FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Yan, HG Blaszczyk, J Xiao, B Shi, GB Ji, XH AF Yan, HG Blaszczyk, J Xiao, B Shi, GB Ji, XH TI Structure and dynamics of 6-Hydroxymethyl-6,8-dihydropterin pyrophosphokinase SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING CT Workshop on Protein Flexibility and Folding CY AUG 13-17, 2000 CL TRAVERSE CITY, MICHIGAN SP Michigan State Univ, Pharmacia AB Folates are essential or life. Unlike mammals, most microorganisms must synthesize folates de novo. 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in folate pathway, and therefore, is an ideal target for developing novel antimicrobial agents. Because of its small size and high thermal stability. E, coli HPPK is also an excellent model enzyme for studying the mechanisms of enzymatic pyrophosphoryl transfer. We have determined the crystal structures at HPPK in the unligated form and in complex with HP, two Mg2+ ions, and AMPCPP (nn ATP analog that inhibits the enzymatic reaction), Comparison of the two crystal structures reveals dramatic conformational changes of three flexible loops and many side chains and possible roles of the active sire residues. (C) 2001 hy Elsevier Science Inc. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 SN 1093-3263 PY 2001 VL 19 IS 1 BP 70 EP 77 DI 10.1016/S1093-3263(00)00135-2 UT WOS:000168679000006 PM 11381532 ER PT J AU Boger, ET Sellers, JR Friedman, TB AF Boger, ET Sellers, JR Friedman, TB TI Human myosin XVBP is a transcribed pseudogene SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY AB A novel human myosin gene located at 17q25 was identified through evaluation of genomic DNA sequence and designated myosin XVBP since it resembled human myosin XVA. In humans, myosin XVBP along with an adjacent gene, Lethal Giant Larvae 2 (LLGL2) appears to have arisen from a genomic duplication of a chromosomal interval that included LLGL and an ancestral myosin XV. Inspection of human myosin XVBP predicted amino acid sequence from genomic DNA revealed that 36 of the 131 conserved amino acid residues of the motor domain are substituted or deleted, including sequence changes within the regions involved in the binding of ATP and actin. Twelve myosin XVBP overlapping cDNAs from kidney and stomach mRNA samples were cloned and sequenced. Analyses of these myosin XVBP cDNAs revealed numerous additional disablements including translational reading frame shifts resulting in stop codons. From these data we conclude that myosin XVBP is a transcribed, unprocessed pseudogene. SN 0142-4319 PY 2001 VL 22 IS 5 BP 477 EP 483 DI 10.1023/A:1014507705858 UT WOS:000174272700009 PM 11964073 ER PT J AU Kuroda, M Mimaki, Y Yokosuka, A Sashida, Y Beutler, JA AF Kuroda, M Mimaki, Y Yokosuka, A Sashida, Y Beutler, JA TI Cytotoxic cholestane glycosides from the bulbs of Ornithogalum saundersiae SO JOURNAL OF NATURAL PRODUCTS AB Further phytochemical analysis of the bulbs of Ornithogalum saundersiae has yielded two new cytotoxic cholestane triglycosides (1 and 2). The structures of these compounds were determined by spectroscopic analysis, including 2D NMR spectroscopic data, and the results of hydrolytic cleavage. Compounds 1 and 2 and several analogues were evaluated for their cytotoxicity against HL-60 cells. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 SN 0163-3864 PD JAN PY 2001 VL 64 IS 1 BP 88 EP 91 DI 10.1021/np0003084 UT WOS:000166696400020 PM 11170674 ER PT J AU Rashid, MA Gustafson, KR Cartner, AK Shigematsu, N Pannell, LK Boyd, MR AF Rashid, MA Gustafson, KR Cartner, AK Shigematsu, N Pannell, LK Boyd, MR TI Microspinosamide, a new HIV-inhibitory cyclic depsipeptide from the marine sponge Sidonops microspinosa SO JOURNAL OF NATURAL PRODUCTS AB Microspinosamide (1), a new cyclic depsipeptide incorporating 13 amino acid residues, was isolated from extracts of an Indonesian collection of the marine sponge Sidonops microspinosa. Its structure was elucidated by extensive NMR and mass spectral analyses, and by chemical degradation and derivatization studies. The tridecapeptide 1 incorporates numerous uncommon amino acids, and it is the first naturally occurring peptide to contain a beta -hydroxy-p-bromophenylalanine residue. Microspinosamide (1) inhibited the cytopathic effect of HIV-1 infection in an XTT-based in vitro assay with an EC50 value of approximately 0.2 mug/mL. RI Shigematsu, Naoyuki/B-9374-2014 SN 0163-3864 PD JAN PY 2001 VL 64 IS 1 BP 117 EP 121 DI 10.1021/np0002379 UT WOS:000166696400030 PM 11170684 ER PT J AU Drandarevski, N Marburger, A Walther, D Reum, T Uhl, G Morgenstern, R AF Drandarevski, N Marburger, A Walther, D Reum, T Uhl, G Morgenstern, R TI Dopaminergic mRNA expression in the intact substantia nigra of unilaterally 6-OHDA-lesioned and grafted rats: an in situ hybridization study SO JOURNAL OF NEURAL TRANSMISSION AB The present study was performed to investigate the influence of intrastriatal fetal mesencephalic grafts on dopaminergic mRNA expression in the non-lesioned substantia nigra pars compacta of unilaterally 6-hydroxydopamine-lesioned rats. The expression of dopamine transporter mRNA, synaptic vesicular monoamine transporter mRNA and tyrosine hydroxylase mRNA was assessed in adjacent cryostat sections using in situ hybridization. Rotational behavior induced by apomorphine and amphetamine as well as hybridization of striatal sections cut at the grafting coordinates were used to prove the functional recovery and the presence of grafted cells, respectively. After grafting, the number of rotations was decreased and hybridization signals overlying cells in the grafted striatum were detected. Mean grain densities overlying labeled neurons in the substantia nigra pars compacta of grafted rats were compared to those of shamgrafted rats and revealed differential expression of dopamine transporter mRNA, whereas synaptic vesicular monoamine transporter mRNA and tyrosine hydroxylase mRNA expression showed no difference. The results will be discussed in relation to previous in vitro and in vivo studies suggesting a reduction of functional dopamine transporter molecules in the contralateral striatum. SN 0300-9564 PY 2001 VL 108 IS 2 BP 141 EP 151 DI 10.1007/s007020170084 UT WOS:000167014500002 PM 11314769 ER PT J AU Nelson, PG McCune, SK Ades, AM Nelson, KB AF Nelson, PG McCune, SK Ades, AM Nelson, KB TI Glial-neurotrophic mechanisms in Down syndrome SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT AB Complex interactions and interconnectivity between neurons are hallmarks of normal neuronal differentiation and development. Neurons also interact with other cell types, notably glia, and rely on substances released by glia for their normal function. A deficit in glial response may disturb this critical neuronal-glial-neuronal interaction in Down syndrome (DS), leading to loss of neurons and other defects of development. and contribute to cognitive limitation and early onset of Alzheimer disease. The hypothesis this paper will discuss is that normal neural development involves an activity-dependent release of substances from neurons, and that these substances act upon glia cells which in turn release substances that influence neurons to promote their survival and development. This glial influence affects cortical neurons and also the subcortical cholinergic neurons that project to the cerebral and hippocampal cortices to maintain cortical neuronal excitability and activity. The neuronal activity stimulates glial secretion of sustaining substances, in a reciprocally interactive cycle. Some aspect of this "virtuous cycle" is deficient in Down syndrome. The result is a small but slowly increasing deficit in activity-dependent support by glia cells which produces a gradually increasing abnormality of cortical and subcortical, perhaps especially cholinergic, function. SN 0303-6995 PY 2001 IS 61 BP 85 EP 94 UT WOS:000171970000008 PM 11771763 ER PT J AU Mariani, L Beaudry, C McDonough, WS Hoelzinger, DB Demuth, T Ross, KR Berens, T Coons, SW Watts, G Trent, JM Wei, JS Giese, A Berens, ME AF Mariani, L Beaudry, C McDonough, WS Hoelzinger, DB Demuth, T Ross, KR Berens, T Coons, SW Watts, G Trent, JM Wei, JS Giese, A Berens, ME TI Glioma cell motility is associated with reduced transcription of proapoptotic and proliferation genes: a cDNA microarray analysis SO JOURNAL OF NEURO-ONCOLOGY AB Microarray analysis of complementary DNA (cDNA) allows large-scale, comparative, gene expression profiling of two different cell populations. This approach has the potential for elucidating the primary transcription events and genetic cascades responsible for increased glioma cell motility in vitro and invasion in vivo. These genetic determinants could become therapeutic targets. We compared cDNA populations of a glioma cell line (G112) exposed or not to a motility-inducing substrate of cell-derived extracellular matrix (ECM) proteins using two sets of cDNA microarrays of 5700 and 7000 gene sequences. The data were analyzed considering the level and consistency of differential expression (outliers) and whether genes involved in pathways of motility, apoptosis, and proliferation were differentially expressed when the motility behavior was engaged. Validation of differential expression of selected genes was performed on additional cell lines and human glioblastoma tissue using quantitative RT-PCR. Some genes involved in cell motility, like tenascin C, neuropilin 2, GAP43, PARG1 (an inhibitor of Rho), PLC gamma, and CD44, were over expressed; other genes, like adducin 3 gamma and integrins, were down regulated in migrating cells. Many key cell cycle components, like cyclin A and B, and proliferation markers, like PCNA, were strongly down regulated on ECM. Interestingly, genes involved in apoptotic cascades, like Bcl-2 and effector caspases, were differentially expressed, suggesting the global down regulation of proapoptotic components in cells exposed to cell-derived ECM. Overall, our findings indicate a reduced proliferative and apoptotic activity of migrating cells. cDNA microarray analysis has the potential for uncovering genes linking the phenotypic aspects of motility, proliferation, and apoptosis. OI Hoelzinger, Dominique/0000-0003-0861-9310 SN 0167-594X PY 2001 VL 53 IS 2 BP 161 EP 176 DI 10.1023/A:1012253317934 UT WOS:000171400700008 PM 11716068 ER PT J AU Yan, J Studer, L McKay, RDG AF Yan, J Studer, L McKay, RDG TI Ascorbic acid increases the yield of dopaminergic neurons derived from basic fibroblast growth factor expanded mesencephalic precursors SO JOURNAL OF NEUROCHEMISTRY AB CNS precursors derived from E12 rat mesencephalon proliferate in the presence of basic fibroblast growth factor and differentiate in vitro into functional dopaminergic neurons, which upon transplantation alleviate behavioral symptoms in a rat model of Parkinson's disease. Here we show that the efficiency of dopaminergic differentiation decreases in the mesencephalic precursors that were proliferated or passaged for extended periods in vitro. Ascorbic acid treatment restored dopaminergic differentiation in these precursors and led to a greater than 10-fold increase in dopamine neuron yield compared with untreated cultures. The effect of ascorbic acid was stereospecific and could not be mimicked by any other antioxidants. The expression of sodium-dependent vitamin C transporter, a recently identified stereospecific ascorbic acid transporter, was maintained in mesencephalic precursors for extended in vitro periods. Pre-treatment of in vitro expanded mesencephalic precursors with ascorbic acid might facilitate the large-scale generation of dopaminergic neurons for clinical transplantation. SN 0022-3042 PD JAN PY 2001 VL 76 IS 1 BP 307 EP 311 DI 10.1046/j.1471-4159.2001.00073.x UT WOS:000166154600033 PM 11146004 ER PT J AU Duan, WZ Guo, ZH Mattson, MP AF Duan, WZ Guo, ZH Mattson, MP TI Brain-derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice SO JOURNAL OF NEUROCHEMISTRY AB Dietary restriction (DR; reduced calorie intake) increases the lifespan of rodents and increases their resistance to cancer, diabetes and other age-related diseases. DR also exerts beneficial effects on the brain including enhanced learning and memory and increased resistance of neurons to excitotoxic, oxidative and metabolic insults. The mechanisms underlying the effects of DR on neuronal plasticity and survival are unknown, in the present study we show that levels of brain-derived neurotrophic factor (BDNF) are significantly increased in the hippocampus, cerebral cortex and striatum of mice maintained on an alternate day feeding DR regimen compared to animals fed ad libitum. Damage to hippocampal neurons induced by the excitotoxin kainic acid was significantly reduced in mice maintained on DR, and this neuroprotective effect was attenuated by intraventricular administration of a BDNF-blocking antibody. Our findings show that simply reducing food intake results in increased levels of BDNF in brain cells, and suggest that the resulting activation of BDNF signaling pathways plays a key role in the neuroprotective effect of DR. These results bolster accumulating evidence that DR may be an effective approach for increasing the resistance of the brain to damage and enhancing brain neuronal plasticity. RI Mattson, Mark/F-6038-2012 SN 0022-3042 PD JAN PY 2001 VL 76 IS 2 BP 619 EP 626 DI 10.1046/j.1471-4159.2001.00071.x UT WOS:000166458200031 PM 11208925 ER PT J AU Wray, S AF Wray, S TI Development of luteinizing hormone releasing hormone neurones SO JOURNAL OF NEUROENDOCRINOLOGY AB This review concentrates on some of the recent discoveries and future questions relevant to the development of the neuroendocrine luteinizing hormone releasing hormone (LHRH) cells. Neuroendocrine LHRH cells originate outside the central nervous system, in the nasal placode, and thereafter migrate into the forebrain during prenatal development. It is this population of LHRH cells that is responsible for reproductive function, becoming integral members of the hypothalamo-pituitary-gonadal axis postnatally. Disruption of the development of this system results in reproductive dysfunction. Increasing our understanding of LHRH neuroendocrine cells establishes conditions where we can look with greater precision at the mechanisms controlling reproductive development, both activation and failure. In addition, the ability to manipulate the molecular and cellular biology of the LHRH system opens the route to understanding critical neurobiological issues such as phenotypic commitment, axonal path finding and mechanisms involved in neuronal migration. Each of the topics is discussed in turn and potential mechanisms controlling the development of the neuroendocrine LHRH system are indicated. OI wray, susan/0000-0001-7670-3915 SN 0953-8194 PD JAN PY 2001 VL 13 IS 1 BP 3 EP 11 DI 10.1046/j.1365-2826.2001.00609.x UT WOS:000166322900002 PM 11123510 ER PT J AU Zhang, B Glasgow, E Murase, T Verbalis, JG Gainer, H AF Zhang, B Glasgow, E Murase, T Verbalis, JG Gainer, H TI Chronic hypoosmolality induces a selective decrease in magnocellular neurone soma and nuclear size in the rat hypothalamic supraoptic nucleus SO JOURNAL OF NEUROENDOCRINOLOGY AB The magnocellular neurones of the hypothalamo-neurohypophysial system (HNS) play a vital role in the maintenance of body homeostasis by regulating oxytocin (OT) and vasopressin (VP) secretion from the posterior pituitary. During hyperosmolality, OT and VP mRNA levels are known to increase by approximately two-fold, whereas during chronic hypoosmolality, OT and VP mRNA levels decrease to approximately 10-20% of basal levels. In these studies, we evaluated changes in cell size associated with these physiological conditions. Cell and nuclear sizes of neurones in the supraoptic nucleus (SON), the nucleus of the lateral olfactory tract (LOT) and the medial habenular nucleus (MHB) were measured from neurones identified by in situ hybridization histochemistry for beta (III)-tubulin mRNA, and measurements were made from OT and AVP magnocellular neurones in the SON after phenotypic identification by immunohistochemistry. Under hypoosmolar conditions, the cell and nuclear sizes of OT and VP magnocellular neurones decreased to approximately 60% of basal values, whereas cell and nuclear sizes of OT and VP neurones in hyperosmolar rats increased to approximately 170% of basal values. In contrast, neither hyperosmolality, nor hypoosmolality significantly affected cell and nuclear sizes in the LOT and MHB. These results confirm previous studies that showed that magnocellular neurones increase cell size in response to hyperosmolar conditions and, for the first time, demonstrate a marked decrease in cell size in the SON in response to chronic hypoosmolar conditions. These dramatic changes in cell and nuclear size directly parallel changes in OT and VP gene expression in the magnocellular neurones of the SON and, consequently, are consistent with the pronounced bidirectional changes in gene expression and cellular activity found during these osmotic perturbations. Our results therefore support the concept of global alterations in the synthetic activity of magnocellular OT and AVP neurones in response to extracellular osmolality. OI Glasgow, Eric/0000-0001-7729-3954 SN 0953-8194 PD JAN PY 2001 VL 13 IS 1 BP 29 EP 36 DI 10.1046/j.1365-2826.2001.00593.x UT WOS:000166322900005 PM 11123513 ER PT J AU Hoffman, AF Lupica, CR AF Hoffman, AF Lupica, CR TI Direct actions of cannabinoids on synaptic transmission in the nucleus accumbens: A comparison with opioids SO JOURNAL OF NEUROPHYSIOLOGY AB The nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. The medium spiny GABAergic projection neurons (MSNs) in the NAc receive innervation from intrinsic GABAergic interneurons and glutamatergic innervation from extrinsic sources. Both GABA and glutamate release onto MSNs are inhibited by drugs of abuse, suggesting that this action may contribute to their rewarding properties. To investigate the actions of cannabinoids in the NAc, we performed whole cell recordings from MSNs located in the shell region in rat brain slices. The cannabinoid agonist WIN 55,212-2 (1 muM) had no effect on the resting membrane potential, input resistance, or whole cell conductance, suggesting no direct postsynaptic effects. Evoked glutamatergic excitatory postsynaptic currents (EPSCs) were inhibited to a much greater extent by [Tyr-D-Ala(2), N-CH3-Phe(4), Gly-ol-enkephalin] (DAMGO, similar to 35%) than by WIN 55,212-2 (<20%), and an analysis of miniature EPSCs suggested that the effects of DAMGO were presynaptic, whereas those of WIN 55,212-2 were postsynaptic. However, electrically evoked GABAergic inhibitory postsynaptic currents (evIPSCs), were reduced by WIN 55,212-2 in every neuron tested (EC50 = 123 nM; 60% maximal inhibition), and the inhibition of IPSCs by WIN 55,212-2 was completely antagonized by the CB1 receptor antagonist SR141716A (1 M). In contrast evIPSCs were inhibited in similar to 50% of MSNs by the mu/delta opioid agonist D-Ala(2)-methionine(2)-enkephalin-amide and were completely unaffected by a selective mu -opioid receptor agonist (DAMGO). WIN 55,212-2 also increased paired-pulse facilitation of the evIPSCs and did not alter the amplitudes of tetrodotoxin-resistant miniature IPSCs, suggesting a presynaptic action. Taken together, these data suggest that cannabinoids and opioids differentially modulate inhibitory and excitatory synaptic transmission in the NAc and that the abuse liability of marijuana may be related to the direct actions of cannabinoids in this structure. RI Hoffman, Alexander/H-3035-2012 OI Hoffman, Alexander/0000-0002-2676-0628 SN 0022-3077 PD JAN PY 2001 VL 85 IS 1 BP 72 EP 83 UT WOS:000166319300008 PM 11152707 ER PT J AU Sun, MK Zhao, WQ Nelson, TJ Alkon, DL AF Sun, MK Zhao, WQ Nelson, TJ Alkon, DL TI Theta rhythm of hippocampal CA1 neuron activity: Gating by GABAergic synaptic depolarization SO JOURNAL OF NEUROPHYSIOLOGY AB Information processing and memory consolidation during exploratory behavior require synchronized activity known as hippocampal theta (theta) rhythm. While it is well established that the theta activity depends on cholinergic inputs from the medial septum/vertical limb of the diagonal band nucleus (MS/DBv) and theta discharges of GABAergic interneurons, and can be induced with cholinergic receptor agonists, it is not clear how the increased excitation of pyramidal cells could occur with increased discharges of GABAergic interneurons during theta waves. Here, we show that the characteristic theta activity in adult rat hippocampal CA1 pyramidal cells is associated with GABAergic postsynaptic depolarization and a shift of the reversal potential from Cl- toward HCO3- (whose ionic gradient is regulated by carbonic anhydrase). The theta activity was abolished by GABA(A) receptor antagonists and carbonic anhydrase inhibitors, but largely unaffected by blocking glutamate receptors. Carbonic anhydrase inhibition also impaired spatial learning in a watermaze without affecting other sensory/locomotor behaviors. Thus HCO3--mediated signaling, as regulated by carbonic anhydrase, through reversed polarity of GABAergic postsynaptic responses is implicated in both theta and memory consolidation in rat spatial maze learning. We suggest that this mechanism may be important for the phase forward shift of the place cell discharges for each theta cycle during the animal's traversal of the place field for that cell. SN 0022-3077 PD JAN PY 2001 VL 85 IS 1 BP 269 EP 279 UT WOS:000166319300027 PM 11152726 ER PT J AU Poremba, A Gabriel, M AF Poremba, A Gabriel, M TI Amygdalar efferents initiate auditory thalamic discriminative training-induced neuronal activity SO JOURNAL OF NEUROSCIENCE AB It is well known that neurons of the medial geniculate (MG) nucleus of the thalamus send axonal projections to the amygdala. It has been proposed that these projections supply information that supports amygdalar associative processes underlying acquisition of acoustically cued conditioning and learning. Here we demonstrate the reverse direction of influence. Temporary inactivation of the amygdala using the GABA(A) receptor agonist muscimol just before the onset of discriminative avoidance conditioning permanently blocked the development of training-induced discriminative neuronal activity in the MG nucleus of rabbits. No discriminative activity developed when the amygdala was inactivated or during later training to criterion without muscimol. Thus, amygdalar processing at the outset of training is necessary for the development of training-induced discriminative activity of neurons in the MG nucleus. SN 0270-6474 PD JAN 1 PY 2001 VL 21 IS 1 BP 270 EP 278 UT WOS:000166278500035 PM 11150344 ER PT J AU Bushara, KO Grafman, J Hallett, M AF Bushara, KO Grafman, J Hallett, M TI Neural correlates of auditory-visual stimulus onset asynchrony detection SO JOURNAL OF NEUROSCIENCE AB Intersensory temporal synchrony is an ubiquitous sensory attribute that has proven to be critical for binding multisensory inputs, sometimes erroneously leading to dramatic perceptual illusions. However, little is known about how the brain detects temporal synchrony between multimodal sensory inputs. We used positron emission tomography to demonstrate that detecting auditory-visual stimulus onset asynchrony activates a large-scale neural network of insular, posterior parietal, prefrontal, and cerebellar areas with the highest and task-specific activity localized to the right insula. Interregional covariance analysis further showed significant task-related functional inter-actions between the insula, the posterior thalamus, and superior colliculus. Based on these results and the available electrophysiological and anatomical connectivity data in animals, we propose that the insula, via its known short-latency connections with the tectal system, mediates temporally defined auditory-visual interaction at an early stage of cortical processing permitting phenomena such as the ventriloquist and the McGurk illusions. OI Grafman, Jordan H./0000-0001-8645-4457 SN 0270-6474 PD JAN 1 PY 2001 VL 21 IS 1 BP 300 EP 304 UT WOS:000166278500038 PM 11150347 ER PT J AU Pettit, DL Shao, Z Yakel, JL AF Pettit, DL Shao, Z Yakel, JL TI beta-Amyloid(1-42) peptide directly modulates nicotinic receptors in the rat hippocampal slice SO JOURNAL OF NEUROSCIENCE AB Alzheimer's disease (AD) is a human neurological disorder characterized by an increasing loss of cognitive function and the presence of extracellular neuritic plaques composed of the beta -amyloid peptide (A beta (1-42)). However, the link between these molecular correlates of AD and the loss of cognitive function has not been established. The pathology associated with AD includes the loss of basal forebrain cholinergic neurons, presynaptic terminals in the neocortex and hippocampus, and a decrease in the total amount of neuronal nicotinic acetylcholine receptors (nAChRs). This leads to the hypothesis that failure in the cholinergic system underlies the dementia seen in AD. Cognitive performance has been linked to nAChR function in the hippocampus, and the interneurons expressing nAChRs coordinate the activity of large numbers of principal cells and therefore have a powerful role in the regulation of hippocampal activity. We have found that A beta (1-42) inhibits whole-cell and single-channel nicotinic currents from rat hippocampal interneurons by directly blocking the postsynaptic nAChR channels at concentrations as low as 100 nM. This inhibition appears specific for peptide sequence and neuronal nAChRs, and the magnitude of A beta (1-42) inhibition is dependent on the nAChR channel subtype expressed. Thus, chronic inhibition of cholinergic signaling by A beta (1-42) could contribute to the cognitive deficits associated with AD. SN 0270-6474 PD JAN 1 PY 2001 VL 21 IS 1 AR RC120 UT WOS:000166278500003 PM 11150356 ER PT J AU Mattson, MP Klapper, W AF Mattson, MP Klapper, W TI Emerging roles for telomerase in neuronal development and apoptosis SO JOURNAL OF NEUROSCIENCE RESEARCH AB Telomerase is an enzyme consisting of a reverse transcriptase called TERT and an RNA component that adds repeats of a DNA sequence (TTAGGG) to the ends of chromosomes, thereby preventing their shortening and cell cycle arrest. Telomerase levels are high in neural progenitor cells and neurons during early development, and decrease in association with cell differentiation. A role for TERT in regulation of developmental death of neurons is suggested by a decrease in TERT expression that coincides with the period of neuronal death and by data showing that TERT promotes survival of developing brain neurons. Suppression of telomerase activity and TERT expression promotes apoptosis, whereas overexpression of TERT prevents apoptosis by suppressing cell death at a premitochondrial step in the death cascade Moreover, neurotrophic factors known to play important roles in brain development can regulate telomerase activity and TERT expression in cultured neural cells. A better understanding of the functions of telomerase and TERT in neuronal differentiation and survival may lead to novel approaches for preventing neuronal death and promoting recovery in various neurodegenerative conditions. Published 2001 Wiley-Liss, Inc. RI Klapper, Wolfram/D-2516-2010; Mattson, Mark/F-6038-2012; Klapper, Wolfram/S-6314-2016 SN 0360-4012 PD JAN 1 PY 2001 VL 63 IS 1 BP 1 EP 9 UT WOS:000166155300001 PM 11169608 ER PT J AU Chen, MY Chew, EY Reynolds, JC Chao, DL Oldfield, EH AF Chen, MY Chew, EY Reynolds, JC Chao, DL Oldfield, EH TI Metastatic brainstem pheochromocytoma in a patient with von Hippel-Lindau disease - Case illustration SO JOURNAL OF NEUROSURGERY SN 0022-3085 PD JAN PY 2001 VL 94 IS 1 BP 138 EP 138 DI 10.3171/jns.2001.94.1.0138 UT WOS:000166043900024 PM 11147885 ER PT J AU Dilsizian, V Bacharach, SL Khin, MM Smith, MF AF Dilsizian, V Bacharach, SL Khin, MM Smith, MF TI Fluorine-18-deoxyglucose SPECT and coincidence imaging for myocardial viability: Clinical and technologic issues SO JOURNAL OF NUCLEAR CARDIOLOGY SN 1071-3581 PD JAN-FEB PY 2001 VL 8 IS 1 BP 75 EP 88 DI 10.1067/mnc.2001.111409 UT WOS:000167374300010 PM 11182712 ER PT J AU Phillips, JM Cohen, MZ Tarzian, AJ AF Phillips, JM Cohen, MZ Tarzian, AJ TI African American women's experiences with breast cancer screening SO JOURNAL OF NURSING SCHOLARSHIP AB Purpose: To describe the experience and meaning of breast cancer screening for African American women. Breast cancer screening offers the greatest hope of reducing breast cancer mortality and improving breast cancer outcomes. Despite the proliferation of initiatives targeting African American women, they continue to be first diagnosed only when they have late-stage disease. Design and Methods: Using hermeneutic phenomenological research methods, 23 low- and middle-income African American women were interviewed to gain an understanding of their experiences with breast cancer screening. Findings: Participants varied in their experiences with breast cancer screening. Women spoke of a desire for a holistic approach to health that did not separate the breast from the rest of the body. This desire is indicated in the theme of minding the body, self, and spirit, along with themes of relationships and spreading the word about breast health issues. Conclusions: Interventions for African American women should include a focus on minding the body, self, and spirit to promote breast cancer screening, and should indicate the importance of relationships and spreading the word about breast cancer screening. SN 1527-6546 PY 2001 VL 33 IS 2 BP 135 EP 140 DI 10.1111/j.1547-5069.2001.00135.x UT WOS:000171546700009 PM 11419308 ER PT J AU Jenkins, JF Dimond, E Steinberg, S AF Jenkins, JF Dimond, E Steinberg, S TI Preparing for the future through genetics nursing education SO JOURNAL OF NURSING SCHOLARSHIP AB Purpose: To determine recommendations for curriculum change that are indicated by innovations in genetics. Methods: Both quantitative and qualitative. The sample (n = 356) consisted of nurses identified as experts in genetics (n = 228) and nurses identified as potential users of genetics education (n = 128). Nurses' opinions of core components of a genetics curriculum were elicited via a mailed survey questionnaire. Participants also provided demographic information and completed the Jones Innovativeness Scale (1997). Findings: Recommended content in genetics education for practicing nurses was identified by both groups of nurses. Innovativeness characterized 3% of the respondents. Ninety-eight percent of respondents said that adopting genetics education is important. In total, 398 items were identified as potential consequences of education that incorporates genetic information. Conclusions: Identified content provides a template for genetics education programs for nurses. Genetics nursing education was perceived to have positive outcomes for both nurses and clients. SN 1527-6546 PY 2001 VL 33 IS 2 BP 191 EP 195 DI 10.1111/j.1547-5069.2001.00191.x UT WOS:000171546700018 PM 11419317 ER PT J AU Greenwald, P AF Greenwald, P TI Clinical trials of breast and prostate cancer prevention SO JOURNAL OF NUTRITION CT 10th Annual Research Conference on The Role of Nutrition in Preventing and Treating Breast and Prostate Cancer CY AUG 31-SEP 01, 2000 CL WASHINGTON, D.C. SP Amer Inst Canc Res SN 0022-3166 PD JAN PY 2001 VL 131 IS 1 BP 176S EP 178S UT WOS:000166501100031 PM 11208959 ER PT J AU Maymon, E Romero, R Pacora, P Gomez, R Mazor, M Edwin, S Chaiworapongsa, T Kim, JC Yoon, BH Menon, R Fortunato, S Berry, SM AF Maymon, E Romero, R Pacora, P Gomez, R Mazor, M Edwin, S Chaiworapongsa, T Kim, JC Yoon, BH Menon, R Fortunato, S Berry, SM TI A role for the 72 kDa gelatinase (MMP-2) and its inhibitor (TIMP-2) in human parturition, premature rupture of membranes and intraamniotic infection SO JOURNAL OF PERINATAL MEDICINE AB Objective: Degradation of the extracellular matrix in fetal membranes has been implicated in the process of parturition and rupture of membranes. Matrix metalloproteinases (MMPs) are enzymes capable of degrading extracellular matrix including collagen. Tissue inhibitors of matrix metalloproteinases (TIMPs) inhibit the activity of MMPs by covalently binding to the enzymes. MMP-2 degrades Type IV collagen and TIMP-2 is its specific inhibitor. The objective of this study was to determine if human parturition, rupture of membranes (term and preterm) and microbial invasion of the amniotic cavity (MIAC) are associated with changes in the concentrations of MMP-2 and TIMP-2 in amniotic fluid. Study design: A cross-sectional study was conducted with women in the following categories: 1) term with intact membranes, in labor and not in labor; 2) preterm labor and intact membranes who delivered at term, who delivered preterm and preterm labor with MIAC; 3) preterm premature rupture of membranes (PROM) with and without infection; 4) term and preterm PROM not in labor; and 5) midtrimester. MMP-2 and TIMP-2 concentrations in amniotic fluid were determined using sensitive and specific immunoassays, Results: The concentration of TIMP-2 increased with advancing gestational age (r = 0.6, p < 0.001). No correlation was found between MMP-2 concentrations and gestational age. Human parturition and rupture of membranes (term and preterm) and in patients with intact membranes were not associated with changes in the amniotic fluid MMP-2 concentrations. In contrast, 1) patients with spontaneous labor (term and preterm) had significantly lower median concentrations of TIMP-2 compared to those not in labor (p < 0.05 for both); 2) MIAC in women with preterm labor and preterm PROM was associated with a significant decrease in amniotic fluid TIMP-2 concentrations (p < 0.04 for both comparisons); 3) Rupture of the membranes (term and preterm) was also associated with a significant decrease in the amniotic fluid TIMP-2 concentrations (p < 0.05 and p < 0.03, respectively), Conclusions: Human parturition (preterm and term), rupture of fetal membranes (term and preterm) and intraamniotic infection are associated with a significant decrease in amniotic fluid TIMP-2 concentrations. RI Yoon, Bo Hyun/H-6344-2011; Fortunato, Stephen/L-7545-2013 SN 0300-5577 PY 2001 VL 29 IS 4 BP 308 EP 316 DI 10.1515/JPM.2001.044 UT WOS:000170867600006 PM 11565199 ER PT J AU Tran, SD Rudney, JD Sparks, BS Hodges, JS AF Tran, SD Rudney, JD Sparks, BS Hodges, JS TI Persistent presence of Bacteroides forsythus as a risk factor for attachment loss in a population with low prevalence and severity of adult periodontitis SO JOURNAL OF PERIODONTOLOGY AB Background: Previous longitudinal studies investigating the role of microorganisms in periodontitis have focused on subjects with a high prevalence and severity of disease. The complex profile of microbial species in severe cases of periodontitis might not allow us to differentiate which bacterial species initiate disease or which species simply proliferate after disease progression. This prospective longitudinal study followed a group of 205 subjects who showed a low prevalence and severity of adult periodontitis, and thus allowed us to monitor early microbiological changes in the development of periodontitis. Methods: Subgingival plaque was collected from proximal surfaces of a posterior sextant at 6-month intervals for 2 years. During the monitoring period, 44 subjects had either attachment loss or attachment gain. Using multiplex polymerase chain reaction (PCR), all plaque samples from those 44 subjects were analyzed for the presence of Actinobacillus actinomycetemcomitans, Bacteroides forsythus, and Porphyromonas gingivalis. Results: Both subjects with attachment loss and those with attachment gain bad a high prevalence of these 3 periodontal pathogens. The mere presence of any of the 3 species at a site could not predict future attachment loss at that specific site. However, subjects with a persistent presence of B. forsythus at any site across all visits had 5.3 times higher odds of having at least one site in their mouth losing attachment compared to subjects with occasional or no presence of B, forsythus. Conclusions: The persistence of B. forsythus identified subjects at higher risk, but not which specific sites in those subjects would lose attachment. SN 0022-3492 PD JAN PY 2001 VL 72 IS 1 BP 1 EP 10 DI 10.1902/jop.2001.72.1.1 UT WOS:000167491000001 PM 11210065 ER PT J AU Avalos, M Mak, C Randall, PK Trzeciakowski, JP Abell, C Kwan, SW Wilcox, RE AF Avalos, M Mak, C Randall, PK Trzeciakowski, JP Abell, C Kwan, SW Wilcox, RE TI Nonlinear analysis of partial dopamine agonist effects on cAMP in C6 glioma cells SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS AB Most drugs have some efficacy so that improved methods to determine the relative intrinsic efficacy of partial agonists should be of benefit to preclinical and clinical investigators. We examined the effects of partial D-1 or partial D-2 dopamine agonists using a partial agonist interaction model. The dependent variable was the modulation of the dopamine-receptor-mediated cAMP response in C6 glioma cells selectively and stably expressing either D-1 or D-2 recombinant dopamine receptors. The dissociation constant (K-B) and relative intrinsic efficacy (E-r) for each partial agonist were calculated using a partial agonist interaction null model in which the effects of fixed concentrations of each partial agonist on the dopamine dose-response curve were evaluated. This model is an extension of the competitive antagonist null model to drugs with efficacy and assumes only that the log-dose-response curve is monotonic. Generally, the partial agonist interaction model fit the data, as well as fits of the independent logistic curves. Furthermore, the partial agonist K-B values could be shared across partial agonist concentrations without worsening the model fit (by increasing the residual variance). K-B values were also similar to drug affinities reported in the literature. The model was validated in three ways. First, we assumed a common tissue stimulus parameter (beta) and calculated the E-r values. This provided a qualitative check on the interaction model results. Second, we calculated new relative efficacy values, E-r(beta), using the beta estimate. Third, we calculated relative efficacy using relative maxima times midpoint shift ratios (J. Theor. Biol. 198 (1999) 347.). All three methods indicated that the present model yielded reasonable estimates of affinity and relative efficacy for the set of compounds studied. Our results provide a quick and convenient method of quantification of partial agonist efficacy. Special applications and limitations of the model are discussed. In addition, the present results are the first report of the relative intrinsic efficacy values for this set of D-2 ligands. (C) 2001 Elsevier Science Inc. All rights reserved. SN 1056-8719 PD JAN-FEB PY 2001 VL 45 IS 1 BP 17 EP 37 DI 10.1016/S1056-8719(01)00118-6 UT WOS:000170343500002 PM 11489662 ER PT J AU Beni-Adani, L Gozes, I Cohen, Y Assaf, Y Steingart, RA Brenneman, DE Eizenberg, O Trembolver, V Shohami, E AF Beni-Adani, L Gozes, I Cohen, Y Assaf, Y Steingart, RA Brenneman, DE Eizenberg, O Trembolver, V Shohami, E TI A peptide derived from activity-dependent neuroprotective protein (ADNP) ameliorates injury response in closed head injury in mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS AB Brain injury induces disruption of the blood-brain barrier, edema, and release of autodestructive factors that produce delayed neuronal damage. NAPSVIPQ (NAP), a femtomolar-acting peptide, is shown to be neuroprotective in a mouse model of closed head injury. NAP injection after injury reduced mortality and facilitated neurobehavioral recovery (P< 0.005). Edema was reduced by 70% in the NAP-treated mice (P<0.01). Furthermore, in vivo magnetic resonance imaging demonstrated significant brain-tissue recovery in the NAP-treated animals. NAP treatment decreased tumor necrosis factor-alpha levels in the injured brain and was shown to protect pheochromocytoma (PC12 cells) against tumor necrosis factor-alpha -induced toxicity. Thus, NAP provides significant amelioration from the complex array of injuries elicited by head trauma. SN 0022-3565 PD JAN PY 2001 VL 296 IS 1 BP 57 EP 63 UT WOS:000165951800008 PM 11123362 ER PT J AU Hunyady, B Palkovits, M Mozsik, G Molnar, J Feher, K Toth, Z Zolyomi, A Szalayova, I Key, S Sibley, DR Mezey, E AF Hunyady, B Palkovits, M Mozsik, G Molnar, J Feher, K Toth, Z Zolyomi, A Szalayova, I Key, S Sibley, DR Mezey, E TI Susceptibility of dopamine D5 receptor targeted mice to cysteamine SO JOURNAL OF PHYSIOLOGY-PARIS CT Joint Meeting of the 10th International Conference on Ulcer Research/5th International Symposium on Cell Injury and Protection in the Gastrointestinal Tract CY OCT 25-29, 2000 CL BUDAPEST, HUNGARY AB Background. Recently we demonstrated that gastric mucosa of rats can synthesize, store and release dopamine. Out of five different subtypes, mRNA of D5 ( = D Ib) dopamine receptor is very abundant in the gastric epithelium. D I receptor selective dopamine agonists have been shown to protect against experimental gastro-duodenal lesions. Aims. To test the hypothesis that protective effects of dopamine involve D5 receptors, mucosal lesions were induced in D5 receptor deficient (KO) and wild-type (WT) mice using cysteamine. Morphology and gastric acid secretion of D5 KO mice were also studied. Methods. Single doses of 600 mg/kg, 300 mg/kg cysteamine or vehicle were administered subcutaneously to fasted animals. After 24 h, number and severity of gastro-duodenal lesions were analyzed. Basal and histamine-induced maximal gastric acid output were measured by a stomach-sac wash-through method. Results. All the Kos in the 600 mg/kg cysteamine group died within 4 h showing symptoms of toxicity while three out of four WTs survived (P < 0.05). Mortality after 300 mg/kg cysteamine was significantly higher in Kos versus the WTs: 6/ 14 versus 2/11, P < 0.05. Gastric lesion-index was also significantly higher in Kos (median, middle quartile): four (3- 9) wrsus 0 (0-0), P <0.05. Duodenal lesions did not develop from this single dose of cysteamine in either genotype. Basal and histamine-induced maximal gastric acid output were comparable in the two genotypes. Conclusions. This study demonstrates that loss of D5 receptor causes mucosal vulnerability and increased toxicity of cysteamine in genetically manipulated mice. Thus, D5 receptor subtype is indeed likely to be involved in protective effects of dopamine in the stomach. (C) 2001 Elsevier Science Ltd. All rights reserved. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 SN 0928-4257 PD JAN-DEC PY 2001 VL 95 IS 1-6 SI SI BP 147 EP 151 DI 10.1016/S0928-4257(01)00019-5 UT WOS:000171904600019 PM 11595429 ER PT J AU Weinrich, M Stuart, ME AF Weinrich, M Stuart, ME TI Rehabilitation for the 21st century SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT SN 0748-7711 PD JAN-FEB PY 2001 VL 38 IS 1 BP VII EP XII UT WOS:000168149100001 PM 11322476 ER PT J AU Dufau, ML Tsai-Morris, CH Tang, PZ Khanum, A AF Dufau, ML Tsai-Morris, CH Tang, PZ Khanum, A TI Regulation of steroidogenic enzymes and a novel testicular RNA helicase SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY CT 14th International Symposium of the Journal of Steroid Biochemistry and Molecular Biology CY JUN 24-27, 2000 CL CANADA AB Luteinizing hormone (LH) supports steroidogenesis and maintains testicular and ovarian function. Mediators of LH action exert homologous regulation of membrane receptors, steroidogenic enzymes and other regulatable genes of the Leydig cell (LC). Androgen and estrogen induced by LH could act through its cognate receptors in the LC to regulate gene expression. Although androgens are unquestionable essential for spermatogenesis and presumably exert their heterologous action through androgen receptors present in the Sertoli its regulatory mechanism in germinal cell maturation is far from clear. In contrast to physiological concentrations of gonadotropins which maintain the steroidogenic functions and LH and prolactin receptors in the gonads, high concentrations of gonadotropin (hCG) cause receptor down-regulation and desensitization of steroidogenic enzymes of the LCs in vivo (3 beta -hydroxysteroid dehydrogenase types I and II, 17 alpha -hydroxylase/l7,20 lyase, and 17 beta -hydroxysteroid dehydrogenase type III [17 beta -HSD]). In addition, 17 beta -HSD is regulated by compartmentalized endogenous glucose/ATP. The attenuation of steroidogenesis which results from receptor mediated activation by cognate hormone, but is independent of the subsequent phase of receptor down-regulation, is due to changes at the transcriptional level. Among the candidates affecting this regulation are active steroid metabolites (direct or indirect of steroids and other mediator(s) i.e. cAMP, putative transcription factors induced by LH action). Differential display assay revealed another gene which is transcriptionally regulated by gonadotropin termed GRTH (Gonadotropin Regulated Testicular Helicase). GRTH is a novel member of the DEAD-box family of RNA helicases, and is specifically expressed in LCs and meiotic LC of the testis. It is markedly up-regulated by hCG via cAMP-induced androgen formation in LCs at doses that cause down-regulation of receptors and steroidogenic enzymes. GRTH functions as a translational activator. Androgen produced by gonadotropin stimulation exerts intracrine/autocrine actions on GRTH, and also could influence transcription within the seminiferous tubule. GRTH may contribute to the control of steroidogenesis, including the restoration of down regulated cellular functions, and in the paracrine regulation of androgen dependent gene(s) involved in the meiotic process, and could thus have a crucial role in spermatogenesis. (C) 2001 Elsevier Science Ltd. All rights reserved. SN 0960-0760 PD JAN-MAR PY 2001 VL 76 IS 1-5 BP 187 EP 197 DI 10.1016/S0960-0760(01)00051-6 UT WOS:000169310100021 PM 11384877 ER PT J AU Murphy, LD Zimmerman, SB AF Murphy, LD Zimmerman, SB TI A limited loss of DNA compaction accompanying the release of cytoplasm from cells of Escherichia coli SO JOURNAL OF STRUCTURAL BIOLOGY AB The DNA of bacteria is compacted into nucleoids, We have lysed cells of Escherichia coli under conditions in which the cell envelope is retained. The extent of DNA compaction was determined by light microscopy, comparing DAPI fluorescence and phase contrast images. The release of cytoplasm upon lysis allowed the nucleoidal DNA to expand to fill the residual cell boundaries, supporting the role of cytoplasmic crowding in nucleoid compaction. The addition of polylysine allowed lysis with retention of DNA compaction. Furthermore, chloramphenicol treatment of cells resulted in nucleoids which were more resistant to decompaction upon lysis, (C) 2001 Academic Press. SN 1047-8477 PD JAN PY 2001 VL 133 IS 1 BP 75 EP 86 DI 10.1006/jsbi.2001.4331 UT WOS:000169093800008 PM 11356066 ER PT J AU Grant, BF Stinson, FS Harford, T AF Grant, BF Stinson, FS Harford, T TI The 5-year course of alcohol abuse among young adults SO JOURNAL OF SUBSTANCE ABUSE AB Purpose: This study describes the course of alcohol abuse among a nationally representative sample of young adults over a 5-year time period for the purpose of examining the validity of the DSM-IV alcohol abuse category. Methods: DSM-IV diagnoses of alcohol abuse at baseline and follow-up were examined using logistic regression analyses. Results: Alcohol abuse and dependence were shown to have different courses. Very few abusers at Time I became dependent at Time 2, suggesting that abuse is not merely prodromal to dependence. Females, Blacks, and high school dropouts were less likely to receive an abuse diagnosis at baseline. Marital status, family history, earlier onset of drinking, and heavy drinking were also related to abuse at baseline. Alcohol abuse at baseline, in addition to gender, marital status, family history, early onset drinking, and heavy drinking, predicted abuse at follow-up. Exclusion of the hazardous criterion item "driving after drinking too much" from the abuse diagnosis yielded similar results. Discussion: The DSM-IV alcohol abuse category was shown to have some diagnostic utility. (C) 2001 Elsevier Science Inc. All rights reserved. SN 0899-3289 PY 2001 VL 13 IS 3 BP 229 EP 238 DI 10.1016/S0899-3289(01)00078-5 UT WOS:000171781500001 PM 11693449 ER PT J AU Hanna, EZ Yi, HY Dufour, MC Whitmore, CC AF Hanna, EZ Yi, HY Dufour, MC Whitmore, CC TI The relationship of early-onset regular smoking to alcohol use, depression, illicit drug use, and other risky behaviors during early adolescence: Results from the youth supplement to the Third National Health and Nutrition Examination Survey SO JOURNAL OF SUBSTANCE ABUSE AB Purpose: Recently we found that the early onset of regular tobacco use is as predictive of lifetime drug use and depressive disorders as it is of alcohol use disorders [Alcohol.: Clin. Exp. Res. 23 (1999) 513.]. This finding, which paralleled findings regarding early onset of alcohol use [J. Subst. Abuse 10 (1998) 59.], suggested that early regular use of any drug might simply be an indicator of risk for a constellation of problem behaviors. The purpose of the present study is to test this hypothesis as well as to study the strength and patterns of associations among these problem behaviors already present among youth. The results will permit description of more precise profiles to identify groups of children at risk. Methods: Using data for respondents aged 12-16 from the Third National Health and Nutrition Examination Survey (NHANES III), descriptive statistics were calculated and logistic regression models were estimated. Results: Descriptive analyses indicated that in comparison with those who never smoked, or who simply experimented, early-onset regular smokers, both those who began at age 13 or younger and those who did so between 14 and 16, were those most likely to use alcohol and other drugs as well as have school problems and early sexual experiences culminating in pregnancy. Multivariate logistic regression analyses were conducted to assess the associations among these high-risk behaviors. Implications: These results support the hypothesis that early onset of smoking is but an indicator of a syndrome of problem behaviors already in place during childhood. They also suggest that the significance of an age onset variable may differ depending on the age of the sample used. As follow-up data are collected, we expect to learn much about the natural course of the distinct risk groups identified in the analyses by studying longitudinally this nationally representative group of early adolescents. (C) 2001 Elsevier Science Inc. All rights reserved. SN 0899-3289 PY 2001 VL 13 IS 3 BP 265 EP 282 DI 10.1016/S0899-3289(01)00077-3 UT WOS:000171781500003 PM 11693451 ER PT J AU Grant, BF Stinson, FS Harford, TC AF Grant, BF Stinson, FS Harford, TC TI Age at onset of alcohol use and DSM-IV alcohol abuse and dependence: A 12-year follow-up SO JOURNAL OF SUBSTANCE ABUSE AB Purpose: The purpose of this study was to examine the relationship between age at drinking onset and the development of DSM-IV alcohol abuse and dependence in a 12-year prospective study of youth in the United States. Methods: Logistic regression analyses were used to quantify the relationship between age at drinking onset and the development of alcohol abuse and dependence controlling for sociodemographic factors and problem indicators. Results: The odds of alcohol dependence decreased by 5% in 1989 and 9.0% in 1994 for each year drinking onset was delayed. In 1994, the odds of alcohol abuse increased by 7.0% with each decreasing year of age at drinking onset, while age at drinking onset was not related to alcohol abuse in 1989. Several other risk factors were found to be strong and consistent predictors of abuse and dependence in 1989 and 1994, including being male, divorced, separated or never married younger, and having an early history antisocial behaviors and marijuana use. Implications: Implications of the results of this study are discussed in terms of other factors that may impact on the onset-abuse and onset-dependence relationship and the need to focus future prevention efforts. (C) 2001 Elsevier Science Inc. All rights reserved. SN 0899-3289 PY 2001 VL 13 IS 4 BP 493 EP 504 DI 10.1016/S0899-3289(01)00096-7 UT WOS:000172878800006 PM 11775078 ER PT J AU Martin, SE Bryant, K AF Martin, SE Bryant, K TI Gender differences in the association of alcohol intoxication and illicit drug abuse among persons arrested for violent and property offenses SO JOURNAL OF SUBSTANCE ABUSE CT Annual Meeting of the Research-Society-on-Alcoholism CY JUN, 2000 CL DENVER, COLORADO SP Res Soc Alcoholism AB Purpose: To explore the associations between violent and other crimes, and alcohol intoxication and recent use of cocaine, marijuana, and other drugs among men and women arrestees and examine gender differences in these relationships. Methods: We conducted a secondary analysis of 1998 using Arrestee Drug Abuse Monitoring (ADAM) system data using a sample of 9242 male and 2594 women arrested for violent and property offenses in 35 cities. Logistic regression was used to predict arrest for a violent offense (rather than a property crime) from drug- and alcohol-related, and other variables. Results: Both gender and alcohol intoxication are significantly related to arrest for a violent offense. However, the intoxication effects (in the absence of cocaine) are more than three times as great for female (Exp(beta) = 5.59) as male arrestees (Exp(beta) = 1.74), while the combined effects of alcohol and cocaine predict a property offense for women but are insignificant for men. Implications: To achieve further reductions in violent crime, intervention strategies need to focus on reducing alcohol intoxication as well as illicit drug use. Research on the role of alcohol on women's aggression and violence also is suggested. (C) 2001 Elsevier Science Inc. All rights reserved. SN 0899-3289 PY 2001 VL 13 IS 4 BP 563 EP 581 DI 10.1016/S0899-3289(01)00100-6 UT WOS:000172878800011 PM 11775083 ER PT J AU Allen, JP Litten, RZ AF Allen, JP Litten, RZ TI The role of laboratory tests in alcoholism treatment SO JOURNAL OF SUBSTANCE ABUSE TREATMENT AB Although assessment in the field of alcoholism treatment is generally verbal in nature, biological tests can also provide counselors and program evaluators useful and unique information. Five such laboratory measures are briefly described, with particular emphasis on carbohydrate deficient transferrin, a biomarker recently approved by the FDA. Applications for laboratory tests in alcohol screening, motivating patients, and monitoring treatment progress are also proposed. (C) 2001 Elsevier Science Inc. All rights reserved. SN 0740-5472 PD JAN PY 2001 VL 20 IS 1 BP 81 EP 85 DI 10.1016/S0740-5472(00)00144-6 UT WOS:000167491300011 PM 11239731 ER PT J AU DelCarmen-Wiggins, R Carter, AS AF DelCarmen-Wiggins, R Carter, AS TI Introduction - Assessment of infant and toddler mental health: Advances and challenges SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY SN 0890-8567 PD JAN PY 2001 VL 40 IS 1 BP 8 EP 10 DI 10.1097/00004583-200101000-00010 UT WOS:000166156900009 PM 11195568 ER PT J AU Andrews, NP Prasad, A Quyyumi, AA AF Andrews, NP Prasad, A Quyyumi, AA TI N-acetylcysteine improves coronary and peripheral vascular function SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY AB OBJECTIVES We investigated whether N-acetylcysteine (NAC), a reduced thiol that modulates redox state and forms adducts of nitric oxide (NO), improves endothelium-dependent vasomotion. BACKGROUND Coronary atherosclerosis is associated with endothelial dysfunction and reduced NO activity. METHODS In 16 patients undergoing cardiac catheterization, seven with and nine without atherosclerosis, we assessed endothelium-dependent vasodilation with acetylcholine (ACH) and endothelium-independent vasodilation with nitroglycerin (NTG) and sodium nitroprusside (SNP) before and after intracoronary NAG. In 14 patients femoral vascular responses to AGH, NTG and SNP were measured before and after NAG. RESULTS Intraarterial NAC did not change resting coronary or peripheral vascular tone. N-acetylcysteine potentiated AGH-mediated coronary vasodilation; coronary blood flow was 36 +/- 11% higher (p < 0.02), and epicardial diameter changed from -1.2 +/- 2% constriction to 4.7 +/- 2% dilation after NAC (p = 0.03). Acetylcholine-mediated femoral vasodilation was similarly potentiated by NAC (p = 0.001). Augmentation of the ACH response was similar in patients with or without atherosclerosis. N-acetylcysteine did not affect NTG-mediated vasodilation in either the femoral or coronary circulations and did not alter SNP responses in the femoral circulation. In contrast, coronary vasodilation with SNP was significantly greater after NAC (p < 0.05). CONCLUSIONS Thiol supplementation with NAC improves human coronary and peripheral endothelium-dependent vasodilation. Nitroglycerin responses are not enhanced, but SNP-mediated responses are potentiated only in the coronary circulation. These NO-enhancing effects of thiols reflect the importance of the redox state in the control of vascular function and may be of therapeutic benefit in treating acute and chronic manifestations of atherosclerosis. (J Am Cell Cardiol 2001;37:117-23) (C) 2001 by the American College of Cardiology. SN 0735-1097 PD JAN PY 2001 VL 37 IS 1 BP 117 EP 123 DI 10.1016/S0735-1097(00)01093-7 UT WOS:000166238100018 PM 11153725 ER PT J AU Moak, JP Barron, KS Hougen, TJ Wiles, HB Balaji, S Sreeram, N Cohen, MH Nordenberg, A Van Hare, GF Friedman, RA Perez, M Cecchin, F Schneider, DS Nehgme, RA Buyon, JP AF Moak, JP Barron, KS Hougen, TJ Wiles, HB Balaji, S Sreeram, N Cohen, MH Nordenberg, A Van Hare, GF Friedman, RA Perez, M Cecchin, F Schneider, DS Nehgme, RA Buyon, JP TI Congenital heart block: Development of late-onset cardiomyopathy, a previously underappreciated sequela SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY AB OBJECTIVES We report 16 infants with complete congenital heart block (CHB) who developed late-onset dilated cardiomyopathy despite early institution of cardiac pacing. BACKGROUND Isolated CHB has an excellent prognosis following pacemaker implantation. Most early deaths result from delayed initiation of pacing therapy or hemodynamic abnormalities associated with congenital heart defects. METHODS A multi-institutional study was performed to identify common clinical features and possible risk factors associated with late-onset dilated cardiomyopathy in patients born with congenital CHB. RESULTS Congenital heart block was diagnosed in utero in 12 patients and at birth in four patients. Ten of 16 patients had serologic findings consistent with neonatal lupus syndrome (NLS). A pericardial effusion was evident on fetal ultrasound in six patients. In utero determination of left ventricular (LV) function was normal in all. Following birth, one infant exhibited a rash consistent with NLS and two had elevated hepatic transaminases and transient thrombocytopenia. In the early postnatal period, LV function was normal in 15 patients (shortening fraction [SF] = 34 +/- 7%) and was decreased in one (SF = 20%). A cardiac pacemaker was implanted during the first two weeks of life in 15 patients and at seven months in one patient. Left ventricular function significantly decreased during follow-up (14 days to 9.3 years, SF = 9% +/- 5%). Twelve of 16 patients developed congestive heart failure before age 24 months. Myocardial biopsy revealed hypertrophy in 11 patients, interstitial fibrosis in 11 patients, and myocyte degeneration in two patients. Clinical status during follow-up was guarded: four patients died from congestive heart failure; seven required cardiac transplantation; one was awaiting cardiac transplantation; and four exhibited recovery of SF (31 +/- 2%). CONCLUSIONS Despite early institution of cardiac pacing, some infants with CHB develop LV cardiomyopathy. Patients with CHB require dose follow-up not only of their cardiac rate and rhythm, but also ventricular function. a Am Cell Cardiol 2001;37:238 - 42) (C) 2001 by the American College of Cardiology. SN 0735-1097 PD JAN PY 2001 VL 37 IS 1 BP 238 EP 242 DI 10.1016/S0735-1097(00)01048-2 UT WOS:000166238100037 PM 11153745 ER PT J AU Horowitz, AM Siriphant, P Sheikh, A Child, WL AF Horowitz, AM Siriphant, P Sheikh, A Child, WL TI Perspectives of Maryland dentists on oral cancer SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION AB Background. Maryland's mortality rate for oral and pharyngeal cancer is seventh highest overall in highest for men and third highest for African-American men As part of a statewide needs assessment and in following to a mail survey of Maryland general dentists, focus groups were conducted to obtain more in-depth information about why dentists do not provide a comprehensive oral cancer examination for most of their patients and how to solve this from a dentist's perspective. Methods. A trained focus moderator conducted groups of general practice land. Five: major themes emerged from the two groups: inaccurate knowledge cancer examinations when and how to palpate for abnormalities; examinations; and recommendations issues. Conclusions. The focus groups provided a rich source of ideas on how to best provide dentists with continuing education about oral cancer prevention and early detection. Participants also provided opinions about the need to improve the public's awareness of oral cancer and its prevention. Clinical Implications. Dentists need to include comprehensive oral cancer examinations as part of their routine oral examinations for all appropriate patients. SN 0002-8177 PD JAN PY 2001 VL 132 IS 1 BP 65 EP 72 UT WOS:000166403700024 PM 11194401 ER PT J AU Rantanen, T Guralnik, JM Ferrucci, L Penninx, BWJH Leveille, S Sipila, S Fried, LP AF Rantanen, T Guralnik, JM Ferrucci, L Penninx, BWJH Leveille, S Sipila, S Fried, LP TI Coimpairments as predictors of severe walking disability in older women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY AB OBJECTIVE: Severe disabilities are common among older people who have impairments in a range of physiologic systems. It is not known, however, whether the presence of multiple impairments, or coimpairments, is associated with increased risk of developing new disability. The aim of this study was to determine the combined effects of two impairments, decreased knee-extension strength and poor standing balance, on the risk of developing severe walking disability among older, moderately-to-severely disabled women who did not have severe walking disability at baseline. DESIGN: The Women's Health and Aging Study is a 3-year prospective study with 6 semi-annual follow-up data-collection rounds following the baseline. SETTING: At baseline, knee-extension strength and standing balance tests took place in the participants' homes. PARTICIPANTS: 758 women who were not severely walking disabled at baseline. MEASUREMENTS: Severe walking disability was defined as customary walking speed of <0.4 meters/second and inability to walk one quarter of a mile, or being unable to walk. RESULTS: Over the course of the study, 173 women be came severely disabled in walking. The cumulative incidence of severe walking disability from the first to the sixth follow-up was: 7.8%, 12.0%, 15.1% 19.5% 21.2%, and 22.8%. In Cox proportional hazards models, both strength and balance were significant predictors of new walking disability. In the best balance category, the rates of developing severe walking disability expressed per 100 person years were 3.1, 6.1, and 5.3 in the highest- to lowest-strength tertiles. In the middle balance category, the rates were 9.6, 13.2, and 14.7, and in the poorest balance category 21.6, 12.7, and 37.1, correspondingly. The relative risk (RR) of onset of severe walking disability adjusted for age, height, weight, and race was more than five times greater in the group with poorest balance and strength (RR 5.12, 95% confidence limit [95% CI] 2.68-9.80) compared with the group with best balance and strength (the reference group). Among those who had poorest balance and best strength, the RR of severe walking disability was 3.08 (95% CI 1.33-7.14). Among those with best balance and poorest strength, the RR was 0.97 (95% CI 0.49-1.93), as compared with the reference group. CONCLUSION: The presence of coimpairments is a powerful predictor of new, severe walking disability, an underlying cause of dependence in older people. Substantial reduction in the risk of walking disability could be achieved even if interventions were successful in correcting only one of the impairments because a deficit in only one physiologic system may be compensated for by good capacity in another system. RI Rantanen, Taina/O-6579-2016 OI Rantanen, Taina/0000-0002-1604-1945 SN 0002-8614 PD JAN PY 2001 VL 49 IS 1 BP 21 EP 27 DI 10.1046/j.1532-5415.2001.49005.x UT WOS:000168067300004 PM 11207838 ER PT J AU Diehr, P Williamson, J Patrick, DL Bild, DE Burke, GL AF Diehr, P Williamson, J Patrick, DL Bild, DE Burke, GL TI Patterns of self-rated health in older adults before and after sentinel health events SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY AB OBJECTIVES: To describe and compare patterns of change in self-rated health for older adults before death and before and after stroke, myocardial infarction, congestive heart failure, cardiac procedure, hospital admission for cancer, and hip fracture. DESIGN: "Event cohort," measuring time in months before and after the event. SETTING: Four U.S. communities. PARTICIPANTS: 5888 participants in the Cardiovascular Health Study (CHS), sampled from Medicare rolls and followed up to 8 years. Mean age at baseline was 73. MEASUREMENTS: Self-rated health, including a category for death, assessed at 6-month intervals, and ascertainment of events. METHODS: We examined the percentage that was healthy each month in the 5 years before death and in the 2 years before and after the other events, and compared the patterns to a "no event" group and to one another, using graphs and linear regression. RESULTS: For people who died, health status declined slowly until about 9 months before death, when it dropped steeply. Comparing persons equally far from death, health was unrelated to age, but men and whites were healthier than women and blacks. Health for other events declined before the event, dropped steeply at the event, showed some recovery, and then declined further after the event. About 65% to 80% of the subjects were healthy 2 years before their event, but only 35% to 65% were healthy two years afterwards. Patterns were similar although less extreme for the "no event" group. CONCLUSION: Visualizing trajectories of health helps us understand how serious health events changes health. Conclusions about change must be drawn with care because of a variety of possible biases. We have described the trajectories in detail. Work is now needed to explain, predict, and possibly prevent such changes in health. SN 0002-8614 PD JAN PY 2001 VL 49 IS 1 BP 36 EP 44 DI 10.1046/j.1532-5415.2001.49007.x UT WOS:000168067300006 PM 11207840 ER PT J AU Wong, STC Koslow, SH AF Wong, STC Koslow, SH TI Human Brain Program research progress in bioinformatics/neuroinformatics SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION SN 1067-5027 PD JAN-FEB PY 2001 VL 8 IS 1 BP 103 EP 104 UT WOS:000166365600009 PM 11141517 ER PT J AU Aronson, AR AF Aronson, AR TI Effective mapping of biomedical text to the UMLS metathesaurus: The MetaMap Program SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION CT Annual Symposium of the American-Medical-Informatics-Association (AMIA 2001) CY NOV 03-07, 2001 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB The UMLS(R) Metathesaurus(R), the largest thesaurus in the biomedical domain, provides a representation of biomedical knowledge consisting of concepts classified by semantic type and both hierarchical and non-hierarchical relationships among the concepts. This knowledge has proved useful for many applications including decision support systems, management of patient records, information retrieval (IR) and data mining. Gaining effective access to the knowledge is critical to the success of these applications. This paper describes MetaMap, a program developed at the National Library of Medicine (NLM) to map biomedical text to the Metathesaurus or, equivalently, to discover Metathesaurus concepts referred to in text. MetaMap uses a knowledge intensive approach based on symbolic, natural language processing (NLP) and computational linguistic techniques. Besides being applied for both IR and data mining applications, MetaMap is one of the foundations of NLM's Indexing Initiative System which is being applied to both semiautomatic and fully automatic indexing of the biomedical literature at the library. SN 1067-5027 PY 2001 SU S BP 17 EP 21 UT WOS:000172263400005 ER PT J AU Bodenreider, O AF Bodenreider, O TI Circular hierarchical relationships in the UMLS: Etiology, diagnosis, treatment, complications and prevention SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION CT Annual Symposium of the American-Medical-Informatics-Association (AMIA 2001) CY NOV 03-07, 2001 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB The Unified Medical Language System (UMLS) is a large repository of some 800,000 concepts for the biomedical domain, organized by several millions of inter-concept relationships, either inherited from the source vocabularies, or specifically generated. This paper focuses on hierarchical relationships in the UMLS Metathesaurus, and especially, on circular hierarchical relationships. Using the metaphor of a disease, we first analyze the causal mechanisms for circular hierarchical relationships. Then, we discuss methods to identify and remove these relationships. Finally, we briefly discuss the consequences of these relationships for applications based on the UMLS, and we propose some prevention measures. SN 1067-5027 PY 2001 SU S BP 57 EP 61 UT WOS:000172263400013 ER PT J AU Burgun, A Bodenreider, O AF Burgun, A Bodenreider, O TI Mapping the UMLS semantic network into general ontologies SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION CT Annual Symposium of the American-Medical-Informatics-Association (AMIA 2001) CY NOV 03-07, 2001 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB In this study, we analyzed the compatibility between an ontology of the biomedical domain (the UMLS Semantic Network) and two other ontologies: the Upper Cyc Ontology (UCO) and WordNet. 1) We manually mapped UMLS Semantic Types to UCO. One fifth of the UMLS Semantic Types had exact mapping to UCO types. UCO provides generic concepts and a structure that relies on a larger number of categories, despite its lack of depth in the biomedical domain. 2) We compared semantic classes in the UMLS and WordNet. 2% of the UMLS concepts from the Health Disorder class were present in WordNet, and compatibility between classes was 48%. WordNet, as a general language-oriented ontology is a source of lay knowledge, particularly important for consumer health applications. RI Smith, Barry/A-9525-2011 OI Smith, Barry/0000-0003-1384-116X SN 1067-5027 PY 2001 SU S BP 81 EP 85 UT WOS:000172263400018 ER PT J AU Gennari, JH Sklar, D Silva, J AF Gennari, JH Sklar, D Silva, J TI Cross-tool communication: From protocol authoring to eligibility determination SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION CT Annual Symposium of the American-Medical-Informatics-Association (AMIA 2001) CY NOV 03-07, 2001 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB To be effective, informatics tools for clinical trial protocols must inter-operate and share knowledge. We demonstrate a simple XML-based communication of eligibility, criteria information between two independently-developed informatics tools, Using a shared DTD model of criteria, an authoring tool (developed within the Protege environment) can send a list of eligibility criteria to a commercial system for automatic eligibility determination (the "iKnowChart" system by iKnowMed). The criteria model, developed as a Protege ontology, includes both the terminology and the logic needed to compute eligibility for a given patient. As a demonstration of cross-tool communication, we have encoded criteria from an active clinical trial protocol (E1199), and shown how use of the authoring tool can effectively update the eligibility knowledge and the behavior of the commercial iKnowChart system. As part of the cross-tool knowledge sharing, we use Common Data Elements, an oncology terminology developed by the National Cancer Institute. OI Gennari, John/0000-0001-8254-4957 SN 1067-5027 PY 2001 SU S BP 199 EP 203 UT WOS:000172263400042 ER PT J AU Gwaltney, K Chute, C Hageman, D Kibbe, W McCormick, K Reeves, D Wright, L AF Gwaltney, K Chute, C Hageman, D Kibbe, W McCormick, K Reeves, D Wright, L TI An assessment of cancer clinical trials vocabulary and IT infrastructure in the US SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION CT Annual Symposium of the American-Medical-Informatics-Association (AMIA 2001) CY NOV 03-07, 2001 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB Twenty-three cancer research centers in the U.S. were assessed to determine data standards, vocabularies, and information infrastructure used in support of clinical trials. Eighteen of the 23 responded. Major findings were related to: 1) clinical trials infrastructure information, 2) current systems environment, 3) technical details, and 4) vocabulary and data standards. The size of the facility correlated with the quality, features and functionality of the clinical trials system (CTS) One facility had as many as 22 separate CTS. There were only 2 sites that had integrated clinical information systems (CIS) with CTS. The responses included the major vocabularies and data standards used in CTS. The majority used some automation but many also reported manual data entry. CTS had more manual entry than CIS because of regulatory reporting requirements. The assessment identified opportunities for guidance in defining vocabularies and standards for cancer clinical trial systems in the US. RI Kibbe, Warren/B-2106-2010 OI Kibbe, Warren/0000-0001-5622-7659 SN 1067-5027 PY 2001 SU S BP 224 EP 228 UT WOS:000172263400047 ER PT J AU Kim, W Aronson, AR Wilbur, WJ AF Kim, W Aronson, AR Wilbur, WJ TI Automatic MeSH term assignment and quality assessment SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION CT Annual Symposium of the American-Medical-Informatics-Association (AMIA 2001) CY NOV 03-07, 2001 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB For computational purposes documents or other objects are most often represented by a collection of individual attributes that may be strings or numbers. Such attributes are often called features and success in solving a given problem can depend critically on the nature of the features selected to represent documents. Feature selection has received considerable attention in the machine learning literature. In the area of document retrieval we refer to feature selection as indexing. Indexing has not traditionally been evaluated by the same methods used in machine learning feature selection. Here we show how indexing quality may be evaluated in a machine learning setting and apply this methodology to results of the Indexing Initiative at the National Library of Medicine. SN 1067-5027 PY 2001 SU S BP 319 EP 323 UT WOS:000172263400066 ER PT J AU McCray, AT Bodenreider, O Malley, JD Browne, AC AF McCray, AT Bodenreider, O Malley, JD Browne, AC TI Evaluating UMLS strings for natural language processing SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION CT Annual Symposium of the American-Medical-Informatics-Association (AMIA 2001) CY NOV 03-07, 2001 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB The National Library of Medicine's Unified Medical Language System (UMLS) is a rich source of knowledge in the biomedical domain. The UMLS is used for research and development in a range of different applications, including natural language processing (NLP). In this paper we investigate the nature of the strings found in the UMLS Metathesaurus and evaluate them for their usefulness in NLP. We begin by identifying a number of properties that might allow us to predict the likelihood of a given string being found or not found in a corpus. We use a statistical model to test these predictors against our corpus, which is derived from the MEDLINE database. For one set of properties the model correctly predicted 77% of the strings that do not belong to the corpus, and 85% of the strings that do belong to the corpus. For another set of properties the model correctly predicted 96% of the strings that do not belong to the corpus and 29% of the strings that do belong to the corpus. SN 1067-5027 PY 2001 SU S BP 448 EP 452 UT WOS:000172263400092 ER PT J AU Seckman, CA Romano, CA Marden, S AF Seckman, CA Romano, CA Marden, S TI Evaluation of clinician response to wireless technology SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION CT Annual Symposium of the American-Medical-Informatics-Association (AMIA 2001) CY NOV 03-07, 2001 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB The purpose of this study was to investigate the safety, use and response of clinical staff to wireless technology. A convenience sample of clinical staff was surveyed using a variety of assessment tools. The environmental assessment determined there was no interference between the wireless devices and the biomedical equipment on the patient care units. Survey results indicated a high level of acceptance for the wireless technology related to perceived usefulness, perceived ease of use, impact, adoption, advantage and future need. Results indicated a strong, significant relationship between adoption and perceived usefulness (r(s)=.71 p<.01; r(s)(2)=.50). SN 1067-5027 EI 1527-974X PY 2001 SU S BP 612 EP 616 UT WOS:000172263400125 ER PT J AU Weeber, M Mork, JG Aronson, AR AF Weeber, M Mork, JG Aronson, AR TI Developing a test collection for biomedical word sense disambiguation SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION CT Annual Symposium of the American-Medical-Informatics-Association (AMIA 2001) CY NOV 03-07, 2001 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB Ambiguity, the phenomenon that a word has more than one sense, poses difficulties for many current Natural Language Processing (NLP) systems. Algorithms that assist in the resolution of these ambiguities, i.e. which disambiguate a word, or more generally, a text string, will boost performance of these systems. To test such techniques in the biomedical language domain, we have developed a Word Sense Disambiguation (WSD) test collection that comprizes 5,000 disambiguated instances for 50 ambiguous UMLS(R) Metathesaurus(R) strings. SN 1067-5027 PY 2001 SU S BP 746 EP 750 UT WOS:000172263400152 ER PT J AU Carter, JS Brown, SH Nelson, SJ Lincoln, MJ Tuttle, MS AF Carter, JS Brown, SH Nelson, SJ Lincoln, MJ Tuttle, MS TI The creation and use of a reference terminology for inter-agency computer-based patient records: The GCPR RTM Demonstration Project SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION SN 1067-5027 PY 2001 SU S BP 809 EP 809 UT WOS:000172263400170 ER PT J AU Wong, J Kogan, S Cardiff, R Carter, J Nelson, V Tuttle, M Rosse, C De Coronado, S AF Wong, J Kogan, S Cardiff, R Carter, J Nelson, V Tuttle, M Rosse, C De Coronado, S TI Web-based, micro-terminology development: The MMHCC experience SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION SN 1067-5027 PY 2001 SU S BP 842 EP 842 UT WOS:000172263400203 ER PT J AU Lesh, KA Jambou, R O'Reilly, M Patterson, A Rosenthal, E Shih, T Foss, J AF Lesh, KA Jambou, R O'Reilly, M Patterson, A Rosenthal, E Shih, T Foss, J TI GeMCRIS and gene transfer product characterization vocabulary development SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION SN 1067-5027 PY 2001 SU S BP 953 EP 953 UT WOS:000172263400313 ER PT J AU Meadows, B Abrams, J Christian, M Silva, J Valmonte, C West, P Pifer, C AF Meadows, B Abrams, J Christian, M Silva, J Valmonte, C West, P Pifer, C TI The Common Data Element Dictionary - Developing a standard nomenclature for reporting cancer clinical trial data SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION SN 1067-5027 PY 2001 SU S BP 972 EP 972 UT WOS:000172263400332 ER PT J AU Nelson, SJ Johnston, D Powell, T Hole, WT AF Nelson, SJ Johnston, D Powell, T Hole, WT TI Making the marriage: Reconciling views of concepts and meaning in MeSH and the UMLS Metathesaurus SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION SN 1067-5027 PY 2001 SU S BP 985 EP 985 UT WOS:000172263400345 ER PT J AU Roth, L AF Roth, L TI UMLSInfo: A new web-based resource for UMLS users SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION SN 1067-5027 PY 2001 SU S BP 1010 EP 1010 UT WOS:000172263400370 ER PT J AU Woods, AS Huestis, MA AF Woods, AS Huestis, MA TI A study of peptide-peptide interaction by matrix-assisted laser desorption/ionization SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY AB Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry was used to study peptide-peptide interaction. The interaction was seen when 6-aza-2-thiothymine was used as a matrix (pH 5.4), but was disrupted with a more acidic matrix, alpha -cyano-4-hydroxycinnamic acid (pH 2.0). In the present study, we show that dynorphin, an opioid peptide, and five of its fragments that contain two adjacent basic residues (Arg(6)-Arg(7)), all interact noncovalently with peptides that contain two to five adjacent acidic residues (Asp or Glu). Two other nonrelated peptides containing two (Arg(6)Arg(7)) or three (Arg(1)-Lys(2)-Arg(3)) adjacent basic amino acid residues were studied and exhibited the same behavior. However, peptides containing adjacent Lys or His did not form noncovalent complexes with acidic peptides. The noncovalent bonding was sufficiently stable that digestion with trypsin only cleaved Arg and Lys residues that were not involved in hydrogen bonding with the acidic residues. In an equimolar mixture of dynorphin, dynorphin fragments (containing the motif RR), and an acidic peptide (minigastrin), the acidic peptide preferentially complexed with dynorphin. If the concentration of minigastrin was increased 10 fold, noncovalent interaction was seen with dynorphin and all its fragments containing the motif RR. In the absence of dynorphin, minigastrin formed noncovalent complexes with all dynorphin fragments. These findings suggest that conformation, equilibrium, and concentration do play a role in the occurrence of peptide-peptide interaction. Observations from this study include: (1) ionic bonds were not disrupted by enzymatic digests, (2) conformation and concentration influenced complex formation, and (3) the complex did not form with fragments of dynorphin or unrelated peptides that did not contain the motifs RR or RKR, nor with a fragment of dynorphin where Arg(7) was mutated to a phenylalanine residue. These findings strongly suggest that peptide-peptide interaction does occur, and can be studied by MALDI if near physiologic pH is maintained. (C) 2001 American Society for Mass Spectrometry. SN 1044-0305 PD JAN PY 2001 VL 12 IS 1 BP 88 EP 96 DI 10.1016/S1044-0305(00)00197-5 UT WOS:000166066700010 PM 11142364 ER PT J AU Schmidt, MA Freidlin, RZ Ohazama, CJ Jones, M Laurienzo, JM Brenneman, CL Norman, JE von Ramm, OT Panza, JA AF Schmidt, MA Freidlin, RZ Ohazama, CJ Jones, M Laurienzo, JM Brenneman, CL Norman, JE von Ramm, OT Panza, JA TI Anatomic validation of a novel method for left ventricular volume and mass measurements with use of real-time 3-dimensional echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY AB Assessment of left ventricular (LV) volumes and mass is a critical element in the evaluation of patients with cardiovascular disease. However, most noninvasive methods used for the quantitative measurements of LV volume and mass have important intrinsic Limitations. Real-time 3-dimensional echocardiography (RT3D echo) is a new technique capable of acquiring volumetric Images without cardiac or respiratory gating. The purpose of this study was to develop and validate a system for rapid LV volume and mass measurements with the use of RT3D echo images. To this end, in 11 explanted sheep hearts, the left ventricle was instrumented with a latex balloon and filled with known volumes of saline solution. Two independent observers made volume calculations from Images acquired with RTSD echo. In addition, 21 open-chest sheep were Imaged with RT3D echo for LV mass calculation. Anatomic LV mass was determined after removing the heart. A strong correlation was observed between the actual LV volumes and those calculated from the RT3D echo Images (r = 0.99; y = 1.31 + 0.98x; standard error of the estimate = 2.2 mL). An analysis of intraobserver and interobserver variabilities revealed high indexes of agreement. A strong correlation was observed between actual LV mass and that calculated from RT3D echo images (r = 0.94; y = 14.4 + 0.89x; standard error of the estimate = 8.5 gm). Thus RTSD echo images allow rapid and accurate measurements of LV volume and mass. This technique may expand the use of cardiac ultrasonography for the quantitative assessment of heart disease. SN 0894-7317 PD JAN PY 2001 VL 14 IS 1 BP 1 EP 10 DI 10.1067/mje.2001/108132 UT WOS:000166649000002 PM 11174428 ER PT J AU Ecelbarger, CA Kim, GH Knepper, MA Liu, J Tate, M Welling, PA Wade, JB AF Ecelbarger, CA Kim, GH Knepper, MA Liu, J Tate, M Welling, PA Wade, JB TI Regulation of potassium channel Kir 1.1 (ROMK) abundance in the thick ascending limb of Henle's loop SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY AB The renal outer medullary potassium channel (ROMK) of the thick ascending limb (TAL) is a critical component of the counter-current multiplication mechanism. In this study, two new antibodies raised to ROMK were used to investigate changes in the renal abundance of ROMK with treatments known to strongly promote TAL function. These antibodies specifically recognized protein of the predicted size of 45 kD in immunoblots of rat kidney or COS cells transfected with ROMK cDNA. Infusion of 1-deamino-(8-D-arginine)-vasopressin (dDAVP), a vasopressin V2 receptor-selective agonist, for 7 d into Brattleboro rats resulted in dramatic increases in apical membrane labeling of ROMK in the TAL of dDAVP-treated rats, as assessed by immunocytochemical analyses. Using immunoblotting, a more than threefold increase in immunoreactive ROMK levels was observed in the outer medulla after dDAVP infusion. Restriction of water intake to increase vasopressin levels also significantly increased TAL ROMK immunolabeling and abundance in immunoblots. In addition, dietary Na+ levels were varied to determine whether ROMK abundance was also affected under other conditions known to alter TAL transport. Rats fed higher levels of sodium, as either NaCl or NaHCO3 (8 mEq/250 g body wt per d), exhibited significantly increased density of the 45-kD band, compared with the respective control animals. Moreover, in rats fed a low-NaCl diet (0.25 mEq/250 g body wt per d), a 50% decrease in band density for the 45-kD band was observed (relative to control rats fed 2.75 mEq/250 g body wt per d of NaCl). These results demonstrate that long-term adaptive changes in ROMK abundance occur in the TAL with stimuli that enhance transport by this segment. OI Kim, Gheun-Ho/0000-0002-8445-9892 SN 1046-6673 PD JAN PY 2001 VL 12 IS 1 BP 10 EP 18 UT WOS:000166094300002 PM 11134245 ER PT J AU Jiang, WX Kipnis, V Midthune, D Carroll, RJ AF Jiang, WX Kipnis, V Midthune, D Carroll, RJ TI Parameterization and inference for nonparametric regression problems SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY AB We consider local likelihood or local estimating equations, in which a multivariate function Theta(.) is estimated but a derived function lambda(.) of Theta(.) is of interest. In many applications, when most naturally formulated the derived function is a non-linear function of Theta(.). In trying to understand whether the derived non-linear function is constant or linear, a problem arises with this approach: when the function is actually constant or linear, the expectation of the function estimate need not be constant or linear, at least to second order. In such circumstances, the simplest standard methods in nonparametric regression for testing whether a function is constant or linear cannot be applied. We develop a simple general solution which is applicable to nonparametric regression, varying-coefficient models, nonparametric generalized linear models, etc. We show that, in local linear kernel regression, inference about the derived function lambda(.) is facilitated without a loss of power by reparameterization so that lambda(.) is itself a component of Theta(.). Our approach is in contrast with the standard practice of choosing Theta(.) for convenience and allowing lambda(.) to be a non-linear function of Theta(.). The methods are applied to an important data set in nutritional epidemiology. SN 1369-7412 PY 2001 VL 63 BP 583 EP 591 DI 10.1111/1467-9868.00300 PN 3 UT WOS:000170353900009 ER PT J AU Dunson, DB Dinse, GE AF Dunson, DB Dinse, GE TI Bayesian incidence analysis of animal tumorigenicity data SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS AB Statistical inference about tumorigenesis should focus on the tumour incidence rate. Unfortunately, in most animal carcinogenicity experiments, tumours are not observable in live animals and censoring of the tumour onset times is informative. In this paper. we propose a Bayesian method for analysing data from such studies. Our approach focuses on the incidence of tumours acid accommodates occult tumours and censored onset times without restricting tumour lethality, relying on cause-of-death data, or requiring interim sacrifices. We represent the underlying state of nature by a multistate stochastic process and assume general probit models for the time-specific transition rates. These models allow the incorporation of covariates, historical control data and subjective prior information. The inherent flexibility of this approach facilitates the interpretation of results, particularly when the sample size is small or the data are sparse. We use a Gibbs sampler to estimate the relevant poster[or distributions. The methods proposed are applied to data from a US National Toxicology Program carcinogenicity study. SN 0035-9254 PY 2001 VL 50 BP 125 EP 141 DI 10.1111/1467-9876.00224 PN 2 UT WOS:000168551800001 ER PT J AU Parise, H Dinse, GE Ryan, LM AF Parise, H Dinse, GE Ryan, LM TI Flexible estimates of tumour incidence for intermediately lethal tumours in a typical long-term animal bioassay SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS AB The estimation of the incidence of tumours in an animal carcinogenicity study is complicated by the occult nature of the tumours involved (i.e. tumours are not observable before an animal's death). Also, the lethality of tumours is generally unknown, making the tumour incidence function non-identifiable without interim sacrifices, cause-of-death data or modelling assumptions. Although Kaplan-Meier curves for overall survival are typically displayed, obtaining analogous plots for tumour incidence generally requires fairly elaborate model fitting. We present a case-study of tetrafluoroethylene to illustrate a simple method for estimating the incidence of tumours as a function of more easily estimable components. One of the components, tumour prevalence, is modelled by using a generalized additive model, which leads to estimates that are more flexible than those derived under the usual parametric models. A multiplicative assumption for tumour lethality allows for the incorporation of concomitant information, such as the size of tumours. Our approach requires only terminal sacrifice data although additional sacrifice data are easily accommodated. Simulations are used to illustrate the estimator proposed and to evaluate its properties. The method also yields a simple summary measure of tumour lethality, which can be helpful in interpreting the results of a study. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 SN 0035-9254 PY 2001 VL 50 BP 171 EP 185 DI 10.1111/1467-9876.00227 PN 2 UT WOS:000168551800004 ER PT J AU Berger, VW AF Berger, VW TI The p-value interval as an inferential tool SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES D-THE STATISTICIAN AB In the phase III randomized clinical trial setting, design-based analyses for between-group comparisons are permutation tests which strictly preserve the type I error rate. However, the conservatism of permutation tests can cause a loss of power sufficient to prevent statistical significance from being reached. Arguments regarding the use of permutation tests thus tend to be broad brush: permutation tests should be used routinely for strict preservation of the type I error, or permutation tests should not be used at all because of the loss of power due to conservatism. Lost in these arguments is the fact that the conservatism of any particular permutation test can be measured, to allow for a more moderate decision rule: use a permutation test, but only if it is not overly conservative. We propose reversing the measure of conservatism from data independent and alpha dependent to data dependent and alpha independent, to reflect the practice of reporting p-values rather than reject or no-reject decisions at a given alpha -level. Specifically, we define the p-value interval, whose lower end point is the smallest the p-value could have been without conservatism, and whose upper end point is the (generally conservative) traditional p-value. The length of the p-value interval is the null probability of the observed outcome and measures the conservatism of the test. The p-value interval allows for an explicit quantification of the extent to which more discriminating (or secondary) test statistics help to reduce conservatism by generating more outcomes, each with a lower null probability. Higher order p-value intervals can also be used to assess the robustness of statistical significance in terms of the number of patients required to switch treatment groups to break the observed statistical significance. SN 0039-0526 PY 2001 VL 50 BP 79 EP 85 DI 10.1111/1467-9884.00262 PN 1 UT WOS:000167620200007 ER PT J AU Iams, JD AF Iams, JD CA Natl Inst Child Hlth Human Dev Mat TI The preterm prediction study: Maternal serum relaxin, sonographic cervical length, and spontaneous preterm birth in twins SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION AB OBJECTIVE: The risk of spontaneous preterm birth has been related to decreased cervical length and to increased serum relaxin. To explore a relationship between these findings, we used data collected from two prior studies to correlate relaxin levels with cervical length and risk of spontaneous preterm birth in women with twin pregnancies. METHODS: In a secondary analysis of data collected in two previous observational studies of risk factors for preterm birth, relaxin levels in maternal serum and cervical length were measured at 24 (n = 188) and 28 (n = 145) weeks in women with spontaneous twin pregnancies. Relaxin, as a continuous variable, was related by logistic regression analysis to risk of spontaneous preterm birth before 37, 35, and 32 weeks' gestation, and by Spearman correlation coefficients to cervical length at 24 and 28 weeks. Cervical length at 24 weeks was known to be correlated with spontaneous preterm birth before 37, 35, and 32 weeks' (P = .03, .01, and .002, respectively) in this study population. RESULTS: Cervical length did not correlate with relaxin levels at 24 (P = .601) or 28 (P = .304) weeks. Relationships between relaxin and spontaneous preterm birth were observed at 24 weeks for births before 37 weeks (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.00, 2.44; P = .05), and at 28 weeks for births before 35 weeks (OR 1.97, 95% CI 1.05, 3.70; P = .034) and 32 weeks (OR 2.43, 95% CI 1.01, 5.83; P = .048). CONCLUSION: The absence of an association between relaxin and cervical length suggests that increased relaxin does not explain the inverse correlation between cervical length and spontaneous preterm birth in women with spontaneous twin pregnancies. Copyright (C) 2001 by the Society for Gynecologic Investigation. SN 1071-5576 PD JAN-FEB PY 2001 VL 8 IS 1 BP 39 EP 42 DI 10.1016/S1071-5576(00)00093-9 UT WOS:000167264600007 PM 11223356 ER PT J AU Nelson, LM AF Nelson, LM TI Autoimmune ovarian failure: Comparing the mouse model and the human disease SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION CT Workshop on the Ovary - Genesis, Function, and Failure CY MAR 30-31, 2000 CL BETHESDA, MARYLAND SP NICHHD, Natl Inst Aging, NCI, Natl Inst Environm Hlth Sci, NIH, Off Rare Dis, NIH, Off Res Womens Hlth AB The neonatal-thymectomy-induced mouse model of autoimmune oophoritis has two important similarities with human autoimmune oophoritis. First, in both cases there is some defect in the immune system that permits the development of organ-specific autoimmunity. Second, in both there is some ovarian target under attack. In neither case do we fully understand the nature of the immune defect or the ovarian target. Because of its strong analogy with the human disease, murine experimental postthymectomy autoimmune oophoritis may provide insight into the pathogenesis of autoimmune premature ovarian failure in women. Such studies may open new avenues toward the development of specific diagnostic and therapeutic methods. The histologic distribution of the ovarian lymphocytic infiltration is similar in the mouse and the human, and both mice and women with the disorder have reduced natural killer cell activity. Furthermore, susceptibility in both mice and women appears to be associated with genes outside the major histocompatibility complex. Finally, the mouse disorder is associated with a persistent neonatal-like Th2 response that suggests possible similarities with autoimmune polyglandular failure type 1 in humans. There is no currently available validated serum antibody marker that will confirm a clinical diagnosis of autoimmune premature ovarian failure. While investigating this animal model we cloned a novel gene that encodes an ooplasm-specific antigen associated with autoimmune oophoritis in mice. Based on its role in preimplantation development, we have designated this antigen Maternal Antigen That Embryos Require (MATER). MATER provides a new determinant with which to investigate the mechanisms of autoimmune premature ovarian failure. (J Soc Gynecol Investig 2001;8:S55-S57) Copyright (C) 2001 by the Society for Gynecologic Investigation. SN 1071-5576 PD JAN-FEB PY 2001 VL 8 IS 1 SU S BP S55 EP S57 DI 10.1016/S1071-5576(00)00110-6 UT WOS:000167356900017 PM 11223375 ER PT J AU Parrott, EC Leppert, PC Santoro, N AF Parrott, EC Leppert, PC Santoro, N TI The ovary: Genesis, function, and failure - Introduction SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION SN 1071-5576 PD JAN-FEB PY 2001 VL 8 IS 1 SU S BP S1 EP S2 DI 10.1016/S1071-5576(00)00094-0 UT WOS:000167356900001 ER PT J AU Modlin, JF Snider, DE Brooks, DA Clover, RD Guerra, FA Helms, CM Johnson, DR Le, CT Offit, PA Rennels, MB Tompkins, LS Word, BM Bradshaw, D Cheek, JE Evans, GS Graydon, TR Myers, MG Heilman, C Midthun, K Myers, MG Nichol, KL Mahoney, M Pickering, L Abramson, J France, EK Gall, SA Gardner, P Schaffner, W Wilson, HD McKinney, WP Marchessault, V Siegel, JD Katz, SL Santos, JI Jackson, RE Peter, G Howe, BJ Ashford, DA Perkins, B Rotz, LD AF Modlin, JF Snider, DE Brooks, DA Clover, RD Guerra, FA Helms, CM Johnson, DR Le, CT Offit, PA Rennels, MB Tompkins, LS Word, BM Bradshaw, D Cheek, JE Evans, GS Graydon, TR Myers, MG Heilman, C Midthun, K Myers, MG Nichol, KL Mahoney, M Pickering, L Abramson, J France, EK Gall, SA Gardner, P Schaffner, W Wilson, HD McKinney, WP Marchessault, V Siegel, JD Katz, SL Santos, JI Jackson, RE Peter, G Howe, BJ Ashford, DA Perkins, B Rotz, LD CA Advisory Comm Immunization Practic TI Use of anthrax vaccine in the United States: Recommendations of the advisory committee on immunization practices (Reprinted from Morbidity and Mortality Weekly Report, vol 49, pg 1-20, 2000) SO JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY SN 0731-3810 PY 2001 VL 39 IS 1 BP 85 EP 100 UT WOS:000170067300014 ER PT J AU Osuch, EA Brotman, MA Podell, D Geraci, M Touzeau, PL Leverich, GS McCann, UD Post, RM AF Osuch, EA Brotman, MA Podell, D Geraci, M Touzeau, PL Leverich, GS McCann, UD Post, RM TI Prospective and retrospective life-charting in posttraumatic stress disorder (The PTSD-LCM): A pilot study SO JOURNAL OF TRAUMATIC STRESS AB The purpose of this study was to design and conduct a pilot analysis evaluating the utility of a longitudinal, graphic approach to the symptoms of posttraumatic stress disorder (PTSD). Representative patients were instructed in the use of a daily prospective life-chart; they were interviewed and their past medical records were examined for monthly retrospective life-charting. The life charts were used to record life events, activating and inhibiting PTSD symptoms, comorbid symptoms, and treatment. Patients readily completed the prospective life-chart and retrospectively rated symptoms associated with traumatic and nontraumatic life events. Life-charting facilitated longitudinal depiction of the relationship of life experiences to PTSD symptoms and comorbidities, and the tracking of responses to medications. RI Brotman, Melissa/H-7409-2013; Osuch, Elizabeth/B-5009-2015 OI Osuch, Elizabeth/0000-0001-5946-1862 SN 0894-9867 PD JAN PY 2001 VL 14 IS 1 BP 229 EP 239 DI 10.1023/A:1007860204298 UT WOS:000176282900017 ER PT J AU Lu, XB Silver, J AF Lu, XB Silver, J TI Transmission of replication-defective Sindbis helper vectors encoding capsid and envelope proteins SO JOURNAL OF VIROLOGICAL METHODS AB A green fluorescent protein (gfp)-encoding derivative of the replication-defective Sindbis helper vector DHBB was constructed in order to study the rate of packaging of the helper vector. The results show that despite lacking a 'packaging sequence', this vector is co-packaged about 1/300th the rate of packaging of single RNAs containing a packaging sequence. This helps explain the frequent observation of recombinant, replication-competent viruses when using first generation Sindbis packaging systems. Because of their sensitivity, gfp-encoding reporters like the one described here will be useful for measuring transfer of helper RNAs in improved alpha virus packaging systems. (C) 2001 Elsevier Science B.V. All rights reserved. OI Silver, Jonathan/0000-0001-9231-6368 SN 0166-0934 PD JAN PY 2001 VL 91 IS 1 BP 59 EP 65 DI 10.1016/S0166-0934(00)00247-0 UT WOS:000166202000008 PM 11164486 ER PT J AU Perera, R Owen, KE Tellinghuisen, TL Gorbalenya, AE Kuhn, RJ AF Perera, R Owen, KE Tellinghuisen, TL Gorbalenya, AE Kuhn, RJ TI Alphavirus nucleocapsid protein contains a putative coiled coil alpha-helix important for core assembly SO JOURNAL OF VIROLOGY AB The alphavirus nucleocapsid core is formed through the energetic contributions of multiple noncovalent interactions mediated by the capsid protein. This protein consists of a poorly conserved N-terminal region of unknown function and a C-terminal conserved autoprotease domain with a major role in virion formation. In this study, an 18-amino-acid conserved region, predicted to fold into an alpha -helix (helix I) and embedded in a low-complexity sequence enriched with basic and Pro residues, has been identified in the N-terminal region of the alphavirus capsid proteins. In Sindbis virus, helix I spans residues 38 to 55 and contains three conserved leucine residues, L38, L45, and L52, conforming to the heptad amino acid organization evident in leucine zipper proteins. Helix I consists of an N-terminally truncated heptad and two complete heptad repeats,vith beta -branched residues and conserved leucine residues occupying the a and d positions of the helix, respectively. Complete or partial deletion of helix I, or single-site substitutions at the conserved leucine residues (L45 and L52), caused a significant decrease in virus replication. The mutant viruses were more sensitive to elevated temperature than wild-type virus. These mutant viruses also failed to accumulate cores in the cytoplasm of infected cells, although they did not have defects in protein translation or processing. Analysis of these mutants using an in vitro assembly system indicated that the majority were defective in core particle assembly. Furthermore, mutant proteins showed a trans-dominant negative phenotype in in vitro assembly reactions involving mutant and wild-type proteins. We propose that helix I plays a central role in the assembly of nucleocapsid cores through coiled coil interactions. These interactions may stabilize subviral intermediates formed through the interactions of the C-terminal domain of the capsid protein and the genomic RNA and contribute to the stability of the virion. RI Gorbalenya, Alexander/J-4818-2012; Perera, Rushika/E-7183-2017 OI Gorbalenya, Alexander/0000-0002-4967-7341; Perera, Rushika/0000-0001-6798-2537 SN 0022-538X PD JAN PY 2001 VL 75 IS 1 BP 1 EP 10 DI 10.1128/JVI.75.1.1-10.2001 UT WOS:000165863000001 PM 11119567 ER PT J AU Iwashiro, M Peterson, K Messer, RJ Stromnes, IM Hasenkrug, KJ AF Iwashiro, M Peterson, K Messer, RJ Stromnes, IM Hasenkrug, KJ TI CD4(+) T cells and gamma interferon in the long-term control of persistent friend retrovirus infection SO JOURNAL OF VIROLOGY AB We have used the Friend virus model to determine the basic mechanisms by which the immune system can control persistent retroviral infections. Previously we showed that CD4(+) T cells play an essential role in keeping persistent retrovirus in check, The present in vitro experiments with a Friend virus-specific CD4(+) T-cell clone revealed that these cells produce gamma interferon (IPN-gamma), which acts with two distinct mechanisms of antiviral activity. First, IFN-gamma had a direct inhibitory effect on virus production. This inhibitory effect was noncytolytic and, interestingly, was not associated with decreased cell surface expression of viral antigens. The second mechanism of IFN-gamma -mediated antiviral activity was an enhancement of CD4(+) T-cell-mediated cytolytic activity. We also found an in vivo role for IFN-gamma in the control of persistent Friend virus infections, Neutralization of IFN-gamma in persistently infected mice resulted in significantly increased levels of virus in the spleen, and a significant percentage of IFN-gamma -deficient mice were unable to maintain long-term control over Friend virus infections. RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 SN 0022-538X PD JAN PY 2001 VL 75 IS 1 BP 52 EP 60 DI 10.1128/JVI.75.1.52-60.2001 UT WOS:000165863000007 PM 11119573 ER PT J AU Yovandich, JL Chertova, EN Kane, BP Gagliardi, TD Bess, JW Sowder, RC Henderson, LE Gorelick, RJ AF Yovandich, JL Chertova, EN Kane, BP Gagliardi, TD Bess, JW Sowder, RC Henderson, LE Gorelick, RJ TI Alteration of zinc-binding residues of simian immunodeficiency virus p8(NC) results in subtle differences in gag processing and virion maturation associated with degradative loss of mutant NC SO JOURNAL OF VIROLOGY AB In all retroviruses analyzed to date (except for the spumaretroviruses), the Zn2+-coordinating residues of nucleocapsid (NC) perform or assist in crucial reactions necessary to complete the retrovirus life cycle. Six replication-defective mutations have been engineered in the two NC Zn2+ fingers (ZFs) of simian immunodeficiency virus [SIV(Mne)] that change or delete specific Zn2+-interacting Cys residues and were studied by using electron microscopy, reversed-phase high-performance liquid chromatography, immunoblotting, and RNA quantification. We focused on phenotypes of produced particles, specifically morphology, Gag polyprotein processing, and genomic RNA packaging. Phenotypes were similar among viruses containing a point or deletion mutation involving the same ZF. Mutations in the proximal ZF (ZF1) resulted in near-normal Gag processing and full-length genomic RNA incorporation and were most similar to wild-type (WT) virions with electron-dense, conical cores. Mutation of the distal ZF, as well as point mutations in both ZFs, resulted in more unprocessed Gag proteins than a deletion or point mutation in ZF1, with an approximate 30% reduction in levels of full-length genomic RNA in virions. These mutant virions contained condensed teres; however, the cores typically appeared less electron dense and more rod shaped than WT virions. Surprisingly, deletion of both ZFs, including the basic linker region between the ZFs, resulted in the most efficient Gag processing. However, genomic RNA packaging was similar to 10% of WT levels, and those particles produced were highly abnormal with respect to size and core morphology. Surprisingly, all NC mutations analyzed demonstrated a significant loss of processed NC in virus particles, suggesting that Zn2+-coordinated NC is protected from excessive proteolytic cleavage. Together, these results indicate that Zn2+ coordination is important for correct Gag precursor processing and NC protein stability. Additionally, SIV particle morphology appears to be the result of proper and complete Gag processing and relies less on full-length genomic RNA incorporation, as dictated by the Zn2+ coordination in the ZFs of the NC protein. RI Bess, Jr., Julian/B-5343-2012 SN 0022-538X PD JAN PY 2001 VL 75 IS 1 BP 115 EP 124 DI 10.1128/JVI.75.1.115-124.2001 UT WOS:000165863000014 PM 11119580 ER PT J AU Fultz, PN Vance, PJ Endres, MJ Tao, BL Dvorin, JD Davis, IC Lifson, JD Montefiori, DC Marsh, M Malim, MH Hoxie, JA AF Fultz, PN Vance, PJ Endres, MJ Tao, BL Dvorin, JD Davis, IC Lifson, JD Montefiori, DC Marsh, M Malim, MH Hoxie, JA TI In vivo attenuation of simian immunodeficiency virus by disruption of a tyrosine-dependent sorting signal in the envelope glycoprotein cytoplasmic tail SO JOURNAL OF VIROLOGY AB Attenuated simian immunodeficiency viruses (SIVs) have been described that produce low levels of plasma virion RNA and exhibit a reduced capacity to cause disease. These viruses are particularly useful in identifying viral determinants of pathogenesis. In the present study, we show that mutation of a highly conserved tyrosine (Tyr)-containing motif (Yxx phi) in the envelope glycoprotein (Env) cytoplasmic tail (amino acids YRPV at positions 721 to 724) can profoundly reduce the in vivo pathogenicity of SIVmac239. This domain constitutes both a potent endocytosis signal that reduces Env expression on infected cells and a sorting signal that directs Env expression to the basolateral surface of polarized cells. Rhesus macaques were inoculated with SIVmac239 control or SIVmac239 containing either a Tyr-721-to-Ile mutation (SIVmac239Y/I) or a deletion of Tyr-721 and the preceding glycine (Delta GY). To assess the in vivo replication competence, all viruses contained a stop codon in nef that has been shown to revert during in vivo but not in vitro replication. All three control animals developed high viral loads and disease. One of two animals that received SIVmac239Y/I and two of three animals that received SIVmac239 Delta GY remained healthy for up to 140 weeks with low to undetectable plasma viral RNA levels and normal CD4(+) T-cell percentages. These animals exhibited ongoing viral replication as determined by detection of viral sequences and culturing of mutant viruses from peripheral blood mononuclear cells and persistent anti-SN antibody titers. In one animal that received SIVmac239Y/I, the Ile reverted to a Tyr and was associated with a high plasma RNA level and disease, while one animal that received SIVmac239 Delta GY also developed a high viral load that was associated with novel and possibly compensatory mutations in the TM cytoplasmic domain. In all control and experimental animals, the nef stop codon reverted to an open reading frame within the first 2 months of inoculation, indicating that the mutant viruses had replicated well enough to repair this mutation. These findings indicate that the Yxx phi signal plays an important role in SIV pathogenesis. Moreover, because mutations in this motif may attenuate SN through mechanisms that are distinct from those caused by mutations in nef, this Tyr-based sorting signal represents a novel target for future models of SIV and human immunodeficiency virus attenuation that could be useful in new vaccine strategies. RI Marsh, Mark/B-4105-2009; OI Marsh, Mark/0000-0002-0213-3259; Malim, Michael/0000-0002-7699-2064 SN 0022-538X PD JAN PY 2001 VL 75 IS 1 BP 278 EP 291 DI 10.1128/JVI.75.1.278-291.2001 UT WOS:000165863000032 PM 11119598 ER PT J AU Wolffe, EJ Weisberg, AS Moss, B AF Wolffe, EJ Weisberg, AS Moss, B TI The vaccinia virus A33R protein provides a chaperone function for viral membrane localization and tyrosine phosphorylation of the A36R protein SO JOURNAL OF VIROLOGY AB The products of the A33R and A36R genes of vaccinia virus are incorporated into the membranes of intracellular enveloped virions (IEV). When extracts of cells that had been infected with vaccinia virus and labeled with (H3PO4)-P-32 were immunoprecipitated with antibodies against the A33R protein, two prominent bands were resolved. The moderately and more intensely labeled bands were identified as phosphorylated A33R and A36R proteins, respectively. The immunoprecipitated complex contained disulfide-bonded dimers of A33R protein that were noncovalently linked to A36R protein. Biochemical analysis indicated that the two proteins were phosphorylated predominantly on serine residues, with lesser amounts on threonines. The A36R protein was also phosphorylated on tyrosine, as determined by specific binding to an anti-phosphotyrosine antibody. Serine phosphorylation and A33R-A36R protein complex formation occurred even when virus assembly was blocked at an early stage with the drug rifampin. Tyrosine phosphorylation was selectively reduced in cells infected with F13L or A34R gene deletion mutants that were impaired in the membrane-wrapping step of IEV formation. In addition, tyrosine phosphorylation was specifically inhibited in cells infected with an A33R deletion mutant that still formed IEV. Immunofluorescence and immunoelectron microscopy indicated that in the absence of the A33R protein, the A36R protein was localized in Golgi membranes but not in IEV. In the absence of the A36R protein, however, the A33R protein still localized to IEV membranes. These studies together with others suggest that the A33R protein guides the A36R protein to the IEV membrane, where it subsequently becomes tyrosine phosphorylated as a signal for actin tail formation. SN 0022-538X PD JAN PY 2001 VL 75 IS 1 BP 303 EP 310 DI 10.1128/JVI.75.1.303-310.2001 UT WOS:000165863000034 PM 11119600 ER PT J AU Van, PL Yim, KW Jin, DY Dapolito, G Kurimasa, A Jeang, KT AF Van, PL Yim, KW Jin, DY Dapolito, G Kurimasa, A Jeang, KT TI Genetic evidence of a role for ATM in functional interaction between human T-cell leukemia virus type 1 Tax and p53 SO JOURNAL OF VIROLOGY AB Recent evidence from several investigators suggest that the human T-cell leukemia virus type 1 Tax oncoprotein represses the transcriptional activity of the tumor suppressor protein, p53. An examination of published findings reveals serious controversy as to the mechanism(s) utilized by Tax to inhibit p53 activity and whether the same mechanism is used by Tax in adherent and suspension cells. Here, we have investigated Tax-p53 interaction simultaneously in adherent epithelial (HeLa and Saos) and suspension T-lymphocyte (Jurkat) cells. Our results indicate that Tax activity through the CREB/CREB-binding protein (CBP), but not NF-kappaB, pathway is needed to repress the transcriptional activity of p53 in all tested cell lines. However, we did find that while CBP binding by Tax is necessary, it is not sufficient for inhibiting p53 function. Based on knockout cell studies, we correlated a strong genetic requirement for the ATM, but not protein kinase-dependent DNA, protein in conferring a Tax-p53-repressive phenotype. RI Jeang, Kuan-Teh/A-2424-2008 SN 0022-538X PD JAN PY 2001 VL 75 IS 1 BP 396 EP 407 DI 10.1128/JVI.75.1.396-407.2001 UT WOS:000165863000042 PM 11119608 ER PT J AU Earl, PL Sugiura, W Montefiori, DC Broder, CC Lee, SA Wild, C Lifson, J Moss, B AF Earl, PL Sugiura, W Montefiori, DC Broder, CC Lee, SA Wild, C Lifson, J Moss, B TI Immunogenicity and protective efficacy of oligomeric human immunodeficiency virus type 1 gp140 SO JOURNAL OF VIROLOGY AB The biologically active form of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein is oligomeric. We previously described a soluble HIV-1 IIIB Env protein, gp140, with a stable oligomeric structure composed of uncleaved gp120 linked to the ectodomain of gp41 (P. L. Earl, C. C. Broder, D. Long, S. A. Lee, J. Peterson, S. Chakrabarti, R W Doms, and B. Moss, J, Virol. 68:3015-3026, 1994). Here we compared the antibody responses of rabbits to gp120 and gp140 that had been produced and purified in an identical manner. The gp140 antisera exhibited enhanced cross-reactivity with heterologous Env proteins as well as greater neutralization of HIV-1 compared to the gp120 antisera. To examine both immunogenicity and protective efficacy, we immunized rhesus macaques with oligomeric gp140. Strong neutralizing antibodies against a homologous virus and modest neutralization of heterologous laboratory-adapted isolates were elicited. No neutralization of primary isolates was observed. However, a substantial fraction of the neutralizing activity could not be blocked by a V3 loop peptide. After intravenous challenge with simian-HIV virus SHN-HXB2, three of the four vaccinated macaques exhibited no evidence of virus replication. SN 0022-538X PD JAN PY 2001 VL 75 IS 2 BP 645 EP 653 DI 10.1128/JVI.75.2.645-653.2001 UT WOS:000166015000011 PM 11134278 ER PT J AU Dittmer, U Peterson, KE Messer, R Stromnes, IM Race, B Hasenkrug, KJ AF Dittmer, U Peterson, KE Messer, R Stromnes, IM Race, B Hasenkrug, KJ TI Role of interleukin-4 (IL-4), IL-12, and gamma interferon in primary and vaccine-primed immune responses to Friend retrovirus infection SO JOURNAL OF VIROLOGY AB The immunological resistance of a host to viral infections may be strongly influenced by cytokines such as interleukin-12 (IL-12) and gamma interferon (IFN-gamma), which promote T helper type I responses, and IL-4, which promotes T helper type 2 responses. We studied the role of these cytokines during primary and secondary immune responses against Friend retrovirus infections in mice. IL-4- and IL-12-deficient mice were comparable to wild-type B6 mice in the ability to control acute and persistent Friend virus infections. In contrast, more than one-third of the IFN-gamma -deficient mice were unable to maintain long-term control of Friend virus and developed gross splenomegaly with high virus loads. Immunization with a live attenuated vaccine virus prior to challenge protected all three types of cytokine-deficient mice from viremia and high levels of spleen virus despite the finding that the vaccinated IFN-gamma -deficient mice were unable to class switch from immunoglobulin hi (IgM) to IgG virus-neutralizing antibodies. The results indicate that IFN-gamma plays an important role during primary immune responses against Friend virus but is dispensable during vaccine-primed secondary responses. RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 SN 0022-538X PD JAN PY 2001 VL 75 IS 2 BP 654 EP 660 DI 10.1128/JVI.75.2.654-660.2001 UT WOS:000166015000012 PM 11134279 ER PT J AU Driscoll, MD Golinelli, MP Hughes, SH AF Driscoll, MD Golinelli, MP Hughes, SH TI In vitro analysis of human immunodeficiency virus type 1 minus-strand strong-stop DNA synthesis and genomic RNA processing SO JOURNAL OF VIROLOGY AB Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), nucleocapsid protein (NC), genomic RNA, and the growing DNA strand all influence the copying of the HIV-1 RNA genome into DNA, A detailed understanding of these activities is required to understand the process of reverse transcription. HIV-1 viral DNA is initiated from a tRNA(3)(Lys) primer bound to the viral genome at the primer binding site. The U3 and R regions of the RNA genome are the first sequences to be copied. The TAR hairpin, a structure found within the R region of the viral genome, is the site of increased RT pausing, RNase H activity, and RT dissociation. Template RNA was digested approximately 17 bases behind the site where polymerase paused at the base of TAR In most template RNAs, this was the only cleavage made by the RT responsible for initiating polymerization. If the RT that initiated DNA synthesis dissociated from the base of the TAR hairpin and an RT rebound at the end of the primer, there was competition between the polymerase and RNase H activities. After the complete heteroduplex was formed, there were additional RNase H cleavages that did not involve polymerization. Levels of NC that prevented TAR DNA self-priming did not protect genomic RNA from RNase H digestion. RNase H digestion of the 100-bp heteroduplex produced a 14-base RNA from the 5' end of the RNA that remained annealed to the 3' end of the minus-strand strong-stop DNA only if NC was present in the reaction. RI Golinelli, Marie-Pierre/K-4287-2013 OI Golinelli, Marie-Pierre/0000-0002-6738-8631 SN 0022-538X PD JAN PY 2001 VL 75 IS 2 BP 672 EP 686 DI 10.1128/JVI.75.2.672-686.2001 UT WOS:000166015000014 PM 11134281 ER PT J AU Silberstein, E Dveksler, G Kaplan, GG AF Silberstein, E Dveksler, G Kaplan, GG TI Neutralization of hepatitis A virus (HAV) by an immunoadhesin containing the cysteine-rich region of HAV cellular receptor-1 SO JOURNAL OF VIROLOGY AB Hepatitis A virus (HAV) infects African green monkey kidney (AGR IK) cells via the HAV cellular receptor-1 (havcr-1), a mucin-like type 1 integral-membrane glycoprotein of unknown natural function. The ectodomain of havcr-1 contains an N-terminal immunoglobulin-like cysteine-rich region (D1), which binds protective monoclonal antibody (MAb) 190/4, followed by an O-glycosylated mucin-like threonine-serine-proline-rich region that extends D1 well above the cell surface. To study the interaction of HAV with havcr-1, we constructed immunoadhesins fusing the hinge and Fc portion of human IgG1 to D1 (D1-Fc) or the ectodomain of the poliovirus receptor (PVR-Fc) and expressed them in CHO cells. These immunoadhesins,were secreted to the cell culture medium and purified through protein A-agarose columns. In a solid-phase assay, HAV bound to D1-Fc in a concentration-dependent manner whereas background levels of HAV bound to PVR-Fc. Binding of HAV to D1-Fc was blocked by treatment with MAb 190/4 but not with control MAb, M2, which binds to a tag epitope introduced between the D1 and Fe portions of the immunoadhesin. D1-Fc neutralized approximately 1 log unit of the HAV infectivity in AGMK cells, whereas PVR-Fc had no effect in the HAV titers. A similarly poor reduction in HAV titers was observed after treating the same stock of HAV with murine neutralizing MAbs K2-4F2, K3-4C8, and VHA 813. Neutralization of poliovirus by PVR-Fc but not by D1-Fc indicated that the virus-receptor interactions were specific. These results show that D1 is sufficient for binding and neutralization of HAV and provide further evidence that havcr-1 is a functional cellular receptor for HAV. SN 0022-538X PD JAN PY 2001 VL 75 IS 2 BP 717 EP 725 DI 10.1128/JVI.75.2.717-725.2001 UT WOS:000166015000018 PM 11134285 ER PT J AU Dang, Q Hu, WS AF Dang, Q Hu, WS TI Effect of homology length in the repeat region on minus-strand DNA transfer and retroviral replication SO JOURNAL OF VIROLOGY AB Homology between the two repeat (R) regions in the retroviral genome mediates minus strand DNA transfer during reverse transcription. We sought to define the effects of R homology lengths on minus-strand DNA transfer. We generated five murine leukemia virus (MLV)-based vectors that contained identical sequences but different lengths of the 3' R (3, 6, 12, 24 and 69 nucleotides [nt]); 69 nt is the full-length MLV R. After one round of replication, viral titers from the vector with a full-length downstream R were compared with viral titers generated from the other four vectors with reduced R lengths. Viral titers generated from vectors with R lengths reduced to one-third (24 nt) or one-sixth (12 nt) that of the wild type were not significantly affected; however, viral titers generated from vectors with only 3- or 6-nt homology in the R region were significantly lower. Because expression and packaging of the RNA were similar among all the vectors, the differences in the viral titers most likely reflected the impact of the homolog lengths on the efficiency of minus-strand DNA transfer. The molecular nature of minus-strand DNA transfer was characterized in 63 proviruses. Precise R-to-R transfer was observed in most proviruses generated from vectors with 12-, 24-, or 69-nt homology in R, whereas aberrant transfers were predominantly used to generate proviruses from vectors with 3- or 6-nt homology. Reverse transcription using RNA transcribed from an upstream promoter, termed read-in RNA transcripts, resulted in most of the aberrant transfers. These data demonstrate that minus-strand DNA transfer is homolog driven and a minimum homology length is required for accurate and efficient minus-strand DNA transfer. SN 0022-538X PD JAN PY 2001 VL 75 IS 2 BP 809 EP 820 DI 10.1128/JVI.75.2.809-820.2001 UT WOS:000166015000027 PM 11134294 ER PT J AU Manas, S Cena, JC Ruiz-Olmo, J Palazon, S Domingo, M Wolfinbarger, JB Bloom, ME AF Manas, S Cena, JC Ruiz-Olmo, J Palazon, S Domingo, M Wolfinbarger, JB Bloom, ME TI Aleutian mink disease parvovirus in wild riparian carnivores in Spain SO JOURNAL OF WILDLIFE DISEASES AB Serious declines in populations of native European mink (Mustela lutreola) have occurred in Europe. One responsible factor may be infectious diseases introduced by exotic American mink (Mustela vison). In order to investigate a possible role for Aleutian mink disease parovirus (ADV), we surveyed native riparian carnivores and feral American mink. When serum samples from 12 free-ranging European and 16 feral American mink were tested, antibodies to ADV were detected from three of nine European mink. ADV DNA was detected by polymerase chain reaction in whole cell DNA from four of seven carcasses; two American mink, one European mink and a Eurasian otter (Lutra lutra). Lesions typical of Aleutian disease were present in one of the American mink. A portion of the ADV VP2 capsid gene was sequenced and the results suggested that two sequence types of ADV were circulating in Spain, and that the Spanish ADVs differed from other described isolates from North America and Europe. Future conservation and restoration efforts should include measures to avoid introduction or spread of ADV infection to native animals. RI Domingo, Mariano/A-1015-2009 OI Domingo, Mariano/0000-0002-9623-4826 SN 0090-3558 PD JAN PY 2001 VL 37 IS 1 BP 138 EP 144 UT WOS:000167011600017 PM 11272488 ER PT J AU Haller, JW Westerman, B Vannier, MW AF Haller, John W. Westerman, Bryan Vannier, Michael W. TI Multirow detector CT technology: Present and future SO JOURNAL OF X-RAY SCIENCE AND TECHNOLOGY AB Multirow CT detectors coupled with 2, 4, 8 and 16 or more simultaneous data acquisition channels are now used in clinical imaging. Furthermore, multirow CT detectors are used with conventional or flat-panel image intensifiers mounted on c-arms that allow 3D CT scanning in rotational angiography or orthopedic interventions. These multirow, multichannel CT systems provide increased speed that translates into the ability to scan larger segments of anatomy more quickly. The principal drawback of multislice/multidector/multichannel CT scanners are increased computational burden, faster data rates, more voluminous data sets, and most importantly, the requirement to use cone beam rather than slice-by-slice reconstruction algorithms. The future of multichannel CT in clinical applications demands improved radiation dose efficiency, isotropic imaging, tailored cone beam reconstruction algorithms, and post-processing visualization of volume image data. SN 0895-3996 PY 2001 VL 10 IS 1-2 BP 127 EP 138 UT WOS:000207066600010 ER PT J AU Anisimov, SV Volkova, MV Lenskaya, LV Khavinson, VK Solovieva, DV Schwartz, EI AF Anisimov, SV Volkova, MV Lenskaya, LV Khavinson, VK Solovieva, DV Schwartz, EI TI Age-associated accumulation of the apolipoprotein C-III gene T-455C polymorphism C allele in a Russian population SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES AB Apolipoprotein C-III (apoC-III) is the major component of triglyceride-rich lipoproteins. One of six identified polymorphisms in the apoC-III 5'-untranslated region (T-455C) is located within a functional insulin-response element. In a group of 137 elderly individuals (70-106 gears old), the allele distribution was analyzed using restriction fragment length polymorphisms. Statistical analysis of allele frequencies was performed on subgroups selected by age and in elderly patients with arterial hypertension or ischemic heart disease. A greater frequency of the apoC-III -455C allele was demonstrated with aging ( p.005). No statistically significant difference in allele distributions was detected between healthy subjects and groups of elderly patients of the same age with either ischemic heart disease or arterial hypertension. The increased incidence of the C allele with advanced age indicates that this variant promoter is associated with longevity. The greater incidence of this allele is detectable only in adults older than 80 years of age. RI Khavinson, Vladimir/N-9908-2014 OI Khavinson, Vladimir/0000-0001-7547-7725 SN 1079-5006 PD JAN PY 2001 VL 56 IS 1 BP B27 EP B32 UT WOS:000166260000004 PM 11193221 ER PT J AU Resnick, HE Vinik, AI Heimovitz, HK Brancati, FL Guralnik, JM AF Resnick, HE Vinik, AI Heimovitz, HK Brancati, FL Guralnik, JM TI Age 85+years accelerates large-fiber peripheral nerve dysfunction and diabetes contributes even in the oldest-old: The Women's Health and Aging Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES AB Background. Both diabetes mellitus and advancing age are associated with peripheral nerve dysfunction (PND). However, the independent and potentially synergistic effects of these factors in old age are poorly described, especially among the oldest-old and among people with an existing disability. Methods. A total of 894 women aged 65+ years participating in the Women's Health and Aging Study received a baseline home interview and clinical examination during which PND was evaluated by the Vibratron II. Age and diabetes were examined in relation to the level of PND (normal, mild, moderate, or severe). Height, alcohol consumption, smoking, report of neurologic symptoms, and diabetes duration were examined as potential confounders. Results. Eighteen percent of the sample reported diabetes, 42% had normal nerve function, and 23.9%, 14.5%. and 19.5% had mild, moderate, and severe PND, respectively. Women aged 85 + years had 6.5. 7.5, and 13.3 times the odds of mild, moderate, and severe PND relative to women aged 65-74 years, adjusted for diabetes and height. Women who reported diabetes had 1.8, 2.4, and 1.6 times the risk of mild, moderate, and severe PND relative to those who did not, adjusted for age and height. No interaction between age and diabetes was observed. Conclusions, Age is strongly associated with decrements in large-fiber peripheral nerve function in disabled women aged 65+ years, with greatly accelerated risk among those aged 85+ years. Despite the overwhelmingly strong effects of advancing age on PND in this cohort, diabetes remains a significant correlate of PND. Future studies may determine whether prevention or control of diabetes is effective in reducing the occurrence of PND in old age and whether a reduction in PND will translate into reduced disability in this age group. SN 1079-5006 PD JAN PY 2001 VL 56 IS 1 BP M25 EP M31 UT WOS:000166260000012 PM 11193228 ER PT J AU Simonsick, EM Kasper, JD Guralnik, JM Bandeen-Roche, K Ferrucci, L Hirsch, R Leveille, S Rantanen, T Fried, LP AF Simonsick, EM Kasper, JD Guralnik, JM Bandeen-Roche, K Ferrucci, L Hirsch, R Leveille, S Rantanen, T Fried, LP CA WHAS Res Grp TI Severity of upper and lower extremity functional limitation: Scale development and validation with self-report and performance-based measures of physical function SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES AB Objectives. To better understand disablement and transitions from impairment to disability, discrete valid measures of functional limitation are needed. This study reports the development and criterion-related validity of scales that quantify severity of upper and lower extremity functional limitation. Methods. Data are from 3,635 cognitively intact community-dwelling women aged 65 years and older and 1,002 moderately to severely disabled participants in the Women's Health and Aging Study. Scales assessing severity of upper and lower extremity functional limitation were constructed from commonly available questions on functional difficulty. Criterion-related validity was evaluated with self-report and performance-based measures. Results. The upper and lower extremity scales range from 0 to 6 and 0 to 9, respectively. Scale scores were well distributed in the disabled group and discriminated limitations in the broader community. For both scales, rates of difficulty for all ADL and IADL increased (p < .001) with increasing severity score, and percent able and mean performance on respective upper and lower extremity tasks decreased (p < .01). Discussion. These scales, constructed from commonly used self-report measures of function, provide discrete measures of upper and lower functional limitation. Because these scales are distinct from measures of disability and impairment, their use should facilitate increased understanding of the disablement process. RI Rantanen, Taina/O-6579-2016 OI Rantanen, Taina/0000-0002-1604-1945 SN 1079-5014 PD JAN PY 2001 VL 56 IS 1 BP S10 EP S19 UT WOS:000166213500009 PM 11192340 ER PT J AU Lowery, T Dinterman, S Weigand, K Brown, B Walker, L AF Lowery, T Dinterman, S Weigand, K Brown, B Walker, L TI A cart cage for transferring macaques, capuchins, and small dogs SO LAB ANIMAL AB A novel mobile monkey transport cart cage allows ease of handling, safety, secure holding, good visual access to the monkeys, room for large macaques, and ease of assembly, all at a modest cost. SN 0093-7355 PD JAN PY 2001 VL 30 IS 1 BP 45 EP 46 UT WOS:000166161400011 PM 11385727 ER PT J AU Ducatman, B Cox-Ganser, J Stead, J Maymind, M Saffiotti, U AF Ducatman, B Cox-Ganser, J Stead, J Maymind, M Saffiotti, U TI Lymph node silicosis and pulmonary silicosis: An autopsy study SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 12 BP 6A EP 6A UT WOS:000166634900025 ER PT J AU Illei, P Allander, SV Chen, Y Meltzer, PS Antonescu, CR Ladanyi, M AF Illei, P Allander, SV Chen, Y Meltzer, PS Antonescu, CR Ladanyi, M TI Prominent Her2/neu expression in the epithelial component of synovial sarcoma. SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 56 BP 13A EP 13A UT WOS:000166634900069 ER PT J AU Merino, MJ Bryant, B Sobel, M Cowan, K Chiesa, A AF Merino, MJ Bryant, B Sobel, M Cowan, K Chiesa, A TI Frequency of loss of heterozygosity (LOH) of metastasis-related tumor suppressor genes in young women with breast cancer. SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 168 BP 32A EP 32A UT WOS:000166634900181 ER PT J AU Weaver, DL Bocklage, T Platz, CE Key, CR Cronin, K Harlan, LC Ballard-Barbash, R Warren, JL AF Weaver, DL Bocklage, T Platz, CE Key, CR Cronin, K Harlan, LC Ballard-Barbash, R Warren, JL TI Comparison of nuclear grade and overall grade in ductal carcinoma-in-situ (DCIS) SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 222 BP 41A EP 41A UT WOS:000166634900235 ER PT J AU Weaver, DL Bocklage, T Key, CR Platz, CE Cronin, K Harlan, LC Ballard-Barbash, R Warren, JL AF Weaver, DL Bocklage, T Key, CR Platz, CE Cronin, K Harlan, LC Ballard-Barbash, R Warren, JL TI Inter-observer variability in interpretation of ductal carcinoma-in-situ (DCIS) reports as compared to variability in interpretation of slides SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 221 BP 41A EP 41A UT WOS:000166634900234 ER PT J AU Clark, B Vezza, P Abati, A AF Clark, B Vezza, P Abati, A TI Diagnostic sensitivity of pulmonary FNA vs BAL SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 276 BP 50A EP 50A UT WOS:000166634900289 ER PT J AU Dahmoush, L Hijazi, Y Barnes, E Stetler-Stevenson, MA Abati, A AF Dahmoush, L Hijazi, Y Barnes, E Stetler-Stevenson, MA Abati, A TI Adult T-cell leukemia/lymphoma (ATLL): A cytopathological, immunocytochemical and flow cytometric study. SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 281 BP 51A EP 51A UT WOS:000166634900294 ER PT J AU Fetsch, PA Steinberg, SM Riker, AI Marincola, FM Abati, A AF Fetsch, PA Steinberg, SM Riker, AI Marincola, FM Abati, A TI Melanoma antigen expression in serial FNAs in patients with metastatic malignant melanoma participating in immunotherapy clinical trials - A preliminary look. SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 292 BP 52A EP 52A UT WOS:000166634900305 ER PT J AU Fetsch, PA Brosky, K Simsir, A Abati, A AF Fetsch, PA Brosky, K Simsir, A Abati, A TI Preparation of effusion cytology samples for optimal immunocytochemistry: A comparison of cytospins vs. ThinPrep (TM) vs. cell blocks. SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 291 BP 52A EP 52A UT WOS:000166634900304 ER PT J AU Filie, A Simone, N Simone, C Petricoin, E Liotta, LA Abati, A AF Filie, A Simone, N Simone, C Petricoin, E Liotta, LA Abati, A TI Proteomic evaluation of archival FNA patient samples of papillary thyroid carcinoma and follicular variant of papillary thyroid carcinoma yields distinct protein fingerprints with potential diagnostic applications. SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 293 BP 53A EP 53A UT WOS:000166634900306 ER PT J AU Panizo, A Roberts, D Al-Barazi, H Bryant, B Garcia-Macias, MC Chiesa, A Pardo, J Merino, MJ AF Panizo, A Roberts, D Al-Barazi, H Bryant, B Garcia-Macias, MC Chiesa, A Pardo, J Merino, MJ TI Utilization of cytology smears and manual micro-dissection for proteomic analysis. SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 330 BP 59A EP 59A UT WOS:000166634900343 ER PT J AU Simone, N Fetsch, P Filie, A Marincola, F Simone, C Petricoin, E Liotta, LA Abati, A AF Simone, N Fetsch, P Filie, A Marincola, F Simone, C Petricoin, E Liotta, LA Abati, A TI Proteomic evaluation of archival FNAs: New vistas in diagnoses SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 349 BP 62A EP 62A UT WOS:000166634900362 ER PT J AU Simsir, A Fetsch, PA Abati, A AF Simsir, A Fetsch, PA Abati, A TI Comparison of antibodies to HBME-1 and calretinin for the detection of mesothelial cells in effusion cytology. SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 350 BP 62A EP 62A UT WOS:000166634900363 ER PT J AU Rosenblatt, KP Finkelstein, SE Cassarino, DS Fischette, M Barnes, E Duray, PH AF Rosenblatt, KP Finkelstein, SE Cassarino, DS Fischette, M Barnes, E Duray, PH TI Rapidly progressive melanoma (RPA) SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 412 BP 72A EP 72A UT WOS:000166634900425 ER PT J AU Bordi, C Ferraro, G Azzoni, C Corleto, V Gibril, F Delle Fave, G Jensen, RT AF Bordi, C Ferraro, G Azzoni, C Corleto, V Gibril, F Delle Fave, G Jensen, RT TI The antral mucosa as a new site for endocrine tumors in MEN-1/Zollinger-Ellison syndromes SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 422 BP 74A EP 74A UT WOS:000166634900435 ER PT J AU Park, CS Kim, HS Joo, YE Jung, JJ Kang, HS Nam, JH Messam, CA Min, KW AF Park, CS Kim, HS Joo, YE Jung, JJ Kang, HS Nam, JH Messam, CA Min, KW TI Comparative evaluation of angiogenesis in gastric adenocarcinoma by immunoreactivity for nestin and CD34 SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 536 BP 93A EP 93A UT WOS:000166634900549 ER PT J AU Cheng, L Bostwick, DG Li, G Vortmeyer, AO Zhuang, ZP AF Cheng, L Bostwick, DG Li, G Vortmeyer, AO Zhuang, ZP TI Allelic loss of chromosome 9p21 and 17p13 in metastatic progression of bladder cancer SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 603 BP 104A EP 104A UT WOS:000166634900616 ER PT J AU Chiesa, A Sobel, M Bryant, B Panizo, A Linehan, WM Merino, MJ AF Chiesa, A Sobel, M Bryant, B Panizo, A Linehan, WM Merino, MJ TI Somatic mutations and loss of heterozygosity of the VHL tumor suppressor gene in unclassified renal cell carcinomas SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 606 BP 105A EP 105A UT WOS:000166634900619 ER PT J AU Panizo, A Bryant, B Chiesa, A Walther, MM Linehan, WM Merino, MJ AF Panizo, A Bryant, B Chiesa, A Walther, MM Linehan, WM Merino, MJ TI Molecular analysis of aggressive chromophobe renal cell carcinoma. SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 695 BP 120A EP 120A UT WOS:000166634900708 ER PT J AU Staebler, A Heselmeyer-Haddad, K Bell, K Riopel, M Perlman, E Ried, T Kurman, R AF Staebler, A Heselmeyer-Haddad, K Bell, K Riopel, M Perlman, E Ried, T Kurman, R TI Micropapillary serous carcinoma (MPSC) of the ovary has distinct chromosomal imbalances by comparative genomic hybridiation (CGH) compared with atypical proliferative serous tumors (APST) and serous carcinoma (SC). SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 855 BP 146A EP 146A UT WOS:000166634900868 ER PT J AU Beaty, MW Toro, J Sorbara, L Stern, JB Wilson, WW Jaffe, ES AF Beaty, MW Toro, J Sorbara, L Stern, JB Wilson, WW Jaffe, ES TI Cutaneous lymphomatoid granulomatosis: A clinicopathologic study SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 913 BP 156A EP 156A UT WOS:000166634900926 ER PT J AU Cong, PJ Raffeld, M Jaffe, E AF Cong, PJ Raffeld, M Jaffe, E TI Blastic NK cell lymphoma/leukemia: A clinicopathological study of 23 cases SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 938 BP 160A EP 160A UT WOS:000166634900951 ER PT J AU Greiner, TC Fang, N Weisenburger, DD Chan, WC Hock, L Collins, F Hacia, J AF Greiner, TC Fang, N Weisenburger, DD Chan, WC Hock, L Collins, F Hacia, J TI Mutations do not predict outcome or p53 mutation status in mantle cell lymphoma SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 966 BP 165A EP 165A UT WOS:000166634900979 ER PT J AU Hedvat, CV Asherov, M Qin, J Linkov, I Filippa, DA Tosato, G Jaffe, ES Teruya-Feldstein, J AF Hedvat, CV Asherov, M Qin, J Linkov, I Filippa, DA Tosato, G Jaffe, ES Teruya-Feldstein, J TI Monocyte derived chemotactic factor (MDC), is expressed by Reed-Sternberg (RS) cells in classical Hodgkin's disease (CHD) using tissue arrays SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 969 BP 165A EP 165A UT WOS:000166634900982 ER PT J AU Huang, JZ Greiner, TC Lynch, JC Staudt, LM Weisenburger, DD Armitage, JO Chan, WC AF Huang, JZ Greiner, TC Lynch, JC Staudt, LM Weisenburger, DD Armitage, JO Chan, WC TI Gene expression profile associated with T-cell infiltration in diffuse large B-cell lymphoma analyzed by cDNA microarray SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 977 BP 167A EP 167A UT WOS:000166634900990 ER PT J AU Huang, JZ Sanger, WG Pickering, DL Greiner, TC Staudt, LM Lynch, JC Weisenburger, DD Armitage, JO Chan, WC AF Huang, JZ Sanger, WG Pickering, DL Greiner, TC Staudt, LM Lynch, JC Weisenburger, DD Armitage, JO Chan, WC TI CD10, bcl-2, and bcl-6 protein expression and t(14;18)(q32;q21) in two subtypes of diffuse large B-cell lymphoma defined by gene expression profiles SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 978 BP 167A EP 167A UT WOS:000166634900991 ER PT J AU Sobocinski, G Shaw, S Anderson, A Kaldjian, E AF Sobocinski, G Shaw, S Anderson, A Kaldjian, E TI Immunohistochemical localization of extra-cellular matrix proteins of the lymph node reticular network. SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 1052 BP 179A EP 179A UT WOS:000166634901065 ER PT J AU Taddesse-Heath, L Sorbara, L Raffeld, M Jaffe, ES AF Taddesse-Heath, L Sorbara, L Raffeld, M Jaffe, ES TI Marginal zone B-cell lymphoma in pediatric and young adults. SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 1057 BP 180A EP 180A UT WOS:000166634901070 ER PT J AU Lei, JY Mont, E Bryant-Greenwood, P Linehan, WM Merino, MJ Duray, PH AF Lei, JY Mont, E Bryant-Greenwood, P Linehan, WM Merino, MJ Duray, PH TI A new spectrum of the pancreatic tumors in von Hippel-Lindau disease SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 1171 BP 199A EP 199A UT WOS:000166634901184 ER PT J AU Nicholson, SA Khan, MA Welsh, JA McMenamin, MG Travis, WD Harris, CC AF Nicholson, SA Khan, MA Welsh, JA McMenamin, MG Travis, WD Harris, CC TI Inactivation of p14ARF and p53 are inversely correlated in human cell lines. SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 1248 BP 212A EP 212A UT WOS:000166634901261 ER PT J AU Kumaki, F Kawai, T Churg, A Gallateau-Salle, FB Haselton, P Henderson, D Roggli, V Travis, WD Cagle, P Ferrans, VJ AF Kumaki, F Kawai, T Churg, A Gallateau-Salle, FB Haselton, P Henderson, D Roggli, V Travis, WD Cagle, P Ferrans, VJ TI Expression of telomerase reverse transcriptase (TERT) in malignant mesothelioma SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 1309 BP 222A EP 222A UT WOS:000166634901322 ER PT J AU Kumaki, L Matsui, K Valencia, J Yu, Z Kawai, T Ozaki, Y Ferrans, VJ Travis, WD AF Kumaki, L Matsui, K Valencia, J Yu, Z Kawai, T Ozaki, Y Ferrans, VJ Travis, WD TI Expression of matrix metalloproteinases (MMPs) in pulmonary adenocarcinoma showing lepidic growth (ALG) and atypical adenomatous hyperplasia (AAH) SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 1308 BP 222A EP 222A UT WOS:000166634901321 ER PT J AU Nicholson, SA Khan, MA Welsh, JA Travis, WD Bennett, W Battey, J Marrogi, A Jett, JR Tazelaar, HD Trastek, V Pairolero, PC Liotta, LA Caporaso, NE Harris, CC AF Nicholson, SA Khan, MA Welsh, JA Travis, WD Bennett, W Battey, J Marrogi, A Jett, JR Tazelaar, HD Trastek, V Pairolero, PC Liotta, LA Caporaso, NE Harris, CC TI Gastrin-releasing peptide receptor (GRPR) expression in non-small cell lung carcinoma (NSCLC) SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 1321 BP 224A EP 224A UT WOS:000166634901334 ER PT J AU Nicholson, SA Khan, MA Welsh, JA Travis, WD Okby, N Bennett, W Przygodzki, R Jett, JR Tazelaar, HD Trastek, V Pairolero, PC Liotta, LA Caporaso, NE Harris, CC AF Nicholson, SA Khan, MA Welsh, JA Travis, WD Okby, N Bennett, W Przygodzki, R Jett, JR Tazelaar, HD Trastek, V Pairolero, PC Liotta, LA Caporaso, NE Harris, CC TI p14ARF deletion is associated with poor prognosis in non-small cell lung carcinoma (NSCLC) SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 1322 BP 224A EP 224A UT WOS:000166634901335 ER PT J AU Rodrigues, RG Panizo, A Cashel, JA Krutzsch, HC Merino, MJ Roberts, D AF Rodrigues, RG Panizo, A Cashel, JA Krutzsch, HC Merino, MJ Roberts, D TI Proteomic detection of ectopically expressed semenogelins in small cell carcinoma of lung. A possible new marker for diagnosis. SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 1331 BP 226A EP 226A UT WOS:000166634901344 ER PT J AU Valencia, JC Virador, V Escobar, JC Moss, J Ferrans, VJ AF Valencia, JC Virador, V Escobar, JC Moss, J Ferrans, VJ TI Localization of tissue angiotensin system in pulmonary lymphangioleiomyomatosis (LAM) SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 1338 BP 227A EP 227A UT WOS:000166634901351 ER PT J AU Chiesa, A Sobel, M Merino, MJ Linehan, WM Bryant, B AF Chiesa, A Sobel, M Merino, MJ Linehan, WM Bryant, B TI DNA sequencing of microdissected paraffin-embedded tissues SO LABORATORY INVESTIGATION SN 0023-6837 EI 1530-0307 PD JAN PY 2001 VL 81 IS 1 MA 1363 BP 231A EP 231A UT WOS:000166634901376 ER PT J AU Peter, J AF Peter, J TI Take control of your career through personal responsibility SO LABORATORY MEDICINE SN 0007-5027 PD JAN PY 2001 VL 32 IS 1 BP 24 EP 25 UT WOS:000166848600004 ER PT J AU Smith, KA Sequeira, E AF Smith, KA Sequeira, E TI Linking at the US National Library of Medicine SO LEARNED PUBLISHING AB The development of services provided by the National Library of Medicine (NLM), which dates back to 1836, is described. MEDLINE, a database of 10-plus million references and abstracts to the world's biomedical literature, was put on the World Wide Web for free searching in 1997 as a system called PubMed, whose use has grown to over 250 million searches per year. PubMed features a variety of links between MEDLINE references and related information - full-text journal articles, DNA sequence data, medical knowledge bases, etc. - at websites within and outside NLM. PubMed is a major component of a larger NLM system, Entrez, which integrates access to a number of genome-related databases with linking features similar to those of PubMed. The newest linked service, which became a reality in February 2000, is PubMed Central, the National Institutes of Health's free repository fbr primary research reports in all the life sciences. SN 0953-1513 PD JAN PY 2001 VL 14 IS 1 BP 23 EP 28 DI 10.1087/09531510125100232 UT WOS:000166632400004 ER PT J AU Senderowicz, AM AF Senderowicz, AM TI Development of cyclin-dependent kinase modulators as novel therapeutic approaches for hematological malignancies SO LEUKEMIA AB The majority of hematopoietic malignancies have aberrancies in the retinoblastoma (Rb) pathway. Loss in Rb function is, in most cases, a result of the phosphorylation and inactivation of Rb by the cyclin-dependent kinases (cdks), main regulators of cell cycle progression. Flavopiridol, the first cdk modulator tested in clinical trials, is a flavonoid that inhibits several cdks with evidence of cell cycle block. Other interesting preclinical features are the induction of apoptosis, promotion of differentiation, inhibition of angiogenic processes and modulation of transcriptional events. Initial clinical trials with infusional flavopiridol demonstrated activity in some patients with non-Hodgkin's lymphoma, renal, prostate, colon and gastric carcinomas. Main side-effects were secretory diarrhea and a pro-inflammatory syndrome associated with hypotension. Phase 2 trials with infusional flavopiridol in CLL and mantle cell lymphoma, other schedules and combination with standard chemotherapies are ongoing. The second cdk modulator tested in clinical trials, UCN-01, is a potent protein kinase C inhibitor that inhibits cdk activity in vitro as well. UCN-01 blocks cell cycle progression and promotes apoptosis in hematopoietic models. Moreover, UCN-01 is able to abrogate checkpoints induced by genotoxic stress due to modulation in chk1 kinase, The first clinical trial of UCN-01 demonstrated very prolonged half-life (similar to 600 h), 100 times longer than the half-life observed in preclinical models. This effect is due to high binding affinity of UCN-01 to the human plasma protein alpha-1-acid glycoprotein, Main side-effects in this trial were headaches, nausea/vomiting, hypoxemia and hyperglycemia. Clinical activity was observed in patients with melanoma, non-Hodgkin's lymphoma and leiomyosarcoma, Of interest, a patient with anaplastic large cell lymphoma refractory to high-dose chemotherapy showed no evidence of disease after 3 years of UCN-01 therapy. Trials of infusional UCN-01 in combination with Ara-C or gemcitabine in patients with acute leukemia and CLL, respectively, have commenced, In conclusion, flavopiridol and UCN-01 are cdk modulators that reach biologically active concentrations effective in modulating CDK in vitro,and show encouraging results in early clinical trials in patients with refractory hematopoietic malignancies. Although important questions remain to be answered, these positive experiences will hopefully increase the therapeutic modalities in hematological malignancies. SN 0887-6924 PD JAN PY 2001 VL 15 IS 1 BP 1 EP 9 DI 10.1038/sj.leu.2401994 UT WOS:000166704300001 PM 11243375 ER PT J AU Chervinsky, DS Lam, DH Zhao, XF Melman, MP Aplan, PD AF Chervinsky, DS Lam, DH Zhao, XF Melman, MP Aplan, PD TI Development and characterization of T cell leukemia cell lines established from SCL/LMO1 double transgenic mice SO LEUKEMIA AB We have established a panel of nine immortal cell lines from T cell malignancies which arose in mice transgenic for the SCL end LMO1 genes. Cells from the primary malignancies initially grew very slowly in vitro, loosely attached to a stromal layer, before gaining the ability to proliferate independently. Upon gaining the ability to proliferate in the absence of a stromal layer, these cell lines grew rapidly, doubling every 14-23 h, to a very high density, approaching 10(7) cells/ml. Whereas the tumors which arise in SCL/LMO1 double transgenic mice are typically diploid or pseudodiploid, the cell lines were all grossly aneuploid, suggesting the possibility that additional genetic events were selected for in vitro. Given that SCL and LMO1 gene activation are both commonly seen in human patients with T cell acute lymphoblastic leukemia, these cell lines may be a useful in vitro model for the human disease. RI Aplan, Peter/K-9064-2016 SN 0887-6924 PD JAN PY 2001 VL 15 IS 1 BP 141 EP 147 DI 10.1038/sj.leu.2401997 UT WOS:000166704300020 PM 11243382 ER PT J AU Monni, O Knuutila, S AF Monni, O Knuutila, S TI 11q deletions in hematological malignancies SO LEUKEMIA & LYMPHOMA AB Structural aberrations involving 11q are among the most common aberrations in a number of hematological malignancies. Most of the aberrations, such as translocations: and deletions, often harbor a breakpoint at 11q23, which suggests that this region might contain a tumor suppressor gene important for the genesis of lymphoproliferative disorders. Interestingly, deletions are concentrated only in some subtypes of hematological malignancies, where they are detected at a relatively high frequency. In B-cell chronic lymphocytic leukemia (B-CLL), deletions have been detected in 20-30% of the cases, whereas almost half of the mantle cell lymphomas (MCL) show deletion at 11q23 in fluorescence in situ hybridization analysis. In T-cell prolymphocytic leukemia (T-PLL) deletions involving the region 11q23.3-23.1 have also been detected to be frequent. In B-cell chronic lymphocytic leukemia, 11q deletion is associated with more rapid disease progression and poor survival in a younger subgroup of patients. The putative tumor suppressor genes have remained unrevealed until recently, when the ATM gene was found to carry mutations in cases with deletion in B-CLL, MCL and T-PLL. These data suggest that 11q deletions and dysfunction of the ATM gene might have significance in the tumorigenesis of certain subsets of hematological malignancies. Importance of 11q deletion as a diagnostic marker needs to be further studied in a larger series of patients. Another issue that remains to be investigated is the involvement of other target gents in the deletion. SN 1042-8194 PD JAN PY 2001 VL 40 IS 3-4 BP 259 EP 266 DI 10.3109/10428190109057924 UT WOS:000168296400004 PM 11426547 ER PT J AU White, JD Wharfe, G Stewart, DM Maher, VE Eicher, D Herring, B Derby, M Jackson-Booth, PG Marshall, M Lucy, D Jain, A Cranston, B Hanchard, B Lee, CC Top, LE Fleisher, TA Nelson, DL Waldmann, TA AF White, JD Wharfe, G Stewart, DM Maher, VE Eicher, D Herring, B Derby, M Jackson-Booth, PG Marshall, M Lucy, D Jain, A Cranston, B Hanchard, B Lee, CC Top, LE Fleisher, TA Nelson, DL Waldmann, TA TI The combination of zidovudine and interferon alpha-2B in the treatment of adult T-cell leukemia/lymphoma SO LEUKEMIA & LYMPHOMA AB Adult T-cell leukemia/lymphoma (ATL) is frequently a very aggressive malignancy with a poor survival despite aggressive multiagent chemotherapy. The combination of the antiretroviral drug zidovudine (AZT) and inrterferon alpha (IFN alpha) has been reported to induce remissions in patients with ATL. The purpose of this study was to evaluate the clinical response and toxicity following administration of a combination of IFN alpha -2b and AZT in patients with human T-cell lymphotropic virus type I (HTLV-I)-associated ATL. Eighteen patients with ATL (chronic. crisis, acute or lymphoma type) were treated with the combination of AZT (50 - 200 mg orally 5 times it day) and IFN alpha -2b (2.5 - 10 million units subcutaneously daily). Three patients had objective responses lasting more than one month. One patient had a clinical complete remission. lasting 21.6 months and two patients had partial remissions lasting 3.7 and 26.5 months. Six patients were not considered evaluable for response due to short and/or interrupted periods of treatment. Seventeen patients have died with a median survival rime after initiation of therapy of 6 months. Neutropenia and thrombocytopenia were the dose limiting toxicities. In conclusion, the response rate in this study was lower than noted in the two previous published series. This may be due to the amount and type of prior treatment our patients had received. SN 1042-8194 PD JAN PY 2001 VL 40 IS 3-4 BP 287 EP 294 DI 10.3109/10428190109057927 UT WOS:000168296400007 PM 11426550 ER PT J AU Takada, K Illei, GG Boumpas, DT AF Takada, K Illei, GG Boumpas, DT TI Cyclophosphamide for the treatment of systemic lupus erythematosus SO LUPUS AB Aggressive immunosuppressive therapy with cyclophosphamide has improved the outcome of major organ disease in lupus patients. Controlled trials have shown that pulse cyclophosphamide is the treatment of choice for patients with moderate to severe proliferative nephritis. Long-term follow-up of patients participating in these controlled trials suggests that combining pulse cyclophoshamide with pulse methylprednisolone increases efficacy but not toxicity. Retrospective case series have also shown that pulse cyclophosphamide therapy may be effective for the management of severe or refractory to standard therapy neuropsychiatric, pulmonary, cardiovascular and hematologic disease. Pulse cyclophosphamide is associated with an increased risk for herpes tester infections in the short term and with sustained amenorrhea in the long-term. Recent studies have also drawn attention to the lack of response (or incomplete response) and fare of lupus after an initial response. In an effort to circumvent these limitations, current investigations explore the therapeutic potential of high-dose, immunoablative cyclophosphamide therapy or tow-dose cyclophosphamide in combination with nucleoside analogs or biologic response modifiers. SN 0961-2033 PY 2001 VL 10 IS 3 BP 154 EP 161 DI 10.1191/096120301671376017 UT WOS:000168235300005 PM 11315345 ER PT J AU Welniak, LA Richards, SM Murphy, WJ AF Welniak, LA Richards, SM Murphy, WJ TI Effects of prolactin on hematopoiesis SO LUPUS AB The presence of extra-pituitary prolactin and its cognitive receptors in the hematopoietic microenvironment raises the question of whether prolactin plays a role in lympho-hematopoiesis and under what conditions. Current studies suggest that endogenous prolactin does not play a significant role under normal steady-state conditions. Rather, prolactin has been implicated as a 'stress hormone', functioning to restore hematopoietic homeostasis under conditions of dysregulation. The stress response of prolactin as well as its complex relationship with other hormones and factors has resulted in conflicting reports in the literature regarding prolactin's role in lympho-hematopoiesis. A review of this literature is provided as well as discussion of conditions under which lymphohematopoietic activity of prolactin may be evident. SN 0961-2033 PY 2001 VL 10 IS 10 BP 700 EP 705 DI 10.1191/096120301717164930 UT WOS:000172123800007 PM 11721696 ER PT J AU Mickley, L Jain, P Miyake, K Schriml, LM Rao, K Fojo, T Bates, S Dean, M AF Mickley, L Jain, P Miyake, K Schriml, LM Rao, K Fojo, T Bates, S Dean, M TI An ATP-binding cassette gene (ABCG3) closely related to the multidrug transporter ABCG2 (MXR/ABCP) has an unusual ATP-binding domain SO MAMMALIAN GENOME RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Schriml, Lynn/0000-0001-8910-9851 SN 0938-8990 PD JAN PY 2001 VL 12 IS 1 BP 86 EP 88 DI 10.1007/s003350010237 UT WOS:000166167000016 PM 11178751 ER PT J AU Kirchner, JM Ivanova, V Samson, A Noskov, VN Volff, JN Resnick, MA Walter, RB AF Kirchner, JM Ivanova, V Samson, A Noskov, VN Volff, JN Resnick, MA Walter, RB TI Transformation-associated recombination (TAR) cloning of tumor-inducing xmrk2 gene from Xiphophorus maculatus SO MARINE BIOTECHNOLOGY CT Conference on Aquaria Fish Models of Human Disease CY SEP 20-23, 2000 CL SW TEXAS STATE UNIV, SAN MARCOS, TX SP NCI, Chem & Phys Carcinogenesis Branch HO SW TEXAS STATE UNIV AB We modified the TAR methodology of YAC clone construction for application to fish genomic DNA isolated from Xiphophorus maculatus. YAC libraries were developed using the XIR1 repeat sequence as the recombinational hook. Construction of these libraries demonstrates that Xiphophorus DNA sequences can function as hooks in the yeast recombination system and that X. maculatus genomic DNA contains sequences that provide origin of replication function in yeast. By screening a subset of Xiphophorus YAC clones, we isolated a clone harboring the Xmrk2 locus that is associated with spontaneous and induced melanomagenesis. Modifications of the TAR technique allowed the targeted cloning of specific genes from genomic regions ranging in size from cDNAs to several hundred kilobases. Specific genomic regions can be isolated in a directional manner from fixed map locations to saturate these areas with physical markers. We discuss the applications of these and other yeast recombinational processes to fish genetics. SN 1436-2228 EI 1436-2236 PY 2001 VL 3 SU 1 BP S168 EP S176 DI 10.1007/s1012601-0039-9 UT WOS:000170592900021 PM 14961313 ER PT B AU Liu, J Ginis, I Spatz, M Hallenbeck, JM AF Liu, J Ginis, I Spatz, M Hallenbeck, JM BE Bazan, NG Ito, U Marcheselli, VL Kuroiwa, T Klatzo, I TI TNF-alpha and ceramide as mediators of neuronal tolerance to brain ischemia SO MATURATION PHENOMENON IN CEREBRAL ISCHEMIA IV: APOPTOSIS AND/OR NECROSIS, NEURONAL RECOVERY VS. DEATH, AND PROTECTION AGAINST INFARCTION CT 4th International Workshop on Maturation Phenomenon in Cerebral Ischemia CY OCT 30-NOV 03, 1999 CL NEW ORLEANS, LA AB In an in vitro model of tolerance to hypoxia in cortical neurons from 2-day old Sprague-Dawley rats we have demonstrated that preconditioning with hypoxia or TNF-alpha (25 ng/ml) can induce tolerance to a subsequent severe hypoxia. The preconditioning hypoxia induces an early release of TNF-alpha and if this release is neutralized by an anti-TNF-alpha antibody, the preconditioning does not result in tolerance to a subsequent severe hypoxia. Both hypoxic preconditioning and TNF-alpha preconditioning lead to a delayed rise in the level of ceramide, and this rise can be blocked by fumonisin B-1, an inhibitor of ceramide synthase. Addition of 10 muM ceramide to the cultures at the time of severe hypoxia provides the same level of cytoprotection as does hypoxic preconditioning or TNF-alpha preconditioning. The results indicate that both TNF-alpha and ceramide are involved in the signaling that regulates the development of tolerance to hypoxia in this model. BN 3-540-41107-0 PY 2001 BP 113 EP 121 UT WOS:000169016500014 ER PT J AU Shevach, EM McHugh, RS Thornton, AM Piccirillo, C Natarajan, K Margulies, DH AF Shevach, EM McHugh, RS Thornton, AM Piccirillo, C Natarajan, K Margulies, DH TI Control of autoimmunity by regulatory T cells SO MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION VIII: AUTOIMMUNITY 2000 AND BEYOND SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 SN 0065-2598 PY 2001 VL 490 BP 21 EP 32 UT WOS:000171041500003 PM 11505971 ER PT J AU Chun, HJ Lenardo, MJ AF Chun, HJ Lenardo, MJ TI Autoimmune lymphoproliferative syndrome: Types I, II and beyond SO MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION VIII: AUTOIMMUNITY 2000 AND BEYOND SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY RI Chun, Hyung/K-1859-2013 SN 0065-2598 PY 2001 VL 490 BP 49 EP 57 UT WOS:000171041500006 PM 11505974 ER PT J AU Wimmer, K Zhu, XX Lamb, BJ Kuick, R Ambros, P Kovar, H Thoraval, D Elkahloun, A Meltzer, P Hanash, SM AF Wimmer, K Zhu, XX Lamb, BJ Kuick, R Ambros, P Kovar, H Thoraval, D Elkahloun, A Meltzer, P Hanash, SM TI Two-dimensional DNA electrophoresis identifies novel CpG islands frequently coamplified with MYCN in neuroblastoma SO MEDICAL AND PEDIATRIC ONCOLOGY CT Advances in Neuroblastoma Research Meeting CY JUN 15-17, 1998 CL BATH, ENGLAND AB Background. Amplification of the oncogene MYCN in neuroblastoma has been found to correlate with aggressive tumour growth and is used as a predictor of clinical outcome. The MYCN amplicon is known to involve coamplification of extensive DNA regions. Therefore it is possible that other genes are coamplified in this amplicon and that they may play a role in the poor outcome of MYCN amplified tumours. Procedure. We have implemented an approach for the two-dimensional separation of human genomic restriction fragments to detect and isolate as yet unknown amplified sequences in the MYCN amplicon in neuroblastoma. Using this approach we have recently cloned a novel gene referred to as NAG that is frequently coamplified with MYCN in neuroblastoma. Results and Conclusions. We report here the identification and cloning of two ad-ditional CpG islands that are amplified in neuroblastoma. One contains a sequence that is identical to the first intron of DDX1. The other represents a novel CpG island that is associated with an as yet unidentified gene. We show that the novel CpG island is located in close proximity to the MYCN locus on chromosome 2 and is as frequently coamplified with MYCN in neuroblastoma as NAG and DDX1. Med. Pediatr. Oncol. 36:75-79, 2001. (C) 2001 Wiley-Liss, Inc. SN 0098-1532 PD JAN PY 2001 VL 36 IS 1 BP 75 EP 79 DI 10.1002/1096-911X(20010101)36:1<75::AID-MPO1018>3.0.CO;2-O UT WOS:000166167300018 PM 11464910 ER PT J AU Matsuo, T Seth, P Thiele, CJ AF Matsuo, T Seth, P Thiele, CJ TI Increased expression of p27Kip1 arrests neuroblastoma cell growth SO MEDICAL AND PEDIATRIC ONCOLOGY CT Advances in Neuroblastoma Research Meeting CY JUN 15-17, 1998 CL BATH, ENGLAND AB Background and Procedure. To investigate the molecular mechanisms by which retinoic acid (RA) alters cell growth, the expression and activity of components of the cell cycle machinery were analyzed. Results and Conclusions. Within 2 days of RA treatment, and prior to the arrest of NE cells in the G(1) phase of the cell cycle, there was a complete downregulation of Cl cyclin/cdk activities. Protein levels for the G(1) cyclin/cdk were essentially unchanged during this time, although there was a decrease in the steady-state levels of hyperphosphorylated Rb and p60N-MYC proteins. The cdk inhibitors, p21Cip1 and p27Kip1 were constitutively expressed in KCNR, while p15 INK4B and p16 INK4A mRNA were undetected. Within 24 hr of RA treatment, there was a 4-fold increase in the expression of p27Kip1, although p27 mRNA levels were unchanged. Levels of p21Cip1 were unaltered. Coincident with the decreasein kinase activity there was an increase in p27 bound to G(1) cyclin/cdk. The increase in p21 was not due to an increase in transcription. In other cell systems, increased expression of c-MYC has been shown to lead to a decrease in p27 levels that is regulated at the post-transcriptional level (sequestration). To determine whether increased levels of N-MYC could affect the level of p27, we evaluated the expression of p27 in a series of N-MYC transfected cells and found that constitutive overexpression of N-MYC led to a decrease in the steady-state levels of p27 and in p27 bound to G(1) cyclin/cdk complexes. Using adenoviral vectors expressing p27 we found that infection leads to increased p27 expression, which causes a decrease in cdk activity and an accumulation of cells in G(1). Med. Pediatr. Oncol. 36: 97-99, 2001. Published 2001 Wiley-Liss, Inc. SN 0098-1532 PD JAN PY 2001 VL 36 IS 1 BP 97 EP 99 DI 10.1002/1096-911X(20010101)36:1<97::AID-MPO1022>3.0.CO;2-X UT WOS:000166167300022 PM 11464914 ER PT J AU Janusauskas, A Marozas, V Engdahl, B Hoffman, HJ Svensson, O Sornmo, L AF Janusauskas, A Marozas, V Engdahl, B Hoffman, HJ Svensson, O Sornmo, L TI Otoacoustic emissions and improved pass/fail separation using wavelet analysis and time windowing SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING AB A new method is presented for the purpose of improving pass/fail separation during transient evoked otoacoustic emission (TEOAE) hearing screening. The method combines signal decomposition in scales using the discrete wavelet transform, non-linear denoising and scale-dependent time windowing. The crosscorrelation coefficient between two subaveraged, processed TEOAE signals is used as a pass/fail criterion and assessed in relation to the pure-tone, mean hearing level. The performance is presented in terms of receiver operating characteristics for a database of 5214 individuals. The results show that the specificity improves from 68% to 83% at a sensitivity of 90% when compared with the conventional wave reproducibility parameter. SN 0140-0118 PD JAN PY 2001 VL 39 IS 1 BP 134 EP 139 DI 10.1007/BF02345277 UT WOS:000166793200020 PM 11214265 ER PT J AU Lipkus, IM Samsa, G Rimer, BK AF Lipkus, IM Samsa, G Rimer, BK TI General performance on a numeracy scale among highly educated samples SO MEDICAL DECISION MAKING AB Background. Numeracy, how facile people are with basic probability and mathematical concepts, is associated with how people perceive health risks. Performance on simple numeracy problems has been poor among populations with little as well as more formal education. Here, we examine how highly educated participants performed on a general and an expanded numeracy scale. The letter was designed within the context of health risks. Method. A total of 463 men and women aged 40 and older completed a 3-item general and an expanded 7-item numeracy scale. The expanded scale assessed how well people 1) differentiate and perform simple mathematical operations on risk magnitudes using percentages and proportions, 2) convert percentages to proportions, 3) convert proportions to percentages, and 4) convert probabilities to proportions. Results. On average, 18% and 32% of participants correctly answered all of the general and expanded numeracy scale items, respectively. Approximately 16% to 20% incorrectly answered the most straightforward questions pertaining to risk magnitudes (e.g., Which represents the larger risk: 1%, 5%, or 10%?). A factor analysis revealed that the general and expanded risk numeracy items tapped the construct of global numeracy. Conclusions. These results suggest that even highly educated participants have difficulty with relatively simple numeracy questions, thus replicating in part earlier studies. The implication is that usual strategies for communicating numerical risk may be flawed. Methods and consequences of communicating health risk information tailored to a person's level of numeracy should be explored further. RI Lindskog, Marcus/C-1383-2009 SN 0272-989X PD JAN-FEB PY 2001 VL 21 IS 1 BP 37 EP 44 UT WOS:000170801600005 PM 11206945 ER PT S AU McGarry, D Cook, J Subramanian, S Devasahayam, N Cherukuri, MK Johnson, C AF McGarry, D Cook, J Subramanian, S Devasahayam, N Cherukuri, MK Johnson, C BE Sonka, M Hanson, KM TI Reconstruction of electron paramagnetic resonance images using iterative methods SO MEDICAL IMAGING: 2001: IMAGE PROCESSING, PTS 1-3 SE Proceedings of SPIE CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol AB Electron Paramagnetic Resonance (EPR) allows for the non-invasive imaging of free radicals in biological systems. Although a. number of physical factors have hindered the development of EPR as an imaging modality, EPR offers the potential for tissue oxymetry. EPR images are typically reconstructed using a traditional filtered back-projection technique. We are attempting to improve the quality of EPR images by using maximum-entropy based iterative image reconstruction algorithms. Our investigation has so far focused on two methods, the multiplicative algebraic reconstruction technique (MART), and an algorithm that is motivated by interior-point reconstruction. MART is a row-action method that maintains strict equality in the constraints while minimizing the entropy functional. The latter method, which we have named Least-Squares Barder Entropy (LSBEnt), transforms the constrained problem into an unconstrained problem and maximizes entropy at a prescribed distance from the measured data. EPR studies are frequently characterized by low signal-to-noise ratios and wide line widths. The effect of the backprojection streaking artifact can be quite severe and can seriously compromise a study. We have compared the iterative results with filtered backprojection on two-dimensional (2-D) EPR acquisitions of various phantoms. Encouraging preliminary results have demonstrated that one of the clear advantages of the iterative methods is their lack of streaking artifacts that plague filtered backprojection. SN 0277-786X BN 0-8194-4008-6 PY 2001 VL 4322 BP 24 EP 29 DI 10.1117/12.431097 UT WOS:000172146600003 ER PT S AU Long, LR Thoma, GR AF Long, LR Thoma, GR BE Sonka, M Hanson, KM TI Identification and classification of spine vertebrae by automated methods SO MEDICAL IMAGING: 2001: IMAGE PROCESSING, PTS 1-3 SE Proceedings of SPIE CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol AB We are currently working toward developing computer-assisted methods for the indexing of a collection of 17,000 digitized x-ray images by biomedical content. These images were collected as part of a nationwide health survey and form a research resource for osteoarthitis and bone morphometry. This task requires the development of algorithms to robustly analyze the xray contents for key landmarks, to segment the vertebral bodies, to accurately measure geometric features of the individual vertebrae and inter-vertebral areas, and to classify the spine anatomy into normal or abnormal classes for conditions of interest, including anterior osteophytes and disc space narrowing. Subtasks of this work have been created and divided among collaborators. In this paper, we provide a technical description of the overall task, report on progress made by collaborators, and provide the most recent results of our own research into obtaining first-order location of the spine region of interest by automated methods. We are currently concentrating on images of the cervical spine, but win expand the work to include the lumbar spine as well. Development of successful image processing techniques for computer-assisted indexing of medical image collections is expected to have a significant impact within the medical research and patient care systems. SN 0277-786X BN 0-8194-4008-6 PY 2001 VL 4322 BP 1478 EP 1489 DI 10.1117/12.431029 UT WOS:000172146600156 ER PT S AU Summers, RM Cebral, JR AF Summers, RM Cebral, JR BE Chen, CT Clough, AV TI Tracheal and central bronchial aerodynamics using virtual bronchoscopy SO MEDICAL IMAGING 2001: PHYSIOLOGY AND FUNCTION FROM MULTIDIMENSIONAL IMAGES SE Proceedings of SPIE CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol AB Virtual bronchoscopy reconstructions of the airway noninvasively provide useful morphologic information of structural abnormalities such as stenoses and masses. In this paper, we show how virtual bronchoscopy can be used to perform aerodynamic calculations in anatomically realistic models. Pressure and flow patterns in a human airway were computed noninvasively. These showed decreased pressure and increased shear stress in the region of a stenosis. SN 0277-786X BN 0-8194-4007-8 PY 2001 VL 4321 BP 22 EP 31 DI 10.1117/12.428154 UT WOS:000171469100003 ER PT S AU Yim, PJ Cebral, JR Lohner, R Soto, O Marcos, H Choyke, PL AF Yim, PJ Cebral, JR Lohner, R Soto, O Marcos, H Choyke, PL BE Chen, CT Clough, AV TI Interpretation of arterial velocity waveforms SO MEDICAL IMAGING 2001: PHYSIOLOGY AND FUNCTION FROM MULTIDIMENSIONAL IMAGES SE Proceedings of SPIE CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol AB Blood flow temporal waveforms change with position along an artery, The change in the flow waveforms can be accounted for by a transmission line model of flow. According to this model, pulse waves propagate at a finite velocity in both directions along the artery. In principle, given flow waveforms measured at three locations along an artery, the pulse-wave velocity, (c) can be determined from the wave equation (d(2)Q/dt(2)=c(2)d(2)Q/dz(2), Q is flow, t is time, z is position). Given the vessel diameter, the vessel-wall compliance can be derived from pulse-wave velocity. However, direct solution of the wave equation for pulse-wave velocity is highly susceptible to flow-measurement error. Thus, we propose a new method for estimating pulse-wave velocity from arterial flow waveforms. In our method, ideal flow waveforms are reconstructed from three measured flow waveforms. The ideal waveforms are reconstructed by minimization of the total error between the ideal and measured waveforms subject to constraints of the wave equation. Ideal flow waveforms are reconstructed for a range of assumed pulse-wave velocities. The true pulse-wave velocity is considered to be that which produces the minimum total error. The method applies to blood flow measurements made with phase-contrast magnetic resonance imaging. SN 0277-786X BN 0-8194-4007-8 PY 2001 VL 4321 BP 81 EP 91 DI 10.1117/12.428123 UT WOS:000171469100009 ER PT S AU Petridou, N Bodurka, J Loew, M Bandettini, PA AF Petridou, N Bodurka, J Loew, M Bandettini, PA BE Chen, CT Clough, AV TI Neuronal current imaging using MRI: a feasibility study SO MEDICAL IMAGING 2001: PHYSIOLOGY AND FUNCTION FROM MULTIDIMENSIONAL IMAGES SE Proceedings of SPIE CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol AB Current functional MRI techniques are essentially based on detection of hemodynamic changes induced by neuronal activation. This study is an exploration of the feasibility of direct detection of neuronal current induced NMR phase and/or magnitude changes. Our analysis was based on the approximation that neurons exist in an infinite homogeneous conducting medium, and are represented by an infinitely long cylindrical conductor, carrying uniform current. Neuronal activation was modeled by a current dipole. Simulations were performed to evaluate the effects of the local neuronal magnetic fields on the MRI signal at 3T. The magnetic field changes and the corresponding phase changes induced from a current range of 2nA to 100 muA were estimated. The conductor diameter was varied from 10 mum to 1mm corresponding to the sizes ranging from that of a single axon to that of a patch of functionally similar cortex. Current induced magnetic field effects were assessed as resolution and neuronal orientation with respect to Bo were modulated. Simulation results were compared with measurements obtained from a current phantom at 3T, for a current range of 10-100 muA. Based on the dipole model formulated we found that neuronal currents can produce magnetic fields on the order of 1.3pT; 0.0006 degrees to 9nT; 4 degrees depending on the neuronal bundle diameter, orientation, and current capacity. The mechanism for signal changes is that of Bo shifts. This is fundamentally similar to that of BOLD contrast, but caused by current changes rather than susceptibility changes from changes in blood oxygenation. If the bundles are of random orientations within a voxel, the estimated fields and NMR magnitude changes (decrease in T2*) are on the order of present system detection levels of approximately 1nT; 0.5 degrees or 0.01% signal change. Conversely, if the bundle orientation is homogeneous, then neuronal current effects are above system detection levels. The spatial scale of the current distribution also determines the net phase shift and magnitude change. The simulation and phantom experiment results demonstrated the feasibility of using MRI to directly detect local magnetic field perturbations that can result from neuronal currents on the order of a few muA. This study provides a simple model for the evaluation of the feasibility to directly measure neuronal currents with MRI. Additionally it gives a starting point for the design of appropriate imaging methods towards detecting low signal level neuronal currents. A more extensive modeling of cortical and neuronal geometry, tissue inhomogeneity, timing mechanisms, and current distributions, will provide further insight in the development of MRI experimental techniques. SN 0277-786X BN 0-8194-4007-8 PY 2001 VL 4321 BP 188 EP 194 DI 10.1117/12.428136 UT WOS:000171469100021 ER PT S AU Cannata, JM Ritter, TA Chen, WH Shung, KK AF Cannata, JM Ritter, TA Chen, WH Shung, KK BE Insana, MF Shung, KK TI Design of focused single element (50-100 MHz) transducers using lithium niobate SO MEDICAL IMAGING 2001: ULTRASONIC IMAGING AND SIGNAL PROCESSING SE Proceedings of SPIE CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol AB This paper discusses two fabrication procedures used to build LiNbO3 single element ultrasonic transducers with center frequencies in the 50-100 MHz range. Transducers of varying dimensions were built for an f-number range of 1.5-3.0. A conductive quarter wavelength silver epoxy matching layer, and a conductive silver epoxy backing, were used in all designs. The desired focal depths were achieved by either casting an acoustic lens on the transducer face or press-focusing the piezoelectric into a spherical curvature. For lens-focusing transducers the lens material EPO-TEK 301 was modeled as a second matching layer. The pressed-focused transducer design utilized parylene as the second matching layer. For devices that required electrical impedance matching, a low impedance transmission line coaxial cable was used. All transducers were tested in a pulse-echo insertion loss arrangement, whereby the center frequency, bandwidth, insertion loss, and focal depth were measured. Several transducers were fabricated with center frequencies in the 50 to 100 MHz range. The measured -6 dB bandwidths and two-way insertion loss values ranged from 33% to 70% and 12.5 dB to 23.0 dB, respectively. Both the lens-focusing and press-focusing techniques were successful in producing the desired focal depth without significantly compromising device sensitivity and bandwidth. SN 0277-786X BN 0-8194-4011-6 PY 2001 VL 4325 BP 28 EP 35 DI 10.1117/12.428215 UT WOS:000171334900004 ER PT S AU Ritter, TA Shrout, TR Shung, KK AF Ritter, TA Shrout, TR Shung, KK BE Insana, MF Shung, KK TI A high frequency synthetic ultrasound array incorporating an actuator SO MEDICAL IMAGING 2001: ULTRASONIC IMAGING AND SIGNAL PROCESSING SE Proceedings of SPIE CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol AB Ultrasound imaging at frequencies above 20 MHz relies almost exclusively on single-element transducers. In order to apply array technology at these frequencies, several practical problems must be solved, including spatial scale and fabrication limitations, low device capacitance, and lack of a hardware beamformer. One method of circumventing these problems is to combine an array, an actuator, and a synthetic aperture software beamformer. The array can use relatively wide elements spaced on a coarse pitch. The actuator is used to move the array in short steps (less than the element pitch), and pulse-echo data is acquired at intermediate sample positions. The synthetic aperture beamformer reconstructs the image from the pulse-echo data. A 50 MHz example is analyzed in detail. Estimates of signal-to-noise reveal performance comparable to a standard phased array; furthermore, the actuated array requires half the number of elements, the elements are 8x wider, and only one channel is required. Simulated three-dimensional point spread functions demonstrate side lobe levels approaching -40 dB and main beam widths of 50 to 100 microns. A 50 MHz piezo-composite array design has been tested which displays experimental bandwidth of 70% while maintaining high sensitivity. Individual composite sub-elements are 18 microns wide. Once this array is integrated with a suitable actuator, it is anticipated that a tractable method of imaging with high frequency arrays will result. SN 0277-786X BN 0-8194-4011-6 PY 2001 VL 4325 BP 36 EP 46 DI 10.1117/12.428225 UT WOS:000171334900005 ER PT S AU Guttman, MA McVeigh, ER AF Guttman, MA McVeigh, ER BE Mun, SK TI 3D MR imaging in real-time SO MEDICAL IMAGING 2001: VISUALIZATION, DISPLAY, AND IMAGE-GUIDED PROCEDURES SE Proceedings of SPIE CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol AB A system has been developed to produce `live' 3D volume renderings from an MR scanner. Whereas realtime 2D MR imaging has been demonstrated by several groups, 3D volumes are currently rendered off-line to gain greater understanding of anatomical structures. For example, surgical planning is sometimes performed by viewing 2D images or 3D renderings from previously acquired image data. A disadvantage of this approach is misregistration which could occur if the anatomy changes due to normal muscle contractions or surgical manipulation. The ability to produce volume renderings in real-time and present them in the magnet room could eliminate this problem, and enable or benefit other types of interventional procedures. The system uses the data stream generated by a fast 2D multi-slice pulse sequence to update a volume rendering immediately after a new slice is available. We demonstrate some basic types of user interaction with the rendering during imaging at a rate of up to 20 frames per second. SN 0277-786X BN 0-8194-4005-1 PY 2001 VL 4319 BP 394 EP 400 DI 10.1117/12.428080 UT WOS:000171468900047 ER PT S AU Morris, HD AF Morris, HD BE Mun, SK TI Ubiquitous remote operation collaborative interface for MRI scanners SO MEDICAL IMAGING 2001: VISUALIZATION, DISPLAY, AND IMAGE-GUIDED PROCEDURES SE Proceedings of SPIE CT Medical Imaging 2001 Conference CY FEB 18-22, 2001 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol AB We have developed a remote control interface for research class magnetic resonance imaging (MRI) spectrometers. The goal of the interface is to provide a better collaborative environment for geographically dispersed researchers and a tool that can teach students of medical imaging in a network-based laboratory using state-of-the-art MR instrumentation that would not otherwise be available. The interface for the remote operator(s) is the now ubiquitous web browser, which was chosen for the ease of controlling the operator interface, the display of both image and text information, and the wide availability on many computer platforms. The remote operator is presented with an active display in which they may select and control most of the parameters in the MRI experiment. The MR parameters are relayed via web browser to a CGI program running in a standard web server, which passes said parameters to the MRI manufacturers control software. The data returned to the operator(s) consists of the parameters used in acquiring that image, a flat 8-bit grayscale GIF representation of the image, and a 16-bit grayscale image that can be viewed by an appropriate application. It is obvious that the utility of this interface would be helpful for researchers of regional and national facilities to more closely collaborate with colleagues across their region, the nation; or the world. And medical imaging students can put much of their classroom discussions into practice on machinery that would not normally be available to them. SN 0277-786X BN 0-8194-4005-1 PY 2001 VL 4319 BP 574 EP 581 DI 10.1117/12.428101 UT WOS:000171468900066 ER PT J AU Smith, MF Daube-Witherspoon, ME Plascjak, PS Szajek, LP Carson, RE Everett, JR Green, SL Territo, PR Balaban, RS Bacharach, SL Eckelman, WC AF Smith, MF Daube-Witherspoon, ME Plascjak, PS Szajek, LP Carson, RE Everett, JR Green, SL Territo, PR Balaban, RS Bacharach, SL Eckelman, WC TI Device-dependent activity estimation and decay correction of radionuclide mixtures with application to Tc-94m PET studies SO MEDICAL PHYSICS AB Multi-instrument activity estimation and decay correction techniques were developed for radionuclide mixtures, motivated by the desire for accurate quantitation of Tc-94m positron emission tomography (PET) studies. Tc-94m and byproduct Tc isotopes were produced by proton irradiation of enriched Mo-94 and natural Mo targets, Mixture activities at the end of bombardment were determined with a calibrated high purity germanium detector. The activity fractions of the greatest mixture impurities relative to 100% for Tc-94m averaged 10.0% (Tc-94g) and 3.3% (Tc-93) for enriched targets and 10.1% (Tc-94g), 11.0% (Tc-95), 255.8% (Tc-96m), and 7.2% (Tc-99m) for natural targets. These radioisotopes have different half-lives (e.g., 52.5 min for Tc-94m, 293 min for Tc-94g), positron branching ratios (e.g., 0.72 for Tc-94m, 0.11 for Tc-94g) and gamma ray emissions for themselves and their short-lived, excited Mo daughters. This complicates estimation of injected activity with a dose calibrator, in vivo activity with PET and blood sample activity with a gamma counter. Decay correction using only the Tc-94m half-life overestimates activity and is inadequate. For this reason analytic formulas for activity estimation and decay correction of radionuclide mixtures were developed. Isotope-dependent sensitivity factors for a PET scanner, dose calibrator, and gamma counter were determined using theoretical sensitivity models and fits of experimental decay curves to sums of exponentials with fixed decay rates. For up to 8 h after the end of bombardment with activity from enriched and natural Mo targets, decay-corrected activities were within 3% of the mean for three PET studies of a uniform cylinder, within 3% of the mean for six dose calibrator decay studies, and within 6% of the mean for four gamma counter decay studies. Activity estimation and decay correction for Tc-94m mixtures enable routine use of Tc-94m in quantitative PET, as illustrated by application to a canine Tc-94m sestamibi study. (C) 2001 American Association of Physicists in Medicine. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 SN 0094-2405 PD JAN PY 2001 VL 28 IS 1 BP 36 EP 45 DI 10.1118/1.1333411 UT WOS:000166762300007 PM 11213920 ER PT J AU Sosa, C Benetucci, J Hanna, C Sieczkowski, L Deluchi, G Canizal, AM Mantina, H Klaskala, W Baum, M Wood, C AF Sosa, C Benetucci, J Hanna, C Sieczkowski, L Deluchi, G Canizal, AM Mantina, H Klaskala, W Baum, M Wood, C TI Human herpesvirus 8 can be transmitted through blood in drug addicts SO MEDICINA-BUENOS AIRES AB Human Herpes virus type-8 (HHV-8) seroprevalence was studied in a population of HIV positive intravenous drug users (IVDUs) from Argentina. Analysis of this population also indirectly made it possible to study HHV-8 blood transmission, because these individuals frequently engage in needle sharing behavior and are capable of acquiring a broad array of blood borne pathogens, including Hepatitis B/C virus. The seroprevalence of HHV-8 in IVDUs was compared to a group of non-IVDUs and HIV negative individuals. Of the 223 individuals tested, 13.45% were HHV-8 positive, 16.99% in the IVDUs group, and 5.71% in the non-IVDUs. Among HIV positive IVDUs, 25/144 (17.36%) were also HHV-8 seropositive. The seropositivity rate of HHV-8 in HIV negative IVDUs was 11.1%. In contrast, HHV-8 seroprevalence in HIV negative heterosexual individuals without drug usage behavior was even lower (5.71%). The rate of HHV-8 infection in HIV positive IVDUs was three times as high compared to the non IVDU HIV negative individuals, suggesting that IVDU is a risk for HHV-8 infection. Furthermore, it was found that IVDUs showed a very high rate of Hepatitis Bic (52.77%), which also correlate with HHV-8 infection in this population (23.68%). All Hepatitis B/C positive individuals were also HIV positive. Our data confirm other studies showing that individuals who share needles are at risk for acquiring Hepatitis B/C and HIV infections. In addition, our results suggest that they are also at risk to acquiring HHV-8 infection by the same route. SN 0025-7680 PY 2001 VL 61 IS 3 BP 291 EP 294 UT WOS:000169779600008 PM 11474876 ER PT J AU Wolff, J AF Wolff, J TI Physiology and pharmacology of iodized oil in goiter prophylaxis SO MEDICINE SN 0025-7974 EI 1536-5964 PD JAN PY 2001 VL 80 IS 1 BP 20 EP 36 DI 10.1097/00005792-200101000-00003 UT WOS:000166380200003 PM 11204500 ER PT S AU Yoo, TS Morse, B Subramanian, KR Rheingans, P Ackerman, MJ AF Yoo, TS Morse, B Subramanian, KR Rheingans, P Ackerman, MJ BE Westwood, JD Hoffman, HM Mogel, GT Stredney, D Robb, RA TI Anatomic modeling from unstructured samples using variational implicit surfaces SO MEDICINE MEETS VIRTUAL REALITY 2001: OUTER SPACE, INNER SPACE, VIRTUAL SPACE SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS CT Conference on Medicine Meets Virtual Reality 2001 CY JAN 24-27, 2001 CL NEWPORT BEACH, CA AB We describe the use of variational implicit surfaces (level sets of an embedded generating function modeled using radial basis interpolants) in anatomic modeling. This technique allows the practitioner to employ sparsely and unevenly sampled data to represent complex biological surfaces, including data acquired as a series of non-parallel image slices. The method inherently accommodates interpolation across irregular spans. In addition, shapes with arbitrary topology are easily represented without interpolation or aliasing errors arising from discrete sampling. To demonstrate the medical use of variational implicit surfaces, we present the reconstruction of the inner surfaces of blood vessels from a series of endovascular ultrasound images. SN 0926-9630 BN 1-58603-143-0 PY 2001 VL 81 BP 594 EP 600 UT WOS:000169103300112 PM 11317816 ER PT S AU Siegel, ER Royall, J Bennett, M AF Siegel, ER Royall, J Bennett, M BE Patel, VL Rogers, R Haux, R TI Enhancing communications and connectivity in Africa: The Multilateral Initiative on Malaria (MIM) model SO MEDINFO 2001: PROCEEDINGS OF THE 10TH WORLD CONGRESS ON MEDICAL INFORMATICS, PTS 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS CT 10th World Congress on Medical Informatics (MEDINFO 2001) CY 2001 CL LONDON, ENGLAND SP McGill Univ, Ctr Med Educ, Columbia Univ, Dept Med Informat AB The U.S. National Library of Medicine, working in concert with the Multilateral initiative on Malaria (MIM) has developed and implemented a unique organizational and technical strategy to connect malaria research sites to the Internet for purposes of facilitating North-South scientific communications and access to electronic information resources on the Web. The model employs microwave and VSAT technologies, and shares bandwidth and costs among participating malaria research sites and their respective research finders in Mali, Kenya, Ghana, Tanzania and other sub-Saharan locations affiliated with MIM. The concept of institutional partnership is an essential element of this information technology capacity building effort, which may find applicability in other developing regions of the world with similar communications and research networking needs and capabilities. SN 0926-9630 BN 1-58603-194-5 PY 2001 VL 84 BP 48 EP 52 UT WOS:000172901700010 PM 11604704 ER PT S AU Silva, JS Ball, MJ Douglas, JV AF Silva, JS Ball, MJ Douglas, JV BE Patel, VL Rogers, R Haux, R TI The Cancer Informatics Infrastructure (CII): An architecture for translating clinical research into patient care SO MEDINFO 2001: PROCEEDINGS OF THE 10TH WORLD CONGRESS ON MEDICAL INFORMATICS, PTS 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS CT 10th World Congress on Medical Informatics (MEDINFO 2001) CY 2001 CL LONDON, ENGLAND SP McGill Univ, Ctr Med Educ, Columbia Univ, Dept Med Informat AB Today, the clinical trial process remains slow and paper-based. The creation of a Cancer Informatics Infrastructure (CII) can provide the architectural base across the continuum of cancer research and cancer care. Recommendations of a Long Range Planning Committee identified near-term activities for the Office of Informatics at the National Cancer Institute (NCI). These include participating in national standards development; fostering oncology-related terminology and standards, e.g., Common Data Elements (CDEs); and leveraging mainstream informatics and Internet technologies, using the successful Internet model that focuses on facilitating stakeholder participation, sponsoring the CII rather than subsidizing it, and providing a test bed as well as an infrastructure. Diffusion tactics Include extending the CII concept beyond its "early adopters" to the wider community through recommendations for the near-term and development of a major document defining next-phase activities. SN 0926-9630 BN 1-58603-194-5 PY 2001 VL 84 BP 114 EP 117 UT WOS:000172901700025 PM 11604717 ER PT S AU Bodenreider, O AF Bodenreider, O BE Patel, VL Rogers, R Haux, R TI An object-oriented model for representing semantic locality in the UMLS SO MEDINFO 2001: PROCEEDINGS OF THE 10TH WORLD CONGRESS ON MEDICAL INFORMATICS, PTS 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS CT 10th World Congress on Medical Informatics (MEDINFO 2001) CY 2001 CL LONDON, ENGLAND SP McGill Univ, Ctr Med Educ, Columbia Univ, Dept Med Informat AB Several information models have been developed for the Unified Medical Language System (UMLS). While some models are term-oriented, a knowledge-oriented model is needed for representing semantic locality, i.e. the various semantic links among concepts. We propose an object-oriented model in which the semantic features of the UMLS are made available through four major classes for representing Metathesaurus concepts, semantic types, interconcept relationships and Semantic Network relationships. Additional semantic methods for reducing the complexity of the hierarchical relationships represented in the UMLS are proposed. Implementation details are presented, as well as examples of use. The interest of this approach is discussed. SN 0926-9630 BN 1-58603-194-5 PY 2001 VL 84 BP 161 EP 165 UT WOS:000172901700038 PM 11604725 ER PT S AU Burgun, A Bodenreider, O AF Burgun, A Bodenreider, O BE Patel, VL Rogers, R Haux, R TI Methods for exploring the semantics of the relationships between co-occurring UMLS concepts SO MEDINFO 2001: PROCEEDINGS OF THE 10TH WORLD CONGRESS ON MEDICAL INFORMATICS, PTS 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS CT 10th World Congress on Medical Informatics (MEDINFO 2001) CY 2001 CL LONDON, ENGLAND SP McGill Univ, Ctr Med Educ, Columbia Univ, Dept Med Informat AB Objective: To characterize the relationships among UMLS concepts that co-occur as MeSH descriptors in MEDLINE citations (1990-1999). Design: 18,485 UMLS concepts involved in 7,928,608 directed pairs of co-occurring concepts were studied. For each directed pair of concepts C1-C2: (i) the "family" of Cl was built, using the UMLS Metathesaurus, and we tested whether or not C2 belonged to C1's family; (ii) we used the semantic categorization of Metathesaurus concepts through the UMLS Semantic Network and Semantic Groups to represent the semantics of the relationships between C1 and C2. Results: In 6.5% of the directed pairs, the co-occurring concept C2 was found within the "family" of Cl. Detailed results are given. The most frequent co-occurrences involved "Chemicals & Drugs" and "Chemicals & Drugs", as well as "Disorders" and "Chemicals & Drugs". Discussion: This work takes advantage of both symbolic and statistical information represented in the UMLS, and analyzes their overlap. Further research is suggested. SN 0926-9630 BN 1-58603-194-5 PY 2001 VL 84 BP 171 EP 175 UT WOS:000172901700040 PM 11604727 ER PT S AU McCray, AT Burgun, A Bodenreider, O AF McCray, AT Burgun, A Bodenreider, O BE Patel, VL Rogers, R Haux, R TI Aggregating UMLS semantic types for reducing conceptual complexity SO MEDINFO 2001: PROCEEDINGS OF THE 10TH WORLD CONGRESS ON MEDICAL INFORMATICS, PTS 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS CT 10th World Congress on Medical Informatics (MEDINFO 2001) CY 2001 CL LONDON, ENGLAND SP McGill Univ, Ctr Med Educ, Columbia Univ, Dept Med Informat AB The conceptual complexity of a domain can make it difficult for users of information systems to comprehend and interact with the knowledge embedded in those systems. The Unified Medical Language System (R) (UMLS) currently integrates over 730,000 biomedical concepts from more than fifty biomedical vocabularies. The UMLS semantic network reduces the complexity of this construct by grouping concepts according to the semantic types that have been assigned to them. For certain purposes, however, an even smaller and coarser-grained set of semantic type groupings may be desirable. In this paper, we discuss our approach to creating such a set. We present six basic principles, and then apply those principles in aggregating the existing 134 semantic types into a set of 15 groupings. We present some of the difficulties we encountered and the consequences of the decisions we have made. We discuss some possible uses of the semantic groups, and we conclude with implications for future work. SN 0926-9630 BN 1-58603-194-5 PY 2001 VL 84 BP 216 EP 220 UT WOS:000172901700049 PM 11604736 ER PT S AU Ackerman, MJ Yoo, T Jenkins, D AF Ackerman, MJ Yoo, T Jenkins, D BE Patel, VL Rogers, R Haux, R TI From data to knowledge - The visible human projecto continues SO MEDINFO 2001: PROCEEDINGS OF THE 10TH WORLD CONGRESS ON MEDICAL INFORMATICS, PTS 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS CT 10th World Congress on Medical Informatics (MEDINFO 2001) CY 2001 CL LONDON, ENGLAND SP McGill Univ, Ctr Med Educ, Columbia Univ, Dept Med Informat AB The U.S. National Library of Medicine (NLM) has long been a world leader in the archiving and distribution of the print-based images of biology and medicine. NLM has also been a pioneer in the use of computer systems to encode and distribute textual knowledge of the life sciences. NLMs Long Range Planning effort of 1985-86 foresaw a coming era where NLM's Bibliographic and factual database services would be complemented by libraries of digital images, distributed over high speed computer networks. The NLM Planning Panel on Electronic Imaging recommended that NLM should undertake the building a digital image library consisting of computerized tomography (CT) and magnetic resonance (MR) images, and cryosection images of a representative, carefully selected and prepared male and female cadaver -- the "Visible Human Project." The male and female Visible Human data sets are now being made available through a license agreement with the NLM. The data sets are supporting a wide range of educational, diagnostic, treatment planning, and commercial uses. The NLM, in partnership with other U.S. government research agencies has begun a three prong effort within the Visible Human Project to address: the creation of a new online, interactive, digital head-and-neck atlas; the development of a tool kit of computational programs capable of automatically performing many of the basic data handling functions required for using Visible Human data in applications; and the improved resolution of future Visible Human data sets through the reduction of the anatomical artifacts introduced by the methods used to stabilize and section the anatomical materials and the development of staining and wide-spectrum methods for increasing tissue contrast. SN 0926-9630 BN 1-58603-194-5 PY 2001 VL 84 BP 887 EP 890 UT WOS:000172901700237 PM 11604860 ER PT J AU Montenegro, SML Abath, FGC Domingues, ALC Melo, W de Morais, CNL Coutinho, EM Mahanty, S Wynn, T AF Montenegro, SML Abath, FGC Domingues, ALC Melo, W de Morais, CNL Coutinho, EM Mahanty, S Wynn, T TI Preliminary results on the effects of CD40/CD40L interactions and SAC-induction on IFN-gamma expression in human schistosomiasis SO MEMORIAS DO INSTITUTO OSWALDO CRUZ CT 7th International Symposium on Schistosomiasis CY DEC 05-09, 1999 CL RIO DE JANEIRO, BRAZIL SP Oswaldo Cruz Fdn AB In this communication the authors analyzed the pattern of expression of IFN-gamma as a surrogate type 1 response in different clinical forms of schistosomiasis in response to stimulation involving T-cell dependent and T-cell independent pathways, to investigate which pathways were functional in human schistosomiasis, and to further characterize the nature of Th1 response impairment in this parasitic disease. SN 0074-0276 PY 2001 VL 96 SU S BP 103 EP 105 DI 10.1590/S0074-02762001000900014 UT WOS:000171200700014 PM 11586433 ER PT J AU Schroeder, SR Oster-Granite, ML Berkson, G Bodfish, JW Breese, GR Cataldo, MF Cook, EH Crnic, LS DeLeon, I Fisher, W Harris, JC Horner, RH Iwata, B Jinnah, HA King, BH Lauder, JM Lewis, MH Newell, K Nyhan, WL Rojahn, J Sackett, GP Sandman, C Symons, F Tessel, RE Thompson, T Wong, DF AF Schroeder, SR Oster-Granite, ML Berkson, G Bodfish, JW Breese, GR Cataldo, MF Cook, EH Crnic, LS DeLeon, I Fisher, W Harris, JC Horner, RH Iwata, B Jinnah, HA King, BH Lauder, JM Lewis, MH Newell, K Nyhan, WL Rojahn, J Sackett, GP Sandman, C Symons, F Tessel, RE Thompson, T Wong, DF TI Self-injurious behavior: Gene-brain-behavior relationships SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS AB This paper summarizes a conference held at the National institute of Child Health and Human Development on December 6-7, 1999, on self-injurious behavior [SIB] in developmental disabilities. Twenty-six of the top researchers in the U.S. from this field representing 13 different disciplines discussed environmental mechanisms, epidemiology, behavioral and pharmacological intervention strategies, neurochemical substrates, genetic syndromes in which SIB is a prominent behavioral phenotype, neurobiological and neurodevelopmental factors affecting SIE in humans as well as a variety of animal models of SIE. Findings over the last decade, especially new discoveries since 1995, were emphasized, SIB is a rapidly growing area of scientific interest to both basic and applied researchers. In many respects it is a model for the study of gene-brain-behavior relationships in developmental disabilities. (C) 2001 Wiley-Liss, Inc. RI Iwata, Brian/A-7391-2009 OI Iwata, Brian/0000-0001-8217-2049 SN 1080-4013 PY 2001 VL 7 IS 1 BP 3 EP 12 DI 10.1002/1098-2779(200102)7:1<3::AID-MRDD1002>3.0.CO;2-# UT WOS:000167286800002 PM 11241877 ER PT J AU Weibel, TD Brady, RO AF Weibel, TD Brady, RO TI Systematic approach to the diagnosis of lysosomal storage disorders SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS AB Disorders that arise as a result of lysosomal dysfunction represent some of the most challenging diagnostic problems in medicine. Not only are these disorders infrequently seen, but they may also present with signs and symptoms that mimic perinatal injury, food intolerance, or the sequellae of neonatal infection. Misidentification can lead to significant delay in diagnosis. Ironically, as the prevailing economic climate places increasing time constraints on practicing physicians, medical research is providing treatment strategies and management techniques that are most effective if applied early in the course of the disease. Most lysosomal storage disorders can now be definitively diagnosed once the signs are recognized. In many cases the benefits of early diagnosis, enlightened management, and appropriate referral are considerable. The aim of this paper is to demystify this elusive class of diseases, to promote clinical vigilance in their detection, and to provide a systematic approach to diagnosis when clinical suspicion is aroused. (C) 2001 Wiley-Liss, Inc. SN 1080-4013 PY 2001 VL 7 IS 3 BP 190 EP 199 DI 10.1002/mrdd.1027 UT WOS:000170893900007 PM 11553935 ER PT J AU Holmes, KL Lantz, LM AF Holmes, KL Lantz, LM TI Protein labeling with fluorescent probes SO METHODS IN CELL BIOLOGY, VOL 63 SE METHODS IN CELL BIOLOGY SN 0091-679X PY 2001 VL 63 BP 185 EP 204 UT WOS:000166441200009 PM 11060842 ER PT J AU Bortner, CD Cidlowski, JA AF Bortner, CD Cidlowski, JA TI Flow cytometric analysis of cell shrinkage and monovalent ions during apoptosis SO METHODS IN CELL BIOLOGY, VOL 66 SE METHODS IN CELL BIOLOGY SN 0091-679X PY 2001 VL 66 BP 49 EP + UT WOS:000169819400003 PM 11396018 ER PT S AU Nemes, Z Madi, A Marekov, LN Piacentini, M Steinert, PM Fesus, L AF Nemes, Z Madi, A Marekov, LN Piacentini, M Steinert, PM Fesus, L BE Schwartz, LM Ashwell, JD TI Analysis of protein transglutamylation in apoptosis SO METHODS IN CELL BIOLOGY, VOL 66: APOPTOSIS SE Methods in Cell Biology RI Madi, Andras/B-6837-2012; Piacentini, Mauro/I-2411-2016 OI Piacentini, Mauro/0000-0003-2919-1296 SN 0091-679X BN 0-12-632447-6; 0-12-544165-7 PY 2001 VL 66 BP 111 EP + UT WOS:000169819400005 PM 11396000 ER PT J AU Fearnhead, HO AF Fearnhead, HO TI Cell-free systems to study apoptosis SO METHODS IN CELL BIOLOGY, VOL 66 SE METHODS IN CELL BIOLOGY RI Fearnhead, Howard/D-4826-2012; OI Fearnhead, Howard/0000-0002-8054-9794 SN 0091-679X PY 2001 VL 66 BP 167 EP 185 UT WOS:000169819400007 PM 11396002 ER PT J AU Liu, ZG Lewis, J Wang, TH Cook, A AF Liu, ZG Lewis, J Wang, TH Cook, A TI Role of c-Jun N-terminal kinase in apoptosis SO METHODS IN CELL BIOLOGY, VOL 66 SE METHODS IN CELL BIOLOGY SN 0091-679X PY 2001 VL 66 BP 187 EP 195 UT WOS:000169819400008 PM 11396003 ER PT J AU Valavanis, C Hu, YH Yang, YL Osborne, BA Chouaib, S Greene, L Ashwell, JD Schwartz, LM AF Valavanis, C Hu, YH Yang, YL Osborne, BA Chouaib, S Greene, L Ashwell, JD Schwartz, LM TI Model cell lines for the study of apoptosis in vitro SO METHODS IN CELL BIOLOGY, VOL 66 SE METHODS IN CELL BIOLOGY RI Chouaib, Salem/F-7939-2016 SN 0091-679X PY 2001 VL 66 BP 417 EP 436 UT WOS:000169819400018 PM 11396014 ER PT B AU Le, SY Liu, WM Maizel, JV AF Le, SY Liu, WM Maizel, JV BE Valafar, F TI Searching for gene regulatory elements related to the unusual folding regions in genome sequences SO METMBS'01: PROCEEDINGS OF THE INTERNATIONAL CONFERENCE ON MATHEMATICS AND ENGINEERING TECHNIQUES IN MEDICINE AND BIOLOGICAL SCIENCES CT International Conference on Mathematics and Engineering Techniques in Medicine and Biological Sciences CY JUN 25-28, 2001 CL LAS VEGAS, NV SP Comp Sci Res, Educ & Appl Press, Int Technol Inst, Korea Informat Proc Soc, World Acad Sci Informat Technol, PACT Corp, Comp Vis Res & Appl Tech, Java High Performance Comp Res Grp, Sundance Digital Signal Proc Inc AB Numerous experiments and analyses of RNA structures have revealed that the local distinct structure closely correlates with the biological function. In this study, the knowledge of such distinct structure different from an random folding in an RNA sequence is evaluated by two z-scores, significance score and stability score. Statistical analyses indicate that the distributions of the two scores in the sequence do not follow a normal distribution, however they can be fitted very well by a linearly transformed, noncentral Student's t distribution (LTNSTD). Using the derived LTNSTD, we can extract these unusual folding regions (UFR) from the sequence database. Our data mining method is successfully applied to the complete genome of Mycoplasma genitalium (M.gen) and discovers these statistical extremes. By comparison with the artificial, randomly shuffled sequence from the complete M.gen genome, our results demonstrate that the UFRs in the genome are not selected by chance. These UFRs reveal the biological knowledge of structure roles involved in their sequence information and can be considered as candidates for searching gene regulatory elements. BN 1-892512-77-7 PY 2001 BP 33 EP 39 UT WOS:000173108700006 ER PT S AU Suh, EB Dougherty, ER Kim, S Russ, DE Martino, RL AF Suh, EB Dougherty, ER Kim, S Russ, DE Martino, RL BE Bittner, ML Chen, YD Dorsel, AN Dougherty, ER TI Parallel computing methods for analyzing gene expression relationships SO MICROARRAYS: OPTICAL TECHNOLOGIES AND INFORMATICS SE Proceedings of SPIE CT Conference on Microarrays - Optical Technologies and Informatics CY JAN 21-22, 2001 CL SAN JOSE, CA SP SPIE AB This paper presents a parallel program for assessing the codetermination of gene transcriptional states from large-scale simultaneous gene expression measurements with cDNA microarrays. The parallel program is based on a nonlinear statistical framework recently proposed for the analysis of gene interaction via multivariate expression arrays. Parallel computing is key in the application of the statistical framework to a large set of genes because a prohibitive amount of computer time is required on a classical single-CPU machine. Our parallel program, named the Parallel Analysis of Gene Expression (PAGE) program, exploits inherent parallelism exhibited in the proposed codetermination prediction models. By running PAGE on 64 processors in Beowulf, a clustered parallel system, an analysis of melanoma cDNA microarray expression data has been completed within 12 days of computer time, an analysis that would have required about one and half years on a single-CPU computing system. A data visualization program, named the Visualization of Gene Expression (VOGE) program, has been developed to help interpret the massive amount of quantitative information produced by PAGE. VOGE provides graphical data visualization and analysis tools with filters, histograms, and accesses to other genetic databanks for further analyses of the quantitative information. OI Russ, Daniel/0000-0003-4040-4416 SN 0277-786X BN 0-8194-3944-4 PY 2001 VL 4266 BP 213 EP 221 DI 10.1117/12.427990 UT WOS:000171277300023 ER PT J AU Schoolnik, GK Voskuil, MI Schnappinger, D Yildiz, FH Meibom, K Dolganov, NA Wilson, MA Chong, KH AF Schoolnik, GK Voskuil, MI Schnappinger, D Yildiz, FH Meibom, K Dolganov, NA Wilson, MA Chong, KH TI Whole genome DNA microarray expression analysis of biofilm development by Vibrio cholerae O1 El Tor SO MICROBIAL GROWTH IN BIOFILMS, PT A R BIOLOGICAL ASPECTS SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 336 BP 3 EP 18 DI 10.1016/S0076-6879(01)36573-4 UT WOS:000169760800001 PM 11398407 ER PT J AU Palmer, RJ Wu, R Gordon, S Bloomquist, CG Liljemark, WE Kilian, M Kolenbrander, PE AF Palmer, RJ Wu, R Gordon, S Bloomquist, CG Liljemark, WE Kilian, M Kolenbrander, PE TI Retrieval of biofilms from the oral cavity SO MICROBIAL GROWTH IN BIOFILMS, PT B SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 337 BP 393 EP 403 UT WOS:000169760900027 PM 11398445 ER PT J AU Yamauchi, A Yu, LX Potgens, AJG Kuribayashi, F Nunoi, H Kanegasaki, S Roos, D Malech, HL Dinauer, MC Nakamura, M AF Yamauchi, A Yu, LX Potgens, AJG Kuribayashi, F Nunoi, H Kanegasaki, S Roos, D Malech, HL Dinauer, MC Nakamura, M TI Location of the epitope for 7D5, a monoclonal antibody raised against human flavocytochrome b(558), to the extracellular peptide portion of primate gp91(phox) SO MICROBIOLOGY AND IMMUNOLOGY AB Flavocytochrome b(558) is the membrane component of the phagocyte NADPH oxidase, and is a heterodimer composed of gp91(phox) and p22(phox) subunits. Human flavocytochrome b(558) is recognized by monoclonal antibody 7D5 at an unidentified extracellular domain, although our previous study suggested it might recognize p22(phox). 7D5 has proven useful in rapid screening of individuals for X-linked chronic granulomatous disease by flow-cytometry. Therefore, we re-evaluated the location of the 7D5 epitope using gene-engineered cell lines expressing hybrid flavocytochromes composed of human and murine subunit homologues. The current study demonstrates that the 7D5 recognizes epitope only of primate gp91(phox). Flow-cytometric analyses showed that 7D5 consistently bound to cells expressing human gp91(phox). In addition, 7D5 immunoprecipitated the similar to 58 kDa unglycosylated gp91(phox) protein from solubilized membrane fractions of tunicamycin-treated PLB-985 granulocytes, indicating that glycans were not required for 7D5 binding. Transgenic COS7 cells expressing human gp91(phox) but not p22(phox) were recognized by 7D5. These results localized the epitope of 7D5 to an extracellular peptide portion of primate gp91(phox) and indicate that the antibody will be useful for monitoring the efficiency of gene therapy in patients with flavocytochrome b(558)-deficient chronic granulomatous disease and for elucidating structural characteristics of flavocytochrome b(558). RI Yamauchi, Akira/F-2202-2010 OI Yamauchi, Akira/0000-0001-9205-6922 SN 0385-5600 PY 2001 VL 45 IS 3 BP 249 EP 257 UT WOS:000167322800008 PM 11345535 ER PT J AU Ducatman, B Cox-Ganser, J Stead, J Maymind, M Saffiotti, U AF Ducatman, B Cox-Ganser, J Stead, J Maymind, M Saffiotti, U TI Lymph node silicosis and pulmonary silicosis: An autopsy study SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 12 BP 6A EP 6A UT WOS:000166622400020 ER PT J AU Illei, P Allander, SV Chen, Y Meltzer, PS Antonescu, CR Ladanyi, M AF Illei, P Allander, SV Chen, Y Meltzer, PS Antonescu, CR Ladanyi, M TI Prominent Her2/neu expression in the epithelial component of synovial sarcoma. SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 56 BP 13A EP 13A UT WOS:000166622400064 ER PT J AU Bocklage, T Key, CR Platz, CE Weaver, DL Croning, KA Harlan, LC Ballard-Barbash, R Warren, JL AF Bocklage, T Key, CR Platz, CE Weaver, DL Croning, KA Harlan, LC Ballard-Barbash, R Warren, JL TI Assessing prognostic factors in ductal carcinoma in situ (DCIS): Do pathology report extractions reflect what is obtained by slide review? SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 114 BP 23A EP 23A UT WOS:000166622400122 ER PT J AU Merino, MJ Bryant, B Sobel, M Cowan, K Chiesa, A AF Merino, MJ Bryant, B Sobel, M Cowan, K Chiesa, A TI Frequency of loss of heterozygosity (LOH) of metastasis-related tumor supressor genes in young women with breast cancer. SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 168 BP 32A EP 32A UT WOS:000166622400176 ER PT J AU Weaver, DL Bocklage, T Platz, CE Key, CR Cronin, K Harlan, LC Ballard-Barbash, JL Warren, JL AF Weaver, DL Bocklage, T Platz, CE Key, CR Cronin, K Harlan, LC Ballard-Barbash, JL Warren, JL TI Comparison of nuclear grade and overall grade in ductal carcinoma-in-situ (DCIS) SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 222 BP 41A EP 41A UT WOS:000166622400230 ER PT J AU Weaver, DL Bocklage, T Key, CR Platz, CE Cronin, K Harlan, LC Ballard-Barbash, R Warren, JL AF Weaver, DL Bocklage, T Key, CR Platz, CE Cronin, K Harlan, LC Ballard-Barbash, R Warren, JL TI Inter-observer variability in interpretation of ductal carcinoma-in-situ (DCIS) reports as compared to variability in interpretation of slides SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 221 BP 41A EP 41A UT WOS:000166622400229 ER PT J AU Clark, B Vezza, P Abati, A AF Clark, B Vezza, P Abati, A TI Diagnostic sensitivity of pulmonary FNA vs BAL SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 276 BP 50A EP 50A UT WOS:000166622400284 ER PT J AU Dahmoush, L Hijazi, Y Barnes, E Stetler-Stevenson, MA Abati, A AF Dahmoush, L Hijazi, Y Barnes, E Stetler-Stevenson, MA Abati, A TI Adult T-cell leukemia/lymphoma (ATLL): A cytopathological immunocytochemical and flow cytometric study. SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 281 BP 51A EP 51A UT WOS:000166622400289 ER PT J AU Fetsch, PA Steinberg, SM Riker, AI Marincola, FM Abati, A AF Fetsch, PA Steinberg, SM Riker, AI Marincola, FM Abati, A TI Melanoma antigen expression in serial FNAs in patients with metastatic malignant melanoma participating in immunotherapy clinical trials - A preliminary look. SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 292 BP 52A EP 52A UT WOS:000166622400300 ER PT J AU Fetsch, PA Brosky, K Simsir, A Abati, A AF Fetsch, PA Brosky, K Simsir, A Abati, A TI Preparation of effusion cytology samples for optimal immunocytochemistry: A comparison of cytospins vs. ThinPrep (TM) vs. cell blocks. SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 291 BP 52A EP 52A UT WOS:000166622400299 ER PT J AU Filie, A Simone, N Simone, C Petricoin, A Liotta, LA Abati, A AF Filie, A Simone, N Simone, C Petricoin, A Liotta, LA Abati, A TI Proteomic evaluation of archival FNA patient samples of papillary thyroid carcinoma and follicular variant of papillary thyroid carcinoma yields distinct protein fingerprints with potential diagnostic applications. SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 293 BP 53A EP 53A UT WOS:000166622400301 ER PT J AU Panizo, A Roberts, D Al-Barazi, H Bryant, B Garcia-Macias, MC Chiesa, A Pardo, J Merino, MJ AF Panizo, A Roberts, D Al-Barazi, H Bryant, B Garcia-Macias, MC Chiesa, A Pardo, J Merino, MJ TI Utilization of cytology smears and manual micro-dissection for proteomic analysis. SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 330 BP 59A EP 59A UT WOS:000166622400338 ER PT J AU Simone, N Fetsch, P Filie, A Marincoia, F Simone, C Petricoin, E Liotta, LA Abati, A AF Simone, N Fetsch, P Filie, A Marincoia, F Simone, C Petricoin, E Liotta, LA Abati, A TI Proteomic evaluation of archival FNAs: New vistas in diagnoses SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 349 BP 62A EP 62A UT WOS:000166622400357 ER PT J AU Simsir, A Fetsch, PA Abati, A AF Simsir, A Fetsch, PA Abati, A TI Comparison of antibodies to HBME-1 and Calretinin for the detection of mesothelial cells in effusion cytology. SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 350 BP 62A EP 62A UT WOS:000166622400358 ER PT J AU Rosenblatt, KP Finkelstein, SE Cassarino, DS Fischette, M Barnes, E Duray, PH AF Rosenblatt, KP Finkelstein, SE Cassarino, DS Fischette, M Barnes, E Duray, PH TI Rapidly progressive melanoma (RPA) SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 412 BP 72A EP 72A UT WOS:000166622400419 ER PT J AU Bordi, C Ferraro, G Azzoni, C Corleto, V Gibril, F Delle Fave, G Jensen, RT AF Bordi, C Ferraro, G Azzoni, C Corleto, V Gibril, F Delle Fave, G Jensen, RT TI The antral mucosa as a new site for endocrine tumors in MEN-1/Zollinger-Ellison syndromes SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 422 BP 74A EP 74A UT WOS:000166622400429 ER PT J AU Park, CS Kim, HS Joo, YE Jung, JJ Kang, HS Nam, JH Messam, CA Min, KW AF Park, CS Kim, HS Joo, YE Jung, JJ Kang, HS Nam, JH Messam, CA Min, KW TI Comparative evaluation of angiogenesis in gastric adenocarcinoma by immunoreactivity for nestin and CD34 SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 536 BP 93A EP 93A UT WOS:000166622400543 ER PT J AU Cheng, L Bostwick, DG Li, G Vortmeyer, AO Zhuang, ZP AF Cheng, L Bostwick, DG Li, G Vortmeyer, AO Zhuang, ZP TI Allelic loss of chromosome 9p21 and 17p13 in metastatic progression of bladder cancer SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 603 BP 104A EP 104A UT WOS:000166622400610 ER PT J AU Chiesa, A Sobel, M Bryant, B Panizo, A Linehan, WM Merino, MJ AF Chiesa, A Sobel, M Bryant, B Panizo, A Linehan, WM Merino, MJ TI Somatic mutations and loss of heterozygosity of the VHL tumor supressor gene in unclassified renal cell carcinomas SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 606 BP 105A EP 105A UT WOS:000166622400613 ER PT J AU Panizo, A Bryant, B Chiesa, A Walther, MM Linehan, WM Merino, MJ AF Panizo, A Bryant, B Chiesa, A Walther, MM Linehan, WM Merino, MJ TI Molecular analysis of aggressive chromophobe renal cell carcinoma. SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 695 BP 120A EP 120A UT WOS:000166622400702 ER PT J AU Staebler, A Heselmeyer-Haddad, K Bell, K Riopel, M Perlman, E Ried, T Kurman, R AF Staebler, A Heselmeyer-Haddad, K Bell, K Riopel, M Perlman, E Ried, T Kurman, R TI Micropapillary serous carcinoma (MPSC) of the ovary has distinct chromosomal imbalances by comparative hybridiation (CGH) compared with atypical proliferative serous tumors (APST) and serous carcinomas (SC). SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 855 BP 146A EP 146A UT WOS:000166622400864 ER PT J AU Beaty, MW Toro, J Sorbara, L Stern, JB Wilson, WW Jaffe, ES AF Beaty, MW Toro, J Sorbara, L Stern, JB Wilson, WW Jaffe, ES TI Cutaneous lymphomatoid granulomatosis: A clinicopathologic study SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 913 BP 156A EP 156A UT WOS:000166622400922 ER PT J AU Cong, PJ Raffeld, M Jaffe, E AF Cong, PJ Raffeld, M Jaffe, E TI Blastic NK cell lymphoma/leukemia: A clinicopathological study of 23 cases SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 938 BP 160A EP 160A UT WOS:000166622400947 ER PT J AU Greiner, TC Fang, N Weisenburger, DD Chan, WC Hock, L Collins, F Hacia, J AF Greiner, TC Fang, N Weisenburger, DD Chan, WC Hock, L Collins, F Hacia, J TI ATM mutations do not predict outcome or p53 mutation status in mantle cell lymphoma SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 966 BP 165A EP 165A UT WOS:000166622400975 ER PT J AU Hedvat, CV Asherov, M Qin, J Linkov, I Filippa, DA Tosato, G Jaffe, ES Teruya-Feldstein, J AF Hedvat, CV Asherov, M Qin, J Linkov, I Filippa, DA Tosato, G Jaffe, ES Teruya-Feldstein, J TI Monocyte derived chemotactic factor (MDC), is expressed by Reed-Sternberg (RS) cells in classical Hodgkin's disease (CHD) using tissue arrays SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 969 BP 165A EP 165A UT WOS:000166622400978 ER PT J AU Huang, JZ Sanger, WG Pickering, DL Greiner, TC Staudt, LM Lynch, JC Weisenburger, DD Armitage, JO Chan, WC AF Huang, JZ Sanger, WG Pickering, DL Greiner, TC Staudt, LM Lynch, JC Weisenburger, DD Armitage, JO Chan, WC TI CD10, Bcl-2, and Bcl-6 protein expression and t(14;18)(q32;q21) in two subtypes of diffuse large B-cell lymphoma defined by gene expression profiles SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 978 BP 167A EP 167A UT WOS:000166622400987 ER PT J AU Huang, JZ Greiner, TC Lynch, JC Staudt, LM Weisenburger, DD Armitage, JO Chan, WC AF Huang, JZ Greiner, TC Lynch, JC Staudt, LM Weisenburger, DD Armitage, JO Chan, WC TI Gene expression profile associated with T-cell infiltration in diffuse large B-cell lymphoma analyzed by cDNA microarray SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 977 BP 167A EP 167A UT WOS:000166622400986 ER PT J AU Sobocinski, G Shaw, S Anderson, A Kaldjian, E AF Sobocinski, G Shaw, S Anderson, A Kaldjian, E TI Immunohistochemical localization of extra-cellular matrix proteins of the lymph node reticular network. SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 1052 BP 179A EP 179A UT WOS:000166622401061 ER PT J AU Taddesse-Heath, L Sorbara, L Raffeld, M Jaffe, ES AF Taddesse-Heath, L Sorbara, L Raffeld, M Jaffe, ES TI Marginal zone B-cell lymphoma in pediatric and young adults. SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 1057 BP 180A EP 180A UT WOS:000166622401066 ER PT J AU Lei, JY Mont, E Bryant-Greenwood, P Linehan, WM Merino, MJ Duray, PH AF Lei, JY Mont, E Bryant-Greenwood, P Linehan, WM Merino, MJ Duray, PH TI A new spectrum of the pancreatic tumors in von Hippel-Lindau disease SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 1171 BP 199A EP 199A UT WOS:000166622401180 ER PT J AU Nicholson, SA Khan, MA Welsh, JA McMenamin, MG Travis, WD Harris, CC AF Nicholson, SA Khan, MA Welsh, JA McMenamin, MG Travis, WD Harris, CC TI Inactivation of p14ARF and p53 are inversely correlated in human cell lines. SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 1248 BP 212A EP 212A UT WOS:000166622401257 ER PT J AU Kumaki, F Kawai, T Churg, A Gallateau-Salle, FB Haselton, P Henderson, D Roggli, V Travis, WD Cagle, P Ferrans, VJ AF Kumaki, F Kawai, T Churg, A Gallateau-Salle, FB Haselton, P Henderson, D Roggli, V Travis, WD Cagle, P Ferrans, VJ TI Expression of telomerase reverse transcriptase (TERT) in malignant mesothelioma SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 1309 BP 222A EP 222A UT WOS:000166622401318 ER PT J AU Kumaki, F Matsui, K Valencia, J Yu, Z Kawai, T Ozeki, Y Ferrans, VJ Travis, WD AF Kumaki, F Matsui, K Valencia, J Yu, Z Kawai, T Ozeki, Y Ferrans, VJ Travis, WD TI Expression of matrix metalloproteinases (MMPs) in pulmonary adenocarcinoma showing lipidic growth (ALG) and atypical adenomatous hyperplasia (AAH) SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 1308 BP 222A EP 222A UT WOS:000166622401317 ER PT J AU Nicholson, SA Khan, MA Welsh, JA Travis, WD Bennett, W Battey, J Marrogi, A Jett, JR Tazelaar, HD Trastek, V Pairolero, PC Liotta, LA Caporaso, NE Harris, CC AF Nicholson, SA Khan, MA Welsh, JA Travis, WD Bennett, W Battey, J Marrogi, A Jett, JR Tazelaar, HD Trastek, V Pairolero, PC Liotta, LA Caporaso, NE Harris, CC TI Gastrin-releasing peptide receptor (GRPR) expression in non-small cell lung carcinoma (NSCLC) SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 1321 BP 224A EP 224A UT WOS:000166622401330 ER PT J AU Nicholson, SA Khan, MA Welsh, JA Travis, WD Okby, N Bennett, W Przygodzki, R Jett, JR Tazelaar, HD Trastek, V Pairolero, PC Liotta, LA Caporaso, NE Harris, CC AF Nicholson, SA Khan, MA Welsh, JA Travis, WD Okby, N Bennett, W Przygodzki, R Jett, JR Tazelaar, HD Trastek, V Pairolero, PC Liotta, LA Caporaso, NE Harris, CC TI p14ARF deletion is associated with poor prognosis in non-small cell lung carcinoma (NSCLC) SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 1322 BP 224A EP 224A UT WOS:000166622401331 ER PT J AU Rodrigues, RG Panizo, A Cashel, JA Krutzsch, HC Merino, MJ Roberts, D AF Rodrigues, RG Panizo, A Cashel, JA Krutzsch, HC Merino, MJ Roberts, D TI Proteomic detection of ectopically expressed semenogelins in small cell carcinoma of lung. A possible new marker for diagnosis. SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 1331 BP 226A EP 226A UT WOS:000166622401340 ER PT J AU Valencia, JC Virador, V Escobar, JC Moss, J Ferrans, VJ AF Valencia, JC Virador, V Escobar, JC Moss, J Ferrans, VJ TI Localization of tissue angiotensin system in pulmonary lymphangioleiomyomatosis (LAM) SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 1338 BP 227A EP 227A UT WOS:000166622401347 ER PT J AU Chiesa, C Sobel, M Merino, MJ Linehan, WM Bryant, B AF Chiesa, C Sobel, M Merino, MJ Linehan, WM Bryant, B TI DNA sequencing of microdissected paraffin-embedded tissues SO MODERN PATHOLOGY SN 0893-3952 EI 1530-0285 PD JAN PY 2001 VL 14 IS 1 MA 1363 BP 231A EP 231A UT WOS:000166622401372 ER PT J AU Singh, BB Curdt, I Shomburg, D Bisen, PS Bhome, H AF Singh, BB Curdt, I Shomburg, D Bisen, PS Bhome, H TI Valine 77 of heterocystous ferredoxin FdxH2 in Anabaena variabilis strain ATCC 29413 is critical for its oxygen sensitivity SO MOLECULAR AND CELLULAR BIOCHEMISTRY AB Ferredoxins are small iron sulfur proteins necessary for electron donation. FdxH1 and FdxH2 are associated with two different nif gene clusters where they transfer electrons for the reduction of nitrogenase complex. FdxH1 was observed to be stable towards oxygen, whereas, FdxH2 was relatively unstable. We had identified the amino acid involved in oxygen sensitivity of ferredoxin protein using protein modeling. The exchange of valine to leucine at position 77 was critical for ferredoxin proteins in relation to its oxygen sensitivity. This exchange leads to a longer side chain, which inhibits the accessibility of oxygen to the iron sulfur cluster. Site directed mutagenesis and in vitro experiments confirms that valine indeed is involved in the oxygen sensitivity. The exchange of leucine to valine in FdxH1 makes it oxygen unstable. Thus, from the above results we can conclude that the position of leucine at position 77 is critical for oxygen sensitivity of ferredoxin and protein modeling can be used to identify specific amino acids in other oxygen-sensitive proteins. OI Singh, Brij/0000-0003-0535-5997 SN 0300-8177 PD JAN PY 2001 VL 217 IS 1-2 BP 137 EP 142 DI 10.1023/A:1007228929662 UT WOS:000166774700017 PM 11269658 ER PT J AU Safran, N Shneyvays, V Balas, N Jacobson, KA Nawrath, H Shainberg, A AF Safran, N Shneyvays, V Balas, N Jacobson, KA Nawrath, H Shainberg, A TI Cardioprotective effects of adenosine A(1) and A(3) receptor activation during hypoxia in isolated rat cardiac myocytes SO MOLECULAR AND CELLULAR BIOCHEMISTRY AB Adenosine (ADO) is a well-known regulator of a variety of physiological functions in the heart. In stress conditions, like hypoxia or ischemia, the concentration of adenosine in the extracellular fluid rises dramatically, mainly through the breakdown of ATP. The degradation of adenosine in the ischemic myocytes induced damage in these cells, but it may simultaneously exert protective effects in the heart by activation of the adenosine receptors. The contribution of ADO to stimulation of protective effects was reported in human and animal hearts, but not in rat hearts. The aim of this study was to evaluate the role of adenosine A(1) and A(3) receptors (A(1)R and A(3)R), in protection of isolated cardiac myocytes of newborn rats from ischemic injury. The hypoxic conditions were simulated by exposure of cultured rat cardiomyocytes (4-5 days in vitro), to an atmosphere of a N-2 (95%) and CO2 (5%) mixture, in glucose-free medium for 90 min. The cardiotoxic and cardioprotective effects of ADO ligands were measured by the release of lactate dehydrogenase (LDH) into the medium. Morphological investigation includes immunohistochemistry, image analysis of living and fixed cells and electron microscopy were executed. Pretreatment with the adenosine deaminase considerably increased the hypoxic damage in the cardiomyocytes indicating the importance of extracellular adenosine. Blocking adenosine receptors with selective A(1) and A(3) receptor antagonists abolished the protective effects of adenosine. A(1)R and A(3)R activation during the hypoxic insult delays onset of irreversible cell injury and collapse of mitochondrial membrane potential as assessed using DASPMI fluorochrom. Cardioprotection induced by the A(1)R agonist, CCPA, was abolished by an A(1)R antagonist, DPCPX, and was not affected by an A(3)R antagonist, MRS1523. Cardioprotection caused by the A(3)R agonist, Cl-IB-MECA, was antagonized completely by MRS1523 and only partially by DPCPX. Activation of both A(1)R and A(3)R together was more efficient in protection against hypoxia than by each one alone. Our study indicates that activation of either A(1) or A(3) adenosine receptors in the rat can attenuate myocyte injury during hypoxia. Highly selective A(1)R and A(3)R agonists may have potential as cardioprotective agents against ischemia or heart surgery. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 SN 0300-8177 PD JAN PY 2001 VL 217 IS 1-2 BP 143 EP 152 DI 10.1023/A:1007209321969 UT WOS:000166774700018 PM 11269659 ER PT J AU Zhang, SL DuBois, W Ramsay, ES Bliskovski, V Morse, HC Taddesse-Heath, L Vass, WC DePinho, RA Mock, BA AF Zhang, SL DuBois, W Ramsay, ES Bliskovski, V Morse, HC Taddesse-Heath, L Vass, WC DePinho, RA Mock, BA TI Efficiency alleles of the Pctr1 modifier locus for plasmacytoma susceptibility SO MOLECULAR AND CELLULAR BIOLOGY AB The susceptibility of BALB/c mice to pristane-induced plasmacytomas is a complex genetic trait involving multiple loci, while DBA/2 and C57BL/6 strains are genetically resistant to the plasmacytomagenic effects of pristane. In this model system for human B-cell neoplasia, one of the BALB/c susceptibility and modifier loci, Pctr1, was mapped to a 5.7-centimorgan (cM) chromosomal region that included Cdkn2a, which encodes p16(INK4a) and p19(ARF), and the coding sequences for the BALB/c p16(INK4a) and p19(ARF) alleles were found to be polymorphic with respect to their resistant Pctr1 counterparts in DBA/2 and C57BL/6 mice (45), In the present study, alleles of Pctr1, Cdkn2a, and D4Mit15 from a resistant strain (BALB/cDAG) carrying DBA/2 chromatin were introgressively backcrossed to the susceptible BALB/c strain. The resultant C.DAG-Pctr1 Cdkn2a D4Mit15 congenic was more resistant to plasmacytomagenesis than BALB/c, thus narrowing Pctr1 to a 1.5-cM interval, Concomitantly, resistant C57BL/6 mice, from which both gene products of the Cdkn2a gene have been eliminated, developed pristane-induced plasma cell tumors over a shorter latency period than the traditionally susceptible BALB/cAn strain. Biological assays of the p16(INK4a) and p19(ARF) alleles from BALB/c and DBA/2 indicated that the BALB/c p16(INK4a) allele was less active than its DBA/2 counterpart in inducing growth arrest of mouse plasmacytoma cell lines and preventing ras-induced transformation of NIH 3T3 cells, while the two p19(ARF) alleles displayed similar potencies in both assays. We propose that the BALB/c susceptibility/modifier locus, Pctr1, is an "efficiency" allele of the p16(INK4a) gene. OI Morse, Herbert/0000-0002-9331-3705 SN 0270-7306 PD JAN PY 2001 VL 21 IS 1 BP 310 EP 318 DI 10.1128/MCB.21.1.310-318.2001 UT WOS:000165847300030 PM 11113205 ER PT J AU Maraia, RJ Intine, RVA AF Maraia, RJ Intine, RVA TI Recognition of nascent RNA by the human La antigen: Conserved and divergent features of structure and function SO MOLECULAR AND CELLULAR BIOLOGY SN 0270-7306 PD JAN PY 2001 VL 21 IS 2 BP 367 EP 379 DI 10.1128/MCB.21.2.367-379.2001 UT WOS:000166094500001 PM 11134326 ER PT J AU Shen, CH Leblanc, BP Alfieri, JA Clark, DJ AF Shen, CH Leblanc, BP Alfieri, JA Clark, DJ TI Remodeling of yeast CUP1 chromatin involves activator-dependent repositioning of nucleosomes over the entire gene and flanking sequences SO MOLECULAR AND CELLULAR BIOLOGY AB The yeast CUP1 gene is activated by the copper-dependent binding of the transcriptional activator, Ace1p. An episome containing transcriptionally active or inactive CUP1 was purified in its native chromatin structure from yeast cells. The amount of RNA polymerase II on CUP1 in the purified episomes correlated with its transcriptional activity in vivo. Chromatin structures were examined by using the monomer extension technique to map translational positions of nucleosomes. The chromatin structure of an episome containing inactive CUP1 isolated from ace1 Delta cells is organized into clusters of overlapping nucleosome positions separated by linkers. Novel nucleosome positions that include the linkers are occupied in the presence of Ace1p. Repositioning was observed over the entire CUP1 gene and its flanking regions, possibly over the entire episome. Mutation of the TATA boxes to prevent transcription did not prevent repositioning, implicating a chromatin remodeling activity recruited by Ace1p. These observations provide direct evidence in vivo for the nucleosome sliding mechanism proposed for remodeling complexes in vitro and indicate that remodeling is not restricted to the promoter but occurs over a chromatin domain including CUP1 and its flanking sequences. SN 0270-7306 EI 1098-5549 PD JAN PY 2001 VL 21 IS 2 BP 534 EP 547 DI 10.1128/MCB.21.2.534-547.2001 UT WOS:000166094500016 PM 11134341 ER PT J AU Boitchenko, VE Alimzhanov, MB Turetskaya, RL Ruhlmann, A Nordheim, A Kuprash, DV Nedospasov, SA AF Boitchenko, VE Alimzhanov, MB Turetskaya, RL Ruhlmann, A Nordheim, A Kuprash, DV Nedospasov, SA TI Comparative characterization of lymphotoxin transcripts from human B- and T-cell lines, peripheral lymphocytes, and normal tissues SO MOLECULAR BIOLOGY AB Membrane lymphotoxin (LT) is a heterotrimer LT alpha (1)beta (2), and its production depends on two genes. Northern blotting was employed in studying their transcription in human B- and T-lymphoma cell lines and in peripheral blood lymphocytes before and after induction with phorbol myristate acetate (PMA). Transcription of either gene proved to be similarly regulated in several cell lines and in blood lymphocytes. Activation of the LT alpha gene was associated with induction of transcription factor NF-kappaB (p50/p65) upon cell treatment with PMA. On evidence of RT-PCR, two transcripts of the LTP gene were present in equimolar amounts in all lymphoid cells. A product of alternative splicing contained an open reading frame coding for the cytoplasmic portion of LTP. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; SN 0026-8933 PD JAN-FEB PY 2001 VL 35 IS 1 BP 115 EP 121 DI 10.1023/A:1004867205038 UT WOS:000167417300016 ER PT J AU Malide, D Yewdell, JW Bennink, JR Cushman, SW AF Malide, D Yewdell, JW Bennink, JR Cushman, SW TI The export of major histocompatibility complex class I molecules from the endoplasmic reticulum of rat brown adipose cells is acutely stimulated by insulin SO MOLECULAR BIOLOGY OF THE CELL AB Major histocompatibility complex class I (MHC-I) molecules have been implicated in several nonimmunological functions including the regulation and intracellular trafficking of the insulin-responsive glucose transporter GLUT4. We have used confocal microscopy to compare the effects of insulin on the intracellular trafficking of MHC-I and GLUT4 in freshly isolated rat brown adipose cells. We also used a recombinant vaccinia virus (rVV) to express influenza virus hemagglutinin (HA) as a generic integral membrane glycoprotein to distinguish global versus specific enhancement of protein export from the endoplasmic reticulum (ER) in response to insulin. In the absence of insulin, MHC-I molecules largely colocalize with the ER-resident protein calnexin and remain distinct from intracellular pools of GLUT4. Surprisingly, insulin induces the rapid export of MHC-I molecules from the ER with a concomitant approximately three-fold increase in their level on the cell surface. This ER export is blocked by brefeldin A and wortmannin but is unaffected by cytochalasin D, indicating that insulin stimulates the rapid transport of MHC-I molecules from the ER to the plasma membrane via the Golgi complex in a phosphatidylinositol 3-kinase-dependent and actin-independent manner. We further show that the effect of insulin on MHC-I molecules is selective, because insulin does not affect the intracellular distribution or cell-surface localization of rVV-expressed HA. These results demonstrate that in rat brown adipose cells MHC-I molecule export from the ER is stimulated by insulin and provide the first evidence that the trafficking of MHC-I molecules is acutely regulated by a hormone. RI yewdell, jyewdell@nih.gov/A-1702-2012 SN 1059-1524 PD JAN PY 2001 VL 12 IS 1 BP 101 EP 114 UT WOS:000166353800009 PM 11160826 ER PT J AU El-Osta, A Baker, EK Wolffe, AP AF El-Osta, A Baker, EK Wolffe, AP TI Profiling methyl-CpG specific determinants on transcriptionally silent chromatin SO MOLECULAR BIOLOGY REPORTS AB Transcriptional activity is closely associated with DNA methylation and chromatin remodelling. Evidence is emerging that a family of methylation specific (methyl-CpG binding domain, MBD) proteins have the capacity to bind to methylated sequences and repress transcription. Recent advances in this area reveal that many of the MBD proteins are associated with histone deacetylase (HDAC) dependant repression. The capacity of MBD association to repress transcription would largely be defined by promoter structure and this is best explained by the position and density of DNA methylation. The mechanism of specific targeting of MBD family members to methylated sequences remains largely unknown. In order to understand the mechanistic details of silencing the current challenge is to identify and map these molecular determinants assembled on native chromatin in model systems of human development and disease. Downstream targets such as the methylated Fragile X Mental Retardation gene 1 (FMR1) gene and tumour suppressor genes are likely candidates. In this article, we describe a powerful strategy that involves the immunoprecipitation of in vivo formaldehyde fixed chromatin to identify MBD binding complexes directly isolated from the natural chromosomal environment. We demonstrate the methylated human Multidrug Resistance gene 1 (MDR1) is enriched with transcriptional repressors that belong to the MBD family and this would account for transcriptional silencing. SN 0301-4851 PY 2001 VL 28 IS 4 BP 209 EP 215 DI 10.1023/A:1015744625049 UT WOS:000175974200004 PM 12153140 ER PT J AU Duan, HJ Tsvetkov, LM Liu, YL Song, Y Swaroop, M Wen, R Kung, HF Zhang, H Sun, Y AF Duan, HJ Tsvetkov, LM Liu, YL Song, Y Swaroop, M Wen, R Kung, HF Zhang, H Sun, Y TI Promotion of S-Phase entry and cell growth under serum starvation by SAC/ROC2/Rbx2/Hrt2, an E3 ubiquitin ligase component: Association with inhibition of p27 accumulation SO MOLECULAR CARCINOGENESIS AB The sensitive-to-apoptosis gene (SAG) was initially identified as a redox-inducible, apoptosis-protective protein and subsequently found to be the second family member of regulator of cullins (ROC)/RING box protein (Rbx)/Hrt, which acts as a component of E3 ubiquitin ligase. We report here that SAG promoted cell growth under serum starvation. Microinjection of SAC mRNA into quiescent NIH/3T3 cells induced S-phase entry as determined by [H-3]-thymidine incorporation. Likewise, overexpression of SAG by either adenovirus infection of immortalized human epidermal keratinocytes (Rhek-1) or DNA transfection of SY5Y human neuroblastoma cells induced cell proliferation under serum starvation. Because cyclin-dependent kinase inhibitors (CKIs), including p21, p27, and p57, are degraded through the ubiquitin pathway, we tested whether SAG-induced cell growth is associated with CKI degradation. Although there was no significant difference in the levels of p21 and p57 between the Vector controls and SAG-overexpressing cells, serum starvation induced 10- to 18-fold accumulation of p27 in control Rhek-1 cells. Accumulation of p27 was remarkably inhibited (only 2 to 5-fold) in SAG-infected cells. Inhibition of p27 accumulation was also observed in stably SAG-overexpressing SY5Y cells. Significantly, SAG-associated inhibition of p27 accumulation was largely abolished by the treatment with a proteasome inhibitor. In vivo binding of SAG and Skp2, an F-box protein that promotes p27 ubiquitination, was detected, and the binding was enhanced in SAG-overexpressing cells grown under serum starvation. Thus, SAG-induced growth with serum withdrawal appears to be associated with SAG-mediated p27 degradation. (C) 2001 Wiley-Liss, Inc. SN 0899-1987 PD JAN PY 2001 VL 30 IS 1 BP 37 EP 46 DI 10.1002/1098-2744(200101)30:1<37::AID-MC1011>3.0.CO;2-7 UT WOS:000166837500003 PM 11255262 ER PT J AU Junop, MS Obmolova, G Rausch, K Hsieh, P Yang, W AF Junop, MS Obmolova, G Rausch, K Hsieh, P Yang, W TI Composite active site of an ABC ATPase: MutS uses ATP to verify mismatch recognition and authorize DNA repair SO MOLECULAR CELL AB The MutS protein initiates DNA mismatch repair by recognizing mispaired and unpaired bases embedded in duplex DNA and activating endo- and exonucleases to remove the mismatch. Members of the MutS family also possess a conserved ATPase activity that belongs to the ATP binding cassette (ABC) superfamily. Here we report the crystal structure of a ternary complex of MutS-DNA-ADP and assays of initiation of mismatch repair in conjunction with perturbation of the composite ATPase active site by mutagenesis. These studies indicate that MutS has to bind both ATP and the mismatch DNA simultaneously in order to activate the other mismatch repair proteins. We propose that the MutS ATPase activity plays a proofreading role in DNA mismatch repair, verification of mismatch recognition, and authorization of repair. RI Yang, Wei/D-4926-2011; Junop, Murray/E-4160-2015 OI Yang, Wei/0000-0002-3591-2195; Junop, Murray/0000-0001-6676-5717 SN 1097-2765 PD JAN PY 2001 VL 7 IS 1 BP 1 EP 12 DI 10.1016/S1097-2765(01)00149-6 UT WOS:000166601300001 PM 11172706 ER PT J AU Nossal, NG Dudas, KC Kreuzer, KN AF Nossal, NG Dudas, KC Kreuzer, KN TI Bacteriophage T4 proteins replicate plasmids with a preformed R loop at the T4 ori(uvsY) replication origin in vitro SO MOLECULAR CELL AB Bacteriophage T4 DNA replication proteins catalyze complete unidirectional replication of plasmids containing the T4 ori(uvsY) replication origin in vitro, beginning with a preformed R loop at the position of the origin R loop previously identified in vivo. T4 DNA polymerase, clamp, clamp loader, and 32 protein are needed for initial elongation of the RNA, which serves as the leading-strand primer. Normal replication is dependent on T4 41 helicase and 61 primase and is strongly stimulated by the 59 helicase loading protein. 59 protein slows replication without the helicase. As expected, leading-strand synthesis stalls prematurely in the absence of T4 DNA topoisomerase. A DNA unwinding element (DUE) is essential for replication, but the ori(uvsY) DUE can be replaced by other DUE sequences. SN 1097-2765 PD JAN PY 2001 VL 7 IS 1 BP 31 EP 41 DI 10.1016/S1097-2765(01)00152-6 UT WOS:000166601300004 PM 11172709 ER PT J AU Raval, A Howcroft, TK Weissman, JD Kirshner, S Zhu, XS Yokoyama, K Ting, J Singer, DS AF Raval, A Howcroft, TK Weissman, JD Kirshner, S Zhu, XS Yokoyama, K Ting, J Singer, DS TI Transcriptional coactivator, CIITA, is an acetyltransferase that bypasses a promoter requirement for TAF(II)250 SO MOLECULAR CELL AB The CIITA coactivator is essential for transcriptional activation of MHC class II genes and mediates enhanced MHC class I transcription. We now report that CIITA contains an intrinsic acetyltransferase (AT) activity that maps to a region within the N-terminal segment of CIITA, between amino acids 94 and 132. The AT activity is regulated by the C-terminal GTP-binding domain and is stimulated by GTP. CIITA-mediated transactivation depends on the AT activity. Further, we report that, although constitutive MHC class I transcription depends on TAF(II)50, CIITA activates the promoter in the absence of functional TAF(II)250. SN 1097-2765 PD JAN PY 2001 VL 7 IS 1 BP 105 EP 115 DI 10.1016/S1097-2765(01)00159-9 UT WOS:000166601300011 PM 11172716 ER PT J AU Venkataraman, S Varghese, B Sadashiva, BK Subramanian, S AF Venkataraman, S Varghese, B Sadashiva, BK Subramanian, S TI Crystal structure and EPR studies of bis[1,3-di(p-n-octylphenyl)propane-1,3-dionato]oxovanadium(IV) SO MOLECULAR CRYSTALS AND LIQUID CRYSTALS AB We report here the synthesis, crystal structure and Electron Paramagnetic Resonance (EPR) studies of the compound bis[1,3-di(p-n-octylphenyl)propane-1,3-dionato]oxovanadium(IV) abbreviated as C-8(VO)C-8. The molecular crystalline properties of this compound are dealt with in this paper. The compound crystallizes in the triclinic, P1 space group with a = 11.956(4), b = 15.802(5), c = 16.293(4) Angstrom, alpha = 103.22(2), beta = 110.61(2), and gamma = 90.88(3): Z=2. The two vanadium centers are crystallographically equivalent and the shortest V-V bond distance is 9.5803 Angstrom. The hyperfine splitting pattern in single crystal EPR spectrum clearly shows the presence of weak pair-wise magnetic interaction. The splitting originates in a combination of hyperfine and One structure caused by dipolar and exchange coupling of nearest-neighboring molecules related by inversion through the unit cell origin. The sign and the value of the exchange coupling constant, J = + 30 G, was determined by simulation of EPR spectra. The principal g and A values obtained are g(\) = 1.934 and g(perpendicular to) = 1.982, A(\) = 192 G and A(perpendicular to) = 69 G. RI Sadashiva, B./E-5135-2012 SN 1058-725X PY 2001 VL 357 BP 199 EP 219 DI 10.1080/10587250108028254 UT WOS:000168788200015 ER PT J AU Eizirik, E Kim, JH Menotti-Raymond, M Crawshaw, PG O'Brien, SJ Johnson, WE AF Eizirik, E Kim, JH Menotti-Raymond, M Crawshaw, PG O'Brien, SJ Johnson, WE TI Phylogeography, population history and conservation genetics of jaguars (Panthera onca, Mammalia, Felidae) SO MOLECULAR ECOLOGY AB The jaguar (Panthera onca), the largest felid in the American Continent, is currently threatened by habitat loss, fragmentation and human persecution. We have investigated the genetic diversity, population structure and demographic history of jaguars across their geographical range by analysing 715 base pairs of the mitochondrial DNA (mtDNA) control region and 29 microsatellite loci in approximate to 40 individuals sampled from Mexico to southern Brazil. Jaguars display low to moderate levels of mtDNA diversity and medium to high levels of microsatellite size variation, and show evidence of a recent demographic expansion. We estimate that extant jaguar mtDNA lineages arose 280 000-510 000 years ago (95% CI 137 000-830 000 years ago), a younger date than suggested by available fossil data. No strong geographical structure was observed, in contrast to previously proposed subspecific partitions. However, major geographical barriers such as the Amazon river and the Darien straits between northern South America and Central America appear to have restricted historical gene flow in this species, producing measurable genetic differentiation. Jaguars could be divided into four incompletely isolated phylogeographic groups, and further sampling may reveal a finer pattern of subdivision or isolation by distance on a regional level. Operational conservation units for this species can be defined on a biome or ecosystem scale, but should take into account the historical barriers to dispersal identified here. Conservation strategies for jaguars should aim to maintain high levels of gene flow over broad geographical areas, possibly through active management of disconnected populations on a regional scale. RI Eizirik, Eduardo/K-8034-2012; Johnson, Warren/D-4149-2016 OI Eizirik, Eduardo/0000-0002-9658-0999; Johnson, Warren/0000-0002-5954-186X SN 0962-1083 EI 1365-294X PD JAN PY 2001 VL 10 IS 1 BP 65 EP 79 DI 10.1046/j.1365-294X.2001.01144.x UT WOS:000166647100008 PM 11251788 ER PT J AU Yavuz, S Grammer, AC Yavuz, AS Nanki, T Lipsky, PE AF Yavuz, S Grammer, AC Yavuz, AS Nanki, T Lipsky, PE TI Comparative characteristics of mu chain and alpha chain transcripts expressed by individual tonsil plasma cells SO MOLECULAR IMMUNOLOGY AB Plasma cells (PCs) are one of the two major cell types generated during germinal center reactions. To test the hypothesis that PCs express a unique repertoire of immunoglobulin (Ig) genes resulting from intensive antigenic stimulation and selection, the mutational pattern and distribution of VH gene segments within 178 transcripts amplified from individual IgM and IgA secreting tonsil PCs were analyzed. The results demonstrated that both mu and alpha transcripts expressed repertoires with limited diversity. Moreover, both mu and alpha transcripts were heavily mutated, with a significantly increased mutational frequency noted for alpha compared to mu transcripts (5.0 x 10(-2) vs 1.8 x 10(-2), P < 0.001). In addition, both and alpha transcripts showed significantly greater targeting of mutations to RGYW motifs (purine/guanine/pyrimidine/A or T) compared to memory B cells. Finally, clonally expanded cells were detected in alpha but not mu PC compartments. These results indicate that antigen driven stimulation and selection shape the entire expressed PC repertoire, but the impact is greater in alpha expressing PCs. Published by Elsevier Science Ltd. SN 0161-5890 PD JAN PY 2001 VL 38 IS 1 BP 19 EP 34 DI 10.1016/S0161-5890(01)00036-0 UT WOS:000170583800003 PM 11483207 ER PT J AU Mamoun, CB Gluzman, IY Hott, C MacMillan, SK Amarakone, AS Anderson, DL Carlton, JMR Dame, JB Chakrabarti, D Martin, RK Brownstein, BH Goldberg, DE AF Mamoun, CB Gluzman, IY Hott, C MacMillan, SK Amarakone, AS Anderson, DL Carlton, JMR Dame, JB Chakrabarti, D Martin, RK Brownstein, BH Goldberg, DE TI Co-ordinated programme of gene expression during asexual intraerythrocytic development of the human malaria parasite Plasmodium falciparum revealed by microarray analysis SO MOLECULAR MICROBIOLOGY AB Plasmodium falciparum is a protozoan parasite responsible for the most severe forms of human malaria. All the clinical symptoms and pathological changes seen during human infection are caused by the asexual blood stages of Plasmodium. Within host red blood cells, the parasite undergoes enormous developmental changes during its maturation. In order to analyse the expression of genes during intraerythrocytic development, DNA microarrays were constructed and probed with stage-specific cDNA. Developmental upregulation of specific mRNAs was found to cluster into functional groups and revealed a co-ordinated programme of gene expression. Those involved in protein synthesis (ribosomal proteins, translation factors) peaked early in development, followed by those involved in metabolism, most dramatically glycolysis genes. Adhesion/invasion genes were turned on later in the maturation process. At the end of intraerythrocytic development (late schizogony), there was a general shut-off of gene expression, although a small set of genes, including a number of protein kinases, were turned on at this stage. Nearly all genes showed some regulation over the course of development. A handful of genes remained constant and should be useful for normalizing mRNA levels between stages. These data will facilitate functional analysis of the P. falciparum genome and will help to identify genes with a critical role in parasite progression and multiplication in the human host. SN 0950-382X PD JAN PY 2001 VL 39 IS 1 BP 26 EP 36 DI 10.1046/j.1365-2958.2001.02222.x UT WOS:000166576700003 ER PT J AU Zhou, DG Chen, LM Hernandez, L Shears, SB Galan, JE AF Zhou, DG Chen, LM Hernandez, L Shears, SB Galan, JE TI A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization SO MOLECULAR MICROBIOLOGY AB A central feature of Salmonella pathogenicity is the bacterium's ability to enter into non-phagocytic cells. Bacterial internalization is the consequence of cellular responses characterized by Cdc42- and Rac-dependent actin cytoskeleton rearrangements. These responses are triggered by the co-ordinated function of bacterial proteins delivered into the host cell by a specialized protein secretion system termed type III. We report here that SopB, a Salmonella inositol polyphosphatase delivered to the host cell by this secretion system, mediates actin cytoskeleton rearrangements and bacterial entry in a Cdc42-dependent manner. SopB exhibits overlapping functions with two other effectors of bacterial entry, the Rho family GTPase exchange factors SopE and SopE2. Thus, Salmonella strains deficient in any one of these proteins can enter into cells at high efficiency, whereas a strain lacking all three effectors is completely defective for entry. Consistent with an important role for inositol phosphate metabolism in Salmonella-induced cellular responses, a catalytically defective mutant of SopB failed to stimulate actin cytoskeleton rearrangements and bacterial entry. Furthermore, bacterial infection of intestinal cells resulted in a marked increase in Ins(1,4,5,6)P-4, a consumption of InsP(5) and the activation of phospholipase C. In agreement with the in vivo findings, purified SopB specifically dephosphorylated InsP(5) to Ins(1,4,5,6)P-4 in vitro. Surprisingly, the inositol phosphate fluxes induced by Salmonella were not caused exclusively by SopB. We show that the SopB-independent inositol phosphate fluxes are the consequence of the SopE-dependent activation of an endogenous inositol phosphatase. The ability of Salmonella to stimulate Rho GTPases signalling and inositol phosphate metabolism through alternative mechanisms is an example of the remarkable ability of this bacterial pathogen to manipulate host cellular functions. SN 0950-382X PD JAN PY 2001 VL 39 IS 2 BP 248 EP 259 DI 10.1046/j.1365-2958.2001.02230.x UT WOS:000166577200004 PM 11136447 ER PT J AU Alugupalli, KR Michelson, AD Barnard, MR Robbins, D Coburn, J Baker, EK Ginsberg, MH Schwan, TG Leong, JM AF Alugupalli, KR Michelson, AD Barnard, MR Robbins, D Coburn, J Baker, EK Ginsberg, MH Schwan, TG Leong, JM TI Platelet activation by a relapsing fever spirochaete results in enhanced bacterium-platelet interaction via integrin alpha(IIb)beta(3) activation SO MOLECULAR MICROBIOLOGY AB Borrelia hermsii, a spirochaete responsible for relapsing fever in humans, grows to high density in the bloodstream and causes thrombocytopenia. We show here that B. hermsii binds to human platelets. Extended culture in bacteriological medium resulted in both diminished infectivity in vivo and diminished platelet binding in vitro. Platelet binding was promoted by the platelet integrin alpha (IIb)beta (3): the bacterium bound to purified integrin alpha (IIb)beta (3), and bacterial binding to platelets was diminished by alpha (IIb)beta (3) antagonists or by a genetic defect in this integrin. Integrin alpha (IIb)beta (3) undergoes a conformational change upon platelet activation, and bacteria bound more efficiently to activated rather than resting platelets. Nevertheless, B. hermsii bound at detectable levels to preparations of resting platelets. The bacterium did not recognize a point mutant of alpha (IIb)beta (3) that cannot acquire an active conformation. Rather, B. hermsii was capable of triggering platelet and integrin alpha (IIb)beta (3) activation, as indicated by the expression of the platelet activation marker P-selectin and integrin alpha (IIb)beta (3) in its active conformation. The degree of platelet activation varied depending upon bacterial strain and growth conditions. Prostacyclin I-2, an inhibitor of platelet activation, diminished bacterial attachment, indicating that activation enhanced bacterial binding. Thus, B. hermsii signals the host cell to activate a critical receptor for the bacterium, thereby promoting high-level bacterial attachment. SN 0950-382X PD JAN PY 2001 VL 39 IS 2 BP 330 EP 340 DI 10.1046/j.1365-2958.2001.02201.x UT WOS:000166577200011 PM 11136454 ER PT J AU Gao, ZH Li, BS Day, YJ Linden, J AF Gao, ZH Li, BS Day, YJ Linden, J TI A(3) adenosine receptor activation triggers phosphorylation of protein kinase B and protects rat basophilic leukemia 2H3 mast cells from apoptosis SO MOLECULAR PHARMACOLOGY AB Adenosine accumulates to high levels in inflamed or ischemic tissues and activates A(3) adenosine receptors (ARs) on mast cells to trigger degranulation. Here we show that stimulation of rat basophilic leukemia (RBL)-2H3 mast-like cells with the A(3) AR agonists N-6-(3-iodo) benzyl-5'-N-methylcarboxamidodoadenosine (IB-MECA; 10 nM) or inosine (10 muM) stimulates phosphorylation of protein kinase B (Akt). IB-MECA (1 muM) also causes a >50% reduction in apoptosis caused by exposure of RBL-2H3 cells to UV light. Akt phosphorylation is not stimulated by 100 nM N-6-cyclopentyladenosine (A(1)-selective) or CGS21680 (A(2A)-selective) and is absent in cells pretreated with wortmannin or pertussis toxin. The K-I values of the AR antagonists BW-1433 and 8-sulfophenyltheophylline (8-SPT) were determined in radioligand binding assays for all four subtypes of rat ARs: BW-1433 (A(1), 5.8 +/- 1.0 nM; A(2A), 240 +/- 37; A(2B),30 +/- 10; A(3), 12,300 +/- 3,700); 8-SPT (A(1), 3.2 +/- 1.2 muM; A(2A),57 +/- 4; A(2B), 2.2 +/- 0.8; A(3), >100). BW-1433 and the A(3)-slective antagonist MRS1523 (5 muM), but not 8-SPT (100 muM), block IB-MECA-induced protection from apoptosis, confirming the A(3) AR as the mediator of the antiapoptotic response. The data suggest that adenosine and inosine activate Gi-coupled A(3) ARs to protect mast cells from apoptosis by a pathway involving the beta gamma subunits of Gi, phosphatidylinositol 3-kinase beta, and Akt. We speculate that activation of A(3) ARs on mast cells or other cells that express A(3) ARs (e.g., eosinophils) may facilitate their survival and accumulation in inflamed tissues. SN 0026-895X PD JAN PY 2001 VL 59 IS 1 BP 76 EP 82 UT WOS:000165971300011 PM 11125027 ER PT B AU Bungay, PM AF Bungay, PM BE OConnor, WT Lowry, JP OConnor, JJ ONeill, RD TI Model for effect of insertion trauma on microdialysis measurements SO MONITORING MOLECULES IN NEUROSCIENCE CT 9th International Conference on In Vivo Methods CY JUN 16-19, 2001 CL UNIV COLL DUBLIN, DUBLIN, IRELAND HO UNIV COLL DUBLIN BN 1-902277-47-3 PY 2001 BP 91 EP 92 UT WOS:000175403700045 ER PT B AU Chefer, VI Shippenberg, TS AF Chefer, VI Shippenberg, TS BE OConnor, WT Lowry, JP OConnor, JJ ONeill, RD TI Changes in basal and cocaine-evoked dopamine neurotransmition in the rat nucleus accumbens during abstinence from chronic cocaine: quantitative determination under transient conditions. SO MONITORING MOLECULES IN NEUROSCIENCE CT 9th International Conference on In Vivo Methods CY JUN 16-19, 2001 CL UNIV COLL DUBLIN, DUBLIN, IRELAND HO UNIV COLL DUBLIN BN 1-902277-47-3 PY 2001 BP 263 EP 264 UT WOS:000175403700126 ER PT B AU Taltavull, J Slusher, BS Shippenberg, TS Zapata, A AF Taltavull, J Slusher, BS Shippenberg, TS Zapata, A BE OConnor, WT Lowry, JP OConnor, JJ ONeill, RD TI Differential effects of NAALADase inhibition upon cocaine-evoked locomotor activity and dialysate dopamine levels in the mouse SO MONITORING MOLECULES IN NEUROSCIENCE CT 9th International Conference on In Vivo Methods CY JUN 16-19, 2001 CL UNIV COLL DUBLIN, DUBLIN, IRELAND HO UNIV COLL DUBLIN BN 1-902277-47-3 PY 2001 BP 274 EP 275 UT WOS:000175403700131 ER PT B AU Zapata, A Shippenberg, TS AF Zapata, A Shippenberg, TS BE OConnor, WT Lowry, JP OConnor, JJ ONeill, RD TI D-3 receptor knock out mice are less sensitive to the effects of (+)-PD 128907 on dialysate dopamine SO MONITORING MOLECULES IN NEUROSCIENCE CT 9th International Conference on In Vivo Methods CY JUN 16-19, 2001 CL UNIV COLL DUBLIN, DUBLIN, IRELAND HO UNIV COLL DUBLIN BN 1-902277-47-3 PY 2001 BP 278 EP 279 UT WOS:000175403700133 ER PT J AU Herrmann, DJ Schooler, C Caplan, LJ Lipman, PD Grafman, J Schoenbach, C Schwab, K Johnson, ML AF Herrmann, DJ Schooler, C Caplan, LJ Lipman, PD Grafman, J Schoenbach, C Schwab, K Johnson, ML TI The latent structure of memory: A confirmatory factor-analytic study of memory distinctions SO MULTIVARIATE BEHAVIORAL RESEARCH CT Meeting of the Psychonomic-Society CY NOV, 1990 CL NEW ORLEANS, LOUISIANA SP Psychon Soc AB Confirmatory factor analysis was used to investigate the nature of memory distinctions underlying the performance of two samples: a sample of male Vietnam War veterans who had not received head injuries, and a second sample of male Vietnam War veterans who had suffered penetrating head injuries resulting in relatively small lesions (< 10 cc volume loss). For these two groups, comparisons were made of the fit of seven theory-based memory models, comprising from one to four factors. The four-component model with a verbal-episodic component, a visual-episodic component, a semantic component, and a short-term memory component provided a significantly better account of memory performance than the others. The implications of these findings and some advantages of this approach as a supplement to a purely experimental approach to memory are discussed. OI Grafman, Jordan H./0000-0001-8645-4457 SN 0027-3171 PY 2001 VL 36 IS 1 BP 29 EP 51 DI 10.1207/S15327906MBR3601_02 UT WOS:000168462400002 ER PT J AU Ponten, I Waters, LS Sayer, JM Pilcher, AS Dipple, A Jerina, DM AF Ponten, I Waters, LS Sayer, JM Pilcher, AS Dipple, A Jerina, DM TI Influence of adduct position and sequence length on the ligation of oligonucleotides containing benzo[c]phenanthrene diol epoxide-deoxyadenosine adducts into M13mp7L2 SO MUTAGENESIS AB The adduct that would arise from cis opening of (+)-(1S,2R,3R,4S)-3,4-dihydroxy-1,2-epoxy-benzo[c]phenanthrene (benzo[c]phenanthrene diol epoxide-2, where the benzylic hydroxyl group and the epoxide oxygen are traits) by the exocyclic N-6-amino group of deoxyadenosine was incorporated at the underlined site into four oligonucleotides, 5'-CAGATTTAGAGTCTGC-3', 5'-CAGTGCAGATTTAGAG-3', 5'-GTGCAGATTTAGA-3' and 5'-TGCAGATTTA-3'. The oligonucleotides were inserted into M13mp7L2 acid the vector transfected into SOS-induced Escherichia coli SMH77 which were then plated on agar plates, The experiments reported here were designed to test the effect of the lesion position (the underlined A in the sequences above) on the ligation efficiency of the insert and the frequency of failed constructs, as well as any possible effects on the mutagenic consequences of the lesion, The construct survival was estimated from the number of plaques formed following transformation, and mutation frequencies were estimated from sequencing of randomly picked plaques. Moving the adduct site to the middle of the sequence increased considerably the ligation efficiency regardless of the length of the inserted oligonucleotide, and changing the insert length or the adduct location did not markedly affect the frequency (40-58.6%) or distribution of mutations observed. Thus, so long as the local sequence (five or six bases surrounding the adduct) remains constant, the size of the oligonucleotide insert and the position of the adduct in it can be adjusted to give optimal ligation efficiency without altering the mutagenic consequences of the lesion. SN 0267-8357 PD JAN PY 2001 VL 16 IS 1 BP 65 EP 69 DI 10.1093/mutage/16.1.65 UT WOS:000166378100009 PM 11139600 ER PT J AU Rashid, MA Gustafson, KR Cardellina, JH Boyd, MR AF Rashid, MA Gustafson, KR Cardellina, JH Boyd, MR TI HIV-inhibitory natural products part 61 - Absolute stereochemistry and anti-HIV activity of minquartynoic acid, a polyacetylene from Ochanostachys amentacea SO NATURAL PRODUCT LETTERS AB Anti-HIV bioassay-guided fractionation of an organic extract of Ochanostachys amentacea provided an HIV-inhibitory polyacetylenic acid. The identity of this compound was established as (-)-17-hydroxy-9,11,13,15-octadecatetraynoic acid (1), also known as minquartynoic acid, by comparison of its physical and spectral data with previously reported values. Analysis of Mosher's ester derivatives of the methyl ester of 1 allowed assignment of S absolute stereochemistry to the lone chiral center. In an in vitro XTT-based anti-HIV assay, 2-5 mug/mL of minquartynoic acid (1) effectively inhibited human lymphoblastoid cell killing by HIV-1. SN 1057-5634 PY 2001 VL 15 IS 1 BP 21 EP 26 DI 10.1080/10575630108041253 UT WOS:000167940500004 PM 11547419 ER PT J AU Lee, MH Lu, K Hazard, S Yu, HW Shulenin, S Hidaka, H Kojima, H Allikmets, R Sakuma, N Pegoraro, R Srivastava, AK Salen, G Dean, M Patel, SB AF Lee, MH Lu, K Hazard, S Yu, HW Shulenin, S Hidaka, H Kojima, H Allikmets, R Sakuma, N Pegoraro, R Srivastava, AK Salen, G Dean, M Patel, SB TI Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption SO NATURE GENETICS AB The molecular mechanisms regulating the amount of dietary cholesterol retained in the body, as well as the body's ability to exclude selectively other dietary sterols, are poorly understood. An average western diet will contain about 250-500 mg of dietary cholesterol and about 200-400 mg of non-cholesterol sterols. About 50-60% of the dietary cholesterol is absorbed and retained by the normal human body, but less than 1% of the non-cholesterol sterols are retained. Thus, there exists a subtle mechanism that allows the body to distinguish between cholesterol and non-cholesterol sterols. In sitosterolemia, a rare autosomal recessive disorder, affected individuals hyperabsorb not only cholesterol but also all other sterols, including plant and shellfish sterols from the intestine(1,2). The major plant sterol species is sitosterol; hence the name of the disorder. Consequently, patients with this disease have very high levels of plant sterols in the plasma and develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease(3). We previously mapped the STSL locus to human chromosome 2p21 (ref. 4) and further localized it to a region of less than 2 cM bounded by markers D2S2294 and D2S2291 (M.-H.L. et al., manuscript submitted). We now report that a new member of the ABC transporter family, ABCG5, is mutant in nine unrelated sitosterolemia patients. RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Patel, Shailendra/0000-0003-0046-5513 SN 1061-4036 PD JAN PY 2001 VL 27 IS 1 BP 79 EP 83 UT WOS:000166187900020 PM 11138003 ER PT J AU Di Palma, F Holme, RH Bryda, EC Belyantseva, IA Pellegrino, R Kachar, B Steel, KP Noben-Trauth, K AF Di Palma, F Holme, RH Bryda, EC Belyantseva, IA Pellegrino, R Kachar, B Steel, KP Noben-Trauth, K TI Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D SO NATURE GENETICS AB Mouse chromosome 10 harbors several loci associated with hearing loss, including waltzer (v), modifier-of deaf waddler (mdfw) and Age-related hearing loss(1) (Ahl). The human region that is orthologous to the mouse 'waltzer' region is located at 10q21-q22 and contains the human deafness loci DFNB12 and USH1D (refs. 2,3). Numerous mutations at the waltzer locus have been documented causing erratic circling and hearing loss(4-7). Here we report the identification of a new gene mutated in v. The 10.5-kb Cdh23 cDNA encodes a very large, single-pass transmembrane protein, that we have called otocadherin. It has an extracellular domain that contains 27 repeats; these show significant homology to the cadherin ectodomain. In v(6J), a GT transversion creates a premature stop codon. In v(Alb), a Cr exchange generates an ectopic donor splice site, effecting deletion of 119 nucleotides of exonic sequence. In v(2J), a GA transition abolishes the donor splice site, leading to aberrant splice forms. All three alleles are predicted to cause loss of function. We demonstrate Cdh23 expression in the neurosensory epithelium and show that during early hair-cell differentiation, stereocilia organization is disrupted in v(2J) homozygotes. Our data indicate that otocadherin is a critical component of hair bundle formation. Mutations in human CDH23 cause Usher syndrome type 1D and thus, establish waltzer as the mouse model for USH1D. SN 1061-4036 PD JAN PY 2001 VL 27 IS 1 BP 103 EP 107 UT WOS:000166187900025 PM 11138008 ER PT J AU Anderson, H Hiltbold, E Roche, P AF Anderson, H Hiltbold, E Roche, P TI Rafts for antigen presentation? Response SO NATURE IMMUNOLOGY SN 1529-2908 PD JAN PY 2001 VL 2 IS 1 BP 3 EP 3 DI 10.1038/83156 UT WOS:000166261500003 ER PT J AU Kirk, AD AF Kirk, AD TI Hitting the reset button for immune tolerance SO NATURE MEDICINE AB Migratory cells can lead both to rejection and tolerance following organ transplantation, suggesting a direction for protolerant immunomodulatory therapies. RI Kirk, Allan/B-6905-2012 SN 1078-8956 PD JAN PY 2001 VL 7 IS 1 BP 24 EP 25 DI 10.1038/83304 UT WOS:000166243100023 PM 11135608 ER PT J AU Chinetti, G Lestavel, S Bocher, V Remaley, AT Neve, B Torra, IP Teissier, E Minnich, A Jaye, M Duverger, N Brewer, HB Fruchart, JC Clavey, V Staels, B AF Chinetti, G Lestavel, S Bocher, V Remaley, AT Neve, B Torra, IP Teissier, E Minnich, A Jaye, M Duverger, N Brewer, HB Fruchart, JC Clavey, V Staels, B TI PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway SO NATURE MEDICINE AB Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate lipid and glucose metabolism and cellular differentiation. PPAR-alpha and PPAR-gamma are both expressed in human macrophages where they exert anti-inflammatory effects. The activation of PPAR-gamma may promote foam-cell formation by inducing expression of the macrophage scavenger receptor CD36. This prompted us to investigate the influence of different PPAR- activators on cholesterol metabolism and foam-cell formation of human primary and THP-1 macrophages. Here we show that PPAR-alpha and PPAR-gamma activators do not influence acetylated low density lipoprotein-induced foam-cell formation of human macrophages. In contrast, PPAR-alpha and PPAR-gamma activators induce the expression of the gene encoding ABCA1, a transporter that controls apoAI-mediated cholesterol efflux from macrophages. These effects are likely due to enhanced expression of liver-x-receptor alpha, an oxysterol-activated nuclear receptor which inducer ABCA1- promoter transcription. Moreover, PPAR-alpha and PPAR-gamma activators increase apoAI-induced cholesterol efflux from normal macrophages. In contrast, PPAR-alpha or PPAR-gamma activation does not influence cholesterol efflux from macrophages isolated from patients with Tangier disease, which is due to a genetic defect in ABCA1. Here we identify a regulatory role for PPAR-alpha and PPAR-gamma in the first steps of the reverse-cholesterol-transport pathway through the activation of ABCA1-mediated cholesterol efflux in human macrophages. RI Neve, B/J-6008-2014; Staels, Bart/N-9497-2016; chinetti, giulia/Q-6901-2016; Lestavel, Sophie/B-4658-2017 OI Staels, Bart/0000-0002-3784-1503; chinetti, giulia/0000-0001-8048-8138; Lestavel, Sophie/0000-0001-7839-4757 SN 1078-8956 PD JAN PY 2001 VL 7 IS 1 BP 53 EP 58 UT WOS:000166243100035 PM 11135616 ER PT J AU Anderson, CC Matzinger, P AF Anderson, CC Matzinger, P TI Immunity or tolerance: Opposite outcomes of microchimerism from skin grafts SO NATURE MEDICINE AB Solid organ transplants contain small numbers of leukocytes that can migrate into the host and establish long-lasting microchimerism. Although such microchimerism is often associated with graft acceptance and tolerance, it has been difficult to demonstrate a true causal link. Using skin from mutant mice deficient for leukocyte subsets, we found that donor T-cell chimerism Is a 'double-edged sword' that can result in very different outcomes depending on the host's immunological maturity and the antigenic disparities involved. In immunologically mature hosts, chimerism resulted in immunity and stronger graft rejection. In immature hosts, it resulted in tolerance to the chimeric T cells, but not to graft antigens not expressed by the chimeric cells. Clinical efforts aimed at augmenting chimerism to induce tolerance must take into account the maturation state of host T cells, the type of chimerism produced by each organ and the antigenic disparities involved, lest the result be increased rejection rather than tolerance. SN 1078-8956 PD JAN PY 2001 VL 7 IS 1 BP 80 EP 87 DI 10.1038/83393 UT WOS:000166243100039 PM 11135620 ER PT J AU Yang, F He, XP Feng, LY Mizuno, K Liu, XW Russell, J Xiong, WC Lu, B AF Yang, F He, XP Feng, LY Mizuno, K Liu, XW Russell, J Xiong, WC Lu, B TI PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation SO NATURE NEUROSCIENCE AB Signaling mechanisms underlying neurotrophic regulation of synaptic transmission are not fully understood. Here we show that neurotrophin-3 (NT3)-induced potentiation of synaptic transmission at the neuromuscular synapses is blocked by inhibition of phosphoinositide-3 kinase, phospholipase C-gamma or the downstream IP3 receptors of phospholipase C-gamma, but not by inhibition of MAP kinase. However, neither stimulation of Ca2+ release from intracellular stores by photolysis of caged IP3, nor expression of a constitutively active phosphoinositide-3 kinase (PI3K(star)) in presynaptic motoneurons alone is sufficient to enhance transmission. Photo-uncaging of IP3 in neurons expressing PI3K(star) elicits a marked synaptic potentiation, mimicking the NT3 effect. These results reveal an involvement of PI3 kinase in transmitter release, and suggest that concomitant activation of PI3 kinase and IP3 receptors is both necessary and sufficient to mediate the NTS-induced synaptic potentiation. RI Yang, Feng/C-9530-2011; Lu, Bai/A-4018-2012 SN 1097-6256 PD JAN PY 2001 VL 4 IS 1 BP 19 EP 28 UT WOS:000167178000010 PM 11135641 ER PT J AU McBain, CJ Fisahn, A AF McBain, CJ Fisahn, A TI Interneurons unbound SO NATURE REVIEWS NEUROSCIENCE AB Local-circuit, gamma -aminobutyric acid-releasing inhibitory interneurons of the hippocampus and cortex have traditionally been considered as the regulators of principal neuron activity - the yin to the excitatory yang. Recent evidence indicates that, in addition to that role, their network connectivity and the properties of their intrinsic voltage-gated currents are finely tuned to permit inhibitory interneurons to generate and control the rhythmic output of large populations of both principal cells and other populations of inhibitory interneurons. This review brings together recently described properties and emerging principles of interneuron function that indicate a much more complex role for these cells than just providers of inhibition. SN 1471-0048 PD JAN PY 2001 VL 2 IS 1 BP 11 EP 23 DI 10.1038/35049047 UT WOS:000166056100014 PM 11253355 ER PT J AU Lombardi, DM Viswanathan, M Vio, CP Saavedra, JM Schwartz, SM Johnson, RJ AF Lombardi, DM Viswanathan, M Vio, CP Saavedra, JM Schwartz, SM Johnson, RJ TI Renal and vascular injury induced by exogenous angiotensin II is AT1 receptor-dependent SO NEPHRON AB Angiotensin II (Ang II) infusion in rats augments vascular injury in balloon-injured carotid arteries and induces marked vascular and tubulointerstitial injury in kidneys. We examined how the AT1 receptor is modulated and whether blockade of the receptor with losartan could prevent the phenotypic and cellular changes, We also examined the role of the local renin-angiotensin system (RAS) by examining the expression of angiotensin-converting enzyme (ACE) and the effect of treatment with the ACE inhibitor, ramipril. Ang II infusion resulted in systemic hypertension and accelerated intimal and medial thickening in balloon-injured carotid arteries. Renal injury was manifested by proteinuria, glomerular phenotypic changes (mesangial expression of alpha -actin and podocyte expression of desmin), and tubulointerstitial injury with the tubular upregulation of the macrophage-adhesive protein, osteopontin, the interstitial accumulation of macrophages and myofibroblasts, and the deposition of collagen types III and IV. Ang II infusion decreased AT1 receptor number in the renal interstitium but not in glomeruli. Losartan completely blocked the Ang II-mediated hypertension, proteinuria, and injury to both carotid and kidney. Ang II infusion was also associated with an in crease in ACE protein in both the proximal tubular brush border as well as at interstitial sites of injury, but despite evidence for activation of the local RAS, treatment with ramipril was without effect. These studies demonstrate that the renal and vascular injury induced by Ang II infusion is mediated by the AT1 receptor despite downregulation of the receptor in the interstitium. In addition, although there is evidence for local RAS activation, the injury appears to be mediated solely by the exogenous Ang II. Copyright (C) 2001 S. Karger AG, Basel. OI Vio, Carlos/0000-0003-1850-5958 SN 0028-2766 PD JAN PY 2001 VL 87 IS 1 BP 66 EP 74 DI 10.1159/000045886 UT WOS:000166687500009 PM 11174028 ER PT J AU Beggs, JM AF Beggs, JM TI A statistical theory of long-term potentiation and depression SO NEURAL COMPUTATION AB The synaptic phenomena of long-term potentiation (LTP) and long-term depression (LTD) have been intensively studied for over twenty-five years. Although many diverse aspects of these forms of plasticity have been observed, no single theory has offered a unifying explanation for them. Here, a statistical "bin" model is proposed to account for a variety of features observed in LTP and LTD experiments performed with field potentials in mammalian cortical slices. It is hypothesized that long-term synaptic changes will be induced when statistically unlikely conjunctions of pre- and postsynaptic activity occur. This hypothesis implies that finite changes in synaptic strength will be proportional to information transmitted by conjunctions and that excitatory synapses will obey a Hebbian rule (Hebb, 1949). Using only one set of constants, the bin model offers an explanation as to why synaptic strength decreases in a decelerating manner during LTD induction (Mulkey & Malenka, 1992); why the induction protocols for LTP and LTD are asymmetric (Dudek & Bear, 1992; Mulkey & Malenka, 1992); why stimulation over a range of frequencies produces a frequency-response curve similar to that proposed by the BCM theory (Bienenstock, Cooper, & Munro, 1982; Dudek & Bear, 1992); and why this curve would shift as postsynaptic activity is changed (Kirkwood, Rioult, & Bear, 1996). In addition, the bin model offers an alternative to the BCM theory by predicting that changes in postsynaptic activity will produce vertical shifts in the curve rather than merely horizontal shifts. SN 0899-7667 PD JAN PY 2001 VL 13 IS 1 BP 87 EP 111 DI 10.1162/089976601300014646 UT WOS:000166714100004 PM 11177429 ER PT J AU Davatzikos, C Li, HH Herskovits, E Resnick, SH AF Davatzikos, C Li, HH Herskovits, E Resnick, SH TI Accuracy and sensitivity of detection of activation foci in the brain via statistical parametric mapping: A study using a PET simulator SO NEUROIMAGE AB Statistical parametric mapping (SPM) is currently the most widely used method for analysis of functional activation images. This paper reports a quantitative evaluation of the sensitivity and accuracy of SPM, using a realistic simulator of PET image formation, which accounted for the main physical processes involved in PET, including attenuation, scatter, randoms, Poisson noise, and limited detector resolution. Activation foci of the brain were simulated by placing spheres of specified activities in particular locations. Using these data, the sensitivity and accuracy of SPM in detecting activation foci was measured for different versions of the SPM spatial normalization method and for an elastic warping method referred to as STAR (spatial transformation algorithm for registration). The STAR method resulted in relatively better registration and hence better detection of the activation foci. A secondary goal of the paper was to evaluate the improvement in detection sensitivity obtained by applying an atlas-based adaptive smoothing method instead of the usual Gaussian filtering method. The results indicate some limitations of statistical parametric mapping, assist in the correct interpretation of the SPM maps, and point to future research directions in functional image analysis. (C) 2001 Academic Press. SN 1053-8119 PD JAN PY 2001 VL 13 IS 1 BP 176 EP 184 DI 10.1006/nimg.2000.0655 UT WOS:000166376000017 PM 11133320 ER PT S AU Wilder, RL Griffiths, MM Cannon, GW Caspi, R Gulko, PS Remmers, EF AF Wilder, RL Griffiths, MM Cannon, GW Caspi, R Gulko, PS Remmers, EF BE Friedman, H Klein, TW Madden, JJ TI Genetic factors involved in central nervous system/immune interactions SO NEUROIMMUNE CIRCUITS, DRUGS OF ABUSE, AND INFECTIOUS DISEASES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY CT 7th Annual Symposium on Neuroimmune Circuits, Drugs of Abuse, and Infectious Diseases CY OCT 07-09, 1999 CL BETHESDA, MARYLAND SP Natl Inst Drug Abuse AB Analysis of several inbred rat strains has led us to hypothesize that HPA axis abnormalities may contribute, in part, to susceptibility to both autoimmune disease and addiction. In this article we review the evidence for this hypothesis and describe our ongoing efforts to genetically characterize these traits. We have mapped the locations of 23 loci that regulate autoimmune disease in rats, and are currently constructing QTL congenic lines in which a genomic region from the resistant strain is transferred to the susceptible strain or vice versa, These QTL congenic lines will be valuable to test whether genes encoding autoimmune regulation also control neuroendocrine traits. Further genetic dissection and identification of the underlying genes will be necessary to infer a mechanistic link between autoimmune and neuroendocrine traits. SN 0065-2598 BN 0-306-46466-7 PY 2001 VL 493 BP 59 EP 67 UT WOS:000172534300007 PM 11727781 ER PT S AU Szabo, I Wetzel, M McCarthy, L Steele, A Henderson, EE Howard, OMZ Oppenheim, JJ Rogers, TJ AF Szabo, I Wetzel, M McCarthy, L Steele, A Henderson, EE Howard, OMZ Oppenheim, JJ Rogers, TJ BE Friedman, H Klein, TW Madden, JJ TI Interactions of opioid receptors, chemokines, and chemokine receptors SO NEUROIMMUNE CIRCUITS, DRUGS OF ABUSE, AND INFECTIOUS DISEASES SE Advances in Experimental Medicine and Biology CT 7th Annual Symposium on Neuroimmune Circuits, Drugs of Abuse, and Infectious Diseases CY OCT 07-09, 1999 CL BETHESDA, MD SP Natl Inst Drug Abuse RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 SN 0065-2598 BN 0-306-46466-7 PY 2001 VL 493 BP 69 EP 74 UT WOS:000172534300008 PM 11727782 ER PT J AU Kleef, R Jonas, WB Knogler, W Stenzinger, W AF Kleef, R Jonas, WB Knogler, W Stenzinger, W TI Fever, cancer incidence and spontaneous remissions SO NEUROIMMUNOMODULATION AB Objective: Accumulating evidence exists for (1) an inverse correlation between the incidence of infectious diseases and cancer risk and (2) an inverse correlation between febrile infections and remissions of malignancies. This review is part of an effort of the Office of Alternative Medicine at the National Institutes of Health to examine this evidence. Methods: A review of the literature to a key word search was undertaken, using the following key words: fever, infectious diseases, neoplasm, cancer incidence and spontaneous remission. Results: The data reviewed in this article support earlier observations on the topic, i.e. that the occurrence of fever in childhood or adulthood may protect against the later onset of malignant disease and that spontaneous remissions are often preceded by feverish infections. Conclusion: Pyrogenic substances and the more recent use of whole-body hyperthermia to mimic the physiologic response to fever have successfully been administered in palliative and curative treatment protocols for metastatic cancer. Further research in this area is warranted. Copyright (C) 2001 S. Karger AG, Basel. SN 1021-7401 PY 2001 VL 9 IS 2 BP 55 EP 64 DI 10.1159/000049008 UT WOS:000171173900001 PM 11549887 ER PT J AU Baker, DG Ekhator, NN Kasckow, JW Hill, KK Zoumakis, E Dashevsky, BA Chrousos, GP Geracioti, TD AF Baker, DG Ekhator, NN Kasckow, JW Hill, KK Zoumakis, E Dashevsky, BA Chrousos, GP Geracioti, TD TI Plasma and cerebrospinal fluid interleukin-6 concentrations in posttraumatic stress disorder SO NEUROIMMUNOMODULATION AB Background: Interleukin-6 (IL-6) secretion is suppressed by glucocorticoids and stimulated by catecholamines. Patients with posttraumatic stress disorder (PTSD) have decreased cortisol and increased catecholamine secretion. The purpose of this study was to assess the relation of IL-6 levels and hypothalamic-pituitary-adrenal and noradrenergic activity in patients with well-characterized PTSD. Methods: Cerebrospinal fluid (CSF) was withdrawn via a lumbar subarachnoid catheter over 6 h from 11 combat veterans with PTSD and 8 age- and sex-matched healthy controls. Blood was withdrawn concurrently. We measured IL-6, CRH and norepinephrine concentrations in the CSF and IL-6, ACTH, cortisol and norepinephrine in plasma. Results: Mean and median CSF IL-6 concentrations were higher in PTSD than in controls (mean = 24.0 vs. 14.6, p = 0.05; median = 26.7 vs. 14.3, p < 0.03): plasma IL-6 concentrations, however, were not different between the two groups. Plasma IL-6 and norepinephrine were positively correlated in the PTSD group (r= +0.74, p < 0.04), but not in normals (r = -0.55, p = 0.20). Conclusions: PTSD patients have increased CSF concentrations of IL-6. Their plasma IL-6 is not elevated but is more tightly associated with noradrenergic output in these patients than in normals. Both findings might be explained by the low cortisol secretion previously reported in PTSD as a result of lowered glucocorticoid suppression of IL-6 secretion. High levels of CSF IL-6 may reflect neurodegeneration or compensatory neuroprotection. Copyright (C) 2002 S. Karger AG, Basel. SN 1021-7401 EI 1423-0216 PY 2001 VL 9 IS 4 BP 209 EP 217 DI 10.1159/000049028 UT WOS:000174184700005 PM 11847483 ER PT J AU Vitkovic, L Maeda, S Sternberg, E AF Vitkovic, L Maeda, S Sternberg, E TI Anti-inflammatory cytokines: Expression and action in the brain SO NEUROIMMUNOMODULATION AB Transforming growth factor-beta(1) (TGF-beta(1)) and interleukin (IL)-10 gene expression is equivocal in normal brain and upregulated in over a dozen central and peripheral diseases/disorders. The patterns of specific expression of cytokines differ in these diseases. Published data indicate that these cytokines are produced by and act on both neurons and glial cells. Although their actions are commonly viewed as 'anti-inflammatory', they protect neurons and downregulate the responses of glial cells to diseases/disorders in the absence of inflammation. Their actions counterbalance the actions of elevated IL-1 and/ or tumor necrosis factor-a to maintain homeostasis. Their therapeutic potential will be realized by improving our understanding of their place in neural cytokine networks. Copyright (C) 2002 S. KargerAG, Basel. SN 1021-7401 PY 2001 VL 9 IS 6 BP 295 EP 312 DI 10.1159/000059387 UT WOS:000176284300001 PM 12045357 ER PT J AU Shafiq, M Nee, L Grafman, J Tresser, N Lee, VMY Trojanowski, JQ Lippa, CF AF Shafiq, M Nee, L Grafman, J Tresser, N Lee, VMY Trojanowski, JQ Lippa, CF TI Frontotemporal dementia: Report of a familial case SO NEUROLOGY AB The authors describe a 49-year-old woman (R.K.) who presented with one year of progressive frontal lobe dysfunction, including signs of expressive aphasia. Signs of parkinsonism were absent until late in the clinical course. Neuropsychologic testing and neuroimaging studies are described. The patient died at age 55, after 7 years of symptoms. Family history was remarkable for a mother who died at the age of 45, after experiencing 7 years of progressive aphasia. R.K.'s brain showed asymmetric frontotemporal atrophy, which was more severe on the left side. Histopathologic analysis was remarkable for numerous tau-positive neurons with some classic-appearing Pick bodies and many ballooned neurons. Tau-positive glial cells were also present. The authors suggest that the abnormal tau aggregates are related to the symptoms experienced by affected members of this family. SN 0028-3878 PY 2001 VL 56 IS 11 SU 4 BP S31 EP S34 UT WOS:000169350700008 PM 11402148 ER PT S AU Mattson, MP Gary, DS Chan, SL Duan, WZ AF Mattson, MP Gary, DS Chan, SL Duan, WZ BE ONeill, C Anderton, B TI Perturbed endoplasmic reticulum function, synaptic apoptosis and the pathogenesis of Alzheimer's disease SO NEURONAL SIGNAL TRANSDUCTION AND ALZHEIMER'S DISEASE SE BIOCHEMICAL SOCIETY SYMPOSIUM CT Annual Symposium of the Biochemical-Society CY SEP, 1999 CL UNIV COLL CORK, CORK, IRELAND SP Biochem Soc HO UNIV COLL CORK AB Endoplasmic reticulum (ER) appears to be a focal point for alterations that result in neuronal dysfunction and death in Alzheimer's disease (AD). Aberrant proteolytic processing and/or trafficking of the beta -amyloid precursor protein (APP) in ER may promote neuronal degeneration by increasing the levels of the neurotoxic forms of beta -amyloid (A beta) and by decreasing the levels of the neuroprotective secreted form of APP (sAPP alpha). Some cases of AD are caused by mutations in the genes encoding presenilin 1 (PS1). When expressed in cultured neuronal cells and transgenic mice, PS1 mutations cause abnormalities in ER calcium homoeostasis, enhancing the calcium responses to stimuli that activate IP3- and ryanodine-sensitive ER calcium pools. Two major consequences of this disrupted ER calcium regulation are altered proteolytic processing of APP and increased vulnerability of neurons to apoptosis and excitotoxicity. The impact of PS1 mutations and aberrant APP processing is particularly great in synaptic terminals. Perturbed synaptic calcium homoeostasis promotes activation of apoptotic cascades involving production of Par-4 (prostate apoptosis response-4), mitochondrial dysfunction and caspase activation. A beta 42 (the 42-amino-acid form of A beta) induces membrane lipid peroxidation in synapses and dendrites resulting in impairment of membrane ion-motive ATPases and glucose and glutamate transporters. This disrupts synaptic ion and energy homoeostasis thereby promoting synaptic degeneration. In contrast, sAPP alpha activates signalling pathways that protect synapses against excitotoxicity and apoptosis. In the more common sporadic forms of AD, the initiating causes of the neurodegenerative cascade are less well defined, but probably involve increased levels of oxidative stress and impaired energy metabolism. Such alterations have been shown to disrupt neuronal calcium homoeostasis in experimental models, and may therefore feed into the same neurodegenerative cascade initiated by mutations in presenilins and APP. Perturbed synaptic ER calcium homoeostasis and consequent alterations in APP processing appear to be pivotal events in both sporadic and familial forms of AD. RI Mattson, Mark/F-6038-2012 SN 0067-8694 BN 1-85578-133-6 PY 2001 IS 67 BP 151 EP 162 UT WOS:000171310800015 ER PT J AU Rogawski, MA Kurzman, PS Yamaguchi, S Li, H AF Rogawski, MA Kurzman, PS Yamaguchi, S Li, H TI Role of AMPA and GluR5 kainate receptors in the development and expression of amygdala kindling in the mouse SO NEUROPHARMACOLOGY AB The role of AMPA and GluR5-containing kainate receptors in the development and expression of amygdala kindling was examined using the selective 2,3 -benzodiazepine AMPA receptor antagonist GYKI 52466 [(1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine] and the decahydroisoquinoline mixed AMPA receptor and GluR5 kainate receptor antagonist LY293558 ((3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl] decahydroisoquinoline-3-carboxylic acid)). Administration of GYKI 52466 (5-40 mg/kg, intraperitoneally) and LY293558 (10-40 mg/kg, intraperitoneally) prior to daily kindling stimulation in mice produced a dose-dependent suppression of the rate of development of behavioral kindled seizure activity and reduced the duration of the stimulation-induced electrographic afterdischarge. In drug-free stimulation sessions after the initial drug-treatment sessions, there was an acceleration in the rate of kindling development compared with the rate during the preceding drug-administration period; the "rebound" rate was also greater than the kindling rate in saline-treated control animals. In fully kindled animals, both GYKI 52466 and LY293558 produced a dose-dependent suppression of evoked seizures (ED50, 19.3 and 16.7 mg/kg, respectively). Although AMPA receptors appear to be critical to the expression of kindled seizures, since kindling development progressed despite the suppression of behavioral seizure activity, AMPA receptors are less important to the kindling process. LY293558 was modestly less effective at suppressing behavioral seizures during kindling and was not superior to GYKI 52466 in retarding the overall extent of kindling development, indicating that GluR5 kainate receptors do not contribute to epileptogenesis in this model. Published by Elsevier Science Ltd. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 SN 0028-3908 PY 2001 VL 40 IS 1 BP 28 EP 35 UT WOS:000165562500004 PM 11077068 ER PT S AU Abbracchio, MP Camurri, A Ceruti, S Cattabeni, F Falzano, L Giammarioli, AM Jacobson, KA Trincavelli, L Martini, C Malorni, W Fiorentini, C AF Abbracchio, MP Camurri, A Ceruti, S Cattabeni, F Falzano, L Giammarioli, AM Jacobson, KA Trincavelli, L Martini, C Malorni, W Fiorentini, C BE Slikker, W Trembly, B TI The A(3) adenosine receptor induces cytoskeleton rearrangement in human astrocytoma cells via a specific action on Rho proteins SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT 5th International Conference on Neuroprotective Agents CY SEP 17-21, 2000 CL LAKE TAHOE, NEVADA SP Natl Ctr Toxicol Res /FDA, Cent Arkansas Chapter Sigma Xi AB In previous studies, we have demonstrated that exposure of astroglial cells to A(3) adenosine receptor agonists results in dual actions on cell survival, with "trophic" and antiapoptotic effects at nanomolar concentrations and induction of cell death at micromolar agonist concentrations. The protective actions of A(3) agonists have been associated with a reinforcement of the actin cytoskeleton, which likely results in increased resistance of cells to cytotoxic stimuli. The molecular mechanisms at the basis of this effect land the signalling pathway(s) linking the A(3) receptor to the actin cytoskeleton have never been elucidated. Based on previous literature data suggesting that the actin cytoskeleton is controlled by small GTP-binding proteins of the, Rho family, in the study reported here we investigated the involvement of these proteins in the effects induced by A(3) agonists on human astrocytoma ADF cells. The presence of the A3 adenosine receptor in these cells has been confirmed by immunoblotting analysis. As expected, exposure of human astrocytoma ADF cells to nanomolar concentrations of the selective A(3) agonist 2-chloro-N-6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA) resulted in formation of thick actin positive stress fibers. Preexposure of cells to the C3B toxin that inactivates Rho-proteins completely prevented the actin changes induced by Cl-IB-MECA. Exposure to the A(3) agonist also resulted in significant reduction of Rho-GDI, an inhibitory protein known to maintain Rho proteins in their inactive state, suggesting a potentiation of Rho-mediated effects. This effect was fully counteracted by the concomitant exposure to the selective A(3) receptor antagonist MRS1191. These results suggest that the reinforcement of the actin cytoskeleton induced by A3 receptor agonists is mediated by an interference with the activation/inactivation cycle of Rho proteins, which may, therefore, represent a biological target for the identification of novel neuroprotective strategies. RI Ceruti, Stefania/A-6376-2008; Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014; Fiorentini, Carla/Q-2088-2015; Malorni, Walter/G-5874-2016; OI Ceruti, Stefania/0000-0003-1663-4211; Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388; Fiorentini, Carla/0000-0003-1707-6282; Trincavelli, Maria Letizia/0000-0001-8124-977X; Martini, Claudia/0000-0001-9379-3027 SN 0077-8923 BN 1-57331-352-1 PY 2001 VL 939 BP 63 EP 73 UT WOS:000172028600009 PM 11462805 ER PT S AU Imam, SZ El-Yazal, J Newport, GD Itzhak, Y Cadet, JL Slikker, W Ali, SF AF Imam, SZ El-Yazal, J Newport, GD Itzhak, Y Cadet, JL Slikker, W Ali, SF BE Slikker, W Trembly, B TI Methamphetamine-induced dopaminergic neurotoxicity: Role of peroxynitrite and neuroprotective role of antioxidants and peroxynitrite decomposition catalysts SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT 5th International Conference on Neuroprotective Agents CY SEP 17-21, 2000 CL LAKE TAHOE, NEVADA SP Natl Ctr Toxicol Res /FDA, Cent Arkansas Chapter Sigma Xi AB Oxidative stress, reactive oxygen (ROS), and nitrogen (RNS) species have been known to be involved in a multitude of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). Both ROS and RNS have very short half-lives, thereby making their identification very difficult as a specific cause of neurodegeneration. Recently, we have developed a high performance liquid chromatography/electrochemical detection (HPLC/EC) method to identify 3-nitrotyrosine (3-NT), an in vitro and in vivo biomarker of peroxynitrite production, in cell cultures and brain to evaluate if an agent-driven neurotoxicity is produced by the generation of peroxynitrite. We show that a single or multiple injections of methamphetamine (METH) produced a significant increase in the formation of 3-NT in the striatum. This formation of 3-NT correlated with the striatal dopamine depletion caused by METH administration. We also show that PC12 cells treated with METH has significantly increased formation of 3-NT and dopamine depletion. Furthermore, we report that pretreatment with antioxidants such as selenium and melatonin can completely protect against the formation of 3-NT and depletion of striatal dopamine. We also report that pretreatment with peroxynitrite decomposition catalysts such as 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) and 5, 10, 15, 20-tetrakis (2,4,6-trimethyl-3,5-suffonatophenyl) porphinato iron III (FETPPS) significantly protect against METH-induced 3-NT formation and striatal dopamine depletion. We used two different approaches, pharmacological manipulation and transgenic animal models, in order to further investigate the role of peroxynitrite. We show that a selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI), significantly protect against the formation of 3-NT as well as striatal dopamine depletion. Similar results were observed with nNOS knockout and copper zinc superoxide dismutase (CuZnSOD)-overexpressed transgenic mice models. Finally, using the protein data bank crystal structure of tyrosine hydroxylase, we postulate the possible nitration of specific tyrosine moiety in the enzyme that can be responsible for dopaminergic neurotoxicity. Together, these data clearly support the hypothesis that the reactive nitrogen species, peroxynitrite, plays a major role in METH-induced dopaminergic neurotoxicity and that selective antioxidants and peroxynitrite decomposition catalysts can protect against METH-induced neurotoxicity. These antioxidants and decomposition catalysts may have therapeutic potential in the treatment of psychostimulant addictions. SN 0077-8923 BN 1-57331-352-1 PY 2001 VL 939 BP 366 EP 380 UT WOS:000172028600042 PM 11462792 ER PT S AU Chuang, DM AF Chuang, DM BE Slikker, W Trembly, B TI Emerging role of lithium as a neuroprotective drug - Therapeutic implications SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT 5th International Conference on Neuroprotective Agents CY SEP 17-21, 2000 CL LAKE TAHOE, NEVADA SP Natl Ctr Toxicol Res /FDA, Cent Arkansas Chapter Sigma Xi SN 0077-8923 BN 1-57331-352-1 PY 2001 VL 939 BP 404 EP 404 UT WOS:000172028600046 ER PT S AU Herning, RI Better, WE Tate, K Cadet, JL AF Herning, RI Better, WE Tate, K Cadet, JL BE Slikker, W Trembly, B TI Antiviral medications improve cerebrovascular perfusion in HIV plus non-drug users and HIV plus cocaine abusers SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT 5th International Conference on Neuroprotective Agents CY SEP 17-21, 2000 CL LAKE TAHOE, NEVADA SP Natl Ctr Toxicol Res /FDA, Cent Arkansas Chapter Sigma Xi AB Antiviral medications have been useful in delaying the time course of HIV infection. Antiviral medications have also been reported to delay or reduce symptoms associated with AIDS related dementia and to improve cortical perfusion. The mechanism for this improvement is unclear. Thus, this report studies the effects of antiviral medications on cerebral blood flow velocity in HIV+ cocaine abusers, HIV+ control individuals and appropriate control individuals. Thirty-two unmedicated HIV+ individuals (28 cocaine abusers and 4 control individuals), 22 HIV+ individuals using antiviral medications (16 cocaine abusers and 6 HIV+ control individuals), 47 HIV- cocaine abusers, and 27 control HIV- subjects were studied. Blood flow velocities were determined for the anterior and middle cerebral arteries using transcranial Doppler sonography. HIV+ individuals on antiviral medications had lower pulsatility values, suggesting decreased resistance in the cerebral blood vessels, in comparison to HIV+ individuals not taking antiviral medications. HIV+ cocaine abusers and HIV+ control individuals using antiviral medications had pulsatility values similar to HIV- control subjects. Antiviral medications appear to reduce these cerebrovascular perfusion deficits in HIV+ individuals. The antiviral medications appear to have a direct neuroprotective effect iin addition to their antiviral effects. The neuroprotective role of antiviral medications requires further investigation. SN 0077-8923 BN 1-57331-352-1 PY 2001 VL 939 BP 405 EP 412 UT WOS:000172028600047 PM 11462795 ER PT S AU Herning, RI Better, WE Tate, K Cadet, JL AF Herning, RI Better, WE Tate, K Cadet, JL BE Slikker, W Trembly, B TI Marijuana abusers are at increased risk for stroke - Preliminary evidence from cerebrovascular perfusion data SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT 5th International Conference on Neuroprotective Agents CY SEP 17-21, 2000 CL LAKE TAHOE, NEVADA SP Natl Ctr Toxicol Res /FDA, Cent Arkansas Chapter Sigma Xi AB We have recorded blood flow velocity in the anterior and middle cerebral arteries by transcranial Doppler sonography in abstinent marijuana abusers (n = 16) and control subjects (n = 19) to assess the effects of prolonged marijuana use of the cerebrovascular system. The pulsatility index, a measure of cerebrovascular resistance, and systolic velocity were significantly (p < 0.005) increased in marijuana abusers compared to the control subjects. These findings suggest that cerebral perfusion observed in 18-30 year old marijuana abusers is comparable to that of normal 60 year-olds. Thus, chronic abuse of marijuana might be a risk factor for stroke. SN 0077-8923 BN 1-57331-352-1 PY 2001 VL 939 BP 413 EP 415 UT WOS:000172028600048 PM 11462796 ER PT J AU Roy, A Rylander, G Forslund, K Asberg, M Mazzanti, CM Goldman, D Nielsen, DA AF Roy, A Rylander, G Forslund, K Asberg, M Mazzanti, CM Goldman, D Nielsen, DA TI Excess tryptophan hydroxylase 17 779C allele in surviving cotwins of monozygotic twin suicide victims SO NEUROPSYCHOBIOLOGY AB Objective: To evaluate the relationship of the tryptophan hydroxylase (TPH) genotype to suicidality by the study of surviving monozygotic (MZ) cotwins of twins who committed suicide, Method: Twenty-four surviving Swedish MZ twins whose MZ cotwins had committed suicide were compared to 158 demographically sampled Swedish general population controls for TPH alleles, We also examined serotonin transporter alleles, Results: The living MZ cotwins of suicide victims had a significantly higher TPH 17 779C allele frequency than controls, No significant difference was observed for serotonin transporter alleles, Conclusion: These results, in a small sample, suggest the possibility that the 17 779C allele of the TPH gene may be associated with an increased risk of suicide, further studies in larger samples are needed, Copyright (C) 2001 S. Karger AG, Basel. RI Nielsen, David/B-4655-2009; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 SN 0302-282X PY 2001 VL 43 IS 4 BP 233 EP 236 DI 10.1159/000054895 UT WOS:000168706300002 PM 11340361 ER PT J AU Tierney, MC Varga, M Hosey, L Grafman, J Braun, A AF Tierney, MC Varga, M Hosey, L Grafman, J Braun, A TI PET evaluation of bilingual language compensation following early childhood brain damage SO NEUROPSYCHOLOGIA AB We report a positron emission tomography (PET) study in a 37-year-old, right handed, bilingual (English and American Sign Language) male with left frontal lobe damage, without evidence of language or general intellectual dysfunction. A brain MRI scan demonstrated an atrophic lesion of the left dorsolateral prefrontal, orbital, and opercular cortices extending from the frontal pole to precentral gyrus and including parts of anterior cingulate cortex, due to an probable infantile encephalitis. H(2) (15)O PET scans found evidence of increased right hemisphere activity compared to normal controls during spontaneous generation of narrative in both English and ASL. Neuropsychological data were within normal limits with the exception of visuospatial function. The results suggest the possibility that plasticity, unmasking of neural pathways, and or other adaptations of language function in the right hemisphere may have occurred, and are discussed with regard to the crowding hypothesis. (C) 2000 Published by Elsevier Science Ltd. OI Grafman, Jordan H./0000-0001-8645-4457 SN 0028-3932 PY 2001 VL 39 IS 2 BP 114 EP 121 DI 10.1016/S0028-3932(00)00106-8 UT WOS:000166054800002 PM 11163369 ER PT J AU Zalla, T Plassiart, C Pillon, B Grafman, J Sirigu, A AF Zalla, T Plassiart, C Pillon, B Grafman, J Sirigu, A TI Action planning in a virtual context after prefrontal cortex damage SO NEUROPSYCHOLOGIA AB Patients with frontal lobe lesions are known to encounter severe problems in the organisation of their behaviour in everyday life. Script generation tasks assess the subject's conceptual ability to formulate and evaluate a coherent and structured plan of action. In the present study, we investigated to what extent neuropsychological deficits observed at the conceptual level of action knowledge lead to impairments in action execution. We examined seven patients with prefrontal cortex damage and sixteen normal subjects. Subjects were first asked to verbally formulate a plan of action and then to use this knowledge for 'executing' the actions in a virtual 3-dimensional interactive apartment presented on a computer screen. The results indicated that the presence of the realistic context improved patients' performance. However, specific impairments were observed in patients in the execution condition, namely actions slips, omissions, failure in initiating actions and purposeless displacements. Moreover, an analysis of planning time showed that, differently of the patients group, normal subjects spent more time during plan execution as compared to plan generation. These results suggest that after a frontal lobe lesion a defective formulation of a routine plan might affect the execution of the corresponding course of actions. (C) 2001 Elsevier Science Ltd. All rights reserved. OI Grafman, Jordan H./0000-0001-8645-4457 SN 0028-3932 PY 2001 VL 39 IS 8 BP 759 EP 770 DI 10.1016/S0028-3932(01)00019-7 UT WOS:000169307400001 PM 11369400 ER PT J AU Bichot, NP Rao, SC Schall, JD AF Bichot, NP Rao, SC Schall, JD TI Continuous processing in macaque frontal cortex during visual search SO NEUROPSYCHOLOGIA AB A central issue in mental chronometry is whether information is transferred between processing stages such as stimulus evaluation and response preparation in a continuous or discrete manner. We tested whether partial information about a stimulus influences the response stage by recording the activity of movement-related neurons in the frontal eye field of macaque monkeys performing a conjunction visual search and a feature visual search with a singleton distracter. While movement-related neurons were activated maximally when the target of the search array was in their movement field, they were also activated for distracters even though a saccade was successfully made to the target outside the movement field. Most importantly, the level of activation depended on the properties of the distractor. with greater activation for distracters that shared a target feature or were the target during the previous session during conjunction search, and fur the singleton distracter during feature search. These results support the model of continuous information processing and argue against a strictly discrete model, (C) 2001 Elsevier Science Ltd. All rights reserved. SN 0028-3932 PY 2001 VL 39 IS 9 BP 972 EP 982 DI 10.1016/S0028-3932(01)00022-7 UT WOS:000170074600011 PM 11516449 ER PT J AU Kastner, S Ungerleider, LG AF Kastner, S Ungerleider, LG TI The neural basis of biased competition in human visual cortex SO NEUROPSYCHOLOGIA AB A typical scene contains many different objects that compete for neural representation due to the limited processing capacity of the visual system. At the neural level, competition among multiple stimuli is evidenced by the mutual suppression of their visually evoked responses and occurs most strongly at the level of the receptive field. The competition among multiple objects can be biased by both bottom-up sensory-driven mechanisms and top-down influences, such as selective attention. Functional brain imaging studies reveal that biasing signals due to selective attention can modulate neural activity in visual cortex not only in the presence, but also in the absence of visual stimulation. Although the competition among stimuli for representation is ultimately resolved within visual cortex, the source of top-down biasing signals likely derives from a distributed network of areas in frontal and parietal cortex. Attention-related activity in frontal and parietal areas does not reflect attentional modulation of visually evoked responses, but rather the attentional operations themselves. Published by Elsevier Science Ltd. SN 0028-3932 PY 2001 VL 39 IS 12 SI SI BP 1263 EP 1276 DI 10.1016/S0028-3932(01)00116-6 UT WOS:000171405500003 PM 11566310 ER PT J AU Westergaard, GC Lussier, ID Higley, JD AF Westergaard, GC Lussier, ID Higley, JD TI Between-species variation in the development of hand preference among macaques SO NEUROPSYCHOLOGIA AB This research examined between-species variation in the development of hand preference among Macaca. Specifically, we examined hand preference using juveniles and adults of three macaque species that differ in social and reactive tendencies in order to examine whether the correlation between temperament and handedness that has been noted within Macaca mulatta occurs between closely related species. Each of the species studied exhibited a different pattern of hand preference development. Both juvenile and adult M. mulatta exhibited group-level left-hand bias. Juvenile Macaca nemestrina were not biased towards either hand at the group-level, whereas adults exhibited a group-level left-hand bias. Neither juvenile nor adult Macaca fascicularis exhibited manual bias at the group-level. Analysis of variance indicated statistically significant main effects of species and age class on hand preference measures. Post-hoc analysis indicated greater use of the left- versus right-hand, and greater hand preference strength independent of direction, among M. mulatta and M. nemestrina than among Af. fascicularis, and among adults than among juveniles. These results indicate significant between-species variation in the development of hand preference within the genus Macaca, and are inconsistent with any one single-factor theory yet offered to explain the etiology of primate laterality. We hypothesize that the relationship between handedness and temperament that has been shown within M. mulatta may generalize across closely related primate species. (C) 2001 Elsevier Science Ltd. All rights reserved. SN 0028-3932 PY 2001 VL 39 IS 13 BP 1373 EP 1378 DI 10.1016/S0028-3932(01)00105-1 UT WOS:000171902100001 PM 11585604 ER PT J AU Elvevag, B Weinberger, DR Goldberg, TE AF Elvevag, B Weinberger, DR Goldberg, TE TI Short-term memory for serial order in schizophrenia: A detailed examination of error types SO NEUROPSYCHOLOGY AB Cognitive deficits in schizophrenia have been associated with working memory problems. Schizophrenic patients (n = 24) and controls (n = 29) participated in simple short-term memory tasks, recalling a list of letters from the first to last item in the order of presentation. The authors hypothesized that deficient sequential representations would increase movement errors (e.g.. ABCD being recalled as ABDC) or intrusion errors (e.g., ABCD being recalled as ABCX), whereas simple trace decay would lead to omission errors (e.g., ABCD being recalled as ABC_). Patients made disproportionately more omissions toward the end of 6-item lists. There were no group differences in movements or intrusions as a function of serial position. Schizophrenic patients' limited short-term memory span may be due to greater forgetting during recall and not to a selective deficit in the mechanisms responsible for maintaining serial order information. SN 0894-4105 PD JAN PY 2001 VL 15 IS 1 BP 128 EP 135 DI 10.1037/0894-4105.15.1.128 UT WOS:000166727800011 PM 11216883 ER PT J AU Stuart, M Weinrich, M AF Stuart, M Weinrich, M TI Protecting the most vulnerable: Home mechanical ventilation as a case study in disability and medical care: Report from an NIH conference SO NEUROREHABILITATION AND NEURAL REPAIR AB Patients requiring chronic mechanical ventilation represent a particularly vulnerable segment of the expanding Population of individuals with chronic disabilities. Many of these individuals can live successfully at home, but face significant obstacles. Current policies in health care coverage, durable medical equipment coverage, eligibility for assisted living, and licensing of caregivers all restrict the abilities of these individuals to live in the community. Prolonged home mechanical ventilation was pioneered in France, where a current international "best practice" provides a model for developing comprehensive, cost-effective care for these individuals. SN 0888-4390 PY 2001 VL 15 IS 3 BP 159 EP 166 DI 10.1177/154596830101500302 UT WOS:000174509100002 PM 11944736 ER PT J AU Tapia, JC Mentis, GZ Navarrete, R Nualart, F Figueroa, E Sanchez, A Aguayo, LG AF Tapia, JC Mentis, GZ Navarrete, R Nualart, F Figueroa, E Sanchez, A Aguayo, LG TI Early expression of glycine and GABA(A) receptors in developing spinal cord neurons. Effects on neurite outgrowth SO NEUROSCIENCE AB Using fluorometric and immunocytochemical techniques, we found that high glycine concentrations or blockade of glycine receptors increases neurite outgrowth in developing mouse spinal cord neurons. Glycine- and GABA(A)-activated currents were demonstrated during applications of glycine and GABA (50-100 muM) in 5 days in vitro (DIV) neurons. Long application (greater than or equal to 10 min) of 100 muM glycine desensitized the membrane response by more than 95%. Application of glutamate in the absence of external Mg2+, at several membrane potentials, did not produce any detectable membrane response in these cells. Immunocytochemical studies with NR1 and G1uR1 antibodies showed a delayed appearance of N-methyl-D-aspartate (NMDA) and alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors respectively. Spontaneous synaptic activity was readily observed in 5 DIV neurons. The use of various receptor antagonists (strychnine, bicuculline, DL-2-amino-5-phosphonovalerate [APV], 6-cyano-7-nitroquinoxaline-2,3-dione [CNQX]) revealed that this activity was predominantly glycinergic, and to a smaller extent, GABAergic. In the presence of bicuculline, APV and CNQX, we detected abundant spontaneous depolarizing potentials which often reached the action potential threshold. Further evidence for functional synaptic activity was provided by the detection of co-localization of gephyrin and synaptophysin at 5 DIV using confocal microscopy. Fluorometric studies with Fluo-3, a Ca2+ indicator, in 5 DIV cultures showed the presence of spontaneous fluctuations associated with tetrodotoxin-sensitive synaptic events. The number of neurons displaying these fluctuations was significantly increased (> 100%) when the cells were bathed in a strychnine-containing solution. On the other hand, these synaptically mediated Ca2+ events were blocked by the co-application of strychnine and bicuculline. This suggests that glycine and GABA(A) receptors provide a fundamental regulation of both neuronal excitability and intracellular Ca2+ at this early time of development. The neurotrophic effects of agonists and antagonists for glycine, GABA(A) and glutamate receptors were examined in neurons cultured for 2 or 5 DIV. From all the agonists used, only high concentrations of glycine increased neurite outgrowth in 5 DIV neurons. We found that strychnine also increased neurite outgrowth, whereas tetrodotoxin (1 muM), nimodipine (4 muM) and bicuculline (20 muM) completely blocked it. On the other hand, APV (50 muM) and CNQX (20 muM) were unable to affect neurite outgrowth. These data suggest that spinal glycine receptors depress neurite outgrowth by shunting neuronal excitability. Outgrowth induction possibly results from the enhanced activity found after the inhibition of glycinergic activity. We postulate that this resets the intracellular calcium at a concentration that favors neurite outgrowth. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved. SN 0306-4522 PY 2001 VL 108 IS 3 BP 493 EP 506 DI 10.1016/S0306-4522(01)00348-7 UT WOS:000172996600013 PM 11738262 ER PT J AU Krasnova, IN Ladenheim, B Jayanthi, S Oyler, J Moran, TH Huestis, MA Cadet, JL AF Krasnova, IN Ladenheim, B Jayanthi, S Oyler, J Moran, TH Huestis, MA Cadet, JL TI Amphetamine-induced toxicity in dopamine terminals in CD-1 and C57BL/6J mice: Complex roles for oxygen-based species and temperature regulation SO NEUROSCIENCE AB In order to examine differential strain susceptibility to neurotoxic effects of amphetamine and to assess the potential role of superoxide radicals in am phetamine-induced dopaminergic damage, the drug was injected to mice with different levels or copper/zinc superoxide dismutase (Cu/Zn SOD) enzyme. Administration of amphetamine (10 mg/kg, i.p.. given every 2 h, a total of four times) to wild-type CD-I and C57BL/6J mice caused significant decreases in dopamine and 3,4-dihydroxyphenylacetic acid levels, in [I-125]RTI-121-labeled dopamine transporters as well as a significant depletion in the concentration of dopamine transporter and vesicular monoamine transporter 2 proteins. The amphetamine-induced toxic effects were less prominent in CD-1 mice, which have much higher levels of Cu/Zn SOD activity (0.69 units/mg of protein) in their striata than C57BL/6J animals (0.007 units/mg of protein). Transgenic mice on CD-1 and C57BL/6J background, which had striatal levels of Cu/Zn SOD 2.57 and 1.67 units/mg of protein, respectively, showed significant protection against all the toxic effects of amphetamine. The attenuation of toxicity observed in transgenic mice was not caused by differences in amphetamine accumulation in wild-type and mutant animals. However, CD-1-SOD transgenic mice showed marked hypothermia to amphetamine whereas C57-SOD transgenic mice did not show a consistent thermic response to the drug. The data obtained demonstrate distinctions in the neurotoxic profile of amphetamine in CD-I and C57BL/6J mice, which show some differences in Cu/Zn SOD activity and in their thermic responses to amphetamine administration. Thus, these observations provide evidence for possible complex interactions between thermoregulation and free radical load in the long-term neurotoxic effects of this illicit drug of abuse. Published by Elsevier Science Ltd on behalf of IBRO. SN 0306-4522 PY 2001 VL 107 IS 2 BP 265 EP 274 DI 10.1016/S0306-4522(01)00351-7 UT WOS:000172475500008 PM 11731100 ER PT J AU Wrenn, CC Wiley, RG AF Wrenn, CC Wiley, RG TI Lack of effect of moderate Purkinje cell loss on working memory SO NEUROSCIENCE AB 192 immunoglobulin G-saporin (192-sap) is an immunotoxin which targets the cholinergic basal forebrain after injection into either the ventricular system or the parenchyma of the rat brain. When injected by the i.c.v. route, 192-sap kills some cerebellar Purkinje cells in addition to its more extensive killing of the cholinergic basal forebrain. Behaviorally, i.c.v, injections of 192-sap result in impaired performance in a variety of experimental paradigms of learning and memory including a working memory task in the radial maze. The current study examined the contribution. if any, of immunotoxin-induced Purkinje cell loss to impaired performance in the radial maze. To meet this aim, we used i.c.v. injection of another immunotoxin, OX7-saporin (OX7-sap), at a dose that produced Purkinje cell loss of similar extent to that produced by i.c.v. 192-sap. We then compared these OX7-sap-injected rats with 192-sap-injected rats in a radial maze working memory task. We found a working memory impairment only in the 192-sap-injected rats. These data show that moderate Purkinje cell loss alone is insufficient to impair working memory. Furthermore. the data are consistent with the idea that the working memory deficit observed in 192-sap-injected animals is likely due to lesioning of the cholinergic basal forebrain. Published by Elsevier Science Ltd on behalf of IBRO. SN 0306-4522 PY 2001 VL 107 IS 3 BP 433 EP 445 DI 10.1016/S0306-4522(01)00326-8 UT WOS:000172661500007 PM 11718998 ER PT J AU You, ZB Chen, YQ Wise, RA AF You, ZB Chen, YQ Wise, RA TI Dopamine and glutamate release in the nucleus accumbens and ventral tegmental area of rat following lateral hypothalamic self-stimulation SO NEUROSCIENCE AB Rewarding hypothalamic brain stimulation is thought to depend on trans-synaptic activation of high-threshold (and thus rarely directly depolarized by rewarding stimulation) dopaminergic fibers of the medial forebrain bundle. We used in vivo microdialysis and high-performance liquid chromatography coupled with electrochemical or fluorometric detection to investigate the concurrent release of dopamine and glutamate in the nucleus accumbens septi and in the ventral tegmental area. as a function of lateral hypothalamic self-stimulation. Self-stimulation at a variety of stimulation frequencies and pulse widths increased levels of dopamine and its primary metabolites, dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens. Lateral hypothalamic self-stimulation also induced significant increases in ventral tegmental area dopamine and metabolite levels. and the percentage increase of dopamine was higher in this region than in the nucleus accumbens. Local perfusion with the dopamine uptake inhibitor nomifensine (10 muM) increased dopamine levels in the nucleus accumbens about three-fold and potentiated the increase of dopamine levels induced by self-stimulation. Nomifensine perfusion also induced a delayed decrease in nucleus accumbens glutamate levels, and self-stimulation did not modify this effect of the drug. Local perfusion with the D2-type dopamine receptor antagonist raclopride significantly increased both basal and self-stimulation induced dopamine release in the nucleus accumbens. Neither nomifensine nor raclopride perfusion significantly affected the maximal rates of self-stimulation. Perfusion with tetrodotoxin (2 muM) into nucleus accumbens significantly decreased basal and prevented stimulation-induced increases in accumbens dopamine levels but only slightly decreased the rate of self-stimulation. In contrast, perfusion of tetrodotoxin (0.5 muM) into the ventral tegmental area decreased basal and blocked stimulation-induced increases in both nucleus accumbens and ventral tegmental area dopamine levels; this treatment also blocked or strongly inhibited self-stimulation. While it had no effect on glutamate levels in the nucleus accumbens. lateral hypothalamic self-stimulation induced a significant and tetrodotoxin-sensitive increase in glutamate levels in the ventral segmental area. Taken together, the present results indicate that, across a broad range Of Stimulation parameters, rewarding lateral hypothalamus stimulation causes major and persistent activation of the mesolimbic dopamine system, and suggest descending glutamatergic fibers in the medial forebrain bundle as a candidate for the directly activated descending pathway in lateral hypothalamus brain stimulation reward. Published by Elsevier Science Ltd on behalf of IBRO. RI Wise, Roy/A-6465-2012 SN 0306-4522 PY 2001 VL 107 IS 4 BP 629 EP 639 DI 10.1016/S0306-4522(01)00379-7 UT WOS:000172661600009 PM 11720786 ER PT J AU Tao-Cheng, JH Vinade, L Smith, C Winters, CA Ward, R Brightman, MW Reese, TS Dosemeci, A AF Tao-Cheng, JH Vinade, L Smith, C Winters, CA Ward, R Brightman, MW Reese, TS Dosemeci, A TI Sustained elevation of calcium induces Ca2+/calmodulin-dependent protein kinase II clusters in hippocampal neurons SO NEUROSCIENCE AB Treatment of cultured hippocampal. neurons with the mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) in the absence of glucose mimics ischemic energy depletion and induces formation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) clusters, spherical structures with diameters of 75-175 nm [Dosemeci et al., J. Neurosci. 20 (2000) 3076-3084]. The demonstration that CaMKII clustering occurs in the intact, adult rat brain upon interruption of blood flow indicates that clustering is not confined to cell cultures. Application of N-methyl-Daspartate (250 muM, 15 min) to hippocampal cultures also induces cluster formation, suggesting a role for Ca2+. Indeed, intracellular Ca2+ monitored with Fluo3-AM by confocal microscopy reaches a sustained high level within 5 min of CCCP treatment. The appearance of immunolabeled CaMKII clusters, detected by electron microscopy, follows the onset of the sustained increase in intracellular Ca2+. Moreover, CaMKII does not cluster when the rise in intracellular Ca2+ is prevented by the omission of extracellular Ca2+ during CCCP treatment, confirming that clustering is Ca2+-dependent. A lag period of 1-2 min between the onset of high intracellular Ca2+ levels and the formation of CaMKII clusters suggests that a sustained increase in Ca2+ level is necessary for the clustering. CaMKII clusters disappear within 2 h of returning the cultures to normal incubation conditions, at which time no significant cell death is detected. These results indicate that pathological conditions that promote sustained episodes of Ca2+ overload result in a transitory clustering of CaMKII into spherical structures. CaMKII clustering may represent a cellular defense mechanism to sequester a portion of the CaMKII pool, thereby preventing excessive protein phosphorylation. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved. SN 0306-4522 PY 2001 VL 106 IS 1 BP 69 EP 78 DI 10.1016/S0306-4522(01)00262-7 UT WOS:000171242700007 PM 11564417 ER PT J AU Schmidt, BL Tambeli, CH Gear, RW Levine, JD AF Schmidt, BL Tambeli, CH Gear, RW Levine, JD TI Nicotine withdrawal hyperalgesia and opioid-mediated analgesia depend on nicotine receptors in nucleus accumbens SO NEUROSCIENCE AB The nucleus accumbens, as part of the mesolimbic dopaminergic reward pathway, mediates both addiction to and withdrawal from substances of abuse. In addition, activity of substances of abuse such as opioids in the nucleus accumbens has been implicated in pain modulation. Because nucleus accumbens nicotinic receptors are important in nicotine addiction and because nicotinic activity can interact with opioid action, we investigated the contribution of nucleus accumbens nicotinic receptors to opioid-mediated analgesia/antinociception. The response of the nociceptive jaw-opening reflex to opioids was studied in the rat, both before and during chronic nicotine exposure. In nicotine-naive rats, intra-accumbens injection of the nicotinic receptor antagonist mecamylamine blocked antinociception produced by either systemic morphine, intra-accumbens co-administration of a mu- and a delta -opioid receptor agonist, or noxious stimulation (i.e., subdermal capsaicin in the hindpaw); intra-accumbens mecamylamine alone had no effect. The antinociceptive effect of either morphine or noxious stimulation was unchanged during nicotine tolerance; however, intra-accumbens mecamylamine lost its ability to block antinociception produced by either treatment. Intra-accumbens mecamwylamine by itself precipitated significant hyperalgesia in nicotine-tolerant rats which could be suppressed by noxious stimulation as well as by morphine. These results indicate that nucleus accumbens nicotinic receptors play an important role in both opioid- and noxious stimulus-induced antinociception in nicotine-naive rats. This role was attenuated in the nicotine-dependent state. The suppression of withdrawal hyperalgesia by noxious stimulation suggests that pain can ameliorate the symptoms of withdrawal, thus suggesting a possible mechanism for pain-seeking behavior. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved. RI Tambeli, Claudia/D-4356-2012; OI Schmidt, Brian/0000-0002-2409-8984 SN 0306-4522 PY 2001 VL 106 IS 1 BP 129 EP 136 DI 10.1016/S0306-4522(01)00264-0 UT WOS:000171242700013 PM 11564423 ER PT J AU Wei, H Qin, ZH Senatorov, VV Wei, W Wang, Y Qian, Y Chuang, DM AF Wei, H Qin, ZH Senatorov, VV Wei, W Wang, Y Qian, Y Chuang, DM TI Lithium suppresses excitotoxicity-induced striatal lesions in a rat model of Huntington's disease SO NEUROSCIENCE AB Huntington's disease is a progressive, inherited neurodegenerative disorder characterized by the loss of subsets of neurons primarily in the striatum. In this study, we assessed the neuroprotective effect of lithium against striatal lesion formation in a rat model of Huntington's disease in which quinolinic acid was unilaterally infused into the striatum. For this purpose, we used a dopamine receptor autoradiography and glutamic acid decarboxylase mRNA in situ hybridization analysis, methods previously shown to be adequate for quantitative analysis of the excitotoxin-induced striatal lesion size. Here we demonstrated that subcutaneous injections of LiCl for 16 days prior to quinolinic acid infusion considerably reduced the size of quinolinic acid-induced striatal lesion. Furthermore, these lithium pre-treatments also decreased the number of striatal neurons labeled with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Immunohistochemistry and western blotting demonstrated that lithium-elicited neuroprotection was associated with an increase in Bcl-2 protein levels, Our results raise the possibility that lithium may be considered as a neuroprotective agent in treatment of neurodegenerative diseases such as Huntington's disease. Published by Elsevier Science Ltd on behalf of IBRO. SN 0306-4522 PY 2001 VL 106 IS 3 BP 603 EP 612 DI 10.1016/S0306-4522(01)00311-6 UT WOS:000171640800011 PM 11591460 ER PT J AU Sharp, AH Black, JL Dubel, SJ Sundarraj, S Shen, JP Yunker, AMR Copeland, TD McEnery, MW AF Sharp, AH Black, JL Dubel, SJ Sundarraj, S Shen, JP Yunker, AMR Copeland, TD McEnery, MW TI Biochemical and anatomical evidence for specialized voltage-dependent calcium channel gamma isoform expression in the epileptic and ataxic mouse, stargazer SO NEUROSCIENCE AB Inherited forms of ataxia and absence seizures in mice have been linked to defects in voltage-dependent calcium channel subunits. However, a correlation between the sites of neuronal dysfunction and the impact of the primary lesion upon calcium channel subunit expression or function has not been clearly established. For example, the mutation in stargazer mice has pleiotropic consequences including synaptic alterations in cerebellar granule cells, hippocampal CA3/mossy fibers, and cortical neurons in layer V that, presumably, lead to ataxia and seizures. Genetic analysis of stargazer mice determined that the defective gene encodes a protein expressed in brain (gamma2) with limited homology to the skeletal muscle L-type calcium channel gamma1 subunit. Although additional gamma isoforms have been subsequently identified primarily in neural tissue, little was known about the proteins they encode. Therefore, this study explored the distribution and biochemical properties of gamma2 and other gamma isoforms in wild-type and stargazer brain. We cloned human gamma2, gamma3, and gamma4 isoforms, produced specific anti-peptide antibodies to gamma isoforms and characterized both heterologously expressed and endogenous gamma. We identified regional specificity in the expression of gamma isoforms by western analysis and immunohistochemistry. We report for the first time that the mutation in the stargazer gene resulted in the loss of gamma2 protein. Furthermore, no compensatory changes in the expression of gamma3 or gamma4 protein were evident in stargazer brain. In contrast to other voltage-dependent calcium channel subunits, gamma immunostaining was striking in that it was primarily detected in regions highly enriched in excitatory glutamatergic synapses and faintly detected in cell bodies, suggesting a role for gamma in synaptic functions. Sites of known synaptic dysfunction in stargazer (the hippocampal CA3 region, dentate gyrus, and cerebellar molecular layer) were revealed as relying primarily upon gamma2, as total gamma isoform expression was dramatically decreased in these regions. Electron microscopy localized anti-gamma antibody immunostaining to dendritic structures of hippocampal mossy fiber synapses, with enrichment at postsynaptic densities. To assess the association of native gamma with voltage-dependent calcium channel or alpha -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits, gamma isoforms (gamma2, gamma3 and gamma4) were detergent solubilized from mouse forebrain. Antibodies against a highly conserved C-terminal epitope present in gamma2, gamma3 and gamma4 immunoprecipitated voltage-dependent calcium channel subunits (alpha 1B), providing the first in vivo evidence that gamma and voltage-dependent calcium channels form stable complexes. Furthermore, both anti-gamma2 antibodies and anti-alpha 1B antibodies independently immunoprecipitated the AMPA receptor subunit, G1uR1, from mouse forebrain homogenates. In summary, loss of gamma2 immunoreactivity in stargazer is precisely localized so as to contribute to previously characterized synaptic defects. The data in this paper provide compelling evidence that gamma isoforms form complexes in vivo with voltage-dependent calcium channels as well as AMPA receptors, are selectively and differentially expressed in neuronal processes, and localize primarily to dendritic structures in the hippocampal mossy fiber region. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved. SN 0306-4522 PY 2001 VL 105 IS 3 BP 599 EP 617 DI 10.1016/S0306-4522(01)00220-2 UT WOS:000170933300009 PM 11516827 ER PT J AU De Leonibus, E Mele, A Oliverio, A Pert, A AF De Leonibus, E Mele, A Oliverio, A Pert, A TI Locomotor activity induced by the non-competitive N-methyl-D-aspartate antagonist, MK-801: Role of nucleus accumbens efferent pathways SO NEUROSCIENCE AB We have recently shown that focal administration of dizocilpine hydrogen maleate (MK-801, a non-competitive N-methyl-(D)-aspartate antagonist) within the nucleus accumbens increases locomotor activity in a dopamine-independent manner. The purpose of this study was to investigate the neural network underlying locomotor stimulation induced by N-methyl-(D)-aspartate receptor blockade in the accumbens. In the first experiment, we examined the effect of different doses (1, 5 and 25 nmol) of the active and inactive enantiomers of the N-methyl-(D)-aspartate antagonist. (+)- and ( -)-MK-801, respectively, focally administered in the nucleus accumbens. Only the active enantiomer induced a significant increase in locomotor activity: furthermore, the effect induced by the two highest doses of (+)-MK-801 was significantly different from that induced by (-)-MK-801. In the second part of the study, we performed ibotenic acid lesions to the major output nuclei of the accumbens, the ventral pallidum, mediodorsal thalamus. ventrolateral/ventromedial thalamus and pedunculopontine tegmental nucleus. to observe their effect on locomotor activity induced by focal (+)-MK-801 (35 nmol) administration into the accumbens. None of the lesions had any effect on spontaneous locomotor activity. Hyperactivity induced by accumbens MK-801 administrations was unaffected by ibotenic acid lesions of the pedunculopontine tegmental nucleus, while lesions of the mediodorsal thalamus induced only a partial inhibition. In contrast, ibotenic acid lesions of the ventral pallidum and ventrolateral/ventromedial thalamus completely blocked the motor response induced by accumbens MK-801. These data indicate that the intact mediodorsal thalamus, which has been proposed ah a part of the loop that relays accumbens information to the prefrontal cortex, does not seem to be a structure of primary importance in MK-801 locomotor activity. On the contrary, the motor nuclei of the thalamus appear to play a more relevant role. suggesting that different neural substrates may mediate dopamine and glutamate functional output from the nucleus accumbens. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved. RI Mele, Andrea/E-7741-2015 SN 0306-4522 PY 2001 VL 104 IS 1 BP 105 EP 116 DI 10.1016/S0306-4522(01)00047-1 UT WOS:000168350800010 PM 11311535 ER PT J AU Schutz, B Weihe, E Eiden, LE AF Schutz, B Weihe, E Eiden, LE TI Independent patterns of transcription for the products of the rat cholinergic gene locus SO NEUROSCIENCE AB The cholinergic phenotype requires the expression of the vesicular acetylcholine transporter and choline acetyltransferase proteins. Both genes are encoded at one chromosomal location called the cholinergic gene locus. We have identified by in situ hybridization histochemistry distinct patterns of transcription from the cholinergic gene locus in the subdivisions of the rat cholinergic nervous system. The vesicular acetylcholine transporter and choline acetyltransferase are co-expressed in cholinergic neurons at all developmental stages in all major types of cholinergic neurons. The relative levels of vesicular acetylcholine transporter and choline acetyltransferase transcripts, however, change substantially during development in the CNS. They also differ dramatically in distinct subdivisions of the mature cholinergic nervous system, with vesicular acetylcholine transporter mRNA expressed at high levels relative to choline acetyltransferase mRNA in the peripheral nervous system. but at equivalent levels in the CNS. Expression of the R-exon, the presumptive first non-coding exon common to both the vesicular acetylcholine transporter and choline acetyltransferase, was not detectable at any developmental stage in any of the cholinergic neuronal subtypes in the rat nervous system. Thus, in contrast to less complex metazoan organisms, production of the vesicular acetylcholine transporter and choline acetyltransferase via a common differentially spliced transcript does not seem to occur to a significant extent in the rat. We suggest that separate transcriptional start sites within the cholinergic gene locus control vesicular acetylcholine transporter and choline acetyltransferase transcription. while additional elements are responsible for the specific transcriptional control of the entire locus in cholinergic versus non-cholinergic neurons. independent transcription of the vesicular acetylcholine transporter and choline acetyltransferase genes provides a mechanism for regulating the relative expression of these two proteins to fine-tune acetylcholine quantal sire in different types of cholinergic neurons, both centrally and peripherally. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved. OI Eiden, Lee/0000-0001-7524-944X SN 0306-4522 PY 2001 VL 104 IS 3 BP 633 EP 642 DI 10.1016/S0306-4522(01)00100-2 UT WOS:000169933100005 PM 11440797 ER PT J AU Ma, W Pancrazio, JJ Andreadis, JD Shaffer, KM Stenger, DA Li, BS Zhang, L Barker, JL Maric, D AF Ma, W Pancrazio, JJ Andreadis, JD Shaffer, KM Stenger, DA Li, BS Zhang, L Barker, JL Maric, D TI Ethanol blocks cytosolic Ca2+ responses triggered by activation of GABA(A) receptor/Cl- channels in cultured proliferating rat neuroepithelial cells SO NEUROSCIENCE AB GABA(A) receptor/Cl- channels and voltage-gated Ca2+ channels are believed to be important sites of ethanol action in the CNS. Acute exposure of ethanol potentiates GABAA receptor/Cl- channel activity and inhibits voltage-gated Ca2+ channels in a number of preparations. mostly post-mitotic neurons. The effects of ethanol on these channels in primary cultures of undifferentiated neural precursor cells remain unknown. To address this issue, wr examined the effects of ethanol on GABAA agonist-activated elevation of cytosolic Ca2+ in an in vitro model of the cortical neuroepithelium derived from rat basic fibroblast growth factor-expanded neural precursor cells. We found a potent inhibition of GABA(A)-activated elevation of cytosolic Ca2+ by ethanol in actively proliferating cells. Since we had recently demonstrated that GABAA receptor activation depolarizes these cells and elevates their cytosolic Ca2+, we tested whether the effects of ethanol involved both GABAA receptors and voltage-gated Ca'' channels. Both extracellular K-- and muscimol-induced cytosolic Ca2+ elevations were abolished by nitrendipine, indicating that both depolarizing stimuli triggered Ca2+ influx through L-type voltage-gated Ca2+ channels. Exposure of proliferating cells to different concentrations of ethanol revealed that the drug was more potent in blocking muscimol-induced compared to K+-evoked cytosolic Ca2+ elevations. These results raise the possibility that ethanol blocks GABAergic stimulation of cytosolic Ca2+ levels in proliferating precursors primarily by interacting with GABA(A) receptoriC1 channels and secondarily with voltage-gated Ca2+ channels. Published by Elsevier Science Ltd on behalf of IBRO. RI Pancrazio, Joseph/M-3206-2015 OI Pancrazio, Joseph/0000-0001-8276-3690 SN 0306-4522 PY 2001 VL 104 IS 3 BP 913 EP 922 DI 10.1016/S0306-4522(01)00084-7 UT WOS:000169933100028 PM 11440820 ER PT J AU Kowalska, DM Kusmierek, P Kosmal, A Mishkin, M AF Kowalska, DM Kusmierek, P Kosmal, A Mishkin, M TI Neither perirhinal/entorhinal nor hippocampal lesions impair short-term auditory recognition memory in dogs SO NEUROSCIENCE AB Visual, tactile, and olfactory recognition memory in animals is mediated in part by the perirhinal/entorhinal (or rhinal) cortices and, possibly, the hippocampus. To examine the role of these structures in auditory memory, we performed rhinal. hippocampal, and combined lesions in groups of dogs trained in auditory delayed matching-to-sample with trial-unique sounds. The sample sound was presented through a central speaker and. after a delay. the sample sound and a different sound were played alternately through speakers placed on either side of the animal; the animal was rewarded for responding to the side emitting the sample sound. None of the lesion groups showed significant impairment in comparison either to their own preoperative performance or to the performance of intact control dogs. This was the case both for relearning the delayed matching rule at a delay of 1.5 s and for task performance at variable delays ranging from 10 to 90 s. From these findings we suggest that the tissue critical for auditory recognition memory is located outside both the perirhinal/entorhinal cortices and the hippocampus. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved. SN 0306-4522 PY 2001 VL 104 IS 4 BP 965 EP 978 DI 10.1016/S0306-4522(01)00140-3 UT WOS:000170140700006 PM 11457584 ER PT J AU Umegaki, H Munoz, J Meyer, RC Spangler, EL Yoshimura, J Ikari, H Iguchi, A Ingram, DK AF Umegaki, H Munoz, J Meyer, RC Spangler, EL Yoshimura, J Ikari, H Iguchi, A Ingram, DK TI Involvement of dopamine D-2 receptors in complex maze learning and acetylcholine release in ventral hippocampus of rats SO NEUROSCIENCE AB In the current study we focus on the involvement of dopamine D-2 receptors in the ventral hippocampus in memory performance and acetylcholine release. Using the aversively motivated 14-unit T-maze (Stone maze) the injection of raclopride, a D-2 receptor antagonist. into the ventral hippocampus (8 mug/kg) was found to impair memory performance. Co-injection of quinpirole, a D-2 receptor agonist (8 mug/kg), overcame the impairment in performance. Microdialysis study revealed that quinpirole infusion (10-500 muM) into the ventral hippocampus stimulated acetylcholine release in a dose-dependent manner, and systemic injection of quinpirole (0.5 mg/kg, i.p.) also stimulated acetylcholine release in the ventral hippocampus. Infusion of eticlopride, another D-2 receptor antagonist, into the ventral hippocampus suppressed acetylcholine release in the hippocampus induced by systemic injection of quinpirole. Taken together, we suggest that D-2 receptors in the ventral hippocampus are involved in memory performance, possibly through the regulation of acetylcholine. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved. SN 0306-4522 EI 1873-7544 PY 2001 VL 103 IS 1 BP 27 EP 33 DI 10.1016/S0306-4522(00)00542-X UT WOS:000167494600004 PM 11311785 ER PT J AU Yang, HYT Wilkening, S Iadarola, MJ AF Yang, HYT Wilkening, S Iadarola, MJ TI Spinal cord genes enriched in rat dorsal horn and induced by noxious stimulation identified by subtraction cloning and differential hybridization SO NEUROSCIENCE AB Persistent nociceptive input increases neuronal excitability and induces a program of gene expression in the dorsal spinal cord. The alteration in gene expression commences with phosphorylation and induction of immediate early genes and proceeds to target genes. Only a few target genes have been identified as yet. The present report uses a polymerase chain reaction-based subtraction cloning procedure to obtain an "anatomically focused" complementary DNA library enriched in transcripts related to sensory spinal cord (rat dorsal horn minus ventral horn). A subset of clones from this library (n = 158) was screened to verify dorsal horn enrichment and to identify those regulated by carrageenan-induced peripheral inflammation. Molecular classes which displayed enriched expression included a proto-oncogene not previously associated with sensory processes, two regulators of the Rho/Rac pathway which controls cell shape, and three genes involved in cytoskeletal regulation and scaffolding. Additional transcripts coded for proteins involved in intercellular communication or intracellular function. Within the set of 158 transcripts, one known and two unknown genes were induced by persistent noxious input. The known gene codes for the secreted cysteine proteinase inhibitor, cystalin C, suggesting that modulation of extracellular proteolytic activity occurs. Since it is secreted, cystatin C may also provide a cerebrospinal fluid bio-marker for persistent pain states. Using a combined anatomical and functional approach, we have extended the molecular repertoire of genes expressed and induced in second-order neurons or supporting glial cells in several new directions, with particular emphasis on regulation of cell morphology and plasma membrane dynamics. Some of these proteins reveal new pathways for information signaling in the sensory half of the spinal cord and require further research to understand their role in the adult spinal cord. The induced genes may provide new molecular targets for therapeutic development and provide new probes for investigating the dynamic state of cellular activity that occurs during persistent pain states. Published by Elsevier Science Ltd on behalf of IBRO. SN 0306-4522 PY 2001 VL 103 IS 2 BP 493 EP 502 DI 10.1016/S0306-4522(00)00573-X UT WOS:000167695300019 PM 11246163 ER PT J AU Das, KP Chao, SL White, LD Haines, WT Harry, GJ Tilson, HA Barone, S AF Das, KP Chao, SL White, LD Haines, WT Harry, GJ Tilson, HA Barone, S TI Differential patterns of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNA and protein levels in developing regions of rat brain SO NEUROSCIENCE AB The present studies were undertaken to characterize the regional and temporal patterns of neurotrophin messenger RNA and protein levels for p-nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the developing CNS. We have examined the levels of these neurotrophin messenger RNAs with ribonuclease protection assays and corresponding protein levels with enzyme-linked immunosorbent assays in the developing Long-Evans rat hippocampus, neocortex and cerebellum on postnatal days 1,7, 14, 21, and 92. In addition, immunohistochemistry was used to localize the neurotrophins in these developing brain regions. Results indicated that in neocortex and hippocampus, messenger RNA for both nerve growth factor and brain-derived neurotrophic factor increased in an age-dependent manner, reaching a plateau by postnatal day 14. In the neocortex, nerve growth factor and brain-derived neurotrophic factor protein levels both peaked at postnatal day 14. In hippocampus, nerve growth factor protein peaked at postnatal day 7 while brain-derived neurotrophic factor peaked at postnatal day 14. In cerebellum, nerve growth factor messenger RNA levels were flat, while nerve growth factor protein peaked at postnatal day 7. Brain-derived neurotrophic factor messenger RNA increased in an age-dependent manner while the pattern for its protein levels was mixed. Neurotrophin-3 messeger RNA levels increased in an age-dependent manner in hippocampus, peaked at postnatal day 14 in cerebellum, and no changes occurred in neocortex. Neurotrophin-3 protein was at its peak at postnatal day 1 and thereafter decreased at other postnatal days in all three brain regions. Results of neurotrophin immunohistochemistry often paralleled and complemented enzyme-linked immunosorbent assay data, demonstrating specific cell groups containing neurotrophin proteins in these regions. Within each region, patterns with regard to messenger RNA and respective protein levels for each neurotrophin were unique. No consistent relationship between patterns of neurotrophin messenger RNAs and their cognate proteins was observed between regions. The different regional patterns for neurotrophin messenger RNA and protein levels in each brain region indicate that messenger RNA studies of neurotrophin messenger RNA must be augmented by protein determination to fully characterize spatial and temporal neurotrophin distribution. Published by Elsevier Science Ltd on behalf of IBRO. SN 0306-4522 PY 2001 VL 103 IS 3 BP 739 EP 761 DI 10.1016/S0306-4522(01)00011-2 UT WOS:000167773900013 PM 11274792 ER PT J AU Chen, X Levine, JD AF Chen, X Levine, JD TI Hyper-responsivity in a subset of C-fiber nociceptors in a model of painful diabetic neuropathy in the rat SO NEUROSCIENCE AB While clinical characteristics of diabetic painful neuropathy are well described, the underlying electrophysiological basis of the exaggerated painful response to stimuli, as well as the presence of spontaneous pain, are poorly understood. In order to elucidate peripheral contributions to painful diabetic neuropathy, we quantitatively evaluated the function of C-fibers in a rat model of painful diabetic neuropathy, diabetes induced by the pancreatic beta -cell toxin streptozotocin. While there was no significant effect of diabetes on conduction velocity, mechanical threshold or spontaneous activity, the number of action potentials in response to sustained threshold and suprathreshold mechanical stimuli was significantly increased in the diabetic rats. Moreover, there was a clustering of responses of C-fibers in diabetic rats; while two-thirds of C-fibers fired at the same mean frequency as C-fibers in control rats, one-third of C-fibers in diabetic rats were markedly hyper-responsive, demonstrating a threefold increase in firing frequency. The high-firing-frequency C-fibers in rats with diabetes also had faster conduction velocity than the low-firing-frequency C-fibers in rats with diabetes or in C-fibers in control rats. The hyper-responsiveness was characterized by a selective increase of the shortest interspike intervals (< 100 ms) in the burst component (first 10 s) of the response to a sustained suprathreshold stimulus; in the plateau phase (last 50 s) of the response to a 60-s suprathreshold stimulus, we found a selective increase of interspike intervals between 100 and 300 ms in hyper-responsive C-fibers in rats with diabetes. The hyper-responsiveness did not correlate with mechanical threshold, presence of spontaneous activity or location of the fiber's receptive field. In summary, in an established model of painful diabetic neuropathy in the rat, a subset of C-fibers demonstrated a marked hyper-responsiveness to mechanical stimuli. The subset was also found to have a greater mean conduction velocity than the fibers not demonstrating this hyper-responsivity. The present findings suggest that study of individual neurons in vitro may allow elucidation of the ionic basis of enhanced nociception in diabetic neuropathy. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved. SN 0306-4522 PY 2001 VL 102 IS 1 BP 185 EP 192 DI 10.1016/S0306-4522(00)00454-1 UT WOS:000166562300018 PM 11226682 ER PT J AU Aeschbach, D Postolache, TT Sher, L Matthews, JR Jackson, MA Wehr, TA AF Aeschbach, D Postolache, TT Sher, L Matthews, JR Jackson, MA Wehr, TA TI Evidence from the waking electroencephalogram that short sleepers live under higher homeostatic sleep pressure than long sleepers SO NEUROSCIENCE AB We used the waking electroencephalogram to study the homeostatic sleep regulatory process in human short sleepers and long sleepers. After sleeping according to their habitual schedule, nine short sleepers (sleep duration <6 h) and eight lung sleepers (>9 h) were recorded half-hourly during similar to 40 h of wakefulness in a constant routine protocol. Within the Frequency range of 0.25-20.0 Hz, spectral power density in the 5.25-9.0 and 17.25-18.0 Hz ranges was higher in short sleepers than in long sleepers. In both groups, increasing time awake was associated with an increase of theta/low-frequency alpha activity (5.25-9.0 Hz), whose kinetics followed a saturating exponential function. The time constant did not differ between groups and was similar to the previously obtained time constant of the wake-dependent increase of slow-wave activity (0.75-4.5 Hz) in the sleep electroencephalogram. In addition, the time constant of the decrease of slow-wave activity during extended recovery sleep following the constant routine did not differ between groups. However, short sleepers showed an abiding enhancement of theta/low-frequency alpha activity during wakefulness after recovery sleep that was independent of the homeostatic process. It is concluded that, while the kinetics of the homeostatic process do not differ between the two groups, short sleepers live under and tolerate higher homeostatic sleep pressure than long sleepers. The homeostat-independent enhancement of theta/ low-frequency alpha activity in the waking electroencephalogram in the short sleepers may he genetically determined or be the result of long-term adaptation to chronically short sleep. Published by Elsevier Science Ltd. SN 0306-4522 PY 2001 VL 102 IS 3 BP 493 EP 502 DI 10.1016/S0306-4522(00)00518-2 UT WOS:000166890100001 PM 11226688 ER PT J AU Wasserman, GA Liu, XH Pine, DS Graziano, JH AF Wasserman, GA Liu, XH Pine, DS Graziano, JH TI Contribution of maternal smoking during pregnancy and lead exposure to early child behavior problems SO NEUROTOXICOLOGY AND TERATOLOGY AB Maternal smoking during pregnancy elevates risk for later child behavior problems. Because prior studies considered only Western settings, where smoking cooccurs with social disadvantage, we examined this association in Yugoslavia, a different cultural setting. Mothers enrolled in pregnancy as the low-exposure group in a prospective study of lead exposure were interviewed about health, including smoking history. A total of 199 children were assessed on the Child Behavior Checklist (CBCL) at ages 4, 4 1/2, and 5 years. Average cumulative blood lead (BPb) was determined from serial samples taken biannually since delivery. Longitudinal analyses were derived from 191 children with available data on behavior and covariates. Smoking was unrelated to social adversity. Controlling for age, gender, birthweight, ethnicity, maternal education, and Home Observation for Measurement of the Environment (HOME) Acceptance, smoking was associated with worse scores on almost all subscales; BPb concentration was related to small increases in the Delinquency subscale. Daughters of smokers received significantly higher scores on Somatic Complaints compared to daughters of nonsmokers, consistent with other work relating biological factors and internalizing problems in young girls. Because the present smoking/child behavior associations persist after control for individual and social factors also related to behavior problems, possible biological mediators are considered. (C) 2001 Elsevier Science Inc. All rights reserved. SN 0892-0362 PD JAN-FEB PY 2001 VL 23 IS 1 BP 13 EP 21 DI 10.1016/S0892-0362(00)00116-1 UT WOS:000167811700002 PM 11274872 ER PT S AU Bielekova, B Martin, R AF Bielekova, B Martin, R BE Pozzilli, C Pozzilli, P Kapp, JF TI Specific immunotherapy of multiple sclerosis by altered peptide ligands - Risk or benefit? SO NEW CONCEPTS IN PATHOLOGY AND TREATMENT OF AUTOIMMUNE DISORDERS SE ERNST SCHERING RESEARCH FOUNDATION WORKSHOP CT Workshop on New Concepts in Pathology and Treatment of Autoimmune Disorders CY DEC 02-03, 1999 CL BERLIN, GERMANY SN 0947-6075 BN 3-540-41479-7 PY 2001 IS S7 BP 69 EP 87 UT WOS:000176885700005 ER PT S AU Proia, RL AF Proia, RL BE Endo, M Harata, S Saito, Y Munakata, A Sasaki, M Tsuchida, S TI The G(M2) gangliosidoses: pathophysiology to therapy SO NEW DEVELOPMENTS IN GLYCOMEDICINE SE INTERNATIONAL CONGRESS SERIES CT 4th Hirosaki International Forum of Medical Science CY OCT 17, 2000 CL KIROSAKI, JAPAN AB A family of extremely severe diseases, known as the glycosphingolipidoses, is caused by inherited defects in the lysosomal degradation pathway for glycosphingolipids (GSLs). In most of these disorders, GSLs accumulate in lysosomes, causing neurodegeneration and a shortened life span. No effective treatment currently exists for most of these diseases, and their mechanisms of pathogenesis are only beginning to be understood. This review will discuss new findings for a representative group of these disorders - the G(M2) gangliosidoses - including the development of a new approach for treatment that targets the synthesis pathway of GSLs to retard their cellular accumulation. Published by Elsevier Science B.V. SN 0531-5131 BN 0-444-50603-9 PY 2001 VL 1223 BP 17 EP 22 DI 10.1016/S0531-5131(01)00431-9 UT WOS:000173897900002 ER PT S AU Wada, R Tifft, CJ Proia, RL AF Wada, R Tifft, CJ Proia, RL BE Endo, M Harata, S Saito, Y Munakata, A Sasaki, M Tsuchida, S TI Microglial activation and inflammatory reaction preceding neurodegeneration in Sandhoff disease SO NEW DEVELOPMENTS IN GLYCOMEDICINE SE INTERNATIONAL CONGRESS SERIES CT 4th Hirosaki International Forum of Medical Science CY OCT 17, 2000 CL KIROSAKI, JAPAN AB Sandhoff disease is a lysosomal storage disorder characterized by the absence of P-hexosaminidase and storage of G(M2) ganglioside and related glycolipids in the central nervous system. The glycolipid storage causes severe neuro degeneration and progressive decline of neurological function that leads to death at an early stage of life. The pathogenetic mechanisms of neurodegeneration in this disease are poorly understood. In Sandhoff disease model, mice apoptotic cell death was prominent in the brainstem and spinal cord during the rapid decline of neurological function. By global gene expression and histological analyses, we identified an inflammatory reaction mediated by microglia/ macrophages that precedes neuronal apoptosis. When the inflammatory response was suppressed by bone marrow transplantation, neuronal apoptosis was suppressed. We suggest that the inflammatory reaction may have a direct role in the neurodegenerative process. Thus, this lysosomal storage disease may have similarities to other neurodegenerative disorders, such as Alzheimer's, HIV dementia and prion diseases, where inflammatory processes are believed to participate directly in neuronal cell death. (C) 2001 Elsevier Science B.V. All rights reserved. SN 0531-5131 BN 0-444-50603-9 PY 2001 VL 1223 BP 23 EP 27 DI 10.1016/S0531-5131(01)00437-X UT WOS:000173897900003 ER PT S AU Skarlatos, SL Dzau, V AF Skarlatos, SL Dzau, V BE Skarlotos, SI Velletri, P Morris, M Davies, P TI New vistas in therapeutics from drug design to gene therapy - Introduction SO NEW VISTAS IN THERAPEUTICS, FROM DRUG DESIGN TO GENE THERAPY: DRUG-RESISTANT TUBERCULOSIS, FROM MOLECULES TO MACRO-ECONOMICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT Conference on New Vistas in Therapeutics: From Drug Design to Gene Therapy CY JUN 03-04, 2000 CL BOSTON, MASSACHUSETTS SP Dupont Pharmaceut Co, ISIS Pharmaceut, Astrazeneca, Vertex Pharmaceut Incorp SN 0077-8923 BN 1-57331-335-1 PY 2001 VL 953 BP 1 EP 2 DI 10.1111/j.1749-6632.2001.tb11355.x UT WOS:000173960900001 ER PT S AU Cragg, GM Newman, DJ AF Cragg, GM Newman, DJ BE Skarlotos, SI Velletri, P Morris, M Davies, P TI Medicinals for the millennia - The historical record SO NEW VISTAS IN THERAPEUTICS, FROM DRUG DESIGN TO GENE THERAPY: DRUG-RESISTANT TUBERCULOSIS, FROM MOLECULES TO MACRO-ECONOMICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT Conference on New Vistas in Therapeutics: From Drug Design to Gene Therapy CY JUN 03-04, 2000 CL BOSTON, MASSACHUSETTS SP Dupont Pharmaceut Co, ISIS Pharmaceut, Astrazeneca, Vertex Pharmaceut Incorp AB Nature has been a source of medicinal agents for thousands of years, and an impressive number of modern drugs have been isolated from natural sources, many based on their use in traditional medicine. The use of herbal drugs is once more escalating in the form of complementary and alternative medicine. The past century, however, has seen an increasing role played by microorganisms in the production of the antibiotics and other drugs for the treatment of some serious diseases. With less than 1% of the microbial world currently known, advances in procedures for microbial cultivation and the extraction of nucleic acids from environmental samples from soil and marine habitats, and from symbiotic and endophytic microbes associated with terrestrial and marine macro-organisms, will provide access to a vast untapped reservoir of genetic and metabolic diversity. By use of combinatorial chemical and biosynthetic technology, novel natural product leads will be optimized on the basis of their biological activities to yield effective chemotherapeutic and other bioactive agents. SN 0077-8923 BN 1-57331-335-1 PY 2001 VL 953 BP 3 EP 25 DI 10.1111/j.1749-6632.2001.tb11356.x UT WOS:000173960900002 PM 11795420 ER PT S AU Gorbalenya, AE AF Gorbalenya, AE BE Lavi, E Weiss, SR Hingley, ST TI Big nidovirus genome - When count and order of domains matter SO NIDOVIRUSES (CORONAVIRUSES AND ARTERIVIRUSES) SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY CT 8th International Symposium on Nidoviruses CY MAY 20-25, 2000 CL PHILADELPHIA, PENNSYLVANIA SP Univ Pennsylvania, Dept Microbiol, Univ Pennsylvania, Dept Pathol, Natl Multiple Sclerosis Soc, Centocor, Elanco Anim Hlth, Sorvall RI Gorbalenya, Alexander/J-4818-2012 OI Gorbalenya, Alexander/0000-0002-4967-7341 SN 0065-2598 BN 0-306-46634-1 PY 2001 VL 494 BP 1 EP 17 UT WOS:000173543300001 PM 11774451 ER PT J AU Bax, A Kontaxis, G Tjandra, N AF Bax, A Kontaxis, G Tjandra, N TI Dipolar couplings in macromolecular structure determination SO NUCLEAR MAGNETIC RESONANCE OF BIOLOGICAL MACROMOLECULES, PT B SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 339 BP 127 EP 174 PN B UT WOS:000170035400008 PM 11462810 ER PT J AU Qin, J Vinogradova, O Gronenborn, AM AF Qin, J Vinogradova, O Gronenborn, AM TI Protein-protein interactions probed by nuclear magnetic resonance spectroscopy SO NUCLEAR MAGNETIC RESONANCE OF BIOLOGICAL MACROMOLECULES, PT B SE METHODS IN ENZYMOLOGY OI Vinogradova, Olga/0000-0001-5101-7361 SN 0076-6879 PY 2001 VL 339 BP 377 EP 389 PN B UT WOS:000170035400018 PM 11462822 ER PT J AU Tycko, R AF Tycko, R TI Solid-state nuclear magnetic resonance techniques for structural studies of amyloid fibrils SO NUCLEAR MAGNETIC RESONANCE OF BIOLOGICAL MACROMOLECULES, PT B SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 339 BP 390 EP 413 PN B UT WOS:000170035400019 PM 11462823 ER PT J AU Baxevanis, AD AF Baxevanis, AD TI The Molecular Biology Database Collection: an updated compilation of biological database resources SO NUCLEIC ACIDS RESEARCH AB The Molecular Biology Database Collection is an online resource listing key databases of value to the biological community. This Collection is intended to bring fellow scientists' attention to high-quality databases that are available throughout the world, rather than just be a lengthy listing of all available databases. As such, this up-to-date listing is intended to serve as the initial point from which to find specialized databases that may be of use in biological research. The databases included in this Collection provide new value to the underlying data by virtue of curation, new data connections or other innovative approaches. Short, searchable summaries of each of the databases included in the Collection are available through the Nucleic Acids Research Web site, at http:/www.nar.oupjournals.org. SN 0305-1048 PD JAN 1 PY 2001 VL 29 IS 1 BP 1 EP 10 DI 10.1093/nar/29.1.1 UT WOS:000166360300001 PM 11125037 ER PT J AU Wheeler, DL Church, DM Lash, AE Leipe, DD Madden, TL Pontius, JU Schuler, GD Schriml, LM Tatusova, TA Wagner, L Rapp, BA AF Wheeler, DL Church, DM Lash, AE Leipe, DD Madden, TL Pontius, JU Schuler, GD Schriml, LM Tatusova, TA Wagner, L Rapp, BA TI Database resources of the National Center for Biotechnology Information SO NUCLEIC ACIDS RESEARCH AB In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources that operate on the data in GenBank and a variety of other biological data made through NCBI's Web site. NCBI data retrieval resources include Entrez, PubMed, LocusLink and the Taxonomy Browser. Data analysis resources include BLAST, Electronic PCR, OrfFinder, RefSeq, UniGene, HomolGene, Database of Single Nucleotide Polymorphisms (dbSNP), Human Genome Sequencing, Human MapViewer, GeneMap'99, Human-Mouse Homology Map, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes, Clusters of Ortholgous Groups (COGs) database, Retroviral Genotyping Tools, Cancer Genome Anatomy Project (CGAP), SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB) and the Conserved Domain Database (CDD). Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at: http:/www.ncbi.nlm.nih.gov. OI Lash, Alex/0000-0003-3787-1590; Schriml, Lynn/0000-0001-8910-9851 SN 0305-1048 PD JAN 1 PY 2001 VL 29 IS 1 BP 11 EP 16 DI 10.1093/nar/29.1.11 UT WOS:000166360300002 PM 11125038 ER PT J AU Tatusov, RL Natale, DA Garkavtsev, IV Tatusova, TA Shankavaram, UT Rao, BS Kiryutin, B Galperin, MY Fedorova, ND Koonin, EV AF Tatusov, RL Natale, DA Garkavtsev, IV Tatusova, TA Shankavaram, UT Rao, BS Kiryutin, B Galperin, MY Fedorova, ND Koonin, EV TI The COG database: new developments in phylogenetic classification of proteins from complete genomes SO NUCLEIC ACIDS RESEARCH AB The database of Clusters of Orthologous Groups of proteins (COGs), which represents an attempt on a phylogenetic classification of the proteins encoded in complete genomes, currently consists of 2791 COGs including 45 350 proteins from 30 genomes of bacteria, archaea and the yeast Saccharomyces cerevisiae (http://www.ncbi.nlm.nih,gov/COG). In addition, a supplement to the COGs is available, in which proteins encoded in the genomes of two multicellular eukaryotes, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, and shared with bacteria and/or archaea were included. The new features added to the COG database include information pages with structural and functional details on each COG and literature references, improvements of the COGNITOR program that is used to fit new proteins into the COGs, and classification of genomes and COGs constructed by using principal component analysis. RI Galperin, Michael/B-5859-2013; Abrams, Natalie/F-4845-2011 OI Galperin, Michael/0000-0002-2265-5572; Abrams, Natalie/0000-0001-9698-2819 SN 0305-1048 EI 1362-4962 PD JAN 1 PY 2001 VL 29 IS 1 BP 22 EP 28 DI 10.1093/nar/29.1.22 UT WOS:000166360300004 PM 11125040 ER PT J AU Stein, L Sternberg, P Durbin, R Thierry-Mieg, J Spieth, J AF Stein, L Sternberg, P Durbin, R Thierry-Mieg, J Spieth, J TI WormBase: network access to the genome and biology of Caenorhabditis elegans SO NUCLEIC ACIDS RESEARCH AB WormBase (hffp://www.wormbase.org) is a web-based resource for the Caenorhabdifis elegans genome and its biology. it builds upon the existing ACeDB database of the C.elegans genome by providing data curation services, a significantly expanded range of subject areas and a user-friendly front end. RI THIERRY-MIEG, Jean/F-1975-2017 OI THIERRY-MIEG, Jean/0000-0002-0396-6789 SN 0305-1048 EI 1362-4962 PD JAN 1 PY 2001 VL 29 IS 1 BP 82 EP 86 DI 10.1093/nar/29.1.82 UT WOS:000166360300020 PM 11125056 ER PT J AU Pruitt, KD Maglott, DR AF Pruitt, KD Maglott, DR TI RefSeq and LocusLink: NCBI gene-centered resources SO NUCLEIC ACIDS RESEARCH AB Thousands of genes have been painstakingly identified and characterized a few genes at a time. Many thousands more are being predicted by large scale cDNA and genomic sequencing projects, with levels of evidence ranging from supporting mRNA sequence and comparative genomics to computing ab initio models. This, coupled with the burgeoning scientific literature, makes it critical to have a comprehensive directory for genes and reference sequences for key genomes. The NCBI provides two resources, LocusLink and RefSeq, to meet these needs. LocusLink organizes information around genes to generate a central hub for accessing gene-specific information for fruit fly, human, mouse, rat and zebrafish, RefSeq provides reference sequence standards for genomes, transcripts and proteins; human, mouse and rat mRNA RefSeqs, and their corresponding proteins, are discussed here. Together, RefSeq and LocusLink provide a non-redundant view of genes and other loci to support research on genes and gene families, variation, gene expression and genome annotation, Additional information about LocusLink and RefSeq is available at http ://www, ncbi,nIm,gov/LocusLink/. SN 0305-1048 PD JAN 1 PY 2001 VL 29 IS 1 BP 137 EP 140 DI 10.1093/nar/29.1.137 UT WOS:000166360300035 PM 11125071 ER PT J AU Morley, M Arcaro, M Burdick, J Yonescu, R Reid, T Kirsch, IR Cheung, VG AF Morley, M Arcaro, M Burdick, J Yonescu, R Reid, T Kirsch, IR Cheung, VG TI GenMapDB: a database of mapped human BAC clones SO NUCLEIC ACIDS RESEARCH AB GenMapDB (http:Ngenomics.med.upem.edu/genmal;db) is a repository of human bacterial artificial chromosome (BAC) clones mapped by our laboratory to sequence-tagged site markers. Currently, GenMapDB contains over 3000 mapped clones that span 19 chromosomes, chromosomes 2, 4, 5, 9-22, X and Y. This database provides positional information about human BAC clones from the RPCI-11 human male BAC library. It also contains restriction fragment analysis data and end sequences of the clones. GenMapDB is freely available to the public. The main purpose of GenMapDB is to organize the mapping data and to allow the research community to search for mapped BAC clones that can be used in gene mapping studies and chromosomal mutation analysis projects. SN 0305-1048 PD JAN 1 PY 2001 VL 29 IS 1 BP 144 EP 147 DI 10.1093/nar/29.1.144 UT WOS:000166360300037 PM 11125073 ER PT J AU Garavelli, JS Hou, ZL Pattabiraman, N Stephens, RM AF Garavelli, JS Hou, ZL Pattabiraman, N Stephens, RM TI The RESID Database of protein structure modifications and the NRL-3D Sequence-Structure Database SO NUCLEIC ACIDS RESEARCH AB The RESID Database is a comprehensive collection of annotations and structures for protein post-translational modifications including N-terminal, C-terminal and peptide chain cross-link modifications. The RESID Database includes systematic and frequently observed alternate names, Chemical Abstracts Service registry numbers, atomic formula and weights, enzyme activities, taxonomic range, keywords, literature citations with database crossreferences, structural diagrams and molecular models. The NRL-3D Sequence-Structure Database is derived from the three-dimensional structure of proteins deposited with the Research Collaboratory for Structural Bioinformatics Protein Data Bank. The NRL-3D Database includes standardized and frequently observed alternate names, sources, keywords, literature citations, experimental conditions and searchable sequences from model coordinates, These databases are freely accessible through the National Cancer Institute-Frederick Advanced Biomedical Computing Center at these web sites: http://www.ncifcrf.gov/RESID, http://www.ncifcrf.gov/ NRL-3D; or at these National Biomedical Research Foundation Protein Information Resource web sites: http://pir.georgetown.edu/pirwww/dbinfo/resid.html,http://pir.georgetown.edu/pirwww/dbinfo/nrl3d.html. SN 0305-1048 PD JAN 1 PY 2001 VL 29 IS 1 BP 199 EP 201 DI 10.1093/nar/29.1.199 UT WOS:000166360300054 PM 11125090 ER PT J AU Banerjee-Basu, S Sink, DW Baxevanis, AD AF Banerjee-Basu, S Sink, DW Baxevanis, AD TI The Homeodomain Resource: sequences, structures, DNA binding sites and genomic information SO NUCLEIC ACIDS RESEARCH AB The Homeodomain Resource is an annotated collection of non-redundant protein sequences, three-dimensional structures and genomic information for the homeodomain protein family. Release 3.0 contains 795 full-length homeodomain-containing sequences, 32 experimental ly-derived structures and 143 homeobox loci implicated in human genetic disorders. Entries are fully hyperlinked to facilitate easy retrieval of the original records from source databases. A simple search engine with a graphical user interface is provided to query the component databases and assemble customized data sets. A new feature for this release is the addition of DNA recognition sites for all human homeodomain proteins described in the literature. The Homeodomain Resource is freely available through the World Wide Web at http:// genome.nhgri.nih.gov/homeodomain. SN 0305-1048 PD JAN 1 PY 2001 VL 29 IS 1 BP 291 EP 293 DI 10.1093/nar/29.1.291 UT WOS:000166360300080 PM 11125116 ER PT J AU Sherry, ST Ward, MH Kholodov, M Baker, J Phan, L Smigielski, EM Sirotkin, K AF Sherry, ST Ward, MH Kholodov, M Baker, J Phan, L Smigielski, EM Sirotkin, K TI dbSNP: the NCBI database of genetic variation SO NUCLEIC ACIDS RESEARCH AB In response to a need for a general catalog of genome variation to address the large-scale sampling designs required by association studies, gene mapping and evolutionary biology, the National Center for Biotechnology information (NCBI) has established the dbSNP database [S.T.Sherry, M.Ward and K,Sirotkin (1999) Genome Res., 9, 677-679]. Submissions to dbSNP will be integrated with other sources of information at NCBI such as GenBank, PubMed, LocusLink and the Human Genome Project data. The complete contents of dbSNP are available to the public at website: http://www.ncbi.nlm.nih.gov/SNP. The complete contents of dbSNP can also be downloaded in multiple formats via anonymous FTP at ftp:// ncbi.nlm.nih.gov/snp/. SN 0305-1048 PD JAN 1 PY 2001 VL 29 IS 1 BP 308 EP 311 DI 10.1093/nar/29.1.308 UT WOS:000166360300086 PM 11125122 ER PT J AU Jacobson, KA Ravi, RG Nandanan, E Kim, HS Moro, S Kim, YC Lee, K Barak, D Marquez, VE Ji, XD AF Jacobson, KA Ravi, RG Nandanan, E Kim, HS Moro, S Kim, YC Lee, K Barak, D Marquez, VE Ji, XD TI Ribose modified nucleosides and nucleotides as ligands for purine receptors SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS CT XIVth International Roundtable on Nucleosides, Nucleotides and their Biological Applications CY SEP 10-14, 2000 CL SAN FRANCISCO, CALIFORNIA AB Molecular modeling of receptors for adenosine and nucleotide (P2) receptors with docked ligand, based on mutagenesis, was carried out. Adenosine 3',5'-bisphosphate derivatives act as selective P2Y(1) antagonists/partial agonists. The ribose moiety was replaced with carbocyclics, smaller and larger rings, conformationally constrained rings, and acyclics, producing compounds that retained receptor affinity. Conformational constraints were built into the ribose rings of nucleoside and nucleotide ligands using the methanocarba approach, i.e. fused cyclopropane and cyclopentane rings in place of ribose, suggesting a preference for the Northern (N) conformation among ligands for P2Y(1) and A(1) and A(3)ARs. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009; Erathodiyil, Nandanan/A-8333-2010 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493; SN 1525-7770 PY 2001 VL 20 IS 4-7 BP 333 EP 341 DI 10.1081/NCN-100002305 UT WOS:000170690500008 PM 11563046 ER PT J AU Marquez, VE Wang, PY Nicklaus, MC Maier, M Manoharan, M Christman, JK Banavali, NK Mackerell, AD AF Marquez, VE Wang, PY Nicklaus, MC Maier, M Manoharan, M Christman, JK Banavali, NK Mackerell, AD TI Inhibition of (cytosine C5)-methyltransferase by oligonucleotides containing flexible (cyclopentane) and conformationally constrained (bicyclo[3.1.0]hexane) abasic sites SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS CT XIVth International Roundtable on Nucleosides, Nucleotides and their Biological Applications CY SEP 10-14, 2000 CL SAN FRANCISCO, CALIFORNIA AB Pseudorotationally locked sugar analogues based on bicyclo[3.1.0]-hexane templates were placed in DNA duplexes as abasic target sites in the M.HhaI recognition sequence. The binding affinity of the enzyme increases when the abasic site is constrained to the South conformation and decreases when it is constrained to the North conformation. A structural understanding of these differences is provided. RI Nicklaus, Marc/N-4183-2014; OI Banavali, Nilesh/0000-0003-2206-7049; MacKerell, Alex/0000-0001-8287-6804 SN 1525-7770 PY 2001 VL 20 IS 4-7 BP 451 EP 459 DI 10.1081/NCN-100002319 UT WOS:000170690500022 PM 11563060 ER PT J AU Milner, JA McDonald, SS Anderson, DE Greenwald, P AF Milner, JA McDonald, SS Anderson, DE Greenwald, P TI Molecular targets for nutrients involved with cancer prevention SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL AB Dietary nutrients can influence cancer risk by inhibiting or enhancing carcinogenesis through diverse mechanisms of action. The identification and elucidation of their sites of action have been a focus of nutrition and cancer research for more than four decades. Transforming nutrition and cancer research from a predominantly observational to a molecular approach offers exciting opportunities for truly identifying those who will and will not benefit from dietary intervention strategies. The emerging field of nutritional genomics, defined here as the study of any genetic or epigenetic interaction with a nutrient, will be key to this evolution. Unraveling which genetic upregulation or downregulation leads to subsequent phenotype changes will not be easy. There is evidence that genetic polymorphisms can influence the dynamics between nutrients and molecular targets and, thus, contribute to variation in response among individuals. Because many molecular targets will likely be identified, it may be necessary to credential nutrients, that is, to determine which specific nutrient-related genetic and epigenetic changes bring about phenotypic changes, to establish which interactions are the most important and under what circumstances. Vitamin D, calcium, folate, selenium, genistein, and resveratrol are highlighted, because they represent specific classes of nutrients and illustrate the need to credential various nutrients to understand their physiological significance in cancer prevention. As the science of nutrition unfolds, a clearer understanding will emerge about how nutrients can modulate cancer risk through molecular interactions and how foods might be changed by agronomic approaches and/or biotechnology. Undeniably, embracing new genomic technologies offers exciting opportunities for advances in the broad area of nutrition, especially those related to cancer prevention. SN 0163-5581 PY 2001 VL 41 IS 1-2 BP 1 EP 16 DI 10.1207/S15327914NC41-1&2_1 UT WOS:000176358900001 PM 12094610 ER PT J AU Cerhan, JR Putnam, SD Bianchi, GD Parker, AS Lynch, CF Cantor, KP AF Cerhan, JR Putnam, SD Bianchi, GD Parker, AS Lynch, CF Cantor, KP TI Tea consumption and risk of cancer of the colon and rectum SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL AB The association between tea consumption and risk of colon and rectal cancers was investigated in a population-based case-control study conducted in Iowa (United States). Colon (n = 685) and rectal (n = 655) cancer cases age 40-85 yr were identified through the Iowa Surveillance, Epidemiology, and End Results (SEER) Cancer Registry (86% response rate); controls (h = 2,434) were frequency matched by sex and 5-yr age group (80% response rate). The usual adult consumption of tea (hot and iced), along with other information including dietary data, was self-reported using a mailed questionnaire. Total tea consumption (cups/day) was categorized as none (reference category), low (<3.1), medium (3.1-5.0), and high (>5.0), with cut points for tea consumers based on the 75th and 90th percentiles of use among controls. Unconditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals. There was no association between total tea consumption and colon cancer (ORs = 1.0, 1.1, 1.3, and 0.7) or rectal cancer (ORs = 1.0, 0.9, 1.4, and 1.0) after adjustment for age, sex, education, physical activity, smoking history, and intake of coffee, fiber, and fruits and vegetables. Results were similar when hot tea and iced tea were evaluated individually. Further adjustment for other colorectal cancer risk factors did not alter these results. There was no association with proximal or distal colon cancer. There was also no interaction between tea consumption and any of the dietary variables or total fluid on risk of colon or rectal cancer, with the exception of a suggestive positive association between an increasing frequency of tea consumption and colon cancer risk among current smokers (multivariate ORs = 1.0, 1.4, 2.0, and 1.8; P for trend = 0.1), but not among never smokers (multivariate ORs = 1. 0, 1. 0, 1.1, and 0.4; P for trend = 0.3). These data do not support an overall association, either positive or negative, between tea consumption and risk of colon or rectal cancer in this Midwestern US population. SN 0163-5581 PY 2001 VL 41 IS 1-2 BP 33 EP 40 DI 10.1207/S15327914NC41-1&2_4 UT WOS:000176358900004 PM 12094626 ER PT J AU Kim, YS Milner, J AF Kim, YS Milner, J TI Molecular targets for selenium in cancer prevention SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL AB Mounting evidence reveals that selenium is a dietary constituent with anticarcinogenic and antitumorigenic properties. Various forms of selenium appear to be effective in bringing about these effects, although preclinical studies suggest that differences may arise as the quantity provided is reduced. The literature also documents the greater sensitivity of neoplastic cells to selenium than their nonneoplastic counterparts. Unfortunately, the minimal amount needed to bring about a positive effect in humans remains elusive. If there is a positive response to exaggerated intakes, it will likely be dependent on many factors, including the consumption of other dietary constituents, as well as variation in a host of genetic pathways involved with cancer. Although the biological basis of the reduction in cancer risk ascribed to selenium remains to be established, its consistency in retarding various experimentally induced tumors and suppressing the growth of various types of neoplasms in vitro and in vivo suggests that several mechanisms are involved. Depressed carcinogen bioactivation, reduced cell proliferation, and increased apoptosis raise the possibility that selenium works at a number of specific molecular targets involved with the cancer process. This review will focus on molecular targets involved with cell proliferation and apoptosis as possible mechanisms by which selenium might alter the cancer process. SN 0163-5581 PY 2001 VL 40 IS 1 BP 50 EP 54 DI 10.1207/S15327914NC401_10 UT WOS:000172947100010 PM 11799923 ER PT S AU Ciolino, HP Yeh, GC AF Ciolino, HP Yeh, GC GP AICR TI The effects of resveratrol on CYP1A1 expression and aryl hydrocarbon receptor function in vitro SO NUTRITION AND CANCER PREVENTION: NEW INSIGHTS INTO THE ROLE OF PHYTOCHEMICALS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY CT 9th Annual Research Conference of the American-Institute-for-Cancer-Research CY SEP 02-03, 1999 CL WASHINGTON, D.C. SP Amer Inst Canc Res SN 0065-2598 BN 0-306-46545-0 PY 2001 VL 492 BP 183 EP 193 UT WOS:000171156300014 PM 11480665 ER PT S AU Greenwald, P McDonald, SS AF Greenwald, P McDonald, SS GP AICR TI The beta-carotene story SO NUTRITION AND CANCER PREVENTION: NEW INSIGHTS INTO THE ROLE OF PHYTOCHEMICALS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY CT 9th Annual Research Conference of the American-Institute-for-Cancer-Research CY SEP 02-03, 1999 CL WASHINGTON, D.C. SP Amer Inst Canc Res SN 0065-2598 BN 0-306-46545-0 PY 2001 VL 492 BP 219 EP 231 UT WOS:000171156300017 PM 11480669 ER PT J AU Weyer, C Wolford, JK Foley, JE Hanson, RL Tataranni, PA Bogardus, C Pratley, RE AF Weyer, C Wolford, JK Foley, JE Hanson, RL Tataranni, PA Bogardus, C Pratley, RE TI Subcutaneous abdominal adipocyte size, a predictor of type 2 diabetes, is linked to chromosome 1q21-q23 and is associated with a common polymorphism in LMNA in Pima Indians SO OBESITY RESEARCH SN 1071-7323 PD JAN PY 2001 VL 9 IS 1 MA HT05 BP 69 EP 69 UT WOS:000168413100014 ER PT J AU Murgo, AJ AF Murgo, AJ TI Clinical trials of arsenic trioxide in hematologic and slid tumors: Overview of the national cancer institute cooperative research and development studies SO ONCOLOGIST CT Scientific Roundtable on Arsenic Trioxide: Scientific and Clinical Progress CY JUL 19, 2000 CL NEW YORK, NEW YORK AB Arsenic trioxide inhibits growth and promotes apoptosis in many different cancer cell lines. The National Cancer Institute is working cooperatively with research centers across the U.S. to evaluate its clinical activity in hematologic malignancies, such as acute promyelocytic leukemia, acute myeloid leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, myelodysplastic syndrome, and multiple myeloma. It is also supporting research in solid tumors, such as advanced hormone-refractory prostate cancer and renal cell cancer and in cervical cancer and refractory transitional cell carcinoma of the bladder. The safety and pharmacokinetics of arsenic trioxide are also being evaluated in pediatric patients with refractory leukemia and lymphoma. The results of these ongoing studies should provide important insights into the clinical utility of arsenic trioxide in these diseases. SN 1083-7159 PY 2001 VL 6 SU 2 BP 22 EP 28 DI 10.1634/theoncologist.6-suppl_2-22 UT WOS:000175117200005 PM 11331437 ER PT J AU Fojo, T AF Fojo, T TI Novel_Target.com SO ONCOLOGIST SN 1083-7159 PY 2001 VL 6 IS 4 BP 313 EP 314 DI 10.1634/theoncologist.6-4-313 UT WOS:000174250300003 PM 11524547 ER PT J AU Curt, GA AF Curt, GA TI Terrorism and cancer SO ONCOLOGIST SN 1083-7159 PY 2001 VL 6 IS 5 BP 401 EP 401 DI 10.1634/theoncologist.6-5-401 UT WOS:000174321200002 PM 11675516 ER PT J AU Elsayed, YA Sausville, EA AF Elsayed, YA Sausville, EA TI Selected novel anticancer treatments targeting cell signaling proteins SO ONCOLOGIST AB Empirical approaches to discovery of anticancer drugs and cancer treatment have made limited progress in the cure of cancer in the last several decades. Recent advances in technology and expanded knowledge of the molecular basis of tumorigenesis and metastasis have provided unique opportunities to design novel compounds that rationally target the abnormal molecular and biochemical signals leading to cancer. Several such novel agents have completed advanced stages in clinical development. The excellent clinical results achieved by some of these compounds are creating new paradigms in management of patients with neoplastic diseases. Clinical development of these agents also raises challenges to the traditional methods of drug evaluation and measurement of efficacy. SN 1083-7159 PY 2001 VL 6 IS 6 BP 517 EP 537 DI 10.1634/theoncologist.6-6-517 UT WOS:000174321300007 PM 11743214 ER PT J AU Shin, SW Breathnach, OS Linnoila, RI Williams, J Gillespie, JW Kelly, MJ Johnson, BE AF Shin, SW Breathnach, OS Linnoila, RI Williams, J Gillespie, JW Kelly, MJ Johnson, BE TI Genetic changes in contralateral bronchioloalveolar carcinomas of the lung SO ONCOLOGY AB Objective: The pattern of metastases and recurrence of bronchioloalveolar carcinoma (BAC) differs from adenocarcinoma of the lung, occurring more frequently within the lung without extrapulmonary involvement. Analyses of genetic differences of contralateral BACs may help to explain these clinical differences. Methods: We compared paired tumors from 5 patients with contralateral metachronous BACs for loss of heterozygosity (LOH) on 6 chromosomal arms (2q, 3p, 5q, 9p, 13q and 17p) and mutational analysis of p53 and K-ras. Results: Two patients, patients 1 and 2, had discordant patterns of LOH on 2 and 3 of the chromosome arms, respectively. in addition, patient 2 had a detectable K-ras mutation in his initial tumor but not in his second. These results suggest that in patients 1 and 2, the contralateral tumors were clonally unrelated. Patient 3 had no mutations in the K-ras or p53 gene and no LOH on any of the 5 informative chromosome arms. Patient 4 had LOH of 9p and mutated K-ras in both the fi rst and the second tu mor, with a mutation in the p53 gene in the first but not in the second tumor. Patient 5 had LOH of 17p and the same p53 mutations in both the first and the second tumor, with a mutation of K-ras in the first tumor but not in the second. Conclusions: The preponderance of evidence suggests that in patients 3, 4 and 5, the paired tumors were clonally related. The different patterns of LOH and mutations in clinically similar contralateral metachronous BACs provide evidence of genetic heterogeneity in the tumors of this patient group. Copyright (C) 2001 S. Karger AG, Basel. OI Kelley, Michael/0000-0001-9523-6080 SN 0030-2414 PY 2001 VL 60 IS 1 BP 81 EP 87 DI 10.1159/000055301 UT WOS:000166275200013 PM 11150913 ER PT J AU Miglietta, L Marenghi, C Nizzo, R Foglia, G Ragni, N Boccardo, F AF Miglietta, L Marenghi, C Nizzo, R Foglia, G Ragni, N Boccardo, F TI Paclitaxel by 72-hour continuous infusion followed by bolus intravenous ifosfamide or epirubicin: Results of two phase I studies SO ONCOLOGY AB Study Purposes: To determine the maximum-tolerated dose (MTD) of paclitaxel administered by 72-hour continuous infusion followed by bolus intravenous ifosfamide on days 4 and 5 or epirubicin on day 4, every 21 days. To assess the toxicity and preliminary activity in patients with advanced refractory solid tumors. Patients and Methods: Sixteen patients with progressive disease after standard chemotherapy for advanced disease were treated with the combination paclitaxel-ifosfamide and 10 patients with the combination paclitaxel-epirubicin. Results: In the first phase I study the MTDs were: paclitaxel 135 mg/m(2) and ifosfamide 2.5 mg/m(2)/day; hematologic toxicity was the dose-limiting toxicity (DLT) during the fi rst cycle of therapy at dose level 4. Paclitaxel administered at 135 mg/m(2) and epirubicin 50 mg/m(2) were the MTDs in the second phase I study; grade 4 stomatitis was the DLT of this combination. Conclusions: Paclitaxel by 72-hour continuous infusion followed by bolus ifosfamide was a manageable regimen with an acceptable hematologic toxicity in the absence of neurotoxicity. Preliminary activity of this combination was encouraging in a group of patients with ovarian cancer. The optimal way to combine paclitaxel and epirubicin and the best schedule relative to such a long paclitaxel infusion time in this combination regimen remain to be determined. Copyright (C) 2001 S. Karger AG, Basel. RI Marenghi, Cristina/E-5377-2017 OI Marenghi, Cristina/0000-0002-6867-7646 SN 0030-2414 PY 2001 VL 60 IS 2 BP 116 EP 122 DI 10.1159/000055307 UT WOS:000167456700003 PM 11244325 ER PT J AU Ballestrero, A Rubagotti, A Stura, P Ferrando, F Amoroso, D Rinaldini, M Sismondi, P Genta, F Mesiti, M Brema, F Patrone, F Boccardo, F AF Ballestrero, A Rubagotti, A Stura, P Ferrando, F Amoroso, D Rinaldini, M Sismondi, P Genta, F Mesiti, M Brema, F Patrone, F Boccardo, F CA Grocta Italian Breast Canc Study G TI Adjuvant chemotherapy with high-dose cyclophosphamide, etoposide and cisplatin intensification without progenitor cell support in breast cancer patients with ten or more involved nodes: 5-year results of a pilot trial SO ONCOLOGY AB Objectives: The purpose of this study was to evaluate the clinical efficacy and tolerability of high-dose (HD) chemotherapy with growth factor support in primary breast cancer with extensive nodal involvement. Patients and Methods: Fifty-three patients with ten or more involved nodes were recruited and were given three cycles of standard-dose fluorouracil, epidoxorubicin and cyclophosphamide followed by one single course of high-dose CEP (cyclophosphamide, etoposide and cisplatin). No autologous progenitor support was used. Results: Five-year actuarial disease-free and overall survival were 40 and 60%, respectively. High-dose CEP required a median of 22 days of hospitalization and was associated with grade G3-G4 nausea and vomiting in two thirds of the cases. Hematological toxicity was comparable to that of high-dose therapies delivered with autologous progenitor support. No therapy-related mortality was observed. Conclusions: The efficacy of treatment was comparable to the best results of conventional therapy, with only a trend for improved survival. High-dose CEP was feasible with acceptable toxicity. Although this regimen does not require stem cell harvesting and storage, it requires clinical support comparable To autotransplantation procedures and side effects are not so manageable to recommend its use outside specialized units. Copyright (C) 2001 S. Karger AG, Basel. OI Sismondi, Piero/0000-0002-2505-5716 SN 0030-2414 PY 2001 VL 60 IS 3 BP 221 EP 227 DI 10.1159/000055322 UT WOS:000168334500005 PM 11340373 ER PT J AU Danforth, DN AF Danforth, DN TI Breast cancer during pregnancy - The Gwyn/Theriault article reviewed SO ONCOLOGY-NEW YORK SN 0890-9091 PD JAN PY 2001 VL 15 IS 1 BP 46 EP + UT WOS:000167229300011 ER PT J AU Kawakami, M Leland, P Kawakami, K Puri, RK AF Kawakami, M Leland, P Kawakami, K Puri, RK TI Mutation and functional analysis of IL-13 receptors in human malignant glioma cells SO ONCOLOGY RESEARCH AB We have previously demonstrated that human brain tumor cells, in particular glioblastoma multiforme (GBM), express abundant receptors for interleukin-13 on the cell surface. These receptors are composed of IL-13 receptor (IL-13R)alpha1, IL-13Ralpha2, and IL-4Ralpha chains. The significance of overexpression of H-13R on tumor cells is not known. Because expression of IL-13R on glioma cells is an unexpected phenomenon, we examined whether these receptors are polymorphic. Therefore, we analyzed cDNA for IL-13Ralpha1 and IL-13Ralpha2 chain genes by PCR-based single-strand conformation polymorphism and direct sequencing techniques for a possible polymorphism in 19 GBM, one normal human astrocyte, and two fibroblast cell lines. All analyzed samples except normal astrocytes overexpressed IL-13Ralpha2; however, none of these cell lines showed a mutation in cDNA for IL-13Ra2 chain. In contrast, all GBM samples, normal astrocytes, and fibroblasts expressed mRNA for IL-13Ralpha1 with apparent single nucleotide polymorphism in the transmembrane domain. To study the function of IL-13R on brain tumor cells, we investigated the regulation of adhesion molecules by IL-13 as assessed by flow cytometric analysis. A172 cell line expressed a low level of vascular cell adhesion molecule-1 (VCAM-1), while U251 and LA(1)-5g cell lines expressed intercellular adhesion molecule-1 (ICAM-1). On the other hand E-selectin was not expressed in any cell lines. Interestingly, IL-13 increased the expression level of VCAM-l in A172 cell line in a dose- and time-dependent manner. However, IL-13 did not modulate any other adhesion molecules. These results suggest that IL-13R on GBM cells are not rearranged but appear to be functional. SN 0965-0407 PY 2001 VL 12 IS 11-12 BP 459 EP 467 UT WOS:000174533800003 PM 11939409 ER PT S AU Simonsen, L AF Simonsen, L BE Osterhaus, ADM Cox, N Hampson, AW TI Influenza-related morbidity and mortality among children in developed and developing countries SO OPTIONS FOR THE CONTROL OF INFLUENZA IV SE INTERNATIONAL CONGRESS SERIES CT 4th World Congress on Options for the Control of Influenza CY SEP 23-28, 2000 CL HERSONISSOS, GREECE AB More than 20% of all childhood deaths are thought to be acute respiratory (ARI) deaths; most of these occur in developing countries. Bacterial pathogens are implied in 70-90% of pediatric ARI deaths, while 10-30% are attributed to respiratory syncytial viruses (RSV). This implies that influenza is not an important cause of severe pediatric ARI. Influenza A,B virus infections may nevertheless cause ARI deaths by triggering bacterial superinfections. The mechanism of triggering is still poorly understood, as well as the consequences in terms of disease burden. However, recent studies have shed additional light on the triggering mechanism and provided an example of an influenza-triggered outbreak of severe pediatric pneumococcal disease. Further, new studies have quantified the impact of influenza on pediatric hospitalizations in the US-and argued that they may be similar in magnitude to that of RSV. In the tropics, the year-round circulation of influenza viruses prohibits the use of traditional tools to observe and quantify the attributable burden as the increase in severe ARI outcomes during influenza periods. Also, several studies of pathogens isolated from ARI-hospitalized children suggest a minor role of influenza viruses. However, since influenza may trigger bacterial super infections it is likely that undiagnosed influenza infections cause a significant subset of ARI deaths in developing countries. The void of data demonstrating the impact on ARI hospitalizations and deaths in the tropics has put influenza viruses at a disadvantage in terms of being recognized as serious pathogens. With the availability of new mucosal live-attenuated influenza vaccine formulations, it may be prudent to re-examine this issue for children living in tropical developing countries. Vaccine probe studies are needed to assess the true influenza-related disease burden. (C) 2001 Elsevier Science B.V. All rights reserved. OI Simonsen, Lone/0000-0003-1535-8526 SN 0531-5131 BN 0-444-50575-X PY 2001 VL 1219 BP 13 EP 19 DI 10.1016/S0531-5131(01)00322-3 UT WOS:000173897700003 ER PT J AU Zavras, AI Douglass, CW Joshipura, K Wu, T Laskaris, G Petridou, E Dokianakis, G Segas, J Lefantzis, D Nomikos, P Wang, YF Diehl, SR AF Zavras, AI Douglass, CW Joshipura, K Wu, T Laskaris, G Petridou, E Dokianakis, G Segas, J Lefantzis, D Nomikos, P Wang, YF Diehl, SR TI Smoking and alcohol in the etiology of oral cancer: gender-specific risk profiles in the south of Greece SO ORAL ONCOLOGY AB Oral and pharyngeal cancer (OC) mortality is very low in Greece, especially among men, compared to other European countries. We conducted a case-control study of OC in Athens, and obtained information on tobacco, alcohol use and other potential risk factors and confounding variables for 110 incident cases and 115 hospital-based controls. We used multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Tobacco smoking (packyears, P-trend = 0.01) and alcohol use (drinks/week, P-trend = 0.07) were independent risk factors, with a multiplicative effect for combined exposures (OR, 8.3; 95% CI, 2.4 - 29.1. for > 28 alcohol drinks/week and > 50 packyears of cigarette smoking). The type of alcoholic beverage also seemed important: drinking ouzo and tsipouro (liquors of high ethanol concentration) was associated with greater increased OC risk than drinking comparable amounts of wine, beer or dark spirits. While alcohol drinking is more common for male cases Versus controls, few men reported regularly consuming large quantities of ethanol associated with highest risk of OC in other studies. This may partially explain the low rates of male OC mortality in Greece. Among the 38% of our cases who were women, however, neither smoking nor alcohol drinking frequencies were significantly elevated compared to controls, and so the etiology of OC risk in females requires further investigation, (C) Published by Elsevier Science Ltd. SN 0964-1955 PD JAN PY 2001 VL 37 IS 1 BP 28 EP 35 DI 10.1016/S1368-8375(00)00060-9 UT WOS:000166562400003 PM 11120480 ER PT J AU Langlois, JA Mussolino, ME Visser, M Looker, AC Harris, T Madans, J AF Langlois, JA Mussolino, ME Visser, M Looker, AC Harris, T Madans, J TI Weight loss from maximum body weight among middle-aged and older white women and the risk of hip fracture: The NHANES I epidemiologic follow-up study SO OSTEOPOROSIS INTERNATIONAL AB Although weight loss increases bone loss and hip fracture risk in older women, little is known about the relation between weight loss in middle-aged women and subsequent hip fracture risk. The objective of this study was to determine the association between weight loss from reported maximum body weight in middle-aged and older women and the risk of hip fracture. Data were from a nationally representative sample of 2180 community-dwelling white women aged 50-74 years from the Epidemiologic Follow-up Study of the first National Health and Nutrition Examination Survey (NHEFS). In this prospective cohort study, incident hip fracture was ascertained during 22 years of follow-up. The adjusted relative risks associated with weight loss of 10% or more from maximum body weight were elevated for both middle-aged (RR 2.54; 95% CI 1. 10-5.86) and older women (RR 2.04, 95% Cl 1.37-3.04). For both ages combined, women in the lowest tertile of body mass index at maximum who lost 10% or more of weight had the highest risk of hip fracture (RR 2.37; 95% CI 1.32-4.27). Weight loss from maximum reported body weight in women aged 50-64 years and 65-74 years increased their risk of hip fracture, especially among those who were relatively thin. Weight loss of 10% or more from maximum weight among both middle-aged and older women is an important indicator of hip fracture risk. SN 0937-941X PY 2001 VL 12 IS 9 BP 763 EP 768 DI 10.1007/s001980170053 UT WOS:000171513200010 PM 11605743 ER PT J AU Cyrus, CB Bielamowicz, S Evans, FJ Ludlow, CL AF Cyrus, CB Bielamowicz, S Evans, FJ Ludlow, CL TI Adductor muscle activity abnormalities in abductor spasmodic dysphonia SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 26-29, 1999 CL NEW ORLEANS, LOUISIANA SP Amer Acad Otolaryngol Head & Neck Surg AB OBJECTIVE: To determine laryngeal muscle activation abnormalities associated with speech symptoms in abductor spasmodic dysphonia (ABSD). STUDY DESIGN: Bilateral laryngeal muscle recordings from the posterior cricoarytenoid, thyroarytenoid, and cricothyroid muscles were conducted in 12 ABSD patients, Patients' measures were compared during speech breaks and during speech without breaks and with In normal controls. RESULTS: Significant group differences were found in the thyroarytenoid muscle; the patients had significantly greater activity on the right side both during speech breaks and nonbreaks in comparison with the controls, Cricothyroid muscle levels were also increased on the right in the patients. CONCLUSION: An asymmetry in adductor muscle tone between the 2 sides in ABSD may account for difficulties with maintaining phonation and voice onset after voiceless consonants, SIGNIFICANCE,. These abnormalities may indicate why PCA BOTOX injections have not been as effective in ABSD as thyroarytenoid injections have been in adductor spasmodic dysphonia. OI Ludlow, Christy/0000-0002-2015-6171 SN 0194-5998 PD JAN PY 2001 VL 124 IS 1 BP 23 EP 30 DI 10.1067/mhn.2001.112572 UT WOS:000166506700006 PM 11228447 ER PT J AU Chase, TN Konitsiotis, S Oh, JD AF Chase, TN Konitsiotis, S Oh, JD TI Striatal molecular mechanisms and motor dysfunction in Parkinson's disease SO PARKINSON'S DISEASE SE ADVANCES IN NEUROLOGY SN 0091-3952 PY 2001 VL 86 BP 355 EP 360 UT WOS:000173954800036 PM 11553996 ER PT J AU Brown, MD Wick, TM Eckman, JR AF Brown, MD Wick, TM Eckman, JR TI Activation of vascular endothelial cell adhesion molecule expression by sickle blood cells SO PEDIATRIC PATHOLOGY & MOLECULAR MEDICINE AB Microvascular complications in sickle cell disease occur as a result of obstruction of small vessels Microvascular by deoxygenated sickle cells. Cerebrovascular complications are also common and result from obstruction of large blood vessels by thrombosis with changes in vessels that have some similarity to those found in arteriosclerotic vascular disease. Endothelial damage and activation from sickle cell-endothelial interactions may contribute to both. We find that endothelial cells have increased expression of VCAM-1, E-selectin, and ICAM-1 when exposed to sickle blood cells. The concentration-dependent, sickle-induced, adhesion molecule expression is significantly greater than that promoted by normal cells. The time course of Cell Adhesion Molecule ( CAM) expression is similar to that induced by TNF-alpha and IL1. Studies after white cell enrichment and reduction suggest leukocytes are the primary mediators. CAM expression by endothelial cells appears stimulated by soluble factors. Antibody inhibition studies support TNF-alpha and IL-1, produced by sickle leukocytes, as the primary soluble factors responsible for the observed CAM expression. Both the induction of endothelial CAM expression and subsequent endothelial adherence of sickle erythrocytes may play significant roles in the pathophysiology of sickle-related complications, and reduction in CAM expression may provide a new approach to treatment. OI Wick, Timothy/0000-0001-8922-0939 SN 1522-7952 PD JAN PY 2001 VL 20 IS 1 BP 47 EP 72 UT WOS:000167156800004 PM 12673844 ER PT J AU Lemons, JA Bauer, CR Oh, W Korones, SB Papile, LA Stoll, BJ Verter, J Temprosa, M Wright, LL Ehrenkranz, RA Fanaroff, AA Stark, A Carlo, W Tyson, JE Donovan, EF Shankaran, S Stevenson, DK AF Lemons, JA Bauer, CR Oh, W Korones, SB Papile, LA Stoll, BJ Verter, J Temprosa, M Wright, LL Ehrenkranz, RA Fanaroff, AA Stark, A Carlo, W Tyson, JE Donovan, EF Shankaran, S Stevenson, DK CA NICHD Neonatal Res Network TI Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996 SO PEDIATRICS AB Objectives. To determine the mortality and morbidity for infants weighing 401 to 1500 g (very low birth weight [VLBW]) at birth by gestational age, birth weight, and gender. Study Design. Perinatal data were collected prospectively on an inborn cohort from January 1995 through December 1996 by 14 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network and were compared with the corresponding data from previous reports. Sociodemographic factors, perinatal events, and the neonatal course to 120 days of life, discharge, or death were evaluated. Results. Eighty four percent of 4438 infants weighing 501 to 1500 g at birth survived until discharge to home or to a long-term care facility (compared with 80% in 1991 and 74% in 1988). Survival to discharge was 54% for infants 501 to 750 g at birth, 86% for those 751 to 1000 g, 94% for those 1001 to 1250 g, and 97% for those 1251 to 1500g. The incidence of chronic lung disease (CLD; defined as receiving supplemental oxygen at 36 weeks' postmenstrual age; 23%), proven necrotizing enterocolitis (NEC; 7%), and severe intracranial hemorrhage (ICH; grade III or IV; 11%) remained unchanged between 1991 and 1996. Furthermore, 97% of all VLBW infants and 99% of infants weighing <1000 g at birth had weights less than the 10th percentile at 36 weeks' postmenstrual age. Mortality for 195 infants weighing 401 to 500 g was 89%, with nearly all survivors developing CLD. Mortality in infants weighing 501 to 600 g was 71%; among survivors, 62% had CLD, 35% had severe ICH, and 15% had proven NEC. Conclusions. Survival for infants between 501 and 1500 g at birth continued to improve, particularly for infants weighing <1000 g at birth. This improvement in survival was not associated with an increase in major morbidities, because the incidence of CLD, proven NEC, and severe ICH did not change. However, poor postnatal growth remains a major concern, occurring in 99% of infants weighing <1000 g at birth. Mortality and major morbidity (CLD, severe ICH, and NEC) remain high for the smallest infants, particularly those weighing <600 g at birth. SN 0031-4005 PD JAN PY 2001 VL 107 IS 1 BP art. no. EP e1 DI 10.1542/peds.107.1.e1 UT WOS:000166150600001 PM 11134465 ER PT J AU Visser, M Bouter, LM McQuillan, GM Wener, MH Harris, TB AF Visser, M Bouter, LM McQuillan, GM Wener, MH Harris, TB TI Low-grade systemic inflammation in overweight children SO PEDIATRICS AB Objective. Human adipose tissue expresses and releases the proinflammatory cytokine interleukin-6, potentially inducing low-grade systemic inflammation in persons with excess body fat. To limit potential confounding by inflammation-related diseases and subclinical cardiovascular disease, we tested the hypothesis that overweight is associated with low-grade systemic inflammation in children. Design and Setting. The third National Health and Nutrition Examination Survey, 1988-1994, a representative sample of the US population. Participants. A total of 3512 children 8 to 16 years of age. Outcome Measures. Elevated serum C-reactive protein concentration (CRP; >.22 mg/dL) and white blood cell count (10(9) cells/L). Results. Elevated CRP was present in 7.1% of the boys and 6.1% of the girls. Overweight children (defined as having a body mass index or a sum of 3 skinfolds (triceps, subscapula, and supra-iliac) above the gender-specific 85th percentile) were more likely to have elevated CRP than were their normal-weight counterparts. After adjustment for potential confounders, including smoking and health status, the odds ratio (OR) was 3.74 (95% confidence interval [CI]: 1.66-8.43) for overweight boys and the OR was 3.17 (95% CI: 1.60-6.28) for overweight girls, based on the body mass index. Based on the sum of 3 skinfolds, these ORs were 5.11 (95% CI: 2.36-11.06) and 2.89 (95% CI: 1.49-5.59) for boys and girls, respectively. Overweight was also associated with statistically significant higher white blood cell counts. The results were similar when restricted to healthy, non-smoking, nonestrogen-using children. Conclusions. In children 8 to 16 years of age, overweight is associated with higher CRP concentrations and higher white blood cell counts. These findings suggest a state of low-grade systemic inflammation in overweight children. SN 0031-4005 PD JAN PY 2001 VL 107 IS 1 BP art. no. EP e13 DI 10.1542/peds.107.1.e13 UT WOS:000166150600013 PM 11134477 ER PT J AU Moody, TW Chiles, J Casibang, M Moody, E Chan, D Davis, TP AF Moody, TW Chiles, J Casibang, M Moody, E Chan, D Davis, TP TI SR48692 is a neurotensin receptor antagonist which inhibits the growth of small cell lung cancer cells SO PEPTIDES AB Neurotensin (NT) is an autocrine growth factor for some small cell lung cancer (SCLC) cells. in this communication, the effects of a non-peptide NT receptor antagonist, SR48692, were investigated using SCLC cells. H-3-SR48692 bound with high affinity (IC50 = 20 nM) to NCI-H209 cells. Also, NT and SR48692 inhibited specific I-125-NT binding with high affinity (IC50 values of 2 and 200 nM). In contrast, the NT, receptor agonist, levocabastine, had little effect on specific I-125-NT binding, second messenger production and proliferation using NCI-H209 cells. SR-48692 (5 muM) antagonized the ability of NT (10 nM) to cause elevated cytosolic Ca2+ in Fura-2 AM loaded NCI-H309 cells. SR48692 antagonized the ability of NT to cause elevation of c-fos mRNA in these cells. Using a MTT proliferation assay, SR48692 inhibited NCI-H209 and H345 proliferation in a concentration-dependent manner. Using a clonogenic assay, 1 muM SR48692, reduced NCI-H209 colony number. Also, SR486392 (0.4 mg/kg per day) inhibited NCI-H209 xenograft proliferation in nude mice. These results suggest that SR48692 is: a NT1 receptor antagonist which inhibits SCLC growth. (C) 2001 Published by Elsevier Science Inc. RI davis, thomas/F-3244-2015 OI davis, thomas/0000-0001-8465-4973 SN 0196-9781 PD JAN PY 2001 VL 22 IS 1 BP 109 EP 115 DI 10.1016/S0196-9781(00)00362-4 UT WOS:000167125400013 PM 11179604 ER PT J AU Droll, JA Bisley, J Pasternak, T AF Droll, J. A. Bisley, J. Pasternak, T. TI Activity in MT neurons during a memory-for-visual-motion task SO PERCEPTION SN 0301-0066 PY 2001 VL 30 BP 108 EP 109 UT WOS:000207113100334 ER PT J AU Rahman, S Hasnat, A Hasan, CM Rashid, MA Ilias, M AF Rahman, S Hasnat, A Hasan, CM Rashid, MA Ilias, M TI Pharmacological evaluation of Bangladeshi medicinal plants - a review SO PHARMACEUTICAL BIOLOGY AB The results of pharmacological studies on 64 medicinal plants of Bangladesh have been reviewed. The results encountered in various investigations reveal important pharmacological activities of the plants which may be used as leads in developing novel therapeutic agents. SN 1388-0209 PY 2001 VL 39 IS 1 BP 1 EP 6 DI 10.1076/phbi.39.1.1.5939 UT WOS:000167621200001 ER PT J AU Cragg, GM Newman, DJ AF Cragg, GM Newman, DJ TI Natural product drug discovery in the next millennium SO PHARMACEUTICAL BIOLOGY CT Annual Meeting of the American-Association-for-the-Advancement-of-Science CY FEB 17-22, 2000 CL WASHINGTON, D.C. SP Amer Assoc Advancement Sci AB Nature has been a source of medicinal agents for thousands of years, and an impressive number of modern drugs have been isolated from natural sources, many based on their use in traditional medicine. In the past century, however, an increasing role has been played by microorganisms in the production of antibiotics and other drugs for the treatment of some serious diseases. Advances in the description of the human genome, as well as the genomes of pathogenic microbes and parasites, is permitting the determination of the structures of many proteins associated with disease processes. With the development of new molecular targets based on these proteins, there is an increasing demand for novel molecular diversity for screening. Natural products will play a crucial role in meeting this demand through the continued investigation of world's biodiversity, much of which remains unexplored. With less than 1% of the microbial world currently known, advances in procedures for microbial cultivation and the extraction of nucleic acids from environmental samples from soil and marine habitats, will provide access to a vast untapped reservoir of genetic and metabolic diversity. The same holds true for nucleic acids isolated from symbiotic and endophytic microbes associated with terrestrial and marine macroorganisms. By use of combinatorial chemical and biosynthetic technology, novel natural product leads will be optimized on the basis of their biological activities to yield effective chemotherapeutic and other bioactive agents. The investigation of these resources requires multi-disciplinary, national, and international collaboration in the discovery and development process. SN 1388-0209 PY 2001 VL 39 SU S BP 8 EP 17 DI 10.1076/phbi.39.7.8.5868 UT WOS:000175141800003 PM 21554167 ER PT B AU Bryant, LH Bulte, JWM AF Bryant, LH Bulte, JWM BE DeCuyper, M Bulte, JWM TI Dendrimers: Chemical principles and biotechnology applications SO PHYSICS AND CHEMISTRY BASIS OF BIOTECHNOLOGY, VOL 7 SE FOCUS ON BIOTECHNOLOGY CT 9th European Congress on Biotechnology (ECB9) CY JUL 11-15, 1999 CL BRUSSELS, BELGIUM SP Commiss European Comm, Gen Director Technol, Res & Energy Wallonia Reg, J Chabert, Minist Econ Brussels Capit Reg AB Dendrimers have received enormous amount of attention in the last ten years and several recent review articles have appeared in the literature that address their potential applications [1-3]. Stoddart et al [1] have stated that: "We are now approaching a time when the study of dendrimers becomes inextricably linked with many other fields, leaving the comprehensive reviewer of the subject a near-impossible task to fulfil". On that note, this review provides a brief introduction to the chemical principles of dendrimers by highlighting main synthetic strategies and methods for characterisation. Dendrimers containing heteroatoms will not be reviewed per se since these have recently been reviewed [4]. The major thrust of this review is the potential applications of dendrimers in such areas as boron neutron capture therapy, as contrast agents in magnetic resonance imaging, as vaccines, as cellular transfection agents and as bioconjugate dendrimers i.e., in-vitro immunoassays for antigens. The outline used in this review proved to be effective in classifying most published papers about dendrimers, but it must be kept in mind that some articles not only transcended two different classifications, such as synthesis and characterisation, but several classifications such as synthesis, characterisation and at least one potential application covered in this review. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 BN 0-7923-7091-0 PY 2001 VL 7 BP 47 EP 69 UT WOS:000171368300002 ER PT B AU Bulte, JWM Bryant, LH AF Bulte, JWM Bryant, LH BE DeCuyper, M Bulte, JWM TI Molecular and cellular magnetic resonance contrast agents SO PHYSICS AND CHEMISTRY BASIS OF BIOTECHNOLOGY, VOL 7 SE FOCUS ON BIOTECHNOLOGY CT 9th European Congress on Biotechnology (ECB9) CY JUL 11-15, 1999 CL BRUSSELS, BELGIUM SP Commiss European Comm, Gen Director Technol, Res & Energy Wallonia Reg, J Chabert, Minist Econ Brussels Capit Reg AB Certain chemical structures have magnetic properties that enable faster proton relaxation, allowing their use as MR contrast agents or magnetopharmaceuticals when found biocompatible. Larger complexes such as macromolecular or particulate contrast agents have recently emerged as a distinct subgroup of magnetic materials, suitable for contrast enhancement of the blood pool and specific tissues. This chapter describes the latest advances in chemical engineering and molecular/cellular biology, which are producing, an entirely new class of (targeted) MR contrast agents that can be used for high-resolution imaging of biologic processes at the molecular and cellular level. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 BN 0-7923-7091-0 PY 2001 VL 7 BP 197 EP 211 UT WOS:000171368300008 ER PT J AU Gelbart, WM Bruinsma, RF Pincus, PA Parsegian, VA AF Gelbart, WM Bruinsma, RF Pincus, PA Parsegian, VA TI Flexible polymers also counterattract - Reply SO PHYSICS TODAY SN 0031-9228 PD JAN PY 2001 VL 54 IS 1 BP 72 EP 72 UT WOS:000166200500025 ER PT J AU Pierre, PJ Skjoldager, P Bennett, AJ Renner, MJ AF Pierre, PJ Skjoldager, P Bennett, AJ Renner, MJ TI A behavioral characterization of the effects of food deprivation on food and nonfood object interaction: an investigation of the information-gathering functions of exploratory behavior SO PHYSIOLOGY & BEHAVIOR AB Previous research has shown that exploratory behavior serves not only to procure food, but also as a means of general information gathering. The purpose of this experiment was to investigate the function of exploratory behavior in rats by measuring behavior as they interacted with food and nonfood stimuli under different levels of food deprivation. Rats were food-deprived (0, 24, and 48 h), given free access to an open-field arena, and videotaped for a 20-min test session. The rats' behavior was assessed in a manner that isolated locomotor-, object-, and nonobject-related components. Deprivation did not affect locomotor activity levels; however, a decrease in rearing and propping against the test arena was shown. Rats distinguished between the food and nonfood objects because they attempted to ingest the food but not the nonfood object. Deprivation did result in increased contact with food objects; however, nonfood object interactions were maintained throughout the test session. These results suggest that exploratory behavior is separable from food seeking and functions in acquisition of information relating to multiple aspects of the environment. (C) 2001 Elsevier Science Inc. All rights reserved. SN 0031-9384 PD JAN PY 2001 VL 72 IS 1-2 BP 189 EP 197 DI 10.1016/S0031-9384(00)00392-9 UT WOS:000167251500024 PM 11239997 ER PT J AU Bachrach, C AF Bachrach, Christine TI Comment: The puzzling persistence of postmodern fertility preferences SO POPULATION AND DEVELOPMENT REVIEW SN 0098-7921 PY 2001 VL 27 SU S BP 332 EP 338 UT WOS:000202895600018 ER PT S AU Weed, DL AF Weed, DL BE Weinstein, M Hermalin, AI Stoto, MA TI Theory and practice in epidemiology SO POPULATION HEALTH AND AGING: STRENGTHENING THE DIALOGUE BETWEEN EPIDEMIOLOGY AND DEMOGRAPHY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT Conference on Demography and Epidemiology: Frontiers in Population Health and Aging CY FEB 08-10, 2001 CL GEORGETOWN UNIV, WASHINGTON, D.C. SP Natl Inst Aging, Behav & Social Res Program, Univ Michigan, Inst Social Res, Michigan Ctr Demog Aging, Populat Stud Ctr HO GEORGETOWN UNIV AB Scientific and ethical theories are examined in terms of the practice of epidemiology., the study of the determinants and distributions of disease, and the application of the knowledge gained to prevent disease and improve the health of populations. Scientific theories provide explanations and predictions for epidemiologic studies of disease etiology and prevention. Causal theory is the key example for epidemiologic science, although theories of selection processes, theories of health, and theories of probability and statistics are also core. Theories of ethics provide principles, warrants, and methods for acting upon the knowledge gained in the scientific pursuits of epidemiology and for obtaining that knowledge appropriately. Ethical theories guide practitioners in making justified decisions about when and under what conditions public health interventions should be undertaken and how research participants should be treated. Theories of midlevel bioethical principles have received the most attention in epidemiology, but other theories, such as virtue theory and communitarian theory, are also relevant. Many theories matter to the practice of epidemiology: theories of biology, aging, evolution, and medicine; theories of history, religion, law, economics, and politics, as well as the theories of the physical, behavioral, and social sciences. These theories matter because epidemiologists study many different biological and social phenomena, and preventive interventions occur at many different levels of explanation. Development of theory is not a high priority in contemporary epidemiology. Identifying the responsibilities of the discipline to be public health intervention and rigorous science is a first step toward developing and applying theory in epidemiology. SN 0077-8923 BN 1-57331-372-6 PY 2001 VL 954 BP 52 EP 62 UT WOS:000173961000005 PM 11797865 ER PT S AU Stoto, MA Hermalin, AL Li, R Martin, L Wallace, RB Weed, DL AF Stoto, MA Hermalin, AL Li, R Martin, L Wallace, RB Weed, DL BE Weinstein, M Hermalin, AI Stoto, MA TI Advocacy in epidemiology and demography SO POPULATION HEALTH AND AGING: STRENGTHENING THE DIALOGUE BETWEEN EPIDEMIOLOGY AND DEMOGRAPHY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT Conference on Demography and Epidemiology: Frontiers in Population Health and Aging CY FEB 08-10, 2001 CL GEORGETOWN UNIV, WASHINGTON, D.C. SP Natl Inst Aging, Behav & Social Res Program, Univ Michigan, Inst Social Res, Michigan Ctr Demog Aging, Populat Stud Ctr HO GEORGETOWN UNIV AB This paper is a summary of a panel discussion at the Conference on Epidemiology and Demography held at Georgetown University, in Washington D.C. on February 8-9, 2001. The participants were Al Hermalin, Linda Martin, Mike Stoto, Robert Wallace, Douglas Weed, and Rose Li (who chaired the session). A list of questions similar to the section headings in this paper was prepared in advance of the conference, and each of the participants was asked to address specific issues, although the presentations typically covered a range of topics. This summary also includes comments from the floor. SN 0077-8923 BN 1-57331-372-6 PY 2001 VL 954 BP 76 EP 87 UT WOS:000173961000007 PM 11797868 ER PT S AU Hartge, P AF Hartge, P BE Weinstein, M Hermalin, AI Stoto, MA TI Epidemiologic tools for today and tomorrow SO POPULATION HEALTH AND AGING: STRENGTHENING THE DIALOGUE BETWEEN EPIDEMIOLOGY AND DEMOGRAPHY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT Conference on Demography and Epidemiology: Frontiers in Population Health and Aging CY FEB 08-10, 2001 CL GEORGETOWN UNIV, WASHINGTON, D.C. SP Natl Inst Aging, Behav & Social Res Program, Univ Michigan, Inst Social Res, Michigan Ctr Demog Aging, Populat Stud Ctr HO GEORGETOWN UNIV AB As the premier population sciences, epidemiology and demography face common challenges as the U.S. population ages, as the genomic revolution unfolds, and as computing power changes the scale of analysis by several orders of magnitude. Each discipline does need to develop new tools to address the changing research questions, and the best strategy for success includes increased collaboration between the disciplines. The paradigms of each discipline still offer important insights into the problems of both disciplines, so cross-training would be a simple step to begin enlarging the tool box for population science. SN 0077-8923 BN 1-57331-372-6 PY 2001 VL 954 BP 295 EP 310 UT WOS:000173961000016 PM 11797862 ER PT S AU Weinstein, M Hermalin, AL Stoto, MA Evans, VJ Ewbank, D Haaga, J Ibrahim, M Madans, J AF Weinstein, M Hermalin, AL Stoto, MA Evans, VJ Ewbank, D Haaga, J Ibrahim, M Madans, J BE Weinstein, M Hermalin, AI Stoto, MA TI Greater collaboration across the disciplines - Challenges and opportunities SO POPULATION HEALTH AND AGING: STRENGTHENING THE DIALOGUE BETWEEN EPIDEMIOLOGY AND DEMOGRAPHY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT Conference on Demography and Epidemiology: Frontiers in Population Health and Aging CY FEB 08-10, 2001 CL GEORGETOWN UNIV, WASHINGTON, D.C. SP Natl Inst Aging, Behav & Social Res Program, Univ Michigan, Inst Social Res, Michigan Ctr Demog Aging, Populat Stud Ctr HO GEORGETOWN UNIV AB This paper reports a panel discussion-Opportunities for and Limitations to Greater Collaboration Across the Disciplines-held at the conference. It highlights the need for greater collaboration between demographers and epidemiologists and notes the institutional and disciplinary challenges to and opportunities for promoting greater cooperation. SN 0077-8923 BN 1-57331-372-6 PY 2001 VL 954 BP 311 EP 321 UT WOS:000173961000017 PM 11797863 ER PT J AU Han, JY Lee, YH Sin, SD Park, JI Kim, IH Je, GH Rodgers, GP AF Han, JY Lee, YH Sin, SD Park, JI Kim, IH Je, GH Rodgers, GP TI Enrichment and detection of fetal erythroid cells from maternal peripheral blood using liquid culture SO PRENATAL DIAGNOSIS AB Isolating fetal cells from maternal blood for prenatal genetic analysis is the least invasive method currently being investigated. In order to enrich these fetal erythroid cells we employed a two-phase liquid culture system that supports the growth and differentiation of erythroid progenitor cells. Mononuclear cells were separated from ten maternal blood samples at 8-14(+3) weeks of gestation and cultured in the first phase. After 4-5 days, the non-adherent cells were harvested and recultured with erythropoietin for another 3-4 days. The mean number of rotal erythroid cells reached approximately 0.77 x 10(6)/ml with an average purity of 90.5%. Hb F stain disclosed fetal erythroid cells averaging similar to5.7%. therefore the mean number of fetal erythroid cells isolated was 0.49 x 10(5)/ml. Female karyotypes were only observed while counting 5-66 metaphases. However, male DNA (SRY or DYZ1) was detected by PCR in 7/10 cases; in four of these cases and in one SRY-negative pregnancy the 46,XY karyotype: was Found by amniocentesis performed during the second trimester. This liquid culture system provided an enriched source of fetal cells without the need for more complicated separation or sorting procedures. Copyright (C) 2001 John Wiley & Sons, Ltd. SN 0197-3851 PD JAN PY 2001 VL 21 IS 1 BP 22 EP 26 DI 10.1002/1097-0223(200101)21:1<22::AID-PD987>3.3.CO;2-4 UT WOS:000166732100004 PM 11180235 ER PT J AU Li, YM Chrambach, A AF Li, YM Chrambach, A TI Gel electrophoretic isolation, in the hundred microgram range, of recombinant SDS-syntaxin from sea urchin egg cortical vesicles SO PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY AB Recombinant urchin syntaxin [Xa cut], electrophoresed at pH 9.0 (25 degreesC) or 10.2 (0 degreesC) in a discontinuous Tris-chloride-glycinate buffer system in the presence of 0.03% SDS in the catholyte, exhibits a multicomponent pattern in gels of a polyacrylamide concentration of 12% and 3% crosslinking. The position in the pattern of the syntaxin band was identified by reference to electropherograms of a previous study (P. Backlund, pers. comm.). The complexity of the protein composition of the preparation was reduced by selective stacking of proteins with mobilities greater than that of syntaxin. This provides a gel pattern consisting of two bands with mobilities close to that identified as syntaxin, as well as a minor, more slowly migrating, contaminant. The two major components are designated as S1 and S2, the latter being the larger species. In the absence of SDS, the preparation exhibits two pairs of protein components. Three of the proteins are charge isomers, i.e., of equal size, differing only in net charge, assumed to be forms of S1, while the fourth component is larger and is assumed to be S2. Aliquots of the preparation, containing 150 mug of protein were loaded on a cylindrical polyacrylamide gel of 18 mm. diameter, and separated S1 and S2 were excised in a position defined by their characteristic values of relative mobility (R-f). Two or three gel slices, corresponding in R-f to S1 or S2, were pooled and loaded onto a Stacking Gel (5% polyacrylamide, 20% crosslinked) of 18 mm diameter, equipped with a collection chamber of 200 muL volume. The protein was electroeluted from the gel slices and concentrated into a stack by electrophoresis. The stack, marked by bromphenolblue, was allowed to migrate into the collection chamber, was collected and analyzed by protein assay and re-electrophoresis. Re-electrophoresis of S1 shows that it consists of at least three components. Recovered S1 constitutes 47% of the preparation, based on protein assay, S2 4%. S1, isolated from SDS-PAGE, exhibits an apparent M-r of 22.7 kDa, S2 one of 34.5 kDa, similar to the value of 32.6 kDa expected from the structure of syntaxin. The absence of S2 from the electroeluate re-electrophoresed at 0 degrees C and their molecular weight relationship suggest a proteolytic transformation of S2 to S1. SN 1082-6068 PY 2001 VL 31 IS 4 BP 369 EP 387 DI 10.1081/PB-100107483 UT WOS:000172575900003 PM 11765901 ER PT S AU Thompson, KG AF Thompson, KG GP IEEE IEEE IEEE TI Neural mechanisms of bottom-up selection during visual search SO PROCEEDINGS OF THE 23RD ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4: BUILDING NEW BRIDGES AT THE FRONTIERS OF ENGINEERING AND MEDICINE SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY CT 23rd Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY OCT 25-28, 2001 CL ISTANBUL, TURKEY SP Natl Sci Fdn, TUBITAK, Sci & Tech Res Ctr Turkey, ISIK Univ, COMNET, EREL Techno Grp, GUZEL SANATLAR Printinghouse, JOHNSON&JOHNSON Med, PFIZER, SIEMENS Med, TURKCELL Iletism Hizmetler A S, ALSTOM Elect Ltd Co, GANTEK Technol & SUN Microsyst, TURCOM Co Grp AB Models of attention and saccade target selection propose that within the brain there is a topographic map of visual salience that selects, through a winner-take-all mechanism, locations for further processing. The results of a series of recent experiments in monkeys performing pop-out visual search tasks suggest that the frontal eye field (FEF) functions as a map of visual salience. FEF is located at the interface of sensory and motor processing and participates in the transformation of visual information into a command to move the eyes. Visually responsive neurons in FEF identify conspicuous objects in a search array regardless of the feature that renders conspicuousness. Furthermore, selection occurs at a constant interval following search array presentation and is dissociated from saccade production. The finding of a visual salience map in FEF validates models of visual selection and can serve to guide future empirical and theoretical investigations. SN 1094-687X BN 0-7803-7211-5 PY 2001 VL 23 BP 776 EP 779 PN 1-4 UT WOS:000178871900221 ER PT S AU Bichot, NP AF Bichot, NP GP IEEE IEEE IEEE TI Neural mechanisms of top-down selection during visual search SO PROCEEDINGS OF THE 23RD ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4: BUILDING NEW BRIDGES AT THE FRONTIERS OF ENGINEERING AND MEDICINE SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY CT 23rd Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY OCT 25-28, 2001 CL ISTANBUL, TURKEY SP Natl Sci Fdn, TUBITAK, Sci & Tech Res Ctr Turkey, ISIK Univ, COMNET, EREL Techno Grp, GUZEL SANATLAR Printinghouse, JOHNSON&JOHNSON Med, PFIZER, SIEMENS Med, TURKCELL Iletism Hizmetler A S, ALSTOM Elect Ltd Co, GANTEK Technol & SUN Microsyst, TURCOM Co Grp AB The brain's representation of visual information depends greatly on the behavioral relevance of the viewed stimuli. While in some instances behavioral significance is derived from conspicuity, in many situations significance depends on top-down factors such as the viewer's goals and knowledge. Studies combining neural recordings and behavioral observations have begun to elucidate how the brain selects visual stimuli based on top-down information. While many visual areas of the brain that are selective for visual attributes participate in the selection process, the outcome of the selection process across these areas appears to be represented in structures like the frontal eye field, a key stage in the transformation of visual selection into a command to move the eyes. Evidence shows that the frontal eye field exhibits all the characteristics of a visual salience map in which the behavioral significance of stimuli derived from bottom-up and top-down influences is represented. The patterns of neural modulation in structures like the frontal eye field can be used to design more efficient machine-vision algorithms for target selection. SN 1094-687X BN 0-7803-7211-5 PY 2001 VL 23 BP 780 EP 783 PN 1-4 UT WOS:000178871900222 ER PT S AU Optican, LM Quaia, C AF Optican, LM Quaia, C GP IEEE IEEE IEEE TI From sensory space to motor commands: Lessons from saccades SO PROCEEDINGS OF THE 23RD ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4: BUILDING NEW BRIDGES AT THE FRONTIERS OF ENGINEERING AND MEDICINE SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY CT 23rd Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY OCT 25-28, 2001 CL ISTANBUL, TURKEY SP Natl Sci Fdn, TUBITAK, Sci & Tech Res Ctr Turkey, ISIK Univ, COMNET, EREL Techno Grp, GUZEL SANATLAR Printinghouse, JOHNSON&JOHNSON Med, PFIZER, SIEMENS Med, TURKCELL Iletism Hizmetler A S, ALSTOM Elect Ltd Co, GANTEK Technol & SUN Microsyst, TURCOM Co Grp AB Our distributed model of the saccadic system faithfully reproduces saccadic waveforms and the patterns of neuronal activity observed in several brain areas. However, our model is not based on principles found in classical theories of motor control. In this paper we attempt to extract from our model some general principles about neural motor controllers. We conclude that intrinsic brain signals might represent non-physical signals, such as desired sensory states, approximate motor drives, and distributed motor commands, rather than physical signals (e.g., desired displacement or motor error). Furthermore, our model demonstrates that the critical transformation from maps of sensory space to temporal motor commands is not necessarily carried out explicitly. Instead, the transformation can be implicit, emerging from network connections within a feedback loop. SN 1094-687X BN 0-7803-7211-5 PY 2001 VL 23 BP 820 EP 823 PN 1-4 UT WOS:000178871900232 ER PT S AU McVeigh, ER Epstein, F AF McVeigh, ER Epstein, F GP IEEE IEEE IEEE TI Myocardial tagging during real-time MRI SO PROCEEDINGS OF THE 23RD ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-4: BUILDING NEW BRIDGES AT THE FRONTIERS OF ENGINEERING AND MEDICINE SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY CT 23rd Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY OCT 25-28, 2001 CL ISTANBUL, TURKEY SP Natl Sci Fdn, TUBITAK, Sci & Tech Res Ctr Turkey, ISIK Univ, COMNET, EREL Techno Grp, GUZEL SANATLAR Printinghouse, JOHNSON&JOHNSON Med, PFIZER, SIEMENS Med, TURKCELL Iletism Hizmetler A S, ALSTOM Elect Ltd Co, GANTEK Technol & SUN Microsyst, TURCOM Co Grp AB The advent of high performance gradients and parallel imaging schemes has made real-time MRI a stable mode of scanning. Cardiac tagging techniques have been shown to give extremely precise and accurate estimates of the evaluation of myocardial function. We have implemented a real-time mode of MRI that allows myocardial tagging to be performed without breath-holds, or gating. This will make the quantitative evaluation of myocardial function simpler in those patients with arhythmias and those who cannot hold their breath. SN 1094-687X BN 0-7803-7211-5 PY 2001 VL 23 BP 2284 EP 2285 PN 1-4 UT WOS:000178871900624 ER PT B AU Memarzadeh, F Manning, A AF Memarzadeh, F Manning, A GP CUHK CUHK CUHK TI Assessing thermal comfort and ventilation effectiveness in patient rooms SO PROCEEDINGS OF THE 4TH INTERNATIONAL CONFERENCE ON INDOOR AIR QUALITY, VENTILATION AND ENERGY CONSERVATION IN BUILDINGS, VOLS I-III CT 4th International Conference on Indoor Air Quality, Ventilation and Energy Conservation in Buildings (IAQVEC 2001) CY OCT 02-05, 2001 CL CHANGSHA, PEOPLES R CHINA SP City Univ Hong Kong, Minist Educ, K C Wong Educ Fdn, Broad Air Conditioning Co Ltd, Int Energy Agcy, WHO, Int Council Building Res Stud & Documentat, Amer Soc Heating, Refrigerating & Air-Conditioning Engineers, Int Soc Indoor Air Quality & Climate, Air Infiltrat & Ventilat Ctr, Amer Ind Hygiene Assoc, Chartered Inst Building Serv Engineers, China Assoc Refrigerat, Comm Heating, Ventilat & Air Conditioning, Chinese Architecture Assoc, Hong Kong Inst Engineers, Natl Resource Canada, Building Grp, CANMET Energy Technol Ctr, Hunan Univ AB This paper assesses the performance of the ventilation system as applied to a typical patient room using Computational Fluid Dynamics technique (CFD) coupled with the calculation of various ventilation indices. BN 962-442-190-0 PY 2001 BP 865 EP 872 UT WOS:000178473300109 ER PT J AU Wang, K Forbes, JG Jin, AJ AF Wang, K Forbes, JG Jin, AJ TI Single molecule measurements of titin elasticity SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY AB Titin, with a massive single chain of 3-4 MDa and multiple modular motifs, spans the half-sarcomere of skeletal and cardiac muscles and serves important, multifaceted functions. In recent years, titin has become a favored subject of single molecule observations by atomic force microscopy (AFM) and laser optical trap (LOT). Here we review these single titin molecule extension studies with an emphasis on understanding their relevance to titin elasticity in muscle function. Some fundamental aspects of the methods for single titin molecule investigations, including the application of dynamic force, the elasticity models for filamentous titin motifs, the technical foundations and calibrations of AFM and LOT, and titin sample preparations are provided. A chronological review of major publications on recent single titin extension observations is presented. This is followed by summary evaluations of titin domain folding/unfolding results and of elastic properties of filamentous titin motifs. Implications of these single titin measurements for muscle physiology/pathology are discussed and forthcoming advances in single titin studies are anticipated. Published by Elsevier Science Ltd. OI Jin, Albert/0000-0003-3826-1081 SN 0079-6107 PY 2001 VL 77 IS 1 BP 1 EP 44 DI 10.1016/S0079-6107(01)00009-8 UT WOS:000170516700002 PM 11473785 ER PT J AU Lu, B AF Lu, B TI Neurotrophic regulation of synapse development and plasticity SO PROGRESS IN NATURAL SCIENCE AB Neurotrophic factors are traditionally thought to be secretory proteins that regulate long-term survival and differentiation of neurons. Recent studies have revealed a previously unexpected role for these factors in synaptic development and plasticity in diverse neuronal populations. Here we review experiments carried out in our own laboratory in the last few years. me hale made two important discoveries. First, rye were among the first to report that brain-derived neurotrophic factor (BDNF) facilitates hippocampal long-term potentiation (LTP), a form of synaptic plasticity believed to be involved in learning and memory. BDNF modulates LTP at CAI synapses by enhancing synaptic responses to high frequency, tetanic stimulation. This is achieved primarily by facilitating synaptic vesicle docking, possibly due to an increase ill the levels of the vesicle protein synaptobrevin and synaptophysin in the nerve terminals. Gene knockout study demonstrates that the effects of BDNF are primarily mediated through presynaptic mechanisms. Second, we demonstrated a form of long-term, neurotrophin-mediate synaptic regulation. me showed that long-term treatment of the neuromuscular synapses with neurotrophin-3 (NT3) resulted in an enhancement of both spontaneous and evoked synaptic currents, as well as profound changes in the number of synaptic varicosities and synaptic vesicle proteins in motoneurons, all of which are indicative of more mature synapses. Our current work addresses the following issues:(i) activity-dependent trafficking of neurotrophin receptors, and its role in synapse-specific modulation; (ii) signal transduction mechanisms mediating the acute enhancement of synaptic transmission by neurotrophins; (iii) acute and long-term synaptic actions of the GDNF family; (iv) role of BC)NF in late-phase LTP and in the development of hippocampal circuit. SN 1002-0071 PD JAN PY 2001 VL 11 IS 1 BP 1 EP 5 UT WOS:000166811800001 ER PT J AU Rausch, DM Stover, ES AF Rausch, DM Stover, ES TI Neuroscience research in AIDS SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY AB 1. The human immunodeficiency virus invades the central nervous system early after infection where it later gives rise to cognitive, motor, and behavioral manifestations in children and adults. 2. Ranging from mild impairments to frank dementia, CNS manifestations can be diagnosed and measured with standard neuropsychological test batteries. 3. Great strides have been made with treatment: CNS manifestations are treatable, as are depression, psychosis, and delirium which sometimes accompany HIV disease at different stages. 4. With startling advances in antiretroviral therapy and lower mortality, patients face a constellation of new concerns stemming from HIV's transformation to a more chronic disease. 5. There are many compelling research directions ahead, including the psychosocial impact of living with HIV as a chronic disease, the development of medications expressly targeted to the CNS, and basic research on neuropathogenesis, including trafficking of virus into the CNS. SN 0278-5846 PD JAN PY 2001 VL 25 IS 1 BP 231 EP 257 DI 10.1016/S0278-5846(00)00154-8 UT WOS:000166941400011 PM 11263754 ER PT J AU Wrenn, CC Crawley, JN AF Wrenn, CC Crawley, JN TI Pharmacological evidence supporting a role for galanin in cognition and affect SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY AB 1. Galanin is localized in brain pathways involved in both cognition and affect. 2. Galanin has inhibitory actions on a variety of memory tasks including the Morris water maze, delayed nonmatching to position, T-maze delayed alternation, starburst maze, passive avoidance, active avoidance, and spontaneous alternation. 3. Galanin may inhibit learning and memory by inhibiting neurotransmitter release and neuronal firing rate. 4. Two signal transduction mechanisms through which galanin exerts its inhibitory actions are the inhibition of phosphatidyl inositol hydrolysis and the inhibition of adenylate cyclase. 5. Galanin released during periods of burst firing from noradrenergic locus coeruleus terminals in the ventral tegmental area (VTA) may lead to symptoms of depression through inhibition of dopaminergic VTA neurons. 6. Intraventricular galanin has anxiolytic effects in a punished drinking test. Intra-amygdala galanin has anxiogenic effects in a punished drinking test. SN 0278-5846 PD JAN PY 2001 VL 25 IS 1 BP 283 EP 299 DI 10.1016/S0278-5846(00)00156-1 UT WOS:000166941400013 PM 11263757 ER PT J AU Shi, YB Ishizuya-Oka, A AF Shi, YB Ishizuya-Oka, A TI Thyroid hormone regulation of apoptotic tissue remodeling: Implications from molecular analysis of amphibian metamorphosis SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 65 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY SN 0079-6603 PY 2001 VL 65 BP 53 EP 100 UT WOS:000165500700002 PM 11008485 ER PT J AU Shakur, Y Holst, LS Landstrom, TR Movsesian, M Degerman, E Manganiello, V AF Shakur, Y Holst, LS Landstrom, TR Movsesian, M Degerman, E Manganiello, V TI Regulation and function of the cyclic nucleotide phosphodiesterase (PDE3) gene family SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 66 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY SN 0079-6603 PY 2001 VL 66 BP 241 EP 277 UT WOS:000165500600007 PM 11051766 ER PT J AU Hager, GL AF Hager, GL TI Understanding nuclear receptor function: From DNA to chromatin to the interphase nucleus SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 66 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY SN 0079-6603 PY 2001 VL 66 BP 279 EP 305 UT WOS:000165500600008 PM 11051767 ER PT J AU Sobol, RW Wilson, SH AF Sobol, RW Wilson, SH TI Mammalian DNA beta-polymerase in base excision repair of alkylation damage SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 68 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY RI Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 SN 0079-6603 PY 2001 VL 68 BP 57 EP 74 UT WOS:000172044400005 PM 11554313 ER PT J AU Dianov, GL Souza-Pinto, N Nyaga, SG Thybo, T Stevnsner, T Bohr, VA AF Dianov, GL Souza-Pinto, N Nyaga, SG Thybo, T Stevnsner, T Bohr, VA TI Base excision repair in nuclear and mitochondrial DNA SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 68 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X SN 0079-6603 PY 2001 VL 68 BP 285 EP 297 UT WOS:000172044400019 PM 11554304 ER PT J AU Jetten, AM Kurebayashi, S Ueda, E AF Jetten, AM Kurebayashi, S Ueda, E TI The ROR nuclear orphan receptor subfamily: Critical regulators of multiple biological processes SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 69 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY OI Jetten, Anton/0000-0003-0954-4445 SN 0079-6603 PY 2001 VL 69 BP 205 EP 247 DI 10.1016/S0079-6603(01)69048-2 UT WOS:000172043800006 PM 11550795 ER PT J AU Hartman, TJ Dorgan, JF Woodson, K Virtamo, J Tangrea, JA Heinonen, OP Taylor, PR Barrett, MJ Albanes, D AF Hartman, TJ Dorgan, JF Woodson, K Virtamo, J Tangrea, JA Heinonen, OP Taylor, PR Barrett, MJ Albanes, D TI Effects of long-term alpha-tocopherol supplementation on serum hormones in older men SO PROSTATE AB BACKGROUND. alpha -tocopherol supplementation significantly reduced risk of prostate cancer in the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study. Sex hormones are thought to be involved in the etiology of prostate cancer. We examined whether long-term supplementation with alpha -tocopherol modified serum hormone levels. METHODS. Men who were cancer-free consumed greater than or equal to 90% of the study capsules, and who had both baseline and follow-up blood available, were eligible for the study. One hundred men who received alpha -tocopherol were matched on age, study center, and length of time between blood draws to 100 men who received a placebo. Multivariate linear regression models which allowed for a separate intercept for each matched pair were used to evaluate the effect of alpha -tocopherol supplementation on follow-up hormone concentrations. RESULTS. Compared to men who received a placebo, we found significantly lower serum androstenedione (P = 0.04) and testosterone (P = 0.04) concentrations among men who received alpha -tocopherol, after controlling for baseline hormone level, follow-up serum cholesterol concentration, body mass index, smoking, and fasting time. Geometric mean (95% confidence interval; CI) androstenedione concentration among men who received alpha-tocopherol was 145 ng/dl (CI, 137-153) after adjusting for covariates, compared to 158 ng/dl (CI, 148-167) among men who received a placebo. Mean testosterone concentrations for men who received alpha -tocopherol and placebo were 539 (CI, 517-562) and 573 (CI, 549-598) ng/dl, respectively CONCLUSIONS. These results suggest that long-term alpha -tocopherol supplementation decreases serum androgen concentrations, and could have been one of the factors contributing to the observed reduction in incidence and mortality of prostate cancer in the alpha -tocopherol treatment group of the ATBC Study. Prostate 46:33-38, 2001. (C) 2001 Wiley-Liss, Inc. RI Albanes, Demetrius/B-9749-2015 SN 0270-4137 PD JAN 1 PY 2001 VL 46 IS 1 BP 33 EP 38 DI 10.1002/1097-0045(200101)46:1<33::AID-PROS1005>3.3.CO;2-Y UT WOS:000166752100005 PM 11170129 ER PT J AU Chang, S Hursting, SD Contois, JH Strom, SS Yamamura, Y Babaian, RJ Troncoso, P Scardino, PT Wheeler, TM Amos, CI Spitz, MR AF Chang, S Hursting, SD Contois, JH Strom, SS Yamamura, Y Babaian, RJ Troncoso, P Scardino, PT Wheeler, TM Amos, CI Spitz, MR TI Leptin and prostate cancer SO PROSTATE AB BACKGROUND. Higher prostate cancer mortality rates among US immigrants from countries with lower rates suggest environmental influences on prostate carcinogenesis (e.g., diet, body composition). METHODS. In a study identifying determinants of clinically relevant prostate cancer, we compared plasma concentrations of leptin, an adiposity-related hormone, in 48 men with tumors less than or equal to0.5 cc measured after radical prostatectomy and 151 men with tumors >0.5 cc in volume or with histologic evidence of extraprostatic extension but without metastases ("high-volume disease"), matched by age(+/-5 years) and year at diagnosis (fl year). RESULTS. Men with high-volume disease exhibited higher leptin concentrations overall and after stratification by age, testosterone level, height, and body mass index (BMI). Analysis revealed that men with elevated leptin concentrations had an increased risk of diagnosis with high-volume disease (odds ratio (OR) = 2.35, 95% confidence interval (CI) = 1.01-5.44), as did men with high leptin and high testosterone (OR = 9.73, 95% CI = 2.05-46.24) and men greater than or equal to5'8" with high leptin (OR = 3.67, 95% CI = 1.40-9.63). CONCLUSIONS. Leptin may affect the risk of clinically relevant prostate cancer through testosterone and factors related to stature and obesity. Prostate 46:62-67, 2001. (C) 2001 Wiley-Liss, Inc. SN 0270-4137 PD JAN 1 PY 2001 VL 46 IS 1 BP 62 EP 67 UT WOS:000166752100009 PM 11170133 ER PT J AU Liu, YQ Kyle, E Patel, S Housseau, F Hakim, F Lieberman, R Pins, M Blagosklonny, MV Bergan, RC AF Liu, YQ Kyle, E Patel, S Housseau, F Hakim, F Lieberman, R Pins, M Blagosklonny, MV Bergan, RC TI Prostate cancer chemoprevention agents exhibit selective activity against early stage prostate cancer cells SO PROSTATE CANCER AND PROSTATIC DISEASES AB Preclinical models for the identification of prostate cancer chemoprevention agents are lacking. Based upon the notion that clinically useful chemoprevention agents should exhibit selective activity against early stage disease, studies were undertaken to assess whether chemoprevention agents selectively inhibited the growth of early stage prostate cancer, as compared to late stage cancer. First, a series of cell and molecular studies were performed, which, when taken together, validated the use of a panel of prostate cell lines as a model of the different stages of carcinogenesis. Next, therapeutic responsiveness to ten different cytotoxic or chemoprevention agents was evaluated. Chemoprevention agents exhibited selective activity against normal and early transformed prostate tissue, whereas cytotoxic agents were non-specific. Selective activity against early versus advanced prostate cancer cells is identified as a potential screening method for chemoprevention agents. SN 1365-7852 PY 2001 VL 4 IS 2 BP 81 EP 91 DI 10.1038/sj.pcan.4500506 UT WOS:000169837000003 ER PT S AU Lapidus, LJ Hofrichter, J Eaton, WA AF Lapidus, LJ Hofrichter, J Eaton, WA BE Shakhnovich, EI Broglia, RA Tiana, G TI Dynamics of end-to-end contact formation in polypeptides SO PROTEIN FOLDING, EVOLUTION AND DESIGN SE NATO SCIENCE SERIES, SUB-SERIES I: LIFE AND BEHAVIOURAL SCIENCES CT NATO Advanced Study Institute on Protein Folding, Evolution and Design CY JUL 11-21, 2000 CL VARENNA, ITALY SP NATO SN 1566-7693 BN 1-58603-169-4 PY 2001 VL 333 BP 3 EP 12 UT WOS:000175524500001 ER PT S AU Hurley, JH Tsujishita, Y Pearson, MA AF Hurley, JH Tsujishita, Y Pearson, MA BE Heilmeyer, L Friedrich, P TI Floundering about at cell membranes: A structural view of phospholipid signaling SO PROTEIN MODULES IN CELLULAR SIGNALLING SE NATO SCIENCE SERIES, SERIES A: LIFE SCIENCE CT Conference of the NATO Advanced-Study-Institute on Protein Modules in Cellular Signalling CY SEP 13-22, 2000 CL ST MARTIN DE LONDRES, FRANCE SP NATO, ASI AB Structures are now available for the majority of enzyme families involved in the phosphorylation, dephosphorylation, and hydrolysis of signaling phospholipids. Lipid kinase and phosphatase structures recapitulate catalytic motifs from protein phosphorylation and dephosphorylation, while cytosolic phospholipase A, manifests novel catalytic geometry. Structures have been determined for most known intracellular phospholipid "receptor" domains, both those that bind membrane-embedded phospholipids and those that bind lipid monomers. SN 1387-6686 BN 1-58603-180-5 PY 2001 VL 318 BP 311 EP 323 UT WOS:000174226500034 ER PT J AU Sham, YY Ma, BY Tsai, CJ Nussinov, R AF Sham, YY Ma, BY Tsai, CJ Nussinov, R TI Molecular dynamics simulation of Escherichia coli dihydrofolate reductase and its protein fragments: Relative stabilities in experiment and simulations SO PROTEIN SCIENCE AB We have carried out molecular dynamics simulations of the native dihydrofolate reductase from Escherichia coli and several of its folded protein fragments at standard temperature. The simulations have shown fragments 1-36, 37-88, and 89-159 to be unstable, with a CalphaRMSD (C-alpha root mean squared deviation) >5 Angstrom after 3.0 nsec of simulation. The unfolding of fragment 1-36 was immediate, whereas fragments 37-88 and 89-159 gradually unfolded because of the presence of the beta -sheet core structure. In the absence of residues 1-36, the two distinct domains comprising fragment 39-159 associated with each other, resulting in a stable conformation. This conformation retained most of its native structural elements. We have further simulated fragments derived from computational protein cutting. These were also found to be unstable, with the exception of fragment 104-159. In the absence of alpha (4), the loose loop region of residues 120-127 exhibited a beta -strand-like behavior, associating itself with the beta -sheet core of the protein fragment. The current study suggests that the folding of dihydrofolate reductase involves cooperative folding of distinct domains which otherwise would have been unstable as independent folded units in solution. Finally, the critical role of residues 1-36 in allowing the two distinct domains of fragment 104-159 to fold into the final native conformation is discussed. RI Sham, Yuk/A-6472-2011; Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X SN 0961-8368 PD JAN PY 2001 VL 10 IS 1 BP 135 EP 148 DI 10.1110/ps.33301 UT WOS:000167925800016 PM 11266602 ER PT J AU Hummer, G Garcia, AE Garde, S AF Hummer, G Garcia, AE Garde, S TI Helix nucleation kinetics from molecular simulations in explicit solvent SO PROTEINS-STRUCTURE FUNCTION AND GENETICS AB We study the reversible folding/unfolding of short Ala and Gly-based peptides by molecular dynamics simulations of all-atom models in explicit water solvent. A kinetic analysis shows that the formation of a first alpha-helical turn occurs within 0.1-1 ns, in agreement with the analyses of laser temperature jump experiments. The unfolding times exhibit Arrhenius temperature dependence. For a rapidly nucleating all-Ala peptide, the helix nucleation time depends only weakly on temperature. For a peptide with enthalpically competing turn-like structures, helix nucleation exhibits an Arrhenius temperature dependence, corresponding to the unfolding of enthalpic traps in the coil ensemble. An analysis of structures in a "transition-state ensemble" shows that helix-to-coil transitions occur predominantly through breaking of hydrogen bonds at the helix ends, particularly at the C-terminus. The temperature dependence of the transition-state ensemble and the corresponding folding/unfolding pathways illustrate that folding mechanisms can change with temperature, possibly complicating the interpretation of high-temperature unfolding simulations. The timescale of helix formation is an essential factor in molecular models of protein folding. The rapid helix nucleation observed here suggests that transient helices form early in the folding event. Proteins 2001;42:77-84. (C) 2000 Wiley-Liss, Inc. RI Garde, Shekhar/C-3060-2008; Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X SN 0887-3585 PD JAN 1 PY 2001 VL 42 IS 1 BP 77 EP 84 DI 10.1002/1097-0134(20010101)42:1<77::AID-PROT80>3.0.CO;2-# UT WOS:000166077200008 PM 11093262 ER PT J AU McCrae, RR AF McCrae, RR TI Traits through time SO PSYCHOLOGICAL INQUIRY SN 1047-840X PY 2001 VL 12 IS 2 BP 85 EP 87 UT WOS:000169596000004 ER PT J AU Morf, CC Rhodewalt, F AF Morf, CC Rhodewalt, F TI Unraveling the paradoxes of narcissism: A dynamic self-regulatory processing model SO PSYCHOLOGICAL INQUIRY AB Me propose a dynamic self-regulatory processing model of narcissism and review supporting evidence, The model casts narcissism in terms of motivated self-construction, in that the narcissist's self is shaped by the dynamic interaction of cognitive and affective intrapersonal processes and interpersonal self-regulatory strategies that are played out in the social arena. A grandiose yet vulnerable self-concept appears to underlie the chronic goal of obtaining continuous external self-affirmation. Because narcissists are insensitive to others' concerns and social constraints and view others as inferior, their self-regulatory efforts often are counterproductive and ultimately prevent the positive feedback that they seek-thus undermining the self they are trying to create and maintain. We draw connections between this model and other processing models in personality, and employ these models to further elucidate the construct of narcissism. Reconceptualizing narcissism as a self-regulatory processing system promises to resolve many of its apparent paradoxes, because by understanding how narcissistic cognition, affect, and motivation interrelate, their internal subjective logic and coherence come into focus. SN 1047-840X PY 2001 VL 12 IS 4 BP 177 EP 196 DI 10.1207/S15327965PLI1204_1 UT WOS:000172639300001 ER PT J AU Morf, CC Rhodewalt, F AF Morf, CC Rhodewalt, F TI Expanding the dynamic self-regulatory processing model of narcissism: Research directions for the future SO PSYCHOLOGICAL INQUIRY AB The "self-regulatory processing model of narcissism" described in the target article conceptualizes narcissism as a set of intra- and interpersonal processes employed in the service of motivated self-construction. In response to the insightful and constructive commentaries, this article theoretically expands this model to elaborate more fully the paradoxical coexistence of grandiosity and vulnerability in narcissists. Toward this goal, we consider the characteristics of the processing system and cognitive-affective dynamics that might underlie narcissistic grandiosity-vulnerability, as well as possible developmental antecedents. We discuss the possible concurrent operations of two systems-one implicit, hot, impulsive, and affect driven, the other explicit, rational, or cool. This analysis allowed the model to be extended in ways that further illuminates some of narcissists' paradoxical elements and enables specific predictions about the situational features likely to activate and maintain the narcissistic pattern. It is our hope that the model will stimulate additional research and theorizing about narcissism and serve more generally as a framework for the study of other personality types. SN 1047-840X PY 2001 VL 12 IS 4 BP 243 EP 251 DI 10.1207/S15327965PLI1204_3 UT WOS:000172639300015 ER PT J AU Gabbay, FH Duncan, CC Morris, EK Mirsky, AF AF Gabbay, FH Duncan, CC Morris, EK Mirsky, AF TI Disinhibition and risk for drug abuse: Amphetamine effects on auditory P300 SO PSYCHOPHYSIOLOGY SN 0048-5772 PY 2001 VL 38 SU 1 BP S43 EP S43 UT WOS:000171018100171 ER PT J AU Merritt, MM Abernethy, DR Evans, MK Sollers, JJ Zonderman, AB Thayer, JF AF Merritt, MM Abernethy, DR Evans, MK Sollers, JJ Zonderman, AB Thayer, JF TI Effect of emotionally salient sentences and faces on the cardiovascular responses of a community-based African-American sample SO PSYCHOPHYSIOLOGY SN 0048-5772 PY 2001 VL 38 SU 1 BP S66 EP S66 UT WOS:000171018100265 ER PT J AU Mordecai, KL Sollers, JJ Maki, PM Thayer, JF AF Mordecai, KL Sollers, JJ Maki, PM Thayer, JF TI Temporal stability of cardiovascular response in healthy older adults SO PSYCHOPHYSIOLOGY SN 0048-5772 PY 2001 VL 38 SU 1 BP S68 EP S68 UT WOS:000171018100273 ER PT J AU Sollers, JJ Morgan, CA Thayer, JF AF Sollers, JJ Morgan, CA Thayer, JF TI Heart rate variability and performance in military personnel enrolled in combat dive training. SO PSYCHOSOMATIC MEDICINE SN 0033-3174 PD JAN-FEB PY 2001 VL 63 IS 1 MA 1385 BP 94 EP 94 UT WOS:000166843200022 ER PT J AU Merritt, MM Bennett, GG Williams, RB AF Merritt, MM Bennett, GG Williams, RB TI Low hostility and high state negative affect are linked with elevated blood pressure responses to mental stress in Black males SO PSYCHOSOMATIC MEDICINE SN 0033-3174 PD JAN-FEB PY 2001 VL 63 IS 1 MA 1339 BP 117 EP 117 UT WOS:000166843200097 ER PT J AU Muehrer, PR AF Muehrer, PR TI NIMH funding opportunities for research on health and behavior, including co-morbid mental and medical disorders SO PSYCHOSOMATIC MEDICINE SN 0033-3174 PD JAN-FEB PY 2001 VL 63 IS 1 MA 1031 BP 143 EP 143 UT WOS:000166843200183 ER PT J AU Thayer, JF Jacob, RG AF Thayer, JF Jacob, RG TI Left venticular mass, blood pressure and the structure of emotional space SO PSYCHOSOMATIC MEDICINE SN 0033-3174 PD JAN-FEB PY 2001 VL 63 IS 1 MA 1619 BP 153 EP 153 UT WOS:000166843200219 ER PT J AU Thayer, JF Nabors-Oberg, R Sollers, JJ Friedman, BH AF Thayer, JF Nabors-Oberg, R Sollers, JJ Friedman, BH TI Heart period variability and 24-hr blood pressure variability: Gender differences SO PSYCHOSOMATIC MEDICINE SN 0033-3174 PD JAN-FEB PY 2001 VL 63 IS 1 MA 1378 BP 169 EP 169 UT WOS:000166843200272 ER PT J AU Amundson, SA Fornace, AJ AF Amundson, SA Fornace, AJ TI Gene expression profiles for monitoring radiation exposure SO RADIATION PROTECTION DOSIMETRY CT Symposium on 21st Century Biodosimetry: Quantifying the Past and Predicting the Future CY FEB 22, 2001 CL ARLINGTON, VA AB Previous demonstrations that the dose, dose rate, radiation quality, and elapsed time since ionising radiation exposure result in variations in the response of stress genes suggest that gene expression signatures may be informative markers of radiation exposure. Defining sets of genes that are specific for different outcomes of interest will be key to such an approach. A generalised post-exposure profile may identify exposed individuals within a population, while more specific fingerprints may reveal details of a radiation exposure. Changes in gene expression in human cell lines occur after as little as 0.02 Gy gamma rays, and in peripheral blood lymphocytes after as little as 0.2 Gy. Diverse genes are also elevated in vivo in mice 24 h after 0.2 Gy irradiation. Ongoing microarray analyses meanwhile continue to identify large numbers of potential biomarkers from varied irradiation protocols, Development of computation-intensive informatics analysis methods will be needed for management of the complex gene expression profiles resulting from such experiments. Although the preliminary data are encouraging, significant work remains before meaningful correlations with risk or practical assessment of exposure can be made by gene expression profiling. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X SN 0144-8420 PY 2001 VL 97 IS 1 BP 11 EP 16 UT WOS:000172373000003 PM 11763352 ER PT J AU Newton, DL Kaur, G Rhim, JS Sausville, EA Rybak, SM AF Newton, DL Kaur, G Rhim, JS Sausville, EA Rybak, SM TI RNA damage and inhibition of neoplastic endothelial cell growth: Effects of human and amphibian ribonucleases SO RADIATION RESEARCH CT Satellite Meeting on In Vitro Transformation held at the 11th International Congress of Radiation Research CY JUL 24-25, 1999 CL CORK, IRELAND SP Int Assoc Radiat Res, Radiat Sci Ctr, Dublin Inst Technol, NASA Johnson Space Ctr, Procter & Gamble Pharmaceut Inc AB Angiogenesis defines the many steps involved in the growth and migration of endothelial cell-derived blood vessels, This process is necessary for the growth and metastasis of tumors, and considerable effort is being expended to find inhibitors of tumor angiogenesis. This usually involves screening of potential anti-angiogenic compounds on endothelial cells, To this end, two candidate anti-angiogenic RNA-damaging agents, onconase and (-4)rhEDN, were screened for their effects on endothelial cell proliferation using three distinct types of endothelial cells in culture: HPV-16 E6/E7-immortalized human umbilical vein endothelial cells (HUVECs), a Kras-transformed HPV-16 E6/E7 HUVEC (Rhim et at, Carcinogenesis 4, 673-681, 1998), and primary HUVECs. Onconase similarly inhibited proliferation in all three cell lines (IC50 = 0.3-1.0 muM) while (-4)rhEDN was more effective on immortalized HUVEC cell lines (IC50 = 0.02-0.06 muM) than on primary HUVECs (IC50 > 0.1 muM). Differential sensitivity to these agents implies that more than one endothelial cell type must be used in proliferation assays to screen for novel anti-angiogenic compounds. (C) 2001 by Radiation Research Society. SN 0033-7587 PD JAN PY 2001 VL 155 IS 1 BP 171 EP 174 DI 10.1667/0033-7587(2001)155[0171:RDAION]2.0.CO;2 PN 2 UT WOS:000166370500008 PM 11121230 ER PT J AU Lechner, JF Fugaro, JM Wong, YX Pass, HI Harris, CC Belinsky, SA AF Lechner, JF Fugaro, JM Wong, YX Pass, HI Harris, CC Belinsky, SA TI Perspective: Cell differentiation theory may advance early detection of and therapy for lung cancer SO RADIATION RESEARCH CT Satellite Meeting on In Vitro Transformation held at the 11th International Congress of Radiation Research CY JUL 24-25, 1999 CL CORK, IRELAND SP Int Assoc Radiat Res, Radiat Sci Ctr, Dublin Inst Technol, NASA Johnson Space Ctr, Procter & Gamble Pharmaceut Inc AB Worldwide, 1,000,000 people succumb to lung cancer annually. Many of these deaths could be prevented if there were better screening methods to uncover the disease when it is limited and most responsive to intervention. Novel biomarkers of early-stage disease are therefore needed. By applying the principle of "oncology recapitulates ontogeny", we have discovered three homeobox (HOX) genes that are inappropriately expressed in the majority of lung tumors. Understanding the role of these inappropriately expressed genes in lung epithelial cell carcinogenesis may not only augment early detection, but may also offer new avenues of treatment of this disease. (C) 2001 by Radiation Research Society. SN 0033-7587 PD JAN PY 2001 VL 155 IS 1 BP 235 EP 238 DI 10.1667/0033-7587(2001)155[0235:PCDTMA]2.0.CO;2 PN 2 UT WOS:000166370500018 PM 11121240 ER PT B AU Austin, KH Johnson, RH AF Austin, KH Johnson, RH GP HPS HPS TI Radiation safety training: The basis for maintaining ALARA SO RADIATION SAFETY AND ALARA CONSIDERATIONS FOR THE 21ST CENTURY CT 34th Midyear Topical Meeting CY FEB 04-07, 2001 CL ANAHEIM, CA AB Appreciation of ALARA considerations begins with the radiation safety training program at every facility. Whether it is in introductory or refresher training courses, all employees need to be instructed on the ALARA concept and to understand the theory behind this practice. When presented as a method of protecting the employee, proper ALARA training can lead to a cooperative team effort to minimize radiation exposures for everyone involved. Simply reciting the mantra of "Perform surveys, prevent spills, minimize time, utilize shielding and maximize distance" is not enough. In order to elicit the cooperation of the employees, it is imperative to demonstrate exactly what the facility is doing to minimize radiation exposures and to then encourage the employees to investigate and develop their own methods as well. Several beneficial training tools involve videotaped interviews or summaries of successful procedures used by other employees within the facility demonstrating their success in minimizing exposures. Seeing and learning what others have achieved stimulates creative ideas among the employees and assists in maintaining exposures ALARA. BN 1-930524-02-1 PY 2001 BP 205 EP 210 UT WOS:000179202700031 ER PT J AU Garraffo, HM Spande, TF Jain, P Kaneko, T Jones, TH Blum, MS Ali, TMM Snelling, RR Isbell, LA Robertson, HG Daly, JW AF Garraffo, HM Spande, TF Jain, P Kaneko, T Jones, TH Blum, MS Ali, TMM Snelling, RR Isbell, LA Robertson, HG Daly, JW TI Ammonia chemical ionization tandem mass spectrometry in structural determination of alkaloids. II. Tetraponerines from pseudomyrmecine ants SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY AB Chemical ionization tandem mass spectrometry (CI-MS/MS) of alkaloids with ammonia reagent gas and collision-activated dissociation as well as EI-MS/MS were applied to the tetraponerine alkaloids in extracts from six pseudomyrmecine ants of the genus Tetraponera. The MS/MS techniques along with gas chromatography Fourier transform infrared (GC/FTIR) spectra allowed identification in two extracts of seven of the eight known tetraponerines. The EI-MS/MS fragmentations proved diagnostic for the ring system and the CI-MS/MS patterns for the C-8 or C-9 substitution, while the Bohlmann bands in FTIR spectra were diagnostic for the C-8 or C-9 configurations. An Indian ant (T. allaborans) had T-2, T-4 and T-8, while a Chinese ant (T. binghami) had T-5, T-6, T-7 and T-8. Four other ants, T. rufonigra (India), T. penzigi (Africa), T. clypeata (Africa) and T. sp. cf. emeryi (Africa), had no tetraponerines. Copyright (C) 2001 John Wiley & Sons, Ltd. SN 0951-4198 PY 2001 VL 15 IS 16 BP 1409 EP 1415 DI 10.1002/rcm.382 UT WOS:000170552500004 PM 11507752 ER PT J AU Doyle, ME Egan, JM AF Doyle, ME Egan, JM TI Glucagon-like peptide-1 SO RECENT PROGRESS IN HORMONE RESEARCH, VOL 56 SE RECENT PROGRESS IN HORMONE RESEARCH AB There is a progressive impairment in beta-cell function with age. As a result, 19 percent of the U.S. population over the age of 65 is diagnosed with type 2 diabetes mellitus (DM). Glucagon-like peptide-1 (GLP-1) is a potent insulin secretagogue that has multiple synergetic effects on the glucose-dependent insulin secretion pathways of the beta -cell. This peptide and its longer-acting analog exendin-4 are currently under review as treatments for type 2 DM. In our work on the rodent model of glucose intolerance in aging, we found that GLP-1 is capable of rescuing the age-related decline in beta -cell function. We have shown that this is due to the ability of GLP-1 to 1) recruit beta -cells into a secretory mode; 2) upregulate the genes of the beta -cell glucose-sensing machinery; and 3) cause beta -cell differentiation and neogenesis. Our investigations into the mechanisms of action of GLP-1 began by using the reverse hemolytic plaque assay to quantify insulin secretion from individual cells of the RIN 1046-38 insulinoma cell line in response to acute treatment with the peptide. GLP-1 increases both the number of cells secreting insulin and the amount secreted per cell. This response to GLP-1 is retained even in the P cell of the old (i.e., 22-month), glucose-intolerant Wistar rat, which exhibits a normal, first-phase insulin response to glucose following an acute bolus of GLP-1. Preincubation with GLP-1 (24 hours) potentiates glucose- and GLP-1-dependent insulin secretion and increases insulin content in the insulinoma cells. Treatment of old Wistar rats for 48 hours with GLP-1 leads to normalization of the insulin response acid an increase in islet insulin content and mRNA levels of GLUT 2 and glucokinase. PDX-1, a transcriptional factor activator of these three genes, also is upregulated in the insulinoma cell line in aged rats and diabetic mice following treatment with GLP-1. Administration of GLP-1 to old rats leads to pancreatic cell proliferation, insulin-positive clusters, and an increase in beta -cell mass. This evidence led us to believe that GLP-1 is an endocrinotrophic factor. We used an acinar cell line to show that GLP-1 can directly cause the conversion of a putative pro-endocrine cell into an endocrine one. Thus, the actions of GLP-1 on the beta -cell are complex, with possible benefits to the diabetic patient that extend beyond a simple glucose-dependent increase in insulin secretion. The major limitation to GLP-1 as a clinical treatment is its short biological half-life. We have shown that the peptide exendin-4, originating in the saliva of the Gila monster, exhibits the same insulinotropic and endocrinotrophic properties as GLP-1 but is more potent and longer acting in rodents and humans. SN 0079-9963 PY 2001 VL 56 BP 377 EP 399 DI 10.1210/rp.56.1.377 UT WOS:000167911000018 PM 11237222 ER PT J AU Wolffe, AP AF Wolffe, AP TI Transcriptional regulation in the context of chromatin structure SO REGULATION OF GENE EXPRESSION SE ESSAYS IN BIOCHEMISTRY SN 0071-1365 PY 2001 VL 37 BP 45 EP 57 UT WOS:000175159700004 PM 11758456 ER PT J AU Donaldson, JG Radhakrishna, M AF Donaldson, JG Radhakrishna, M TI Expression and properties of ADP-ribosylation factor (ARF6) in endocytic pathways SO REGULATORS AND EFFECTORS OF SMALL GTPASES, PT E SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 329 BP 247 EP 256 UT WOS:000167096500026 PM 11210541 ER PT J AU Pacheco-Rodriguez, G Moss, J Vaughan, M AF Pacheco-Rodriguez, G Moss, J Vaughan, M TI Isolation, cloning, and characterization of brefeldin A-inhibited guanine nucleotide-exchange protein for ADP-ribosylation factor SO REGULATORS AND EFFECTORS OF SMALL GTPASES, PT E SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 329 BP 300 EP 306 UT WOS:000167096500032 PM 11210548 ER PT J AU Randazzo, PA Miura, K Jackson, TR AF Randazzo, PA Miura, K Jackson, TR TI Assay and purification of phosphoinositide-dependent ADP-ribosylation factor (ARF) GTPase activating proteins SO REGULATORS AND EFFECTORS OF SMALL GTPASES, PT E SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 329 BP 343 EP 354 UT WOS:000167096500037 PM 11210554 ER PT J AU Pacheco-Rodriguez, G Moss, J Vaughan, M AF Pacheco-Rodriguez, G Moss, J Vaughan, M TI Preparation and assay of recombinant ADP-ribosylation factor-like protein-1 (ARL1) SO REGULATORS AND EFFECTORS OF SMALL GTPASES, PT E SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 329 BP 424 EP 428 UT WOS:000167096500044 PM 11210562 ER PT J AU O'Bryan, JP AF O'Bryan, JP TI Determining involvement of She proteins in signaling pathways SO REGULATORS AND EFFECTORS OF SMALL GTPASES, PT G SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 333 BP 3 EP 15 UT WOS:000169760600001 PM 11400346 ER PT J AU Urano, J Ellis, C Clark, GJ Tamanoi, F AF Urano, J Ellis, C Clark, GJ Tamanoi, F TI Characterization of Rheb functions using yeast and mammalian systems SO REGULATORS AND EFFECTORS OF SMALL GTPASES, PT G SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 333 BP 217 EP 231 UT WOS:000169760600020 PM 11400338 ER PT J AU Couse, JF Mahata, D Eddy, EM Korach, KS AF Couse, JF Mahata, D Eddy, EM Korach, KS TI Molecular mechanism of estrogen action in the male: insights from the estrogen receptor null mice SO REPRODUCTION FERTILITY AND DEVELOPMENT CT Boden Research Conference on Estrogens and Male Health CY NOV 02-03, 2000 CL MARITIME MUSEUM, SYDNEY, AUSTRALIA HO MARITIME MUSEUM AB Until recently, 17 beta -estradiol was thought to be of little importance in male fertility. However, the descriptions of testicular dysfunction and behavioral deficits leading to complete infertility in male mice lacking estrogen receptor alpha (ER alpha) have indicated the importance of estrogen action in fertility of the male rodent. In contrast, male mice lacking the newly discovered estrogen receptor beta (ER beta) exhibit no compromised fertility. Recently, elaborate sperm transplantation studies have shown that the altered sperm function characteristic of the ER alpha knockout male are the result of the loss of ER alpha actions in the supporting somatic cells of the testis and epididymis rather than in the germ cell. This brief review will discuss the roles of estrogen action in male reproduction as revealed by mice lacking both known forms of the ER. A brief review of the estrogen signaling system is also included. OI Korach, Kenneth/0000-0002-7765-418X SN 1031-3613 PY 2001 VL 13 IS 4 BP 211 EP 219 DI 10.1071/RD00128 UT WOS:000172464300002 PM 11800160 ER PT J AU Ryu, JC Seo, YR Smith, ML Han, SS AF Ryu, JC Seo, YR Smith, ML Han, SS TI The effect of methyl methanesulfonate (MMS)-induced excision repair on p53-dependent apoptosis in human lymphoid cells SO RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY AB The tumor suppressor p53 product has been shown to play an important role in preventing carcinogenesis by at least two different mechanisms, by evoking cell cycle arrest and eliciting DNA repair on one hand, or by eliminating damaged cells by induction of apoptosis on the other hand. As a first step toward understanding the relationship between protective responses and apoptosis after genotoxic stress, we examined the effect of DNA strand breaks generated from repair processes in respect to acute cellular responses against DNA damage, and on p53-dependent apoptosis in human lymphoid cells. We used two isogenic cell lines, TK6 harboring wild-type p53, and WI-L2-NS, which carries a mutant p53. A significant difference in sensitivity was observed at 50 mug/ml methyl methanesulfonate (MMS) between the two cell lines used. In addition, a clear p53-mediated contribution to apoptosis in MMS-induced cell death was observed. However, we did not observe any differences in repair of MMS-lesions, as determined by comet assay, between the two cell lines. These data suggest that the differences in apoptosis induction in the two lines are not a reflection of differences in strand-break frequency or repair capacity. SN 1078-0297 PY 2001 VL 109 IS 1-2 BP 35 EP 51 UT WOS:000170034400004 PM 11458984 ER PT B AU Anderson, DE AF Anderson, DE BE Haruki, Y Homma, I Umezawa, A Masaoka, Y TI Environmental stress, hypoventilatory breathing and blood pressure regulation SO RESPIRATION AND EMOTION CT International Interdisciplinary Symposium on Respiration and Emotion CY JUL 23-25, 1999 CL TOKYO, JAPAN AB Research in our laboratory is based on the hypothesis that chronic breathing suppression associated with stressful environments can contribute to high blood pressure via its effects on PCO2, acid-base balance, and renal regulation of sodium. This hypothesis first emerged in the context of studies that investigated the role of behavioral stress in the development of experimental hypertension in laboratory animals. Those studies showed that regular exposure of animals to familar avoidance tasks evoked an anticipatory hypoventilatory breathing pattern associated with sustained increases in PCO2. Repeated evocation of this breathing pattern potentiated the development of experimental hypertension when combined with high sodium intake. Subsequent studies of ambulatory monitoring of human breathing showed that people also engage in episodes of breathing inhibition in the natural environment. Experimental studies found that when hydrated humans voluntarily decreased breathing frequency and thereby increased PCO2, they retained sodium and increased plasma volume. It was hypothesized that humans with high resting PCO2 might show the same blood pressure sensitivity to high sodium intake as observed in the animal studies in which PCO2 was increased via behavioral stress. This hypothesis was confirmed in two experimental studies, suggesting that high resting PCO2 Might be a useful clinical marker for sodium sensitivity. Recent studies have also found that older women with high resting end tidal CO2 tend to have higher resting systolic blood pressure than other women with lower resting end tidal CO2. Additional studies are needed to further clarify the role of breathing habits in pCO(2) regulation and its role in blood pressure adaptations' to high sodium diet. BN 4-431-70286-5 PY 2001 BP 149 EP 159 UT WOS:000170638900015 ER PT J AU Domachowske, JB Bonville, CA Rosenberg, HF AF Domachowske, JB Bonville, CA Rosenberg, HF TI Gene expression in epithelial cells in response to pneumovirus infection SO RESPIRATORY RESEARCH AB Respiratory syncytial virus (RSV) and pneumonia virus of mice (PVM) are viruses of the family Paramyxoviridae, subfamily pneumovirus, which cause clinically important respiratory infections in humans and rodents, respectively. The respiratory epithelial target cells respond to viral infection with specific alterations in gene expression, including production of chemoattractant cytokines, adhesion molecules, elements that are related to the apoptosis response, and others that remain incompletely understood. Here we review our current understanding of these mucosal responses and discuss several genomic approaches, including differential display reverse transcription-polymerase chain reaction (PCR) and gene array strategies, that will permit us to unravel the nature of these responses in a more complete and systematic manner. SN 1465-993X PY 2001 VL 2 IS 4 BP 225 EP 233 DI 10.1186/rr61 UT WOS:000170300500005 PM 11686888 ER PT J AU Peebles, RS Graham, BS AF Peebles, RS Graham, BS TI Viruses, dendritic cells and the lung SO RESPIRATORY RESEARCH AB The interaction between viruses and dendritic cells (DCs) is varied and complex. DCs are key elements in the development of a host response to pathogens such as viruses, but viruses have developed survival tactics to either evade or diminish the immune system that functions to kill and eliminate these micro-organisms. In the present review we summarize current concepts regarding the function of DCs in the immune system, our understanding of how viruses alter DC function to attenuate both the virus-specific and global immune response, and how we may be able to exploit DC function to prevent or treat viral infections. SN 1465-993X PY 2001 VL 2 IS 4 BP 245 EP 249 DI 10.1186/rr63 UT WOS:000170300500007 PM 11686890 ER PT J AU Freed, WJ Vawter, MP AF Freed, WJ Vawter, MP TI Microarrays: Applications in neuroscience to disease, development, and repair SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE SN 0922-6028 PY 2001 VL 18 IS 2-3 BP 53 EP 56 UT WOS:000172438500001 PM 11847427 ER PT J AU Cai, NS McCoy, MT Cadet, JL AF Cai, NS McCoy, MT Cadet, JL TI Profile of genes showing increased expression following dopamine and methamphetamine exposure in an immortalized neuronal cell line SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE AB Methamphetamine (METH) is a drug of abuse with well-described neurodegenerative effects. Some of the METH-induced degenerative manifestations are thought to be due to increased dopamine (DA) release in the cytoplasm of nerve terminals and subsequent extravasation in the synaptic cleft. Using an immortalized neural cell line, we have made use of the comprehensive cDNA array technology in order to compare and contrast the molecular effects of DA and METH. We found that the two compounds do have many similar but also different effects. Since these neural cells produce no DA, these results demonstrate that many of the METH-induced responses attributed to DA might, in fact, be intrinsic to METH itself. More biochemical studies are needed to investigate DA-independent METH deleterious events in the central nervous system. SN 0922-6028 PY 2001 VL 18 IS 2-3 BP 57 EP 65 UT WOS:000172438500002 PM 11847428 ER PT J AU Truckenmiller, ME Vawter, MP Cheadle, C Coggiano, M Donovan, DM Freed, WJ Becker, KG AF Truckenmiller, ME Vawter, MP Cheadle, C Coggiano, M Donovan, DM Freed, WJ Becker, KG TI Gene expression profile in early stage of retinoic acid-induced differentiation of human SH-SY5Y neuroblastoma cells SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE AB Purpose: The human SH-SY5Y cell line is an established model for retinoic acid (RA)-induced neural differentiation. We employed a broad human 15K microarray (15,000 genes) and focused Neuroarray (1152 genes) to examine changes in gene expression early in the process of differentiation (6 hr), before morphology or growth changes are observed. Methods: P-33-labeled cDNA probes prepared from RNA extracts of RA-treated and control cultures were hybridized to array membranes, and levels of expression were quantified and compared. Results: In the 15K array, 19 % of the genes were decreased (0.4 % were named genes and the remainder were expressed sequence tags (ESTs) or unknowns), and 9 % were increased (4.2 % named genes). In the Neuroarray, 3 % were decreased and 8 % were increased. Conclusions: Summary gene profiles are presented, which include transcription factors, genes associated with cell cycle, cell shape, neurotransmission, intermediary filaments, and others. The prevalence of down-regulated genes in the broad 15K array and up-regulated genes in the neuro-focused array suggests a pattern shift in gene expression associated with differentiation. The predominance of ESTs among the down-regulated genes indicates a great number of as-yet-unidentified genes are repressed in early stage neural differentiation. OI Becker, Kevin/0000-0002-6794-6656 SN 0922-6028 PY 2001 VL 18 IS 2-3 BP 67 EP 80 UT WOS:000172438500003 PM 11847429 ER PT J AU Barrett, T Cheadle, C Wood, WH Teichberg, D Donovan, DM Freed, WJ Becker, KG Vawter, MP AF Barrett, T Cheadle, C Wood, WH Teichberg, D Donovan, DM Freed, WJ Becker, KG Vawter, MP TI Assembly and use of a broadly applicable neural cDNA microarray SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE AB cDNA microarrays provide an efficient method to analyze gene expression patterns in thousands of genes in parallel. In some cases, large unfocused collections of cDNAs have been used in hybridization studies, in others small logically defined collections of tissue specific arrays have been used. Here we describe the bioinformatic selection of 1152 named human cDNAs specifically designed for neuroscience applications, arrayed on nylon membranes at high density. cDNAs were chosen which represent all the major cellular types of the brain including; neurons, astrocytes, microglia, and oligodendrocytes. Gene families chosen include cell type specific markers, ion-channels, transporters, receptors, and cell adhesion molecules among many others. These arrays were used with region specific samples from human brain to determine mRNA expression profiles for each region. Used with (33)-P labeled complex probes, this is a low cost, highly sensitive approach for the investigator to focus on tissue specific genes of interest where samples of limiting amounts of RNA are used. This selected set of brain-relevant cDNAs should be widely useful in the analysis of gene expression patterns from brain tissues as well as neural cell lines. OI Becker, Kevin/0000-0002-6794-6656 SN 0922-6028 PY 2001 VL 18 IS 2-3 BP 127 EP 135 UT WOS:000172438500009 PM 11847435 ER PT J AU Tsilou, E Rubin, BI Caruso, RC Kaiser-Kupfer, M AF Tsilou, E Rubin, BI Caruso, RC Kaiser-Kupfer, M TI A case of Alport's syndrome and retinal degeneration SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES SN 0275-004X PY 2001 VL 21 IS 1 BP 89 EP 92 DI 10.1097/00006982-200102000-00025 UT WOS:000167042600025 PM 11217946 ER PT J AU Levy-Clarke, GA Byrnes, GA Buggage, RR Shen, DF Filie, AC Caruso, RC Nussenblatt, RB Chan, CC AF Levy-Clarke, GA Byrnes, GA Buggage, RR Shen, DF Filie, AC Caruso, RC Nussenblatt, RB Chan, CC TI Primary intraocular lymphoma diagnosed by fine needle aspiration biopsy of a subretinal lesion SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES SN 0275-004X PY 2001 VL 21 IS 3 BP 281 EP 284 DI 10.1097/00006982-200106000-00023 UT WOS:000169241600023 PM 11421029 ER PT J AU Yamani, A Myers-Powell, BA Whitcup, SM Cohen, SB Kanter, ED Kaplan, B Zarbin, MA AF Yamani, A Myers-Powell, BA Whitcup, SM Cohen, SB Kanter, ED Kaplan, B Zarbin, MA TI Visual loss after renal transplantation SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES SN 0275-004X PY 2001 VL 21 IS 5 BP 553 EP 559 DI 10.1097/00006982-200110000-00029 UT WOS:000171559000029 PM 11642396 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI A natural classification of ribonucleases SO RIBONUCLEASES, PT A SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 341 BP 3 EP 28 UT WOS:000171842700001 PM 11582786 ER PT J AU Rosenberg, HF Domachowske, JB AF Rosenberg, HF Domachowske, JB TI Eosinophil-derived neurotoxin SO RIBONUCLEASES, PT A SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 341 BP 273 EP 286 UT WOS:000171842700017 PM 11582783 ER PT J AU Crouch, RJ Arudchandran, A Cerritelli, SM AF Crouch, RJ Arudchandran, A Cerritelli, SM TI RNase H1 of Saccharomyces cerevisiae: Methods and nomenclature SO RIBONUCLEASES, PT A SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 341 BP 395 EP 413 UT WOS:000171842700025 PM 11582793 ER PT J AU Hartley, RW AF Hartley, RW TI Barnase-barstar interaction SO RIBONUCLEASES, PT A SE METHODS IN ENZYMOLOGY SN 0076-6879 PY 2001 VL 341 BP 599 EP 611 UT WOS:000171842700038 PM 11582808 ER PT J AU Ooi, SL Dann, C Nam, K Leahy, DJ Damha, MJ Boeke, JD AF Ooi, SL Dann, C Nam, K Leahy, DJ Damha, MJ Boeke, JD TI RNA lariat debranching enzyme SO RIBONUCLEASES, PT B SE METHODS IN ENZYMOLOGY RI Damha, Masad/B-5522-2013 SN 0076-6879 PY 2001 VL 342 BP 233 EP 248 UT WOS:000171842900019 PM 11586896 ER PT J AU Kumon, Y Suehiro, T Hashimoto, K Sipe, JD AF Kumon, Y Suehiro, T Hashimoto, K Sipe, JD TI Dexamethasone, but not IL-1 alone, upregulates acute-phase serum amyloid A gene expression and production by cultured human aortic smooth muscle cells SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY AB Although the SAA1 and SAA2 protein isoforms (A-SAA) of the serum amyloid A (SAA) family of acute phase reactants have been found in a number of extrahepatic tissues; the site of synthesis of extrahepatic SAA remains to be clarified. To investigate site(s) of synthesis of the SAA protein localized to atherosclerotic plaque, expression of the SAA1 and SAA2 genes by cultured human aortic smooth muscle cells (HASMC) was investigated, A-SAA protein isoforms were detectable by immunoblot analysis in the culture medium of HASMC. Both A-SAA and C-SAA (SAA4) mRNA isoforms were constitutively expressed by HASMC, but not, however, by the human umbilical vein endothelial cells. Expression of A-SAA mRNA by HASMC was upregulated by corticoid hormones including dexamethasone (Dex), corticosterone, hydrocortisone, and aldosterone, but not by the cytokines interleukin (IL)-1, IL-6, and tumour necrosis factor (TNF)-alpha alone. Dex stimulation of A-SAA mRNA was time and dose dependent from 6 to 48 h. The threshold concentration for upregulation of A-SAA mRNA in HASMC by Dex was between 0.1 and 1 nM. IL-1, known to upregulate extrahepatic A-SAA gene expression in other cell systems only slightly, if at all, upregulated Dex-induced A-SAA expression by HASMC. Thus, it is possible that some of the A-SAA protein in the vascular wall (atherosclerotic plaques) can originate from smooth muscle cells. In consideration of recent reports that A-SAA modulates the inflammatory process and lipid synthesis, A-SAA can potentially serve as a physiological regulator of smooth muscle cell homeostasis within that, in a disease state, participates in the formation of atherosclerotic plaques. SN 0300-9475 PD JAN PY 2001 VL 53 IS 1 BP 7 EP 12 DI 10.1046/j.1365-3083.2001.00829.x UT WOS:000166794100002 PM 11169201 ER PT J AU Brown, LM Thomas, TL Ma, JL Chang, YS You, WC Liu, WD Zhang, L Gail, MH AF Brown, LM Thomas, TL Ma, JL Chang, YS You, WC Liu, WD Zhang, L Gail, MH TI Helicobacter pylori infection in rural China: Exposure to domestic animals during childhood and adulthood SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES AB Little is known about the mode of transmission of Helicobacter pylori, one of the most common human bacterial infections. Some domestic animals, including the cat, have been suggested as a reservoir of H. pylori disease, but the data have been inconsistent. This paper evaluates the role of exposure to pets and other domestic animals in the etiology of H. pylori in a rural area of China with a high prevalence of H. pylori infection. In this double-blind, population-based, cross-sectional investigation, interviews were completed with 3288 (1994 seropositive, 1019 seronegative, 275 indeterminate) H. pylori-infected adults enrolled in a randomized intervention trial in Linqu County, Shandong Province, China. We found no evidence to suggest that exposure to pets or other domestic animals during either childhood or adulthood was related to the prevalence of H. pylori infection. In fact, odds ratios (ORs) were reduced for subjects who had kept a cat (OR = 0.7, 95% CI 0.4-1.0) or any animal (OR = 0.5, 95% CI = 0.3-0.9) in the house as an adult, or a cat as a child (OR = 0.7, 95% CI 0.5-1.0). ORs were also reduced for all 11 types of animal studied that subjects had kept in their courtyard as an adult. These findings suggest that zoonotic transmission, including that from domestic cats, is an unlikely route of H. pylori infection in this rural Chinese population. SN 0036-5548 PY 2001 VL 33 IS 9 BP 686 EP 691 UT WOS:000171504800008 PM 11669227 ER PT J AU Ben-Dor, S AF Ben-Dor, S TI Personal account SO SCHIZOPHRENIA BULLETIN AB The article that follows is part of the Schizophrenia Bulletin's ongoing First person Account series. We hope that mental health professionals-the Bulletin's primary audience-will take this opportunity to learn about the issues and difficulties confronted by consumers of mental health care. In addition, we hope that these accounts will give patients and families a better sense of not being alone in confronting the problems that can be anticipated by persons with serious emotional difficulties. We welcome other contributions from patients, ex-patients, or family members. Our major editorial requirement is that such contributions be dearly written and organized, and that a novel or unique aspect of schizophrenia be described, with special emphasis on points that will be important for professionals. Clinicians who see articulate patients with experiences they believe should be shared might encourage these patients to submit their articles to Schizophrenia Bulletin. SN 0586-7614 PY 2001 VL 27 IS 2 BP 329 EP 332 UT WOS:000168512400016 PM 11354599 ER PT J AU Meinecke, DL AF Meinecke, DL TI The developmental etiology of schizophrenia hypothesis: What is the evidence? Editor's introduction SO SCHIZOPHRENIA BULLETIN SN 0586-7614 PY 2001 VL 27 IS 3 BP 335 EP 336 UT WOS:000171223200001 ER PT J AU Zahn, TP Pickar, D van Kammen, DP AF Zahn, TP Pickar, D van Kammen, DP TI Neuroleptic effects on autonomic activity in schizophrenia: Between-group and within-subject paradigms and comparisons with controls SO SCHIZOPHRENIA BULLETIN AB Effects of fluphenazine on electrodermal activity (EDA) and heart rate (HR) were studied in patients with schizophrenia and normal control subjects during rest periods, presentation of innocuous tones, and a reaction time (RT) task. Two types of analyses were used: (1) between-group analyses-patients taking placebo were compared with patients taking fluphenazine and with control subjects using only data from the first test session; and (2) within-subject analyses-the same patients were tested when taking fluphenazine and when taking placebo. Results showed higher resting EDA and HR and smaller increments to task performance In placebo patients than in control subjects. Fluphenazine attenuated EDA levels but not the tonic response. Fluphenazine attenuated the HR response but did not affect FIR level. Placebo patients were electrodermally hyporesponsive to the RT stimuli but not to simple tones. Fluphenazine markedly attenuated responsivity to simple tones but it attenuated responsivity less for RT stimuli. Testing medicated patients may thus produce misleading results with respect to many, but not all, purported autonomic markers of diagnosis in schizophrenia studies. SN 0586-7614 PY 2001 VL 27 IS 3 BP 503 EP 515 UT WOS:000171223200013 PM 11596851 ER PT S AU Margolis, R AF Margolis, R BE Anthony, M Dunn, BK Sherman, S TI The basic biology of SERMs - Introduction SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 1 EP 2 UT WOS:000173775800001 PM 11795341 ER PT S AU Emmen, JMA Korach, KS AF Emmen, JMA Korach, KS BE Anthony, M Dunn, BK Sherman, S TI Developing animal models for analyzing SERM activity SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res AB Estrogens have effects on many organ systems, beyond the reproductive system, in both females and males. Estrogen effects are exerted through specific receptors, of which there are two types: estrogen receptor (ER) alpha and estrogen receptor (ER) beta. To study the roles of each receptor in vivo, a series of mice were generated lacking either a functional ERalpha or ERbeta or both. These mice, labeled alphaERKO, betaERKO, or alphabetaERKO, respectively, have been useful in defining the tissue specificities, localization, and functions of each of the estrogen receptors. These mouse models also show great promise for use in defining the effectiveness of putative SERMs. OI Korach, Kenneth/0000-0002-7765-418X SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 36 EP 43 UT WOS:000173775800005 PM 11795377 ER PT S AU Dunn, BK Kramer, B AF Dunn, BK Kramer, B BE Anthony, M Dunn, BK Sherman, S TI Cancer treatment and prevention - Introduction SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 68 EP 71 UT WOS:000173775800008 PM 11795382 ER PT S AU Wolmark, N Dunn, BK AF Wolmark, N Dunn, BK BE Anthony, M Dunn, BK Sherman, S TI The role of tamoxifen in breast cancer prevention - Issues sparked by the NSABP Breast Cancer Prevention Trial (P-1) SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res AB The Breast Cancer Prevention Trial (P-1: BCPT) of the National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized 13,388 women, greater than or equal to 35 years of age, at increased risk for breast cancer [greater than or equal to1.66 by Gail model criteria or with a history of lobular carcinoma in situ (LCIS)] to 5 years of tamoxifen or placebo. A 49% reduction (P < 0.00001) in invasive breast cancers occurred, 175 with placebo versus 89 with tamoxifen, mainly among estrogen receptor (ER)-positive tumors (130 with placebo vs. 41 with tamoxifen). The major toxicities of tamoxifen were endometrial cancer (15 with placebo vs. 36 with tamoxifen) and thromboembolic disease, both predominantly in women who were greater than or equal to50 years old. Ramifications emerging from the P-1 results regarding the efficacy and toxicities of preventive tamoxifen include the following: (1) Does tamoxifen induce more virulent breast cancers? (2) Does tamoxifen induce more virulent endometrial cancers? (3) Tamoxifen is especially efficacious in reducing breast cancer risk in LCIS (18 invasive breast cancers with placebo vs. 8 with tamoxifen group) and atypical ductal hyperplasia (AH) (23 invasive breast cancers with placebo vs. 3 with tamoxifen). (4) Does tamoxifen reduce breast cancer risk in women at increased risk due to genetic mutations? (5) How can we prevent tamoxifen-resistant breast cancers? (6) What do the BCPT results tell us about who should take preventive tamoxifen? In its ongoing effort to lower the incidence of breast cancer, the NSABP is now implementing its second breast cancer prevention trial, the Study of Tamoxifen and Raloxifene (STAR), which is comparing the two agents with regard to efficacy and toxicity. SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 99 EP 108 UT WOS:000173775800012 PM 11795386 ER PT S AU Gordon, DJ AF Gordon, DJ BE Anthony, M Dunn, BK Sherman, S TI Selective estrogen receptor modulators and cardiovascular disease - Introduction SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 151 EP 152 UT WOS:000173775800018 ER PT S AU Blum, A Cannon, RO AF Blum, A Cannon, RO BE Anthony, M Dunn, BK Sherman, S TI Selective estrogen receptor modulator effects on serum lipoproteins and vascular function in postmenopausal women and in hypercholesterolemic men SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res AB Epidemiological observations, clinical mechanistic studies, and basic laboratory research suggest that estrogen therapy is associated with beneficial cardiovascular effects in postmenopausal women. Estrogen has a multitude of biological effects that may account for this apparent benefit (which remains to be proved in randomized clinical trials), including favorable effects on the lipid profile, increased endothelial nitric oxide bioactivity, and enhanced fibrinolysis. However, long-term estrogen therapy increases the risk of breast and endometrial cancers. Raloxifene, a benzothiophene derivative that binds to the estrogen receptor, is a selective estrogen receptor modulator, producing estrogen-agonist effects in some tissues (liver, bone) and estrogen-antagonistic effects in others (breast, uterus), and may prove to be an option for women with atherosclerosis or its risk factors. This review updates the current knowledge of the biological effects of selective estrogen receptor modulators of potential cardiovascular importance in postmenopausal women. SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 168 EP 174 UT WOS:000173775800021 PM 11795350 ER PT S AU Sherman, S AF Sherman, S BE Anthony, M Dunn, BK Sherman, S TI Preventing and treating osteoporosis - Strategies at the millennium SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res AB Osteoporosis has been defined as "a progressive systemic disease characterized by low bone density and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture." Osteoporosis and the consequences of compromised bone strength-particularly vertebral and hip fractures-are a significant cause of frailty, and increased morbidity and even mortality and hence are a serious and costly public health problem in the elderly population However, due to remarkable advances in basic and clinical research and in drug design, development, and testing, a number of efficacious, evidence-based options are available for the prevention and treatment of osteoporosis. These options extend far beyond estrogen/progestin therapy and include lifestyle and dietary changes such as increasing weight-bearing activity, enhancing calcium and vitamin D intake, as well as incorporating pharmacologic agents such as the bisphosphonates and selective estrogen receptor modulators (SERMs) such as raloxifene. In addition to its efficacy in increasing bone mineral density and reducing vertebral fractures by almost 40% in women with osteoporosis, the SERM raloxifene appears to promote a cardioprotective profile and to offer some protection against breast cancer. The potential of raloxifene to prevent or delay the development of a number of chronic diseases of aging such as osteoporosis, cardiovascular disease, and perhaps even Alzheimer's disease has stimulated the development and refinement of subsequent generations of SERMs aimed at maximizing beneficial effects in a wide variety of tissues while eliminating deleterious outcomes and side effects. SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 188 EP 197 UT WOS:000173775800025 PM 11795353 ER PT S AU Monjan, AA AF Monjan, AA BE Anthony, M Dunn, BK Sherman, S TI SERMs, estrogen, and cognitive function - Introduction SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 202 EP 202 UT WOS:000173775800027 ER PT S AU Resnick, SM Maki, PM AF Resnick, SM Maki, PM BE Anthony, M Dunn, BK Sherman, S TI Effects of hormone replacement therapy on cognitive and brain aging SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res AB Recent reports suggest that hormone therapy may be associated with a reduced risk for Alzheimer's disease and may offer some protection against age-associated declines in specific cognitive functions. The majority of these reports are based on observational studies, which are confounded by the "healthy user" bias-the tendency for women receiving hormone therapy to be younger, better educated, and have fewer medical problems. In one attempt to address these limitations, we conducted a series of studies examining effects of hormone therapy on cognitive and brain functioning in nondemented postmenopausal women in the Baltimore Longitudinal Study of Aging (BLSA). In this sample, women receiving hormone therapy and women who never received hormone therapy were comparable with respect to educational attainment, general medical health, and performance on a test of verbal knowledge. Despite these similarities, women receiving hormone therapy performed better on tests of verbal and visual memory compared to never-treated women. The two groups also differed in the patterns of regional brain activation evoked during performance of delayed verbal and figural memory tasks. Furthermore, longitudinal comparisons revealed greater relative blood flow increases over two years in women receiving hormone therapy for the hippocampus and other mesial temporal lobe structures that subserve memory. These observational findings from our studies in the BLSA have led to the development of a large-scale randomized clinical trial of hormone therapy and cognitive aging, the ancillary Women's Health Initiative Study of Cognitive Aging (WHISCA), and have important implications for studies of the effects of SERM's on cognitive and brain functioning. SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 203 EP 214 UT WOS:000173775800028 PM 11795355 ER PT S AU Miller, MM Monjan, AA Buchholtz, NS AF Miller, MM Monjan, AA Buchholtz, NS BE Anthony, M Dunn, BK Sherman, S TI Estrogen replacement therapy for the potential treatment or prevention of Alzheimer's disease SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res AB Alzheimer's disease (AD) is an irreversible, progressive brain disorder that occurs gradually and results in memory loss, behavior and personality changes, and a decline in cognitive abilities. Although basic biological data suggest that estrogen may have neuroprotective and neuroenhancing functions, a number of studies have produced conflicting findings on the use of estrogen for maintaining cognitive function in older people. This review summarizes clinical studies that have examined the effects of estrogen in women with AD. SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 223 EP 234 UT WOS:000173775800030 PM 11795357 ER PT S AU Parrott, EC AF Parrott, EC BE Anthony, M Dunn, BK Sherman, S TI Reproductive and related endocrine considerations - Introduction SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 235 EP 236 UT WOS:000173775800031 ER PT S AU Bellino, FL Finnegan, L AF Bellino, FL Finnegan, L BE Anthony, M Dunn, BK Sherman, S TI Translation of basic research: Finding the perfect SERM - Introduction SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 259 EP 260 UT WOS:000173775800035 PM 11795361 ER PT S AU Anthony, M Williams, JK Dunn, BK AF Anthony, M Williams, JK Dunn, BK BE Anthony, M Dunn, BK Sherman, S TI What would be the properties of an ideal SERM? SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res AB Selective estrogen receptor modulators (SERMs) are drugs that bind to the estrogen receptor (ER); in some tissues they act like estrogen (agonists), while in other tissues they oppose the action of estrogen (antagonists). The SERM tamoxifen acts as an estrogen antagonist in the breast in that it prevents and treats breast cancer, but it acts as an estrogen agonist in the endometrium, where it can induce cancer. Estrogen, and to a lesser extent SERMs, are effective in preventing and treating osteoporosis. Contrary to the prevalent hypothesis that estrogen provides benefit to women with regard to secondary prevention of coronary heart disease (CHD), randomized clinical trials have demonstrated that estrogen is associated with an increased risk of CHD in this population of women. Conflicting results have been reported on the effect of estrogens on cognitive function. The latest and largest randomized clinical trials have demonstrated a beneficial role in short-term memory in nondemented women, in contrast to the absence of such benefit in improving symptoms in women with Alzheimer's disease. Although estrogens have been used successfully to treat some menopausal symptoms such as hot flashes, the SERMs tamoxifen and raloxifene actually induce or increase hot flashes. Data on the beneficial and adverse effects of estrogen and SERMs are reported along with an elaboration of the constellation of properties that would characterize an ideal SERM working through the ER. SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 261 EP 278 UT WOS:000173775800036 PM 11795362 ER PT S AU McCaskill-Stevens, W AF McCaskill-Stevens, W BE Anthony, M Dunn, BK Sherman, S TI Weighing the benefits and risks in clinical trials and practice - Introduction SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 279 EP 279 UT WOS:000173775800037 ER PT S AU Gail, MH AF Gail, MH BE Anthony, M Dunn, BK Sherman, S TI The estimation and use of absolute risk for weighing the risks and benefits of selective estrogen receptor modulators for preventing breast cancer SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res AB In order to weigh the risks and benefits of intervention with selective estrogen response modifiers for preventing breast cancer, one needs to consider the effects of intervention on several health outcomes. For example, tamoxifen was shown to reduce the risks of breast cancer and hip fracture while increasing the risks of endometrial cancer and cardiovascular end points, including stroke. One approach to weighing risks and benefits is to estimate the net effect of the intervention on the absolute risk of each of the relevant health outcomes. To estimate this net effect, one needs to know not only the relative risk from the intervention, but also the absolute risk of the health outcome in the absence of intervention. Intervention trials yield unbiased estimates of intervention relative risks, but data are usually too limited to estimate these relative risks precisely for subgroups or for rare health outcomes. Moreover, intervention trials are usually too small to provide data for developing a model for estimating the individualized absolute risk of various health outcomes in the absence of intervention. The model of Gail et al. for projecting the individualized risk of breast cancer, as modified for use in the Breast Cancer Prevention Trial, has been validated. To weigh various risks and benefits of interventions, there is a need for research to develop such models for a range of health outcomes. SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 286 EP 291 UT WOS:000173775800039 PM 11795364 ER PT S AU Johnson, SR Dunn, BK Anthony, M AF Johnson, SR Dunn, BK Anthony, M BE Anthony, M Dunn, BK Sherman, S TI Defining benefits and risks for SERMs in clinical trials and clinical practice SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res AB Differences between clinical trials and clinical practice with respect to defining benefits and benefit/risk ratios for SERMs are discussed. These differences stem from the perception that there is discordance between the statistical significance and the "clinical meaningfulness" of research data in the minds of the practitioner and patient. One way that we can obtain data that are more clinically meaningful is to solicit input in the planning stages of clinical trials from practicing community clinicians and their patients. However, there are drawbacks to community input, such as potentially unrealistic expectations. A further issue is the need to characterize clinically meaningful drug benefits and acceptable benefit/risk ratios for a drug. Individual patients have differences regarding their views of optimal benefits and acceptable risks, so a method or tool for determining what is clinically meaningful would be helpful in presenting comprehensive information to the patient. To present useful information to clinicians, head-to-head comparisons of a new drug with a standard agent should be undertaken. NIH's support in this area of comparator trials is critical to their implementation. Estrogen has been considered the standard for comparison of agents for conditions associated with menopause in clinical trials. Estrogen has been the "gold standard" in clinical practice as well. In fact, challenging the position of estrogen, even where scientifically supported, has proven to be an uphill battle. In the practice setting, we elaborate the challenges of keeping up with the scientific literature and of then communicating this information in a fashion that is relevant to the individual patient. SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 304 EP 314 UT WOS:000173775800042 PM 11795368 ER PT S AU Anthony, M Johnson, K AF Anthony, M Johnson, K BE Anthony, M Dunn, BK Sherman, S TI Roles of industry, government, and academia in SERM development - Introduction SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 315 EP 316 UT WOS:000173775800043 PM 11795369 ER PT S AU Ansher, SS Scharf, R AF Ansher, SS Scharf, R BE Anthony, M Dunn, BK Sherman, S TI The Cancer Therapy Evaluation Program (CTEP) at the National Cancer Institute - Industry collaborations in new agent development SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res AB The mission of the Cancer Therapy Evaluation Program (CTEP), a clinical research program of the National Cancer Institute (NCI), is to reduce the burden of cancer. CTEP plans, reviews, and coordinates clinical trials for investigational anticancer agents, from the inception of protocols through the preparation and submission of Investigational New Drug Applications (INDs) to the Food and Drug Administration (FDA). CTEP also serves as a liaison to the FDA for the extramural clinical research community and industry collaborators. Other CTEP functions include managing, tracking, and reviewing clinical protocols as well as monitoring, planning, and maintaining regulatory compliance of the clinical trials. In addition, CTEP coordinates the distribution of the investigational agents from industry collaborators for use in all NCI-sponsored clinical trials. The advantages of collaborating with CTEP are de. scribed as well as details about the contractual framework, either a Clinical Trials Agreement (CTA) or a Cooperative Research and Development Agreement (CRADA), for such a collaboration. Many of the concerns raised by industry collaborators with respect to intellectual property, data access, and publications are also addressed. SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 333 EP 340 UT WOS:000173775800046 PM 11795372 ER PT S AU Dunn, BK Anthony, M Sherman, S Costantino, JP AF Dunn, BK Anthony, M Sherman, S Costantino, JP BE Anthony, M Dunn, BK Sherman, S TI Conclusions - Considerations regarding SERMs SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE Annals of the New York Academy of Sciences CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MD SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res AB The "considerations" addressed in this section consist of a number of thought-provoking issues and unresolved questions that emerge from the papers in this volume. The evidence for tamoxifen carcinogenicity in animal models and, to a more restricted extent, in humans has led some investigators to question whether SERMs are ready or appropriate for clinical testing-specifically, in a disease prevention setting involving healthy but high-risk individuals. There is, however, inconsistency in both efficacy and toxicity-specifically, carcinogenicity-between animal models and humans, leading others to question the value of basing the decision to proceed with clinical studies on preclinical results in animals. Although the molecular basis for SERM action is rapidly being clarified, the cellular activity of these agents is still elusive. We discuss the view that the efficacy of tamoxifen in breast cancer is based on its treatment of "occult cancers," or small collections of cancer cells that are not clinically apparent, not only in the context of prevention but also in the treatment setting. As part of our approach that assumes estrogen activity to be the foundation upon which SERM development is being modeled, we discuss the inconsistency between the epidemiologic data and prospective randomized data with respect to the relationship between estrogen use and cardiovascular disease. The need to validate surrogate markers of SERM action is discussed in relation to bone but is clearly relevant to all disease sites. The semantics used in describing SERM action as agonistic or antagonistic in relation to estrogen at various target sites has been inconsistent, especially in the clinical context. We attempt to dissect out some of the inconsistencies in semantics in the hope that this will contribute to improved communication of data resulting from SERM research. In the clinical arena, we begin with the premise that the large, simple randomized trial offers the optimal design for the testing of SERMs. In view of limited resources, however, we counter this position with alternative, if less desirable, approaches to the clinical format for SERM testing. Finally, we SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 352 EP 365 UT WOS:000173775800050 PM 11795376 ER PT S AU Sherman, S Dunn, BK AF Sherman, S Dunn, BK BE Anthony, M Dunn, BK Sherman, S TI Opportunities for future research SO SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS) SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT NIH Workshop on Selective Estrogen Receptor Modulators (SERMs) CY APR 26-28, 2000 CL BETHESDA, MARYLAND SP NIA, NCI, Div Canc Prevent, NHLBI, NIDDKD, NIAMSK, NIDCR, NIEHS, NICHHD, NIH Off Res Womens Hlth, Dept Hlth & Human Serv, Amer Federat Aging Res AB Remarkable progress has been made in SERM development. Profiles of new SERMs indicate great potential for efficacy in the prevention and treatment settings, in more than one physiological system, and with improved risk/benefit ratios. The concept of what is achievable with respect to broad-spectrum disease prevention and what constitutes an "ideal" SERM is likely to undergo considerable reevaluation over time. The development of new, more broadly efficacious SERMs will require continued exploration of the effects of estrogen at the cellular and molecular level in tissues and physiologic systems throughout the body. A better understanding is needed of the mechanisms of the biological actions that are mediated through major forms of the estrogen receptor. High priority must be placed on elucidation of the role of the coregulators of estrogen receptor (ER) action. The quest for a SERM(s) with the "optimal clinical profile" also constitutes a major research challenge with respect to designing clinical trials that are simultaneously parsimonious with respect to time, monetary, and human resources and yet capable of delivering unequivocal outcomes with respect to primary end points. A vigorous research effort is needed to identify highly sensitive and specific surrogate measures to facilitate future clinical studies. Research to identify and validate relevant measures of safety is also essential to inform the risk[benefit balance and, thus, the ultimate usefulness of SERMs and their potential for long-term use. Future advances in the modulation of ER action are likely to have profound effects-not only on diseases and conditions known (or later discovered) to be related to estrogen action, but on the development of paradigms for understanding and modifying the action of other nuclear hormone receptors in the prevention and treatment of additional age- and disease-related pathologies. SN 0077-8923 BN 1-57331-358-0 PY 2001 VL 949 BP 366 EP 374 UT WOS:000173775800051 PM 11795378 ER PT J AU Zullo, SJ AF Zullo, SJ TI Gene therapy of mitochondrial DNA mutations: A brief, biased history of allotopic expression in mammalian cells SO SEMINARS IN NEUROLOGY AB Successful treatment of mitochondrial DNA (mtDNA) mutations might be possible by construction of mtDNA-encoded protein genes so that they can be inserted into the nuclear genome and the protein expressed in the mitochondria (allotopic expression). This technique would require individual assembly of all 13 mtDNA-encoded protein genes with an aminoterminal leader peptide that directs the cytoplasmic translated protein to the mitochondrial membrane. The 13 allotopic genes could be inserted into the nuclear genome of a patient's stem cell that had been "cured" of its nascent mtDNA via ethidium bromide treatment (tho-zero cell). The rho-zero cell would be a uridine auxotroph, and recovery from uridine auxotrophy would indicate successful transformation. The patient's own cells could then be returned to the patient's body. With a selective advantage of recovered oxidative phosphorylation, the transformed cells could replace cells with mtDNA mutations. Results of experiments by us on allotopically expressed CHO ATPase6 and of experiments by other workers suggest that there might be competition with endogenous mtDNA-encoded proteins if the particular protein gene is not removed from the endogenous mitochondrial genomes. Thus, it is likely that an 13 mtDNA-encoded protein genes will need to be allotopically expressed, with concomitant removal of all mtDNA genomes, in order for this form of mtDNA gene therapy to be successful. SN 0271-8235 PY 2001 VL 21 IS 3 BP 327 EP 335 DI 10.1055/s-2001-17949 UT WOS:000171764900011 PM 11641822 ER PT J AU Sullivan, DC Hoffman, JM AF Sullivan, DC Hoffman, JM TI In vivo imaging of gene expression SO SEMINARS IN RADIATION ONCOLOGY SN 1053-4296 PD JAN PY 2001 VL 11 IS 1 BP 37 EP 46 DI 10.1053/srao.2001.18102 UT WOS:000166395600005 PM 11146041 ER PT J AU Krishna, MC Subramanian, S Kuppusamy, P Mitchell, JB AF Krishna, MC Subramanian, S Kuppusamy, P Mitchell, JB TI Magnetic resonance imaging for in vivo assessment of tissue oxygen concentration SO SEMINARS IN RADIATION ONCOLOGY SN 1053-4296 PD JAN PY 2001 VL 11 IS 1 BP 58 EP 69 DI 10.1053/srao.2001.18104 UT WOS:000166395600007 PM 11146043 ER PT J AU Bennink, ML Pope, LH Leuba, SH de Grooth, BG Greve, J AF Bennink, ML Pope, LH Leuba, SH de Grooth, BG Greve, J TI Single chromatin fibre assembly using optical tweezers SO SINGLE MOLECULES CT 3rd Linz Wintern Workshop CY FEB 02-05, 2001 CL LINZ, AUSTRIA AB Here we observe the formation of a single chromatin fibre using optical tweezers. A single lambda-DNA molecule was suspended between two micron-sized beads, one held by a micropipette and the other in an optical trap. The constrained DNA molecule was incubated with Xenopus laevis egg extract in order to reconstitute a single chromatin fibre. An eight-fold compaction of the DNA molecule was observed in real-time. The compaction kinetics were found to be strongly dependent upon the tension applied to the DNA molecule. We incorporated the analysis of Brownian motion to accurately determine the tension throughout the compaction process. At forces exceeding 10 pN complete inhibition of compaction was observed for the time scale of the experiment. We have previously shown that stretching of a reconstituted chromatin fibre results in discrete and quantized structural opening events that we can attribute to the unravelling of single nucleosomes. Assembly kinetics therefore provide insight into rates of nucleosome formation and we demonstrate the possibility of probing these kinetics under different experimental conditions. SN 1438-5163 PY 2001 VL 2 IS 2 BP 91 EP 97 DI 10.1002/1438-5171(200107)2:2<91::AID-SIMO91>3.3.CO;2-J UT WOS:000174074500007 ER PT J AU Leshner, A AF Leshner, A TI Drug abuse and addiction research into the 21st century: Where are we going from here? SO SOCIAL WORK IN HEALTH CARE SN 0098-1389 PY 2001 VL 33 IS 1 BP 5 EP 15 DI 10.1300/J010v33n01_02 UT WOS:000171932900004 PM 11718537 ER PT J AU Gordis, E AF Gordis, E TI Improving the old, embracing the new: Implications of alcohol research for future practice SO SOCIAL WORK IN HEALTH CARE CT 8th Colloquium of the Doris Siegel Momorial CY OCT 15, 1999 CL NEW YORK, NEW YORK AB Alcohol research has two important goals. The first of these is to evaluate existing therapies for treating alcoholism. The second, more long term goal is to increase understanding of the biology of alcoholism. The second, more long term goal is to increase understanding of the biology of alcoholism and to use this understanding to develop new targeted medications to prevent alcohol use problems and to improve treatment outcome. Considerable research progress has been made over the past three decades toward achieving each goal. The careful study of existing therapies and the development of both behavioral strategics and medications, such as naltrexone, have helped improve treatment success. New neuroscience techniques have led to an increased understanding of how alcohol's actions in the brain are related to the phenomenon of addiction, and new imaging techniques have permitted scientists to Study alcohol's effects on the brain and to link these effects to behavior in ways not even possible just a few years ago. Finally, genetics researchers are using both animal and human genetics techniques to identify the genes that con fer vulnerability to alcoholism and developing ways to apply this information to clinical populations. As a result of increased understanding of the biology of alcohol dependence, future clinicians will need to understand not,just the traditional behavioral nuances of alcoholism treatment, but the biology of alcohol dependence as well. (C) 2001 by The Haworth Press, Inc. All rights reserved. SN 0098-1389 PY 2001 VL 33 IS 1 BP 17 EP 41 DI 10.1300/J010v33n01_03 UT WOS:000171932900005 PM 11718535 ER PT J AU Hou, JW Hollenberg, J Charlson, ME AF Hou, JW Hollenberg, J Charlson, ME TI Can physicians' admission evaluation of patients' status help to identify patients requiring social work interventions? SO SOCIAL WORK IN HEALTH CARE AB Objective: To evaluate the utility of these physicians' initial clinical assessments in identifying patients admitted from their homes who subsequently require social work intervention for discharge planning. Design: Retrospective chart review of discharge disposition correlated with a prospective physician evaluation of patients. Setting: An academic medical center. Participants: Consecutive patients, (2,571) men and women, admitted at the New York Hospital between July 1, 1997 and October 31, 1997. Measurement: Prospective evaluation of clinical status, functional status, illness severity and stability by physicians within 24 hours of admission. Results: Older patients, sicker and less functional, have higher needs for social work intervention (P < 0.001). New nursing home placement patients were older and had worse function (P < 0.001). Total cost of hospitalization and length of stay were predicted by discharge disposition. Conclusion: Early discharge intervention has often been targeted as a potential mechanism to lower hospitalization cost and reduce length of stay. Age and physician evaluation of functional status at admission may provide early identification or those who require social work assistance. (C) 2001 by The Haworth Press, Inc. All rights reserved. SN 0098-1389 PY 2001 VL 33 IS 2 BP 17 EP 29 DI 10.1300/J010v33n02_02 UT WOS:000172317400002 PM 11760113 ER PT B AU Klausner, RD AF Klausner, RD BE Roco, MC Bainbridge, WS TI Challenges and vision for nanoscience and nanotechnology in medicine: Cancer as a model SO SOCIETAL IMPLICATIONS OF NANOSCIENCE AND NANOTECHNOLOGY CT Workshop on Societal Implications of Nanoscience and Nanotechnology CY SEP 28-29, 2000 CL NATL SCI FDN, ARLINGTON, VA HO NATL SCI FDN BN 0-7923-7178-X PY 2001 BP 203 EP 204 UT WOS:000178107000025 ER PT J AU Nishinaga, N Tatsumi, H Gill, M Akashi, H Nogawa, H Reategui, I AF Nishinaga, N Tatsumi, H Gill, M Akashi, H Nogawa, H Reategui, I TI Trans-Pacific Demonstration of Visible Human (TPD-VH) SO SPACE COMMUNICATIONS AB This paper describes the Visible Human (VH) part of the Trans-Pacific Demonstrations of the G7 Information Society-Global Interoperability for Broadband Network (GIBN) Projects. Aiming at a world-wide Visible Human Anatomical Co-laboratory, an application (VHP Viewer) was developed, which was used for data transmission testing (Trans-Pacific Demonstration of Visible Human) through broadband satellite links between the US and Japan. The demonstration includes (1) remote VH database access and (2) network multi-parallel computing access. It is shown that wide-area database access and high-speed multi-parallel computing could be effectively demonstrated via broadband satellite networks by circumventing a large time-delay by using the Mentat SkyX Gateway system and Personal File System (PFS). Elements of the demonstration verified here could be also applied to distance education and telemedicine as well as a postgenome project. SN 0924-8625 PY 2001 VL 17 IS 4 BP 303 EP 311 UT WOS:000174626800006 ER PT J AU Hawley, TS Telford, WG Hawley, RG AF Hawley, TS Telford, WG Hawley, RG TI "Rainbow" reporters for multispectral marking and lineage analysis of hematopoietic stem cells SO STEM CELLS AB Hematologic diseases potentially benefiting from gene-based therapies involving hematopoietic stem cells (HSCs) include hereditary hemoglobinopathies, immunodeficiency syndromes, and congenital bleeding disorders such as hemophilia A, as well as acquired diseases like AIDS, Successful treatment of these blood diseases with gene-modified HSCs requires high efficiency gene delivery to the target cell population and persistence of transgene expression following differentiation. We review flow cytometric procedures that permit simultaneous, noninvasive measurements of transgene expression and phenotypic discrimination of hematopoietic cell subsets. Central to this approach has been the recent development of a spectrum of blue, cyan, and yellowish-green fluorescent reporters based on the jellyfish Aequorea victor ia green fluorescent protein and the discovery of a red fluorescent protein in Discosoma coral. This methodology should facilitate the optimization of oncoretroviral and lentiviral vectorology and HSC transduction protocols for the ultimate purpose of HSC-directed gene therapy. SN 1066-5099 PY 2001 VL 19 IS 2 BP 118 EP 124 DI 10.1634/stemcells.19-2-118 UT WOS:000167577400007 PM 11239166 ER PT J AU Lekstrom-Himes, JA AF Lekstrom-Himes, JA TI The role of C/BPE epsilon in the terminal stages of granulocyte differentiation SO STEM CELLS AB As a consequence of its characterization using both in vitro and knockout mouse models, the myeloid-specific transcription factor, CCAAT/enhancer binding protein (C/EBP)epsilon, has been identified as a critical regulator of terminal granulopoiesis and one of the causative mutations in the human disease, neutrophil-specific granule deficiency. C/EBPs are a family of transcription factors sharing numerous structural and functional features and to date include C/EBP alpha, -beta, -gamma, -delta, -epsilon, and -zeta. C/EBP alpha was the first family member isolated and characterized, its essential role in hepatocyte and adipocyte differentiation demonstrated in knockout mouse models. Subsequent analysis of the hematopoietic elements in fetal mouse liver revealed its critical role in myelopoiesis. Understanding the role of C/EBP epsilon in terminal granulopoiesis in the context of other known transcription factors is ongoing with analysis of deficient and conditionally expressing cell lines and knockout models. Mouse models with targeted gene disruptions have contributed greatly to our understanding of the transcriptional regulation of granulopoiesis. Further manipulation of these models and other conditional expression systems have bypassed some of the limitations of knockout models and helped delineate the interactions of different transcription factors in affecting granulocyte development. Phenotypic expression of the loss of C/EBP epsilon in mice is extreme, resembling absolute neutropenia with systemic infection with P. aeruginosa. Future work will need to explore the regulation of C/EBP epsilon expression, its functional interactions with other transcriptional regulators such as PU.1, and its role in monocyte differentiation and function in the mouse. SN 1066-5099 PY 2001 VL 19 IS 2 BP 125 EP 133 DI 10.1634/stemcells.19-2-125 UT WOS:000167577400008 PM 11239167 ER PT J AU Bianco, P Riminucci, M Gronthos, S Robey, PG AF Bianco, P Riminucci, M Gronthos, S Robey, PG TI Bone marrow stromal stem cells: Nature, biology, and potential applications SO STEM CELLS AB Bone marrow stromal cells are progenitors of skeletal tissue components such as bone, cartilage, the hematopoiesis-supporting stroma, and adipocytes, In addition, they may be experimentally induced to undergo unorthodox differentiation, possibly forming neural and myogenic cells. As such, they represent an important paradigm of post-natal nonhematopoietic stem cells, and an easy source for potential therapeutic use, Along with an overview of the basics of their biology, we discuss here their potential nature as components of the vascular wall, and the prospects for their use in local and systemic transplantation and gene therapy. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 SN 1066-5099 PY 2001 VL 19 IS 3 BP 180 EP 192 DI 10.1634/stemcells.19-3-180 UT WOS:000168989700002 PM 11359943 ER PT S AU Long, LR Thoma, GR AF Long, LR Thoma, GR BE Yeung, MM Li, CS Lienhart, RW TI Feature indexing in a database of digitized x-rays SO STORAGE AND RETRIEVAL FOR MEDIA DATABASES 2001 SE Proceedings of SPIE CT Conference on Storage and Retrieval for Media Databases 2001 CY JAN 24-26, 2001 CL SAN JOSE, CA SP Soc Imaging Sci & Technol, SPIE AB We have the goal of developing computer algorithms for indexing a collection of digitized x-ray images for biomedical features important to researchers in the fields of osteoarthritis and vertebral morphometry. This indexing requires the segmentation of the image contents, identification of relevant anatomy in the segmented images, and classification of the identified anatomy into categories by which the image contents may be indexed. An example of the indexing detail that we have as a goal is, "disc space narrowing at vertebra location C5-6 ". This is a work in progress, with much current activity still in the segmentation step. We approach this segmentation as a hierarchical procedure with the distinctive regions of the image, including the general spine region, first being segmented at a gross level of detail, followed by a finer level segmentation of the spine region into individual vertebrae. In this paper we report on work done toward the gross level segmentation and also describe the image-level characteristics of one of the features targeted for the final indexing step. SN 0277-786X BN 0-8194-3993-2 PY 2001 VL 4315 BP 393 EP 403 DI 10.1117/12.410950 UT WOS:000168020500039 ER PT J AU Latour, LL Warach, S AF Latour, LL Warach, S TI Conventional diffusion weighted imaging in acute stroke overestimates apparent diffusion coefficient (ADC): Improved accuracy of ADC measurements of brain using Fluid-Inversion Prepared Diffusion (FLIPD) imaging SO STROKE SN 0039-2499 PD JAN PY 2001 VL 32 IS 1 MA 13 BP 318 EP 318 UT WOS:000166234300081 ER PT J AU Ezzeddine, MA Lev, MH McDonald, CT Rordorf, GA Oliveira-Filho, J Aksoy, F Segal, AZ Gonzalez, G Koroshetz, WJ AF Ezzeddine, MA Lev, MH McDonald, CT Rordorf, GA Oliveira-Filho, J Aksoy, F Segal, AZ Gonzalez, G Koroshetz, WJ TI Impact of contrast CT angiography and whole brain contrast CT perfusion study on the accuracy of cerebrovascular diagnosis in patients presenting with a major stroke-like syndrome SO STROKE SN 0039-2499 PD JAN PY 2001 VL 32 IS 1 MA 52 BP 325 EP 325 UT WOS:000166234300120 ER PT J AU Howard, G Shelton, BJ Brott, TG Baker, EA White, R Kuntz, RE Hobson, RW Marler, JR AF Howard, G Shelton, BJ Brott, TG Baker, EA White, R Kuntz, RE Hobson, RW Marler, JR CA CREST Investigators TI Parallel hypothesis testing for science and industry in a large randomized clinical trial SO STROKE SN 0039-2499 PD JAN PY 2001 VL 32 IS 1 MA 67 BP 328 EP 328 UT WOS:000166234300135 ER PT J AU Ezzeddine, MA Koroshetz, WJ Lah, S Gonzalez, G Lev, MH AF Ezzeddine, MA Koroshetz, WJ Lah, S Gonzalez, G Lev, MH TI Hemispheric infarct volume prediction by CT perfusion imaging SO STROKE SN 0039-2499 PD JAN PY 2001 VL 32 IS 1 MA P24 BP 343 EP 343 UT WOS:000166234300213 ER PT J AU Bernick, CB Kuller, LH Longstreth, WT Dulberg, C Manolio, TA Beauchamp, NJ Price, TR AF Bernick, CB Kuller, LH Longstreth, WT Dulberg, C Manolio, TA Beauchamp, NJ Price, TR TI Silent brain MRI infarcts and subsequent stroke type in the Cardiovascular Health Study SO STROKE SN 0039-2499 PD JAN PY 2001 VL 32 IS 1 MA P136 BP 363 EP 363 UT WOS:000166234300324 ER PT J AU Nyquist, PA Hamm, T Nagle, J Kauffman, D DeGraba, TJ AF Nyquist, PA Hamm, T Nagle, J Kauffman, D DeGraba, TJ TI New single nucleotide polymorphisms in the shear responsive MCP-1 promoter region in atherosclerosis. SO STROKE SN 0039-2499 PD JAN PY 2001 VL 32 IS 1 MA P160 BP 368 EP 368 UT WOS:000166234300348 ER PT J AU Warach, S Rodriguez, SU Olan, WJ AF Warach, S Rodriguez, SU Olan, WJ TI Routine screening for IV tPA therapy less than 3 hours with MRI: initial clinical experience SO STROKE SN 0039-2499 PD JAN PY 2001 VL 32 IS 1 MA P177 BP 371 EP 371 UT WOS:000166234300365 ER PT J AU Rodriguez, SU DeGraba, T Hamm, T Nyquist, P Hallenbeck, J Warach, S AF Rodriguez, SU DeGraba, T Hamm, T Nyquist, P Hallenbeck, J Warach, S TI The impact of establishing a stroke center at a community hospital on the use of thrombolytic therapy: the NINDS-Suburban Hospital Stroke Center experience SO STROKE SN 0039-2499 PD JAN PY 2001 VL 32 IS 1 MA P192 BP 374 EP 374 UT WOS:000166234300380 ER PT J AU Rothman, RB Baumann, MH Dersch, CM Romero, DV Rice, KC Carroll, FI Partilla, JS AF Rothman, RB Baumann, MH Dersch, CM Romero, DV Rice, KC Carroll, FI Partilla, JS TI Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin SO SYNAPSE AB A large body of evidence supports the hypothesis that mesolimbic dopamine (DA) mediates, in animal models, the reinforcing effects of central nervous system stimulants such as cocaine and amphetamine. The role DA plays in mediating amphetamine-type subjective effects of stimulants in humans remains to be established. Both amphetamine and cocaine increase norepinephrine (NE) via stimulation of release and inhibition of reuptake, respectively. If increases in NE mediate amphetamine-type subjective effects of stimulants in humans, then one would predict that stimulant medications that produce amphetamine-type subjective effects in humans should share the ability to increase NE. To test this hypothesis, we determined, using in vitro methods, the neurochemical mechanism of action of amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), (+)-methamphetamine, ephedrine, phentermine, and aminorex. As expected, their rank order of potency for DA release was similar to their rank order of potency in published self-administration studies. Interestingly, the results demonstrated that the most potent effect of these stimulants is to release NE. Importantly, the oral dose of these stimulants, which produce amphetamine-type subjective effects in humans, correlated with the their potency in releasing NE, not DA, and did not decrease plasma prolactin, an effect mediated by DA release. These results suggest that NE may contribute to the amphetamine-type subjective effects of stimulants in humans. Published 2001 Wiley-Liss, Inc. SN 0887-4476 PD JAN PY 2001 VL 39 IS 1 BP 32 EP 41 DI 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 UT WOS:000165493100005 PM 11071707 ER PT J AU Grimm, JW Chapman, MA Zahm, DS See, RE AF Grimm, JW Chapman, MA Zahm, DS See, RE TI Decreased choline acetyltransferase immunoreactivity in discrete striatal subregions following chronic haloperidol in rats SO SYNAPSE AB Neuronal loss within the basal ganglia has been hypothesized to play a role in movement disorders (e.g., tardive dyskinesia) that often occur following chronic neuroleptic treatment. Previous studies in animal models have provided some support to this possibility, but have not assessed regionally specific changes after chronic neuroleptic administration. The present study examined whether counts of neurons containing acetylcholine, described as large aspiny type II neurons, were altered in subregions of the corpus striatum and nucleus accumbens following chronic haloperidol administration in rats. Rats were administered haloperidol decanoate (21 mg/kg, i.m.) or vehicle every third week for 24 weeks. Following 4 weeks of withdrawal from the drug, predefined regions were examined for choline acetyltransferase (ChAT) immunoreactive (ir) cells. Compared to the vehicle group, the haloperidol group showed significant reductions in ChAT-ir cell counts in the ventrolateral striatum, nucleus accumbens core, and nucleus accumbens lateral shell. No significant differences were found in the other regions examined: dorsolateral striatum, dorsomedial striatum, ventromedial striatum, nucleus accumbens medial shell, and horizontal limb of the diagonal band. These findings indicate that there may be regionally specific alterations in ChAT-ir cells following chronic haloperidol treatment, supporting previous hypotheses of striatal cholinergic cell loss resulting from chronic neuroleptic treatment. More importantly, the regions affected (ventrolateral striatum and nucleus accumbens) are critical in the regulation of oral movement, thus suggesting that alterations in cholinergic cell activity, and perhaps actual loss of cholinergic cells in these regions, may be important in the manifestation of late-onset oral dyskinesia. (C) 2001 Wiley-Liss, Inc. SN 0887-4476 PD JAN PY 2001 VL 39 IS 1 BP 51 EP 57 DI 10.1002/1098-2396(20010101)39:1<51::AID-SYN7>3.0.CO;2-Z UT WOS:000165493100007 PM 11071709 ER PT J AU Xu, H Hashimoto, A Rice, KC Jacobson, AE Thomas, JB Carroll, FI Lai, J Rothman, RB AF Xu, H Hashimoto, A Rice, KC Jacobson, AE Thomas, JB Carroll, FI Lai, J Rothman, RB TI Opioid peptide receptor studies. 14. Stereochemistry determines agonist efficacy and intrinsic efficacy in the [S-35]GTP-gamma-S functional binding assay SO SYNAPSE AB Previous data obtained with the cloned rat mu opioid receptor demonstrated that stereochemistry affects the four parameters of the ligand-receptor interaction: potency (ED50), efficacy (maximal stimulation), intrinsic efficacy (effect as a function of receptor occupation), and binding affinity. This study evaluated the activities of structurally diverse opioid receptor ligands in the [S-35]GTP-gamma -S binding assay, comparing the relationship between receptor binding, activation, efficacy, and intrinsic efficacy. The data, obtained with cloned rat mu receptors, demonstrated that an analgetic, (-)-5-m-hydroxyphenyl-2-methylmorphan (NIH8508), and its (+)-isomer (NIH8509), behave as partial agonists, but had different intrinsic efficacy in the [S-35]GTP-gamma -S binding assay. Replacement of the methyl group with the phenethyl group on the piperidine nitrogen of NIH8508 and NIH8509 [(1R,5S)-AH019 and (1S,5R)-AH019] increased affinity for the mu receptor and eliminated any agonist effect, supporting the hypothesis that certain structural features make these compounds antagonists. These study also show that all of the fully efficacious mu agonists studied here had high levels of intrinsic efficacy, producing a 50% response at about 10% receptor occupancy. Comparison of the binding K-i in competitively inhibiting [I-125]IOXY binding to the functional K-i for opioid antagonists [K-i(IOXY)/K-i(GTP-gamma -S)] provides more detailed evidence that the [S-35]GTP-gamma -S binding assay can be used to reliably determine apparent functional antagonist K-i values in addition to agonist ED50, efficacy and intrinsic efficacy. Published 2001 Wiley-Liss, Inc. SN 0887-4476 PD JAN PY 2001 VL 39 IS 1 BP 64 EP 69 DI 10.1002/1098-2396(20010101)39:1<64::AID-SYN9>3.0.CO;2-J UT WOS:000165493100009 PM 11071711 ER PT J AU Dawson, NM Hamid, EH Egan, MF Meredith, GE AF Dawson, NM Hamid, EH Egan, MF Meredith, GE TI Changes in the pattern of brain-derived neurotrophic factor immunoreactivity in the rat brain after acute and subchronic haloperidol treatment SO SYNAPSE AB Our earlier work has shown that repeated administration of classical neuroleptic drugs gives rise to structural alterations in target regions of the mesolimbic pathway, most notably, nucleus accumbens. Such changes could be responsible for the efficacious or motor side effects associated with these drugs. Growth factors such as brain-derived neurotrophic factor (BDNF) provide trophic support for dopaminergic neurons during development and mediate synaptic and morphological plasticity in numerous regions of the adult CNS. The present study examines whether BDNF is altered in the mesolimbic pathway by classical neuroleptic treatment. Animals were administered haloperidol, 0.5 mg/kg, or vehicle, i.p., for either 3 or 21 days, followed by transcardiac perfusion with fixative. Three days of haloperidol administration dramatically decreased BDNF immunostaining in the neurons and fibers of the prefrontal cortex, hippocampus (dentate gyrus, CA2, and CA3), extended amygdala, and ventral tegmental area. BDNF-immunoreactive fibers virtually disappeared from the neostriatum and nucleus accumbens. Subchronic (21 days) treatment led to a rebound in BDNF immunoreactivity in most cell bodies but not in fibers. These results show that blockade of dopaminergic receptors with haloperidol rapidly downregulates BDNF in reward and emotional centers of the brain. Such rapid inactivation and subsequent reappearance of BDNF immunoreactivity could affect synaptic strength and plasticity and therefore be important preliminary steps in the cascade of neuronal events that lead to the efficacious or detrimental side effects of classical neuroleptic drugs. (C) 2001 Wiley-Liss, Inc. SN 0887-4476 PD JAN PY 2001 VL 39 IS 1 BP 70 EP 81 DI 10.1002/1098-2396(20010101)39:1<70::AID-SYN10>3.0.CO;2-J UT WOS:000165493100010 PM 11071712 ER PT J AU Ramesha, AR Roy, AK AF Ramesha, AR Roy, AK TI Convenient synthesis of 2-(2-phenylethyl)benzoic acid: A key intermediate in the synthesis of dibenzosuberone SO SYNTHETIC COMMUNICATIONS AB A convenient and improved synthesis of 2-(2-phenylethyl) benzoicacid, a key intermediate in the synthesis of dibenzosuberone is described. SN 0039-7911 PY 2001 VL 31 IS 16 BP 2419 EP 2422 DI 10.1081/SCC-100105118 UT WOS:000170711400005 ER PT B AU Oldfield, EH DeVroom, HL Heiss, JD AF Oldfield, EH DeVroom, HL Heiss, JD BE Tamaki, N Batzdorf, U Nagashima, T TI Hydrodynamics of syringomyelia SO SYRINGOMYELIA: CURRENT CONCEPTS IN PATHOGENESIS AND MANAGEMENT CT International Symposium on Syringomyelia CY JUN 16-17, 2000 CL KOBE, JAPAN SP Japanese Minist Educ, Sci Sports & Culture, Osaka Pharmaceut Manufacturers Assoc, Tsutomu Nakauchi Fdn, Kobe Convent & Visitors Assoc AB Our studies demonstrate a mechanism of the pathogenesis of syringomyelia in which (1) the Chiari malformation partially obstructs the cerebrospinal fluid (CSF) pathways at the foramen magnum; (2) the normally rapid efflux and influx of CSF between the head and the spine, which normally compensates for brain expansion and contraction during the cardiac cycle, is blocked; (3) the cerebellar tonsils are displaced during the cardiac cycle, in lieu of CSF, creating a piston effect on the partially entrapped spinal subarachnoid space; (4) enlarged cervical subarachnoid pressure waves are created, which compress the spinal cord from without, direct CSF into the spinal cord, and cause pulsatile syrinx flow; which in turn (5) leads to syrinx progression. These findings are consistent with an origin of the syrinx fluid by pulsatile-facilitated transmission of CSF through the spinal cord. This mechanism of syrinx origin, progression, and resolution arises outside, not inside, the spinal cord. Thus, extraarachnoidal craniocervical decompression and duroplasty reverses the mechanism of syringomyelia progression without invading the central nervous system parenchyma or the CSF pathways and consistently provides a safe and effective treatment of patients with Chiari I and syringomyelia. BN 4-431-70305-5 PY 2001 BP 75 EP 89 UT WOS:000172736800009 ER PT J AU Brady, RO AF Brady, RO TI Tay-Sachs disease: The search for the enzymatic defect SO TAY-SACHS DISEASE SE ADVANCES IN GENETICS INCORPORATING MOLECULAR GENETIC MEDICINE SN 0065-2660 PY 2001 VL 44 BP 51 EP 60 UT WOS:000172294800006 PM 11596998 ER PT J AU Proia, RL AF Proia, RL TI Cloning the beta-hexosaminidase genes SO TAY-SACHS DISEASE SE ADVANCES IN GENETICS INCORPORATING MOLECULAR GENETIC MEDICINE RI Proia, Richard/A-7908-2012 SN 0065-2660 PY 2001 VL 44 BP 127 EP 135 UT WOS:000172294800011 PM 11596978 ER PT J AU Proia, RL AF Proia, RL TI Targeting the hexosaminidase genes: Mouse models of the G(M2) gangliosidoses SO TAY-SACHS DISEASE SE ADVANCES IN GENETICS INCORPORATING MOLECULAR GENETIC MEDICINE RI Proia, Richard/A-7908-2012 SN 0065-2660 PY 2001 VL 44 BP 225 EP 231 UT WOS:000172294800018 PM 11596985 ER PT J AU Silverman, DT AF Silverman, DT TI Risk factors for pancreatic cancer: A case-control study based on direct interviews SO TERATOGENESIS CARCINOGENESIS AND MUTAGENESIS AB The etiology of pancreatic cancer is poorly understood, partly because of the inconsistency of findings among case-control studies of pancreatic cancer. Because of the unfavorable prognosis for pancreatic cancer, many case-control studies have been based largely on interviews with next of kin, who are known to report less reliable information on potential risk factors than original respondents. The purpose of this study was to estimate the effects of speculative risk factors such as dietary/nutritional factors and alcohol drinking, as well as those of established risk factors such as cigarette smoking, diabetes mellitus, and family history of pancreatic cancer, on pancreatic cancer risk based solely on direct interviews. This investigation was a population-based case-control study of pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and ten New Jersey counties from August 1986 through April 1989. Direct interviews were conducted with 526 incident cases and 2,153 population controls. This study revealed a significant interaction between body mass index and caloric intake that was consistent by both race and gender. Subjects with elevated body mass index and caloric intake had increased risk, whereas those with elevated values for one of these factors but not the other experienced no increased risk. This finding suggests that energy balance may play a major role in pancreatic carcinogenesis. Diabetes mellitus was also a risk factor for pancreatic cancer, as well as a possible complication of the tumor. Our data are consistent with a key role for hyperinsulinemia in pancreatic carcinogenesis, particularly among non-diabetics with an elevated body mass index. A three-fold risk of pancreatic cancer among first-degree relatives of affected individuals was apparent. An increased risk also was associated with a family history of colon, endometrial, ovary, and breast cancer, suggesting a possible link to hereditary non-polyposis colon cancer. Our findings support a causal role for cigarette smoking in pancreatic carcinogenesis. Alcohol drinking at levels typically consumed by the general population of the United States did not appear to be a risk factor for pancreatic cancer, although heavy drinking may be related to risk, particularly in blacks. Teratogenesis Carcinog. Mutagen. 21:7-25, 2001. Published 2001 Wiley-Liss, Inc.(dagger) OI Kleeff, Jorg/0000-0003-3432-6669 SN 0270-3211 PY 2001 VL 21 IS 1 BP 7 EP 25 DI 10.1002/1520-6866(2001)21:1<7::AID-TCM3>3.0.CO;2-A UT WOS:000166205400003 PM 11135318 ER PT J AU Aronson, DL Krizek, DM Rick, ME AF Aronson, DL Krizek, DM Rick, ME TI A rapid assay for the vWF protease SO THROMBOSIS AND HAEMOSTASIS SN 0340-6245 PD JAN PY 2001 VL 85 IS 1 BP 184 EP 185 UT WOS:000166544100034 PM 11204576 ER PT J AU Shopland, DR AF Shopland, DR TI Historical perspective: the low tar lie SO TOBACCO CONTROL SN 0964-4563 PY 2001 VL 10 SU 1 BP I1 EP I3 UT WOS:000172833100001 PM 11740037 ER PT J AU Davis, BJ Travlos, G McShane, T AF Davis, BJ Travlos, G McShane, T TI Reproductive endocrinology and toxicological pathology over the life span of the female rodent SO TOXICOLOGIC PATHOLOGY AB Understanding the pathology of the female reproductive system with respect to toxicology requires a basic understanding of morphology and function of the system over time because the nature of the female reproductive system is cyclical. Thus, the morphology and the endocrinology is dependent on age and time, as form follows function follows form. The life span of the rodent is used as an outline to present an overview of key morphological and endocrinological events important for toxicologic pathologists to consider in study evaluations. Environmental and pharmaceutical compounds differentially impact the organs individually and/or the system in its entirety in a time- and dose-dependent way. Examples are used to illustrate the consequences of exposures at different times with different outcomes. SN 0192-6233 PD JAN-FEB PY 2001 VL 29 IS 1 BP 77 EP 83 DI 10.1080/019262301301418874 UT WOS:000166894000009 PM 11215687 ER PT J AU Bennett, LM McAllister, KA Ward, T Malphurs, J Collins, NK Seely, JC Davis, BJ Wiseman, RW AF Bennett, LM McAllister, KA Ward, T Malphurs, J Collins, NK Seely, JC Davis, BJ Wiseman, RW TI Mammary tumor induction and premature ovarian failure in Apc(Min) mice are not enhanced by Brca2 deficiency SO TOXICOLOGIC PATHOLOGY AB Inherited BRCA2 mutations predispose individuals to breast cancer and increase risk at other sites. Recent studies have suggested a role for the APC I1307K allele as a low-penetrance breast cancer susceptibility gene that enhances the phenotypic effects of BRCA1 and BRCA2 mutations. To model the consequences of inheriting mutant alleles of the BRCA2 and APC tumor suppressor genes, we examined tumor outcome in C57BL/6 mice with mutations in the Brca2 and Ape genes. We hypothesized that if the Brca2 and Ape genes were interacting to influence mammary tumor susceptibility. then mammary tumor incidence and/or multiplicity would be altered in mice that had inherited mutations in both genes. Female and male offspring treated with a single IP injection of 50 mg/kg N-ethyl-N-nitrosourea (ENU) at 35 days of age developed mammary adenoacanthomas by 100 days of age. The female Ape-mutant and Brca2/Apc double-mutant progeny had mean mammary tumor multiplicities of 6.7 +/- 2.8 and 7.2 +/- 2.7, respectively. compared to wild-type and Brca2-mutant females, which had mean mammary tumor multiplicities of 0.1 +/- 0.4 and 0.3 +/- 0.5. respectively. Female ENU-treated Ape-mutant and Brca2/Apc double heterozygotes were also susceptible to premature ovarian failure. Thus, the inheritance of an Ape mutation predisposes ENU-treated female and male mice to mammary tumors and, in the case of female mice, to ovarian failure. These results indicate that mammary tumor development in Ape-mutant mice can progress independently of ovarian hormones. The Ape mutation-driven phenotypes were not modified by mutation of Brca2, perhaps because Brca2 acts in a hormonally dependent pathway of mammary carcinogenesis. SN 0192-6233 PD JAN-FEB PY 2001 VL 29 IS 1 BP 117 EP 125 UT WOS:000166894000014 PM 11215675 ER PT J AU Travlos, GS Wilson, RE Murrell, JA Chignell, CF Boorman, GA AF Travlos, GS Wilson, RE Murrell, JA Chignell, CF Boorman, GA TI The effect of short intermittent light exposures on the melatonin circadian rhythm and NMU-induced breast cancer in female F344/N rats SO TOXICOLOGIC PATHOLOGY AB We investigated the effects of altered endogenous nighttime melatonin concentrations on mammary tumor production in an N-nitroso-N-methylurea (NMU)-induced breast cancer model in female Fischer 344 (F344)/N rats. Experiments were designed 1) to evaluate whether short-duration intermittent exposures to light at night would affect the nocturnal rise of melatonin, resulting in a decrease in nighttime serum melatonin concentrations. 2) to evaluate whether any suppression of nighttime serum melatonin concentrations could be maintained for a period of weeks, and 3) to determine the effects of suppressed serum melatonin concentrations on the incidence and progression of NMU-induced breast cancer. In vivo studies were used to assess serum melatonin concentrations after 1 day and 2 and 10 weeks of nightly administration of short-duration intermittent light exposure at night and incidence of NMU-induced tumors. Five 1-minute exposures to incandescent light every 2 hours after the start of the dark phase of the light:dark cycle decreased the magnitude of the nocturnal rise of serum melatonin concentrations in rats by approximately 65%. After 2 weeks of nightly intermittent light exposures. an average decrease of the peak nighttime serum melatonin concentrations of approximately 35% occurred. The amelioration continued and, at 10 weeks, peak nighttime serum melatonin concentrations were still decreased, by approximately 25%. Because peak endogenous nighttime serum melatonin values could be moderately suppressed for at least 10 weeks, a 26-week NMU mammary tumor study was conducted. Serum melatonin concentrations and incidence, multiplicity, and weight of NMU-induced mammary tumors were assessed. A group of pinealectomized (Px) animals was also included in the tumor study. No effect on the development of mammary tumors in an NMU-induced tumor model in rats occurred when endogenous nighttime serum melatonin concentrations were moderately suppressed by short-duration intermittent light exposures at night. At necropsy, there were no alterations in mammary tumor incidence (28/40 NMU controls, 28/40 NMU + light, 31/40 NMU + Pr). multiplicity (2.18 tumors/tumor-bearing NMU control. 1.89 NMU + light, 2.39 NMU + Pr). or average tumor weight (1.20 g NMU control, 1.19 g NMU + light, 0.74 g NMU + Pr). Tumor burden had no effect on the serum melatonin cycle. At 26 weeks, however, animals exposed to intermittent light at night exhibited approximately 3-fold higher serum melatonin concentrations as compared with controls. Additionally, rats that had been pinealectomized at 4 weeks of age had serum melatonin concentrations that were markedly higher than the expected baseline concentrations for pinealectomized rats (<15 pg/ml), suggesting the reestablishment of a melatonin cycle. This finding was unexpected and suggests that melatonin can be produced by an organ or tissue other than the pineal gland. SN 0192-6233 PD JAN-FEB PY 2001 VL 29 IS 1 BP 126 EP 136 DI 10.1080/019262301301418937 UT WOS:000166894000015 PM 11215676 ER PT J AU Hursting, SD Perkins, SN Donehower, LA Davis, BJ AF Hursting, SD Perkins, SN Donehower, LA Davis, BJ TI Cancer prevention studies in p53-deficient mice SO TOXICOLOGIC PATHOLOGY AB Future progress in mechanism-based cancer prevention research may be facilitated by animal models displaying specific genetic susceptibilities for cancer, such as mice deficient in 1 (+/-) or both (-/-) alleles of the p53 tumor suppressor gene. We observed in p53-/- mice that calorie restriction (CR) increased the latency of spontaneous tumor development (mostly lymphomas) by approximately 75%, decreased serum insulin-like growth factor-1 (IGF-1) and leptin levels, slowed thymocyte cell cycle traverse, and induced apoptosis in immature thymocytes. In p53+/- mice, CR and a 1 d/wk fast each delayed spontaneous tumor development (a mix of Lymphomas, sarcomas, and epithelial tumors) and decreased serum IGF-I and leptin levels, even when begun late in life. In p53 +/-Wnt-I transgenic mice, a mammary tumor model, the same interventions increased mammary tumor latency and reduced mean serum IGF-1 and leptin levels to <50% of those of control mice. We capitalized on the susceptibility of p53+/- mice to chronic, low-dose aromatic amine-induced bladder carcinogenesis to develop a useful model for evaluating bladder cancer prevention approaches. These examples clearly indicate that mice with specific land humanlike) genetic susceptibilities for cancer are powerful models for testing interventions that may inhibit carcinogenesis in humans. SN 0192-6233 PD JAN-FEB PY 2001 VL 29 IS 1 BP 137 EP 141 DI 10.1080/019262301301418946 UT WOS:000166894000016 PM 11215677 ER PT J AU Rier, SE Turner, WE Martin, DC Morris, R Lucier, GW Clark, GC AF Rier, SE Turner, WE Martin, DC Morris, R Lucier, GW Clark, GC TI Serum levels of TCDD and dioxin-like chemicals in rhesus monkeys chronically exposed to dioxin: Correlation of increased serum PCB levels with endometriosis SO TOXICOLOGICAL SCIENCES AB Humans and animals are exposed daily to a complex mixture of polyhalogenated aromatic hydrocarbons (PHAHs). Previous work has shown that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with a dose-dependent increase in the incidence and severity of endometriosis in the rhesus monkey. Dioxin-like chemicals can also exert effects in combination with TCDD via the aryl hydrocarbon receptor. This study demonstrates that the serum levels of TCDD and specific dioxin-like PHAH congeners were increased in TCDD-treated animals with endometriosis 13 years after the TCDD exposure. Nine TCDD-exposed and 6 unexposed female rhesus monkeys were evaluated for serum content of relevant compounds and for endometriosis by surgical laparoscopy. Additional studies were done on 4 animals that died 7 to 11 years after exposure to TCDD and 4 lead-treated animals with no history of PHAH treatment. For TCDD-exposed and unexposed animals, TCDD exposure correlated with an increased serum TCDD concentration. Furthermore, TCDD exposure and an elevated serum TCDD concentration were associated with increased serum levels of triglycerides, 1,2,3,6,7,8-hexachlorodibenzofuran, 3,3',4,4'-tetrachlorobiphenyl (TCB) and 3,3'4,4',5-pentachlorobiphenyl (PnCB). Importantly, the animals with elevated serum levels of 3,3',4,4'-TCB, 3,3',4,4',5-PnCB and an increased total serum TEQ had a high prevalence of endometriosis, and the severity of disease correlated with the serum concentration of 3,3',4,4'-TCB. Increased serum concentrations of coplanar PCBs were also present in lead-treated animals. Implications of these findings for human health and the prevalence of endometriosis in humans will be discussed. SN 1096-6080 PD JAN PY 2001 VL 59 IS 1 BP 147 EP 159 DI 10.1093/toxsci/59.1.147 UT WOS:000166392500016 PM 11134554 ER PT J AU Liu, T Liu, J LeCluyse, EL Zhou, YS Cheng, ML Waalkes, MP AF Liu, T Liu, J LeCluyse, EL Zhou, YS Cheng, ML Waalkes, MP TI Application of cDNA microarray to the study of arsenic-induced liver diseases in the population of Guizhou, China SO TOXICOLOGICAL SCIENCES AB Arsenic is an environmental toxicant and a human carcinogen. Epidemiology studies link human arsenic exposure to various diseases and cancers, including liver diseases and hepatocellular carcinoma. However, the molecular mechanisms for arsenic toxicity and carcinogenicity are poorly understood. To better understand these mechanisms, we used the human cancer cDNA expression array to profile aberrant gene expression in arsenic-exposed populations in Guizhou, China. The selected patients had a history of exposure to environmental arsenic for at least 6-10 years, and had arsenic-induced skin lesions and hepatomegaly. Samples were obtained by liver needle biopsy. Histology showed degenerative liver lesions, such as chronic inflammation, vacuolation, and focal necrosis. The University of North Carolina Hospitals provided normal human liver tissues from surgical resection or rejected transplants, Microarray was performed with total RNA from liver samples, and signal intensities were analyzed with AtlasImage software and normalized with 9 housekeeping genes. Means and SEM were calculated for statistical analysis. Approximately 60 genes (10%) were differentially expressed in arsenic-exposed human livers compared to controls. The differentially expressed genes included those involved in cell-cycle regulation, apoptosis, DNA damage response, and intermediate filaments. The observed gene alterations appear to be reflective of hepatic degenerative lesions seen in the arsenic-exposed patients. This array analysis revealed important patterns of aberrant gene expression occurring with arsenic exposure in human livers. Aberrant expressions of several genes were consistent with the results of array analysis of chronic arsenic-exposed mouse livers and chronic arsenic-transformed rat liver cells. Clearly, a variety of gene expression changes may play an integral role in arsenic hepatotoxicity and possibly carcinogenesis. OI LeCluyse, Edward/0000-0002-2149-8990 SN 1096-6080 PD JAN PY 2001 VL 59 IS 1 BP 185 EP 192 UT WOS:000166392500020 ER PT J AU Rose, ML Bradford, BU Germolec, DR Lin, M Tsukamoto, H Thurman, RG AF Rose, ML Bradford, BU Germolec, DR Lin, M Tsukamoto, H Thurman, RG TI Gadolinium chloride-induced hepatocyte proliferation is prevented by antibodies to tumor necrosis factor alpha SO TOXICOLOGY AND APPLIED PHARMACOLOGY AB Gadolinium chloride (GdCl3) destroys large Kupffer cells and has been used extensively in mechanistic studies in a number of disease and toxicity processes; however, it cannot be used to study hepatocyte turnover since it increases cell proliferation itself. The mechanism by which GdCl3 activates cell turnover in liver is unknown, but several possibilities exist. Here it was demonstrated that a direct mitogenic action on hepatocytes is unlikely since GdCl3 did not stimulate the growth of primary rat hepatocyte in vitro. Therefore, it was hypothesized that GdCl3 acts indirectly through mitogenic cytokines of nonparenchymal cell origin. Antibodies to tumor necrosis factor alpha (TNF alpha) were used to evaluate if TNF alpha is causally responsible for GdCl3-induced cell proliferation. GdCl3 treatment of rats in vivo increased hepatocyte replication 5-fold in 24 h and 3-fold in 48 h. Pretreatment with specific anti-TNF alpha antibodies completely prevented these effects. However, when antibody treatment was delayed until 24 h after GdCl3,, increased cell proliferation was not prevented, suggesting that TNF alpha production during the first 24 h after treatment is responsible for activation of a signaling cascade involving other mitogens that sustain hepatocyte replication at 48 h. Twenty-four hours after treatment with GdCl3, TNF alpha mRNA transcripts were increased 2-fold over control, an effect that was prevented by pretreatment with anti-TNF alpha antibody. NF kappaB, which is known to be involved in TNF alpha transcription, was activated by GdCl3 about 4.5-fold over control 8 h after treatment in vivo, an increase not observed when antibodies to TNF alpha were present. When GdCl3, was added to macrophages in culture, TNF alpha was nearly doubled 4 h after treatment. Additionally, conditioned media harvested from macrophages treated with GdCl3 for 2 to 8 h stimulated the growth of HepG2 cells in culture about 2-fold, while antibodies to TNF alpha completely prevented this effect. Taken together, these data are consistent with the hypothesis that TNF alpha released from Kupffer cells at early time points prior to their destruction is causally responsible for triggering a cascade of events responsible for GdCl3-induced cell proliferation. (C) 2001 Academic Press. SN 0041-008X PD JAN 1 PY 2001 VL 170 IS 1 BP 39 EP 45 DI 10.1006/taap.2000.9077 UT WOS:000166515100005 PM 11141354 ER PT J AU Stroncek, DF Carter, LB Procter, JL Dale, JK Straus, SE AF Stroncek, DF Carter, LB Procter, JL Dale, JK Straus, SE TI RBC autoantibodies in autoimmune lymphoproliferative syndrome SO TRANSFUSION AB BACKGROUND: Patients with autoimmune lymphoproliferative syndrome (ALPS) have an autosomal dominant genetic defect that affects lymphocyte apoptosis and is associated with chronic nonmalignant lymphadenopathy, splenomegaly, and autoimmunity, particularly affecting RBGs, WBCs, and platelets. STUDY DESIGN AND METHODS: DATs were performed on 34 consecutive patients with ALPS and 37 of their clinically unaffected relatives. The effects of age, sex, race, and immunoglobulin levels on the incidence of autoantibodies and clinical hemolysis were assessed. RESULTS: The DAT was positive in 21 (62%) of ALPS patients but in only 1 (3%) of their relatives (p = 0.001). The DAT reacted because of IgG alone in 43 percent, complement alone in 5 percent, and IgG plus complement in 19 percent; 33 percent of the patients' cells had a positive reaction with polyspecific reagent only. All 10 ALPS patients with a history of hemolytic anemia had a positive DAT Sixty percent of them had only IgG on their cells, 30 percent had IgG and complement, and 10 percent reacted only with polyspecific reagent. Of the II patients with a positive DAT and no history of hemolytic anemia, IgG alone was present in 27 percent, complement alone in 9%, and IgG plus complement in 9 percent; 55 percent had positive DATs only with polyspecific reagent. Among ALPS patients, those with a positive DAT had greater quantities of cells with increased a and p T-cell receptors that phenotyped as CD4-CD8- and higher IgG levels. CONCLUSIONS: The DAT results in ALPS patients are most similar to those found in warm autoimmune hemolytic anemia. The DAT is useful to distinguish affected and unaffected persons within an ALPS family. SN 0041-1132 PD JAN PY 2001 VL 41 IS 1 BP 18 EP 23 DI 10.1046/j.1537-2995.2001.41010018.x UT WOS:000166582400005 PM 11161240 ER PT B AU Hyman, SE Moldin, SO AF Hyman, SE Moldin, SO BE Weissman, MM TI Genetic science and depression - Implications for research and treatment SO TREATMENT OF DEPRESSION: BRIDGING THE 21ST CENTURY CT 89th Annual Meeting of the American-Psychopathological-Association CY MAR, 1999 CL NEW YORK, NY SP Amer Psychopathol Assoc AB Data from family, twin, and adoption studies demonstrate the involvement of genetic factors in the transmission of major depression. However, the mode of inheritance is complex, and familial transmission is not accounted for by a single major gene. Indeed, the evidence to date suggests that vulnerability is produced by multiple loci of small effect, some of which may have small independent additive effects and others of which may act epistatically. In addition, nongenetic effects appear to play a role both in creating vulnerability and in triggering episodes. As a result, the correlation between genotype and phenotype is obscured; that is, genotype is connected to phenotype more loosely in depression than it is in illnesses such as Huntington disease. Despite these challenges, as the Human Genome Project and other initiatives provide denser genetic maps, faster sequencing methods, state-of-the-art DNA array technologies, and full-length complementary DNA (cDNA) clones containing an entire protein coding sequence, the stage will be set for a new era of gene identification and functional studies in psychiatry. Perhaps of greatest relevance to clinical care is the promise the isolation of vulnerability genes holds for significantly advancing drug discovery and individualized treatment selection. This current genetic revolution will have major public health implications and is expected to revolutionize our understanding of pathophysiology, diagnosis, treatment; and ultimately prevention of major depression. Genetic factors contribute to virtually every human disease by conferring susceptibility or resistance, affecting the severity or progression of disease, and interacting with environmental factors that modify disease course and expression. Much of current biomedical research is based on the expectation that understanding the genetic basis of disease will revolutionize diagnosis, treatment, and prevention. Human molecular genetics may ultimately prove to be the single most powerful tool we have for understanding how the brain malfunctions in depression and other mental disorders (Hyman 1999). Defining and understanding the role of genetic factors in depression will also facilitate our ability to understand environmental contributions that interact with genes to cause disease. Tremendous advances have occurred in mapping and cloning genes for rare diseases that are attributable to a single major locus, so-called Mendelian disorders (Bassett et al. 1997). In a historical trend that would have defied credulity not long ago, systematic discovery of these disease genes has generally occurred without any prior biologic knowledge of how they function. In contrast, the discovery of genes that influence vulnerability to major depression, schizophrenia, bipolar disorder, autism, and other mental disorders has proceeded slowly (Risch and Botstein 1996; Risch et al. 1999). The complex etiology of these diseases, in which vulnerability is produced by the interaction of multiple genes of small effect and nongenetic factors, poses major challenges for gene hunters and for the neurobiologists, pharmacologists, and epidemiologists who hope to use those genes. A common assumption is that the biggest direct clinical payoff from discovering genes for depression will be the development of a genetic test, presumably used to identify at-risk individuals. However, the greater the level of complexity underlying the penetrance of a disease phenotype and the manner in which it is expressed, the lesser the likelihood of a truly useful predictive test. The greatest benefits from genetic research are likely to result from the generation of powerful new tools to understand pathophysiology, development of new therapeutic compounds, and a revitalization of the epidemiologic study of risk. In this chapter, we briefly review our knowledge of the genetics of depression and discuss new genomic tools and technologies (Table 5-1) that will be brought to bear to understand the etiology and pathophysiology of depression. (Burmeister [1999] provides nongeneticists with a useful review of basic terminology and concepts used when studying complex genetic diseases.) Finally, we discuss how such tools and technologies may be used to develop new compounds and enhance the efficiency of drug regimens. BN 0-88048-397-0 PY 2001 BP 83 EP 103 UT WOS:000170062600006 ER PT J AU Kohn, LD Suzuki, K Nakazato, M Royaux, I Green, ED AF Kohn, LD Suzuki, K Nakazato, M Royaux, I Green, ED TI Effects of thyroglobulin and pendrin on iodide flux through the thyrocyte SO TRENDS IN ENDOCRINOLOGY AND METABOLISM AB Iodide transport by thyrocytes involves porters on the apical and basal surfaces of the cell facing the follicular rumen and bloodstream, respectively. Recent work identifies pendrin as an apical porter and shows that follicular thyroglobulin is a transcriptional regulator of the gene encoding pendrin and other thyroid-restricted genes. For example, whereas follicular thyroglobulin suppresses the gene expression and activity of the sodium iodide symporter (NIS), it increases pendrin gene expression. A potential new dynamic for iodide flux and thyroid hormone formation in thyrocytes has thus emerged and is supported by in vivo data. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X SN 1043-2760 PD JAN-FEB PY 2001 VL 12 IS 1 BP 10 EP 16 DI 10.1016/S1043-2760(00)00337-4 UT WOS:000168720500003 PM 11137035 ER PT J AU Jordan, IK Makarova, KS Wolf, YI Koonin, EV AF Jordan, IK Makarova, KS Wolf, YI Koonin, EV TI Gene conversions in genes encoding outer-membrane proteins in H-pylori and C-pneumoniae SO TRENDS IN GENETICS AB Helicobacter pylori and Chlamydia pneumoniae are both pathogenic to humans. Their genomes have recently been completed, allowing detailed study of their evolution and organization. Here we describe an evolutionary analysis of the H. pylori and C. pneumoniae genes that encode their outer-membrane proteins. By comparing complete genome sequences of two H. pylori strains and two C. pneumoniae strains, we identify multiple independent conversions among these genes. Such recombination events might provide a selective advantage for these bacterial pathogens. SN 0168-9525 PD JAN PY 2001 VL 17 IS 1 BP 7 EP 10 DI 10.1016/S0168-9525(00)02151-X UT WOS:000168717900004 PM 11163905 ER PT J AU Overwijk, WW Restifo, NP AF Overwijk, WW Restifo, NP TI Creating therapeutic cancer vaccines: notes from the battlefield SO TRENDS IN IMMUNOLOGY AB With the identification of tumor antigens and a knowledge of how to vaccinate against them, the field of tumor immunology faces new challenges, In this article, the authors argue that successful immunotherapies of the future will activate anti-tumorT cells without inducing their anergy or apoptotic death. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 SN 1471-4906 PD JAN PY 2001 VL 22 IS 1 BP 5 EP 7 DI 10.1016/S1471-4906(00)01793-2 UT WOS:000169935400003 PM 11286676 ER PT J AU Murphy, WJ Longo, DL AF Murphy, WJ Longo, DL TI Alternative strategies other than growth hormone for the treatment of immune diseases - Response SO TRENDS IN IMMUNOLOGY SN 1471-4906 PD JAN PY 2001 VL 22 IS 1 BP 15 EP 16 DI 10.1016/S1471-4906(00)01820-2 UT WOS:000169935400005 ER PT J AU Neurath, MF Finotto, S Fuss, I Boirivant, M Galle, PR Strober, W AF Neurath, MF Finotto, S Fuss, I Boirivant, M Galle, PR Strober, W TI Regulation of T-cell apoptosis in inflammatory bowel disease: to die or not to die, that is the mucosal question SO TRENDS IN IMMUNOLOGY AB T-cell resistance against apoptosis contributes to inappropriate T-cell accumulation and the perpetuation of chronic mucosal inflammation in inflammatory bowel diseases (IBDs). Anti-interleukin-12 (IL-12) and anti-IL-6 receptor antibodies suppress colitis activity by the induction of T-cell apoptosis. These findings have important implications for the design of effective treatment regimens in IBD. RI BOIRIVANT, MONICA/B-9977-2016 SN 1471-4906 PD JAN PY 2001 VL 22 IS 1 BP 21 EP 26 DI 10.1016/S1471-4906(00)01798-1 UT WOS:000169935400009 PM 11286687 ER PT J AU Staudt, LM AF Staudt, LM TI Gene expression physiology and pathophysiology of the immune system SO TRENDS IN IMMUNOLOGY AB Genomic-scale gene expression profiling can reveal cellular physiology with unprecedented richness. This technology is being used to define the gene expression targets of individual regulatory proteins and signaling pathways. Comprehensive databases of gene expression measurements can be used to understand the pathological mechanisms underlying disease processes. SN 1471-4906 PD JAN PY 2001 VL 22 IS 1 BP 35 EP 40 DI 10.1016/S1471-4906(00)01792-0 UT WOS:000169935400012 PM 11286690 ER PT J AU Barry, C Cole, S Fourie, B Geiter, L Gosey, L Grosset, J Kanyok, T Laughon, B Mitchison, D Nunn, P O'Brien, R Robinson, T Annick-Mouries, M Cynamon, M Duncan, K Goldberger, M Gutteridege, W Kioy, D Pablos-Mendez, A Orme, I Rieder, H Roscigno, G Vernon, A AF Barry, C Cole, S Fourie, B Geiter, L Gosey, L Grosset, J Kanyok, T Laughon, B Mitchison, D Nunn, P O'Brien, R Robinson, T Annick-Mouries, M Cynamon, M Duncan, K Goldberger, M Gutteridege, W Kioy, D Pablos-Mendez, A Orme, I Rieder, H Roscigno, G Vernon, A TI Scientific blueprint for tuberculosis drug development - Global alliance for TB drug development SO TUBERCULOSIS RI Barry, III, Clifton/H-3839-2012 SN 1472-9792 PY 2001 VL 81 SU 1 BP 1 EP 52 UT WOS:000169686900001 ER PT J AU Tsujino, H Jones, M Shiota, T Qin, JX Greenberg, NL Cardon, LA Morehead, AJ Zetts, AD Travaglini, A Bauer, F Panza, JA Thomas, JD AF Tsujino, H Jones, M Shiota, T Qin, JX Greenberg, NL Cardon, LA Morehead, AJ Zetts, AD Travaglini, A Bauer, F Panza, JA Thomas, JD TI Real-time three-dimensional color Doppler echocardiography for characterizing the spatial velocity distribution and quantifying the peak flow rate in the left ventricular outflow tract SO ULTRASOUND IN MEDICINE AND BIOLOGY AB Quantification of flow with pulsed-wave Doppler assumes a "flat" velocity profile in the left ventricular outflow tract (LVOT), which observation refutes. Recent development of real-time, three-dimensional (3-D) color Doppler allows one to obtain an entire cross-sectional velocity distribution of the LVOT, which is not possible using conventional 2-D echo. In an animal experiment, the cross-sectional color Doppler images of the LVOT at peak systole were derived and digitally transferred to a computer to visualize and quantify spatial velocity distributions and peak flow rates. Markedly skewed profiles, with higher velocities toward the septum, were consistently observed. Reference peak flow rates by electromagnetic flow meter correlated well with 3-D peak flow rates (r = 0.94), but with an anticipated underestimation. Real-time 3-D color Doppler echocardiography was capable of determining cross-sectional velocity distributions and peak flow rates, demonstrating the utility of this new method for better understanding and quantifying blood flow phenomena. (E-mail: shiotat@ccf.org) (C) 2001 World Federation for Ultrasound in Medicine & Biology. SN 0301-5629 PD JAN PY 2001 VL 27 IS 1 BP 69 EP 74 DI 10.1016/S0301-5629(00)00270-2 UT WOS:000167903700008 PM 11295272 ER PT J AU Verhage, BAJ Baffoe-Bonnie, AB Baglietto, L Smith, DS Bailey-Wilson, JE Beaty, TH Catalona, WJ Kiemeney, LA AF Verhage, BAJ Baffoe-Bonnie, AB Baglietto, L Smith, DS Bailey-Wilson, JE Beaty, TH Catalona, WJ Kiemeney, LA TI Autosomal dominant inheritance of prostate cancer: A confirmatory study SO UROLOGY AB Objectives. To confirm, in a study of a large, independent cohort of families with prostate cancer, the findings of three segregation analyses that have suggested the existence of an inherited form of prostate cancer with an autosomal dominant inheritance mode. Methods. Between January 1991 and December 1993, 1199 pedigrees were ascertained through single, unrelated, prostate cancer probands who presented for radical prostatectomy at the Division of Urologic Surgery, Washington University Medical Center in St. Louis, Missouri. Maximum likelihood segregation analysis was used to test specifically for mendelian inheritance of prostate cancer. Results. Segregation analyses revealed that the familial aggregation of prostate cancer can be best explained by the autosomal dominant inheritance of a rare (q = 0.0037) high-risk allele. According to the best-fitting autosomal dominant model, 97% of all carriers will be affected by 85 years of age compared with 10% of noncarriers. furthermore, the autosomal dominant model predicts that the high-risk allele accounts for a large proportion (65%) of all patients diagnosed with prostate cancer before 56 years of age. However, of all prostate cancer cases, a relatively small proportion is inherited (8% by 85 years old). Conclusions. These results are in agreement with earlier reports of segregation analyses of prostate cancer and strengthen the evidence that prostate cancer is inherited in a mendelian fashion within a subset of families. UROLOGY 57: 97-101, 2001. (C) 2001, Elsevier Science Inc. RI Kiemeney, Lambertus/D-3357-2009; OI Kiemeney, Lambertus/0000-0002-2368-1326; Bailey-Wilson, Joan/0000-0002-9153-2920 SN 0090-4295 PD JAN PY 2001 VL 57 IS 1 BP 97 EP 101 DI 10.1016/S0090-4295(00)00891-8 UT WOS:000166663000019 PM 11164151 ER PT J AU Arseven, A Guralnik, JM O'Brien, E Liu, K McDermott, MM AF Arseven, A Guralnik, JM O'Brien, E Liu, K McDermott, MM TI Peripheral arterial disease and depressed mood in older men and women SO VASCULAR MEDICINE AB The objective of this study was to determine whether lower extremity peripheral arterial disease (PAD) is associated with depressive symptoms and whether PAD-related disability mediates the association between PAD and depressive symptoms. The study used a cross-sectional design set in an academic medical center. A cohort of men and women aged 55 years and older with (n = 93) or without (n = 74) PAD was recruited. PAD subjects were identified from a blood flow laboratory and a general medicine practice. Non-PAD subjects were identified from the same general medicine practice. PAD was diagnosed and quantified using the ankle-brachial index (ABI). Depressive symptoms were assessed by the 15-item short version of the Geriatric Depression Scale (GDS-S; score range 0-15, 0 = no depressive symptoms). The six-minute walk test and the Walking Impairment Questionnaire (WIQ) distance score (score range 0-100, 100 = better walking ability) were measures of walking impairment. PAD subjects had depressive mood (DM) (defined by GDS-S score >5) twice as often as controls (24% vs 12%, p = 0.06). After adjustment for age, education, and number of comorbidities, the prevalence of depressive mood among PAD subjects was increased, but this association was not significant (OR = 1.8, 95% CI 0.7-4.4). The WIQ distance score weakened the association between PAD and DM, and higher distance scores were associated with a lower likelihood of DM (OR = 0.98 per one unit of the WIQ, 95% CI 0.96-0.99). Among PAD subjects, severe PAD (ABI <0.5) was not significantly associated with DM (OR = 1.4, 95% CI 0.5-4.1), but a greater 6-min walk distance was associated with a lower likelihood of DM (OR = 0.8 per 100 feet, 95% CI 0.70-0.97). Substituting the WIQ scores for six-min walk distance in the model showed that higher WIQ scores were associated with lower likelihood of DM among PAD subjects (OR = 0.98 per one unit of the WIQ, 95% CI 0.95-1.0), though the association did not achieve statistical significance. In conclusion, these data suggest that PAD may be associated with an increased risk of DM and that this relationship may be related to PAD-associated disability. An evaluation for depression may be appropriate in men and women with PAD. Findings should be evaluated in a larger study cohort. SN 1358-863X PY 2001 VL 6 IS 4 BP 229 EP 234 AR UNSP 1358-863X(01)EM395OA DI 10.1177/1358836X0100600405 UT WOS:000174707600005 PM 11958388 ER PT S AU Thalmann, R Ignatova, E Kachar, B Ornitz, DM Thalmann, I AF Thalmann, R Ignatova, E Kachar, B Ornitz, DM Thalmann, I BE Goebel, J Highstein, SM TI Development and maintenance of otoconia - Biochemical considerations SO VESTIBULAR LABYRINTH IN HEALTH AND DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES CT Conference on the Vestibular Labyrinth in Health and Disease CY NOV 16-18, 2000 CL ST LOUIS, MISSOURI SP Natl Inst Deafness & Other Commun Disorders, NASA, Natl Sci Fdn, Deafness Res Fdn, Neurocom Int Inc, Micromed Technologies Inc, Nicolet Biomed, Alcon Labs AB The first part of this review deals with recent advances in the understanding of biochemical mechanisms of otoconial morphogenesis. Most important in this regard is the molecular characterization of otoconin 90, the principal matrix protein of mammalian calcitic otoconia, which was found to be a homologue of the phospholytic enzyme PLA2. The unique and unexpected expression pattern of this protein required radical rethinking of traditional concepts. The new data, when integrated with existing information, provide a rational basis for an explanation of the mechanisms leading to crystal nucleation and growth. Based on this information, a hypothetical model is presented that posits interaction of otoconin 90 with microvesicles derived from the supporting cells as a key event in the formation of otoconia. The second part of the review is directed at the controversial subject of maintenance of mature otoconia and systematically analyzes the available indirect information on this topic. A synthesis of these theoretical considerations is viewed in relation to the pathogenesis of the important otoneurologic entities of BPPN and senile otoconial degeneration. The last part of the review deals with several animal models that promise to help elucidate normal and abnormal mechanisms of otoconial morphogenesis, including mineral deficiencies, mutations with selective otoconial agenesis, as well as targeted disruption of essential genes. OI Ornitz, David/0000-0003-1592-7629 SN 0077-8923 BN 1-57331-289-4 PY 2001 VL 942 BP 162 EP 178 UT WOS:000172619200014 PM 11710459 ER PT J AU He, XS Rehermann, B Boisvert, J Mumm, J Maecker, HT Roederer, M Wright, TL Maino, VC Davis, MM Greenberg, HB AF He, XS Rehermann, B Boisvert, J Mumm, J Maecker, HT Roederer, M Wright, TL Maino, VC Davis, MM Greenberg, HB TI Direct functional analysis of epitope-specific CD8+ T cells in peripheral blood SO VIRAL IMMUNOLOGY AB The functional status of virus-specific CD8(+) T cells is important for the outcome and the immunopathogenesis of viral infections. We have developed an assay for the direct functional analysis of antigen-specific CD8(+) T cells, which does not require prolonged in vitro cultivation and amplification of T cells. Whole blood samples were incubated with peptide antigens for <5 h, followed by staining with peptide-MHC tetramers to identify epitope-specific T cells, The cells were also stained for the activation marker CD69 or for the production of cytokines such as interferon-gamma (IFN) or turner necrosis factor-alpha (TNF alpha). With the combined staining with tetramer and antibodies to CD69 or cytokines the number of antigen-specific CD8(+) T cells as well as the functional response of each individual cell to the cognate antigen can be determined in a single experiment. Virus-specific CD8(+) T cells that are nonfunctional, as well as those that are functional under the same stimulating conditions can be simultaneously detected with this assay, which is not possible by using other T-cell functional assays including cytotoxicity assay, intracellular cytokine staining, and enzyme-linked immunospot (ELISPOT) assay. RI Roederer, Mario/G-1887-2011 SN 0882-8245 PY 2001 VL 14 IS 1 BP 59 EP 69 DI 10.1089/08828240151061400 UT WOS:000167575500005 PM 11270597 ER PT J AU Yunus, AS Khattar, SK Collins, PL Samal, SK AF Yunus, AS Khattar, SK Collins, PL Samal, SK TI Rescue of bovine respiratory syncytial virus from cloned cDNA: Entire genome sequence of BRSV strain A51908 SO VIRUS GENES AB Infectious bovine respiratory syncytial virus (BRSV) was produced by intracellular co-expression of five plasmid borne cDNAs, each under the control of a T7 RNA polymerase promoter. These separately encoded a full-length, genetically-marked copy of BRSV antigenome along with either BRSV or human respiratory syncytial virus (HRSV) support plasmids, which express N, P, L and M2-1 proteins. HEp2 cells were used in transfection and recombinant vaccinia virus (MVA-T7) provided T7 RNA polymerase to drive the transcription. The recovery of recombinant BRSV (rBRSV) was confirmed by immunological staining of plaques, restriction enzyme digestion and nucleotide sequencing of PCR fragments carrying the genetic markers from the rescued virus. The rBRSV was indistinguishable from its parental wild-type virus in its growth characteristics in cell culture. The present work has completed the entire genome sequence of BRSV strain A51908 (15,140 nt) and has also identified changes in sequence and growth characteristics in cell culture from the original BRSV strain A51908 laboratory isolate. SN 0920-8569 PY 2001 VL 23 IS 2 BP 157 EP 164 DI 10.1023/A:1011888019966 UT WOS:000171064400005 PM 11724268 ER PT J AU Mohan, KVK Atreya, CD AF Mohan, KVK Atreya, CD TI Nucleotide sequence analysis of rotavirus gene 11 from two tissue culture-adapted ATCC strains, RRV and Wa SO VIRUS GENES AB We report here nucleotide sequence and characterization of gene 11 from two tissue culture-adapted ATCC(1) rhesus (RRV) and human (Wa) strains of rotavirus. Gene 11 sequence encodes a nonstructural protein, NSP5 and also encodes NSP6, from an out of phase open reading frame. Sequence of RRVATCC gene 11 represents the first report from a rhesus rotavirus which has more than 90% homology at the nucleotide and deduced amino acid sequence level with that of its closely related simian SA11 strain. The Wa(ATCC) gene sequence differed from that of published Wa (Wa(Pub)) at three nucleotide positions, one at 264 (G(Wa-Pub) to A(ATCC-Wa)), another a nucleotide insertion (A) at position 388 and the third, a deletion (A) at 416. The latter two changes in Wa(ATCC) NSP5 resulted in drastic amino acid changes within a 10-residue region (123-132) from VHVYQFQLTN in Wa(Pub) to DSCVSISTNH in Wa(ATCC) NSP5 protein. In this region, Wa(ATCC) NSP5 is closer to published sequences from other strains, suggesting the authenticity of the present sequence. The nucleotide difference between Wa(Pub) and Wa(ATCC) NSP5 sequences, however, did not affect the NSP6 deduced amino acid sequence, which is overall highly conserved among all the strains compared. Sequence-based phylogenetic analysis of gene 11 identified a high degree of conservation within the Group A rotaviruses. In addition, it also separated RRVATCC and Wa(ATCC), suggesting rotavirus segregation by genogroup. An anti-NSP5 monoclonal antibody of SA11 recognized RRV NSP5 protein but not Wa(ATCC) NSP5 from the infected cells, further supporting the phylogenetic segregation of RRVATCC and Wa(ATCC) strains based on their NSP5 coding sequence. SN 0920-8569 PY 2001 VL 23 IS 3 BP 321 EP 329 UT WOS:000172031600009 PM 11778700 ER PT J AU Masson, GS Busettini, C Yang, DS Miles, FA AF Masson, GS Busettini, C Yang, DS Miles, FA TI Short-latency ocular following in humans: sensitivity to binocular disparity SO VISION RESEARCH AB We show that the initial ocular following responses elicited by motion of a large pattern are modestly attenuated when that pattern is shifted out of the plane of fixation by altering its binocular disparity. If the motion is applied to only restricted regions of the pattern, however, then altering the disparity of those regions severely attenuates their ability to generate ocular following. This sensitivity of the ocular tracking mechanism to local binocular disparity would help the observer who moves through a cluttered 3-D world to stabilize objects in the plane of fixation and ignore all others. (C) 2001 Elsevier Science Ltd. All rights reserved. RI MASSON, Guillaume/G-4615-2012 SN 0042-6989 PY 2001 VL 41 IS 25-26 BP 3371 EP 3387 DI 10.1016/S0042-6989(01)00029-3 UT WOS:000173087300015 PM 11718780 ER PT J AU Wurtz, RH Sommer, MA Pare, M Ferraina, S AF Wurtz, RH Sommer, MA Pare, M Ferraina, S TI Signal transformations from cerebral cortex to superior colliculus for the generation of saccades SO VISION RESEARCH AB The ability of primates to make rapid and accurate saccadic eye movements for exploring the natural world is based on a neuronal system in the brain that has been studied extensively and is known to include multiple brain regions extending throughout the neuraxis. We examined the characteristics of signal flow in this system by recording from identified output neurons of two cortical regions, the lateral intraparietal area (LIP) and the frontal eye field (FEF), and from neurons in a brainstem structure targeted by these output neurons, the superior colliculus (SC). We compared the activity of neurons in these three populations while monkeys performed a delayed saccade task that allowed us to quantify visual responses, motor activity, and intervening delay activity. We examined whether delay activity was related to visual stimulation by comparing the activity during interleaved trials when a target was either present or absent during the delay period. We examined whether delay activity was related to movement by using a Go/Nogo task and comparing, the activity during interleaved trials in which a saccade was either made (Go) or not (Nogo). We found that LIP output neurons, FEF output neurons, and SC neurons can all have visual responses, delay activity, and presaccadic bursts; hence in this way they are all quite similar. However, the delay activity tended to be more related to Visual stimulation in the cortical output neurons than in the SC neurons. Complementing this, the delay activity tended to be more related to movement in the SC neurons than in the cortical output neurons. We conclude, first, that the signal flow leaving the cortex represents activity at nearly every stage of visuomotor transformation, and second, that there is a gradual evolution of signal processing as one proceeds from cortex to colliculus. Published by Elsevier Science Ltd. SN 0042-6989 PY 2001 VL 41 IS 25-26 BP 3399 EP 3412 DI 10.1016/S0042-6989(01)00066-9 UT WOS:000173087300017 PM 11718782 ER PT B AU Thompson, KG Bichot, NP Schall, JD AF Thompson, KG Bichot, NP Schall, JD BE Braun, J Koch, C Davis, JL TI From attention to action in frontal cortex SO VISUAL ATTENTION AND CORTICAL CIRCUITS CT Workshop on Visual Attention and Cortical Circuits CY 1999 CL SANTA CATALINA, CA SP USN Off Res, Natl Sci Fdn BN 0-262-02493-4 PY 2001 BP 137 EP 157 UT WOS:000171392300008 ER PT J AU Padgett, DK Yedidia, MJ Kerner, J Mandelblatt, J AF Padgett, DK Yedidia, MJ Kerner, J Mandelblatt, J TI The emotional consequences of false positive mammography: African-American women's reactions in their own words SO WOMEN & HEALTH AB High false positive rates associated with screening for breast cancer in the United States have an unintended psychological consequence for women (Lerman et al., 1991) that has raised concerns in recent years (Sox, 1998). This study uses inductive qualitative analysis of open-ended interviews with 45 African American women living in New York City who were part of a larger study of women and their experiences after receiving an abnormal mammogram. Themes resulting from the analyses included: inadequate provider-patient communication, anxieties exacerbated by waiting and wondering, and fears of iatrogenic effects of follow-up tests such as biopsies and repeat mammograms. While more research is needed on message-framing strategies for women entering mammographic testing and follow-up, modest changes in service de-livery such as improved medical communication can help to alleviate fears and enhance trust. (C) 2001 by The Haworth Press, Inc. All rights reserved. SN 0363-0242 PY 2001 VL 33 IS 3-4 BP 1 EP 14 DI 10.1300/J013v33n03_01 UT WOS:000170981900001 PM 11527098 ER PT J AU Siefert, K Heflin, CM Corcoran, ME Williams, DR AF Siefert, K Heflin, CM Corcoran, ME Williams, DR TI Food insufficiency and the physical and mental health of low-income women SO WOMEN & HEALTH AB Poor women with children are disproportionately represented among the fi,od insufficient. Recent research has linked food insufficiency with dietary deficiencies, but further research linking this problem to health and mental health problems is needed to inform health and social policy. We analyzed the relationship between food insufficiency and physical and mental health in a random sample of 724 single women who were welfare recipients in February, 1997. Food insufficiency was significantly associated with poor or fair self-rated health and physical limitations, and with respondents' meeting DSM-III-R criteria for recent major depression. Although the cross-sectional design of this study precludes causal inference, these findings add to a growing body of evidence that food insufficiency is associated with serious adverse physical and mental health consequences. (C) 2001 by The Haworth Press, Inc. All rights reserved. SN 0363-0242 EI 1541-0331 PY 2001 VL 32 IS 1-2 BP 159 EP 177 DI 10.1300/J013v32n01_08 UT WOS:000170060400009 PM 11459368 ER PT J AU Allen, R AF Allen, R TI Panel 1 - Framing issues in rural women's health issues - Speaker 2 SO WOMENS HEALTH ISSUES CT Conference on Setting the Agenda for Rural Womens Health CY 2000 CL PENN STATE UNIV, HERSHEY, PENNSYLVANIA HO PENN STATE UNIV SN 1049-3867 PD JAN-FEB PY 2001 VL 11 IS 1 BP 22 EP 25 DI 10.1016/S1049-3867(00)00080-3 UT WOS:000166829700005 PM 11166594 ER EF