, JC van Roon, AMM Meeuwenoord, NJ Stuivenberg, HR Bayly, SF Chen, L van der Marel, GA Torrence, PF van Boom, JH AF Verheijen, JC van Roon, AMM Meeuwenoord, NJ Stuivenberg, HR Bayly, SF Chen, L van der Marel, GA Torrence, PF van Boom, JH TI Incorporation of a 4-hydroxy-N-acetylprolinol nucleotide analogue improves the 3 '-exonuclease stability of 2 '-5 '-oligoadenylate-antisense conjugates SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID ACID NUCLEIC-ACIDS; MESSENGER-RNA; ANTISENSE OLIGONUCLEOTIDES; HYBRIDIZATION PROPERTIES; 2-5A ANTISENSE; VIRUS-REPLICATION; TARGETING RNA; DEGRADATION; OLIGODEOXYNUCLEOTIDES; CHIMERAS AB Incorporation of a 4-hydroxy-N-acetylprolinol nucleotide analogue at the 3'-terminus of DNA or 2-5A-DNA sequences resulted in a significantly enhanced 3'-exonuclease resistance while the affinity for complementary RNA was only slightly decreased. Furthermore, the binding to and activation of human RNase L by thus modified 2-5A-DNA conjugates was not altered as compared to the parent unmodified 2-5A-DNAs. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Leiden Inst Chem, Gorlaeus Labs, NL-2300 RA Leiden, Netherlands. NIDDK, Med Chem Lab, Mol Biomed Chem, NIH, Bethesda, MD 20982 USA. No Arizona Univ, Dept Chem, Flagstaff, AZ 86011 USA. RP van Boom, JH (reprint author), Leiden Inst Chem, Gorlaeus Labs, POB 9502, NL-2300 RA Leiden, Netherlands. NR 28 TC 5 Z9 5 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 17 PY 2000 VL 10 IS 8 BP 801 EP 804 DI 10.1016/S0960-894X(00)00100-1 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 304JP UT WOS:000086480300027 PM 10782690 ER PT J AU Garcia-Barrio, M Dong, JS Ufano, S Hinnebusch, AG AF Garcia-Barrio, M Dong, JS Ufano, S Hinnebusch, AG TI Association of GCN1-GCN20 regulatory complex with the N-terminus of elF2 alpha kinase GCN2 is required for GCN2 activation SO EMBO JOURNAL LA English DT Article DE eIF2 alpha kinase; GCN2; regulation; translation; yeast ID INITIATION FACTOR-II; AMINO-ACID AVAILABILITY; FACTOR 2-ALPHA KINASE; PROTEIN-KINASE; SACCHAROMYCES-CEREVISIAE; TRANSFER-RNA; TRANSLATION INITIATION; EIF-2-ALPHA KINASE; ALPHA-SUBUNIT; TRANSCRIPTIONAL ACTIVATOR AB Stimulation of GCN4 mRNA translation due to phosphorylation of the a-subunit of initiation factor 2 (eIF2) by its specific kinase, GCN2, requires binding of uncharged tRNA to a histidyl-tRNA synthetase (HisRS)-like domain in GCN2. GCN2 function in vivo also requires GCN1 and GCN20, but it was unknown whether these latter proteins act directly to promote the stimulation of GCN2 by uncharged tRNA, We found that the GCN1-GCN20 complex physically interacts with GCN2, binding to the N-terminus of the protein, Overexpression of N-terminal GCN2 segments had a dominant-negative phenotype that correlated with their ability to interact with GCN1-GCN20 and impede association between GCN1 and native GCN2, Consistently, this Gcn(-) phenotype was suppressed by overexpressing GCN2, GCN1-GCN20 or tRNA(His). The requirement for GCN1 was also reduced by overexpressing tRNA(His) in a gcn1 Delta strain. We conclude that binding of GCN1-GCN20 to GCN2 is required for its activation by uncharged tRNA, The homologous N-terminus of Drosophila GCN2 interacted with yeast GCN1-GCN20 and had a dominant Gcn(-) phenotype, suggesting evolutionary conservation of this interaction. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. NR 39 TC 60 Z9 63 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD APR 17 PY 2000 VL 19 IS 8 BP 1887 EP 1899 DI 10.1093/emboj/19.8.1887 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 307LR UT WOS:000086655200014 PM 10775272 ER PT J AU Rehermann, B AF Rehermann, B TI Intrahepatic T cells in hepatitis B: Viral control versus liver cell injury SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID VIRUS TRANSGENIC MICE; LYMPHOCYTE RESPONSE; INFECTION; RESPONSIVENESS; PATHOGENESIS; RESOLUTION; PEPTIDES; RECEPTOR; CORE C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), NIDDK, Liver Dis Sect, NIH, Bldg 10,Rm 9B16,10 Ctr Dr, Bethesda, MD 20892 USA. NR 36 TC 80 Z9 92 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 17 PY 2000 VL 191 IS 8 BP 1263 EP 1268 DI 10.1084/jem.191.8.1263 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 307JU UT WOS:000086650800002 PM 10770794 ER PT J AU Iwasaki, A Kelsall, BL AF Iwasaki, A Kelsall, BL TI Localization of distinct Peyer's patch dendritic cell subsets and their recruitment by chemokines macrophage inflammatory protein (MIP)-3 alpha, MIP-3 beta, and secondary lymphoid organ chemokine SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE chemokine; migration; T cell region; mucosal immunity; follicle-associated epithelium ID T-CELLS; IN-VIVO; TISSUES; AREAS; RECEPTOR; PATHWAYS; COMPLEX; NODES AB We describe the anatomical localization of three distinct dendritic cell (DC) subsets in the murine Peyer's patch (PP) and explore the role of chemokines in their recruitment, By two-color in situ immunofluorescence, CD11b(+) myeloid DCs were determined to be present in the subepithelial dome (SED) region, whereas CD8 alpha(+) lymphoid DCs are present in the T cell-rich interfollicular region (IFR), DCs that lack expression of CD8 alpha or CD11b (double negative) are present in both the SED and IFR. By in situ hybridization, macrophage inflammatory protein (MIP)-3 alpha mRNA was dramatically expressed only by the follicle-associated epithelium overlying the SED, while its receptor, CCR6, was concentrated in the SED, In contrast, CCR7 was expressed predominantly in the IFR. Consistent with these findings, reverse transcriptase polymerase chain reaction analysis and in vitro chemotaxis assays using freshly isolated DCs revealed that CCR6 was functionally expressed only by DC subsets present in the SED, while all subsets expressed functional CCR7. Moreover, none of the splenic DC subsets migrated toward MIP-3 alpha. These data support a distinct role for MIP-3 alpha/CCR6 in recruitment of CD11b(+) DCs toward the mucosal surfaces and for MIP-3 beta/CCR7 in attraction of CD8 alpha(+) DCs to the T cell regions, Finally, we demonstrated that all DC subsets expressed an immature phenotype when freshly isolated and maintained expression of subset markers upon maturation in vitro. In contrast, CCR7 expression by myeloid PP DCs was enhanced with maturation in vitro. In addition, this subset disappeared from the SED and appeared in the IFR after microbial stimulation in vivo, suggesting that immature myeloid SED DCs capture antigens and migrate to IFR to initiate T cell responses after mucosal microbial infections. C1 NIAID, Immune Cell Interact Unit, Mucosal Immun Sect, Lab Clin Invest,NIH, Bethesda, MD 20892 USA. RP Kelsall, BL (reprint author), NIAID, Immune Cell Interact Unit, Mucosal Immun Sect, Lab Clin Invest,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 33 TC 395 Z9 410 U1 2 U2 5 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 APR 17 PY 2000 VL 191 IS 8 BP 1381 EP 1393 DI 10.1084/jem.191.8.1381 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 307JU UT WOS:000086650800012 PM 10770804 ER PT J AU Yin, DL Tuthill, D Mufson, RA Shi, YF AF Yin, DL Tuthill, D Mufson, RA Shi, YF TI Chronic restraint stress promotes lymphocyte apoptosis by modulating CD95 expression SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE stress; fas antigen; lymphocyte; apoptosis; endogenous opioid ID CELL-MEDIATED-IMMUNITY; FAS-LIGAND; IN-VIVO; SYSTEM; ACTIVATION; DEATH; PERSONALITY; IMMUNOLOGY; RECEPTORS; EXERCISE AB Depending on the duration and severity, psychological tension and physical stress can enhance or suppress the immune system in both humans and animals. Although it is well established that stress alters the release of various hormones and neurotransmitters, the mechanisms by which stress affects immune responses remain elusive. We report here that mice subjected to chronic 12-hour daily physical restraint for two days exhibited a significant reduction in splenocytes, a process likely mediated by apoptosis as demonstrated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. CD95 (Fas/APO-1) expression in splenic lymphocytes of stressed mice was substantially increased. Interestingly, Fas-immunoglobulin fusion protein and blocking antibodies against CD95 ligand inhibit stress-induced reduction in lymphocytes. The stress-induced changes in CD95 expression and lymphocyte number could be blocked by naltrexone or naloxone, specific opioid receptor antagonists, indicating a pivotal role of endogenous opioids in this process. In addition, the reduction of splenocytes in this model system seems to be independent of the hypothalamo-pituitary-adrenal axis, as both adrenalectomized and sham-operated mice exhibited similar responses to chronic stress. Moreover, chronic physical restraint failed to induce a decrease in lymphocyte numbers in CD95-deficient (Fas(lpr/lpr)) mice. Therefore, stress modulates the immune system through CD95-mediated apoptosis dependent on endogenous opioids. C1 Amer Red Cross, Jerome H Holland Lab, Dept Immunol, Rockville, MD 20855 USA. Amer Red Cross, Jerome H Holland Lab, Dept Plasma Derivat, Rockville, MD 20855 USA. NCI, Canc Immunol Branch, Bethesda, MD 20892 USA. RP Shi, YF (reprint author), Amer Red Cross, Jerome H Holland Lab, Dept Immunol, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. FU NCI NIH HHS [CA53609]; NIAID NIH HHS [AI43384, R01 AI043384, R21 AI043384] NR 39 TC 103 Z9 112 U1 2 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 17 PY 2000 VL 191 IS 8 BP 1423 EP 1428 DI 10.1084/jem.191.8.1423 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 307JU UT WOS:000086650800015 PM 10770807 ER PT J AU Honkakoski, P Negishi, M AF Honkakoski, P Negishi, M TI Regulation of cytochrome P450 (CYP) genes by nuclear receptors SO BIOCHEMICAL JOURNAL LA English DT Review DE endobiotic metabolism; gene expression; gene transcription; ligand-activated; xenobiotic metabolism ID PROLIFERATOR-ACTIVATED RECEPTOR; ARYL-HYDROCARBON RECEPTOR; STEROIDOGENIC FACTOR-I; BREAST-CANCER CELLS; TISSUE-SPECIFIC EXPRESSION; THYROID-HORMONE RECEPTORS; RETINOIC ACID METABOLISM; PRIMARY RAT HEPATOCYTES; PREGNANE-X-RECEPTOR; CHOLESTEROL 7-ALPHA-HYDROXYLASE GENE AB Members of the nuclear-receptor superfamily mediate crucial physiological functions by regulating the synthesis of their target genes. Nuclear receptors are usually activated by ligand binding. Cytochrome P450 (CYP) isoforms often catalyse both formation and degradation of these ligands. CYPs also metabolize many exogenous compounds, some of which may act as activators of nuclear receptors and disrupters of endocrine and cellular homoeostasis. This review summarizes recent findings that indicate that major classes of CYP genes are selectively regulated by certain ligand-activated nuclear receptors, thus creating tightly controlled networks. C1 Univ Kuopio, Dept Pharmaceut, FIN-70211 Kuopio, Finland. NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Honkakoski, P (reprint author), Univ Kuopio, Dept Pharmaceut, POB 1627, FIN-70211 Kuopio, Finland. OI Honkakoski, Paavo/0000-0002-4332-3577 NR 302 TC 312 Z9 332 U1 0 U2 23 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 15 PY 2000 VL 347 BP 321 EP 337 DI 10.1042/0264-6021:3470321 PN 2 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309WT UT WOS:000086792800001 PM 10749660 ER PT J AU Weinberger, DR AF Weinberger, DR TI Neuroimaging in the postgenome era SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, IRP, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 2 BP 1S EP 1S DI 10.1016/S0006-3223(00)00254-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200003 ER PT J AU Hyman, SE AF Hyman, SE TI Psychiatry in the new millennium SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 5 BP 2S EP 2S DI 10.1016/S0006-3223(00)00257-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200007 ER PT J AU Rubinow, DR Schmidt, PJ Zhang, L AF Rubinow, DR Schmidt, PJ Zhang, L TI Sex and drain development SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 12 BP 4S EP 4S DI 10.1016/S0006-3223(00)00265-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200014 ER PT J AU Daly, RC Kim, MY Bloch, M Schmidt, PJ Purdy, RM Rubinow, DR AF Daly, RC Kim, MY Bloch, M Schmidt, PJ Purdy, RM Rubinow, DR TI Neurosteroids in reproductive endocrine-related mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NIAAA, Div Intramural Clin & Biol Res, Bethesda, MD 20892 USA. Rambam Med Ctr, Div Psychiat, Haifa, Israel. Scripps Res Inst, Res Inst, La Jolla, CA 92037 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 15 BP 5S EP 5S DI 10.1016/S0006-3223(00)00268-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200017 ER PT J AU Roca, CA Schmidt, PJ Altemus, MA Cizza, G Deuster, P Gold, PW Chrousos, GP Rubinow, DR AF Roca, CA Schmidt, PJ Altemus, MA Cizza, G Deuster, P Gold, PW Chrousos, GP Rubinow, DR TI Effects of gonadal steroids on the HPA axis response to stress SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. Cornell Univ, Dept Psychiat, New York, NY 10021 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Mil Med, Bethesda, MD 20814 USA. NICHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 14 BP 5S EP 5S DI 10.1016/S0006-3223(00)00267-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200016 ER PT J AU Schmidt, PJ Berman, KF Danaceau, MA Keenan, P Nieman, LK Rubinow, DR AF Schmidt, PJ Berman, KF Danaceau, MA Keenan, P Nieman, LK Rubinow, DR TI Gonadal steroids, brain, and behavior SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NICHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Harper Grace Hosp, Detroit, MI 48201 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 13 BP 5S EP 5S DI 10.1016/S0006-3223(00)00266-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200015 ER PT J AU Higley, JD Bennett, AJ Heils, A Long, J Lorenz, J Champoux, M Suomi, SJ Lesch, KP AF Higley, JD Bennett, AJ Heils, A Long, J Lorenz, J Champoux, M Suomi, SJ Lesch, KP TI Early rearing & genotypic influences on CNS serotonin & behavior in nonhuman primates SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA, Clin Studies Lab, Primate Unit, NIH, Poolesville, MD 20837 USA. Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NICHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 35 BP 10S EP 11S DI 10.1016/S0006-3223(00)00468-6 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200033 ER PT J AU Nicolson, R Lenane, M Usiskin, SI Brookner, F Gochman, P Egan, MF Pickar, D Weinberger, DR Rapoport, JL AF Nicolson, R Lenane, M Usiskin, SI Brookner, F Gochman, P Egan, MF Pickar, D Weinberger, DR Rapoport, JL TI Familial schizophrenia spectrum disorders in childhood and adult-onset schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. RI Nicolson, Robert/E-4797-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 41 BP 12S EP 13S DI 10.1016/S0006-3223(00)00303-6 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200039 ER PT J AU Malhotra, AK Goldman, D AF Malhotra, AK Goldman, D TI Reverse pharmacogenetics: A new approach to rapid relapse in schizophrenia? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Hillside Hosp, Unit Mol Psychiat, Glen Oaks, NY 11004 USA. NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 52 BP 16S EP 16S DI 10.1016/S0006-3223(00)00314-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200050 ER PT J AU Crook, JM Hyde, TM Law, B Weickert, CS Kleinman, JE AF Crook, JM Hyde, TM Law, B Weickert, CS Kleinman, JE TI Muscarinic receptor protein and mRNA in DLPFC of schizophrenia and affective disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 136 BP 41S EP 41S DI 10.1016/S0006-3223(00)00398-X PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200134 ER PT J AU Tomaskovic-Crook, E Crook, JM Kleinman, JE Weickert, CS AF Tomaskovic-Crook, E Crook, JM Kleinman, JE Weickert, CS TI Extraction of total RNA in human brain post-mortem tissue: Effect of diagnosis on RNA yield SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RI Tomaskovic-Crook, Eva/C-9339-2016 OI Tomaskovic-Crook, Eva/0000-0002-7818-9013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 137 BP 41S EP 41S DI 10.1016/S0006-3223(00)00399-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200135 ER PT J AU Keczkemethy, C Akil, M Colvin, SM Hyde, TM Kleinman, JE AF Keczkemethy, C Akil, M Colvin, SM Hyde, TM Kleinman, JE TI Altered gene expression of dopaminergic markers in the midbrain of schizophrenic patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 148 BP 45S EP 45S DI 10.1016/S0006-3223(00)00410-8 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200146 ER PT J AU Williams, KA Valentine, MG Lund, I Tidman, S Weinberger, DR Lipska, BK AF Williams, KA Valentine, MG Lund, I Tidman, S Weinberger, DR Lipska, BK TI Effects of lesion size, age and strain on behavioral responsiveness to hippocampal damage in mice SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. RI Lipska, Barbara/E-4569-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 155 BP 47S EP 47S DI 10.1016/S0006-3223(00)00417-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200153 ER PT J AU Goldman, D Tsuang, MT Knowles, JA Friedman, TB AF Goldman, D Tsuang, MT Knowles, JA Friedman, TB TI Molecular genetics of substance abuse: Analyzing complex traits SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. New York State Psychiat Inst, Boston, MA USA. NIDCD, Mol Genet Lab, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 186 BP 56S EP 57S DI 10.1016/S0006-3223(00)00449-2 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200184 ER PT J AU Riddle, MA Vitiello, B Jensen, PS Greenhill, LL March, JS Scahill, L AF Riddle, MA Vitiello, B Jensen, PS Greenhill, LL March, JS Scahill, L TI Pediatric psychopharmacology: NIMH-sponsored multisite studies SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIMH, NIH, Bethesda, MD 20892 USA. New York State Psychiat Inst, New York, NY 10032 USA. Duke Univ, Med Ctr, Durham, NC USA. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 189 BP 57S EP 58S DI 10.1016/S0006-3223(00)00452-2 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200187 ER PT J AU Khin, NA Bauer, L Cannon-Spoor, E Fleisher, T Brown, M Bock, J Lasser, R Sunderland, T AF Khin, NA Bauer, L Cannon-Spoor, E Fleisher, T Brown, M Bock, J Lasser, R Sunderland, T TI Biopsychological profile of normal, bereaved and post-bereaved depressed elderly SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Geriatr Psychiat Branch, Intramural Res Program, Bethesda, MD 20892 USA. NIH, Clin Pathol Immunol Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 200 BP 61S EP 61S DI 10.1016/S0006-3223(00)00461-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200198 ER PT J AU Leibenluft, E Gobbini, I Santiago, N Haxby, JV AF Leibenluft, E Gobbini, I Santiago, N Haxby, JV TI Impact of familiarity and emotional attachment on the visual processing of faces SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Pediat & Dev Neuropsychiat Branch, IRP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 201 BP 61S EP 61S DI 10.1016/S0006-3223(00)00462-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200199 ER PT J AU Callicott, JH Bertolino, A Mattay, VS Meyer-Lindenberg, A Bone, AD Verchinski, B Holt, J Coppola, R Berman, KF Goldberg, TE Weinberger, DR AF Callicott, JH Bertolino, A Mattay, VS Meyer-Lindenberg, A Bone, AD Verchinski, B Holt, J Coppola, R Berman, KF Goldberg, TE Weinberger, DR TI Dorsal and ventral PFC responses to working memory differ in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 206 BP 63S EP 63S DI 10.1016/S0006-3223(00)00297-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200204 ER PT J AU Meyer-Lindenberg, A Holt, J Egan, M Weinberger, DR Berman, KF AF Meyer-Lindenberg, A Holt, J Egan, M Weinberger, DR Berman, KF TI Task-independent and task-dependent disturbances in functional connectivity in schizophrenia: PET studies SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, Unit Integrat Neuroimaging, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 212 BP 64S EP 65S DI 10.1016/S0006-3223(00)00476-5 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200210 ER PT J AU Cohen, LG Wittenberg, G AF Cohen, LG Wittenberg, G TI Study of anatomical connectivity with TMS-PET in intact humans SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NINDS, Human Cort Physiol Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 213 BP 65S EP 65S DI 10.1016/S0006-3223(00)00477-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200211 ER PT J AU Weinberger, DR Bertolino, A Callicott, JH Egan, MF Esposito, G Mattay, VS Brier, A Knable, MB Berman, KF AF Weinberger, DR Bertolino, A Callicott, JH Egan, MF Esposito, G Mattay, VS Brier, A Knable, MB Berman, KF TI Studies of prefrontal cortical functional connectivity in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 214 BP 65S EP 65S DI 10.1016/S0006-3223(00)00478-9 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200212 ER PT J AU Smith, MJ Greenberg, BD Adams, LF Nguyen, M Schmidt, PJ Rubinow, DR Wassermann, EM AF Smith, MJ Greenberg, BD Adams, LF Nguyen, M Schmidt, PJ Rubinow, DR Wassermann, EM TI Menstrual-related changes in cortical excitability in women with PMS and controls SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 227 BP 69S EP 69S DI 10.1016/S0006-3223(00)00491-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200225 ER PT J AU Gerald, MS Habib, KE Weld, KP Pushkas, J Listwak, S Champoux, M Chrousos, GP Suomi, S Gold, PW Higley, JD AF Gerald, MS Habib, KE Weld, KP Pushkas, J Listwak, S Champoux, M Chrousos, GP Suomi, S Gold, PW Higley, JD TI Effects of acute and chronic social stress on levels of CSF corticotropin-releasing hormone SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA, Primate Unit, Clin Studies Lab, NIH, Poolesville, MD 20837 USA. NIMH, CNB, NIH, Bethesda, MD 20892 USA. NICHD, LCE, NIH, Poolesville, MD 20837 USA. NICHD, DEB, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 232 BP 71S EP 71S DI 10.1016/S0006-3223(00)00496-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200230 ER PT J AU Negrao, AB AF Negrao, AB TI HPA axis response to graded exercise in atypical depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RI Negrao, Andre Brooking/C-9526-2014 OI Negrao, Andre Brooking/0000-0002-8133-6723 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 247 BP 75S EP 75S DI 10.1016/S0006-3223(00)00511-4 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200244 ER PT J AU Negro, PJ Michelson, D Elliott, EA Avery, S Palladino-Negro, P Sciullo, DA Negrao, AB Habib, KE Prolo, P Ayala, A Cizza, G Fitzpatrick, L Collins, M Reynolds, JC Chrousos, GP Gold, PW AF Negro, PJ Michelson, D Elliott, EA Avery, S Palladino-Negro, P Sciullo, DA Negrao, AB Habib, KE Prolo, P Ayala, A Cizza, G Fitzpatrick, L Collins, M Reynolds, JC Chrousos, GP Gold, PW TI Body composition and regional fat content in patients with major depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Neuroendocrinol Branch, IRP, NIH, Bethesda, MD 20892 USA. NIH, IRP, CC, Bethesda, MD 20892 USA. Mayo Clin, Endocrine Res Unit, Rochester, MN 55905 USA. NIDCR, CSDB, IRP, NIH, Bethesda, MD 20892 USA. NICHD, Pediat & Reprod Endocrinol Branch, IRP, NIH, Bethesda, MD 20892 USA. RI Negrao, Andre Brooking/C-9526-2014 OI Negrao, Andre Brooking/0000-0002-8133-6723 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 255 BP 77S EP 78S DI 10.1016/S0006-3223(00)00519-9 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200252 ER PT J AU Sher, L Rosenthal, NE Wehr, TA AF Sher, L Rosenthal, NE Wehr, TA TI Thyroid function tests in patients with seasonal affective disorder and control subjects SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Sect Biol Rhythms, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 257 BP 78S EP 78S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200254 ER PT J AU Sher, L Hamer, DH Greenberg, BD Murphy, DL Rosenthal, NE AF Sher, L Hamer, DH Greenberg, BD Murphy, DL Rosenthal, NE TI The serotonin transporter gene influences seasonality independently of personality SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Sect Biol Rhythms, Bethesda, MD 20892 USA. NCI, Biochem Lab, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 256 BP 78S EP 78S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200253 ER PT J AU Frye, MA Bertolino, A Callicott, JH Repella, JD Rakow, RL Post, RM Weinberger, DR AF Frye, MA Bertolino, A Callicott, JH Repella, JD Rakow, RL Post, RM Weinberger, DR TI A 1H-MRSI hippocampal study in bipolar patients with a history of alcohol abuse SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 260 BP 79S EP 79S DI 10.1016/S0006-3223(00)00524-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200257 ER PT J AU Little, JT Ketter, TA Kimbrell, TA Dunn, RM Willis, MW Benson, BE Luckenbaugh, DA Post, RM AF Little, JT Ketter, TA Kimbrell, TA Dunn, RM Willis, MW Benson, BE Luckenbaugh, DA Post, RM TI Antidepressant response and regional cerebral blood flow SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 272 BP 82S EP 83S DI 10.1016/S0006-3223(00)00536-9 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200269 ER PT J AU Lomarev, M Shastri, A Ziemann, U Wassermann, EM McConnell, KA Nahas, Z Lorberbaum, JP Vincent, DJ George, MS Bohning, DE AF Lomarev, M Shastri, A Ziemann, U Wassermann, EM McConnell, KA Nahas, Z Lorberbaum, JP Vincent, DJ George, MS Bohning, DE TI Can interleaved TMS and fMRI demonstrate changes in an activated circuit? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MUSC, Dept Radiol, Funct Neuroimaging Res Div, Charleston, SC USA. MUSC, Dept Psychiat, Charleston, SC USA. MUSC, Dept Neurol, Charleston, SC USA. NINDS, Intramural Res Program, Bethesda, MD 20892 USA. Inst Human Brain, St Petersburg, Russia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 323 BP 97S EP 97S DI 10.1016/S0006-3223(00)00587-4 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200319 ER PT J AU Speer, AM Willis, MW Herscovitch, P Daube-Witherspoon, M Repella, J Post, RM Wassermann, EM AF Speer, AM Willis, MW Herscovitch, P Daube-Witherspoon, M Repella, J Post, RM Wassermann, EM TI Intensity-dependent rCBF during 1Hz rTMS over the left primary motor and prefrontal cortices SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 349 BP 105S EP 105S DI 10.1016/S0006-3223(00)00613-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200345 ER PT J AU Benson, BE Willis, MW Ketter, TA Kimbrell, TA Osuch, EA Speer, AM Post, RM AF Benson, BE Willis, MW Ketter, TA Kimbrell, TA Osuch, EA Speer, AM Post, RM TI Altered relationships in rCMRglu associativity in bipolar and unipolar illness SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Vet Adm Med Ctr, N Little Rock, AR 72114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 357 BP 108S EP 108S DI 10.1016/S0006-3223(00)00621-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200353 ER PT J AU Willis, MW Benson, BE Ketter, TA Kimbrell, TA Osuch, EA Speer, AM Post, RM AF Willis, MW Benson, BE Ketter, TA Kimbrell, TA Osuch, EA Speer, AM Post, RM TI Interregional associations of cerebral glucose metabolism in healthy adults SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Vet Adm Med Ctr, N Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 358 BP 108S EP 108S DI 10.1016/S0006-3223(00)00622-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200354 ER PT J AU Bertolino, A Callicott, JH Mattay, VS van der Veen, JW Duyn, JH Rakow, R Weidenhammer, KM Weinberger, DR AF Bertolino, A Callicott, JH Mattay, VS van der Veen, JW Duyn, JH Rakow, R Weidenhammer, KM Weinberger, DR TI Reproducibility of water acquired H-1-MRSI data in healthy subjects SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 364 BP 110S EP 110S DI 10.1016/S0006-3223(00)00628-4 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200360 ER PT J AU Podruchny, TA Connolly, CA Kiesewetter, DO Carson, RE Eckelman, WC Cohen, RM Sunderland, T AF Podruchny, TA Connolly, CA Kiesewetter, DO Carson, RE Eckelman, WC Cohen, RM Sunderland, T TI Muscarinic 2 receptors in cognitively normal young and old volunteers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Geriatr Psychiat Serv, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Deaconess, Dept Gerontol, Boston, MA 02115 USA. NIH, Warren G Magnuson Clin Ctr, PET Dept, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 368 BP 111S EP 111S DI 10.1016/S0006-3223(00)00632-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200364 ER PT J AU Lynch, MR Volman, SF Frascella, J AF Lynch, MR Volman, SF Frascella, J TI Frontal cortical function and drug abuse SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 378 BP 115S EP 115S DI 10.1016/S0006-3223(00)00642-9 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200374 ER PT J AU Becker, KG AF Becker, KG TI cDNA arrays in neuroscience research: A practical approach SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIA, DNA Array Unit, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 384 BP 117S EP 117S DI 10.1016/S0006-3223(00)00649-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200380 ER PT J AU Goldman, D Cravchik, A AF Goldman, D Cravchik, A TI Genetic variation in dopamine and serotonin function SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Celera Genom, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 386 BP 117S EP 118S DI 10.1016/S0006-3223(00)00652-1 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200382 ER PT J AU Lipska, BK Bertolino, A O'Donnell, P Weinberger, DR AF Lipska, BK Bertolino, A O'Donnell, P Weinberger, DR TI Neonatal damage of the rat hippocampus results in a constellation of schizophrenia-like phenomena SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. RI Lipska, Barbara/E-4569-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 390 BP 119S EP 119S DI 10.1016/S0006-3223(00)00657-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200386 ER PT J AU Iwata, N Ozaki, N Inada, T Goldman, D AF Iwata, N Ozaki, N Inada, T Goldman, D TI An association of a 5-HT5A receptor polymorphism, Pro15Ser, to Japanese schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan. Natl Ctr Neurol & Psychiat, Natl Inst Mental Hlth, Chiba, Japan. NIAAA, DICBR, LNG, Rockville, MD 20854 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 432 BP 132S EP 132S DI 10.1016/S0006-3223(00)00702-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200428 ER PT J AU Roca, CA Harlow, BL Davis, CL Schmidt, PJ Mazzanti, CM Lappalainen, J Ozaki, N Goldman, D Rubinow, DR AF Roca, CA Harlow, BL Davis, CL Schmidt, PJ Mazzanti, CM Lappalainen, J Ozaki, N Goldman, D Rubinow, DR TI Role of polymorphisms in serotonin genes in PMDD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 431 BP 132S EP 132S DI 10.1016/S0006-3223(00)00701-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200427 ER PT J AU Negro, PJ Drinkard, B Yanovski, S Chrousos, GP Gold, PW Yanovski, J AF Negro, PJ Drinkard, B Yanovski, S Chrousos, GP Gold, PW Yanovski, J TI Hypothalamic-pituitary-adrenal axis activity and personality assessment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Rehabil Med, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 461 BP 140S EP 141S DI 10.1016/S0006-3223(00)00731-9 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200457 ER PT J AU Nguyen, M Greenberg, BD Murphy, DL Smith, MJ Wasserman, EM AF Nguyen, M Greenberg, BD Murphy, DL Smith, MJ Wasserman, EM TI Personality traits are correlated with motor cortex excitability: A transcranial magnetic stimulation (TMS) study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 465 BP 142S EP 142S DI 10.1016/S0006-3223(00)00735-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200461 ER PT J AU Westergaard, GC Suomi, SJ Higley, JD AF Westergaard, GC Suomi, SJ Higley, JD TI CSF5-HIAA and aggression in primates: Species and interindividual differences SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 LABS Virginia Inc, Div Res & Dev, Yemassee, SC 29945 USA. NICHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. NIAAA, Clin Studies Lab, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 479 BP 146S EP 146S DI 10.1016/S0006-3223(00)00749-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200475 ER PT J AU Nicolson, R Giedd, JN Blumenthal, J Hamburger, DS Lenane, M Wudarsky, M Gochman, P Rapoport, JL AF Nicolson, R Giedd, JN Blumenthal, J Hamburger, DS Lenane, M Wudarsky, M Gochman, P Rapoport, JL TI A longitudinal MRI study of children and adolescents with atypical psychotic disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Nicolson, Robert/E-4797-2011; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 494 BP 150S EP 150S DI 10.1016/S0006-3223(00)00764-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200490 ER PT J AU Bachus, SE Holt, DJ Agrawal, Y Hyde, TM Herman, MM Saper, CB Kleinman, JE AF Bachus, SE Holt, DJ Agrawal, Y Hyde, TM Herman, MM Saper, CB Kleinman, JE TI Striatal preprosomatostatin mRNA in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. Beth Israel Hosp, Dept Neurol, Boston, MA 02215 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 505 BP 153S EP 153S DI 10.1016/S0006-3223(00)00775-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200501 ER PT J AU Hyman, SE Shore, D AF Hyman, SE Shore, D TI An NIMH perspective on the use of placebos SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Hyman, SE (reprint author), NIMH, 6001 Execut Blvd,Room 8235, Bethesda, MD 20892 USA. NR 2 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 BP 689 EP 691 DI 10.1016/S0006-3223(99)00292-9 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 303GM UT WOS:000086414200002 PM 10773173 ER PT J AU Miller, FG AF Miller, FG TI Placebo-controlled trials in psychiatric research: An ethical perspective SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT National Depressive-and-Manic-Depressive-Association Consensus Conference CY SEP 14-15, 1999 CL WASHINGTON, D.C. SP Depressive & Manic Depressive Assoc DE ethics; psychiatric research; clinical trials; placebos ID CLINICAL RESEARCH; SCHIZOPHRENIA; MEDICATION; CONSENT AB The placebo-controlled trial is widely regarded as the gold standard for testing the efficacy of new treatments; however, this research design is subject to ethical controversy, especially when standard treatments of proven efficacy exist. After examining regulatory standards and ethical codes relevant to placebo-controlled trials, I offer a critique of arguments against the use of placebo control groups in psychiatric research. An absolute ethical prohibition of placebo-controlled trials in psychiatric disorders for which standard, effective treatments exist is rejected because it is based on a flawed conception of research ethics, ignores important contextual factors characteristic of psychiatric research, and could lead to the approval and use of new medications that appear equivalent in efficacy to standard treatments bur may he no more effective than placebos. Four standards governing the ethical use of placebos in psychiatric clinical trials are explicated: I) placebo-controlled trials should have scientific and clinical merit; 2) risks should be minimized and justified by the anticipated benefits of generating clinically relevant scientific knowledge and the expected benefits, if any, to individual patient volunteers; 3) patient volunteers should give informed consent; and 4) investigators should offer short-term treatment optimization to patient volunteers after completion of research participation. C1 NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20892 USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Ctr Clin, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. NR 45 TC 44 Z9 44 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 BP 707 EP 716 DI 10.1016/S0006-3223(00)00833-7 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 303GM UT WOS:000086414200006 PM 10773177 ER PT J AU Post, RM Denicoff, KD Leverich, GS AF Post, RM Denicoff, KD Leverich, GS TI Special issues in trial design and use of placebo in bipolar illness SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID RANDOMIZED CLINICAL-TRIALS; WORKSHOP REPORT; DISORDER; CARBAMAZEPINE; DEPRESSION C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, NIH, Bldg 10,Room 3N212,10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. NR 30 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 BP 727 EP 732 DI 10.1016/S0006-3223(99)00315-7 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 303GM UT WOS:000086414200009 PM 10773180 ER PT J AU Perkins, DO Wyatt, RJ Bartko, JJ AF Perkins, DO Wyatt, RJ Bartko, JJ TI Penny-wise and pound-foolish: The impact of measurement error on sample size requirements in clinical trials SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT National Depressive-and-Manic-Depressive-Association Consensus Conference CY SEP 14-15, 1999 CL WASHINGTON, D.C. SP Depressive & Manic Depressive Assoc DE reliability; measurement error; interrater reliability; power; research methods ID INTERRATER RELIABILITY AB Background: Clinical research studies must compensate for measurement error by increasing the number of subjects that are studied, thereby increasing the financial costs of research and exposing greater numbers of subjects to study risks. In this article, we model the relationship between reliability and sample-size requirements and consider the potential tangible cost savings resulting from the decreased number of subjects needed when reliability, Of raters is improved or multiple ratings are used. Methods: Standard methods are used to model reliability based on the intraclass correlation coefficient (R) and to perform power calculations. The impact of multiple raters on reliability for a given baseline level of reliability is modeled according to the Spearman Brown formula. Results: Our models demonstrate that meaningful reductions in sample size requirements are gained from improvements in reliability. For example, improving reliability from R = .7 to R = .9 will decreases sample size requirements by 22%. Reliability is improved by training and by the use of the mean of multiple ratings. For example, if the reliability of a single rating is 0.7, the reliability of the mean of two ratings will be 0.8. Conclusions: The costs to improve reliability either through rater training efforts or use of the mean of multiple ratings is cost effective because of the consequent reduction in number of subjects needed. Efforts to improve reliability and thus reduce subject requirements in a study also may lead to fewer patients bearing the burden of research participation and to a shortening of the duration of studies. C1 Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. NIMH, Neuropsychiat Branch, NIH, Bethesda, MD 20892 USA. RP Perkins, DO (reprint author), Univ N Carolina, Sch Med, Dept Psychiat, CB 7160, Chapel Hill, NC 27599 USA. FU NIMH NIH HHS [MH-33127] NR 6 TC 66 Z9 67 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 BP 762 EP 766 DI 10.1016/S0006-3223(00)00837-4 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 303GM UT WOS:000086414200015 PM 10773186 ER PT J AU Sidorova, NY Rau, DC AF Sidorova, NY Rau, DC TI The dissociation rate of the EcoR1-DNA-specific complex is linked to water activity SO BIOPOLYMERS LA English DT Article ID NONSPECIFIC DNA-SEQUENCES; ECORI ENDONUCLEASE; GEL-ELECTROPHORESIS; BINDING; RECOGNITION; SPECIFICITY; REPRESSOR; CLEAVAGE; RELEASE; THERMODYNAMICS C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Sidorova, NY (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. NR 33 TC 16 Z9 17 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD APR 15 PY 2000 VL 53 IS 5 BP 363 EP 368 DI 10.1002/(SICI)1097-0282(20000415)53:5<363::AID-BIP1>3.0.CO;2-Q PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 304DM UT WOS:000086467600001 PM 10738198 ER PT J AU Janssen, JWG Vaandrager, JW Heuser, T Jauch, A Kluin, PM Geelen, E Bergsagel, PL Kuehl, WM Drexler, HG Otsuki, T Bartram, CR Schuuring, E AF Janssen, JWG Vaandrager, JW Heuser, T Jauch, A Kluin, PM Geelen, E Bergsagel, PL Kuehl, WM Drexler, HG Otsuki, T Bartram, CR Schuuring, E TI Concurrent activation of a novel putative transforming gene, myeov, and cyclin D1 in a subset of multiple myeloma cell lines with t(11;14)(q13;q32) SO BLOOD LA English DT Article ID IN-SITU HYBRIDIZATION; GROWTH-FACTOR RECEPTOR-3; CHROMOSOME 11Q13 REGION; CYTOGENETIC ANALYSIS; TRANSLOCATION; LYMPHOMA; BREAKPOINTS; REARRANGEMENTS; MALIGNANCIES; LEUKEMIA AB Through the application of the NIH/3T3 tumorigenicity assay to DNA from a gastric carcinoma, we have identified a novel transforming gene, designated myeov (myeloma overexpressed gene in a subset of t[11;14]-positive multiple myelomas), Sequence analyses did not reveal any homology with sequences present in the GenBank, except the deduced protein structure predicts a transmembrane localization. Myeov was mapped to chromosome 11q13 and localized by DNA fiber fluorescence in situ hybridization (FISH) 360-kilobase (kb) centromeric of cyclin D1. In 3 of 7 multiple myeloma (MM) cell lines with a t(11;14)(q13;q32) and cyclin-D1 overexpression, Northern blot analysis revealed overexpression of myeov as well. In all 7 cell lines, the translocation breakpoint was mapped within the 360-kb region between myeov and cyclin D1, DNA fiber FISH with a contig of probes covering the constant region of the immunoglobulin heavy chain (IgH) revealed that exclusively in the 3 myeov-overexpressing cell lines (KMS-12, KMS-21, and XG-5), either the 5' E mu enhancer or the most telomeric 3' for enhancer was juxtaposed to myeov, Although cyclin D1 overexpression represents a characteristic feature of all NIM cell lines with t(11;14), our results demonstrate aberrant expression of a second putative oncogene in a subset of these cases, due to juxtaposition to IgH enhancers. The clinical relevance of this dual activation remains to be elucidated. (Blood.2000;95:2691-2698) (C) 2000 by The American Society of Hematology. C1 Univ Heidelberg, Inst Humangenet, D-69120 Heidelberg, Germany. Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands. Cornell Univ, Weill Med Coll, Dept Med, Div Hematol & Oncol, New York, NY USA. NCI, Med Branch, Dept Genet, Bethesda, MD 20892 USA. DSMZ, German Collect Microorganisms & Cell Cultures, Dept Human & Anim Cell Cultures, Braunschweig, Germany. Kawasaki Med Sch, Dept Hyg, Kurashiki, Okayama, Japan. RP Janssen, JWG (reprint author), Univ Heidelberg, Inst Humangenet, Neuenheimer Feld 328, D-69120 Heidelberg, Germany. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 NR 52 TC 74 Z9 80 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2000 VL 95 IS 8 BP 2691 EP 2698 PG 8 WC Hematology SC Hematology GA 303KH UT WOS:000086420700033 PM 10753852 ER EF