FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Rosentreter, SM Davenport, RW Loschinger, J Huf, J Jung, JG Bonhoeffer, F AF Rosentreter, SM Davenport, RW Loschinger, J Huf, J Jung, JG Bonhoeffer, F TI Response of retinal ganglion cell axons to striped linear gradients of repellent guidance molecules SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE axon guidance; growth cone; molecular gradients; topographic maps; Eph-related receptor tyrosine kinases and ligands ID GROWTH-CONE COLLAPSE; RETINOTECTAL PROJECTION; TECTAL PROJECTION; IN-VITRO; TOPOGRAPHIC MAPS; NERVOUS-SYSTEM; OPTIC TECTUM; CHICK; ARBORIZATION; OUTGROWTH AB Although molecular gradients have long been postulated to play a role in the development of topographic projections in the nervous system, relatively little is known about how axons evaluate gradients. Do growth cones respond to concentration or to slope? Do they react suddenly or gradually? Is there adaptation? In the developing retinotectal system, temporal retinal ganglion cell axons have previously been shown to avoid repellent cell-surface activities distributed in gradients across the optic tectum. We confronted temporal retinal axons with precisely formed striped linear gradients of repellent tectal membranes and of two candidate repellent molecules, ephrin-A2 and -A5. Axons entered gradient stripes independently of their slope and extended unhindered in the uphill direction until they suddenly avoided an apparent threshold concentration of repellent material that was independent of slope. This: critical concentration was similar in both linear and nonlinear gradients, and hence independent of gradient shape. When gradients of identical slope were formed on different basal levels of repellent material, axons grew uphill for a fixed increment of concentration, possibly measured from the lowest point of the gradient, rather than up to a fixed absolute concentration. The speed of growth cones was not affected by repellent unstriped gradients below the critical concentration level. Similar results were found with membranes from cell lines stably transfected with either ephrin-A5 or ephrin-A2, two previously identified growth cone repellent cell-surface proteins. These data suggest that growth cones or axons can integrate guidance information over large distances, probably by a combined memory and adaptation mechanism, (C) 1998 John Wiley & Sons, Inc. C1 Max Planck Inst Entwicklungsbiol, Abt Phys Biol, D-72076 Tubingen, Germany. NIH, Dev Neurobiol Lab, Bethesda, MD 20892 USA. RP Rosentreter, SM (reprint author), Max Planck Inst Entwicklungsbiol, Abt Phys Biol, Spemannstr 35-I, D-72076 Tubingen, Germany. NR 53 TC 67 Z9 67 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD DEC PY 1998 VL 37 IS 4 BP 541 EP 562 DI 10.1002/(SICI)1097-4695(199812)37:4<541::AID-NEU4>3.0.CO;2-L PG 22 WC Neurosciences SC Neurosciences & Neurology GA 142GW UT WOS:000077193000004 PM 9858257 ER PT J AU Sokolov, BP AF Sokolov, BP TI Expression of NMDAR1, GluR1, GluR7, and KA1 glutamate receptor mRNAs is decreased in frontal cortex of "neuroleptic-free" schizophrenics: Evidence on reversible up-regulation by typical neuroleptics SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE schizophrenia; neuroleptic; glutamate receptor mRNAs; postmortem; frontal cortex ID CHRONIC HALOPERIDOL TREATMENT; AFFINITY KAINATE RECEPTOR; MEDIAL TEMPORAL-LOBE; AMINO-ACID RECEPTORS; PREFRONTAL CORTEX; MESSENGER-RNAS; GENE-EXPRESSION; HIPPOCAMPAL-FORMATION; ANTIPSYCHOTIC-DRUGS; SUBUNIT EXPRESSION AB Schizophrenics exhibit abnormalities in many memory-associated functions mediated by the frontal cortex. Glutamate receptors play key roles in learning and memory. Hence, abnormalities in glutamate receptors within the frontal cortex may be associated with schizophrenia. In addition, emerging evidence indicates that glutamate receptors may be involved in the actions of antipsychotic drugs. To test these hypotheses, we measured mRNAs encoding the NMDAR1, GluR1, GluR7, and KA1 subunits of glutamate receptor in the left superior frontal gyrus from 21 elderly schizophrenics with varying histories of antipsychotic drug treatment and nine normal drug-free elderly controls. There were significant negative correlations between NMDAR1, GluR1, GluR7, and KA1 mRNA levels and time without neuroleptic medication before death in schizophrenics, indicating that levels of the glutamate receptor mRNAs decline rapidly after drug withdrawal. Further analysis revealed that in ''neuroleptic-free" (>6 months) schizophrenics, levels of NMDAR1, GluR1, GluR7, and KA1 mRNAs were significantly lower than in controls. By contrast, in schizophrenics who were receiving neuroleptics until death, levels of NMDAR1, GluR1, GluR7, and KA1 mRNAs did not differ significantly from controls. These findings indicate that decreased levels of NMDAR1, GluR1, GluR7, and KA1 mRNAs may be present in the frontal cortex of some schizophrenics and that typical neuroleptics may reversibly increase levels of these mRNAs. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Sokolov, BP (reprint author), NIDA, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. NR 54 TC 115 Z9 117 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1998 VL 71 IS 6 BP 2454 EP 2464 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 139QH UT WOS:000077040400025 PM 9832144 ER PT J AU Demaimay, R Harper, J Gordon, H Weaver, D Chesebro, B Caughey, B AF Demaimay, R Harper, J Gordon, H Weaver, D Chesebro, B Caughey, B TI Structural aspects of Congo red as an inhibitor of protease-resistant prion protein formation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Congo red; scrapie; transmissible spongiform encephalopathies; prion protein; protease resistance; cell-free system; structural modifications; energy minimization calculations ID SCRAPIE PRION; CULTURED-CELLS; PRP ACCUMULATION; CONVERSION; FIBRILS; BINDING; FORM; CONFORMATION; INFECTIVITY; SEPARATION AB Congo red (CR) has been shown to inhibit the accumulation in scrapie-infected cells of prion protein (PrP) in the abnormal protease-resistant form (PrP-res). However, it was not clear if this effect was due to a direct interaction of CR with either PrP-res or its protease-sensitive precursor (PrP-sen) or to a less direct effect on living cells. Here we show that CR inhibits PrP-res formation in a simple cell-free reaction composed predominantly of purified PrP-res and PrP-sen. Structurally modified CR analogues were also compared in both the cell-free conversion reaction and scrapie-infected neuroblastoma cells. Methylation of the central phenyl groups at the 2,2' positions diminished the inhibitory potency by greater than or equal to 10-fold. In contrast, there was little effect of 3,3' methylation of the phenyls, deletion of one phenyl, or addition of an amido group between the phenyls, The relative activities of these compounds were well correlated in both cellular and acellular systems. Molecular modeling indicated that CR and 3,3'-methyl-CR have little rotational restriction about the biphenyl bond and can readily adopt a planar conformation, as can phenyl-CR and amido-CR. In contrast, 2,2'-methyl-CR is restricted to a nonplanar conformation of the biphenyl group. Thus, planarity and/or torsional mobility of the central phenyl rings of CR and its analogues is probably important for inhibition of PrP-res formation. On the other hand, variations in the intersulfonate distance in these molecules had little effect on PrP-res inhibition. These results indicated a high degree of structural specificity in the inhibition of PrP-res formation by CR and related compounds. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. Neurochem Inc, St Laurent, PQ, Canada. Queens Univ, Dept Med, Kingston, ON, Canada. Queens Univ, Dept Chem, Kingston, ON, Canada. RP Chesebro, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 42 TC 71 Z9 74 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1998 VL 71 IS 6 BP 2534 EP 2541 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 139QH UT WOS:000077040400034 PM 9832153 ER PT J AU Tenhunen, K Uusitalo, A Autti, T Joensuu, R Kettunen, M Kauppinen, RA Ikonen, S LaMarca, ME Haltia, M Ginns, EI Jalanko, A Peltonen, L AF Tenhunen, K Uusitalo, A Autti, T Joensuu, R Kettunen, M Kauppinen, RA Ikonen, S LaMarca, ME Haltia, M Ginns, EI Jalanko, A Peltonen, L TI Monitoring the CNS pathology in aspartylglucosaminuria mice SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE aspartylglucosaminuria; knock-out mouse; lysosomal storage disease ID HUMAN LYSOSOMAL DISEASE; TARGETED DISRUPTION; ASPARTYLGLYCOSAMINURIA; PHENOTYPE; DELETION; MOUSE; GENE AB Aspartylglucosaminuria (AGU) is a recessively inherited lysosomal storage disorder caused by the deficiency of the aspartylglucosaminidase (AGA) enzyme. The hallmark of AGU is slowly progressing mental retardation but the progression of brain pathology has remained uncharacterized in humans. Here we describe the long-term follow-up of mice carrying a targeted AGU-mutation in both alleles. Immunohistochemistry, histology, electron microscopy, quantitative magnetic resonance imaging (MRI) and behavioral studies were carried out to evaluate the CNS affection of the disease during development. The lysosomal storage vacuoles of the AGA -/- mice were most evident in central brain regions where MRI also revealed signs of brain atrophy similar to that seen in the older human patients. By immunohistochemistry and MRI examinations, a subtle delay of myelination was observed in AGA -/- mice. The life span of the AGA -/- mice was not shortened. Similar to the slow clinical course observed in human patients, the AGA -/- mice have behavioral symptoms that emerge at older age. Thus, the AGU knock-out mice represent an accurate model for AGU, both histopathologically and phenotypically. C1 Natl Publ Hlth Inst, Dept Human Mol Genet, SF-00300 Helsinki, Finland. Univ Helsinki, Dept Radiol, Helsinki, Finland. Univ Kuopio, NMR Res Grp, AI Virtanen Inst, FIN-70211 Kuopio, Finland. Univ Kuopio, Dept Neurol & Neurosci, FIN-70211 Kuopio, Finland. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Univ Helsinki, Dept Pathol, Helsinki, Finland. Univ Helsinki, Cent Hosp, Helsinki, Finland. RP Peltonen, L (reprint author), Natl Publ Hlth Inst, Dept Human Mol Genet, Mannerheimintie 166, SF-00300 Helsinki, Finland. RI Kauppinen, Risto/F-3274-2011; Kettunen, Mikko/K-2299-2012 OI Kettunen, Mikko/0000-0002-2004-660X NR 29 TC 9 Z9 9 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 DEC PY 1998 VL 57 IS 12 BP 1154 EP 1163 DI 10.1097/00005072-199812000-00007 PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 150EU UT WOS:000077651200007 PM 9862638 ER PT J AU Chen, R Tam, A Butefisch, C Corwell, B Ziemann, U Rothwell, JC Cohen, LG AF Chen, R Tam, A Butefisch, C Corwell, B Ziemann, U Rothwell, JC Cohen, LG TI Intracortical inhibition and facilitation in different representations of the human motor cortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; CORTICOSPINAL PROJECTIONS; CORTICOCORTICAL INHIBITION; CORTICAL EXCITABILITY; INTRINSIC CONNECTIONS; LIMB MOTONEURONS; UNIT RESPONSES; SURFACE EMG; MONKEY; RECOVERY AB Intracortical inhibition (ICI) and intracortical facilitation (ICF) of the human motor cortex can be studied with paired transcranial magnetic stimulation (TMS). Plastic changes and some neurological disorders in humans are associated with changes in ICI and ICF. Although well characterized in the hand representation, it is not known if ICI and ICF vary across different body part representations. Therefore we studied ICI and ICF in different motor representations of the human motor cortex. The target muscles were rectus abdominus (RA), biceps brachii (BB), abductor pollicis brevis (APB), quadriceps femoris (QF), and abductor hallucis (AH). For each muscle, we measured the rest and active motor thresholds (MTs), the motor-evoked potential (MEP) stimulus-response curve (MEP recruitment), ICI, and ICF. The effects of different interstimulus intervals (ISIs) were studied with a conditioning stimulus (CS) intensity of 80% active MT. The effects of different CS intensities were studied at ISI of 2 ms for ICI and ISI of 15 ms for ICF. MT was lowest for APE, followed by BE, AH, and QF, and was highest for RA. Except for BE, MEP recruitment was generally steeper for muscles with lower MT. ICI and ICF were present in all the motor representations tested. The stimulus intensity necessary to elicit ICI was consistently lower than that required to elicit ICF, suggesting that they are mediated by separate mechanisms. Despite wide differences in MT and MEP recruitment, the absolute CS intensities (expressed as percentage of the stimulator's output) required to elicit ICI and ICF appear unrelated to MT and MEP recruitment in the different muscles tested. These findings suggest that the intracortical mechanisms for inhibition and facilitation in different motor representations are not related to the strength of corticospinal projections. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20982 USA. Inst Neurol, MRC, Human Movement & Balance Unit, London WC1N 3BG, England. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bldg 10,Room 5N234,10 Ctr Dr,MSC-1430, Bethesda, MD 20982 USA. RI Chen, Robert/B-3899-2009; OI Chen, Robert/0000-0002-8371-8629; Rothwell, John/0000-0003-1367-6467 NR 47 TC 276 Z9 277 U1 2 U2 16 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1998 VL 80 IS 6 BP 2870 EP 2881 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 153LR UT WOS:000077835000007 PM 9862891 ER PT J AU Chelazzi, L Duncan, J Miller, EK Desimone, R AF Chelazzi, L Duncan, J Miller, EK Desimone, R TI Responses of neurons in inferior temporal cortex during memory-guided visual search SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID FRONTAL EYE FIELD; POSTERIOR PARIETAL CORTEX; PRIMATE PREFRONTAL CORTEX; SACCADE TARGET SELECTION; SHORT-TERM-MEMORY; NEURAL MECHANISMS; CORTICAL AREAS; SINGLE NEURONS; ATTENTION; MACAQUE AB A typical scene will contain many different objects, few of which are relevant to behavior at any given moment. Thus attentional mechanisms are needed to select relevant objects for visual processing and control over behavior. We examined this role of attention in the inferior temporal cortex of macaque monkeys, using a visual search paradigm. While the monkey maintained fixation, a cue stimulus was presented at the center of gaze, followed by a blank delay period. After the delay, an array of two to five choice stimuli was presented extrafoveally, and the monkey was rewarded for detecting a target stimulus matching the cue. The behavioral response was a saccadic eye movement to the target in one version of the task and a lever release in another. The array was composed of one "good" stimulus (effective in driving the cell when presented alone) and one or more "poor" stimuli (ineffective in driving the cell when presented alone). Most cells showed higher delay activity after a good stimulus used as the cue than after a poor stimulus. The baseline activity of cells was also higher preceding a good cue, if the animal expected it to occur. This activity may depend on a top-down bias in favor of cells coding the relevant stimulus. When the choice array was presented, most cells showed suppressive interactions between the stimuli as well as strong attention effects. When the choice array was presented in the contralateral visual field, most cells initially responded the same, regardless of which stimulus was the target. However, within 150-200 ms of array onset, responses were determined by the target stimulus. If the target was the good stimulus, the response to the array became equal to the response to the good stimulus presented alone. If the target was a poor stimulus, the response approached the response to that stimulus presented alone. Thus the influence of the nontarget stimulus was eliminated. These effects occurred well in advance of the behavioral response. When the array was positioned with stimuli on opposite sides of the vertical meridian, the contralateral stimulus appeared to dominate the response, and this dominant effect could not be overcome by attention. Overall, the results support a "biased competition" model of attention, according to which 1) objects in the visual field compete for representation in the cortex, and 2) this competition is biased in favor of the behaviorally relevant object by virtue of ''top-down'' feedback from structures involved in working memory. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Univ Verona, Dipartimento Sci Neurol & Vis, Sez Fisiol, I-37134 Verona, Italy. MRC, Appl Psychol Unit, Cambridge CB2 2EF, England. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Ctr Learning & Memory, Cambridge, MA 02139 USA. RP Desimone, R (reprint author), NIMH, Neuropsychol Lab, Bldg 49,Rm 1B80,49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA. RI Chelazzi, Leonardo/B-6084-2011 OI Chelazzi, Leonardo/0000-0001-8566-0611 NR 54 TC 417 Z9 431 U1 1 U2 21 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1998 VL 80 IS 6 BP 2918 EP 2940 PG 23 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 153LR UT WOS:000077835000012 PM 9862896 ER PT J AU Degtyarenko, AM Simon, ES Burke, RE AF Degtyarenko, AM Simon, ES Burke, RE TI Locomotor modulation of disynaptic EPSPs from the mesencephalic locomotor region in cat motoneurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LATENCY CUTANEOUS EXCITATION; FLEXOR DIGITORUM LONGUS; FICTIVE LOCOMOTION; SPINAL-CORD; LUMBOSACRAL MOTONEURONS; REFLEX PATHWAYS; BRAIN-STEM; STIMULATION; MUSCLES; INTERNEURONS AB When low-frequency tetanization of the mesencephalic locomotor region (MLR) produce fictive locomotion in unanesthetized, decerebrate cats, each MLR stimulus produces a distinctive cord dorsum potential (CDP) and oligosynaptic excitatory postsynaptic potentials (EPSPs) in many lumbosacral motoneurons. The average segmental latency from the initial CDP wave [mean delay from stimulus: 4.3 +/- 0.9 (SD) ms] to the onset of detectable MLR EPSPs was 1.6 +/- 0.4 ms, suggesting a disynaptic segmental connection. In gastrocnemius/soleus, flexor hallucis longus, flexor digitorum longus, tibialis anterior, and posterior biceps-semitendinosus motoneurons (35/38 cells), MLR EPSPs either appeared or were enhanced during the phase of fictive stepping in which the target motoneurons were depolarized and the motor pool was active (the ON phase), with parallel changes between EPSP amplitudes and membrane depolarization. In contrast, MLR stimulation produced small (1/10) or no EPSPs in extensor digitorum longus (EDL) motoneurons, with no ON phase enhancement (4/10) or oligosynaptic inhibitory postsynaptic potentials during the ON phase (5/10). Eight of 10 flexor digitorum longus (FDL) cells exhibited membrane depolarization in the early flexion phase of fictive stepping, and five of these showed parallel enhancement of disynaptic MLR EPSPs during early flexion. Three cases were studied when the FDL motor pool exhibited exclusively extensor phase firing. In these cases, the disynaptic MLR EPSPs were enhanced only during the extensor phase, accompanied by membrane depolarizations. We conclude that the last-order interneurons that produce disynaptic MLR EPSPs may well participate in producing the depolarizing locomotor drive potentials (LDPs) found in hindlimb motoneurons during fictive locomotion. However, the absence of linkage between MLR EPSP enhancement and LDP depolarizations in EDL motoneurons suggests that other types of excitatory interneurons also must be involved at least in some motor pools. We compared these patterns with the modulation of disynaptic EPSPs produced in FDL cells by stimulation of the medial longitudinal fasciculus (MLF). In all seven FDL motoneurons tested, disynaptic MLF EPSPs appeared only during the extension phase, regardless of when the FDL motoneurons were active. The fact that the modulation patterns of MLR and MLF disynaptic EPSPs is different in FDL motoneurons indicates that the two pathways do not converge on common last-order interneurons to that motor pool. C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP Burke, RE (reprint author), NINDS, Neural Control Lab, NIH, Bldg 49,Rm 3A50, Bethesda, MD 20892 USA. NR 24 TC 21 Z9 21 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1998 VL 80 IS 6 BP 3284 EP 3296 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 153LR UT WOS:000077835000038 PM 9862922 ER PT J AU Sommer, MA Wurtz, RH AF Sommer, MA Wurtz, RH TI Frontal eye field neurons orthodromically activated from the superior colliculus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Sommer, MA (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,room 2A50,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 70 Z9 70 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1998 VL 80 IS 6 BP 3331 EP 3335 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 153LR UT WOS:000077835000043 PM 9862927 ER PT J AU Antoni, FA Palkovits, M Simpson, J Smith, SM Leitch, AL Rosie, R Fink, G Paterson, JM AF Antoni, FA Palkovits, M Simpson, J Smith, SM Leitch, AL Rosie, R Fink, G Paterson, JM TI Ca2+/calcineurin-inhibited adenylyl cyclase, highly abundant in forebrain regions, is important for learning and memory SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cAMP; protein phosphatase; hippocampus; neocortex; striatum; adenylyl cyclase I; calcium ID DEPENDENT PROTEIN-KINASE; RAT-BRAIN; SIGNAL-TRANSDUCTION; CALCIUM-RELEASE; CYCLIC-AMP; CALCINEURIN; CELLS; CA2+; BETA; EXPRESSION AB Activation of cAMP synthesis by intracellular Ca2+ is thought to be the main mode of cAMP generation in the brain. Accordingly, the Ca2+-activated adenylyl cyclases I and VIII are expressed prominently in forebrain neurons. The present study shows that the novel adenylyl cyclase type IX is inhibited by Ca2+ and that this effect is blocked selectively by inhibitors of calcineurin such as FK506 and cyclosporin A. Moreover, adenylyl cyclase IX is inhibited by the same range of intracellular free Ca2+ concentrations that stimulate adenylyl cyclase I. Adenylyl cyclase IX is expressed prominently in the forebrain. Substantial arrays of neurons positive for AC9 mRNA were found in the olfactory lobe, in limbic and neocortical areas, in the striatum, and in the cerebellar system. These data show that the initiation of the cAMP signal by adenylyl cyclase may be controlled by Ca2+/calcineurin and thus provide evidence for a novel mode of tuning the cAMP signal by protein phosphorylation/dephosphorylation cascades. C1 Univ Edinburgh, Dept Neurosci, MRC, Brain Metab Unit, Edinburgh EH8 9JZ, Midlothian, Scotland. NIMH, Genet Sect, NIH, Bethesda, MD 20892 USA. RP Antoni, FA (reprint author), Univ Edinburgh, Dept Neurosci, MRC, Brain Metab Unit, Edinburgh EH8 9JZ, Midlothian, Scotland. RI Palkovits, Miklos/F-2707-2013 NR 61 TC 72 Z9 73 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 DEC 1 PY 1998 VL 18 IS 23 BP 9650 EP 9661 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 141XP UT WOS:000077169800009 PM 9822726 ER PT J AU Drago, J Padungchaichot, P Wong, JYF Lawrence, AJ McManus, JF Sumarsono, SH Natoli, AL Lakso, M Wreford, N Westphal, H Kola, I Finkelstein, DI AF Drago, J Padungchaichot, P Wong, JYF Lawrence, AJ McManus, JF Sumarsono, SH Natoli, AL Lakso, M Wreford, N Westphal, H Kola, I Finkelstein, DI TI Targeted expression of a toxin gene to D1 dopamine receptor neurons by Cre-mediated site-specific recombination SO JOURNAL OF NEUROSCIENCE LA English DT Article DE D1 dopamine receptor; basal ganglia; Cre recombinase; gene targeting; striatum; Parkinson's disease ID IDIOPATHIC PARKINSONS-DISEASE; BASAL GANGLIA; HUNTINGTONS-DISEASE; CLINICAL-DIAGNOSIS; TRANSFECTED CELLS; MOUSE; ACTIVATION; APOPTOSIS; SEQUENCE; MICE AB Idiopathic Parkinson's disease involves the loss of midbrain dopaminergic neurons, resulting in the presynaptic breakdown of dopaminergic transmission in the striatum. Huntington's disease and some neurodegenerative diseases with Parkinsonian features have postsynaptic defects caused by striatal cell death. Mice were generated in which an attenuated form of the diphtheria toxin gene (tox-176) was expressed exclusively in D1 dopamine receptor (D1R)-positive cells with the aim of determining the effect of this mutation on development of the basal ganglia and on the locomotor phenotype. Transgenic mice expressing Cre, a site-specific DNA recombinase, were crossed with a second line in which a transcriptionally silenced tox-176 gene was inserted into the D1R gene locus by homologous recombination. Young doubly transgenic mutant mice expressing the tox-176 gene displayed bradykinesia, dystonia, and had falls caused by myoclonic jerks. The mutant brain had evidence of apoptosis and reactive gliosis and, consistent with the D1R expression pattern, the striatum was reduced in volume, and the Islands of Calleja were absent. In contrast, the cortex was of normal thickness. D1Rs were not detectable in mutants by in situ hybridization or ligand autoradiography, whereas D2 dopamine receptor (D2R) mRNA and protein was present in the striatum. In addition, substance P and dynorphin, neuropeptides known to be expressed in D1R-positive striatonigral projection neurons were not detectable. Enkephalin, a marker found in D2-positive striatopallidal projection neurons was expressed in the mutant brain. The mutant represents a novel neurodegenerative disease model with a dramatic extrapyramidal phenotype. C1 Monash Univ, Dept Anat, Neurosci Grp, Clayton, Vic 3168, Australia. Monash Univ, Dept Pharmacol, Clayton, Vic 3168, Australia. Monash Univ, Inst Reprod & Dev, Mol Genet & Dev Grp, Clayton, Vic 3168, Australia. BioTeknia, AI Virtanen Inst, Kuopio 70210, Finland. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Drago, J (reprint author), Monash Univ, Dept Anat, Neurosci Grp, Wellington Rd, Clayton, Vic 3168, Australia. RI Kola, Ismail/C-5254-2013 NR 58 TC 45 Z9 46 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 1998 VL 18 IS 23 BP 9845 EP 9857 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 141XP UT WOS:000077169800026 PM 9822743 ER PT J AU Watson, JC Shawker, TH Nieman, LK DeVroom, HL Doppman, JL Oldfield, EH AF Watson, JC Shawker, TH Nieman, LK DeVroom, HL Doppman, JL Oldfield, EH TI Localization of pituitary adenomas by using intraoperative ultrasound in patients with Cushing's disease and no demonstrable pituitary tumor on magnetic resonance imaging SO JOURNAL OF NEUROSURGERY LA English DT Article DE Cushing's disease; Cushing's syndrome; pituitary adenoma; ultrasound; magnetic resonance imaging ID TRANSSPHENOIDAL SURGERY; MR; MICROADENOMAS; EXPERIENCE; HORMONE; GLAND AB Object. Pituitary surgery has been reported to produce remission of Cushing's disease with preservation of pituitary function in only 60 to 70% of patients. The inability to identify an adenoma accounts for most failed sellar explorations. Most negative surgical explorations occur in patients in whom magnetic resonance (MR) imaging of the pituitary demonstrates normal findings, which happens in at least 35 to 45% of patients with Cushing's disease. Methods. To examine the usefulness of intraoperative ultrasonography (IOUS) for identifying an adenoma in patients with no demonstrable tumor (negative findings) on pituitary MR imaging, we prospectively assessed the results of IOUS in 68 patients with a negative (59 patients) or equivocal (nine patients) MR image from a consecutive series of 107 patients with Cushing's disease (64%). We compared surgical findings and outcomes in these 68 patients with a group of 68 patients with Cushing's disease and negative findings on MR imaging in whom IOUS was not available. Intraoperative ultrasonography localized a tumor in 47 (69%) of 68 patients with negative findings on MR imaging. Surprisingly, the size of the adenomas that were detected with IOUS compared with the size of those not detected did not differ (6.8 +/- 3.4 mm compared with 6.1 +/- 2.8 mm [mean +/- standard deviation], respectively [p = 0.5]). In four patients, no adenoma was found at surgery or in the pathological specimen ("true negative"). In eight patients, nine abnormalities detected by IOUS that were suspected adenomas were negative on exploration ("false positive"). Thus, IOUS has a sensitivity of 73% and a positive predictive value of 84% for detecting pituitary adenomas in patients with Cushing's disease and negative findings on MR imaging. Compared with the 68 patients who did not undergo IOUS, remission after surgery was improved (61 patients [90%] compared with 57 patients [84%]), the number of tumors found on exploration was increased (61 tumors compared with 51 tumors; p = 0.02), and the number of hemihypophysectomies was decreased (five compared with 15; p = 0.02) with IOUS. When the groups were compared after excluding patients with prior pituitary surgery, tumors were found in 91% versus 72% (p = 0.008), and remission occurred in 95% versus 87% of patients, respectively, in the groups that had or did not have IOUS. Conclusions. The IOUS is a sensitive imaging modality when used in patients with Cushing's disease in whom findings on pituitary MR imaging are negative. The improved ability to detect and localize these tumors by using IOUS positively affects surgical outcome. C1 Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. Warren Grant Magnuson Clin Ctr, Diagnost Radiol Dept, Bethesda, MD USA. NICHHD, NIH, Bethesda, MD USA. RP Oldfield, EH (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Natl Inst Hlth, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. NR 21 TC 56 Z9 56 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 1998 VL 89 IS 6 BP 927 EP 932 DI 10.3171/jns.1998.89.6.0927 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 168TF UT WOS:000078708200004 PM 9833817 ER PT J AU Zhang, L Looney, D Taub, D Chang, SL Way, D Witte, MH Graves, MC Fiala, M AF Zhang, L Looney, D Taub, D Chang, SL Way, D Witte, MH Graves, MC Fiala, M TI Cocaine opens the blood-brain barrier to HIV-1 invasion SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE cocaine; HIV-1; apoptosis; endothelial cells; tumor necrosis factor-alpha; macrophage inflammatory protein-1 alpha; monocyte chemoattractant protein-1 ID IMMUNODEFICIENCY-VIRUS TYPE-1; NECROSIS-FACTOR-ALPHA; CEREBROSPINAL-FLUID; MONONUCLEAR-CELLS; DRUG-USERS; TNF-ALPHA; IN-VITRO; INFECTION; IDENTIFICATION; INDIVIDUALS AB Cocaine abuse has been associated with vasculitis and stroke, and is suspected to influence the progression of AIDS dementia. Cocaine may enhance HIV-1 neuroinvasion by actions directed at the blood-brain barrier. HIV-1 appears to penetrate the human brain microvascular endothelial cell barrier by a paracellular route breached by tumor necrosis factor-alpha (TNF-alpha). Cocaine's effects on the blood-brain barrier were investigated using human brain microvascular endothelial cells and peripheral blood monocytes. Cocaine (10(-5) M and 10(-6) M) increased molecular permeability of the barrier and viral invasion by the macrophage-tropic HIV-1(JR-FL) into the brain chamber. Cocaine also augmented apoptosis of brain endothelial cells and monocytes, increased secretion of four chemokines (interleukin-8, interferon-inducible protein-10, macrophage inflammatory protein-1 alpha, and monocyte chemoattractant protein-1) and the cytokine, TNF-alpha, by human monocytes. TNF-alpha enhanced invasion of the brain compartment by macrophage-tropic, lymphotropic, and bitropic HIV-1 strains. These data indicate that HIV-1 neuroinvasion can be increased by (a) cocaine's direct effects on brain microvascular endothelial cells and (b) paracrine effects of cocaine-induced pro-inflammatory cytokines and chemokines on the blood-brain barrier. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. VA San Diego Healthcare Ctr, San Diego, CA 92161 USA. NIA, Baltimore, MD 21224 USA. Seton Hall Univ, Dept Biol, S Orange, NJ 07079 USA. Univ Arizona, Dept Surg, Tucson, AZ 85724 USA. RP Fiala, M (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. FU NIDA NIH HHS [DA 07058, DA 10442]; NINDS NIH HHS [NS 26126] NR 39 TC 75 Z9 79 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 1998 VL 4 IS 6 BP 619 EP 626 DI 10.3109/13550289809114228 PG 8 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 161BM UT WOS:000078268100005 PM 10065903 ER PT J AU Ma, FC Lee, DJ Fleming, LE Dosemeci, M AF Ma, FC Lee, DJ Fleming, LE Dosemeci, M TI Race-specific cancer mortality in US firefighters: 1984-1993 SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID FIRE-FIGHTERS; DEATH CERTIFICATES; RATIO; OCCUPATION; INDUSTRY; RISK; SURVEILLANCE; COHORT AB A mortality odds ratio (MOR) study of race-specific cancer risk among firefighters was conducted using 1984-1993 death certificate data from 24 states. The Bureaus of the Census Index of Industries and Occupations was used to code occupation on death certificates. The overall cancer mortality was slightly elevated among white firefighters (MOR = 1.1; 95% confidence interval [CI] = 1.1-1.2), but the increase in overall cancer mortality among black firefighters was not significant (MOR = 1.2; 95% CI = 0.9-1.5). Only prostate cancer risk was elevated in both groups (whites: MOR = 1.2; 95% CI = 1.0-1.3; blacks: MOR = 1.9; 95% CI = 1.2-3.2). Among white firefighters, elevated site-specific cancer mortality risks were found for the following cancer sites: lip (MOR = 5.9; 95% CI = 1.9-18.3), pancreas (MOR = 1.2; 95% CI = 1.0-1.5), soft tissue sarcoma (MOR = 1.6; 95% CI = 1.0-2.7), melanoma (MOR = 1.4; 95% CI = 1.0-1.9), kidney and renal pelvis (MOR = 1.3; 95% CI = 1.0-1.7), non-Hodgkin's lymphoma (MOR = 1.4; 95% CI = 1.1-1.7), and Hodgkin's disease (MOR = 2.4; 95% CI = 1.4-4.1). We also observed a slightly elevated risk for bronchus and lung cancer (MOR = 1.1; 95% CI = 1.0-1.2). Among black firefighters, excess risks were found for cancers of the brain and central nervous system (MOR = 6.9; 95% CI = 3.0-16.0), colon (MOR = 2.1; 95% CI = 1.1-4.0), and nasopharynx (MOR = 7.6; 95% CI = 1.3-46.4). Future studies are needed to confirm the existence of differential cancer mortality risks among firefighters of different race/ethnic subpopulations. C1 Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33101 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Lee, DJ (reprint author), Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, POB 016069 R-669, Miami, FL 33101 USA. NR 34 TC 21 Z9 21 U1 2 U2 2 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 DEC PY 1998 VL 40 IS 12 BP 1134 EP 1138 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 151LM UT WOS:000077721600014 PM 9871891 ER PT J AU Li, P Tabibi, SE Yalkowsky, SH AF Li, P Tabibi, SE Yalkowsky, SH TI Combined effect of complexation and pH on solubilization SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID CYCLODEXTRINS; COMBINATION AB Both pH control and complexation are widely used as solubilization techniques in drug formulation studies. Although these two techniques are often utilized in combination, few theoretical studies have shown why the combined approach would work better than either one alone. This study constructs a background in which both the pH effect and complexation constants are used to explain the synergism between these techniques. The total solubility is determined by the addition of the concentrations of the four components present in the solution: free un-ionized drug [D-u], free ionized drug [D-i], un-ionized drug complex [DuL], and ionized drug complex [DiL]. A detailed description of [D-i] and [DiL] reveals that the complexation constants and the pH at which the drug may ionize are both critical. The weakly basic drug flavopiridol is used as a test compound to examine the validity of the equation. Although the complexation constant for ionized flavopiridol (K-i = 124 M-1) is less than one-third of that of the unionized species (K-u = 445 M-1, the solubility of the ionized drug complex [DiL] is 6-fold greater than that of the un-ionized drug complex [DuL]. This unexpected result is due to the 25-fold greater solubility of the ionized drug [D-i] at pH 4.3 over that of the free un-ionized species [D-u] at pH 8.4. The results of this and other complexation studies of several drugs taken from the literature lend the support to the following: if [D-i]/[D-u] > K-u/K-i, then [DiL] > [DuL]. C1 Univ Arizona, Coll Pharm, Dept Pharmaceut Sci, Tucson, AZ 85721 USA. NCI, Bethesda, MD 20892 USA. RP Yalkowsky, SH (reprint author), Univ Arizona, Coll Pharm, Dept Pharmaceut Sci, Tucson, AZ 85721 USA. FU NCI NIH HHS [N01-CM-27757] NR 8 TC 50 Z9 55 U1 0 U2 6 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD DEC PY 1998 VL 87 IS 12 BP 1535 EP 1537 DI 10.1021/js9801889 PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 145EC UT WOS:000077357200011 PM 10189262 ER PT J AU Bauer, KS Kohn, EC Lush, RM Steinberg, SM Davis, P Kohler, D Reed, E Figg, WD AF Bauer, KS Kohn, EC Lush, RM Steinberg, SM Davis, P Kohler, D Reed, E Figg, WD TI Pharmacokinetics and relative bioavailability of carboxyamido-triazole with respect to food and time of administration: Use of a single model for simultaneous determination of changing parameters SO JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS LA English DT Article DE carboxyamido-triazole; bioavailability; chronopharmacology; pharmacokinetics; food ID CALCIUM INFLUX INHIBITOR; SIGNAL-TRANSDUCTION; CELL-LINES; CAI AB Carboxyamido-triazole (CAI) is an anti-invasive, antimetastatic, antiangiogenic agent in clinical development for cancer treatment. It has been postulated that food might enhance the oral absorption of micronized CAI based on an apparent discrepancy in steady stale maximum concentrations when taken without regard to meals vs, fasting. The purpose of this study was to determine if a standardized meal affects the absorption and pharmacokinetics of this agent. Twelve patients with refractory cancers and good end organ function were randomized to receive tno doses of CAI (250 mg/m(2)) with and without a standardized high fat meal One cohort of 6 patients received these doses at 9 AM, and the remaining 6 patients received CAI at 9 PM. Blood was obtained prior to each dose, and serially thereafter. A series of pharmacokinetic (PK) models were fit to the concentration-lime data. PK parameters were ultimately calculated using a model which allows simultaneous estimation of parameters from both test doses using nonlinear least squares analysis with ADAPT II. This model estimates independent absorption rate constants and relative fraction absorbed for each condition. AUC(0-t) was determined using the trapezoidal method extrapolated to infinity, and used to calculate the relative bioavailability. No significant differences in PK parameters were noted between the morning and evening cohorts. However:, the relative bioavailability, as measured by AUC(0-infinity), of CAI was significantly increased when administered with a high fat meal compared to fasting (138.9 vs. 52.2 mu g * hr/ml; p = 0.0005). The magnitude of the increase in relative bioavailability of CAI taken with food could have profound implications for patients who may inadvertently take this medication shortly after eating. C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Branch, Div Clin Sci, NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 16 TC 8 Z9 8 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-466X J9 J PHARMACOKINET BIOP JI J. Pharmacokinet. Biopharm. PD DEC PY 1998 VL 26 IS 6 BP 673 EP 687 DI 10.1023/A:1020750923542 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 198EU UT WOS:000080410400003 PM 10485080 ER PT J AU Selwitz, RH Nowjack-Raymer, RE Kingman, A Driscoll, WS AF Selwitz, RH Nowjack-Raymer, RE Kingman, A Driscoll, WS TI Dental caries and dental fluorosis among schoolchildren who were lifelong residents of communities having either low or optimal levels of fluoride in drinking water SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Association-for-Dental-Research CY MAR 08-12, 1995 CL SAN ANTONIO, TEXAS SP Amer Assoc Dent Res DE dental caries; dental fluorosis; mottled enamel; fluoride; water fluoridation ID FOLLOW-UP SURVEY; UNITED-STATES; PREVALENCE; AREAS; TRENDS AB Objective: This paper reports findings for dental caries and dental fluorosis in 8-10- and 13-16-year-old schoolchildren who were lifelong residents of communities having either naturally occurring low (Broken Bow and Holdrege, NE; <0.3 ppm) or optimal (Kewanee, IL; 1 ppm) levels of fluoride in drinking water. Methods: Findings are reported for participants who received both dental caries and dental fluorosis examinations (n=495). The DMFS and TSIF indices, respectively, were used to assess dental caries and dental fluorosis. Results: The mean DMFS score adjusted for age, sealant presence, and fluoride use was significantly lower in Kewanee (1.8) than was the adjusted mean caries score in either Holdrege (2.9) or Broken Bow (3.6). Adjusted mean DMFS scores in Broken Bow and Holdrege were not statistically different The mean percent of fluorosed tooth surfaces per person, adjusted for age and use of dietary fluoride supplements, was similar in the three communities (approximately 15%); more than 80 percent of tooth surfaces in all participants were fluorosis-free. Conclusions: Findings from the present study suggest that water fluoridation still is beneficial and that dental sealants can play a significant role in preventing dental caries. In addition, findings from this survey appear to support the premise that the difference in dental fluorosis prevalence between fluoridated and nonfluoridated communities has narrowed considerably in recent years. C1 NIDR, Div Intramural Res, Bethesda, MD 20892 USA. RP Selwitz, RH (reprint author), NIDR, Div Intramural Res, Natcher Bldg,Room 3AN-44D,45 Ctr Dr,MSC 6401, Bethesda, MD 20892 USA. EM selwitzr@de45.nidr.nih.gov NR 40 TC 16 Z9 18 U1 1 U2 5 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 1998 VL 58 IS 1 BP 28 EP 35 DI 10.1111/j.1752-7325.1998.tb02987.x PG 8 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA ZN322 UT WOS:000073634300005 PM 9608443 ER PT J AU Moon, HS Paik, DI Horowitz, AM Kim, JB AF Moon, HS Paik, DI Horowitz, AM Kim, JB TI National survey of Korean dentists' knowledge and opinions: Dental caries etiology and prevention SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE knowledge of caries etiology and prevention; perceived effectiveness of preventive procedures for children and adults Korean dentists; national survey ID FLUORIDE AB Objectives: Dentists have the potential to influence what their patients know and do regarding dental caries prevention. The practices of dentists and what they tell their patients are influenced in part, by their own knowledge and opinions. The purposes of this study were to determine the level of knowledge and opinions about caries etiology and prevention among Korean dentists and to describe related factors. Methods: A pretested, 27-item questionnaire was mailed to 2,047 dentists, selected by a stratified random sampling allocated proportionately. A postcard reminder was sent to all dentists after one week. Nonrespondents were sent additional complete mailings after three, seven, and nine weeks. The response rate was 83 percent (0=1,700 dentists). Results: Analysis of six factors thought to be related to knowledge about caries etiology and prevention showed that recent graduates and dentists who worked in public health centers were likely to be more knowledgeable about caries etiology and prevention than their counterparts (P<.05). In regression analysis of perceived effectiveness of caries preventive procedures for children, recent graduates, males, and dentists who worked in public health centers tended to rate caries-preventive procedures more effective than other dentists (P<.05). Dentists who had experience with school-based preventive programs and dentists in rural areas were likely to rate caries-preventive procedures for adults more effective than other dentists (P<.05). Conclusions: Overall, results of this study suggest that the majority of dentists do not know current information concerning etiology and prevention of dental caries, mechanisms of action of fluoride, and effectiveness of preventive procedures for children and adults. Efforts to enhance the level of knowledge and practices of Korean dentists about caries prevention should focus on strategies to educate older graduates and female dentists, especially those in private practice. C1 NIDR, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Dent, Dept Prevent & Publ Hlth Dent, Seoul 110749, South Korea. RP Horowitz, AM (reprint author), NIDR, NIH, Natcher Bldg Room 3An-44B,45 Ctr Dr,MSC 6401, Bethesda, MD 20892 USA. NR 29 TC 8 Z9 9 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 1998 VL 58 IS 1 BP 51 EP 56 DI 10.1111/j.1752-7325.1998.tb02990.x PG 6 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA ZN322 UT WOS:000073634300008 PM 9608446 ER PT J AU Loehlin, JC McCrae, RR Costa, PT John, OP AF Loehlin, JC McCrae, RR Costa, PT John, OP TI Heritabilities of common and measure-specific components of the big five personality factors SO JOURNAL OF RESEARCH IN PERSONALITY LA English DT Article DE Big Five; heredity; environment; twins; model fitting; sex differences ID CALIFORNIA PSYCHOLOGICAL INVENTORY; TWINS REARED APART; 5-FACTOR MODEL; SIMILARITY; SCALES AB Three different measures of the Big Five personality dimensions were developed from the battery of questionnaires used in the National Merit Twin Study: one from trait self-rating scales, one from personality inventory items, and one from an adjective check list. Behavior-genetic models were fit to what the three measures had in common, and to the variance distinctive to each. The results of the model fitting agreed with other recent studies in showing the Big Five dimensions to be substantially and about equally heritable, with little or no contribution of shared family environment. Heritabilities for males and females did not differ significantly. For Agreeableness and Conscientiousness, some effect of shared environment was found for measure-specific variance on the personality inventory, and for Extraversion and Neuroticism, models involving nonadditive genetic variance or twin contrast effects provided slightly better fits. (C) 1998 Academic Press. C1 Univ Texas, Dept Psychol, Austin, TX 78712 USA. NIA, Gerontol Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Loehlin, JC (reprint author), Univ Texas, Dept Psychol, Austin, TX 78712 USA. OI Costa, Paul/0000-0003-4375-1712 NR 31 TC 145 Z9 147 U1 3 U2 43 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0092-6566 J9 J RES PERS JI J. Res. Pers. PD DEC PY 1998 VL 32 IS 4 BP 431 EP 453 DI 10.1006/jrpe.1998.2225 PG 23 WC Psychology, Social SC Psychology GA 140EZ UT WOS:000077075400004 ER PT J AU Jefferson, T Herbst, JH McCrae, RR AF Jefferson, T Herbst, JH McCrae, RR TI Associations between birth order and personality traits: Evidence from self-reports and observer ratings SO JOURNAL OF RESEARCH IN PERSONALITY LA English DT Article ID EXPERIENCE; OPENNESS AB Sulloway (1996) proposed that personality traits developed in childhood mediate the association of birth order with scientific radicalism. Birth-order effects on traits within the five-factor model of personality were examined in three studies. Self-reports on brief measures of Neuroticism, Extraversion, and Openness in a national sample (N = 9664) were unrelated to birth order. Self-reports on the 30 facet scales of the Revised NEO Personality Inventory (NEO-PI-R) in an adult sample (N = 612) showed only small effects for Altruism and Tender-Mindedness. Peer ratings (N = 166) supported the hypotheses that laterborn children would be higher in facets of Openness and Agreeableness, but spouse ratings (N = 88) did not replicate those findings. Birth order may have subtle effects on perceived personality, but it is unlikely that this effect mediates associations with scientific radicalism. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Jefferson, T (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr,Box 3, Baltimore, MD 21224 USA. NR 36 TC 27 Z9 28 U1 4 U2 33 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0092-6566 J9 J RES PERS JI J. Res. Pers. PD DEC PY 1998 VL 32 IS 4 BP 498 EP 509 DI 10.1006/jrpe.1998.2233 PG 12 WC Psychology, Social SC Psychology GA 140EZ UT WOS:000077075400007 ER PT J AU Rost, K Owen, RR Smith, J Smith, GR AF Rost, K Owen, RR Smith, J Smith, GR TI Rural-urban differences in service use and course of illness in bipolar disorder SO JOURNAL OF RURAL HEALTH LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; MANIC-DEPRESSIVE ILLNESS; PROSPECTIVE FOLLOW-UP; MEDICAL OUTCOMES; UNITED-STATES; EFFICACY; LITHIUM AB Policy analysts have long been concerned that the reduced availability of mental health professionals in rural areas prohibits rural individuals from getting the care they need for serious psychiatric conditions like bipolar disorder. Through a community-based telephone survey, the researchers recruited 54 subjects with bipolar disorder who were currently experiencing depressive episodes. Forty-six (85.1%) of them were reinterviewed one year after the first survey. Multivariate models indicate that while rural subjects were just as likely to receive nonacute services for mental health problems as their urban counterparts, the rural residents had 22.1 times the odds (95% confidence interval 2.5 to 198.3, P=0.006) of receiving such services exclusively from a general medical provider. Rural subjects had 5.8 times the odds (95% confidence interval 0.8 to 40.7, P=0.07) of using hospital or emergency room services and 4 times the odds (95% confidence interval 0.8 to 20.5, P=0.10) of experiencing a manic episode during the year following baseline. While rural individuals with bipolar disorder have a comparable likelihood of receiving care for their mental health problems, they utilize more acute services and experience worse outcomes. Further research is warranted to determine what causes these differences before developing cost-effective ways to improve the care delivered to individuals with this serious illness. C1 Univ Arkansas, Ctr Mental Healthcare Res, Little Rock, AR 72204 USA. Vet Affairs Hlth Serv Res & Dev Field Program Men, Little Rock, AR USA. Univ Arkansas Med Sci, Mental Hlth Res Ctr, Dept Psychiat, Little Rock, AR 72205 USA. NIMH, Ctr Mental Healthcare Res, Bethesda, MD USA. RP Rost, K (reprint author), Univ Arkansas, Ctr Mental Healthcare Res, 5800 W 10th St,Suite 605, Little Rock, AR 72204 USA. NR 30 TC 13 Z9 13 U1 0 U2 0 PU NATL RURAL HEALTH ASSOC PI KANSAS CITY PA ONE WEST ARMOUR BLVD, STE 301, KANSAS CITY, MO 64111 USA SN 0890-765X J9 J RURAL HEALTH JI J. Rural Health PD WIN PY 1998 VL 14 IS 1 BP 36 EP 43 DI 10.1111/j.1748-0361.1998.tb00860.x PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA ZH856 UT WOS:000073154300006 ER PT J AU Rendell, MS Milliken, BK Finnegan, MF Finney, DE Healy, JC Bonner, RF AF Rendell, MS Milliken, BK Finnegan, MF Finney, DE Healy, JC Bonner, RF TI The microvascular composition of the healing wound compared at skin sites with nutritive versus arteriovenous perfusion SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE laser doppler; microvasculature; capillaries; arterioles ID BLOOD-FLOW; GROWTH-FACTORS; MODEL AB Background. In the rat, there is a significantly greater blood flow response to wounding at the back, a site perfused mainly by small capillaries, than at the paw, which has a much higher density of arterioles and venules. Materials and methods. We characterized the microvascular composition of wounds at the two skin sites in 11 Wistar Kyoto rats using a quantitative imaging program. Blood flow was compared using laser Doppler technology. Results. Prior to wounding, skin blood flow was much greater at the paw (7.1 +/- 0.5 ml 100 g tissue(-1) min(-1)) than at the back (2.1 +/- 0.1 ml 100 g tissue(-1) min(-1), P < 0.01) at baseline. Seven days after wounding, blood flow both at the center (8.3 +/- 1.4 mi 100 g tissue(-1) min-l) and at the perimeter of the back wound (4.1 +/- 0.5 ml 100 g tissue(-1) min(-1)) had increased substantially. In contrast, skin blood flow at the perimeter of the paw wound had increased moderately (12.7 +/- 2.0 ml 100 g tissue(-1) min(-1)), but there was no change at the center of the wound (6.9 +/- 0.9 ml 100 g tissue(-1) min(-1)). There were three times more microvessels per mm(2) at the paw site (39.3 +/- 3.6) than at the back (13.1 +/- 1.5) prior to wounding. The wound granulation tissue was very vascular; the numerical density of vessels was identical at back (166 +/- 9) and at paw (154 +/- 6), Despite the marked increase in blood how at the perimeter of the back wound, there was no difference in the microvascular density (15.2 +/- 1.4) compared to baseline, nor was there a difference at the paw perimeter (39.4 +/- 3.6) compared to baseline. Conclusions. This study demonstrates that the microvascular constitutions of granulation tissues at the paw and back are identical, Thus, the rise in flow at the back wound and reduction in flow at the paw wound are entirely consistent with similar microvascular compositions of these two sites. Yet, there is increased how at the back wound perimeter where there is no significant change in microvascular constitution compared to unwounded skin. Therefore, a microvascular structure no different from that prior to wounding functions very differently after wounding. Clearly vasoregulatory factors impact on the wound to modify flow through the microvascular network. (C) 1998 Academic Press. C1 Creighton Univ, Sch Med, Dept Med, Omaha, NE 68131 USA. Creighton Univ, Sch Med, Dept Pathol, Omaha, NE 68131 USA. NIH, Ctr Res Resources, Biomed Engn & Instrumentat Program, Bethesda, MD 20205 USA. RP Rendell, MS (reprint author), Creighton Univ, Sch Med, Dept Med, 601 N 30th St, Omaha, NE 68131 USA. RI Bonner, Robert/C-6783-2015 NR 21 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD DEC PY 1998 VL 80 IS 2 BP 373 EP 379 DI 10.1006/jsre.1998.5463 PG 7 WC Surgery SC Surgery GA 153MR UT WOS:000077837300040 PM 9878340 ER PT J AU Dutta, SK Procaccino, F Aamodt, R AF Dutta, SK Procaccino, F Aamodt, R TI Zinc metabolism in patients with exocrine pancreatic insufficiency SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE zinc metabolism; exocrine pancreas; zinc excretion; zinc absorption; alcoholism ID URINARY ZINC; ABSORPTION; RAT; INTESTINE; BINDING; METALLOTHIONEIN; DEFICIENCY; TRANSPORT; PROTEIN AB Objective: Metabolism of zinc was studied by administering radioactive zinc (Zn-65), and by performing metabolic balance studies in eight patients with exocrine pancreatic insufficiency and eighteen control subjects. Methods: Retention of radioactive zinc was measured by total body counter, and its urinary and fecal excretion by gamma scintillation counter. Metabolic balance studies were carried out by measuring dietary zinc intake as well as fecal and urinary excretion of zinc by atomic absorption spectrophotometry in this group of patients. Results: These studies revealed a 50% reduction in intestinal absorption of Zn-65 in patients with exocrine pancreatic insufficiency as compared to alcoholic and non-alcoholic control subjects. In addition, there was a 2 to 4 fold increase (p<0.05) in urinary excretion of zinc in subjects with pancreatic disease. In pancreatic insufficiency, reduced zinc absorption and increased urinary zinc excretion were balanced by lower (p<0.05) endogenous excretion of zinc as evidenced by reduced excretion of Zn-65 in feces during the second 4-day period. The mean biological half-life of Zn-65 tended to be lower in patients with pancreatic insufficiency as compared to alcoholic control subjects, however the difference did not reach statistical significance. Conclusion: These observations indicate marked alterations in zinc metabolism in patients with advanced chronic pancreatic disease and provide greater insight into development of zinc deficiency in this group of patients. C1 Sinai Hosp, Dept Med, Hoffberger Profess Ctr, Div Gastroenterol, Baltimore, MD 21215 USA. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. RP Dutta, SK (reprint author), Sinai Hosp, Dept Med, Hoffberger Profess Ctr, Div Gastroenterol, Suite 51,2435 W Belvedere Ave, Baltimore, MD 21215 USA. NR 38 TC 16 Z9 17 U1 0 U2 0 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD DEC PY 1998 VL 17 IS 6 BP 556 EP 563 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 143HU UT WOS:000077250100006 PM 9853534 ER PT J AU Slavkin, HC AF Slavkin, HC TI Facing the new century with the National Institute of Dental and Craniofacial Research SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material ID DISEASES C1 NIDCR, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), NIDCR, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 24 TC 2 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 DEC PY 1998 VL 129 IS 12 BP 1760 EP 1763 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 145JT UT WOS:000077368200027 PM 9854930 ER PT J AU Fillenbaum, GG Landerman, LR Simonsick, EM AF Fillenbaum, GG Landerman, LR Simonsick, EM TI Equivalence of two screens of cognitive functioning: The Short Portable Mental Status Questionnaire and the Orientation-Memory-Concentration test SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 50th Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV 07-18, 1997 CL CINCINNATI, OHIO SP Gerontol Soc Amer ID WHITE COMMUNITY RESIDENTS; ALZHEIMERS-DISEASE CERAD; EXAMINATION MMSE; SOCIAL-CLASS; IMPAIRMENT; POPULATION; DEMENTIA; EDUCATION; ASSOCIATION; INSTRUMENTS AB OBJECTIVE: To determine the equivalence of two screens of cognitive functioning: the Short Portable Mental Status Questionnaire (SPMSQ) and the Orientation-Memory-Concentration (OMC) test. DESIGN: The design was cross-sectional and longitudinal. SETTING: Four rural and one urban county in the Piedmont region of North Carolina (n = 3210). PARTICIPANTS: A stratified random cluster sample (n = 3210) of people 68 years of age and older. MEASUREMENTS: SPMSQ and OMC at the fourth wave of the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE); disability, depression, and death measurements from the fourth through seventh waves of EPESE; demographic characteristics. RESULTS: On the SPMSQ and the OMC (r = .80), 15.3% and 38.4%, respectively, of those tested were rated cognitively impaired. Poorer scores were associated with older age, black race, and less education. These associations were attenuated on the dichotomized SPMSQ but not on the OMC. Both measures predicted disability and depressive symptomatology currently and 3 years hence and death. CONCLUSIONS: The SPMSQ and OMC, although highly correlated, are not equivalent. Association with race and education are greater for the OMC, whereas an association with age exists for both measures. The milder level of impairment identified by the OMC increases predictive capacity. C1 Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Fillenbaum, GG (reprint author), Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Box 3003, Durham, NC 27710 USA. FU NIA NIH HHS [N01-AG-1-2102] NR 55 TC 18 Z9 18 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 1998 VL 46 IS 12 BP 1512 EP 1518 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 145EU UT WOS:000077358700004 PM 9848811 ER PT J AU Khan, K Locatis, C AF Khan, K Locatis, C TI Searching through cyberspace: The effects of link cues and correspondence on information retrieval from hypertext on the World Wide Web SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE LA English DT Article ID HYPERMEDIA; ENVIRONMENT; KNOWLEDGE AB The effects of link cues and link correspondence on search performance were investigated using a core hypertext document with external links to other resources on the World Wide Web. Although subjects were to search for information in the core document, cues indicating links were to resources outside the search space did not affect performance. Subjects were not explicitly told the meaning of the cues and the duration of the search tasks was not sufficient for subjects to surmise their meaning. Correspondence of wording in search tasks to wording in links positively affected search efficiency, but not search accuracy. The implications of this finding and the need for further research are discussed. C1 Univ Illinois, Urbana, IL 61801 USA. Natl Lib Med, Bethesda, MD 20894 USA. RP Khan, K (reprint author), Univ Illinois, Urbana, IL 61801 USA. EM khan@nlm.nih.gov; locatis@nlm.nih.gov NR 31 TC 15 Z9 15 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-8231 J9 J AM SOC INFORM SCI JI J. Am. Soc. Inf. Sci. PD DEC PY 1998 VL 49 IS 14 BP 1248 EP 1253 DI 10.1002/(SICI)1097-4571(1998)49:14<1248::AID-ASI3>3.3.CO;2-7 PG 6 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA 141AD UT WOS:000077119700003 ER PT J AU Solowiejczyk, DE Yamada, I Cape, EG Manduley, RA Gersony, WM Jones, M Valdes-Cruz, LM AF Solowiejczyk, DE Yamada, I Cape, EG Manduley, RA Gersony, WM Jones, M Valdes-Cruz, LM TI Simultaneous Doppler and catheter transvalvular pressure gradients across St Jude bileaflet mitral valve prosthesis: In vivo study in a chronic animal model with pediatric valve sizes SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID STARR-EDWARDS; BJORK-SHILEY; HEART-VALVE; HYDRODYNAMIC CHARACTERISTICS; ECHOCARDIOGRAPHIC EVALUATION; HEMODYNAMIC EVALUATION; AORTIC POSITION; TILTING DISK; DISCREPANCIES; INVITRO AB A mixture of valve types has been used in previous in vivo studies to assess the accuracy of Doppler echocardiography compared with catheter-measured pressure gradients across prosthetic mitral valves. However, limited data exist regarding the most commonly used bileaflet mechanical valve. We studied 14 sheep with St Jude Medical mechanical mitral valves. Continuous wave Doppler data were obtained across each of the 3 valve orifices. Hemodynamic data were obtained simultaneously by direct measurements with catheters. Valve sizes commonly used in the pediatric population in the mitral position (23 mm, 25 mm, and 27 mm) were studied. Linear regression analyses of Doppler-predicted versus catheter-measured gradients provided correlation coefficients ranging from 0.75 to 0.91. Agreement analysis demonstrated a scatter of Doppler data about the regression line. Although a reasonably good correlation of Doppler-predicted peak and mean pressure gradients across bileaflet mechanical valves exists in the mitral position, caution Is needed when this method is applied to patients. Doppler overestimation was greatest across the 23-mm valves. Analyses of the specific orifice interrogated demonstrated higher estimated pressure gradients across the central orifice compared with the side orifices. C1 Columbia Presbyterian Med Ctr, Div Pediat Cardiol, New York, NY 10032 USA. NHLBI, Lab Anim Med & Surg, Bethesda, MD 20892 USA. Childrens Hosp Pittsburgh, Div Pediat Cardiol, Pittsburgh, PA 15213 USA. Univ Colorado, Hlth Sci Ctr, Childrens Hosp, Div Pediat Cardiol, Denver, CO USA. RP Solowiejczyk, DE (reprint author), Columbia Presbyterian Med Ctr, Babies & Childrens Hosp, Div Pediat Cardiol, 3959 Broadway, New York, NY 10032 USA. EM des6@columbia.edu NR 27 TC 6 Z9 6 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD DEC PY 1998 VL 11 IS 12 BP 1145 EP 1154 DI 10.1016/S0894-7317(98)80011-4 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 148HJ UT WOS:000077499000008 PM 9923995 ER PT J AU Earm, JH Christensen, BM Frokiaer, J Marples, D Han, JS Knepper, MA Nielsen, S AF Earm, JH Christensen, BM Frokiaer, J Marples, D Han, JS Knepper, MA Nielsen, S TI Decreased aquaporin-2 expression and apical plasma membrane delivery in kidney collecting ducts of polyuric hypercalcemic rats SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID WATER CHANNEL EXPRESSION; INDUCED DOWN-REGULATION; CONCENTRATING DEFECT; HEART-FAILURE; VASOPRESSIN; PERMEABILITY; MECHANISM; RECEPTOR; CLONING; MEDULLA AB Hypercalcemia is frequently associated with a urinary concentrating defect and overt polyuria. The molecular mechanisms underlying this defect are poorly understood. Dysregulation of aquaporin-2 (AQP2), the predominant vasopressin-regulated water channel, is known to be associated with a range of congenital and acquired water balance disorders including nephrogenic diabetes insipidus and states of water retention. This study examines the effect of hypercalcemia on the expression of AQP2 in rat kidney. Rats were treated orally for 7 d with dihydrotachysterol, which produced significant hypercalcemia with a 15 +/- 2% increase in plasma calcium concentration. Immunoblotting and densitometry of membrane fractions revealed a significant decrease in AQP2 expression in kidney inner medulla of hypercalcemic rats to 45.7 +/- 6.8% (n = 11) of control levels (100 +/- 12%, n = 9). A similar reduction in AQP2 expression was seen in cortex (36.9 +/- 4.2% of control levels, n = 6). Urine production increased in parallel, from 11.3 +/- 1.4 to a maximum of 25.3 +/- 1.9 ml/d (P < 0.01), whereas urine osmolality decreased from 2007 +/- 186 mosmol/kg.H2O to 925 +/- 103 mosmol/kg.H2O (P < 0.01). Immunocytochemistry confirmed a decrease in total AQP2 labeling of collecting duct principal cells from kidneys of hypercalcemic rats, and reduced apical labeling. Immunoelectron microscopy demonstrated a significant reduction in AQP2 labeling of the apical plasma membrane, consistent with the development of polyuria. In summary, the results strongly suggest that AQP2 downregulation and reduced apical plasma membrane delivery of AQP2 play important roles in the development of polyuria in association with hypercalcemia. C1 Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus C, Denmark. Univ Aarhus, Inst Expt Clin Res, Aarhus, Denmark. Univ Leeds, Dept Physiol, Leeds LS2 9JT, W Yorkshire, England. Seoul Natl Univ, Dept Internal Med, Seoul, South Korea. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus C, Denmark. RI Han, Jin-Suk/J-5711-2012; OI Christensen, Birgitte Monster/0000-0002-6140-4629 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 48 TC 83 Z9 87 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 1998 VL 9 IS 12 BP 2181 EP 2193 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 142CJ UT WOS:000077182100001 PM 9848772 ER PT J AU Gharagozloo, F Trachiotis, G Wolfe, A Dubree, KJ Cox, JL AF Gharagozloo, F Trachiotis, G Wolfe, A Dubree, KJ Cox, JL TI Pleural space irrigation and modified Clagett procedure for the treatment of early postpneumonectomy empyema SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 03-06, 1998 CL BOSTON, MASSACHUSETTS SP Amer Assoc Thorac Surg ID POST-PNEUMONECTOMY EMPYEMA; BRONCHOPLEURAL FISTULA; COMPLETION PNEUMONECTOMY; EXPERIENCE; MANAGEMENT AB Objective: The incidence of postpneumonectomy empyema is 5 % to 10 %. Approximately half of postpneumonectomy empyemas occur within 4 weeks of pneumonectomy. A bronchopleural fistula is found in more than 80% of the patients. The classic treatment of postpneumonectomy empyema includes parenteral antibiotics, drainage of the pleural space, removal of necrotic tissue, and open pleural packing for many weeks followed by obliteration of the empyema space with antibiotic fluid or muscle. This approach results in prolonged hospitalization, repeated operations, and significant morbidity, As a possible means of decreasing morbidity with the classic treatment of postpneumonectomy empyema, we studied the use of pleural space irrigation in these patients. Method: In a 5-year period, we treated 22 patients with early postpneumonectomy empyema, All patients had a bronchopleural fistula, All patients underwent emergency drainage of the pleural space followed by thoracotomy, debridement of necrotic tissue, closure of the bronchial stump with absorbable monofilament suture, and pleural space irrigation. After a negative Gram stain from the pleural fluid, the pleural space was filled with 2 L of debridement antibiotic solution (DAB solution) (gentamicin 80 mg/L, neomycin 500 mg/L, and polymyxin B 100 mg/L), and the irrigation and drainage catheters were removed. Results: Twenty patients had negative Gram stains on day 9, and 2 patients had a negative Gram stain on day 16, The mean duration of hospitalization was 12.9 +/- 3.4 days. There was no recurrence of empyema or a bronchopleural fistula. Conclusions: Pleural space irrigation followed by obliteration of the pleural space with an antibiotic solution required one surgical procedure and resulted in significantly shorter hospitalization and decreased morbidity in patients with early postpneumonectomy empyema. C1 Georgetown Univ, Med Ctr, Dept Cardiovasc & Thorac Surg, Washington, DC 20007 USA. Natl Canc Inst, Washington, DC USA. RP Gharagozloo, F (reprint author), Georgetown Univ, Med Ctr, Dept Cardiovasc & Thorac Surg, 3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 26 TC 31 Z9 34 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 1998 VL 116 IS 6 BP 943 EP 946 DI 10.1016/S0022-5223(98)70044-3 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 144RQ UT WOS:000077329200010 PM 9832684 ER PT J AU Cahn, MA Selden, CR Auston, I AF Cahn, MA Selden, CR Auston, I TI Web-based resources for retrieving health policy information: NLM and beyond SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article; Proceedings Paper CT 4th Annual Margaret E Mahoney Symposium on the State of the Nations Health CY MAR 23, 1998 CL NEW YORK ACAD MED, NEW YORK, NEW YORK HO NEW YORK ACAD MED AB This paper identifies Web-based resources of interest to the health policy community. Both information useful for developing health policy and information about existing health policy are included. Resources described are classified into three major categories: traditional and grey literature, statistical and epidemiological data, and legal and legislative material. National Library of Medicine (NLM) resources include MEDLINE, DIRLINE, HealthSTAR, HSRProj, and HSTAT. In addition, NLM's National Information Center on Health Services Research and Health Care Technology (NICHSR) has a Web page (http://www.nlm.nih.gov/nichsr/nichsr.html) that provides an extensive Listing of health-policy-related Web sites. Some of the other resources highlighted include those available from the Health Care Financing Administration (HCFA), the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC), the National. Committee for Vital and Health Statistics (NCVHS) and the Library of Congress. C1 Natl Lib Med, Natl Informat Ctr Hlth Serv Res & Hlth Care Techn, Bethesda, MD 20894 USA. RP Cahn, MA (reprint author), Natl Lib Med, Natl Informat Ctr Hlth Serv Res & Hlth Care Techn, 8600 Rockville Pike,Bldg 38,Room 1W22E,Mail Stop, Bethesda, MD 20894 USA. NR 22 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD DEC PY 1998 VL 75 IS 4 BP 826 EP 841 DI 10.1007/BF02344511 PG 16 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 145KH UT WOS:000077369800020 PM 9854243 ER PT J AU Humphreys, BL AF Humphreys, BL TI Meeting information needs in health policy and public health: Priorities for the National Library of Medicine and the National Network of Libraries of Medicine SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article; Proceedings Paper CT 4th Annual Margaret E Mahoney Symposium on the State of the Nations Health CY MAR 23, 1998 CL NEW YORK ACAD MED, NEW YORK, NEW YORK HO NEW YORK ACAD MED AB Those seeking information in health policy and public health are not as well served as those seeking clinical information. Problems inhibiting access to health policy and public health information include the heterogeneity of professionals seeking the information, the distribution of relevant information across disciplines and information sources, scarcity of synthesized information useful to practitioners, lack of awareness of available services or training in their use, and lack of access to information technology or to knowledgeable librarians and information specialists. Since 1990, the National Library of Medicine and the National Network of Libraries of Medicine have been working to enhance information services in health policy and public health through expanding the coverage of the NLM collection, building new databases, and engaging in targeted outreach and training initiatives directed toward segments of the health policy and public health communities. Progress has been made, but more remains to be done. Recommendations arising from the meeting, Accessing Useful Information: Challenges in Health Policy and Public Health, will help NLM and the National Network of Libraries of Medicine to establish priorities and action plans for the next several years. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Humphreys, BL (reprint author), Natl Lib Med, 8600 Rockville Pike,Bldg 38,Room 2W06, Bethesda, MD 20894 USA. NR 3 TC 8 Z9 8 U1 2 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD DEC PY 1998 VL 75 IS 4 BP 878 EP 883 DI 10.1007/BF02344515 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 145KH UT WOS:000077369800024 PM 9854247 ER PT J AU McDermott, MM Liu, KA Guralnik, JM Martin, GJ Criqui, MH Greenland, P AF McDermott, MM Liu, KA Guralnik, JM Martin, GJ Criqui, MH Greenland, P TI Measurement of walking endurance and walking velocity with questionnaire: Validation of the walking impairment questionnaire in men and women with peripheral arterial disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ANKLE-ARM INDEX; EXERCISE PERFORMANCE; DEFINED POPULATION; FUNCTIONAL STATUS; CLAUDICATION; DISABILITY AB Objectives: The Walking Impairment Questionnaire (WIQ) was designed to measure community walking ability in patients with peripheral arterial disease (PAD) and intermittent claudication. We compared the WIQ scores to objective measures of walking in a heterogeneous group of patients with and without PAD. Methods: The study was designed as a cross-sectional study, with the setting in an academic medical center. The subjects were patients with PAD (n = 145) who were identified from a noninvasive vascular laboratory at an academic medical center. The patients without PAD (n = 65) were identified from a general medicine practice. The average number of comorbidities was 2.03 for patients with PAD and 1.52 for patients without PAD. Among the patients with PAD, 28% had classical intermittent claudication symptoms and 55% had exertional leg symptoms other than claudication. The main outcome measures were the WIQ estimates of the patient-reported walking distance and walking speed on a scale of 0 to 100. Walking endurance was measured objectively with the 6-minute walk. Walking velocity was measured with a 4-m walk. PAD and PAD severity were defined with the ankle brachial index. Results: The Spearman rank correlation coefficients (rho) between the WIQ distance score and the 6-minute walk score were 0.557 among patients with PAD (P < .001) and 0.484 among patients without PAD (P < .001). The correlation coefficients between the WIQ speed score and the usual-paced 4-m walk score were 0.528 among patients with PAD (P < .001) and 0.524 among patients without PAD (P < .001). The correlations were not affected by the presence versus the absence of intermittent claudication, by PAD severity, or by the presence of 2 or more versus less than 2 comorbid illnesses. The WIQ scores in the highest and lowest quartiles were the most closely associated with the objective measures of function. Conclusion: The WIQ is a valid measure of community walking ability in a heterogeneous group of patients with and without PAD. The WIQ discriminates best among patients in the highest and the lowest quartiles of walking speed and endurance. C1 Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. RP McDermott, MM (reprint author), Northwestern Univ, Sch Med, Dept Med, 303 E Ohio St,Ste 300, Chicago, IL 60611 USA. RI van Doorn, Louk/G-5326-2010 OI van Doorn, Louk/0000-0003-1493-0973 FU NCRR NIH HHS [RR-00048] NR 22 TC 105 Z9 105 U1 1 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 1998 VL 28 IS 6 BP 1072 EP 1081 DI 10.1016/S0741-5214(98)70034-5 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 148QN UT WOS:000077543600023 PM 9845659 ER PT J AU Ting, YT Wilson, CA Farrell, KB Chaudry, GJ Eiden, MV AF Ting, YT Wilson, CA Farrell, KB Chaudry, GJ Eiden, MV TI Simian sarcoma-associated virus fails to infect Chinese hamster cells despite the presence of functional Gibbon ape leukemia virus receptors SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS; MURINE CELLS; FUSION; GLYCOPROTEINS; REQUIREMENTS; RETROVIRUS; PROTEIN; TYPE-1; SYSTEM; HIV-1 AB We have sequenced the envelope genes from each of the five members of the gibbon ape leukemia virus (GALV) family of type C retroviruses. Four of the GALVs, including GALV strain SEATO (GALV-S), were originally isolated from gibbon apes, whereas the fifth member of this family, simian sarcoma-associated virus (SSAV), was isolated from a woolly monkey and shares 78% amino acid identity with GALV-S, To determine whether these viruses have identical host ranges, we evaluated the susceptibility of several tell lines to either GALV-S or SSAV infection. GALV-S and SSAV have the same host range with the exception of Chinese hamster lung E36 cells, which are susceptible to GALV-S but not SSAV. We used retroviral vectors that differ only in their envelope composition (e.g., they contain either SSAV or GALV-S envelope protein) to show that the envelope of SSAV restricts entry into E36 cells. Although unable to infect E36 cells, SSAV infects GALV-resistant murine cells expressing the E36-derived viral receptor, HaPit2. These results suggest that the receptors present on E36 cells function for SSAV. We have constructed several vectors containing GALV-S/SSAV chimeric envelope proteins to map the region of the SSAV envelope that blocks infection of E36 cells. Vectors bearing chimeric envelopes comprised of the N-terminal region of the GALV-S SU protein and the C-terminal region of SSAV infect E36 cells, whereas vectors containing the N-terminal portion of the SSAV SU protein and C-terminal portion of GALV-S fail to infect E36 cells. This finding indicates that the region of the SSAV envelope protein responsible for restricting SSAV infection of E36 cells lies within its amino-terminal region. C1 NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Cellular Immunol Lab, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Eiden, MV (reprint author), NIMH, Lab Cellular & Mol Regulat, Bldg 36,Room 2A11, Bethesda, MD 20892 USA. EM m_eiden@codon.nih.gov RI Chaudry, Ghulam/F-9761-2011 NR 35 TC 30 Z9 31 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 DEC PY 1998 VL 72 IS 12 BP 9453 EP 9458 PG 6 WC Virology SC Virology GA 137AW UT WOS:000076892100005 PM 9811678 ER PT J AU Wersto, RP Rosenthal, ER Seth, PK Eissa, NT Donahue, RE AF Wersto, RP Rosenthal, ER Seth, PK Eissa, NT Donahue, RE TI Recombinant, replication-defective adenovirus gene transfer vectors induce cell cycle dysregulation and inappropriate expression of cyclin proteins SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS; EPITHELIAL-CELLS; IMMUNE-RESPONSES; AIRWAY EPITHELIA; TRANSGENE EXPRESSION; NASAL EPITHELIUM; FLOW-CYTOMETRY; DNA HISTOGRAMS; TUMOR-CELLS AB First-generation adenovirus (Ad) vectors that had been rendered replication defective by removal of the El region of the viral genome (Delta E1) or lacking the Ad E3 region in addition to El sequences (Delta E1 Delta E3) induced G(2) cell cycle arrest and inhibited traverse across G(1)/S in primary and immortalized human bronchial epithelial cells. Cell cycle arrest was independent of the cDNA contained in the expression cassette and was associated with the inappropriate expression and increase in cyclin A, cyclin B1, cyclin D, and cyclin-dependent kinase p33(cdc2) protein levels. In some instances, infection with Delta E1 or Delta E1 Delta E3 Ad vectors produced aneuploid DNA histogram patterns and induced polyploidization as a result of successive rounds of cell division without mitosis. Cell cycle arrest was absent in cells infected with a second-generation Delta E1Ad vector in which all of the early region E4 except the sixth open reading frame was also deleted. Consequently, E4 viral gene products present in Delta E1 or Delta E1 Delta E3 Ad vectors induce G(2) growth arrest, which may pose new and unintended consequences for human gene transfer and gene therapy. C1 NHLBI, Hematol Branch, NIH, Rockville, MD 20850 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Rockville, MD 20850 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Wersto, RP (reprint author), NHLBI, Hematol Branch, NIH, Room 1B-05,5 Res Court, Rockville, MD 20850 USA. EM werstor@gwgate.nhlbi.nih.gov NR 87 TC 67 Z9 68 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1998 VL 72 IS 12 BP 9491 EP 9502 PG 12 WC Virology SC Virology GA 137AW UT WOS:000076892100009 PM 9811682 ER PT J AU Kiernan, RE Freed, EO AF Kiernan, RE Freed, EO TI Cleavage of the murine leukemia virus transmembrane env protein by human immunodeficiency virus type 1 protease: Transdominant inhibition by matrix mutations SO JOURNAL OF VIROLOGY LA English DT Article ID PFIZER-MONKEY-VIRUS; ENVELOPE GLYCOPROTEIN; CYTOPLASMIC DOMAIN; FUSION ACTIVITY; HOST-RANGE; PARTICLE-PRODUCTION; TERMINAL REGION; GENE-PRODUCT; GAG PROTEIN; CELL-FUSION AB We have identified mutations in the human immunodeficiency virus type 1 (HIV-1) matrix protein (MA) which block infectivity of virions pseudotyped with murine leukemia virus (MuLV) envelope (Env) glycoproteins without affecting infectivity conferred by HIV-1 Env or vesicular stomatitis virus G glycoproteins. This inhibition is very potent and displays a strong transdominant effect; infectivity is reduced more than 100-fold when wild-type and mutant molecular clones are cotransfected at a 1:I ratio. This phenomenon is observed with both ecotropic and amphotropic MuLV Env. The MA mutations do not affect the incorporation of MuLV Env into virions. We demonstrate that in HIV-I virions pseudotyped with MuLV Env, the HIV-I protease (PR) efficiently catalyzes the cleavage of the p15(E) tansmembrane (TM) protein to p12(E). Immunoprecipitation analysis of pseudotyped virions reveals that the mutant MA blocks this HIV-1 PR-mediated cleavage of MuLV TM. Furthermore, the transdominant inhibition exerted by the mutant MA on wild-type infectivity correlates with the relative level of p15(E) cleavage. Consistent,vith the hypothesis that abrogation of infectivity imposed by the mutant MA is due to inhibition of p15(E) cleavage, mutant virions are significantly more infectious when pseudotyped with a truncated p12(E) form of MuLV Env. These results indicate that HIV-1 Gag sequences can influence the viral PR-mediated processing of the MuLV TM Env protein p15(E). These findings have implications for the development of HIV-1-based retroviral vectors pseudotyped with MuLV Env, since p15(E) cleavage is essential far activating membrane fusion and virus infectivity. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Freed, EO (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 307, Bethesda, MD 20892 USA. NR 71 TC 23 Z9 23 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 DEC PY 1998 VL 72 IS 12 BP 9621 EP 9627 PG 7 WC Virology SC Virology GA 137AW UT WOS:000076892100022 PM 9811695 ER PT J AU Graff, J Cha, J Blyn, LB Ehrenfeld, E AF Graff, J Cha, J Blyn, LB Ehrenfeld, E TI Interaction of poly(rC) binding protein 2 with the 5 ' noncoding region of hepatitis A virus RNA and its effects on translation SO JOURNAL OF VIROLOGY LA English DT Article ID RIBOSOME ENTRY SITE; MOUTH-DISEASE VIRUS; A VIRUS; POLIOVIRUS RNA; NONTRANSLATED REGION; 5'-NONCODING REGION; IN-VITRO; INTERNAL INITIATION; RETICULOCYTE LYSATE; SECONDARY STRUCTURE AB Utilization of internal ribosome entry segment (IRES) structures in the 5' noncoding region (5'NCR) of piconavirus RNAs for initiation of translation requires a number of host cell factors whose distribution may vary in different cells and whose requirement may vary for different picornaviruses. We have examined the requirement of the cellular protein poly(rC) binding protein 2 (PCBP2) for hepatitis A virus (HAV) RNA translation. PCBP2 has recently been identified as a factor required for translation and replication of poliovirus (PV) RNA. PCBP2 was shown to be present in FRhK-4 cells, which are permissive for growth of HAV, as it is in HeLa cells, which support translation of HAV RNA but which have not been reported to host replication of the virus. Competition RNA mobility shift assays showed that the 5'NCR of HAV RNA competed for binding of PCBP2 with a probe representing stem-loop IV of the PV 5'NCR. The binding site on HAV RNA was mapped to nucleotides 1 to 157, which includes a pyrimidine-rich sequence. HeLa cell extracts that had been depleted of PCBP2 by passage over a PV stem-loop IV RNA affinity column supported only low levels of HAV RNA translation. Translation activity was restored upon addition of recombinant PCBP2 to the depleted extract. Removal of the 5'-terminal 138 nucleotides of the HAV RNA, or removal of the entire IRES, eliminated the dependence of HAV RNA translation on PCBP2. C1 Univ Calif Irvine, Dept Biochem & Mol Biol, Irvine, CA 92697 USA. RP Graff, J (reprint author), NIAID, LID, Mol Hepatitis Sect, NIH, Bldg 7,Room 200,7 Ctr Dr, Bethesda, MD 20892 USA. EM jgraff@atlas.niaid.nih.gov FU NIAID NIH HHS [AI12387, AI26350] NR 45 TC 54 Z9 57 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 DEC PY 1998 VL 72 IS 12 BP 9668 EP 9675 PG 8 WC Virology SC Virology GA 137AW UT WOS:000076892100027 PM 9811700 ER PT J AU Meng, XJ Halbur, PG Shapiro, MS Govindarajan, S Bruna, JD Mushahwar, IK Purcell, RH Emerson, SU AF Meng, XJ Halbur, PG Shapiro, MS Govindarajan, S Bruna, JD Mushahwar, IK Purcell, RH Emerson, SU TI Genetic and experimental evidence for cross-species infection by swine hepatitis E virus SO JOURNAL OF VIROLOGY LA English DT Article ID UNITED-STATES; MOLECULAR-CLONING; PROTOTYPE STRAIN; BLOOD-DONORS; HEV; ANTIBODY; ISOLATE; SEROREACTIVITY; SEROPREVALENCE; PREVALENCE AB Prior to the recent discovery of the swine hepatitis E virus (swine HEV) in pigs from the midwestern United States, HEV was not considered endemic to this country. Since swine HEV is antigenically and genetically related to human strains of HEV, it was important to characterize this new virus further. The infectivity titer of a pool of swine HEV in pigs was determined in order to prepare a standardized reagent and to evaluate the dose response in pigs. Although the sequence of swine HEV varied extensively from those of most human strains of HEV, it was very closely related to the two strains of human HEV (US-1 and US-2) isolated in the United States. The U.S. strains which were recently recovered from two patients with clinical hepatitis E in the United States shared greater than or equal to 97% amino acid identity with swine HEV in open reading frames 1 and 2. Phylogenetic analyses of different regions of the genome revealed that swine HEV and the U.S. strains grouped together and formed a distinct branch. These results suggested that swine HEV may infect humans. When we inoculated rhesus monkeys and a chimpanzee, experimental surrogates of humans, with swine HEV, the primates became infected. Furthermore, in a reciprocal experiment, specific-pathogen-free pigs were experimentally infected with the US-2 strain of human HEV that is genetically similar to swine HEV. These results provided experimental evidence for cross-species infection by the swine virus. Thus, humans appear to be at risk of infection with swine HEV or closely related viruses. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Iowa State Univ, Coll Vet Med, Dept Vet Diagnost & Prod Anim Med, Ames, IA 50011 USA. Bioqual Inc, Rockville, MD 20850 USA. Univ So Calif, Rancho Los Amigos Med Ctr, Pathol & Clin Labs, Downey, CA 90242 USA. Abbott Labs, Viral Discovery Grp, N Chicago, IL 60064 USA. RP Meng, XJ (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 7,Rm 206,7 Ctr Dr MSC 0740, Bethesda, MD 20892 USA. RI Meng, X.J./B-8769-2009 OI Meng, X.J./0000-0002-2739-1334 NR 46 TC 377 Z9 412 U1 4 U2 13 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 DEC PY 1998 VL 72 IS 12 BP 9714 EP 9721 PG 8 WC Virology SC Virology GA 137AW UT WOS:000076892100032 PM 9811705 ER PT J AU Monao, MCG Jensen, PN Hou, J Durham, LC Major, EO AF Monao, MCG Jensen, PN Hou, J Durham, LC Major, EO TI Detection of JC virus DNA in human tonsil tissue: Evidence for site of initial viral infection SO JOURNAL OF VIROLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; PERIPHERAL-BLOOD LEUKOCYTES; RENAL-TRANSPLANT PATIENTS; HUMAN POLYOMAVIRUS; HUMAN-BRAIN; BK-VIRUS; BONE-MARROW; IMMUNOCOMPETENT INDIVIDUALS; URINE SAMPLES; STROMAL CELLS AB Progressive multifocal leukoencephalopathy is a demyelinating disease of the human central nervous system that results from lytic infection of oligodendrocytes by the polyomavirus JC (JCV). Originally, JCV was thought to replicate exclusively in human glial cells, specifically oligodendrocytes. However, we have recently shown that JCV can replicate in cells of lymphoid origin such as hematopoietic precursor cells, B lymphocytes, and tonsillar stromal cells. To determine whether tonsils harbor JCV, we tested a total of 54 tonsils, 38 from children and 16 from adult donors. Nested PCRs with primer sets specific for the viral T protein and regulatory regions were used for the detection of JCV DNA. JCV DNA was detected in 21 of 54 tonsil tissues, or 39% (15 of 38 children and 6 of 16 adults) by using regulatory-region primers and in 19 of 54 tonsil tissues, or 35% (13 of 38 children and 6 of 16 adults) by using the T-protein primers. The DNA extracted from children's nondissected tonsil tissue, isolated tonsillar lymphocytes; and isolated stromal cells that demonstrated PCR amplification of the JCV regulatory region underwent cloning and nucleotide sequencing. Of the regulatory-region sequences obtained, nearly all contained tandem repeat arrangements. Clones originating from non-dissected tonsil tissue and tonsillar lymphocytes were found to have sequences predominantly of the Mad-1 Prototype strain, whereas the majority of clones from the DNA of tonsillar stromal cells had sequences characteristic of the Mad-8(br) strain of JCV. A few clones demonstrated structures other than tandem repeats but were isolated only from tonsillar lymphocytes. These data provide the first evidence of the JCV genome in tonsil tissue and suggest that tonsils may serve as an initial site of viral infection. 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 5W21, Bethesda, MD 20892 USA. EM eomajor@codon.nih.gov NR 42 TC 165 Z9 168 U1 0 U2 2 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 DEC PY 1998 VL 72 IS 12 BP 9918 EP 9923 PG 6 WC Virology SC Virology GA 137AW UT WOS:000076892100055 PM 9811728 ER PT J AU Robert-Guroff, M Kaur, H Patterson, LJ Leno, M Conley, AJ McKenna, PM Markham, PD Richardson, E Aldrich, K Arora, K Murty, L Carter, L Zolla-Pazner, S Sinangil, F AF Robert-Guroff, M Kaur, H Patterson, LJ Leno, M Conley, AJ McKenna, PM Markham, PD Richardson, E Aldrich, K Arora, K Murty, L Carter, L Zolla-Pazner, S Sinangil, F TI Vaccine protection against a heterologous, non-syncytium-inducing, primary human immunodeficiency virus SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; IMMUNE-RESPONSES; RHESUS MACAQUES; HIV-1 CHALLENGE; CHIMPANZEES; INFECTION; TYPE-1; ADENOVIRUS; ENVELOPE; NEUTRALIZATION AB Vaccine-induced protection of chimpanzees against laboratory-adapted and syncytium-inducing, multiply passaged primary human immunodeficiency virus type 1 (HIV-1) isolates, but not against non-syncytium-inducing, minimally passaged ones, has been demonstrated. Following challenge with such an isolate, HIV-1(5016), we obtained complete protection in one of three chimpanzees previously protected against low- and high-dose HIV-1(SF2) exposures after immunization with an adenovirus-HIV-1(MN) gp160 priming-HIV-1(SF2) gp120 boosting regimen. At challenge, the protected chimpanzee exhibited broad humoral immunity, including neutralizing antibody activity. These results demonstrate the potential of this combination vaccine strategy and suggest that vaccine protection against an HN isolate relevant to infection of people is feasible. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Merck Res Labs, W Point, PA 19486 USA. Adv BioSci Labs Inc, Kensington, NSW 20895, Australia. NYU Med Ctr, New York, NY 10010 USA. Chiron Corp, Emeryville, CA 94608 USA. RP Robert-Guroff, M (reprint author), NCI, Basic Res Lab, NIH, Bldg 37,Room 6B03, Bethesda, MD 20892 USA. EM guroffm@dc37a.nci.nih.gov NR 38 TC 56 Z9 57 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 DEC PY 1998 VL 72 IS 12 BP 10275 EP 10280 PG 6 WC Virology SC Virology GA 137AW UT WOS:000076892100102 PM 9811775 ER PT J AU Mahieux, R Chappey, C Georges-Courbot, MC Dubreuil, G Mauclere, P Georges, A Gessain, A AF Mahieux, R Chappey, C Georges-Courbot, MC Dubreuil, G Mauclere, P Georges, A Gessain, A TI Simian T-cell lymphotropic virus type 1 from Mandrillus sphinx as a simian counterpart of human T-cell lymphotropic virus type 1 subtype D SO JOURNAL OF VIROLOGY LA English DT Article ID BABOON PAPIO-HAMADRYAS; I STLV-I; LEUKEMIA-VIRUS; PHYLOGENETIC ANALYSIS; CENTRAL-AFRICA; INTERSPECIES TRANSMISSION; HTLV-I; HUMAN-POPULATIONS; SEQUENCE; DISTINCT AB A recent serological and molecular survey of a semifree-ranging colony of mandrills (Mandrillus sphinx) living in Gabon, central Africa, indicated that 6 of 102 animals, all males, were infected with simian T-cell lymphotropic virus type 1 (STLV-1). These animals naturally live in the same forest area as do human inhabitants (mostly Pygmies) who are infected by the recently described human T-cell lymphotropic virus type 1 (HTLV-I) subtype D. We therefore investigated whether these mandrills were infected with an STLV-1 related to HTLV-1 subtype D. Nucleotide and/or amino acid sequence analyses of complete or partial long terminal repeat (LTR), env, and rex regions showed that HTLV-1 subtype D-specific mutations were found in three of four STLV-1-infected mandrills, while the remaining monkey was infected by a different STLV-1 subtype. Phylogenetic studies conducted on the LTR as well as on the env gp21 region showed that these three new STLV-1 strains from mandrills fall in the same monophyletic clade, supported by high bootstrap values, as do the sequences of HTLV-1 subtype D. These data show, for the first time, the presence of the same subtype of primate T-cell lymphotropic virus type 1 in humans and wild-caught monkeys originating from the same geographical area. This strongly supports the hypothesis that mandrills are the natural reservoir of HTLV-1 subtype D, although the possibility that another monkey species living in the same area could be the original reservoir of both human and mandrill viruses cannot be excluded. Due to the quasi-identity of both human and monkey viruses, interspecies transmission episodes leading to such a clade may have occurred recently. C1 Inst Pasteur, Unite Epidemiol Virus Oncogenes, F-75724 Paris 15, France. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. Ctr Pasteur Cameroun, Yaounde, Cameroon. Ctr Int Rech Med Franceville, Franceville, Gabon. RP Gessain, A (reprint author), Inst Pasteur, Unite Oncol Virale, 28 Rue Docteur Roux, F-75724 Paris 15, France. NR 34 TC 67 Z9 67 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 DEC PY 1998 VL 72 IS 12 BP 10316 EP 10322 PG 7 WC Virology SC Virology GA 137AW UT WOS:000076892100110 PM 9811783 ER PT J AU Bondy, CA Nelson, LM Kalantaridou, SN AF Bondy, CA Nelson, LM Kalantaridou, SN TI The genetic origins of ovarian failure SO JOURNAL OF WOMENS HEALTH LA English DT Review ID FOLLICLE-STIMULATING-HORMONE; RECEPTOR GENE; BETA-SUBUNIT; MUTATION; DEFECTS; MOUSE; MICE; INFERTILITY; DISRUPTION; MENOPAUSE AB Premature ovarian failure (POF) is a condition characterized by cessation of ovarian function before the age of 40. The recent meeting at the National Institute of Child Health and Human Development brought together experts from diverse disciplines to share current perspectives on the genetic and physiologic origins of POF, with the idea that insights gained from these studies may provide important clues about the regulation of normal ovarian aging and perhaps aging processes in general. It was suggested that several murine genes, including Zfx, c = kit, and the kit ligand, should be fertile candidates for investigation of the etiology of POF in human families. The specific roles of the human DIA and FMR1 gene products in germ cell development need clarification in murine models, and there are more as yet unidentified genes residing on the long arm of the X chromosome that are also implicated in the regulation of human ovarian function. Genes acting at later stages of oocyte or ovarian follicle function, such as gonadotropin hormones and receptors, are responsible for POF in some women. POF has been found to be a heterogeneous disorder, the dissection of which offers promising insights into mechanisms governing germ cell origination, migration, and proliferation, meiotic mechanisms, and factors governing oocyte maturation and survival. C1 NIH, NICHHD, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NIH, NICHHD, 10 Ctr Dr MSC 1862,Bldg 10,Room 10N262, Bethesda, MD 20892 USA. NR 23 TC 15 Z9 17 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1059-7115 J9 J WOMENS HEALTH JI J. Womens Health PD DEC PY 1998 VL 7 IS 10 BP 1225 EP 1229 DI 10.1089/jwh.1998.7.1225 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 160QD UT WOS:000078241700013 PM 9929855 ER PT J AU Emanuel, EJ AF Emanuel, EJ TI The blossoming of bioethics at NIH SO KENNEDY INSTITUTE OF ETHICS JOURNAL LA English DT Article AB The establishment of the Department of Clinical Bioethics at the Warren G. Magnuson Clinical Center of the National Institutes of Health (NIH) has coincided with a burgeoning of interest and activity related to bioethical issues at NIH. The department has precipitated a reexamination and revitalization of existing bioethics activities in the Clinical Center and has launched new programs especially in the areas of education and research. In addition, the department contributes to the work of others throughout NIH who address bioethical issues. C1 NIH, Warren G Magnuson Clin Ctr, Dept Bioeth, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Bioeth, Bethesda, MD 20892 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1054-6863 J9 KENNEDY INST ETHIC J JI Kennedy Inst. Ethics J. PD DEC PY 1998 VL 8 IS 4 BP 455 EP 466 DI 10.1353/ken.1998.0030 PG 12 WC Ethics; Philosophy; Social Issues SC Social Sciences - Other Topics; Philosophy; Social Issues GA 191ZF UT WOS:000080051700006 PM 11657322 ER PT J AU Zheng, F Striker, GE Esposito, C Lupia, E Striker, LJ AF Zheng, F Striker, GE Esposito, C Lupia, E Striker, LJ TI Strain differences rather than hyperglycemia determine the severity of glomerulosclerosis in mice SO KIDNEY INTERNATIONAL LA English DT Article DE sclerosis; diabetes; susceptibility to GS; insulin; nephropathy; glomerular lesions ID FAWN-HOODED RAT; DIABETIC NEPHROPATHY; GENETIC SUSCEPTIBILITY; GLOMERULAR HYPERTROPHY; MESSENGER-RNA; PROTEINURIA; MOUSE; HYPERTENSION; EXPRESSION; INSULIN AB Background. We reported that ROP, but not C57, mice were prone to glomerulosclerosis (GS) after nephron reduction (J Clin Invest 97:1242, 1996). Methods. In this study, we induced diabetes in ROP and C57 mice to determine if the glomerulosclerotic response was stimulus specific. We used the oligosyndactyly mutation (Os), to produce a congenital 50% reduction in nephron number. Stable hyperglycemia was induced by streptozotocin and mice were maintained for 12 weeks without insulin treatment. Results. Glomerular hypertrophy occurred in diabetic ROP +/+ and C57 +/+ mice, but glomeruli of diabetic ROP +/+ mice had 1.92-fold higher laminin B1 and 1.5-fold higher tenascin mRNA levels than diabetic C57 +/+ mice. Diabetic ROP Os/+ mice had severe glomerulosclerosis with arteriolar and tubulointerstitial lesions while there was only moderate mesangial sclerosis in diabetic C57 Os/+ mice. Glomerular size was increased in all non-diabetic Os/+ mice. It was further increased in diabetic ROP Os/+ mice, but not in diabetic C57 Os/+ mice. Glomerular mRNA levels were higher in diabetic ROP OS/+ than in diabetic C57 OS/+ mice [alpha 1 (IV) collagen 3.2-fold, laminin B1 2.1-fold, and tenascin 1.6-fold]. Conclusion. Overall, our data further support the hypothesis that the susceptibility to glomerulosclerosis is inherited, and suggest that hyperglycemia serves principally as a triggering event in the development of diabetic nephropathy. Since the acceleration of diabetic nephropathy by nephron reduction was also largely strain dependent, it appears that the propensity to glomerulosclerosis is a general renal response and is not stimulus specific. C1 Univ Miami, Sch Med, Dept Med, Div Nephrol,Lab Renal Cell Biol, Miami, FL 33101 USA. NIDDK, Renal Cell Biol Sect, NIH, Bethesda, MD USA. Ivax Corp, Ivax Res Inst, Miami, FL USA. RP Striker, LJ (reprint author), Univ Miami, Sch Med, Dept Med, Div Nephrol,Lab Renal Cell Biol, POB 016910 R126, Miami, FL 33101 USA. NR 36 TC 65 Z9 65 U1 1 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1998 VL 54 IS 6 BP 1999 EP 2007 DI 10.1046/j.1523-1755.1998.00219.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 141EE UT WOS:000077129000019 PM 9853264 ER PT J AU Nelson, RG Morgenstern, H Bennett, PH AF Nelson, RG Morgenstern, H Bennett, PH TI An epidemic of proteinuria in Pima Indians with Type 2 diabetes mellitus SO KIDNEY INTERNATIONAL LA English DT Article DE proteinuria; incidence rates; time-dependent proportional hazards analysis; generalized additive models; Pima Indians; heritage; blood pressure ID URINARY ALBUMIN EXCRETION; RENAL-DISEASE; PERSISTENT PROTEINURIA; DECLINING INCIDENCE; IDDM PATIENTS; RISK-FACTORS; NEPHROPATHY; OBESITY; NIDDM; MICROALBUMINURIA AB Background. The risk of proteinuria in Type 1 diabetes declined greater than or equal to 30% over the past 50 years, and improvements in metabolic control are believed to be largely responsible. Little is known about secular changes in the risk of proteinuria in Type 2 diabetes. Methods. We examined trends in the incidence rate of proteinuria in Pima Indians greater than or equal to 20 years of age with diabetes diagnosed between January 1, 1955 and December 31, 1994. Results. Among 1305 initially non-proteinuric diabetic subjects, 433 developed proteinuria during a median follow-up of 8.0 years (range 0.8 to 30.2 years). With subjects with diabetes diagnosed between 1955 and 1964 serving as the reference group, the rate of proteinuria was similar (rate ratio 1.0; 95% confidence interval, 0.79 to 1.3) in the cohort diagnosed between 1965 and 1974, 1.5 times as high (95% confidence interval, 1.1 to 2.0) in the cohort diagnosed between 1975 and 1984, and 1.9 times as high (95% confidence interval, 1.1 to 3.0) in the cohort diagnosed between 1985 and 1994, after adjusting for potential confounders in a generalized additive proportional hazards model. Between the first and last cohorts, plasma glucose concentration declined, on average, by 17% (P = 0.0001) and the mean arterial pressure declined by 11% (P = 0.0001). Conclusions. The incidence rate of proteinuria in Pima Indians with Type 2 diabetes increased nearly twofold in the last 40 years, despite improvements in plasma glucose and blood pressure. Rapidly changing environmental or behavioral factors must play an important role in the pathogenesis of diabetic renal disease in this population. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. RP Nelson, RG (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Nelson, Robert/B-1470-2012 NR 51 TC 37 Z9 43 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1998 VL 54 IS 6 BP 2081 EP 2088 DI 10.1046/j.1523-1755.1998.00191.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 141EE UT WOS:000077129000028 PM 9853273 ER PT J AU Vaitukaitis, JL AF Vaitukaitis, JL TI Animal models of human disease for the 21st century SO LABORATORY ANIMAL SCIENCE LA English DT Article; Proceedings Paper CT Registry of Comparative Pathology Symposium 1997 - Animal Models of Human Disease for the 21st-Century CY DEC 08-10, 1997 CL WASHINGTON, D.C. C1 NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Vaitukaitis, JL (reprint author), NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD DEC PY 1998 VL 48 IS 6 BP 562 EP 564 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 157DC UT WOS:000078043600004 PM 10090076 ER PT J AU Teruya-Feldstein, J Zauber, P Setsuda, JE Berman, EL Sorbara, L Raffeld, M Tosato, G Jaffe, ES AF Teruya-Feldstein, J Zauber, P Setsuda, JE Berman, EL Sorbara, L Raffeld, M Tosato, G Jaffe, ES TI Expression of human herpesvirus-8 oncogene and cytokine homologues in an HIV-seronegative patient with multicentric Castleman's disease and primary effusion lymphoma SO LABORATORY INVESTIGATION LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; PROTEIN-COUPLED RECEPTOR; EPSTEIN-BARR-VIRUS; KAPOSIS-SARCOMA; MULTIPLE-MYELOMA; BCL-2 HOMOLOG; CELLS; KSHV; ENCODES AB Human herpesvirus-8 (HHV-8) has been described in association with two lymphoproliferative disorders: one benign, multicentric Castleman's disease (MCD), and one malignant, primary effusion lymphoma (PEL). The factors that lead to malignant transformation of lymphoid cells are unknown, although most cases of PEL also are positive for EBV, suggesting a role for EBV as a cofactor in malignant transformation. We encountered a rare case of an HHV-8-associated MCD, followed by the development of an HHV-8-positive pleural PEL and a gastric large cell lymphoma in an HIV-seronegative male patient. The lesions were negative for Epstein-Barr virus (EBV). The combination of these diverse HHV-8-associated lymphoproliferative disorders in a single patient afforded us the ability to study potential differences in gene expression in these conditions. HHV-8 DNA was demonstrated by PCR in lymphoid tissues involved by MCD and PEL. By reverse transcriptase-PCR, HHV-8-related transcripts, including vG-coupled protein receptor, vbcl2, vcyclin D, vIL-6, vMIPI, and vMIPII, were detected in the PEL from the pleural cavity and the gastric lymphoma, whereas these transcripts, except for vIL-6, were not detected in a lymph node biopsy with MCD. Expression of hIL-10 was weak in the PEL from the pleural cavity, and expression of hIL-6 was undetectable in all three lesions. These data suggest that vIL-6 may be integral to the pathogenesis of MCD, whereas other viral transcripts that encode oncogene and chemokine homologues are important for HHV-8 tumorigenicity. C1 NCI, Hematol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. St Barnabas Med Ctr, Livingston, NJ USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Jaffe, ES (reprint author), NCI, Hematol Sect, Pathol Lab, NIH, Bldg 10,Room 2N202,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. NR 30 TC 65 Z9 66 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 1998 VL 78 IS 12 BP 1637 EP 1642 PG 6 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 153YF UT WOS:000077860600022 PM 9881964 ER PT J AU Dent, P Jarvis, WD Birrer, MJ Fisher, PB Schmidt-Ullrich, RK Grant, S AF Dent, P Jarvis, WD Birrer, MJ Fisher, PB Schmidt-Ullrich, RK Grant, S TI The roles of signaling by the p42/p44 mitogen-activated protein (MAP) kinase pathway; a potential route to radio- and chemo-sensitization of tumor cells resulting in the induction of apoptosis and loss of clonogenicity SO LEUKEMIA LA English DT Review DE MAP kinase; SAP kinase; growth factor; proliferation; differentiation; apoptosis; cyclin kinase inhibitor protein ID COLONY-STIMULATING FACTOR; MYELOID-LEUKEMIA CELLS; NERVE GROWTH-FACTOR; RADIATION-INDUCED APOPTOSIS; TERNARY COMPLEX FACTORS; NIH 3T3 CELLS; CYCLE ARREST; IONIZING-RADIATION; PLASMA-MEMBRANE; RAF-1 PROTEIN AB During the last 10 years, multiple signal transduction pathways within cells have been discovered. These pathways have been linked to the regulation of many diverse cellular events such as proliferation, senescence, differentiation and apoptosis. This review will focus upon the many roles of signaling by the p42/p44 mitogen-activated protein (MAP) kinase pathway. Recent evidence suggests that signaling by the MAP kinase pathway can both enhance proliferation by increased expression of molecules such as cyclin D1, but also cause growth arrest by increased expression of molecules such as the cyclin kinase inhibitor protein p21(Cip-1/MDA6/WAF1). These differential effects on growth have been correlated to the amplitude and duration of the MAP kinase activity signal. Furthermore several laboratories are reporting data suggesting that inhibition of the MAP kinase pathway, as well as a family of upstream MAP kinase activators, the protein kinase C family, represent an important route to both radio- and chemo-sensitization of tumor cells. Herein, we describe the historical discovery and characterization of the MAP kinase pathway. In addition we describe potential mechanisms by which inhibition of protein kinase C, the MAP kinase pathway, and potentially Of p21(Cip-1/MDA6/WAF1) expression, may alter the sensitivities of leukemic and carcinoma cells to cytotoxic insults, leading to increased apoptosis and toss of clonogenicity. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Med, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Microbiol, Richmond, VA 23298 USA. NCI, Biomarkers Branch, Div Clin Sci, Rockville, MD USA. Columbia Univ Coll Phys & Surg, Dept Pathol & Urol, New York, NY 10032 USA. RP Dent, P (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, 401 Coll St, Richmond, VA 23298 USA. FU NCI NIH HHS [R01-CA65896, P01-CA72955]; NIDDK NIH HHS [R01-DK52825] NR 119 TC 90 Z9 96 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 1998 VL 12 IS 12 BP 1843 EP 1850 DI 10.1038/sj.leu.2401222 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 148YY UT WOS:000077563400001 PM 9844914 ER PT J AU Rozemuller, H Terpstra, W Rombouts, EJC Lawler, M Byrne, C FitzGerald, DJP Kreitman, RJ Wielenga, JJ Lowenberg, B Touw, IP Hagenbeek, A Martens, ACM AF Rozemuller, H Terpstra, W Rombouts, EJC Lawler, M Byrne, C FitzGerald, DJP Kreitman, RJ Wielenga, JJ Lowenberg, B Touw, IP Hagenbeek, A Martens, ACM TI GM-CSF receptor targeted treatment of primary AML in SCID mice using Diphtheria toxin fused to huGM-CSF SO LEUKEMIA LA English DT Article DE Diphtheria toxin GM-CSF fusion protein; AML; SCID mouse ID ACUTE MYELOID-LEUKEMIA; COLONY-STIMULATING FACTOR; COMBINED IMMUNODEFICIENT MICE; ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN HEMATOPOIETIC-CELLS; ACUTE MYELOCYTIC-LEUKEMIA; POLYMERASE CHAIN-REACTION; FUSION PROTEIN; BONE-MARROW; PSEUDOMONAS EXOTOXIN AB The severe combined immunodeficient (SCID) mouse model may be used to evaluate new approaches for the treatment of acute myeloid leukemia (AML). We have previously demonstrated the killing of SCID mouse leukemia initiating cells by in vitro incubation with human GM-CSF fused to Diphtheria toxin (DT-huGM-CSF). In this report, we show that in vivo treatment with DI-huGM-CSF eliminates AML growth in SCID mice. Seven cases of AML were studied. SCID mice were treated intraperitoneally with the maximally tolerated dose of 75 mu g/kg/day for 7 days. Antileukemic efficacy was determined at days 40 and 80 after transplantation, by enumerating the percentages of human cells in SCID bone marrow using flow cytometry and short tandem repeat polymerase chain reaction (STR-PCR) analysis. Four out of seven AML cases were sensitive to in vivo treatment with DT-huGM-CSF at both evaluation time points. In three of these cases, elimination of human cells was demonstrated by flow cytometry and STR-PCR. One AML case showed moderate sensitivity for DT-huGM-CSF, and growth of the two remaining AML cases was not influenced by DT-huGM-CSF. Sensitivity was correlated with GM-CSFR expression. Our data show that DT-huGM-CSF can be used in vivo to reduce growth of AML and warrant further development of DT-I huGM-CSF for the treatment of human AML. C1 Univ Utrecht Hosp, Dept Haematol, NL-3508 GA Utrecht, Netherlands. Erasmus Univ, Inst Hematol, Rotterdam, Netherlands. Dr Daniel Den Hoed Canc Ctr, NL-3008 AE Rotterdam, Netherlands. Sir Patrick Duns Res Labs, Dept Haematol & Oncol, Dublin, Ireland. NCI, Mol Biol Lab, DCBDC, Bethesda, MD 20892 USA. RP Martens, ACM (reprint author), Univ Utrecht Hosp, Dept Haematol, Room G03-647,POB 85500, NL-3508 GA Utrecht, Netherlands. NR 53 TC 6 Z9 6 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 1998 VL 12 IS 12 BP 1962 EP 1970 DI 10.1038/sj.leu.2401205 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 148YY UT WOS:000077563400013 PM 9844926 ER PT J AU Yongbi, MN Branch, CA Helpern, JA AF Yongbi, MN Branch, CA Helpern, JA TI Perfusion imaging using FOCI RF pulses SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE FAIR; FOCI; hyperbolic secant; perfusion; slice profile ID RECOVERY FAIR TECHNIQUE; CEREBRAL BLOOD-FLOW; MAGNETIC-RESONANCE; ARTERIAL WATER; NMR-SPECTROSCOPY; BRAIN PERFUSION; SPIN INVERSION; FREQUENCY; SLICE AB Pulsed arterial spin-tagging techniques for perfusion measurements (e.g., echo planar MR imaging and signal targeting with alternating radiofrequency (EPISTAR), flow-sensitive alternating inversion recovery (FAIR), quantitative imaging of perfusion using a single subtraction (QUIPPS), uninverted FAIR (UNFAIR)) generally use hyperbolic secant (HS) pulses for spin inversion, The performance of these techniques depends on the inversion efficiency, as well as the sharpness of the slice profiles. Frequency offset corrected inversion (FOCI) pulses, a recently proposed HS variant, can provide slice profiles with edges that can be up to 10 times sharper than those obtained with conventional HS pulses, In this communication, the implementation and application of the C-shape FOCI pulse for perfusion imaging in rat brain with the FAIR technique is summarized. Despite providing a more rectangular slice profile than a conventional HS pulse, it is demonstrated both theoretically and experimentally that the FAIR perfusion signal is not increased by using a FOCI tagging pulse, However, the use of a FOCI inversion pulse is shown to significantly minimize static signal subtraction errors that are common with conventional HS pulses. Finally, the suitability of the pulse for perfusion studies is demonstrated, in vivo, on rat brain. C1 Nathan S Kline Inst Psychiat Res, Ctr Adv Brain Imaging, Orangeburg, NY 10962 USA. Albert Einstein Coll Med, Dept Radiol & Neurosci, New York, NY USA. NYU, Sch Med, Dept Psychiat & Radiol, New York, NY USA. RP Yongbi, MN (reprint author), NIH, Lab Diagnost Radiol Res, Room BIN256,Bldg 10, Bethesda, MD 20892 USA. NR 18 TC 27 Z9 29 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD DEC PY 1998 VL 40 IS 6 BP 938 EP 943 DI 10.1002/mrm.1910400622 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 141MP UT WOS:000077148000021 PM 9840841 ER PT J AU Qi, CF Bonhomme, F Buckler-White, A Buckler, C Orth, A Lander, MR Chattopadhyay, SK Morse, HC AF Qi, CF Bonhomme, F Buckler-White, A Buckler, C Orth, A Lander, MR Chattopadhyay, SK Morse, HC TI Molecular phylogeny of Fv-1 SO MAMMALIAN GENOME LA English DT Article ID MURINE LEUKEMIA VIRUSES; LOCUS AFFECTING RESISTANCE; ENDOGENOUS RETROVIRUS; RESTRICTION GENE; HOUSE MOUSE; SEQUENCE; MICE; CONSTRUCTION; RADIATION; EVOLUTION AB Alleles at the Fv-1 gene of inbred mice confer resistance to infection and spread of vertically or horizontally transmitted murine leukemia viruses (MuLV). The nucleotide sequence of Fv-1 bears similarity to the gag of a human endogenous retrovirus, HERV-L, but is more closely related to the gag-coding sequence of a newly described class of HERV-L-related mouse endogenous retroviruses designated MuERV-L. Both observations suggest an origin of Fv-1 from endogenous gag sequences. The molecular definition of Fv-1 provided an opportunity to determine the phylogeny of the gene among wild mice and its relation to MuERV-L. PCR primers, chosen to include most of the coding region of Fv-1 for both the n and b alleles, were used to amplify sequences from animals of the genus Mus, which were then sequenced. Closely related products were obtained from almost all animals examined that evolved after the separation from Rattus, in which the homologous gene was shown to be absent. A phylogenetic tree generated with Fv-1 sequence data differs noticeably from that developed with sequence data from other genes. In addition, nonsynonymous changes were found to be present twice as frequently as synonymous changes, a fact that departs from the standard behavior of a structural gene. These observations suggest that the Fv-1 gene may have been subjected to possible horizontal transfers as well as to positive Darwinian selection. C1 NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. Univ Montpellier 2, Lab Genome & Populat, Montpellier, France. Georgetown Univ, Sch Med, Washington, DC USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Morse, HC (reprint author), NIAID, Immunopathol Lab, NIH, Bldg 7,Room 304,MSC 0760, Bethesda, MD 20892 USA. RI Bonhomme, Francois/C-6290-2012; OI Bonhomme, Francois/0000-0002-8792-9239; Morse, Herbert/0000-0002-9331-3705 NR 26 TC 36 Z9 36 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD DEC PY 1998 VL 9 IS 12 BP 1049 EP 1055 DI 10.1007/s003359900923 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 155FD UT WOS:000077934900023 PM 9880676 ER PT J AU Forlino, A Keene, DR Schmidt, K Marini, JC AF Forlino, A Keene, DR Schmidt, K Marini, JC TI An alpha 2(I) glycine to aspartate substitution is responsible for the presence of a kink in type I collagen in a lethal case of Osteogenesis Imperfecta SO MATRIX BIOLOGY LA English DT Article DE extracellular matrix; kink; Osteogenesis Imperfecta ID TRIPLE-HELICAL DOMAIN; N-PROTEINASE; CYSTEINE; PROCOLLAGEN; CHAIN; RNA; FIBROBLASTS; MUTATION; MOLECULE; MATRIX AB Type I collagen synthesized by cultured skin fibroblasts was analyzed biochemically and molecularly to characterize the defect in a patient affected by lethal Osteogenesis Imperfecta. The SDS-Urea-PAGE of procollagen and collagen revealed a broad alpha 1(I) band, a normal alpha 2(I) and another alpha 2(I) band migrating equidistant between al and a2. When synthesized in the presence of alpha alpha'-dipyridyl, an inhibitor of prolyl and lysyl hydroxylation, procollagen and collagen of media and cell layers contained both normal and slower alpha 2(I), but only normal alpha 1(I). The persistence of the two forms of alpha 2(I) chains suggested a mutation in a COL1A2 gene. CNBr cleavage of collagen yielded overmodified alpha 1(I) CB3 and CB7 peptides and delayed migration of the alpha 2(I) CB3-5 peptide. A delayed CB3-5 was also found after alpha,alpha'-dipyridyl treatment. These data localized the mutation between aa 353 and 551 in alpha 2(I) (CB3-5). Sequencing the subcloned alleles in this region revealed a G-->A transition at nt 1671 in one allele, changing Gly 421 to Asp in an alpha 2(I) chain. The mutation was demonstrated to occur on the paternally derived allele, using a common G-->A polymorphism at alpha 2(I) nt 1585 and by the presence of a rare variant, Arg618-->Gln (Phillips et al., 1990), in the paternal genomic DNA and the proband's mutant allele. Procollagen processing was normal. The T-m of the slow alpha 2(I) collagen was 2 degrees C lower than the control, indicating decreased triple helix stability. Mutant collagen was incorporated in the extracellular matrix deposited by cultured fibroblasts. The dramatic delay in alpha 2(I) electrophoretic mobility must be induced by the Gly-->Asp substitution, since the Arg-->Gln variant causes only mild electrophoretic delay. Substantial delay in gel mobility even in the absence of overmodification suggested the presence of a kink in the mutated alpha 2(I) chains. Rotary shadowing electron microscopy of secreted fibroblast procollagen confirmed the presence of a kink in the region of the helix containing the glycine substitution. The kinking of the collagen helix occurs in the absence of dimer formation. Kinking may interfere with normal helix folding, as well as with the interactions of collagen fibrils with the collagenous and non-collagenous extracellular matrix proteins. C1 NICHD, SCTD, HDB, NIH, Bethesda, MD 20892 USA. Shriners Hosp Children, Portland, OR USA. Rockford Mem Hosp, Rockford, IL USA. RP Marini, JC (reprint author), NICHD, SCTD, HDB, NIH, Bldg 10,Room 9S241,10 Ctr Dr,MSC-1830, Bethesda, MD 20892 USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 20 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD DEC PY 1998 VL 17 IS 8-9 BP 575 EP 584 DI 10.1016/S0945-053X(98)90109-3 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168RA UT WOS:000078705300004 PM 9923651 ER PT J AU Cannon, RO AF Cannon, RO TI Can measures of coronary dynamics explain chest pain without coronary artery disease? SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID RISK-FACTORS; ENDOTHELIAL DYSFUNCTION; RESISTANCE VESSELS; ANGINA-PECTORIS; SYNDROME-X; ANGIOGRAMS C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B-15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD DEC PY 1998 VL 73 IS 12 BP 1226 EP 1228 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 147ME UT WOS:000077486300015 PM 9868424 ER PT J AU Yenbutr, P Hilakivi-Clarke, L Passaniti, A AF Yenbutr, P Hilakivi-Clarke, L Passaniti, A TI Hypomethylation of an exon I estrogen receptor CpG island in spontaneous and carcinogen-induced mammary tumorigenesis in the rat SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE methylation; estrogen receptor; tumors; rat; age ID BREAST-CANCER CELLS; DNA METHYLATION; GENE; TUMORS; MICE; FAT AB Loss of methylation at a CpG island in exon I of the rat ER gene was observed in 48% of the spontaneous mammary tumors in old female Wistar rats and 22% of the contralateral normal mammary tissues. The majority of the methylation losses were total. Similarly, 50% of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in young Sprague-Dawley rats exhibited a partial or total loss of methylation at this site, while all normal mammary tissues in young rats were fully methylated. Loss of ER methylation also increased with age in normal mammary tissues of tumor-free rats approaching 12.5% in middle-aged and 43% in old rats. In addition, 66% of mammary glands obtained from young rats that are subsequently at an increased risk to develop breast cancer due to manipulation of in utero dietary fat intake, exhibited methylation loss while no methylation changes were observed in rats at no increased risk for breast cancer. Therefore, the loss of ER methylation is more extensive in mammary glands of rats at high than low breast cancer risk, in old than young, and in mammary tumors than in normal tissues. The data suggest that hypomethylation of a growth-associated ER gene may be a common event in mammary tumorigenesis in the rat and may be of predictive value as a marker of increased breast cancer risk in aged individuals. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NIA, Biol Chem Lab, Gerontol Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA. Georgetown Univ, Sch Med, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. RP Passaniti, A (reprint author), NIA, Biol Chem Lab, Gerontol Res Ctr, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 21 TC 18 Z9 19 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD DEC 1 PY 1998 VL 106 IS 1-2 BP 93 EP 102 DI 10.1016/S0047-6374(98)00093-1 PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 150TG UT WOS:000077680900003 PM 9883975 ER PT J AU Jones, EA Basile, AS AF Jones, EA Basile, AS TI Does ammonia contribute to increased GABA-ergic neurotransmission in liver failure? SO METABOLIC BRAIN DISEASE LA English DT Article; Proceedings Paper CT Hannover Consensus Conference on Pathophysiology of Hepatic Encephalopathy CY MAY, 1997 CL HANNOVER, GERMANY ID BENZODIAZEPINE RECEPTOR LIGANDS; GAMMA-AMINOBUTYRIC-ACID; FULMINANT HEPATIC-FAILURE; VISUAL EVOKED-POTENTIALS; ANIMAL-MODEL; RABBIT MODEL; HYPERAMMONEMIC SYNDROMES; PREGNENOLONE-SULFATE; BRAIN CONCENTRATIONS; ELEVATED LEVELS AB The ammonia and GABAergic neurotransmission hypotheses of the pathogenesis of hepatic encephalopathy (HE) have appeared to be unrelated and perhaps mutually exclusive. Observations in animal models of fulminant hepatic failure, that are consistent with increased GABAergic inhibitory neurotransmission contributing to the manifestations of HE, include: (i) abnormal visual evoked potential waveforms that resemble those induced by GABA(A)/benzodiazepine (BZ) receptor complex agonists; (ii) GABA(A)/BZ receptor complex antagonist-induced ameliorations of encephalopathy; (iii) increased resistance to drugs which decrease GABAergic tone; and (iv) hypersensitivity of CNS neurons to depression by GABA(A)/BZ receptor complex agonists. Mechanisms of increased GABAergic tone in HE may include the following: (i) increased brain concentrations of natural BZs; and (ii) increased GABA concentrations in synaptic clefts, possibly due to increased blood-brain-barrier permeability to GABA and a decrease in GABA(B) receptor density. Both neuroelectrophysiological and behavioral data indicate that ammonia concentrations in the range 0.75-2 mM induce increased excitatory neurotransmission. In contrast, recently, ammonia concentrations in the range 0.15-0.75 mM, i.e. concentrations that commonly occur in plasma in precoma HE, have been shown: (i) to increase GABA-induced chloride current in cultured neurons; and (ii) to enhance synergistically the binding of GABA(A)/BZ receptor agonists. In addition, increased ammonia concentrations enhance synthesis of neurosteroids in astrocytes, and some neurosteroids potently augment GABAergic neurotransmission. Thus, the modestly elevated concentrations of ammonia, that commonly occur in liver failure, may contribute to the manifestations of HE by enhancing GABAergic inhibitory neurotransmission. This concept appears to unify the ammonia and GABAergic neurotransmission hypotheses. C1 Univ Amsterdam, Acad Med Ctr, Dept Gastro & Liver Dis, NL-1105 AZ Amsterdam, Netherlands. NIDDK, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Jones, EA (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Gastro & Liver Dis, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. NR 46 TC 33 Z9 35 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD DEC PY 1998 VL 13 IS 4 BP 351 EP 360 DI 10.1023/A:1020693026810 PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 162EH UT WOS:000078332200009 PM 10206826 ER PT J AU Snitker, S Nicolson, M Shuldiner, AR Silver, K Ravussin, E AF Snitker, S Nicolson, M Shuldiner, AR Silver, K Ravussin, E TI No effect of Trp64Arg beta(3)-adrenoceptor polymorphism on the plasma leptin concentration in Pima Indians SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID RECEPTOR MESSENGER-RNA; BETA(3)-ADRENERGIC-RECEPTOR GENE; EXPRESSION; DISRUPTION; SECRETION; OBESITY AB In rodents, administration of leptin promotes beta(3)-adrenergic stimulation of thermogenesis in brown adipose tissue. Conversely, administration of a beta(3)-adrenoceptor (beta(3)-AR) agonist decreases leptin mRNA expression and secretion, suggesting that leptin and sympathetic nervous system activity mediated through the beta(3)-AR comprise a negative-feedback loop. It has recently been proposed that a defect in the beta(3)-AR in humans may contribute to a resistance to the sympathetically mediated effects of leptin on thermogenesis and lipolysis, thus leading to obesity and type 2 diabetes mellitus. We thus hypothesized that the Trp64Arg variant in the human beta(3)-AR would be associated with elevated plasma leptin concentrations. We studied 101 healthy nondiabetic Pima Indians: 11 Arg64 homozygotes, 35 Trp64 homozygotes. and 55 heterozygotes. The fasting plasma leptin concentration as an absolute value or after adjustment for percent body fat and sex was not associated with the beta(3)-AR genotype. Thus, the data do not support an influence of the Trp64Arg variant on the plasma leptin concentration. Copyright (C) 1998 by W.B. Saunders Company. C1 NIDDK, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Univ Maryland, Baltimore, MD 21201 USA. Amgen, Thousand Oaks, CA USA. RP Snitker, S (reprint author), NIDDK, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Room 5-41, Phoenix, AZ 85016 USA. NR 18 TC 4 Z9 4 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 1998 VL 47 IS 12 BP 1525 EP 1527 DI 10.1016/S0026-0495(98)90081-6 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 150AK UT WOS:000077640100017 PM 9867085 ER PT J AU Rybak, SM Newton, DL AF Rybak, SM Newton, DL TI Antibody targeted ribonucleases for cancer therapy SO MINERVA BIOTECNOLOGICA LA English DT Article DE ribonucleases; antibodies; neoplasms; immunotoxins ID SINGLE-CHAIN FV; EOSINOPHIL-DERIVED NEUROTOXIN; RAY CRYSTALLOGRAPHIC STRUCTURE; TRANSFERRIN RECEPTOR; FUSION PROTEIN; MONOCLONAL-ANTIBODIES; ESCHERICHIA-COLI; P-30 PROTEIN; PRODRUG ACTIVATION; BINDING-PROPERTIES AB Targeted ribonucleases are antibody-enzyme chimeras in which the antibody is either genetically fused or chemically linked to the ribonuclease. In this article we highlight both the RNase effector and antibody targeting domains with respect to their structure and function. Protocols for the construction and purification of both chemical conjugates and fusion proteins are described. RNases conjugated to several antibodies via chemical linkages exhibit a 50 (Onconase) to 5000 fold (RNase A) increase in specific cytotoxicity to turner cells in vitro over the unconjugated enzyme. Genetically engineered RNase fusion proteins designed with site specific linkage are two to four logs (nM vss mu M, respectively) more potent than chemical conjugates due to the inability to control the sites of derivatization and linkage in the latter reagents. Due to lack of non-specific toxic side effects to normal tissues effective treatment concentrations are easily achievable in murine antitumor models. Continued advances in the design, production and function of targeted RNases demonstrate that they are progressing toward becoming a new class of anticancer therapeutics. C1 NCI, Pharmacol & Exptl Therapeut Sect, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Frederick, MD 21701 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NR 77 TC 3 Z9 3 U1 0 U2 1 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 1120-4826 J9 MINERVA BIOTECNOL JI Minerva Biotechnol. PD DEC PY 1998 VL 10 IS 4 BP 162 EP 173 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 189BZ UT WOS:000079885400004 ER PT J AU Brown, MT Andrade, J Radhakrishna, H Donaldson, JG Cooper, JA Randazzo, PA AF Brown, MT Andrade, J Radhakrishna, H Donaldson, JG Cooper, JA Randazzo, PA TI ASAP1, a phospholipid-dependent Arf GTPase-activating protein that associates with and is phosphorylated by Src SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ADP-RIBOSYLATION-FACTOR; PLECKSTRIN-HOMOLOGY DOMAINS; TRIMERIC-G-PROTEIN; ZINC-FINGER MOTIF; TYROSINE KINASE; EXCHANGE FACTOR; CELLULAR SRC; C-SRC; MONOCLONAL-ANTIBODIES; SRC-HOMOLOGY-3 DOMAIN AB Membrane trafficking is regulated in part by small GTP-binding proteins of the ABP-ribosylation factor (Arf) family. Arf function depends on the controlled exchange and hydrolysis of GTP. We have purified and cloned two variants of a 130-kDa phosphatidylinositol 4,5-biphosphate (PIP2)-dependent Arf1 GTPase-activating protein (GAP), which we call ASAP1a and ASAP1b. Both contain a pleckstrin homology (PH) domain, a zinc finger similar to that found in another Arf GAP, three ankyrin (ANK) repeats, a proline-rich region with alternative splicing and SH3 binding motifs, eight repeats of the sequence E/DLPPKP, and an SH3 domain. Together, the PH, zinc finger, and ANK repeat regions possess PIP2-dependent GAP activity on Arf1 and Arf5, less activity on Arf6, and no detectable activity on Ar12 in vitro. The cDNA for ASAP1 was independently identified in a screen for proteins that interact with the SH3 domain of the tyrosine kinase Src. ASAP1 associates in vitro with the SH3 domains of Src family members and with the Crk adapter protein. ASAP1 coprecipitates with Src from cell lysates and is phosphorylated on tyrosine residues in cells expressing activated Src. Both coimmunoprecipitation and tyrosine phosphorylation depend on the same proline-rich class II Src SH3 binding site required for in vitro association. By directly interacting with both Arfs and tyrosine kinases involved in regulating cell growth and cytoskeletal organization, ASAP1 could coordinate membrane remodeling events with these processes. C1 NCI, Div Basic Sci, Lab Cellular Oncol, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. NHLBI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Randazzo, PA (reprint author), NCI, Div Basic Sci, Lab Cellular Oncol, 37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. EM randazzo@helix.nih.gov FU NCI NIH HHS [CA41072, CA62598, F32 CA062598, R01 CA041072, R37 CA041072] NR 97 TC 151 Z9 159 U1 0 U2 6 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 DEC PY 1998 VL 18 IS 12 BP 7038 EP 7051 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 140QK UT WOS:000077099700016 PM 9819391 ER PT J AU Haft, CR Sierra, MD Barr, VA Haft, DH Taylor, SI AF Haft, CR Sierra, MD Barr, VA Haft, DH Taylor, SI TI Identification of a family of sorting nexin molecules and characterization of their association with receptors SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; RAT ADIPOSE-CELLS; INSULIN-RECEPTOR; SACCHAROMYCES-CEREVISIAE; LEPTIN RECEPTOR; PDGF RECEPTORS; PROTEIN; INTERNALIZATION; KINASE; SIGNAL AB Sorting nexin 1 (SNX1) is a protein that binds to the epidermal growth factor (EGF) receptor and is proposed to play a role in directing EGF receptors to lysosomes for degradation (R.C. Kurten, D. L. Cadena, and G. N. Gill, Science 272:1008-1010, 1996), We have obtained full-length cDNAs and deduced the amino acid sequences of three novel homologous proteins, which were denoted human sorting nexins (SNX2, SNX3, and SNX4), In addition, we identified a presumed splice variant isoform of SNX1 (SNX1A). These molecules contain a conserved domain of similar to 100 amino acids, which was termed the phox homology (PX) domain. Human SNX1 (522 amino acids), SNX1A (457 amino acids), SNX2 (519 amino acids), SNX3 (162 amino acids), and SNX4 (450 amino acids) are part of a larger family of hydrophilic molecules including proteins identified in Caenorhabditis elegans and Saccharomyces cerevisiae, Despite their hydrophilic nature, the sorting nexins are found partially associated with cellular membranes. They are widely expressed, although the tissue distribution of each sorting nexin mRNA varies. When expressed in COS7 cells, epitope-tagged sorting nexins SNX1, SNX1A, SNX2, and SNX4 coimmunoprecipitated with receptor tyrosine kinases for EGF, platelet-derived growth factor, and insulin. These sorting nexins also associated with the long isoform of the leptin receptor but not with the short and medium isoforms. Interestingly, endogenous COS7 transferrin receptors associated exclusively with SNX1 and SNX1A, while SNX3 was not found to associate with any of the receptors studied. Our demonstration of a large conserved family of sorting nexins that interact with a variety of receptor types suggests that these proteins may be involved in several stages of intracellular trafficking in mammalian cells. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Natl Biomed Res Fdn, Washington, DC USA. RP Haft, CR (reprint author), NIDDKD, Diabet Branch, NIH, Bldg 10,Room 8S-235A,10 Ctr Dr MSC-1770, Bethesda, MD 20892 USA. EM carol_haft@nih.gov NR 41 TC 169 Z9 187 U1 1 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 DEC PY 1998 VL 18 IS 12 BP 7278 EP 7287 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 140QK UT WOS:000077099700039 PM 9819414 ER PT J AU Romano, PR Zhang, F Tan, SL Garcia-Barrio, MT Katze, MG Dever, TE Hinnebusch, AG AF Romano, PR Zhang, F Tan, SL Garcia-Barrio, MT Katze, MG Dever, TE Hinnebusch, AG TI Inhibition of double-stranded RNA-dependent protein kinase PKR by vaccinia virus E3: Role of complex formation and the E3 N-terminal domain SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BINDING-PROTEIN; IN-VIVO; FUNCTIONAL-CHARACTERIZATION; INITIATION FACTOR-2-ALPHA; SACCHAROMYCES-CEREVISIAE; TRANSLATIONAL CONTROL; GENE-PRODUCTS; INTERFERON; ACTIVATION; YEAST AB The human double-stranded RNA (dsRNA)-dependent protein kinase PKR inhibits protein synthesis by phosphorylating translation initiation factor 2 alpha (eIF2 alpha), Vaccinia virus E3L encodes a dsRNA binding protein that inhibits PKR in virus-infected cells, presumably by sequestering dsRNA activators, Expression of PKR in Saccharomyces cerevisiae inhibits protein synthesis by phosphorylation of eIF2 alpha, dependent on its two dsRNA binding motifs (DRBMs), We found that expression of E3 in yeast overcomes the lethal effect of PKR in a manner requiring key residues (Lys-167 and Arg-168) needed for dsRNA binding by E3 in vitro. Unexpectedly, the N-terminal half of E3, and residue Trp-66 in particular, also is required for anti-PKR function. Because the E3 N-terminal region does not contribute to dsRNA binding in vitro, it appears that sequestering dsRNA is not the sole function of E3 needed for inhibition of PKR, This conclusion was supported by the fact that E3 activity was antagonized, not augmented, by overexpressing the catalytically defective PKR-K296R protein containing functional DRBMs. Coimmunoprecipitation experiments showed that a majority of PKR in yeast extracts was in a complex with E3, whose formation was completely dependent on the dsRNA binding activity of E3 and enhanced by the N-terminal half of E3. In yeast two-hybrid assays and in vitro protein binding experiments, segments of E3 and PKR containing their respective DRBMs interacted in a manner requiring E3 residues Lys-167 and Arg-168, We also detected interactions between PKR and the N-terminal half of E3 in the yeast two hybrid and lambda repressor dimerization assays. In the latter case, the N-terminal half of E3 interacted with the kinase domain of PKR, dependent on E3 residue Trp-66, We propose that effective inhibition of PKR in yeast requires formation of an E3-PKR-dsRNA complex, in which the N-terminal half of E3 physically interacts with the protein kinase domain of PKR. C1 NICHHD, Lab Eucaryot Gene Regulat, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Eucaryot Gene Regulat, Bldg 6A,Room B1A-13A, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov NR 55 TC 123 Z9 127 U1 0 U2 2 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 DEC PY 1998 VL 18 IS 12 BP 7304 EP 7316 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 140QK UT WOS:000077099700042 PM 9819417 ER PT J AU Suzuki, K Lavaroni, S Mori, A Okajima, F Kimura, S Katoh, R Kawaoi, A Kohn, LD AF Suzuki, K Lavaroni, S Mori, A Okajima, F Kimura, S Katoh, R Kawaoi, A Kohn, LD TI Thyroid transcription factor 1 is calcium modulated and coordinately regulates genes involved in calcium homeostasis in C cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID THYROTROPIN RECEPTOR GENE; ENHANCER-BINDING PROTEIN; FACTOR-I; SENSING RECEPTOR; EXTRACELLULAR CALCIUM; PHOSPHOINOSITIDE TURNOVER; THYROGLOBULIN PROMOTER; CA2+-SENSING RECEPTOR; CALCITONIN SECRETION; RESPONSE ELEMENT AB Thyroid transcription factor 1 (TTF-1) was identified for its critical role in thyroid-specific gene expression; its level in the thyroid is regulated by thyrotropin-increased cyclic AMP levels. TTF-1 was subsequently found in lung tissue, where it regulates surfactant expression, and in certain neural tissues, where its function is unknown. Ligands or signals regulating TTF-1 levels in lung or neural tissue are unknown. We recently identified TTF-1 in rat parafollicular C cells and parathyroid cells. In this report, we show that TTF-1 is present in the parafollicular C cells of multiple species and that it interacts with specific elements on the 5'-flanking regions of the extracellular Ca2+-sensing receptor (CaSR), calmodulin, and calcitonin genes in C cells. When intracellular Ca2+ levels are increased or decreased in C cells, by the calcium ionophore A23187, by physiologic concentrations of the P-2 purinergic receptor ligand ATP, or by changes in extracellular Ca2+ levels, the promoter activity, RNA levels, and binding of TTF-1 to these genes are, respectively, decreased or increased. The changes in TTF-1 inversely alter CaSR gene and calcitonin gene expression. We show, therefore, that TTF-1 is a Ca2+-modulated transcription factor that coordinately regulates the activity of genes critical for Ca2+ homeostasis by parafollicular C cells. We hypothesize that TTF-1 similarly coordinates Ca2+-dependent gene expression in all cells in which TTF-1 and the CaSR are expressed, i.e., parathyroid cells, neural cells in the anterior pituitary or hippocampus, and keratinocytes. C1 NIDDK, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Lab, NIH, Bethesda, MD 20892 USA. Yamanashi Med Univ, Dept Pathol, Yamanashi 40938, Japan. Gunma Univ, Inst Mol & Cellular Regulat, Lab Signal Transduct, Maebashi, Gumma 371, Japan. RP Kohn, LD (reprint author), NIDDK, Cell Regulat Sect, Metab Dis Branch, NIH, Bldg 10,Room 9C101B, Bethesda, MD 20892 USA. EM lenk@bdg10.niddk.nih.gov NR 68 TC 61 Z9 62 U1 1 U2 3 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 DEC PY 1998 VL 18 IS 12 BP 7410 EP 7422 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 140QK UT WOS:000077099700052 PM 9819427 ER PT J AU Adya, N Stacy, T Speck, NA Liu, PP AF Adya, N Stacy, T Speck, NA Liu, PP TI The leukemic protein core binding factor beta (CBF beta)-smooth-muscle myosin heavy chain sequesters CBF alpha 2 into cytoskeletal filaments and aggregates SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; FETAL LIVER HEMATOPOIESIS; TRANSCRIPTION FACTOR; AML1 GENE; OSTEOBLAST DIFFERENTIATION; CLEIDOCRANIAL DYSPLASIA; DNA-BINDING; IN-VIVO; FUSION AB The fusion gene CBFB-MYH11 is generated by the chromosome 16 inversion associated with acute myeloid leukemias. This gene encodes a chimeric protein involving the core binding factor beta (CBF beta) and the smooth-muscle myosin heavy chain (SMMHC). Mouse model studies suggest that this chimeric protein CBF beta-SMMHC dominantly suppresses the function of CBF, a heterodimeric transcription factor composed of DNA binding subunits (CBF alpha 1 to 3) and a non-DNA binding subunit (CBF beta). This dominant suppression results in the blockage of hematopoiesis in mice and presumably contributes to leukemogenesis, We used transient-transfection assays, in combination with immunofluorescence and green fluorescent protein-tagged proteins, to monitor subcellular localization of CBF beta-SMMHC, CBF beta, and CBF alpha 2 (also known as AML1 or PEBP2 alpha B). When expressed individually, CBF alpha 2 was located in the nuclei of transfected cells, whereas CBF beta was distributed throughout the cell. On the other hand, CBF beta-SMMHC formed filament-like structures that colocalized with actin filaments, Upon cotransfection, CBF alpha 2 was able to drive localization of CBF beta into the nucleus in a dose-dependent manner. In contrast, CBF alpha 2 colocalized with CBF beta-SMMHC along the filaments instead of localizing to the nucleus. Deletion of the CBF alpha-interacting domain within CBF beta-SMMHC abolished this CBF alpha 2 sequestration, whereas truncation of the C-terminal-end SMMHC domain led to nuclear localization of CBF beta-SMMHC when coexpressed with CBF alpha 2. CBF alpha 2 sequestration by CBF beta-SMMHC was further confirmed in vivo in a knock-in mouse model. These observations suggest that CBF beta-SHMMC plays a dominant negative role by sequestering CBFa2 into cytoskeletal filaments and aggregates, thereby disrupting CBF alpha 2-mediated regulation of gene expression. C1 Natl Human Genome Res Inst, Oncogenesis & Dev Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Dartmouth Med Sch, Dept Biochem, Hanover, NH 03755 USA. RP Liu, PP (reprint author), Natl Human Genome Res Inst, Oncogenesis & Dev Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Room 3C28, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU NCI NIH HHS [R01 CA058343, R01 CA075611, R01 CA58343, R01 CA75611] NR 56 TC 95 Z9 97 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 DEC PY 1998 VL 18 IS 12 BP 7432 EP 7443 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 140QK UT WOS:000077099700054 PM 9819429 ER PT J AU Pinkas-Kramarski, R Shelly, M Guarino, BC Wang, LM Lyass, L Alroy, I Alimandi, M Kuo, A Moyer, JD Lavi, S Eisenstein, M Ratzkin, BJ Seger, R Bacus, SS Pierce, JH Andrews, GC Yarden, Y AF Pinkas-Kramarski, R Shelly, M Guarino, BC Wang, LM Lyass, L Alroy, I Alimandi, M Kuo, A Moyer, JD Lavi, S Eisenstein, M Ratzkin, BJ Seger, R Bacus, SS Pierce, JH Andrews, GC Yarden, Y TI ErbB tyrosine kinases and the two neuregulin families constitute a ligand-receptor network (vol 18, pg 6090, 1998) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction C1 Weizmann Inst Sci, Dept Mol Biol, IL-76100 Rehovot, Israel. Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. Weizmann Inst Sci, Dept Membrane Res & Recognit, IL-76100 Rehovot, Israel. Pfizer Inc, Pfizer Cent Res, Groton, CT 06340 USA. NCI, Bethesda, MD 20892 USA. Adv Cellular Diagnost Inc, Elmhurst, IL 60126 USA. Amgen Inc, Amgen Ctr, Thousand Oaks, CA 91320 USA. RP Pinkas-Kramarski, R (reprint author), Weizmann Inst Sci, Dept Mol Biol, IL-76100 Rehovot, Israel. RI YARDEN, YOSEF/K-1467-2012 NR 1 TC 5 Z9 5 U1 0 U2 2 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 DEC PY 1998 VL 18 IS 12 BP 7602 EP 7602 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 140QK UT WOS:000077099700071 ER PT J AU Lu, ZM McLaren, RS Winters, CA Ralston, E AF Lu, ZM McLaren, RS Winters, CA Ralston, E TI Ribosome association contributes to restricting mRNAs to the cell body of hippocampal neurons SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID MESSENGER-RNA LOCALIZATION; PROTEIN-SYNTHETIC MACHINERY; SUBCELLULAR-LOCALIZATION; TRANSLATIONAL REGULATION; TRANSPORT; DENDRITES; IRON; POLYRIBOSOMES; CYTOSKELETON; FERRITIN AB In neurons, mRNAs are differentially sorted to axons, dendrites, and the cell body. Recently, regions of certain mRNAs have been identified that target those mRNAs for translocation to the processes. However, the mechanism by which many, if not most mRNAs are retained in the cell body is not understood. Total inhibition of translation, by puromycin or cycloheximide, results in the mislocalization of cell body mRNAs to dendrites. We have examined the effect of translational inhibitors on the localization of ferritin mRNA, the translation of which can also be inhibited specifically by reducing iron levels. Using nonisotopic in situ hybridization, ferritin mRNA is found restricted to the cell body of cultured rat hippocampal neurons. Following treatment with either puromycin or cycloheximide, it migrates into dendrites. Control experiments reveal that the drugs affect neither the viability of the neuronal cultures, nor the steady-state level of ferritin mRNA. When transcription and protein synthesis are inhibited simultaneously, ferritin mRNA is found in the dendrites of puromycin, but not of cycloheximide-treated neurons. However, the localization of ferritin mRNA is unaffected by changes in iron concentration that regulate its translation rate specifically. We propose a model whereby cell body-restricted mRNAs are maintained in that location by association with ribosomes and with another cell component, which traps mRNAs when they are freed of ribosome association. The release of all mRNA species, as happens after total protein synthesis inhibition, floods the system and allows cell body mRNAs to diffuse into dendrites. In contrast, the partial release of the single ferritin mRNA species does not saturate the trapping system and the mRNA is retained in the cell body. C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Lu, ZM (reprint author), NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 42 TC 30 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD DEC PY 1998 VL 12 IS 6 BP 363 EP 375 DI 10.1006/mcne.1998.0723 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 158ZW UT WOS:000078148200004 PM 9888989 ER PT J AU Santos, N Clark, HF Hoshino, Y Gouvea, V AF Santos, N Clark, HF Hoshino, Y Gouvea, V TI Relationship among serotype G3P5A rotavirus strains isolated from different host species SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE rotavirus typing; restriction endonuclease assay; interspecies transmission; neutralization assay; human rotavirus; animal rotavirus ID LENGTH-POLYMORPHISM ASSAY; POLYMERASE CHAIN-REACTION; INTERSPECIES TRANSMISSION; ANIMAL ROTAVIRUSES; FELINE; SPECIFICITY; SPECIMENS; DIARRHEA; HUMANS; GENES AB The relationship among G3P5A rotavirus strains was analysed by restriction endonuclease assay of the VP4, VP6 and VP7 encoding genes, neutralization assay and phylogenetic analysis. The restriction patterns of the capsid encoding genes were species specific allowing the differentiation among the strains of different origin. The VP7 profiles differentiated human from animal strains more efficiently. The phylogenetic analysis of the VP4 gene demonstrated that HCR3A and K9 are closer related to each other than to other P5A strains. The same occurs to strains Ro1845 and Cat 97. The CU-1 virus appears to be an ancestor of the P5A strains by neutralization and phylogenetic analysis. The results placed the RRV strain definitely in a separate VP4 serotype and genotype from that of P5A strains. Restriction endonuclease assay of the capsid encoding genes seems to be a useful tool to identify the host species of rotavirus strains belonging to the same serotype and/or genotype. (C) 1998 Academic Press. C1 Univ Fed Rio de Janeiro, Dept Virol, Inst Microbiol, BR-21941950 Rio De Janeiro, Brazil. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NIH, Infect Dis Lab, Bethesda, MD 20892 USA. RP Santos, N (reprint author), Univ Fed Rio de Janeiro, Dept Virol, Inst Microbiol, Cidade Univ,CCS-BI 1,POB 68040, BR-21941950 Rio De Janeiro, Brazil. EM imvinos@microbio.ufrj.br RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 NR 26 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD DEC PY 1998 VL 12 IS 6 BP 379 EP 386 DI 10.1006/mcpr.1998.0198 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 148WN UT WOS:000077557000005 PM 9843655 ER PT J AU van der Heijden, O Chiu, HC Park, TC Takahashi, H LiVolsi, VA Risinger, JI Barrett, JC Berchuck, A Evans, AC Behbakht, K Menzin, AW Liu, PC Benjamin, I Morgan, MA King, SA Rubin, SC Boyd, J AF van der Heijden, O Chiu, HC Park, TC Takahashi, H LiVolsi, VA Risinger, JI Barrett, JC Berchuck, A Evans, AC Behbakht, K Menzin, AW Liu, PC Benjamin, I Morgan, MA King, SA Rubin, SC Boyd, J TI Allelotype analysis of uterine leiomyoma: Localization of a potential tumor suppressor gene to a 4-cM region of chromosome 7q SO MOLECULAR CARCINOGENESIS LA English DT Article DE fibroid; myometrium; tumor; benign; smooth muscle ID CYTOGENETIC ANALYSIS; HMGI-C; SARCOMAS; PROFILE AB Uterine leiomyoma is a benign smooth muscle tumor of the myometrium and is the most commonly encountered neoplasm in women of reproductive age. As for most benign tumors, the pathogenesis of leiomyoma remains obscure, especially at the molecular genetic level. The purpose of this study was to perform a genome-wide allelotype analysis to identify potential sites of tumor suppressor gene inactivation. Fifty-two cases of uterine leiomyoma were subjected to allelotype analysis by using matched pairs of tumor and blood DNA. Loss of heterozygosity (LOH) was assessed at 61 microsatellite markers distributed throughout the genome and representing all 41 chromosome arms. In general, LOH was very rare except on chromosome 7q, where LOH was observed in 34% of all informative tumors. Fine-deletion mapping with 25 microsatellite markers from the 7q22 region revealed a minimal deletion unit of approximately 4 cM, bounded by the markers D7S2453 proximally and D7S496 distally, that probably harbors a novel tu mor suppressor gene involved in the etiology of this tumor. (C) 1998 Wiley-Liss, Inc. C1 Univ Penn, Med Ctr, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. Univ Penn, Med Ctr, Dept Genet, Philadelphia, PA 19104 USA. RP Boyd, J (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave,Box 201, New York, NY 10021 USA. RI van der Heijden, Olivier/O-8270-2015; OI Behbakht, Kian/0000-0003-4793-9958 NR 22 TC 31 Z9 31 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD DEC PY 1998 VL 23 IS 4 BP 243 EP 247 DI 10.1002/(SICI)1098-2744(199812)23:4<243::AID-MC7>3.0.CO;2-E PG 5 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 150AP UT WOS:000077640500007 PM 9869453 ER PT J AU Cleghon, V Feldmann, P Ghiglione, C Copeland, TD Perrimon, N Hughes, DA Morrison, DK AF Cleghon, V Feldmann, P Ghiglione, C Copeland, TD Perrimon, N Hughes, DA Morrison, DK TI Opposing actions of CSW and RasGAP modulate the strength of torso RTK signaling in the Drosophila terminal pathway SO MOLECULAR CELL LA English DT Article ID RECEPTOR TYROSINE KINASE; GTPASE-ACTIVATING PROTEIN; PHOSPHOTYROSINE PHOSPHATASE; GENE-EXPRESSION; BETA RECEPTOR; BINDING-SITE; MAP KINASE; TRANSDUCTION; CORKSCREW; SEVENLESS AB In Drosophila, specification of embryonic terminal cells is controlled by Torso receptor tyrosine kinase. here, we analyze the molecular basis of positive (Y630) and negative (Y918) phosphotyrosine (pY) signaling sites on Torso. We find that the Drosophila homolog of RasGAP associates with pY918 and is a negative effector of Torso signaling. Further, we show that the tyrosine phosphatase Corkscrew (CSW), which associates with pY630 Torso signaling site, thus identifying Torso to be a substrate of CSW in the terminal pathway. CSW also serves as an adaptor protein for DRK binding, physically linking Torso to Ras activation. The opposing actions of CSW and RasGAP modulate the strength of the Torso signal, contributing to the establishment of precise boundaries for terminal structure development. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mol Basis Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Special Program Prot Chem, Frederick, MD 21702 USA. Inst Canc Res, Chester Beatty Labs, London SW3 6JB, England. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. RP Morrison, DK (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mol Basis Carcinogenesis Lab, Frederick, MD 21702 USA. FU Wellcome Trust NR 51 TC 72 Z9 73 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 1998 VL 2 IS 6 BP 719 EP 727 DI 10.1016/S1097-2765(00)80287-7 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 153WQ UT WOS:000077856600002 PM 9885560 ER PT J AU Ge, H Si, YZ Wolffe, AP AF Ge, H Si, YZ Wolffe, AP TI A novel transcriptional coactivator, p52, functionally interacts with the essential splicing factor ASF/SF2 SO MOLECULAR CELL LA English DT Article ID RNA-POLYMERASE-II; PRE-MESSENGER-RNA; C-TERMINAL DOMAIN; PROTEIN-PROTEIN INTERACTIONS; SR-PROTEINS; PREMESSENGER RNA; GENE-TRANSCRIPTION; LARGEST SUBUNIT; SITE SELECTION; NUCLEAR MATRIX AB Increasing evidence suggests that pre-mRNA splicing can take place cotranscriptionally in vivo. However, insight into how these two processes are linked has been lacking, Here, we describe that a novel transcriptional coactivator, p52, interacts not only with transcriptional activators and general transcription Factors to enhance activated transcription but also with the essential splicing factor ASF/SF2 both in vitro and in vivo to modulate ASF/SF2-mediated pre-mRNA splicing. Furthermore, immunofluorescence studies indicate that the majority of endogenous p52 is colocalized with ASF/SF2 in the nucleoplasm of HeLa cells. Together, these observations suggest that, in addition to functioning as a transcriptional coactivator, p52 may also act as an adaptor to coordinate pre-mRNA splicing and transcriptional activation of class ii genes. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Ge, H (reprint author), NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. NR 80 TC 114 Z9 118 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 1998 VL 2 IS 6 BP 751 EP 759 DI 10.1016/S1097-2765(00)80290-7 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 153WQ UT WOS:000077856600005 PM 9885563 ER PT J AU Land, T Rouault, TA AF Land, T Rouault, TA TI Targeting of a human iron-sulfur cluster assembly enzyme, nifs, to different subcellular compartments is regulated through alternative AUG utilization SO MOLECULAR CELL LA English DT Article ID ELEMENT BINDING-PROTEIN; MESSENGER-RNA; TRANSLATION INITIATION; CELLS; LIVER; MITOCHONDRIAL; METABOLISM; EXPRESSION; ACONITASE; PRECURSOR AB Iron-sulfur clusters are prosthetic groups that are required for the function of numerous enzymes in the cell, including enzymes important in respiration, photosynthesis, and nitrogen fixation. Here we report cloning of the human homolog of NifS, a cysteine desulfurase that is proposed to supply the inorganic sulfur in iron-sulfur clusters, In human cells, different forms of NifS that localize either to mitochondria or to the cytosol and nucleus ave synthesized from a single transcript: through initiation et;alternative in-frame AUGs, and initiation site selection varies according to the pn of the medium or cytosol. Thus, a novel form of translational regulation permits rapid redistribution of NifS proteins into different compartments of the cell in response to changes in metabolic status. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 31 TC 126 Z9 130 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 1998 VL 2 IS 6 BP 807 EP 815 DI 10.1016/S1097-2765(00)80295-6 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 153WQ UT WOS:000077856600010 PM 9885568 ER PT J AU Xue, YT Wong, JM Moreno, GT Young, MK Cote, J Wang, WD AF Xue, YT Wong, JM Moreno, GT Young, MK Cote, J Wang, WD TI NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities SO MOLECULAR CELL LA English DT Article ID TRANSCRIPTIONAL REPRESSION; NEGATIVE REGULATOR; MI-2 AUTOANTIGEN; SWI/SNF COMPLEX; BINDING PROTEIN; N-COR; YEAST; ACETYLTRANSFERASE; ACTIVATION; RECEPTOR AB ATP-dependent chromatin-remodeling complexes are known to facilitate transcriptional activation by opening chromatin structures. We report a novel human complex, named NURD, which contains not only ATP-dependent nucleosome disruption activity, but also histone deacetylase activity, which usually associates with transcriptional repression. The deacetylation is stimulated by ATP on nucleosomal templates, suggesting that nucleosome disruption aids the deacetylase to access its substrates. One subunit of NURD was identified as MTA1, a metastasis-associated protein with a region similar to the nuclear receptor corepressor, N-CoR; and antibodies against NURD partially relieve transcriptional repression by thyroid hormone receptor. These results suggest that ATP-dependent chromatin remodeling can participate in transcriptional repression by assisting repressors in gaining access to chromatin. C1 NIA, Genet Lab, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. Beckman Res Inst City Hope, Div Immunol, Duarte, CA 91010 USA. Univ Laval, Ctr Canc Res, Hotel Dieu, Quebec City, PQ G1R 2J6, Canada. RP Wang, WD (reprint author), NIA, Genet Lab, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wangw@grc.nia.nih.gov RI Cote, Jacques/I-8901-2014 OI Cote, Jacques/0000-0001-6751-555X NR 52 TC 580 Z9 602 U1 1 U2 24 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 1998 VL 2 IS 6 BP 851 EP 861 DI 10.1016/S1097-2765(00)80299-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 153WQ UT WOS:000077856600014 PM 9885572 ER PT J AU Vassilev, A Yamauchi, J Kotani, T Prives, C Avantaggiati, ML Qin, J Nakatani, Y AF Vassilev, A Yamauchi, J Kotani, T Prives, C Avantaggiati, ML Qin, J Nakatani, Y TI The 400 kDa subunit of the PCAF histone acetylase complex belongs to the ATM superfamily SO MOLECULAR CELL LA English DT Article ID NUCLEOSOME CORE PARTICLE; CELL-CYCLE; PROTEIN-KINASE; DNA-BINDING; P53; ACETYLTRANSFERASE; ACTIVATION; TRANSCRIPTION; COACTIVATORS; YEAST AB PCAF histone acetylase is found in a complex with more than 20 associated polypeptides. Here we report cloning and characterization of the 400 kDa PCAF-associated factor referred to as PAF400. PAF400 is almost identical to TRRAP, which binds to c-Myc and E2F, and has significant sequence similarities to the ATM superfamily including FRAP, ATM, ATR, and the catalytic subunit of DNA-PK. Remarkably, PAF400 and FRAP share sequence similarity in broad regions that cover 80% of the entire PAF400 sequence. However, unlike the other members of the ATM superfamily, PAF400 is not: a protein kinase as judged from the lack of kinase motif and autophosphorylation activity. We discuss the possibility that PAF400 may play a role in signaling of DNA damage to p53 by stimulation of p53 acetylation. C1 NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Sch Med, Dept Microbiol, Buffalo, NY 14214 USA. Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. RP Nakatani, Y (reprint author), NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. EM yoshi@helix.nih.gov NR 56 TC 135 Z9 142 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 1998 VL 2 IS 6 BP 869 EP 875 DI 10.1016/S1097-2765(00)80301-9 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 153WQ UT WOS:000077856600016 PM 9885574 ER PT J AU Carroll, IR Wang, J Howcroft, TK Singer, DS AF Carroll, IR Wang, J Howcroft, TK Singer, DS TI HIV Tat represses transcription of the beta(2)-microglobulin promoter SO MOLECULAR IMMUNOLOGY LA English DT Article DE transcription; HIV Tat; beta(2)-microglobulin; promoter; LTR ID IMMUNODEFICIENCY-VIRUS TYPE-1; LONG-TERMINAL REPEAT; RNA-POLYMERASE-II; TRANSACTIVATOR TAT; BETA-2-MICROGLOBULIN; GENE; EXPRESSION; CELLS; ACTIVATION; INTERACTS AB The MHC class I complex, which binds and presents peptide antigen, is composed of a class I heavy chain and the beta(2)-microglobulin light chain. HIV-1, which induces a profound immunodeficiency in infected individuals, encodes proteins that cause decreased expression of class I heavy chain. We now report that the HIV Tat protein, which is a potent transactivator of viral transcription, is also a potent repressor of the beta(2)-microglobulin gene. Repression is mediated through the basal promoter of the beta(2)-microglobulin gene, which is shown to be predominantly regulated by an initiator element. Tat repression is further augmented by the short viral transcript, TAR, which interacts with Tat. Tat-mediated repression of beta(2)-microglobulin expression, together with its known repression of class I gene transcription, provides an effective mechanism by which HIV could prevent cell surface expression of the MHC class I complex and avoid immune surveillance. Published by Elsevier Science Ltd. C1 NCI, Mol Regulat Sect, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Singer, DS (reprint author), NCI, Mol Regulat Sect, Expt Immunol Branch, NIH, Bldg 10,Room 4B-17, Bethesda, MD 20892 USA. NR 33 TC 30 Z9 30 U1 0 U2 1 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 DEC PY 1998 VL 35 IS 18 BP 1171 EP 1178 DI 10.1016/S0161-5890(98)00107-2 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 181TP UT WOS:000079458800003 PM 10199391 ER PT J AU Tsuboi, T Kaslow, DC Gozar, MMG Tachibana, M Cao, YM Torii, M AF Tsuboi, T Kaslow, DC Gozar, MMG Tachibana, M Cao, YM Torii, M TI Sequence polymorphism in two novel Plasmodium vivax ookinete surface proteins, Pvs25 and Pvs28, that are malaria transmission-blocking vaccine candidates SO MOLECULAR MEDICINE LA English DT Article ID PAPUA-NEW-GUINEA; SACCHAROMYCES-CEREVISIAE; FALCIPARUM-MALARIA; CONSERVED REGIONS; MINIMAL VARIATION; ANTIGENS; IMMUNITY; ANTIBODIES; BERGHEI; GENE AB Background: For many malarious regions outside of Africa, development of effective transmission-blocking vaccines will require coverage against both Plasmodium falciparum and P. vivax. Work on P. vivax transmission-blocking vaccines has been hampered by the inability to clone the vaccine candidate genes from this parasite. Materials and Methods: To search for genes encoding the ookinete surface proteins from P. vivax, the DNA sequences of the eight known proteins in the P25 subfamily (Pfs25, Pgs25, Pys25, Pbs25) and in the P21/28 subfamily (Pfs28, Pgs28, Pys21, Pbs21) of zygote/ookinete surface proteins were aligned. Regions of highest identity were used to design degenerate PCR oligonucleotides. Genomic DNA from the Sal I strain of P. vivax and genomic and splinkerette DNA libraries were used as PCR templates. To characterize the polymorphisms of Pvs25 and Pvs28, these two genes were PCR amplified and the DNA sequences were determined from genomic DNA extracted from patients infected with P. vivax. Results: Analysis of the deduced amino add sequence of Pvs28 revealed a secretory signal sequence, lour epidermal growth factor (EGF)-like domains, six copies of the heptad amino acid repeat (GSGCE/D), and a short hydrophobic region. Because the fourth EGF-like domain has four rather than six cysteines, the gene designated Pvs28 is the presumed homologue of P21/28 subfamily members. Analysis of the deduced amino acid sequence of Pvs25 revealed a similar structure to that of Pvs28. The presence of six rather than four cysteines in the fourth EGF-like domain suggested that Pvs25 is the homologue of P25 subfamily members. Several regions of genetic polymorphisms in Pvs25 and Pvs28 were identified in field isolates of P. vivax. Conclusions: The genes encoding two ookinete surface proteins, Pvs28 and Pvs25, from P. vivax have been isolated and sequenced. Comparison of the primary structures of Pvs25, Pvs28, Pfs25, and Pfs28 suggest that there are regions of genetic polymorphism in the P25 and P21/28 subfamilies. C1 Ehime Univ, Sch Med, Dept Parasitol, Shigenobu, Ehime 79102, Japan. NIAID, Malaria Vaccines Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Torii, M (reprint author), Ehime Univ, Sch Med, Dept Parasitol, Shigenobu, Ehime 79102, Japan. NR 35 TC 81 Z9 90 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD DEC PY 1998 VL 4 IS 12 BP 772 EP 782 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 172DM UT WOS:000078908000003 PM 9990863 ER PT J AU Morris, JA Carstea, ED AF Morris, JA Carstea, ED TI Niemann-Pick C disease: cholesterol handling gone awry SO MOLECULAR MEDICINE TODAY LA English DT Review ID LIPOPROTEIN-DERIVED CHOLESTEROL; STORAGE DISORDER; INTRACELLULAR-TRANSPORT; BALB/C MICE; ESTERIFICATION; FIBROBLASTS; MOUSE; ACCUMULATION; HOMEOSTASIS; METABOLISM AB Niemann-Pick C disease (NPC) is a debilitating, recessive disorder in humans that causes unrelenting neurological deterioration and is complicated by the presence of lipid-laden foamy cells in the major organs of the body. NPC fibroblasts cultured with an excess of low density lipoprotein (LDL) abnormally sequester cholesterol in their lysosomes. Biochemical analyses of NPC cells suggest an impairment in the intracellular transport of cholesterol to post-lysosomal destinations occurs in NPC. The recent identification of the NPC gene, NPC1, provides a definitive diagnosis of the disease and a means of studying this key component of intracellular cholesterol transport and homeostasis. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. St Marys Hosp, Saccomanno Res Inst, Grand Junction, CO 81502 USA. RP Morris, JA (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gcarstea@stmarygj.com NR 49 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD DEC PY 1998 VL 4 IS 12 BP 525 EP 531 DI 10.1016/S1357-4310(98)01374-4 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 148LB UT WOS:000077505800008 PM 9866822 ER PT J AU Chew, LJ Gallo, V AF Chew, LJ Gallo, V TI Regulation of ion channel expression in neural cells by hormones and growth factors SO MOLECULAR NEUROBIOLOGY LA English DT Review DE ligand-gated; voltage-gated; neurotransmitter receptors; neural development; glia; gene expression; transcription; nerve growth factor; steroid hormones ID NICOTINIC ACETYLCHOLINE-RECEPTOR; METHYL-D-ASPARTATE; SUBUNIT MESSENGER-RNAS; GABA-A RECEPTOR; CHRONIC NEUROSTEROID TREATMENT; ROOT GANGLION NEURONS; DEVELOPING RAT-BRAIN; CILIARY NEUROTROPHIC FACTOR; LEUKEMIA INHIBITORY FACTOR; VOLTAGE-DEPENDENT CALCIUM AB Voltage-and ligand-gated ion channels are key players in synaptic transmission and neuron-glia communication in the nervous system. Expression of these proteins can be regulated at several levels (transcriptional, translational, or posttranslational) and by multiple extracellular factors in the developing and mature nervous system. A wide variety of hormones and growth factors have been identified as important in neural cell differentiation, which is a complex process involving the acquisition of cell-type-specific ion channel phenotypes. Much literature has already accumulated describing the structural and functional characteristics of ion channels, but relatively little is known about the factors that influence their synthesis and cell surface expression, although this area has generated considerable interest in the context of neural cell development. This article reviews several examples of regulated expression of these channels by cellular factors, namely peptide growth factors and steroid hormones, and discusses, where applicable, current understanding of molecular mechanisms underlying such regulation of voltage-and neurotransmitter-gated ion channels. C1 NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Chew, LJ (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bldg 49,Room 5A-78,49 Convent Dr, Bethesda, MD 20892 USA. NR 400 TC 9 Z9 9 U1 3 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD DEC PY 1998 VL 18 IS 3 BP 175 EP 225 DI 10.1007/BF02741300 PG 51 WC Neurosciences SC Neurosciences & Neurology GA 179RD UT WOS:000079341900001 PM 10206469 ER PT J AU Smith, RD Hunyady, L Olivares-Reyes, JA Mihalik, B Jayadev, S Catt, KJ AF Smith, RD Hunyady, L Olivares-Reyes, JA Mihalik, B Jayadev, S Catt, KJ TI Agonist-induced phosphorylation of the angiotensin AT(1a) receptor is localized to a serine/threonine-rich region of its cytoplasmic tail SO MOLECULAR PHARMACOLOGY LA English DT Article ID 3RD INTRACELLULAR LOOP; PROTEIN-KINASE-C; II RECEPTOR; BETA(2)-ADRENERGIC RECEPTOR; DEPENDENT PHOSPHORYLATION; INDUCED INTERNALIZATION; DESENSITIZATION; SPECIFICITY; SIGNAL; IDENTIFICATION AB The agonist-induced phosphorylation sites of the rat AT(1a) angiotensin receptor were analyzed using epitope-tagged mutant receptors expressed in Cos-7 cells. Angiotensin If-stimulated receptor phosphorylation was unaffected by truncation of the cytoplasmic tail of the receptor at Ser342 (Delta 342) but was abolished by truncation at Ser325 (Delta 325). Truncation at Ser335 (Delta 335), or double-point mutations of Ser335 and Thr336 to alanine (ST-AA), reduced receptor phosphorylation by similar to 50%, indicating that in addition to Ser335 and/or Thr336, amino acids within the Ser326-Thr332 segment are also phosphorylated. Agonist-induced phosphorylation of the ST-AA and Delta 335 receptors was partially inhibited by staurosporine, suggesting that the single protein kinase C consensus site in the Ser326-Thr332 segment (Ser331) is phosphorylated. The impairment of receptor phosphorylation was broadly correlated with the attenuation of agonist-induced internalization rates (Delta 325 < Delta 335 < ST-AA < Delta 342 wild-type) and with the increasing rank order of magnitude of inositol phosphate production normalized to an equal number of receptors (Delta 325 > Delta 335 > ST-AA = Delta 342 > wild-type). These results demonstrate that agonist-induced phosphorylation of the AT(1a) receptor is confined to an 11-amino-acid serine/threonine-rich segment of its carboxyl-terminal cytoplasmic tail and implicate this region in the mechanisms of receptor internalization and desensitization. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Semmelweis Univ Med, Dept Physiol, H-1088 Budapest, Hungary. RP Catt, KJ (reprint author), NICHD, ERRB, NIH, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. NR 36 TC 60 Z9 60 U1 0 U2 1 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 DEC PY 1998 VL 54 IS 6 BP 935 EP 941 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 149CB UT WOS:000077586600001 PM 9855619 ER PT J AU Fidock, DA Nomura, T Wellems, TE AF Fidock, DA Nomura, T Wellems, TE TI Cycloguanil and its parent compound proguanil demonstrate distinct activities against Plasmodium falciparum malaria parasites transformed with human dihydrofolate reductase SO MOLECULAR PHARMACOLOGY LA English DT Article ID THYMIDYLATE SYNTHASE GENE; PYRIMETHAMINE RESISTANCE; PS-15; DRUGS; TRANSFECTION; ATOVAQUONE; METABOLITE; MUTATIONS; WR99210; MUTANTS AB The lack of suitable antimalarial agents to replace chloroquine and pyrimethamine/sulfadoxine threatens efforts to control the spread of drug-resistant strains of the malaria parasite Plasmodium falciparum. Here we describe a transformation system, involving WR99210 selection of parasites transformed with either wild-type or methotrexate-resistant human dihydrofolate reductase (DHFR), that has application for the screening of P. falciparum-specific DHFR inhibitors that are active against drug-resistant parasites. Using this system, we have found that the prophylactic drug cycloguanil has a mode of pharmacological action distinct from the activity of its parent compound proguanil. Complementation assays demonstrate that cycloguanil acts specifically on P. falciparum DHFR and has no other significant target. The target of proguanil itself is separate from DHFR. We propose a strategy of combination chemotherapy incorporating the use of multiple parasite-specific inhibitors that act at the same molecular target and thereby maintain, in combination, their effectiveness against alternative forms of resistance that arise from different sets of point mutations in the target. This approach could be combined with traditional forms of combination chemotherapy in which two or more compounds are used against separate targets. C1 NIAID, Malaria Genet Sect, LPD, NIH, Bethesda, MD 20892 USA. Inst Pasteur, Unite Parasitol Biomed, F-75724 Paris 15, France. RP Wellems, TE (reprint author), NIAID, Malaria Genet Sect, LPD, NIH, Bldg 4,Room 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. OI Fidock, David/0000-0001-6753-8938 NR 40 TC 101 Z9 101 U1 0 U2 2 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 DEC PY 1998 VL 54 IS 6 BP 1140 EP 1147 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 149CB UT WOS:000077586600027 PM 9855645 ER PT J AU Redmond, TM Yu, S Lee, E Bok, D Hamasaki, D Chen, N Goletz, P Ma, JX Crouch, RK Pfeifer, K AF Redmond, TM Yu, S Lee, E Bok, D Hamasaki, D Chen, N Goletz, P Ma, JX Crouch, RK Pfeifer, K TI Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle SO NATURE GENETICS LA English DT Article ID PIGMENT-EPITHELIUM; BINDING-PROTEIN; GENE-TRANSFER; VITAMIN-A; MICROSOMAL PROTEIN; MOUSE RETINA; CELLS; MICE; ISOMERASE; RHODOPSIN AB Mutation of RPE65 can cause severe blindness from birth or early childhood, and RPE65 protein is associated with retinal pigment epithelium (RPE) vitamin A metabolism. Here. we show that Rpe65-deficient mice exhibit changes in retinal physiology and biochemistry. Outer segment discs of rod photoreceptors in Rpe65(-/-) mice are disorganized compared with those of Rpe65(+/+) and Rpe65(+/-) mice. Rod function, as measured by electroretinography, is abolished in Rpe65(-/-) mice, although cone function remains. Rpe65(-/-) mice lack rhodopsin, but not opsin apoprotein. Furthermore, all-trans-retinyl esters over-accumulate in the RPE of Rpe65(-/-) mice, whereas 11-cis-retinyl esters are absent. Disruption of the RPE-based metabolism of all-trans-retinyl esters to 11-cis-retinal thus appears to underlie the Rpe65(-/-) phenotype, although cone pigment regeneration may be dependent on a separate pathway. C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Brain Res Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Miami, Sch Med, Bascom Palmer Eye Inst, Miami, FL 33101 USA. Med Univ S Carolina, Storm Eye Inst, Charleston, SC 29425 USA. RP Redmond, TM (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM redmond@helix.nih.gov OI Redmond, T. Michael/0000-0002-1813-5291; Pfeifer, Karl/0000-0002-0254-682X FU NEI NIH HHS [EY00331, EY00444, EY12231] NR 48 TC 577 Z9 586 U1 2 U2 16 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1998 VL 20 IS 4 BP 344 EP 351 DI 10.1038/3813 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 142KM UT WOS:000077199600020 PM 9843205 ER PT J AU Richard, G Smith, LE Bailey, RA Itin, P Hohl, D Epstein, EH DiGiovanna, JJ Compton, JG Bale, SJ AF Richard, G Smith, LE Bailey, RA Itin, P Hohl, D Epstein, EH DiGiovanna, JJ Compton, JG Bale, SJ TI Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis SO NATURE GENETICS LA English DT Article ID GAP JUNCTION PROTEINS; MOLECULAR-CLONING; EXPRESSION; SKIN; EPIDERMIS; DEAFNESS; FAMILY; MODULATION; LINKAGE AB Erythrokeratodermia variabilis (EKV, OMIM 133200) is an autosomal dominant genodermatosis with considerable intra- and interfamilial variability(1). It has a disfiguring phenotype characterized by the independent occurrence of two morphologic features: transient figurate red patches and localized or generalized hyperkeratosis (Fig. 1). Both features can be triggered by external factors such as trauma to the skin. After initial linkage to the RH locus on 1p (refs 2,3). EKV was mapped to an an interval of 2.6 cM on 1p34-p35. and a candidate gene (GJA4) encoding the gap junction protein alpha-4 (connexin 31. Cx31) was excluded by sequence analysis(4). Evidence in mouse suggesting that the EKV region harbours a cluster of epidermally expressed connexin genes(5,6) led us to characterize the human homologues of GJB3 (encoding Cx31) and GJB5 (encoding Cx31.1). GJB3, GJB5 and GJA4 were localized to a 1.1-Mb YAC in the candidate interval. We detected heterozygous missense mutations in GJB3 in four EKV families leading to substitution of a conserved glycine by charged residues (G12R and G12D). or change of a cysteine (C865). These mutations are predicted to interfere with normal Cx31 structure and function, possibly due to a dominant inhibitory effect. Our results implicate Cx31 in the pathogenesis of EKV, and provide evidence that intercellular communication mediated by Cx31 is crucial for epidermal differentiation and response to external factors. C1 NIAMSD, Genet Studies Sect, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Basel, Dept Dermatol, Basel, Switzerland. Beaumont Hosp, Dept Dermatol, Lausanne, Switzerland. Univ Calif San Francisco, San Francisco Gen Hosp, Dept Dermatol, San Francisco, CA 94143 USA. Brown Univ, Rhode Isl Hosp, Dept Dermatol, Div Dermatopharmacol, Providence, RI 02903 USA. RP Bale, SJ (reprint author), NIAMSD, Genet Studies Sect, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NR 30 TC 235 Z9 249 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1998 VL 20 IS 4 BP 366 EP 369 DI 10.1038/3840 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 142KM UT WOS:000077199600024 PM 9843209 ER PT J AU Puel, A Ziegler, SF Buckley, RH Leonard, WJ AF Puel, A Ziegler, SF Buckley, RH Leonard, WJ TI Defective IL7R expression in T-B+NK+ severe combined immunodeficiency SO NATURE GENETICS LA English DT Article ID RECEPTOR-GAMMA-CHAIN; NATURAL-KILLER-CELLS; IL-2 RECEPTOR; INTERLEUKIN-7 RECEPTOR; FUNCTIONAL COMPONENT; PROGENITOR CELLS; LIGAND-BINDING; DIFFERENTIATION; MUTATION; JAK3 AB Severe combined immunodeficiency (SCID) is caused by multiple genetic defects(1-3). The most common form of SCID, X-linked SCID (XSCID), results from mutations in IL2RG (ref. 4), which encodes the common cytokine receptor gamma chain (gamma(c)) that is shared by the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors(1,5-10). In XSCID and SCID resulting from mutations in JAK3, which encodes a Janus family tyrosine kinase that couples to gamma(c) (refs 9,11,12) and is required for gamma(c)-dependent signalling, T- and natural killer (NK)-cells are decreased but B-cell numbers are normal(1-3,13,14) (T-B+NK- SCID). Some SCID patients lack T cells but retain NK cells. Given diminished T-cell development in IL7- or IL7r-deficient mice(15,16) and that Il7r-deficient mice have NK cells(17), we hypothesized that T-B+NK+ SCID might result from defective IL-7 signalling, although apparent differences in the role of the IL-7/IL-7R pathway in humans and mice in T-cell and B-cell development have been suggested(1,18). We now demonstrate medium control that defective IL7R expression causes T-B+NK+ SCID, indicating that the T-cell, but not the NK-cell, defect in XSCID results from inactivation of IL-7 alpha signalling. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. Duke Univ, Sch Med, Dept Immunol, Durham, NC 27710 USA. Duke Univ, Sch Med, Dept Pediat, Durham, NC 27710 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 29 TC 484 Z9 489 U1 1 U2 16 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1998 VL 20 IS 4 BP 394 EP 397 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 142KM UT WOS:000077199600031 PM 9843216 ER PT J AU Ambs, S Merriam, WG Ogunfusika, MO Bennett, WP Ishibe, N Hussain, SP Tzeng, EE Geller, DA Billiar, TR Harris, CC AF Ambs, S Merriam, WG Ogunfusika, MO Bennett, WP Ishibe, N Hussain, SP Tzeng, EE Geller, DA Billiar, TR Harris, CC TI P53 and vascular endothelial growth factor regulate tumor growth of NOS2-expressing human carcinoma cells SO NATURE MEDICINE LA English DT Article ID NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; INDUCED APOPTOSIS; SUPPRESSOR GENE; MESSENGER-RNA; IN-VITRO; EXPRESSION; ANGIOGENESIS; HEPATOCYTES; INHIBITION AB The finding of frequent nitric oxide synthase expression in human cancers indicates that nitric oxide has a pathophysiological role in carcinogenesis. To determine the role of nitric oxide in tumor progression, we generated human carcinoma cell lines that produced nitric oxide constitutively. Cancer cells expressing inducible nitric oxide synthase that had wild-type p53 had reduced tumor growth in athymic nude mice, whereas those with mutated p53 had accelerated tumor growth associated with increased vascular endothelial growth factor expression and neovascularization. Our data indicate that tumor-associated nitric oxide production may promote cancer progression by providing a selective growth advantage to tumor cells with mutant p53, and that inhibitors of inducible nitric oxide synthase may have therapeutic activity in these tumors. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15261 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov NR 33 TC 211 Z9 215 U1 1 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 1998 VL 4 IS 12 BP 1371 EP 1376 DI 10.1038/3957 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 144VW UT WOS:000077336900031 PM 9846573 ER PT J AU Hirsch, VM Sharkey, ME Brown, CR Brichacek, B Goldstein, S Wakefield, J Byrum, R Elkins, WR Hahn, BH Lifson, JD Stevenson, M AF Hirsch, VM Sharkey, ME Brown, CR Brichacek, B Goldstein, S Wakefield, J Byrum, R Elkins, WR Hahn, BH Lifson, JD Stevenson, M TI Vpx is required for dissemination and pathogenesis of SIVSM PBj: Evidence of macrophage-dependent viral amplification SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELL-CYCLE ARREST; INFECTION; HIV-1; MACAQUES; REPLICATION; GENE; TRANSMISSION; PROTEIN; AIDS AB The viral accessory protein Vpx is required for productive in vitro infection of macrophages by simian immunodeficiency virus from sooty mangabey monkeys (SIVSM). To evaluate the roles of Vpx and macrophage infection in vivo, we inoculated pigtailed macaques intravenously or intrarectally with the molecularly cloned, macrophage tropic, acutely pathogenic virus SIVSM PBj 6.6, or accessory gene deletion mutants (Delta Vpr or Delta Vpx) of this virus. Both wild-type and SIVSM PBj Delta Vpx viruses were readily transmitted across the rectal mucosa. A subsequent 'stepwise' process of local amplification of infection and dissemination was observed for wild-type virus, but not for SIVSM PBj Delta Vpx, which also showed considerable impairment of the overall kinetics and extent of its replication. In animals co-inoculated with equivalent amounts of wild-type and SIVSM Pbj Delta Vpx intravenously ol intrarectally, the Delta Vpx mutant was at a strong competitive disadvantage. Vpx-dependent viral amplification at local sites of initial infection, perhaps through a macrophage-dependent mechanism, may be a prerequisite for efficient dissemination of infection and pathogenic consequences after exposure through either mucosal or intravenous routes. C1 Univ Massachusetts, Med Ctr, Program Mol Med, Worcester, MA 01605 USA. NIAID, Mol Microbiol Lab, Twin Facil, Rockville, MD 20852 USA. Univ Alabama, Birmingham, AL 35294 USA. Bioqual Inc, Rockville, MD 20850 USA. NIAID, Infect Dis Lab, Rockville, MD 20852 USA. NCI, Lab Retroviral Pathogenesis, AIDS Vaccine Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Stevenson, M (reprint author), Univ Massachusetts, Med Ctr, Program Mol Med, Worcester, MA 01605 USA. FU NCRR NIH HHS [RR11589]; NHLBI NIH HHS [HL57880]; NIAID NIH HHS [AI37475] NR 45 TC 135 Z9 137 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 1998 VL 4 IS 12 BP 1401 EP 1408 DI 10.1038/3992 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 144VW UT WOS:000077336900036 PM 9846578 ER PT J AU Gurunathan, S Prussin, C Sacks, DL Seder, RA AF Gurunathan, S Prussin, C Sacks, DL Seder, RA TI Vaccine requirements for sustained cellular immunity to an intracellular parasitic infection SO NATURE MEDICINE LA English DT Article ID LEISHMANIA-MAJOR INFECTION; INTERFERON-GAMMA PRODUCTION; CD4(+) T-CELLS; BALB/C MICE; INTERLEUKIN-12; IL-12; DNA; RESPONSES; ANTIGEN; RESISTANCE AB The humoral immunity induced by many viral and bacterial vaccines mediates protection that is maintained over a long period of time. In contrast, for other intracellular infections (such as with Leishmania major or Mycobacterium tuberculosis) for which cell-mediated immunity is required for protection, the mechanisms for developing durable responses after vaccination have not been well defined. Here we demonstrate that vaccination with plasmid DNA encoding a specific leishmanial antigen is more effective than leishmanial protein plus recombinant IL-12 in eliciting long-term immunity capable of controlling L. major infection. We also show that leishmanial protein plus IL-12 DNA produces an immunity that lasts much longer than does immunity elicited by leishmanial protein plus IL-12 protein, indicating that the persistence of IL-12 may be the essential determinant in maintaining durable cell-mediated immune responses for an intracellular parasitic infection. C1 NIH, Bethesda, MD 20892 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Seder, RA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM rseder@nih.gov OI Prussin, Calman/0000-0002-3917-3326 NR 32 TC 175 Z9 179 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 1998 VL 4 IS 12 BP 1409 EP 1415 DI 10.1038/4000 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 144VW UT WOS:000077336900037 PM 9846579 ER PT J AU Machelska, H Cabot, PJ Mousa, SA Zhang, Q Stein, C AF Machelska, H Cabot, PJ Mousa, SA Zhang, Q Stein, C TI Pain control in inflammation governed by selectins SO NATURE MEDICINE LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; PERIPHERAL OPIOID ANALGESIA; INFLAMED TISSUE; POLYSACCHARIDE FUCOIDIN; GENE-EXPRESSION; BETA-ENDORPHIN; IMMUNE CELLS; P-SELECTIN; RECEPTORS; RATS AB Opioid-containing immune cells migrate preferentially to inflamed sites, where they release beta-endorphin which activates peripheral opioid receptors to inhibit pain(1,2). Immunocyte recruitment is a multistep, sequential engagement of various adhesion molecules located on immune cells and vascular endothelium. Selectins mediate the initial phase of immunoctye extravasation into inflamed sites(3,4). Here we show that anti-selectin treatment abolishes peripheral opioid analgesia elicited either endogenously (by stress) or by corticotropin-releasing factor. This results from a blockade of the infiltration of immunocytes containing beta-endorphin and the consequent decrease of the beta-endorphin content in the inflamed tissue. These findings indicate that the immune system uses mechanisms of cell migration not only to fight pathogens but also to control pain in injured tissue. Thus, pain is exacerbated by measures inhibiting the immigration of opioid-producing cells or, conversely, analgesia might be conveyed by adhesive interactions that recruit those cells to injured tissue. C1 Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. NIDA, Preclin Pharmacol Lab, IRP, NIH, Baltimore, MD 21224 USA. Free Univ Berlin, Klinikum Benjamin Franklin, Klin Anaesthesiol & Operat Intens Med, D-12200 Berlin, Germany. RP Machelska, H (reprint author), Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, 600 N Wolfe St, Baltimore, MD 21287 USA. RI Cabot, Peter/B-2424-2013; OI Cabot, Peter/0000-0003-1778-3753; Machelska, Halina/0000-0001-6315-2958; Stein, Christoph/0000-0001-5240-6836 NR 27 TC 125 Z9 129 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 1998 VL 4 IS 12 BP 1425 EP 1428 DI 10.1038/4017 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 144VW UT WOS:000077336900040 PM 9846582 ER PT J AU Chuang, RSI Jaffe, H Cribbs, L Perez-Reyes, E Swartz, KJ AF Chuang, RSI Jaffe, H Cribbs, L Perez-Reyes, E Swartz, KJ TI Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin SO NATURE NEUROSCIENCE LA English DT Article ID VERTEBRATE SENSORY NEURONS; HIGH-AFFINITY BINDING; FUNCTIONAL EXPRESSION; SODIUM-CHANNEL; ALPHA-SUBUNIT; BETA-SUBUNIT; CA-CHANNEL; K+ CHANNEL; CELLS; CURRENTS AB The biophysical properties of T-type voltage-gated calcium channels are well suited to pacemaking and to supporting calcium flux near the resting membrane potential in both excitable and nonexcitable cells. We have identified a new scorpion toxin (kurtoxin) that binds to the alpha(1G) T-type calcium channel with high affinity and inhibits the channel by modifying voltage-dependent gating. This toxin distinguishes between alpha(1G) T-type calcium channels and other types of voltage-gated calcium channels, including alpha(1A), alpha(1B), alpha(1C) and alpha(1E). Like the other alpha-scorpion toxins to which it is related, kurtoxin also interacts with voltage-gated sodium channels and slows their inactivation. Kurtoxin will facilitate characterization of the subunit composition of T-type calcium channels and help determine their involvement in electrical and biochemical signaling. C1 NINDS, Mol Physiol & Biophys Unit, NIH, Bethesda, MD 20892 USA. NINDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA. Loyola Univ, Med Ctr, Dept Physiol, Maywood, IL 60153 USA. RP Swartz, KJ (reprint author), NINDS, Mol Physiol & Biophys Unit, NIH, Bldg 36,Rm 2CI9,36 Convent Dr,MSC 4066, Bethesda, MD 20892 USA. EM kjswartz@codon.nih.gov FU Intramural NIH HHS [ZIA NS002945-13] NR 44 TC 123 Z9 131 U1 0 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 1998 VL 1 IS 8 BP 668 EP 674 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 144PR UT WOS:000077323400010 PM 10196582 ER PT J AU Lenz, O Zheng, F Vilar, J Doublier, S Lupia, E Schwedler, S Striker, LJ Striker, GE AF Lenz, O Zheng, F Vilar, J Doublier, S Lupia, E Schwedler, S Striker, LJ Striker, GE TI The inheritance of glomerulosclerosis in mice is controlled by multiple quantitative trait loci SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE genetics; glomerulosclerosis; mice; oligosyndactyly ID DIABETES-MELLITUS; MOUSE STRAINS; RENAL-DISEASE; RAT; MUTATION; GENOME AB Background. Glomerulosclerosis, the common terminal event in chronic glomerular diseases such as diabetic nephropathy or IgA nephropathy, leads to end-stage renal disease. The considerable variation in both the risk of developing glomerulosclerosis and the rate of progression in individual patients suggest a role for genetic factors which have not been identified so far. In this study we sought to examine the mode of inheritance of glomerulosclerosis in mice. Methods. F1 animals of a mating between glomerulosclerosis-prone ROP-Os/+ male and non-sclerotic C3H female mice were backcrossed to the ROP strain. We took advantage of the radiation-induced mutation oligosyndactylism (Os) to identify glomerulosclerosis at the age of 3 months. Kidneys were perfused in situ with PBS/Formalin 10%. The extent of glomerulosclerotic lesions was evaluated on PAS stained paraffin sections using computer-aided morphometry. Results. F1 mice did not show any glomerulosclerosis. In the backcross offspring, we found a wide distribution of glomerular lesions between individual animals, ranging from normal to very severe. We calculated that at least 8-10 loci determine the severity of glomerulosclerosis in mice. Conclusions. Our data show that glomerulosclerosis is inherited in a recessive fashion involving at least 8-10 loci. C1 NIDDK, Renal Cell Biol Sect, Metab Dis Branch, NIH, Bethesda, MD USA. INSERM, U319, Paris, France. Ivax Res Inst, Miami, FL USA. RP Striker, GE (reprint author), Univ Miami, Sch Med, Dept Med, Div Nephrol,Renal Cell Biol Lab, POB 016960,R-126, Miami, FL 33101 USA. RI Lenz, Oliver/M-4672-2016 OI Lenz, Oliver/0000-0003-2997-3976 NR 27 TC 28 Z9 28 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD DEC PY 1998 VL 13 IS 12 BP 3074 EP 3078 DI 10.1093/ndt/13.12.3074 PG 5 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 147CW UT WOS:000077471200022 PM 9870468 ER PT J AU Metman, LV Del Dotto, P van den Munckhof, P Fang, J Mouradian, MM Chase, TN AF Metman, LV Del Dotto, P van den Munckhof, P Fang, J Mouradian, MM Chase, TN TI Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease SO NERVENHEILKUNDE LA German DT Article DE amantadine; Parkinson's disease; levodopa; dyskinesias; motor fluctuations ID TARDIVE-DYSKINESIA; NMDA; COMPLICATIONS; PATHOGENESIS; ANTAGONIST; BLOCKADE; LEVODOPA; BRAIN; SITE AB Objective: To determine the effects of the N-methyl-D-aspartate (NMDA) antagonist amantadine on levodopa-associated dyskinesias and motor fluctuations in Parkinson's disease (PD). Background: NMDA receptor blockade can ameliorate levodopa-induced dyskinesias in primates and PD patients. Amantadine, a well-tolerated and modestly effective antiparkinsonian agent, was recently found to possess NMDA antagonistic properties. Methods: Eighteen patients with advanced PD participated in a double-blind, placebo-controlled, cross-over study. At the end of each 3-week treatment arm, parkinsonian and dyskinesia scores were obtained during a steady-state intravenous levodopa infusion. Motor fluctuations and dyskinesias were also documented with patient-kept diaries and Unified Parkinson's Disease Rating Scale (UPDRS) interviews. Results. In the 14 patients completing this trial, amantadine reduced dyskinesia averity by 60% (p = 0.001) compared to placebo, without altering the antiparkinsonian effect of levodopa. Motor everity by 60% (p = 0.001) compared to placebo, without altering the antiparkinsonian effect of levodopa. Motor fluctuations occurring with patients' regular oral levodopa regimen also improved according to UPDRS and patient-kept diaries. Conclusions: These findings suggest that amantadine given as adjuvant to levodopa can markedly improve motor response complications and support the view that hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa-associated motor complications. C1 NIH, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NIH, Bldg 10,Room 5C104,10 Ctr Dr Msc 1406, Bethesda, MD 20892 USA. NR 24 TC 1 Z9 1 U1 1 U2 2 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0722-1541 J9 NERVENHEILKUNDE JI Nervenheilkunde PD DEC PY 1998 VL 17 IS 10 BP 480 EP 484 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 154TC UT WOS:000077904100012 ER PT J AU Burchard, JF Nguyen, DH Richard, L Young, SN Heyes, MP Block, E AF Burchard, JF Nguyen, DH Richard, L Young, SN Heyes, MP Block, E TI Effects of electromagnetic fields on the levels of biogenic amine metabolites, quinolinic acid, and beta-endorphin in the cerebrospinal fluid of dairy cows SO NEUROCHEMICAL RESEARCH LA English DT Article DE cows; electric field; magnetic field; biogenic amines; quinolinic acid; beta-endorphin; tryptophan; 5-hydroxyindoleacetic acid; homovanillic acid; 3-methoxy-4-hydroxyphenylethylene glycol ID MORPHINE-INDUCED ANALGESIA; BRAIN-BARRIER PERMEABILITY; MAGNETIC-FIELDS; CHRONIC EXPOSURE; 5-HYDROXYINDOLEACETIC ACID; MICE; PRIMATES; RATS; TRYPTOPHAN; INHIBITION AB Eight multiparous non-lactating pregnant Holstein cows at 198 +/- 35 d of gestation, weighing 608 +/- 24 kg, were confined to wooden metabolic cages in an electric and magnetic field chamber with a 12:12 h light:dark cycle. Subarachnoidal catheters were installed 5 d before the activation of the electric and magnetic fields. The cows were exposed to electric and magnetic fields (60 Hz, 10 kV/m and 30 mu T) continuously except for the feeding and cleaning time for an average of 21.44 +/- 1.4 h per day for a period of 30 d. Cerebrospinal fluid samples were collected on three consecutive days before an exposure period of 30 d, on the last 3 d of the exposure period, and for 3 d starting 5 d after the exposure period. The concentrations of beta-endorphin, tryptophan, 5-hydroxyindoleacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylethyleneglycol and quinolinic acid in cerebrospinal fluid were determined. There was a significant increase in quinolinic acid, and a trend towards an increase in tryptophan, findings consistent with a weakening of the blood-brain barrier due to exposure to the electric and magnetic fields. C1 McGill Univ, Dept Psychiat, Montreal, PQ H3A 1A1, Canada. McGill Univ, Dept Anim Sci, St Anne De Bellevue, PQ H9X 3V9, Canada. Inst Rech Hydro Quebec, Varennes, PQ J3X 1S1, Canada. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. RP Young, SN (reprint author), McGill Univ, Dept Psychiat, 1033 Pine Ave W, Montreal, PQ H3A 1A1, Canada. EM mc51@musica.mcgill.ca RI Young, Simon/A-1865-2008; Block, Eric/D-3989-2014 OI Young, Simon/0000-0001-9666-8096; NR 27 TC 12 Z9 12 U1 1 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD DEC PY 1998 VL 23 IS 12 BP 1527 EP 1531 DI 10.1023/A:1020975903631 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 137GK UT WOS:000076906200010 PM 9821157 ER PT J AU Bolla, KI McCann, UD Ricaurte, GA AF Bolla, KI McCann, UD Ricaurte, GA TI Memory impairment in abstinent MDMA ("Ecstasy") users SO NEUROLOGY LA English DT Article ID CENTRAL SEROTONERGIC NEURONS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; CEREBROSPINAL-FLUID; 5-HYDROXYINDOLEACETIC ACID; NEUROTOXICITY; METHYLENEDIOXYMETHAMPHETAMINE; SOLVENTS; PRIMATES; SYSTEMS; HUMANS AB Background: Methylenedioxymethamphetamine (MDMA,, or "Ecstasy") is a popular recreational drug of abuse that is known to damage brain serotonergic neurons in animals and possibly humans. Few functional consequences of MDMA-induced serotonin (5-HT) neurotoxicity have been identified, either in animals or humans. This study sought to determine whether individuals with a history of extensive MDMA use showed evidence of memory impairment, because brain serotonin has been implicated in mnemonic function. Method: The authors compared 24 abstinent MDMA users and 24 control subjects on several standardized tests of memory, after matching subjects for age, gender, educational level, and vocabulary score (a surrogate of verbal intelligence). The authors also explored correlations between changes in memory function and decrements in CSF 5-hydroxyindoleacetic acid (5-HIAA), which serves as a marker of central 5-HT neural function. Results: Greater use of MDMA (total milligrams per month) was associated with greater impairment in immediate verbal memory (p < 0.02) and delayed visual memory (p < 0.06). Furthermore, lower vocabulary scores were associated with stronger dose-related effects, with men having greater dose-related deficits than women. Lastly, lower concentrations of CSF 5-HIAA were associated with poorer memory performance. Conclusion: Abstinent MDMA users have impairment in verbal and visual memory. The extent of memory impairment correlates with the degree of MDMA exposure and the reduction in brain 5-HT, as indexed by CSF 5-HIAA. C1 Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21205 USA. NIMH, Biol Psychiat Branch, Unit Anxiety, Bethesda, MD 20892 USA. RP Bolla, KI (reprint author), Johns Hopkins Bayview Med Ctr, Dept Neurol, 4940 Eastern Ave, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA05707, DA05938, R01 DA06275] NR 43 TC 258 Z9 261 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1998 VL 51 IS 6 BP 1532 EP 1537 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 147DX UT WOS:000077473900007 PM 9855498 ER PT J AU Kieburtz, K Simpson, D Yiannoutsos, C Max, MB Hall, CD Ellis, RJ Marra, CM McKendall, R Singer, E Dal Pan, GJ Clifford, DB Tucker, T Cohen, B AF Kieburtz, K Simpson, D Yiannoutsos, C Max, MB Hall, CD Ellis, RJ Marra, CM McKendall, R Singer, E Dal Pan, GJ Clifford, DB Tucker, T Cohen, B CA AIDS Clinical Trial Grp 242 Protocol Team TI A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection SO NEUROLOGY LA English DT Article; Proceedings Paper CT 122nd Annual Meeting of the American-Neurological-Association CY SEP 28-OCT 01, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Neurol Assoc ID DIABETIC NEUROPATHY; POSTHERPETIC NEURALGIA; INTRAVENOUS LIDOCAINE; PERIPHERAL NEUROPATHY; SENSORY NEUROPATHY; ORAL MEXILETINE; AIDS; PLACEBO; COHORT; DESIPRAMINE AB Background: Painful sensory neuropathy is a common complication of HIV infection. Based on prior uncontrolled observations, we hypothesized that amitriptyline or mexiletine would improve the pain symptoms. Method: A randomized, double-blind, 10-week trial of 145 patients assigned equally to amitriptyline, mexiletine, or matching placebo. The primary outcome measure was the change in pain intensity between baseline and the final visit. Results: The improvement in amitriptyline group (0.31 +/- 0.31 units [mean +/- SD]) and mexiletine group (0.23 +/- 0.41) was not significantly different from placebo (0.20 +/- 0.30). Both interventions were generally well tolerated. Conclusions: Neither amitriptyline nor mexiletine provide significant pain relief in patients with HIV-associated painful sensory neuropathy. C1 Univ Rochester, Med Ctr, Rochester, NY 14620 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Ctr Biostat AIDS Res, Boston, MA USA. NIDR, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Washington, Seattle, WA 98195 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Calif Los Angeles, ACTG, Los Angeles, CA USA. Univ Calif Los Angeles, CARE Ctr, Los Angeles, CA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Washington Univ, Sch Med, St Louis, MO USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Northwestern Univ, AIDS Clin Trials Unit, Chicago, IL 60611 USA. RP Kieburtz, K (reprint author), Univ Rochester, Med Ctr, 1351 Mt Hope Ave,Suite 220, Rochester, NY 14620 USA. RI Ellis, Ronald/K-3543-2015 OI Ellis, Ronald/0000-0003-4931-752X FU NCRR NIH HHS [RR00044, RR00772]; NINDS NIH HHS [NS 32228] NR 33 TC 142 Z9 146 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1998 VL 51 IS 6 BP 1682 EP 1688 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 147DX UT WOS:000077473900032 PM 9855523 ER PT J AU Weiss, MD Luciano, CA Semino-Mora, C Dalakas, MC Quarles, RH AF Weiss, MD Luciano, CA Semino-Mora, C Dalakas, MC Quarles, RH TI Molecular mimicry in chronic inflammatory demyelinating polyneuropathy and melanoma SO NEUROLOGY LA English DT Article ID MYELIN; LOCALIZATION; GLYCOPROTEIN; ANTIBODIES AB Polyclonal immunoglobulin M antibodies to the monosialoganglioside GM2, sulfoglucuronyl glycolipids, and sulfatide were detected by thin-layer chromatography and enzyme-linked immunosorbent assay in the serum of a patient with melanoma and chronic inflammatory demyelinating polyneuropathy. Both the patient's serum and polyclonal antibodies against GM2 reacted strongly with a biopsy of melanomatous tissue from the patient, suggesting a process of molecular mimicry. C1 NINDS, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Weiss, MD (reprint author), NINDS, Mol & Cellular Neurobiol Lab, NIH, Bldg 49,Room 2A-35,49 Convent Dr, Bethesda, MD 20892 USA. NR 10 TC 46 Z9 46 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD DEC PY 1998 VL 51 IS 6 BP 1738 EP 1741 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 147DX UT WOS:000077473900046 PM 9855537 ER PT J AU Dalakas, MC AF Dalakas, MC TI Mechanism of action of intravenous immunoglobulin and therapeutic considerations in the treatment of autoimmune neurologic diseases SO NEUROLOGY LA English DT Article ID MULTIFOCAL MOTOR NEUROPATHY; IMMUNE GLOBULIN THERAPY; GUILLAIN-BARRE-SYNDROME; GAMMA-GLOBULIN; MYASTHENIA-GRAVIS; KAWASAKI SYNDROME; CROSS-LINKING; DRUG-THERAPY; ANTIBODIES; DERMATOMYOSITIS AB On the basis of controlled clinical trials, high-dose intravenous immunoglobulin (Mg) has emerged as a critical therapy in the management of patients with various autoimmune neurologic diseases. Different interpretations of the clinical trial results, the expected benefit of Mg compared to that of alternate therapies, off-label use, results from anecdotal or empirical clinical trials, issues about safety and cost and, most importantly, the uncertainty about mechanisms of action of Mg have generated concerns among practicing neurologists. Understanding the mechanisms of action of IVIg and its potential risks or side effects is expected to help us make more judicious use of this powerful immunodulating agent. This article provides evidence that Mg has multiple actions which may operate in concert with each other but that for each disease a predominant mechanism may prevail according to the underlying immunopathogenetic cause of the respective disorder. The most relevant actions of Mg in the therapy of neurological diseases include (a) inhibition of complement binding and prevention of MAC formation, (b) neutralization of certain pathogenic cytokines, (c) downregulation of antibody production, and (d) modulation of Fc-receptor mediated phagocytosis. Additional actions include the effect of Mg on superantigens, modulation of T-cell function and antigen recognition, and enhancement of remyelination. On the basis of our experience with more than 130 closely monitored patients, I provide guidelines on how to use the drug, kinetics of Mg adverse reactions, and risk factors. In addition, the incidence, morbidity prevention and treatment of the common or rare side effects, including thromboembolic events, increased serum viscosity, aseptic meningitis, headaches, skin reactions, renal failure, and hemolysis are described. Spurious results of serologic tests, such as false hyponatremia and elevated sedimentation rate, as well as a transient rise in various viral titers, are described in an effort to avoid misinterpretations by treating neurologists. Finally, details on the latest findings of viral safety of IVIg are provided. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. NR 69 TC 74 Z9 77 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 DEC PY 1998 VL 51 IS 6 SU 5 BP S2 EP S8 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 149JQ UT WOS:000077601700002 PM 9851723 ER PT J AU Dalakas, MC AF Dalakas, MC TI The use of intravenous immunoglobulin for neurologic diseases SO NEUROLOGY LA English DT Editorial Material C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1998 VL 51 IS 6 SU 5 BP S1 EP S1 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 149JQ UT WOS:000077601700001 ER PT J AU Dalakas, MC AF Dalakas, MC TI Controlled studies with high-dose intravenous immunoglobulin in the treatment of dermatomyositis, inclusion body myositis, and polymyositis SO NEUROLOGY LA English DT Article ID CONTROLLED TRIAL; GAMMA-GLOBULIN; MYOPATHIES AB There are three major subsets of the inflammatory myopathies: polymyositis (PM), dermatomyositis (DM), and inclusion-body myositis (IBM). High-dose intravenous immunoglobulin (IVIg) has been tried in controlled clinical trials in patients with DM and IBM but not with PM. In patients with DM that is resistant or partially responsive to conventional therapies, Mg was very effective. The treated patients experienced dramatic improvement not only in muscle strength but also of their skin rash. Repeated muscle biopsies with quantitative histologic studies showed the Mg-treated patients had a statistically significant improvement of the muscle cytoarchitecture, with resolution of the aberrant immunopathologic parameters. In two controlled clinical trials conducted in IBM patients, Mg showed marginal improvements in muscle strength which were nonsignificant. However, a few IBM patients had a definite clinical improvement with increased activities of daily living, but when analyzed within the entire Mg-treated group, their total gains in muscle strength did not reach statistical significance compared to the placebo-treated group. Of interest is that certain muscle groups in the Mg-treated patients, such as the muscles of swallowing, showed significant improvement compared to those of the placebo-treated patients, implying mild regional effects. In PM, uncontrolled trials have shown improvements in muscle strength, but the controlled clinical trial is still ongoing. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. NR 30 TC 45 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1998 VL 51 IS 6 SU 5 BP S37 EP S45 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 149JQ UT WOS:000077601700008 PM 9851729 ER PT J AU Clifford, JJ Tighe, O Croke, DT Sibley, DR Drago, J Waddington, JL AF Clifford, JJ Tighe, O Croke, DT Sibley, DR Drago, J Waddington, JL TI Topographical evaluation of the phenotype of spontaneous behaviour in mice with targeted gene deletion of the D-1A dopamine receptor: paradoxical elevation of grooming syntax SO NEUROPHARMACOLOGY LA English DT Article DE dopamine D-1A receptor; targeted gene deletion; behavioural phenotype; grooming behaviour; topography; dopamine D-1-like receptors ID ANTAGONIST SCH-23390; MUTANT MICE; MOUSE; EXPRESSION; DEFICIENT; AGONISTS; BRAIN; ACTIVATION; RESPONSES; SKF-38393 AB The phenotype of spontaneous behaviour in mice with targeted gene deletion of the D-1A dopamine receptor was investigated topographically. Via direct visual observation, individual elements of behaviour were resolved and quantified using an ethologically-based, rapid time-sampling behavioural check-list procedure. Relative to wildtypes (D-1A(+/+)), D-1A-null ((-/-)) mice evidenced over initial exploration significant reductions in rearing free, sifting and chewing, but significant increases in locomotion, grooming and intense grooming. Sniffing and rearing to a wall habituated less readily in D-1A-null mice uch that these behaviours occurred subsequently to significant excess: increases in locomotion were persistent. The ethogram of spontaneous behaviour in D-1A-null mice was characterised by neither 'hypoactivity' or 'hyperactivity' but. rather, by prominent topographical shifts between individual elements of behaviour that could not be encapsulated by either term. Given the substantial body of evidence that grooming and particularly intense grooming constitute the most widely accepted behavioural index of D-1-like receptor function, the elevation of such behaviour in D-1A-null mice was paradoxical: it may reflect (over)compensatory processes subsequent to developmental absence of D-1A receptors and/or the involvement of a D-1-like receptor other than/additional to the D-1A subtype. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Royal Coll Surg Ireland, Dept Clin Pharmacol, Dublin 2, Ireland. Royal Coll Surg Ireland, Dept Biochem, Dublin 2, Ireland. NINDS, Expt Therapeut Branch, Bethesda, MD 20892 USA. Monash Univ, Dept Anat, Clayton, Vic 3168, Australia. RP Waddington, JL (reprint author), Royal Coll Surg Ireland, Dept Clin Pharmacol, St Stephens Green, Dublin 2, Ireland. NR 29 TC 68 Z9 71 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD DEC PY 1998 VL 37 IS 12 BP 1595 EP 1602 DI 10.1016/S0028-3908(98)00116-6 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 151ZP UT WOS:000077750900016 PM 9886682 ER PT J AU Lipska, BK Al-Amin, HA Weinberger, DR AF Lipska, BK Al-Amin, HA Weinberger, DR TI Excitotoxic lesions of the rat medial prefrontal cortex - Effects on abnormal behaviors associated with neonatal hippocampal damage SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; animal models; MK-801; amphetamine; apomorphine; ibotenic acid ID HALOPERIDOL-INDUCED CATALEPSY; INDUCED STEREOTYPIC BEHAVIORS; VENTRAL TEGMENTAL AREA; IBOTENIC ACID LESIONS; FRONTAL-CORTEX; DOPAMINE RELEASE; SUBCORTICAL DOPAMINE; INDUCED LOCOMOTION; NUCLEUS ACCUMBENS; DIRECT PROJECTION AB Neonatal excitotoxic damage of the ventral hippocampus (VH) is a heuristic model of schizophrenia. We investigated whether: (1) neonatal damage of the medial prefrontal cortex (mPFC) has effects similar to the neonatal VH lesion; and (2) intrinsic mPFC neurons contribute to the abnormal behaviors associated with VH lesions. Neonatal rats were lesioned in the mPFC. In adulthood, they showed attenuated locomotion in response to novelty, amphetamine, and MK-801, and enhanced apomorphine-induced stereotypies as compared to controls. Striatal D-1 and D-2 receptor mRNAs were unaltered. Another group was lesioned in the VH and additionally in the mPFC in adulthood. Destroying mPFC neurons normalized hyperlocomotion to novelty and amphetamine of the neonatally VH lesioned rats. Thus, neonatal damage of the mPFC does not provide a heuristic model of schizophrenia-like phenomena, in contrast to analogous damage of the VH. However, mPFC intrinsic neurons that have developed in the context of abnormal hippocampal connectivity may be responsible for abnormal behaviors in the neonatally VH lesioned vats. Published by Elsevier Science Inc. C1 NIMH, Intramural Res Program, Clin Brain Disorders Branch, NIH,Neurosci Ctr, Washington, DC 20032 USA. RP Lipska, BK (reprint author), NIMH, Intramural Res Program, Clin Brain Disorders Branch, NIH,Neurosci Ctr, 2700 Martin Luther King Ave SE, Washington, DC 20032 USA. RI Lipska, Barbara/E-4569-2017; OI Al-Amin, Hassen/0000-0001-6358-1541 NR 68 TC 90 Z9 92 U1 2 U2 5 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 DEC PY 1998 VL 19 IS 6 BP 451 EP 464 DI 10.1016/S0893-133X(98)00045-1 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 128TX UT WOS:000076423600001 PM 9803421 ER PT J AU Joyce, JN Murray, AM Hurtig, HI Gottlieb, GL Trojanowski, JQ AF Joyce, JN Murray, AM Hurtig, HI Gottlieb, GL Trojanowski, JQ TI Loss of dopamine D-2 receptors in Alzheimer's disease with parkinsonism but not Parkinson's or Alzheimer's disease SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE D-2 receptor; D-1 receptor; striatum; basal ganglia; receptor autoradiography ID STRIATAL DOPAMINE; HUMAN-BRAIN; SENILE DEMENTIA; SCHIZOPHRENIA; D1; HIPPOCAMPUS; EXPRESSION; BINDING; DENSITY AB A significant proportion of patients with Alzheimer's disease (AD) exhibit extrapyramidal features that are referred to as parkinsonism (AD/Park) to distinguish the clinical and pathological features that differ from Parkinson's disease (PD). Previous results from this laboratory have shown that, although the presynaptic components of the dopamine (DA) system are markedly affected in AD/Park, the pathology is not similar to PD (Murray et al. 1995; Joyce et al. 1997). In the present study, we determined whether the parkinsonian symptoms in AD/Park might also reflect changes in numbers of postsynaptic DA receptors. We analyzed the binding of[I-125]epidepride biding to DA D-2/D-3 receptors and [H-3]SCH 23390 to D-1 receptors by autoradiography in the striatum of six patients with PD, nine patients with AD, seven patients with AD/Park, and 14 neurologically intact control subjects. D-2 receptors were reduced in the caudate and putamen of the AD/Park group (by 42 and 27% of controls, respectively) but not reduced in AD or PD. D1 receptors were elevated by 36% in the putamen of the PD group. Dopamine receptor changes are, therefore, not similar in PD, AD, and Ad/Park. The elevation in D-1 receptors in PD may contribute to the unwanted side effects of L-dopa treatment. The loss of D-2 receptors in Ad/Park, not observed in AD lacking overt parkinsonian symptomatology, may contribute to the presence of parkinsonian features and lack of responsiveness to L-dopa. Published by Elsevier Science Inc. C1 Sun Hlth Res Inst, Christopher Ctr Parkinsons Dis Res, Sun City, AZ 85372 USA. NIMH, Clin Brain Disorders Branch, Washington, DC USA. Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Joyce, JN (reprint author), Sun Hlth Res Inst, Christopher Ctr Parkinsons Dis Res, POB 1278,10515 W Santa Fe Dr, Sun City, AZ 85372 USA. FU NIA NIH HHS [AG 10124, AG 09215]; NIMH NIH HHS [MH 56824] NR 46 TC 25 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 1998 VL 19 IS 6 BP 472 EP 480 DI 10.1016/S0893-133X(98)00044-X PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 128TX UT WOS:000076423600003 PM 9803423 ER PT J AU Gordis, E AF Gordis, E TI V. Markku I. Linnoila, 1947-1998 - In memoriam SO NEUROPSYCHOPHARMACOLOGY LA English DT Biographical-Item C1 NIAAA, NIH, Bethesda, MD 20205 USA. RP Gordis, E (reprint author), NIAAA, NIH, 6000 Execut Blvd,Suite 400, Bethesda, MD 20205 USA. NR 1 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 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 1998 VL 19 IS 6 BP 525 EP 526 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 128TX UT WOS:000076423600010 ER PT J AU Donevan, SD Rogawski, MA AF Donevan, SD Rogawski, MA TI Allosteric regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors by thiocyanate and cyclothiazide at a common modulatory site distinct from that of 2,3-benzodiazepines SO NEUROSCIENCE LA English DT Article DE AMPA receptor; flip and flop; 2,3-benzodiazepine; thiocyanate; cyclothiazide; desensitization ID XENOPUS-LAEVIS OOCYTES; D-ASPARTATE RECEPTOR; HIPPOCAMPAL-NEURONS; RAT-BRAIN; GLUTAMATE-RECEPTOR; AMPA RECEPTORS; MEDIATED RESPONSES; ACTIVATED CURRENTS; KAINATE RECEPTORS; DESENSITIZATION AB Allosteric regulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors include 2,3-benzodiazepines such as GYKI 52466 and GYKI 53655 and the chaotropic anion thiocyanate that inhibit, and benzothiadiazines such as cyclothiazide that potentiate AMPA receptor currents. Here we sought to determine whether the allosteric regulators modulate AMPA receptors at a common or distinct allosteric sites by comparing their actions on AMPA- and kainate-evoked currents in cultured rat hippocampal neurons and Xenopus oocytes expressing recombinant AMPA receptor subunits. GYKI 52466 and thiocyanate blocked AMPA-evoked currents in a concentration-dependent manner (IC50 values, 8.2 mu M and 1.1 mM, respectively); in contrast, kainate-evoked currents were blocked by GYKI 52466, but were potentiated by high concentrations of thiocyanate (greater than or equal to 3 mM). Thiocyanate enhanced the rate of desensitization and slowed recovery from desensitization of AMPA-evoked currents. whereas GYKI 52466 failed to affect desensitization. Among neurons in the hippocampal cultures, there was cell-to-cell variability in the sensitivity to block of AMPA-evoked currents by thiocyanate that was correlated with the degree of potentiation by cyclothiazide. Moreover, cyclothiazide caused a parallel rightward shift in the concentration-response curve for thiocyanate block, and slowed the onset of thiocyanate block to a rate that was similar to that of cyclothiazide dissociation. Together. these observations suggest that thiocyanate and cyclothiazide act at non-distinct allosteric sites. GYKI 52466 blocked AMPA receptor responses to a similar extent, irrespective of the degree of cyclothiazide potentiation. Moreover, the kinetics of GYKI 53655 block in the presence of cyclothiazide were not consistent with a competitive interaction. As is the case for cyclothiazide, SCN- exhibited greater affinity for Pip than for pop AMPA receptor splice variants. In particular, GluR1(flip)/GluR2(flip) was especially sensitive to thiocyanate block. We conclude that thiocyanate, a flip-preferring allosteric modulator like cyclothiazide, appears to act by enhancing desensitization at a site that may overlap the site where cyclothiazide reduces desensitization, whereas 2.3-benzodiazepines act at a distinct site and the block does not involve a modification of desensitization. C1 NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 30 TC 29 Z9 29 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1998 VL 87 IS 3 BP 615 EP 629 DI 10.1016/S0306-4522(98)00109-2 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 126AJ UT WOS:000076270200010 PM 9758228 ER PT J AU Domachowske, JB Bonville, CA Dyer, KD Rosenberg, HF AF Domachowske, JB Bonville, CA Dyer, KD Rosenberg, HF TI Evolution of antiviral activity in the ribonuclease A gene superfamily: evidence for a specific interaction between eosinophil-derived neurotoxin (EDN/RNase 2) and respiratory syncytial virus SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEIN-CODING GENES; CATIONIC PROTEIN; MOLECULAR-CLONING; ACID COMPOSITION; FAMILY; SEQUENCE; RATES; SUBSTITUTION; NUCLEOTIDE; ORIGIN AB We have demonstrated that the human eosinophil-derived neurotoxin (EDN, RNase 2), a rapidly evolving secretory protein derived from eosinophilic leukocytes, mediates the ribonucleolytic destruction of extracellular virions of the single-stranded RNA virus respiratory syncytial virus (RSV). While RNase activity is crucial to antiviral activity, it is clearly not sufficient, as our results suggest that EDM has unique structural features apart from RNase activity that are necessary to promote antiviral activity. We demonstrate here that the interaction between EDN and extracellular virions of RSV is both saturatable and specific. Increasing concentrations of the antivirally inactivated, ribonucleolytically inactivated point mutant form of recombinant human EDN, rhEDNdK(38), inhibits rhEDN's antiviral activity, while increasing concentrations of the related RNase, recombinant human RNase k6, have no effect whatsoever. Interestingly, acquisition of antiviral activity parallels the evolutionary development of the primate EDN lineage, having emerged some time after the divergence of the Old World from the New World monkeys. Using this information, we created ribonucleotytically active chimeras of human and New World monkey orthologs of EDN and, by evaluating their antiviral activity, we have identified an N-terminal segment of human EDN that contains one or more of the sequence elements that mediate its specific interaction with RSV. C1 SUNY Syracuse, Hlth Sci Ctr, Dept Pediat, Div Infect Dis, Syracuse, NY 13210 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), SUNY Syracuse, Hlth Sci Ctr, Dept Pediat, Div Infect Dis, Syracuse, NY 13210 USA. EM hr2k@nih.gov NR 45 TC 50 Z9 52 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 1 PY 1998 VL 26 IS 23 BP 5327 EP 5332 DI 10.1093/nar/26.23.5327 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 147WE UT WOS:000077487400013 PM 9826755 ER PT J AU Rouse, DJ Andrews, WW Lin, FYC Mott, CW Ware, JC Philips, JB AF Rouse, DJ Andrews, WW Lin, FYC Mott, CW Ware, JC Philips, JB TI Antibiotic susceptibility profile of group B streptococcus acquired vertically SO OBSTETRICS AND GYNECOLOGY LA English DT Article AB Objective: To determine the contemporary antibiotic susceptibility profile of vertically acquired group B streptococcal isolates. Methods: Susceptibility to ampicillin, penicillin G, erythromycin, clindamycin, cefazolin, and gentamicin was assessed by two methods, minimal inhibitory concentration and disc diffusion. Results: The susceptibility profiles of 119 colonizing and eight invasive strains of group B streptococcus isolated from January 1996 to September 1997 at two hospitals in Birmingham, Alabama-University of Alabama at Birmingham and Cooper Green-were studied. Minimal inhibitory concentration determinations indicated that all colonizing strains were susceptible or moderately susceptible to ampicillin and penicillin G. Resistance was noted by at least one strain to each of the other antibiotics; all were resistant to gentamicin, whereas 27 (21%) were resistant to erythromycin, five (4%) to clindamycin, and one (1%) to cefazolin. All of the eight invasive strains were susceptible or moderately susceptible to ampicillin, penicillin G, clindamycin, and cefazolin; one (13%) was resistant to erythromycin, and all were resistant to gentamicin. Disc diffusion results generally were concordant with minimal inhibitory concentration results, although by disc diffusion fewer isolates were classified as susceptible, and more as moderately susceptible, to ampicillin and penicillin G than by minimal inhibitory concentration. Conclusion: Universal susceptibility of group B streptococcus to members of the penicillin family supports the continued use of penicillin G or ampicillin for early onset neonatal group B streptococcal disease prevention. For patients allergic to beta-lactam agents, clindamycin (4% resistance) may be a better alternative than erythromycin (21% resistance). (Obstet Gynecol 1998;92:931-4. (C) 1998 by The American College of Obstetricians and Gynecologists.). C1 Univ Alabama, Dept Obstet & Gynecol, Div Maternal Fetal Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Pediat, Div Neonatol, Birmingham, AL USA. NICHHD, Bethesda, MD 20892 USA. RP Rouse, DJ (reprint author), Univ Alabama, Dept Obstet & Gynecol, Div Maternal Fetal Med, Birmingham, AL 35294 USA. FU NICHD NIH HHS [N01 HD 4-3219]; PHS HHS [290-92-0055] NR 10 TC 27 Z9 31 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 DEC PY 1998 VL 92 IS 6 BP 931 EP 934 DI 10.1016/S0029-7844(98)00263-4 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 140ZT UT WOS:000077118700008 PM 9840552 ER PT J AU Klier, CM Roble, AG Kolenbrander, PE AF Klier, CM Roble, AG Kolenbrander, PE TI Actinomyces serovar WVA963 coaggregation-defective mutant strain PK2407 secretes lactose-sensitive adhesin that binds to coaggregation partner Streptococcus oralis 34 SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Actinomyces; adhesin; coaggregation-defective mutant ID UROPATHOGENIC ESCHERICHIA-COLI; FIMBRIAE; PROTEIN; PILUS; IDENTIFICATION; DISTINCT; BACTERIA AB Actinomyces serovar WVA963 strain PK1259 mediates intergeneric coaggregation with several oral streptococci. These lactose-inhibitable coaggregations appear to involve a 95-kDa putative actinomyces adhesin in complex with type 2 fimbriae. A coaggregation-defective strain PK2407 lacking type 2 fimbriae synthesizes the putative adhesin but appears unable to present it properly on its surface. Antiserum was raised against surface sonicates of PK2407 and was absorbed with a different coaggregation-defective mutant PK3092 that synthesizes type 2 fimbriae but no adhesin. This absorbed antiserum specifically blocked lacrose-inhibitable coaggregation of wild-type strain PK1259 and Streptococcus oralis 34 and identified a 95-kDa protein in ammonium sulfate precipitates of culture supernatant of the coaggregation-defective mutant PK2407. The 95-kDa secreted protein was bound to the streptococcal partner cells and to lactose-agarose affinity beads and was released by lactose from both the affinity beads and partner, indicating that the secreted and precipitated protein is biochemically active and may mediate coaggregation with streptococci. C1 NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Kolenbrander, PE (reprint author), NIDR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 310,30 Convent Dr MSC 4350, Bethesda, MD 20892 USA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD DEC PY 1998 VL 13 IS 6 BP 337 EP 340 PG 4 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 139YW UT WOS:000077059700002 PM 9872108 ER PT J AU Shahabuddin, M Cociancich, S Zieler, H AF Shahabuddin, M Cociancich, S Zieler, H TI The search for novel malaria transmission-blocking targets in the mosquito midgut SO PARASITOLOGY TODAY LA English DT Article ID ANOPHELES-GAMBIAE; PLASMODIUM-GALLINACEUM; SPOROGONIC DEVELOPMENT; AEDES-AEGYPTI; SUSCEPTIBLE STRAINS; VECTOR MOSQUITO; SEPHADEX BEADS; IN-VITRO; PARASITES; INFECTIVITY AB The need for new malaria control strategies has led to increased efforts to understand more clearly the mosquito stages of Plasmodium. The absolute requirement of gamete maturation and fertilization, transformation of sedentary zygote to motile ookinete, ookinete interaction and invasion of gut epithelium, and the survival of the mosquito against immune attack suggest that numerous unidentified targets exist, which could be modified to achieve transmission-blocking of malaria. In the search for new transmission-blocking targets in the mosquito gut, Mohammed Shahabuddin, Stephane Cociancich and Helge Zieler here summarize recent studies to identify the cellular and biochemical factors that affect the malaria parasite's development; in particular, factors influencing the early development of Plasmodium, receptor-mediated interactions between the parasite and the mosquito midgut, and the gut-associated immune responses directed against Plasmodium. C1 NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Shahabuddin, M (reprint author), NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI COCIANCICH, Stephane/C-4267-2014 OI COCIANCICH, Stephane/0000-0001-8601-3598 NR 32 TC 25 Z9 26 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD DEC PY 1998 VL 14 IS 12 BP 493 EP 497 DI 10.1016/S0169-4758(98)01348-9 PG 5 WC Parasitology SC Parasitology GA 146CU UT WOS:000077411100008 PM 17040863 ER PT J AU Nakajima, M Kawanami, O Jin, E Ghazizadeh, M Honda, M Asano, G Horiba, K Ferrans, VJ AF Nakajima, M Kawanami, O Jin, E Ghazizadeh, M Honda, M Asano, G Horiba, K Ferrans, VJ TI Immunohistochemical and ultrastructural studies of basal cells, Clara cells and bronchiolar cuboidal cells in normal human airways SO PATHOLOGY INTERNATIONAL LA English DT Article DE airway basal cells; bronchiolar cuboidal cells; Clara cells; cytokeratins; type VII collagen ID IDIOPATHIC PULMONARY FIBROSIS; FIBROTIC LUNG DISORDERS; VII COLLAGEN; EPIDERMOLYSIS-BULLOSA; MONOCLONAL-ANTIBODIES; ANCHORING FIBRILS; EPITHELIAL-CELLS; GROWING RAT; EXPRESSION; DIFFERENTIATION AB Immunohistochemical studies were made of the distribution of various cytokeratins (CK), Clara cell secretory protein (CC10), surfactant protein A (SP-A) and type VII collagen in normal human airways. Electron microscopic studies were made to identify hemidesmosomes and anchoring fibrils on the basal surfaces of the epithelial cells, CK19 was detected in all epithelial cells, and CK17 in all basal cells. CK14 was coexpressed in a few basal cells, and this coexpression was decreased in the distal airways, Two types of basal cells were recognized, One type, found mainly in large airways, was characterized by abundant intermediate filaments and well-developed hemidesmosomes and anchoring fibrils. The second type contained few intermediate filaments and poorly developed hemidesmosomes and anchoring fibrils. Reactivity for type VII collagen was found along the basement membrane throughout the airways, but not in the alveoli. Clara cells were reactive for CC10 and CK17, but not for CK14 and SP-A, The bronchiolar cuboidal cells in the respiratory bronchioles were positive only for CK19. Surfactant protein A was present only in type II alveolar epithelial cells, Thus, two types of basal cells are present in airways, and the bronchiolar cuboidal cells appear distinct from these basal cells, Clara cells and type II alveolar epithelial cells. C1 Nippon Med Sch, Dept Dermatol, Tokyo 113, Japan. Nippon Med Sch, Dept Pathol, Tokyo 113, Japan. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. Nippon Med Sch, Inst Gerontol, Dept Mol Pathol, Nakahara Ku, Kawasaki, Kanagawa 2118533, Japan. RP Kawanami, O (reprint author), Nippon Med Sch, Inst Gerontol, Dept Mol Pathol, Nakahara Ku, Kosugi Cho 1-396, Kawasaki, Kanagawa 2118533, Japan. NR 38 TC 26 Z9 29 U1 2 U2 4 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1320-5463 J9 PATHOL INT JI Pathol. Int. PD DEC PY 1998 VL 48 IS 12 BP 944 EP 953 PG 10 WC Pathology SC Pathology GA 165JJ UT WOS:000078517400003 PM 9952338 ER PT J AU Rapoport, JL Fiske, A AF Rapoport, JL Fiske, A TI The new biology of obsessive-compulsive disorder: Implications for evolutionary psychology SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; BASAL GANGLIA; SYMPTOM PROVOCATION; SYDENHAMS CHOREA; CHILDHOOD; CHILDREN; PSYCHOPATHOLOGY; ADOLESCENTS; BEHAVIOR C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Anthropol, Los Angeles, CA 90024 USA. RP Rapoport, JL (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 3N202,10 Ctr Dr, Bethesda, MD 20892 USA. NR 75 TC 28 Z9 28 U1 4 U2 8 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0031-5982 EI 1529-8795 J9 PERSPECT BIOL MED JI Perspect. Biol. Med. PD WIN PY 1998 VL 41 IS 2 BP 159 EP 175 PG 17 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA YY576 UT WOS:000072162000001 PM 9493398 ER PT J AU Zhou, YY Jiang, R Ling, S Tseng, GN AF Zhou, YY Jiang, R Ling, S Tseng, GN TI Stabilization of a channel's open state by a hydrophobic residue in the sixth membrane-spanning segment (S6) of rKv1.4 SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE mammalian A-type K channel; mutagenesis; gating model; voltage-dependent gating process ID SHAKER K+-CHANNELS; POTASSIUM CHANNELS; SODIUM-CHANNEL; S3-S4 LINKER; VOLTAGE; ACTIVATION; S4; INACTIVATION; REGION; SUBSTITUTION AB We report the effects of mutating a threonine residue at position 529 (T529) in the middle of the S6 segment of rKv1.4 on the voltage-dependence and kinetics of activation and deactivation. Replacing T529 with glycine (no side chain) or with a residue that has a hydrophobic side chain (T529L, T529I, T529V, T529A, or T529F) caused a slowing of deactivation, along with a negative shift in the activation curve and a voltage-dependent slowing of activation. Numerical simulation showed that these effects could be reproduced by decreasing the rate constant for a transition from open to closed states. The degree of slowing of deactivation largely correlated with the degree of increase in 529 side-chain hydrophobicity. Specifically the 529 mutation-induced alteration in free energy change accompanying deactivation per channel could be accounted for by the increase in free energy needed to transfer the 529 side chain of one subunit from a hydrophobic environment to an aqueous environment. We propose that in the open state, the 529 side chain faces a hydrophobic protein interior. The rate-limiting step in channel deactivation includes a conformational change in one subunit's S6 segment, moving its 529 side chain to face the aqueous lumen of the pore. C1 Columbia Univ, Dept Pharmacol, New York, NY 10032 USA. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Tseng, GN (reprint author), Columbia Univ, Dept Pharmacol, 630 W 168th St, New York, NY 10032 USA. FU NHLBI NIH HHS [HL-46451] NR 44 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD DEC PY 1998 VL 437 IS 1 BP 114 EP 122 DI 10.1007/s004240050755 PG 9 WC Physiology SC Physiology GA 145DL UT WOS:000077355700017 PM 9817795 ER PT J AU Steele, VE Wargovich, MJ McKee, K Sharma, S Wilkinson, BP Wyatt, GP Gao, P Kelloff, GJ AF Steele, VE Wargovich, MJ McKee, K Sharma, S Wilkinson, BP Wyatt, GP Gao, P Kelloff, GJ TI Cancer chemoprevention drug development strategies for resveratrol SO PHARMACEUTICAL BIOLOGY LA English DT Article DE chemoprevention; colon cancer; resveratrol; grape extracts; aberrant colon crypts; prevention; rat tracheal epithelial cells ID PERSPECTIVES; PREVENTION; PROGRESS; AGENTS; TRIALS AB Cancer chemoprevention refers to the reduction of cancer incidence by administration of agents or drugs which inhibit, reverse, or retard the cancer process. Resveratrol has demonstrated a wide variety of biological activities which make it a good candidate for a chemopreventive agent. Many agents, such as resveratrol are currently being tested with the goal of developing safe and effective chemopreventive drugs for human use. Resveratrol was investigated as a potential chemopreventive agent using two in vitro assays to determine preliminary efficacy. In the first assay anchorage-independent growth was inhibited in the human lung tumor cells. In the second assay B[a]P induced transformation was inhibited in primary rat tracheal epithelial cells. With these two positive in vitro results and a mechanistic hypothesis of action, animal testing was begun. The azoxymethane-induced aberrant colon crypt model is typically the next step in developmental strategy. Resveratrol was tested for its ability to inhibit aberrant colon crypts in the colon of F344 rats which had been treated with azoxymethane. One test protocol showed significant inhibition of aberrant colon crypts in a carcinogen treated rat model. Further development of this agent includes demonstration of the preventive efficacy in an in vivo tumorigenesis model, followed by preclinical pharmacology and toxicology testing. Phase I, II, and III clinical chemoprevention trials would be then performed to determine pharmacokinetics, safe dose levels, and chemopreventive effectiveness for New Drug Approval by the FDA. C1 NCI, Chemoprevent Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. Mantech Environm Sci, Res Triangle Pk, NC 27709 USA. RP Steele, VE (reprint author), NCI, Chemoprevent Branch, NIH, 6130 Execut Blvd,MSC 7322, Bethesda, MD 20892 USA. NR 22 TC 2 Z9 2 U1 1 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PD DEC PY 1998 VL 36 SU S BP 62 EP 68 DI 10.1076/phbi.36.6.62.4552 PG 7 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 157AG UT WOS:000078036100010 ER PT J AU McLeod, HL Collie-Duguid, ESR Vreken, P Johnson, MR Wei, X Sapone, A Diasio, RB Fernandez-Salguero, P van Kuilenberg, ABP van Gennip, AH Gonzalez, FJ AF McLeod, HL Collie-Duguid, ESR Vreken, P Johnson, MR Wei, X Sapone, A Diasio, RB Fernandez-Salguero, P van Kuilenberg, ABP van Gennip, AH Gonzalez, FJ TI Nomenclature for human DPYD alleles SO PHARMACOGENETICS LA English DT Article DE allele nomenclature; DPYD; dihydropyrimidine dehydrogenase; pyrimidine metabolism ID DIHYDROPYRIMIDINE DEHYDROGENASE-DEFICIENCY; 5-FLUOROURACIL TOXICITY; MONONUCLEAR-CELLS; CANCER-PATIENTS; MOLECULAR-BASIS; GENE; IDENTIFICATION; CHEMOTHERAPY; POPULATION; LIVER AB To standardize DPYD allele nomenclature and to conform with international human gene nomenclature guidelines, an alternative to the current arbitrary system is described. Based on recommendations for human genome nomenclature, we propose that each distinct allele be designed by DPYD followed by an asterisk and an Arabic numeral. The number specifies the key mutation and, where appropriate, a letter following the number indicates an additional mutation on the mutant allele, Criteria for classification as a distinct allele are also presented. Pharmacogenetics 8:455-459. (C) 1998 Lippincott Williams & Wilkins. C1 Univ Aberdeen, Inst Med Sci, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland. Emma Childrens Hosp, Amsterdam Med Ctr, Dept Clin Chem, Amsterdam, Netherlands. Univ Alabama, Dept Pharmacol & Toxicol, Birmingham, AL USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NCI, Lab Metab, NIH, Bethesda, MD USA. Univ Extremadura, Fac Ciencias, Lab Bioquim & Biol Mol, E-06071 Badajoz, Spain. RP McLeod, HL (reprint author), Univ Aberdeen, Inst Med Sci, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland. EM h.l.mcleod@abdn.ac.uk RI Sapone, Andrea/E-6704-2013; Collie-Duguid, Elaina/A-4432-2017; OI Sapone, Andrea/0000-0001-8496-6977; Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 34 TC 66 Z9 72 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 1998 VL 8 IS 6 BP 455 EP 459 DI 10.1097/00008571-199812000-00001 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 157JY UT WOS:000078058800001 PM 9918128 ER PT J AU Przygodzki, RM Bennett, WP Guinee, DG Khan, MA Freedman, A Shields, PG Travis, WD Jett, JR Tazelaar, H Pairolero, P Trastek, V Liotta, LA Harris, CC Caporaso, NE AF Przygodzki, RM Bennett, WP Guinee, DG Khan, MA Freedman, A Shields, PG Travis, WD Jett, JR Tazelaar, H Pairolero, P Trastek, V Liotta, LA Harris, CC Caporaso, NE TI p53 mutation spectrum in relation to GSTM1, CYP1A1 and CYP2E1 in surgically treated patients with non-small cell lung cancer SO PHARMACOGENETICS LA English DT Article DE lung cancer; CYP1A1; GSTM1; CYP2E1; p53 ID S-TRANSFERASE M1; HYDROCARBON HYDROXYLASE-ACTIVITY; FRAGMENT-LENGTH-POLYMORPHISM; GERM-LINE POLYMORPHISMS; TUMOR-SUPPRESSOR GENE; DNA ADDUCT LEVELS; GLUTATHIONE TRANSFERASE; CYTOCHROME-P450IA1 GENE; CARCINOGEN METABOLISM; CIGARETTE-SMOKING AB p53 mutation status was analysed in relation to DNA polymorphisms of GSTM1, CYP1A1 and CYP2E1 from 105 surgically resected non-small cell lung cancer cases. Demographic factors, smoking, occupation, family history, tumour histology, grade and stage were taken into account. p53 mutations, detected either directly by DNA sequencing (P = 0.04, adjusted for smoking) or indirectly by immunostaining (P = 0.06), were overrepresented among CYP1A1 variants. Mutations in exon 8 and transitions at CpG sites in the p53 gene were favoured in this subset. There was no relation between the individual gene polymorphisms or p53 mutations and disease-free survival by Kaplan-Meier analysis, The finding of excess CYP1A1 heterozygotes in individuals with p53 mutations after adjustment for smoking suggests that CYP1A1 activation contributes to lung cancer via p53 inactivation. Pharmacogenetics 8:503-511. (C) 1998 Lippincott Williams & Wilkins. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Cellular Pathol, Washington, DC 20306 USA. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. RI Shields, Peter/I-1644-2012; OI Przygodzki, Ronald/0000-0002-1238-262X NR 49 TC 27 Z9 28 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 1998 VL 8 IS 6 BP 503 EP 511 DI 10.1097/00008571-199812000-00007 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 157JY UT WOS:000078058800007 PM 9918134 ER PT J AU Leathart, JBS London, SJ Steward, A Adams, JD Idle, JR Daly, AK AF Leathart, JBS London, SJ Steward, A Adams, JD Idle, JR Daly, AK TI CYP2D6 phenotype-genotype relationships in African-Americans and Caucasians in Los Angeles SO PHARMACOGENETICS LA English DT Article DE cytochrome P450; CYP2D6; debrisoquine; polymorphism ID POOR METABOLIZER PHENOTYPE; DRUG-METABOLISM; MOLECULAR-BASIS; DEBRISOQUINE HYDROXYLATION; GENETIC-POLYMORPHISM; EUROPEAN POPULATION; LOWER PREVALENCE; ALLELIC VARIANT; DNA-SEQUENCE; CYTOCHROME-P450 AB CYP2D6 genotyping (CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*13, CYP2D6*16 alleles and gene duplications) was previously performed on 1053 Caucasian and African-American lung cancer cases and control individuals and no significant difference in allele frequencies between cases and control individuals detected. We have carried out additional genotyping (CYP2D6*6, CYP2D6*7, CYP2D6*8, CYP2D6*9, CYP2D6*10, CYP2D6*17 alleles) and debrisoquine phenotyping on subgroups from this study to assess phenotype-genotype relationships. African-Americans showed significant differences from Caucasians with respect to frequency of defective CPP2D6 alleles, particularly CYP2D6*4 and CYP2D6*5, The CYP2D6*17 allele occurred at a frequency of 0.26 among 87 African-Americans and appeared to explain higher average metabolic ratios among African-Americans compared with Caucasians. CYP2D6*6, CYP2D6*8, CYP2D6*9 and CYP2D6*10 were rare in both ethnic groups but explained approximately 40% of higher than expected metabolic ratios among extensive metabolizers. Among individuals phenotyped with debrisoquine, 32 out of 359 were in the poor metabolizer range with 24 of these (75%) also showing two defective CYP2D6 alleles, Additional single strand conformational polymorphism analysis screening of samples showing large phenotype - genotype discrepancies resulted in the detection of three novel polymorphisms. If subjects taking potentially interfering drugs were excluded, this additional screening enabled the positive identification of 88% of phenotypic poor metabolizers by genotyping, This sensitivity was comparable with that of phenotyping, which identified 90% of those with two defective alleles as poor metabolizers, Pharmacogenetics 8:529-541. (C) 1998 Lippincott Williams & Wilkins. C1 Univ Newcastle Upon Tyne, Sch Med, Dept Pharmacol Sci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90033 USA. Inst Canc Res & Mol Biol, Med Tekn Senter, Trondheim, Norway. RP Daly, AK (reprint author), Univ Newcastle Upon Tyne, Sch Med, Dept Pharmacol Sci, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. EM A.K.Daly@newcastle.ac.uk RI Daly, Ann/H-3144-2011; OI Daly, Ann/0000-0002-7321-0629; Idle, Jeff/0000-0002-6143-1520; London, Stephanie/0000-0003-4911-5290 NR 44 TC 86 Z9 91 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 1998 VL 8 IS 6 BP 529 EP 541 DI 10.1097/00008571-199812000-00010 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 157JY UT WOS:000078058800010 PM 9918137 ER PT J AU Wess, J AF Wess, J TI Molecular basis of receptor/G-protein-coupling selectivity SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE G-protein-coupled receptors; G-proteins; receptor activation; G-protein activation; receptor/G-protein interactions; receptor/G-protein coupling selectivity ID 3RD INTRACELLULAR LOOP; GUANINE-NUCLEOTIDE-BINDING; MUSCARINIC ACETYLCHOLINE-RECEPTORS; BETA-ADRENERGIC RECEPTORS; METABOTROPIC GLUTAMATE RECEPTORS; SIGNAL-TRANSDUCTION PATHWAYS; PUTATIVE PHEROMONE RECEPTORS; SITE-DIRECTED MUTAGENESIS; MEMBRANE-SPANNING SEGMENT; HETEROTRIMERIC G-PROTEINS AB Molecular cloning studies have shown that G-protein coupled receptors form one of the largest protein families found in nature, and it is estimated that approximately 1000 different such receptors exist in mammals. Characteristically, when activated by the appropriate ligand, an individual receptor can recognize and activate only a limited set of the many structurally closely related heterotrimeric G-proteins expressed within a cell. To understand how this selectivity is achieved at a molecular level has become the focus of an ever increasing number of laboratories. This review provides an overview of recent structural, molecular genetic, biochemical, and biophysical studies that have led to novel insights into the molecular mechanisms governing receptor-mediated G-protein activation and receptor/G protein coupling selectivity. PHARMACOL. THER. 80(3):231-264, 1998. (C) 1998 Elsevier Science Inc. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 281 TC 303 Z9 312 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD DEC PY 1998 VL 80 IS 3 BP 231 EP 264 DI 10.1016/S0163-7258(98)00030-8 PG 34 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 141QM UT WOS:000077155000001 PM 9888696 ER PT J AU Balbach, JJ Conradi, MS Hoffmann, MM Udovic, TJ Adolphi, NL AF Balbach, JJ Conradi, MS Hoffmann, MM Udovic, TJ Adolphi, NL TI Nuclear magnetic resonance evidence of disorder and motion in yttrium trideuteride SO PHYSICAL REVIEW B LA English DT Article ID SWITCHABLE OPTICAL-PROPERTIES; LANTHANUM HYDRIDE FILMS; THEORETICAL PREDICTION; ELECTRONIC-STRUCTURE; HYDROGEN DIFFUSION; INSULATING YH3; METAL-HYDRIDES; NMR; DYNAMICS; SITE AB Three samples of YDx, with x ranging from 2.9 to nearly 3.0, were studied with deuterium nuclear magnetic resonance to gain insight into the locations of the D atoms in the lattice and their motions. Line shapes at low temperatures (200-330 K) show substantial disorder at some of the deuterium sites. Near 355 K, the spectrum sharpens to yield three uniaxial Fake patterns, reflecting a motional averaging process. However, the three measured intensities do not match the ratios expected from the neutron-determined, HoD3-like structure. This is strong evidence that the structure and space group of YD3 are different than reported, or that the current model needs adjustment. At still higher temperatures near 400 K, the Fake doublet features broaden, and a single sharp resonance develops, signalling a diffusive motion that carries all D atoms over all sites. The temperature at which line shape changes occur depends on the number of deuterium vacancies, 3-x. The changes occur at lower temperatures in the most defective sample, indicating the role of D-atom vacancies in the motional processes. The longitudinal relaxation rate T-1(-1) displays two regimes, being nearly temperature independent below 300 K and strongly thermally activated above. The relaxation rate depends on the number of deuterium vacancies, 3-x, varying an order of magnitude over the range of stoichiometries studied and suggesting that D-atom diffusion is involved. Also, the activation energy describing T-1(-1) (similar or equal to k(B)x 5500 K) approximately matches that for diffusion. An unusual omega(0)(-0.7) frequency dependence of T-1(-1) is observed. A relaxation mechanism is proposed in which diffusion is the Pate-determining step and in which frequency dependence arises from a field-dependent radius of the relaxation zones. [S0163-1829(98)07845-X]. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Washington Univ, Dept Phys, St Louis, MO 63130 USA. Pacific NW Natl Lab, Richland, WA 99352 USA. NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. Knox Coll, Dept Phys, Galesburg, IL 61401 USA. RP Balbach, JJ (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. NR 31 TC 20 Z9 20 U1 0 U2 1 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1098-0121 EI 1550-235X J9 PHYS REV B JI Phys. Rev. B PD DEC 1 PY 1998 VL 58 IS 22 BP 14823 EP 14832 DI 10.1103/PhysRevB.58.14823 PG 10 WC Physics, Condensed Matter SC Physics GA 146XW UT WOS:000077460000036 ER PT J AU Nagle, JF Petrache, HI Gouliaev, N Tristram-Nagle, S Liu, YF Suter, RM Gawrisch, K AF Nagle, JF Petrache, HI Gouliaev, N Tristram-Nagle, S Liu, YF Suter, RM Gawrisch, K TI Multiple mechanisms for critical behavior in the biologically relevant phase of lecithin bilayers SO PHYSICAL REVIEW E LA English DT Article ID MULTILAMELLAR LIPID BILAYERS; X-RAY-SCATTERING; PHOSPHATIDYLCHOLINE BILAYERS; BENDING ELASTICITY; FLUID MEMBRANES; PHOSPHOLIPID-BILAYERS; MODEL MEMBRANES; LAMELLAR PHASE; FLUCTUATIONS; TEMPERATURE AB Lipid bilayer membranes manifest critical behavior in the lamellar D spacing observed by x-ray and neutron diffraction as the main phase transition is approached from the biologically relevant high temperature phase. The freezing out of conformational disorder of the hydrocarbon chains drives the main transition, but how this causes critical behavior of D(T) has been an interesting puzzle and various models are under investigation. This paper presents x-ray scattering and NMR data to test the various models. One model involves the straightforward lengthening of hydrocarbon chains as T-M is approached, but it is shown that this accounts only for about half the anomalous increase in D. Another model of fluctuation induced expansion of the water region is shown to be inconsistent with two kinds of data. The first inconsistency is the lack of an increase in the Caille fluctuation parameter eta(1). The second inconsistency is with D(T) data taken under osmotic pressure. Accurate simulations are employed to predict the theoretical values. A third model considers that the water spacing could expand because other interactions between bilayers may change as T-M is approached, but there is no quantitative support for this model at present. A fourth model involving expansion of the headgroup region is tested with NMR data; results are qualitatively consistent but quantitatively inconclusive. While the precise mixture of models is still unresolved, it is concluded that multiple mechanisms must be operating in this critical regime. [S1063-651X(98)12212-2]. C1 Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. NIAAA, Natl Inst Hlth, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. RP Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA. EM nagle+@andrew.cmu.edu RI Tristram-Nagle, Prof. Stephanie/N-7811-2014; Suter, Robert/P-2541-2014; Nagle, John/B-1917-2015 OI Tristram-Nagle, Prof. Stephanie/0000-0003-2271-7056; Suter, Robert/0000-0002-0651-0437; Nagle, John/0000-0002-9844-5934 NR 42 TC 58 Z9 62 U1 3 U2 6 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2470-0045 EI 2470-0053 J9 PHYS REV E JI Phys. Rev. E PD DEC PY 1998 VL 58 IS 6 BP 7769 EP 7776 DI 10.1103/PhysRevE.58.7769 PN B PG 8 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 148PW UT WOS:000077541900035 ER PT J AU Wan, RQ Hartman, H Corbett, R AF Wan, RQ Hartman, H Corbett, R TI Alteration of dopamine metabolites in CSF and behavioral impairments induced by neonatal hippocampal lesions SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE cerebrospinal fluid; 3,4-dihydroxyphenylacetic acid; hippocampus; homovanillic acid; 5-hydroxyindoleacetic acid; locomotion; neonatal lesions; stress ID FREELY MOVING RATS; STRESS-INDUCED CHANGES; CEREBROSPINAL-FLUID; NUCLEUS-ACCUMBENS; PREFRONTAL CORTEX; BRAIN 5-HYDROXYTRYPTAMINE; MONOAMINE METABOLITE; INHIBITORY INFLUENCE; RESTRAINT STRESS; FRONTAL-CORTEX AB Alterations of monoamine metabolites in CSF and behavioral abnormalities were studied in rats with neonatal hippocampal lesions and controls. Lesions of the ventral hippocampus were produced bilaterally by ibotenic acid on postnatal day 7. Lesion-induced neurochemical alterations and behavioral impairments were examined concurrently when rats were 12 weeks old. CSF from the cisterna magna was sampled repeatedly from freely moving rats. The levels of free 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in CSF were determined. An exposure to a novel environment induced hyperexploratory behavior and elevated the level of free DOPAC in CSF in lesioned rats. Although a swim stress increased the levels of free DOPAC and 5-HIAA in CSF in both control and lesioned groups, rats with hippocampal lesions had a further elevation of free DOPAC in CSF and greater spontaneous activity relative to controls shortly after stress. Amphetamine (1.5 mg/kg, i.p.) induced hyperlocomotion in lesioned rats compared to controls. For the control group, the levels of the three monoamine metabolites in CSF were not significantly influenced by amphetamine. However, for the lesioned group, the level of DOPAC significantly decreased compared to preinjection of amphetamine. The results indicate that neonatal hippocampal lesion-induced impairments can be manifested by behavioral and neurochemical abnormalities. Alterations of monoamine metabolites in CSF may be determined quantitatively and used as indices for monitoring lesion-impaired monoaminergic function in the central nervous system. (C) 1998 Elsevier Science Inc. C1 Hoechst Marion Roussel Inc, Neurosci PGU, Somerville, NJ 08876 USA. RP Wan, RQ (reprint author), NIMH, Biol Psychiat Branch, Bldg 10-3N212,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 78 TC 17 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD DEC 1 PY 1998 VL 65 IS 3 BP 429 EP 436 DI 10.1016/S0031-9384(98)00179-6 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 150HW UT WOS:000077659900005 PM 9877408 ER PT J AU Paulus, MP Geyer, MA Sternberg, E AF Paulus, MP Geyer, MA Sternberg, E TI Differential movement patterns but not amount of activity in unconditioned motor behavior of Fischer, Lewis, and Sprague-Dawley rats SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE locomotor activity; patterns; strains ID TYROSINE-HYDROXYLASE; DISPLAY DIFFERENCES; LOCOMOTOR BEHAVIOR; SCALING HYPOTHESIS; RECEPTOR; COCAINE; STRAINS; CORTICOSTERONE; SENSITIZATION; APOMORPHINE AB Histocompatible Fischer 344 and Lewis rats have been shown to differ on a wide variety of behavioral, chemical, and molecular measures. This investigation aimed to clarify strain differences in unconditioned motor behavior with respect to the amount and patterns of movements. Twenty female Fischer 344, Lewis, and Sprague-Dawley were tested in the Behavioral Pattern Monitor for 30 min. The locomotor activity and movement patterns, quantified by counts of photobeam breaks and the spatial scaling exponent, d, were assessed. The level of locomotor activity did not differ significantly between Fischer, Lewis, and Sprague-Dawley rats. In contrast, movement patterns differed significantly between the strains. Specifically, Sprague-Dawley rats exhibited significantly more straight movements than both Fischer and Lewis rats. Moreover, Lewis rats showed significantly more straight movements compared to Fischer rats during the first 10 min in the enclosures. Differences in movement patterns across strains may provide an important behavioral variable to further explore the genetic and developmental aspects of behavior. (C) 1998 Elsevier Science Inc. C1 Univ Calif San Diego, Sch Med, Biol Dynam & Theoret Med Lab, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Dept Psychiat 0804, La Jolla, CA 92093 USA. NIMH, Bethesda, MD 20892 USA. RP Paulus, MP (reprint author), Univ Calif San Diego, Sch Med, Biol Dynam & Theoret Med Lab, La Jolla, CA 92093 USA. FU NIDA NIH HHS [DA11277]; NIMH NIH HHS [MH52885] NR 29 TC 18 Z9 18 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD DEC 1 PY 1998 VL 65 IS 3 BP 601 EP 606 DI 10.1016/S0031-9384(98)00195-4 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 150HW UT WOS:000077659900026 PM 9877429 ER PT J AU Marquez, B Verdier-Pinard, P Hamel, E Gerwick, WH AF Marquez, B Verdier-Pinard, P Hamel, E Gerwick, WH TI Curacin D, an antimitotic agent from the marine cyanobacterium Lyngbya majuscula SO PHYTOCHEMISTRY LA English DT Article DE Lyngbya majuscula; Oscillatoriaceae; cyanobacteria; blue-green alga; thiazoline alkaloid; antiproliferative ID BRINE SHRIMP AB Curacin D is a novel brine shrimp toxic metabolite isolated from a Virgin Islands collection of the marine cyanobacterium Lyngbya majuscula. Structure elucidation of curacin D was accomplished through multidimensional NMR, GC/MS, and comparisons with curacin A. Curacin D provides new insights into structure-activity relationships iii this natural product class as well as some aspects of the likely biosynthetic pathway of the curacins. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Oregon State Univ, Coll Pharm, Corvallis, OR 97331 USA. NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag,Dev Therapuet Program, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. RP Gerwick, WH (reprint author), Oregon State Univ, Coll Pharm, Corvallis, OR 97331 USA. OI Verdier-Pinard, Pascal/0000-0002-6149-6578 FU NCI NIH HHS [CA 52955] NR 7 TC 41 Z9 42 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9422 J9 PHYTOCHEMISTRY JI Phytochemistry PD DEC PY 1998 VL 49 IS 8 BP 2387 EP 2389 DI 10.1016/S0031-9422(98)00365-3 PG 3 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 152ZB UT WOS:000077807100031 PM 9887531 ER PT J AU Romero, R AF Romero, R TI A testimonial to Baha Sibai SO PRENATAL AND NEONATAL MEDICINE LA English DT Biographical-Item C1 Wayne State Univ, Perinatol Res Branch, NICHD, Hutzel Hosp, Detroit, MI 48202 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, Hutzel Hosp, Detroit, MI 48202 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1359-8635 J9 PRENAT NEONAT MED JI Prenat. Neonatal Med. PD DEC PY 1998 VL 3 IS 6 BP 511 EP 512 PG 2 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 161DK UT WOS:000078273000001 ER PT J AU Metcalfe, DD AF Metcalfe, DD TI Food allergy SO PRIMARY CARE LA English DT Article ID ATOPIC-DERMATITIS; ADVERSE REACTIONS; MILK ALLERGY; HYPERSENSITIVITY; SENSITIVITY; ANAPHYLAXIS; PREVALENCE; POPULATION; CHALLENGE; CHILDREN AB Food allergies are immunologic reactions to food allergens or food components. Several distinct clinical entities fall under this term, including immediate-in-time allergic reactions, which are IgE-dependent and involve mast cells and basophils, and delayed-in-time reactions to foods, such as food-induced enterocolitis, which involve additional effector systems. Most food allergies are precipitated by a small number of foods. The diagnosis of these diseases depends on history, physical examination, specific diagnostic assays, and oral food challenge. The differential diagnosis of these diseases is extensive. Treatment of food allergies relies on identification of the food substance that induces the reaction and subsequent avoidance measures. When an individual inadvertently consumes food to which he or she is sensitized, pharmacologic treatment is available. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Allergy & Immunol Training Program, Bethesda, MD 20892 USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. EM dean_metcalfe@nih.gov NR 30 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0095-4543 J9 PRIMARY CARE JI Primary Care PD DEC PY 1998 VL 25 IS 4 BP 819 EP + DI 10.1016/S0095-4543(05)70090-7 PG 12 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 146RN UT WOS:000077444400008 PM 9735121 ER PT J AU Metcalfe, DD AF Metcalfe, DD TI Future role of the allergist-immunologist SO PRIMARY CARE LA English DT Article ID US PHYSICIAN WORKFORCE AB The future role of the allergist/immunologist is dictated by current training and research, which promise to broaden the expertise of practitioners of this discipline. Specialists in allergy and immunology are certified by the American Board of Allergy and Immunology following specialized training in allergic diseases, clinical immunology, procedural skills, clinical principles and analytic methods, clinical laboratory test proficiency, and research. The expanding role of clinical immunology in the management of multiple diseases suggests that specialists in allergy and immunology will continue to broaden their expertise in the care of disorders with an immune component. The discipline of allergy and immunology offers a number of career advantages in both the practice of allergy and immunology and in the application of training in allergy and immunology to opportunities in the pharmaceutical industry and academics. Manpower assessments suggest that the number of allergists and immunologists in training are insufficient to meet the current needs. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Allergy & Immunol Training Program, Bethesda, MD 20892 USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0095-4543 J9 PRIMARY CARE JI Primary Care PD DEC PY 1998 VL 25 IS 4 BP 885 EP + DI 10.1016/S0095-4543(05)70094-4 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 146RN UT WOS:000077444400012 PM 9735125 ER PT J AU Suzuki, H Dong, JT Gao, AC Barrett, JC Isaacs, JT AF Suzuki, H Dong, JT Gao, AC Barrett, JC Isaacs, JT TI Identification of the rat homologue of KAI1 and its expression in Dunning rat prostate cancers SO PROSTATE LA English DT Article DE KAI1; metastasis suppressor gene; prostate cancer; Dunning tumors ID METASTASIS SUPPRESSOR GENE; TRANSMEMBRANE PROTEINS; SYNCYTIUM FORMATION; MOLECULAR-CLONING; ALLELIC LOSS; SHORT ARM; ANTIGEN; PROGRESSION; FAMILY; CHROMOSOME-11 AB BACKGROUND. We previously isolated the human KAI1 gene encoding a transmembrane protein which suppresses metastatic ability in Dunning R3327 AT6.1 rat prostate cancer cells when transfected into these cells. The AT6.1 subline is one of the more aggressive sublines among the Dunning R-3327 system of rat prostate cancers. This raises the issue of whether downregulation of KAI1 expression consistently occurs during the acquisition of high metastatic ability by members of the Dunning system of rat prostate cancers. METHODS. To investigate this possibility, the rat homologue of the KAI1 gene was identified, using a combination of cDNA library screening and 5'-RACE and DNA sequencing. Based on this information, a rat-specific cDNA probe was developed and used for Northern blot analysis of KAI1 expression in normal rat tissues and a series of sublines of Dunning R3327 cells that vary widely in their metastatic abilities. RESULTS. The rat KAI1 gene encoded a protein of 266 amino acids which has 77% identity to the human KAI1 protein. In normal tissues, KAI1 is expressed predominantly as a 2.0-kb-sized transcript. Several tissues (e.g., skeletal muscle and prostate) also express a minor 1.8-kb-sized RNA. Northern blot analysis of a series of Dunning sublines demonstrated that all sublines expressed both the 2.0- and 1.8-kb KAI1 RNA transcripts. However, quantitative levels of the 2.0- vs. 1.8-kb KAI1 RNA were variable among sublines. Downregulation of expression of the 2.0-kb KAI1 transcript was statistically correlated with the acquisition of high metastatic ability within this system of prostate cancer sublines. In contrast, the 1.8-kb transcript was upregulated in all of the more aggressive sublines, but this enhanced expression was not specifically correlated with metastatic ability. CONCLUSIONS. These studies demonstrated that downregulation of the 2.0-kb KAI1 mRNA is associated with the acquisition of high metastatic ability by prostate cancer cells. (C) 1998 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA USA. Univ Virginia, Hlth Sci Ctr, Dept Biochem & Mol Genet, Charlottesville, VA USA. Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Environm Carcinogenesis Program, Res Triangle Pk, NC USA. RP Isaacs, JT (reprint author), Johns Hopkins Oncol Ctr, 422 N Bond St, Baltimore, MD 21231 USA. FU NCI NIH HHS [CA58236] NR 30 TC 9 Z9 10 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0270-4137 J9 PROSTATE JI Prostate PD DEC 1 PY 1998 VL 37 IS 4 BP 253 EP 260 DI 10.1002/(SICI)1097-0045(19981201)37:4<253::AID-PROS7>3.0.CO;2-3 PG 8 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 139KN UT WOS:000077028000007 PM 9831222 ER PT J AU Demirel, MC Atilgan, AR Jernigan, RL Erman, B Bahar, I AF Demirel, MC Atilgan, AR Jernigan, RL Erman, B Bahar, I TI Identification of kinetically hot residues in proteins SO PROTEIN SCIENCE LA English DT Article DE CheY; chymotrypsin inhibitor; conserved residues; cytochrome c; folding pathway; hot residues; thermal fluctuations; vibrational dynamics ID X-RAY STRUCTURE; CYTOCHROME-C; TRANSITION-STATE; MOLTEN GLOBULE; CHYMOTRYPSIN INHIBITOR-2; HYDROGEN-EXCHANGE; SINGLE-PARAMETER; ESCHERICHIA-COLI; FOLDING UNITS; RESOLUTION AB A number of recent studies called attention to the presence of kinetically important residues underlying the formation and stabilization of folding nuclei in proteins, and to the possible existence of a correlation between conserved residues and those participating in the folding nuclei. Here, we use the Gaussian network model (GNM), which recently proved useful in describing the dynamic characteristics of proteins for identifying the kinetically hot residues in folded structures. These are the residues involved in the highest frequency fluctuations near the native state coordinates. Their high frequency is a manifestation of the steepness of the energy landscape near their native state positions. The theory is applied to a series of proteins whose kinetically important residues have been extensively explored: chymotrypsin inhibitor 2, cytochrome c, and related C2 proteins. Most of the residues previously pointed out to underlie the folding process of these proteins, and to be critically important for the stabilization of the tertiary fold, are correctly identified, indicating a correlation between the kinetic hot spots and the early forming structural elements in proteins. Additionally, a strong correlation between kinetically hot residues and loci of conserved residues is observed. Finally, residues that may be important for the stability of the tertiary structure of CheY are proposed. C1 Bogazici Univ, Polymer Res Ctr, TR-80815 Bebek, Istanbul, Turkey. TUBITAK Adv Polymer Mat Res Ctr, TR-80815 Bebek, Istanbul, Turkey. NCI, Mol Struct Sect, Lab Expt & Computat Biol, Div Basic Sci,NIH, Bethesda, MD 20892 USA. Sabanci Univ, TR-80745 Sabanci Ctr, Turkey. RP Jernigan, RL (reprint author), NCI, Mol Struct Sect, Math Biol Lab, Div Basic Sci,NIH, MSC 5677,Room B-116,Bldg 12B, Bethesda, MD 20892 USA. EM jernigan@structure.nci.nih.gov RI Atilgan, Ali Rana/A-7805-2011; Demirel, Melik/E-4495-2010; Jernigan, Robert/A-5421-2012; Demirel, Melik/E-3775-2016; OI ERMAN, BURAK/0000-0002-2496-6059 NR 61 TC 96 Z9 97 U1 1 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD DEC PY 1998 VL 7 IS 12 BP 2522 EP 2532 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 146CR UT WOS:000077410900005 PM 9865946 ER PT J AU Keskin, O Bahar, I Badretdinov, AY Ptitsyn, OB Jernigan, RL AF Keskin, O Bahar, I Badretdinov, AY Ptitsyn, OB Jernigan, RL TI Empirical solvent-mediated potentials hold for both intra-molecular and inter-molecular inter-residue interactions SO PROTEIN SCIENCE LA English DT Article DE knowledge-based potentials; protein interfaces; protein solvation ID QUASI-CHEMICAL APPROXIMATION; PROTEIN-PROTEIN INTERFACES; SEQUENCE-STRUCTURE MATCHES; KNOWLEDGE-BASED POTENTIALS; GLOBULAR-PROTEINS; ENERGY FUNCTIONS; RECOGNITION; CORRECT AB Whether knowledge-based intra-molecular inter-residue potentials are valid to represent inter-molecular interactions taking place at protein-protein interfaces has been questioned in several studies. Differences in the chain connectivity effect and in residue packing geometry between interfaces and single chain monomers have been pointed out as possible sources of distinct energetics for the two cases. In the present study, the interfacial regions of protein-protein complexes are examined to extract inter-molecular inter-residue potentials, using the same statistical methods as those previously adopted for intra-molecular residue pairs. Two sets of energy parameters are derived, corresponding to solvent-mediation and "average residue" mediation. The former set is shown to be highly correlated (correlation coefficient 0.89) with that previously obtained for inter-residue interactions within single chain monomers, while the latter exhibits a weaker correlation (0.69) with its intra-molecular counterpart. In addition to the close similarity of intra- and inter-molecular solvent-mediated potentials, they are shown to be significantly mon residue-specific and thereby discriminative compared to the residue-mediated ones, indicating that solvent-mediation plays a major role in controlling the effective inter-residue interactions, either at interfaces, or within single monomers. Based on this observation, a reduced set of energy parameters comprising 20 one-body and 3 two-body terms is proposed (as opposed to the 20 x 20 tables of inter-residue potentials), which reproduces the conventional 20 x 20 tables with a correlation coefficient of 0.99. C1 Bogazici Univ, Dept Chem Engn, TR-80815 Bebek, Istanbul, Turkey. Bogazici Univ, Polymer Res Ctr, TR-80815 Bebek, Istanbul, Turkey. TUBITAK Adv Polymer Mat Res Ctr, TR-80815 Bebek, Istanbul, Turkey. NCI, Mol Struct Sect, Lab Expt & Computat Biol, Div Basic Sci,NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Lab Mol Biophys, New York, NY 10021 USA. Russian Acad Sci, Inst Prot Res, Pushchino 142292, Moscow Region, Russia. RP Jernigan, RL (reprint author), NCI, Mol Struct Sect, Math Biol Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012 NR 25 TC 69 Z9 70 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD DEC PY 1998 VL 7 IS 12 BP 2578 EP 2586 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 146CR UT WOS:000077410900011 PM 9865952 ER PT J AU Cai, ML Huang, Y Caffrey, M Zheng, RL Craigie, R Clore, GM Gronenborn, AM AF Cai, ML Huang, Y Caffrey, M Zheng, RL Craigie, R Clore, GM Gronenborn, AM TI Solution structure of the His12 -> Cys mutant of the N-terminal zinc binding domain of HIV-1 integrase complexed to cadmium SO PROTEIN SCIENCE LA English DT Article DE cadmium; conformational states; HIV-1; integrase; N-terminal domain ID PROTEIN NMR; SITE AB The solution structure of His12 --> Cys mutant of the N-terminal zinc binding domain (residues 1-55; IN1-55) of HIV-1 integrase complexed to cadmium has been solved by multidimensional heteronuclear NMR spectroscopy. The overall structure is very similar to that of the wild-type N-terminal domain complexed to zinc. In contrast to the wild-type domain, however, which exists in two interconverting conformational states arising from different modes of coordination of the two histidine side chains to the metal, the cadmium complex of the His12 --> Cys mutant exists in only a single form at low pH. The conformation of the polypeptide chain encompassing residues 10-18 is intermediate between the two forms of the wild-type complex. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM clore@speck.niddk.nih.gov; gronenborn@vger.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 25 TC 31 Z9 32 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD DEC PY 1998 VL 7 IS 12 BP 2669 EP 2674 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 146CR UT WOS:000077410900021 PM 9865962 ER PT J AU Narrow, WE Regier, DA Goodman, SH Rae, DS Roper, MT Bourdon, KH Hoven, C Moore, R AF Narrow, WE Regier, DA Goodman, SH Rae, DS Roper, MT Bourdon, KH Hoven, C Moore, R TI A comparison of federal definitions of severe mental illness among children and adolescents in four communities SO PSYCHIATRIC SERVICES LA English DT Article ID ADDICTIVE-DISORDERS; SERVICES AB Objective: Using data from an epidemiological survey the study compared existing definitions of severe mental illness and serious emotional disturbance among children and adolescents to demonstrate the range of prevalence rates resulting from application of different definitions to the same population. Methods: Three definitions of severe mental illness and serious emotional disturbance were applied to data from the Methods for the Epidemiology of Child and Adolescent Mental Disorders survey, with a sample of 1,285, conducted in 1991-1992 by the National Institute of Mental Health. The resulting proportions of cases identified, demographic characteristics, serc ice use, and perceived need for sen ices were compared. Results: From 3 to 23 percent of the sampled youth met criteria for sec;ere mental illness or serious emotional disturbance. From 40 percent to as many as 78 percent of the defined youth used a mental health service in the year before the survey. School and ambulatory specialty settings were used most frequently. Generally, more than half of the parents of children with severe mental illness or serious emotional disturbance thought that their child needed services. Conclusions: The prevalence and characteristics of severe mental illness and serious emotional disturbance among children ale sensitive to the definition used and its operationalization, Care should be taken by policy makers and service planners to avoid either over- ol underestimating the prevalence of impaired youth in need of intensive interventions. C1 NIMH, Off Associate Director Epidemiol & Hlth Policy Re, Bethesda, MD 20892 USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. NIMH, Div Mental Disorders Behav Res & AIDS, Bethesda, MD 20892 USA. Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. New York State Psychiat Inst, New York, NY 10032 USA. RP Narrow, WE (reprint author), NIMH, Off Associate Director Epidemiol & Hlth Policy Re, 31 Ctr Dr,Room 4A52 MSC 2475, Bethesda, MD 20892 USA. FU NIMH NIH HHS [UO1-MH46717, UO1-MH46718, UO1-MH46725] NR 26 TC 16 Z9 16 U1 1 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD DEC PY 1998 VL 49 IS 12 BP 1601 EP 1608 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 144FV UT WOS:000077304100015 PM 9856624 ER PT J AU Sheu, YS AF Sheu, YS TI Drug abuse and acquired immune deficiency syndrome SO PSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article DE acquired immune deficiency syndrome; drug abuse; human immunodeficiency virus ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTION; RISK AB Acquired immune deficiency syndrome (AIDS) is a modern plague. The first sign of the disease was the appearance of Pneumocystis carinii and Kaposi's sarcoma among young homosexual patients. The virus transmission is from an infected individual to a susceptible host through blood-related, sexual, and perinatal routes. Exchange of body fluid occurs when sharing syringes, drugs, and drug paraphernalia. Although the largest number of people infected with human immunodeficiency virus (HIV) is in subSaharan Africa, the most rapid growth of HIV infection during the 1990s was seen in South-East Asia. Asia showed a steer increase from 1992. Given the experiences in Thailand,India and China, a similar spread of AIDS in other parts of Asia is possible. The risk behaviors that enable the spread of HIV are present in all Pacific Asian countries. Risk behaviors are considered to be the injection of illicit drugs, male patronage of prostitutes, high rates of sexually transmitted diseases, and low condom use. C1 NIDA, Div Clin Res & Serv, Rockville, MD 20857 USA. RP Sheu, YS (reprint author), NIDA, Div Clin Res & Serv, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 18 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1323-1316 J9 PSYCHIAT CLIN NEUROS JI Psychiatry Clin. Neurosci. PD DEC PY 1998 VL 52 SU S BP S167 EP S169 PG 3 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 167TU UT WOS:000078650200003 PM 9895137 ER PT J AU Butler, SF Newman, FL Cacciola, JS Frank, A Budman, SH McLellan, AT Ford, S Blaine, J Gastfriend, D Moras, K Salloum, IM Barber, JP AF Butler, SF Newman, FL Cacciola, JS Frank, A Budman, SH McLellan, AT Ford, S Blaine, J Gastfriend, D Moras, K Salloum, IM Barber, JP TI Predicting Addiction Severity Index (ASI) Interviewer Severity Ratings for a computer-administered ASI SO PSYCHOLOGICAL ASSESSMENT LA English DT Article ID LINEAR-MODELS; RELIABILITY; VALIDITY AB The Addiction Severity Index (ASI) is a reliable and valid measure of problem severity among addicted patients. Concerns have been raised about the reliability of the Interviewer Severity Rating (ISR), a summary score for each of 7 domains. As part of an effort to build a computer-administered ASI, regression equations were developed to predict the ISR. Repeated resampling of a large dataset, consisting of 1,124 ASIs conducted by trained interviewers, permitted derivation of stable regression equations predicting the ISR for each ASI domain from patients' answers to preselected interview items. The resulting 7 Predicted Severity Ratings (PSRs) were tested on 8, standardized vignettes, with "gold standard," expert-generated ISRs. Reliabilities compared well with those of intensively trained interviewers. The PSRs could provide an alternative to potentially unreliable interviewer ratings, enhancing the ASI's role in treatment planning and treatment matching and make possible a computer-administered version of the ASI. C1 Innovat Training Syst, Newton, MA 02159 USA. Florida Int Univ, Hlth Serv Adm, Sch Policy & Management, Miami, FL 33199 USA. Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Swarthmore Coll, Psychol Serv, Swarthmore, PA 19081 USA. Brookside Hosp, Nashua, NH USA. NIDA, Treatment Res Branch, Lexington, KY 40583 USA. Massachusetts Gen Hosp, Addict Serv, Dept Psychiat, Boston, MA 02114 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Penn, Dept Psychiat, Ctr Psychotherapy Res, Philadelphia, PA 19104 USA. RP Butler, SF (reprint author), Innovat Training Syst, 199 Wells Ave,Suite 108, Newton, MA 02159 USA. EM sfbutler@aol.com OI Butler, Stephen/0000-0002-6132-5883; barber, jacques/0000-0002-8762-2595 NR 22 TC 18 Z9 18 U1 1 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD DEC PY 1998 VL 10 IS 4 BP 399 EP 407 DI 10.1037/1040-3590.10.4.399 PG 9 WC Psychology, Clinical SC Psychology GA 155RJ UT WOS:000077959900008 ER PT J AU Jaszyna, M Gasior, M Shoaib, M Yasar, S Goldberg, SR AF Jaszyna, M Gasior, M Shoaib, M Yasar, S Goldberg, SR TI Behavioral effects of nicotine, amphetamine and cocaine under a fixed-interval schedule of food reinforcement in rats chronically exposed to caffeine SO PSYCHOPHARMACOLOGY LA English DT Article DE nicotine; amphetamine; cocaine; caffeine; drug interaction; schedule-controlled behavior; rat ID LOCOMOTOR-ACTIVITY; RHESUS-MONKEYS; ROTATIONAL BEHAVIOR; PHYSICAL-DEPENDENCE; DOPAMINE AGONISTS; CEREBRAL-CORTEX; TAKING BEHAVIOR; TOLERANT RATS; ADENOSINE; MICE AB Epidemiological surveys demonstrate that caffeine, the main psychoactive ingredient of coffee, is a positive correlate in drug abuse. To characterize the behavioral nature of caffeine interactions with other psychomotor stimulants, we examined the effects of chronic caffeine exposure on the behavioral responses to nicotine, amphetamine, cocaine, the selective D-1 agonist SKF-82958 and the selective D-2 receptor agonist NPA, in rats responding under a fixed interval (FI) schedule of food reinforcement. Following stabilization of rates and temporal patterns of responding (mathematically expressed as quarter-life values, QL), twenty-one Sprague-Dawley rats responding under a 5-min FI schedule of food reinforcement were divided into two groups; one (twelve rats) maintained on tap water (control) and the other (nine rats) on caffeine (3 mg/ml added to the drinking water). Following the substitution of caffeine solution for tap water, behavior was temporarily disrupted as evidenced by decreases in responding and QL values which reached a maximum after 72 h (rate 60% and QL 30% below baseline levels), Rats developed complete tolerance to these effects of caffeine over 5 days of caffeine exposure. After response rate and QL values stabilized, effects of drugs were evaluated. Nicotine (0.01-1.0 mg/kg; SC), amphetamine (0.1-5.6; IP), and cocaine (1.0-17; IP) each produced biphasic dose-dependent changes in response rate with maximum increases in response rate following intermediate doses and decreases in response rates following higher doses. The increase in rates of responding produced by amphetamine or cocaine (but not nicotine) were greater (P<0.05) in caffeine-drinking than in water-drinking rats. Both SKF-82958 (0.001-0.3 mg/kg; IP) and NPA (0.0001-0.1; IP) produced only dose-dependent decreases in rates of responding. Caffeine-drinking rats were less sensitive to the rate-depressant effects of SKF-82958 (P<0.05) than water-drinking rats. However, similar changes (P>0.05) were produced by NPA in both groups. Except for amphetamine, the remaining drugs produced similar (P>0.05) dose-dependent decreases in QL values in water- and caffeine-drinking rats. Amphetamine produced smaller decreases in QL values in caffeine-drinking rats than in water-drinking rats (P<0.05). Chronic exposure to caffeine produced complete insurmountable tolerance to the response-rate increasing (stimulant) effects of acute caffeine (3.0-17 mg/kg; IP) in caffeine-drinking rats. In conclusion, our study revealed that chronic caffeine exposure potentiates the behavioral response to amphetamine and cocaine but not to that of nicotine in rats responding under a FI schedule of food reinforcement. Thus, it is likely that these effects are mediated through different pharmacological mechanisms. C1 NIDA, Preclin Pharmacol Lab, IRP, NIH, Baltimore, MD 21224 USA. Inst Psychiat, London, England. Greater Baltimore Med Ctr, Div Med, Towson, MD 21263 USA. Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Lab, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 88 TC 24 Z9 24 U1 2 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 1998 VL 140 IS 3 BP 257 EP 271 DI 10.1007/s002130050766 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 147EP UT WOS:000077475600002 PM 9877005 ER PT J AU Greenberg, DB Benjamin, J Martin, JD Keuler, D Huang, SJ Altemus, M Murphy, DL AF Greenberg, DB Benjamin, J Martin, JD Keuler, D Huang, SJ Altemus, M Murphy, DL TI Delayed obsessive compulsive disorder symptom exacerbation after a single dose of a serotonin antagonist in fluoxetine-treated but not untreated patients SO PSYCHOPHARMACOLOGY LA English DT Article DE obsessive-compulsive disorder; anxiety; serotonin reuptake inhibitor; serotonin antagonist; metergoline; fluoxetine ID REUPTAKE INHIBITORS; META-CHLOROPHENYLPIPERAZINE; TRYPTOPHAN DEPLETION; HEALTHY-VOLUNTEERS; 5HT-2 RECEPTOR; METERGOLINE; BINDING; CLOMIPRAMINE; RESPONSIVITY; FLUVOXAMINE AB Enhanced serotonergic transmission may underlie therapeutic effects of serotonin reuptake inhibitors in obsessive-compulsive disorder. However, such treatment may decrease serotonin receptor responsivity. We investigated whether the serotonin antagonist metergoline would exacerbate or further improve systems in fluoxetine-responsive patients. Pilot results suggested open metergoline produced delayed symptom worsening in fluoxetine-treated patients. Fourteen patients continuing fluoxetine received metergoline and placebo (double-blind, randomized). Symptom ratings continued for 1 week afterwards. Ten unmedicated patients underwent the same procedures. Symptoms improved 4 h after both metergoline and placebo. The day after metergoline but not placebo, fluoxetine-treated patients had significantly increased anxiety, obsessions and compulsions, abating over several days. Depression was unchanged. Metergoline had no similar delayed effects in unmedicated patients. Metergoline levels were higher in fluoxetine-treated patients. These results, consistent with less conclusive earlier findings, suggest that prolonged changes in brain serotonin function underlie symptom re-emergence following administration of metergoline to fluoxetine-treated patients with obsessive-compulsive disorder. C1 NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Greenberg, DB (reprint author), NIMH, Clin Sci Lab, Bldg 10,Room 3D41,10 Ctr Dr,MSC 1264, Bethesda, MD 20892 USA. NR 45 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 1998 VL 140 IS 4 BP 434 EP 444 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 150GF UT WOS:000077655300008 ER PT J AU Allen, JP Mattson, ME Miller, WR Tonigan, JS Connors, GJ Rychtarik, RG Randall, CL Anton, RF Kadden, RM Litt, M Cooney, NL DiClemente, CC Carbonari, J Zweben, A Longabaugh, RH Stout, RL Donovan, D Babor, TF DelBoca, FK Rounsaville, BJ Carroll, KM Wirtz, PW AF Allen, JP Mattson, ME Miller, WR Tonigan, JS Connors, GJ Rychtarik, RG Randall, CL Anton, RF Kadden, RM Litt, M Cooney, NL DiClemente, CC Carbonari, J Zweben, A Longabaugh, RH Stout, RL Donovan, D Babor, TF DelBoca, FK Rounsaville, BJ Carroll, KM Wirtz, PW CA Project MATCH Res Grp TI Therapist effects in three treatments for alcohol problems SO PSYCHOTHERAPY RESEARCH LA English DT Article ID PROBLEM DRINKERS; COUNSELOR; BEHAVIOR; DRINKING; SUCCESS; MOTIVATION; OUTCOMES AB Prior research indicates that therapist effects can be sizeable in substance-abuse treatment. Therapist differences were examined within a multisite (N = 1726) randomized trial of three psychosocial treatments for alcohol problems: twelve-step facilitation (TSF), cognitive-behavioral skills training (CBT), and motivational enhancement therapy (MET). Therapists (N = 80) were nested within treatments, selected and trained for expertise in a specific approach. This report describes: (1) differences in therapist characteristics across the three treatments; (2) the magnitude of therapist effects within each treatment; and (3) exploratory analyses of therapist attributes associated with successful outcomes. Therapist characteristics differed between TSF and the other two conditions. Significant therapist effects were found in client satisfaction and outcomes, even after covarying for effects of treatment sites and client baseline characteristics. Specific therapist attributes were predictive of client outcomes. Outlier therapists whose caseloads showed unusually poor outcomes accounted for most of the observed effects. C1 NIAAA, Sci Commun Branch, Bethesda, MD 20892 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Res Inst Addict, Buffalo, NY USA. Med Univ S Carolina, Charleston, SC 29425 USA. Vet Affairs Med Ctr, Charleston, SC 29403 USA. Univ Connecticut, Sch Med, Farmington, CT USA. Vet Affairs Connecticut Healthcare Syst, New Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Houston, Houston, TX USA. Univ Wisconsin, Milwaukee, WI 53201 USA. Brown Univ, Providence, RI 02912 USA. Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Connecticut, Farmington, CT USA. Yale Univ, New Haven, CT USA. George Washington Univ, Washington, DC USA. RP Allen, JP (reprint author), NIAAA, Sci Commun Branch, Willco Bldg,Suite 409,6000 Execut Blvd, Bethesda, MD 20892 USA. RI Carroll, Kathleen/A-7526-2009; Cooney, Ned/C-5176-2014; OI Cooney, Ned/0000-0001-6698-8312; Carroll, Kathleen/0000-0003-3263-3374; Litt, Mark/0000-0002-8319-6090 NR 70 TC 87 Z9 87 U1 3 U2 13 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 1050-3307 J9 PSYCHOTHER RES JI Psychother. Res. PD WIN PY 1998 VL 8 IS 4 BP 455 EP 474 PG 20 WC Psychology, Clinical SC Psychology GA 148QE UT WOS:000077542700007 ER PT J AU Quadri, SM Vriesendorp, HM AF Quadri, SM Vriesendorp, HM TI Effects of linker chemistry on the pharmacokinetics of radioimmunoconjugates SO QUARTERLY JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE radiolabeled linker; immunoconjugates; pharmacokinetics ID RADIOLABELED IMMUNOGLOBULIN THERAPY; B-CELL LYMPHOMA; MONOCLONAL-ANTIBODIES; CROSS-LINKING; DIAGNOSIS; CANCER; TUMOR; RADIOIMMUNODETECTION; RADIOIMMUNOTHERAPY; REAGENT AB Radiolabeled monoclonal antibodies reactive with tumor associated antigens can selectively deliver cytotoxic or diagnostic isotopes to malignant cells in vivo. To achieve maximum retention of radiolabel iu. tumor and a more rapid clearance of radioisotope from normal tissues, six Linker immunoconjugates were evaluated in studies using nude mice and beagle dogs. All radioimmunoconjugates contained a mouse monoclonal IgG (QCI) reactive with human ferritin, Different chemical Linkages mere inserted between immunoglobulins and the radiolabeled chelate (DTPA), Three Linkers (ITCB, DSS and BSOCOES) were stable in in vitro and in vivo studies. Three Linkers (EGS, DST and DSP) mere labile in in vitro and in vivo studies. Indium-111 labeled antiferritin-containing ITCB or DSS Linker showed high uptake in human hepatoma xenografts in nude mice. In addition, long blood half-lives and higher normal Liver uptakes were noted. Studies of whole body retention of radioimmunoconjugates showed approximately three-fold faster elimination of radioimmunoconjugates containing a labile linker (EGS), EGS linker is the labile linker with the highest therapeutic ratio: higher tumor uptake, but low normal liver uptake and a shortened blood half-life of the radioimmunoconjugate. The differences in normal tissue uptake (liver) between EGS and ITCB were confirmed in beagle dogs. Urine elimination studies and incubation of radioimmunoconjugates in serum or tissue homogenates of tumor, liver or muscle, showed that enzymes in serum and liver homogenates were able to cleave the labile Linkers, which led to a more rapid elimination of low molecular weight radioactive metabolites in urine. The metabolism of linker radioimmunoconjugates in tumor was less effective, The labile linker DSP appears less useful because sulphydryl groups that are generated by cleavage of cause higher uptake radioactivity in normal kidney. Biodistribution studies in nude mice were confirmed by serial immunoscintigraphy studies on individual mice. The immunoscintigraphy studies are semi-quantitative only, but enable the use of lower numbers of experimental animals, This is of particular significance in large experimental animals such as beagle dogs. The labile linker approach can reduce normal tissue radiation exposure. The study also provides an example of preclinical optimization of radioimmunoconjugates. Continued use of the appropriate preclinical animal models will accelerate more successful applications of radioimmunoconjugates in cancer patients. C1 NIH, Ctr Sci Review, Bethesda, MD 20892 USA. Arlington Canc Ctr, Arlington, TX USA. RP Quadri, SM (reprint author), NIH, Ctr Sci Review, 6701 Rockledge Dr,Room 4144, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA43791, CA51161] NR 33 TC 17 Z9 17 U1 2 U2 3 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 1125-0135 J9 Q J NUCL MED JI Q. J. Nucl. Med. PD DEC PY 1998 VL 42 IS 4 BP 250 EP 261 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 154PA UT WOS:000077896400004 PM 9973840 ER PT J AU Peculis, BA Greer, CL AF Peculis, BA Greer, CL TI The structure of the ITS2-proximal stem is required for pre-rRNA processing in yeast SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE ITS2; nucleolus; processing; rRNA; snoRNA; Xenopus; yeast ID SMALL NUCLEOLAR RNAS; 18S RIBOSOMAL-RNA; INTERNAL TRANSCRIBED SPACER-2; SMALL NUCLEAR-RNA; SACCHAROMYCES-CEREVISIAE; PRERIBOSOMAL RNA; FUNCTIONAL-ANALYSIS; XENOPUS-OOCYTES; CLEAVAGE SITE; POLYMERASE-I AB Accurate and efficient processing of pre-rRNA is critical to the accumulation of mature functional ribosomal subunits for maintenance of cell growth. Processing requires numerous factors which act in trans as well as RNA sequence/structural elements which function in cis. To examine the latter, we have used directed mutagenesis and expression of mutated pre-rRNAs in yeast. Specifically, we tested requirements for formation of an ITS2-proximal stem on processing, a structure formed by an interaction between sequences corresponding to the 3' end of 5.8S rRNA and the 5' end of 25S. Pre-rRNA processing is inhibited in templates encoding mutations that prevent the formation of the ITS2-proximal stem. Compensatory, double mutations, which alter the sequence of this region but restore the structure of the stem, also restore processing, although at lower efficiency. This reduction in efficiency is reflected in decreased levers of mature 5.8S and 25S rRNA and increased levels of 35S pre-rRNA and certain processing intermediates. This phenotype is reminiscent of the biochemical depletion of U8 snoRNA in vertebrates for which the ITS2-proximal stem has been proposed as a potential site for interaction with U8 RNP. Thus, formation of the ITS2-proximal stem may be a requirement common to yeast and vertebrate pre-rRNA processing. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20982 USA. Univ Calif Irvine, Coll Med, Dept Biol Chem, Irvine, CA 92697 USA. RP Peculis, BA (reprint author), NIDDK, Genet & Biochem Branch, NIH, 10 Ctr Dr,MSC 1766,Bldg 10,Room 8N322, Bethesda, MD 20982 USA. FU NIGMS NIH HHS [GM35955] NR 53 TC 38 Z9 39 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD DEC PY 1998 VL 4 IS 12 BP 1610 EP 1622 DI 10.1017/S1355838298981420 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 145JE UT WOS:000077366700012 PM 9848657 ER PT J AU Roselli, M Buonomo, O Piazza, A Guadagni, F Vecchione, A Brunetti, E Cipriani, C Amadei, G Nieroda, C Greiner, JW Casciani, CU AF Roselli, M Buonomo, O Piazza, A Guadagni, F Vecchione, A Brunetti, E Cipriani, C Amadei, G Nieroda, C Greiner, JW Casciani, CU TI Novel clinical approaches in monoclonal antibody-based management in colorectal cancer patients: Radioimmunoguided surgery and antigen augmentation SO SEMINARS IN SURGICAL ONCOLOGY LA English DT Article DE colonic neoplasms; colorectal neoplasms; monoclonal antibodies; biological response modifiers; interferons; radioimmunoguided surgery; neoplasm staging; radioimmuno-detection; radioisotopes; lymph nodes; lymphatic metastasis; up-regulation; radiopharmaceuticals; polymerase chain reaction; glycoproteins; immunohistochemistry; mucins ID TUMOR-ASSOCIATED ANTIGENS; CARCINOEMBRYONIC ANTIGEN; GAMMA-INTERFERON; LYMPH-NODES; RECOMBINANT INTERFERON; CARCINOMA PATIENTS; SIALOSYL-TN; EXPRESSION; CELLS; ENHANCEMENT AB Surgery, the most effective treatment for colon and rectal cancer, is based on empirical knowledge of the patterns of tumor spread, gross findings at laparotomy, and histologic confirmation of tumor-free margins. In spite of the many technical improvements in surgery, there has not been a significant change in cure rates for colon and rectal cancers. In fact, one-half of affected patients will not survive 5 years. It is in this arena of treatment for primary colon and rectal cancer patients that radioimmunoguided surgery (RIGS) technology may provide the most benefit. RIGS is an intraoperative procedure for detection of carcinoma lesions that are targeted with a radiolabeled monoclonal antibody (MAb) to provide the surgeon with immediate intraoperative definition of tumor margins and identification of occult disease. To optimize this technique, our studies were designed to increase tumor uptake by higher affinity CC-49 (a second-generation MAb) and to increase tumor antigen expression using biological response modifiers (BRMs). The ability of BRMs, such as interferons (IFNs), to enhance the expression of tumor-associated antigens, may play an important role in an adjuvant setting for MAb-based treatment. Preclinical and clinical data provided evidence for the use of IFN as an adjuvant to enhance MAb-targeting of human carcinoma lesions. A combination protocol with IFN and RIGS is ongoing at, our institution. Semin. Surg. Oncol. 15:254-262, 1998. (C) 1998 Wiley-Liss, Inc. C1 Univ Rome Tor Vergata, Dept Surg, Rome, Italy. CNR, Inst Tissue Typing, Rome, Italy. Regina Elena Canc Inst, Rome, Italy. Univ Rome La Sapienza, Dept Pathol, Rome, Italy. S Pietro Fatebenefratelli Hosp, Dept Surg, Rome, Italy. S Eugenio Hosp, Dept Nucl Med, Rome, Italy. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Roselli, M (reprint author), Univ Roma Tor Vergata, CO S Eugenio Hosp, Dept Surg, P Le Umanesimo 10, I-00144 Rome, Italy. EM rosellimario@uni.net RI Guadagni, Fiorella/J-4432-2013; OI Guadagni, Fiorella/0000-0003-3652-0457; PIAZZA, ANTONINA/0000-0002-9250-9183 NR 49 TC 4 Z9 4 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 8756-0437 J9 SEMIN SURG ONCOL JI Semin. Surg. Oncol. PD DEC PY 1998 VL 15 IS 4 BP 254 EP 262 DI 10.1002/(SICI)1098-2388(199812)15:4<254::AID-SSU14>3.0.CO;2-V PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 135WW UT WOS:000076826500014 PM 9829383 ER PT J AU Muntaner, C Eaton, WW Diala, C Kessler, RC Sorlie, PD AF Muntaner, C Eaton, WW Diala, C Kessler, RC Sorlie, PD TI Social class, assets, organizational control and the prevalence of common groups of psychiatric disorders SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE social class; depression; anxiety; substance misuse; psychiatric disorders ID DIAGNOSTIC-INTERVIEW-SCHEDULE; EPIDEMIOLOGIC CATCHMENT-AREA; NATIONAL-COMORBIDITY-SURVEY; SOCIOECONOMIC-STATUS; UNITED-STATES; MAJOR DEPRESSION; EARNINGS FUNCTION; RISK-FACTORS; LIFE EVENTS; HEALTH AB This study provides an update on the association between social class and common types of psychiatric disorder in the US. In addition to usual measures of social class, we provide hypotheses for the expectation that assets and organizational control are associated with specific varieties of psychiatric disorders (mood, anxiety, alcohol and drug use disorders). We analyzed two surveys. The National Comorbidity Survey conducted in 1990-1992 yielded 12-month prevalence rates in a probability sample of 8098 respondents in the 48 contiguous states. The Epidemiologic Catchment Area Follow-up conducted in 1993-1996 provided similar rates among 1920 East Baltimore residents. Analyses of the National Comorbidity Survey showed an inverse association between financial and physical assets and mood, anxiety, alcohol, and drug disorders. The Epidemiologic Catchment Area Followup provided additional evidence for the inverse association between financial and physical assets and anxiety, alcohol and drug disorders. Also in the Epidemiologic Catchment Area, lower level supervisors presented higher rates of depression and anxiety disorders than higher level managers. Inequalities in assets and organizational control, as well as typical measures of social class, are associated with specific psychiatric disorders. These constructs can provide additional explanations for why social inequalities in psychiatric disorders occur. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 W Virginia Univ, Sch Med, Inst Occupat & Environm Hlth, Morgantown, WV 26506 USA. W Virginia Univ, Prevent Res Ctr, Morgantown, WV 26506 USA. NIMH, Lab Socioenvironm Studies, NIH, Rockville, MD 20857 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy, Cambridge, MA 02138 USA. RP Muntaner, C (reprint author), W Virginia Univ, Sch Med, Inst Occupat & Environm Hlth, POB 9190, Morgantown, WV 26506 USA. RI Muntaner, C/A-5043-2010; Page, Andrew/G-5438-2012 OI Page, Andrew/0000-0003-3133-2844 FU NIMH NIH HHS [MH47447, MH46376, MH49098] NR 53 TC 113 Z9 114 U1 11 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 1998 VL 47 IS 12 BP 2043 EP 2053 DI 10.1016/S0277-9536(98)00309-8 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 156DJ UT WOS:000077985900017 PM 10075245 ER PT J AU Fortney, JA Zhang, J AF Fortney, JA Zhang, J TI Maternal death and birth spacing SO STUDIES IN FAMILY PLANNING LA English DT Letter C1 NICHD, Bethesda, MD USA. NR 2 TC 4 Z9 4 U1 2 U2 3 PU POPULATION COUNCIL PI NEW YORK PA ONE DAG HAMMARSKJOLD PLAZA, NEW YORK, NY 10017 USA SN 0039-3665 J9 STUD FAMILY PLANN JI Stud. Fam. Plan. PD DEC PY 1998 VL 29 IS 4 BP 436 EP 436 DI 10.2307/172258 PG 1 WC Demography; Public, Environmental & Occupational Health SC Demography; Public, Environmental & Occupational Health GA 158FX UT WOS:000078106300010 PM 9919637 ER PT J AU Park, BJ Alexander, HR Libutti, SK Huang, J Royalty, D Skarulis, MC Jensen, RT Gorden, P Doppman, JL Shawker, TH Fraker, DL Norton, JA Bartlett, DL AF Park, BJ Alexander, HR Libutti, SK Huang, J Royalty, D Skarulis, MC Jensen, RT Gorden, P Doppman, JL Shawker, TH Fraker, DL Norton, JA Bartlett, DL TI Operative management of islet-cell tumors arising in the head of the pancreas SO SURGERY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 26-28, 1998 CL ORLANDO, FLORIDA SP Amer Assoc Endocrine Surgeons ID ENDOCRINE TUMORS; INSULINOMAS; PANCREATICODUODENECTOMY; LOCALIZATION AB Background. Pancreatic islet cell tumors (ICTs) can be treated by enucleation or pancreatic resection. We reviewed our experience with ICTs in the head of the pancreas to define indications for enucleation versus pancreaticoduodenectomy. Methods. Between January 1982 and December 1997, 48 patients underwent surgical resection for presumed ICTs of the pancreatic head. Of these, 18 were found on pathologic examination to be disease in ct lymph node. Thirty patients had 32 true pancreatic head ICTs. We reviewed the operative results and postoperative courses in these patients. Results. Mean diameter of the ICTs was 15 mm. Twenty-seven patients (90 %) underwent successful enucleations. Three patients failed enucleation and underwent pancreaticoduodenectomy. There was no operative mortality. The median time to regular diet was 7 days. The median time to removal of all drains was 22 days. The most common complication was pancreatic fistula (15 %). No patient required reoperation for treatment of a fistula. Conclusion. Most ICTs of the pancreatic head can be removed with enucleation, preserving pancreatic tissue and avoiding the morbidity of pancreaticoduodenectomy. The Primary indication for pancreaticoduodenectomy is not the size of the lesion but its proximity to the pancreatic duct. C1 NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NIDDKD, Clin & Cellular Biol Sect, Diabet Branch, Digest Dis Branch, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Bartlett, DL (reprint author), NCI, Metab Sect, Surg Branch, NIH, 10 Ctr Dr,Room 2B16, Bethesda, MD 20892 USA. NR 13 TC 44 Z9 45 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1998 VL 124 IS 6 BP 1056 EP 1061 DI 10.1067/msy.1998.92171 PG 6 WC Surgery SC Surgery GA 145UA UT WOS:000077388700029 PM 9854583 ER PT J AU Norton, JA Doherty, GM Fraker, DL Alexander, R Doppman, JL Venzon, DJ Gibril, F Jensen, RT AF Norton, JA Doherty, GM Fraker, DL Alexander, R Doppman, JL Venzon, DJ Gibril, F Jensen, RT TI Surgical treatment of localized gastrinoma within the liver: A prospective study SO SURGERY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 26-28, 1998 CL ORLANDO, FLORIDA SP Amer Assoc Endocrine Surgeons ID ZOLLINGER-ELLISON SYNDROME; SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; PANCREATIC ENDOCRINE TUMORS; GASTROENTEROPANCREATIC TUMORS; AGGRESSIVE RESECTION; SURGERY; METASTASES; MANAGEMENT AB Background. Studies demonstrate that liver metastases of gastrinoma significantly reduce survival. Methods. Since 1982 we have prospectively studied 213 patients with Zollinger-Ellison syndrome. For this report the results of surgery for localized liver gastrinoma were analyzed. Results. Zollinger-Ellison syndrome was diagnosed biochemically in all patients and acid output was controlled with medications. Imaging studies demonstrated liver gastrinoma in 69 patients (32 %). Fifty-two had diffuse unresectable disease, whereas 17 (10 %) had localized disease. All patients with localized liver gastrinoma and 2 patients with diffuse disease who needed surgery are the subject of this report. Major hepatic lobectomy was performed in 10 patients and wedge resections in 9. Three patients had apparent liver primary gastrinomas and 16 had metastatic disease. Seventeen of 19 patients were able to have all identifiable gastrinoma resected. Extrahepatic tumor was also removed at the same procedure. Extirpation of liver gastrinoma required hepatic lobectomy in 10 patients and wedge resections in the others. Five-year survival was 85 %. Five of 17 completely resected patients (29 %) remained disease free. Conclusions, Resectable localized liver gastrinoma is rare. Primary liver gastrinomas can occur Surgical resection of localized liver gastrinoma provides a cure rate similar to that of extrahepatic gastrinoma and an excellent long-term survival. C1 San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. NCI, Surg Branch, Surg Metab Sect, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NIDDKD, Digest Dis Branch, Bethesda, MD 20892 USA. RP Norton, JA (reprint author), San Francisco Vet Affairs Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. RI Venzon, David/B-3078-2008 NR 25 TC 39 Z9 41 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1998 VL 124 IS 6 BP 1145 EP 1152 DI 10.1067/msy.1998.93110 PG 8 WC Surgery SC Surgery GA 145UA UT WOS:000077388700056 PM 9854596 ER PT J AU Libutti, SK Choyke, PL Bartlett, DL Vargas, H Walther, M Lubensky, I Glenn, G Linehan, WM Alexander, HR AF Libutti, SK Choyke, PL Bartlett, DL Vargas, H Walther, M Lubensky, I Glenn, G Linehan, WM Alexander, HR TI Pancreatic neuroendocrine tumors associated with vonHippel Lindau disease: Diagnostic and management recommendations SO SURGERY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 26-28, 1998 CL ORLANDO, FLORIDA SP Amer Assoc Endocrine Surgeons ID ISLET CELL TUMORS; PREVALENCE; LESIONS AB Background. von Hippel Lindau disease (VHL) is an inherited syndrome characterized by tumors of the kidney, adrenal, central nervous system and pancreas. The incidence and natural history of pancreatic neuroendocrine tumors occurring in VHL are not known. Methods. From December 1988 through November 1997, 256 patients with VHL were screened with imaging studies, and these data were reviewed from a prospective database. Results. Thirty (12 %) of 256 patients had solid pancreatic lesions consistent with neu neuroendocrine tumors. Fourteen patients underwent resection, and 4 with metastases on imaging studies underwent biopsy only. Of the 14 patients who underwent resection, 11 remain free of disease, 2 have experienced recurrence, and 1 has died of unrelated causes (mean follow-up, 25 months; range, 3 to 73 months). The size of the primary tumor (median, 5 cm; range, 3 to 8 cm) in patients with liver metastases was significantly larger than the size of the primary tumor (median, 2 cm; range, 1 to 5 cm) in patients without liver metastases (P = .0013). Conclusions. Solid pancreatic lesions were detected in 12 % of patients with VHL. Larger primary tumors were associated with liver metastases. Pancreatic imaging to identify neuroendocrine tumors and resection when they reach 2 to 3 cm may prevent the development of hepatic metastases. C1 NCI, Surg Branch, Surg Metab Sect, NIH, Bethesda, MD 20892 USA. NCI, Dept Radiol, Warren G Magnuson Clin Ctr, NIH,Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, Surg Metab Sect, NIH, Bldg 10,Room 2B07, Bethesda, MD 20892 USA. NR 13 TC 106 Z9 109 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1998 VL 124 IS 6 BP 1153 EP 1159 DI 10.1067/msy.1998.91823 PG 7 WC Surgery SC Surgery GA 145UA UT WOS:000077388700058 PM 9854597 ER PT J AU Alexander, HR Bartlett, DL Venzon, DJ Libutti, SK Doppman, JL Fraker, DL Norton, JA Gibril, F Jensen, RT AF Alexander, HR Bartlett, DL Venzon, DJ Libutti, SK Doppman, JL Fraker, DL Norton, JA Gibril, F Jensen, RT TI Analysis of factors associated with longterm (five or more years) cure in patients undergoing operation for Zollinger-Ellison syndrome SO SURGERY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 26-28, 1998 CL ORLANDO, FLORIDA SP Amer Assoc Endocrine Surgeons ID ISLET-CELL TUMORS; MULTIPLE ENDOCRINE NEOPLASIA; GASTRINOMA EXCISION; MANAGEMENT; LOCALIZATION; RESECTION AB Background. Only 30% to 40% of patients with Zollinger-Ellison syndrome (ZES) undergoing operation with curative intent have biochemical cures. The purpose of this analysis was to identify perioperative factors associated with long-term (greater than or equal to 5 years) biochemical cures. Methods. From December 1981 to September 1997, 128 patients with potentially curable ZES underwent 152 abdominal explorations with resection of all identifiable disease. Of these, 31 outcomes were identified with documented cures at greater than or equal to 5 years from operation and were compared with outcomes of 110 patients who were not cured. Univariate and multivariate statistical analyses were performed. Results. The results of a normal immediate postoperative fasting serum gastrin and secretin stimulation test were significantly and independently correlated with 5-year cure (P-2 = .005 and .0099, respectively). A diagnosis of multiple endocrine neoplasia type 1 was significantly inversely correlated with cure on univariate analysis (P-2 = .027). Gender; age, duration of symptoms, results of diagnostic tests, or results of imaging studies did not correlate with outcome. Conclusions. All patients with sporadic potentially curable ZES should undergo exploration because outcome is not associated with preoperative tests. Only 5% of patients with ZES and multiple endocrine neoplasia type 1 were cured at 5 years. A normal fasting serum gastrin or secretin stimulation value value immediately postoperatively provides important prognostic information. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B07, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 25 TC 24 Z9 24 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1998 VL 124 IS 6 BP 1160 EP 1166 DI 10.1067/msy.1998.92010 PG 7 WC Surgery SC Surgery GA 145UA UT WOS:000077388700060 PM 9854598 ER PT J AU McKenna, IM Gordon, T Chen, LC Anver, MR Waalkes, MP AF McKenna, IM Gordon, T Chen, LC Anver, MR Waalkes, MP TI Expression of metallothionein protein in the lungs of Wistar rats and C57 and DBA mice exposed to cadmium oxide fumes SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT 4th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 1996 CL BARCELONA, SPAIN SP Natl Ctr Toxicol Res, Food & Drug Adm, NCI, Assoc Reg Enseignement & Rech Sci Champagne Ardenne, Int Res Inst Metal Ions, Univ Rovira Virgili, Univ Barcelona, Escola Profess Med Treball, Direcc Gen Investigac Cient & Tecn, Commiss Univ Rec CIRIT Generalitat Catalunya ID PULMONARY CARCINOGENICITY; ALVEOLAR MACROPHAGES; MOLECULAR-CLONING; INHALED CADMIUM; DOWN-REGULATION; RNA SEQUENCE; CELLS; AEROSOLS; CHLORIDE; SENSITIVITY AB Chronic exposure to inhaled cadmium (Cd) has been shown to induce lung tumors in rats (Wistar strain) but not in mice (NMRI strain). The protein metallothionein (MT) plays an important role in Cd detoxification, and it has been suggested that differential inducibility of pulmonary MT may lead to interspecies susceptibility differences to inhaled Cd. Interstrain differences in the pulmonary response of the MT gene to Cd stimuli have not been examined in rats or mice. We compared pulmonary MT expression in Wistar Furth (WF) rats with that in DBA and C57 mice, following a single 3-h exposure to CdO fumes containing 1 mg Cd/m(3). Induction of the MT gene was assessed by the levels of MT-I and MT-II transcripts, MT-protein content, and number of MT-labeled alveolar and bronchiolar epithelial cells immediately after Cd exposure and 1, 3, and 5 days later. Control animals were exposed to air/argon furnace gases. We observed differential intra- and interspecies inducibility of the MT gene in the lung following Cd inhalation. DBA mice exhibited greater levels of MT-mRNA, mainly for the MT-I isoform, MT-protein content, and number of MT positive cells relative to C57 mice. WF rats showed lower transcription and translation responses of the MT gene upon Cd stimuli than C57 mice. The present results, in concert with our previous findings of higher lung cell proliferation in Cd-exposed C57 relative to DBA mice, predict greater susceptibility of C57 to the carcinogenic effects of inhaled Cd. Furthermore, the low transcriptional and translation responses of the MT gene to Cd stimuli in WF rats might explain the higher susceptibility of this rat strain to develop malignant lung tumors after chronic exposure to Cd via inhalation. Parallel to our findings in mice, differences in the responsiveness of lung MT gene may exist across rat strains. Thus intraspecies genetic variability in pulmonary MT may influence the susceptibility of rats or mice to lung carcinogenesis induced by inhalation of Cd compounds, (C) 1998 Academic Press. C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Frederick Canc Res & Dev Ctr, SAIC, Pathol Histotechnol Lab, Frederick, MD 21702 USA. NYU, Med Ctr, Inst Environm Med, Tuxedo Park, NY 10987 USA. RP McKenna, IM (reprint author), US EPA, OPPT, RAD 7403, 401 M St SW, Washington, DC 20460 USA. RI Cjem, Lung-Chi/H-5030-2012 NR 44 TC 21 Z9 21 U1 0 U2 0 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 DEC PY 1998 VL 153 IS 2 BP 169 EP 178 DI 10.1006/taap.1998.8399 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 156WG UT WOS:000078024700004 PM 9878588 ER PT J AU Lee, KM Dill, JA Chou, BJ Roycroft, JH AF Lee, KM Dill, JA Chou, BJ Roycroft, JH TI Physiologically based pharmacokinetic model for chronic inhalation of 2-butoxyethanol SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID AGE-RELATED-CHANGES; ALDEHYDE DEHYDROGENASE-ACTIVITIES; GLYCOL MONOBUTYL ETHER; DERMAL ABSORPTION; BUTOXYACETIC ACID; FISCHER-344 RATS; METABOLISM; LIVER; EXPOSURE; BINDING AB 2-Butoxyethanol (2BE) is used extensively in the production of cleaning agents and as a general solvent. It is primarily metabolized in the liver to 2-butoxyacetic acid (2BAA), which is excreted in urine. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model describing the toxicokinetic behavior of 2BE and 2BAA in different species following repeated, long-term exposures. The PBPK model was first developed for short-term 2BE exposure to male rats. Allometric scaling was employed to estimate physiological and biochemical model parameters based on body weight. To accommodate differences in 2BE toxicokinetics in female rats, a higher V-max for 2BE metabolism to 2BAA, higher plasma protein binding sites for 2BAA, and lower V-max for 2BAA excretion through the kidney were incorporated into the model. For mice, a higher V-max for 2BE metabolism to 2BAA for both sexes and higher plasma protein binding sites for 2BAA for female mice were also incorporated into the model. Subsequently, the model was expanded to simulate 2BE and 2BAA toxicokinetics far long-term, repeated exposures by incorporating time-dependent changes in model parameters. To reflect physiological/biochemical changes in animals during a chronic exposure, parameters for cardiac output, body composition, metabolic capacity, protein binding, or capacity of renal excretion were adjusted over time depending on species and sex. Sensitivity analysis was performed to better understand how sensitive model responses were to uncertainties in input parameters. The resulting PBPK model was used to simulate toxicokinetic data acquired during a 2-year inhalation toxicity and carcinogenicity study in male and female F344/N rats and B6C3F1 mice. (C) 1998 Academic Press. C1 Battelle Mem Inst, Preclin Drug Dev NW Operat, Richland, WA 99352 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Lee, KM (reprint author), Battelle Mem Inst, Preclin Drug Dev NW Operat, Richland, WA 99352 USA. NR 57 TC 10 Z9 12 U1 0 U2 0 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 DEC PY 1998 VL 153 IS 2 BP 211 EP 226 DI 10.1006/taap.1998.8518 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 156WG UT WOS:000078024700008 PM 9878592 ER PT J AU Dill, JA Lee, KM Bates, DJ Anderson, DJ Johnson, RE Chou, BJ Burka, LT Roycroft, JH AF Dill, JA Lee, KM Bates, DJ Anderson, DJ Johnson, RE Chou, BJ Burka, LT Roycroft, JH TI Toxicokinetics of inhaled 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in F344 rats and B6C3F1 mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID GLYCOL MONOBUTYL ETHER; PHYSIOLOGICALLY-BASED PHARMACOKINETICS; ALDEHYDE DEHYDROGENASE-ACTIVITIES; BUTOXYACETIC ACID; BUTYL ETHER; TOXICITY; HUMANS; ABSORPTION; ALCOHOL; VAPOR AB 2-Butoxyethanol (2BE) is used extensively in the production of cleaning agents and solvents. It is primarily metabolized in the liver to 2-butoxyacetic acid (2BAA), which is believed to be responsible for 2BE toxicities associated with hemolysis of red blood cells. The objective of the study was to characterize the systemic disposition of 2BE and 2BAA in rats and mice during 2-year 2BE inhalation toxicity studies. Male and female F344 rats and B6C3F1 mice (6-7 weeks old) were exposed to target 2BE concentrations of 0, 31.2, 62.5, or 125 ppm (rats), or 0, 62.5, 125, or 250 ppm (mice), by whole-body inhalation for 6 h/day, 5 days/ week far up to 18 months. Postexposure blood samples were collected after 1 day, 2 weeks, and 3, 6, 12, and 18 months of exposure. Postexposure 16-h urine samples were collected after 2 weeks and 3, 6, 12, and 18 months of exposure. A separate set of mice was kept in the control chamber and exposed to 2BE for 3 weeks when they were approximately 19 months old. Postexposure blood samples were collected after 1 day and 3 weeks of exposure and 16-h urine samples were collected after 2 weeks of exposure from these aged mice. Blood samples were analyzed for both 2BE and 2BAA and urine samples were analyzed for 2BAA using GC/MS, and their kinetic parameters were estimated through the curve-fitting method using SAS. Systemically absorbed 2BE was rapidly cleared from blood (t(1/2-RAT) < 10 min; t(1/2-MOUSE) < 5 min after the 1-day exposure) independent of exposure concentration. proportional increases in AUC(2BE) relative to increases in exposure concentration indicated linear 2BE kinetics. In contrast, the rate of 2BAA elimination from blood decreased as the exposure concentration increased. Nonproportional increases in AUC(2BAA) also indicated that 2BAA is eliminated following dose-dependent, nonlinear kinetics. Overall, mice eliminated both 2BE and 2BAA from blood faster than rats. Sex-related differences in 2BAA elimination were most significant with rats, in that females were less efficient in clearing 2BAA from the blood. Differences in renal excretion of 2BAA are possibly responsible for the sex-related difference in the 2BAA blood profiles in rats. As exposure continued, the rates of elimination for both 2BE and 2BAA decreased in both species, resulting in longer residence times in the blood. When 19-month-old naive mice were exposed to 125 ppm, 2BE was rapidly cleared from the systemic circulation, exhibiting clearance profiles similar to young mice. However, old mice eliminated 2BAA from blood > 10 times slower than young mice after 1-day of exposure. This delayed elimination of 2BAA in old mice was less obvious after 3 weeks of exposure, suggesting that there might be other factors in addition to the age of animals that could influence the apparent difference in 2BAA kinetics between old and young mice. It was concluded that the elimination kinetics of 2BE and 2BAA following repeated 2BE exposure appear to be dependent on species, sex, age, time of exposure, as well as the exposure concentration. (C) 1998 Academic Press. C1 Pacific NW Lab, Preclin Drug Dev NW Operat, Richland, WA 99352 USA. Pacific NW Lab, Engn & Analyt Sci Dept, Richland, WA 99352 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Dill, JA (reprint author), Pacific NW Lab, Preclin Drug Dev NW Operat, Richland, WA 99352 USA. NR 34 TC 14 Z9 16 U1 0 U2 0 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 DEC PY 1998 VL 153 IS 2 BP 227 EP 242 DI 10.1006/taap.1998.8524 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 156WG UT WOS:000078024700009 PM 9878593 ER PT J AU Nussenblatt, RB Schiffman, R Fortin, E Robinson, M Smith, J Rizzo, L Csaky, K Gery, I Waldmann, T Whitcup, SM AF Nussenblatt, RB Schiffman, R Fortin, E Robinson, M Smith, J Rizzo, L Csaky, K Gery, I Waldmann, T Whitcup, SM TI Strategies for the treatment of intraocular inflammatory disease SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 3rd International Conference on New Trends in Clinical and Experimental Immunosuppression CY FEB 12-15, 1998 CL GENEVA, SWITZERLAND ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; ORAL TOLERANCE; TRIAL; SUPPRESSION; MECHANISMS; INDUCTION; ANTIGENS; UVEITIS C1 NEI, Natl Canc Ctr, NIH, Div Clin Sci,Lab Immunol, Bethesda, MD 20892 USA. NEI, Natl Canc Ctr, NIH, Div Clin Sci,Clin Branch, Bethesda, MD 20892 USA. NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, Natl Canc Ctr, NIH, Div Clin Sci,Lab Immunol, Bethesda, MD 20892 USA. NR 13 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 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1998 VL 30 IS 8 BP 4124 EP 4125 DI 10.1016/S0041-1345(98)01364-5 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 149EW UT WOS:000077593000068 PM 9865319 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI The HD domain defines a new superfamily of metal-dependent phosphohydrolases SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID ESCHERICHIA-COLI; DGTP TRIPHOSPHOHYDROLASE; PHOSPHOLIPID SYNTHASES; PPGPP SYNTHESIS; PROTEIN; BINDING; GENE; IDENTIFICATION; DEGRADATION; PREDICTION C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 26 TC 270 Z9 275 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD DEC PY 1998 VL 23 IS 12 BP 469 EP 472 DI 10.1016/S0968-0004(98)01293-6 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 148LT UT WOS:000077507300009 PM 9868367 ER PT J AU Reiter, Y Pastan, I AF Reiter, Y Pastan, I TI Recombinant Fv immunotoxins and Fv fragments as novel agents for cancer therapy and diagnosis SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID DISULFIDE-STABILIZED FV; SINGLE-CHAIN IMMUNOTOXIN; PSEUDOMONAS EXOTOXIN; FUSION PROTEIN; ANTITUMOR-ACTIVITY; COMPLETE REGRESSION; ESCHERICHIA-COLI; BETA-LACTAMASE; PHAGE DISPLAY; MUTANT FORM AB Recombinant immunotoxins are new agents being developed for cancer therapy. They are composed of Fv fragments of antibodies that bind to cancer cells fused to a truncated form of a very potent bacterial toxin. The antibody moiety directs the toxin to cancer cells, which are killed, while normal cells are not recognized and thus survive. The excellent preclinical results in vitro and in vivo have led to the initiation of several clinical trials. C1 Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Reiter, Y (reprint author), Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel. EM pasta@helix.nih.gov NR 53 TC 82 Z9 89 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD DEC PY 1998 VL 16 IS 12 BP 513 EP 520 DI 10.1016/S0167-7799(98)01226-8 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 147AP UT WOS:000077466300004 PM 9881483 ER PT J AU Crane-Robinson, C Wolffe, AP AF Crane-Robinson, C Wolffe, AP TI Immunological analysis of chromatin: FIS and CHIPS SO TRENDS IN GENETICS LA English DT Editorial Material ID INACTIVE X-CHROMOSOME; DNASE-I SENSITIVITY; HISTONE ACETYLATION; TELOMERIC HETEROCHROMATIN; SEQUENCES; CORE; H4; DROSOPHILA; CELLS; YEAST C1 Univ Portsmouth, Biophys Labs, Portsmouth PO1 2DT, Hants, England. NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Crane-Robinson, C (reprint author), Univ Portsmouth, Biophys Labs, St Michaels Bldg,White Swan Rd, Portsmouth PO1 2DT, Hants, England. NR 27 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD DEC PY 1998 VL 14 IS 12 BP 477 EP 480 DI 10.1016/S0168-9525(98)01621-7 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 148BW UT WOS:000077533500001 PM 9865151 ER PT J AU Dawid, IB AF Dawid, IB TI LIM protein interactions: Drosophila enters the stage SO TRENDS IN GENETICS LA English DT Editorial Material ID HOMEODOMAIN PROTEINS; RHOMBOTIN; BINDING C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM idawid@nih.gov NR 18 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD DEC PY 1998 VL 14 IS 12 BP 480 EP 482 DI 10.1016/S0168-9525(98)01615-1 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 148BW UT WOS:000077533500002 PM 9865152 ER PT J AU Alkon, DL Nelson, TJ Zhao, WQ Cavallaro, S AF Alkon, DL Nelson, TJ Zhao, WQ Cavallaro, S TI Time domains of neuronal Ca2+ signaling and associative memory: steps through a calexcitin, ryanodine receptor, K+ channel cascade SO TRENDS IN NEUROSCIENCES LA English DT Review ID PROTEIN-KINASE-C; CYCLIC ADP-RIBOSE; INDUCED CALCIUM-RELEASE; SKELETAL-MUSCLE; RAT-BRAIN; SARCOPLASMIC-RETICULUM; POTASSIUM CURRENTS; ADENINE-NUCLEOTIDE; MEMBRANE CURRENTS; SMOOTH-MUSCLE AB Synaptic changes that underlie associative learning and memory begin with temporally related activity of two or more independent synaptic inputs to common postsynaptic targets. In turn, temporally related molecular events regulate cytosolic Ca2+ during progressively longer-lasting time domains,Associative learning behaviors of living animals have been correlated with changes of neuronal voltage-dependent K+ currents, protein kinase C-mediated phosphorylation and synthesis of the Ca2+ and GTP-binding protein, calexcitin (CE), and increased expression of the Ca2+-releasing ryanodine receptor (type II), These molecular events, some of which have been found to be dysfunctional in Alzheimer's disease, provide means of altering dendritic excitability and thus synaptic efficacy during induction, consolidation and storage of associative memory. Apparently, such stages of behavioral learning correspond to sequential differences of Ca2+ signaling that could occur in spatially segregated dendritic compartments distributed across brain structures, such as the hippocampus. C1 NINDS, Lab Adapt Syst, Bethesda, MD 20892 USA. CNR, Ist Bioimmagini & Fisiopatol Sistema, Italian Natl Res Council, Catania, Italy. RP Alkon, DL (reprint author), NINDS, Lab Adapt Syst, Bethesda, MD 20892 USA. RI Cavallaro, Sebastiano/F-3104-2010 OI Cavallaro, Sebastiano/0000-0001-7590-1792 NR 93 TC 112 Z9 115 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD DEC PY 1998 VL 21 IS 12 BP 529 EP 537 DI 10.1016/S0166-2236(98)01277-6 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 146CA UT WOS:000077409000007 PM 9881851 ER PT J AU Ornstein, DK Colberg, JW Virgo, KS Chan, D Johnson, ET Oh, J Johnson, FE AF Ornstein, DK Colberg, JW Virgo, KS Chan, D Johnson, ET Oh, J Johnson, FE TI Evaluation and management of men whose radical prostatectomies failed: Results of an international survey SO UROLOGY LA English DT Article ID RETROPUBIC PROSTATECTOMY; PROSTATIC-CARCINOMA; LOCAL RECURRENCE; ANTIGEN LEVELS; CANCER; TOMOGRAPHY; BIOPSY; TRENDS AB Objectives. To determine how urologists evaluate and treat men who develop recurrent prostate cancer after radical prostatectomy. Methods. Surveys were mailed to 4467 American Urological Association members comprising 3205 U.S. and 1262 non-U.S. urologists randomly selected from a total membership of approximately 12,000. One thousand four hundred sixteen were returned and 1050 (760 U.S. and 290 non-U.S.) surveys were evaluable. Results. To evaluate men with an elevated or rising prostate-specific antigen (PSA) level more than I year after radical prostatectomy, 98% of respondents use digital rectal examination, 68% use bone scan, 54% use transrectal ultrasound with biopsy, 36% use abdominal or pelvic computed tomography scan, 31% use transrectal ultrasound without biopsy, 25% use prostatic acid phosphatase, 11% use monoclonal antibody scan, and 5% use abdominal or pelvic magnetic resonance imaging. Respondents evaluate men with an elevated or rising PSA within 1 year of radical prostatectomy similarly. To treat documented local recurrence, 81% of respondents recommend radiation therapy, 7% recommend orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonists, 6% recommend observation only, and 5% recommend combined androgen ablation. To treat documented distant recurrence, 50% recommend combined androgen ablation, 42% recommend orchiectomy or LHRH agonists, and 7% recommend observation only. To treat PSA-only recurrence, 54% recommend observation only, 16% recommend combined androgen ablation, 15% recommend orchiectomy or LHRH agonists, and 13% recommend radiation therapy. Conclusions. The evaluation of men whose radical prostatectomy failed varies among urologists and does not depend on time of recurrence. Radiation therapy is used by most urologists to treat local recurrence. Hormonal manipulation is used by more than 90% of urologists to treat distant recurrence. More than 50% of urologists recommend observation for men with biochemical-only recurrence. (C) 1998, Elsevier Science Inc. All rights reserved. C1 Washington Univ, Div Urol Surg, St Louis, MO USA. St Louis Univ, Hlth Sci Ctr, Dept Surg, St Louis, MO 63103 USA. John Cochran Vet Affairs Med Ctr, Surg Serv, St Louis, MO USA. RP Ornstein, DK (reprint author), NCI, Urol Oncol Branch, 9000 Rockville Pike,Bldg 10,Room 2B47, Bethesda, MD 20892 USA. NR 25 TC 62 Z9 62 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD DEC PY 1998 VL 52 IS 6 BP 1047 EP 1054 DI 10.1016/S0090-4295(98)00403-8 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 141EV UT WOS:000077130400021 PM 9836553 ER PT J AU Muller-Hocker, J Schafer, S Copeland, WC Wiesner, R Seibel, P AF Muller-Hocker, J Schafer, S Copeland, WC Wiesner, R Seibel, P TI Immunohistochemical detection of human mtDNA polymerase gamma and of human mitochondrial transcription factor A in cytochrome-c-oxidase-deficient oxyphil cells of hyperfunctional parathyroids SO VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY LA English DT Article DE cytochrome-c-oxidase; mitochondrial DNA; in situ hybridization; mtDNA polymerase gamma; human mitochondrial transcription factor A ID KEARNS-SAYRE SYNDROME; FACTOR-A; RESPIRATORY-CHAIN; GENE-EXPRESSION; INSITU HYBRIDIZATION; DNA MAINTENANCE; DISEASES; REPLICATION; DEFECTS; ENCEPHALOMYOPATHIES AB Immunohistochemical studies were performed in 18 hyperfunctional parathyroids with oxyphil cell aggregates for the detection of cytochrome-c-oxidase (complex IV of the respiratory chain), mitochondrial DNA polymerase gamma and human mitochondrial transcription factor A (h-mtTFA). Seventy-three oxyphil areas exhibiting a defect of cytochrome-c-oxidase were found. The defect involved both the mitochondrially coded subunits II/III and the nuclear derived subunits Vab. There was no loss of mtDNA polymerase gamma or of h-mtTFA in these foci, corresponding to a high content of mtDNA revealed by in situ hybridization. Isolated defects of h-mtTFA were also not found. In contrast, isolated defects of mtDNA polymerase gamma were present in 22 oxyphil foci. These results show that defects of cytochrome-c-oxidase in oxyphil cells are not due to altered expression of h-mtTFA or DNA polymerase gamma, indicating that other nuclear factors involved in the generation of the respiratory chain may be impaired. The low incidence of defects of mtDNA polymerase gamma and the absence of alterations of h-mtTFA and cytochrome-c-oxidase in these foci suggest that defects of mtDNA polymerase gamma are of minor pathogenetic significance. C1 Univ Munich, Inst Pathol, D-80336 Munich, Germany. NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. Univ Heidelberg, Inst Physiol 2, D-69120 Heidelberg, Germany. Univ Dresden, Neurol Klin, Dresden, Germany. RP Muller-Hocker, J (reprint author), Univ Munich, Inst Pathol, Thalkirchnerstr 36, D-80336 Munich, Germany. NR 51 TC 8 Z9 8 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. Int. J. Pathol. PD DEC PY 1998 VL 433 IS 6 BP 529 EP 536 DI 10.1007/s004280050285 PG 8 WC Pathology SC Pathology GA 148BA UT WOS:000077531400007 PM 9870686 ER PT J AU Penrod, J Dellasega, C AF Penrod, J Dellasega, C TI Caregivers' experiences in making placement decisions SO WESTERN JOURNAL OF NURSING RESEARCH LA English DT Article ID NURSING-HOME; CARE; PARENT AB Demographic trends indicate a growth in the older adult population, and in turn, are affecting the availability and use of health services. Although placement of an older adult charge into nursing home care is often described as a logical progression through the continuum of available services, informal caregivers often view placement as a last resort or as an indication of failure. This qualitative study used grounded theory methods to explore the experiences of care-givers actively involved in the process of placing an older adult in a long-term care facility upon discharge from acute care. Four themes (uncertainty, surrendering to the system, urgency, and validating) were interwoven throughout caregivers' perspectives of the conflictive decision to use nursing home care after hospitalization. C1 NIA, Bethesda, MD 20892 USA. Penn State Univ, Sch Nursing, University Pk, PA 16802 USA. RP Penrod, J (reprint author), NIA, Bethesda, MD 20892 USA. NR 43 TC 21 Z9 21 U1 3 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0193-9459 J9 WESTERN J NURS RES JI West. J. Nurs. Res. PD DEC PY 1998 VL 20 IS 6 BP 706 EP 722 DI 10.1177/019394599802000604 PG 17 WC Nursing SC Nursing GA 142UW UT WOS:000077219600010 PM 9842288 ER PT J AU Wickner, RB AF Wickner, RB TI This year in YEAST SO YEAST LA English DT Editorial Material C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0749-503X J9 YEAST JI Yeast PD DEC PY 1998 VL 14 IS 16 BP 1437 EP 1438 DI 10.1002/(SICI)1097-0061(199812)14:16<1437::AID-YEA365>3.0.CO;2-D PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 152TG UT WOS:000077792400001 PM 9885149 ER PT J AU Oh, JD Russell, D Vaughan, CL Chase, TN AF Oh, JD Russell, D Vaughan, CL Chase, TN TI Enhanced tyrosine phosphorylation of striatal NMDA receptor subunits: effect of dopaminergic denervation and L-DOPA administration SO BRAIN RESEARCH LA English DT Article DE Parkinson's disease; 6-hydroxydopamine lesion; basal ganglia; NMDA antagonist; genistein; motor response alteration ID D-ASPARTATE RECEPTOR; LONG-TERM POTENTIATION; MOTOR RESPONSE ALTERATIONS; CEREBRAL METABOLIC RESPONSES; DEPENDENT PROTEIN-KINASE; PARKINSONS-DISEASE; BASAL GANGLIA; GLUTAMATE ANTAGONIST; RAT STRIATUM; 2B SUBUNIT AB Sensitization of striatal N-methyl-D-aspartate receptors (NMDAR) has been linked to events leading to the motor response changes associated with the administration of dopaminomimetics to parkinsonian animals and patients. To determine whether tyrosine phosphorylation of NMDAR subunits contributes to the apparent long-term enhancement in synaptic efficacy of these receptors, we examined the effect of unilateral nigrostriatal dopamine system ablation with 6-hydroxydopamine followed by twice-daily treatment with L-DOPA on the phosphorylation state of rat striatal NR2A and NR2B subunits. Three weeks of intermittent L-DOPA administration produced a shortening in the duration of the rotational response to dopaminergic challenge and other changes mimicking those occurring in patients with Parkinson's disease. Concurrently, tyrosine phosphorylation of NR2A and especially of NR2B subunits increased ipsilateral to the lesion (20 +/- 5% and 46 +/- 7% of intact striatum, respectively; p < 0.01) without attendant changes in subunit protein levels. Selective blockade of NR2B subunits with ACEA 10-1244, but not of NR2A subunits with MDL 100,453, reversed the L-DOPA-induced response alterations. The intrastriatal injection of a tyrosine kinase inhibitor, genistein, at a dose (2.0 mu g) that normalized the response shortening, attenuated the NR2A and NR2B phosphorylation increase by about 12% and 24%, respectively(p < 0.01). Taken together, these results suggest that augmented tyrosine phosphorylation of NR2B subunits, alone or in combination with the smaller rise in NR2A subunit phosphorylation, contributes to the apparent enhancement in striatal NMDAR sensitivity and thus to the plastic alterations in dopaminergic responses in L-DOPA-treated parkinsonian rats. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06508 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06508 USA. RP NINDS, Expt Therapeut Branch, NIH, Bldg 10,Rm 5C103,Rm 5C211,90900 Rockville Pike, Bethesda, MD 20892 USA. EM chase@helix.nih.gov NR 70 TC 128 Z9 131 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD NOV 30 PY 1998 VL 813 IS 1 BP 150 EP 159 DI 10.1016/S0006-8993(98)01049-X PG 10 WC Neurosciences SC Neurosciences & Neurology GA 142HF UT WOS:000077194100019 PM 9824689 ER PT J AU Markovic, I Pulyaeva, H Sokoloff, A Chernomordik, LV AF Markovic, I Pulyaeva, H Sokoloff, A Chernomordik, LV TI Membrane fusion mediated by baculovirus gp64 involves assembly of stable gp64 trimers into multiprotein aggregates SO JOURNAL OF CELL BIOLOGY LA English DT Article DE viral fusion; baculovirus gp64; fusion protein assembly; fusion inhibitors; thiol/disulfide exchange ID NUCLEAR POLYHEDROSIS-VIRUS; HEMAGGLUTININ SURFACE-DENSITY; CELL-CELL FUSION; INFLUENZA HEMAGGLUTININ; ENVELOPE GLYCOPROTEIN; RADIATION INACTIVATION; PROTEIN; PH; PORE; OLIGOMERIZATION AB The baculovirus fusogenic activity depends on the low pH conformation of virally-encoded trimeric glycoprotein, gp64. We used two experimental approaches to investigate whether monomers, trimers, and/or higher order oligomers are functionally involved in gp64 fusion machine. First, dithiothreitol (DTT)-based reduction of intersubunit disulfides was found to reversibly inhibit fusion, as assayed by fluorescent probe redistribution between gp64-expressing and target cells (i.e., erythrocytes or Sf9 cells). This inhibition correlates with disappearance of gp64 trimers and appearance of dimers and monomers in SDS-PAGE. Thus, stable (i.e., with intact intersubunit disulfides) gp64 trimers, rather than independent monomers, drive fusion. Second, we established that merger of membranes is preceded by formation of large (greater than 2 MDa), short-lived gp64 complexes. These complexes were stabilized by cell-surface cross-linking and characterized by glycerol density gradient ultracentrifugation. The basic structural unit of the complexes is stable gp64 trimer. Although DTT-destabilized trimers were still capable of assuming the low pH conformation, they failed to form multimeric complexes. The fact that formation of these complexes correlated with fusion in timing, and was dependent on (a) low pH application, (b) stable gp64 trimers, and (c) cell-cell contacts, suggests that such multimeric complexes represent a fusion machine. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Chernomordik, LV (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bldg 10,Room 10D04,10 Ctr Dr, Bethesda, MD 20892 USA. NR 46 TC 72 Z9 76 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 30 PY 1998 VL 143 IS 5 BP 1155 EP 1166 DI 10.1083/jcb.143.5.1155 PG 12 WC Cell Biology SC Cell Biology GA 145XU UT WOS:000077398300003 PM 9832546 ER PT J AU Gu, JG Tamura, M Yamada, KM AF Gu, JG Tamura, M Yamada, KM TI Tumor suppressor PTEN inhibits integrin- and growth factor-mediated mitogen-activated protein (MAP) kinase signaling pathways SO JOURNAL OF CELL BIOLOGY LA English DT Article DE PTEN; integrin; growth factor; MAP kinase; cell spreading ID FOCAL ADHESION KINASE; GERMLINE MUTATIONS; CELL-ADHESION; EXTRACELLULAR-MATRIX; TYROSINE KINASES; COWDEN-DISEASE; RAS PATHWAY; GENE; TRANSFORMATION; TRANSDUCTION AB The tumor suppressor PTEN dephosphorylates focal adhesion kinase (FAK) and inhibits integrin-mediated cell spreading and cell migration. We demonstrate here that expression of PTEN selectively inhibits activation of the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway. PTEN expression in glioblastoma cells lacking the protein resulted in inhibition of integrin-mediated MAP kinase activation. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF)-induced MAPK activation were also blocked. To determine the specific point of inhibition in the Ras/Raf/MEK/ERK pathway, we examined these components after stimulation by fibronectin or growth factors. She phosphorylation and Ras activity were inhibited by expression of PTEN, whereas EGF receptor autophosphorylation was unaffected. The ability of cells to spread at normal rates was partially rescued by coexpression of constitutively activated MEK1, a downstream component of the pathway. In addition, focal contact formation was enhanced as indicated by paxillin staining. The phosphatase domain of PTEN was essential for all of these functions, because PTEN with an inactive phosphatase domain did not suppress MAP kinase or Pas activity. In contrast to its effects on ERK, PTEN expression did not affect c-Jun NH2-terminal kinase (JNK) or PDGF-stimulated Akt. Our data suggest that a general function of PTEN is to down-regulate FAK and She phosphorylation, Ras activity, downstream MAP kinase activation, and associated focal contact formation and cell spreading. C1 NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Yamada, KM (reprint author), NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Room 421,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 46 TC 251 Z9 290 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 30 PY 1998 VL 143 IS 5 BP 1375 EP 1383 DI 10.1083/jcb.143.5.1375 PG 9 WC Cell Biology SC Cell Biology GA 145XU UT WOS:000077398300021 PM 9832564 ER PT J AU Smith, JD Kyes, S Craig, AG Fagan, T Hudson-Taylor, D Miller, LH Baruch, DI Newbold, CI AF Smith, JD Kyes, S Craig, AG Fagan, T Hudson-Taylor, D Miller, LH Baruch, DI Newbold, CI TI Analysis of adhesive domains from the A4VAR Plasmodium falciparum erythrocyte membrane protein-1 identifies a CD36 binding domain SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; variant antigen; PfEMP1; CIDR; DBL; CD36 ID HUMAN CEREBRAL MALARIA; INFECTED ERYTHROCYTES; PARASITIZED ERYTHROCYTES; CHONDROITIN SULFATE; GENE FAMILY; RECEPTOR; CYTOADHERENCE; ADHERENCE; CELLS; MOLECULE-1 AB The A4VAR is a variant antigen expressed by a clonal line that binds CD36 and intercellular adhesion molecule-1, ICAM-1. We have cloned and sequenced the extracellular domain coded by the A4var gene. To probe the relationship between A4var expression and parasite adhesion to ICAM-1, var mRNA and protein expression were analyzed in an enriched population of A4 parasites that displayed higher ICAM-1 binding. By Northern analyses, A4var was the predominant var message and antisera raised against a recombinant A4VAR protein reacted with the majority of infected erythrocytes, reinforcing previous conclusions that A4VAR binds ICAM-1. A4VAR contains five Duffy-binding like (DBL) domains, and two cysteine-rich interdomain regions (CIDR) domains. DBL and CIDR domains from A4VAR were expressed in mammalian cells to determine which regions mediate binding to CD36 and ICAM-1. Using several different binding assays, the A4VAR CIDR1 was the only domain found to bind CD36. In contrast, the same assays were unable to identify the ICAM-1 binding domain in A4VAR. This is the first time that each of the DBL and CIDR domains from a Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) have been systematically expressed and tested for binding. These results confirm that CIDR1 is sufficient to bind CD36 without any apparent contribution from other domains. (C) 1998 Elsevier Science B.V. AII rights reserved. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. John Radcliffe Hosp, Nuffield Dept Med, Inst Mol Med, Mol Parasitol Grp, Oxford OX3 9DU, England. RP Baruch, DI (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. OI Newbold, Chris/0000-0002-9274-3789 FU Wellcome Trust NR 50 TC 64 Z9 64 U1 0 U2 2 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 NOV 30 PY 1998 VL 97 IS 1-2 BP 133 EP 148 DI 10.1016/S0166-6851(98)00145-5 PG 16 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 152KG UT WOS:000077776100012 PM 9879893 ER PT J AU Vawter, MP Hemperly, JJ Freed, WJ Garver, DL AF Vawter, MP Hemperly, JJ Freed, WJ Garver, DL TI CSF N-CAM in neuroleptic-naive first-episode patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; neural cell adhesion molecule; cerebrospinal fluid; neuroleptic ID CELL-ADHESION MOLECULE; CEREBRAL VENTRICULAR ENLARGEMENT; PREFRONTAL CORTEX; POSTMORTEM BRAIN; EXPRESSION; HIPPOCAMPUS; RECEPTOR; DISORDER; PSYCHOPATHOLOGY; ABNORMALITIES AB An increased concentration of neural cell adhesion molecule (N-CAM) 105-115 kDa has been reported in patients with schizophrenia in both CSF and in post-mortem brain samples; To determine whether increased N-CAM is integral to the disease process or, alternatively, results from early treatment, CSF N-CAM was measured in a blind study of first episode (FE) patients, who were either neuroleptic-naive (NN) or neuroleptic-treated (NT, < 100 mg Haldol equivalents), multi-episode (ME) patients, and controls. Overall, the FE patients displayed lower N-CAM concentrations as compared to controls (p=0.043). This decrease in N-CAM in FE patients was seen only in the FE-NT group as compared to both controls (p=0.0006). The FE-NT group also showed a lower CSF N-CAM compared to that in the FE-NN (p=0.025) group. No difference in CSF N-CAM between the FE-NN and control group was found. ME patients showed an increased N-CAM as compared with FE patients (p=0.018), but not as compared to controls (p=0.93). Neuroleptic-naive first-episode patients do not display a phenotypic increase in N-CAM. Thus, N-CAM is altered in first-episode patients following acute neuroleptic treatment and withdrawal, as compared to neuroleptic-naive first-episode patients. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIDA, Addict Res Ctr, Sect Dev & Plast, Baltimore, MD 21224 USA. Becton Dickinson & Co, Res Ctr, Neurobiol Sect, Res Triangle Pk, NC 27709 USA. Univ Texas, SW Med Ctr, Schizophrenia Res Ctr, Dallas, TX 75216 USA. Dallas VAMC, Dallas, TX 75216 USA. RP Vawter, MP (reprint author), NIDA, Addict Res Ctr, Sect Dev & Plast, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 49 TC 19 Z9 19 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV 30 PY 1998 VL 34 IS 3 BP 123 EP 131 DI 10.1016/S0920-9964(98)00103-0 PG 9 WC Psychiatry SC Psychiatry GA 140QU UT WOS:000077100500001 PM 9850978 ER PT J AU Courtney, SM Petit, L Haxby, JV Ungerleider, LG AF Courtney, SM Petit, L Haxby, JV Ungerleider, LG TI The role of prefrontal cortex in working memory: examining the contents of consciousness SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Nervous-and-Mental-Disease on the Conscious Brain - Normal and Abnormal CY DEC 05-06, 1997 CL NEW YORK, NEW YORK SP Assoc Res Nervous & Mental Dis DE functional brain imaging; human cognition; functional magnetic resonance imaging; positron emission tomography; visual processing ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; FRONTAL-CORTEX; FUNCTIONAL MRI; NEURAL SYSTEMS; HUMAN BRAIN; PET-RCBF; ACTIVATION; DISSOCIATION; OBJECT AB Working memory enables us to hold in our 'mind's eye' the contents of our conscious awareness, even in the absence of sensory input, by maintaining an active representation of information for a brief period of time. In this review we consider the functional organization of the prefrontal cortex and its role in this cognitive process. First, we present evidence from brain-imaging studies that prefrontal cortex shows sustained activity during the delay period of visual working memory tasks, indicating that this cortex maintains on-line representations of stimuli after they are removed from view. We then present evidence for domain specificity within frontal cortex based on the type of information, with object working memory mediated by more ventral frontal regions and spatial working memory mediated by more dorsal frontal regions. We also propose that a second dimension for domain specificity within prefrontal cortex might exist for object working memory on the basis of the type of representation, with analytic representations maintained preferentially in the left hemisphere and image-based representations maintained preferentially in the right hemisphere. Furthermore, we discuss the possibility that there are prefrontal areas brought into play during the monitoring and manipulation of information in working memory in addition to those engaged during the maintenance of this information. Finally we consider the relationship of prefrontal areas important for working memory, both to posterior visual processing areas and to prefrontal areas associated with long-term memory. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Ungerleider, LG (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C104, Bethesda, MD 20892 USA. EM lgu@ln.nimh.nih.gov RI GINSPAN, All/B-8714-2008; Petit, Laurent/D-6583-2011 OI Petit, Laurent/0000-0003-2499-5367 NR 59 TC 149 Z9 153 U1 1 U2 10 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD NOV 29 PY 1998 VL 353 IS 1377 BP 1819 EP 1828 DI 10.1098/rstb.1998.0334 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 140LT UT WOS:000077089300003 PM 9854254 ER PT J AU Ioannidis, JPA Contopoulos-Ioannidis, DG AF Ioannidis, JPA Contopoulos-Ioannidis, DG TI Reporting of safety data from randomised trials SO LANCET LA English DT Article ID CLINICAL-TRIALS C1 NIAID, Therapeut Res Program, Div Aids, Rockville, MD 20852 USA. George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Infect Dis, Washington, DC 20052 USA. RP Ioannidis, JPA (reprint author), NIAID, Therapeut Res Program, Div Aids, Rockville, MD 20852 USA. RI Ioannidis, John/G-9836-2011 NR 5 TC 54 Z9 57 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 28 PY 1998 VL 352 IS 9142 BP 1752 EP 1753 DI 10.1016/S0140-6736(05)79825-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 143GH UT WOS:000077246500014 PM 9848355 ER PT J AU Wu, YL Kwon, KS Rhee, SG AF Wu, YL Kwon, KS Rhee, SG TI Probing cellular protein targets of H2O2 with fluorescein-conjugated iodoacetamide and antibodies to fluorescein SO FEBS LETTERS LA English DT Article DE hydrogen peroxide; intracellular messenger; cysteine oxidation; growth factor; protein tyrosine phosphatase ID HYDROGEN-PEROXIDE; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; GENERATION; ACTIVATION; PHOSPHATASE AB Recent studies suggest that H2O2, at subtoxic concentrations generated in response to the activation of a variety of cell surface receptors, functions as an intracellular messenger. However the intracellular targets of H2O2 action have not; been identified. A procedure to detect proteins with reactive cysteine residues susceptible to oxidation by intracellularly generated H2O2 is now described, This approach is based on the labeling of proteinaceous cysteine with 5-iodoacetamido-fluorescein at pH 5.5 and immunoblot analysis of the labeled proteins with antibodies specific to fluorescein. With this procedure, many proteins in human A431 cells were shown to contain reactive cysteines and to be readily oxidized by H2O2 generated in response to cellular stimulation with epidermal growth factor. One of these H2O2-sensitive proteins was identified as protein tyrosine phosphatase 1B. (C) 1998 Federation of European Biochemical Societies. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Rhee, SG (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 3,Room 122, Bethesda, MD 20892 USA. NR 19 TC 72 Z9 77 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 27 PY 1998 VL 440 IS 1-2 BP 111 EP 115 DI 10.1016/S0014-5793(98)01415-X PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 145AK UT WOS:000077348700025 PM 9862437 ER PT J AU Lin, BC Annabi, B Hiraiwa, H Pan, CJ Chou, JY AF Lin, BC Annabi, B Hiraiwa, H Pan, CJ Chou, JY TI Cloning and characterization of cDNAs encoding a candidate glycogen storage disease type 1b protein in rodents SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUCOSE-6-PHOSPHATE TRANSPORT-SYSTEM; MICROSOMAL GLUCOSE-6-PHOSPHATASE; ENZYME-DEFICIENT; MESSENGER-RNA; GENE; MUTATIONS; IB; 1A; STIMULATION; MEMBRANE AB Glycogen storage disease type 1 (GSD-I) is a group of genetic disorders caused by a deficiency in the activity of the enzyme glucose-6-phosphatase. (G6Pase). GSD-la and GSD-lb, the two major subgroups, have been confirmed at the molecular genetic level. The gene responsible for GSD-lb maps to human chromosome 11q23 and a candidate human GSD-lb cDNA that encodes a microsomal transmembrane protein has been identified. In this study, we show that this cDNA maps to chromosome 11q23; thus it is a strong candidate for GSD-lb. Furthermore, we isolated and characterized candidate murine and rat GSD-lb cDNAs. Both encode transmembrane proteins sharing 93-95% sequence homology to the human GSD-lb protein. The expression profiles of murine GSD-lb and G6Pase differ both in the liver and in the kidney; the GSD-lb transcript appears before the G6Pase mRNA during development. In addition to G6Pase deficiency, GSD-lb patients suffer neutropenia, neutrophil dysfunction, and recurrent bacterial infections. Interestingly, although the G6Pase mRNA is expressed primarily in the liver, kidney, and intestine, the GSD-lb mRNA is expressed in numerous tissues, including human neutrophils/monocytes. C1 NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Chou, JY (reprint author), NICHD, Heritable Disorders Branch, NIH, Bldg 10,Rm 9S241, Bethesda, MD 20892 USA. RI Lin, Baochuan/A-8390-2009 OI Lin, Baochuan/0000-0002-9484-0785 NR 37 TC 62 Z9 62 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 NOV 27 PY 1998 VL 273 IS 48 BP 31656 EP 31660 DI 10.1074/jbc.273.48.31656 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 142NR UT WOS:000077207000008 PM 9822626 ER PT J AU Kobayashi, T Imokawa, G Bennett, DC Hearing, VJ AF Kobayashi, T Imokawa, G Bennett, DC Hearing, VJ TI Tyrosinase stabilization by Tyrp1 (the brown locus protein) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COAT-COLOR MUTANTS; MAMMALIAN TYROSINASE; DOPACHROME TAUTOMERASE; MELANIN BIOSYNTHESIS; MOUSE MUTATION; WILD-TYPE; MELANOCYTES; GENE; MELANOGENESIS; GLYCOPROTEIN AB Mammalian melanogenesis is regulated directly or indirectly by over 85 distinct loci. The Tyr/albino locus, in which mutations cause a lack of pigmentation, encodes tyrosinase (Tyr), the critical and rate-limiting melanogenic enzyme. Other melanogenic enzymes include Tyrp1 (or TRP1) and 3,4-dihydroxyphenylalaninechrome tautomerase (Dct or TRP2) encoded at the Tyrp1/brown and Dct/slaty loci, respectively. Murine Tyrp1 can oxidize 5,6-dihydroxyindole-2-carboxylic acid (DHICA) produced by Dct, but mutations in Tyrp1 also affect the catalytic functions of Tyr. All three enzymes are membrane-bound melanosomal proteins with similar structural features and are thought to interact within and stabilize a melanogenic complex. We have now further investigated the effect of a Tyrp1(b) mutation on Tyr stability. Pulse/chase labeling experiments show that Tyr is degraded more quickly in Tyrp1(b) mutant melanocytes than in melanocytes wild type at that locus. This reduced stability of Tyr can be partly rescued by infection with the wild type Tyrp1 gene, and this is accompanied by phenotypic rescue of infected melanocytes. In sum, these results suggest that, in addition to its catalytic function in oxidizing DHICA, Tyrp1 may play an important role in stabilizing Tyr, a second potential role in the regulation of melanin formation. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. St George Hosp, Sch Med, Dept Anat, London SW17 0RE, England. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 1B25, Bethesda, MD 20892 USA. RI Bennett, Dorothy/C-2418-2008 OI Bennett, Dorothy/0000-0002-3639-7527 NR 42 TC 109 Z9 112 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 27 PY 1998 VL 273 IS 48 BP 31801 EP 31805 DI 10.1074/jbc.273.48.31801 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 142NR UT WOS:000077207000028 PM 9822646 ER PT J AU Huang, Y Takahashi, M Tanazawa, K Putney, JW AF Huang, Y Takahashi, M Tanazawa, K Putney, JW TI Effect of adenophostin A on Ca2+ entry and calcium release-activated calcium current (I-crac) in rat basophilic leukemia cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PENICILLIUM-BREVICOMPACTUM; POTENT AGONISTS; MAST-CELLS; DEPLETION; RECEPTOR; INOSITOL-1,4,5-TRISPHOSPHATE; INACTIVATION; FEEDBACK; INFLUX; STORES AB In most non-excitable cells, calcium influx is signaled by depletion of intracellular calcium stores, a process known as capacitative calcium entry. Adenophostin A, a potent activator of the inositol 1,4,5-trisphosphate receptor, has been reported to activate Ca2+ entry in Xenopus oocytes to a greater extent than expected on the basis of its ability to release calcium stores. In this study, we compared the abilities of adenophostin A and inositol 2,4,5-trisphosphate ((2,4,5)IP3) to release Ca2+ from intracellular stores, to activate Ca2+ entry, and to activate calcium release-activated calcium current (I-crac) in rat basophilic leukemia cells. Under conditions of low intracellular Ca2+ buffering (0.1 mM BAPTA), adenophostin A-induced Ca2+ release and activation of I-crac could be monitored simultaneously. However, other reagents that would be expected to deplete Ca2+ stores ((2,4,5)IP3, 3-fluoro-inositol 1,4,5-trisphosphate, thapsigargin, and ionomycin) were unable to activate I-crac under this low Ca2+ buffering condition. Adenophostin A activated I-crac after a significant delay, longer than the delay for Ca2+ release. Thus, adenophostin A activates I-crac as a consequence of release of intracellular Ca2+, rather than directly acting on store-operated channels. The unique ability of adenophostin A to activate I-crac under conditions of low intracellular Ca2+ buffering suggests an additional site of action, perhaps in preventing or reducing rapid Ca2+-dependent inactivation of store-operated Ca2+ channels. C1 NIEHS, Calcium Regulat Sect, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Sankyo Co Ltd, Biol Res Labs, Tokyo 140, Japan. RP Putney, JW (reprint author), NIEHS, Calcium Regulat Sect, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 23 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 27 PY 1998 VL 273 IS 48 BP 31815 EP 31821 DI 10.1074/jbc.273.48.31815 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 142NR UT WOS:000077207000030 PM 9822648 ER PT J AU Caughey, B Raymond, GJ Bessen, RA AF Caughey, B Raymond, GJ Bessen, RA TI Strain-dependent differences in beta-sheet conformations of abnormal prion protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSMISSIBLE MINK ENCEPHALOPATHY; INFECTED BRAIN; SCRAPIE; FORM; PRP; SPECTROSCOPY; AGGREGATION; CONVERSION; DIVERSITY; PEPTIDES AB Strain diversity in the transmissible spongiform encephalopathies (TSEs) has been proposed to be determined by variations in the conformation of the abnormal, protease-resistant form of prion protein (PrP-res). me have investigated whether infection of hamsters with three TSE strains resulted in the formation of PrP-res with different conformations using limited proteinase K (PK) digestion and infrared spectroscopy. PrP-res isolated from the brains of hamsters infected with the hyper (HY), drowsy (DY), and 263K TSE strains yielded similar SDS-polyacrylamide gel electrophoresis profiles prior to PK treatment. However, after limited digestion with PK, the PrP-res from the DY strain exhibited a fragmentation pattern that was distinct from that of the other two strains. Infrared spectra of HY and 263K PrP-res each had major absorption bands in the amide I region at 1626 and 1636 cm(-1) both prior to and after digestion with PK. These bands were not evident in the DY PrP-res spectra, which had a unique band at 1629-1630 cm(-1) and stronger band intensity at both 1616 and 1694-1695 cm(-1). Because absorbances from 1616 to 1636 cm(-1) of protein infrared spectra are attributed primarily to beta-sheet structures, these findings indicate that the conformations of HY and 263K PrP-res differ hom DY PrP-res at least in structural regions with beta-sheet secondary structure. These results support the hypothesis that strain-specific PrP-res conformers can self-propagate by converting the normal prion protein to the abnormal conformers that induce phenotypically distinct TSE diseases. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. Creighton Univ, Dept Med Microbiol & Immunol, Omaha, NE 68178 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM byron_caughey@nih.gov NR 38 TC 215 Z9 219 U1 2 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 NOV 27 PY 1998 VL 273 IS 48 BP 32230 EP 32235 DI 10.1074/jbc.273.48.32230 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 142NR UT WOS:000077207000083 PM 9822701 ER PT J AU Kotani, T Miyake, T Tsukihashi, Y Hinnebusch, AG Nakatani, Y Kawaichi, M Kokubo, T AF Kotani, T Miyake, T Tsukihashi, Y Hinnebusch, AG Nakatani, Y Kawaichi, M Kokubo, T TI Identification of highly conserved amino-terminal segments of dTAF(II)-230 and yTAF(II)145 that are functionally interchangeable for inhibiting TBP-DNA interactions in vitro and in promoting yeast cell growth in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE-II; TATA-BINDING PROTEIN; MEDIATE TRANSCRIPTIONAL ACTIVATION; GENE ACTIVATION; BOX-BINDING; IN-VIVO; PREINITIATION COMPLEX; DOMAIN; HOLOENZYME; CORE AB TFIID is a multiprotein complex composed of TBP and several TAF(II)s, Small amino-terminal segments (TAF N-terminal domain (TAND)) of Drosophila TAF(II)230 (dTAF(II)230) and yeast TAF(II)145 (yTAF(II)145) bind strongly to TBP and inhibit TBP-DNA interactions. yTAF(II)145 TAND (yTAND) was divided into two subdomains, yTaNDI(10-37) and yTANDII(46-71), that function cooperatively, Here, we identify dTANDII: within the amino terminus of dTAF(II)230 at 118-143 amino acids in addition to dTANDI(18-77), reported previously, dTANDII exhibits pronounced sequence similarity to yTANDII, and the two were shown to be functionally equivalent in binding to TBP and inhibiting TBP-DNA interactions in vitro. Alanine scanning mutation analysis demonstrated that Phe-57 (yTANDII) and Tyr-129 (dTANDII) are critically required for the interaction with TBP, Yeast strains containing mutant yTAF(II)145 lacking yTANDI or yTANDII showed a temperature-sensitive growth phenotype, The conserved core of dTANDII could substitute for the yTANDII core, and Phe-57 or Tyr-129 described above was critically required for the function of this segment in promoting normal cell growth at 37 degrees C, In these respects, the impact of yTANDII mutations on cell growth paralleled their effects on TBP binding in vitro, strongly suggesting that the yTAF(II)145-TBP interaction and its negative effects on TFIID binding to core promoters are physiologically important. C1 Nara Inst Sci & Technol, Div Gene Funct Anim, Nara 6300101, Japan. NICHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. NICHD, Labs Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Kokubo, T (reprint author), Nara Inst Sci & Technol, Div Gene Funct Anim, Nara 6300101, Japan. NR 42 TC 44 Z9 45 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 27 PY 1998 VL 273 IS 48 BP 32254 EP 32264 DI 10.1074/jbc.273.48.32254 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 142NR UT WOS:000077207000086 PM 9822704 ER PT J AU Hsiou, Y Das, KY Ding, JP Clark, AD Kleim, JP Rosner, M Winkler, I Riess, G Hughes, SH Arnold, E AF Hsiou, Y Das, KY Ding, JP Clark, AD Kleim, JP Rosner, M Winkler, I Riess, G Hughes, SH Arnold, E TI Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: Inhibitor flexibility is a useful design feature for reducing drug resistance SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE AIDS; drug design; drug resistance mechanisms; polymerase structure; X-ray crystallography ID IMMUNODEFICIENCY-VIRUS TYPE-1; NONNUCLEOSIDE INHIBITOR; CONFORMATIONAL-CHANGES; ANGSTROM RESOLUTION; ZIDOVUDINE; MUTATIONS; REPLICATION; DIDANOSINE; LAMIVUDINE; MECHANISMS AB The second generation Hoechst-Bayer non-nucleoside inhibitor, HBY 097 (S-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3,4-dihydroquinoxalin-2(1H)-thione), is an extremely potent inhibitor of HIV-1 reverse transcriptase (RT) and of HIV-1 infection in cell culture. HEY 097 selects for unusual drug-resistance mutations in HIV-1 RT (e.g. Gly190Glu) when compared with other non-nucleoside RT inhibitors (NNRTIs), such as nevirapine, alpha-APA and TIBO. We have determined the structure of HEY 097 complexed with wild-type HIV-1 RT at 3.1 Angstrom resolution. The HIV-1 RT/KBY 097 structure reveals an overall inhibitor geometry and binding mode differing significantly from RT/NNRTI structures reported earlier, in that HEY 097 does not adopt the usual butterfly-like shape. We have determined the structure of the Tyr188Leu HIV-1 RT drug-resistant mutant in complex with HEY 097 at 3.3 Angstrom resolution. HEY 097 binds to the mutant RT in a manner similar to that seen in the wild-type RT/HBY 097 complex, although there are some repositioning and conformational alterations of the inhibitor. Conformational changes of the structural elements forming the inhibitor-binding pocket, including the orientation of some side-chains, are observed. Reduction in the size of the 188 side-chain and repositioning of the Phe227 side-chain increases the volume of the binding cavity in the Tyr188Leu HIV-1 RT/HBY 097 complex. Loss of important protein-inhibitor interactions may account for the reduced potency of HEY 097 against the Tyr188Leu HIV-1 RT mutant. The loss of binding energy may be partially offset by additional contacts resulting from conformational changes of the inhibitor and nearby amino acid residues. This would suggest that inhibitor flexibility can help to minimize drug resistance. (C) 1998 Academic Press. C1 Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA. Hoechst Marion Roussel Chem Res, D-65926 Frankfurt, Germany. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Arnold, E (reprint author), Rutgers State Univ, Ctr Adv Biotechnol & Med, 679 Hoes Lane, Piscataway, NJ 08854 USA. FU NIAID NIH HHS [AI 36144] NR 32 TC 111 Z9 117 U1 1 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 27 PY 1998 VL 284 IS 2 BP 313 EP 323 DI 10.1006/jmbi.1998.2171 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 140KU UT WOS:000077087100009 PM 9813120 ER PT J AU Krebsbach, PH Mankani, MH Satomura, K Kuznetsov, SA Robey, PG AF Krebsbach, PH Mankani, MH Satomura, K Kuznetsov, SA Robey, PG TI Repair of craniotomy defects using bone marrow stromal cells SO TRANSPLANTATION LA English DT Article ID FREEZE-DRIED BONE; POROUS HYDROXYAPATITE; MORPHOGENETIC PROTEIN; IN-VIVO; REGENERATION; FIBROBLASTS; MOUSE; MICE; TRANSPLANTATION; AUGMENTATION AB Background. Techniques used to repair craniofacial skeletal defects parallel the accepted surgical therapies for bone lass elsewhere in the skeleton and include the use of autogenous bone and alloplastic materials. Transplantation of a bone marrow stromal cell population that contains osteogenic progenitor cells may be an additional modality for the generation of new bone. Methods. Full thickness osseous defects (5 mm) were prepared in the cranium of immunocompromised mice and were treated with gelatin sponges containing murine alloplastic bone marrow stromal cells derived from transgenic mice carrying a type I collagen-chloramphenicol acetyltransferase reporter gene to follow the fate of the transplanted cells. Control surgical sites were treated with spleen stromal cells or gelatin sponges alone, or were left untreated. The surgical defects were analyzed histologically for percent closure of the defect al 2, 3, 4, 6, and 12 weeks. Results. Cultured bone marrow stromal cells transplanted within gelatin sponges resulted in osteogenesis that repaired greater than 99.0+/-2.20% of the original surgical defect within 2 weeks. In contrast, cranial defects treated with splenic fibroblasts, vehicle alone,, or sham-operated controls resulted in minimal repair that was limited lo the surgical margins, Bone marrow stromal cells carrying the collagen transgene were immunodetected only in the newly formed bone and thus confirmed the donor origin of the transplanted cells. Conclusions. These studies demonstrate that mitotically expanded bone marrow cells can serve as an abundant source of osteoprogenitor cells that are capable of repairing craniofacial skeletal defects in mice without the addition of growth or morphogenetic factors. C1 Univ Michigan, Sch Dent, Dept Oral Med Pathol & Surg, Ann Arbor, MI 48109 USA. NIDR, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. RP Krebsbach, PH (reprint author), Univ Michigan, Sch Dent, Dept Oral Med Pathol & Surg, Room 4207, Ann Arbor, MI 48109 USA. EM paulk@umich.edu RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 50 TC 178 Z9 186 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 1998 VL 66 IS 10 BP 1272 EP 1278 DI 10.1097/00007890-199811270-00002 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 144VV UT WOS:000077336800002 PM 9846508 ER PT J AU Burbelo, PD Finegold, AA Kozak, CA Yamada, Y Takami, H AF Burbelo, PD Finegold, AA Kozak, CA Yamada, Y Takami, H TI Cloning, genomic organization and chromosomal assignment of the mouse p190-B gene SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE genomic organization; chromosomal assignment; mouse p190-B gene; cloning ID ADRENERGIC-RECEPTOR GENE; ACTIN STRESS FIBERS; PROTEIN; RHO; RAS; GTPASES; FAMILY; LOCALIZATION; FILOPODIA AB The p190 family of GTPases consists of at least two different isoforms both containing an N-terminal GTPase and a C-terminal Rho GAP domain. Here we have isolated and characterized genomic and cDNA clones spanning the entire coding region of the mouse p190-B gene. Genomic data were obtained by sequencing plasmid subclones of two overlapping mouse genomic phage clones. Interestingly, a single 3.9 kb exon was found to contain approx. 80% of the coding region of the mouse p190-B protein (amino acid residues 1-1238) including the 5'-untranslated region, the N-terminal GTPase domain and a middle domain of unknown function. Missing from this exon, however, was the C-terminal Rho GAP domain, which was cloned from mouse brain mRNA using reverse transcriptase polymerase chain reaction. Comparison of the mouse with the human p190-B proteins revealed that approx. 97% of the amino acid residues were identical. Northern analysis of total RNA from a variety of mouse tissues detected ubiquitous expression of two p190-B transcripts of 4.0 and 6.8 kb in size. Analysis of two multilocus genetic crosses localized the mouse gene, Gfi2, to a position on chromosome 12, consistent with the mapping of the human gene to a position of conserved synteny on chromosome 14. The high level of sequence homology between the human and the mouse suggests that there is a strong selective pressure to maintain the p190-B protein structure. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. NIDR, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. NIDR, Lab Craniofacial Dev Biol, NIH, Bethesda, MD 20892 USA. NIDR, Regenerat Branch, NIH, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Burbelo, PD (reprint author), Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. RI Burbelo, Peter/B-1027-2009 FU NCI NIH HHS [R29-CA 77459-01] NR 35 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD NOV 26 PY 1998 VL 1443 IS 1-2 BP 203 EP 210 DI 10.1016/S0167-4781(98)00207-3 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 152MM UT WOS:000077781400019 PM 9838117 ER PT J AU Jiang, RL Norton, CR Copeland, NG Gilbert, DJ Jenkins, NA Gridley, T AF Jiang, RL Norton, CR Copeland, NG Gilbert, DJ Jenkins, NA Gridley, T TI Genomic organization, expression and chromosomal localization of the mouse Slug (Slugh) gene SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE mouse slug (Slugh) gene; genomic organization; genomic expression; chromosomal localization ID NEURAL CREST; ABLATION; PROTEIN AB The Slug gene encodes a zinc finger protein implicated in the generation and migration of neural crest cells in several vertebrate species. Here we describe the genomic organization and chromosomal localization of the mouse Slug (Slugh) gene. The mouse Slug gene consists of three exons spanning approx. 4 kb. Northern blot analysis of RNA isolated from several tissues of adult mice revealed the presence of a single 2.1 kb transcript. The chromosomal location of mouse Slug was determined by interspecific backcross analysis, The mapping results indicated that Slugh is located in the proximal region of mouse chromosome 16. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Jackson Lab, Bar Harbor, ME 04609 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Gridley, T (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM gridley@jax.org FU NCI NIH HHS [CA34196]; NICHD NIH HHS [R01HD34883] NR 16 TC 11 Z9 12 U1 0 U2 1 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 NOV 26 PY 1998 VL 1443 IS 1-2 BP 251 EP 254 DI 10.1016/S0167-4781(98)00225-5 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 152MM UT WOS:000077781400027 PM 9838149 ER PT J AU Ma, JX Xu, L Othersen, DK Redmond, TM Crouch, RK AF Ma, JX Xu, L Othersen, DK Redmond, TM Crouch, RK TI Cloning and localization of RPE65 mRNA in salamander cone photoreceptor cells SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE RPE65 mRNA; cone photoreceptor cell; retinal pigment epithelium; (salamander) ID RETINAL-PIGMENT EPITHELIUM; MEMBRANE-RECEPTOR; BINDING PROTEIN; ROD PHOTORECEPTORS; MICROSOMAL PROTEIN; VERTEBRATE RETINA; MOLECULAR-CLONING; MUTATIONS; LIGHT; GENE AB RPE65 is a potential retinoid-processing protein expressed in the retinal pigment epithelium. Mutations in the RPE65 gene have been shown to cause certain inherited retinal dystrophies. Previous studies have shown that salamander cone photoreceptor cells have a unique retinoid processing mechanism which is distinct from that of rods. To determine whether RPE65 is expressed in photoreceptors, the RPE65 cDNA was cloned from a salamander retinal cDNA library. The deduced protein consists of 533 amino acids and is 85% identical to human and bovine RPE65. The RPE65 mRNA was detected in all of the single cone cells isolated from the salamander retina, as well as in the retinal pigment epithelium by RT-PCR, but not in the isolated rods. The RT-PCR products have been confirmed to be RPE65 by DNA sequencing. The results indicate that this potential retinoid processing protein is expressed in the cone photoreceptor cells but not in rods. Therefore, this protein may contribute to the unique retinoid processing capabilities in salamander cones. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. NEI, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. RP Ma, JX (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave,7th Floor,POB 250676, Charleston, SC 29425 USA. OI Redmond, T. Michael/0000-0002-1813-5291 FU NEI NIH HHS [EY04939, EY12231] NR 27 TC 36 Z9 37 U1 0 U2 1 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 NOV 26 PY 1998 VL 1443 IS 1-2 BP 255 EP 261 DI 10.1016/S0167-4781(98)00221-8 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 152MM UT WOS:000077781400028 PM 9838153 ER PT J AU Yu, DG Court, DL AF Yu, DG Court, DL TI A new system to place single copies of genes, sites and lacZ fusions on the Escherichia coli chromosome SO GENE LA English DT Article; Proceedings Paper CT Symposium Entitled a Wisconsin Gathering Honoring Waclaw Szybalski CY AUG 10-11, 1997 CL UNIV WISCONSIN MADISON, MADISON, WI HO UNIV WISCONSIN MADISON DE phage lambda; DNA minicircle; gene expression; gene complementation; gene cloning ID VECTORS; EXPRESSION; CLONING; GROWTH; OPERON AB To place a single-copy lacZ fusion on the E. coli chromosome, a method was developed based on in vivo homologous DNA recombination through P1 transduction. The fusions, initially constructed on plasmids, are crossed to lambda lacZ fusion vectors which are then lysogenized at the chromosomal lambda att site. The features of the new system are: (1) lambda lysogens carrying the fusion are made without regard for copy number; (2) P1 transduction from the lysogenic strain into an appropriate recipient generates the single-copy fusion; (3) The lacZ fusion has no prophage associated with it; (4) the lacZ fusion can be transferred by P1 transduction to other strains, simply by selecting for an antibiotic marker; (5) the system can be widely applied to construct single copies of any gene or site placed between bla and lacZ on the standard lacZ fusion plasmid vectors; and (6) the single-copy construct flanked by prophage atl sites can be excised by site-specific recombination to generate non-replicating circular DNA of the clone or a cell cured of the construct. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Mol Control & Genet Sect, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP NCI, Mol Control & Genet Sect, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. EM court@ncifcrf.gov NR 15 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD NOV 26 PY 1998 VL 223 IS 1-2 BP 77 EP 81 DI 10.1016/S0378-1119(98)00163-2 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 155YE UT WOS:000077973600010 PM 9858691 ER PT J AU Ryu, S Fujita, N Ishihama, A Adhya, S AF Ryu, S Fujita, N Ishihama, A Adhya, S TI GalR-mediated repression and activation of hybrid lacUV5 promoter: differential contacts with RNA polymerase SO GENE LA English DT Article; Proceedings Paper CT Symposium entitled a Wisconsin Gathering Honoring Waclaw Szybalski CY AUG 10-11, 1997 CL UNIV WISCONSIN MADISON, MADISON, WISCONSIN HO UNIV WISCONSIN MADISON DE transcription; alpha CTD; repressor; operator; activation; differential contacts ID C-TERMINAL REGION; ESCHERICHIA-COLI; ALPHA-SUBUNIT; TRANSCRIPTIONAL ACTIVATION; FUNCTIONAL MAP; DNA-BINDING; PROTEIN P4; ELEMENT; SUPEROXIDE; INVOLVEMENT AB The GalR repressor regulates expression of genes of the gal regulon in Escherichia coli. We studied the regulatory effect of GalR in vitro on a heterologous promoter, lacUV5, by placing the GalR-binding site, O-E, at different locations upstream of this promoter. Despite the fact that the lacUV5 promoter is transcribed efficiently by RNA polymerase (RNP) alone, GalR modulated transcription from many of the PlacUV5 variants. Depending on the location of O-E and the neighboring DNA sequence, GalR repressed, activated or had no effect on the promoter. Both repression and activation involved formation of GalR-RNP-DNA ternary complexes and required an intact c-domain of the alpha subunit of the holoenzyme. These results support the differential contact model of a regulator action, in which a regulator differentially binds to, and lowers the energy of, intermediates of transcription initiation either to hinder or to facilitate a step of initiation. The nature of the contacts depends upon the context, i.e. the geometry of the ternary complex. The observed repression and activation effect of GalR on a heterologous promoter also underscores the point that a regulator is not a dedicated protein for repression or for activation. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Genet, Dept Mol Genet, Mishima, Shizuoka 411, Japan. RP Adhya, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,2E16, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov NR 35 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 26 PY 1998 VL 223 IS 1-2 BP 235 EP 245 DI 10.1016/S0378-1119(98)00237-6 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 155YE UT WOS:000077973600027 PM 9858739 ER PT J AU Sambuughin, N Sivakumar, K Selenge, B Lee, HS Friedlich, D Baasanjav, D Dalakas, MC Goldfarb, LG AF Sambuughin, N Sivakumar, K Selenge, B Lee, HS Friedlich, D Baasanjav, D Dalakas, MC Goldfarb, LG TI Autosomal dominant distal spinal muscular atrophy type V (dSMA-V) and Charcot-Marie-Tooth disease type 2D (CMT2D) segregate within a single large kindred and map to a refined region on chromosome 7p15 SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE distal spinal muscular atrophy; Charcot-Marie-Tooth disease type 2; chromosome 7p; genetic linkage analysis; genotype phenotype correlation ID LINKAGE ANALYSIS; GENE; LOCALIZATION; MARKERS; LOCUS AB Two separate disorders, autosomal dominant distal spinal muscular atrophy type V (dSMA-V) characterized by marked bilateral weakness in the hands and atrophy of thenar eminence and the first interosseous muscle, and Charcot-Marie-Tooth disease type 2D (CMT2D) characterized by sensory deficits in addition to the upper limb weakness and wasting, have been independently linked to chromosome 7p. We identified a multigenerational Mongolian kindred with 17 members affected with either dSMA-V or CMT2D and mapped both syndromes to the same region on chromosome 7p15. A maximum two-point lod score of 4.74 at recombination fraction zero was obtained with marker D7S474. Tight linkage without recombination was also detected with markers D7S526 and D7S632. A multipoint lod score of 6.07 suggested that the gene is located between markers D7S526 and D7S474. A single conserved haplotype was associated with dSMA-V and CMT2D. Based on informative recombination events, the disease locus was placed between markers D7S516 and D7S1514 within the 7p15 band. Data obtained from this study suggest that a single gene is responsible for both syndromes, dSMA-V and CMT2D, and extend our knowledge of the candidate region. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Barrow Neurol Inst, Phoenix, AZ 85013 USA. Mongolian Natl Inst Hlth, Ulaanbaatar, Mongol Peo Rep. RP Goldfarb, LG (reprint author), NINDS, Med Neurol Branch, NIH, Bldg 36,Room 4D03,36 Convent Dr, Bethesda, MD 20892 USA. EM goldfarb@codon.nih.gov NR 24 TC 48 Z9 50 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 26 PY 1998 VL 161 IS 1 BP 23 EP 28 DI 10.1016/S0022-510X(98)00264-0 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 149KW UT WOS:000077605200005 PM 9879677 ER PT J AU Jeffers, M Koochekpour, S Fiscella, M Sathyanarayana, BK Vande Woude, GF AF Jeffers, M Koochekpour, S Fiscella, M Sathyanarayana, BK Vande Woude, GF TI Signaling requirements for oncogenic forms of the Met tyrosine kinase receptor SO ONCOGENE LA English DT Article DE Met; oncogene; signaling ID HEPATOCYTE GROWTH-FACTOR; GRB2 BINDING-SITE; SCATTER FACTOR; EPITHELIAL-CELLS; TRANSFORMING ACTIVITY; FACTOR/SCATTER FACTOR; CARBOXY-TERMINUS; PROTOONCOGENE; MUTATIONS; GENE AB The Met tyrosine kinase receptor has been implicated in human cancer. Here we have examined the signaling requirements of three oncogenic forms of this molecule: wild type Met in response to ligand/autocrine stimulation, Met which has been mutationally activated, and Tpr-Met (a constitutively active truncated Met fusion protein). Previous studies have demonstrated the importance of a Grb2 binding site, and of specific tyrosine residues (i.e. Y8,9 and Y14,15) for Met function, and we have now explored the relevance of these and other sites for oncogenic Met signaling. Following substitution of various intracellular tyrosines for phenylalanine, we find that the transforming activity of each Met oncogene is dependent upon tyrosines Y8,9 and Y14,15, in addition to two novel tyrosines (Y6 and Y10) not previously implicated in Met signaling. Tyrosines Y6 and Y10 influence a variety of Met-mediated responses both in vitro (transformation, mitogenicity and invasion), and in vivo (tumorigenicity and metastasis). We also show that Tpr-Met is much more dependent on its Grb2 binding site for biological activity than are the other oncogenic forms of the Met receptor. Thus, although the three Met oncogenes examined are similar in their dependency on a number of specific tyrosines for activity, the signaling strategy employed by Tpr-Met can be differentiated from that of the other two. C1 NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP Vande Woude, GF (reprint author), NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, POB B, Ft Detrick, MD 21702 USA. NR 62 TC 35 Z9 37 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 26 PY 1998 VL 17 IS 21 BP 2691 EP 2700 DI 10.1038/sj.onc.1202209 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 141MA UT WOS:000077146700002 PM 9840933 ER PT J AU Wagner, KU Dierisseau, P Rucker, EB Robinson, GW Hennighausen, L AF Wagner, KU Dierisseau, P Rucker, EB Robinson, GW Hennighausen, L TI Genomic architecture and transcriptional activation of the mouse and human tumor susceptibility gene TSG101: Common types of shorter transcripts are true alternative splice variants SO ONCOGENE LA English DT Article DE TSG101 protein; mice; human; genomic DNA; pseudogene; mammary gland ID HUMAN BREAST-CANCER; MAMMARY-GLAND; PROTEIN; IDENTIFICATION; CHROMOSOME-11; TUMORIGENESIS; FAMILY; INT3 AB The functional inactivation of the tumor susceptibility gene tsg101 in mouse NIH3T3 cells leads to cell transformation and the formation of metastatic tumors in nude mice. We cloned, mapped and sequenced the mouse tsg101 gene and further identified a processed pseudogene that is 98% identical to the tsg101 cDNA. Based on Northern blot analysis, tsg101 is expressed ubiquitously in mouse tissues. A comparison of the coding region of the mouse tsg101 gene with the human TSG101 cDNA revealed that both the mouse and human gene encode ten additional highly conserved amino acids at the N-terminus. Based on the mouse tsg101 genomic structure, we predicted four additional introns within the human TSG101 gene. Their location was confirmed using PCR and sequencing analysis. The presence of these so far unidentified introns now explains published data on aberrantly spliced mRNA products that were frequently observed in primary breast tumors. We show that a majority of shorter TSG101 transcripts are not the result of aberrant splicing events, but represent a fraction of true alternative splice variants. Finally, we examined tsg101 expression patterns during different stages of mammary gland development and in different transgenic mouse models for breast tumorigenesis. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Room 101, Bethesda, MD 20892 USA. RI Wagner, Kay-Uwe/B-6044-2009; Robinson, Gertraud/I-2136-2012 FU FDA HHS [369VFDK013712] NR 27 TC 32 Z9 36 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 26 PY 1998 VL 17 IS 21 BP 2761 EP 2770 DI 10.1038/sj.onc.1202529 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 141MA UT WOS:000077146700009 PM 9840940 ER PT J AU Vogel, K Kantor, J Wood, L Rivera, R Schlom, J AF Vogel, K Kantor, J Wood, L Rivera, R Schlom, J TI Oval immunization with enterocoated microbeads induces antigen-specific cytolytic T-cell responses SO CELLULAR IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MUCOSAL IMMUNE-SYSTEM; MYELIN BASIC-PROTEIN; ORAL TOLERANCE; SOLUBLE-ANTIGEN; ACTIVATION PATTERNS; TUMOR-CELLS; INDUCTION; SUPPRESSION; LYMPHOCYTES AB A cytolytic T-lymphocyte (CTL) response has been generated to a protein antigen via oral administration in an experimental murine system, This was achieved by the formulation of the test antigen ovalbumin (OVA) in a pH-sensitive microsphere particle (microbead) with an acrylic-based coating to avoid its degradation by gastric enzymes. Comparative studies of orally administered enterocoated microbead-OVA particles, versus the more traditional. formulation of OVA in adjuvant (DETOX-PC) given subcutaneously as immunogen, were conducted; both elicited comparable responses in the generation of antigen-specific lymphoproliferative and CTL responses. CTL lines generated via oral administration of antigen were shown to be CD3(+), CD4(-), and CD8(+), CTL lysis of OVA peptide-pulsed targets was shown to be inhibited by anti-CD8 antibody. Whereas oral administration of pH-sensitive enterocoated microbeads containing proteins has previously been shown to elicit antibody and lymphoproliferative T-cell responses to protein antigens, this is the first demonstration of the generation of an antigen-specific cytolytic T-cell response via oral administration of a protein immunogen formulated in such microbeads. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Allergen Inc, Cincinnati, OH 45242 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 8B07, Bethesda, MD 20892 USA. NR 35 TC 5 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV 25 PY 1998 VL 190 IS 1 BP 61 EP 67 DI 10.1006/cimm.1998.1384 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 144YJ UT WOS:000077343200007 PM 9826447 ER PT J AU Albuquerque, MLC Akiyama, SK Schnaper, HW AF Albuquerque, MLC Akiyama, SK Schnaper, HW TI Basic fibroblast growth factor release by human coronary artery endothelial cells is enhanced by matrix proteins, 17 beta-estradiol, and a PKC signaling pathway SO EXPERIMENTAL CELL RESEARCH LA English DT Article; Proceedings Paper CT Experimental Biology 97 Conference CY APR 06-10, 1997 CL NEW ORLEANS, LOUISIANA DE extracellular matrix; endothelial cell; FGF-2; signal transduction ID PLASMINOGEN-ACTIVATOR PRODUCTION; EXTRACELLULAR-MATRIX; ANGIOGENESIS; MIGRATION; ESTROGEN; BINDING; INVITRO; STIMULATION; MOLECULE; MEMBRANE AB Endothelial cell function is regulated by interactions among cells, the extracellular matrix (ECM), and soluble mediators. We investigated this interaction by examining the effect of 17 beta-estradiol (E2) on release of basic fibroblast growth factor (FGF-2) by human coronary artery endothelial cells (HCAEC) cultured on ECM proteins. After estrogen-depleted HCAEC were treated with E2 for 2 h, the conditioned media and cell layers were evaluated by immunoblot or ELISA for FGF-2. Release of FGF-2 into conditioned media was enhanced 10-fold compared to that on plastic and a further 2.4-fold by E2, As FGF-2 release from cells into the media increases, there is a corresponding decrease in the cellular content of FGF-2. By ELISA, FGF-2 release increased 406, 179, and 262%, on type TV collagen, laminin, or fibronectin, respectively. HCAEC cultured on type I collagen did not show ES-enhanced FGF-2 release by ELISA or immunoblot analysis. No changes were noted in HCAEC release of lactate dehydrogenase, tested as a control protein for cellular integrity. The estrogen receptor antagonist ICI182,780 blocked E2-induced, but not basal, FGF-2 release. Increased FGF-2 release occurred via a cycloheximide-insensitive pathway. Neither brefeldin-A nor genistein inhibited E2 enhancement of FGF-2 release by HCAEC cultured on fibronectin. However, the protein kinase C inhibitor calphostin C inhibited the E2-augmented FGF-2 release. These data show that E2 enhances FGF-2 release by HCAEC cultured on basement membrane proteins in the absence of wounding. This action requires the estrogen receptor and PKC activity, but does not require new protein synthesis, endoplasmic reticulum-to-Golgi-mediated secretion, or protein tyrosine phosphorylation. E2-enhanced FGF-2 release could contribute to the cardioprotective effects of estrogen. (C) 1998 Academic Press. C1 Northwestern Univ, Sch Med, Dept Pediat, Chicago, IL 60611 USA. Northwestern Mem Hosp, Intramural Res Grants Award, Div Pulm Crit Care Med, Chicago, IL USA. Northwestern Mem Hosp, Intramural Res Grants Award, Div Nephrol, Chicago, IL USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Albuquerque, MLC (reprint author), Northwestern Univ, Sch Med, Dept Pediat, Pediat W-140,303 E Chicago Ave,Ward 12-110, Chicago, IL 60611 USA. FU NHLBI NIH HHS [HL-53918]; NIDDK NIH HHS [R01 DK049362, DK-49362] NR 32 TC 31 Z9 31 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 25 PY 1998 VL 245 IS 1 BP 163 EP 169 DI 10.1006/excr.1998.4243 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 145DY UT WOS:000077356800018 PM 9828112 ER PT J AU Engelgau, MM Narayan, KMV Thompson, TJ Boyle, JP Williamson, DF Manninen, DL Dong, FB Orians, CE Dasbach, EJ Teutsch, SM Eastman, R Herman, WH Songer, TJ AF Engelgau, MM Narayan, KMV Thompson, TJ Boyle, JP Williamson, DF Manninen, DL Dong, FB Orians, CE Dasbach, EJ Teutsch, SM Eastman, R Herman, WH Songer, TJ CA CDC Diabetes Cost-Effect Study Grp TI The cost-effectiveness of screening for type 2 diabetes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CLINICAL-DIAGNOSIS; NIDDM; COMPLICATIONS; MELLITUS; PREVALENCE; ROCHESTER; HEALTH; TRIAL; ONSET; RETINOPATHY AB Context.-Type 2 diabetes mellitus is a common and serious disease in the United States, but one third of those affected are unaware they have it. Objective.-To estimate the cost-effectiveness of early detection and treatment of type 2 diabetes. Design.-A Monte Carlo computer simulation model was developed to estimate the lifetime costs and benefits of 1-time opportunistic screening (ie, performed during routine contact with the medical care system) for type 2 diabetes and to compare them with current clinical practice. Cost-effectiveness was estimated for all persons aged 25 years or older, for age-specific subgroups, and for African Americans. Data were obtained from clinical trials, epidemiologic studies, and population surveys, and a single-payer perspective was assumed. Costs and benefits are discounted at 3% and costs are expressed in 1995 US dollars. Setting.-Single-payer health care system. Participants.-Hypothetical cohort of 10000 persons with newly diagnosed diabetes from the general US population. Main Outcome Measures.-Cost per additional life-year gained and cost per quality-adjusted life-year (QALY) gained. Results.-The incremental cost of opportunistic screening among all persons aged 25 years or older is estimated at $236 449 per life-year gained and $56 649 per QALY gained. Screening is more cost-effective among younger people and among African Americans. The benefits of early detection and treatment accrue more from postponement of complications and the resulting improvement in quality of life than from additional life-years. Conclusions.-Early diagnosis and treatment through opportunistic screening of type 2 diabetes may reduce the lifetime incidence of major microvascular complications and result in gains in both life-years and QALYs. Incremental increases in costs attributable to screening and earlier treatment are incurred but may well be in the range of acceptable cost-effectiveness for US health care systems, especially for younger adults and for some subpopulations (eg, minorities) who are at relatively high risk of developing the major complications of type 2 diabetes. Although current recommendations are that screening begin at age 45 years, these results suggest that screening is more cost-effective at younger ages. The selection of appropriate target populations for screening should consider factors in addition to the prevalence of diabetes. C1 Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. Emory Univ, Sch Publ Hlth, Div Epidemiol, Atlanta, GA USA. Ctr Publ Hlth Res, Seattle, WA USA. Merck & Co Inc, Blue Bell, PA USA. Merck & Co Inc, W Point, PA USA. NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Med, Div Endocrinol & Metab, Ann Arbor, MI 48109 USA. Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. RP Engelgau, MM (reprint author), Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Mailstop K-10,4770 Buford Hwy NE, Atlanta, GA 30341 USA. RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 NR 54 TC 148 Z9 152 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 25 PY 1998 VL 280 IS 20 BP 1757 EP 1763 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 140HF UT WOS:000077081400031 ER PT J AU Rapoport, JL AF Rapoport, JL TI Child psychopharmacology comes of age SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID OBSESSIVE-COMPULSIVE DISORDER; DOUBLE-BLIND; CLOMIPRAMINE; ADOLESCENTS C1 NIH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Rapoport, JL (reprint author), NIH, Child Psychiat Branch, Bldg 10,Room 3N202,MSC 1600, Bethesda, MD 20892 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 25 PY 1998 VL 280 IS 20 BP 1785 EP 1785 DI 10.1001/jama.280.20.1785 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 140HF UT WOS:000077081400037 PM 9842957 ER PT J AU Carpenter, MA Brown, EW MacDonald, DW O'Brien, SJ AF Carpenter, MA Brown, EW MacDonald, DW O'Brien, SJ TI Phylogeographic patterns of feline immunodeficiency virus genetic diversity in the domestic cat SO VIROLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; ENVELOPE GLYCOPROTEINS; PHYLOGENETIC ANALYSIS; EVOLUTIONARY RATES; SUBTYPE-B; INFECTION; RECOMBINATION; PREVALENCE; SUPERINFECTION; IDENTIFICATION AB Feline immunodeficiency virus (FIV) has a worldwide distribution among feral and domesticated cats and in many cases induces immunodeficiency disease analogous to that of human acquired immune deficiency syndrome. FIV is genetically homologous to human immunodeficiency virus (HIV) in both genome organization and gene sequence and, like HIV, exhibits enormous sequence variation throughout the range of host species. We sampled 91 feral cats from six disparate locales and studied the phylogenetic relationships of viral DNA from infected cats using both pol and env genes (520 and 684 bp, respectively). The patterns from the two genes recapitulated previously described major FIV clades and showed concordance between phylogenetic patterns of the pol and env genes. Evidence for recombination between the pol and env genes was not found among a sampling of nine isolates, although evidence for intragenic exchange within the env gene was observed in two isolates. A small local population of cats from a rural farm in the United Kingdom had a remarkably high FIV antibody prevalence (47%), but displayed 8-fold less overall diversity of FIV genomic variation compared with FIV from different parts of the world. We interpret this low variation as a consequence of a recent monophyletic introduction of FIV into the population. (C) 1998 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. SAIC, Biol Carcinogenesis & Dev Program, Frederick, MD USA. Wildlife Conservat Res Unit, Dept Zool, Oxford OX1 3PS, England. RP O'Brien, SJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. EM obrien@ncifcrf.gov OI Carpenter, Margaret/0000-0003-1606-1986 NR 42 TC 36 Z9 36 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 NOV 25 PY 1998 VL 251 IS 2 BP 234 EP 243 DI 10.1006/viro.1998.9402 PG 10 WC Virology SC Virology GA 141FB UT WOS:000077131000003 PM 9837787 ER PT J AU Bloom, ME Fox, JM Berry, BD Oie, KL Wolfinbarger, JB AF Bloom, ME Fox, JM Berry, BD Oie, KL Wolfinbarger, JB TI Construction of pathogenic molecular clones of Aleutian mink disease parvovirus that replicate both in vivo and in vitro SO VIROLOGY LA English DT Article ID ACUTE INTERSTITIAL PNEUMONIA; MINUTE VIRUS; CANINE PARVOVIRUS; NUCLEOTIDE-SEQUENCE; DNA-REPLICATION; 5'-TERMINAL PALINDROME; VIRAL REPLICATION; POLYOMAVIRUS VP1; CAPSID PROTEIN; INFECTED MINK AB The ADV-G isolate of Aleutian mink disease parvovirus (ADV) replicates permissively in Crandell feline kidney (CRFK) cells but is nonpathogenic for mink, whereas the highly pathogenic ADV-Utah isolate is nonviable in CRFK cells. To assign control of host range in CRFK cells and pathogenicity to specific regions of the ADV genome, we constructed a full-length molecular clone chimeric between ADV-G and ADV-Utah. If either the map unit (MU) 54-65 (clone G/U-5) or MU 65-88 (clone G/U-7) sections were ADV-Utah, viability in CRFK cells was abolished, thus indicating that in vitro host range was controlled by two independent determinants: A in the MU 54-65 segment and B in the MU 65-88 segment. Determinant B could be divided into two subregions, B1 (MU 65-69) and B2 (MU 73-88), neither of which alone could inhibit replication in CRFK cells, an observation suggesting that expression of the B determinant required interaction between noncontiguous sequences. Adult mink of Aleutian genotype inoculated with G/U-8 or G/U-10 developed viremia, antiviral antibody, and histopathological changes characteristic of progressive Aleutian disease. The capsid sequences of G/U-8 and G/U-10 differed from ADV-G at five and four amino acid residues, respectively. Our results suggested that the host range and pathogenicity of ADV are regulated by sequences in the capsid protein gene. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Bloom, ME (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. EM mbloom@nih.gov NR 59 TC 14 Z9 16 U1 0 U2 3 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 NOV 25 PY 1998 VL 251 IS 2 BP 288 EP 296 DI 10.1006/viro.1998.9426 PG 9 WC Virology SC Virology GA 141FB UT WOS:000077131000009 PM 9837793 ER PT J AU Wyatt, LS Carroll, MW Czerny, CP Merchlinsky, M Sisler, JR Moss, B AF Wyatt, LS Carroll, MW Czerny, CP Merchlinsky, M Sisler, JR Moss, B TI Marker rescue of the host range restriction defects of modified vaccinia virus Ankara SO VIROLOGY LA English DT Article ID ATTENUATED MVA STRAIN; HAMSTER OVARY CELLS; RECOMBINANT VECTOR; GENE-EXPRESSION; RNA-POLYMERASE; DELETION; SEQUENCE; MUTANTS; GENOME; TRANSPOSITION AB The severely attenuated and host range (HR) restricted modified vaccinia virus Ankara (MVA) was derived by >500 passages in chick embryo fibroblasts, during which multiple deletions and mutations occurred. To determine the basis of the HR defect, we prepared cosmids from the parental vaccinia virus Ankara genome and transfected them into nonpermissive monkey BS-C-1 cells that had been infected with MVA. Recombinant viruses that formed macroscopic plaques were detected after transfections with DNA segments that mapped near the left end of the viral genome. Plaque-forming viruses, generated by transfections with four individual cosmids and one pair of minimally overlapping cosmids, were purified, and their HRs were evaluated in BS-C-1 cells, rabbit RK-13 cells, and human HeLa, MRC-5, and A549 cells. The acquisition of the K1L and SPI-1 HR genes and the repair of large deletions were determined by polymerase chain reaction or pulse-field gel electrophoresis of Notl restriction enzyme digests of genomic DNA. The following results indicated the presence of previously unrecognized vaccinia virus HR genes: (1) the major mutations that restrict HR are within the left end of the MVA genome because the phenotypes of some recombinants approached that of the parental virus, (2) acquisition of the K1L gene correlated with the ability of recombinant viruses to propagate in RK-13 cells but did not enhance replication in human or monkey cell lines, (3) acquisition of the SPI-1 gene correlated with virus propagation in A549 cells but not with the extent of virus spread in monkey or other human cell lines, (4) there are at least two impaired HR genes because rescue occurred with nonoverlapping or minimally overlapping cosmids and recombinant viruses with intermediate HRs were isolated, and (5) at least one of the new HR genes did not map within any of the major deletions because the size of the left terminal Notl fragment was not appreciably altered in some recombinant viruses. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab DNA Viruses, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 46 TC 52 Z9 53 U1 0 U2 3 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 NOV 25 PY 1998 VL 251 IS 2 BP 334 EP 342 DI 10.1006/viro.1998.9397 PG 9 WC Virology SC Virology GA 141FB UT WOS:000077131000014 PM 9837798 ER PT J AU Reddy, SM Williams, M Cohen, JI AF Reddy, SM Williams, M Cohen, JI TI Expression of a uracil DNA glycosylase (UNG) inhibitor in mammalian cells: Varicella-zoster virus can replicate in vitro in the absence of detectable UNG activity SO VIROLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; VIRAL REPLICATION; IN-VITRO; TYPE-1; ENZYMES; NUCLEAR; MUTATIONS; ENCODES; REPAIR; ALTER AB Uracil DNA glycosylase (UNG) functions as a DNA repair or proofreading enzyme. The UNG gene is present in nearly all prokaryotes and eukaryotes screened to dale and is found in herpesviruses and poxviruses. Prior studies showed that viral UNG is essential for poxvirus replication. Although viral UNG is not required for herpesvirus replication, cellular UNG was thought to be essential for virus replication. To study the role of UNG in herpesvirus replication, we first showed that varicella-zoster virus (VZV) ORF59 encodes a functional UNG. We then constructed a VZV mutant with a deletion in the UNG gene and showed that the mutant was unimpaired for replication in vitro. Because cultured cells express their own endogenous UNG, we next inserted a bacteriophage UNG inhibitor UGI gene into the VZV genome. Infection of cells with VZV lacking viral UNG and expressing UGI completely abrogated detectable cellular UNG activity in vitro. Parental VN, VZV lacking viral UNG, and VZV expressing UGI all grew to similar titers in cell culture, indicating that VZV can replicate in vitro in the absence of detectable viral or cellular UNG activity. (C) 1998 Academic Press. C1 NIAID, Clin Invest Lab, Med Virol Sect, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Dept Med Microbiol & Immunol, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Cohen, JI (reprint author), NIAID, Clin Invest Lab, Med Virol Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 29 TC 21 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 0042-6822 J9 VIROLOGY JI Virology PD NOV 25 PY 1998 VL 251 IS 2 BP 393 EP 401 DI 10.1006/viro.1998.9428 PG 9 WC Virology SC Virology GA 141FB UT WOS:000077131000019 PM 9837803 ER PT J AU Masaki, KH Schatz, IJ Burchfiel, CM Sharp, DS Chiu, D Foley, D Curb, JD AF Masaki, KH Schatz, IJ Burchfiel, CM Sharp, DS Chiu, D Foley, D Curb, JD TI Orthostatic hypotension predicts mortality in elderly men - The Honolulu Heart Program SO CIRCULATION LA English DT Article DE mortality; aging; men; blood pressure ID POSTURAL HYPOTENSION; BLOOD-PRESSURE; PHYSICAL-ACTIVITY; PREVALENCE; HYPERTENSION; HEALTH; SYNCOPE; DISEASE AB Background-Population-based data are unavailable concerning the predictive value of orthostatic hypotension on mortality in ambulatory elderly patients, particularly minority groups. Methods and Results-With the use of data from the Honolulu Heart Program's fourth examination (1991 to 1993), orthostatic hypotension was assessed in relation to subsequent LE-year all-cause mortality among a cohort of 3522 Japanese American men 71 to 93 years old. Blood pressure was measured in the supine position and after 3 minutes of standing, with the use of standardized methods. Orthostatic hypotension was defined as a drop in systolic blood pressure (SBP) of greater than or equal to 20 mm Hg or in diastolic blood pressure of greater than or equal to 10 mm Hg. Overall prevalence of orthostatic hypotension was 6.9% and increased with age. There was a total of 473 deaths in the cohort over 4 years; of those who died, 52 had orthostatic hypotension. Four-year age-adjusted mortality rates in those with and without orthostatic hypotension were 56.6 and 38.6 per 1000 person-years, respectively. With the use of Cox proportional hazards models, after adjustment for age, smoking, diabetes mellitus, body mass index, physical activity, seated systolic blood pressure, antihypertensive medications, hematocrit, alcohol intake, and prevalent stroke, coronary heart disease and cancer, orthostatic hypotension was a significant independent predictor of 4-year all-cause mortality (relative risk 1.64, 95% CI 1.19 to 2.26). There was a significant linear association between change in systolic blood pressure from supine position to standing and 4-year mortality rates (test for linear trend, P<0.001), suggesting a dose-response relation. Conclusions-Orthostatic hypotension is relatively uncommon, may be a marker for physical frailty, and is a significant independent predictor of 4-year all-cause mortality in this cohort of elderly ambulatory men. C1 Kuakini Med Ctr, Honolulu Heart Program, Honolulu, HI 96817 USA. Univ Hawaii, John A Burns Sch Med, Div Clin Epidemiol, Honolulu, HI 96822 USA. Univ Hawaii, John A Burns Sch Med, Div Geriatr, Honolulu, HI 96822 USA. NHLBI, Div Epidemiol & Clin Applicat, Honolulu Epidemiol Res Unit, Honolulu, HI USA. NIA, Epidemiol Demography & Biometry Program, Bethesda, MD 20892 USA. RP Masaki, KH (reprint author), 347 N Kuakini St,HPM-9, Honolulu, HI 96817 USA. EM kamal@hhp2.hawaii-health.com FU NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149] NR 36 TC 259 Z9 271 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 24 PY 1998 VL 98 IS 21 BP 2290 EP 2295 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140DY UT WOS:000077072700012 PM 9826316 ER PT J AU Moskovitz, J Flescher, E Berlett, BS Azare, J Poston, JM Stadtman, ER AF Moskovitz, J Flescher, E Berlett, BS Azare, J Poston, JM Stadtman, ER TI Overexpression of peptide-methionine sulfoxide reductase in Saccharomyces cerevisiae and human T cells provides them with high resistance to oxidative stress SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RESIDUES; PROTEINS; EXPRESSION; GENE; CLONING AB The yeast peptide-methionine sulfoxide reductase (MsrA) was overexpressed in a Saccharomyces cerevisiae null mutant of msrA by using a high-copy plasmid harboring the msrA gene and its promoter. The resulting strain had about 25-fold higher MsrA activity than its parent strain. When exposed to either hydrogen peroxide, paraquat, or 2,2'-azobis-(2-amidinopropane) dihydrochloride treatment, the MsrA overexpressed strain grew better, had lower free and protein-bound methionine sulfoxide and had a better survival rate under these conditions than did the msrA mutant and its parent strain. Substitution of methionine with methionine sulfoxide in a medium lacking hydrogen peroxide had little effect on the growth pattern, which suggests that the oxidation of free methionine in the growth medium was not the main cause of growth inhibition of the msrA mutant, Ultraviolet A radiation did not result in obvious differences in survival rates among the three strains, An enhanced resistance to hydrogen peroxide treatment was shown in human T lymphocyte cells (Molt-4) that were stably transfected with the bovine msrA and exposed to hydrogen peroxide. The survival rate of the transfected strain was much better than its parent strain when grown in the presence of hydrogen peroxide. These results support the proposition that the msrA gene is involved in the resistance of yeast and mammalian cells to oxidative stress. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Fac Med, Dept Human Microbiol, IL-69978 Ramat Aviv, Israel. NYU, Med Ctr, Nelson Inst Environm Med, Tuxedo Park, NY 10987 USA. RP Moskovitz, J (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3,Room 207, Bethesda, MD 20892 USA. NR 21 TC 201 Z9 205 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 1998 VL 95 IS 24 BP 14071 EP 14075 DI 10.1073/pnas.95.24.14071 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200017 PM 9826655 ER PT J AU Premont, RT Claing, A Vitale, N Freeman, JLR Pitcher, JA Patton, WA Moss, J Vaughan, M Lefkowitz, RJ AF Premont, RT Claing, A Vitale, N Freeman, JLR Pitcher, JA Patton, WA Moss, J Vaughan, M Lefkowitz, RJ TI beta(2)-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; CHOLERA-TOXIN; ARF PROTEINS; IDENTIFICATION; SEQUESTRATION; G(BETA-GAMMA); SUBUNITS; ALPHA; CAMP AB G protein-coupled receptor activation leads to the membrane recruitment and activation of G protein-coupled receptor kinases, which phosphorylate receptors and lead to their inactivation. We have identified a novel G protein-coupled receptor kinase-interacting protein, GIT1, that is a GTPase-activating protein (GAP) for the ADP ribosylation factor (ARF) family of small GTP-binding proteins. Overexpression of GIT1 leads to reduced beta(2)-adrenergic receptor signaling and increased receptor phosphorylation, which result from reduced receptor internalization and resensitization. These cellular effects of GIT1 require its intact ARF GAP activity and do not reflect regulation of GRK kinase activity. These results suggest an essential role for ARF proteins in regulating beta(2)-adrenergic receptor endocytosis. Moreover, they provide a mechanism for integration of receptor activation and endocytosis through regulation of ARF protein activation by GRK-mediated recruitment of the GIT1 ARF GAP to the plasma membrane. C1 Duke Univ, Med Ctr, Dept Med Cardiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Howard Hughes Med Inst, Durham, NC 27710 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Duke Univ, Med Ctr, Dept Med Cardiol, Box 3821, Durham, NC 27710 USA. RI Vitale, nicolas/G-5967-2014; OI Vitale, nicolas/0000-0002-4752-4907; Premont, Richard/0000-0002-8053-5026 FU NHLBI NIH HHS [HL16037, R01 HL016037] NR 29 TC 209 Z9 225 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 1998 VL 95 IS 24 BP 14082 EP 14087 DI 10.1073/pnas.95.24.14082 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200019 PM 9826657 ER PT J AU Zheng, ZM Huynen, M Baker, CC AF Zheng, ZM Huynen, M Baker, CC TI A pyrimidine-rich exonic splicing suppressor binds multiple RNA splicing factors and inhibits spliceosome assembly SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PRE-MESSENGER-RNA; IMMUNODEFICIENCY-VIRUS TYPE-1; ALTERNATIVE 3'-SPLICE-SITE SELECTION; SR-PROTEINS; IN-VIVO; SITE SELECTION; FACTOR SF2; ENHANCER; ELEMENTS; DISTINCT AB The bovine papillomavirus type I (BPV-1) exonic splicing suppressor (ESS) is juxtaposed immediately downstream of BPV-1 splicing enhancer 1 and negatively modulates selection of a suboptimal 3' splice site at nucleotide 3225. The present study demonstrates that this pyrimidine-rich ESS inhibits utilization of upstream 3' splice sites by blocking early steps in spliceosome assembly. Analysis of the proteins that bind to the ESS showed that the U-rich 5' region binds U2AF(65) and polypyrimidine tract binding protein, the C-rich central part binds 35- and 54-55-kDa serine/arginine-rich (SR) proteins, and the AG-rich 3' end binds alternative splicing factor/splicing factor 2. Mutational and functional studies indicated that the most critical region of the ESS maps to the central C-rich core (GGCUCCCCC). This core sequence, along with additional nonspecific downstream nucleotides, is sufficient for partial suppression of spliceosome assembly and splicing of BPV-1 pre-mRNAs. The inhibition of splicing by the ESS can be partially relieved by excess purified HeLa SR proteins, suggesting that the ESS suppresses pre-mRNA splicing by interfering with normal bridging and recruitment activities of SR proteins. C1 NCI, Basic Res Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. RP Zheng, ZM (reprint author), NCI, Basic Res Lab, Div Basic Sci, NIH, Bldg 41,Room D305, Bethesda, MD 20892 USA. NR 47 TC 52 Z9 52 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 1998 VL 95 IS 24 BP 14088 EP 14093 DI 10.1073/pnas.95.24.14088 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200020 PM 9826658 ER PT J AU Perera, LP Waldmann, TA AF Perera, LP Waldmann, TA TI Activation of human monocytes induces differential resistance to apoptosis with rapid down regulation of caspase-8/FLICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-NECROSIS-FACTOR; DOMAIN-CONTAINING RECEPTOR; FAS-MEDIATED APOPTOSIS; SIGNALING COMPLEX DISC; CELL-DEATH APOPTOSIS; NF-KAPPA-B; CHROMOSOMAL ASSIGNMENT; INFLAMMATORY CYTOKINES; MOLECULAR-CLONING; MYELOID CELLS AB Cells of the monocyte/macrophage lineage play a central role in both innate and acquired immunity of the host. However, the acquisition of functional competence and the ability to respond to a variety of activating or modulating signals require maturation and differentiation of circulating monocytes and entail alterations in both biochemical and phenotypic profiles of the cells. The process of activation also confers survival signals essential for the functional integrity of monocytes enabling the cells to remain viable in microenvironments of immune or inflammatory lesions that are rich in cytotoxic inflammatory mediators and reactive free-radical species. However, the molecular mechanisms of activation-induced survival signals in monocytes remain obscure. To define the mechanistic basis of activation-induced resistance to apoptosis in human monocytes at the molecular level, we evaluated the modulation of expression profiles of genes associated with the cellular apoptotic pathways upon activation and demonstrate the following: (i) activation results in selective resistance to apoptosis particularly to that induced by signaling via death receptors and DNA damage; (ii) concurrent with activation, the most apical protease in the death receptor pathway, caspase-8/FLICE is rapidly down-regulated at the mRNA level representing a novel regulatory mechanism; and (iii) activation of monocytes also leads to dramatic induction of the Bfl-1 gene, an anti apoptotic member of the Bcl-2 family. Our findings thus provide a potential mechanistic basis for the activation-induced resistance to apoptosis in human monocytes. C1 NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Perera, LP (reprint author), NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. EM lperera@atlas.niaid.nih.gov NR 75 TC 61 Z9 64 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 1998 VL 95 IS 24 BP 14308 EP 14313 DI 10.1073/pnas.95.24.14308 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200058 PM 9826696 ER PT J AU Langley, RJ Prince, GA Ginsberg, HS AF Langley, RJ Prince, GA Ginsberg, HS TI HIV type-1 infection of the cotton rat (Sigmodon fulviventer and S-hispidus) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELL-LINES; SCID MICE; AIDS; RABBITS; LYMPHOCYTES; RECEPTOR; VACCINE; DISEASE; ENTRY AB Cotton rats (Sigmodon hispidus and S. fulviventer) are susceptible to many viruses that infect humans (e.g., poliovirus, respiratory syncytial virus, influenza virus, adenovirus, and parainfluenza virus) and have been influential in developing therapeutic clinical intervention strategies for many viral infections of man. This study set out to determine whether cotton rats are susceptible to infection with HIV type 1 (HIV-1), Results indicate that HIV-1 does infect the cotton rat and S, fulviventer is more susceptible than S. hispidus, The virus was passaged from animal to animal for a total of three serial passages; but HIV replicated poorly in vivo, was only detectable as proviral DNA, and never exceeded one provirus per 1.8 x 10(5) cotton rat peripheral blood mononuclear cells. Infection induced a distinct and characteristic anti-HIV antibody response that, in some animals, included neutralizing antibodies, recognized all of the major HIV-1 antigens and the antibodies lasted out to 52 wk post-infection. Neonate S, fulviventer were not more susceptible to infection than adults. In vitro culture studies produced indirect evidence of viral replication by detection of viral gag gene RNA in reverse transcriptase-PCR assays on viral culture supernatants, Collectively, these results indicate that HIV-1 can replicate in a nontransgenic rodent and that this system may have potential as an animal model for HIV-1 infection if viral replication rates can be improved in vivo. C1 NIAID, Infect Dis Lab, Immunodeficiency Viruses Sect, NIH, Rockville, MD 20852 USA. Virion Syst Inc, Rockville, MD 20850 USA. RP Ginsberg, HS (reprint author), NIAID, Infect Dis Lab, Immunodeficiency Viruses Sect, NIH, Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. FU NIAID NIH HHS [Z01 AI00730] NR 36 TC 16 Z9 16 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 1998 VL 95 IS 24 BP 14355 EP 14360 DI 10.1073/pnas.95.24.14355 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200066 PM 9826704 ER PT J AU Song, S Morgan, M Ellis, T Poirier, A Chesnut, K Wang, JM Brantly, M Muzyczka, N Byrne, BJ Atkinson, M Flotte, TR AF Song, S Morgan, M Ellis, T Poirier, A Chesnut, K Wang, JM Brantly, M Muzyczka, N Byrne, BJ Atkinson, M Flotte, TR TI Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECOMBINANT ADENOASSOCIATED VIRUS; GENE-THERAPY; SKELETAL-MUSCLE; EXPRESSION; INVIVO; MICE; DELIVERY AB Recombinant adeno-associated virus (AAV) vectors have been used to transduce murine skeletal muscle as a platform for secretion of therapeutic proteins. The utility of this approach for treating alpha-1-antitrypsin (AAT) deficiency was tested in murine myocytes in vitro and in vivo. AAV vectors expressing the human AAT gene from either the cytomegalovirus (CMV) promoter (AAV-C-AT) or the human elongation factor 1-alpha promoter (AAV-E-AT) were examined. in vitro in C2C12 murine myoblasts, the expression levels in transient transfections mere similar between the two vectors. One month after transduction, however, the human elongation factor 1 promoter mediated 10-fold higher stable human AAT expression than the CMV promoter. In vivo transduction was performed by injecting doses of up to 1.4 x 10(13) particles into skeletal muscles of several mouse strains (C57BL/6, BALB/c, and SCID). In vivo, the CMV vector mediated higher levels of expression, with sustained serum levels over 800 mu g/ml in SCID and over 400 mu g/ml in C57BL/6 mice. These serum concentrations are 100,000-fold higher than those previously observed with AAV vectors in muscle and are at levels which would be therapeutic if achieved in humans. High level expression was delayed for several weeks but was sustained for over 15 wk Immune responses were dependent upon the mouse strain and the vector dosage. These data suggest that recombinant AAV vector transduction of skeletal muscle could provide a means for replacing AAT or other essential serum proteins but that immune responses may be elicited under certain conditions. C1 Univ Florida, Gene Therapy Ctr, Gainesville, FL 32610 USA. Univ Florida, Dept Pathol, Gainesville, FL 32610 USA. NHLBI, Pulm Branch, Bethesda, MD 20892 USA. RP Flotte, TR (reprint author), Univ Florida, Gene Therapy Ctr, Box 100266, Gainesville, FL 32610 USA. FU NCRR NIH HHS [M01 RR000082, RR00082]; NHLBI NIH HHS [HL59412, P01 HL059412, P50 HL059412]; NIDDK NIH HHS [DK51809] NR 24 TC 215 Z9 219 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 1998 VL 95 IS 24 BP 14384 EP 14388 DI 10.1073/pnas.95.24.14384 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200071 PM 9826709 ER PT J AU Jeffers, M Fiscella, M Webb, CP Anver, M Koochekpour, S Vande Woude, GF AF Jeffers, M Fiscella, M Webb, CP Anver, M Koochekpour, S Vande Woude, GF TI The mutationally activated Met receptor mediates motility and metastasis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; RENAL-CELL CARCINOMA; TYROSINE KINASE; PROTEIN-KINASE; PROTOONCOGENE PRODUCT; FACTOR/SCATTER FACTOR; EXPRESSION; GENE; TRANSFORMATION AB Mutations in Met have been identified in human papillary renal carcinomas. We have shown previously that these mutations deregulate the enzymatic activity of Met and that NIH 3T3 cells expressing mutationally activated Met are transformed in vitro and are tumorigenic in vivo. In the present investigation, we find that mutant Met induces the motility of Madin-Darby canine kidney cells in vitro and experimental metastasis of NIH 3T3 cells in vivo, and that the Ras-Raf-MEK-ERK signaling pathway, which has been implicated previously in cellular motility and metastasis, is constitutively activated by the Met mutants. We also report that transgenic mice harboring mutationally activated Met develop metastatic mammary carcinoma. These data confirm the tumorigenic activity of mutant Met molecules and dem onstrate their ability to induce the metastatic phenotype. C1 NCI, Frederick Canc Res & Dev Ctr, NIH, Div Basic Sci, Frederick, MD 21702 USA. Sci Applicat Int Corp, Frederick, MD 21702 USA. Adv BioSci Labs, Basic Res Program, Frederick, MD 21702 USA. RP Vande Woude, GF (reprint author), NCI, Frederick Canc Res & Dev Ctr, NIH, Div Basic Sci, POB B, Frederick, MD 21702 USA. EM woude@ncifcrf.gov RI Webb, Craig/I-8123-2012 FU NCI NIH HHS [N01-CO-56000] NR 45 TC 183 Z9 185 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 1998 VL 95 IS 24 BP 14417 EP 14422 DI 10.1073/pnas.95.24.14417 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200077 PM 9826715 ER PT J AU Puri, A Hug, P Jernigan, K Barchi, J Kim, HY Hamilton, J Wiels, J Murray, GJ Brady, RO Blumenthal, R AF Puri, A Hug, P Jernigan, K Barchi, J Kim, HY Hamilton, J Wiels, J Murray, GJ Brady, RO Blumenthal, R TI The neutral glycosphingolipid globotriaosylceramide promotes fusion mediated by a CD4-dependent CXCR4-utilizing HIV type 1 envelope glycoprotein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCLONAL-ANTIBODY; RESISTANT FACTORS; MEMBRANE-FUSION; CELLS; RECEPTORS; REPLICATION; INFECTION; ENTRY; INHIBITOR AB Previously, we showed that the addition of human erythrocyte glycosphingolipids (GSLs) to nonhuman CD4(+) or GSL-depleted human CD4(+) cells rendered those cells susceptible to HIV-1 envelope glycoprotein-mediated cell fusion. Individual components in the GSL mixture were isolated by fractionation on a silica-gel column and incorporated into the membranes of CD4(+) cells. GSL-supplemented target cells were then examined for their ability to fuse with TF228 cells expressing HIV-1(LAI) envelope glycoprotein, We found that one GSL fraction, fraction 3, exhibited the highest recovery of fusion after incorporation into CD4(+) nonhuman and GSL-depleted HeLa-CD4 cells and that fraction 3 contained a single GSL fraction. Fraction 3 was characterized by MS, NMR spectroscopy, enzymatic analysis, and immunostaining with an antiglobotriaosylceramide (Gb3) antibody and was found to be Gal(alpha 1-->4)Gal(beta 1-->4) Glc-Cer (Gb3), The addition of fraction 3 or Gb3 to GSL-depleted HeLa-CD4 cells recovered fusion, but the addition of galactosylceramide, glucosylceramide, the monosialoganglioside, GM3, lactosylceramide, globoside, the disialoganglioside, GD3, or alpha-galactosidase A-digested fraction 3 had no effect. Our findings show that the neutral GSL, Gb3, is required for CD4/CXCR4-dependent HIV-1 fusion. C1 NCI, Sect Membrane Struct & Funct, Lab Expt & Computat Biol, Div Basic Sci,NIH, Frederick, MD 21702 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. Inst Gustave Roussy, CNRS UMR 1598, F-94805 Villejuif, France. RP Blumenthal, R (reprint author), NCI, Sect Membrane Struct & Funct, Lab Expt & Computat Biol, Div Basic Sci,NIH, Frederick, MD 21702 USA. EM blumen@helix.nih.gov NR 41 TC 96 Z9 99 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 1998 VL 95 IS 24 BP 14435 EP 14440 DI 10.1073/pnas.95.24.14435 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200080 PM 9826718 ER PT J AU Frerichs, KU Smith, CB Brenner, M DeGracia, DJ Krause, GS Marrone, L Dever, TE Hallenbeck, JM AF Frerichs, KU Smith, CB Brenner, M DeGracia, DJ Krause, GS Marrone, L Dever, TE Hallenbeck, JM TI Suppression of protein synthesis in brain during hibernation involves inhibition of protein initiation and elongation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DIPHTHERIA-TOXIN; ADP-RIBOSYLATION; FACTOR-II; MAMMALIAN HIBERNATION; CEREBRAL-ISCHEMIA; SYNTHESIS INVIVO; GENE-EXPRESSION; METABOLIC-RATE; PHOSPHORYLATION; MECHANISM AB Protein synthesis (PS) has been considered essential to sustain mammalian life, yet was found to be virtually arrested for weeks in brain and other organs of the hibernating ground squirrel, Spermophilus tridecemlineatus, PS, in vivo, was below the limit of autoradiographic detection in brain sections and, in brain extracts, was determined to be 0.04% of the average rate from active squirrels. Further, it was reduced 3-fold in cell-free extracts from hibernating brain at 37 degrees C, eliminating hypothermia as the only cause for protein synthesis inhibition (active, 0.47 +/- 0.08 pmol/mg protein per min; hibernator, 0.16 +/- 0.05 pmol/mg protein per min, P < 0.001), PS suppression involved blocks of initiation and elongation, and its onset coincided with the early transition phase into hibernation. An increased monosome peak with moderate ribosomal disaggregation in polysome profiles and the greatly increased phosphorylation of eIF2 alpha are both consistent with an initiation block in hibernators. The elongation block was demonstrated by a 3-fold increase in ribosomal mean transit times in cell-free extracts from hibernators (active, 2.4 +/- 0.7 min; hibernator, 7.1 +/- 1.4 min, P < 0.001), No abnormalities of ribosomal function or mRNA levels were detected. These findings implicate suppression of PS as a component of the regulated shutdown of cellular function that permits hibernating ground squirrels to tolerate "trickle" blood flow and reduced substrate and oxygen availability. Further study of the factors that control these phenomena may lead to identification of the molecular mechanisms that regulate this state. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. Wayne State Univ, Dept Emergency Med, Detroit, MI 48201 USA. RP Frerichs, KU (reprint author), NINDS, Stroke Branch, NIH, Bldg 36 Room 4A03,36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. FU NINDS NIH HHS [R01 NS033196] NR 48 TC 194 Z9 201 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 1998 VL 95 IS 24 BP 14511 EP 14516 DI 10.1073/pnas.95.24.14511 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200093 PM 9826731 ER PT J AU McNamara, RK Stumpo, DJ Morel, LM Lewis, MH Wakeland, EK Blackshear, PJ Lenox, RH AF McNamara, RK Stumpo, DJ Morel, LM Lewis, MH Wakeland, EK Blackshear, PJ Lenox, RH TI Effect of reduced myristoylated alanine-rich C kinase substrate expression on hippocampal mossy fiber development and spatial learning in mutant mice: Transgenic rescue and interactions with gene background SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE protein kinase C; hippocampus; Macs ID MOLECULAR CHARACTERIZATION; MARCKS DEFICIENCY; RAT-BRAIN; PROTEIN; LOCALIZATION; BEHAVIOR; FAMILY AB The myristoylated alanine-rich C kinase substrate (MARCKS) is a prominent protein kinase C (PKC) substrate in brain that is expressed highly in hippocampal granule cells and their axons, the mossy fibers. Here, we examined hippocampal infrapyramidal mossy fiber (IP-MF) limb length and spatial learning in heterozygous Macs mutant mice that exhibit an approximate to 50% reduction in MARCKS expression relative to wild-type controls. On a 129B6(N3) background, the Macs mutation produced IP-MF hyperplasia, a significant increase in hippocampal PKC epsilon expression, and proficient spatial learning relative to wild-type controls. However, wild-type 129B6(N3) mice exhibited phenotypic characteristics resembling inbred 129Sv mice, including IP-MF hypoplasia relative to inbred C57BL/6J mice and impaired spatial-reversal learning, suggesting a significant contribution of 129Sv background genes to wild-type and possibly mutant phenotypes. Indeed, when these mice were backcrossed with inbred C57BL/6J mice for nine generations to reduce 129Sv background genes, the Macs mutation did not effect IP-MF length or hippocampal PKC epsilon expression and impaired spatial learning relative to wild-type controls, which now showed proficient spatial learning. Moreover, in a different strain (B6SJL(N1), the Macs mutation also produced a significant impairment in spatial learning that was reversed by transgenic expression of MARCKS. Collectively, these data indicate that the heterozygous Macs mutation modifies the expression of linked 129Sv gene(s), affecting hippocampal mossy fiber development and spatial learning performance, and that MARCKS plays a significant role in spatial learning processes. C1 Univ Penn, Sch Med, Dept Psychiat, Abramson Res Ctr, Philadelphia, PA 19104 USA. Univ Florida, Coll Med, Dept Pathol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Psychiat, Gainesville, FL 32610 USA. Inst Brain, Gainesville, FL 32610 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP McNamara, RK (reprint author), Univ Penn, Sch Med, Dept Psychiat, Abramson Res Ctr, Room 802,24th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM rkm@mail.med.upenn.edu RI McNamara, Robert/J-4309-2014 FU NIMH NIH HHS [R01 MH59959-01] NR 25 TC 63 Z9 65 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 1998 VL 95 IS 24 BP 14517 EP 14522 DI 10.1073/pnas.95.24.14517 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200094 PM 9826732 ER PT J AU Kim, GH Masilamani, S Turner, R Mitchell, C Wade, JB Knepper, MA AF Kim, GH Masilamani, S Turner, R Mitchell, C Wade, JB Knepper, MA TI The thiazide-sensitive Na-Cl cotransporter is an aldosterone-induced protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fluorocortisone; sodium chloride transport; distal convoluted tubule; collecting duct ID CHLORIDE COTRANSPORT; ISOLATED TUBULES; RAT; SODIUM; BINDING; IMMUNOLOCALIZATION; LOCALIZATION; RECEPTOR; NEPHRON; KIDNEY AB Although the collecting duct is regarded as the primary site at which mineralocorticoids regulate renal sodium transport in the kidney, recent evidence points to the distal convoluted tubule as a possible site of mineralocorticoid action. To investigate whether mineralocorticoids regulate the expression of the thiazide-sensitive Na-Cl cotransporter (TSC), the chief apical sodium entry pathway of distal convoluted tubule cells, we prepared an affinity-purified, peptide-directed antibody to TSC, On immunoblots, the antibody recognized a prominent 165-kDa band in membrane fractions from the renal cortex but not from the renal medulla. Immunofluorescence immunocytochemistry showed TSC labeling only in distal convoluted tubule cells, Semiquantitative immunoblotting studies demonstrated a large increase in TSC expression in the renal cortex of rats on a low-NaCl diet (207 +/- 21% of control diet). Immunofluorescence localization in tissue sections confirmed the strong increase in TSC expression, Treatment of rats for 10 days with a continuous subcutaneous infusion of aldosterone also increased TSC expression (380 +/- 58% of controls). Furthermore, 7-day treatment of rats with an orally administered mineralocorticoid, fludrocortisone, increased TSC expression (656 +/- 114% of controls), We conclude that the distal convoluted tubule is an important site of action of the mineralocorticoid aldosterone, which strongly up-regulates the expression of TSC. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Coll Med, Dept Physiol, Baltimore, MD 21201 USA. RP Knepper, MA (reprint author), NIH, Bldg 10,Room 6N260,10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. OI Kim, Gheun-Ho/0000-0002-8445-9892 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-0282-KE]; NIDDK NIH HHS [DK27847, R01 DK027847] NR 31 TC 284 Z9 288 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 1998 VL 95 IS 24 BP 14552 EP 14557 DI 10.1073/pnas.95.24.14552 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142GE UT WOS:000077191200100 PM 9826738 ER PT J AU Goff, DC Sellers, DE McGovern, PG Meischke, H Goldberg, RJ Bittner, V Hedges, JR Allender, PS Nichaman, MZ AF Goff, DC Sellers, DE McGovern, PG Meischke, H Goldberg, RJ Bittner, V Hedges, JR Allender, PS Nichaman, MZ CA REACT Study Grp TI Knowledge of heart attack symptoms in a population survey in the United States - The REACT trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-CARE UNIT; PRE-HOSPITAL PHASE; CHEST PAIN; PREHOSPITAL DELAY; THROMBOLYTIC THERAPY; ARRIVAL; HEALTH; DISEASE; REASONS AB Background: Greater use of thrombolysis for patients with myocardial infarction has been limited by patient delay in seeking care for heart attack symptoms. Deficiencies in knowledge of Symptoms may contribute to delay and could be a target for intervention. We sought to characterize symptom knowledge. Methods: Rapid Early Action for Coronary Treatment is a community trial designed to reduce this delay. dt baseline, a random-digit dialed survey was conducted among 1294 adult respondents in the 20 study communities. TWO open-ended questions were asked about heart attack symptom knowledge. Results: Chest pain or discomfort was reported as a symptom by 89.7% of respondents and was thought to be the most important symptom by 56.6%. Knowledge of arm pain or numbness (67.3%), shortness of breath (50.8%), sweating (21.3%), and other heart attack symptoms was less common. The median number of correct symptoms reported was 3 (of 11). In a multivariable-adjusted model, significantly higher mean numbers of correct symptoms were reported by non-Hispanic whites than by other racial or ethnic groups, by middle-aged persons than by older and younger persons, by persons with higher socioeconomic status than by those with lower, and by persons with previous experience with heart attack than by those without. Conclusions: Knowledge of chest pain as an important heart attack symptom is high and relatively uniform; however, knowledge of the complex constellation of heart attack symptoms is deficient in the US population, especially in low socioeconomic and racial or ethnic minority groups. Efforts to reduce delay in seeking medical care among persons with heart attack symptoms should address these deficiencies in knowledge. C1 Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27157 USA. New England Res Inst, Watertown, MA 02172 USA. Univ Minnesota, Sch Publ Hlth, Dept Epidemiol, Minneapolis, MN USA. Univ Washington, Dept Emergency Med Serv, Seattle, WA 98195 USA. Univ Massachusetts, Sch Med, Dept Cardiol, Worcester, MA USA. Univ Alabama, Sch Med, Dept Internal Med, Birmingham, AL USA. Oregon Hlth Sci Univ, Dept Emergency Med, Portland, OR USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Discipline Epidemiol, Houston, TX USA. RP Goff, DC (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM dgoff@rc.phs.wfubmc.edu FU NHLBI NIH HHS [HL-53142, HL-53149, HL-53155] NR 47 TC 107 Z9 107 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 23 PY 1998 VL 158 IS 21 BP 2329 EP 2338 DI 10.1001/archinte.158.21.2329 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 139TK UT WOS:000077045600005 PM 9827784 ER PT J AU Garboczi, DN AF Garboczi, DN TI Hot papers - Immunology - Structure of the complex between human T-cell receptor, viral peptide, and HLA-A2 by D.N. Garboczi, P. Ghosh, U. Utz, Q.R. Fan, W.E. Biddison, D.C. Wiley - Comments SO SCIENTIST LA English DT Editorial Material C1 NIAID, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Garboczi, DN (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD NOV 23 PY 1998 VL 12 IS 23 BP 11 EP 11 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 140FQ UT WOS:000077077300016 ER PT J AU Moody, EJ Knauer, CS Granja, R Strakhovaua, M Skolnick, P AF Moody, EJ Knauer, CS Granja, R Strakhovaua, M Skolnick, P TI Distinct structural requirements for the direct and indirect actions of the anaesthetic etomidate at GABA(A) receptors SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 5th International Conference on Molecular and Cellular Mechanisms of Anaesthesia CY JUN 18-20, 1997 CL UNIV CALGARY, CALGARY, CANADA HO UNIV CALGARY DE anaesthetic etomidate; GABA(A) receptors; structural requirements ID A RECEPTOR; ANESTHETIC ETOMIDATE; SUBUNIT COMPOSITION; BETA-SUBUNIT; RAT-BRAIN; ACID; POTENTIATION; LORECLEZOLE; MECHANISMS; COMPLEX AB 1. The intravenous anaesthetic etomidate augments GABA-gated chloride currents (indirect action) and, at higher concentrations, evokes chloride currents in the absence of GABA (direct action). 2. In order to identify amino acid residues essential for these actions, site directed mutagenesis was performed on the beta 3 subunit. 3. Mutation of an asparagine to a serine residue at position 290 dramatically reduced both etomidate-induced chloride currents and its ability to enhance [H-3]flunitrazepam binding in HEK293 cells expressing alpha 1 beta 3 gamma 2 recombinant GABA(A) receptors. 4. In contrast, the indirect effect of etomidate was retained, though its potency was reduced. 5. These findings indicate that there are distinct requirements for these dual actions of etomidate at GABA(A) receptors. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 NIDDK, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Hosp, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. Lilly Res Labs, Neurosci Discovery, Indianapolis, IN USA. RP Moody, EJ (reprint author), NIDDK, Neurosci Lab, NIH, Bldg 8,Room 106, Bethesda, MD 20892 USA. NR 24 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD NOV 23 PY 1998 VL 101 BP 209 EP 215 PG 7 WC Toxicology SC Toxicology GA 160EL UT WOS:000078217400031 ER PT J AU Cairns, JS Sarver, N AF Cairns, JS Sarver, N TI New viral vectors for HIV vaccine delivery SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Review ID HERPES-SIMPLEX VIRUS; VARICELLA-ZOSTER VIRUS; POLIOVIRUS REPLICONS; IMMUNE-RESPONSES; GLYCOPROTEIN-D; FOREIGN GENES; IMMUNIZATION; CHALLENGE; EXPRESSION; PROTEINS C1 NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. RP Sarver, N (reprint author), NIAID, Div AIDS, NIH, 2C01 Solar Bldg,6003 Execut Blvd, Bethesda, MD 20892 USA. EM ns18p@nih.gov NR 26 TC 9 Z9 9 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV 20 PY 1998 VL 14 IS 17 BP 1501 EP 1508 DI 10.1089/aid.1998.14.1501 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 141XD UT WOS:000077168800001 PM 9840283 ER PT J AU Fowke, KR Dong, T Rowland-Jones, SL Oyugi, J Rutherford, WJ Kimani, J Krausa, P Bwayo, J Simonsen, JN Shearer, GM Plummer, FA AF Fowke, KR Dong, T Rowland-Jones, SL Oyugi, J Rutherford, WJ Kimani, J Krausa, P Bwayo, J Simonsen, JN Shearer, GM Plummer, FA TI HIV type 1 resistance in Kenyan sex workers is not associated with altered cellular susceptibility to HIV type 1 infection or enhanced beta-chemokine production SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article; Proceedings Paper CT 19th International Congress of Chemotherapy CY JUL 16-21, 1995 CL MONTREAL, CANADA ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD8(+) T-CELLS; DISEASE PROGRESSION; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; EOTAXIN RECEPTOR; INDIVIDUALS; CCR5; TRANSMISSION; NAIROBI AB A small group of women (n = 80) within the Nairobi-based Pumwani Sex Workers Cohort demonstrates epidemiologic resistance to HIV-1 infection. Chemokine receptor polymorphisms and beta-chemokine overproduction have been among the mechanisms suggested to be responsible for resistance to HIV-1 infection, This study attempts to determine if any of those mechanisms are protecting the HIV-1-resistant women. Genetic analysis of CCR5 and CCR3 from the resistant women demonstrated no polymorphisms associated with resistance. Expression levels of CCR5 among the resistant women were shown to be equivalent to that found in low-risk seronegative (negative) controls, while CXCR4 expression was greater among some of the resistant women. In vitro infection experiments showed that phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from resistant women mere as susceptible to infection to T cell- and macrophage-tropic North American and Kenyan HIV-1 isolates as were the PBMCs from negative controls, No significant difference in circulating plasma levels of MIP-1 alpha and MIP-1 beta were found between the resistant women and negative or HIV-1-infected controls. In vitro cultures of media and PHA-stimulated PBMCs indicated that the resistant women produced significantly less MIP-1 alpha and MIP-1 beta than did negative controls and no significant difference in RANTES levels were observed. In contrast to studies in Caucasian cohorts, these data indicate that CCR5 polymorphisms, altered CCR5 and CXCR4 expression levels, cellular resistance to in vitro HIV-1 infection, and increased levels of beta-chemokine production do not account for the resistance to HIV-1 infection observed among the women of the Pumwani Sex Workers Cohort. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. John Radcliffe Hosp, Inst Mol Med, Mol Immunol Grp, Oxford OX3 9DS, England. Univ Nairobi, Dept Med Microbiol, Nairobi, Kenya. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0W3, Canada. RP Fowke, KR (reprint author), NCI, Expt Immunol Branch, NIH, 10-4B36 9000 Rockville Pike, Bethesda, MD 20892 USA. EM fowkek@exchange.nih.gov OI Fowke, Keith/0000-0001-8227-6649 NR 54 TC 54 Z9 54 U1 1 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV 20 PY 1998 VL 14 IS 17 BP 1521 EP 1530 DI 10.1089/aid.1998.14.1521 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 141XD UT WOS:000077168800003 PM 9840285 ER PT J AU Kokoshka, JM Vaughan, RA Hanson, GR Fleckenstein, AE AF Kokoshka, JM Vaughan, RA Hanson, GR Fleckenstein, AE TI Nature of methamphetamine-induced rapid and reversible changes in dopamine transporters SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE methamphetamine; dopamine transporter; dopamine ID PROTEIN-KINASE-C; TYROSINE-HYDROXYLASE ACTIVITY; RAT-BRAIN; STRIATAL SYNAPTOSOMES; FUNCTIONAL-ACTIVITY; NUCLEUS-ACCUMBENS; COCAINE BINDING; UPTAKE SITES; LIGAND; ACID AB The nature of methamphetamine-induced rapid and transient decreases in dopamine transporter activity was investigated. Regional specificity was demonstrated, since [H-3]dopamine uptake was decreased in synaptosomes prepared from the striatum, but not nucleus accumbens, of methamphetamine-treated rats. Differences among effects on dopamine transporter activity and ligand binding were also observed, since a single methamphetamine administration decreased [3H]dopamine uptake without altering [H-3]WIN35428 ([H-3](-)-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane 1,5-naphthalenedisulfonate) binding in synaptosomes prepared 1 h after injection. Moreover, multiple methamphetamine injections caused a greater decrease in [H-3]dopamine uptake than [H-3]WIN35428 binding in synaptosomes prepared 1 h after dosing. Finally, decreases in [H-3]dopamine uptake, but not [H-3]WIN35428 binding, were partially reversed 24 h after multiple methamphetamine injections. Western blotting indicated that saline- and methamphetamine-affected dopamine transporters co-migrated on sodium dodecyl sulfate (SDS) gels at approximately 80 kDa, and that acute, methamphetamine-induced decreases in [H-3]dopamine uptake were not due to loss of dopamine transporter protein. These findings demonstrate heretofore-uncharacterized features of the acute effect of methamphetamine on dopamine transporters. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Utah, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA. NIDA, NIH, Intramural Program, Baltimore, MD 21224 USA. RP Fleckenstein, AE (reprint author), Univ Utah, Dept Pharmacol & Toxicol, 112 Skaggs Hall, Salt Lake City, UT 84112 USA. FU NIDA NIH HHS [DA00869, DA04222, DA11389] NR 41 TC 78 Z9 80 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 20 PY 1998 VL 361 IS 2-3 BP 269 EP 275 DI 10.1016/S0014-2999(98)00741-9 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 144UC UT WOS:000077332700013 PM 9865517 ER PT J AU Lavandero, S Chappuzeau, A Sapag-Hagar, M Oka, T AF Lavandero, S Chappuzeau, A Sapag-Hagar, M Oka, T TI In vivo and in vitro evidence of basic fibroblast growth factor action in mouse mammary gland development SO FEBS LETTERS LA English DT Article DE basic fibroblast growth factor; growth factor; milk protein; mammary gland; gene expression ID EPITHELIAL-CELLS; FACTOR RECEPTORS; GENE-EXPRESSION; HUMAN BREAST; CULTURE; DIFFERENTIATION; PROTEIN; PROLIFERATION; INHIBITION; INSULIN AB Basic fibroblast growth factor (bFGF) stimulated [H-3]thymidine incorporation at all stages of development, although the magnitude of this effect was the greatest in cells derived from pregnant mice. Cells primed with insulin and bFGF synthesized more casein than cells not exposed to either hormone. bFGF inhibited casein synthesis and decreased the amounts of B-casein and alpha-lactalbumin transcripts in cells from pregnant animals simultaneously incubated with insulin, hydrocortisone and prolactin, bFGF content in mammary gland increased with puberty and pregnancy, but decreased markedly in lactation; the number of bFGF receptors in epithelial cells changed in parallel. These data suggest that bFGF may have a physiological role both in stimulating growth and in inhibiting functional differentiation of normal mouse mammary epithelial cells. (C) 1998 Federation of European Biochemical Societies. C1 Univ Chile, Fac Ciencias Quim & Farmaceut, Dept Bioquim & Biol Mol, Santiago, Chile. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Lavandero, S (reprint author), Univ Chile, Fac Ciencias Quim & Farmaceut, Dept Bioquim & Biol Mol, POB 233, Santiago, Chile. EM slavande@il.ciq.uchile.cl OI Lavandero, Sergio/0000-0003-4258-1483 NR 33 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 20 PY 1998 VL 439 IS 3 BP 351 EP 356 DI 10.1016/S0014-5793(98)01370-2 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 143CW UT WOS:000077238300031 PM 9845352 ER PT J AU Dunbar, CE Kohn, DB Schiffmann, R Barton, NW Nolta, JA Esplin, JA Pensiero, M Long, ZF Lockey, C Emmons, RVB Csik, S Leitman, S Krebs, CB Carter, C Brady, RO Karlsson, S AF Dunbar, CE Kohn, DB Schiffmann, R Barton, NW Nolta, JA Esplin, JA Pensiero, M Long, ZF Lockey, C Emmons, RVB Csik, S Leitman, S Krebs, CB Carter, C Brady, RO Karlsson, S TI Retroviral transfer of the glucocerebrosidase gene into CD34(+) cells from patients with Gaucher disease: In vivo detection of transduced cells without myeloablation SO HUMAN GENE THERAPY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW CELLS; MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; LONG-TERM ENGRAFTMENT; PERIPHERAL-BLOOD; ADENOSINE-DEAMINASE; ENZYME DEFICIENCY; PROGENITOR CELLS; IN-VIVO; MEDIATED TRANSFER AB Retroviral gene transfer of the glucocerebrosidase gene to hematopoietic progenitor and stem cells has shown promising results in animal models and corrected the enzyme deficiency in cells from Gaucher patients in vitro, Therefore, a clinical protocol was initiated to explore the safety and feasibility of retroviral transduction of peripheral blood (PB) or bone marrow (BM) CD34(+) cells with the G1Gc vector, This vector uses the viral LTR promoter to express the human glucocerebrosidase cDNA, Three adult patients have been entered with follow-up of 6-15 months. Target cells were G-CSF-mobilized and CD34-enriched PB cells or CD34-enriched steady state BM cells, and were transduced ex vivo for 72 hr, Patient 1 had PB cells transduced in the presence of autologous stromal marrow cells. Patient 2 had PB cells transduced in the presence of autologous stroma, IL-3, IL-6, and SCF, Patient 3 had BM cells transduced in the presence of autologous stroma, IL-3, IL-6, and SCF, At the end of transduction, the cells were collected and infused immediately without any preparative treatment of the patients. The transduction efficiency of the CD34(+) cells at the end of transduction was approximately 1, 10, and I for patients 1, 2, and 3, respectively, as estimated by semiquantitative PCR on bulk samples and PCR analysis of individual hematopoietic colonies, Gene marking in vivo was demonstrated in patients 2 and 3. Patient 2 had vector-positive PB granulocytes and mononuclear bone marrow cells at I month postinfusion and positive PB mononuclear cells at 2 and 3 months postinfusion, Patient 3 had a positive BM sample at 1 month postinfusion but was negative thereafter. These results indicate that gene-marked cells can engraft and persist for at least 3 months postinfusion, even without myeloablation, However, the level of corrected cells (<0.02%) is too low to result in any clinical benefit, and glucocerebrosidase enzyme activity did not increase in any patient following infusion of transduced cells, Modifications of vector systems and transduction conditions, along with partial myeloablation to allow higher levels of engraftment, may be necessary to achieve beneficial levels of correction in patients with Gaucher disease. C1 Childrens Hosp Los Angeles, Div Res Immunol & Bone Marrow Transplantat, Los Angeles, CA 90027 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ So Calif, Sch Med, Norris Cotton Canc Ctr, Los Angeles, CA 90089 USA. Genet Therapy Inc, Gaithersburg, MD USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Lund, S-22362 Lund, Sweden. RP Kohn, DB (reprint author), Childrens Hosp Los Angeles, Div Res Immunol & Bone Marrow Transplantat, Los Angeles, CA 90027 USA. RI Kohn, Donald/N-5085-2016; OI Kohn, Donald/0000-0003-1840-6087; Nolta, Jan/0000-0003-4576-8542 FU NCRR NIH HHS [MO1 RR-43]; NIDDK NIH HHS [R01 DK053041, R01 DK053041-05A1] NR 52 TC 123 Z9 126 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 20 PY 1998 VL 9 IS 17 BP 2629 EP 2640 DI 10.1089/hum.1998.9.17-2629 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 142VV UT WOS:000077221800018 PM 9853529 ER PT J AU Lacourciere, GM Stadtman, TC AF Lacourciere, GM Stadtman, TC TI The NIFS protein can function as a selenide delivery protein in the biosynthesis of selenophosphate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; SELENOCYSTEINE LYASE; SYNTHETASE; ENZYME; GENE; PURIFICATION; MECHANISM; LIVER; RAT AB The NIFS protein from Azobacter vinelandii is a pyridoxal phosphate-containing homodimer that catalyzes the formation of equimolar amounts of elemental sulfur and L-alanine from the substrate L-cysteine (Zheng, L,, White, R, H,, Cash, V, L,, Jack, R, F,, and Dean, D. R, (1993) Proc. Natl, Acad Sci, U.S.A. 90, 2754-2758), A sulfur transfer role of NIFS in which the enzyme donates sulfur for iron sulfur center formation in nitrogenase was suggested. The fact that NIFS also can catalyze the decomposition of L-selenocysteine to elemental selenium and L-alanine suggested the possibility that this enzyme might serve as a selenide delivery protein for the in vitro biosynthesis of selenophosphate. In agreement with this hypothesis, we have shown that replacement of selenide with NIFS and L-selenocysteine in the in vitro selenophosphate synthetase assay results in an increased rate of formation of selenophosphate. These results thus support the view that a selenocysteine specific enzyme similar to NIFS may be involved as an in vivo selenide delivery protein for selenophosphate biosynthesis. A kinetic characterization of the two NIFS catalyzed reactions carried out in the present study indicates that the enzyme favors L-cysteine as a substrate compared with its selenium analog. A specific activity for L-cysteine of 142 nmol/min/mg compared with 55 nmol/min/mg for L-selenocysteine was determined. This level of enzyme activity on the selenoamino acid substrate is adequate to deliver selenium to selenophosphate synthetase in the in vitro assay system described. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, TC (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3,Rm 103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 18 TC 47 Z9 49 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 20 PY 1998 VL 273 IS 47 BP 30921 EP 30926 DI 10.1074/jbc.273.47.30921 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141HG UT WOS:000077136900014 PM 9812986 ER PT J AU Rai, SS Wolff, J AF Rai, SS Wolff, J TI Localization of critical histidyl residues required for vinblastine-induced tubulin polymerization and for microtubule assembly SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BRAIN TUBULIN; INHIBITION; PROTEINS AB Vinblastine-induced tubulin polymerization is electrostatically regulated and shows pH dependence with a pI similar to 7.0 suggesting the involvement of histidyl residues. Modification of histidyl residues of tubulin with diethylpyrocarbonate (DEPC) at a mole ratio of 0.74 (DEPC/total His residues) for 3 min at 25 degrees C completely inhibited vinblastine-induced polymerization with little effect on microtubule assembly. Under these conditions DEPC reacts only with histidyl residues. For complete inhibition two histidyl residues have to be modified. Demodification of the carboxyethyl histidyl derivatives by hydroxylamine led to nearly complete recovery of polymerization competence. Labeling with [C-14]DEPC localized both of these histidyl residues on beta-tubulin at beta 227 and beta 264. Similarly, tubulin modification with DEPC for longer times (8 min) resulted in complete inhibition of microtubule assembly, at which time similar to 4 histidyl residues had been modified. This inhibition by DEPC was also reversed by hydroxylamine. The third histidyl residue was found on alpha-tubulin at alpha 88. Thus, two charged histidyl residues are obligatorily involved in vinblastine-induced polymerization, whereas a different histidyl residue on a different tubulin monomer is involved in microtubule assembly. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wolff, J (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM janw@bdg8.niddk.nih.gov NR 33 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 20 PY 1998 VL 273 IS 47 BP 31131 EP 31137 DI 10.1074/jbc.273.47.31131 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141HG UT WOS:000077136900044 PM 9813016 ER PT J AU Lischke, A Moriggl, R Brandlein, S Berchtold, S Kammer, W Sebald, W Groner, B Liu, XW Hennighausen, L Friedrich, K AF Lischke, A Moriggl, R Brandlein, S Berchtold, S Kammer, W Sebald, W Groner, B Liu, XW Hennighausen, L Friedrich, K TI The interleukin-4 receptor activates STAT5 by a mechanism that relies upon common gamma-chain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING ACTIVITY; COLONY-STIMULATING FACTOR; MAMMARY-GLAND FACTOR; HUMAN IL-4 RECEPTOR; SIGNAL-TRANSDUCTION; ALPHA-CHAIN; TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTOR; CYTOPLASMIC DOMAIN; GENE-EXPRESSION AB Interleukin (IL)-4 signaling proceeds via cytoplasmic activation of the Janus kinases JAK1 and JAK3 and the signal transducer and activator of transcription STAT6. We show that the IL-4 receptor, like other cytokine receptor systems utilizing the common receptor gamma-chain (gamma c), is also connected to a signaling pathway that involves STATE. Both STAT5a and STAT5b become tyrosine-phosphorylated and acquire specific DNA-binding properties in response to IL-4 receptor stimulation in the murine pro-B cell line Ba/F3. In preactivated human T cells, STATE became activated in an IL-4-dependent fashion as assayed by IL-Li-induced STATE translocation from the cytoplasm to the cell nucleus and by binding to cognate DNA. Moreover, stimulation of preactivated human T cells by IL-4 led to specific transcriptional upregulation of STATE target genes. IL-4 receptor-mediated STATE activation is dependent on the presence of gamma c and JAK3 within the receptor complex. In COS-7 cells, the JAK/STAT pathway leading from the IL-4 receptor to STATE-dependent regulation of a reporter gene relied largely on coexpression of JAK3. In Ba/F3 cells, studies on signal transduction evoked by directed specific receptor homo- or heterodimerization revealed that STATE activation can be triggered exclusively by IL-4R heterodimers containing gamma c. C1 Theodor Boveri Inst Biowissensch, Biozentrum, D-97074 Wurzburg, Germany. Inst Expt Canc Res, Tumor Biol Ctr, D-79106 Freiburg, Germany. NIDDK, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Liu, XW (reprint author), Theodor Boveri Inst Biowissensch, Biozentrum, Hubland, D-97074 Wurzburg, Germany. NR 62 TC 61 Z9 61 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 20 PY 1998 VL 273 IS 47 BP 31222 EP 31229 DI 10.1074/jbc.273.47.31222 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141HG UT WOS:000077136900057 PM 9813029 ER PT J AU Glathe, S Kervinen, J Nimtz, M Li, GH Tobin, GJ Copeland, TD Ashford, DA Wlodawer, A Costa, J AF Glathe, S Kervinen, J Nimtz, M Li, GH Tobin, GJ Copeland, TD Ashford, DA Wlodawer, A Costa, J TI Transport and activation of the vacuolar aspartic proteinase phytepsin in barley (Hordeum vulgare L.) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CATHEPSIN-D; PROCATHEPSIN-D; ACTIVE-SITE; PURIFICATION; EXPRESSION; MATURATION; DISTINCT; CLEAVAGE; VARIANTS; CELLS AB The primary translation product of barley aspartic proteinase, phytepsin (EC 3.4.23.40), consists of a signal sequence, a propart, and mature enzyme forms. Here, we describe post-translational processing and activation of phytepsin during its transport to the vacuole in roots, as detected by using metabolic labeling and immunoprecipitation. After removal of the signal sequence, the glycosylated precursor of 53 kDa (P53) was produced and further processed to polypeptides of 31 and 15 kDa (P31 + P15) and, subsequently, to polypeptides of 26 and 9 kDa (P26 + P9), 45 min and 24 h after synthesis, respectively. The processing occurred in a late-Golgi compartment or post-Golgi compartment, because brefeldin A inhibited the processing, and P53 acquired partial endoglycosidase H resistance 30 min after synthesis, whereas P15 was completely resistant. The N-glycosylation inhibitor tunicamycin had no effect on transport, but the absence of glycans on P53 accelerated the proteolytic processing. Phytepsin was also expressed in baculovirus-infected insect cells. The recombinant prophytepsin underwent autoproteolytic activation in vitro and showed enzymatic properties similar to the enzyme purified from grains. However, a comparison of the in vitro/in vivo processing sites revealed slight differences, indicating that additional proteases are needed for the completion of the maturation in vivo. C1 Univ Nova Lisboa, Inst Tecnol Quim & Biol, IBET, P-2780 Oeiras, Portugal. NCI, Lab Cell & Mol Struct Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. Gesell Biotechnol Forsch GmbH, D-38124 Braunschweig, Germany. Univ York, Dept Biol, Glycobiol Res & Analyt Facil, York YO1 5DD, N Yorkshire, England. Univ Algarve, Unidad Ciencias Exactas & Humanas, P-8000 Faro, Portugal. RP Costa, J (reprint author), Univ Nova Lisboa, Inst Tecnol Quim & Biol, IBET, Apartado 12, P-2780 Oeiras, Portugal. RI Costa, Julia/B-7131-2008 OI Costa, Julia/0000-0001-7782-6319 NR 27 TC 45 Z9 46 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 20 PY 1998 VL 273 IS 47 BP 31230 EP 31236 DI 10.1074/jbc.273.47.31230 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141HG UT WOS:000077136900058 PM 9813030 ER PT J AU Andley, UP Song, Z Wawrousek, EF Bassnett, S AF Andley, UP Song, Z Wawrousek, EF Bassnett, S TI The molecular chaperone alpha A-crystallin enhances lens epithelial cell growth and resistance to UVA stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK PROTEIN; B-CRYSTALLIN; ULTRAVIOLET-RADIATION; INCLUSION-BODIES; EYE LENS; PHOSPHORYLATION; DEATH; EXPRESSION; GENE; THERMORESISTANCE AB alpha A-Crystallin (alpha A) is a member of the small heat shock protein (sHSP) family and has the ability to prevent denatured proteins from aggregating in vitro. Lens epithelial cells express relatively low levels of alpha A, but in differentiated fiber cells, alpha A is the most abundant soluble protein. The lenses of alpha A-knock-out mice develop opacities at an early age, implying a critical role for alpha A in the maintenance of fiber cell transparency. However, the function of alpha-crystallin in the lens epithelium is unknown. To investigate the physiological function of alpha A in lens epithelial cells, we used the following two systems: alpha A knock-out (alpha A(-/-)) mouse lens epithelial cells and human lens epithelial cells that overexpress cuk The growth rate of alpha A(-/-) mouse lens epithelial cells was reduced by 50% compared with wild type cells. Cell cycle kinetics, measured by fluorescence-activated cell. sorter analysis of propidium iodide-stained cells, indicated a relative deficiency of alpha A(-/-) cells in the G(2)/M phases. Exposure of mouse lens epithelial cells to physiological levels of WA resulted in an increase in the number of apoptotic cells in the cultures. Four hours after irradiation the fraction of apoptotic cells in the alpha A(-/-) cultures was increased 40-fold over wild type. In cells lacking alpha A, WA exposure modified F-actin, but actin was protected in cells expressing alpha A Stably transfected cell lines overexpressing human alpha A were generated by transfecting extended life span human lens epithelial cells with the mammalian expression vector construct pCI-neo alpha A Cells overexpressing alpha A were resistant to WA stress, as determined by clonogenic survival. alpha A remained cytoplasmic after exposure to either WA or thermal stress indicating that, unlike other sHSPs, the protective effect of alpha A was not associated with its relocalization to the nucleus. These results indicate that alpha A has important cellular functions in the lens over and above its well characterized role in refraction. C1 Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Andley, UP (reprint author), Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, 660 S Euclid Ave,Campus Box 8096, St Louis, MO 63110 USA. EM andley@seer.wustl.edu RI Wawrousek, Eric/A-4547-2008 FU NEI NIH HHS [EY02687, R01-EY05681, R01-EY09852] NR 44 TC 88 Z9 92 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 20 PY 1998 VL 273 IS 47 BP 31252 EP 31261 DI 10.1074/jbc.273.47.31252 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141HG UT WOS:000077136900061 PM 9813033 ER PT J AU Delgado, M Munoz-Elias, EJ Kan, YQ Gozes, I Fridkin, M Brenneman, DE Gomariz, RP Ganea, D AF Delgado, M Munoz-Elias, EJ Kan, YQ Gozes, I Fridkin, M Brenneman, DE Gomariz, RP Ganea, D TI Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit tumor necrosis factor alpha transcriptional activation by regulating nuclear factor-kB and cAMP response element-binding protein/c-Jun SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; HUMAN MONOCYTIC CELLS; MURINE T-LYMPHOCYTES; C-JUN; CYTOKINE PRODUCTION; GENE-EXPRESSION; MESSENGER-RNA; CYCLIC-AMP; PRIMARY MACROPHAGES; TERMINAL KINASE AB Tumor necrosis factor alpha (TNF alpha) an early cytokine produced by activated macrophages, plays an essential role in normal and pathological inflammatory reactions. The excessive production of TNF alpha is prevented by the so-called "macrophage-deactivating factors." This study examines the role of two structurally related neuropeptides, the vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating peptide (PACAP), as inhibitors of TNF alpha. Both VIP and PACAP inhibit TNF alpha production from lipopolysaccharide-stimulated RAW 246.7 cells in a dose- and time-dependent manner. Although the activated cells express mRNA for all three VIP/PACAP receptors, agonist and antagonist studies indicate that the major receptor involved is VIP1R. VIP/PACAP inhibit TNF alpha gene expression by affecting both NF-kB binding and the composition of the cAMP responsive element binding complex (CREB/c-Jun). Two transduction pathways, a cAMP-dependent and a cAMP-independent pathway, are involved in the inhibition of TNF alpha gene expression and appear to differentially regulate the transcriptional factors involved. Because TNF alpha plays a central role in various inflammatory diseases such as endotoxic shock, multiple sclerosis, cerebral malaria, and various autoimmune conditions, the down-regulatory effect of VIP/PACAP may have a significant therapeutic potential. C1 Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA. Univ Complutense Madrid, Dept Biol Celular, E-28040 Madrid, Spain. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. NICHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bethesda, MD 20895 USA. RP Ganea, D (reprint author), Rutgers State Univ, Dept Biol Sci, 101 Warren St, Newark, NJ 07102 USA. RI Delgado, Mario/P-1524-2016 OI Delgado, Mario/0000-0003-1893-5982 FU NIAID NIH HHS [AI 41786-01] NR 64 TC 141 Z9 142 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 20 PY 1998 VL 273 IS 47 BP 31427 EP 31436 DI 10.1074/jbc.273.47.31427 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141HG UT WOS:000077136900082 PM 9813054 ER PT J AU Cao, WS Adya, N Britos-Bray, M Liu, PP Friedman, AD AF Cao, WS Adya, N Britos-Bray, M Liu, PP Friedman, AD TI The core binding factor (CBF) alpha interaction domain and the smooth muscle myosin heavy chain (SMMHC) segment of CBF beta-SMMHC are both required to slow cell proliferation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; FETAL LIVER HEMATOPOIESIS; TRANSCRIPTION FACTOR; DNA-BINDING; MURINE MYELOPEROXIDASE; FUNCTIONAL DISSECTION; VIRUS ENHANCERS; FUSION GENE; PROTEIN AB We have expressed several variants of core binding factor beta (CBF beta)-smooth muscle myosin heavy chain (SMMHC) from the metallothionein promoter in Ba/F3 cells. Deletion of amino acids 2-11 from the CBF beta segment, required for interaction with CBF alpha, prevented CBF beta-SMMHC from inhibiting CBF DNA binding and cell cycle progression. Deletion of 283 carboxyl-terminal residues from the SMMHC domain, required for multimerization, also inactivated CBF beta-SMMHC. Nuclear expression of CBF beta(Delta 2-11)-SMMHC was decreased relative to CBF beta-SMMHC. CBF beta(Delta 2-11)-SMMHC linked to a nuclear localization signal still did not slow cell growth. The ability of each CBF beta-SMMHC variant to inhibit CBF DNA binding and cell proliferation correlated with its ability to inhibit transactivation by an AML1-VP16 fusion protein. Thus, CBF beta-SMMHC slows cell cycle progression from G(1) to S phase by inhibiting CBF DNA binding and transactivation. C1 Johns Hopkins Oncol Ctr, Div Pediat Oncol, Baltimore, MD 21287 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Friedman, AD (reprint author), Johns Hopkins Oncol Ctr, Div Pediat Oncol, Rm 3-109,600 N Wolfe St, Baltimore, MD 21287 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU NHLBI NIH HHS [HL51388] NR 44 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 20 PY 1998 VL 273 IS 47 BP 31534 EP 31540 DI 10.1074/jbc.273.47.31534 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141HG UT WOS:000077136900096 PM 9813068 ER PT J AU Acharya, S Rodriguez, IR Moreira, EF Midura, RJ Misono, K Todres, E Hollyfield, JG AF Acharya, S Rodriguez, IR Moreira, EF Midura, RJ Misono, K Todres, E Hollyfield, JG TI SPACR, a novel interphotoreceptor matrix glycoprotein in human retina that interacts with hyaluronan SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; CHONDROITIN SULFATE; ROD PHOTORECEPTORS; SEQUENCE-ANALYSIS; DERMATAN SULFATE; BINDING-PROTEINS; PROTEOGLYCAN; GLYCOSAMINOGLYCAN; CALCIUM; DOMAINS AB SPACR (sialoprotein associated with cones and rods), is the major 147-150-kDa glycoprotein present in the insoluble interphotoreceptor matrix of the human retina. Immunocytochemistry localizes SPACR to the matrix surrounding rods and cones (Acharya, S., Rayborn, M. E., and Hollyf'ield, J. G. (1998) Glycobiology 8, 997-1006), From affinity-purified SPACR, we obtained seven peptide sequences showing 100% identity to the deduced sequence of IMPG1, a purported chondroitin 6-sulfate proteoglycan core protein, which binds peanut agglutinin and is localized to the interphotoreceptor matrix. We show here that SPACR is the most prominent 147-150-kDa band present in the interphotoreceptor matrix and is the gene product of IMPG1. SPACR is not a chondroitin sulfate proteoglycan, since it is not a product of chondroitinase ABC digestion and does not react to a specific antibody for chondroitin B-sulfate proteoglycan. Moreover, the deduced amino acid sequence reveals no established glycosaminoglycan attachment site. One hyaluronan binding motif is present in the predicted sequence of SPACR. We present evidence that SPACR has a functional hyaluronan binding domain, suggesting that interactions between SPACR and hyaluronan may serve to form the basic macromolecular scaffold, which comprises the insoluble interphotoreceptor matrix. C1 Cleveland Clin Fdn, Inst Eye, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Acharya, S (reprint author), Cleveland Clin Fdn, Inst Eye, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NEI NIH HHS [EY 02362] NR 46 TC 42 Z9 44 U1 13 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 20 PY 1998 VL 273 IS 47 BP 31599 EP 31606 DI 10.1074/jbc.273.47.31599 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141HG UT WOS:000077136900104 PM 9813076 ER PT J AU Kim, ES Kim, RS Ren, RF Hawver, DB Flanders, KC AF Kim, ES Kim, RS Ren, RF Hawver, DB Flanders, KC TI Transforming growth factor-beta inhibits apoptosis induced by beta-amyloid peptide fragment 25-35 in cultured neuronal cells SO MOLECULAR BRAIN RESEARCH LA English DT Article DE transforming growth factor-beta; apoptosis; neuroprotection; bcl-2 family ID AMYOTROPHIC-LATERAL-SCLEROSIS; RAT HIPPOCAMPAL-NEURONS; ALZHEIMERS-DISEASE; BCL-X; MEDIATED APOPTOSIS; IN-VITRO; DEATH; EXPRESSION; GROWTH-FACTOR-BETA-1; INDUCTION AB Previously, we demonstrated that transforming growth factor-beta (TGF-beta) pretreatment protects neuroblastoma cell lines, human hNT neurons, and primary rat embryo hippocampal neurons (REHIPs) from degeneration caused by incubation with beta-amyloid peptide (A beta). Here we present evidence suggesting that TGF-beta interferes with an apoptotic pathway induced by A beta. TGF-beta pretreatment decreases the amount of DNA laddering seen following A beta treatment in neuroblastoma cells, while in REHIPs, TGF-beta decreases the number of positive cells detected in situ by Klenow labelling following A beta treatment. RT-PCR shows that in REHIPs, A beta decreases mRNA expression of Bcl-2, as well as the ratio of Bcl-x(L)/Bcl-x(S), with little effect on Bar expression. These changes are expected to promote apoptosis. When REHIPs are incubated with TGF-beta before addition of A beta, the Bcl-x(L)/Bcl-x(S) ratio and Bcl-2 levels are increased compared to cells treated with A beta alone. Again there is little effect on Bar expression. Western blotting and immunohistochemistry experiments also show that TGF-beta maintains increased levels of Bcl-2 and Bcl-x(L) protein in REHIPs even in the presence of A beta. This pattern of gene expression should function to decrease apoptosis. Similarly, RT-PCR analysis of mRNA prepared from hNT cells shows that TGF-beta pretreatment before addition of A beta maintains a higher level of Bcl-2 expression and an increased Bcl-x(L)/Bcl-x(S) ratio as compared to cells treated with A beta alone. In neuronal cell types treated with A beta, TGF-beta appears to regulate expression of genes in the Bcl-2 family to favor an anti-apoptotic pathway. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NIA, Biochem Lab, Baltimore, MD 21224 USA. RP Flanders, KC (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room C-629,41 Lib Dr MSC 5055, Bethesda, MD 20892 USA. EM flanderk@dce41.nci.nih.gov NR 59 TC 37 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD NOV 20 PY 1998 VL 62 IS 2 BP 122 EP 130 DI 10.1016/S0169-328X(98)00217-4 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 140YK UT WOS:000077115700002 ER PT J AU Cannon, RO AF Cannon, RO TI Potential mechanisms for the effect of angiotensin-converting enzyme inhibitors on endothelial dysfunction: The role of nitric oxide SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Endothelial Function and Cardiovascular Disease - Potential Mechanisms and Interventions, at the Vascular-Biology-Working-Group Meeting CY MAY, 1998 CL UNIV FLORIDA, COLL MED, GAINESVILLE, FLORIDA SP Univ Florida, Coll Med, Vascular Biol Working Grp HO UNIV FLORIDA, COLL MED ID CORONARY-ARTERY DISEASE; ATHEROSCLEROSIS; QUINAPRIL; INCREASES; RELEASE C1 NIH, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NIH, Bldg 10,Room 7B15,10 Ctr Dr MSC 1650, Bethesda, MD 20892 USA. NR 10 TC 5 Z9 5 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 19 PY 1998 VL 82 IS 10A SI SI BP 8S EP 10S DI 10.1016/S0002-9149(98)90422-2 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 150YP UT WOS:000077693900005 PM 9860347 ER PT J AU Quyyumi, AA AF Quyyumi, AA TI Effects of aspirin on endothelial dysfunction in atherosclerosis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Endothelial Function and Cardiovascular Disease - Potential Mechanisms and Interventions, at the Vascular-Biology-Working-Group Meeting CY MAY, 1998 CL UNIV FLORIDA, COLL MED, GAINESVILLE, FLORIDA SP Univ Florida, Coll Med, Vascular Biol Working Grp HO UNIV FLORIDA, COLL MED ID DEPENDENT RESPONSES; HEART-FAILURE; ACETYLCHOLINE; VASODILATION; HYPERTENSION C1 NIH, Cardiac Catheterizat Lab, Bethesda, MD 20892 USA. RP Quyyumi, AA (reprint author), NIH, Cardiac Catheterizat Lab, Bldg 10,Room 7B15, Bethesda, MD 20892 USA. NR 11 TC 6 Z9 6 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 19 PY 1998 VL 82 IS 10A SI SI BP 31S EP 33S DI 10.1016/S0002-9149(98)90429-5 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 150YP UT WOS:000077693900017 PM 9860354 ER PT J AU Klena, JD Gray, SA Konkel, ME AF Klena, JD Gray, SA Konkel, ME TI Cloning, sequencing, and characterization of the lipopolysaccharide biosynthetic enzyme heptosyltransferase I gene (waaC) from Campylobacter jejuni and Campylobacter coli SO GENE LA English DT Article DE enteric pathogen; heptosyltransferase I; recombinant DNA ID GUILLAIN-BARRE-SYNDROME; SALMONELLA-TYPHIMURIUM; POLYACRYLAMIDE GELS; RFAC GENE; K-12; OLIGOSACCHARIDE; MUTANTS AB Campylobacter jejuni and Campylobacter coli ae common causes of gastrointestinal disease and a proportion of C. jejuni infections have been shown to be associated with the Guillain-Barre syndrome. The waaC gene from Campylobacter coli, involved in lipopolysaccharide core biosynthesis, was cloned by complementation of a heptose-deficient strain of Salmonella typhimurium, as judged by novobiocin sensitivity, lipopolysaccharide (LPS)-specific phage sensitivity, and polyacrylamide-resolved lipopolysaccharide profiles. The C. jejuni waaC gene was subsequently cloned using the waaC gene isolated from C. coli as a probe. The C. jejuni and C. coli waaC gens are capable of encoding proteins of 342 amino acids with calculated molecular masses of 39 381 Da and 39 317 Da, respectively. Sequence and in-vitro analyses suggested that the C. coli waaC gene may be transcribed from its own promoter. Translation of the C. coli waaC gene in a cell-free system yielded a protein with a M-r of 39 000. The waaC gene was detected in every C. jejuni and C. coli isolate tested as judged by dot-blot hybridization analysis. Southern hybridization analysis indicated that both Campylobacter species contain a single copy of the waaC gene. Unlike Escherichia coli and S. typhimurium isolates, the waaC gene in C. jejuni and C. coli isolates does not appear to be linked to the waaF (rfaF) gene. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, Hamilton, MT 59840 USA. Univ Canterbury, Dept Plant & Microbial Sci, Christchurch 1, New Zealand. RP Konkel, ME (reprint author), Washington State Univ, Dept Microbiol, Pullman, WA 99164 USA. NR 26 TC 20 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 19 PY 1998 VL 222 IS 2 BP 177 EP 185 DI 10.1016/S0378-1119(98)00501-0 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 146UH UT WOS:000077449500004 PM 9831648 ER PT J AU Morell, RJ Kim, HJ Hood, LJ Goforth, L Friderici, K Fisher, R Van Camp, G Berlin, CI Oddoux, C Ostrer, H Keats, B Friedman, TB AF Morell, RJ Kim, HJ Hood, LJ Goforth, L Friderici, K Fisher, R Van Camp, G Berlin, CI Oddoux, C Ostrer, H Keats, B Friedman, TB TI Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID JEWISH POPULATION; HEARING IMPAIRMENT; PREVALENCE; EMISSIONS; FREQUENCY AB Background Mutations in the GJB2 gene cause one form of nonsyndromic recessive deafness. Among Mediterranean Europeans, more than 80 percent of cases of nonsyndromic recessive deafness result from inheritance of the 30delG mutant allele of GJB2. We assessed the contribution of mutations in GJB2 to the prevalence of the condition among Ashkenazi Jews. Methods We tested for mutations in GJB2 in DNA samples from three Ashkenazi Jewish families with nonsyndromic recessive deafness, from Ashkenazi Jewish persons seeking carrier testing for other conditions, and from members of other ethnic groups. The hearing of persons who were heterozygous for mutations in GJB2 was assessed by means of pure-tone audiometry, measurement of middle-ear immittance, and recording of otoacoustic emissions. Results Two frame-shift mutations in GJB2, 167delT and 30delG, were observed in the families with nonsyndromic recessive deafness. In the Ashkenazi Jewish population the prevalence of heterozygosity for 167delT, which is rare in the general population, was 4.03 percent (95 percent confidence interval, 2.5 to 6.0 percent), and for 30delG the prevalence was 0.73 percent (95 percent confidence interval, 0.2 to 1.8 percent). Genetic-linkage analysis showed conservation of the haplotype for 167delT but the existence of several haplotypes for 30delG. Audiologic examination of carriers of the mutant alleles who had normal hearing revealed subtle differences in their otoacoustic emissions, suggesting that the expression of mutations in GJB2 may be semidominant. Conclusions The high frequency of carriers of mutations in GJB2(4.76 percent) predicts a prevalence of 1 deaf person among 1765 people, which may account for the majority of cases of nonsyndromic recessive deafness in the Ashkenazi Jewish population. Conservation of the haplotype flanking the 167delT mutation suggests that this allele has a single origin, whereas the multiple haplotypes with the 30delG mutation suggest that this site is a hot spot for recurrent mutations. (N Engl J Med 1998;339:1500-5.) (C) 1998, Massachusetts Medical Society. C1 NIDCD, Genet Mol Lab, NIH, Rockville, MD 20850 USA. Louisiana State Univ, Med Ctr, Dept Otorhinolaryngol & Biocommun, Kresge Hearing Res Lab, New Orleans, LA USA. Michigan State Univ, Coll Human Med, Dept Pediat & Human Dev, E Lansing, MI 48824 USA. Univ Antwerp, Dept Med Genet, Antwerp, Belgium. NYU Med Ctr, Dept Pediat, Human Genet Program, New York, NY 10016 USA. RP Morell, RJ (reprint author), NIDCD, Genet Mol Lab, NIH, 5 Res Ctr,Rm 2A19, Rockville, MD 20850 USA. RI Van Camp, Guy/F-3386-2013; OI Van Camp, Guy/0000-0001-5105-9000; Morell, Robert/0000-0003-1537-7356 FU NIDCD NIH HHS [Z01 DC 00039-01]; PHS HHS [P0100379] NR 32 TC 348 Z9 378 U1 1 U2 8 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 19 PY 1998 VL 339 IS 21 BP 1500 EP 1505 DI 10.1056/NEJM199811193392103 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 139VT UT WOS:000077051800003 PM 9819448 ER PT J AU Bishop, PC Elwood, PC AF Bishop, PC Elwood, PC TI Chylous effusion in Hodgkin's disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 NIH, Bethesda, MD 20892 USA. RP Bishop, PC (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 19 PY 1998 VL 339 IS 21 BP 1515 EP 1515 DI 10.1056/NEJM199811193392105 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 139VT UT WOS:000077051800005 PM 9819450 ER PT J AU Liang, TJ AF Liang, TJ TI Combination therapy for hepatitis C infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INTERFERON-ALFA; RIBAVIRIN; EFFICACY; METAANALYSIS C1 NIH, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 17 TC 29 Z9 29 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 19 PY 1998 VL 339 IS 21 BP 1549 EP 1550 DI 10.1056/NEJM199811193392112 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 139VT UT WOS:000077051800012 PM 9819457 ER PT J AU Kawahara, A Kobayashi, T Nagata, S AF Kawahara, A Kobayashi, T Nagata, S TI Inhibition of Fas-induced apoptosis by Bcl-2 SO ONCOGENE LA English DT Article DE apoptosis; Bcl-2; caspase; Fas ID SIGNALING COMPLEX DISC; MEDIATED CELL-DEATH; PROTEASE ACTIVATION; T-CELLS; FAMILY; LIGAND; FLICE; REGULATORS; RESISTANCE; EXPRESSION AB Jurkat cells express Fas, and rapidly undergo apoptosis in response to Fas ligand or an agonistic anti-Fas antibody. This apoptotic pathway is mediated by a cascade of caspases, In this report, we show that Fas activation induced the processing of caspase 8 in Jurkat cells with a time frame similar to the activation of caspase 3 and the proteolysis of nuclear proteins. Jurkat cell transformants that overexpress Bcl-2 were partially but not completely resistant to the Fas-induced apoptosis. Little processing of caspase 8 was observed upon Fas activation in these transformants. Furthermore, although caspase 8 was recruited to Fas upon Fas activation in the parental Jurkat cells, the recruitment of caspase 8 to Fas was inhibited in the transformants overexpressing Bcl-2, These results suggest that Bcl-2 inhibits Fas-induced apoptosis by preventing the formation of the death-inducing signaling complex that is composed of Fas, FADD/MORT1, and caspase 8. C1 Osaka Biosci Inst, Osaka 5650874, Japan. Osaka Univ, Sch Med, Dept Genet, Osaka 5650871, Japan. MBL Co Ltd, Ina Labs, Nagano 3960002, Japan. RP Nagata, S (reprint author), NICHHD, Mol Genet Lab, NIH, Bldg 6B,Room 420, Bethesda, MD 20892 USA. NR 38 TC 55 Z9 62 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 19 PY 1998 VL 17 IS 20 BP 2549 EP 2554 DI 10.1038/sj.onc.1202192 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 139YN UT WOS:000077058900001 PM 9840917 ER PT J AU Sheikh, MS Antinore, MJ Huang, Y Fornace, AJ AF Sheikh, MS Antinore, MJ Huang, Y Fornace, AJ TI Ultraviolet-irradiation-induced apoptosis is mediated via ligand independent activation of tumor necrosis factor receptor 1 SO ONCOGENE LA English DT Article DE UV; TNF alpha; caspase cascade; DNA damage ID KAPPA-B ACTIVATION; RADIATION-INDUCED APOPTOSIS; DOMAIN-CONTAINING RECEPTOR; BREAST-CARCINOMA CELLS; DEATH DOMAIN; CYSTEINE PROTEASES; CD95 FAS/APO-1; PROTEIN; LIGHT; TRAIL AB Ultraviolet (UV)-irradiation has been shown to induce jun N-terminal kinase activity via aggregation-mediated activation of tumor necrosis factor receptor 1 (TNFR1) but the role of TNFR1 in mediating UV-induced apoptosis has not been explored. Using p53-null cells, me demonstrate that UV-stimulated ligand independent activation of TNFR1 plays a major role in mediating the apoptotic effects of UV-irradiation. UV-irradiation and TNF alpha acted in a synergistic manner to induce apoptosis, UV-irradiation stimulated the aggregation-mediated activation of TNFR1 which was coupled with activation of caspase 8, the most proximal caspase in TNF alpha signaling pathway, CrmA and the dominant negative versions of FADD, caspase 8 and caspase 10, that block the apoptotic axis of TNFR1 at different levels, also independently inhibited the UV-induced apoptosis, The engagement of the membrane initiated events was specific for UV-irradiation since neither CrmA nor the dominant negative FADD, caspase 8 or caspase 10 blocked the ionizing radiation-induced apoptosis, Cisplatin and melphalan, the UV-mimetic agents known to elicit UV-type DNA damage, also induced apoptosis but differed from UV in that both of the former agents engaged the caspase cascade at a level distal to FADD. Consistent with these findings cisplatin also did not stimulate TNFR1 aggregation. Together these results indicate that DNA damage pel se was not sufficient to activate the membrane TNFR1. Based on our results we propose that the plasma membrane initiated events play a predominant role in mediating UV-irradiation-induced apoptosis and that UV-irradiation appears to engage the apoptotic axis of TNFR1 and perhaps those of other membrane death receptors to transduce its apoptotic signals. C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NIA, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. RP Sheikh, MS (reprint author), NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 38 TC 107 Z9 108 U1 1 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 19 PY 1998 VL 17 IS 20 BP 2555 EP 2563 DI 10.1038/sj.onc.1202292 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 139YN UT WOS:000077058900002 PM 9840918 ER PT J AU Takeoka, H Iehara, N Uematsu-Yanagita, M Abe, H Sunamoto, M Yamada, Y Kita, T Doi, T AF Takeoka, H Iehara, N Uematsu-Yanagita, M Abe, H Sunamoto, M Yamada, Y Kita, T Doi, T TI A multifunctional transcription factor (A1p145) regulates the smooth muscle phenotype in mesangial cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BINDING-PROTEIN; COLLAGEN GENES; GLOMERULAR CELLS; EXPRESSION; DIFFERENTIATION; PROMOTER; DNA; CULTURE; SEQUENCE; ELEMENT AB Alp145, a novel DNA binding protein for type IV collagen gene (COL4), has multiple functions including DNA replication factor C and DNA binding for several other genes. To elucidate the mechanisms underlying the differentiation process of mesangial cells (MCs), we investigated the effects of Alp145 on rat MCs. Cells in the early passages showed a smooth muscle-like phenotype such as low cell turnover, high levels of expression for COL4, and smooth muscle a-actin (SMA). Cells in the late passages lost their phenotype. The amount of binding activity to COL4 promoter was inversely correlated with the level of COL4 mRNA. Introduction of antisense for Alp145 into late passage cells enhanced the levels of mRNA for COL4 and SMA. The levels of proliferating cell nuclear antigen mRNA were also suppressed. These results suggest that Alp145 is a negative transcription factor for COL4 and may be a phenotypic modulator. (C) 1998 Academic Press. C1 Kyoto Univ, Fac Med, Div Artificial Kidneys, Sakyo Ku, Kyoto 606, Japan. Kyoto Univ, Fac Med, Div Clin Bioregulatory Sci,Dept Geriatr Med, Sakyo Ku, Kyoto 606, Japan. NIDR, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Takeoka, H (reprint author), Kyoto Univ, Fac Med, Div Artificial Kidneys, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 606, Japan. NR 32 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 18 PY 1998 VL 252 IS 2 BP 290 EP 295 DI 10.1006/bbrc.1998.9530 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 141BP UT WOS:000077123000002 PM 9826522 ER PT J AU Ferris, DK Maloid, SC Li, CCH AF Ferris, DK Maloid, SC Li, CCH TI Ubiquitination and proteasome mediated degradation of polo-like kinase SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SACCHAROMYCES-CEREVISIAE CDC5; CELL-CYCLE REGULATION; PROTEIN-KINASE; SERINE/THREONINE KINASE; DROSOPHILA POLO; GENE; PLK; IDENTIFICATION; CLONING; HOMOLOG AB Polo-like kinase (Plk) is a cell cycle-regulated, cyclin-independent serine/threonine protein kinase. Plk protein levels are low or undetectable in terminally differentiated cells and tissues and its expression is strongly correlated with cell growth. Plk protein and enzymatic activity are regulated by multiple mechanisms during cell cycle progression. During G(1) Plk levels are low but increasing amounts of protein are detected during S phase and the highest amounts during G(2)M. Transcription of Plk message is specifically repressed during G(1) but that cannot entirely account for the rapid disappearance of Plk protein at the end of mitosis. In this report we show that Plk protein can be degraded in vitro by partially purified proteasomes and that specific proteasome inhibitors can block Plk protein degradation both in vitro and in vivo. We also detected high molecular weight poly-ubiquitinated forms of Plk by immunoprecipitation and immunoblotting and confirmed that Plk, like other mitotic regulators, is targeted for destruction at the end of mitosis through the ubiquitin-proteasome mediated degradation pathway. C1 NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. RP Ferris, DK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 37 TC 26 Z9 26 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 NOV 18 PY 1998 VL 252 IS 2 BP 340 EP 344 DI 10.1006/bbrc.1998.9648 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 141BP UT WOS:000077123000011 PM 9826531 ER PT J AU Putilina, T Jaworski, C Gentleman, S McDonald, B Kadiri, M Wong, P AF Putilina, T Jaworski, C Gentleman, S McDonald, B Kadiri, M Wong, P TI Analysis of a human cDNA containing a tissue-specific alternatively spliced LIM domain SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN; GENE; HOMEODOMAIN; MOTIF; ZYXIN; ZINC; DIFFERENTIATION; CLONING; ELEGANS AB A unique clone, isolated from a human pancreatic cDNA library, was sequenced and characterized. Northern blot analysis showed that the gene is active in a number of fetal and adult tissues, and immunoblots showed expression in nuclear and cytosolic cell fractions. The gene corresponding to the clone was localized to chromosome 13 by human/rodent somatic cell hybrid panels. The largest open reading frame contains a LIM domain, and the deduced peptide from the open reading frame appears to have the characteristics of a LIM-only protein, designated LMO7. RT-PCR and genomic sequence analyses indicate that expression of this gene product is subject to tissue-specific modulation by elimination of the LIM domain by alternative splicing in neural tissues. (C) 1998 Academic Press. C1 NEI, Retinal Cell & Mol Biol Lab, Natl Inst Hlth, Bethesda, MD USA. Univ Alberta, Dept Sci Biol, Edmonton, AB T6C 2E9, Canada. RP Putilina, T (reprint author), Univ Penn, Inst Environm Med, 1 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA. NR 20 TC 17 Z9 18 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 18 PY 1998 VL 252 IS 2 BP 433 EP 439 DI 10.1006/bbrc.1998.9656 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 141BP UT WOS:000077123000027 PM 9826547 ER PT J AU Pfeifer, A Mark, G Leung, S Dougherty, M Spillare, E Kasid, U AF Pfeifer, A Mark, G Leung, S Dougherty, M Spillare, E Kasid, U TI Effects of c-raf-1 and c-myc expression on radiation response in an in vitro model of human small-cell-lung carcinoma SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CANCER; RAF; LINES; TRANSFORMATION; PROLIFERATION; PROTEIN AB In this study we examined the radiation survival response of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells (BEAS-2B) stably transfected with c-raf-l and/or c-myc. C-raf-l transfectants (2B-raf), and c-raf-l and c-myc double transfectants (2B-raf/myc) were relatively radioresistant compared with c-myc (2B-myc) or control vector transfectants (2B-neo) (2B-raf, D-0 = 2.445 Gy; 2B-raf/myc, D-0 = 2.46 Gy; 2B-myc, D-0 = 1.501 Gy; 2B-neo, D-0 = 2.029 Gy). The steady state level of superoxide dismutase (SOD) mRNA was higher in radioresistant cells (2B-raf and 2B-raf/myc). In addition, 2B-raf but not 2B-raf/myc or 2B-myc transfectants revealed relatively higher number of cells in G2+M phase of the cell cycle. These findings present experimental evidence that Raf-l expression correlates with the radiation-resistant response of 2B-raf or 2B-raf/myc transfectants and suggest a role of SOD in Raf-1-associated radiation resistance. Because 2B-raf transfectants are non-tumorigenic, and double transfectants (2B-raf/myc) are tumorigenic with some phenotypic traits found in small-cell lung carcinomas, our data imply a dissociation between the Raf-l-mediated mechanisms of radiation protection and progression of lung neoplasia. (C) 1998 Academic Press. C1 Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Dept Radiat Med, Washington, DC 20007 USA. NCI, Human Carcinogenesis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. Merck Sharp & Dohme Res Labs, W Point, NJ USA. RP Kasid, U (reprint author), Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Dept Radiat Med, E208 Res Bldg,3970 Reservoir Rd NW, Washington, DC 20007 USA. EM kasidu@gunet.georgetown.edu FU NCI NIH HHS [CA68322, CA58984, P30-CA51008] NR 28 TC 14 Z9 15 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 NOV 18 PY 1998 VL 252 IS 2 BP 481 EP 486 DI 10.1006/bbrc.1998.9660 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 141BP UT WOS:000077123000036 PM 9826556 ER PT J AU Litvan, I AF Litvan, I TI Parkinsonian features - When are they Parkinson disease? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CLINICAL-DIAGNOSIS; ACCURACY C1 Henry M Jackson Fdn, Def & Vet Head Injury Program, Neuropharmacol Unit, Bethesda, MD USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Litvan, I (reprint author), Fed Bldg,Room 714, Bethesda, MD 20892 USA. EM Litvan1@helix.nih.gov OI Litvan, Irene/0000-0002-3485-3445 NR 12 TC 16 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 18 PY 1998 VL 280 IS 19 BP 1654 EP 1655 DI 10.1001/jama.280.19.1654 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 138PD UT WOS:000076980700012 PM 9831984 ER PT J AU Zhang, J Yu, KF AF Zhang, J Yu, KF TI What's the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB Logistic regression is used frequently in cohort studies and clinical trials. When the incidence of an outcome of interest is common in the study population (>10%), the adjusted odds ratio derived from the logistic regression can no longer approximate the risk ratio. The more frequent the outcome, the more the odds ratio overestimates the risk ratio when it is more than 1 or underestimates it when it is less than 1. We propose a simple method to approximate a risk ratio from the adjusted odds ratio and derive an estimate of an association or treatment effect that better represents the true relative risk. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Zhang, J (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. NR 6 TC 1862 Z9 1886 U1 3 U2 39 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 18 PY 1998 VL 280 IS 19 BP 1690 EP 1691 DI 10.1001/jama.280.19.1690 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 138PD UT WOS:000076980700035 PM 9832001 ER PT J AU Gonzalez, FJ Peters, JM Cattley, RC AF Gonzalez, FJ Peters, JM Cattley, RC TI Mechanism of action of the nongenotoxic peroxisome proliferators: Role of che peroxisome proliferator-activated receptor alpha SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID <4-CHLORO-6-(2,3-XYLIDINO)-2-PYRIMIDINYLTHIO>ACETIC ACID WY-14,643; HAMSTER EMBRYO CELLS; LONG-TERM EXPOSURE; PPAR-ALPHA; SYRIAN-HAMSTER; DNA-SYNTHESIS; LIVER DNA; F344 RATS; DI(2-ETHYLHEXYL) PHTHALATE; CHEMICAL CARCINOGENS AB Peroxisome proliferators are a diverse group of chemicals that include several therapeutically used drugs (e.g., hypolipidemic agents), plasticizers and organic solvents used in the chemical industry, herbicides, and naturally occurring hormones. As the name implies, peroxisome proliferators cause an increase in the number and size of peroxisomes in the liver, kidney, and heart tissue of susceptible species, such as rats and mice. Long-term administration of peroxisome proliferators can cause liver cancer in these animals, a response that has been the central issue of research on peroxisome proliferators for many years, Peroxisome proliferators are representative of the class of nongenotoxic carcinogens that cause cancer through mechanisms that do not involve direct DNA damage, The fact that humans are frequently exposed to these agents makes them of particular concern to government regulatory agencies responsible for assuring human safety, Whether frequent exposure to peroxisome proliferators represents a hazard to humans is unknown; however, increased cancer risk has not been shown to be associated with long-term therapeutic administration of the hypolipidemic drugs gemfibrozil, fenofibrate, and clofibrate, To make sound judgments regarding the safety of peroxisome proliferators, the validity of extrapolating results from rodent bioassays to humans must be based on the agents' mechanism of action and species differences in biologic activity and carcinogenicity, The peroxisome proliferator-activated receptor alpha (PPAR alpha), a member of the nuclear receptor superfamily, has been found to mediate the activity of peroxisome proliferators in mice. Gene-knockout mice lacking PPAR alpha are refractory to peroxisome proliferation and peroxisome proliferator-induced changes in gene expression, Furthermore, PPAR alpha-null mice are resistant to hepatocarcinogenesis when fed a diet containing a potent nongenotoxic carcinogen WY-14,643. Recent studies have revealed that humans have considerably lower levels of PPAR alpha in liver than rodents, and this difference may, in part, explain the species differences in the carcinogenic response to peroxisome proliferators. C1 NCI, Bethesda, MD 20892 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. RP Gonzalez, FJ (reprint author), NIH, Bldg 37,Rm 3E-24, Bethesda, MD 20892 USA. RI Peters, Jeffrey/D-8847-2011 NR 77 TC 218 Z9 222 U1 0 U2 6 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 18 PY 1998 VL 90 IS 22 BP 1702 EP 1709 DI 10.1093/jnci/90.22.1702 PG 8 WC Oncology SC Oncology GA 140VC UT WOS:000077108200012 PM 9827524 ER PT J AU Silverman, DT Swanson, CA Gridley, G Wacholder, S Greenberg, RS Brown, LM Hayes, RB Swanson, GM Schoenberg, JB Pottern, LM Schwartz, AC Fraumeni, JF Hoover, RN AF Silverman, DT Swanson, CA Gridley, G Wacholder, S Greenberg, RS Brown, LM Hayes, RB Swanson, GM Schoenberg, JB Pottern, LM Schwartz, AC Fraumeni, JF Hoover, RN TI Dietary and nutritional factors and pancreatic cancer: A case-control study based on direct interviews SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PAST MEDICAL HISTORY; UNITED-STATES; RISK-FACTORS; EXOCRINE PANCREAS; NUTRIENT INTAKE; COFFEE; ALCOHOL; CHOLECYSTOKININ; CARCINOGENESIS; CARCINOMA AB Background: The relationship between diet and pancreatic cancer remains unclear, In this study, we assessed the role of diet and nutrition as risk factors for pancreatic cancer, using data obtained from direct interviews only, rather than data from less reliable interviews with next of kin. We evaluated whether dietary factors could explain the higher incidence of pancreatic cancer experienced by black Americans compared with white Americans. Methods: We conducted a population-based ease-control study of pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and 10 New Jersey counties from August 1986 through April 1989, Reliable dietary histories were obtained for 436 patients and 2003 general-population control subjects aged 30-79 years. Results: Obesity was associated with a statistically significant 50%-60% increased risk of pancreatic cancer that was consistent by sex and race. Although the magnitude of risk associated with obesity was identical in blacks and whites, a higher percentage of blacks mere obese than were whites (women: 38% versus 16%; men: 27% versus 22%), A statistically significant positive trend in risk was observed with increasing caloric intake, with subjects in the highest quartile of calorie intake experiencing a 70% higher risk than those in the lowest quartile, A statistically significant interaction between body mass index (weight in kg/height in m(2) for men and weight in kg/height in m(1.5) for women) and total caloric intake was observed that was consistent by sex and race. Subjects in the highest quartile of both body mass index and caloric intake had a statistically significant 180% higher risk than those in the lowest, quartile, Conclusions: Obesity is a risk factor for pancreatic cancer and appears to contribute to the higher risk of this disease among blacks than among whites in the United States, particularly among women. Furthermore, the interaction between body mass index and caloric intake suggests the importance of energy balance in pancreatic carcinogenesis. C1 NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NIH, Off Director, Bethesda, MD 20892 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. New Jersey State Dept Hlth, Special Epidemiol Program, Trenton, NJ 08625 USA. Allegheny Univ Hlth Sci, MCP Hahnemann Sch Med, Philadelphia, PA 19102 USA. RP Silverman, DT (reprint author), NIH, Div Canc Epidemiol & Genet, Execut Plaza N,Rm 418, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01CP51089, N01CP51090, N01CP51092] NR 59 TC 171 Z9 178 U1 1 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 NOV 18 PY 1998 VL 90 IS 22 BP 1710 EP 1719 DI 10.1093/jnci/90.22.1710 PG 10 WC Oncology SC Oncology GA 140VC UT WOS:000077108200013 PM 9827525 ER PT J AU Shiao, YH Rice, JM Anderson, LM Diwan, BA Hard, GC AF Shiao, YH Rice, JM Anderson, LM Diwan, BA Hard, GC TI von Hippel-Lindau gene mutations in N-nitrosodimethylamine-induced rat renal epithelial tumors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SUPPRESSOR GENE; VHL GENE; SOMATIC MUTATIONS; CELL CARCINOMAS; KIDNEY TUMORS; DIMETHYLNITROSAMINE; CARCINOGENESIS; PERSISTENCE; INDUCTION; INJURY AB Background: Mutations in the von Hippel-Lindau (VHL) gene are common in human clear cell kidney cancers, Carcinogens in cigarette smoke, especially nitrosamines, are known to induce kidney turners of a variety of histologic types in rodents-but, with no evidence of VHL mutations; however, none of these tumors resembled human clear cell carcinomas. We examined N-nitrosodimethylamine-induced kidney tumors of the clear or mixed clear/granular cell type in Wistar rats to assess the presence of VHL mutations. Methods: Sections of eight clear or mixed clear/granular cell kidney tumors that had been formalin fixed and paraffin embedded were microdissected, DNA was extracted from the microdissected tissue, and exons 1-3 of the rat VHL gene were examined by use of polymerase chain reaction and cycle sequencing techniques. Results: Four VHL gene mutations (three G:C to A:T and one A:T to G:C) were detected in three of the tumors in contrast to no mutations in 40 previously reported rat kidney turners of other histologic types (three of eight tumors versus none of 40; two-sided Fisher's exact test; P = .003), Only turners showing prominent swollen clear cell cytology with a signet-ring appearance had VHL mutations. Conclusions: To our knowledge, this is the first report of VHL mutations in kidney tumors after direct chemical exposure and provides a possible molecular pathway linking tobacco smoking to kidney cancer. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. Int Agcy Res Canc, Lyon, France. Amer Hlth Fdn, Valhalla, NY 10595 USA. RP Shiao, YH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Bldg 538,Rm 205, Frederick, MD 21702 USA. EM Shiao@mail.ncifcrf.gov FU NCI NIH HHS [N01CO56000] NR 27 TC 25 Z9 25 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 NOV 18 PY 1998 VL 90 IS 22 BP 1720 EP 1723 DI 10.1093/jnci/90.22.1720 PG 4 WC Oncology SC Oncology GA 140VC UT WOS:000077108200014 PM 9827526 ER PT J AU Zheng, W Gustafson, DR Sinha, R Cerhan, JR Moore, D Hong, CP Anderson, KE Kushi, LH Sellers, TA Folsom, AR AF Zheng, W Gustafson, DR Sinha, R Cerhan, JR Moore, D Hong, CP Anderson, KE Kushi, LH Sellers, TA Folsom, AR TI Well-done meat intake and the risk of breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HETEROCYCLIC AMINES; METABOLIC-ACTIVATION; DIETARY-FAT; NORWEGIAN WOMEN; FOOD MUTAGENS; MAMMARY-GLAND; COOKED FOODS; OLDER WOMEN; FRIED MEAT; FOLLOW-UP AB Background: Heterocyclic amines, mutagens formed in meats cooked at high temperatures, have been demonstrated as mammary carcinogens in animals. We conducted a nested, case-control study among 41 836 cohort members of the Iowa Women's Health Study to evaluate the potential role of heterocyclic amines and intake of well-done meat in the risk fur human breast cancer. Methods: A questionnaire was mailed to individuals in the cohort who had breast cancer diagnosed during the period from 1992 through 1994 and a random sample of cancer-free cohort members to obtain information on usual intake of meats and on meat preparation practices, Color photographs showing various doneness levels of hamburger, beefsteak, and bacon were included, Multivariate analysis was performed on data from 273 ease subjects and 657 control subjects who completed the survey. Results: A dose-response relationship was found between doneness levels of meat consumed and breast cancer risk. The adjusted odds ratios (ORs) for very well-done meat versus rare or medium-done meat were 1.54 (95% confidence interval [CI] = 0.96-2.47) for hamburger, 2.21 (95% CI = 1.30-3.77) for beef steak, and 1.64 (95% CI = 0.92-2.93) for bacon. Women who consumed these three meats consistently very well done had a 4.62 times higher risk (95% CI = 1.36-15.70) than that of women who consumed the meats rare or medium done. Risk of breast cancer was also elevated with increasing intake of well-done to very well-done meat. Conclusions: Consumption of well-done meats and, thus, exposures to heterocyclic amines (or other compounds) formed during high-temperature cooking may play an important role in the risk of breast cancer. C1 Univ S Carolina, Sch Publ Hlth, S Carolina Canc Ctr, Div Epidemiol, Columbia, SC 29203 USA. Natl Canc Inst, Dept Canc Epidemiol & Genet, Bethesda, MD USA. Univ Iowa, Coll Med, Dept Prevent Med & Environm Hlth, Iowa City, IA USA. RP Zheng, W (reprint author), Univ S Carolina, Sch Publ Hlth, S Carolina Canc Ctr, Div Epidemiol, 15 Richland Med Pk 301, Columbia, SC 29203 USA. RI Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Kushi, Lawrence/0000-0001-9136-1175 FU NCI NIH HHS [R01CA39742]; WHI NIH HHS [OWH-284] NR 34 TC 207 Z9 209 U1 0 U2 6 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 18 PY 1998 VL 90 IS 22 BP 1724 EP 1729 DI 10.1093/jnci/90.22.1724 PG 6 WC Oncology SC Oncology GA 140VC UT WOS:000077108200015 PM 9827527 ER PT J AU Sayers, I Cain, SA Swan, JRM Pickett, MA Watt, PJ Holgate, ST Padlan, EA Schuck, P Helm, BA AF Sayers, I Cain, SA Swan, JRM Pickett, MA Watt, PJ Holgate, ST Padlan, EA Schuck, P Helm, BA TI Amino acid residues that influence Fc epsilon RI-mediated effector functions of human immunoglobulin E SO BIOCHEMISTRY LA English DT Article ID HIGH-AFFINITY RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; 3RD CONSTANT DOMAIN; BINDING-SITE; MAST-CELLS; HUMAN IGE; CHAIN FRAGMENT; ESCHERICHIA-COLI; MONOCLONAL-ANTIBODIES; LIGAND-BINDING AB Immunoglobulin E (IgE) mediates its effector functions via the Fc region of the molecule. IgE binding to and subsequent aggregation of the high-affinity receptor (Fc epsilon RI) by allergen plays a pivotal role in type I hypersensitivity responses. Earlier studies implicated the C epsilon 2 and 3 interface and the A-B loop in C epsilon 3 in the IgE-Fc epsilon RI interaction. These regions and glycosylation sites in C epsilon 3 were now targeted by site-specific mutagenesis. IgE binding to Fc epsilon RI was compared with surface plasmon resonance (SPR) measurements, which assessed the binding of the soluble extracellular domain of Fc epsilon RI to IgE. Kinetic analysis based on a pseudo-first-order model agrees with previous determinations. A more refined SPR-based kinetic analysis suggests a biphasic interaction. A model-free empirical analysis, comparing the binding strength and kinetics of native and mutant forms of IgE, identified changes in the kinetics of IgE-Fc epsilon RI interaction. Conservative substitutions introduced into the A-B loop have a small effect on binding, suggesting that the overall conformation of the loop is important for the complementary interaction, but multiple sites across the C epsilon 3 domain may influence IgE-Fc epsilon RI interactions. Asn394 is essential for the generation of a functional IgE molecule in mammalian cells. A role of Pro333 in the maintenance of a constrained conformation at the interface between C epsilon 2-3 emerged by studying the functional consequences of replacing this residue by Ala and Gly. These substitutions cause a dramatic decrease in the ability of the Ligand to mediate stimulus secretion coupling, although only small changes in the association and dissociation rates are observed. Understanding the molecular basis of this phenomenon may provide important information for the design of inhibitors of mast cell degranulation. C1 Univ Sheffield, MBB, Krebs Inst Biomolec Res, Sheffield S10 2UH, S Yorkshire, England. Hlth & Safety Lab, Sheffield, S Yorkshire, England. Univ Southampton, Southampton Gen Hosp, Dept Univ Med, Southampton, Hants, England. Univ Southampton, Southampton Gen Hosp, Dept Mol Microbiol, Southampton, Hants, England. NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. NIH, OD, Bioengn & Phys Sci Program, Bethesda, MD 20892 USA. RP Helm, BA (reprint author), Univ Sheffield, MBB, Krebs Inst Biomolec Res, Sheffield S10 2UH, S Yorkshire, England. EM B.Helm@Sheffield.ac.uk FU Wellcome Trust NR 61 TC 31 Z9 33 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 17 PY 1998 VL 37 IS 46 BP 16152 EP 16164 DI 10.1021/bi981456k PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141AH UT WOS:000077120100014 PM 9819207 ER PT J AU Jaffe, H Veeranna Pant, HC AF Jaffe, H Veeranna Pant, HC TI Characterization of serine and threonine phosphorylation sites in beta-elimination ethanethiol addition-modified proteins by electrospray tandem mass spectrometry and database searching SO BIOCHEMISTRY LA English DT Article ID PHOSPHOSERINE-CONTAINING PEPTIDES; AMINO-ACID-SEQUENCES; S-ETHYLCYSTEINE; POSTTRANSLATIONAL MODIFICATION; NEUROFILAMENT PROTEINS; LIQUID-CHROMATOGRAPHY; NF-H; IDENTIFICATION; SUBUNIT; KINASE AB A new method for the characterization of serine and threonine phosphorylation sites in proteins has been developed. After modification of a phosphoprotein by beta-elimination/ethanethiol addition and conversion of phosphoserine and phosphothreonine residues to S-ethylcysteinyl or beta-methyl-S-ethylcysteinyl residues, the modified protein was subjected to proteolytic digestion. Resulting digests were analyzed by a combination of microbore liquid chromatography, electrospray ionization tandem (MS/MS) ion trap mass spectrometry and database searching to identify original phosphorylated residues. The computer program utilized (SEQUEST) is capable of identifying peptides and modified residues from uninterpreted MS/MS spectra, and using this method, all of the five known phosphorylation sites in bovine beta-casein were identified. Application of the method to multiply phosphorylated human high molecular weight neurofilament protein (NF-H) resulted in the identification of 21 peptides and their modified residues and hence, the in vivo phosphorylation sites. These included 26 KSP and 1 KTP site, all of which occur in the KSP repeat C-terminal tail domain (residues 502-823). One site at residue 518 was previously uncharacterized. A novel non-KSP serine at residue 421 near the KLLEGEE region in a IPFSLPE motif was characterized as phosphorylated (or glycosylated). The 27 characterized phosphorylation sites occur at S/TP residues in the following motifs: KSPVKEE, KSPAEAK, KSPEKEE, KSPAEVK, KSPEKAK, KSPPEAK, KSPVKAE, and KTPAKEE. On the basis of kinase consensus sequences, all of these motifs, including the previously unreported KTPAKEE motif, can be phosphorylated by proline-directed kinases. Advantages of the new method vis-a-vis our previously reported method [Jaffe, H,, Veeranna, Shetty, K. T., and Pant, H. C. (1998) Biochemistry 37, 3931-3940] include (i) production of diastereomers eluting at different retention times increased the chances of peptide identification, (ii) increased hydrophobicity and hence retention time of the modified peptides, (iii) facilitation of positive ion production, and (iv) increased susceptibility to tryptic digestion as a result of conversion of negatively charged phosphorylated residues to neutral S-ethylcysteine or beta-methyl-S-ethylcysteine residues. C1 NINDS, Protein Peptide Sequencing Fac, LNC, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Jaffe, H (reprint author), NINDS, Protein Peptide Sequencing Fac, LNC, NIH, Bethesda, MD 20892 USA. NR 43 TC 97 Z9 103 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 17 PY 1998 VL 37 IS 46 BP 16211 EP 16224 DI 10.1021/bi981264p PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141AH UT WOS:000077120100020 PM 9819213 ER PT J AU Hafkemeyer, P Dey, S Ambudkar, SV Hrycyna, CA Pastan, I Gottesman, MM AF Hafkemeyer, P Dey, S Ambudkar, SV Hrycyna, CA Pastan, I Gottesman, MM TI Contribution to substrate specificity and transport of nonconserved residues in transmembrane domain 12 of human P-glycoprotein SO BIOCHEMISTRY LA English DT Article ID DRUG-RESISTANCE PROFILES; VACCINIA VIRUS; FUNCTIONAL CONSEQUENCES; MULTIDRUG TRANSPORTER; EXPRESSION SYSTEM; MUTATIONS; CELLS; SITES; PROTEINS AB P-glycoprotein (Pgp), the product of the MDR1 gene, confers multidrug resistance on cancer cells by ATP-dependent extrusion of anticancer drugs. Biochemical and genetic studies with Pgp have identified the putative transmembrane (TM) region 12 (residues 974-994) as a major region involved in drug interactions with amino acid residues conserved among Pgp family members shown to be essential for transport. To determine whether nonconserved residues might be involved in substrate specificity, seven amino acid residues were identified within TM 12 that were not strictly conserved among the MDR1 and MDR2 family of proteins from different mammalian species. We replaced all seven of these amino acid residues with alanine, one at a time and in combinations, and used a vaccinia virus based transient expression system to analyze function. None of the single replacements caused any alteration in transport function. However, when residues L975, V981, and F983 were replaced collectively, drug transport, drug-stimulated ATP hydrolysis, and photoaffinity labeling with the drug analogue, [I-125]iodoarylazidoprazosin (IAAP), were abrogated, with Little effect on [alpha-P-32]-8-azido-ATP labeling and basal ATPase activity. Pairwise alanine substitutuions showed variable effects on function. Substitutions including L975A in combination with any one of the other two replacements had the least effect on Pgp function. The V981A and F983A double mutant showed the most effect on transport of fluorescent substrates. In contrast, alanine substitutions of all four nonconserved residues M986, V988, Q990, and V991 at the putative carboxy-terminal half of TM 12 showed no effect on drug transport except for a partial reduction in bodipy-verapamil extrusion. These results suggest that nonconserved residues in the putative amino-proximal half of TM 12 of Pgp play a more direct role in determining specificity of drug transport function than those in the putative carboxy-terminal half of TM 12. C1 NCI, Labs Cell Bio & Mol Biol, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Labs Cell Bio & Mol Biol, Div Basic Sci, NIH, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Ambudkar, Suresh/B-5964-2008 NR 27 TC 69 Z9 71 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 NOV 17 PY 1998 VL 37 IS 46 BP 16400 EP 16409 DI 10.1021/bi980871+ PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141AH UT WOS:000077120100039 PM 9819232 ER PT J AU Thomas, JB Mascarella, SW Burgess, JP Xu, H McCullough, KB Rothman, RB Flippen-Anderson, JL George, CF Cantrell, BE Zimmerman, DM Carroll, FY AF Thomas, JB Mascarella, SW Burgess, JP Xu, H McCullough, KB Rothman, RB Flippen-Anderson, JL George, CF Cantrell, BE Zimmerman, DM Carroll, FY TI N-substituted octahydro-4a-(3-hydroxyphenyl)-10a-methylbenzo[g]isoquinolines are opioid receptor pure antagonists SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article AB N-Methyl- and N-phenylethyl-(+/-)-1,2,3,4,4a,5,10,10a-octahydro-4a-(3-hydroxyphenyl)-10a-methyl- benzo[g]isoquinolines (4 and 5, respectively) were found to be pure opioid antagonists. These compounds were shown to share many of the characteristics identified with the N-methyl- and N-phenylethyl trans-3,4-dimethyl-4(3-hydroxyphenyl)piperidine (1 and 2, respectively) including N-substituent mediated potency and a lack of N-substituent mediated antagonism. These data suggest that compounds 4 and 5 and the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines (1 and 2) may interact with opioid receptors similarly. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIDA, Addict Res Sect, Clin Psychopharmacol, Baltimore, MD 21224 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Carroll, FY (reprint author), Res Triangle Inst, POB 12194, Res Triangle Pk, NC 27709 USA. FU NIDA NIH HHS [DA09045] NR 8 TC 5 Z9 5 U1 0 U2 0 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 NOV 17 PY 1998 VL 8 IS 22 BP 3149 EP 3152 DI 10.1016/S0960-894X(98)00576-9 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 155HW UT WOS:000077941800009 PM 9873693 ER PT J AU Cheng, L Mantile, G Pauly, R Nater, C Felici, A Monticone, R Bilato, C Gluzband, YA Crow, MT Stetler-Stevenson, W Capogrossi, MC AF Cheng, L Mantile, G Pauly, R Nater, C Felici, A Monticone, R Bilato, C Gluzband, YA Crow, MT Stetler-Stevenson, W Capogrossi, MC TI Adenovirus-mediated gene transfer of the human tissue inhibitor of metalloproteinase-2 blocks vascular smooth muscle cell invasiveness in vitro and modulates neointimal development in vivo SO CIRCULATION LA English DT Article DE genes; viruses; metalloproteinases; restenosis ID ARTERIAL INJURY; MATRIX METALLOPROTEINASES; IN-VIVO; IV COLLAGENASE; PROLIFERATION; EXPRESSION; GROWTH; MIGRATION; RAT; ACCUMULATION AB Background-Endovascular injury induced by balloon withdrawal leads to the increased activation of matrix metalloproteinases (MMPs) in the vascular wall, allowing smooth muscle cells (SMCs) to digest the surrounding extracellular matrix (ECM) and migrate from the media into the intima. The objective of this study was to examine the effects of a replication-deficient adenovirus carrying the cDNA for human tissue inhibitor of metalloproteinase-2 (AdCMV.hTIMP-2) on SMC function in vitro and neointimal development in the injured rat carotid artery. Methods and Results-Infection of cultured rat aortic SMCs at a multiplicity of infection of 100 with AdCMV.hTIMP-2 resulted in high-level expression of hTIMP-2 mRNA and protein secretion into the medium. Conditioned media (CM) from AdCMV.hTIMP-2-infected but not control virus (AdCMV.null or AdCMV.beta gal)-infected SMCs inhibited MMP-2 activity on gelatin zymograms as well as the chemoattractant-directed migration of SMCs across reconstituted basement membrane proteins in the Boyden chamber assay. In contrast, AdCMV.hTIMP-2 CM had no effect on chemoattractant-directed migration of SMCs occurring in the absence of an ECM barrier or on the proliferation of cultured neointimal SMCs, Delivery of AdCMV.hTIMP-2 (2.5 X 10(9) pfu) to the carotid artery wall at the time of balloon withdrawal injury inhibited SMC migration into the intima by 36% (P < 0.05) at 4 days and neointimal area by 53% (P < 0.01) at 8 days and by 12% (P=NS) at 21 days after injury. AdCMV.hTIMP-2 had no effect on medial area. Conclusions-Adenovirus-mediated hTIMP-2 gene transfer inhibits SMC invasiveness in vitro and in vivo and delays neointimal development after carotid injury. C1 Ist Ricovero & Cura Carattere Sci, Ist Dermopat Immacolata, Lab Patol Vasc, I-00167 Rome, Italy. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Capogrossi, MC (reprint author), Ist Ricovero & Cura Carattere Sci, Ist Dermopat Immacolata, Lab Patol Vasc, Via Monti di Creta 104, I-00167 Rome, Italy. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 33 TC 99 Z9 111 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 17 PY 1998 VL 98 IS 20 BP 2195 EP 2201 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 137YU UT WOS:000076945300014 PM 9815875 ER PT J AU Stratakis, CA AF Stratakis, CA TI Prader-Willi syndrome phenotype in X chromosome anomalies: Evidence for a distinct syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter ID KARYOTYPE; OBESITY C1 NICHD, Unit Genet & Endocrinol, SPE, DEB,NIH, Bethesda, MD 20892 USA. Georgetown Univ, Childrens Med Ctr, Dept Pediat, Washington, DC 20007 USA. RP Stratakis, CA (reprint author), NICHD, Unit Genet & Endocrinol, SPE, DEB,NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC1862, Bethesda, MD 20892 USA. NR 13 TC 5 Z9 5 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 16 PY 1998 VL 80 IS 3 BP 294 EP 295 DI 10.1002/(SICI)1096-8628(19981116)80:3<294::AID-AJMG24>3.3.CO;2-6 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 140ZG UT WOS:000077117700024 PM 9843058 ER PT J AU Safrany, ST Caffrey, JJ Yang, XN Bembenek, ME Moyer, MB Burkhart, WA Shears, SB AF Safrany, ST Caffrey, JJ Yang, XN Bembenek, ME Moyer, MB Burkhart, WA Shears, SB TI A novel context for the 'MutT' module, a guardian of cell integrity, in a diphosphoinositol polyphosphate phosphohydrolase SO EMBO JOURNAL LA English DT Article DE inositol phosphates; MutT; phosphohydrolase ID ESCHERICHIA-COLI MUTT; INOSITOL HEXAKISPHOSPHATE; IN-VITRO; PHOSPHATES; PURIFICATION; PROTEIN; METABOLISM; MECHANISM; TURNOVER; CLONING AB Diphosphoinositol pentakisphosphate (PP-InsP(5) or 'InsP(7)') and bisdiphosphoinositol tetrakisphosphate ([PP](2)-InsP(4) or 'InsP(8)') are the most highly phosphorylated members of the inositol-based cell signaling family. We have purified a rat hepatic diphosphoinositol polyphosphate phosphohydrolase (DIPP) that cleaves a beta-phosphate from the diphosphate groups in PP-InsP(5) (K-m = 340 nM) and [PP](2)-InsP(4) (K-m = 34 nM). Inositol hexakisphophate (InsP(6)) was not a substrate, but it inhibited metabolism of both [PP](2)-InsP(4) and PP-InsP(5) (IC50 = 0.2 and 3 mu M, respectively). Microsequencing of DIPP revealed a 'MutT' domain, which in other contests guards cellular integrity by dephosphorylating 8-oxo-dGTP, which causes AT to CG transversion mutations. The MutT domain also metabolizes some nucleoside phosphates that may play roles in signal transduction. The rat DIPP MutT domain is conserved in a novel recombinant human uterine DIPP. The nucleotide sequence of the human DIPP cDNA was aligned to chromosome 6; the candidate gene contains at least four exons. The dependence of DIPP's catalytic activity upon its MutT domain was confirmed by mutagenesis of a conserved glutamate residue. DIPP's low molecular size, Mg2+ dependency and catalytic preference for phosphoanhydride bonds are also features of other MutT-type proteins, Because overlapping substrate specificity is a feature of this class of proteins, our data provide new directions for future studies of higher inositol phosphates. C1 NIEHS, Inositide Signaling Grp, NIH, Res Triangle Pk, NC 27709 USA. NEN Life Sci Prod Inc, Boston, MA 02118 USA. Glaxo Wellcome Inc, Res & Dev, Dept Analyt Chem, Res Triangle Pk, NC 27709 USA. RP Safrany, ST (reprint author), NIEHS, Inositide Signaling Grp, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM safrany@niehs.nih.gov NR 36 TC 110 Z9 114 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 16 PY 1998 VL 17 IS 22 BP 6599 EP 6607 DI 10.1093/emboj/17.22.6599 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 145WC UT WOS:000077393700016 PM 9822604 ER PT J AU Ge, H Si, YZ Roeder, RG AF Ge, H Si, YZ Roeder, RG TI Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation SO EMBO JOURNAL LA English DT Article DE coactivators; p52; p75; PC4; transcriptional activation ID RNA-POLYMERASE-II; TATA-BINDING PROTEIN; DNA TOPOISOMERASE-I; DEPENDENT TRANSCRIPTION; PROMOTER SELECTIVITY; GENE-TRANSCRIPTION; PREINITIATION COMPLEX; BASAL TRANSCRIPTION; DOWNSTREAM; YEAST AB Transcriptional activation in human cell-free systems containing RNA polymerase II and general initiation factors requires the action of one or more additional coactivators. Here, we report the isolation of cDNAs encoding two novel human transcriptional coactivators (p52 and p75) that are derived from alternatively spliced products of a single gene and share a region of 325 residues, but show distinct coactivator properties. p52 and p75 both show strong interactions with the VP16 activation domain and several components of the general transcriptional machinery. p52, like the previously described PC4, is a potent broad-specificity coactivator, whereas p75 is less active for most activation domains. These results suggest that p52 is a general transcriptional coactivator that mediates functional interactions between upstream sequence-specific activators and the general transcription apparatus, possibly through a novel mechanism. C1 NICHHD, Mol Embryol Lab, Bethesda, MD 20892 USA. Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. RP Ge, H (reprint author), NICHHD, Mol Embryol Lab, Bethesda, MD 20892 USA. EM geh@box-g.nih.gov NR 66 TC 200 Z9 209 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 16 PY 1998 VL 17 IS 22 BP 6723 EP 6729 DI 10.1093/emboj/17.22.6723 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 145WC UT WOS:000077393700027 PM 9822615 ER PT J AU Velayutham, M Varghese, B Subramanian, S AF Velayutham, M Varghese, B Subramanian, S TI Single-crystal EPR and X-ray studies of magnetic exchange interactions and the molecular structure of Dipropylenetriamineethylenediaminecopper(II) perchlorate, [Cu(dpt)(en)](ClO4)(2) SO INORGANIC CHEMISTRY LA English DT Article ID ELECTRONIC-PROPERTIES; COMPLEXES; COPPER(II); SPECTRA; LIGANDS; CHAINS; CU-2+; ESR AB The monomeric copper complexes [Cu(dpt)(en)](ClO4)(2) (1) and [Zn/Cu(dpt)(en)](ClO4)(2) (2) (dpt = dipropylenetriamine; en = ethylenediamine) were synthesized. The complexes crystallize in space group Pbca with cell parameters a 14.311(5) Angstrom, b = 16.638(2) Angstrom, c = 15.234(4) Angstrom, alpha = beta = gamma = 90 degrees, V = 3627(2) Angstrom(3), and Z = 8. The molecular structure of the complex tends toward trigonal bipyramidal symmetry. Angular, frequency-dependent EPR line widths and line shapes have been studied in detail to estimate the intrastack (J) as well as the interstack (J') exchange interactions. The calculated correlation time t(c) for interchain spin diffusion is 1.2 x 10(-9) s using the dependence of line width at X- and Q- band frequencies. The ratio J'/J = 6 x 10(-2) at 298 K and the line shapes indicate quasi-one-dimensional behavior. The exchange interaction pathway is most probably favored by the perchlorate anion. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Indian Inst Technol, Reg Sophisticated Instrumentat Ctr, Madras 600036, Chennai, India. RP Subramanian, S (reprint author), NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. NR 25 TC 17 Z9 17 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD NOV 16 PY 1998 VL 37 IS 23 BP 5983 EP 5991 DI 10.1021/ic980071n PG 9 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 140EA UT WOS:000077072900005 ER PT J AU Shi, GY Faundez, V Roos, J Dell'Angelica, EC Kelly, RB AF Shi, GY Faundez, V Roos, J Dell'Angelica, EC Kelly, RB TI Neuroendocrine synaptic vesicles are formed in vitro by both clathrin-dependent and clathrin-independent pathways SO JOURNAL OF CELL BIOLOGY LA English DT Article DE synaptic vesicles; clathrin; plasma membrane; PC12 cells; VAMP ID PROTEIN COMPLEX; BREFELDIN-A; MEDIATED ENDOCYTOSIS; TARGETING SIGNAL; COATED VESICLES; PC12 CELLS; MEMBRANE; DYNAMIN; RECEPTOR; COMPARTMENT AB In the neuroendocrine cell line, PC12, synaptic vesicles can be generated from endosomes by a sorting and vesiculation process that requires the heterotetrameric adaptor protein AP3 and a small molecular weight GTPase of the ADP ribosylation factor (ARF) family. We have now discovered a second pathway that sorts the synaptic vesicle-associated membrane protein (VAMP) into similarly sized vesicles. For this pathway the plasma membrane is the precursor rather than endosomes. Both pathways require cytosol and ATP and are inhibited by GTP gamma S. The second pathway, however, uses AP2 instead of AP3 and is brefeldin A insensitive. The AP2-dependent pathway is inhibited by depletion of clathrin or by inhibitors of clathrin binding, whereas the AP3 pathway is not. The VAMP-containing, plasma membrane-derived vesicles can be readily separated on sucrose gradients from transferrin (Tf)-containing vesicles generated by incubating Tf-labeled plasma membrane preparations at 37 degrees C. Dynamin-interacting proteins are required for the AP2-mediated vesiculation from the plasma membrane, but not from endosomes. Thus, VAMP is sorted into small vesicles by AP3 and ARF1 at endosomes and by AP2 and clathrin at the plasma membrane. C1 Univ Calif San Francisco, Hormone Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Kelly, RB (reprint author), Univ Calif San Francisco, Hormone Res Inst, Box 0534,513 Parnassus Ave,1090 HSW, San Francisco, CA 94143 USA. OI Faundez, Victor/0000-0002-2114-5271 FU NIDA NIH HHS [P01 DA010154]; NINDS NIH HHS [NS19878, NS15927, R01 NS015927] NR 45 TC 81 Z9 84 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 16 PY 1998 VL 143 IS 4 BP 947 EP 955 DI 10.1083/jcb.143.4.947 PG 9 WC Cell Biology SC Cell Biology GA 141NJ UT WOS:000077149800007 PM 9817753 ER PT J AU Chen, WJ Jin, WW Wahl, SM AF Chen, WJ Jin, WW Wahl, SM TI Engagement of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) induces transforming growth factor beta (TGF-beta) production by murine CD4(+) T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE CD4(+) T cells; cytotoxic T lymphocyte-associated antigen 4 transforming growth factor beta ID IN-VIVO; NEGATIVE REGULATOR; HELPER-CELLS; ACTIVATION; FACTOR-BETA-1; TGF-BETA-1; TOLERANCE; EFFECTOR; MICE; CD28 AB Evidence indicates that cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) may negatively regulate T cell activation, bur the basis for the inhibitory effect remains unknown. We report here that cross-linking of CTLA-4 induces transforming growth factor beta (TGF-beta) production by murine CD4(+) T cells. CD4(+) T helper type 1 (Th1), Th2, and Th0 clones all secrete TGF-beta after antibody cross-linking of CTLA-4, indicating that induction of TGF-beta by CTLA-4 signaling represents a ubiquitous feature of murine CD4(+) T cells. Stimulation of the CD3-T cell antigen receptor complex does not independently induce TGF-beta, but is required for optimal CTLA-4-mediated TGF-beta production. The consequences of cross-linking of CTLA-4, together with CD3 and CD28, include inhibition of T cell proliferation and interleukin (IL)-2 secretion, as well as suppression of both interferon gamma (Th1) and IL-4 (Th2). Moreover, addition of anti-TGF-beta partially reverses this T cell suppression. When CTLA-4 was cross-linked in T cell populations from TGF-beta 1 gene-deleted (TGF-beta 1(-/-)) mice, the T cell responses were only suppressed 38% compared with 95% in wild-type mice. Our data demonstrate that engagement of CTLA-4 leads to CD4(+) T cell production of TGF-beta, which, in part, contributes to the downregulation of T cell activation. CTLA-4, through TGF-beta, may serve as a counterbalance for CD28 costimulation of IL-2 and CD4(+) T cell activation. C1 NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), NIDR, Oral Infect & Immun Branch, NIH, Bldg 30,Rm 332, Bethesda, MD 20892 USA. EM smwahl@yoda.nidr.nih.gov RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 52 TC 284 Z9 294 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 16 PY 1998 VL 188 IS 10 BP 1849 EP 1857 DI 10.1084/jem.188.10.1849 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 141FL UT WOS:000077132100009 PM 9815262 ER PT J AU Boirivant, M Fuss, IJ Chu, A Strober, W AF Boirivant, M Fuss, IJ Chu, A Strober, W TI Oxazolone colitis: A murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE hapten; inflammation; cytokine; T helper cell type 2; transforming growth factor-beta ID INFLAMMATORY BOWEL-DISEASE; GROWTH-FACTOR-BETA; ALPHA-MUTANT MICE; MYELIN BASIC-PROTEIN; HAPTEN-INDUCED MODEL; CONTACT SENSITIVITY; CROHNS-DISEASE; COLONIC INFLAMMATION; IL-2-DEFICIENT MICE; IMMUNE-RESPONSES AB In this study we describe oxazolone colitis, a new form of experimental colitis. This model is induced in SJL/J mice by the rectal instillation of the haptenating agent, oxazolone, and is characterized by a rapidly developing colitis confined to the distal half of the colon; it consists of a mixed neutrophil/lymphocyte infiltration limited to the superficial layer of the mucosa which is associated with ulceration. Oxazolone colitis is a T helper cell type 2 (Th2)-mediated process since stimulated T cells from lesional tissue produce markedly increased amounts of interleukin (IL)-4 and IL-5; in addition, antr-IL-4 administration leads to a striking amelioration of disease, whereas anti-IL-12 administration either has no effect or exacerbates disease. Finally, this proinflammatory Th2 cytokine response is counterbalanced by a massive transforming growth factor-beta (TGF-beta) response which limits both the extent and duration of disease: lesional (distal) T cells manifest a 20-30-fold increase in TGF-beta production, whereas nonlesional (proximal) T cells manifest an even greater 4-50-fold increase. In addition, anti-TGF-beta administration leads to more severe inflammation which now involves the entire colon. The histologic features and distribution of oxazolone colitis have characteristics that resemble ulcerative colitis (UC) and thus sharply distinguish this model from most other models, which usually resemble Crohn's disease. This feature of oxazolone colitis as well as its cytokine profile have important implications to the pathogenesis and treatment of UC. C1 NIAID, Mucosal Immun Sect, LCI, NIH, Bethesda, MD 20892 USA. Ist Super Sanita, Immunol Lab, I-00161 Rome, Italy. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, LCI, NIH, Bldg 10,Rm 11N238, Bethesda, MD 20892 USA. RI BOIRIVANT, MONICA/B-9977-2016 NR 43 TC 303 Z9 318 U1 3 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 16 PY 1998 VL 188 IS 10 BP 1929 EP 1939 DI 10.1084/jem.188.10.1929 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 141FL UT WOS:000077132100017 PM 9815270 ER PT J AU Belkaid, Y Kamhawi, S Modi, G Valenzuela, J Noben-Trauth, N Rowton, E Ribeiro, J Sacks, DL AF Belkaid, Y Kamhawi, S Modi, G Valenzuela, J Noben-Trauth, N Rowton, E Ribeiro, J Sacks, DL TI Development of a natural model of cutaneous leishmaniasis: Powerful effects of vector saliva and saliva preexposure on the long-term outcome of Leishmania major infection in the mouse ear dermis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE Leishmania major; sand flies; saliva; skin; cytokines ID DELTA T-CELLS; IXODES-RICINUS TICKS; SAND FLY SALIVA; BALB/C MICE; INTERFERON-GAMMA; IMMUNE-RESPONSE; IFN-GAMMA; IN-VIVO; SKIN; EXPRESSION AB We have developed a model of cutaneous leishmaniasis due to Leishmania major that seeks to mimic the natural conditions of infection. 1,000 metacyclic promastigotes were coinoculated with a salivary gland sonicate (SGS) obtained from a natural vector, Phlebotomus payatasii, into the ear dermis of naive mice or of mice preexposed to SGS. The studies reveal a dramatic exacerbating effect of SGS on lesion development in the dermal site, and a complete abrogation of this effect in mice preexposed to salivary components. In both BALB/c and C57B1/6 (B/6) mice, the dermal lesions appeared earlier, were more destructive, and contained greater numbers of parasites after infection ill the presence of SGS. Furthermore, coinoculation of SGS converted B/6 mice into a nonhealing phenotype. No effect of SGS was seen in either IL-4-deficient or in SCID mice. Disease exacerbation in both BALB/c and B/6 mice was associated with an early (6 h) increase in the frequency of epidermal cells producing type 2 cytokines. SGS did not elicit type 2 cytokines in the epidermis of mice previously injected with SGS. These mice made antisaliva antibodies that were able to neutralize the ability of SGS to enhance infection and to elicit IL-4 and IL-5 responses in the epidermis. These results are the first to suggest that for individuals at risk of vector-borne infections, history of exposure to vector saliva, might influence the outcome of exposure to transmitted parasites. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Entomol, Washington, DC 20307 USA. RP Sacks, DL (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Rm 126,Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. RI Rowton, Edgar/A-1975-2011; Rowton, Edgar/A-4474-2012; OI Rowton, Edgar/0000-0002-1979-1485; Ribeiro, Jose/0000-0002-9107-0818 NR 42 TC 269 Z9 275 U1 3 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 16 PY 1998 VL 188 IS 10 BP 1941 EP 1953 DI 10.1084/jem.188.10.1941 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 141FL UT WOS:000077132100018 PM 9815271 ER PT J AU Borlongan, CV Hida, H Nishino, H AF Borlongan, CV Hida, H Nishino, H TI Early assessment of motor dysfunctions aids in successful occlusion of the middle cerebral artery SO NEUROREPORT LA English DT Article DE asymmetrical behaviors; cerebral ischemia; embolism; locomotor deficits; stroke ID BODY SWING TEST; 6-HYDROXYDOPAMINE-INDUCED HEMIPARKINSONISM; NEURAL TRANSPLANTATION; RATS; ISCHEMIA; BEHAVIOR; LESIONS; MODEL; DEATH AB OCCLUSION of the rodent middle cerebral artery by embolism, using an intraluminal filament, produces behavioral alterations which resemble many symptoms associated with stroke. This model has been used to examine treatment interventions for the disease, however, variable success rate in completely blocking the middle cerebral artery may present inconclusive interpretation of the data. To detect successful occlusion of the middle cerebral artery, we demonstrate here sensitive and reliable behavioral parameters including the elevated body swing test, the postural tail-hang test, the spontaneous rotational test, and the forelimb akinesia test. These assays provide a criterion for identifying animals with incomplete occlusion which could promote host-related spontaneous recovery and might confound true effects of experimental therapies on ischemia-induced dysfunctions. From a practical standpoint, the early reliable identification of partial cerebral ischemia aids in immediate and efficient adjustments of the surgical procedure to create a complete and stable ischemia stroke animal model. NeuroReport 9: 3615-3621 (C) 1998 Lippincott Williams & Wilkins. C1 NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Nagoya City Univ, Sch Med, Dept Physiol, Mizuho Ku, Nagoya, Aichi 467, Japan. RP Borlongan, CV (reprint author), NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Borlongan, Cesar/0000-0002-2966-9782 NR 18 TC 49 Z9 51 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 16 PY 1998 VL 9 IS 16 BP 3615 EP 3621 DI 10.1097/00001756-199811160-00012 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 148FE UT WOS:000077493400015 PM 9858369 ER PT J AU Borlongan, CV Tajima, Y Trojanowski, J Lee, VMY Sanberg, PR AF Borlongan, CV Tajima, Y Trojanowski, J Lee, VMY Sanberg, PR TI Cerebral ischemia and CNS transplantation: differential effects of grafted fetal rat striatal cells and human neurons derived from a clonal cell line SO NEUROREPORT LA English DT Article DE fetal cells; hNT neurons; locomotor activity; neural transplantation; striatum; stroke ID PARKINSONS-DISEASE; BRAIN; OCCLUSION; SURVIVE; ARTERY; NUDE AB STROKE mortality has declined over recent decades, prompting a demand for the development of effective rehabilitative therapies for stroke survivors. This effort has been facilitated by significant progress in replicating the behavioral and neuropathological changes of authentic human cerebral ischemia using relevant animal models. Since the rodent model of middle cerebral artery occlusion mimics several motor abnormalities seen in clinical cerebral ischemia, we have utilized this model to investigate treatment strategies for stroke. The present study explored the potential benefits of neural transplantation of fetal rat striatal cells or human neurons derived from a clonal embryonal carcinoma cell line to correct the abnormalities associated with cerebral ischemia. We report here that ischemia-induced behavioral dysfunctions were ameliorated by the neural grafts as early as I month post-transplantation. Of note, transplantation of human neurons induced a significantly more robust recovery than fetal rat striatal grafts. Thus, the logistical and ethical concerns about the use of fetal striatal cells for transplantation therapy can be eliminated by exploiting cell line-derived human neurons as alternative graft sources. Transplantation of human neurons has a therapeutic potential for treatment of behavioral deficits associated with cerebral ischemia. NeuroReport 9: 3703-3709 (C) 1998 Lippincott Williams & Wilkins. C1 NIDA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ S Florida, Coll Med, Dept Surg, Div Neurol Surg,Neurosci Program, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Pharmacol, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Psychiat, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Psychol, Tampa, FL 33612 USA. RP Borlongan, CV (reprint author), NIDA, NIH, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Borlongan, Cesar/0000-0002-2966-9782 NR 30 TC 65 Z9 67 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 16 PY 1998 VL 9 IS 16 BP 3703 EP 3709 DI 10.1097/00001756-199811160-00025 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 148FE UT WOS:000077493400029 PM 9858383 ER PT J AU Knox, SS Siegmund, KD Weidner, G Ellison, RC Adelman, A Paton, C AF Knox, SS Siegmund, KD Weidner, G Ellison, RC Adelman, A Paton, C TI Hostility, social support, and coronary heart disease in the National Heart, Lung, and Blood Institute Family Heart Study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB This cross-sectional study investigated the association of hostility and social support to coronary heart disease (CHD) in 2 groups of men and women: those with a familial predisposition for CHD (high-risk sample) and a randomly selected group. The hypothesis was that hostility and low social support would be associated with CHD, and would have a greater effect in the high-risk group. The random sample contained 2,447 individuals (47.1% male) from 576 families, and the high-risk sample consisted of 2,300 people (45.5% male) from 542 families. Odds ratios (OR) and their 95% confidence intervals were calculated using generalized estimating equations (GEE) for logistic regression. Family was specified as the clustering variable, and robust SEEs were obtained to account for dependence of the data within families, After controling for age, education, body mass index, exercise, smoking history, drinking history, and drinking >5 drinks a day, hostility was associated with a history of coronary bypass surgery or coronary angioplasty in high-risk men (OR 1.21) and a history of myocardial infarction in high-risk women (OR 1.39), High-risk women with high social support had reduced odds of a previous myocardial infarction (OR 0.76), whereas women with high network adequacy in the random sample had reduced risk of myocardial infarction (OR 0.41) and angina (OR 0.49), A ratio of high hostility to law social support was associated with past myocardial infarction in high-risk women (OR 2.47) and a history of angina (OR 2.02) in the random sample men. These results suggest that high hostility and low social support are associated with some manifestations of CHD after controlling for adverse health behaviors. (C) 1998 by Excerpta Medico, Inc. C1 NHLBI, Rockledge Ctr 2, Bethesda, MD 20892 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Washington Univ, Sch Med, St Louis, MO USA. Univ N Carolina, Chapel Hill, NC 27515 USA. RP Knox, SS (reprint author), NHLBI, Rockledge Ctr 2, 6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-25106, N01-HC-25104, N01-HC 25105] NR 8 TC 52 Z9 52 U1 1 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 1998 VL 82 IS 10 BP 1192 EP 1196 DI 10.1016/S0002-9149(98)00599-2 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 139AL UT WOS:000077005200007 PM 9832093 ER PT J AU Callicott, JH Egan, MF Bertolino, A Mattay, VS Langheim, FJP Frank, JA Weinberger, DR AF Callicott, JH Egan, MF Bertolino, A Mattay, VS Langheim, FJP Frank, JA Weinberger, DR TI Hippocampal N-acetyl aspartate in unaffected siblings of patients with schizophrenia: A possible intermediate neurobiological phenotype SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; sibling; spectroscopy; endophenotype; prefrontal; glutamate ID MONOZYGOTIC TWINS DISCORDANT; EYE TRACKING DYSFUNCTION; MAGNETIC-RESONANCE SPECTROSCOPY; GENETICALLY COMPLEX TRAITS; LINKAGE STRATEGIES; CANAVANS-DISEASE; RELATIVES; BRAIN; DISORDERS; DEFICITS AB Background: Shared neurobiological characteristics of patients with schizophrenia and their siblings may represent "intermediate phenotypes" that may more closely reflect the genetic susceptibility underlying this illness. We sought evidence of such phenotypes wing magnetic resonance spectroscopy based on previously described regional abnormalities in levels of the neuronal marker N-acetyl-aspartate (NAA) in the hippocampal area and dorsolateral prefrontal cortex of patients with schizophrenia. Methods: We studied 47 schizophrenics, 60 unaffected siblings, and 66 healthy control subjects with long echo time multislice proton magnetic resonance spectroscopic imaging, primarily measuring NAA, creatine plus phosphocreatine (CRE), and choline-containing compounds. Results: Both patients and their unaffected siblings had significant reductions in hippocampal area NAA/CRE as compared with control subjects. As exploratory analyses, estimates of heritability were performed. Although quantitative correlation of hippocampal NAA between patients and sibs was low (likely reflecting measurement noise), qualitatively defined "low hippocampal NAA/CRE phenotypes" yielded relative risk estimates (lambda(S)) of between 3.8 and 8.8, suggesting this characteristic is heritable. Conclusions: Our finding adds to the evidence that hippocampal abnormalities are associated with schizophrenia and may represent a novel biological phenotype for genetic studies of schizophrenia. Published by Society of Biological Psychiatry. C1 NIH, Lab Diagnost Radiol Res, OIRR, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Neurosci Ctr St Elizabeths,IRP, Washington, DC 20032 USA. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Neurosci Ctr St Elizabeths,IRP, 2700 Martin Luther King Jr Ave SE, Washington, DC 20032 USA. RI Callicott, Joseph/C-9102-2009; Bertolino, Alessandro/O-6352-2016 OI Callicott, Joseph/0000-0003-1298-3334; Bertolino, Alessandro/0000-0002-1251-1380 NR 65 TC 103 Z9 105 U1 1 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 NOV 15 PY 1998 VL 44 IS 10 BP 941 EP 950 DI 10.1016/S0006-3223(98)00264-9 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 137WA UT WOS:000076938700002 PM 9821558 ER PT J AU Nordahl, TE Stein, MB Benkelfat, C Semple, WE Andreason, P Zametkin, A Uhde, TW Cohen, RM AF Nordahl, TE Stein, MB Benkelfat, C Semple, WE Andreason, P Zametkin, A Uhde, TW Cohen, RM TI Regional cerebral metabolic asymmetries replicated in an independent group of patients with panic disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE panic disorder; regional cerebral glucose metabolism; hemispheric asymmetries ID OBSESSIVE-COMPULSIVE DISORDER; POSITRON EMISSION TOMOGRAPHY; GLUCOSE-UTILIZATION; PREFRONTAL CORTEX; BLOOD-FLOW; DEPRESSION; ANXIETY; RATES; ADULTS AB Background: Abnormal left/right (L/R) hemispheric ratios of regional cerebral glucose metabolic rates (rCMRglc) (hippocampus and inferior prefrontal cortex) have been noted in unmedicated panic disorder patients, Methods: An independent group of panic disorder patients placed on imipramine was studied with positron-emission tomography, testing for evidence of normalization versus persistence of the abnormal rCMRglc ratios, Differences in orbital frontal rCMRglc values between the imipramine-treated and the previously reported unmedicated panic disorder patients were tested examining for evidence that the differences would resemble those noted in obsessive-compulsive disorder (OCD) patients treated with clomipramine. Results: We found the same abnormally low UR hippocampal and posterior inferior prefrontal rCMRglc ratios in the imipramine-treated panic disorder patients, In addition, we found posterior orbital frontal rCMRglc decreases in the imipramine-treated panic disorder patients compared with the unmedicated panic disorder patients, Conclusions: These abnormal asymmetries found in unmedicated panic disorder patients and now, in imipramine-treated panic disorder patients may reflect a trait abnormality, The orbital frontal rCMRglc differences between the imipramine-treated and unmedicated patients are similar to changes noted in OCD patients treated with clomipramine and may reflect direct or indirect effects of imipramine treatment in panic disorder patients, (C) 1998 Society of Biological Psychiatry. C1 Univ Calif Berkeley, Lawrence Berkeley Lab, Ctr Funct Imaging, Berkeley, CA 94720 USA. Univ Calif Davis, Med Ctr, Dept Psychiat, Sacramento, CA 95817 USA. Napa State Hosp, Napa, CA USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. McGill Univ, Dept Psychiat, Neurobiol Psychiat Unit, Montreal, PQ, Canada. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. US FDA, Rockville, MD 20857 USA. NIMH, Bethesda, MD 20892 USA. Wayne State Univ, Dept Psychiat, Detroit, MI USA. RP Nordahl, TE (reprint author), Univ Calif Berkeley, Lawrence Berkeley Lab, Ctr Funct Imaging, MS 55-121,1 Cyclotron Rd, Berkeley, CA 94720 USA. RI Nordahl, Thomas/J-7643-2013 OI Nordahl, Thomas/0000-0002-8627-0356 NR 30 TC 50 Z9 53 U1 1 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 NOV 15 PY 1998 VL 44 IS 10 BP 998 EP 1006 DI 10.1016/S0006-3223(98)00026-2 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 137WA UT WOS:000076938700008 PM 9821564 ER PT J AU Kim, AC Lutchman, M Pack, S Zhuang, Z Chishti, AH AF Kim, AC Lutchman, M Pack, S Zhuang, Z Chishti, AH TI Reassignment of the protein 4.1 gene (EPB4.1) to human chromosome 1p36.1, a region frequently deleted in neuroblastomas and meningiomas. SO BLOOD LA English DT Meeting Abstract C1 St Elizabeths Med Ctr, Tumor Cell Biol Lab, Boston, MA USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 9 BP 6A EP 6A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300010 ER PT J AU Kollia, P Stavroyianni, N Stamatopoulos, K Zoi, K Mantzourani, M Paterakis, G Loukopoulos, D Noguchi, CT AF Kollia, P Stavroyianni, N Stamatopoulos, K Zoi, K Mantzourani, M Paterakis, G Loukopoulos, D Noguchi, CT TI Modulation of transferrin receptor expression in K562 erythroleukemic cells by hemin and hydroxyurea: Evidence for transcriptional and post-transcriptional regulation. SO BLOOD LA English DT Meeting Abstract C1 Univ Athens, Dept Med 1, Athens, Greece. NIH, Biol Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3003 BP 6B EP 6B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400017 ER PT J AU Gallagher, PG Sabatino, DE Garrett, LJ Bodine, DM Forget, BG AF Gallagher, PG Sabatino, DE Garrett, LJ Bodine, DM Forget, BG TI Expression of the human ankyrin 1 (Ank1) gene in vitro and in vivo is mediated by a promoter that requires GATA-1 and CACCC-binding proteins for its activity. SO BLOOD LA English DT Meeting Abstract C1 Yale Univ, New Haven, CT USA. NHGRI, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 14 BP 7A EP 7A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300015 ER PT J AU Rivera, CE Wilson, O Hansmann, K Nunez, O Dunn, D AF Rivera, CE Wilson, O Hansmann, K Nunez, O Dunn, D TI Low normal plasma heparin cofactor II levels in paroxysmal nocturnal hemoglobinuria (PNH) patients. SO BLOOD LA English DT Meeting Abstract C1 NIH, Hematol Serv, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3008 BP 7B EP 7B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400022 ER PT J AU Dunn, DE Tanawattanacharoen, P Boccuni, P Nagakura, S Bonilla, L Maung, C Green, S Kirby, MR Rosenfeld, S Young, NS AF Dunn, DE Tanawattanacharoen, P Boccuni, P Nagakura, S Bonilla, L Maung, C Green, S Kirby, MR Rosenfeld, S Young, NS TI Paroxysmal nocturnal hemoglobinuria populations in patients with bone marrow failure: Prevalence, progression, and relationship to immunosuppressive therapy. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3041 BP 15B EP 15B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400055 ER PT J AU Hitt, N Russell, R Wilt, S Holland, S Kleinberg, M AF Hitt, N Russell, R Wilt, S Holland, S Kleinberg, M TI Phagocyte NADPH oxidase-derived reactive oxygen species potentiate ischemia-reperfusion injury. SO BLOOD LA English DT Meeting Abstract C1 Vet Adm Med Ctr, Baltimore, MD 21218 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 50 BP 15A EP 15A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300051 ER PT J AU Giri, N Tisdale, JF Kim, S Caples, M Young, NS Dunbar, CE AF Giri, N Tisdale, JF Kim, S Caples, M Young, NS Dunbar, CE TI Diamond-Blackfan-anemia: in vitro and in vivo assessment of multi lineage hematopoiesis and natural history. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3044 BP 16B EP 16B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400058 ER PT J AU Altarescu, G Kaneski, CR Kreps, C Barton, NW Schiffmann, R AF Altarescu, G Kaneski, CR Kreps, C Barton, NW Schiffmann, R TI The overall response to enzyme replacement therapy (ERT) in type III Gaucher with aggressive systemic disease SO BLOOD LA English DT Meeting Abstract C1 NIH,NINDS, DMNB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 68 BP 19A EP 19A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302975 ER PT J AU Chrobak, P Gress, RE AF Chrobak, P Gress, RE TI Veto activity of activated bone marrow does not require perforin and Fas ligand. SO BLOOD LA English DT Meeting Abstract C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 76 BP 20A EP 21A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121300074 ER PT J AU Otsuki, T Nagakura, S Wang, J Bloom, M Liu, JM AF Otsuki, T Nagakura, S Wang, J Bloom, M Liu, JM TI Tumor necrosis factor-alpha and CD95 ligation suppress erythropoiesis in Fanconi anemia C gene knock-out mice. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3062 BP 20B EP 20B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400076 ER PT J AU Powell, JD Lerner, CG Schwartz, RH AF Powell, JD Lerner, CG Schwartz, RH TI Inhibition of cell cycle progression by rapamycin induces T cell clonal anergy even in the presence of costimulation. SO BLOOD LA English DT Meeting Abstract C1 NIAID, LCMI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 77 BP 21A EP 21A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300075 ER PT J AU Tisdale, JF Dunn, DE Rosenfeld, SE Nunez, O Barrett, AJ Dunbar, CE Young, NS AF Tisdale, JF Dunn, DE Rosenfeld, SE Nunez, O Barrett, AJ Dunbar, CE Young, NS TI A preliminary report on a randomized trial comparing ATG and cyclosporine vs cyclophosphamide and cyclosporine as initial treatment for severe aplastic anemia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3081 BP 24B EP 25B PN 2 PG 2 WC Hematology SC Hematology GA 141AX UT WOS:000077121400095 ER PT J AU Brown, KE Dickstein, B Mat, B Binh, TV Be, TV Young, NS AF Brown, KE Dickstein, B Mat, B Binh, TV Be, TV Young, NS TI Prevalence of a newly described human DNA virus TTV in American and Vietnamese sera. SO BLOOD LA English DT Meeting Abstract C1 Blood Transfus & Hematol Ctr, Ho Chi Minh City, Vietnam. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 202 BP 51A EP 51A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300199 ER PT J AU Stroncek, DF Leitman, SF AF Stroncek, DF Leitman, SF TI Fall in pH accompanies storage of granulocyte colony-stimulating factor (G-CSF)-mobilized granulocyte concentrates. SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 212 BP 53A EP 53A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300209 ER PT J AU Rao, VK Knutsen, T Noll, L Flynn, M Wangsa, D Cole, D Balis, F Steinberg, S Ried, T Schrock, E Sieber, S Bates, S Fojo, T AF Rao, VK Knutsen, T Noll, L Flynn, M Wangsa, D Cole, D Balis, F Steinberg, S Ried, T Schrock, E Sieber, S Bates, S Fojo, T TI Study of chemotherapy induced chromosomal aberrations in Rhesus monkey bone marrows using giemsa staining and Spectral Karyotyping. SO BLOOD LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 293 BP 72A EP 72A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300290 ER PT J AU Rivera, CE Lindstrom, KJ Weil, MK Krizek, DM Williams, S Saunthararajah, Y Rick, ME AF Rivera, CE Lindstrom, KJ Weil, MK Krizek, DM Williams, S Saunthararajah, Y Rick, ME TI Identification of a new mutation in platelet glycoprotein IX (GP IX) in a patient with Bernard Soulier syndrome. SO BLOOD LA English DT Meeting Abstract C1 NIH, Warren Grant Magnuson Clin Ctr, Hematol Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3365 BP 89B EP 89B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400381 ER PT J AU Giri, N Kaushiva, A Wu, T Sellers, SE Tisdale, JF Dunbar, CE AF Giri, N Kaushiva, A Wu, T Sellers, SE Tisdale, JF Dunbar, CE TI The effects of SCF/G-CSF pre-stimulation on radiation sensitivity and engraftment in nonmyeloablated mice. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 456 BP 112A EP 112A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300452 ER PT J AU Childs, R Bahceci, E Clave, E van Rhee, F Jayasekera, D Mayo, G Barrett, J AF Childs, R Bahceci, E Clave, E van Rhee, F Jayasekera, D Mayo, G Barrett, J TI Non-myeloablative allogeneic peripheral blood stem cell transplants (PBSCT) for malignant diseases reduces transplant-related mortality (TRM). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bone Marrow Transplant Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 552 BP 137A EP 137A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300548 ER PT J AU Stroncek, DF Yau, YY Carr, JM Leitman, SF AF Stroncek, DF Yau, YY Carr, JM Leitman, SF TI Blood counts and serum chemistry determinations in granulocyte donors given granulocyte colony-stimulating factor (G-CSF) and dexamethasone (DEX). SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3566 BP 138B EP 138B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400585 ER PT J AU Barrett, AJ Bahceci, E Childs, R van Rhee, F Dunbar, C Young, NS Carter, C Sing, A Jacobs, C Read, EJ AF Barrett, AJ Bahceci, E Childs, R van Rhee, F Dunbar, C Young, NS Carter, C Sing, A Jacobs, C Read, EJ TI Low incidence of GVHD following T depleted peripheral blood stem cell transplant (PBSCT) followed by limited delayed T cell add-back. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bone Marrow Transplant Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 560 BP 139A EP 139A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300556 ER PT J AU Barrett, J Bahceci, E Childs, R Carter, C Read, EJ AF Barrett, J Bahceci, E Childs, R Carter, C Read, EJ TI High CD34+ cell dose lowers relapse risk in standard and high rise recipients of allogeneic bone marrow or peripheral blood stem cell transplants (PBSCT). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bone Marrow Transplant Unit, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 559 BP 139A EP 139A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300555 ER PT J AU Hanazono, Y Heim, D Tisdale, J Giri, N Sellers, S Agricola, B Metzger, M Donahue, R Dunbar, C AF Hanazono, Y Heim, D Tisdale, J Giri, N Sellers, S Agricola, B Metzger, M Donahue, R Dunbar, C TI Equivalent in vivo persistence of progeny of CD34+ cells transduced with expressed versus non-expressed xenogeneic genes, with induction of tolerance to subsequent xenogeneic-gene expressing lymphocytes. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 598 BP 148A EP 149A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121300593 ER PT J AU Kim, HJ Tisdale, JF Wu, T Sellers, S Donahue, RE Brown, KE Dunbar, CE AF Kim, HJ Tisdale, JF Wu, T Sellers, S Donahue, RE Brown, KE Dunbar, CE TI Retroviral integration site analysis indicates that marked myeloid progeny in rhesus monkeys are derived from multiple transduced progenitors. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 597 BP 148A EP 148A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300592 ER PT J AU Blake, T Oates, A Zon, L Adya, N Liu, PP AF Blake, T Oates, A Zon, L Adya, N Liu, PP TI Initial characterization of zebrafish CBFB. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Royal Melbourne Hosp, Ludwig Inst Canc Res, Melbourne, Vic, Australia. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3618 BP 150B EP 150B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400637 ER PT J AU Gubin, AN Njoroge, JM Lee, T Miller, JL AF Gubin, AN Njoroge, JM Lee, T Miller, JL TI Gene expression in erythropoietin stimulated blood cells. SO BLOOD LA English DT Meeting Abstract C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3625 BP 152B EP 152B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400644 ER PT J AU Bendandi, M Gocke, C Kobrin, C Benko, F Sternas, L Watson, TM Reynolds, CW Kwak, LW AF Bendandi, M Gocke, C Kobrin, C Benko, F Sternas, L Watson, TM Reynolds, CW Kwak, LW TI Molecular complete remissions induced by patient-specific vaccination in most patients with follicular lymphoma (FL). SO BLOOD LA English DT Meeting Abstract C1 Penn State Univ, Milton S Hershey Med Ctr, Dept Pathol, Hershey, PA 17033 USA. SAIC, Frederick, MD USA. NCI, Dept Expt Transplantat & Immunol, Med Branch, Div Clin Sci, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 616 BP 153A EP 153A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300611 ER PT J AU Chen, R Nagarajan, S Prince, GM Jambunathan, U Terstappen, LWMM Dunn, DE Lazarus, HM Medof, ME AF Chen, R Nagarajan, S Prince, GM Jambunathan, U Terstappen, LWMM Dunn, DE Lazarus, HM Medof, ME TI PIG-A(+) stem cells in primary PNH exhibit impaired growth and elevated levels of CD95. SO BLOOD LA English DT Meeting Abstract C1 Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. Immunicon, Huntington Valley, PA USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 617 BP 153A EP 153A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300612 ER PT J AU Weiler, SR Gooya, J Smith, MR Tsai, S Collins, SJ Keller, JR AF Weiler, SR Gooya, J Smith, MR Tsai, S Collins, SJ Keller, JR TI D3: A nuclear protein induced during the differentiation of hematopoietic progenitor cells with growth inhibitory properties. SO BLOOD LA English DT Meeting Abstract C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, IRSP,LMI, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3646 BP 156B EP 156B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400665 ER PT J AU Maciejewski, JP Kim, S Sloand, E Selleri, C Rosenfeld, SJ Young, NS AF Maciejewski, JP Kim, S Sloand, E Selleri, C Rosenfeld, SJ Young, NS TI Sustained long-term quantitative defect in the stem cell compartment despite hematologic recovery in patients with aplastic anemia. SO BLOOD LA English DT Meeting Abstract C1 Univ Naples Federico II, Div Hematol, Naples, Italy. NHLBI, Hematol Branch, NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 636 BP 158A EP 158A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300631 ER PT J AU Sloand, E Kim, S Maciejewski, JP Chaudhuri, A Kirby, M Young, NS AF Sloand, E Kim, S Maciejewski, JP Chaudhuri, A Kirby, M Young, NS TI Presence of intracellular interferon-gamma (IFN-gamma) in circulating lymphocytes and response to immunosuppressive therapy in patients with aplastic anemia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 635 BP 158A EP 158A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300630 ER PT J AU Wolk, A Simon-Stoos, K Nami, I Concannon, J Mawe, J Tanawattanacharoen, P Maung, C Dunn, D Young, NS Bloom, M AF Wolk, A Simon-Stoos, K Nami, I Concannon, J Mawe, J Tanawattanacharoen, P Maung, C Dunn, D Young, NS Bloom, M TI A mouse model of immune-mediated aplastic anemia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 639 BP 158A EP 159A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121300634 ER PT J AU Lehmbecher, T Foster, CB Zhu, S Leitman, S Huppi, K Chanock, S AF Lehmbecher, T Foster, CB Zhu, S Leitman, S Huppi, K Chanock, S TI Analysis of biologically significant variant alleles of the low affinity Fc gamma receptor cluster in a healthy population: A foundation for genetic annotation studies that further defines the recently identified SH-FCGR3B as an independent locus. SO BLOOD LA English DT Meeting Abstract C1 NCI, POB, NIH, Bethesda, MD 20892 USA. NCI, LG, DBS, NIH, Bethesda, MD 20892 USA. NIH, DTM, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 655 BP 162A EP 163A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121300650 ER PT J AU Rao, VK Dale, J Marques, A Cohen, J Gutierrez, M Bhatia, K Kingma, D Jaffe, ES Magrath, IT Straus, SE AF Rao, VK Dale, J Marques, A Cohen, J Gutierrez, M Bhatia, K Kingma, D Jaffe, ES Magrath, IT Straus, SE TI The spectrum of chronic active Epstein-Barr virus infection. SO BLOOD LA English DT Meeting Abstract C1 NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 683 BP 169A EP 169A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300679 ER PT J AU Schwartz, GN Yan, X Gress, RE AF Schwartz, GN Yan, X Gress, RE TI GM-CSF, PIXY, and IL-3 pretreatment promotes-increased production of negative regulators from normal donor marrow stromal layers. SO BLOOD LA English DT Meeting Abstract C1 NCI, Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3722 BP 172B EP 172B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400740 ER PT J AU Huhn, RD Read, EJ Rick, M Leitman, SF Kimball, J Gratwohl, A Young, NS Barrett, AJ Dunbar, CE AF Huhn, RD Read, EJ Rick, M Leitman, SF Kimball, J Gratwohl, A Young, NS Barrett, AJ Dunbar, CE TI Intensive immunosuppression with high-dose cyclophosphamide and autologous CD34+ selected hematopoietic cell support for chronic refractory autoimmune thrombocytopenia (interim report). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD USA. NIH, Dept Clin Pathol, Bethesda, MD USA. Univ Basel, Basel, Switzerland. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 719 BP 178A EP 178A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300715 ER PT J AU Azorsa, DO Walker, RL Anzick, SL Trent, JM Meltzer, PS AF Azorsa, DO Walker, RL Anzick, SL Trent, JM Meltzer, PS TI Expression of the steroid receptor co-activator AIB1 in the Burkitt lymphoma cell line Raji. SO BLOOD LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3781 BP 185B EP 185B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400799 ER PT J AU Du, J Xin, F Lekstrom-Himes, JA Xanthopoulos, KG Tenen, DG Yamaguchi, Y Ackerman, SJ AF Du, J Xin, F Lekstrom-Himes, JA Xanthopoulos, KG Tenen, DG Yamaguchi, Y Ackerman, SJ TI Differential activities of C/EBPs in the regulation of eosinophil genes and development. SO BLOOD LA English DT Meeting Abstract C1 Univ Illinois, Coll Med, Chicago, IL USA. NIH, Bethesda, MD 20892 USA. Beth Israel Med Ctr, Boston, MA USA. Kumamoto Univ, Kumamoto, Japan. RI DeKoter, Rodney/A-9415-2009 OI DeKoter, Rodney/0000-0002-9201-1983 NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 775 BP 191A EP 191A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300771 ER PT J AU Saikawa, Y Yue, L Goto, Y Nishimura, R Ichihara, T Koizumi, S Elwood, PC AF Saikawa, Y Yue, L Goto, Y Nishimura, R Ichihara, T Koizumi, S Elwood, PC TI Alteration of the transcriptional factors involved in the a human folate receptor gene expression in transport-defective methotrexate resistant KB cells. SO BLOOD LA English DT Meeting Abstract C1 Kanazawa Univ, Dept Pediat, Kanazawa, Ishikawa 920, Japan. Natl Canc Inst, Med Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3829 BP 194B EP 195B PN 2 PG 2 WC Hematology SC Hematology GA 141AX UT WOS:000077121400847 ER PT J AU Tamm, I Sausville, E Scudiero, DA Reed, JC AF Tamm, I Sausville, E Scudiero, DA Reed, JC TI IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas, Bax, and anticancer drugs. SO BLOOD LA English DT Meeting Abstract C1 Burnham Inst, La Jolla, CA 92037 USA. NCI, Dev Therapeut Program, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 805 BP 198A EP 198A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300801 ER PT J AU Kollia, P Stavroyianni, N Stamatopoulos, K Zoi, K Mantzourani, M Noguchi, CT Yataganas, X Loukopoulos, D AF Kollia, P Stavroyianni, N Stamatopoulos, K Zoi, K Mantzourani, M Noguchi, CT Yataganas, X Loukopoulos, D TI Molecular quantitation of transferrin receptor mRNA transcripts in patients with acute myeloid leukemia at diagnosis. SO BLOOD LA English DT Meeting Abstract C1 Univ Athens, Dept Med 1, Athens, Greece. NIH, Biol Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 3863 BP 202B EP 202B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121400882 ER PT J AU Linnekin, D Mou, S AF Linnekin, D Mou, S TI Lyn is activated during late G(1) of stem cell factor-induced cell cycle progression in hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 SAIC, IRSP, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, DBS, Lab Leukocyte Biol, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 820 BP 202A EP 202A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300816 ER PT J AU Akin, C Kirshenbaum, A Scott, LM Semere, T Metcalfe, DD AF Akin, C Kirshenbaum, A Scott, LM Semere, T Metcalfe, DD TI Demonstration of an activating c-kit mutation in myeloid and lymphoid cells in peripheral blood and bone marrow in mastocytosis. SO BLOOD LA English DT Meeting Abstract C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 857 BP 210A EP 210A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300853 ER PT J AU Adya, N Stacy, T Speck, NA Liu, PP AF Adya, N Stacy, T Speck, NA Liu, PP TI The leukemic protein CBF beta-SMMHC plays a dominant negative role by sequestering CBF alpha 2 into cytoskeletal filaments and aggregates. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, GMBB, NIH, Bethesda, MD USA. Dartmouth Med Sch, Hanover, NH 03756 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 871 BP 214A EP 214A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300867 ER PT J AU Castilla, LH Bodine, DM Garrett, L Liu, PP AF Castilla, LH Bodine, DM Garrett, L Liu, PP TI Leukemia development by the induction of a second "hit" in chimeric mice containing Cbfb-MYH11 ES cells. SO BLOOD LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 873 BP 214A EP 214A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300869 ER PT J AU Wang, J Stacey, MW Kearns, WG Redner, RL Kajigaya, S Liu, JM AF Wang, J Stacey, MW Kearns, WG Redner, RL Kajigaya, S Liu, JM TI ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. CHKD, Norfolk, VA USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 876 BP 215A EP 215A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300872 ER PT J AU Vey, N Kantarjian, H Beran, M O'Brien, S Cortes, J Giles, FJ Cheson, B Arbuck, S Estey, E AF Vey, N Kantarjian, H Beran, M O'Brien, S Cortes, J Giles, FJ Cheson, B Arbuck, S Estey, E TI Phase I study of 9-aminocamptothecin colloidal dispersion formulation in patients with refractory or relapsed acute leukemia. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 962 BP 235A EP 235A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121300958 ER PT J AU Deng, M Ozato, K Daley, GQ AF Deng, M Ozato, K Daley, GQ TI The interferon regulatory factor ICSBP in BCR/ABL transformed hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 4046 BP 243B EP 243B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121401066 ER PT J AU Kantarjian, H O'Brien, S Rios, MB Cortes, J Giles, FJ Gajewski, J Beran, M Kornblau, S Mallard, S Keating, M Cheson, B Murgo, A Talpaz, M AF Kantarjian, H O'Brien, S Rios, MB Cortes, J Giles, FJ Gajewski, J Beran, M Kornblau, S Mallard, S Keating, M Cheson, B Murgo, A Talpaz, M TI Homoharringtonine (HHT) and low-dose cytosine arabinoside (LD-ara-C) is effective and safe for the treatment of Philadelphia chromosome (Ph)-positive late chronic phase (CP) chronic myelogenous leukemia (CML). SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 4056.5 BP 246B EP 246B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121401077 ER PT J AU Rozemuller, H Pastan, I Kreitman, RJ AF Rozemuller, H Pastan, I Kreitman, RJ TI Isolation of a new anti-CD30 scFv from DNA-immunized mice by phage display, and cytotoxic activity of the recombinant immunotoxin produced by fusion with truncated Pseudomonas exotoxin SO BLOOD LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1011 BP 248A EP 248A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301007 ER PT J AU O'Brien, S Kantarjian, H Cortes, J Giles, FJ Beran, M Rios, MB Mallard, S Cheson, B Murgo, A Talpaz, M AF O'Brien, S Kantarjian, H Cortes, J Giles, FJ Beran, M Rios, MB Mallard, S Cheson, B Murgo, A Talpaz, M TI Simultaneous homoharringtonine (HHT) and interferon alpha (IFN-alpha) therapy is an effective regimen in Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). SO BLOOD LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1028 BP 251A EP 251A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301024 ER PT J AU Saunthararajah, Y Caples, M Barrett, AJ AF Saunthararajah, Y Caples, M Barrett, AJ TI ATG induced complete remission in a case of MDS/leukemia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 4092 BP 254B EP 254B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121401114 ER PT J AU Engels, F Koski, G Bedrosian, I Xu, S Nowell, P Cohen, PA Czerniecki, BJ AF Engels, F Koski, G Bedrosian, I Xu, S Nowell, P Cohen, PA Czerniecki, BJ TI Calcium signaling induces acquisition of dendritic cell characteristics in myeloid progenitor cells of patients with chronic myelogenous leukemia. SO BLOOD LA English DT Meeting Abstract C1 NCI, Med Branch, Bethesda, MD 20892 USA. Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Cleveland Clin Fdn, Surg Res Ctr, Cleveland, OH 44195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1044 BP 255A EP 255A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301038 ER PT J AU Gabrea, A Martelli, ML Shou, Y Brents, L Chen, L Schrock, E Ried, T Chesi, M Bergsagel, PL Kuehl, M AF Gabrea, A Martelli, ML Shou, Y Brents, L Chen, L Schrock, E Ried, T Chesi, M Bergsagel, PL Kuehl, M TI Ig translocations in myeloma: Universal, but with numerous nonrandom partners? SO BLOOD LA English DT Meeting Abstract C1 Cornell Univ, Coll Med, New York, NY USA. NCI, Bethesda, MD 20892 USA. NCHGR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1051 BP 256A EP 256A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301045 ER PT J AU Thieblemont, C Quintanilla-Martinez, L Fend, F Kumar, S Phillips, T Blum, L Davies-Hill, T Angonin, R Berger, F Jaffe, ES Raffeld, M AF Thieblemont, C Quintanilla-Martinez, L Fend, F Kumar, S Phillips, T Blum, L Davies-Hill, T Angonin, R Berger, F Jaffe, ES Raffeld, M TI Overexpression of cyclin E and loss of expression of the CDK inhibitor p27(Kip1) are associated with aggressive transformation of chronic lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract C1 NCI, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. Hop Edouard Herriot, Pathol Lab, Lyon, France. Hop Besancon, Besancon, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1058 BP 258A EP 258A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301052 ER PT J AU Shou, Y Gabrea, A Martelli, ML Brents, L Schrock, E Reid, T Bersagel, L Kuehl, M AF Shou, Y Gabrea, A Martelli, ML Brents, L Schrock, E Reid, T Bersagel, L Kuehl, M TI Dysregulation of one c-myc allele in multiple myeloma SO BLOOD LA English DT Meeting Abstract C1 Natl Ctr Genome Res, Bethesda, MD USA. NCI, Bethesda, MD 20892 USA. Cornell Univ, Coll Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1064 BP 259A EP 259A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301058 ER PT J AU Husebekk, A Fellowes, VS Read, EJ Williams, JF Petrus, MJ Gress, RE Fowler, DH AF Husebekk, A Fellowes, VS Read, EJ Williams, JF Petrus, MJ Gress, RE Fowler, DH TI Selection and expansion of T cells that mediate FAS-based lysis of autologous CLL cells. SO BLOOD LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 4200 BP 278B EP 278B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121401223 ER PT J AU Lozier, J Metzger, ME Donahue, RE Morgan, R AF Lozier, J Metzger, ME Donahue, RE Morgan, R TI Expression of human factor IX in rhesus macaques by adenovirus-mediated gene transfer. SO BLOOD LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, NIH, Bethesda, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1215 BP 297A EP 297A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301207 ER PT J AU Takenaka, T Ohshima, T Tworek, DM Murray, GJ Quirk, JM Brady, RO Kulkarni, AB Medin, JA AF Takenaka, T Ohshima, T Tworek, DM Murray, GJ Quirk, JM Brady, RO Kulkarni, AB Medin, JA TI Long-term retroviral-mediated correction in alpha-galactosidase a deficient mice. SO BLOOD LA English DT Meeting Abstract C1 NINDS, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. NIDR, Gene Targeting Res & Core Facil, NIH, Bethesda, MD 20892 USA. Univ Illinois, Hematol Oncol Sect, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1222 BP 298A EP 299A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121301214 ER PT J AU Aoki, Y Jaffe, ES Chang, Y Jones, K Teruya-Feldstein, J Moore, PS Tosato, G AF Aoki, Y Jaffe, ES Chang, Y Jones, K Teruya-Feldstein, J Moore, PS Tosato, G TI Angiogenesis and hematopoiesis induced by KSHV-encoded interleukin-6. SO BLOOD LA English DT Meeting Abstract C1 NCI, Hematopathol Sect, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Columbia Univ, Sch Publ Hlth, Dept Pathol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1238 BP 302A EP 303A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121301230 ER PT J AU Quintanilla-Martinez, L Davies-Hill, T Sorbara, L Jaffe, ES Raffeld, M AF Quintanilla-Martinez, L Davies-Hill, T Sorbara, L Jaffe, ES Raffeld, M TI Loss of detectable p27 protein expression in mantle cell lymphomas (MCL) is a result of its sequestration by cyclin D1: Implications for pathogenesis. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1287 BP 314A EP 314A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301279 ER PT J AU Wellmann, A Thieblemont, C Sakai, A Pittaluga, S Siebert, P Jaffe, ES Raffeld, M AF Wellmann, A Thieblemont, C Sakai, A Pittaluga, S Siebert, P Jaffe, ES Raffeld, M TI Detection of differentially expressed genes in lymphomas using c-DNA array filters: Identification of a diagnostic marker for anaplastic large cell lymphoma. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. Clontech Labs Inc, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1290 BP 314A EP 314A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301282 ER PT J AU Sabatino, DE Peterson, K Cline, AP Garrett, LJ Gallagher, PG Bodine, DM AF Sabatino, DE Peterson, K Cline, AP Garrett, LJ Gallagher, PG Bodine, DM TI Substitution of the beta-spectrin promoter for the A gamma-globin promoter in a YAC construct allows expression of human beta-globin in yolk sac derived red cells in transgenic mice. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Hematopoeisis Sect, GMBB, Bethesda, MD USA. Univ Washington, Seattle, WA 98195 USA. Yale Univ, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1363 BP 332A EP 332A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301355 ER PT J AU Noguchi, CT Smith, D Li, J Smith, R Haley, J Schechter, AN AF Noguchi, CT Smith, D Li, J Smith, R Haley, J Schechter, AN TI Drug discovery for hemoglobinopathies: High-throughput screening and assays for inducers of fetal hemoglobin. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. OSI Pharmaceut Inc, Uniondale, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1374 BP 335A EP 335A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301366 ER PT J AU Childs, R Epperson, D Bahceci, E Clave, E van Rhee, F Jayasekara, D Barrett, J AF Childs, R Epperson, D Bahceci, E Clave, E van Rhee, F Jayasekara, D Barrett, J TI Molecular remission of chronic myelogenous leukemia (CML): Evidence for a graft-versus-leukemia (GVL) effect following non-myeloablative allogeneic peripheral blood stem cell transplant (PBSCT). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 4472 BP 341B EP 341B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121401497 ER PT J AU Liu, WL Wang, M Tang, D ROdgers, GP AF Liu, WL Wang, M Tang, D ROdgers, GP TI Identification and characterization of novel full-length cDNAs differentially expressed in human hematopoietic lineages. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1512 BP 367A EP 367A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301504 ER PT J AU Donahue, RE Rowe, TK Sorrentino, BP Hawley, RG An, DS Chen, ISY Wersto, RP AF Donahue, RE Rowe, TK Sorrentino, BP Hawley, RG An, DS Chen, ISY Wersto, RP TI Transduction kinetics of non-human primate immunoselected CD34(+) cells using retroviral and lentiviral vectors that express the green fluorescent protein. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Rockville, MD USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Univ Calif Los Angeles, Sch Med, AIDS Inst, Los Angeles, CA USA. Toronto Hosp, Toronto, ON M5T 2S8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 4617.5 BP 376B EP 376B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121401644 ER PT J AU Wojda, U Goldsmith, P Miller, JL AF Wojda, U Goldsmith, P Miller, JL TI Gene delivery to biotinylated hematopoietic cells using avidin-polyethylenimine bioconjugates. SO BLOOD LA English DT Meeting Abstract C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 4644 BP 382B EP 382B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121401672 ER PT J AU Donahue, RE An, DS Wersto, RP Agricola, BA Metzger, ME Chen, ISY AF Donahue, RE An, DS Wersto, RP Agricola, BA Metzger, ME Chen, ISY TI Transplantation of immunoselected CD34(+) cells transduced with a EGFP-expressing lentiviral vector in non-human primates. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Rockville, MD USA. Univ Calif Los Angeles, Sch Med, AIDS Inst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 4648.5 BP 383B EP 383B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121401677 ER PT J AU Iwata, M Sugimoto, Y Nunoi, H Malech, HL AF Iwata, M Sugimoto, Y Nunoi, H Malech, HL TI MDR1/p47(phox) bicistronic retrovirus transduction of CD34+ stem cells from patients with p47(phox) deficient chronic granulomatous disease allows full restoration of oxidase function following vincristine selection. SO BLOOD LA English DT Meeting Abstract C1 Kumamoto Univ, Sch Med, Dept Pediat, Kumamoto 860, Japan. Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Tokyo 170, Japan. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 4652 BP 384B EP 384B PN 2 PG 1 WC Hematology SC Hematology GA 141AX UT WOS:000077121401681 ER PT J AU Judde, JG Patel, K Magrath, I AF Judde, JG Patel, K Magrath, I TI Transcriptional activation by the EBV EBNA-1 protein: Role of the P32/TAP cellular protein and identification of two separate transactivating domains. SO BLOOD LA English DT Meeting Abstract C1 NCI, Div Clin Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1584 BP 384A EP 384A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301577 ER PT J AU Nachman, JB Heerema, NA Sather, HN Sensel, MG Lee, MK Lange, BJ Bostrom, B Hutchinson, R Steinherz, PG Gaynon, PS Arthur, DC Uckun, FM AF Nachman, JB Heerema, NA Sather, HN Sensel, MG Lee, MK Lange, BJ Bostrom, B Hutchinson, R Steinherz, PG Gaynon, PS Arthur, DC Uckun, FM TI Hypodiploidy with < 45 chromosomes is associated with poor outcome in childhood acute lymphoblastic leukemia (ALL). SO BLOOD LA English DT Meeting Abstract C1 Univ Chicago, Chicago, IL 60637 USA. Childrens Hlth Care, Minneapolis, MN USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Childrens Hosp, Los Angeles, CA 90027 USA. NIH, Los Angeles, CA USA. Childrens Canc Grp, Arcadia, CA USA. Wayne Hughes Inst, St Paul, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1631 BP 395A EP 395A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301623 ER PT J AU Heerema, NA Sather, HN Sensel, MG Lee, MK Hutchinson, R Lange, BJ Bostrom, B Nachman, JB Steinherz, PG Gaynon, PS Arthur, DC Uckun, FM AF Heerema, NA Sather, HN Sensel, MG Lee, MK Hutchinson, R Lange, BJ Bostrom, B Nachman, JB Steinherz, PG Gaynon, PS Arthur, DC Uckun, FM TI Clinical significance of chromosome arm 12p abnormalities in pediatric acute lymphoblastic leukemia (ALL). SO BLOOD LA English DT Meeting Abstract C1 Wayne Hughes Inst, St Paul, MN USA. Univ Chicago, Chicago, IL 60637 USA. Childrens Hlth Care, Minneapolis, MN USA. Childrens Hosp, Philadelphia, PA 19104 USA. Sloan Kettering Mem Hosp, New York, NY USA. Childrens Hosp, Los Angeles, CA 90027 USA. Childrens Canc Grp, Arcadia, CA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1638 BP 396A EP 397A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121301630 ER PT J AU Heerema, NA Sather, HN Sensel, MG Lee, MK Hutchinson, R Lange, BJ Bostrom, B Nachman, JB Steinherz, PG Gaynon, PS Arthur, DC Uckun, FM AF Heerema, NA Sather, HN Sensel, MG Lee, MK Hutchinson, R Lange, BJ Bostrom, B Nachman, JB Steinherz, PG Gaynon, PS Arthur, DC Uckun, FM TI Clinical significance of deletions of chromosome arm 6q in childhood acute lymphoblastic leukemia (ALL). SO BLOOD LA English DT Meeting Abstract C1 Wayne Hughes Inst, St Paul, MN USA. Univ Chicago, Chicago, IL 60637 USA. Childrens Hlth Care, Minneapolis, MN USA. Childrens Hosp, Philadelphia, PA 19104 USA. Sloan Kettering Mem Hosp, New York, NY USA. Childrens Hosp, Los Angeles, CA 90027 USA. Childrens Canc Grp, Arcadia, CA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1637 BP 396A EP 396A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301629 ER PT J AU Heerema, NA Sather, HN Sensel, MG Liu-Mares, W Hutchinson, R Lange, BJ Bostrom, B Nachman, JB Steinherz, PG Gaynon, PS Arthur, DC Uckun, FM AF Heerema, NA Sather, HN Sensel, MG Liu-Mares, W Hutchinson, R Lange, BJ Bostrom, B Nachman, JB Steinherz, PG Gaynon, PS Arthur, DC Uckun, FM TI Abnormalities of chromosome arm 9p are associated with adverse risk in childhood acute lymphoblastic leukemia (ALL). SO BLOOD LA English DT Meeting Abstract C1 Wayne Hughes Inst, St Paul, MN USA. Univ Chicago, Chicago, IL 60637 USA. Childrens Hlth Care, Minneapolis, MN USA. Childrens Hosp, Philadelphia, PA 19104 USA. Sloan Kettering Mem Hosp, New York, NY USA. Childrens Hosp, Los Angeles, CA 90027 USA. Childrens Canc Grp, Arcadia, CA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1636 BP 396A EP 396A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301628 ER PT J AU Gutierrez, MI Quintanilla-Martinez, L Hussain, A Raffeld, M Magrath, I Bhatia, K AF Gutierrez, MI Quintanilla-Martinez, L Hussain, A Raffeld, M Magrath, I Bhatia, K TI Loss of Bax expression is frequently seen in Burkitt's lymphoma biopsies and may result from null mutations in the Bax gene. SO BLOOD LA English DT Meeting Abstract C1 NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1674 BP 406A EP 406A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301666 ER PT J AU Gutierrez, M Kingma, D Sorbara, L Raffeld, M Jaffe, E Magrath, I Bhatia, K AF Gutierrez, M Kingma, D Sorbara, L Raffeld, M Jaffe, E Magrath, I Bhatia, K TI A molecular profile of strain variations in EBV associated with lymphomas from HIV and non-HIV individuals. SO BLOOD LA English DT Meeting Abstract C1 NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1692 BP 410A EP 410A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301684 ER PT J AU Grillo-Lopez, AJ Cheson, B Horning, S Peterson, B Carter, W Varns, C Shen, D Klippenstein, D AF Grillo-Lopez, AJ Cheson, B Horning, S Peterson, B Carter, W Varns, C Shen, D Klippenstein, D TI Response criteria (RC) for NHL: Importance of "normal" lymph node (LN) size and correlations with response. SO BLOOD LA English DT Meeting Abstract C1 IDEC Pharmaceut, San Diego, CA USA. NCI, Rockville, MD USA. Stanford Univ, Palo Alto, CA USA. Univ Minnesota, Minneapolis, MN USA. San Diego Diagnost Radiol, San Diego, CA USA. Roswell Pk Canc Inst, Buffalo, NY USA. NR 0 TC 6 Z9 6 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1701 BP 412A EP 412A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302976 ER PT J AU Varterasian, M Mohammad, R Shurafa, M Eilender, D Murgo, A Hulburd, K Rodriguez, D Pemberton, P LaGrone, F Manica, B Spadoni, V Al-Katib, A AF Varterasian, M Mohammad, R Shurafa, M Eilender, D Murgo, A Hulburd, K Rodriguez, D Pemberton, P LaGrone, F Manica, B Spadoni, V Al-Katib, A TI Phase II clinical evaluation of bryostatin-1 in patients with relapsed low grade non-Hodgkin's lymphoma (LGL) and CLL. SO BLOOD LA English DT Meeting Abstract C1 Barbara Ann Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. Henry Ford Hosp, Detroit, MI 48202 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1702 BP 412A EP 412A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301693 ER PT J AU Kreitman, RJ Wilson, W Waldmann, TA White, JD Pearson, D Dyer, V Margulies, I Stetler-Stevenson, MA Pastan, I AF Kreitman, RJ Wilson, W Waldmann, TA White, JD Pearson, D Dyer, V Margulies, I Stetler-Stevenson, MA Pastan, I TI Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. SO BLOOD LA English DT Meeting Abstract C1 NCI, Labs Mol Biol & Pathol, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1708 BP 413A EP 413A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301699 ER PT J AU Davis, T Levy, R White, CA Czuczman, M McLaughlin, P Link, B Varns, C Weaver, R Grillo-Lopez, AJ AF Davis, T Levy, R White, CA Czuczman, M McLaughlin, P Link, B Varns, C Weaver, R Grillo-Lopez, AJ TI Rituximab: Phase II (PII) retreatment (ReRx) study in patients (pts) with low-grade or follicular (LG/F) NHL. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, Md Anderson Canc Ctr, Houston, TX USA. Univ Iowa, Iowa City, IA USA. NCI, Rockville, MD USA. Stanford Univ, Palo Alto, CA 94304 USA. Idec Pharmaceut Corp, San Diego, CA USA. Roswell Pk Canc Inst, Buffalo, NY USA. NR 0 TC 10 Z9 10 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1710 BP 414A EP 414A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301702 ER PT J AU Davis, TA White, CA Grillo-Lopez, AJ Velasquez, WS Link, B Maloney, DG Dillman, RO Williams, ME Mohrbacher, A Weaver, R Dowden, S Levy, R AF Davis, TA White, CA Grillo-Lopez, AJ Velasquez, WS Link, B Maloney, DG Dillman, RO Williams, ME Mohrbacher, A Weaver, R Dowden, S Levy, R TI Rituximab: First report of a phase II (PII) trial in NHL patients (pts) with bulky disease. SO BLOOD LA English DT Meeting Abstract C1 NCI, CTEP, Rockville, MD USA. Idec Pharmaceut Corp, San Diego, CA USA. St Louis Univ, Med Ctr, St Louis, MO USA. Univ Iowa, Gen Hosp, Iowa City, IA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22903 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Hoag Ca Ctr, Newport Beach, CA USA. NR 0 TC 10 Z9 10 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1711 BP 414A EP 414A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301703 ER PT J AU Kreitman, RJ Wilson, W Waldmann, TA White, JD Pearson, D Dyer, V Margulies, J Robbins, D Stetler-Stevenson, MA Pastan, I AF Kreitman, RJ Wilson, W Waldmann, TA White, JD Pearson, D Dyer, V Margulies, J Robbins, D Stetler-Stevenson, MA Pastan, I TI Responses in patients with hairy cell leukemia to recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2). SO BLOOD LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1708.5 BP 414A EP 414A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301700 ER PT J AU Williams, JF Petrus, MJ Gress, RE Fowler, DH AF Williams, JF Petrus, MJ Gress, RE Fowler, DH TI Regulation of the fas cytolytic pathway in CLL cells: Differential role of type I vs. type II cytokines. SO BLOOD LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1780 BP 430A EP 430A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301772 ER PT J AU Clave, E Childs, R Jayasekera, D van Rhee, F Bahceci, E Barrett, AJ AF Clave, E Childs, R Jayasekera, D van Rhee, F Bahceci, E Barrett, AJ TI Hematopoietic chimerism predicts relapse in T-cell depleted bone marrow transplantation followed by delayed T cell add-back. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bone Marrow Transplantat Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1801 BP 435A EP 435A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301793 ER PT J AU Read, EJ Vigue, FE Carter, CS Sing, A Jacobs, C Phang, S Barrett, AJ AF Read, EJ Vigue, FE Carter, CS Sing, A Jacobs, C Phang, S Barrett, AJ TI Clinical trial of automated 2-step T cell depletion of peripheral blood progenitor cells for matched related allogeneic transplant. SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. CellPro Inc, Bothell, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1846 BP 446A EP 446A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301837 ER PT J AU Hensel, NF Agarwala, V Barrett, AJ AF Hensel, NF Agarwala, V Barrett, AJ TI Donor anti-recipient helper T cell precursor frequency (HTLPf) and precursor dose are not predictive of acute GVHD (aGVHD) after T cell depleted bone marrow transplant (BMI) with delayed lymphocyte add-back. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1870 BP 452A EP 453A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121301861 ER PT J AU Hakim, FT Cepeda, R Zujewski, J Cowan, K Gress, RE AF Hakim, FT Cepeda, R Zujewski, J Cowan, K Gress, RE TI Long term repopulation of CD4(+) T cells following depletion by chemotherapy is correlated with recovery of CD45RA(+)CD45RO(-) subpopulation. SO BLOOD LA English DT Meeting Abstract C1 NCI, Med Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1872 BP 453A EP 453A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301863 ER PT J AU Barrette, S Orlic, D Anderson, SM Bodine, DM AF Barrette, S Orlic, D Anderson, SM Bodine, DM TI Increased PiT-2 mRNA levels and improved amphotropic retrovirus mediated gene transfer into mouse hematopoietic stem cells after 6 days in-vitro culture in IL-3, IL-6 and SCF. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1931 BP 468A EP 468A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301921 ER PT J AU Turturro, F Seth, P Link, CJ AF Turturro, F Seth, P Link, CJ TI Efficient apoptosis induced by adenoviral vector expressing wild type p53 in a cell line derived from anaplastic large cell lymphoma. SO BLOOD LA English DT Meeting Abstract C1 Iowa Methodist Med Ctr, John Stoddard Canc Ctr, Human Gene Therapy Res Inst, Des Moines, IA USA. Natl Canc Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1936 BP 469A EP 469A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301926 ER PT J AU Gutierrez, MI Hussain, A Zacharchuk, C Cherney, B Magrath, IT Bhatia, K AF Gutierrez, MI Hussain, A Zacharchuk, C Cherney, B Magrath, IT Bhatia, K TI Placement of the proapoptic protein bax in the Fas mediated death pathway in Burkitts lymphomas. SO BLOOD LA English DT Meeting Abstract C1 NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. US FDA, Div Hematol Prod, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 1994 BP 484A EP 484A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121301984 ER PT J AU Wang, M Rodgers, GP AF Wang, M Rodgers, GP TI Identification of gene expression difference in polycythemia vera by differential display. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2012 BP 488A EP 488A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302002 ER PT J AU Byrd, JC Shinn, CA Kanakry, C Ravi, R Willis, CW Drabick, JJ Sausville, E Grever, MR AF Byrd, JC Shinn, CA Kanakry, C Ravi, R Willis, CW Drabick, JJ Sausville, E Grever, MR TI Spicamycin derivative KRN5500 has marked in vitro activity against human B-chronic lymphocytic leukemia (B-CLL) cells concomitent with decreased expression of p27(kip1) and cleavage of caspase-3. SO BLOOD LA English DT Meeting Abstract C1 Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. Johns Hopkins Oncol Ctr, Div Hematol Malignancy, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2023 BP 491A EP 491A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302013 ER PT J AU Foster, CB Lehrnbecher, T Mol, F Steinberg, SM Venzon, DJ Walsh, TJ Noack, D Rae, J Winkelstein, JA Curnutte, JT Chanock, SJ AF Foster, CB Lehrnbecher, T Mol, F Steinberg, SM Venzon, DJ Walsh, TJ Noack, D Rae, J Winkelstein, JA Curnutte, JT Chanock, SJ TI Polymorphisms in host defense molecules influence the risk for immune-mediated complications in chronic granulomatous disease. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD USA. NCI, BDMS, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, La Jolla, CA USA. Genentech Inc, San Francisco, CA 94080 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. RI Venzon, David/B-3078-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2053 BP 498A EP 498A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302043 ER PT J AU Lin, L Corten, L Murthy, KK Corash, L Alter, HJ AF Lin, L Corten, L Murthy, KK Corash, L Alter, HJ TI Photochemical inactivation of hepatitis B (HBV) and hepatitis C (HCV) virus in human platelet concentrates as assessed by a chimpanzee infectivity model. SO BLOOD LA English DT Meeting Abstract C1 Cerus Corp, Concord, CA USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. NIH, Bethesda, MD USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2066 BP 502A EP 502A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302056 ER PT J AU Chaudhuri, A Sloand, E Crapnell, K Zanjani, E St Jeor, S Young, NS Maciejewski, JP AF Chaudhuri, A Sloand, E Crapnell, K Zanjani, E St Jeor, S Young, NS Maciejewski, JP TI Interleukin converting enzyme blockade promotes survival of hematopoietic progenitor and stem cells in serum free conditions due to inhibition of cell death and differentiation. SO BLOOD LA English DT Meeting Abstract C1 Univ Nevada, Sch Med, Dept Microbiol, Va Med Ctr, Reno, NV 89557 USA. Univ Nevada, Sch Med, Dept Internal Med, Va Med Ctr, Reno, NV 89557 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2082 BP 506A EP 506A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302072 ER PT J AU Childs, R Clave, E Bahceci, E Hensel, N Barrett, J AF Childs, R Clave, E Bahceci, E Hensel, N Barrett, J TI Kinetics of engraftment in non-myeloablative allogenic peripheral blood stem cell transplant: An analysis of hematopoietic-lineage chimerism. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Bone Marrow Transplantat Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2137 BP 520A EP 520A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302127 ER PT J AU Hrinczenko, BW Brockner-Ryan, B Alayash, AI Pannell, LK Wojtkowski, T Noguchi, CT Rodgers, GP Schechter, AN AF Hrinczenko, BW Brockner-Ryan, B Alayash, AI Pannell, LK Wojtkowski, T Noguchi, CT Rodgers, GP Schechter, AN TI Selective nitrosylation of the beta-chains of hemoglobin by nitric oxide donor compounds. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2152 BP 524A EP 524A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302142 ER PT J AU Witkowska, HE Asakura, T Tang, D Matsunaga, A Kleman, K Bleibaum, JL Vichinsky, E Lubin, BH Shackleton, CHL Rodgers, GP AF Witkowska, HE Asakura, T Tang, D Matsunaga, A Kleman, K Bleibaum, JL Vichinsky, E Lubin, BH Shackleton, CHL Rodgers, GP TI Compound heterozygote for Hb S and Hb Matsue-Oki alpha 75(EF4)Asp -> Asn presents with a mild sickle cell disease phenotype. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp Oakland, Oakland, CA USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. Roche Biosci, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2154 BP 525A EP 525A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302144 ER PT J AU Smith, RD Li, J Noguchi, CT Schechter, AN AF Smith, RD Li, J Noguchi, CT Schechter, AN TI Real time, quantitative PCR analysis differentiates induction of fetal hemoglobin by butyric acid, hydroxyurea and 5-azacytidine in human primary adult erythroid cells. SO BLOOD LA English DT Meeting Abstract C1 NIH, Lab Chem Biol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2174 BP 530A EP 530A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302164 ER PT J AU Sloand, E Maciejewski, J Kim, S Kumar, P Chaudhuri, A Young, NS AF Sloand, E Maciejewski, J Kim, S Kumar, P Chaudhuri, A Young, NS TI Protease inhibitors increase hematopoiesis in vivo and decrease apoptosis and ice expression in CD34 cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2204 BP 537A EP 537A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302193 ER PT J AU Rivera, CE Mostowski, H Max, EE AF Rivera, CE Mostowski, H Max, EE TI Epstein-Barr virus infection occurs at a high percentage in human IgE producing B lymphocytes. SO BLOOD LA English DT Meeting Abstract C1 NIH, Warren G Magnuson Clin Ctr, Hematol Serv, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2236 BP 544A EP 544A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302225 ER PT J AU Ikonomi, P Rivera, C Schechter, AN Noguchi, CT AF Ikonomi, P Rivera, C Schechter, AN Noguchi, CT TI Overexpression of GATA-2 inhibits erythroid and promotes megakaryocyte differentiation. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, Ctr Clin, NIH, Bethesda, MD USA. NIH, Dept Clin Pathol, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2341 BP 569A EP 569A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302328 ER PT J AU Broudy, VC Lin, NL Liles, WC Mou, S Linnekin, D AF Broudy, VC Lin, NL Liles, WC Mou, S Linnekin, D TI Signaling via the Src family kinase Lyn is required for internalization of the stem cell factor receptor c-Kit. SO BLOOD LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2378 BP 577A EP 577A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302365 ER PT J AU Liu, WL Wang, M Tang, D Rodgers, GP AF Liu, WL Wang, M Tang, D Rodgers, GP TI Thrombopoietin has a differentiative effect on late stage human erythropoiesis. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2390 BP 580A EP 580A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302377 ER PT J AU Goi, K Kurosawa, H Inaba, T Meltzer, PS Look, AT AF Goi, K Kurosawa, H Inaba, T Meltzer, PS Look, AT TI Downstream target genes for E2A-HLF identified by cDNA microarray analysis. SO BLOOD LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Dept Expt Oncol, Memphis, TN 38105 USA. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. Jichi Med Sch, Minami Kawachi, Tochigi 32904, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2432 BP 590A EP 590A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302419 ER PT J AU Berg, PE Fu, S Karp, JE Ross, DD Williams, DM Hankins, WD Behm, F Ruscetti, FW Haga, S AF Berg, PE Fu, S Karp, JE Ross, DD Williams, DM Hankins, WD Behm, F Ruscetti, FW Haga, S TI Overexpression of BP1/Dlx9 in acute myeloid leukemia. SO BLOOD LA English DT Meeting Abstract C1 Univ Maryland, Sch Med, Dept Pediat, Div Human Genet, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. St Jude Childrens Res Hosp, Pediat Oncol Grp, Knoxville, TN USA. NCI, FRDC, Lab Leukocyte Biol, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2488 BP 603A EP 603A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302475 ER PT J AU Findley, HW Nambiar, M Zhou, M Gu, L FitzGerald, DJ Yeager, AM Pastan, I Kreitman, RJ AF Findley, HW Nambiar, M Zhou, M Gu, L FitzGerald, DJ Yeager, AM Pastan, I Kreitman, RJ TI Cytotoxicity of an anti-CD19 disulfide-linked variable region (dsFv) recombinant immunotoxin for CD19+ leukemic cells from pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. SO BLOOD LA English DT Meeting Abstract C1 Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2529 BP 613A EP 613A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302516 ER PT J AU Hall, PD Kreitman, RJ Willingham, MC Frankel, AE AF Hall, PD Kreitman, RJ Willingham, MC Frankel, AE TI DT388-GM-CSF, a fusion toxin targeting the granulocyte-macrophage colony stimulating factor (GM-CSF) receptor, improves survival of SCID mice bearing human acute myeloid leukemia (AML) blasts over ARA-C. SO BLOOD LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Wake Forest Med Sch, Winston Salem, NC USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2535 BP 615A EP 615A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302522 ER PT J AU Kaufmann, SH Svingen, PA Kottke, TJ Sausville, EA Tefferi, A AF Kaufmann, SH Svingen, PA Kottke, TJ Sausville, EA Tefferi, A TI Evaluation of the effect of AG957 (NSC 654705) on chronic myelogenous leukemia cells in vitro. SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin & Mayo Fdn, Dept Med, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Oncol, Rochester, MN 55905 USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2584 BP 627A EP 627A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302571 ER PT J AU Hakim, FT Cepeda, R Gress, R AF Hakim, FT Cepeda, R Gress, R TI Increased susceptibility to apoptosis during recovery of CD4(+) T cell populations following depletion with cytoxan. SO BLOOD LA English DT Meeting Abstract C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2641 BP 640A EP 640A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302628 ER PT J AU Welniak, LA Blazar, BR Longo, DL Murphy, WJ AF Welniak, LA Blazar, BR Longo, DL Murphy, WJ TI Loss of interferon gamma results in protection or acceleration of graft-vs-host disease dependent on the conditioning regimen. SO BLOOD LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN USA. Univ Minnesota, Dept Pediat, BMT Div, Minneapolis, MN USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2647 BP 641A EP 641A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302634 ER PT J AU Nolta, JA Arakawa-Hoyt, J Dao, MA Barsky, L Uribe, L Puck, J Weinberg, K AF Nolta, JA Arakawa-Hoyt, J Dao, MA Barsky, L Uribe, L Puck, J Weinberg, K TI IL-2 responsive human T lymphocytes develop in bnx-hu mice from X-SCID CD34+ progenitors transduced with a normal gamma c gene. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp Los Angeles, Div Immunol Res, BMT, Los Angeles, CA 90027 USA. NCHGR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2746 BP 666A EP 666A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302732 ER PT J AU Licht, T Love, D Hanover, JA Akiyama, SI Gottesman, MM Pastan, I AF Licht, T Love, D Hanover, JA Akiyama, SI Gottesman, MM Pastan, I TI Exclusion of anthracyclines from nuclei of multidrug-resistant cancer cells associated with sequestration in cytoplasmic vesicles. SO BLOOD LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Lab Cell Biol & Biochem, NIH, Bethesda, MD USA. Kagoshima Univ, Inst Canc Res, Kagoshima 890, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2787 BP 676A EP 676A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302773 ER PT J AU Mladenovic, J Sevin, A Chiu, S Pomerantz, R Campbell, TB Bell, D Ambruso, D Wong, R Landay, A Coombs, R Schooley, RT AF Mladenovic, J Sevin, A Chiu, S Pomerantz, R Campbell, TB Bell, D Ambruso, D Wong, R Landay, A Coombs, R Schooley, RT TI Decreased mobilization of CD34+ cells in advanced HIV-1 disease: Results of a multicenter prospective study. SO BLOOD LA English DT Meeting Abstract C1 Univ Colorado, Dept Med, ACTG Study Team 285, Boulder, CO 80309 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. BonFils Blood Ctr, Denver, CO USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Rush Med Coll, Chicago, IL 60612 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2808 BP 681A EP 681A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302794 ER PT J AU Heim, DA Hanazono, Y Childs, R Metzger, M Donahue, RE Dunbar, CE AF Heim, DA Hanazono, Y Childs, R Metzger, M Donahue, RE Dunbar, CE TI In vivo persistence of rhesus monkey lymphocytes transduced with a non-expressing retroviral vector compared to rapid clearance of lymphocytes transduced with a neo-expressing vector. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2833 BP 688A EP 688A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302818 ER PT J AU Wu, T Sellers, SE Kim, HJ Agricola, BA Metzger, ME Donahue, RE Dunbar, CE Tisdale, JF AF Wu, T Sellers, SE Kim, HJ Agricola, BA Metzger, ME Donahue, RE Dunbar, CE Tisdale, JF TI The use of cytokines active on primitive hematopoietic cells and stromal or fibronectin support during transduction improves stable retroviral gene transfer into primate CD34+ hematopoietic cells to clinically relevant levels. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2837 BP 689A EP 689A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302821 ER PT J AU Donahue, RE Wersto, RP Allay, JA Agricola, BA Metzger, ME Persons, DA Nienhuis, AW Sorrentino, BP AF Donahue, RE Wersto, RP Allay, JA Agricola, BA Metzger, ME Persons, DA Nienhuis, AW Sorrentino, BP TI High proportions of circulating leukocytes express a green fluorescent protein-containing retroviral vector in non-human primates transplanted with transduced peripheral blood CD34+ cells. SO BLOOD LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NHLBI, Hematol Branch, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2841 BP 690A EP 691A PN 1 PG 2 WC Hematology SC Hematology GA 141AW UT WOS:000077121302825 ER PT J AU Malech, HL Horwitz, ME Linton, GF Theobald-Whiting, N Brown, MR Farrell, CJ Butz, RE Carter, CS DeCarlo, E Miller, JA Van Epps, DE Read, EJ Fleisher, TA AF Malech, HL Horwitz, ME Linton, GF Theobald-Whiting, N Brown, MR Farrell, CJ Butz, RE Carter, CS DeCarlo, E Miller, JA Van Epps, DE Read, EJ Fleisher, TA TI Extended production of oxidase normal neutrophils in X-linked chronic granulomatous disease (CGD) following gene therapy with gp91(phox) transduced CD34+ cells. SO BLOOD LA English DT Meeting Abstract C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 15 Z9 15 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2839 BP 690A EP 690A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302826 ER PT J AU Otsuki, T Mercurio, F Liu, JM AF Otsuki, T Mercurio, F Liu, JM TI The Fanconi anemia group A gene product is a component of the I kappa B kinase signalsome complex involved in NF-kappa B activation. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, San Diego, CA USA. Signal Pharmaceut, San Diego, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2847 BP 692A EP 692A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302831 ER PT J AU Verbeek, W Gombart, A Lekstrom-Himes, J Xanthopoulos, K Koeffler, HP AF Verbeek, W Gombart, A Lekstrom-Himes, J Xanthopoulos, K Koeffler, HP TI Transcription factor C EBP epsilon is essential for the expression of the precursor protein of the cathelin related antimicrobial peptides 1 and 2 and the bacteriostatic secondary granule protein lactoferrin in neutrophils. SO BLOOD LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Cedars Sinai Med Ctr, Div Hematol, Los Angeles, CA USA. NIH, Lab Human Genome Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2868 BP 697A EP 697A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302852 ER PT J AU Sloand, E Maciejewski, JP Kim, S Young, NS AF Sloand, E Maciejewski, JP Kim, S Young, NS TI Cyclosporin a can inhibit apoptosis of human lymphocytes and affect the balance between T-H1 and T-H2 cells in vivo and in vitro. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2882 BP 701A EP 701A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302869 ER PT J AU Barrett, AJ Molldrem, JJ Saunthrajarian, Y Caples, M Young, NS AF Barrett, AJ Molldrem, JJ Saunthrajarian, Y Caples, M Young, NS TI Prolonged transfusion independence and disease stability in patients with myelodysplastic syndrome (MDS) responding to antithymocyte globulin (ATG). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 4 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2932 BP 713A EP 713A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302916 ER PT J AU Bergsagel, PL Nardini, E Lim, RSC Smith, KD Kuehl, WM Chesi, M AF Bergsagel, PL Nardini, E Lim, RSC Smith, KD Kuehl, WM Chesi, M TI The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSSET, resulting in IgH/MMSET hybrid transcripts. SO BLOOD LA English DT Meeting Abstract C1 Cornell Univ, Coll Med, New York, NY USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2942 BP 716A EP 716A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302930 ER PT J AU Fry, T Christensen, B Mackall, C AF Fry, T Christensen, B Mackall, C TI Restoration of immune responses in T cell depleted hosts by inhibition of programmed cell death. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Div Pediat Oncol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 SU 1 MA 2960 BP 721A EP 721A PN 1 PG 1 WC Hematology SC Hematology GA 141AW UT WOS:000077121302949 ER PT J AU Hisada, M Okayama, A Shioiri, S Spiegelman, DL Stuver, SO Mueller, NE AF Hisada, M Okayama, A Shioiri, S Spiegelman, DL Stuver, SO Mueller, NE TI Risk factors for adult T-cell leukemia among carriers of human T-lymphotropic virus type I SO BLOOD LA English DT Article ID HTLV-I; PROVIRAL DNA; ASYMPTOMATIC CARRIERS; ABNORMAL LYMPHOCYTES; PERIPHERAL-BLOOD; GENE-EXPRESSION; TAX PROTEIN; ANTIBODY; JAPAN; INDIVIDUALS AB The presence of circulating "flower cells" and a low prevalence of antibody to Tax regulatory protein of human T-lymphotropic virus type I (HTLV-I) are characteristics of adult T-cell leukemia (ATL). To examine the predictability of levels of HTLV-I antibodies and of flower cell-like abnormal lymphocytes (Ably) for the risk of AIL among asymptomatic HTLV-I carriers, we prospectively evaluated the levels of viral markers of five HTLV-I carriers who developed ATL and 38 age-, sex-, and screen-matched HTLV-I-positive controls in the Miyazaki Cohort Study. After accounting for matching factors, Ably level was slightly, but not significantly, higher among cases than among controls (P = .13). Anti-HTLV-l (odds ratio [OR] = 1.6 per twofold dilution; 95% confidence interval [CI] 0.94, 3.8) was associated with ATL diagnosis, but antibody to Tax regulatory protein (anti-Tax) was not (OR = 0.78: 95% CI 0.26, 1.7). Anti-Tax level was low for all ATL cases for up to 10 years preceding their diagnosis, independent of the level of anti-HTLV-l titer. HILV-I carriers with a higher anti-HTLV-l titer and a lower anti-Tax reactivity may be at greatest risk of ATL. (C) 1998 by The American Society of Hematology. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Miyazaki Med Sch, Dept Internal Med 2, Miyazaki, Japan. RP Hisada, M (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6130 Execut Blvd,EPN434, Rockville, MD 20852 USA. FU NCI NIH HHS [2RO1-CA38450] NR 34 TC 52 Z9 55 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 BP 3557 EP 3561 PG 5 WC Hematology SC Hematology GA 138GB UT WOS:000076962500008 PM 9808547 ER PT J AU Balis, FM Holcenberg, JS Poplack, DG Ge, J Sather, HN Murphy, RF Ames, MM Waskerwitz, MJ Tubergen, DG Zimm, S Gilchrist, GS Bleyer, WA AF Balis, FM Holcenberg, JS Poplack, DG Ge, J Sather, HN Murphy, RF Ames, MM Waskerwitz, MJ Tubergen, DG Zimm, S Gilchrist, GS Bleyer, WA TI Pharmacokinetics and pharmacodynamics of oral methotrexate and mercaptopurine in children with lower risk acute lymphoblastic leukemia: A joint Children's Cancer Group and Pediatric Oncology Branch Study SO BLOOD LA English DT Article ID 6-MERCAPTOPURINE METABOLITES; MAINTENANCE CHEMOTHERAPY; CHILDHOOD LEUKEMIA; DOSE METHOTREXATE; BIOAVAILABILITY; SERUM; RELAPSE; ASSAY AB We prospectively assessed the pharmacokinetics of methotrexate, mercaptopurine, and erythrocyte thioguanine nucleotide levels in a homogenous population of children with lower risk acute lymphoblastic leukemia and correlated pharmacokinetic parameters with disease outcome. The maintenance therapy regimen included daily oral mercaptopurine (75 mg/m(2)) and weekly oral methotrexate (20 mg/m(2)). One hundred ninety-one methotrexate doses and 190 mercaptopurine doses were monitored in 89 patients. Plasma drug concentrations of both agents were highly variable. The area under the plasma concentration-time curve (AUC) of methotrexate ranged from 0.63 to 12 (mu mol.h/L, and the AUC of mercaptopurine ranged from 0.11 to 8 mu mol.h/L. Drug dose, patient age, and duration of therapy did not account for the variability. Methotrexate AUC was significantly higher in girls than boys (P = .007). There was considerable intrapatient variability for both agents. Erythrocyte thioguanine nucleotide levels were also highly variable (range, 0 to 10 pmol/g Hgb) and did not correlate with mercaptopurine dose or AUG. A Cox regression analysis showed th at mercaptopurine AUC was a marginally significant (P = .0433 predictor of outcome, but a direct comparison of mercaptopurine AUC in the remission and relapsed patient groups failed to show a significant difference. Methotrexate and mercaptopurine plasma concentrations and erythrocyte thioguanine nucleotide levels were highly variable, but measurement of these pharmacokinetic parameters at the start of maintenance will not distinguish patients who are more likely to relapse. This is a US government work. There are no restrictions on its use. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Childrens Canc Grp, Arcadia, CA USA. RP Balis, FM (reprint author), NCI, Pediat Oncol Branch, NIH, Bldg 10,Room 13N240,10 Ctr Dr,MSC 1928, Bethesda, MD 20892 USA. NR 25 TC 63 Z9 65 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 BP 3569 EP 3577 PG 9 WC Hematology SC Hematology GA 138GB UT WOS:000076962500010 PM 9808549 ER PT J AU Mongini, PKA Liu, QY Vilensky, MA Highet, PF Inman, JK AF Mongini, PKA Liu, QY Vilensky, MA Highet, PF Inman, JK TI Evidence for an upper affinity threshold for anti-IgM-induced apoptosis in a human B-cell lymphoma SO BLOOD LA English DT Article ID TYROSINE PHOSPHORYLATION; MONOCLONAL-ANTIBODIES; CROSS-LINKING; LYMPHOCYTES-B; SURFACE-IGM; RECEPTOR OCCUPANCY; CYCLE PROGRESSION; CLONAL EXPANSION; IMMUNOGLOBULIN-E; WEHI-231 CELLS AB The influence of ligand:receptor affinity on B-cell antigen receptor (BCR)-induced apoptosis in the IgM(+) Burkitt lymphoma line, Ramos, was evaluated with a group of affinity-diverse murine monoclonal antibodies (MoAbs) specific for human B-cell IgM. The studies showed not only a minimal affinity threshold for the induction of apoptosis, but, interestingly, also a maximal affinity threshold above which increases in affinity were associated with diminished apoptosis. The lesser capacity of high-affinity MoAb to induce apoptosis was paralleled by a lesser capacity to induce receptor cross-linking. At high ligand concentration, high MoAb affinity was also associated with a diminished capacity to induce early protein tyrosine phosphorylation. The compromised capacity of two high-affinity MoAbs to trigger apoptosis may be, at least in part, explained by two separate phenomena that can impair the formation of mlgM crosslinks: (1) more stable univalent binding and (2) a tendency for monogamous binding of both MoAb Fab to two Fab epitopes on mlgM. These in vitro studies suggest that the use of the highest affinity MoAbs for antireceptor immunotherapies that depend on receptor Cross-linking might, on occasion, be contraindicated. (C) 1998 by The American Society of Hematology. C1 Hosp Joint Dis, Dept Rheumatol, New York, NY 10003 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, Dept Pathol, New York, NY USA. NIH, Immunol Lab, Bethesda, MD 20892 USA. RP Mongini, PKA (reprint author), Hosp Joint Dis, Dept Rheumatol, 301 E 17th St, New York, NY 10003 USA. FU NIGMS NIH HHS [GM-35174] NR 70 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 BP 3756 EP 3771 PG 16 WC Hematology SC Hematology GA 138GB UT WOS:000076962500031 PM 9808570 ER PT J AU Byrd, JC Shinn, C Waselenko, JK Fuchs, EJ Lehman, TA Nguyen, PL Flinn, IW Diehl, LF Sausville, E Grever, MR AF Byrd, JC Shinn, C Waselenko, JK Fuchs, EJ Lehman, TA Nguyen, PL Flinn, IW Diehl, LF Sausville, E Grever, MR TI Flavopiridol induces apoptosis in chronic lymphocytic leukemia cells via activation of caspase-3 without evidence of bcl-2 modulation or dependence on functional p53 SO BLOOD LA English DT Article ID BREAST-CARCINOMA CELLS; DRUG-RESISTANCE; GENE MUTATION; CYTOCHROME-C; IN-VITRO; EXPRESSION; SURVIVAL; ARREST; KINASE; CHEMOTHERAPY AB Flavopiridol has been reported to induce apoptosis in lymphoid cell lines via downregulation of bcl-2. The in vitro activity of flavopiridol against human chronic lymphocytic leukemia (CLL) cells and potential mechanisms of action for inducing cytotoxicity were studied. The in vitro viability of mononuclear cells from CLL patients (n = Il)was reduced by 50% at 4 hours, 24 hours, and 4 days at a flavopiridol concentration of 1.15 mu mol/L (95% confidence interval [CI] +/-0.31). 0.18 mu mol/L (95% Cl +/-0.04), and 0.16 mu mol/L (95% CI +/-0.04), respectively. Loss of viability in human CLL cells correlated with early induction of apoptosis. Exposure of CLL cells to 0.18 mu mol/L of flavopiridol resulted in both decreased expression of p53 protein and cleavage of the caspase-3 zymogen 32-kD protein with the appearance of its 20-kD subunit. Contrasting observations of others in tumor cell lines, flavopiridol cytotoxicity in CLL cells did not correlate with changes in bcl-2 protein expression alterations. We evaluated flavopiridol's dependence on intact 953 by exposing splenocytes from wild-type (p53(+/+)) and p53 null (p53(-/-)) mice that demonstrated no preferential cytotoxicity as compared with a marked differential with F-ara-a and radiation. Incubation of CLL cells with antiapoptotic cytokine interleukin-4 (IL-4) did not alter the LC50 Of flavopiridol. as compared with a marked elevation noted with F-ara-a in the majority of patients tested. These data demonstrate that flavopiridol has significant in vitro activity against human CLL cells through activation of caspase-3, which appears to occur independently of bcl-2 modulation, the presence of IL-4, or 953 status. Such findings strongly support the early introduction of flavopiridol into clinical trials for patients with B-CLL. (C) 1998 by The American Society of Hematology. C1 Walter Reed Army Med Ctr, Hematol Oncol Serv, Div Hematol Oncol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. Johns Hopkins Oncol Ctr, Div Hematol Malignancies, Baltimore, MD USA. Biotechnol Ltd, Laurel, MD USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. RP Byrd, JC (reprint author), Walter Reed Army Med Ctr, Hematol Oncol Serv, Div Hematol Oncol, Ward 78, Washington, DC 20307 USA. NR 33 TC 227 Z9 230 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1998 VL 92 IS 10 BP 3804 EP 3816 PG 13 WC Hematology SC Hematology GA 138GB UT WOS:000076962500035 PM 9808574 ER PT J AU Devesa, SS Blot, WJ Fraumeni, JF AF Devesa, SS Blot, WJ Fraumeni, JF TI Changing patterns in the incidence of esophageal and gastric carcinoma in the United States SO CANCER LA English DT Article DE esophagus; stomach; neoplasms; adenocarcinoma; squamous cell carcinoma ID GASTROESOPHAGEAL REFLUX DISEASE; LOW-RISK POPULATION; SOCIOECONOMIC-FACTORS; MEDICAL CONDITIONS; HISTOLOGIC TYPE; ADENOCARCINOMA; CARDIA; ALCOHOL; TOBACCO; CANCER AB BACKGROUND. Incidence rates for esophageal adenocarcinoma previously were reported to be increasing rapidly, especially among white males. Rates for gastric cardia adenocarcinoma also were observed to be rising, although less rapidly. In this article, the authors update the incidence trends through 1994 and further consider the trends by age group. METHODS, Surveillance, Epidemiology, and End Results (SEER) program data were used to calculate age-adjusted incidence rates for esophageal carcinoma by histologic type and gastric adenocarcinoma by anatomic subsite. RESULTS. Among white males, the incidence of adenocarcinoma of the esophagus rose > 350% since the mid-1970s, surpassing squamous cell carcinoma around 1990. Rates also rose among black males, but remained at much lower levels. To a lesser extent, there were continuing increases in gastric cardia adenocarcinoma among white and black males, which nearly equaled the rates for noncardia tumors of the stomach in white men. The upward trend for both tumors was much greater among older than younger men. Although the incidence also rose among females, rates remained much lower than among males. CONCLUSIONS. Previously reported increases of esophageal adenocarcinoma are continuing, most notably among white males. Cigarette smoking may contribute to the trend through an early stage carcinogenic effect, along with obesity, which may increase intraabdominal pressure and predispose to gastroesophageal reflux disease. Further research into esophageal and gastric cardia adenocarcinoma is needed to clarify the risk factors and mechanisms responsible for the upward trends as well as the racial and gender disparities in incidence. Cancer 1998;83: 2049-53. (C) 1998 American Cancer Society. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Int Epidemiol Inst, Rockville, MD USA. RP Devesa, SS (reprint author), NCI, Div Canc Epidemiol & Genet, Execut Plaza N,Room 415, Bethesda, MD 20892 USA. NR 33 TC 1459 Z9 1513 U1 5 U2 38 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 1998 VL 83 IS 10 BP 2049 EP 2053 DI 10.1002/(SICI)1097-0142(19981115)83:10<2049::AID-CNCR1>3.3.CO;2-U PG 5 WC Oncology SC Oncology GA 138YP UT WOS:000077000900001 PM 9827707 ER PT J AU Worobec, AS Semere, T Nagata, H Metcalfe, DD AF Worobec, AS Semere, T Nagata, H Metcalfe, DD TI Clinical correlates of the presence of the Asp816Val c-kit mutation in the peripheral blood mononuclear cells of patients with mastocytosis SO CANCER LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 19-26, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Allergy Asthma & Immunol DE c-kit; mutation; mastocytosis; osteosclerosis ID CONSTITUTIVELY ACTIVATING MUTATIONS; RECEPTOR TYROSINE KINASE; EXPRESSING CELLS; BONE-MARROW; SYSTEMIC MASTOCYTOSIS; INTERSTITIAL-CELLS; MAST-CELLS; DISEASE; IDENTIFICATION; INTERLEUKIN-6 AB BACKGROUND. The Asp816Val mutation in the catalytic domain of the c-kit receptor has been identified in patients with systemic mastocytosis. METHODS. To determine whether this mutation is associated with identifiable clinical patterns of disease and prognosis, a total of 65 patients with mastocytosis were screened for the presence of the Asp816Val mutation in peripheral blood mononuclear cells (PBMCs). RESULTS. By analysis of HinfI digestion products, the authors found that the overall prevalence of this mutation in the current patient series was 25%. The presence of the Asp816Val mutation in PBMCs was observed in 15 adults (of 16 Asp816Val mutation positive patients) and 1 infant, but not in any children with mastocytosis. Patients whose PBMCs were positive for this mutation (category II and a subset of category Ib mastocytosis patients) manifested a more severe disease pattern, with clinical features ranging in severity from early to advanced myelodysplastic or myeloproliferative syndromes. These patients more commonly had osteosclerotic bone involvement (a clinical feature primarily observed in mastocytosis patients with an associated hematologic disorder) as well as immunoglobulin dysregulation and peripheral blood abnormalities. Furthermore, pedigree analysis of three families provided evidence that the mutation was somatic. CONCLUSIONS. Twenty-five percent of all patients with mastocytosis had the Asp816Val mutation in PBMCs; 56% of these patients had evidence of a myelodysplastic or myeloproliferative syndrome, and 44% had been clinically placed in the indolent mastocytosis category, suggesting that the current classification scheme used to assign prognosis may be inadequate. Therefore, determination of the presence or absence of this mutation in PBMCs of mastocytosis patients offers a useful adjunct in determining the extent of workup and assigning prognosis in this complex and heterogeneous disease. Cancer 1998;83:2120-9. (C) 1998 American Cancer Society. C1 NIAID, Lab Allerg DIs, NIH, Bethesda, MD 20892 USA. Chiba Univ, Sch Med, Dept Otolaryngol, Chiba 280, Japan. RP Worobec, AS (reprint author), NIAID, Lab Allerg DIs, NIH, Bldg 10,Room 11C-205,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. NR 30 TC 104 Z9 105 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 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 1998 VL 83 IS 10 BP 2120 EP 2129 DI 10.1002/(SICI)1097-0142(19981115)83:10<2120::AID-CNCR10>3.0.CO;2-C PG 10 WC Oncology SC Oncology GA 138YP UT WOS:000077000900010 PM 9827716 ER PT J AU Khan, J Simon, R Bittner, M Chen, YD Leighton, SB Pohida, T Smith, PD Jiang, Y Gooden, GC Trent, JM Meltzer, PS AF Khan, J Simon, R Bittner, M Chen, YD Leighton, SB Pohida, T Smith, PD Jiang, Y Gooden, GC Trent, JM Meltzer, PS TI Gene expression profiling of alveolar rhabdomyosarcoma with cDNA microarrays SO CANCER RESEARCH LA English DT Article ID CYTOGENETIC CHARACTERIZATION; DNA MICROARRAY; HUMAN GENOME; AMPLIFICATION; CANCER; CELLS; TRANSLOCATIONS; PATTERNS; MYC AB Several forms of human sarcoma, lymphoma, and leukemia are characterized by somatically acquired chromosome translocations that result in fusion genes that encode chimeric transcription factors with oncogenic properties. We have used cDNA microarrays containing 1238 cDNAs to investigate the gene expression profile of a group of seven alveolar rhabdomyosarcoma (ARMS) cell lines characterized by the presence of the PAX3-FKHR fusion gene. Using the method of multidimensional scaling to represent the relationships among the cell lines in two-dimensional Euclidean space, we determined that ARMS cells show a consistent pattern of gene expression, which allows the cells to be clustered together. By searching across the seven ARMS cell lines, we found that 37 of 1238 genes were most consistently expressed in ARMS relative to a reference cell line. Only three of these genes have been previously reported to be expressed in ARMS. Among these 37 were genes related to both primary (PAX3-FKHR) and secondary (CDK4) genetic alterations in AIL-MS. These results in ARMS demonstrate the potential of cDNA microarray technology to elucidate tumor-specific gene expression profiles in human cancers. C1 Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NIH, Biomed Engn & Instrumentat Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NIH, Computat Biosci & Engn Lab, Off Res Serv, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bldg 49,Room 4A10,49 Convent Dr, Bethesda, MD 20892 USA. RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 25 TC 353 Z9 370 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1998 VL 58 IS 22 BP 5009 EP 5013 PG 5 WC Oncology SC Oncology GA 138YJ UT WOS:000077000400004 PM 9823299 ER PT J AU Schmutte, C Marinescu, RC Copeland, NG Jenkins, NA Overhauser, J Fishel, R AF Schmutte, C Marinescu, RC Copeland, NG Jenkins, NA Overhauser, J Fishel, R TI Refined chromosomal localization of the mismatch repair and hereditary nonpolyposis colorectal cancer genes hMSH2 and hMSH6 SO CANCER RESEARCH LA English DT Article ID DNA-BASE PAIRS; COLON-CANCER; MUTATIONS; INSTABILITY; LINKAGE; HOMOLOG; GENOME; TUMORS; BINDS; CELLS AB The genomic loci for the mismatch repair genes hMSH2 and hMSH6 were mapped by fluorescence in situ hybridization, analysis of radiation hybrid panel markers, and linkage analysis of syntenic chromosome regions between human and mouse, Both genes were localized to chromosome 2p21, adjacent to the luteinizing hormone/choriogonadotropin receptor gene (LHCGR; 2p21), telomeric to the D2S123 polymorphic marker, and centromeric to the calmodulin-2 gene (CALM-2; 2p22-21) and son-of-sevenless gene (SOS; 2p22-21). The genomic locations of hMSH2 and hMSH6 appears to be within 1 Mb of each other because they could not be separated by interphase fluorescence in situ hybridization, These results clarify the position of the chromosome 2 hereditary nonpolyposis colorectal cancer locus, which was originally reported to be associated with an adjacent region (chromosome 2p14-16). C1 Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Fishel, R (reprint author), Thomas Jefferson Univ, Kimmel Canc Ctr, 233 S 10th St,Room 933, Philadelphia, PA 19107 USA. FU NCI NIH HHS [CA56542, CA57007] NR 32 TC 13 Z9 13 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1998 VL 58 IS 22 BP 5023 EP 5026 PG 4 WC Oncology SC Oncology GA 138YJ UT WOS:000077000400007 PM 9823302 ER PT J AU Matteucci, A Faenza, I Gilmour, RS Manzoli, L Billi, AM Peruzzi, D Bavelloni, A Rhee, SG Cocco, L AF Matteucci, A Faenza, I Gilmour, RS Manzoli, L Billi, AM Peruzzi, D Bavelloni, A Rhee, SG Cocco, L TI Nuclear but not cytoplasmic phospholipase C beta(1) inhibits differentiation of erythroleukemia cells SO CANCER RESEARCH LA English DT Article ID ENVELOPE SIGNAL-TRANSDUCTION; SWISS 3T3 CELLS; GROWTH-FACTOR-I; FRIEND-CELLS; DIACYLGLYCEROL; TRANSLOCATION; LOCALIZATION; ACTIVATION; METABOLISM; ISOZYMES AB A body of evidence has shown the existence of a nuclear phosphoinositide cycle in different cell types. The cycle is endowed with kinases as well as phosphatases and phospholipase C (PLC), Among the PLC isozymes, the beta family is characterized by a long COOH-terminal tail that contains a cluster of lysine residues responsible for nuclear localization. Indeed, PLC beta(1) is the major isoform that has been detected in the nucleus of several cells, This isoform is activated by insulin-like growth factor I, and when this isoform is lacking, as a result of gene ablation, the onset of DNA synthesis induced by this hormone is abolished. On the contrary, PLC beta(1) is down-regulated during the erythroid differentiation of Friend erythroleukemia cells. A key question is how PLC beta(1) signaling at the nucleus fits into the erythroid differentiation program of Friend erythroleukemia cells, and whether PLC beta(1) signaling activity is directly responsible for the maintenance of the undifferentiated state of erythroleukemia cells. Here we present evidence that nuclear PLC beta(1) but not the isoform located at the plasma membrane is directly involved in maintaining the undifferentiated state of Friend erythroleukemia cells. Indeed, when wild-type PLC beta(1) is overexpressed in these cells, differentiation in response to DMSO is inhibited in that the expression of beta-globin is almost completely abolished, whereas when a mutant lacking the ability to localize to the nucleus is expressed, the cells differentiate, and the expression of beta-globin is the same as in wild-type cells. C1 Univ Bologna, Inst Anat, Cellular Signaling Lab, I-40126 Bologna, Italy. CNR, Inst Cytomorphol, I-40136 Bologna, Italy. Ist Rizzoli, Cell Biol Lab, I-40136 Bologna, Italy. Univ Auckland, Fac Med, Auckland 1, New Zealand. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Cocco, L (reprint author), Univ Bologna, Inst Anat, Cellular Signaling Lab, Via Irnerio 48, I-40126 Bologna, Italy. EM lcocco@biocfarm.unibo.it NR 24 TC 70 Z9 73 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1998 VL 58 IS 22 BP 5057 EP 5060 PG 4 WC Oncology SC Oncology GA 138YJ UT WOS:000077000400015 PM 9823310 ER PT J AU Otsuka, T Takayama, H Sharp, R Celli, G LaRochelle, WJ Bottaro, DP Ellmore, N Vieira, W Owens, JW Anver, M Merlino, G AF Otsuka, T Takayama, H Sharp, R Celli, G LaRochelle, WJ Bottaro, DP Ellmore, N Vieira, W Owens, JW Anver, M Merlino, G TI c-Met autocrine activation induces development of malignant melanoma and acquisition of the metastatic phenotype SO CANCER RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; EPITHELIAL-CELLS; TRANSGENIC MICE; TYROSINE KINASE; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3-KINASE; PROTOONCOGENE PRODUCT; FACTOR/SCATTER FACTOR; ABNORMAL-DEVELOPMENT AB The molecular and genetic events that contribute to the genesis and progression of cutaneous malignant melanoma, a complex and aggressive disease with a high propensity for metastasis, are poorly understood due in large part to the dearth of relevant experimental animal models. Here we used transgenic mice ectopically expressing hepatocyte growth factor/scatter factor (HGF/SF) to show that the Met signaling pathway is an important in vivo regulator of melanocyte function, whose subversion induces malignant melanoma. Tumorigenesis occurred in stages, beginning with the abnormal accumulation of melanocytes in the epidermis and dermis and culminating in the development of metastatic melanoma. Oncogenesis in this model was driven by creation of HGF/SF-Met autocrine loops through forced expression of the transgenic ligand and apparent selection of melanocytes overexpressing endogenous receptor, rather than paracrine stimulation or mutational activation of c-met. Preference for liver as a metastatic target correlated with high HGF/SF-Met autocrine activity, consistent with the notion that such activity may influence colonization. Although basic fibroblast growth factor and its receptor were both weakly expressed In the majority of melanomas examined, high levels were found only in those rare neoplasms with low or undetectable HGF/SF and Met expression, suggesting that these two tyrosine kinase receptor autocrine loops serve a critical overlapping function in melanocytic tumorigenesis, Our data support a causal role for HGF/SF-Met signaling in the development of melanoma and acquisition of the metastatic phenotype, Moreover, this transgenic mouse should serve as a highly useful model, facilitating our understanding of mechanisms by which human melanoma progresses to malignancy and expediting the development of efficacious therapeutic modalities designed to constrain metastasis. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Vet Res Program, Off Res Serv, Bethesda, MD 20892 USA. NCI, Pathol Histotechnol Lab, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Merlino, G (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 2E24, Bethesda, MD 20892 USA. EM gmerlino@helix.nih.gov RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 FU NCI NIH HHS [N01-CO-56000] NR 95 TC 192 Z9 194 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1998 VL 58 IS 22 BP 5157 EP 5167 PG 11 WC Oncology SC Oncology GA 138YJ UT WOS:000077000400032 PM 9823327 ER PT J AU Kodama, S Kashino, G Suzuki, K Takatsuji, T Okumura, Y Oshimura, M Watanabe, M Barrett, JC AF Kodama, S Kashino, G Suzuki, K Takatsuji, T Okumura, Y Oshimura, M Watanabe, M Barrett, JC TI Failure to complement abnormal phenotypes of Simian Virus 40-transformed Werner syndrome cells by introduction of a normal human chromosome 8 SO CANCER RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; XERODERMA PIGMENTOSUM-CELLS; CULTURED SKIN FIBROBLASTS; SYNDROME GENE; MOLECULAR ANALYSIS; MISMATCH REPAIR; HPRT(-) MUTANTS; LARGE DELETIONS; SOUTHERN BLOT; DNA HELICASE AB The Werner syndrome (WS) gene (WRN) was isolated by positional cloning, based on mapping to chromosome 8p12, and the WRY protein was recently shown to encode an active helicase, To examine functional complementation of WS phenotypes by expression of the WRN gene, we introduced a normal human chromosome 8 into a SV40-transformed WS fibroblastoid cell line (WS780) by microcell fusion and studied several cellular phenotypes associated previously with WS cell lines, including cell growth rate, 4-nitroquinoline-1-oxide (4NQO) sensitivity, and spontaneous mutation rate and type of mutation at the hypoxanthine-guanine phosphoribosyl transferase locus. The WRN gene was expressed in two of three microcell hybrids introduced with chromosome 8. We failed to observe a difference between normal and WS cell lines in terms of growth rates and spontaneous mutation rates. However, we found that the WS cell line was highly sensitive to 4NQO-induced cytotoxicity and showed an unusually high proportion of deletion mutations at the hypoxanthine-guanine phosphoribosyl transferase locus as compared to a control cell line, as shown previously. Here, we report that these phenotypes were not corrected by introduction of the WRN gene, although the WRN protein was expressed. Our results suggest that the hypersensitivity to 4NQO and the extensive deletion mutations observed in the WS cell line are caused by a defect that is secondary to the WRN gene mutation, possibly a repair gene defect that controls the phenotypes of hypersensitivity to carcinogen(s) and/or the extensive deletion mutations. C1 Nagasaki Univ, Sch Pharmaceut Sci, Dept Hlth Sci, Lab Radiat & Life Sci, Nagasaki 8528521, Japan. Nagasaki Univ, Fac Environm Studies, Dept Environm Studies, Nagasaki 8528521, Japan. Nagasaki Univ, Sch Med, Inst Atom Dis, Dept Radiat Biophys, Nagasaki 8528523, Japan. Tottori Univ, Fac Med, Sch Life Sci, Dept Mol & Cell Genet, Yonago, Tottori 6388503, Japan. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Kodama, S (reprint author), Nagasaki Univ, Sch Pharmaceut Sci, Dept Hlth Sci, Lab Radiat & Life Sci, 1-14 Bunkyo Machi, Nagasaki 8528521, Japan. NR 46 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1998 VL 58 IS 22 BP 5188 EP 5195 PG 8 WC Oncology SC Oncology GA 138YJ UT WOS:000077000400036 PM 9823331 ER PT J AU Boland, CR Thibodeau, SN Hamilton, SR Sidransky, D Eshleman, JR Burt, RW Meltzer, SJ Rodriguez-Bigas, MA Fodde, R Ranzani, GN Srivastava, S AF Boland, CR Thibodeau, SN Hamilton, SR Sidransky, D Eshleman, JR Burt, RW Meltzer, SJ Rodriguez-Bigas, MA Fodde, R Ranzani, GN Srivastava, S TI A National Cancer Institute Workshop on Microsatellite Instability for Cancer Detection and Familial Predisposition: Development of International Criteria for the Determination of Microsatellite Instability in Colorectal Cancer SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; II RECEPTOR GENE; MISMATCH REPAIR GENES; REPLICATION ERROR PHENOTYPE; POORLY DIFFERENTIATED TYPE; MULTIPLE GASTRIC CANCERS; SHORT TANDEM REPEATS; ENDOMETRIAL CARCINOMAS; CELL-LINES; MUTATOR PHENOTYPE AB In December 1997, the National Cancer Institute sponsored "The International Workshop on Microsatellite Instability and RER Phenotypes in Cancer Detection and Familial Predisposition," to review and unify the field. The following recommendations were endorsed at the workshop. (a) The form of genomic instability associated with defective DNA mismatch repair in tumors is to be called microsatellite instability (MSI). (b) A panel of five microsatellites has been validated and is recommended as a reference panel for future research in the field. Tumors may be characterized on the basis of: high-frequency MSI (MSI-H), if two or more of the five markers show instability (i.e., have insertion/deletion mutations), and low-frequency MSI (MSI-I), if only one of the five markers shows instability. The distinction between microsatellite stable (MSS) and low frequency MSI (MSI-L) can only be accomplished if a greater number of markers is utilized. (c) A unique clinical and pathological phenotype is identified for the MSI-H tumors, which comprise &sim15% of colorectal cancers, whereas MSI-L and MSS tumors appear to be phenotypically similar. MSI-H colorectal tumors are found predominantly in the proximal colon, have unique histopathological features, and are associated with a less aggressive clinical course than are stage-matched MSI-L or MSS tumors. Preclinical models suggest the possibility that these tumors may be resistant to the cytotoxicity induced by certain chemotherapeutic agents. The implications for MSI-L are not yet clear. (d) MSI can be measured in fresh or fixed tumor specimens equally well; microdissection of pathological specimens is recommended to enrich for neoplastic tissue; and normal tissue is required to document the presence of MSI. (e) The "Bethesda guidelines," which were developed in 1996 to assist in the selection of tumors for microsatellite analysis, are endorsed, (f) The spectrum of microsatellite alterations in noncolonic tumors was reviewed, and it was concluded that the above recommendations apply only to colorectal neoplasms. (g) A research agenda was recommended. C1 Univ Calif San Diego, La Jolla, CA 92093 USA. Mayo Clin, Mol Genet Lab, Rochester, MN 55905 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Head & Neck Canc Res, Baltimore, MD 21205 USA. Univ Utah, Hlth Sci Ctr, Salt Lake City, UT 84132 USA. Univ Maryland Hosp, Baltimore, MD 21201 USA. Roswell Pk Canc Inst, Dept Surg, Buffalo, NY 14263 USA. Leiden Univ, Dept Human Genet, NL-2333 AL Leiden, Netherlands. Univ Pavia, Dept Genet & Microbiol, I-27100 Pavia, Italy. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Boland, CR (reprint author), Univ Calif San Diego, 4028 BSB,9500 Gilman Dr, La Jolla, CA 92093 USA. EM crboland@ucsd.edu RI Huang, Yvonne/D-3808-2011; OI Fodde, Riccardo/0000-0001-9839-4324 NR 117 TC 2758 Z9 2848 U1 8 U2 104 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1998 VL 58 IS 22 BP 5248 EP 5257 PG 10 WC Oncology SC Oncology GA 138YJ UT WOS:000077000400045 PM 9823339 ER PT J AU Grechez-Cassiau, A Bernard, M Ladjali, K Rodriguez, IR Voisin, P AF Grechez-Cassiau, A Bernard, M Ladjali, K Rodriguez, IR Voisin, P TI Structural analysis of the chicken hydroxyindole-O-methyltransferase gene SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE chicken; pineal; retina; melatonin; HIOMT gene ID N-ACETYLTRANSFERASE ACTIVITY; PINEAL-GLAND; MESSENGER-RNA; BINDING-PROTEIN; IMMUNOCYTOCHEMICAL LOCALIZATION; CIRCADIAN OSCILLATION; TRANSCRIPTION FACTOR; MELATONIN SECRETION; MOLECULAR-CLONING; RETINA AB Hydroxyindole-O-methyltransferase (HIOMT) catalyzes the final step of melatonin synthesis, a neurohormone involved in photoperiodism and produced specifically in the pineal gland and in the retina. In the chicken, HIOMT gene transcription appears to be controlled by a circadian oscillator located in the pineal gland. We have characterized the chicken HIOMT gene over 17 kb, including 2.9 kb of 5'-flanking sequence. The major transcript (1.6 kb) is composed of eight exons distributed over 7.5 kb of genomic DNA. A ninth alternative exon was identified 6 kb downstream of exon 8. It was found in minor transcripts in the pineal gland and in the retina. Sequence similarity between exons 8 and 9 suggests their origin by exon duplication. Due to early stop codons, inclusion of exon 9 truncates the open reading frame by up to 33%. A restriction fragment length polymorphism was detected for a Bg/II site in intron 8. Fluorescence hybridization localized the HIOMT gene on chicken chromosome 1q22. The 5'-flanking region contains GATTAA and TAATCC sequences that may be related to tissue-specific expression. An ATTTAAAT sequence at position -29 would play the role of a TATA box, as evidenced by electrophoretic mobility shift assay. Information obtained in this study open the way to further studies aimed at analyzing the circadian rhythm of transcription at promoter level. C1 Lab Cellular Neurobiol, UMR CNRS 6558, UFR Sci, F-86022 Poitiers, France. Inst Embryol, UPR CNRS 9064, Nogent Sur Marne, France. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Voisin, P (reprint author), Lab Cellular Neurobiol, UMR CNRS 6558, UFR Sci, 40 Ave Recteur Pineau, F-86022 Poitiers, France. NR 41 TC 6 Z9 6 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD NOV 15 PY 1998 VL 258 IS 1 BP 44 EP 52 DI 10.1046/j.1432-1327.1998.2580044.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 139XY UT WOS:000077057600005 PM 9851690 ER PT J AU Southan, GJ Salzman, AL Szabo, C AF Southan, GJ Salzman, AL Szabo, C TI Hydroxyguanidines inhibit peroxynitrite-induced oxidation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE nitric oxide; peroxynitrite; hydroxyguanidines; N-G-hydroxy-L-arginine; oxygen radicals; mitochondrial respiration; nitrosation; free radical ID NITRIC-OXIDE SYNTHASE; HYDROXY-L-ARGININE; MITOCHONDRIAL ELECTRON-TRANSPORT; CELLULAR-ENERGY DEPLETION; SMOOTH-MUSCLE CELLS; DNA STRAND BREAKAGE; IMMUNOSTIMULATED MACROPHAGES; RELAXING FACTOR; SUPEROXIDE; DERIVATIVES AB Hydroxyguanidines (OHGs), including the endogenously formed NG-hydroxy-L-arginine (OH-arg), can react with nitric oxide (NO) and nitrogen oxides (NOx) in vitro. Therefore, we have tested OHGs and related compounds for their ability to scavenge peroxynitrite and to protect against peroxynitrite-induced oxidative processes in cells. Hydroxyguanidine, N-G-hydroxy-L-arginine and other N-substituted OHGs, dose-dependently inhibited the in vitro oxidation of dihydrorhodamine (DHR) by peroxynitrite (PN), with similar or better efficacy than glutathione or cysteine. Amidoximes, aminoguanidines and O-substituted OHGs were less effective, and guanidines were without effect. In contrast to their effects on DHR oxidation, OHGs exerted only minimal inhibitory effects on the hydroxylation of benzoate by PN, suggesting that OHGs do not react with the activated isomer of peroxynitrous acid. Selected compounds were tested for protection against PN-induced suppression of mitochondrial respiration and protein oxidation in cultured J774 murine macrophages. Aminoguanidines afforded some protection against the effects of PN, but substituted-phenyl OHGs were considerably more effective. Analysis of the products of the reaction of 4-methoxybenzyl-OHG with PN showed rapid formation of nitrosated derivatives, as well as 4-methoxybenzylcyanamide and a small amount of 4-mechoxybenzylurea. Nitric oxide and nitrous oxide were also evolved, but indirectly, arising from the decomposition of one of the nitrosation products. The current results demonstrate that hydroxyguanidines react with PN to protect cells against PN-mediated injury and may be more effective than the endogenous antioxidants cysteine and glutathione. (C) 1998 Elsevier Science Inc. C1 Childrens Hosp, Med Ctr, Div Crit Care, Cincinnati, OH 45229 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Szabo, C (reprint author), Childrens Hosp, Med Ctr, Div Crit Care, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM gjsouthan@aol.com FU NIGMS NIH HHS [R29GM54773] NR 38 TC 9 Z9 9 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 15 PY 1998 VL 25 IS 8 BP 914 EP 925 DI 10.1016/S0891-5849(98)00120-8 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 139TZ UT WOS:000077046900006 PM 9840736 ER PT J AU Chin, L Merlino, G DePinho, RA AF Chin, L Merlino, G DePinho, RA TI Malignant melanoma: modern black plague and genetic black box SO GENES & DEVELOPMENT LA English DT Review ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; RECEPTOR TYROSINE KINASE; MET PROTOONCOGENE PRODUCT; CELL-CYCLE REGULATORS; TUMOR-SUPPRESSOR GENE; GRB2 BINDING-SITE; C-MET; NEURAL CREST; CUTANEOUS MELANOMA C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP DePinho, RA (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. FU NEI NIH HHS [R01EY09300]; NIAMS NIH HHS [K08AR02104-01]; NICHD NIH HHS [R01HD28317] NR 170 TC 138 Z9 143 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 1998 VL 12 IS 22 BP 3467 EP 3481 DI 10.1101/gad.12.22.3467 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 144QR UT WOS:000077326700001 PM 9832500 ER PT J AU Becker, RM Darrow, C Zimonjic, DB Popescu, NC Watson, MA Fleming, TP AF Becker, RM Darrow, C Zimonjic, DB Popescu, NC Watson, MA Fleming, TP TI Identification of mammaglobin B, a novel member of the uteroglobin gene family SO GENOMICS LA English DT Article ID HUMAN BREAST-CANCER; BINDING-PROTEIN; TRANSGENIC MICE; LUNG CYTOSOL; LOCALIZATION; RAT; BIPHENYLS; SEQUENCES; ELEMENTS; CELLS AB In this report, we have identified, sequenced, and characterized the expression pattern of a novel human gene, mammaglobin B. Mammaglobin B (MGB2) is highly homologous to mammaglobin (MGB1), a previously characterized human gene whose expression is limited to the mammary epithelium and frequently up-regulated in human breast cancer cells. Based upon amino acid sequence similarities, both mammaglobin and mammaglobin B may be considered members of a larger, mammalian multigene family that includes rabbit uteroglobin, human Clara Cell 10-kDa protein (CC10), and the multimeric rat prostatein protein. Together with the human CC10 gene, mammaglobin and mammaglobin B are closely linked on human chromosome 11q13. However, despite their primary sequence similarity and close chromosomal proximity, the expression of mammaglobin and mammaglobin B is nonconcordant in both nonmalignant and neoplastic tissue, (C) 1998 Academic Press. C1 Washington Univ, Sch Med, Dept Ophthalmol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Fleming, TP (reprint author), Washington Univ, Sch Med, Dept Ophthalmol, Box 8096,660 S Euclid Ave, St Louis, MO 63110 USA. FU NCI NIH HHS [CA 76227-01] NR 21 TC 55 Z9 61 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1998 VL 54 IS 1 BP 70 EP 78 DI 10.1006/geno.1998.5539 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 139YE UT WOS:000077058200009 PM 9806831 ER PT J AU West, A Vojta, PJ Welch, DR Weissman, BE AF West, A Vojta, PJ Welch, DR Weissman, BE TI Chromosome localization and genomic structure of the KiSS-1 metastasis suppressor gene (KISS1) SO GENOMICS LA English DT Article ID CELLS AB The identification and sequence of KiSS-1 (HGMW-approved symbol, KISS1), a human malignant melanoma metastasis-suppressor gene, was recently published. In this report, we present a corrected genomic sequence, genomic structure, and refined chromosomal location for KiSS-1. The genomic organization of the sequence reveals a gene consisting of four exons. The first two exons are not translated; the third exon contains 38 5' noncoding bases followed by the translational start site and another 100 translated bases. The terminal exon contains a further 332 translated bases, the translational stop codon, and the polyadenylation signal The gene maps to chromosome 1q32 as determined by radiation hybrid mapping and FISH analysis, The relatively simple organization of this gene will facilitate analyses for mutations and abnormal expression in human tumors. (C) 1998 Academic Press. C1 Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. Penn State Univ, Coll Med, Jake Gittlen Canc Res Inst, Hershey, PA 17033 USA. RP Weissman, BE (reprint author), Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. RI Welch, Danny/B-7310-2009; Perez , Claudio Alejandro/F-8310-2010 OI Welch, Danny/0000-0002-1951-4947; Perez , Claudio Alejandro/0000-0001-9688-184X FU NCI NIH HHS [CA62168, CA63176] NR 7 TC 87 Z9 106 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1998 VL 54 IS 1 BP 145 EP 148 DI 10.1006/geno.1998.5566 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 139YE UT WOS:000077058200018 PM 9806840 ER PT J AU Lavedan, C Leroy, E Torres, R Dehejia, A Dutra, A Buchholtz, S Nussbaum, RL Polymeropoulos, MH AF Lavedan, C Leroy, E Torres, R Dehejia, A Dutra, A Buchholtz, S Nussbaum, RL Polymeropoulos, MH TI Genomic organization and expression of the human beta-synuclein gene (SNCB) SO GENOMICS LA English DT Article ID PARKINSONS-DISEASE; PROTEIN; BRAIN AB The beta-synuclein protein is highly homologous to the alpha-synuclein protein for which two mutations were reported in some familial cases of Parkinson disease. It has been shown that both alpha- and beta-synucleins may be able to inhibit phospholipase D2 selectively. We have observed that the beta-synuclein gene (HGMW-approved symbol, SNCB) is highly expressed in brain including the substantia nigra, the main region of neuronal degeneration in patients with Parkinson disease. We have determined the intron-exon structure of the beta-synuclein gene and established sequencing assays that will facilitate the search for mutations in the beta-synuclein gene in patients with Parkinson disease or other neurodegenerative disorders. (C) 1998 Academic Press. C1 NIH, Genet Dis Res Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NIH, Lab Gene Transfer, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Johns Hopkins Bayview Med Ctr, Baltimore, MD 21224 USA. RP Polymeropoulos, MH (reprint author), NIH, Genet Dis Res Branch, Natl Human Genome Res Inst, 49 Convent Dr,49-4A66, Bethesda, MD 20892 USA. NR 11 TC 26 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1998 VL 54 IS 1 BP 173 EP 175 DI 10.1006/geno.1998.5556 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 139YE UT WOS:000077058200024 PM 9806846 ER PT J AU Mouri, T Kittaka, N Horio, Y Copeland, NG Gilbert, DJ Jenkins, NA Kurachi, Y AF Mouri, T Kittaka, N Horio, Y Copeland, NG Gilbert, DJ Jenkins, NA Kurachi, Y TI Assignment of mouse inwardly rectifying potassium channel Kcnj16 to the distal region of mouse chromosome 11 SO GENOMICS LA English DT Article C1 Osaka Univ, Fac Med, Dept Pharmacol 2, Suita, Osaka 5650871, Japan. Osaka Univ, Grad Sch Med, Suita, Osaka 5650871, Japan. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Kurachi, Y (reprint author), Osaka Univ, Fac Med, Dept Pharmacol 2, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. NR 5 TC 4 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 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1998 VL 54 IS 1 BP 181 EP 182 DI 10.1006/geno.1998.5572 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 139YE UT WOS:000077058200028 PM 9806850 ER PT J AU Fujita, A Horio, Y Copeland, NG Gilbert, DJ Jenkins, NA Kurachi, Y AF Fujita, A Horio, Y Copeland, NG Gilbert, DJ Jenkins, NA Kurachi, Y TI Assignment of mouse cardiac two-pore background K+ channel gene (Kcnk4) to the proximal region of mouse chromosome 5 SO GENOMICS LA English DT Article C1 Osaka Univ, Fac Med, Dept Pharmacol 2, Suita, Osaka 5650871, Japan. Osaka Univ, Grad Sch Med, Suita, Osaka 5650871, Japan. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Kurachi, Y (reprint author), Osaka Univ, Fac Med, Dept Pharmacol 2, 2-2 Yamada Oka, Suita, Osaka 5650871, Japan. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1998 VL 54 IS 1 BP 183 EP 184 DI 10.1006/geno.1998.5573 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 139YE UT WOS:000077058200029 PM 9806851 ER PT J AU Dubois, M Zemb, T Fuller, N Rand, RP Parsegian, VA AF Dubois, M Zemb, T Fuller, N Rand, RP Parsegian, VA TI Equation of state of a charged bilayer system: Measure of the entropy of the lamellar-lamellar transition in DDABr (vol 108, pg 7855, 1998) SO JOURNAL OF CHEMICAL PHYSICS LA English DT Correction C1 CEA Saclay, Serv Chim Mol, F-91191 Gif Sur Yvette, France. Brock Univ, Dept Biol Sci, St Catharines, ON L2S 3A1, Canada. NIH, Bethesda, MD 20892 USA. RP Dubois, M (reprint author), CEA Saclay, Serv Chim Mol, F-91191 Gif Sur Yvette, France. NR 1 TC 1 Z9 1 U1 0 U2 2 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD NOV 15 PY 1998 VL 109 IS 19 BP 8731 EP 8731 DI 10.1063/1.477540 PG 1 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 139AJ UT WOS:000077005000067 ER PT J AU Bronte, V Wang, M Overwijk, WW Surman, DR Pericle, F Rosenberg, SA Restifo, NP AF Bronte, V Wang, M Overwijk, WW Surman, DR Pericle, F Rosenberg, SA Restifo, NP TI Apoptotic death of CD8(+) T lymphocytes after immunization: Induction of a suppressive population of Mac-1(+)/Gr-1(+) cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; TOTAL LYMPHOID IRRADIATION; TUMOR-ASSOCIATED ANTIGEN; ACUTE VIRAL-INFECTION; BYSTANDER ACTIVATION; BETA-GALACTOSIDASE; IMMUNE SUPPRESSION; NS CELLS; RECOMBINANT; CANCER AB Following an infection or immunization, a primary CD8(+) T cell response generally rises then falls rapidly before giving rise to a "memory" response. When we immunized mice with recombinant viral immunogens optimized to enhance the lytic capability of CD8(+) T cells, we measured a profound depression in Ag-specific effector function after early restimulation, Indeed, a "mirror image" cytolytic capability was observed: the most powerful immunogens, as measured by cytolytic capacity 6 days after immunization, elicited the weakest secondary immune response when evaluated following an additional 6 days after restimulation. To understand the mechanism of this suppression, we examined the fate of splenocytes immunized with a vaccinia virus encoding Ag and IL-2 then restimulated ex vivo. We found that these splenocytes underwent an apoptotic cell death, upon early restimulation, that was not dependent on the engagement of the FasR (CD95). Unlike previously described mechanisms of "propriocidal cell death" and "clonal exhaustion," the cell death we observed was not an inherent property of the CD8(+) T cells but rather was due to a population of splenocytes that stained positive for both the Mac-1 and Gr-l surface markers. Deletion of these cells in vitro or in vivo completely abrogated the observed suppression of cytolytic reactivity of Ag-specific CD8(+) T cells. These observations could account for the apparent absence of Ag-specific immune responses after some current vaccination regimens employing powerful immunogens. Finally, our results may shed new light on a mechanism for the suppression of CD8(+) T cell responses and its effect on vaccine efficacy and on immune memory. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. RP Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42,10 Ctr Dr,MSC 1502, 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 47 TC 168 Z9 179 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1998 VL 161 IS 10 BP 5313 EP 5320 PG 8 WC Immunology SC Immunology GA 137MT UT WOS:000076919100029 PM 9820504 ER PT J AU Sehgal, D Schiaffella, E Anderson, AO Mage, RG AF Sehgal, D Schiaffella, E Anderson, AO Mage, RG TI Analyses of single B cells by polymerase chain reaction reveal rearranged V-H with germline sequences in spleens of immunized adult rabbits: Implications for B cell repertoire maintenance and renewal SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GERMINAL-CENTERS; HEAVY-CHAIN; LYMPHOCYTE PRECURSORS; GENE CONVERSION; VARIABLE GENES; REGION; MOUSE; GENERATION; DIVERSITY; CHICKEN AB We used PCR to amplify rearranged V(H)DJ(H) genes in single cells collected by micromanipulation from splenic germinal centers of immunized adult rabbits, In the course of the study, the objective of which was to analyze diversification of rearranged V(H)DJ(H) sequences, we were surprised to find cells 7 and 10 days after immunization with rearranged V(H)1a2 as well as a-negative (y33 and x32) sequences that were identical or close to germline (10 or fewer changes). About 58% (82/140) of the sequences had unique CDR3 regions and were unrelated. In seven different germinal centers, we found one to four different clones with two to seven members. Clonally related cells underwent diversification by hypermutation and gene conversion. We found that contrary to published reports, adult rabbits indeed have newly diversifying B cell receptors in splenic germinal centers. The attractive idea that the rabbit, like the chicken, develops its B cell repertoire early in life and depends upon self-renewing cells in the periphery to maintain its B lymphocyte pool throughout life, is challenged by the current finding. Although a major population of B lymphocytes may be generated early in life, diversified extensively, and maintained by self-renewal in the periphery, some sources of cells with sequences close to germline do exist in adult rabbits and appear in the developing germinal centers. Although considerable repertoire diversity is generated in young rabbits, mechanisms for continued generation of B cell receptor diversity are retained in adult life, where they may confer survival advantage. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. NR 51 TC 26 Z9 28 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1998 VL 161 IS 10 BP 5347 EP 5356 PG 10 WC Immunology SC Immunology GA 137MT UT WOS:000076919100033 PM 9820508 ER PT J AU Eicher, DM Waldmann, TA AF Eicher, DM Waldmann, TA TI IL-2R alpha on one cell can present IL-2 to IL-2R beta/gamma(c) on another cell to augment IL-2 signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN INTERLEUKIN-2 RECEPTOR; JAK-3 JANUS KINASE; GAMMA-CHAIN; T-CELL; HUMAN NEUTROPHILS; BETA-CHAIN; CYTOPLASMIC DOMAINS; MOLECULAR-CLONING; ALPHA-SUBUNIT; ZETA-CHAIN AB IL-2R alpha augments IL-2 signaling. Although this is generally believed to occur only when the three known components of IL-2R are associated within a single cell membrane, we demonstrate here an intercellular interaction. Cocultivation of cells individually expressing chimerae incorporating the extracellular domain of IL-2Ra alone with cells expressing chimerae of IL-2R beta alone permitted IL-2 dose-dependent oligomerization of the chimerae, Likewise, native IL-2R alpha-bearing cells augmented the IL-2 proliferative response of ex vivo large granular lymphocytic leukemia cells expressing IL-2R beta/gamma(c), but lacking IL-2R alpha. In both cases, the response was inhibitable by an Ab to IL-2R alpha. Intercellular augmentation of cytokine effects, acting in trans, has important implications for biology and medicine. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Eicher, DM (reprint author), Case Western Reserve Univ Hosp, Sch Med, Ireland Canc Ctr, Div Hematol Oncol, 10900 Euclid Ave,BRB, Cleveland, OH 44106 USA. NR 40 TC 34 Z9 35 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1998 VL 161 IS 10 BP 5430 EP 5437 PG 8 WC Immunology SC Immunology GA 137MT UT WOS:000076919100043 PM 9820518 ER PT J AU Dimitrov, DS Xiao, X Chabot, DJ Broder, CC AF Dimitrov, DS Xiao, X Chabot, DJ Broder, CC TI HIV coreceptors SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Review DE HIV; receptors; chemokines; membrane fusion ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHEMOKINE RECEPTOR CXCR4; HUMAN CELL-LINES; ENVELOPE GLYCOPROTEIN; PRIMARY MACROPHAGES; CD4-INDEPENDENT INFECTION; INFLUENZA HEMAGGLUTININ; DISEASE PROGRESSION; MAJOR DETERMINANT; CD4-GP120 COMPLEX C1 NCI, Frederick Canc Res & Dev Ctr, Membrane Struct & Funct Sect, Frederick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. RP Dimitrov, DS (reprint author), NCI, Frederick Canc Res & Dev Ctr, Membrane Struct & Funct Sect, Frederick, MD 21702 USA. NR 112 TC 25 Z9 26 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD NOV 15 PY 1998 VL 166 IS 2 BP 75 EP 90 DI 10.1007/s002329900450 PG 16 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 139ZP UT WOS:000077061400001 PM 9841733 ER PT J AU Cho, SI Ko, J Patton, BL Sanes, JR Chiu, AY AF Cho, SI Ko, J Patton, BL Sanes, JR Chiu, AY TI Motor neurons and Schwann cells distinguish between synaptic and extrasynaptic isoforms of laminin SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE neuromuscular junction; laminin-11; motor neurons; Schwann cells ID FIBER BASAL LAMINA; NEUROMUSCULAR-JUNCTION; S-LAMININ; ACETYLCHOLINE-RECEPTORS; REGENERATING MUSCLE; MOUSE LAMININ; A-CHAIN; CHOLINE-ACETYLTRANSFERASE; CHROMOSOMAL ASSIGNMENT; EXTRACELLULAR-MATRIX AB Laminin is a major component of all basement membranes. However, its composition varies with location because there are numerous forms of each of the three chains (alpha, beta, and gamma) that together comprise this heterotrimeric molecule, In the neuromuscular system, motor neurons and Schwann cells encounter unique trimers of laminin at different sites. The question thus arises as to whether these local differences in laminin composition act to direct the behavior of these two classes of cells. To address this question, we compared the responses of cultured rat motor neurons and Schwann cells to three forms of rodent laminin purified in our laboratory: Laminin-l (Lmn-1; alpha 1 beta 1 gamma 1); Laminin-ll (Lmn-11), a synapse specific isoform consisting of alpha 5 beta 2 gamma 1chains; and a third preparation, a mixture of three kinds of laminin (Lmn-2/4/8), that is enriched for the alpha 2, (alpha 4, beta 1, beta 2, and gamma 1 subunits, Schwann cells attached best to a substrate of Lmn-2/4/8 and showed the weakest adhesion on Lmn-11, Interestingly, no such difference was seen with motor neurons; all three substrates promoted neuronal adhesion, survival, and neurite initiation equally well. With longer time in culture, however, these embryonic motor neurons extended extremely long processes on Lmn-1 and on Lmn-2/4/8, while those on Lmn-11 bore shorter neurites with unusually large, flattened growth cones, These results demonstrate that the behavior of Schwann cells and motor neurons can be regulated directly by the local laminin composition, The precise geometric relationship of these cells at the neuromuscular junction may therefore reflect the unique composition of laminin at this synapse, (C) 1998 John Wiley & Sons, Inc. C1 City Hope Natl Med Ctr, Beckman Res Inst, Div Neurosci, Duarte, CA 91010 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. RP Chiu, AY (reprint author), NINDS, Div Stroke Trauma & Neurodegenerat Disorders, 7550 Wisconsin Ave,Suite 8A-13, Bethesda, MD 20892 USA. FU NINDS NIH HHS [NS029172, NS19195] NR 86 TC 31 Z9 31 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD NOV 15 PY 1998 VL 37 IS 3 BP 339 EP 358 DI 10.1002/(SICI)1097-4695(19981115)37:3<339::AID-NEU1>3.0.CO;2-9 PG 20 WC Neurosciences SC Neurosciences & Neurology GA 135DB UT WOS:000076784300001 PM 9828041 ER PT J AU Stevens, B Tanner, S Fields, RD AF Stevens, B Tanner, S Fields, RD TI Control of myelination by specific patterns of neural impulses SO JOURNAL OF NEUROSCIENCE LA English DT Article DE myelination; impulse activity; L1; DRG neuron; Schwann cell; cell adhesion molecule ID CELL-ADHESION MOLECULE; SCHWANN-CELLS; ELECTRICAL-ACTIVITY; NERVOUS-SYSTEM; NUCLEOTIDE-SEQUENCE; PERIPHERAL MYELIN; MESSENGER-RNA; N-CAM; L1; GLYCOPROTEIN AB A cell culture preparation equipped with stimulating electrodes was used to investigate whether action potential activity can influence myelination of mouse dorsal root ganglia axons by Schwann cells. Myelination was reduced to one-third of normal by low-frequency impulse activity (0.1 Hz), but higher-frequency stimulation (1 Hz) had no effect. The number of Schwann cells and the ultrastructure of compact myelin were not affected. The frequency of stimulation that inhibited myelination decreased expression of the cell adhesion molecule L1, and stimulation under conditions that prevented the reduction in L1 blocked the effects on myelination. This link between myelination and functional activity in the axon at specific frequencies that change axonal expression of L1 could have important consequences for the structural and functional relationship of myelinating axons. C1 NICHHD, Neurocytol & Physiol Unit, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHHD, Neurocytol & Physiol Unit, Dev Neurobiol Lab, NIH, 49 Convent Dr,Bldg 49,Room 5A38, Bethesda, MD 20892 USA. NR 41 TC 93 Z9 93 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 15 PY 1998 VL 18 IS 22 BP 9303 EP 9311 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 136AB UT WOS:000076834300016 PM 9801369 ER PT J AU Petit, L Courtney, SM Ungerleider, LG Haxby, JV AF Petit, L Courtney, SM Ungerleider, LG Haxby, JV TI Sustained activity in the medial wall during working memory delays SO JOURNAL OF NEUROSCIENCE LA English DT Article DE human; working memory; fMRI; supplementary; motor area; pre-SMA; supplementary eye field; anterior cingulum ID POSITRON EMISSION TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; SACCADIC EYE-MOVEMENTS; FUNCTIONAL-ANATOMY; BRAIN ACTIVATION; MOTOR AREAS; PET; SYSTEM; INVOLVEMENT; INFORMATION AB We have taken advantage of the temporal resolution afforded by functional magnetic resonance imaging (fMRI) to investigate the role played by medial wall areas in humans during working memory tasks. We demarcated the medial motor areas activated during simple manual movement, namely the supplementary motor area (SMA) and the cingulate motor area (CMA), and those activated during visually guided saccadic eye movements, namely the supplementary eye field (SEF). We determined the location of sustained activity over working memory delays in the medial wall in relation to these functional landmarks during both spatial and face working memory tasks. We identified two distinct areas, namely the pre-SMA and the caudal part of the anterior cingulate cortex (caudal-AC), that showed similar sustained activity during both spatial and face working memory delays. These areas were distinct from and anterior to the SMA, CMA, and SEF. Both the pre-SMA and caudal-AC activation were identified by a contrast between sustained activity during working memory delays as compared with sustained activity during control delays in which subjects were waiting for a cue to make a simple manual motor response. Thus, the present findings suggest that sustained activity during working memory delays in both the pre-SMA and caudal-AC does not reflect simple motor preparation but rather a state of preparedness for selecting a motor response based on the information held on-line. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Haxby, JV (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 3C104,10 Ctr Dr, Bethesda, MD 20892 USA. RI GINSPAN, All/B-8714-2008; Petit, Laurent/D-6583-2011 OI Petit, Laurent/0000-0003-2499-5367 NR 48 TC 206 Z9 210 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 15 PY 1998 VL 18 IS 22 BP 9429 EP 9437 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 136AB UT WOS:000076834300028 PM 9801381 ER PT J AU Lai, WW Lipshultz, SE Easley, KA Starc, TJ Drant, SE Bricker, JT Colan, SD Moodie, DS Sopko, G Kaplan, S AF Lai, WW Lipshultz, SE Easley, KA Starc, TJ Drant, SE Bricker, JT Colan, SD Moodie, DS Sopko, G Kaplan, S CA P2C2 HIV Study Grp TI Prevalence of congenital cardiovascular malformations in children of human immunodeficiency virus-infected women - The prospective P(2)C(2) HIV multicenter study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID VENTRICULAR SEPTAL-DEFECT; CORONARY-ARTERY FISTULAS; HEART-DISEASE; DUCTUS-ARTERIOSUS; FOLLOW-UP; ECHOCARDIOGRAPHY; ANOMALIES; LIFE AB Objectives. The purpose of the study was to assess the effects of maternal HIV-1 (human immunodeficiency virus) infection and vertically transmitted HIV-1 infection on the prevalence of congenital cardiovascular malformations in children. Background In the United States, an estimated 7000 children are born to HIV-infected women annually. Previous limited reports have suggested an increase in the prevalence of congenital cardiovascular malformations in vertically transmitted HIV-infected children. Methods. In a prospective longitudinal multicenter study, diagnostic echocardiograms were performed at 4-6-month intervals on two cohorts of children exposed to maternal HIV-1 infection: 1) a Neonatal Cohort of 90 HIV-infected, 449 HIV-uninfected and 19 HIV-indeterminate children; and 2) an Older HIV-Infected Cohort of 201 children with vertically transmitted HIV-1 infection recruited after 28 days of age. Results. In the Neonatal Cohort, 36 lesions were seen in 36 patients, yielding an overall congenital cardiovascular malformation prevalence of 6.5% (36/558), with a 8.9% (8/90) prevalence in HIV-infected children and a 5.6% (25/449) prevalence in HIV-uninfected children. Two children (2/558, 0.4%) had cyanotic lesions. In the Older HIV-Infected Cohort, there was a congenital cardiovascular malformation prevalence of 7.5% (15/201). The distribution of lesions did not differ significantly between the groups. Conclusions. There was no statistically significant difference in congenital cardiovascular malformation prevalence in HIV-infected versus HIV-uninfected children born to HIV-infected women. With the use of early screening echocardiography, rates of congenital cardiovascular malformations in both the HIV-infected and HIV-uninfected children were five- to ten-fold higher than rates reported in population-based epidemiologic studies but not higher than in normal populations similarly screened. Potentially important subclinical congenital cardiovascular malformations were detected. (J Am Cell Cardiol 1998;32:1749-55) (C) 1998 by the American College of Cardiology. C1 Mt Sinai Sch Med, Dept Pediat, Div Pediat Cardiol, New York, NY USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Pediat, Div Pediat Cardiol, Cleveland, OH 44195 USA. Columbia Univ, Presbyterian Hosp, Sch Med, Dept Pediat,Div Pediat Cardiol, New York, NY USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Div Pediat Cardiol, Los Angeles, CA 90024 USA. Baylor Coll Med, Dept Pediat, Div Pediat Cardiol, Houston, TX 77030 USA. NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. RP Lai, WW (reprint author), CUNY, Mt Sinai Med Ctr, Div Pediat Cardiol, 1 Gustave L Levy Pl,Box 1201, New York, NY 10029 USA. EM Wyman_Lai@smtplink.mssm.edu RI Easley, Kirk/K-6910-2015 OI Easley, Kirk/0000-0003-4419-2617 FU NCRR NIH HHS [K01 RR000188, M01 RR000188, M01 RR000533, M01 RR000865, M01 RR002172]; NHLBI NIH HHS [N01 HR096037, N01-HR-96038, N01 HR096043, N01-HR-96039] NR 31 TC 19 Z9 21 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 15 PY 1998 VL 32 IS 6 BP 1749 EP 1755 DI 10.1016/S0735-1097(98)00449-5 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 138PM UT WOS:000076981500023 PM 9822105 ER PT J AU Lustig, B Bahar, I Jernigan, RL AF Lustig, B Bahar, I Jernigan, RL TI RNA bulge entropies in the unbound state correlate with peptide binding strengths for HIV-1 and BIV TAR RNA because of improved conformational access SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MAJOR GROOVE; COMPLEX; RECOGNITION AB For the binding of peptides to wild-type HIV-1 and BIV TAR RNA and to mutants with bulges of various sizes, changes in the Delta Delta Gvalues of binding were determined from experimental K-d values. The corresponding entropies of these bulges are estimated by enumerating all possible RNA bulge conformations on a lattice and then applying the Boltzmann relationship. Independent calculations of entropies from fluctuations are also carried out using the Gaussian network model(GNM) recently introduced for analyzing folded structures. Strong correlations are seen between the changes in free energy determined for binding and the two different unbound entropy calculations. The fact that the calculated entropy increase with larger bulge size is correlated with the enhanced experimental binding free energy is unusual. This system exhibits a dependence on the entropy of the unbound form that is opposite to usual binding models. Instead of a large initial entropy being unfavorable since it would be reduced upon binding, here the larger entropies actually favor binding. Several interpretations are possible: (i) the higher conformational freedom implies a higher competence for binding with a minimal strain, by suitable selection amongst the set of already accessible conformations; (ii) larger bulge entropies enhance the probability of the specific favorable conformation of the bound state; (iii) the increased freedom of the larger bulges contributes more to the bound state than to the unbound state; (iv) indirectly the large entropy of the bound state might have an unfavorable effect on the solvent structure. Nonetheless, this unusual effect is interesting. C1 San Jose State Univ, Dept Chem, San Jose, CA 95192 USA. Appl Sci Consultants, San Jose, CA 95134 USA. Bogazici Univ, Ctr Polymer Res, TR-80815 Bebek, Turkey. Bogazici Univ, Dept Chem Engn, TR-80815 Bebek, Turkey. TUBITAK, Adv Polymer Mat Res Ctr, TR-80815 Bebek, Istanbul, Turkey. NCI, Lab Expt & Computat Biol, Mol Struct Sect, NIH, Bethesda, MD 20892 USA. RP Lustig, B (reprint author), Appl Sci Consultants, 621-B River Oaks Pkwy, San Jose, CA 95134 USA. EM lustig@batnet.com RI Jernigan, Robert/A-5421-2012 NR 17 TC 18 Z9 18 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 15 PY 1998 VL 26 IS 22 BP 5212 EP 5217 DI 10.1093/nar/26.22.5212 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 140JV UT WOS:000077084900027 PM 9801321 ER PT J AU Albert, JM Ioannidis, JPA Reichelderfer, P Conway, B Coombs, RW Crane, L Demasi, R Dixon, DO Flandre, P Hughes, MD Kalish, LA Larntz, K Lin, DY Marschner, IC Munoz, A Murray, J Neaton, J Pettinelli, C Rida, W Taylor, JMG Welles, SL AF Albert, JM Ioannidis, JPA Reichelderfer, P Conway, B Coombs, RW Crane, L Demasi, R Dixon, DO Flandre, P Hughes, MD Kalish, LA Larntz, K Lin, DY Marschner, IC Munoz, A Murray, J Neaton, J Pettinelli, C Rida, W Taylor, JMG Welles, SL CA NIAID Workshop TI Statistical issues for HIV surrogate endpoints: Point/counterpoint SO STATISTICS IN MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYNCYTIUM-INDUCING PHENOTYPE; CLINICAL-TRIALS; LYMPHOCYTE COUNTS; VIRAL LOAD; RNA LEVELS; DISEASE PROGRESSION; ZIDOVUDINE THERAPY; CUBIC MILLIMETER; PROGNOSTIC VALUE AB This paper summarizes the proceedings of an NIAID-sponsored workshop on statistical issues for HIV surrogate endpoints. The workshop brought together statisticians and clinicians in an attempt to shed light on some unresolved issues in the use of HIV laboratory markers (such as HIV RNA and CD4 + cell counts) in the design and analysis of clinical studies and in patient management. Utilizing a debate format, the workshop explored a series of specific questions dealing with the relationship between markers and clinical endpoints, and the choice of endpoints and methods of analysis in clinical studies. This paper provides the position statements from the two debaters on each issue. Consensus conclusions, based on the presentations and discussion, are outlined. While not providing final answers, we hope that these discussions have helped clarify a number of issues, and will stimulate further consideration of some of the highlighted problems. These issues will be critical in the proper assessment and use of future therapies for HIV disease. (C) 1998 John Wiley & Sons, Ltd. C1 NIAID, Div Aids, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Washington, Seattle, WA 98195 USA. Wayne State Univ, Detroit Med Ctr, Detroit, MI 48202 USA. London Sch Hyg & Trop Med, London WC1, England. New England Res Inst, Watertown, MA USA. Univ Minnesota, Minneapolis, MN 55455 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. US FDA, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Albert, JM (reprint author), NIAID, Div Aids, Biostat Res Branch, NIH, 6003 Execut Blvd, Bethesda, MD 20892 USA. EM ja24o@nih.gov RI Ioannidis, John/G-9836-2011 FU NIAID NIH HHS [AI27664, AI27757, AI30731] NR 71 TC 31 Z9 32 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 1998 VL 17 IS 21 BP 2435 EP 2462 DI 10.1002/(SICI)1097-0258(19981115)17:21<2435::AID-SIM994>3.3.CO;2-7 PG 28 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 132JF UT WOS:000076626000002 PM 9819838 ER PT J AU Cronin, KA Legler, JM Etzioni, RD AF Cronin, KA Legler, JM Etzioni, RD TI Assessing uncertainty in micro simulation modelling with application to cancer screening interventions SO STATISTICS IN MEDICINE LA English DT Article ID MONTE-CARLO TECHNIQUES; HEART-DISEASE MODELS; PARAMETER SENSITIVITY; COST-EFFECTIVENESS; PROSTATE-CANCER; MICROPOPULATIONS; EPIDEMIOLOGY; SERIES; MEN AB Microsimulation is fast becoming the approach of choice for modelling and analysing complex processes in the absence of mathematical tractability. While this approach has been developed and promoted in engineering contexts for some time, it has more recently found a place in the mainstream of the study of chronic disease interventions such as cancer screening. The construction of a simulation model requires the specification of a model structure and sets of parameter values, both of which may have a considerable amount of uncertainty associated with them. This uncertainty is rarely quantified when reporting microsimulation results. We suggest a Bayesian approach and assume a parametric probability distribution to mathematically express the uncertainty related to model parameters. First, we design a simulation experiment to achieve good coverage of the parameter space. Second, we model a response surface for the outcome of interest as a function of the model parameters using the simulation results. Third, we summarize the variability in the outcome of interest, including variation due to parameter uncertainty, using the response surface in combination with parameter probability distributions. We illustrate the proposed method with an application of a microsimulator designed to investigate the effect of prostate specific antigen (PSA) screening on prostate cancer mortality rates. (C) 1998 John Wiley & Sons, Ltd. C1 NCI, Biometry Branch, Bethesda, MD 20892 USA. NCI, Appl Res Branch, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Cronin, KA (reprint author), NCI, Biometry Branch, EPN 313,6130 Execut Plaza N, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CN-05230] NR 37 TC 16 Z9 16 U1 3 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 1998 VL 17 IS 21 BP 2509 EP 2523 DI 10.1002/(SICI)1097-0258(19981115)17:21<2509::AID-SIM949>3.0.CO;2-V PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 132JF UT WOS:000076626000006 PM 9819842 ER PT J AU Sano, M Williams, S Smith, N Horne, M Gralnick, HR AF Sano, M Williams, S Smith, N Horne, M Gralnick, HR TI Plasma glycocalicin in platelet concentrates: Relationship to other parameters of the storage lesion SO THROMBOSIS RESEARCH LA English DT Article DE glycocalicin; platelets; platelet concentrates ID GLYCOPROTEIN-IB; ACTIVATION; LIGHT C1 NIH, Hematol Serv, Dept Clin Pathol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Gralnick, HR (reprint author), NIH, Hematol Serv, Dept Clin Pathol, Warren Grant Magnuson Clin Ctr, Room 2C-390,Bldg 10, Bethesda, MD 20892 USA. NR 14 TC 6 Z9 6 U1 0 U2 0 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 NOV 15 PY 1998 VL 92 IS 4 BP 195 EP 198 DI 10.1016/S0049-3848(98)00128-5 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 139LH UT WOS:000077029700007 PM 9840029 ER PT J AU Rose, SM Blustein, N Rotrosen, D AF Rose, SM Blustein, N Rotrosen, D CA Expert Panel TI Recommendations of the expert panel on ethical issues in clinical trials of transplant tolerance SO TRANSPLANTATION LA English DT Article AB In April 1998, the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) convened an expert panel to begin developing guidelines for the design, conduct, and monitoring of scientifically and ethically acceptable clinical trials to evaluate the safety and efficacy of new approaches to achieve immune tolerance in transplant recipients. A group of experts in bioethics, law, and basic and clinical research in transplantation joined NIH staff and representatives of the U.S. Food and Drug Administration and the NIH Office of Protection from Research Risks. C1 NIAID, Genet & Transplantat Branch, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. RP Rose, SM (reprint author), NIAID, Genet & Transplantat Branch, Div Allergy Immunol & Transplantat, NIH, 6003 Execut Blvd,Room 4A14, Bethesda, MD 20892 USA. NR 0 TC 23 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 1998 VL 66 IS 9 BP 1123 EP 1125 DI 10.1097/00007890-199811150-00001 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 139BL UT WOS:000077007500001 PM 9825804 ER PT J AU Albanes, D AF Albanes, D TI Height, early energy intake, and cancer - Evidence mounts for the relation of energy intake to adult malignancies SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID RISK C1 NCI, Canc Prevent Studies Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Albanes, D (reprint author), NCI, Canc Prevent Studies Branch, Div Clin Sci, 321, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 NR 11 TC 21 Z9 21 U1 0 U2 7 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD NOV 14 PY 1998 VL 317 IS 7169 BP 1331 EP 1332 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 140HH UT WOS:000077081600001 PM 9812924 ER PT J AU Ban, C Yang, W AF Ban, C Yang, W TI Crystal structure and ATPase activity of MutL: Implications for DNA repair and mutagenesis SO CELL LA English DT Article ID DIRECTED MISMATCH REPAIR; NONPOLYPOSIS COLORECTAL-CANCER; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; GENE; PROTEIN; MUTATIONS; CHAPERONE; RECOMBINATION; REPLICATION AB MutL and its homologs are essential for DNA mismatch repair. Mutations in genes encoding human homologs of MutL cause multiorgan cancer susceptibility. We have determined the crystal structure of a 40 kDa N-terminal fragment of E. coli MutL that retains all of the conserved residues in the MutL family. The structure of MutL is homologous to that of an ATPase-containing fragment of DNA gyrase. We have demonstrated that MutL binds and hydrolyzes ATP to ADP and Pi. Mutations in the MutL family that cause deficiencies in DNA mismatch repair and a predisposition to cancer mainly occur in the putative ATP-binding site. We provide evidence that the flexible, yet conserved, loops surrounding this ATP-binding site undergo conformational changes upon ATP hydrolysis thereby modulating interactions between MutL and other components of the repair machinery. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM wei.yang@nih.gov RI Yang, Wei/D-4926-2011; Ban, Changill/F-5426-2013 OI Yang, Wei/0000-0002-3591-2195; NR 44 TC 276 Z9 278 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 13 PY 1998 VL 95 IS 4 BP 541 EP 552 DI 10.1016/S0092-8674(00)81621-9 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 139VB UT WOS:000077049400012 PM 9827806 ER PT J AU Rao, JK Bujacz, G Wlodawer, A AF Rao, JK Bujacz, G Wlodawer, A TI Crystal structure of rabbit muscle creatine kinase SO FEBS LETTERS LA English DT Article DE creatine kinase; rabbit muscle; enzyme; crystal structure ID IDENTIFICATION; PROTEIN; RESIDUES; SITE AB The crystal structure of rabbit muscle creatine kinase, solved at 2.35 Angstrom resolution by X-ray diffraction methods, clearly identified the active site with bound sulfates surrounded by a constellation of arginine residues. The putative binding site of creatine, which is occupied by a sulfate group in this analysis, has been tentatively identified. The dimeric interface of the enzyme is held together by a small number of hydrogen bonds. (C) 1998 Federation of European Biochemical Societies. C1 NCI, Macromol Struct Lab, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Lodz Tech Univ, Fac Food Chem & Biotechnol, PL-90924 Lodz, Poland. RP Rao, JK (reprint author), NCI, Macromol Struct Lab, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. EM rao@ncifcrf.gov NR 28 TC 129 Z9 134 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 13 PY 1998 VL 439 IS 1-2 BP 133 EP 137 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 140UT UT WOS:000077107300028 PM 9849893 ER PT J AU Sturgeon, BE Sipe, HJ Barr, DP Corbett, JT Martinez, JG Mason, RP AF Sturgeon, BE Sipe, HJ Barr, DP Corbett, JT Martinez, JG Mason, RP TI The fate of the oxidizing tyrosyl radical in the presence of glutathione and ascorbate - Implications for the radical sink hypothesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ELECTRON-SPIN RESONANCE; REDUCED GLUTATHIONE; PHENOXYL RADICALS; SUPEROXIDE; ANTIOXIDANTS; METABOLISM; OXIDATION; ACID; LACTOPEROXIDASE; ACETAMINOPHEN AB Cellular systems contain as much as millimolar concentrations of both ascorbate and GSH, although the GSH concentration is often 10-fold that of ascorbate. It has been proposed that GSH and superoxide dismutase (SOD) act in a concerted effort to eliminate biologically generated radicals. The tyrosyl radical (Tyr(.)) generated by horseradish peroxidase in the presence of hydrogen peroxide can react with GSH to form the glutathione thiyl radical (GS(.)), GS(.) can react with the glutathione anion (GS(-)) to form the disulfide radical anion (GSSG(radical) (anion)). This highly reactive disulfide radical anion will reduce molecular oxygen, forming superoxide and glutathione disulfide (GSSG). In a concerted effort, SOD will catalyze the dismutation of superoxide, resulting in the elimination of the radical. The physiological relevance of this GSH/SOD concerted effort is questionable, In a tyrosyl radical-generating system containing ascorbate (100 mu M) and GSH (8 mM), the ascorbate nearly eliminated oxygen consumption and diminished GS(.) formation. In the presence of ascorbate, the tyrosyl radical will oxidize ascorbate to form the ascorbate radical. When measuring the ascorbate radical directly using fast-flow electron spin resonance, only minor changes in the ascorbate radical electron spin resonance signal intensity occurred in the presence of GSH. These results indicate that in the presence of physiological concentrations of ascorbate and GSH, GSH is not involved in the detoxification pathway of oxidizing free radicals formed by peroxidases. C1 Hampden Sydney Coll, Dept Chem, Hampden Sydney, VA 23943 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Sturgeon, BE (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 41 TC 65 Z9 66 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 13 PY 1998 VL 273 IS 46 BP 30116 EP 30121 DI 10.1074/jbc.273.46.30116 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 139BR UT WOS:000077008100013 PM 9804766 ER PT J AU Yamashita, H Xu, J Erwin, RA Farrar, WL Kirken, RA Rui, H AF Yamashita, H Xu, J Erwin, RA Farrar, WL Kirken, RA Rui, H TI Differential control of the phosphorylation state of proline-juxtaposed serine residues Ser(725) of Stat5a and Ser(730) of Stat5b in prolactin-sensitive cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTIONALLY ACTIVE STAT1; DNA-BINDING; TYROSINE PHOSPHORYLATION; SUBSTRATE RECOGNITION; HORMONE ACTIVATION; INTERFERON-ALPHA; GENE-EXPRESSION; KINASE-ACTIVITY; PROTEIN-KINASE; T-LYMPHOCYTES AB Transcription factors of the Stat family are controlled by protein kinases, Phosphorylation of a positionally conserved tyrosine residue is obligatory for Stat dimerization, nuclear translocation, and specific DNA binding. Studies of Stat1 and Stat3 have suggested that serine phosphorylation may also regulate function. We now identify serine residues located in a conserved PSP motif of Stat5a (Ser(725)) and Stat5b (Ser(730)) as major phosphorylation sites, using mutagenesis, phosphoamino acid analysis, and site-specific anti-Stat5-phosphoserine antibodies. Unexpectedly, phosphorylation control of this PSP motif differed between the highly homologous Stat5a and Stat5b proteins. Whereas Ser(725) of Stat5a was constitutively phosphorylated both in COS-7 cells and Nb2 lymphocytes, phosphorylation of Ser(730) of Stat5b was markedly stimulated by prolactin. The data also suggested the existence of a second major serine phosphorylation site in Stat5a. Interestingly, constitutive phosphorylation of the PSP motif was suppressed by PD98059 but not by staurosporine under conditions in which both agents inhibited mitogen-activated protein kinases. Furthermore, pretreatment of cells with staurosporine, PD98059, H7, or wortmannin did not prevent either Stat5a or Stat5b from becoming maximally serine-phosphorylated after prolactin exposure. We propose that two pathways regulate Stat5 serine phosphorylation, one that is prolactin-activated and PD98059-resistant and one that is constitutively active and PD98059-sensitive and preferentially targets Stat5a, Finally, phosphorylation of the PSP motif of Stat5a or Stat5b was not essential for DNA binding: or transcriptional activation of a beta-casein reporter gene in COS-7 cells, suggesting that serine kinase control of Stat5 activity differs from that of Stat1 and Stat3. C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Sch Med, Bethesda, MD 20814 USA. Univ Texas, Dept Integrat Biol Pharmacol & Physiol, Houston, TX 77030 USA. NIH, Intramural Res Support Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. NCI, Div Basic Sci, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. RP Rui, H (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, Sch Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM hrui@usuhs.mil FU NIDDK NIH HHS [R01 DK52013-01A1] NR 39 TC 118 Z9 119 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 NOV 13 PY 1998 VL 273 IS 46 BP 30218 EP 30224 DI 10.1074/jbc.273.46.30218 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 139BR UT WOS:000077008100026 PM 9804779 ER PT J AU Beard, WA Bebenek, K Darden, TA Li, L Prasad, R Kunkel, TA Wilson, SH AF Beard, WA Bebenek, K Darden, TA Li, L Prasad, R Kunkel, TA Wilson, SH TI Vertical-scanning mutagenesis of a critical tryptophan in the minor groove binding track of HIV-1 reverse transcriptase - Molecular nature of polymerase-nucleic acid interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ANGSTROM RESOLUTION; TEMPLATE-PRIMER; DNA-SYNTHESIS; CRYSTAL-STRUCTURE; THUMB SUBDOMAIN; REACTION PH; FIDELITY; POLYMERIZATION; SITE AB While sequence-specific DNA-binding proteins interact predominantly in the DNA major groove, DNA polymerases bind DNA through interactions in the minor groove that are sequence nonspecific. Through functional analyses of alanine-substituted mutant enzymes that were guided by molecular dynamics modeling of the human immunodeficiency virus type I reverse transcriptase and DNA complex, we previously identified a structural element in reverse transcriptase, the minor groove binding track (MGBT), The MGBT is comprised of five residues (Ile(94), Gln(258), Gly(262), Trp(266), and Gln(269)) which interact 2-6 base pahs upstream from the polymerase active site in the DNA minor groove and are important in DNA binding, processivity, and frameshift fidelity. These residues do not contribute equally; functional analysis of alanine mutants suggests that Trp(266) contributes the most to binding. To define the molecular interactions between Trp(266) and the DNA minor groove, we have analyzed the properties of eight mutants, each with an alternate side chain at this position. A refined molecular dynamics model was used to calculate relative binding free energies based on apolar surface area buried upon complex formation. In general, there was a strong correlation between the relative calculated binding free energies for the alternate residue 266 side chains and the magnitude of the change in the properties which reflect template-primer interactions (template-primer dissociation rate constant, K-i,K-AZTTP, processivity, and frameshift fidelity). This correlation suggests that hydrophobic interactions make a major contribution to the stability of the polymerase-DNA complex. Additionally, tyrosine and arginine substitutions resulted in mutant enzymes with DNA binding properties better than predicted by buried surface area alone, suggesting that hydrogen bonding could also play a role in DNA binding at this position. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. RP NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov NR 45 TC 34 Z9 34 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 13 PY 1998 VL 273 IS 46 BP 30435 EP 30442 DI 10.1074/jbc.273.46.30435 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 139BR UT WOS:000077008100057 PM 9804810 ER PT J AU Valenzuela, JG Charlab, R Galperin, MY Ribeiro, JMC AF Valenzuela, JG Charlab, R Galperin, MY Ribeiro, JMC TI Purification, cloning, and expression of an apyrase from the bed bug Cimex lectularius - A new type of nucleotide-binding enzyme SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOSIDE TRIPHOSPHATE HYDROLASE; ECTO-ATP-DIPHOSPHOHYDROLASE; TOXOPLASMA-GONDII; CD39; PROTEIN; IDENTIFICATION; ARTHROPODS; DATABASE; BRAIN AB An enzyme that hydrolyzes the phosphodiester bonds of nucleoside tri- and diphosphates, but not monophosphates, thus displaying apyrase (EC 3.6.1.5) activity, was purified from salivary glands of the bed bug, Cimex lectularius. The purified C. lectularius apyrase was an acidic protein with a pI of 5.1 and molecular mass of similar to 40 kDa that inhibited ADP-induced platelet aggregation and hydrolyzed platelet agonist ADP with specific activity of 379 units/mg protein, Amplification of C. lectularius cDNA corresponding to the N-terminal sequence of purified apyrase produced a probe that allowed identification of a 1.3 kilobase pair cDNA clone coding for a protein of 364 amino acid residues, the first 35 of which constituted the signal peptide. The processed form of the protein was predicted to have a molecular mass of 37.5 kDa and pI of 4.95. The identity of the product of the cDNA clone with native C. lectularius apyrase was proved by immunological testing and by expressing the gene in a heterologous host. Immune serum made against a synthetic peptide with sequence corresponding to the C-terminal region of the predicted cDNA clone recognized both C. lectularius apyrase fractions eluted from a molecular sieving high pressure liquid chromatography and the apyrase active band from chromatofocusing gels. Furthermore, transfected COS-7 cells secreted a Ca2+-dependent apyrase with a pI of 5.1 and immunoreactive material detected by the anti-apyrase serum, C. lectularius apyrase has no significant sequence similarity to any other known apyrases, but homologous sequences have been found in the genome of the nematode C, elegans and in mouse and human expressed sequence tags from fetal and tumor EST libraries. C1 NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Ribeiro, JMC (reprint author), NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bldg 4,Rm 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. RI Galperin, Michael/B-5859-2013; OI Galperin, Michael/0000-0002-2265-5572; Ribeiro, Jose/0000-0002-9107-0818 NR 40 TC 99 Z9 100 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 NOV 13 PY 1998 VL 273 IS 46 BP 30583 EP 30590 DI 10.1074/jbc.273.46.30583 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 139BR UT WOS:000077008100076 PM 9804829 ER PT J AU Rao, PV Garrow, TA John, F Garland, D Millian, NS Zigler, JS AF Rao, PV Garrow, TA John, F Garland, D Millian, NS Zigler, JS TI Betaine-homocysteine methyltransferase is a developmentally regulated enzyme crystallin in rhesus monkey lens SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METHIONINE METABOLISM; EYE LENS; PURIFICATION; PROTEIN; RAT; MAMMALS; GENE; CHROMATOGRAPHY; CYSTATHIONINE; QUANTITATION AB We describe herein the characterization of a major 45-kDa protein from the soluble beta H-crystallin fraction of rhesus monkey (Macaca mulatta) lens. Based on partial peptide sequence, immunoreactivity, and enzymatic activity, this protein has been identified as betaine-homocysteine S-methyltransferase (BHMT: EC 2.1.1.5), an enzyme that catalyzes the methylation of homocysteine using either betaine or thetins as methyl donors. This protein was found to be expressed abundantly in the nuclear region of the monkey lens, reaching similar to 10% of the total nuclear protein, but was barely detectable in the epithelium and cortex regions of the lens. Because the nucleus represents the early embryonic and fetal stages of lens development, we infer that BHMT expression in the lens of the eye is developmentally regulated. By virtue of its high abundance, BHMT can be considered an enzyme crystallin (psi-crystallin). This is the first enzyme crystallin to be found in primate lenses. C1 NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. RP Zigler, JS (reprint author), NEI, Lab Mech Ocular Dis, NIH, 6 Ctr Dr,MSC 2735,Bldg 6,Rm 237, Bethesda, MD 20892 USA. EM szigler@helix.nih.gov FU NIDDK NIH HHS [DK 52501] NR 49 TC 37 Z9 37 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 13 PY 1998 VL 273 IS 46 BP 30669 EP 30674 DI 10.1074/jbc.273.46.30669 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 139BR UT WOS:000077008100087 PM 9804840 ER PT J AU Brodie, C Bogi, K Acs, P Lorenzo, PS Baskin, L Blumberg, PM AF Brodie, C Bogi, K Acs, P Lorenzo, PS Baskin, L Blumberg, PM TI Protein kinase C delta (PKC delta) inhibits the expression of glutamine synthetase in glial cells via the PKC delta regulatory domain and its tyrosine phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESTER-INDUCED TRANSLOCATION; NIH 3T3 CELLS; SIGNAL-TRANSDUCTION; NEURONAL DEGENERATION; CATALYTIC DOMAIN; RETINAL TISSUE; ACTIVATION; RECEPTOR; GROWTH; DIFFERENTIATION AB Protein kinase C (PKC) plays an important role in the proliferation and differentiation of glial cells. In a recent study we found that overexpression of PKC delta reduced the expression of the astrocytic marker glutamine synthetase (GS). In this study we explored the mechanisms involved in the inhibitory effect of PRC delta on the expression of glutamine synthetase. Using PHC chimeras we first examined the role of the catalytic and regulatory domains of PKC delta on the expression of glutamine synthetase. We found that cells stably transfected with chimeras between the regulatory domain of PKC delta and the catalytic domains of PKC alpha or epsilon inhibited the expression of GS, similar to the inhibition exerted by overexpression of PKC delta itself. In contrast, no significant effects were observed in cells transfected with the reciprocal PKC chimeras between the regulatory domains of PKC alpha or epsilon and the catalytic domain of PKC delta. PKC delta has been shown to undergo tyrosine phosphorylation in response to various activators. Tyrosine phosphorylation of PKC delta in response to phorbol 12-myristate 13-acetate and platelet derived growth factor occurred only in chimeras which contained the PKC delta regulatory domain. Cells transfected with a PKC delta mutant (PKC delta 5), in which the five putative tyrosine phosphorylation sites were mutated to phenylalanine, showed markedly diminished tyrosine phosphorylation in response to phorbol 12-myristate 13-acetate and platelet-derived growth factor and normal levels of GS. Our results indicate that the regulatory domain of PKC delta mediates the inhibitory effect of this isoform on the expression of GS. Phosphorylation of PKC delta on tyrosine residues in the regulatory domain is implicated in this inhibitory effect. C1 NCI, Mol Mech Tumor Promot Sect, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Bar Ilan Univ, Dept Life Sci, IL-52900 Ramat Gan, Israel. RP Brodie, C (reprint author), NCI, Mol Mech Tumor Promot Sect, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37,Rm 3A01,37 Convent Dr, Bethesda, MD 20892 USA. NR 43 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 13 PY 1998 VL 273 IS 46 BP 30713 EP 30718 DI 10.1074/jbc.273.46.30713 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 139BR UT WOS:000077008100093 PM 9804846 ER PT J AU Weitzmann, MN Woodford, KJ Usdin, K AF Weitzmann, MN Woodford, KJ Usdin, K TI The mouse Ms6-hm hypervariable microsatellite forms a hairpin and two unusual tetraplexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN INSULIN GENE; DNA-STRUCTURE; SECONDARY STRUCTURES; MINISATELLITE LOCUS; SOMATIC MUTATION; QUADRUPLEX DNA; TANDEM ARRAYS; HUMAN-DISEASE; SEQUENCE; PROTEIN AB The mouse Ms6-hm microsatellite consists of a tandem array of the pentamer d(CAGGG)(n). This microsatellite is extremely hypervariable, showing a germ line mutation rate of 2.5%/gamete. The mechanism responsible for this instability is not known. The ability to form intrastrand structures is a conserved feature of many hypervariable sequences, and it has been suggested that the formation of such structures might account for instability by affecting DNA replication, repair, or recombination. Here we show that this microsatellite is able to form intrastrand structures as well. Under physiological conditions, the Ms6-hm microsatellite forms a hairpin as well as two different unusual intrastrand tetraplexes. The hairpin forms in the absence of monovalent cation and contains G.A, G.C, and G.G base pairs in a 1:1:1 ratio. In the presence of K+, a tetraplex is formed in which the adenines are unpaired and extrahelical, and the cytosines are involved in C.C pairs. In Na+, a tetraplex forms that contains C.C+ pairs, with the adenines being intrahelical and hydrogen-bonded to guanines. Tetraplex formation in the presence of Na+ requires both cytosines and adenines and might reflect the altered internal dimensions of this tetraplex, perhaps resulting from the ability of the C.C+ pairs to become intercalated in this sequence context. Our demonstration of the stabilization of tetraplexes by hydrogen bonding between adenines and guanines expands the hydrogen-bonding possibilities for tetraplexes and suggests that the category of sequences with tetraplex-forming potential may be larger than previously appreciated. C1 NIDDK, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIDDK, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bldg 8,Rm 202,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. NR 41 TC 23 Z9 24 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 13 PY 1998 VL 273 IS 46 BP 30742 EP 30749 DI 10.1074/jbc.273.46.30742 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 139BR UT WOS:000077008100097 PM 9804850 ER PT J AU Chefer, SI Horti, AG Lee, KS Koren, AO Jones, DW Gorey, JG Links, JM Mukhin, AG Weinberger, DR London, ED AF Chefer, SI Horti, AG Lee, KS Koren, AO Jones, DW Gorey, JG Links, JM Mukhin, AG Weinberger, DR London, ED TI In vivo imaging of brain nicotinic acetylcholine receptors with 5-[I-123]iodo-A-85380 using single photon emission computed tomography SO LIFE SCIENCES LA English DT Article DE nicotinic acetylcholine receptor; single photon emission computed tomography; 5-[I-123]iodo-3(2(S)-azetidinylmethoxy)pyridine (5-[I-123]iodo-A-85380); rhesus monkey ID BINDING-SITES; EPIBATIDINE; AFFINITY; DEMENTIA; ANALOG AB The distribution and kinetics of 5-[I-123]iodo-A-85380, a novel ligand for brain nicotinic acetylcholine receptors (nAChRs), were evaluated in the Rhesus monkey using single photon emission computed tomography (SPECT). Peak levels of radioactivity were measured in brain at 90 min after injection of the tracer. Accumulation of radioactivity was highest in the thalamus, intermediate in the frontal cortex and basal ganglia, and lowest in the cerebellum. The ratio of specific to nonspecific binding (V-3") in the thalamus, estimated from the (thalamic - cerebellar)/cerebellar radioactivity ratio, reached a value of 6 at 4 h post-injection. Specific binding was reduced by subcutaneous injection of 1 mg/kg cytisine at 2.25 h after injection of radiotracer. At 2.5 h after cytisine administration, radioactivity in the thalamus was reduced by 84 %, in the frontal cortex, by 76%, and in the basal ganglia, by 57 % of the level measured at the time of cytisine administration, demonstrating that the binding was reversible. On the basis of these findings, together with other data indicating high affinity, receptor subtype selectivity, low nonspecific binding and lack of toxicity in animals, 5-[I-123]iodo-A-85380 appears to be a promising ligand for SPECT imaging of nAChRs in the human brain. Published by Elsevier Science Inc. C1 NIDA, Brain Imaging Ctr, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIMH, Intramural Res Program, Clin Brain Disorders Branch, Washington, DC 20032 USA. RP London, ED (reprint author), NIDA, Brain Imaging Ctr, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 20 TC 23 Z9 23 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD NOV 13 PY 1998 VL 63 IS 25 BP PL355 EP PL360 DI 10.1016/S0024-3205(98)00514-1 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 139HX UT WOS:000077023400010 PM 9870715 ER PT J AU Saah, AJ Hoover, DR Weng, SG Carrington, M Mellors, J Rinaldo, CR Mann, D Apple, R Phair, JP Detels, R O'Brien, S Enger, C Johnson, P Kaslow, RA AF Saah, AJ Hoover, DR Weng, SG Carrington, M Mellors, J Rinaldo, CR Mann, D Apple, R Phair, JP Detels, R O'Brien, S Enger, C Johnson, P Kaslow, RA CA Multicenter AIDS Cohort Study TI Association of HLA profiles with early plasma viral load, CD4+ cell count and rate of progression to AIDS following acute HIV-1 infection SO AIDS LA English DT Article DE AIDS; HIV-1; natural history; HLA; HIV-1 RNA plasma viral load ID DISEASE PROGRESSION; T-CELLS; PATHOGENESIS; LYMPHOCYTES; COHORT; VIRUS AB Background: Host genetic factors, such as HLA alleles, play an important role in mediating the course of HIV-1 disease progression through largely undefined mechanisms. Objectives: To examine the association of HLA markers with HIV-1 RNA plasma viral load and other factors associated with course of disease progression in HIV-1 infection. Design and methods: A group of 139 HIV-1 seroconverters from the Multicenter AIDS Cohort Study had been typed for a variety of HLA markers. HIV-1 RNA plasma viral load was measured from frozen plasma specimens obtained approximately 9 months following seroconversion. CD4+ cell counts were available from the same study visit. Statistical analysis was performed using survival techniques and linear regression models to quantify the relative associations of an HLA score profile, HIV-1 RNA plasma viral load, CD4+ cell count and age with each other and with rate of progression to AIDS and death. Results: Cox proportional hazards models showed statistically significant differences in time to AIDS by HLA score profile category per unit increase [relative hazard (RH), 0.64; P < 0.0001], HIV-1 RNA plasma viral load per 10-fold increase (RH, 2.04; P = 0.0003), and CD4+ cell count per 100 cell (x 10(6)/l) increase (RH, 0.90; P = 0.02). Multivariate linear regression showed that viral load was 39% lower (P = 0.0001) for each unit increase in HLA score profile and 13% lower (P = 0.002) for each 100 cell (x 10(6)/l increase in CD4+ cell count. Conclusions: The means by which the HLA score profile influences the time to AIDS is probably through immunologic responses that affect the rate of HIV-1 replication, as manifested by the HIV-1 RNA plasma viral load during the first 6-12 months following acute infection. (C) 1998 Lippincott Williams & Wilkins C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Maryland Med Syst, Dept Pathol, Div Immunogenet, Baltimore, MD 21201 USA. Roche Mol Syst, Dept Human Genet, Alameda, CA USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Howard Brown Mem Clin, Chicago, IL USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. Chiron Corp, Emeryville, CA 94608 USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. RP Saah, AJ (reprint author), Merck Res Labs, Clin Res, POB 4,BL3-4, W Point, PA 19486 USA. RI apple, raymond/I-4506-2012 OI apple, raymond/0000-0002-8007-0345 FU NIAID NIH HHS [U01-AI-35043, U01-AI-35039, U01-AI-35042] NR 21 TC 76 Z9 77 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 12 PY 1998 VL 12 IS 16 BP 2107 EP 2113 DI 10.1097/00002030-199816000-00005 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 137FY UT WOS:000076905100005 PM 9833851 ER PT J AU Dunn, DT Tess, BH Rodrigues, LC Ades, AE AF Dunn, DT Tess, BH Rodrigues, LC Ades, AE TI Mother-to-child transmission of HIV: implications of variation in maternal infectivity SO AIDS LA English DT Article DE HIV; breastfeeding; infectivity; vertical transmission ID HUMAN-IMMUNODEFICIENCY-VIRUS; LATE POSTNATAL TRANSMISSION; BREAST-MILK; TYPE-1; INFANT; COUNTRIES; RISK; LOAD AB Objectives: To examine the implications of variation in maternal infectivity on the timing of mother to-child HIV transmission through breastfeeding. Design and methods: A mathematical model of mother-to-child HIV transmission was developed that incorporates two main features: (i) the fetus/child potentially experiences a series of exposures (in utero, intrapartum, and via breastmilk) to HIV; and (ii) variation in maternal infectivity. The model was estimated from different sources of epidemiological data: a retrospective cohort study of children born to HIV-1-infected women in Sao Paulo State, Brazil, the International Registry of HIV Exposed Twins, and the AIDS Clinical Trials Group 076 trial, which assessed the effectiveness of zidovudine in preventing mother-to-child HIV transmission. Results: Variation in maternal infectivity results in higher average risk of breastfeeding-related transmission in the early stages of breastfeeding than in the late stages, even in the absence of a direct relationship between transmission risk and the age of the child. However, the available data were unable to resolve the quantitative importance of this mechanism. Conclusions: Our model has helped identify a previously unrecognized determinant of the timing of breastfeeding-related HIV transmission, which may have adverse implications for the effectiveness of certain interventions to reduce mother-to-child HIV transmission such as maternal antiretroviral therapy in breastfeeding populations and the early cessation of breastfeeding. (C) 1998 Lippincott Williams & Wilkins C1 UCL, Sch Med, Inst Child Hlth, London W1N 8AA, England. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. London Sch Hyg & Trop Med, London WC1, England. RP Dunn, DT (reprint author), Mortimer Market Ctr, MRC, HIV Clin Trials Ctr, Capper St, London WC1E 6AU, England. NR 25 TC 23 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 12 PY 1998 VL 12 IS 16 BP 2211 EP 2216 DI 10.1097/00002030-199816000-00017 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 137FY UT WOS:000076905100017 PM 9833863 ER PT J AU Yoshida, A Sasaki, N Mori, A Taniguchi, S Ueta, Y Hattori, K Tanaka, Y Igawa, O Tsuboi, M Sugawa, H Sato, R Hisatome, I Shigemasa, C Grollman, EF Kosugi, S AF Yoshida, A Sasaki, N Mori, A Taniguchi, S Ueta, Y Hattori, K Tanaka, Y Igawa, O Tsuboi, M Sugawa, H Sato, R Hisatome, I Shigemasa, C Grollman, EF Kosugi, S TI Differences in the electrophysiological response to I- and the inhibitory anions SCN- and ClO4-, studied in FRTL-5 cells SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE sodium iodide symporter; N+/I- symporter; thyroid; FRTL-5; electrophysiology ID THYROID PLASMA-MEMBRANES; IODIDE TRANSPORT; GLUCOSE COTRANSPORTER; PHOSPHOLIPID-VESICLES; NA+/I SYMPORTER; LINE; PERCHLORATE; METHIMAZOLE; THIOCYANATE AB The electrophysiological properties of the Na+/I- symporter (NIS) were examined in a cloned rat thyroid cell line (FRTL-5) using the whole-cell patch-clamp technique. When the holding potential was between -40 mV and -80 mV, 1 mM NaI and NaSCN induced an immediate inward current which was greater with SCN- than with I-. The reversal potential for I- and SCN- induced membrane currents was +50 mV. This is close to the value of +55 mV calculated by the Nernst equation for Na+. These results are consistent with I- and SCN- translocation via the NIS that is energized by the electrochemical gradient of Na+ and coupled to the transport of two or more Na+. There was no change in the membrane current recording with ClO4-, indicating that ClO4- was either not transported into the cell, or the translocation was electroneutral. ClO4- addition, however, did reverse the inward currents induced by I- or SCN-. These effects of I-, SCN- and ClO4- on membrane currents reflect endogenous NIS activity since the responses duplicated those seen in CHO cells transfected with NIS. There were additional currents elicited by SCN- in FRTL-5 cells under certain conditions. For example at holding potentials of 0 and +30 mV, 1 mM SCN- produced an increasingly greater outward current. This outward current was transient. In addition, when SCN- was washed off the cells a transient inward current was detected. Unlike SCN-, 1-10 mM I- had no observable effect on the membrane current at holding potentials of 0 and +30 mV. The results indicate FRTL-5 cells may have a specific SCN- translocation system in addition to the SCN- translocation by the I- porter. Differences demonstrated in current response may explain some of the complicated influx and efflux properties of I-, SCN- and ClO4-, in thyroid cells. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Tottori Univ, Sch Med, Dept Internal Med 1, Yonago, Tottori 683, Japan. Kyoto Univ, Sch Med, Dept Lab Med, Kyoto 60601, Japan. Nippon Med Sch, Dept Internal Med 1, Tokyo 113, Japan. NIDDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Yoshida, A (reprint author), Tottori Univ, Sch Med, Dept Internal Med 1, Yonago, Tottori 683, Japan. NR 24 TC 28 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD NOV 11 PY 1998 VL 1414 IS 1-2 BP 231 EP 237 DI 10.1016/S0005-2736(98)00169-2 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 137WT UT WOS:000076940400019 PM 9804961 ER PT J AU Shlay, JC Chaloner, K Max, MB Flaws, B Reichelderfer, P Wentworth, D Hillman, S Brizz, B Cohn, DL AF Shlay, JC Chaloner, K Max, MB Flaws, B Reichelderfer, P Wentworth, D Hillman, S Brizz, B Cohn, DL CA Terry Beirn Community Programs Clinical Res AID TI Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DIABETIC NEUROPATHY; DESIPRAMINE; FLUOXETINE; RAT AB Context.-Peripheral neuropathy is common in persons infected with the human immunodeficiency virus (HIV) but few data on symptomatic treatment are available. Objective.-To evaluate the efficacy of a standardized acupuncture regimen (SAR) and amitriptyline hydrochloride for the relief of pain due to HIV-related peripheral neuropathy in HIV-infected patients. Design.-Randomized, placebo-controlled, multicenter clinical trial. Each site enrolled patients into 1 of the following 3 options: (1) a modified double-blind 2 x 2 factorial design of SAR, amitriptyline, or the combination compared with placebo, (2) a modified double-blind design of an SAR vs control points, or (3) a double-blind design of amitriptyline vs placebo. Setting.-Terry Beirn Community Programs for Clinical Research on AIDS (HIV primary care providers) in 10 US cities. Patients.-Patients with HIV-associated, symptomatic, lower-extremity peripheral neuropathy. Of 250 patients enrolled, 239 were in the acupuncture comparison (125 in the factorial option and 114 in the SAR option vs control points option), and 136 patients were in the amitriptyline comparison (125 in the factorial option and 11 in amitriptyline option vs placebo option). Interventions.-Standarized acupuncture regimen vs control points, amitriptyline (75 mg/d) vs placebo, or both for 14 weeks. Main Outcome Measure.-Changes in mean pain scores at 6 and 14 weeks, using a pain scale ranging from 0.0 (no pain) to 1.75 (extremely intense), recorded daily. Results.-Patients in all 4 groups showed reduction in mean pain scores at 6 and 14 weeks compared with baseline values. For both the acupuncture and amitriptyline comparisons, changes in pain score were not significantly different between the 2 groups. At 6 weeks, the estimated difference in pain reduction for patients in the SAR group compared with those in the control points group (a negative value indicates a greater reduction for the "active" treatment) was 0.01 (95% confidence interval [CI], -0.11 to 0.12; P=.88) and for patients in the amitriptyline group vs those in the placebo group was -0.07 (95% CI, -0.22 to 0.08; P = .38). At 14 weeks, the difference for those in the SAR group compared with those in the control points group was -0.08 (95% CI, -0.21 to 0.06; P = .26) and for amitriptyline compared with placebo was 0.00 (95% CI, -0.18 to 0.19; P = .99). Conclusions.-In this study, neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy. C1 Denver Community Program Clin Res AIDS, Denver, CO USA. Univ Minnesota, Sch Stat, St Paul, MN 55108 USA. NIAID, NIH, Bethesda, MD 20892 USA. NIDR, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Div Biostat, Minneapolis, MN 55455 USA. Social & Sci Syst Inc, Rockville, MD USA. RP Shlay, JC (reprint author), Denver Publ Hlth, 605 Bannock St, Denver, CO 80204 USA. EM jshlay@dhha.org RI Chaloner, Kathryn/B-5090-2013 NR 39 TC 172 Z9 179 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 11 PY 1998 VL 280 IS 18 BP 1590 EP 1595 DI 10.1001/jama.280.18.1590 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 136GX UT WOS:000076852000026 PM 9820261 ER PT J AU Jonas, WB AF Jonas, WB TI Alternative medicine - Learning from the past, examining the present, advancing to the future SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID COMPLEMENTARY C1 NIH, Off Alternat Med, Bethesda, MD 20892 USA. RP Jonas, WB (reprint author), NIH, Off Alternat Med, 900 Rockville Pike,Bldg 31,Room 5B-37, Bethesda, MD 20892 USA. NR 28 TC 104 Z9 104 U1 20 U2 24 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 11 PY 1998 VL 280 IS 18 BP 1616 EP 1618 DI 10.1001/jama.280.18.1616 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 136GX UT WOS:000076852000031 PM 9820266 ER PT J AU Lee-Kwon, W Park, D Baskar, PV Kole, S Bernier, M AF Lee-Kwon, W Park, D Baskar, PV Kole, S Bernier, M TI Antiapoptotic signaling by the insulin receptor in Chinese hamster ovary cells SO BIOCHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; NERVE GROWTH-FACTOR; C-TERMINAL DOMAIN; NF-KAPPA-B; PHOSPHATIDYLINOSITOL 3-KINASE; HEPATOMA-CELLS; SUBSTRATE PHOSPHORYLATION; DIFFERENTIAL ACTIVATION; HEMATOPOIETIC-CELLS; 3T3-L1 ADIPOCYTES AB We have sought to determine whether insulin can promote cell survival and protect Chinese hamster ovary (CHO) cells from apoptosis induced by serum starvation. Low concentrations of insulin were antiapoptotic for cells overexpressing wild-type insulin receptors but not in cells transfected with kinase-defective insulin receptor mutants that lacked a functional ATP binding site. However, treatment with orthovanadate (50 mu M), a widely used tyrosine phosphatase inhibitor, led a dramatic reduction in internucleosomal DNA fragmentation in both cell lines. Cells transfected with truncated receptor mutants in either the juxtamembrane or C-terminal domain were as responsive as cells overexpressing wild-type receptors in mediating insulin antiapoptotic protection. The mechanisms underlying insulin antiapoptotic protection were investigated using a variety of pharmacological tools known to inhibit distinct signaling pathways. The phosphatidylinositol-3' kinase inhibitors wortmannin and LY294002 had only a modest influence whereas blocking protein farnesylation with manumycin severely disrupted the antiapoptotic capacity of the insulin receptor. Of interest, cells gained antiapoptotic potential following inhibition of extracellular signal-regulated kinase activation with the pharmacological agent PD98059. Insulin induced MKK3/MKK6 phosphorylation and activation of p38 MAP kinase whose activity was inhibited with SB203580. However, the inhibition of p38 MAP kinase had no effect on the protection offered by insulin. We conclude that the antiapoptotic function of the insulin receptor requires intact receptor kinase activity and implicates a farnesylation-dependent pathway. Increase in cellular phosphotyrosine content, however, triggers antiapoptotic signal that may converge downstream of the insulin receptor. C1 NIA, Gerontol Res Ctr, Diabet Sect, Clin Invest Lab,NIH, Baltimore, MD 21224 USA. NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Bernier, M (reprint author), NIA, Gerontol Res Ctr, Diabet Sect, Clin Invest Lab,NIH, 5600 Nathan Shock Dr,Box 23, Baltimore, MD 21224 USA. OI Bernier, Michel/0000-0002-5948-368X NR 75 TC 32 Z9 32 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 NOV 10 PY 1998 VL 37 IS 45 BP 15747 EP 15757 DI 10.1021/bi9805947 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141KT UT WOS:000077143600018 PM 9843380 ER PT J AU Zhu, XY Wess, J AF Zhu, XY Wess, J TI Truncated V2 vasopressin receptors as negative regulators of wild-type V2 receptor function SO BIOCHEMISTRY LA English DT Article ID NEPHROGENIC DIABETES-INSIPIDUS; CARDIAC MUSCARINIC RECEPTORS; PROTEIN-COUPLED RECEPTOR; INTRACELLULAR-TRANSPORT; CYTOPLASMIC DOMAINS; MOLECULAR-CLONING; EXPRESSION; BINDING; COEXPRESSION; MUTATION AB Accumulating evidence suggests that G protein-coupled receptors (GPCRs) can form dimeric or oligomeric arrays. Based on this concept, we have tested the hypothesis that truncated GPCRs can act as negative regulators of wild-type receptor function. Using the G(s)-coupled V2 vasopressin receptor as a model system, we systematically analyzed the ability of N- and C-terminal V2 receptor fragments to interfere with the activity of the wild-type V2 receptor coexpressed in COS-7 cells. Several N-terminal V2 receptor truncation mutants were identified that strongly inhibited the function (as determined in cAMP and radioligand binding assays) and cell surface trafficking of the coexpressed full-length V2 receptor. However, these truncation mutants did not interfere with the function of other G(s)-coupled receptors such as the D1 dopamine and the beta 2-adrenergic receptors. Dominant negative effects were only observed with mutant receptors that contained at least three transmembrane domains. In addition, immunoblotting experiments showed that all V2 receptor truncation mutants displaying dominant negative activity (but not those mutant receptors lacking this activity) were able to form heterodimers with the full-length V2 receptor, suggesting that complex formation between mutant and wild-type V2 receptors underlies the observed inhibition of wild-type receptor function. Given the high degree of structural homology shared by all GPCRs, our findings should also be applicable to other members of this receptor superfamily. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP NIDDKD, Bioorgan Chem Lab, Bldg 8A,Rm B1A-05, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov NR 50 TC 153 Z9 154 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 10 PY 1998 VL 37 IS 45 BP 15773 EP 15784 DI 10.1021/bi981162z PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141KT UT WOS:000077143600020 PM 9843382 ER PT J AU Bolling, SF Benedict, MB Tramontini, NL Kilgore, KS Harlow, HH Su, TP Oeltgen, PR AF Bolling, SF Benedict, MB Tramontini, NL Kilgore, KS Harlow, HH Su, TP Oeltgen, PR TI Hibernation triggers and myocardial protection SO CIRCULATION LA English DT Article; Proceedings Paper CT 70th Scientific Session of the American-Heart-Association Meeting CY NOV 09-13, 1997 CL ORLANDO, FLORIDA SP Amer Heart Assoc DE hibernation; myocardium; cardioplegia ID INDUCTION TRIGGERS; PRESERVATION; OPIOIDS AB Background-Hypothermic cardioplegia provides myocellular protection, yet postischemic dysfunction remains a significant problem. Interestingly, the subcellular changes in hibernation parallel the altered biology of induced cardiac ischemia but are well tolerated by hibernated mammalian myocardium. An uncharacterized factor derived from hibernating animals, hibernation induction trigger (HIT), has been shown to induce hibernation in active animals and afford myocardial protection after ischemia-reperfusion injury. Therefore, it was of interest to further characterize the cardioprotective effects of HIT in the setting of ischemia-reperfusion injury. Methods and Results-To determine whether HIT could improve myocardial recovery after global ischemia, isolated rabbit hearts received either standard cardioplegia or HIT in the cardioplegia or underwent preperfusion with HIT before cardioplegia. Alternatively, to determine whether HIT requires metabolic alteration, additional rabbits had in vivo pretreatment with HIT from 15 minutes to 5 days before ischemia. All hearts underwent 2 hours of global ischemia at 34 degrees C. Recovery of postischemic isovolumic developed pressure, coronary flows, and Mvo(2) Were compared. Compared with vehicle pretreatment, HIT pretreatment (1 hour) significantly enhanced indexes of functional recovery, including developed pressure (38+/-3 versus 69+/-7 mmHg) and coronary flow (46+/-3 versus 82+/-11 mL/min). In addition, ultrastructural morphology was preserved but only with in vivo pretreatment. Liver protein content was not increased in rabbits treated from 12 hours to 5 days with HIT versus controls, belying a protein neosynthesis mechanism. However, the temporal sequences suggested conversion of an inactive HIT prefactor to an active form. Conclusions-Administration of serum derived from hibernating black bears to rabbits affords protection against ischemia-reperfusion injury compared with vehicle (saline)-treated animals in a rabbit isolated heart preparation. It is apparent that HIT deserves further identification and mechanistic study in the setting of ischemia-reperfusion injury. C1 Univ Michigan, Med Ctr, Thorac Surg Sect, Ann Arbor, MI USA. NIDA, Bethesda, MD USA. Univ Kentucky, Dept Pathol, Lexington, KY USA. RP Bolling, SF (reprint author), Univ Michigan Hosp, Thorac Surg Sect, Taubman Ctr 2120D, 1500 E Med Ctr Dr,Box 0344, Ann Arbor, MI 48109 USA. EM sbolling@umich.edu NR 20 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 10 PY 1998 VL 98 IS 19 SU S BP II220 EP II223 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 136YF UT WOS:000076886100058 PM 9852906 ER PT J AU Segura, AM Luna, RE Horiba, K Stetler-Stevenson, WG McAllister, HA Willerson, JT Ferrans, VJ AF Segura, AM Luna, RE Horiba, K Stetler-Stevenson, WG McAllister, HA Willerson, JT Ferrans, VJ TI Immunohistochemistry of matrix metalloproteinases and their inhibitors in thoracic aortic aneurysms and aortic valves of patients with Marfan's syndrome SO CIRCULATION LA English DT Article DE aorta; aneurysms; metalloproteinases; collagen; immunohistochemistry; pathology; valves ID CYSTIC MEDIAL NECROSIS; IN-SITU LOCALIZATION; TISSUE INHIBITORS; CARDIOVASCULAR-DISEASE; IV COLLAGENASE; QUANTIFICATION AB Background-Thoracic aortic aneurysms (TAAs) and valvular insufficiency, the main cardiovascular lesions in Marfan's syndrome, are associated with destruction of connective tissue; however, their pathogenesis remains unclear. Methods and Results-To test the hypothesis that changes in the activity of the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are responsible for the damage to connective tissue in these lesions, histochemical studies of the immunoreactivity (IR) for MMPs and their tissue TIMPs (MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2) were made in TAAs (n=7) and aortic valves (n=5) from 7 patients with Marfan's syndrome. All TAAs showed cystic medial necrosis (CMN), with loss of elastic fibers and smooth muscle cells. Extensive areas of myxoid change were found in all aortic valves. Areas of CMN showed no IR for any MMPs or TIMPs. The IR of smooth muscle cells at the borders of areas of CMN was stronger for all MMPs, especially MMP-2 and MMP-9, than in other regions. The surfaces of disrupted elastic fibers showed IR for MMP-2 and MMP-9. Areas of myxoid change showed similar but less pronounced alterations. Conclusions-We hypothesize that the defect in fibrillin-1 in Marfan's syndrome leads to (1) formation of elastin that is abnormally aggregated and more easily degraded by MMPs than is normal elastin, (2) upregulation of the synthesis of MMPs, (3) progressive destruction of connective tissue by these enzymes, and (4) development of TAAs and valvular lesions. C1 NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. St Lukes Episcopal Hosp, Houston, TX 77030 USA. Texas Heart Inst, Houston, TX 77025 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Ferrans, VJ (reprint author), NHLBI, Pathol Sect, NIH, Bldg 10-2N240,10 Ctr Dr,MSC-1518, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 31 TC 22 Z9 26 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 10 PY 1998 VL 98 IS 19 SU S BP II331 EP II337 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 136YF UT WOS:000076886100086 PM 9852923 ER PT J AU Vishveshwara, S Jacob, R Nadig, G Maizel, JV AF Vishveshwara, S Jacob, R Nadig, G Maizel, JV TI The role of lysine-41 in RNase A catalysis - A quantum chemical study on the active site ligand complex SO JOURNAL OF MOLECULAR STRUCTURE LA English DT Article DE active site; proton transfer; short hydrogen bonds; mechanism of RNA hydrolysis; 3-21G; 6-31G ID MOLECULAR-ORBITAL CALCULATIONS; NUCLEAR-MAGNETIC-RESONANCE; TRANSITION-STATE ANALOG; RIBONUCLEASE-A; HYDROGEN-BONDS; NEUTRON-DIFFRACTION; ENZYMATIC CATALYSIS; URIDINE VANADATE; CARBON ACIDS; PHOSPHATE AB Several mechanisms have been proposed to explain the action of enzymes at the atomic level. Among them, the recent proposals involving short hydrogen bonds as a step in catalysis by Gerlt and Gassman [1] and proton transfer through low barrier hydrogen bonds (LBHBs) [2, 3] have attracted attention. There are several limitations to experimentally testing such hypotheses, Recent developments in computational methods facilitate the study of active site-ligand complexes to high levels of accuracy, Our previous studies, which involved the docking of the dinucleotide substrate UpA to the active site of RNase A [4, 5], enabled us to obtain a realistic model of the ligand-bound active site of RNase A. From these studies, based on empirical potential functions, we were able to obtain the molecular dynamics averaged coordinates of RNase A, bound to the ligand UpA. A quantum mechanical study is required to investigate the catalytic process which involves the cleavage and formation of covalent bonds. In the present study, we have investigated the strengths of some of the hydrogen bonds between the active site residues of RNase A and UpA at the ab initio quantum chemical level using the molecular dynamics averaged coordinates as the starting point. The 49 atom system and other model systems were optimized at the 3-21G level and the energies of the optimized systems were obtained at the 6-31G* level. The results clearly indicate the strengthening of hydrogen bonds between neutral residues due to the presence of charged species at appropriate positions. Such a strengthening manifests itself in the form of short hydrogen bonds and a low barrier for proton transfer. In the present study, the proton transfer between the 2'-OH of ribose (from the substrate) and the imidazole group from the H12 of RNase A is influenced by K41, which plays a crucial role in strengthening the neutral hydrogen bond, reducing the barrier for proton transfer. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Indian Inst Sci, Mol Biophys Unit, Bangalore 560012, Karnataka, India. Madras Christian Coll, Dept Chem, Madras, Tamil Nadu, India. NCI, LECB, Frederick, MD 21702 USA. RP Vishveshwara, S (reprint author), NCI, LECB, Frederick, MD 21702 USA. NR 38 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-2860 J9 J MOL STRUCT JI J. Mol. Struct. PD NOV 10 PY 1998 VL 471 IS 1-3 BP 1 EP 11 DI 10.1016/S0022-2860(98)00388-3 PG 11 WC Chemistry, Physical SC Chemistry GA 142WZ UT WOS:000077224500001 ER PT J AU Kostrouch, Z Kostrouchova, M Love, W Jannini, E Piatigorsky, J Rall, JE AF Kostrouch, Z Kostrouchova, M Love, W Jannini, E Piatigorsky, J Rall, JE TI Retinoic acid X receptor in the diploblast, Tripedalia cystophora SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NUCLEAR RECEPTOR; THYROID-HORMONE; CUBOMEDUSAN JELLYFISH; GENOMIC ORGANIZATION; LENS DEVELOPMENT; CRYSTALLIN GENE; RXR-ALPHA; EVOLUTION; IDENTIFICATION; ULTRASPIRACLE AB Nuclear hormone receptors comprise a characteristic family of transcription factors found in vertebrates, insects and nematodes, Here we show by cDNA and gene cloning that a Cnidarian, Tripedalia cystophora, possesses a retinoid receptor (jRXR) with remarkable homology to vertebrate retinoic acid X receptors (RXRs), Like vertebrate RXRs, jRXR binds 9-cis retinoic acid (K-d = 4 x 10(-10) M) and binds to the DNA sequence, PuGGTCA as a monomer in vitro. jRXR also heterodimerizes with Xenopus TR beta on a thyroid responsive element of a direct repeat separated by 4 bp. A jRXR binding half-site capable of interacting with (His(6))jRXR fusion protein was identified in the promoters of three T. cystophora crystallin genes that are expressed highly in the eye lens of this jellyfish. Because crystallin gene expression is regulated by retionoid signaling in vertebrates, the jellyfish crystallin genes are candidate in vivo targets for jRXR. Finally, an antibody prepared against (Hiss)jRXR showed that full-length jRXR is expressed at all developmental stages of T, cystophora except the ephydra, where a smaller form replaces is. These data show that Cnidaria, a diploblastic phylum ancestral to the triploblastic invertebrate and subsequent vertebrate lineages, already have an RXR suggesting that RXR is an early component of the regulatory mechanisms of metazoa. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rall, JE (reprint author), NIDDKD, Diabet Branch, NIH, Bldg 10,Room 6S201,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Jannini, Emmanuele A./0000-0002-5874-039X NR 35 TC 92 Z9 94 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 10 PY 1998 VL 95 IS 23 BP 13442 EP 13447 DI 10.1073/pnas.95.23.13442 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 138WU UT WOS:000076997000018 PM 9811819 ER PT J AU Krumm, A Madisen, L Yang, XJ Goodman, R Nakatani, Y Groudine, M AF Krumm, A Madisen, L Yang, XJ Goodman, R Nakatani, Y Groudine, M TI Long-distance transcriptional enhancement by the histone acetyltransferase PCAF SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RNA-POLYMERASE-II; CHROMATIN STRUCTURE; GENE-PRODUCTS; IN-VIVO; REPRESSION; PROTEIN; ACTIVATION; P300; CBP; COACTIVATOR AB Enhancers are defined by their ability to stimulate gene activity from remote sites and their requirement for promoter-proximal upstream activators to activate transcription, Here we demonstrate that recruitment of the p300/CBP-associated factor PCAF to a reporter gene is sufficient to stimulate promoter activity. The PCAF-mediated stimulation of transcription from either a distant or promoter-proximal position depends on the presence of an upstream activator (Spl). These data suggest that acetyltransferase activity may be a primary component of enhancer function, and that recruitment of polymerase and enhancement of transcription are separable. Transcriptional activation by PCAF requires both its acetyltransferase activity and an additional activity within its N terminus. We also show that the simian virus 40 enhancer and PCAF itself are sufficient to counteract Mad-mediated repression. These results are compatible with recent models in which gene activity is regulated by the competition between deacetylase-mediated repression and enhancer-mediated recruitment of acetyltransferases. C1 Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. Univ Washington, Sch Med, Dept Radiat Oncol, Seattle, WA 98104 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Vollum Inst, Portland, OR 97201 USA. RP Krumm, A (reprint author), Fred Hutchinson Canc Res Ctr, Div Basic Sci, 1100 Fairview Ave N, Seattle, WA 98109 USA. FU NCI NIH HHS [CA54337] NR 43 TC 54 Z9 54 U1 2 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 10 PY 1998 VL 95 IS 23 BP 13501 EP 13506 DI 10.1073/pnas.95.23.13501 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 138WU UT WOS:000076997000028 PM 9811829 ER PT J AU Kornyshev, AA Leikin, S AF Kornyshev, AA Leikin, S TI Electrostatic interaction between helical macromolecules in dense aggregates: An impetus for DNA poly- and mesomorphism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID B-DNA; MOLECULAR-DYNAMICS; AQUEOUS-SOLUTIONS; NUCLEIC-ACIDS; A-TRANSITION; CONFORMATIONS; ELECTROLYTE; POTENTIALS; SIMULATION; HYDRATION AB DNA exhibits a surprising multiplicity of structures when it is packed into dense aggregates. It undergoes various polymorphous transitions (e.g., from the B to A form) and mesomorphous transformations (from hexagonal to orthorhombic or monoclinic packing, changes in the mutual alignment of nearest neighbors, etc). In this report we show that such phenomena may have their origin in the specific helical symmetry of the charge distribution on DNA surface. Electrostatic interaction between neighboring DNA molecules exhibits strong dependence on the patterns of molecular surface groups and adsorbed counter-ions. As a result, it is affected by such structural parameters as the helical pitch, groove width, the number of base pairs per helical turn, etc, We derive expressions which relate the energy of electrostatic interaction with these parameters and with the packing variables characterizing the axial and azimuthal alignment between neighboring macromolecules. We show, in particular, that the structural changes upon the B-to-A transition reduce the electrostatic energy by approximate to kcal/mol per base pair, at a random adsorption of counter ions. Ion binding into the narrow groove weakens or inverts this effect, stabilizing B-DNA, as it is presumably the case in Li+-DNA assemblies. The packing symmetry and molecular alignment in DNA aggregates are shown to be affected by the patterns of ion binding. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Res Ctr Julich, D-52425 Julich, Germany. RP Leikin, S (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RI Leikin, Sergey/A-5518-2008; Kornyshev, Alexei/C-3404-2008 OI Leikin, Sergey/0000-0001-7095-0739; NR 45 TC 76 Z9 79 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 10 PY 1998 VL 95 IS 23 BP 13579 EP 13584 DI 10.1073/pnas.95.23.13579 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 138WU UT WOS:000076997000041 PM 9811842 ER PT J AU Dent, AL Hu-Li, J Paul, WE Staudt, LM AF Dent, AL Hu-Li, J Paul, WE Staudt, LM TI T helper type 2 inflammatory disease in the absence of interleukin 4 and transcription factor STAT6 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GERMINAL-CENTER FORMATION; CENTER B-CELLS; BCL-6 PROTEIN; TH2 RESPONSES; IL-4; EXPRESSION; CYTOKINE; GENE; MICE; PATHWAYS AB An important signaling pathway for the differentiation of T helper type 2 (TH2) cells from uncommitted CD4 T cell precursors is activation of the STAT6 transcription factor by interleukin 4 (IL-4). The protooncogene BCL-6 is also involved in TH2 differentiation, as BCL-6 -/- mice develop an inflammation of the heart and lungs associated with an overproduction of TH2 cells. Surprisingly, IL-4 -/- BCL-6 -/- and STAT6 -/- BCL-6 -/- double-mutant mice developed the same TH2-type inflammation of the heart and lungs as is characteristic of BCL-6 -/- mice. Furthermore, a TH2 cytokine response developed in STAT6 -/- BCL-6 -/- and IL-4 -/- BCL-6 -/- mice after immunization with a conventional antigen in adjuvant. In contrast to these in vivo findings, STAT6 was required for the in vitro differentiation of BCL-6 -/- T cells into TH2 cells, BCL-6, a transcriptional repressor that can bind to the same DNA binding motifs as STAT transcription factors, seems to regulate TH2 responses in vivo by a pathway independent of IL-4 and STAT6. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 39 TC 116 Z9 117 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 10 PY 1998 VL 95 IS 23 BP 13823 EP 13828 DI 10.1073/pnas.95.23.13823 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 138WU UT WOS:000076997000084 PM 9811885 ER PT J AU Nissley, DV Boyer, PL Garfinkel, DJ Hughes, SH Strathern, JN AF Nissley, DV Boyer, PL Garfinkel, DJ Hughes, SH Strathern, JN TI Hybrid Ty1/HIV-1 elements used to detect inhibitors and monitor the activity of HIV-1 reverse transcriptase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DRUG-RESISTANT MUTANT; NONNUCLEOSIDE INHIBITORS; ANGSTROM RESOLUTION; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; CONFORMATIONAL-CHANGES; DNA-POLYMERASE; TY ELEMENTS; POPULATION-DYNAMICS AB We previously demonstrated that hybrid retrotransposons composed of the yeast Ty1 element and the reverse transcriptase (RT) of HIV-1 are active in the yeast Saccharomyces cerevisiae. The RT activity of these hybrid Ty1/HIV-1 (his3A1/AIDS RT; HART) elements can be monitored by using a simple genetic assay. HART element reverse transcription depends on both the polymerase and RNase H domains of HIV-1 RT. Here we demonstrate that the HART assay is sensitive to inhibitors of HIV-1 RT. (-) -(S)-8-Chloro-4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)imidazo [4,5,1-jk][1,4] -benzodiazepin-2 (1H)-thione monohydrochloride (8 Cl-TIBO), a well characterized non-nucleoside RT inhibitor (NNRTI) of HIV-1 RT, blocks propagation of HART elements. HART elements that express NNRTI-resistant RT variants of HIV-1 are insensitive to 8 Cl-TIBO, demonstrating the specificity of inhibition in this assay, HART elements carrying NNRTI-resistant variants of HIV-1 RT can be used to identify compounds that are active against drug-resistant viruses. C1 NCI, Gene Regulat & Chromosome Biol Lab, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NCI, Mol Biol Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Nissley, DV (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NR 58 TC 11 Z9 11 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 10 PY 1998 VL 95 IS 23 BP 13905 EP 13910 DI 10.1073/pnas.95.23.13905 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 138WU UT WOS:000076997000098 PM 9811899 ER PT J AU Freed, EO AF Freed, EO TI HIV-1 Gag proteins: Diverse functions in the virus life cycle SO VIROLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 NUCLEOCAPSID PROTEIN; ROUS-SARCOMA VIRUS; BACULOVIRUS-INFECTED CELLS; NUCLEAR-LOCALIZATION SIGNAL; MAJOR HOMOLOGY REGION; TERMINAL ZINC-FINGER; VIRAL MATRIX PROTEIN; LATE ASSEMBLY DOMAIN; AMINO-ACID-RESIDUES AB The Gag proteins of HIV-I, like those of other retroviruses, are necessary and sufficient for the assembly of virus-like particles. The roles played by HIV-I Gag proteins during the life cycle are numerous and complex, involving not only assembly but also virion maturation after particle release and early postentry steps in virus replication. As the individual Gag domains carry out their diverse functions, they must engage in interactions with themselves, other Gag proteins, other viral proteins, lipid, nucleic acid (DNA and RNA), and host cell proteins. This review briefly summarizes our current understanding of how HIV-I Gag proteins function in the virus life cycle. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Freed, EO (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 307, Bethesda, MD 20892 USA. EM EFreed@nih.gov NR 164 TC 441 Z9 451 U1 6 U2 59 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 NOV 10 PY 1998 VL 251 IS 1 BP 1 EP 15 DI 10.1006/viro.1998.9398 PG 15 WC Virology SC Virology GA 138WH UT WOS:000076996000001 PM 9813197 ER PT J AU Stauber, RH Afonina, E Gulnik, S Erickson, J Pavlakis, GN AF Stauber, RH Afonina, E Gulnik, S Erickson, J Pavlakis, GN TI Analysis of intracellular trafficking and interactions of cytoplasmic HIV-1 Rev mutants in living cells SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEOLAR LOCALIZATION; TRANS-ACTIVATOR; NUCLEAR EXPORT; I REX; PROTEIN; RNA; IDENTIFICATION; INHIBITION; EXPRESSION AB The HIV-I Rev protein is an essential nuclear regulatory viral protein. Rev mutants that are able to block wild-type (WT) Rev activity in trans have been reported and used in antiviral approaches. Not only nuclear but also cytoplasmic Rev mutants were described and suspected to be transdominant by retaining WT Rev in the cytoplasm. To investigate their potential for cytoplasmic retention, we studied the localization, trafficking, and interactions of cytoplasmic Rev mutants containing mutations in the N-terminal multifunctional domain. Using a novel dual-color autofluorescent protein-tagging system, we found that coexpression of the nucleolar blue-tagged WT Rev protein together with green-labeled cytoplasmic Rev mutants did not result in the retention of WT Rev in the cytoplasm but on the contrary, in colocalization of the mutants to the nucleolus. A combination of mutations abolished the interaction with WT Rev, defining two domains important for Rev protein interaction. The identified domains were also essential for specific Rev responsive element (RRE) RNA binding and nuclear retention. Inactivation of the nuclear export signal Shifted the steady-state distribution of the mutants from the cytoplasm to the nucleus, indicating their capability for nucleo-cytoplasmic shuttling. The cytoplasmic mutants were not transdominant compared to the nuclear mutant RevM10BL. These results emphasize that efficient oligomerization with WT Rev combined with RRE-specific RNA binding are prerequisites for effective transdominance. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Human Retrovirus Sect, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Struct Biochem Program, Frederick, MD 21702 USA. RP Pavlakis, GN (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Human Retrovirus Sect, POB B, Frederick, MD 21701 USA. EM pavlakis@ncifcrf.gov OI Stauber, Roland/0000-0002-1341-4523 NR 35 TC 46 Z9 47 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 NOV 10 PY 1998 VL 251 IS 1 BP 38 EP 48 DI 10.1006/viro.1998.9295 PG 11 WC Virology SC Virology GA 138WH UT WOS:000076996000005 PM 9813201 ER PT J AU Mahieux, R Pecon-Slattery, J Chen, GM Gessain, A AF Mahieux, R Pecon-Slattery, J Chen, GM Gessain, A TI Evolutionary inferences of novel simian T lymphotropic virus type 1 from wild-caught chacma (Papio ursinus) and olive baboons (Papio anubis) SO VIROLOGY LA English DT Article ID CELL-LEUKEMIA-VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; TROPICAL SPASTIC PARAPARESIS; LONG TERMINAL REPEAT; I STLV-I; NON-HUMAN PRIMATES; PAPUA-NEW-GUINEA; HTLV-I; PHYLOGENETIC ANALYSIS; MOLECULAR CHARACTERIZATION AB A serological survey of 22 wild-caught South African (Transvaal) chacma baboons (Papio ursinus) and eight olive baboons (Papio anubis) from Kenya indicates that 13 P. ursinus and one Fl anubis have antibodies reacting with human T cell leukemia/lymphoma virus type 1 (HTLV-I) antigens, whereas three Fl ursinus had a indeterminate reactivity on western blot analysis. With six primer sets specific to either HTLV-l-Simian T-cell leukemia virus type 1 (STLV-1) or HTLV-2 and encompassing long terminal repeat (LTR), gag, pol, env, and tax sequences, polymerase chain reaction was performed on genomic DNA from peripheral blood mononuclear cells of 18 animals, and the presence of HTLV-1-STLV-1-related viruses was determined in 13 seropositive and three seroindeterminate animals but not in the two HTLV seronegative individuals. Proviral DNA sequences from env (522 bp), pol (120 bp), and complete (755 bp) or partial (514 bp) LTR were determined for three STLV-1-infected P. ursinus and one Fl anubis. Comparative and phylogenetic analyses revealed that Fl anubis (Pan-486) sequence clusters with one (Pan-1621) of two previously described P anubis STLV-1. Likewise, Fl ursinus viruses (Pur-529, Pur-539, and Pur-543) form a distinct group, different from all known HTLV-1 but closely affiliated with two STLV-1 strains from South African vervets (Cercopithecus aethiops pygerythrus). This study, reporting the first STLV-1 sequences from wild-caught Fl ursinus and Fl anubis, corroborates the hypothesis of cross-species transmissions of STLV-1 in the wild. Further, phylogenetic analyses indicate that the known HTLV-1 strains do not share a common origin with nonhuman primates STLV in South Africa. (C) 1998 Academic Press. C1 Inst Pasteur, Dept Retrovirus, Unite Epidemiol Virus Oncogenes, F-75724 Paris 15, France. NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD USA. RP Gessain, A (reprint author), Inst Pasteur, Dept Retrovirus, Unite Epidemiol Virus Oncogenes, 28 Rue Dr Roux, F-75724 Paris 15, France. EM agessain@pasteur.fr NR 83 TC 24 Z9 25 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 NOV 10 PY 1998 VL 251 IS 1 BP 71 EP 84 DI 10.1006/viro.1998.9377 PG 14 WC Virology SC Virology GA 138WH UT WOS:000076996000008 PM 9813204 ER PT J AU Olivo, PD Collins, PL Peeples, ME Schlesinger, S AF Olivo, PD Collins, PL Peeples, ME Schlesinger, S TI Detection and quantitation of human respiratory syncytial virus (RSV) using minigenome cDNA and a Sindbis virus replicon: A prototype assay for negative-strand RNA viruses SO VIROLOGY LA English DT Article ID TRANSCRIPTION ELONGATION-FACTOR; VACCINE DEVELOPMENT; SYNTHETIC ANALOGS; REPORTER GENE; MESSENGER-RNA; CLONED CDNA; CELL-LINE; EXPRESSION; REPLICATION; RESCUE AB We describe here a novel approach for detecting and quantitating human respiratory syncytial virus (RSV) based on expression of a reporter gene from an RSV minigenome. BHK cells were cytoplasmically transformed with a noncytopathic Sindbis virus replicon expressing T7 RNA polymerase. These cells were then cotransfected with T7 expression plasmids that contain the cDNA of an RSV minigenome and the genes for RSV nucleocapsid proteins N, Rand L The minigenome contains a reporter gene such as lacZ or CAT flanked by cia-acting RSV transcription signals. Subsequent infection of these cells with RSV resulted in a high level of reporter gene expression which could be inhibited by ribavirin. Mock-infected cells exhibited background levels of expression. This assay can be used to quantitate RSV and titer neutralizing antibody and may be a valuable tool for screening compounds for anti-RSV activity. it serves as a prototype for other negative-strand RNA viruses. (C) 1998 Academic Press. C1 Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Rush Presbyterian St Lukes Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. RP Olivo, PD (reprint author), Washington Univ, Sch Med, Dept Mol Microbiol, 660 S Euclid Ave, St Louis, MO 63110 USA. FU NIAID NIH HHS [AI11377] NR 31 TC 15 Z9 15 U1 0 U2 1 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 NOV 10 PY 1998 VL 251 IS 1 BP 198 EP 205 DI 10.1006/viro.1998.9419 PG 8 WC Virology SC Virology GA 138WH UT WOS:000076996000019 PM 9813215 ER PT J AU Schneider, H Schwartzberg, PL Rudd, CE AF Schneider, H Schwartzberg, PL Rudd, CE TI Resting lymphocyte kinase (Rlk/Txk) phosphorylates the YVKM motif and regulates Pl 3-kinase binding to T-Cell antigen CTLA-4 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; PROTEIN-TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; CD28 COSTIMULATION; DISTINCT ROLES; SRC FAMILY; B7-1; ASSOCIATION; EXPRESSION; ACTIVATION AB CTLA-4 and CD28 are differentially expressed on T-cells. They bind to a common ligand B71/2 (CD80/86), however with different avidities. Unlike CD28 which augments the T-cell response, CTLA-4 operates predominately as a negative regulator of T-cell proliferation. The mechanism by which CTLA-4 can generate these intracellular signals is unclear. Little is known regarding the identity of the protein-tyrosine kinase(s) responsible for CTLA-4 phosphorylation and thus creating conditions for the reported binding to PI 3-kinase and the protein tyrosine phosphatase SHP-2. In this study, we demonstrate that Rlk (resting lymphocyte kinase) is capable of phosphorylating CTLA-4 at the YVKM motif. Consistent with this finding, Rlk is capable of providing conditions for the binding of the SH2 domains of PI 3-kinase to the receptor. CTLA-4 is therefore the first known substrate for Rlk suggesting the possibility that this kinase may participate in CTLA-4 function. (C) 1998 Academic Press. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NIH, Natl Human Genome Res Inst, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Rudd, CE (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Div Tumor Immunol, Boston, MA 02115 USA. NR 45 TC 22 Z9 25 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 NOV 9 PY 1998 VL 252 IS 1 BP 14 EP 19 DI 10.1006/bbrc.1998.9559 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 139FC UT WOS:000077016400004 PM 9813138 ER PT J AU Cho, SH Cho, JJ Kim, IS Vliagoftis, H Metcalfe, DD Oh, CK AF Cho, SH Cho, JJ Kim, IS Vliagoftis, H Metcalfe, DD Oh, CK TI Identification and characterization of the inducible murine mast cell gene, imc-415 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GROWTH-FACTOR; HETEROGENEITY; CLONING AB Activation of mast cells results in the generation and release of bioactive mediators which in turn initiate allergic inflammation. Mast cell function is enhanced following stimulation in part because of the induction of specific genes and their products. To identify additional genes induced in mast cells that support this process, we thus constructed an activation-specific mast cell subtraction library. To date, we have isolated 26 novel inducible murine mast cell time) cDNA clones. Among them, a full-coding region of the murine gene imc-415 was found to have a greater than 90% nueleotide sequence homology and a 97.5% amino acid sequence homology to both a human beta(4) integrin-binding protein (p27(BBP)) and a human translation initiation factor 6 (eIF6), which in turn are identical. In vitro translation of the imc-415 gene yielded a band of an approximately 26 kDa. This is the same as the calculated molecular weight of murine IMC-415 protein based on the predicted amino acid sequence and is the molecular weight of p27(BBP)/eIF6. Murine imc-415 message was also induced in inflamed lung tissues in a mouse model of asthma. These results suggest a role for murine imc-415 in allergic inflammation where it may enhance protein synthesis. Human eIF6/p27(BBP) may also play a role in allergic diseases based on the similarities in sequence and in gene expression patterns, (C) 1998 Academic Press. C1 Univ Calif Los Angeles, Harbor Med Ctr, Dept Pediat, Div Allergy & Immunol, Torrance, CA 90509 USA. NIAID, Allerg Dis Lab, NIH, Bethesda, MD 20892 USA. RP Oh, CK (reprint author), Univ Calif Los Angeles, Harbor Med Ctr, Dept Pediat, Div Allergy & Immunol, Torrance, CA 90509 USA. EM chad_oh@humc.edu RI Vliagoftis, Harissios/C-6480-2013; Cho, Seong/I-7102-2015 NR 18 TC 15 Z9 15 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 9 PY 1998 VL 252 IS 1 BP 123 EP 127 DI 10.1006/bbrc.1998.9609 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 139FC UT WOS:000077016400022 PM 9813156 ER PT J AU Boehm, T O'Reilly, MS Keough, K Shiloach, J Shapiro, R Folkman, J AF Boehm, T O'Reilly, MS Keough, K Shiloach, J Shapiro, R Folkman, J TI Zinc-binding of endostatin is essential for its antiangiogenic activity SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN GROWTH-HORMONE; ANGIOGENESIS; ANGIOSTATIN; INHIBITOR; PROTEINS; ENZYMES AB Endostatin is a potent angiogenesis inhibitor in vitro and in vivo. We used the yeast Pichia pastoris to express and purify soluble endostatin. It was discovered that metal chelating agents can induce N-terminal degradation of endostatin. We theorized that a metal was removed from endostatin which changed the conformation and allowed a contaminating protease to degrade the N-terminus. Atomic absorption and amino acid analysis of endostatin purified from Pichia pastoris and mammalian cells showed a 1:1 molar ratio of Zn2+ to protein. Ding et at have shown that histidines 1, 3, 11, and aspartic acid 76 coordinate the Zn2+ atom (1). An H1/3A double, an H11A, and a D76A single mutant of endostatin were not able to regress Lewis lung carcinoma. We conclude that the ability of endostatin to bind Zn2+ is essential for its antiangiogenic activity. (C) 1998 Academic Press. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cellular Biol, Boston, MA 02115 USA. NIDDKD, Biotechnol Unit, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Biochem & Biophys Sci & Med, Boston, MA 02115 USA. RP Boehm, T (reprint author), Childrens Hosp, Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. NR 13 TC 97 Z9 104 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 9 PY 1998 VL 252 IS 1 BP 190 EP 194 DI 10.1006/bbrc.1998.9617 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 139FC UT WOS:000077016400034 PM 9813168 ER PT J AU Blagosklonny, MV AF Blagosklonny, MV TI The mitogen-activated protein kinase pathway mediates growth arrest or E1A-dependent apoptosis in SKBr3 human breast cancer cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CYCLE ARREST; P21(WAF1/CIP1) EXPRESSION; SIGNALING PATHWAY; DIFFERENTIATION; INDUCTION; RAF-1; PROLIFERATION; SUFFICIENT; P21(CIP1); REQUIRES AB Previously, we have shown that phorbol ester (PMA) induces p21(WAF1/CIP1)-dependent growth arrest in SKBr3 breast cancer and LNCaP prostate cancer cells. Here, I demonstrate that inhibition of Raf-I kinase by dominant-negative Raf-I or pharmacological depletion of Raf-I prevented PMA-mediated induction of p21(WAF1/CIP1). Similarly, PD98059, a specific inhibitor of MEK, abolished p21(WAF1/CIP1) induction and PMA-induced growth arrest. Like PMA, the H-ras oncogene, another activator of the Raf-I/MEK/MAPK pathway, transactivated p21(WAF1/CIP1) in SKBr3 cells. I further investigated PMA-induced growth arrest following infection of SKBr3 cells with 12S EIA expressing adenovirus. Although high levels of EIA oncoprotein prevented both PMA induced p21(WAF1/CIP1) and growth arrest, smaller amounts of EIA abrogated growth arrest without down-regulation of p21(WAF1/CIP1). Therefore, EIA can stimulate proliferation downstream of p21(WAF1/CIP1) Albeit less effective than full activity, either Rb- or p300- binding activity of EIA was sufficient for the abrogation of PMA-mediated growth arrest. EIA-driven proliferation of PMA-treated SKBr3 cells was accompanied by apoptosis. New therapeutic approaches can be envisioned that would utilize stimulation of the Raf-I/MEK/MAPK pathway to inhibit growth of PMA-sensitive cancer cells. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Blagosklonny, MV (reprint author), NCI, Med Branch, NIH, Bldg 10,R 12N226, Bethesda, MD 20892 USA. NR 27 TC 31 Z9 33 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 9 PY 1998 VL 78 IS 4 BP 511 EP 517 DI 10.1002/(SICI)1097-0215(19981109)78:4<511::AID-IJC19>3.0.CO;2-8 PG 7 WC Oncology SC Oncology GA 131TC UT WOS:000076590500019 PM 9797142 ER PT J AU Heinz, A Knable, MB Coppola, R Gorey, JG Jones, DW Lee, KS Weinberger, DR AF Heinz, A Knable, MB Coppola, R Gorey, JG Jones, DW Lee, KS Weinberger, DR TI Psychomotor slowing, negative symptoms and dopamine receptor availability - an IBZM SPECT study in neuroleptic-treated and drug-free schizophrenic patients (vol 31, pg 19, 1998) SO SCHIZOPHRENIA RESEARCH LA English DT Correction C1 NIMH, Neurosci Ctr St Elizabeths, Clin Brain Disorders Branch, Washington, DC 20032 USA. Ruhr Univ Bochum, Dept Neurol, D-4630 Bochum, Germany. RP Knable, MB (reprint author), NIMH, Neurosci Ctr St Elizabeths, Clin Brain Disorders Branch, Washington, DC 20032 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV 9 PY 1998 VL 34 IS 1-2 BP 121 EP 121 PG 1 WC Psychiatry SC Psychiatry GA 137HW UT WOS:000076909500013 ER PT J AU Sakata, SF Tamaoka, K Matsuda, K Kaneko, M Chou, JY Tamaki, N AF Sakata, SF Tamaoka, K Matsuda, K Kaneko, M Chou, JY Tamaki, N TI Effect of glucocorticoids on the mouse methionine adenosyltransferase A1 gene expression, which is regulated by two promoters SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE methionine adenosyltransferase; glucocorticoid; transcription regulation; promoter; TFII-I; Ets ID S-ADENOSYLMETHIONINE SYNTHETASE; TYROSINE AMINOTRANSFERASE GENE; POLYOMAVIRUS ENHANCER; TRANSCRIPTION; DEFICIENCY; ELEMENTS; TRANSFORMATION; PURIFICATION; ACTIVATION; HOMOLOG AB The methionine adenosyltransferase A1 (MATA1) gene encodes the hepatic forms of the enzyme MAT I and III. To determine the molecular mechanisms that regulate MATA1 gene expression, we characterized promoters and the 5'-flanking sequence of MATA1. Transient expression assays demonstrated the presence of two promoters for the MATA1 gene. The pi promoter is contained in the -57 to -2 nucleotide region, and gives rise to the P1 transcript initiated at +1. The p2 promoter is contained in the -248 to -146 nucleotide region. The -229 to -213 nucleotide region of the MATA1 gene, which contains an Ets-binding-site sequence, was necessary for p2 promoter activity. Sequence analysis of 5'-RACE products indicated that there was a transcript (P2) initiated at -156. The -107 to +145 nucleotide region is missing from the mature P2 transcript, which suggests that the -107 to +145 nucleotide sequence is an intron of the P2 transcript. The p2 promoter may give rise to the P2 transcript. The pi promoter activity was increased by glucocorticoids, but the p2 promoter activity was not affected by glucocorticoids. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Kobe Gakuin Univ, Fac Nutr, Nishi Ku, Kobe, Hyogo 6512180, Japan. NICHHD, NIH, Bethesda, MD 20892 USA. RP Sakata, SF (reprint author), Kobe Gakuin Univ, Fac Nutr, Nishi Ku, Kobe, Hyogo 6512180, Japan. NR 29 TC 2 Z9 2 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 NOV 8 PY 1998 VL 1442 IS 2-3 BP 127 EP 136 DI 10.1016/S0167-4781(98)00156-0 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 136ZC UT WOS:000076888100004 PM 9804922 ER PT J AU Farzadegan, H Hoover, DR Astemborski, J Lyles, CM Margolick, JB Markham, RB Quinn, TC Vlahov, D AF Farzadegan, H Hoover, DR Astemborski, J Lyles, CM Margolick, JB Markham, RB Quinn, TC Vlahov, D TI Sex differences in HIV-1 viral load and progression to AIDS SO LANCET LA English DT Article ID MONONUCLEAR CELL COCULTURES; INFECTION; MARKERS; REPLICATION; THERAPY; GROWTH; RNA AB Background Plasma HIV-1 RNA measurements are used for initiation of antiretroviral treatments, Whether the viral-load association with prognosis is similar in women and men is unknown. Methods We studied 812 specimens from 650 injection-drug users (IDUs) participating in a continuous observational study of patients based in a community clinic. HIV-1 load was measured by branched-chain DNA on samples from 527 IDUs from the baseline visit, and by reverse-transcriptase PCR and quantitative microculture on samples from 285 IDUs ai a follow-up visit 3 years later. Findings Women had lower median viral-load measurements than men by branched-chain DNA (3365 vs 8907 copies/mL; p=0.001), reverse-transcriptase PCR (45 416 vs 93 130 copies/mL; p=0.02), and quantitative microculture (5 vs 8 infectious units per million peripheral blood mononuclear cells; p=0.015). This association remained even after adjustment for CD4 cell count, race, and drug use within the previous 6 months. Time to AIDS was statistically similar for men and women in a univariate proportional-hazards model and in a model adjusting for CD4 cell count. Proportional-hazards models showed that women with the same viral load as men had a 1.6-fold higher risk of AIDS (95% CI 1.10-2.32); or, equivalently, that women with half the viral load of men had a similar time to AIDS as men. Interpretation Although a biological mechanism remains unclear, these data suggest that current recommendations for HIV-1 viral-load thresholds to initiate antiretroviral therapy should be revised downwards for women. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Farzadegan, H (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Room E6004, Baltimore, MD 21205 USA. RI Quinn, Thomas/A-2494-2010 FU NIDA NIH HHS [DA04334] NR 17 TC 261 Z9 266 U1 1 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 7 PY 1998 VL 352 IS 9139 BP 1510 EP 1514 DI 10.1016/S0140-6736(98)02372-1 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 136ME UT WOS:000076862300009 PM 9820299 ER PT J AU Gejman, PV Gershon, ES Zhang, J Badner, JA Sanders, AR Cao, Q Markey, C Goldin, LR AF Gejman, PV Gershon, ES Zhang, J Badner, JA Sanders, AR Cao, Q Markey, C Goldin, LR TI Progress of genome scan of the NIMH intramural schizophrenia collection. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH, Unit Mol Clin Invest, Clin Neurogenet Branch, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 6 PY 1998 VL 81 IS 6 BP 453 EP 453 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 123VG UT WOS:000076145700006 ER PT J AU Foroud, T Castellucio, PF Koller, DL Edenberg, HJ Goate, A Detera-Wadleigh, S Stine, OC McMahon, FJ McInnis, MG Rice, J Blehar, M Goldin, LR Badner, J Guroff, J Reich, T DePaulo, JR Gershon, E Nurnberger, JI AF Foroud, T Castellucio, PF Koller, DL Edenberg, HJ Goate, A Detera-Wadleigh, S Stine, OC McMahon, FJ McInnis, MG Rice, J Blehar, M Goldin, LR Badner, J Guroff, J Reich, T DePaulo, JR Gershon, E Nurnberger, JI TI Genomewide scan of affected relative pairs using the NIMH genetics initiative bipolar affective disorder pedigrees. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Bloomington, IN 47405 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. NIMH, Intramural Res Program, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RI McMahon, Francis/A-7290-2009; McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 NR 0 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 6 PY 1998 VL 81 IS 6 BP 462 EP 462 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 123VG UT WOS:000076145700036 ER PT J AU Detera-Wadleigh, SD Yoshikawa, T Padigaru, M Berrettini, WH Badner, JA Sanders, A Goldin, LR Turner, G Rollins, DY Moses, T Esterling, L Gershon, ES AF Detera-Wadleigh, SD Yoshikawa, T Padigaru, M Berrettini, WH Badner, JA Sanders, A Goldin, LR Turner, G Rollins, DY Moses, T Esterling, L Gershon, ES TI Genome screen and candidate gene analysis in bipolar disorder. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH, Clin Neurogenet Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 6 PY 1998 VL 81 IS 6 BP 463 EP 463 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 123VG UT WOS:000076145700039 ER PT J AU McInnis, MG MacKinnon, DF McMahon, FJ Foroud, T Edenberg, HJ Goate, A Detera-Wadleigh, S Stine, OC Rice, J Blehar, M Reich, T Gershon, E Nurnberger, JI Simpson, SG DePaulo, JR AF McInnis, MG MacKinnon, DF McMahon, FJ Foroud, T Edenberg, HJ Goate, A Detera-Wadleigh, S Stine, OC Rice, J Blehar, M Reich, T Gershon, E Nurnberger, JI Simpson, SG DePaulo, JR TI Evidence for a susceptibility locus for bipolar disorder on chromosome 11p11.5. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. NIMH, Bethesda, MD USA. Indiana Univ, Sch Med, Bloomington, IN 47405 USA. RI McMahon, Francis/A-7290-2009; McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 6 PY 1998 VL 81 IS 6 BP 463 EP 463 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 123VG UT WOS:000076145700038 ER PT J AU Rotondo, A Mazzanti, CM Armani, A Bouanani, S Gonnelli, C Tiano, L Masala, I Manzi, C Pardini, L Sarno, N Nielson, DA Cassano, GB Dell'Osso, L Goldman, D AF Rotondo, A Mazzanti, CM Armani, A Bouanani, S Gonnelli, C Tiano, L Masala, I Manzi, C Pardini, L Sarno, N Nielson, DA Cassano, GB Dell'Osso, L Goldman, D TI No association between serotonin transporter or tryptophan hydroxylase promoters and bipolar disorder with or without suicidal behavior. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 Univ Pisa, Dept Psychiat, I-56100 Pisa, Italy. Univ Pisa, Dept Neurobiol, I-56100 Pisa, Italy. Univ Pisa, Dept Pharmacol, I-56100 Pisa, Italy. Univ Pisa, Dept Biotechnol, I-56100 Pisa, Italy. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 6 PY 1998 VL 81 IS 6 BP 467 EP 467 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 123VG UT WOS:000076145700050 ER PT J AU Sommer, S Feng, J Sobell, J Heston, L Goldman, D Cook, E Gelertner, J Kranzler, H AF Sommer, S Feng, J Sobell, J Heston, L Goldman, D Cook, E Gelertner, J Kranzler, H TI Multiconditional SSCP (M-SSCP) for VAPSE-based analysis of complex disorders: A type of candidate gene approach applied to schizophrenia and other psychiatric diseases. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ Washington, Seattle, WA 98195 USA. NIAAA, Bethesda, MD USA. Univ Chicago, Chicago, IL 60637 USA. Yale Univ, New Haven, CT 06520 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 6 PY 1998 VL 81 IS 6 BP 470 EP 470 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 123VG UT WOS:000076145700060 ER PT J AU Goldman, D Lappalainen, J Vallejo, R Robin, RW Virkkunen, M Linnoila, M Long, J AF Goldman, D Lappalainen, J Vallejo, R Robin, RW Virkkunen, M Linnoila, M Long, J TI Linkage of the 5HT1B serotonin receptor to antisocial alcoholism in Finns and Southwestern Indians. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 6 PY 1998 VL 81 IS 6 BP 479 EP 479 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 123VG UT WOS:000076145700089 ER PT J AU Sanders, AR Paylor, R Libbey, M Wang, J Cao, Q Zhang, J Goldin, LR Pickar, D Gershon, ES Crawley, JN Gejman, PV AF Sanders, AR Paylor, R Libbey, M Wang, J Cao, Q Zhang, J Goldin, LR Pickar, D Gershon, ES Crawley, JN Gejman, PV TI Suggestive evidence for a quantitative trait locus on chromosome 3 for prepulse inhibition in the mouse. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH, Unit Mol Clin Invest, Clin Neurogenet Branch, Bethesda, MD 20892 USA. NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 6 PY 1998 VL 81 IS 6 BP 485 EP 485 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 123VG UT WOS:000076145700107 ER PT J AU Mazzanti, C Lappalainen, J Long, JC Naukkarinen, H Eggert, M Virkkunen, M Linnoila, M Goldman, D AF Mazzanti, C Lappalainen, J Long, JC Naukkarinen, H Eggert, M Virkkunen, M Linnoila, M Goldman, D TI Sib-pair linkage and association analysis of the serotonin transporter promoter polymorphism and TPQ personality traits. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NIAAA, Sect Populat Genet & Linkage, NIH, Rockville, MD 20852 USA. NIAAA, Clin Studies Lab, NIH, Rockville, MD 20852 USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 6 PY 1998 VL 81 IS 6 BP 487 EP 488 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 123VG UT WOS:000076145700116 ER PT J AU Smith, CL Storm, N Huong, Z Broude, N Frank, M Torrey, EF AF Smith, CL Storm, N Huong, Z Broude, N Frank, M Torrey, EF TI What does discordance mean in monozygotic twins? SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 Boston Univ, Ctr Adv Biotechnol, Boston, MA 02215 USA. Boston Univ, Dept Biotechnol, Boston, MA 02215 USA. Boston Univ, Dept Biol, Boston, MA 02215 USA. Boston Univ, Dept Pharmacol, Boston, MA 02215 USA. NIMH, NIH, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 6 PY 1998 VL 81 IS 6 BP 489 EP 489 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 123VG UT WOS:000076145700121 ER PT J AU Enoch, MA Mazzanti, CM Rotondo, A Greenberg, BD Altemus, M Murphy, DL Goldman, D AF Enoch, MA Mazzanti, CM Rotondo, A Greenberg, BD Altemus, M Murphy, DL Goldman, D TI Association between 5-HT2A promoter polymorphism -1438G/A and obessive-compulsive disorder. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 6 PY 1998 VL 81 IS 6 BP 502 EP 502 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 123VG UT WOS:000076145700166 ER PT J AU Taylor, J Cao, Q Cravchik, A Badner, J Mowry, BJ Levinson, DF Crowe, RR Silverman, JM Goldin, LR Gershon, ES Gejman, PV AF Taylor, J Cao, Q Cravchik, A Badner, J Mowry, BJ Levinson, DF Crowe, RR Silverman, JM Goldin, LR Gershon, ES Gejman, PV TI Mutational analysis of the 5-HT1B and 5-HT1E serotonin receptor genes in three datasets with schizophrenia. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH, UMCI, CNG, Bethesda, MD 20892 USA. Univ Queensland, Dept Psychiat, Brisbane, Qld, Australia. Wolston Pk Hosp, Queensland Ctr Schizophrenia Res, Brisbane, Qld, Australia. Allegheny Univ Hlth Sci, Dept Psychiat, Philadelphia, PA 19102 USA. Univ Iowa, Coll Med, Mental Hlth Clin Res Ctr, Iowa City, IA USA. Univ Iowa, Coll Med, Dept Psychiat, Iowa City, IA 52242 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 6 PY 1998 VL 81 IS 6 BP 504 EP 504 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 123VG UT WOS:000076145700173 ER PT J AU Marini, AM Rabin, SJ Lipsky, RH Mocchetti, I AF Marini, AM Rabin, SJ Lipsky, RH Mocchetti, I TI Activity-dependent release of brain-derived neurotrophic factor underlies the neuroprotective effect of N-methyl-D-aspartate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NERVE GROWTH-FACTOR; CEREBELLAR GRANULE CELLS; BDNF MESSENGER-RNA; TRK PROTOONCOGENE PRODUCT; FACTOR FAMILY; TYROSINE PHOSPHORYLATION; RECEPTOR ACTIVATION; SIGNALING PATHWAYS; MOLECULAR-CLONING; NEURONAL DEATH AB The molecular mechanism(s) of N-methyl-D-aspartate (NMDA) neuroprotective properties were investigated in primary cultures of cerebellar granule cell neurons. Granule cells express the neurotrophin receptor TrkB but not TrkA or TrkC. In these cells, the TrkB ligand brain-derived neurotrophic factor (BDNF) prevents glutamate toxicity. Therefore, we have tested the hypothesis that NMDA activates synthesis and release of BDNF, which may prevent glutamate toxicity by an autocrine loop. Exposure of granule cells for 2 and 5 min to a subtoxic concentration of NMDA (100 mu M) evoked an accumulation of BDNF in the medium without concomitant changes in the intracellular levels of BDNF protein or mRNA The increase in BDNF in the medium is followed by enhanced TrkB tyrosine phosphorylation, suggesting that NMDA increases the release of BDNF and therefore the activity of TrkB receptors. To examine whether BDNF and TrkB signaling play a role in the NMDA-mediated neuroprotective properties, neurons were exposed to soluble trkB receptor-IgG fusion protein, which is known to inhibit the activity of extracellular BDNF, and to K252a, a tyrosine kinase inhibitor. Both compounds blocked the NMDA-mediated TrkB tyrosine phosphorylation and subsequently its neuroprotective properties. We suggest that NMDA activates the TrkB receptor via a BDNF autocrine loop, resulting in neuronal survival. C1 Georgetown Univ, Dept Cell Biol, Div Neurobiol, Washington, DC 20007 USA. Walter Reed Army Med Ctr, Dept Neurol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Dept Clin Invest, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. NIAAA, Lab Human Neurogenet, NIH, Rockville, MD 20852 USA. RP Mocchetti, I (reprint author), Georgetown Univ, Dept Cell Biol, Div Neurobiol, Med Dent Bldg,3900 Reservoir Rd NW, Washington, DC 20007 USA. EM Moccheti@gunet.georgetown.edu OI Lipsky, Robert/0000-0001-7753-1473 FU NINDS NIH HHS [NS 01675, NS 29664, NS 32671] NR 48 TC 157 Z9 157 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 6 PY 1998 VL 273 IS 45 BP 29394 EP 29399 DI 10.1074/jbc.273.45.29394 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 135JJ UT WOS:000076798300018 PM 9792641 ER PT J AU Yu, M Souaya, J Julin, DA AF Yu, M Souaya, J Julin, DA TI Identification of the nuclease active site in the multifunctional RecBCD enzyme by creation of a chimeric enzyme SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE RecBCD; endonuclease; gene 32 protein; recombination; Chi sequence ID RECOMBINATION HOTSPOT-CHI; SINGLE-STRANDED-DNA; ESCHERICHIA-COLI K-12; RECD SUBUNIT; RESTRICTION-ENDONUCLEASE; HOMOLOGOUS RECOMBINATION; PURIFIED SUBUNITS; CRYSTAL-STRUCTURE; SEQUENCE; PROTEIN AB The recombinational hot spot :a modulates the nuclease and helicase activities of the RecBCD enzyme, leading to generation of an early DNA intermediate for homologous recombination. Here we identify the subunit location of the nuclease active site in RecBCD. The isolated RecB protein cleaves circular single-stranded M13 phage DNA, but RecB(1-929), comprising only the 100 kDa N-terminal domain of RecB, does not. We reported previously that the reconstituted RecB(1-929)CD enzyme also is not a nuclease, suggesting that the C-terminal 30 kDa domain of RecB is a non-specific ssDNA endonuclease. However, we were unable to detect nuclease activity with the subtilisin-generated C-terminal 30 kDa fragment of RecB. Since the subtilisin-generated fragment did not bind to a ssDNA-agarose column, we designed a chimeric enzyme by attaching the C-terminal 30 kDa domain of RecB to the gene 32 protein of T4 phage, a ssDNA binding protein that does not have strand scission ability. In addition, Asp427 in the chimeric enzyme (Asp1080 in RecB), a residue that is conserved among several RecB homologs, was substituted to alanine (the D427A mutant). The wild-type chimeric enzyme cleaves the M13 DNA and the D427A mutation abolishes the endonuclease activity of the chimeric enzyme but does not affect its DNA binding ability. This finding indicates aln unusual bipartite nature in the structural organization of RecB, in which the DNA-binding function is located in the N-terminal 100 kDa domain and the nuclease catalytic domain is located in the C-terminal 30 kDa domain. The purified RecB(D1080A)CD mutant is a processive helicase but not a nuclease, demonstrating that RecBCD has a single nuclease active site in the C-terminal 30 kDa domain of RecB. (C) 1998 Academic Press. C1 Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. RP Julin, DA (reprint author), NIDDKD, Biol Chem Lab, NIH, Bldg 10,Room 9N307,10 Ctr Dr,MSC 1822, Bethesda, MD 20892 USA. EM dj13@umail.umd.edu FU NIGMS NIH HHS [GM39777] NR 59 TC 70 Z9 72 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 6 PY 1998 VL 283 IS 4 BP 797 EP 808 DI 10.1006/jmbi.1998.2127 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 136JB UT WOS:000076854700008 PM 9790841 ER PT J AU Gardner, MJ Tettelin, H Carucci, DJ Cummings, LM Aravind, L Koonin, EV Shallom, S Mason, T Yu, K Fujii, C Pederson, J Shen, K Jing, JP Aston, C Lai, ZW Schwartz, DC Pertea, M Salzberg, S Zhou, LX Sutton, GG Clayton, R White, O Smith, HO Fraser, CM Adams, MD Venter, JC Hoffman, SL AF Gardner, MJ Tettelin, H Carucci, DJ Cummings, LM Aravind, L Koonin, EV Shallom, S Mason, T Yu, K Fujii, C Pederson, J Shen, K Jing, JP Aston, C Lai, ZW Schwartz, DC Pertea, M Salzberg, S Zhou, LX Sutton, GG Clayton, R White, O Smith, HO Fraser, CM Adams, MD Venter, JC Hoffman, SL TI Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum SO SCIENCE LA English DT Article ID COMPLETE GENOME SEQUENCE; ERYTHROCYTE SURFACE-ANTIGEN; BLOOD STAGE ANTIGEN; MOLECULAR-CLONING; MEMBRANE PROTEIN; GENETIC-ANALYSIS; SERINE-STRETCH; REPETITIVE DNA; SERA GENE; DOMAINS AB Chromosome 2 of Plasmodium falciparum was sequenced; this sequence contains 947,103 base pairs and encodes 210 predicted genes. In comparison with the Saccharomyces cerevisiae genome, chromosome 2 has a lower gene density, introns are more frequent, and proteins are markedly enriched in nonglobular domains. A family of surface proteins, rifins, that may play a role in antigenic variation was identified. The complete sequencing of chromosome 2 has shown that sequencing of the A + T-rich P. falciparum genome is technically feasible. C1 USN, Med Res Inst, Malari Program, Rockville, MD 20852 USA. Inst Genome Res, Rockville, MD 20850 USA. Texas A&M Univ, Dept Biol, College Stn, TX USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NYU, Dept Chem, Lab Biomol Imaging, New York, NY 10003 USA. Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA. Inst Genom Res, Rockville, MD 20850 USA. Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA. RP Hoffman, SL (reprint author), USN, Med Res Inst, Malari Program, 12300 Washington Ave, Rockville, MD 20852 USA. RI Salzberg, Steven/F-6162-2011 OI Salzberg, Steven/0000-0002-8859-7432 FU NIAID NIH HHS [R01 AI40125-01] NR 73 TC 383 Z9 403 U1 0 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 6 PY 1998 VL 282 IS 5391 BP 1126 EP 1132 DI 10.1126/science.282.5391.1126 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 136YY UT WOS:000076887700051 PM 9804551 ER PT J AU Andurkar, SV Stables, JP Kohn, H AF Andurkar, SV Stables, JP Kohn, H TI Synthesis and anticonvulsant activities of (R)-(O)-methylserine derivatives SO TETRAHEDRON-ASYMMETRY LA English DT Article ID N-BENZYLACETAMIDE DERIVATIVES; ACID-DERIVATIVES; AMINO-ACIDS; SERIES AB Efficient procedures for the synthesis of (R)-N-benzyl-2-amino-3-methoxypropionamide ((R)-3), 2-acetamido-3-methoxypropionic acid (4), and O-methylserine (5) are described beginning from (R)-Cbz-serine ((R)-7). The reactions proceeded with little or no racemization and permitted the synthesis of the potent anticonvulsant (R)N-benzyl-2-acetamido-3-methoxypropionamide ((R)-2). The anticonvulsant activities of 2-4 were determined revealing the surprising activity of (R)-2. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Houston, Dept Chem, Houston, TX 77204 USA. NINDS, Epilepsy Branch, NIH, Bethesda, MD 20892 USA. RP Kohn, H (reprint author), Univ Houston, Dept Chem, Univ Pk, Houston, TX 77204 USA. EM hkohn@uh.edu NR 23 TC 23 Z9 23 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0957-4166 J9 TETRAHEDRON-ASYMMETR JI Tetrahedron-Asymmetry PD NOV 6 PY 1998 VL 9 IS 21 BP 3841 EP 3854 DI 10.1016/S0957-4166(98)00403-0 PG 14 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic; Chemistry, Physical SC Chemistry GA 143PM UT WOS:000077264600015 ER PT J AU Chao, YH Kuo, SC Wu, CH Lee, CY Mauger, A Sun, IC Morris-Natschke, SL Lee, KH AF Chao, YH Kuo, SC Wu, CH Lee, CY Mauger, A Sun, IC Morris-Natschke, SL Lee, KH TI Synthesis and cytotoxicity of 2-acetyl-4,8-dihydrobenzodithiophene-4,8-dione derivatives SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUMOR-CELL-LINES; ANTITUMOR AGENTS AB 2-Acetyl-4,8-dihydrobenzo[1,2-b:4,5-b']dithiophene-4,8-dione (9) and 2-acetyl-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dione (19), together with 10 related mono- and disubstituted derivatives, were synthesized and evaluated in vitro by NCI against eight cancer types. All compounds showed significant activity against melanoma, HL-60 leukemia, NCI-H23 non-small-cell lung cancer, OVCAR-3 ovarian cancer, and MDA-MB-435 and MDA-N breast cancer cell lines. Compound 11, 2-(1'-acetoxyethyl)-4,8-dihydrobenzo[1,2-b:4,5-b']dithiophene-4,8-dione, showed the highest overall potency (mean GI(50) = 40 nM). C1 China Med Coll, Grad Inst Pharmaceut Chem, Taichung 400, Taiwan. Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Nat Prod Lab, Chapel Hill, NC 27599 USA. NCI, Drug Synth & Chem Branch, NIH, Bethesda, MD 20892 USA. RP Kuo, SC (reprint author), China Med Coll, Grad Inst Pharmaceut Chem, Taichung 400, Taiwan. FU NCI NIH HHS [CA 17625] NR 16 TC 8 Z9 8 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 5 PY 1998 VL 41 IS 23 BP 4658 EP 4661 DI 10.1021/jm980394t PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 136TZ UT WOS:000076876400024 PM 9804705 ER PT J AU Liu, ML Von Lintig, FC Liyanage, M Shibata, MA Jorcyk, CL Ried, T Boss, GR Green, JE AF Liu, ML Von Lintig, FC Liyanage, M Shibata, MA Jorcyk, CL Ried, T Boss, GR Green, JE TI Amplification of Ki-ras and elevation of MAP kinase activity during mammary tumor progression in C3(1)/SV40 Tag transgenic mice SO ONCOGENE LA English DT Article DE CGH; Ki-ras; gene amplification; MAP kinase; mammary gland tumor; transgenic mice; Ras-bound GTP and GDP ID LARGE T-ANTIGEN; HUMAN-BREAST CARCINOMAS; C-MYC; ONCOGENE AMPLIFICATION; PROTO-ONCOGENE; GENE; CELLS; EXPRESSION; CANCER; TUMORIGENESIS AB We have previously documented that transgenic mice expressing SV40 Tag regulated by the rat prostatic steroid-binding protein C3(1) 5'-flanking region display multistage mammary tumorigenesis. To delineate genetic changes associated with mammary tumor progression, comparative genomic hybridization (CGH) was performed. CGH revealed a consistent gain of the telomeric region of chromosome 6, This region contains the Ki-ras proto-oncogene, Analyses of genomic DNA by Southern blot demonstrated up to 40-fold amplification of the Ki-ras gene. Ki-ras amplification was detected in 12, 46 and 68% of tumors from 4, 5 and 6 month old mice, respectively, whereas no amplifications were found in any preneoplastic mammary tissues. Tumors bearing Ki-ras gene amplification exhibited high levels of Ki-ras RNA and protein, The over-expressed Ki-Ras protein in these tumors appeared functionally active as indicated by the elevated MAP kinase activity, These data demonstrate that while Ki-ras amplification might not be an early event, there is a strong association between Ki-ras amplification and over-expression and mammary tumor progression in this model. This study also shows that CGH is a powerful and useful technique for identifying chromosomal copy number changes during tumor progression, and that this model may provide a predictable in vivo system for studying gene amplification. C1 NCI, Div Basic Sci, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NIH, Natl Human Genome Res Inst, Bethesda, MD USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. RP Green, JE (reprint author), NCI, Div Basic Sci, Lab Cell Regulat & Carcinogenesis, Bldg 41 Room C619, Bethesda, MD 20892 USA. NR 33 TC 30 Z9 30 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 5 PY 1998 VL 17 IS 18 BP 2403 EP 2411 DI 10.1038/sj.onc.1202456 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 134BQ UT WOS:000076723300015 PM 9811472 ER PT J AU Levine, MM Tacket, CO Rabinovich, R AF Levine, MM Tacket, CO Rabinovich, R TI Recruiting volunteers for a typhoid vaccine - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID IMMUNOGENICITY; SAFETY; LIVE C1 Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. NIAID, NIH, Baltimore, MD USA. RP Levine, MM (reprint author), Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 4 PY 1998 VL 280 IS 17 BP 1480 EP 1481 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 134RR UT WOS:000076757200012 ER PT J AU Strickler, HD Rosenberg, PS Devesa, SS Fraumeni, JF Goedert, JJ AF Strickler, HD Rosenberg, PS Devesa, SS Fraumeni, JF Goedert, JJ TI Simian virus 40-contaminated polio vaccine and cancer rates - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NCI, NIH, Bethesda, MD 20892 USA. RP Strickler, HD (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 4 PY 1998 VL 280 IS 17 BP 1481 EP 1482 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 134RR UT WOS:000076757200014 ER PT J AU Detels, R Munoz, A McFarlane, G Kingsley, LA Margolick, JB Giorgi, J Scharager, LD Phair, JP AF Detels, R Munoz, A McFarlane, G Kingsley, LA Margolick, JB Giorgi, J Scharager, LD Phair, JP CA Multicenter AIDS Cohort Study Investigators TI Effectiveness of potent antiretroviral therapy on time to AIDS and death in men with known HIV infection duration SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CUBIC MILLIMETER; CONTROLLED TRIAL; MULTICENTER; COHORT; SEROCONVERSION; ZIDOVUDINE; INCUBATION; INDINAVIR; PROTEASE AB Context.-Time to development of acquired immunodeficiency syndrome (AIDS) and time to death have been extended with the increased use of combination therapy and protease inhibitors. Cohort studies following up persons with human immunodeficiency virus (HIV) infection in periods characterized by different therapies offer the opportunity to estimate therapy effectiveness at the population level. Objective.-To assess the effectiveness of self-reported, long-term potent antiretroviral therapy in a cohort of 536 men whose duration of HIV infection was known (seroconverters). Design.-Cohort study. The cohort was compared for time to development of AIDS and time to death in 1984 to 1990, 1990 to 1993, 1993 to July 1995, and July 1995 to July 1997 when the major treatments were no therapy, monotherapy, combined therapy, and potent antiretroviral therapy, respectively. Survival analysis methods with time zero set as the date of seroconversion and incorporating staggered entries into each period were used. Mean CD4 cell change, stratified by infection duration, was determined for each period using a random effects model. Setting.-The Multicenter AIDS Cohort Study (MACS) in 4 urban areas (Baltimore, Md; Chicago, III; Los Angeles, Calif; and Pittsburgh, Pa). Participants.-A total of 5622 men who were 18 years or older were enrolled into MACS. Of the 5622, there were 2191 HIV-positive individuals at enrollment. Of the 3431 men who were HIV-negative, 536 were observed to seroconvert and were followed up for up to 13 years. The group of 536 who seroconverted constituted the study population. Main Outcome Measures.-Time from seroconversion to development of AIDS and to death and change in CD4 cell count. Results.-A total of 231 seroconverters developed AIDS, and 200 men died. Using 1990 to 1993 as the reference period, the relative hazard of AIDS was 1.04 (95% confidence interval [GI], 0.73-1.48) during 1993 to July 1995 and 0.35 (95% CI, 0.20-0.61) during July 1995 to July 1997. Relative hazards of death were 0.87 (95% CI, 0.58-1.31) and 0.62 (95% Cl, 0.38-1.01) for the same periods. The relative time (the factor by which times are contracted or expanded) to development of AIDS was 0.97 (95% CI, 0.86-1.09) for 1993 to July 1995 and 1.63 (95% CI, 1.40-1.89) for July 1995 to July 1997. Relative survival time for 1993 to July 1995 was 1.01 (95% CI, 0.91-1.12) and for July 1995 to July 1997 was 1.21 (95% Cl, 1.07-1.36) relative to 1990 to 1993. The rate of CD4 cell count decline in July 1995 to July 1997 was significantly lower (P<.05) compared with the previous 2 periods. Conclusions.-In the calendar period when potent antiretroviral therapy was introduced, the time to development of AIDS and time to death were extended, and rate of CD4 cell count decline was arrested. C1 Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21218 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. NIAID, Div AIDS, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Chicago, IL USA. RP Detels, R (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, POB 951772, Los Angeles, CA 90095 USA. FU NCRR NIH HHS [5-M01-RR-00722]; NIAID NIH HHS [UO1-AI-35042, UO1-AI-35043] NR 34 TC 527 Z9 541 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 4 PY 1998 VL 280 IS 17 BP 1497 EP 1503 DI 10.1001/jama.280.17.1497 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 134RR UT WOS:000076757200023 PM 9809730 ER PT J AU Karanjawala, ZE Collins, FS AF Karanjawala, ZE Collins, FS TI Genetics in the context of medical practice SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 Univ So Calif, Sch Med, Los Angeles, CA 90089 USA. NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Karanjawala, ZE (reprint author), Univ So Calif, Sch Med, Los Angeles, CA 90089 USA. NR 10 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 4 PY 1998 VL 280 IS 17 BP 1533 EP 1534 DI 10.1001/jama.280.17.1533 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 134RR UT WOS:000076757200031 PM 9809738 ER PT J AU Wahl, LM Kleinman, HK AF Wahl, LM Kleinman, HK TI Tumor-associated macrophages as targets for cancer therapy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID IFN-GAMMA PRODUCTION; BREAST-CANCER; T-CELLS; ANGIOGENESIS; INTERLEUKIN-12; EXPRESSION; INHIBITION; CYTOKINE; CLONING C1 NIDR, Immunopathol Sect, Bethesda, MD 20892 USA. NIDR, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. RP Kleinman, HK (reprint author), NIH, Bldg 30,Rm 433, Bethesda, MD 20892 USA. EM kleinman@yoda.nidr.nih.gov NR 26 TC 62 Z9 64 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 4 PY 1998 VL 90 IS 21 BP 1583 EP 1584 DI 10.1093/jnci/90.21.1583 PG 2 WC Oncology SC Oncology GA 135LC UT WOS:000076802300001 PM 9811301 ER PT J AU Zujewski, J Liu, ET AF Zujewski, J Liu, ET TI The 1998 St. Gallen's Consensus Conference: an assessment SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER C1 NCI, Div Clin Sci, Bethesda, MD 20892 USA. RP Liu, ET (reprint author), NIH, Bldg 31,Rm 3A11, Bethesda, MD 20892 USA. RI Liu, Edison/C-4141-2008 NR 14 TC 37 Z9 37 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 NOV 4 PY 1998 VL 90 IS 21 BP 1587 EP 1589 DI 10.1093/jnci/90.21.1587 PG 3 WC Oncology SC Oncology GA 135LC UT WOS:000076802300003 PM 9811303 ER PT J AU Gilbert, ES Tarone, R Bouville, A Ron, E AF Gilbert, ES Tarone, R Bouville, A Ron, E TI Thyroid cancer rates and I-131 doses from Nevada atmospheric nuclear bomb tests SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RADIATION; EXPOSURE; FALLOUT; DISEASE AB Background: We examined data on death from thyroid cancer across the continental United States and data on incidence from selected areas of the country for evidence of an association between this disease and exposure to radioactive iodine (I-131) from nuclear tests in Nevada in the 1950s, Methods: Analyses involving 4602 thyroid cancer deaths (1957-1994) and 12 657 incident cases of thyroid cancer (1973-1994) were performed. Excess relative risks (ERRs) per Gray (Gy) of radiation were estimated by relating age-, calendar year-, sex-, and county-specific rates to estimates of dose to the thyroid that take age at exposure into account. Results: Analyses of cumulative dose yielded negative ERRs that were not statistically significant. An association was suggested for dose received by children under 1 year of age for both mortality data (ERR per Gy = 10.6; 95% confidence interval [CI] = -1.1 to 29) and incidence data (ERR per Gy = 2.4; 95% CI = -0.5 to 5.6); no association was found for dose received at older ages. For mortality data, but not incidence data, there was an elevated ERR in the 1950-1959 birth cohort of 12.0 (95% CI = 2.8 to 31) per Gy, Conclusions: Risk of thyroid cancer from exposure to I-131 from atmospheric nuclear tests did not increase with cumulative dose or dose received at ages 1-15 years, but associations were suggested for individuals exposed under 1 year of age and for those in the 1950-1959 birth cohort, The absence of increased risk from dose received at ages 1-15 years is not consistent with studies of children exposed to external radiation sources. This inconsistency may result from the limitations and biases inherent in ecologic studies, including the error introduced when studying a mobile population. These problems preclude making a quantitative estimate of risk due to exposure; however, given such limitations, it is perhaps remarkable that any evidence of the effects of 131I emerges from this study. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Biol, Bethesda, MD 20892 USA. RP Gilbert, ES (reprint author), NIH, Execut Plaza N,Rm 408, Bethesda, MD 20892 USA. NR 28 TC 37 Z9 40 U1 1 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 4 PY 1998 VL 90 IS 21 BP 1654 EP 1660 DI 10.1093/jnci/90.21.1654 PG 7 WC Oncology SC Oncology GA 135LC UT WOS:000076802300016 PM 9811315 ER PT J AU McNeil, C AF McNeil, C TI In search of the perfect SERM: Beyond tamoxifen and raloxifene - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 Journal Natl Canc Inst, Bethesda, MD 20892 USA. RP McNeil, C (reprint author), Journal Natl Canc Inst, 10A19 Pepper Bldg,31 Ctr Dr,MSC2580, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 4 PY 1998 VL 90 IS 21 BP 1671 EP 1671 PG 1 WC Oncology SC Oncology GA 135LC UT WOS:000076802300021 ER PT J AU Moon, YW Park, WS Vortmeyer, AO Weil, RJ Lee, YS Winters, TA Zhuang, ZP Fuller, BG AF Moon, YW Park, WS Vortmeyer, AO Weil, RJ Lee, YS Winters, TA Zhuang, ZP Fuller, BG TI Mutation of the uracil DNA glycosylase gene detected in glioblastoma SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE uracil DNA glycosylase gene; glioblastoma multiforme; single strand conformation polymorphism analysis ID BRAIN-TUMORS; REPAIR; INVITRO; CANCER; CELLS AB Despite extensive characterization of genetic changes in gliomas, the underlying etiology of these tumors remains largely unknown. Spontaneous DNA damage due to hydrolysis, methylation, and oxidation is a frequent event in the brain. Failure of DNA repair following this damage may contribute to tumorigenesis of gliomas. Uracil DNA glycosylase (UDG), an enzyme which excises uracil from DNA, is an important component of the base excision repair pathway. The sequence of a human homologue of uracil DNA glycosylase gene (UNG) has been recently identified. We performed PCR-based SSCP mutational analysis of UNG in 11 sporadic gliomas (six glioblastomas, two anaplastic astrocytomas, and three oligodendrogliomas) and eight glioblastoma cell lines. One out of six sporadic glioblastomas had a point mutation in exon 3, which resulted in a missense mutation in codon 143. None of the eight glioblastoma cell lines or the five non-glioblastoma sporadic gliomas showed a mutation. Genetic alterations of UNG may play a role in the development of a subset of primary glioblastomas. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Catholic Univ, Coll Med, Dept Pathol, Seoul, South Korea. RP Fuller, BG (reprint author), NCI, Radiat Oncol Branch, Bldg 10,Room B3B 69,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bgfuller@box-b.nih.gov NR 25 TC 12 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD NOV 3 PY 1998 VL 421 IS 2 BP 191 EP 196 DI 10.1016/S0027-5107(98)00165-1 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 134ZQ UT WOS:000076774400005 PM 9852992 ER PT J AU Wilkin, DJ Mortier, GR Johnson, CL Jones, MC De Paepe, A Shohat, M Wildin, RS Falk, RE Cohn, DH AF Wilkin, DJ Mortier, GR Johnson, CL Jones, MC De Paepe, A Shohat, M Wildin, RS Falk, RE Cohn, DH TI Correlation of linkage data with phenotype in eight families with Stickler syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Stickler syndrome; COL2A1; cartilage; collagen; chondrodysplasia ID II PROCOLLAGEN GENE; HEREDITARY ARTHRO-OPHTHALMOPATHY; EPIPHYSEAL DYSPLASIA EDM2; SYNDROME ARTHROOPHTHALMOPATHY; COL2A1 GENE; SYNDROME TYPE-2; COL11A1 GENE; MUTATION; COLLAGEN; LOCUS AB The clinical findings of eight families with Stickler syndrome were analyzed and compared with the results of linkage studies using a marker for the type II collagen gene (COL2A1). In six families, there was linkage of the phenotype to COL2A1. The manifestations of the affected individuals were similar to those of the original Stickler syndrome family [Stickler et al,, Mayo, Clin. Proc, 40:433-455, 1965] and resembled the phenotype of the previously reported individuals or families with Stickler syndrome in which a dominant mutation in the COL2A1 gene has been identified, Linkage to COL2A1 was excluded in the two remaining families, The most striking difference between these two types of families was the absence of severe myopia and retinal detachment in the two unliked families. In the COL2A1 unlinked families, linkage of the phenotype to genes (COL11A1 and COL11A2) that encode pro alpha chains of type XI collagen, a minor cartilage-specific collagen, was also excluded, Since Stickler syndrome can be produced by mutations in COL2A1, COL11A1, and COL11A2, our data suggest that there is at least a fourth locus for Stickler syndrome. (C) 1998 Wiley-Liss, Inc. C1 NIH, Med Genet Branch, Natl Human Genome Res Inst, Bethesda, MD USA. State Univ Ghent Hosp, Dept Med Genet, B-9000 Ghent, Belgium. MediGene Serv, Calgary, AB, Canada. Childrens Hosp, Dept Med Genet, San Diego, CA USA. Beilinson Med Ctr, Dept Med Genet, IL-49100 Petah Tiqwa, Israel. Oregon Hlth Sci Univ, Dept Med & Mol Genet, Portland, OR 97201 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat,Burns & Allen Cedars Sinai Res Inst, Steven Spielberg Pediat Res Ctr, Los Angeles, CA 90024 USA. RP Cohn, DH (reprint author), Cedars Sinai Med Ctr, 8700 Beverly Blvd,SSB-3, Los Angeles, CA 90048 USA. EM dcohn@xchg.peds.csmc.edu RI Mortier, Geert/D-2542-2012 FU NICHD NIH HHS [HD22657]; NIGMS NIH HHS [GM16219] NR 51 TC 28 Z9 29 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 2 PY 1998 VL 80 IS 2 BP 121 EP 127 DI 10.1002/(SICI)1096-8628(19981102)80:2<121::AID-AJMG6>3.0.CO;2-M PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 132DT UT WOS:000076615600006 PM 9805127 ER PT J AU Pras, E Kochba, I Lubetzky, A Pras, M Sidi, Y Kastner, DL AF Pras, E Kochba, I Lubetzky, A Pras, M Sidi, Y Kastner, DL TI Biochemical and clinical studies in Libyan Jewish cystinuria patients and their relatives SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE cystinuria; Libyan Jews; amino acids; oral loading test ID SLC3A1 GENE; MUTATIONS AB Cystinuria is a hereditary disorder manifested by the development of kidney stones. Three subtypes of the disease have been described, based on urinary excretion of cystine and the dibasic amino acids in heterozygotes, and oral loading tests in homozygotes. Cystinuria is very common among Libyan Jews living in Israel. Recently, we mapped the disease-causing gene in Libyan Jews to 19q, and have shown a very strong founder effect. In this report we present the results of biochemical and clinical studies performed on Libyan Jewish cystinuria patients and members of their families. High levels of cystine and the dibasic amino acids in heterozygotes support previous data that cystinuria in Libyan Jews is a non-type I disease. Oral loading tests performed with lysine showed some degree of intestinal absorption, but less than in normal controls. Previous criteria for determining the disease type, based solely on urinary amino acid levels, proved useless due to a very wide range of cystine and the dibasic amino acids excreted by the heterozygotes. Urinary cystine levels were useful in distinguishing between unaffected relatives and heterozygotes, but were unhelpful in differentiating between heterozygotes and homozygotes. Urinary levels of ornithine or arginine, and the sum of urinary cystine and the dibasic amino acids, could distinguish between the last two groups. Among stone formers, 90% were homozygotes and 10% were heterozygotes; 15% of the homozygotes were asymptomatic. (C) 1998 Wiley-Liss, Inc. C1 Chaim Sheba Med Ctr, Dept Med C, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Inst Human Genet, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Natl Hemophilia Ctr, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Dept Med F, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel. NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. RP Pras, E (reprint author), Chaim Sheba Med Ctr, Dept Med C, IL-52621 Tel Hashomer, Israel. OI sidi, yechezkel/0000-0001-7781-6153 NR 15 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 2 PY 1998 VL 80 IS 2 BP 173 EP 176 DI 10.1002/(SICI)1096-8628(19981102)80:2<173::AID-AJMG16>3.0.CO;2-S PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 132DT UT WOS:000076615600016 PM 9805137 ER PT J AU Stratakis, CA Kirschner, LS Carney, JA AF Stratakis, CA Kirschner, LS Carney, JA TI Carney complex: Diagnosis and management of the complex of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter ID DUCTAL ADENOMA; COLONIC POLYPS; BREAST; ULTRASOUND; TUMORS C1 NICHD, Unit Genet & Endocrinol, SPE, DEB,NIH, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. RP Stratakis, CA (reprint author), NICHD, Unit Genet & Endocrinol, SPE, DEB,NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC1862, Bethesda, MD 20892 USA. NR 21 TC 33 Z9 35 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 2 PY 1998 VL 80 IS 2 BP 183 EP 185 DI 10.1002/(SICI)1096-8628(19981102)80:2<183::AID-AJMG19>3.0.CO;2-I PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 132DT UT WOS:000076615600019 PM 9805140 ER PT J AU Chen, WN London, R Murphy, E Steenbergen, C AF Chen, WN London, R Murphy, E Steenbergen, C TI Regulation of the Ca2+ gradient across the sarcoplasmic reticulum in perfused rabbit heart - A F-19 nuclear magnetic resonance study SO CIRCULATION RESEARCH LA English DT Article DE sarcoplasmic reticulum; F-19 NMR spectroscopy; Ca2+ transport ID RAT-HEART; CARDIAC MYOCYTES; ENERGY-METABOLISM; CALCIUM-RELEASE; PROTEIN-KINASE; MOUSE HEARTS; PHOSPHOLAMBAN; TRANSPORT; MECHANISMS; MUSCLE AB Myocardial contractility depends on Ca2+ release from and uptake into the sarcoplasmic reticulum (SR). The Ca2+ gradient between the SR matrix and the cytosol (SR Ca2+ gradient) is maintained by the SR Ca2+-ATPase using the free energy available from hydrolysis of ATP. The activity of the SR Ca2+-ATPase is not only dependent on the energy state of the cell but is also kinetically regulated by SR proteins such as phospholamban. To evaluate the importance of thermodynamic and kinetic regulation of the SR Ca2+ gradient, we examined the relationship between the energy available from ATP hydrolysis (Delta G(ATP)) and the energy required for maintenance of the SR Ca2+ gradient (Delta G(Ca2+SR)) during physiological and pathological manipulations that alter Delta G(ATP) and the phosphorylation state of phospholamban. We used our previously developed F-19 nuclear magnetic resonance method to measure the ionized [Ca2+] in the SR of Langendorff-perfused rabbit hearts. We found that addition of either pyruvate or isoproterenol resulted in an increase in left ventricular developed pressure and an increase in [Ca2+](SR). Pyruvate increased he,, and the increase in the SR Ca2+ gradient was matched to the increase in Delta G(ATP); Delta G(ATP) increased from 58.3+/-0.5 to 60.4+/-1.0 kJ/mol (P<0.05), and Delta G(Ca2-SR) increased from 47.1+/-0.3 to 48.5+/-0.1 kJ/mol (P<0.05). In contrast, the increase in the SR Ca2+ gradient in the presence of isoproterenol occurred despite a decline in Delta G(ATP) from 58.3+/-0.5 to 55.8+/-0.6 kJ/mol. Thus, the data indicate that the SR Ca2+ gradient can be increased by an increase in Delta G(ATP), and that the positive inotropic effect of pyruvate can be explained by improved energy-linked SR Ca2+ handling, whereas the results with isoproterenol are consistent with removal of the kinetic limitation of phospholamban on the activity of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase, which allows the SR Ca2+ gradient to move closer to its thermodynamic limit. Ischemia decreases Delta G(ATP), and this should also have an effect on SR Ca2+ handling, During 30 minutes of ischemia, Delta G(ATP) decreased by 12 kJ/mol, but the decrease in Delta G(Ca2+SR) was 16 kJ/mol, greater than would be predicted by the fall in Delta G(ATP) and consistent with increased SR Ca2+ release and increased SR Ca2+ cycling. Because ischemic preconditioning is reported to decrease SR Ca2+ cycling during a subsequent sustained period of ischemia, we examined whether ischemic preconditioning affects the relationship between the fall in Delta G(ATP) and the fall in Delta G(Ca2+SR) during ischemia. We found that preconditioning attenuated the fall in Delta G(Ca2+SR) during ischemia; the fall in Delta G(Ca2+SR) was of comparable magnitude to the fall in Delta G(ATP) and this was associated with a significant improvement in functional recovery during reperfusion. The data suggest that there is both thermodynamic regulation of the SR Ca2+ gradient by Delta G(ATP) and kinetic regulation, which can alter the relationship between Delta G(ATP) and Delta G(Ca2+SR). C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Natl Inst Environm Hlth Sci, LSB, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, LMC, Res Triangle Pk, NC USA. RP Steenbergen, C (reprint author), Duke Univ, Med Ctr, Dept Pathol, Box 3712, Durham, NC 27710 USA. FU NHLBI NIH HHS [R01 HL039752, R01-HL39752] NR 44 TC 45 Z9 46 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV 2 PY 1998 VL 83 IS 9 BP 898 EP 907 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 138PH UT WOS:000076981100003 PM 9797338 ER PT J AU Li, Q Herrler, M Landsberger, N Kaludov, N Ogryzko, VV Nakatani, Y Wolffe, AP AF Li, Q Herrler, M Landsberger, N Kaludov, N Ogryzko, VV Nakatani, Y Wolffe, AP TI Xenopus NF-Y pre-sets chromatin to potentiate p300 and acetylation-responsive transcription from the Xenopus hsp70 promoter in vivo SO EMBO JOURNAL LA English DT Review DE acetylation; chromatin; hsp70 promoter; NF-Y; p300; Y-box ID RNA-POLYMERASE-II; STEROID-RECEPTOR COACTIVATOR-1; DROSOPHILA HSP26 PROMOTER; CCAAT-BINDING PROTEIN; HEAT-SHOCK RESPONSE; CELL-FREE SYSTEM; HISTONE ACETYLATION; DNA-BINDING; IN-VIVO; SACCHAROMYCES-CEREVISIAE AB We identify Xenopus NF-Y as a key regulator of acetylation responsiveness for the Xenopus hsp70 promoter within chromatin assembled in Xenopus oocyte nuclei. Y-box sequences are required for the assembly of DNase I-hypersensitive sites in the hsp70 promoter, and for transcriptional activation both by inhibitors of histone deacetylase and by the p300 acetyltransferase. The viral oncoprotein E1A interferes with both of these activation steps. We clone Xenopus NF-YA, NF-YB and NF-YC and establish that NF-Y is the predominant Y-box-binding protein in Xenopus oocyte nuclei. NF-Y interacts with p300 in viva and is itself a target for acetylation by p300. Transcription from the hsp70 promoter in chromatin can be enhanced further by heat shock factor We suggest two steps in chromatin modification at the Xenopus hsp70 promoter: first the binding of NF-Y to the Y-boxes to preset chromatin and second the recruitment of p300 to modulate transcriptional activity. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Univ Varese, Dipartimento Biol Strutturale & Funz, I-2100 Varese, Italy. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. EM awlme@helix.nih.gov RI Ogryzko, Vasily/M-6665-2015; OI Ogryzko, Vasily/0000-0002-8548-1389; Landsberger, Nicoletta/0000-0003-0820-3155; Li, Qiao/0000-0002-5941-1985 NR 134 TC 166 Z9 166 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 2 PY 1998 VL 17 IS 21 BP 6300 EP 6315 DI 10.1093/emboj/17.21.6300 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 138QX UT WOS:000076984900019 PM 9799238 ER PT J AU Sloan-Lancaster, J Presley, J Ellenberg, J Yamazaki, T Lippincott-Schwartz, J Samelson, LE AF Sloan-Lancaster, J Presley, J Ellenberg, J Yamazaki, T Lippincott-Schwartz, J Samelson, LE TI ZAP-70 association with T cell receptor zeta (TCR zeta): Fluorescence imaging of dynamic changes upon cellular stimulation SO JOURNAL OF CELL BIOLOGY LA English DT Article DE ZAP-70; TCR zeta; protein tyrosine kinase; intracellular signaling; GFP ID PROTEIN-TYROSINE KINASES; TANDEM SH2 DOMAINS; SEVERE COMBINED IMMUNODEFICIENCY; ANTIGEN RECEPTOR; LIVING CELLS; SIGNAL-TRANSDUCTION; ACTIVATION MOTIFS; LYMPHOCYTES-T; BINDING; PHOSPHORYLATION AB The nonreceptor protein tyrosine kinase ZAP-70 is a critical enzyme required for successful T lymphocyte activation. After antigenic stimulation, ZAP-70 rapidly associates with T cell receptor (TCR) subunits. The kinetics of its translocation to the cell surface, the properties of its specific interaction with the TCR zeta chain expressed as a chimeric protein (TT zeta and T zeta zeta), and its mobility in different intracellular compartments were studied in individual live HeLa cells, using ZAP-70 and T zeta zeta fused to green fluorescent protein (ZAP-70 GFP and T zeta zeta-GFP, respectively). Time-lapse imaging using confocal microscopy indicated that the activation-induced redistribution of ZAP-70 to the plasma membrane, after a delayed onset, is of long duration. The presence of the TCR zeta chain is critical for the redistribution, which is enhanced when an active form of the protein tyrosine kinase Lck is coexpressed. Binding specificity to TT zeta was indicated using mutant ZAP-70 GFPs and a truncated zeta chimera. Photobleaching techniques revealed that ZAP-70 GFP has decreased mobility at the plasma membrane, in contrast to its rapid mobility in the cytosol and nucleus. T zeta zeta-GFP is relatively immobile, while peripherally located ZAP-70 in stimulated cells is less mobile than cytosolic ZAP-70 in unstimulated cells, a phenotype confirmed by determining the respective diffusion constants. Examination of the specific molecular association of signaling proteins using these approaches has provided new insights into the TCR zeta-ZAP-70 interaction and will be a powerful tool for continuing studies of lymphocyte activation. C1 NICHHD, Sect Lymphocyte Signaling, NIH, Bethesda, MD 20892 USA. NICHHD, Unit Organelle Biol, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NICHD, CBMB, Bldg 18T,Rm 101, Bethesda, MD 20892 USA. RI Ellenberg, Jan/I-4688-2014 OI Ellenberg, Jan/0000-0001-5909-701X NR 54 TC 45 Z9 46 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 2 PY 1998 VL 143 IS 3 BP 613 EP 624 DI 10.1083/jcb.143.3.613 PG 12 WC Cell Biology SC Cell Biology GA 137BQ UT WOS:000076894300005 PM 9813084 ER PT J AU Chen, HX Centola, M Altschul, SF Metzger, H AF Chen, HX Centola, M Altschul, SF Metzger, H TI Characterization of gene expression in resting and activated mast cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE receptor aggregation; signal transduction; exocytosis; cell differentiation; allergy ID MIGRATION INHIBITORY FACTOR; DELAYED-TYPE HYPERSENSITIVITY; BASOPHILIC LEUKEMIA-CELLS; FC-EPSILON-RI; PROTEIN-KINASE; RAT RELAXIN; MONOCLONAL-ANTIBODIES; LHRH RECEPTORS; MESSENGER-RNA; GUINEA-PIGS AB To characterize gene expression in activated mast cells more comprehensively than heretofore, we surveyed the changes in genetic transcripts by the method of serial analysis of gene expression in the RBL-2H3 line of rat mast cells before and after they were stimulated through their receptors with high affinity for immunoglobulin E (Fc epsilon RI). A total of 40,759 transcripts derived from 11,300 genes were analyzed. Among the diverse genes that had not been previously associated with mast cells and that were constitutively expressed were those for the cytokine macrophage migration inhibitory factor neurohormone receptors such as growth hormone-releasing factor and melatonin and components of the exocytotic machinery. In addition, several dozen transcripts were differentially expressed in response to antigen-induced clustering of the Fc epsilon RI. Included among these were the genes for preprorelaxin, mitogen-activated protein kinase kinase 3, and the dual specificity protein phosphatase, rVH6. Significantly, the majority of genes differentially expressed in this well-studied model of mast cell activation have not been identified before this analysis. C1 NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Chen, HX (reprint author), NIAMSD, Arthrit & Rheumatism Branch, 10 Ctr Dr MSC 1820, Bethesda, MD 20892 USA. NR 74 TC 90 Z9 93 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 2 PY 1998 VL 188 IS 9 BP 1657 EP 1668 DI 10.1084/jem.188.9.1657 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 137DB UT WOS:000076898600012 PM 9802978 ER PT J AU Ufret-Vincenty, RL Quigley, L Tresser, N Pak, SH Gado, A Hausmann, S Wucherpfennig, KW Brocke, S AF Ufret-Vincenty, RL Quigley, L Tresser, N Pak, SH Gado, A Hausmann, S Wucherpfennig, KW Brocke, S TI In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE autoimmunity; cross-reactivity; experimental autoimmune encephalomyelitis; molecular mimicry; antigenic peptide ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS PATIENTS; CENTRAL-NERVOUS-SYSTEM; LYMPHOCYTE-T; MOLECULAR MIMICRY; ADOPTIVE TRANSFER; VIRUS-INFECTION; B-CELL; HEALTHY-INDIVIDUALS AB A peptide derived from the human papillomavirus L2 protein is recognized by a myelin basic protein (MBP)-specific T cell clone from a multiple sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue. We now show in mice that low doses of this papillomavirus peptide were optimal in selecting a subpopulation of papillomavirus peptide-specific T cells that cross-reacted with MBP(87-99) and with an unrelated viral peptide derived from the BSLF1 protein of Epstein-Ban virus (EBV). These low dose viral peptide-specific T cell lines were highly encephalitogenic. Splenocytes from mice transferred with viral peptide-specific T cells showed a vigorous response to both the papillomavirus and MBP peptides, indicating that viral antigen-specific T cells survived for a prolonged time in vivo. The EBV peptide, unable to prime and select an autoreactive T cell population, could still activate the low dose papillomavirus peptide-specific cells and induce central nervous system (CNS) autoimmunity. Cytokine profiles of papillomavirus peptide-specific encephalitogenic T cells and histopathology of CNS lesions resembled those induced by MBP. These results demonstrate conserved aspects in the recognition of the self-antigen and a cross-reactive viral peptide by human and murine MBP-specific T cell receptors. We demonstrate that a viral antigen, depending on its nature, dose, and number of exposures, may select autoantigen-specific T cells that survive in vivo and can trigger autoimmune disease after adoptive transfer. C1 NINDS, Neurol Dis Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Brocke, S (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Pathol, POB 12272, IL-91120 Jerusalem, Israel. EM sbrocke@md2.huji.ac.il FU NIAID NIH HHS [AI-41641] NR 61 TC 59 Z9 63 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 NOV 2 PY 1998 VL 188 IS 9 BP 1725 EP 1738 DI 10.1084/jem.188.9.1725 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 137DB UT WOS:000076898600018 PM 9802984 ER PT J AU Michal, CA Tycko, R AF Michal, CA Tycko, R TI Nuclear spin polarization transfer with a single radio-frequency field in optically pumped indium phosphide SO PHYSICAL REVIEW LETTERS LA English DT Article ID GAAS QUANTUM-WELLS; MAGNETIC-RESONANCE; GALLIUM-ARSENIDE; NMR; SHIFT AB We describe a novel spin polarization transfer phenomenon observed in high-field, optically pumped NMR experiments on single-crystal indium phosphide. Polarization transfer from In-115 spins to P-31 spins occurs when a weak radio-frequency field is applied at the P-31 NMR frequency. Unlike other known high-field polarization transfer effects, no rf field near the In-115 frequency is required. We present evidence that the P-31 polarization arises from a state of optically pumped dipolar order in the In-115 spin system and propose two mechanisms that may contribute to the creation of this state. [S0031-9007(98)07539-5]. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Michal, CA (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. RI Michal, Carl/G-5288-2012 OI Michal, Carl/0000-0002-5764-3221 NR 32 TC 26 Z9 26 U1 3 U2 12 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD NOV 2 PY 1998 VL 81 IS 18 BP 3988 EP 3991 DI 10.1103/PhysRevLett.81.3988 PG 4 WC Physics, Multidisciplinary SC Physics GA 135YB UT WOS:000076829500046 ER PT J AU Bezrukov, SM AF Bezrukov, SM TI Stochastic resonance as an inherent property of rate-modulated random series of events SO PHYSICS LETTERS A LA English DT Article DE random events; Poisson time series; noise-facilitated signal transduction; small-signal detection and analysis ID NOISE; NEURONS; SYSTEM AB At the molecular level, processes in physics and biology are intrinsically random. Quite often they can be described as random series of elementary events, Poisson trains, whose event generation rate is a function of an input driving parameter. We analyze the transduction of weak signals by such trains in the presence of additive input noise in terms of transfer coefficient and output signal-to-noise ratio. We show that the noise-facilitated signal transduction, stochastic resonance (SR), is an inherent property of parameter-dependent Poisson trains with a nonlinear relationship between the event generation rate, r(V(t)), and the driving parameter, V(t). We obtain a sufficient condition for the SR onset that shows that for the input noise with a sufficiently broad bandwidth, SR can be observed in a wide variety of such systems. If this relationship is represented by r(V(t)) proportional to 1 + Sigma(1)(3) r(n)V(n)(t), then the system is capable of SR if 6r(3)/r(1) - r(2) > 0 Addition of small noise with a broad bandwidth to the system input increases the output signal quality. To highlight the mechanism of noise-facilitated signal transduction in such systems, we also analyze the "linearizing" effect of the additive noise on signal transduction in rate-modulated Poisson series. (C) 1998 Elsevier Science B.V. C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. St Petersburg Nucl Phys Inst, Gatchina 188350, Russia. RP Bezrukov, SM (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bldg 9,Room 1E-122, Bethesda, MD 20892 USA. NR 20 TC 24 Z9 25 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0375-9601 J9 PHYS LETT A JI Phys. Lett. A PD NOV 2 PY 1998 VL 248 IS 1 BP 29 EP 36 DI 10.1016/S0375-9601(98)00610-0 PG 8 WC Physics, Multidisciplinary SC Physics GA 131RA UT WOS:000076588000006 ER PT J AU Eaton, WA Munoz, V Thompson, PA Henry, ER Hofrichter, J AF Eaton, WA Munoz, V Thompson, PA Henry, ER Hofrichter, J TI Kinetics and dynamics of loops, alpha-helices, beta-hairpins, and fast-folding proteins SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID ENERGY LANDSCAPE; STATISTICAL-MECHANICS; CYTOCHROME-C; FAST EVENTS; STABILITY; PEPTIDE; MODEL; PERSPECTIVE; TEMPERATURE; PATHWAYS C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Biophys Chem Sect, NIH, Bethesda, MD 20892 USA. RP Eaton, WA (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 49 TC 138 Z9 139 U1 1 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD NOV PY 1998 VL 31 IS 11 BP 745 EP 753 DI 10.1021/ar9700825 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 144QN UT WOS:000077326400008 ER PT J AU Dalgaard, JZ Silva, GH Belfort, M Van Roey, P AF Dalgaard, JZ Silva, GH Belfort, M Van Roey, P TI Crystallization and preliminary crystallographic analysis of the archaeal intron-encoded endonuclease I-DmoI SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID SITE-SPECIFIC ENDONUCLEASE; HOMING ENDONUCLEASE; GENE CONVERSION; PROTEIN AB Two forms of the archaeal intron-encoded site-specific endonuclease I-DmoI, namely I-DmoIc and I-DmoIl, have been purified and crystallized. Crystals of I-DmoIc are rod-shaped and diffract to 3.0 Angstrom resolution, but further analysis was hampered by twinning. Crystals of I-DmoIl, which is a six-amino-acid C-terminal truncation of I-DmoIc, are plate shaped and belong to space group C2 with cell parameters a = 93.72, b = 37.03, c = 55.56 Angstrom, beta = 113.4 degrees, with one molecule per asymmetric unit (V-m = 2.01 Angstrom(3) Da(-1)). The crystals diffract to at least 2.3 Angstrom resolution. A complete native data set has been measured and structure determination is on-going. C1 New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY 12201 USA. RP Dalgaard, JZ (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, POB,Bldg 549 Room 154, Frederick, MD 21702 USA. OI Belfort, Marlene/0000-0002-1592-5618 FU NIGMS NIH HHS [GM56966, GM39422, GM44844] NR 16 TC 2 Z9 2 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD NOV 1 PY 1998 VL 54 SI S2 BP 1435 EP 1436 DI 10.1107/S0907444998006222 PN 6 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 144KT UT WOS:000077314300033 PM 10089530 ER PT J AU Yang, JM Lee, S Kang, HJ Lee, JH Yeo, UC Son, IY Park, KB Steinert, PM Lee, ES AF Yang, JM Lee, S Kang, HJ Lee, JH Yeo, UC Son, IY Park, KB Steinert, PM Lee, ES TI Mutations in the 1A rod domain segment of the keratin 9 gene in epidermolytic palmoplantar keratoderma SO ACTA DERMATO-VENEREOLOGICA LA English DT Article DE keratin 9; mutation; epidermolytic palmoplantar keratoderma ID 2 FAMILIES; BULLOSA SIMPLEX; PACHYONYCHIA-CONGENITA; INTERMEDIATE FILAMENTS; HYPERKERATOSIS; DISEASE; VORNER; H1 AB Palmoplantar keratodermas (PPK) constitute a heterogeneous group of diseases marked by the thickening of palms and soles of affected individuals. They are divided into autosomal dominant and autosomal recessive groups by the mode of transmission. The autosomal dominantly transmitted group is further divided into epidermolytic (EPPK, Voerner) and non-epidermolytic (NEPPK, Unna-Thost) types according to the histopathologic findings. Recent development of molecular approaches has confirmed that EPPK and NEPPK are caused by the mutations in keratin 9 and 1 genes, respectively. We have studied three families of EPPK to find the mutation in the keratin 9 gene. DNA sequence analyses revealed single base changes in sequences encoding the highly conserved 1A rod domain segment of the keratin 9 gene in two of the three families. These mutations caused Arg (CGG) to Glu (CAG; R162Q) and Arg (CGG) to Try (TGG; R162W) substitutions. The same arginine position has been mutated in the keratin 10 gene in epidermolytic hyperkeratosis, the keratin 14 gene in epidermolysis bullosa simplex, and the keratin 9 gene in hereditary EPPK in Western patients. In this study we show that unrelated Korean patients have similar mutations. C1 Sungkyunkwan Univ, Dept Dermatol, Coll Med, Samsung Med Ctr,Kangnam Ku, Seoul 135710, South Korea. Samsung Biomed Res Inst, Clin & Basic Res Ctr, Seoul, South Korea. Chungnam Natl Univ, Dept Dermatol, Taejon, South Korea. NIAMSD, Skin Biol Lab, NIH, Bethesda, MD USA. RP Yang, JM (reprint author), Sungkyunkwan Univ, Dept Dermatol, Coll Med, Samsung Med Ctr,Kangnam Ku, 50 Ilwon Dong, Seoul 135710, South Korea. NR 39 TC 12 Z9 14 U1 0 U2 3 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-5555 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PD NOV PY 1998 VL 78 IS 6 BP 412 EP 416 PG 5 WC Dermatology SC Dermatology GA 135UK UT WOS:000076820800003 PM 9833037 ER PT J AU Yang, JM Lee, ES Kang, HJ Choi, GS Yoneda, K Jung, SY Park, KB Steinert, PM Lee, ES AF Yang, JM Lee, ES Kang, HJ Choi, GS Yoneda, K Jung, SY Park, KB Steinert, PM Lee, ES TI A glutamate to lysine mutation at the end of 2B rod domain of keratin 2e gene in ichthyosis bullosa of Siemens SO ACTA DERMATO-VENEREOLOGICA LA English DT Article DE keratin 2e; mutation; ichthyosis bullosa of Siemens ID EPIDERMOLYTIC HYPERKERATOSIS; DIFFERENTIATION; CYTOKERATIN-2; EXFOLIATIVA; DISEASE AB lchthyosis bullosa of Siemens is a rare autosomal dominant skin disorder whose clinical findings are quite similar to those of epidermolytic hyperkeratosis. The differences between those two diseases include absence of erythroderma and different distributions in the shin in ichthyosis bullosa of Siemens. Recent studies have confirmed that ichthyosis bullosa of Siemens is caused by the mutation in the keratin 2e (K2e) gene, which is expressed in the upper spinous and granular layers. We have identified a sporadic case of ichthyosis bullosa of Siemens; based on diagnosis by histopathological findings, the K2e gene of the patient was analysed. Direct sequencing of PCR products revealed a single base change in sequences encoding the highly conserved end of the 2B rod domain segment of the K2e gene. This mutation results in substitution of the codon for glutamic acid by a codon for lysine in position 493 in K2e (E493K). Mutations of the K2e gene involving five different residue positions (Q187P, T485P, L490P, E493D, E493K and E494K) are known to cause ichthyosis bullosa of Siemens. Of these sites, E493, which is conserved in type I and type II keratin genes, is the most frequently altered amino acid in the K2e gene. These data together suggest that this codon constitutes a hot spot for mutations in the K2e gene. C1 Sungkyunkwan Univ, Dept Dermatol, Coll Med, Kangnam Ku, Seoul 135710, South Korea. Ajou Univ, Sch Med, Clin & Basic Res Ctr, Samsung Biomed Res Inst, Seoul, South Korea. Ajou Univ, Sch Med, Dept Dermatol, Seoul, South Korea. Kyoto Natl Univ, Coll Med, Dept Dermatol, Kyoto, Japan. NIAMSD, Skin Biol Lab, NIH, Bethesda, MD USA. RP Yang, JM (reprint author), Sungkyunkwan Univ, Dept Dermatol, Coll Med, Kangnam Ku, 50 Ilwon Dong, Seoul 135710, South Korea. OI Lee, Eun-So/0000-0003-0232-7704 NR 23 TC 4 Z9 6 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-5555 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PD NOV PY 1998 VL 78 IS 6 BP 417 EP 419 PG 3 WC Dermatology SC Dermatology GA 135UK UT WOS:000076820800004 PM 9833038 ER PT J AU Eron, J Falloon, J Masur, H Ait-Khaled, M Thomas, D Manion, D Rogers, M AF Eron, J Falloon, J Masur, H Ait-Khaled, M Thomas, D Manion, D Rogers, M CA CNAA2007 Study Team TI Activity of combination abacavir/amprenavir/efavirenz therapy in HIV-1 infected subjects failing their current protease inhibitor containing regimen SO AIDS LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. NIAID, NIH, Bethesda, MD 20892 USA. Glaxo Wellcome Inc, Stevenage, Herts, England. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. DuPont Pharmaceut, Wilmington, DE USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD NOV PY 1998 VL 12 SU 4 MA OP52 BP S13 EP S13 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 144JP UT WOS:000077311300050 ER PT J AU D'Angelo, LJ Lindsey, J Zimmer, B Culnane, M Futtermann, D AF D'Angelo, LJ Lindsey, J Zimmer, B Culnane, M Futtermann, D CA ACTG 220 Protocol Team TI Attempting to enhance the enrollment of adolescents into AIDS clinical trials: The design of ACTG Protocol 220 SO AIDS PATIENT CARE AND STDS LA English DT Article ID UNITED-STATES; HIV AB The epidemic of HIV infection continues to grow in adolescents and young adults. Unfortunately, because treatment regimens have been developed based on data derived from clinical trials, little data are available on adolescents because they are infrequently included in these trials. In an effort to facilitate the enrollment of more adolescents into AIDS Clinical Trials Group (ACTG) clinical trials, we designed a nontreatment protocol to familiarize adolescents with clinical trials requirements. Two hundred fifty-six adolescents (150 females, 106 males) between the ages of 13 and 21 years were enrolled at 43 different clinical trials sites throughout the United States. The majority of patients (50%) were enrolled at sites that had specific programs for adolescents. Most of the young women (85%) had acquired their infection via heterosexual transmission, whereas the largest transmission categories in men were blood or factor transfusions (43%) or same-sex contact (34%). Admission CD4 counts were lower in males (mean = 396 cells/mm(3)) than in females (mean = 513 cells/mm(3)) (p = 0.01). Psychosocial profiles revealed a variety of ongoing risk behaviors in HIV-infected adolescents. Two years into the study, 223 patients are still being observed. We conclude that adolescents can be enrolled in an observational protocol. The success of this trial will be determined by how many ACTG Protocol 220 participants are ultimately enrolled in therapeutic trials. C1 Childrens Natl Med Ctr, Sect Adolescent & Young Adult Med, Washington, DC 20010 USA. George Washington Univ, Med Ctr, Dept Pediat, Washington, DC 20037 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Pediat AIDS Clin Trials Grp, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn, Buffalo, NY USA. NIAID, Pediat Branch, Div Aids, NIH, Bethesda, MD USA. Montefiore Med Ctr, Adolescent AIDS Program, Bronx, NY 10467 USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. Univ Cincinnati, Cincinnati, OH USA. ACTG Operat Off, Rockville, MD USA. Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. NICHD, Rockville, MD USA. Dept Publ Hlth, San Francisco, CA USA. Texas Childrens Hosp, Houston, TX 77030 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP D'Angelo, LJ (reprint author), Childrens Natl Med Ctr, Sect Adolescent & Young Adult Med, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD NOV PY 1998 VL 12 IS 11 BP 853 EP 859 DI 10.1089/apc.1998.12.853 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 140ZE UT WOS:000077117500007 PM 11362042 ER PT J AU Robbins, PA Roderiquez, GL Peden, KWC Norcross, MA AF Robbins, PA Roderiquez, GL Peden, KWC Norcross, MA TI Human immunodeficiency virus type 1 infection of antigen-specific CD4 cytotoxic T lymphocytes SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; HIV-1 INFECTION; EQUIVALENT RECOGNITION; PERIPHERAL-BLOOD; IMMUNE-RESPONSE; CELL TROPISM; V3 LOOP; CD8+; REPLICATION; RECEPTOR AB The effect of macrophage (M)-tropic and T cell line (T)-tropic human immunodeficiency virus type-1 (HIV-1) infection on antigen-specific CD4 cytotoxic T lymphocytes (CTLs) has been studied using a CD4 CTL line specific for a peptide from influenza B virus hemagglutinin, In the absence of antigen presentation, the production of CC chemokines was low. Both the M-tropic HIV-1 strain (HIV-1(AD)) and the T-tropic HIV-1 strain (HIV-1(LAL)) established productive infections in the CD4 CTLs, decreasing antigen-specific cytotoxicity, Peptide presented to the CD4 CTLs increased their secretion of RANTES and MIP-1 beta, suppressed IM-tropic HIV-1 replication, downmodulated CCR5 expression, and preserved CTL recognition. The suppression of M-tropic HIV-1 replication and downmodulation of the CCR5 receptor likely resulted from CC chemokine secretion since antibodies to CC chemokines restored M-tropic HIV-1 replication, Antigen presentation did not protect CD4 CTLs from T-tropic HIV-1 infection or preserve their CTL recognition. Thus, these CD4 CTLs do not make suppressor factors that inhibit the T-tropic HIV-1(LAI) isolate. The results indicate that these CD4 CTLs can either harbor or suppress M-tropic HIV-1 infection, depending on whether antigen is present. CD4 CTLs might therefore provide some protection in the early stages of HIV-1 infection when M-tropic isolates are present. C1 US FDA, Lab Cell & Viral Regulat, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Lab Retrovirus Res, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Robbins, PA (reprint author), US FDA, Lab Cell & Viral Regulat, Ctr Biol Evaluat & Res, NIH Bldg 29B,Rm 5E14,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 58 TC 7 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV 1 PY 1998 VL 14 IS 16 BP 1397 EP 1406 DI 10.1089/aid.1998.14.1397 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 137VA UT WOS:000076936100001 PM 9824317 ER PT J AU Witt, E Cunningham, C Dudek, B Finn, P Henderson, N Plomin, R Samson, H AF Witt, E Cunningham, C Dudek, B Finn, P Henderson, N Plomin, R Samson, H TI Gene-environment interactions in alcohol research: Round table discussion of conceptual and methodological issues using animal models SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID QUANTITATIVE TRAIT LOCI; ACCESS SITUATION; ETHANOL; MICE; SENSITIVITY; PREFERENCE; RATS C1 NIAAA, Neurosci & Behav Res Branch, Div Basic Res, NIH, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Dept Neurosci, Portland, OR USA. SUNY Albany, Dept Psychol, Albany, NY 12222 USA. Indiana Univ, Dept Psychol, Bloomington, IN USA. Oberlin Coll, Dept Psychol, Oberlin, OH 44074 USA. Inst Psychiat, Psychiat Res Ctr, London, England. Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27103 USA. RP Witt, E (reprint author), NIAAA, Neurosci & Behav Res Branch, Div Basic Res, NIH, Willco Bldg,Suite 402,6000 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. RI Plomin, Robert/B-8911-2008; OI Plomin, Robert/0000-0002-0756-3629 NR 22 TC 1 Z9 1 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1998 VL 22 IS 8 BP 1719 EP 1723 DI 10.1111/j.1530-0277.1998.tb03971.x PG 5 WC Substance Abuse SC Substance Abuse GA 139WG UT WOS:000077053700015 PM 9835286 ER PT J AU Cohen, SG AF Cohen, SG TI Asthma among the famous - A continuing series SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD NOV-DEC PY 1998 VL 19 IS 6 BP 387 EP 399 DI 10.2500/108854198778612690 PG 13 WC Allergy SC Allergy GA 149DN UT WOS:000077590000011 ER PT J AU Marin-Neto, JA Dilsizian, V Arrighi, JA Perrone-Filardi, P Bacharach, SL Bonow, RO AF Marin-Neto, JA Dilsizian, V Arrighi, JA Perrone-Filardi, P Bacharach, SL Bonow, RO TI Thallium scintigraphy compared with F-18-fluorodeoxyglucose positron emission tomography for assessing myocardial viability in patients with moderate versus severe left ventricular dysfunction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; HIBERNATING MYOCARDIUM; TL-201 REINJECTION; VIABLE MYOCARDIUM; BLOOD-FLOW; DOBUTAMINE ECHOCARDIOGRAPHY; SURGICAL REVASCULARIZATION; COMPUTED-TOMOGRAPHY; WALL-MOTION; IDENTIFICATION AB Thallium-201 reinjection imaging and positron emission tomography provide concordant information regarding myocardial viability in many patients with coronary artery disease and left ventricular (LV) dysfunction. It is unclear whether this concordance applies to patients with severe, as well as those with moderate, LV dysfunction. We studied 44 patients with chronic coronary artery disease and LV dysfunction, subgrouped on the basis of severity of dysfunction: 23 patients had moderate and 21 had severe dysfunction (ejection fractions 34 +/- 6% and 19 +/- 6%). Patients underwent exercise thallium single-photon emssion computed tomography (SPECT) with 3- to 4-hour redistribution and reinjection imaging, as well as positron emission tomography (PET) imaging with (18)fluorodeoxyglucose and O-15-water. Data were analyzed quantitatively in aligned transaxial PET and SPECT tomograms. A myocardial region was considered nonviable by PET if (18)fluorodeoxyglucose activity was <50% of that in a normal region, associated with proportional reduction in blood flow. Similarly, regions were considered nonviable by thallium if activity was <50% of activity in normal regions on redistribution and reinjection studies. Thallium SPECT and PET data were concordant regarding viability in 98% and 93% of myocardial regions, respectively, in patients with moderate and with severe LV dysfunction. Lower concordance was observed only when regions with severe irreversible thallium perfusion defects on redistribution images were considered in both groups: 86% and 78%, respectively (p <0.01). Thus, thallium SPECT with reinjection yields information regarding regional myocardial viability that is similar to that provided by PET in patients with severe as well as moderate LV dysfunction. However, there is discordance in >20% of regions manifesting severe irreversible thallium defects in patients with severely reduced LV function. (C)1998 by Excerpta Medica, Inc. C1 NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. RP Bonow, RO (reprint author), Northwestern Univ, Sch Med, Div Cardiol, 250 E Super St,Suite 524, Chicago, IL 60611 USA. NR 30 TC 16 Z9 18 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 1998 VL 82 IS 9 BP 1001 EP 1007 DI 10.1016/S0002-9149(98)00551-7 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 133ZK UT WOS:000076717300001 PM 9817471 ER PT J AU Gray, RS Fabsitz, RR Cowan, LD Lee, ET Howard, BV Savage, PJ AF Gray, RS Fabsitz, RR Cowan, LD Lee, ET Howard, BV Savage, PJ TI Risk factor clustering in the insulin resistance syndrome - The Strong Heart Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE coronary disease; factor analysis; statistical; Indians; North American; insulin resistance ID DEPENDENT DIABETES-MELLITUS; AMERICAN-INDIANS; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; ESSENTIAL-HYPERTENSION; OBESITY; WOMEN; CHOLESTEROL; ASSOCIATION; LIPIDS AB The objective of this study was to examine how the major components of the insulin resistance syndrome relate to each other and to macrovascular disease in American Indians in the Strong Heart Study. The study cohort (4,228 resident tribal members 45-74 years old) underwent a personal interview and a physical examination between July 1989 and January 1992 at three centers: Arizona, Oklahoma, and North and South Dakota; blood samples were drawn and a 75-9 oral glucose tolerance test was performed. Factor analysis was used to assess the clustering and interdependence of groups of insulin resistance syndrome variables. Within both diabetic and nondiabetic groups, three factors emerged. In nondiabetic participants, a cluster of glucose, body mass index, and insulin accounted for 35% (male) and 32% (female) of the total variance in all variables considered, and a cluster of systolic blood pressure and diastolic blood pressure accounted for 25% and 22% in men and women, respectively. Both clusters were positively associated with coronary heart disease but not peripheral vascular disease, In diabetic participants, the combination of systolic and diastolic blood pressures was the most important factor, but the cluster was not associated with coronary heart disease or peripheral vascular disease. A component containing high density lipoprotein cholesterol, triglycerides, and glucose had a positive association with coronary heart disease in diabetic women and with peripheral Vascular disease in both sexes. The association of clusters of risk factors and their relations with coronary heart disease provide important clues that may be used in understanding the metabolic disorders associated with insulin resistance and diabetes. C1 Medlant Res Inst, Washington, DC 20010 USA. Univ Oklahoma, Dept Biostat & Epidemiol, Oklahoma City, OK USA. NHLBI, Bethesda, MD 20892 USA. RP Howard, BV (reprint author), Medlant Res Inst, 108 Irving St NW, Washington, DC 20010 USA. FU NHLBI NIH HHS [U01-HL41642, U01HL41652, UL01HL41654] NR 41 TC 107 Z9 113 U1 1 U2 3 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 1998 VL 148 IS 9 BP 869 EP 878 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 132MR UT WOS:000076634300007 PM 9801017 ER PT J AU Wilcox, AJ Weinberg, CR Lie, RT AF Wilcox, AJ Weinberg, CR Lie, RT TI Distinguishing the effects of maternal and offspring genes through studies of "case-parent triads" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE abnormalities; alleles; case-control studies; epidemiologic methods; genetic markers; linkage disequilibrium; models, genetic; models, statistical ID LINKAGE DISEQUILIBRIUM; TRANSMISSION TEST; RELATIVE RISKS; SPINA-BIFIDA; ASSOCIATION; DISEASE; SAMPLE; FETAL AB A gene variant that increases disease risk will be overrepresented among diseased persons, even compared with their own biologic parents. This insight has led to tests based solely on the asymmetric distribution of a variant allele among cases and their parents (e.g., the transmission/disequilibrium test). Existing methods focus on effects of alleles that operate through the offspring genotype. Alleles can also operate through the mother's genotype, particularly for conditions such as birth defects that have their origins in fetal life. An allele working through the mother would have higher frequency in case-mothers than in case-fathers. The authors develop a log-linear method for estimating relative risks for alleles in the context of case-parent triads. This method is able to detect the effects of genes working through the offspring, the mother, or both. The authors assume Mendelian inheritance, but Hardy-Weinberg equilibrium is unnecessary. Their approach uses standard software, and simulations demonstrate satisfactory power and confidence interval coverage. This method is valid with a self-selected or hospital-based series of cases and helps to protect against misleading inference that can result when cases and controls are randomly sampled from a population not in Hardy-Weinberg equilibrium. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Univ Bergen, Div Med Stat, N-5020 Bergen, Norway. RP Wilcox, AJ (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 15 TC 131 Z9 133 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 1998 VL 148 IS 9 BP 893 EP 901 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 132MR UT WOS:000076634300010 PM 9801020 ER PT J AU Canto, MT Goodman, HS Horowitz, AM Watson, MR Duran-Medina, C AF Canto, MT Goodman, HS Horowitz, AM Watson, MR Duran-Medina, C TI Latino youths' knowledge of oral cancer and use of tobacco and alcohol SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article ID CIGARETTE-SMOKING; HEALTH PROMOTION; PREDICTORS; PREVENTION; ADOLESCENTS; MINORS AB Objective: To assess Latino youths' knowledge of risk factors for oral cancer, tobacco and alcohol use, and access to cigarettes. Methods: Developed from focus groups, and national surveys, instrument was pilot tested and administered to 189 youths. Additionally, trained youths attempted to purchase cigarettes from stores in the community. Results: Major factors for experimenting with cigarettes and alcohol were peer pressure and peer acceptance of the behavior. Latino youths were ill-informed about oral cancer, Further, 60% of the surveyed stores would have sold cigarettes to miners without asking for identification. Conclusion: Hearth promotion interventions need to be comprehensive including schools, family, and business establishments. C1 VA Maryland Hlth Care Syst, Dental Serv 160, Perry Point, MD 21902 USA. Maryland Dept Hlth & Mental Hyg, Baltimore, MD USA. NIDR, NIH, Bethesda, MD 20892 USA. Univ Maryland, Baltimore Coll Dent Surg, Dept Pediat Dent, Baltimore, MD 21201 USA. Latin Amer Youth Ctr, Washington, DC USA. RP Canto, MT (reprint author), VA Maryland Hlth Care Syst, Dental Serv 160, Perry Point, MD 21902 USA. EM CantoM@de45.nidr.nih.gov NR 41 TC 1 Z9 1 U1 2 U2 2 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD NOV-DEC PY 1998 VL 22 IS 6 BP 411 EP 420 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 133YE UT WOS:000076714500002 ER PT J AU Shotelersuk, V Larson, D Anikster, Y McDowell, G Lemons, R Bernardini, I Guo, JR Thoene, J Gahl, WA AF Shotelersuk, V Larson, D Anikster, Y McDowell, G Lemons, R Bernardini, I Guo, JR Thoene, J Gahl, WA TI CTNS mutations in an American-based population of cystinosis patients SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID LEUKOCYTE GRANULAR FRACTIONS; NEPHROPATHIC CYSTINOSIS; CYSTEAMINE THERAPY; COUNTER-TRANSPORT; RENAL-FUNCTION; FIBROBLASTS; LYSOSOMES; GROWTH; 17P13; GENE AB Nephropathic cystinosis is an autosomal recessive lysosomal storage disease characterized by renal failure at 10 years of age and other systemic complications. The gene for cystinosis, CTNS; has 12 exons. Its 2.6-kb mRNA codes for a 367-amino-acid putative cystine transporter with seven transmembrane domains. Previously reported mutations include a 65-kb "European" deletion involving marker D17S829 and II. small mutations, Mutation analysis of 108 American-based nephropathic cystinosis patients revealed that 48 patients (44%) were homozygous for the 65-kb deletion, 2 had a smaller major deletion, 11 were homozygous and 3 were heterozygous for 753G-->A (W138X), and 24 had 21 other mutations. In 20 patients (19%), no mutations were found, Of 82 alleles bearing the 65-kb deletion, 38 derived from Germany, 28 from the British Isles, and 4 from Iceland, Eighteen new mutations were identified, including the first reported missense mutations, two in-frame deletions, and mutations in patients of African American, Mexican, and Indian ancestry. CTNS mutations are spread throughout the leader sequence, transmembrane, and nontransmembrane regions. According to a cystinosis clinical severity score, homozygotes for the 65-kb deletion and for W138X have average disease, whereas mutations involving the first amino acids prior to transmembrane domains are associated with mild disease. By northern blot analysis, CTNS was not expressed in patients homozygous for the 65-kb deletion but was expressed in all 15 other patients tested. These data demonstrate the origins of CTNS mutations. in America and provide a basis for possible molecular diagnosis in this population. C1 NICHHD, Heritable Disorders Branch, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Med Genet Branch, Bethesda, MD USA. Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. RP Gahl, WA (reprint author), NICHHD, Heritable Disorders Branch, Sect Human Biochem Genet, NIH, 10 Ctr Dr,MSC 1830,Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov FU NIDDK NIH HHS [DK25548] NR 36 TC 81 Z9 86 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 1998 VL 63 IS 5 BP 1352 EP 1362 DI 10.1086/302118 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 138QZ UT WOS:000076985200011 PM 9792862 ER PT J AU Young, TL Ronan, SM Alvear, AB Wildenberg, SC Oetting, WS Atwood, LD Wilkin, DJ King, RA AF Young, TL Ronan, SM Alvear, AB Wildenberg, SC Oetting, WS Atwood, LD Wilkin, DJ King, RA TI A second locus for familial high myopia maps to chromosome 12q SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HUMAN GENOME; SULFATE PROTEOGLYCAN; LINKAGE; COLLAGEN; LOCALIZATION; DECORIN; LUMICAN AB dMyopia, or nearsightedness, is the most common eye disorder worldwide. "Pathologic" high myopia, or myopia of less than or equal to -6.00 diopters, predisposes individuals to retinal detachment, macular degeneration, cataract, or glaucoma. A locus for autosomal dominant pathologic high myopia has been mapped to 18p11.31. We now report significant linkage of high myopia to at second locus at the 12q21-23 region in a large German/Italian family. The family had no clinical evidence of connective-tissue abnormalities or glaucoma. The average age at diagnosis of myopia was 5.9 years. The average spherical-component refractive error for the affected individuals was -9.47 diopters. Markers flanking or intragenic to the genes for the 18p locus, Stickler syndromes type I and II (12q13.1-q13.3 and 6p21.3), Marfan syndrome (15q21.1), and juvenile glaucoma (chromosome 1q21-q31) showed no linkage to the myopia in this family The maximum LOD score with two-point linkage analysis in this pedigree was 3.85 at a recombination fraction of .0010, for markers D12S1706 and D12S327. Recombination events identified markers D12S1684 and D12S1605 as flanking markers that define a 30.1-cM interval on chromosome 12q21-23, for the second myopia gene. These results confirm genetic heterogeneity of myopia. The identification of this gene may provide insight into the pathophysiology of myopia and eye development. C1 Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Univ Minnesota, Inst Human Genet, Minneapolis, MN 55455 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD USA. RP Young, TL (reprint author), Univ Minnesota, Dept Ophthalmol, Box 493,420 Delaware St, Minneapolis, MN 55455 USA. NR 23 TC 170 Z9 190 U1 4 U2 13 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 1998 VL 63 IS 5 BP 1419 EP 1424 DI 10.1086/302111 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 138QZ UT WOS:000076985200018 PM 9792869 ER PT J AU Monks, SA Kaplan, NL Weir, BS AF Monks, SA Kaplan, NL Weir, BS TI A comparative study of sibship tests of linkage and/or association SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DISEQUILIBRIUM; TDT AB Population-based tests of association have used data from either case-control studies or studies based on trios (affected child and parents). Case-control studies are more prone to false-positive results caused by inappropriate controls, which can occur if, for example, there is population admixture or stratification. An advantage of family-based tests is that cases and controls are well matched, but parental data may not always be available, especially for late-onset diseases. Three recent family-based tests of association and linkage utilize unaffected siblings as surrogates for untyped parents. Im this paper, we propose an extension of one of these tests. We describe and compare the four tests in the context of a complex disease for both biallelic and multiallelic markers, as well as for sibships of different sizes. We also examine the consequences of having some parental data in the sample. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Stat, Program Stat Genet, Raleigh, NC 27695 USA. RP Monks, SA (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. FU NIGMS NIH HHS [GM45344] NR 9 TC 28 Z9 33 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 1998 VL 63 IS 5 BP 1507 EP 1516 DI 10.1086/302104 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 138QZ UT WOS:000076985200027 PM 9792878 ER PT J AU Warman, ML Tiller, GE Griffith, AJ AF Warman, ML Tiller, GE Griffith, AJ TI Marshall syndrome and a defect at the COL11A1 locus - Reply SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID FAMILY C1 Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Warman, ML (reprint author), Case Western Reserve Univ, Sch Med, Dept Genet, Room BRB-719,2109 Adelbert Rd, Cleveland, OH 44106 USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 1998 VL 63 IS 5 BP 1559 EP 1561 DI 10.1086/302115 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 138QZ UT WOS:000076985200035 ER PT J AU Tsai, TF Raas-Rothschild, A Ben-Neriah, Z Beaudet, AL AF Tsai, TF Raas-Rothschild, A Ben-Neriah, Z Beaudet, AL TI Prenatal diagnosis and carrier detection for a point mutation in UBE3A causing Angelman syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID GENE UBE3A; SNRPN C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Beaudet, AL (reprint author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza,Room T619, Houston, TX 77030 USA. EM abeaudet@bcm.tmc.edu NR 11 TC 10 Z9 10 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 1998 VL 63 IS 5 BP 1561 EP 1563 DI 10.1086/302120 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 138QZ UT WOS:000076985200036 PM 9792887 ER PT J AU Bagrov, AY Droy-Lefaix, MT Dmitrieva, RI AF Bagrov, AY Droy-Lefaix, MT Dmitrieva, RI TI Vasorelaxant effects of cicletanine and its (+)- and (-)-enantiomers in isolated human pulmonary arteries SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE cicletanine; vasorelaxation; endothelin-1; sodium nitroprusside; atrial natriuretic peptide ID PHOSPHODIESTERASES; INHIBITION AB The purpose of the study was to investigate, in isolated human pulmonary artery, the ability of cicletanine and its (-) and (+)-enantiomers to attenuate the endothelin-1 (Et-1) induced vasoconstriction, and to potentiate vasorelaxation (relative to plateau of the effect of Et-1) by sodium nitroprusside (SNP) and human atrial natriuretic peptide (ANP). In pulmonary artery rings, Et-1 induced a concentration-dependent vasoconstriction with median effective concentration (EC50 = 26 +/- 2.8 nmol/L, Pretreatment of the vessels with 100 mu mol/L (+/-)-cicletanine reduced the effect of Et-1 (EC50 = 36 +/- 3.5 nmol/L; P <.01), (-)-enantiomer displayed greater capacity to antagonize the vasoconstrictor action of Et-1 (EC50 = 47 +/- 4.2 nmol/L) v (+)-enantiomer (EC50 - 29.9 +/- 6.5 nmol/L; P <.01). In arterial rings, precontracted with 10 nmol/L Et-1, ANP caused vasorelaxation (EC50 = 9.7 +/- 1.9 nmol/L). The relaxant effect of ANP was potentiated by 100 mu mol/L of (-)-(EC50 = 4.2 +/- 0.6 nmol/L; P <.01), but not (+)-cicletanine (EC50 = 7.6 +/- 0.7 nmol/L). Sodium nitroprusside relaxed pulmonary artery rings precontracted with 10 nmol/L. Et-1 (EC50 = 41 +/- 11 nmol/L). The effect of SNP was potentiated by 10 mu mol/L (rt)-cicletanine (EC,, = 9.0 +/- 0.7 nmol/L; P <.05), The potentiating effect of 10 mu mol/L (+)-cicletanine was weaker (EC50 = 7.9 +/- 1.8 nmol/L) than that of (-)-enantiomer (EC50 = 3.3 +/- 0.54 nmol/L; P <.05), The relaxant effect of SNP was not further potentiated by 100 mu mol/L (+/-)-cicletanine. The present results demonstrate that, cicletanine antagonizes Et-1 induced vasoconstriction in an isolated human pulmonary artery and potentiates vasorelaxation by two guanylate cyclase activators, ANP and SNF. (-)-Cicletanine displays greater vasorelaxant activity v (+)-enantiomer. (C) 1998 American Journal of Hypertension, Ltd. C1 IM Sechenov Evolutionary Physiol & Biochem Inst, Pharmacol Lab, St Petersburg 194223, Russia. IPSEN, Paris, France. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Dmitrieva, Renata/0000-0002-3073-7914 NR 13 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 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD NOV PY 1998 VL 11 IS 11 BP 1386 EP 1389 DI 10.1016/S0895-7061(98)00151-4 PN 1 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 139TW UT WOS:000077046600018 PM 9832185 ER PT J AU Krstev, S Baris, D Stewart, PA Hayes, RB Blair, A Dosemeci, M AF Krstev, S Baris, D Stewart, PA Hayes, RB Blair, A Dosemeci, M TI Risk for prostate cancer by occupation and industry: A 24-state death certificate study SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE prostate cancer; death certificate; case control study; occupation; industry ID ATOMIC-ENERGY-AUTHORITY; PHYSICAL-ACTIVITY; UNITED-STATES; CASE-REFERENT; NEW-ZEALAND; MORTALITY; WORKERS; FARMERS; EMPLOYEES; MONTREAL AB Current knowledge of the etiology of prostate cancer is limited. Numerous studies have suggested that certain occupations and industries may be associated with the occurrence of prostate cancer: Information on occupation and industry on death certificates from 24 states gathered from 1984 to 1993 was used in case control study on prostate cancer. A total of 60,878 men with prostate cancer as underlying cause of death was selected and matched with controls who died of all other causes except cancel: Similar to the findings of our parallel large case control study of prostate cancer; we observed excess risks in some white-collar occupations, such as administrators, managers, teachers, engineers, and sales occupations. However some blue-collar occupations, such as power plant operators and stationary engineers, brickmasons, machinery maintenance workers, airplane pilots, longshoreman, railroad industry workers, and other occupations with potential exposure to PAH also showed risk of excess prostate cancer: Risk was significantly deceased for blue-collar occupations, including farm workers, commercial fishermen, mechanics and repairers, structural metal workers, mining, printing, winding, dry cleaning, textile machine operators, cooks, bakers, and bartenders. Although we observed excess risks of prostate cancer among some low socioeconomic status (SES) occupations, the overall results suggest that the effects of higher SES cannot be oiled out in associations between occupational factors and the risk of prostate cancer: (C) 1998 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. Inst Occupat & Radiol Hlth Dr Dragomir Karajovic, Belgrade, Yugoslavia. RP Dosemeci, M (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat Epidemiol Branch, Bldg EPN,Room 418, Bethesda, MD 20892 USA. EM dosemecm@epndce.nci.nih.gov NR 65 TC 35 Z9 37 U1 2 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 1998 VL 34 IS 5 BP 413 EP 420 DI 10.1002/(SICI)1097-0274(199811)34:5<413::AID-AJIM1>3.0.CO;2-R PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 125GE UT WOS:000076228400001 PM 9787844 ER PT J AU Krstev, S Baris, D Stewart, P Dosemeci, M Swanson, GM Greenberg, RS Schoenberg, JB Schwartz, AG Liff, JM Hayes, RB AF Krstev, S Baris, D Stewart, P Dosemeci, M Swanson, GM Greenberg, RS Schoenberg, JB Schwartz, AG Liff, JM Hayes, RB TI Occupational risk factors and prostate cancer in US blacks and whites SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE case control; prostate cancer; occupation; industry ID UNITED-STATES; MORTALITY; WORKERS; COHORT; FARMERS; FIREFIGHTERS; HAIRDRESSERS; MORBIDITY; HISTORIES; EXPOSURES AB Although prostate cancer is a major disease, causal factors are only partially understood. We examined occupational risk factors for this disease in a large case control study among U.S. blacks and whites. The study included 981 new pathologically confirmed prostate cancer cases (479 blacks and 502 whites) diagnosed between 1986 and 1989, and 1,315 population controls (594 blacks and 721 whites) who resided in Atlanta, Detroit, and 10 counties in New Jersey, covered by population-based cancer registries. Information on occupation, including a lifetime work history, was collected by in-person interview. No clear patterns of risk were found for U.S. whites versus blacks, nor for white-collar versus blue-collar jobs. Farming was related to prostate cancer (OR = 2.17; 95% CI = 1.18-3.98). Risk was restricted, however to short-term workers and workers in crop production. Risk was not limited to those farming after 1950, when widespread use of pesticides started Risks increased with increasing years of employment in firefighting (chi(trend)(2), p = 0.02) and power plant operations (chi(trend)(2), P = 0.03), and were elevated among long-term railroad line-haulers (OR = 5.85; 95% CI = 1.25-27.4); jobs with potential polycyclic aromatic hydrocarbon (PAH) exposures. Risk was elevated among athletes (OR = 5.38; 95% CI = 1.48-19.6). However most of the cases were athletes before 1960, so the potential use of anabolic steroids was excluded Although some clues about potential occupational associations were found the overall results show that occupation is not a major determinant of prostate cancer risk. (C) 1998 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. Inst Occupat & Radiol Hlth, Clin Ctr Serbia, Belgrade, Yugoslavia. Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. Med Univ S Carolina, Charleston, SC 29425 USA. New Jersey State Dept Hlth, Trenton, NJ 08625 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Emory Univ, Sch Publ Hlth, Atlanta, GA USA. RP Hayes, RB (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat Epidemiol Branch, Execut Plaza N,Room 418, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CN-05225, N01-CP-51089, N01-CP-5109] NR 50 TC 34 Z9 35 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 1998 VL 34 IS 5 BP 421 EP 430 DI 10.1002/(SICI)1097-0274(199811)34:5<421::AID-AJIM2>3.0.CO;2-T PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 125GE UT WOS:000076228400002 PM 9787845 ER PT J AU Hoppin, JA Tolbert, PE Flagg, EW Blair, A Zahm, SH AF Hoppin, JA Tolbert, PE Flagg, EW Blair, A Zahm, SH TI Use of a life events calendar approach to elicit occupational history from farmers SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE epidemiology; exposure assessment; farming; questionnaires; survey methods ID CANCER; RISK AB Background Precise and valid exposure assessment is generally the primary challenge in retrospective occupational epidemiology studies, particularly when the only available method for exposure characterization is a personal interview. Agricultural workers may represent a particular challenge; for example, whereas many farmers have worked from childhood at the same location, raising the same crops and animals, they may have used different equipment, chemicals, and protective gear over time. One method to assist in recall is the "life events calendar" a cognitive tool based on the subject's own life history to help anchor occupational activities in time. Methods Unstructured interviews of farmers, focus groups, and pilot interviews among rural men, primarily African-Americans, were conducted to create a questionnaire for obtaining farm history information within the context of personal life events. Results Farmers used both personal events and national events (as well as events relating directly to farming) to recall their activities, These subjects had extensive history of farming (10-75 years) and chemical use (median lifetime chemicals = 13). Conclusion The life events calendar provided a useful tool to facilitate the recall of a lifetime of agricultural activity. Life events calendars are useful additions to the tools available for retrospective occupational exposure assessment. (C) 1998 Wiley-Liss, Inc. C1 Emory Univ, Rollins Sch Publ Hlth, Dept Environm & Occupat Hlth, Atlanta, GA 30322 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. RP Hoppin, JA (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Environm & Occupat Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA. RI Tolbert, Paige/A-5676-2015; Zahm, Shelia/B-5025-2015 FU NCI NIH HHS [1R21CA69764-01] NR 16 TC 19 Z9 19 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 1998 VL 34 IS 5 BP 470 EP 476 DI 10.1002/(SICI)1097-0274(199811)34:5<470::AID-AJIM7>3.0.CO;2-U PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 125GE UT WOS:000076228400008 PM 9787851 ER PT J AU Petralia, SA Chow, WH McLaughlin, J Jin, F Gao, YT Dosemeci, M AF Petralia, SA Chow, WH McLaughlin, J Jin, F Gao, YT Dosemeci, M TI Occupational risk factors for breast cancer among women in Shanghai SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE breast cancer; occupational; benzene; solvents; occupational exposures; Shanghai; China ID FEMALE ELECTRICAL WORKERS; DRY-CLEANING WORKERS; UNITED-STATES; RUBBER WORKERS; MORTALITY; COHORT; HYPOTHESIS; BENZENE; EXPOSURE; NURSES AB Although female breast cancer rates are lower in China than in Western countries, rates have been rising rapidly in China. This increase may be due to changes in established breast cancer risk factors, but it is possible that exposure to occupational and environmental carcinogens in Shanghai also have contributed to the rise in incidence. We used data collected by the Shanghai Cancer Registry and the Chinese Third National Census to study the risk of breast cancer by occupation and by occupational exposures. Standardized incidence ratios (SIRs) were used to compare observed cases to expected numbers of cases, based on the incidence rates for Shanghai and the number of women in each occupation according to the 1982 census. Statistically elevated SIRs for breast cancer were seen for a number of professional occupational categories, with the greatest risk seen among scientific research workers (SIR = 3.3). Administrative clerks, political and security personnel, and makers of rubber and plastics products also had significant excesses. Significant deficits of risk were seen for the categories of production and related workers, construction workers, and transportation equipment operators. For specific occupations, the highest SIRs were observed among doctors of Chinese-Western medicine (SIR = 14.7, 95% CI = 5.9-30.3) and doctors of Chinese medicine (SIR = 7.2, 95% CI = 4.4-11.4). We also found excesses among teachers at each level of education, librarians, clerical workers, electrical and electronic engineers, nurses, lab technicians, accountants and bookkeepers, rubber manufacturing products makers, weavers, and knitters. SIRs were significantly elevated for high probability of exposure to organic solvents (SIR = 1.4). For benzene exposure, we found significant excesses for overall exposure (SIR = 1.1) and for medium level of exposure (SIR = 1.3). There was no evidence of an association between risk and electromagnetic fields (EMF) exposure. Based on a small number of exposed, SIRs were elevated for both medium probability and high level of exposure to pesticides. The elevations in occupations reported here support some previous reports. Our finding of an increased risk associated with benzene also has been reported previously; the finding for organic solvents is new. However the literature on the risk of breast cancer related to occupational exposures is limited and there is no consistent body of literature for any of the exposures studied here. Further many comparisons were made and the problem of multiple hypothesis testing cannot be ignored in a survey such as ours. (C) 1998 Wiley-Liss, Inc.(dagger) C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Int Epidemiol Inst, Rockville, MD USA. Shanghai Canc Inst, Shanghai, Peoples R China. RP Petralia, SA (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, 6130 Execut Blvd,EPN 415, Bethesda, MD 20892 USA. EM sp126i@nih.gov NR 38 TC 47 Z9 48 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 1998 VL 34 IS 5 BP 477 EP 483 DI 10.1002/(SICI)1097-0274(199811)34:5<477::AID-AJIM8>3.0.CO;2-N PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 125GE UT WOS:000076228400009 PM 9787852 ER EF