FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hogner, A Kastrup, JS Jin, R Liljefors, T Mayer, ML Egebjerg, J Larsen, IK Gouaux, E AF Hogner, A Kastrup, JS Jin, R Liljefors, T Mayer, ML Egebjerg, J Larsen, IK Gouaux, E TI Structural basis for AMPA receptor activation and ligand selectivity: Crystal structures of five agonist complexes with the GluR2 ligand-binding core SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE glutamate receptors; X-ray structures; ligand binding; selectivity; electrophysiology ID AMINO-ACID-RESIDUES; GLUTAMATE-RECEPTOR; CONFIGURATIONAL ASSIGNMENT; BIOLOGICAL-ACTIVITY; HETEROARYL ANALOGS; CHANNEL PROPERTIES; KAINATE RECEPTORS; N-GLYCOSYLATION; ION CHANNELS; DOMAIN AB Glutamate is the principal excitatory neurotransmitter within the mammalian CNS, playing an important role in many different functions in the brain such as learning and memory. In this study, a combination of molecular biology, X-ray structure determinations, as well as electrophysiology and binding experiments, has been used to increase our knowledge concerning the ionotropic glutamate receptor GluR2 at the molecular level. Five high-resolution X-ray structures of the ligand-binding domain of GluR2 (S1S2J) complexed with the three agonists (S)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl]propicnic acid (2-Me-Tet-AMPA), (S)-2-amino-3-(3-carboxy-5-methylisoxazol4-yl)propionic acid (ACPA), and (S)-2-amino-3-(4-bromo-3-hydroxy-isoxazol-5-yl)propionic acid (Br-HIBO), as well as of a mutant thereof (S1S2J-Y702F) in complex with ACPA and Br-HIBO, have been determined. The structures reveal that AMPA agonists with an isoxazole moiety adopt different binding modes in the receptor, dependent on the substituents of the isoxazole. Br-HIBO displays selectivity among different AMPA receptor subunits, and the design and structure determination of the S1S2J-Y702F mutant in complex with Br-HIBO and ACPA have allowed us to explain the molecular mechanism behind this selectivity and to identify key residues for ligand recognition. The agonists induce the same degree of domain closure as AMPA, except for Br-HIBO, which shows a slightly lower degree of domain closure. An excellent correlation between domain closure and efficacy has been obtained from electrophysiology experiments undertaken on non-desensitising GluR2i(Q)-L483Y receptors expressed in oocytes, providing strong evidence that receptor activation occurs as a result of domain closure. The structural results, combined with the functional studies on the full-length receptor, form a powerful platform for the design of new selective agonists. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Royal Danish Sch Pharm, Dept Med Chem, DK-2100 Copenhagen, Denmark. NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. Aarhus Univ, Dept Biol Mol & Struct, DK-8000 Aarhus, Denmark. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. RP Kastrup, JS (reprint author), Columbia Univ, Dept Biochem & Mol Biophys, 650 W 168th St, New York, NY 10032 USA. RI Hogner, Anders/A-4647-2009; Mayer, Mark/H-5500-2013; Jin, Rongsheng/M-7797-2013 OI Jin, Rongsheng/0000-0003-0348-7363 NR 59 TC 135 Z9 140 U1 0 U2 9 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 6 PY 2002 VL 322 IS 1 BP 93 EP 109 DI 10.1061/S0022-2836(02)00650-2 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 597CT UT WOS:000178205100009 PM 12215417 ER PT J AU Ermolenko, DN Thomas, ST Aurora, R Gronenborn, AM Makhatadze, GI AF Ermolenko, DN Thomas, ST Aurora, R Gronenborn, AM Makhatadze, GI TI Hydrophobic interactions at the Ccap position of the C-capping motif of alpha-helices SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE helix termination; C-capping motifs; statistical analysis; hydrophobic interactions; differential scanning calorimetry ID CHARGE-CHARGE INTERACTIONS; AMINO-ACIDS; PROTEIN STABILITY; CHYMOTRYPSIN INHIBITOR-2; FORMING PROPENSITIES; UBIQUITIN MOLECULE; SCHELLMAN MOTIF; SIDE-CHAINS; N-TERMINI; PEPTIDES AB We investigated the possible role of residues at the Ccap position in an alpha-helix on protein stability. A set of 431 protein a.-helices containing a C'-Gly from the Protein Data Bank (PDB) was analyzed, and the normalized frequencies for finding particular residues at the Ccap position, the average fraction of buried surface area, and the hydrogen bonding patterns of the Ccap residue side-chain were calculated. We found that on average the Ccap position is 70% buried and noted a significant correlation (R = 0.8) between the relative burial of this residue and its hydrophobicity as defined by the Gibbs energy of transfer from octanol or cyclohexane to water. Ccap residues with polar side-chains are commonly involved in hydrogen bonding. The hydrogen bonding pattern is such that, the longer side-chains of Glu, Gln, Arg, Lys, His form hydrogen bonds with residues distal (>+/-4) in sequence, while the shorter side-chains of Asp, Asn, Ser, Thr exhibit hydrogen bonds with residues close in sequence (<&PLUSMN;4), mainly involving backbone atoms. Experimentally we determined the thermodynamic propensities of residues at the Ccap position using the protein ubiquitin as a model system. We observed a large variation in the stability of the ubiquitin variants depending on the nature of the Ccap residue. Furthermore, the measured changes in stability of the ubiquitin variants correlate with the hydrophobicity of the Ccap residue. The experimental results, together with the statistical analysis of protein structures from the PDB, indicate that the key hydrophobic capping interactions between a helical residue (C3 or C4) and a residue outside the helix (C&DPRIME;, C3' or C4') are frequently enhanced by the hydrophobic interactions with Ccap residues. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Penn State Univ, Coll Med, Dept Biochem & Mol Biol H171, Hershey, PA 17033 USA. Russian Acad Sci, AN Bakh Biochem Inst, Moscow 117071, Russia. Pharmacia Corp, Computat Biol Grp, St Louis, MO 63017 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Makhatadze, GI (reprint author), Penn State Univ, Coll Med, Dept Biochem & Mol Biol H171, 500 Univ Dr, Hershey, PA 17033 USA. RI Aurora, Rajeev/A-4588-2008; OI Aurora, Rajeev/0000-0002-6609-6055; Gronenborn, Angela M/0000-0001-9072-3525 FU NIGMS NIH HHS [GM54537] NR 53 TC 27 Z9 29 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 6 PY 2002 VL 322 IS 1 BP 123 EP 135 DI 10.1016/S0022-2836(02)00734-9 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 597CT UT WOS:000178205100011 PM 12215419 ER PT J AU Wilk, A Chmielewski, MK Grajkowski, A Phillips, LR Beaucage, SL AF Wilk, A Chmielewski, MK Grajkowski, A Phillips, LR Beaucage, SL TI The 3-(N-tert-butylcarboxamido)-1-propyl group as an attractive phosphate/thiophosphate protecting group for solid-phase oligodeoxyribonucleotide synthesis SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SULFUR-TRANSFER REAGENT; OLIGONUCLEOTIDE SYNTHESIS; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; DEOXYNUCLEOSIDE PHOSPHORAMIDITES; DEPROTECTION; MONOMERS; DNA; AMINOLYSIS; CHEMISTRY; LACTONES AB Among the various phosphate/thiophosphate protecting groups suitable for solid-phase oligonucleotide synthesis, the 3-(N-tent-butylcarboxamido)-1-propyl group is one of the most convenient, as it can be readily removed, as needed, under thermolytic conditions at neutral pH. The deprotection reaction proceeds rapidly (t(1/2) similar to100 s) through an intramolecular cyclodeesterification reaction involving the amide function and the release of the phosphate/thiophosphate group as a 2-(tert-butylimino)tetrahydrofuran salt. Incorporation of the 3-(N-tent-butylcarboxamido)-1-propyl group into the deoxyribonucleoside phosphoramidites 1a-d is achieved using inexpensive raw materials. The coupling efficiency of 1a-d in the solid-phase synthesis of d(ATCCGTAGCTAAGGTCATGC) and its phosphorothioate analogue is comparable to that of commercial 2-cyanoethyl deoxyribonucleoside phosphoramidites. These oligonucleotides were phosphate/thiophosphate-deprotected within 30 min upon heating at 90 degreesC in Phosphate-Buffered Saline (PBS buffer, pH 7.2). Since no detectable nucleobase modification or significant phosphorothioate desulfurization occurs, the 3-(N-tert-butylcarboxamido)-1-propyl group represents an attractive alternative to the 2-cyanoethyl group toward the large-scale preparation of therapeutic oligonucleotides. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NCI, Biol Testing Branch, Dev Therapeut Program, Frederick, MD 21701 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 31 TC 28 Z9 28 U1 2 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD SEP 6 PY 2002 VL 67 IS 18 BP 6430 EP 6438 DI 10.1021/jo0258608 PG 9 WC Chemistry, Organic SC Chemistry GA 591LE UT WOS:000177880900020 PM 12201764 ER PT J AU Zhang, ZJ Postma, T Obeng, K Russell, S Weiss, SRB Post, RM AF Zhang, ZJ Postma, T Obeng, K Russell, S Weiss, SRB Post, RM TI The benzodiazepine partial inverse agonist Ro15-4513 alters anticonvulsant and lethal effects of carbamazepine in amygdala-kindled rats SO NEUROSCIENCE LETTERS LA English DT Article DE Ro15-4513; carbamazepine; amygdala kindling; lethality; anticonvulsant; benzodiazepine partial inverse agonist; rat ID SPINAL-CORD NEURONS; CONTINGENT TOLERANCE; RO 15-4513; A RECEPTOR; ETHANOL; RO-15-4513; MICE; ANTAGONISM; MECHANISMS; PHENYTOIN AB Ro15-4513 (ethyl-8-azido-5,6-dihydro-5methyl-6-oxo-4H-imidazo-[1,5-al-1,4-benzodiazepine-3-carboxylate), a benzodiazepine partial inverse agonist of the GABA(A) receptor, is known to protect against alcohol toxicities. The present study was designed to determine the role of Ro15-4513 in preventing anticonvulsant, toxic, and lethal effects of carbamazepine (CBZ) in amygdala-kindled rats. Acute treatment with CBZ (25 mg/kg, i.p.) produced anticonvulsant effects in fully kindled rats characterized by a significant decrease in afterdischarge and seizure duration and stage. Repeated administration of this high dose of CBZ induced sedation and high (56%) lethality. The anticonvulsant and sedative effects of CBZ were strikingly suppressed by pretreatment with Ro15-4513 (2.5 and 5 mg/kg, i.p.), and there was no mortality in animals co-administrated with Ro15-4513 during the entire experimental period. These results indicate that Ro15-4513 protects against CBZ-induced sedation and lethality, while suppressing the anticonvulsant effects of CBZ, suggesting a role for the GABA(A) receptor in CBZ efficacy and side effects. The potential clinical implications for CBZ-induced toxicity and overdose remain to be explored. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Zhang, ZJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 29 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 6 PY 2002 VL 329 IS 3 BP 253 EP 256 AR PII S0304-3940(02)00664-X DI 10.1016/S0304-3940(02)00664-X PG 4 WC Neurosciences SC Neurosciences & Neurology GA 595JA UT WOS:000178104400001 PM 12183024 ER PT J AU Feng, ZH Wang, TG Li, DD Fung, P Wilson, BC Liu, B Ali, SF Langenbach, R Hong, JS AF Feng, ZH Wang, TG Li, DD Fung, P Wilson, BC Liu, B Ali, SF Langenbach, R Hong, JS TI Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine-induced damage of dopaminergic neurons in the substantia nigra SO NEUROSCIENCE LETTERS LA English DT Article DE Parkinson's disease; cyclooxygenase-2; tyrosine hydroxylase; 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine; dopamine ID PARKINSONS-DISEASE; MULTIPLE-SCLEROSIS; REACTIVE OXYGEN; GENE DISRUPTION; MPTP TOXICITY; IN-VIVO; EXPRESSION; NEUROTOXICITY; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; MICROGLIA AB Cyclooxygenases (COX), key enzymes in prostanoid biosynthesis, may represent important therapeutic targets in various neurodegenerative diseases. In the present study, we explored the role of COX in Parkinson's disease (PD) by using 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine (MPTP) as a tool to create a rodent Parkinsonian model. MPTP (20 mg/kg, subcutaneously) was injected daily into COX-1- and COX-2-deficient mice and wild-type (WT) controls for five consecutive days. Immunocytochemical analysis of tissues collected 7 days after the final MPTP treatment showed that MPTP significantly decreased the number of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNc) of WT(40% decrease) and COX-1(-/-) (45% decrease) mutants. However, a much smaller loss of TH-ir neurons in COX-2(-/-) mutants (20% decrease) was observed. Furthermore, electrochemical analysis revealed a more than 70% decrease in the levels of dopamine and its metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid) in the striatum of the WT control COX-1(-/-) and COX-2(-/-) mutant mice. These results indicate that loss of COX-2 activity reduces MPTP-induced damage to the dopaminergic neurons of the SNc, but does not alter the levels of dopamine and its metabolites in the striatum. Interestingly, MPTP caused the same degree of loss of dopaminergic neurons in both COX-2(+/-) and COX-2(-/-) mice (20% loss). The results of this study indicate an important role of COX-2 in MPTP-induced neuronal degeneration and suggest the possibility that manipulation of the COX-2 could be an important target for therapeutic interventions in PD. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Hong Kong, Queen Mary Hosp, Univ Dept Med, Hong Kong, Hong Kong, Peoples R China. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI liu, Bin/A-7695-2009 NR 36 TC 107 Z9 117 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 6 PY 2002 VL 329 IS 3 BP 354 EP 358 AR PII S0304-3940(02)00706-8 DI 10.1016/S0304-3940(02)00704-8 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 595JA UT WOS:000178104400024 PM 12183047 ER PT J AU Shibusawa, Y Misu, N Shindo, H Ito, Y AF Shibusawa, Y Misu, N Shindo, H Ito, Y TI Purification of lactic acid dehydrogenase from crude bovine heart extract by pH-peak focusing counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE pH-peak focusing; counter-current chromatography; lactic acid dehydrogenase ID COIL PLANET CENTRIFUGE; ONE-STEP PURIFICATION; PROTEINS; SEPARATION; APPARATUS; SYSTEMS; DESIGN; PHASE AB pH-peak focusing counter-current chromatography (CCC) was applied to the purification of lactic acid dehydrogenase (LDH) from a crude bovine heart extract using a cross-axis coil planet centrifuge (CPC). The experiment was performed with two sets of polymer phase systems composed of 16% (w/w) polyethylene glycol (PEG) 1000-12.5% (w/w) potassium phosphate buffer and 15% (w/w) PEG 1540-15% (w/w) ammonium sulfate each at various pH values. The best result was achieved from the PEG 1540-ammonium sulfate polymer phase system by adding a retainer (10 mM acetic acid) to the upper stationary phase and an eluter (100 mM sodium hydroxide) to the lower mobile phase. At a flow-rate of 0.5 ml/min, LDH was eluted as a sharp peak which was well resolved from other proteins. Collected fractions were analyzed by the LDH enzymatic activity and by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis to detect contaminated proteins. LDH was purified directly from crude bovine heart extract in a concentrated state. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Analyt Chem, Tokyo 1920392, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shibusawa, Y (reprint author), Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Analyt Chem, 1432-1 Horinouchi, Tokyo 1920392, Japan. NR 22 TC 4 Z9 7 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD SEP 5 PY 2002 VL 776 IS 2 BP 183 EP 189 AR PII S1570-0232(02)00348-3 DI 10.1016/S1570-0232(02)00348-3 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 584DL UT WOS:000177451900006 PM 12138000 ER PT J AU Li, MX Jia, M Yang, LX Dunlap, V Nelson, PG AF Li, MX Jia, M Yang, LX Dunlap, V Nelson, PG TI Pre- and postsynaptic mechanisms in Hebbian activity-dependent synapse modification SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE PKA; PKC; synapse elimination; Hebbian; activity-dependent; neuromuscular junction ID PROTEIN-KINASE-A; NEUROMUSCULAR-JUNCTION; ACETYLCHOLINE-RECEPTORS; MUSCLE-CELLS; PHOSPHORYLATION SITES; PHORBOL ESTER; IN-VITRO; ELIMINATION; NEURONS; PLASTICITY AB We have used a three compartment tissue culture system that involved two separate populations of cholinergic neurons in the side compartments that converged on a common target population of myotubes in the center compartment. Activation of the axons from one population of neurons produced selective down-regulation of the synaptic inputs from the other neuronal population (when the two inputs innervated the same myotubes). The decrease in heterosynaptic inputs was mediated by protein kinase C (PKC). An activity-dependent action of protein kinase A (PKA) was associated with the stimulated input and this served to selectively stabilize this input. These changes associated with PKA and PKC activation were mediated by alterations in the number of acetylcholine receptors at the neuromuscular junction. These results suggest that neuromuscular electrical activity produces postsynaptic activation of both PKA and PKC, with the latter producing generalized synapse weakening and the former a selective synapse stabilization. Treatment of the neuronal cell body and axon to increase PKC activity by putting phorbal ester (PMA) in the side chamber did not affect synaptic transmission (with or without stimulation). By contrast, PKA blockade in the side compartment did produce an activity-dependent decrease in synaptic efficacy, which was due to a decrease in quantal release of neurotransmitter. Thus, when the synapse is activated, it appears that presynaptic PKA action is necessary to maintain transmitter output. (C) 2002 Wiley Periodicals, Inc.* C1 NICHHD, NIH, Neurobiol Sect, Dev Neurobiol Lab, Bethesda, MD 20982 USA. RP Nelson, PG (reprint author), NICHHD, NIH, Neurobiol Sect, Dev Neurobiol Lab, Bethesda, MD 20982 USA. NR 30 TC 9 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD SEP 5 PY 2002 VL 52 IS 3 BP 241 EP 250 DI 10.1002/neu.10089 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 584RP UT WOS:000177482400006 PM 12210107 ER PT J AU Wu, YM Rogers, MJ AF Wu, YM Rogers, MJ TI Shared knowledge can combat malaria SO NATURE LA English DT Letter C1 ATCC, Protlstol MR4, Manassas, VA 20110 USA. NIAID, Bethesda, MD 20892 USA. RP Wu, YM (reprint author), ATCC, Protlstol MR4, 10801 Univ Blvd, Manassas, VA 20110 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 5 PY 2002 VL 419 IS 6902 BP 15 EP 15 DI 10.1038/419015b PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 589YF UT WOS:000177788600016 PM 12214209 ER PT J AU Gearhart, PJ AF Gearhart, PJ TI Immunology - The roots of antibody diversity SO NATURE LA English DT Editorial Material ID SOMATIC HYPERMUTATION; NUCLEOTIDE; GENES; RNA C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 13 TC 20 Z9 20 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 5 PY 2002 VL 419 IS 6902 BP 29 EP + DI 10.1038/419029a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 589YF UT WOS:000177788600026 PM 12214221 ER PT J AU Troiano, RP AF Troiano, RP TI Perspective: Physical inactivity among young people SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Troiano, RP (reprint author), NCI, Bethesda, MD 20892 USA. OI Troiano, Richard/0000-0002-6807-989X NR 0 TC 15 Z9 15 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 5 PY 2002 VL 347 IS 10 BP 706 EP 707 DI 10.1056/NEJMp020085 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 589NH UT WOS:000177765800001 PM 12213940 ER PT J AU Yarchoan, R Davis, DA Rinderknecht, A AF Yarchoan, R Davis, DA Rinderknecht, A TI Development of Kaposi's sarcoma at the site of a biopsy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP Yarchoan, R (reprint author), NCI, Bethesda, MD 20892 USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 5 PY 2002 VL 347 IS 10 BP 763 EP 764 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 589NH UT WOS:000177765800016 PM 12213952 ER PT J AU Drotschmann, K Yang, W Kunkel, TA AF Drotschmann, K Yang, W Kunkel, TA TI Evidence for sequential action of two ATPase active sites in yeast Msh2-Msh6 SO DNA REPAIR LA English DT Article DE MutS; Msh2; Msh6; ATP hydrolysis; Walker B ID DNA MISMATCH REPAIR; HMUTS-ALPHA; ESCHERICHIA-COLI; TRANSLOCATION MECHANISM; MUTATOR PHENOTYPES; CRYSTAL-STRUCTURE; SLIDING CLAMP; GENE-PRODUCT; PROTEIN MUTS; ABC-ATPASE AB sBacterial MutS homodimers contain two ATPase active sites that have non-equivalent functions in DNA mismatch repair. The homologous Msh2-Msh6 complex in eukaryotes also has intrinsic ATPase activity that is essential for mismatch repair. Here, we investigate differences in the two putative ATPase active sites by examining the properties of heterodimers containing alanine substituted for an invariant glutamic acid in the active site of either Msh2, Msh6 or both. Mutation rates in wild type versus Glu --> Ala mutant haploid yeast strains indicate that both ATPase active sites are essential for mismatch repair activity in vivo. The properties of purified heterodimers suggest that the ATPase active site in Msh6 binds ATP with higher affinity and hydrolyzes ATP faster and with higher efficiency than does the ATPase active site in Msh2. This suggests sequential action of the two ATPase active sites, in which ATP binds to Msh6 first to trigger downstream events in mismatch repair. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 NR 52 TC 32 Z9 34 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD SEP 4 PY 2002 VL 1 IS 9 BP 743 EP 753 AR PII S1568-7864(02)00081-2 DI 10.1016/S1568-7864(02)00081-2 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 597YR UT WOS:000178248800005 PM 12509278 ER PT J AU Teufel, A Malik, N Mukhopadhyay, M Westphal, H AF Teufel, A Malik, N Mukhopadhyay, M Westphal, H TI Frcp1 and Frcp2, two novel fibronectin type III repeat containing genes SO GENE LA English DT Article DE development; brain; membrane protein ID EXTRACELLULAR REGION; DOMAIN; MICE; PUNC AB The fibronectin type III (FNIII) repeat is one of three structural motifs originally identified in the fibronectin protein and has been well characterized in recent years. The consensus sequence has since been found in many different proteins including receptors and cell adhesion molecules. We report the cloning and expression analysis of Frcp1 and Frcp2, two members of a new FNIII repeat containing gene family. During embryonic development both genes are primarily expressed in the brain. In adult tissues, Frcp1 is strongly expressed in the liver and Frcp2 in the heart. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Westphal, H (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bldg 6B,Room 413,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 30 Z9 40 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 4 PY 2002 VL 297 IS 1-2 BP 79 EP 83 AR PII S0378-1119(02)00828-4 DI 10.1016/S0378-1119(02)00828-4 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 612KZ UT WOS:000179075600009 PM 12384288 ER PT J AU Lipsitz, RS Sharma, Y Brooks, BR Tjandra, N AF Lipsitz, RS Sharma, Y Brooks, BR Tjandra, N TI Hydrogen bonding in high-resolution protein structures: A new method to assess NMR protein geometry SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID EGG-WHITE LYSOZYME; AB-INITIO; SECONDARY STRUCTURE; GLOBULAR-PROTEINS; ATOMIC-RESOLUTION; CRYSTAL-STRUCTURE; REFINEMENT; ANGSTROM; BARRIER; SERINE AB An analysis of backbone hydrogen bonds has been performed on nine high-resolution protein X-ray crystal structures. Backbone hydrogen-bond geometry is compared in the context of X-ray crystal structure resolution. A strong correlation between the hydrogen-bond distance, R-HO, and the hydrogen-bond angle, theta(NHO), is observed when the X-ray crystal structure resolution is <1.00 Angstrom. Ab initio calculations were performed to substantiate these results. The angle and distance limits found in our correlation for the backbone hydrogen-bond geometry can be used to evaluate the quality of protein structures and for further NMR structure refinement. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Room 3503, Bethesda, MD 20892 USA. NR 41 TC 32 Z9 33 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 4 PY 2002 VL 124 IS 35 BP 10621 EP 10626 DI 10.1021/ja020676p PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 591LH UT WOS:000177881300060 PM 12197765 ER PT J AU White, J AF White, J TI PC-SPES-A lesson for future dietary supplement research SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CHINESE HERBAL PREPARATION; ALTERNATIVE MEDICINE USE; PROSTATE-CANCER; ETHANOLIC EXTRACTS; IN-VITRO; CELLS; CONTAMINATION; APOPTOSIS; BAICALIN; THERAPY C1 NCI, NIH, Bethesda, MD 20892 USA. RP White, J (reprint author), NCI, NIH, Execut Plaza N,Rm 102,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 39 TC 23 Z9 23 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 4 PY 2002 VL 94 IS 17 BP 1261 EP 1263 PG 3 WC Oncology SC Oncology GA 588ZJ UT WOS:000177732100001 PM 12208885 ER PT J AU Michaud, DS Liu, SM Giovannucci, E Willett, WC Colditz, GA Fuchs, CS AF Michaud, DS Liu, SM Giovannucci, E Willett, WC Colditz, GA Fuchs, CS TI Dietary sugar, glycemic load, and pancreatic cancer risk in a prospective study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; CORONARY HEART-DISEASE; NATIONAL DEATH INDEX; MIXED MEALS; CLINICAL IMPLICATIONS; INSULIN RESPONSES; DIRECT INTERVIEWS; NUTRIENT INTAKE; GLUCOSE; WOMEN AB Background: Evidence from both animal and human studies suggests that abnormal glucose metabolism plays an important role in pancreatic carcinogenesis. We investigated whether diets high in foods that increase postprandial glucose levels are associated with an increased risk of pancreatic cancer. Methods: In a cohort of U.S. women (n = 88 802) participating in the Nurses' Health Study, 180 case subjects with pancreatic cancer were diagnosed during 18 years of follow-up. We used frequency of intake of individual foods as reported on a food-frequency questionnaire in 1980 to calculate sucrose, fructose, and carbohydrate intakes; glycemic index (postprandial blood glucose response as compared with a reference food); and glycemic load (glycemic index multiplied by carbohydrate content). Analyses of relative risk (RR) were performed by using multivariable Cox proportional hazards models to adjust for potential confounders. All statistical tests were two-sided. Results: Carbohydrate and sucrose intake were not associated with overall pancreatic cancer risk in this cohort. A statistically nonsignificant 53% increase in risk of pancreatic cancer (RR = 1.53, 95% confidence interval [CI] = 0.96 to 2.45) was observed among women with a high glycemic load intake, and a similar association was observed for fructose intake (RR = 1.57, 95% CI = 0.95 to 2.57). The associations of glycemic load and fructose intakes with pancreatic cancer risk were most apparent among women with elevated body mass index (greater than or equal to25 kg/m(2)) or with low physical activity. Among women who were both overweight and sedentary, a high glycemic load was associated with an RR of 2.67 (95% CI = 1.02 to 6.99; highest versus lowest quartile of intake; P for trend = .03), and high fructose was associated with an RR of 3.17 (95% CI = 1.13 to 8.91; P for trend = .04). Conclusion: Our data support other findings that impaired glucose metabolism may play a role in pancreatic cancer etiology. A diet high in glycemic load may increase the risk of pancreatic cancer in women who already have an underlying degree of insulin resistance. C1 NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. RP Michaud, DS (reprint author), NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Rm 3032, Rockville, MD 20852 USA. RI Liu, Simin/I-3689-2014; Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Liu, Simin/0000-0003-2098-3844; Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA86102, CA87969]; NIDDK NIH HHS [DK02767] NR 47 TC 127 Z9 130 U1 3 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 4 PY 2002 VL 94 IS 17 BP 1293 EP 1300 PG 8 WC Oncology SC Oncology GA 588ZJ UT WOS:000177732100009 PM 12208894 ER PT J AU Auvinen, A Curtis, RE Ron, E AF Auvinen, A Curtis, RE Ron, E TI Risk of subsequent cancer following breast cancer in men SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID 2ND CANCERS; MUTATIONS; EPIDEMIOLOGY; MELANOMA AB The etiology of breast cancer in men is not well understood. We assessed the risk of subsequent cancers among all 1788 men diagnosed with a first primary breast cancer from 1973 through 1996 who were registered with the Surveillance, Epidemiology, and End Results (SEER) Program. Although the overall subsequent cancer risk in men was not increased (standardized incidence ratio [SIR] = 0.99, 95% confidence interval [CI] = 0.86 to 1.1), the risk of contralateral second breast cancer was strongly elevated (12 cases; SIR = 30, 95% CI = 15 to 52). The risk was higher for men diagnosed with their first breast cancer before age 50 years than for older men. There were no major differences in the risk of contralateral breast cancer associated with different treatments received for the first breast cancer. The relative risk of second breast cancer was substantially higher among men than among women with breast cancer, but the absolute excess risk was lower. We conclude that men diagnosed with breast cancer are at high risk of contralateral breast cancer. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Curtis, RE (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza S,Rm 7042, Bethesda, MD 20892 USA. OI Auvinen, Anssi/0000-0003-1125-4818 NR 25 TC 40 Z9 42 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 4 PY 2002 VL 94 IS 17 BP 1330 EP 1332 PG 3 WC Oncology SC Oncology GA 588ZJ UT WOS:000177732100013 PM 12208898 ER PT J AU Davis, BR Cutler, JA Furberg, CD Wright, JT Farber, MA Felicetta, JV Stokes, JD AF Davis, BR Cutler, JA Furberg, CD Wright, JT Farber, MA Felicetta, JV Stokes, JD CA ALLHAT Collaborative Res Grp TI Relationship of antihypertensive treatment regimens and change in blood pressure to risk for heart failure in hypertensive patients randomly assigned to doxazosin or chlorthalidone: Further analyses from the antihypertensive and lipid-lowering treatment to prevent heart attack trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID MULTIPLE IMPUTATION AB Background: The Anti hypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial reported that treatment initiated with doxazosin compared with chlorthalidone doubled the risk for heart failure in high-risk hypertensive patients (relative risk, 2.04 [95% CI, 1.79 to 2.32]). Patients assigned to doxazosin therapy had a mean in-trial systolic/diastolic blood pressure 3/0 mm Hg higher than that in patients assigned to chlorthalidone. Sixty-eight percent (6167 of 9061) of the former patients and 59% (9081 of 15 256) of the latter patients were given additional medications to achieve a target blood pressure of less than 140/90 mm Hg. Objective: To ascertain the influence of open-label antihypertensive drugs and subsequent blood pressure on relative risk for heart failure. Design: Randomized, double-blind, active-controlled clinical trial. Setting: 623 sites in the United States and Canada. Patients: Hypertensive patients 55 years of age or older with at least one additional risk factor for cardiovascular disease. Intervention: Chlorthalidone (12.5 to 25 mg/d) or doxazosin (2 to 8 mg/d) for a planned follow-up of 4 to 8 years. Measurements: Data on blood pressure, medication, and incident heart failure (treated outside hospital, hospitalized, or fatal) from February 1994 through December 1999. Results: After the treatment groups were categorized as having no exposure to open-label medications (monotherapy) or exposure to open-label therapy, the relative risk for heart failure with doxazosin versus chlorthalidone was 3.10 (CI, 2.51 to 3.82) and 1.42 (CI, 1.20 to 1.69), respectively. After adjustment for follow-up systolic/diastolic blood pressure, the overall relative risk was 2.00 (CI, 1.72 to 2.32). Conclusion: In high-risk patients with hypertension, the higher risk for heart failure while taking doxazosin compared with chlorthalidone is attenuated but not eliminated by adding other anti hypertensive drugs. The small observed difference in systolic blood pressure does not explain this increased risk. C1 Univ Texas, Sch Publ Hlth, Houston, TX 77030 USA. NHLBI, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Pitman Internal Med Associates, Pitman, NJ USA. Carl T Hayden Vet Affiars Med Ctr, Phoenix, AZ USA. RP Davis, BR (reprint author), Univ Texas, Sch Publ Hlth, 1200 Herman Pressler St, Houston, TX 77030 USA. FU NHLBI NIH HHS [N0-HC-35130] NR 11 TC 51 Z9 51 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 3 PY 2002 VL 137 IS 5 BP 313 EP 320 PN 1 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 591DZ UT WOS:000177865600002 PM 12204014 ER PT J AU Dybul, M Fauci, AS Bartlett, JG Kaplan, JE Pau, AK AF Dybul, M Fauci, AS Bartlett, JG Kaplan, JE Pau, AK TI Guidelines for using antiretroviral agents among HIV-infected adults and adolescents - The panel on clinical practices for treatment of HIV SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITOR; PNEUMOCYSTIS-CARINII PNEUMONIA; PLACEBO-CONTROLLED TRIAL; TYPE-1 RNA LEVELS; CD4 CELL COUNTS; INDUCED MITOCHONDRIAL TOXICITY; RANDOMIZED CONTROLLED TRIAL; SEVERE LACTIC-ACIDOSIS; BONE-MINERAL LOSS AB The availability of an increasing number of antiretroviral agents and the rapid evolution of new information have introduced substantial complexity into treatment regimens for persons infected with human immunodeficiency virus (HIV). In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for clinical management of HIV-infected adults and adolescents (CDC. Report of the NIH Panel To Define Principles of Therapy of HIV Infection and Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR. 1998;47[RR-5]:1-41). This report, which updates the 1998 guidelines, addresses 1) using testing for plasma HIV ribonucleic acid levels (i.e., viral load) and CD4(+) T cell count; 2) using testing for antiretroviral drug resistance; 3) considerations for when to initiate therapy; 4) adherence to antiretroviral therapy; 5) considerations for therapy among patients with advanced disease; 6) therapy-related adverse events; 7) interruption of therapy, 8) considerations for changing therapy and available therapeutic options; 9) treatment for acute HIV infection; 10) considerations for antiretroviral therapy among adolescents; 11) considerations for antiretroviral therapy among pregnant women; and 12) concerns related to transmission of HIV to others. Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of non-adherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions are critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. In general, treatment should be offered to persons who have <350 CD4(+) T cells/mm(3) or plasma HIV ribonucleic acid (RNA) levels of >55,000 copies/mL (by b-deoxyribonucleic acid [bDNA] or reverse transcriptase-polymerase chain reaction [RT-PCR] assays). The recommendation to treat asymptomatic patients should be based on the willingness and readiness of the pet-son to begin therapy; the degree of existing immunodeficiency as determined by the CD4(+) T cell count; the risk for disease progression as determined by the CD4(+) T cell count and level of plasma HIV RNA; the potential benefits and risks of initiating therapy in an asymptomatic person; and the likelihood, after counseling and education, of adherence to the prescribed treatment regimen. Treatment goals should be maximal and durable suppression of viral load, restoration and preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. Results of therapy are evaluated through plasma HIV RNA levels, which are expected to indicate a 1.0 log(10) decrease at 2-8 weeks and no detectable virus (<50 copies/mL) at 4-6 months after treatment initiation. Failure of therapy at 4-6 months might be ascribed to nonadherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, viral resistance, and other factors that are poorly understood. Patients whose therapy fails in spite of a high level of adherence to the regimen should have their regimen changed; this change should be guided by a thorough drug treatment history and the results of drug-resistance testing. Because of limitations in Me available alternative antiretroviral regimens Mat have documented efficacy optimal changes in therapy might be difficult to achieve for patients in whom the preferred regimen has failed. These decisions are further confounded by problems with adherence, toxicity, and resistance. For certain patients, participating in a clinical trial with or without access to new drugs or using a regimen that might not achieve complete suppression of viral replication might be preferable. Because concepts regarding HIV management are evolving rapidly, readers should check regularly for additional information and updates at the HIV/AIDS Treatment Information Service website (http://www.hivatis.org). C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. CDC, Atlanta, GA 30333 USA. RP Dybul, M (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 253 TC 214 Z9 224 U1 1 U2 16 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 3 PY 2002 VL 137 IS 5 BP 381 EP 433 PN 2 PG 53 WC Medicine, General & Internal SC General & Internal Medicine GA 592TJ UT WOS:000177952700001 PM 12617573 ER PT J AU Masur, H Kaplan, JE Holmes, KK AF Masur, H Kaplan, JE Holmes, KK TI Guidelines for preventing opportunistic infections among HIV-infected persons - 2002 - Recommendations of the US Public Health Service and the Infectious Diseases Society of America SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; PNEUMOCYSTIS-CARINII PNEUMONIA; MYCOBACTERIUM-AVIUM COMPLEX; ACTIVE ANTIRETROVIRAL THERAPY; PLACEBO-CONTROLLED TRIAL; MOTHER-TO-CHILD; DOUBLE-BLIND TRIAL; CYTOMEGALOVIRUS RETINITIS; PRIMARY PROPHYLAXIS; RANDOMIZED TRIAL AB In 1995, the U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) developed guidelines for preventing opportunistic infections (OIs) among persons infected with human immunodeficiency virus (HIV); these guidelines were updated in 1997 and 1999. This fourth edition of the guidelines, made available on the Internet in 2001, is intended for clinicians and other health-care providers who care for HIV-infected persons. The goal of these guidelines is to provide evidence-based guidelines for preventing OIs among HIV-infected adults and adolescents, including pregnant women, and HIV-exposed or infected children. Nineteen OIs, or groups of OIs, are addressed, and recommendations are included for preventing exposure to opportunistic pathogens, preventing first episodes of disease by chemoprophylaxis or vaccination (primary prophylaxis), and preventing disease recurrence (secondary prophylaxis). Major changes since the last edition of the guidelines include 1) updated recommendations for discontinuing primary and secondary OI prophylaxis among persons whose CD4(+) T lymphocyte counts have increased in response to antiretroviral therapy; 2) emphasis on screening all HIV-infected persons for infection with hepatitis C virus; 3) new information regarding transmission of human herpesvirus 8 infection; 4) new information regarding drug interactions, chiefly related to rifamycins and antiretroviral drugs; and 5) revised recommendations for immunizing HIV-infected adults and adolescents and HIV-exposed or infected children. C1 NIH, Bethesda, MD 20892 USA. CDC, Atlanta, GA 30333 USA. Univ Washington, Seattle, WA 98195 USA. RP Masur, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 146 TC 137 Z9 149 U1 1 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 3 PY 2002 VL 137 IS 5 BP 435 EP 477 PN 2 PG 43 WC Medicine, General & Internal SC General & Internal Medicine GA 592TJ UT WOS:000177952700002 PM 12617574 ER PT J AU Wang, TJ Larson, MG Levy, D Benjamin, EJ Kupka, MJ Manning, WJ Clouse, ME D'Agostino, RB Wilson, PWF O'Donnell, CJ AF Wang, TJ Larson, MG Levy, D Benjamin, EJ Kupka, MJ Manning, WJ Clouse, ME D'Agostino, RB Wilson, PWF O'Donnell, CJ TI C-reactive protein is associated with subclinical epicardial coronary calcification in men and women - The Framingham heart study SO CIRCULATION LA English DT Article DE coronary disease; inflammation; imaging ID BEAM COMPUTED-TOMOGRAPHY; BODY-MASS INDEX; ARTERY CALCIUM; RISK FACTOR; DISEASE; ADULTS; ATHEROSCLEROSIS; PREDICTION AB Background-High C-reactive protein (CRP) levels are associated with an increased risk of cardiovascular events, even in apparently healthy individuals. It has not been established whether elevated CRP reflects an increased burden of subclinical coronary atherosclerosis. Methods and Results-We studied a stratified random sample of 321 men and women (mean age 60 years) from the Framingham Heart Study who were free of clinically apparent cardiovascular disease. Subjects underwent electron-beam computed tomography to assess the number of coronary calcifications and the coronary artery calcification (CAC) Agatston score. Spearman correlation coefficients between CRP and CAC score were calculated and adjusted for age, age plus individual risk factors, and age plus the Framingham coronary heart disease risk score. For both sexes, CRP was significantly correlated with the Agatston score (age-adjusted Spearman correlation: 0.25 for men, 0.26 for women; both P < 0.01). After adjustment for age and Framingham risk score, the correlation remained significant (P = 0.01) for both sexes. Further adjustment for body mass index attenuated the correlation coefficient for women (0.14, P = 0.09) but not for men (0.19, P < 0.05). Conclusions-High CRP levels are associated with increased coronary calcification. Among individuals with elevated CRP, subclinical atherosclerosis may contribute to an increased risk for future cardiovascular events. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Dept Med,Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Dept Radiol, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01-HL64753, N01-HC-25195] NR 17 TC 128 Z9 137 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 3 PY 2002 VL 106 IS 10 BP 1189 EP 1191 DI 10.1161/01.CIR.000032135.98011.C4 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 593AG UT WOS:000177968600004 PM 12208790 ER PT J AU Roth, SM Ferrell, RE Peters, DG Metter, EJ Hurley, BF Rogers, MA AF Roth, SM Ferrell, RE Peters, DG Metter, EJ Hurley, BF Rogers, MA TI Influence of age, sex, and strength training on human muscle gene expression determined by microarray SO PHYSIOLOGICAL GENOMICS LA English DT Article DE aging; exercise; gender; transcription; transcriptome ID MAMMALIAN SWI/SNF COMPLEXES; SKELETAL-MUSCLE; MESSENGER-RNAS; OLDER MEN; CDNA MICROARRAYS; CALDESMON; GENDER; ACTIN; YOUNG; EXERCISE AB Influence of age, sex, and strength training on human muscle gene expression determined by microarray. Physiol Genomics 10: 181- 190, 2002. First published July 23, 2002; 10.1152/ physiolgenomics. 00028.2002.- The purpose of this study was to determine the influence of age, sex, and strength training (ST) on large- scale gene expression patterns in vastus lateralis muscle biopsies using high- density cDNA microarrays and quantitative PCR. Muscle samples from sedentary young (20-30 yr) and older (65-75 yr) men and women (5 per group) were obtained before and after a 9-wk unilateral heavy resistance ST program. RNA was hybridized to cDNA filter microarrays representing 4,000 known human genes and comparisons were made among arrays to determine differential gene expression as a result of age and sex differences, and/ or response to ST. Sex had the strongest influence on muscle gene expression, with differential expression (>1.7-fold) observed for 200 genes between men and women (75% with higher expression in men). Age contributed to differential expression as well, as 50 genes were identified as differentially expressed (>1.7-fold) in relation to age, representing structural, metabolic, and regulatory gene classes. Sixty- nine genes were identified as being differentially expressed (>1.7-fold) in all groups in response to ST, and the majority of these were downregulated. Quantitative PCR was employed to validate expression levels for caldesmon, SWI/ SNF (BAF60b), and four- and- a- half LIM domains 1. These significant differences suggest that in the analysis of skeletal muscle gene expression issues of sex, age, and habitual physical activity must be addressed, with sex being the most critical variable. C1 Univ Pittsburgh, Dept Human Genet, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. Univ Maryland, Coll Hlth & Human Performance, Dept Kinesiol, College Pk, MD 20742 USA. NIA, NIH, Baltimore, MD 21224 USA. RP Roth, SM (reprint author), Univ Pittsburgh, Dept Human Genet, Grad Sch Publ Hlth, A300 Crabtree Hall GSPH, Pittsburgh, PA 15261 USA. OI Roth, Stephen/0000-0002-7841-3695 FU NIA NIH HHS [F32 AG005893-03, AG-05893, AG-42148, F32 AG005893, F32 AG005893-01, F32 AG005893-02, R01 AG005893]; NIDDK NIH HHS [DK-46204, P30 DK046204] NR 46 TC 76 Z9 81 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD SEP 3 PY 2002 VL 10 IS 3 BP 181 EP 190 DI 10.1152/physiolgenomics00028.2002 PG 10 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 589WF UT WOS:000177784000006 PM 12209020 ER PT J AU Lee, Y Yu, X Gonzales, F Mangelsdorf, DJ Wang, MY Richardson, C Witters, LA Unger, RH AF Lee, Y Yu, X Gonzales, F Mangelsdorf, DJ Wang, MY Richardson, C Witters, LA Unger, RH TI PPAR alpha is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACTIVATED PROTEIN-KINASE; FATTY-ACID OXIDATION; LEPTIN; EXPRESSION; ENZYMES; FORM; RATS; COA AB Adenovirus-induced hyperleptinemia causes rapid disappearance of body fat in normal rats, presumably by up-regulating fatty acid oxidation within white adipocytes. To determine the role of peroxisomal proliferation-activated receptor (PPAR)alpha expression, which was increased during the rapid loss of fat, we infused adenovirus-leptin into PPARalpha(-/-) and PPARalpha(+/+) mice. Despite similar degrees of hyperleptinemia and reduction in food intake, epididymal fat pad weight declined 55% in wild-type but only 6% in PPARalpha(-/-) mice; liver triacylglycerol fell 39% in the wild-type group but was unchanged in PPAR(-/-) mice. Carnitine palmitoyl transferase-1 mRNA rose 52% in the wild-type mice but did not increase in PPARalpha(-/-) mice. PPARgamma coactivator-1 a rose 3-fold in the fat and 46% in the liver of wild-type mice but was unchanged in PPARalpha(-/-) mice. Although AMP-activated protein kinase could not be implicated in the lipopenic actions of hyperleptinemia, acetyl CoA carboxylase protein was reduced in the liver of wild-type but not in PPARalpha(-/-) mice. Thus, in PPARalpha(-/-) mice, up-regulation of carnitine palmitoyl transferase-1 mRNA in fat, down-regulation of acetyl CoA carboxylase in liver, and up-regulation of PPARgamma coactivator-1 a mRNA in both tissues are abolished, as is the reduction in their triacylglycerol content. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75290 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75290 USA. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75290 USA. Univ Texas, SW Med Ctr, Touchstone Ctr Diabet Res, Dallas, TX 75290 USA. Univ Texas, SW Med Ctr, Vet Affairs Med Ctr, Dallas, TX 75290 USA. NIH, Bethesda, MD 20892 USA. Dartmouth Coll, Dept Biol Sci, Hanover, NH 03755 USA. RP Unger, RH (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75290 USA. FU NIDDK NIH HHS [DK35712, R01 DK035712, R01 DK002700, P01 DK058398, K08 DK002700, DK58398, DK02700] NR 19 TC 121 Z9 125 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 3 PY 2002 VL 99 IS 18 BP 11848 EP 11853 DI 10.1073/pnas.182420899 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 590UW UT WOS:000177843100057 PM 12195019 ER PT J AU Roth, BL Baner, K Westkaemper, R Siebert, D Rice, KC Steinberg, S Ernsberger, P Rothman, RB AF Roth, BL Baner, K Westkaemper, R Siebert, D Rice, KC Steinberg, S Ernsberger, P Rothman, RB TI Salvinorin A: A potent naturally occurring nonnitrogenous kappa opioid selective agonist SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MINT SALVIA-DIVINORUM; 5-HYDROXYTRYPTAMINE(2A) RECEPTORS; NEOCLERODANE DITERPENE; BINDING; SCHIZOPHRENIA; NALTREXONE; DYNORPHIN; DELTA; MU; DESENSITIZATION AB Salvia divinorum, whose main active ingredient is the neoclerodane diterpene Salvinorin A, is a hallucinogenic plant in the mint family that has been used in traditional spiritual practices for its psychoactive properties by the Mazatecs of Oaxaca, Mexico. More recently, S. divinorum extracts and Salvinorin A have become more widely used in the U.S. as legal hallucinogens. We discovered that Salvinorin A potently and selectively inhibited H-3-bremazocine binding to cloned kappa opioid receptors. Salvinorin A had no significant activity against a battery of SO receptors, transporters, and ion channels and showed a distinctive profile compared with the prototypic hallucinogen lysergic acid diethylamide. Functional studies demonstrated that Salvinorin A is a potent kappa opioid agonist at cloned kappa opioid receptors expressed in human embryonic kidney-293 cells and at native kappa opioid receptors expressed in guinea pig brain. Importantly, Salvinorin A had no actions at the 5-HT2A serotonin receptor, the principal molecular target responsible for the actions of classical hallucinogens. Salvinorin A thus represents, to our knowledge, the first naturally occurring nonnitrogenous opioid-receptor subtype-selective agonist. Because Salvinorin A is a psychotomimetic selective for kappa opioid receptors, kappa opioid-selective antagonists may represent novel psychotherapeutic compounds for diseases manifested by perceptual distortions (e.g., schizophrenia, dementia, and bipolar disorders). Additionally, these results suggest that kappa opioid receptors play a prominent role in the modulation of human perception. C1 Case Western Reserve Univ, Sch Med, NIMH, Drug Screening Program, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Pharmacol & Nutr, Cleveland, OH 44106 USA. NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Virginia Commonwealth Univ Med Coll Virginia, Dept Med Chem, Richmond, VA 23298 USA. Salvia Divinorum Res & Informat Ctr, Malibu, CA 90263 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Rothman, RB (reprint author), Case Western Reserve Univ, Sch Med, NIMH, Drug Screening Program, Cleveland, OH 44106 USA. RI Roth, Bryan/F-3928-2010; Ernsberger, Paul/O-2702-2014 OI Ernsberger, Paul/0000-0003-2372-2500 FU NIMH NIH HHS [K02 MH001366, KO2MH01366, N01MH80004, N02MH80004] NR 50 TC 430 Z9 437 U1 3 U2 32 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 3 PY 2002 VL 99 IS 18 BP 11934 EP 11939 DI 10.1073/pnas.182234399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 590UW UT WOS:000177843100072 PM 12192085 ER PT J AU Ferre, S Karcz-Kubicha, M Hope, BT Popoli, P Burgueno, J Gutierrez, MA Casado, V Fuxe, K Goldberg, SR Lluis, C Franco, R Ciruela, F AF Ferre, S Karcz-Kubicha, M Hope, BT Popoli, P Burgueno, J Gutierrez, MA Casado, V Fuxe, K Goldberg, SR Lluis, C Franco, R Ciruela, F TI Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: Implications for striatal neuronal function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID C-FOS EXPRESSION; PROTEIN-COUPLED RECEPTORS; A(2A) RECEPTORS; 6-HYDROXYDOPAMINE-LESIONED RATS; DOPAMINE-D-2 RECEPTORS; MESSENGER-RNA; INDUCTION; TRANSMISSION; LOCALIZATION; INVOLVEMENT AB The physiological meaning of the coexpression of adenosine A2A receptors and group I metabotropic glutamate receptors in aminobutyric acid (GABA)ergic striatal neurons is intriguing. Here we provide in vitro and in vivo evidence for a synergism between adenosine and glutamate based on subtype 5 metabotropic glutamate (mGluR5) and adenosine A2A (A2AR) receptor/receptor interactions. Colocalization of A2AR and mGluR5 at the membrane level was demonstrated in nonpermeabilized human embryonic kidney (HEK)-293 cells transiently cotransfected with both receptors by confocal laser microscopy. Complexes containing A2AR and mGluR5 were demonstrated by Western blotting of immunoprecipitates of either Flag-A2AR or hemagglutinin-mGluR5 in membrane preparations from cotransfected HEK-293 cells and of native A2AR and mGluR5 in rat striatal membrane preparations. In cotransfected HEK-293 cells a synergistic effect on extracellular signal-regulated kinase 1/2 phosphorylation and c-fos expression was demonstrated upon A2AR/mGluR5 costimulation. No synergistic effect was observed at the second messenger level (cAMP accumulation and intracellular calcium mobilization). Accordingly, a synergistic effect on c-fos expression in striatal sections and on counteracting phencyclidine-induced motor activation was also demonstrated after the central coadministration of A2AR and mGluR5 agonists to rats with intact dopaminergic innervation. The results suggest that a functional mGluR5/A2AR interaction is required to overcome the well-known strong tonic inhibitory effect of dopamine on striatal adenosine A2AR function. C1 NIDA, Behav Neurosci Branch, NIH, Intramural Res Program, Baltimore, MD 21224 USA. Ist Super Sanita, Dept Pharmacol, I-00161 Rome, Italy. Univ Barcelona, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. RP Ferre, S (reprint author), NIDA, Behav Neurosci Branch, NIH, Intramural Res Program, POB 5180, Baltimore, MD 21224 USA. RI Popoli, Patrizia/B-5397-2008; Hope, Bruce/A-9223-2010; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014 OI Fuxe, Kjell/0000-0001-8491-4288; Casado, Vicent/0000-0002-1764-3825; Hope, Bruce/0000-0001-5804-7061; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; NR 35 TC 221 Z9 225 U1 3 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 3 PY 2002 VL 99 IS 18 BP 11940 EP 11945 DI 10.1073/pnas.172393799 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 590UW UT WOS:000177843100073 PM 12189203 ER PT J AU Wang, RF Corbett, TH Cheng, YC Drach, JC Kern, ER Mitsuya, H Zemlicka, J AF Wang, RF Corbett, TH Cheng, YC Drach, JC Kern, ER Mitsuya, H Zemlicka, J TI Tryptophanyl phosphoramidates as prodrugs of synadenol and its E-isomer: Synthesis and biological activity SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID NUCLEOSIDE ANALOGS; 3'-AZIDO-3'-DEOXYTHYMIDINE AZT; METHYLENECYCLOPROPANE ANALOGS; ANTIVIRAL ACTIVITY; DERIVATIVES; EFFICACY; DIESTERS AB Phosphorotryptophanates 2c and 3c were synthesized and investigated as prodrugs of synadenol (2a) and its E-isomer 3a. The antiviral activity of 2c corresponds to parent analogue 2a but it is lower than that of phenylphosphoralaninate 2b. This may indicate an enzymatic cleavage of phosphorotryptophanate 2c to 2a before or after entering the host cells. The E-isomer 3c was effective only against EBV with parameters suggesting intracellular delivery of the respective phosphate. Compound 2c has a moderate but selective activity against solid tumors. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA. Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48019 USA. Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. NCI, Expt Retrovirol Sect, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 860, Japan. RP Zemlicka, J (reprint author), Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. FU NCI NIH HHS [R01-CA46560, R01-CA32779]; NIAID NIH HHS [U19-AI31718, N01-AI 385347]; PHS HHS [R01-44358] NR 12 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD SEP 2 PY 2002 VL 12 IS 17 BP 2467 EP 2470 AR PII S0960-894X(02)00423-7 DI 10.1016/S0960-894X(02)00423-7 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 586UE UT WOS:000177603200048 PM 12161159 ER PT J AU Nicholas, GM Eckman, LL Ray, S Hughes, RO Pfefferkorn, JA Barluenga, S Nicolaou, KC Bewley, CA AF Nicholas, GM Eckman, LL Ray, S Hughes, RO Pfefferkorn, JA Barluenga, S Nicolaou, KC Bewley, CA TI Bromotyrosine-derived natural and synthetic products as inhibitors of mycothiol-S-conjugate amidase SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; PSAMMAPLIN-A; SPONGE; METABOLITES; BIOSYNTHESIS; DERIVATIVES; ALKALOIDS; DISULFIDE; THIOLS; MRSA AB A series of bromotyrosine-derived compounds, including marine natural products and members of a psammaplin A-inspired combinatorial synthetic library, were screened for their ability to inhibit the Mycobacterium tuberculosis detoxification enzyme mycothiol-S-conjugate amidase (MCA). Correlations between the structures and their respective IC50 values (which range from 3 muM to 2.7 mM) should prove valuable when optimizing more potent inhibitors of MCA. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. RP Bewley, CA (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 28 TC 51 Z9 55 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD SEP 2 PY 2002 VL 12 IS 17 BP 2487 EP 2490 AR PII S0960-894X(02)00385-2 DI 10.1016/S0960-894X(02)00385-2 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 586UE UT WOS:000177603200053 PM 12161164 ER PT J AU Vazquez, G Wedel, BJ Bird, GSJ Joseph, SK Putney, JW AF Vazquez, G Wedel, BJ Bird, GSJ Joseph, SK Putney, JW TI An inositol 1,4,5-trisphosphate receptor-dependent cation entry pathway in DT40 B lymphocytes SO EMBO JOURNAL LA English DT Article DE B lymphocyte; calcium channels; inositol trisphosphate receptor; phospholipase C; plasma membrane ID CAPACITATIVE CALCIUM-ENTRY; SMOOTH-MUSCLE CELLS; ACTIVATED CA2+ CHANNELS; OPERATED HTRP3 CHANNELS; RAT OLFACTORY NEURONS; PLASMA-MEMBRANE; IP3 RECEPTOR; 2-AMINOETHOXYDIPHENYL BORATE; INSP(3) RECEPTOR; ANTIGEN RECEPTOR AB We examined the roles of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) in calcium signaling using DT40 B lymphocytes, and a variant lacking the three IP3R isoforms (IP3R-KO). In wild-type cells, B cell receptor (BCR) stimulation activates a cation entry route that exhibits significantly greater permeability to Ba2+ than does capacitative calcium entry. This cation entry is absent in IP3R-KO cells. Expression of the type-3 IP3R (IP3R-3) in the IP3R-KO cells rescued not only agonist-dependent release of intracellular Ca2+, but also Ba2+ influx following receptor stimulation. Similar results were obtained with an IP3R-3 mutant carrying a conservative point mutation in the selectivity filter region of the channel (D2477E); however, an IP3R-3 mutant in which this same aspartate was replaced by alanine (D2477A) failed to restore either BCR-induced Ca2+ release or receptor-dependent Ba2+ entry. These results suggest that in DT40 B lymphocytes, BCR stimulation activates a novel cation entry across the plasma membrane that depends upon, or is mediated by, fully functional IP3R. C1 NIEHS, Calcium Regulat Sect, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Thomas Jefferson Univ, Dept Pathol & Cell Biol, Philadelphia, PA 19103 USA. RP Putney, JW (reprint author), NIEHS, Calcium Regulat Sect, Lab Signal Transduct, NIH, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 63 TC 44 Z9 45 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 2 PY 2002 VL 21 IS 17 BP 4531 EP 4538 DI 10.1093/emboj/cdf467 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 589PW UT WOS:000177770100015 PM 12198155 ER PT J AU Wasiak, S Legendre-Guillemin, V Puertollano, R Blondeau, F Girard, M de Heuvel, E Boismenu, D Bell, AW Bonifacino, JS McPherson, PS AF Wasiak, S Legendre-Guillemin, V Puertollano, R Blondeau, F Girard, M de Heuvel, E Boismenu, D Bell, AW Bonifacino, JS McPherson, PS TI Enthoprotin: a novel clathrin-associated protein identified through subcellular proteomics SO JOURNAL OF CELL BIOLOGY LA English DT Article DE clathrin adaptors; endosome; ENTH domain; GGAs; TGN ID MANNOSE 6-PHOSPHATE RECEPTORS; SYNAPTIC VESICLE ENDOCYTOSIS; MEMBRANE-PROTEINS; TRANSPORT; BINDING; COMPLEX AB Despite numerous advances in the identification of the molecular machinery for clathrin-mediated budding at the plasma membrane, the mechanistic details of this process remain incomplete. Moreover, relatively little is known regarding the regulation of clathrin-mediated budding at other membrane systems. To address these issues, we have utilized the powerful new approach of subcellular proteomics to identify novel proteins present on highly enriched clathrin-coated vesicles (CCVs). Among the ten novel proteins identified is the rat homologue of a predicted gene product from human, mouse, and Drosophila genomics projects, which we named enthoprotin. Enthoprotin is highly enriched on CCVs isolated from rat brain and liver extracts. In cells, enthoprotin demonstrates a punctate staining pattern that is concentrated in a perinuclear compartment where it colocalizes with clathrin and the clathrin adaptor protein (AP)l. Enthoprotin interacts with the clathrin adaptors AP1 and with Golgi-localized, gamma-ear-containing, Arf-binding protein 2. Through its COOH-terminal domain, enthoprotin binds to the terminal domain of the clathrin heavy chain and stimulates clathrin assembly. These data suggest a role for enthoprotin in clathrin-mediated budding on internal membranes. Our study reveals the utility of proteomics in the identification of novel vesicle trafficking proteins. C1 McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, CBET Grp, Montreal, PQ H3A 2B4, Canada. McGill Univ, Montreal Proteom Ctr, Montreal, PQ H3A 2B4, Canada. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP McPherson, PS (reprint author), McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, CBET Grp, 3801 Univ St, Montreal, PQ H3A 2B4, Canada. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 31 TC 146 Z9 151 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP 2 PY 2002 VL 158 IS 5 BP 855 EP 862 DI 10.1083/jcb.200205078 PG 8 WC Cell Biology SC Cell Biology GA 590UV UT WOS:000177843000004 PM 12213833 ER PT J AU Friedman, DP Aggleton, JP Saunders, RC AF Friedman, DP Aggleton, JP Saunders, RC TI Comparison of hippocampal, amygdala, and perirhinal projections to the nucleus accumbens: Combined anterograde and retrograde tracing study in the macaque brain SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE nucleus accumbens; ventral striatum; entorhinal cortex; perirhinal cortex; monkey; fornix ID MEDIAL PREFRONTAL CORTEX; INFEROTEMPORAL AREA TE; VENTRAL STRIATUM; RHESUS-MONKEY; CEREBRAL-CORTEX; TEMPORAL-LOBE; FUNCTIONAL-DIFFERENTIATION; EFFERENT PROJECTIONS; THALAMIC PROJECTIONS; RECOGNITION MEMORY AB A combination of anterograde, and retrograde tracing techniques was used to study the projections to the nucleus accumbens from the amygdala, the hippocampal formation (including the entorhinal cortex), and the perirhinal cortex in two species of macaque monkey. To help identify possible subregions within the nucleus accumbens, the distribution of calbindin was examined in two additional monkeys. Although this revealed evidence of "core"- and "shell"-like regions within the accumbens, these different regions could not consistently be related to cytoarchitectonic features. The rostral amygdala sent nearly equivalent projections to both the medial and the lateral portions of nucleus accumbens, whereas projections arising from the middle and caudal amygdala terminated preferentially in the medial division of nucleus accumbens. The basal nucleus was the major source of these amygdala efferents, and there was a crude topography as parts of the basal and accessory basal nuclei terminated in different parts of nucleus accumbens. The subiculum was the major source of hippocampal projections to the nucleus accumbens, but some hippocampal efferents also originated in the parasubiculum, the prosubiculum, the adjacent portion of CA1, and the uncal portion of CA3. These hippocampal projections, which coursed through the fornix, showed a rostrocaudal gradient as more arose in the rostral hippocampus. Hippocampal efferents terminated most densely in the medial and ventral portions of nucleus accumbens, along with light label in the adjacent olfactory tubercle. The entorhinal projections were more evenly distributed between the medial nucleus accumbens and the olfactory tubercle, whereas the perirbinal projections were primarily to the olfactory tubercle. These cortical inputs were less reliant on the fornix. Amygdala and subicular (hippocampal) projections overlapped most completely in the medial division of nucleus accumbens. C1 Cardiff Univ, Sch Psychol, Cardiff CF10 3YG, S Glam, Wales. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27157 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Aggleton, JP (reprint author), Cardiff Univ, Sch Psychol, Pk Pl,POB 901, Cardiff CF10 3YG, S Glam, Wales. RI Friedman, David/G-7842-2011; OI Friedman, David/0000-0003-1732-2404; Aggleton, John/0000-0002-5573-1308 NR 78 TC 115 Z9 118 U1 2 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 2 PY 2002 VL 450 IS 4 BP 345 EP 365 DI 10.1002/cne.10336 PG 21 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 577UR UT WOS:000177081000004 PM 12209848 ER PT J AU Ptasznik, A Urbanowska, E Chinta, S Costa, MA Katz, BA Stanislaus, MA Demir, G Linnekin, D Pan, ZK Gewirtz, AM AF Ptasznik, A Urbanowska, E Chinta, S Costa, MA Katz, BA Stanislaus, MA Demir, G Linnekin, D Pan, ZK Gewirtz, AM TI Crosstalk between BCR/ABL oncoprotein and CXCR4 signaling through a Src family kinase in human leukemia cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE BCR/ABL; Src; chemokine receptors; leukemia; chemotaxis ID HEMATOPOIETIC PROGENITOR CELLS; PROTEIN-COUPLED RECEPTORS; CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE; STEM-CELL; PHOSPHOINOSITIDE 3-KINASE; CHEMOKINE SDF-1; BONE-MARROW; FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE AB Stromal-derived factor (SDF)-1 and its G protein-coupled receptor, CXCR4, regulate stem/ progenitor cell migration and retention in the marrow and are required for hematopoiesis. We show here an interaction between CXCR4 and the Src-related kinase, Lyn, in normal progenitors. We demonstrate that CXCR4-dependent stimulation of Lyn is associated with the activation of phosphatidylinositol 3-kinase (PI3-kinase). This chemokine signaling, which involves a Src-related kinase and PI3-kinase, appears to be a target for BCR/ABL, a fusion oncoprotein expressed only in leukemia cells. We show that the binding of phosphorylated BCR/ABL to Lyn results in the constitutive activation of Lyn and PI3-kinase, along with a total loss of responsiveness of these kinases to SDF-1 stimulation. Inhibition of BCR/ABL tyrosine kinase with STI571 restores Lyn responsiveness to SDF-1 signaling. Thus, BCR/ABL perturbs Lyn function through a tyrosine kinase-dependent mechanism. Accordingly, the blockade of Lyn tyrosine kinase inhibits both BCR/ABL-dependent and CXCR4-dependent cell movements. Our results demonstrate, for the first time, that Lyn-mediated pathological crosstalk exists between BCR/ABL and the CXCR4 pathway in leukemia cells, which disrupts chemokine signaling and chemotaxis, and increases the ability of immature cells to escape from the marrow. These results define a Src tyrosine kinases-dependent mechanism whereby BCR/ABL (and potentially other oncoproteins) dysregulates G protein-coupled receptor signaling and function of mammalian precursors. C1 Univ Penn, Sch Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. Med Univ Warsaw, Dept Hematol Oncol & Internal Med, PL-00097 Warsaw, Poland. NCI, Div Basic Sci, Basic Res Lab, Frederick, MD 21702 USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. RP Ptasznik, A (reprint author), Univ Penn, Sch Med, Div Hematol Oncol, BRB-2,7th Floor,Rm 712,421 Curie Blvd, Philadelphia, PA 19104 USA. FU NIDDK NIH HHS [1P01DK52558-03] NR 60 TC 83 Z9 87 U1 2 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 2 PY 2002 VL 196 IS 5 BP 667 EP 678 DI 10.1084/jem.20020519 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 593HJ UT WOS:000177984700010 PM 12208881 ER PT J AU Li, KCP AF Li, KCP TI Biomedical imaging in the postgenomic era: Opportunities and challenges SO ACADEMIC RADIOLOGY LA English DT Editorial Material ID GENE-EXPRESSION; IN-VIVO; DNA MICROARRAYS; PET; TECHNOLOGIES; VALIDATION; ANTIBODIES; MEDICINE; SCANNER; BIOLOGY C1 NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Li, KCP (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10 1C660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. NR 39 TC 5 Z9 6 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 2002 VL 9 IS 9 BP 999 EP 1003 DI 10.1016/S1076-6332(03)80474-9 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 590AV UT WOS:000177795800001 PM 12238554 ER PT J AU Hofmann, A Iwai, H Hess, S Pluckthun, A Wlodawer, A AF Hofmann, A Iwai, H Hess, S Pluckthun, A Wlodawer, A TI Structure of cyclized green fluorescent protein SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID PANCREATIC TRYPSIN-INHIBITOR; ELECTRON-DENSITY MAPS; CRYSTAL-STRUCTURE; IN-VIVO; CYCLIZATION; MOLSCRIPT; STABILITY; BACKBONE; INTEIN; FORM AB Crystals of cyclic green fluorescent protein (cGFP) engineered by the previously reported split intein technology [Iwai et al. (2001), J. Biol. Chem. 276, 16548-16554] were obtained and the structure was solved using molecular replacement. Although the core of the protein can unambiguously be fitted from the first to the last residue of the genuine sequence, the electron density in the region of the linker peptide is rather poor owing to the high water content of the crystals. Therefore, it is concluded that this part of the protein is highly disordered in the present structure and is very flexible. This is supported by the absence of crystal contacts in the linker-peptide region and the fact that the core of the protein exhibits a very similar conformation to that known from other GFP structures, thereby not implicating any constraints arising from the presence of the artificial linker. Nevertheless, the density is consistent with the loop being intact, as confirmed by mass spectroscopy of dissolved crystals. The present structure contains an antiparallel cGFP dimer where the dimer interface is clearly different from other crystal structures featuring two GFP molecules. This adds further support to the fact that the cylinder surface of GFP is rather versatile and can employ various polar and non-polar patches in protein-protein interactions. C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. Univ Zurich, Inst Biochem, CH-8057 Zurich, Switzerland. NIDDK, Struct Mass Spectrometry Facil, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Hofmann, A (reprint author), Univ Edinburgh, Inst Cell & Mol Biol, Edinburgh EH9 3JR, Midlothian, Scotland. RI Iwai, Hideo/A-6416-2009; Hess, Sonja/K-4842-2013; Pluckthun, Andreas/C-2746-2009; Hofmann, Andreas/B-9515-2008 OI Iwai, Hideo/0000-0001-7376-5264; Hess, Sonja/0000-0002-5904-9816; Pluckthun, Andreas/0000-0003-4191-5306; Hofmann, Andreas/0000-0003-4408-5467 NR 47 TC 10 Z9 10 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD SEP PY 2002 VL 58 BP 1400 EP 1406 DI 10.1107/S0907444902010454 PN 9 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 587DE UT WOS:000177624600003 PM 12198295 ER PT J AU Baniecki, ML McGrath, WJ Dauter, Z Mangel, WF AF Baniecki, ML McGrath, WJ Dauter, Z Mangel, WF TI Adenovirus proteinase: crystallization and preliminary X-ray diffraction studies to atomic resolution SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID 11-AMINO-ACID COFACTOR; SEROTYPE-2 PROTEINASE; CRYSTAL-STRUCTURE; PROTEASE; PEPTIDE; SUBSTRATE; BINDING; PAPAIN; DNA AB Adenovirus proteinase (AVP) is required for the synthesis of infectious virus and is a target for antiviral therapy. The enzyme requires two viral cofactors for activation: pVIc, an 11-amino acid peptide, and the viral DNA. The structure of the enzyme in the absence of cofactors has not been observed. Single crystals of AVP were obtained via microseeding using the hanging-drop vapour-diffusion method with sodium acetate and sodium citrate as precipitants. At the National Synchrotron Light Source at Brookhaven National Laboratory, the native crystal diffracted to a resolution of 0.98 Angstrom and an isomorphous heavy-atom derivative diffracted to 1.9 Angstrom. Comparison of the structure of AVP with that of the AVP-pVIc complex should reveal the structural basis of activation of the enzyme by pVIc. C1 Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. NCI, Synchrotron Radiat Res Sect, Upton, NY 11973 USA. Brookhaven Natl Lab, NSLS, Upton, NY 11973 USA. RP Mangel, WF (reprint author), Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. FU NIAID NIH HHS [AI41599] NR 31 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD SEP PY 2002 VL 58 BP 1462 EP 1464 DI 10.1107/S0907444902008429 PN 9 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 587DE UT WOS:000177624600010 PM 12198302 ER PT J AU Martins, ML Soares, BC Ribas, JG Thorun, GW Johnson, J Kroon, EG Carneiro-Prioetti, A Bonjardim, CA AF Martins, ML Soares, BC Ribas, JG Thorun, GW Johnson, J Kroon, EG Carneiro-Prioetti, A Bonjardim, CA CA GIPH TI Frequency of p12K and p12R alleles of HTLV type 1 in HAM/TSP patients and in asymptomatic HTLV type 1 carriers SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID P12(I) PROTEIN; EXPRESSION; CELLS; BINDS AB HTLV-1 has a complex genome, and contains four open reading frames (ORFs) in the 3' region encoding viral and cellular regulatory proteins. p12 is a small, ORF I-encoded hydrophobic protein, the function of which is not well understood. It has been shown that p12 enhances the E5-transforming ability of bovine papillomavirus; and binds to the 16-kDa subunit of the vacuolar ATPase pump, immature forms of the beta and gamma(c), chains of the interleukin 2 receptor, and the free chain of MHC I. p12 carrying a lysine residue (p12K) at position 88 of its sequence may be rapidly degraded in the cell via proteasome, whereas p12 with an arginine residue (p12R) at the same position is severalfold more stable. These alleles are found in proviral DNA of HTLV-1-infected individuals and it was previously observed that the p12K allele was more frequent in HAM/TSP (HTLV-I-associated myelopathy/tropical spastic paraparesis) patients and was not found at all in asymptomatic carriers, whereas patients with adult T cell leukemia/lymphoma (ATLL) carry the p12R allele. To extend these observations and verify whether the p12K mutation could be used as a marker of progression to HAM/TSP, we analyzed 37 HAM/TSP patients and 40 asymptomatic carriers at different stages of infection. In our cohort, only one HAM/TSP patient carried the p12K phenotype, which accounted for a frequency of 2.7% (1 of 37). We also found, among the 40 asymptomatic HTLV-1 carriers, one who presented the p12K phenotype, contrasting with previous publications. Thus, p12K does not seem to be universally diagnostic for HTLV-1-associated neurological disease. Further screening of HTLV-1-infected individuals in other populations may elucidate this observation. C1 Univ Fed Minas Gerais, Dept Microbiol, Virus Lab, Inst Ciencias Biol, BR-31270901 Belo Horizonte, MG, Brazil. Fdn Hemominas, BR-30130110 Belo Horizonte, MG, Brazil. Hosp Sarah Kubistchek, BR-30510000 Belo Horizonte, MG, Brazil. NCI, Basic Res Lab, Bethesda, MD 20892 USA. RP Bonjardim, CA (reprint author), Univ Fed Minas Gerais, Dept Microbiol, Virus Lab, Inst Ciencias Biol, Av Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil. RI Bonjardim, Claudio/J-2601-2014 NR 9 TC 10 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP 1 PY 2002 VL 18 IS 13 BP 899 EP 902 DI 10.1089/088922202760265560 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 590HW UT WOS:000177814500001 PM 12230932 ER PT J AU Hengel, RL Allende, MC Dewar, RL Metcalf, JA Mican, JM Lane, HC AF Hengel, RL Allende, MC Dewar, RL Metcalf, JA Mican, JM Lane, HC TI Increasing CD4(+) T cells specific for tuberculosis correlate with improved clinical immunity after highly active antiretroviral therapy SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID ADVANCED HIV-1 DISEASE; MYCOBACTERIUM-TUBERCULOSIS; PROTEASE-INHIBITOR; INFECTED PATIENTS; VIRUS-INFECTION; FLOW-CYTOMETRY; IMMUNODEFICIENCY; ANTIGEN; RESPONSES; LYMPHOCYTES AB Treatment advances have led to dramatic clinical improvements for patients with HIV-1 infection. These clinical improvements reflect treatment-related improvements in immune function, which are most striking in individuals who develop exaggerated immune inflammatory responses to occult opportunistic infections. The mechanisms accounting for these exaggerated immune responses are unknown. To gain insight into these mechanisms, we intensively studied a subject untreated for disseminated tuberculosis and HIV-1 coinfection who then began treatment for both diseases. We examined the changing frequencies of Mycobacterium tuberculosis (MTB)-speciric CD4(+) T cells that produced interferon gamma (IFN-gamma) after short-term stimulation with MTB antigen, and we compared these frequencies with those in HIV-1-seronegative subjects with and without prior exposure to MTB antigens. For the HIV-1/MTB-coinfected subject, the proportion of peripheral blood CD4(+) T cells expressing MTB-specific IFN-gamma was 8.6% at 11 days, 11% at 33 days, and 33% at 95 days after starting treatment for HIV-1. CD4(+)IFN-gamma(+) T cells had a CD45RA(-)CD62L(-) (effector memory) phenotype and most coexpressed interleukin 2. Median frequencies of CD4(+)IFN-gamma(+) T cells from six subjects without and nine subjects with prior exposure to MTB antigens were 0.06 and 0.46%, respectively. We conclude that individuals starting treatment for disseminated tuberculosis and HIV-1 coinfection can accumulate remarkably large numbers of MTB-specific CD4(+) T cells in the peripheral blood. The rapid expansion of antigen-specific effector CD4(+) T cells is one mechanism to explain immediate improvements in clinical immunity after HIV-1 treatment. This mechanism provides a theoretical framework to understand the unusual inflammatory responses recently reported to occur after starting HIV-1 treatment. C1 NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Med, Div Infect Dis, Washington, DC 20057 USA. SAIC Frederick, Frederick, MD 21702 USA. NIAID, Off Clin Director, NIH, Bethesda, MD 20892 USA. RP Hengel, RL (reprint author), NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Rm 11B05,Bldg 10-MSC 1880,9800 Rockville Pike, Bethesda, MD 20892 USA. NR 37 TC 15 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP 1 PY 2002 VL 18 IS 13 BP 969 EP 975 DI 10.1089/088922202760265632 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 590HW UT WOS:000177814500008 PM 12230939 ER PT J AU Xi, ZX Stein, EA AF Xi, ZX Stein, EA TI GABAergic mechanisms of opiate reinforcement SO ALCOHOL AND ALCOHOLISM LA English DT Article; Proceedings Paper CT 8th Congress of ESBRA CY SEP 15-18, 2001 CL PARIS, FRANCE SP ESBRA ID VENTRAL TEGMENTAL AREA; CONDITIONED PLACE PREFERENCE; MESOLIMBIC DOPAMINE RELEASE; NUCLEUS-ACCUMBENS DOPAMINE; 5-HT3 RECEPTOR ANTAGONISTS; KAPPA-OPIOID RECEPTORS; FREELY MOVING RATS; IN-VIVO MICRODIALYSIS; METABOTROPIC GLUTAMATE RECEPTORS; 5,7-DIHYDROXYTRYPTAMINE LESIONS AB The neurobiological mechanisms of opiate-induced reinforcement are still not completely understood. Over the past two decades, the vast majority of studies have focused on the role of the mesolimbic dopamine (DA) system. However, current studies strongly suggest that opiate actions on gamma-aminobutyric acid (GABA)-ergic cells in both the ventral tegmental area (VTA) and the nucleus accumbens (NAcc) appear to play critical roles. In this review, we focus on the neurochemical substrates of opiate reinforcement and review the role of DA and non-DA substrates, including opioid, GABA, glutamate and serotonin on opiate-reinforced behaviour and the activity of dopaminergic and GABAergic neurons in the VTA and the NAcc. C1 Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. RP Stein, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Stein, Elliot/C-7349-2008 FU NIDA NIH HHS [DA09465] NR 136 TC 65 Z9 69 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD SEP-OCT PY 2002 VL 37 IS 5 BP 485 EP 494 DI 10.1093/alcalc/37.5.485 PG 10 WC Substance Abuse SC Substance Abuse GA 593PP UT WOS:000178001600017 PM 12217944 ER PT J AU Peters, U Poole, C Arab, L AF Peters, U Poole, C Arab, L TI Re: "Does tea affect cardiovascular disease? A meta-analysis" - Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID STROKE; RISK C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27514 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Peters, U (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27514 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2002 VL 156 IS 5 BP 490 EP 491 DI 10.1093/aje/kwf067 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 589QK UT WOS:000177771400014 ER PT J AU Fisher, D Jeffreys, A Bosworth, H Wang, J Lipscomb, J Provenzale, D AF Fisher, D Jeffreys, A Bosworth, H Wang, J Lipscomb, J Provenzale, D TI Quality of life in patients with Barrett's esophagus undergoing surveillance SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GASTROESOPHAGEAL REFLUX DISEASE; HEALTHY-YEARS EQUIVALENTS; OF-LIFE; ADENOCARCINOMA; SENSITIVITY; RELIABILITY; DIAGNOSIS; VALIDITY; THERAPY AB Objectives: Practice guidelines recommend surveillance for Barrett's esophagus (BE) because of the risk of esophageal cancer. The quality of life of patients undergoing surveillance is unknown. The objectives of this study were to develop a new utility instrument to measure quality of life of patients undergoing BE surveillance and determine if Quality of Life in Reflux and Dyspepsia (QOLRD) scores correlate with utility ratings. Methods: Fifteen patients were administered 16 scenarios describing possible BE surveillance outcomes. Each scenario was rated from 0 (equivalent to being dead) to 10 (equivalent to being in perfect health). Each patient also completed the QOLRD, a validated instrument. A t test was performed to compare the QOLRD means with published means. The Spearman's rank correlation coefficient was calculated for the median QOLRD score and the median utility rating. Results: QOLRD means ranged from 5.80 to 6.65 (previously published means 4.3-5.4). Lower scores denoted a worsened quality of life. The difference was significant (p<0.001). The correlation coefficient of median QOLRD score (6.8) and median utility rating (4.0) was 0.10 (p=0.71). Conclusions: This population of BE patients had significantly higher QOLRD scores than a previously published population referred for endoscopy. Quality of life using the utility measure was reduced. The utility measure did not correlate with the disease-specific instrument, suggesting that the concerns of patients undergoing surveillance are distinct from their reflux symptoms. C1 Durham Vet Affairs Med Ctr, Inst Clin & Epidemiol Res, Durham, NC USA. Duke Univ, Med Ctr, Div Gastroenterol, Durham, NC USA. NCI, Bethesda, MD 20892 USA. RP GI Outcomes Res, 508 Fulton st,Bldg 16,Room 70, Durham, NC 27705 USA. FU NIDDK NIH HHS [K-24 DK-02926-02]; PHS HHS [263-MQ-10167] NR 22 TC 23 Z9 23 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 BP 2193 EP 2200 AR PII S0002-9270(02)04329-0 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PJ UT WOS:000178229700008 PM 12358232 ER PT J AU Strader, DB Bacon, BR Lindsay, KL La Brecque, DR Morgan, T Wright, EC Allen, J Khokar, MF Hoofnagle, JH Seeff, LB AF Strader, DB Bacon, BR Lindsay, KL La Brecque, DR Morgan, T Wright, EC Allen, J Khokar, MF Hoofnagle, JH Seeff, LB TI Use of complementary and alternative medicine in patients with liver disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID SILYMARIN; TRIAL AB OBJECTIVES: Complementary and alternative medicine (CAM) is used by 42% of the U.S. population. Its use among patients with chronic liver disease has not been well defined. Toward that end, we surveyed patients in six geographically diverse liver disease clinics in the United States for use of CAM. METHODS: Patients attending six liver disease clinics were polled via a common questionnaire regarding their use of CAM. Demographic information was obtained to identify predictors of CAM use. Statistical analysis included univariate and multivariate analysis using logistic regression. RESULTS: A total of 989 patients completed the questionnaire. Of these, 389 (39%) admitted to using some form of CAM at least once during the preceding month; 21% admitted to using herbal preparations, and 13% used herbs to treat their liver disease. Five variables were found to be predictive of alternative therapy use: female sex, young age, level of education, annual income, and geographic location. In all, 74% of patients reported using CAM in addition to the medications prescribed by their physician, but 26% did not inform their physician of their CAM use. CONCLUSIONS: CAM use is as common among patients visiting liver disease clinics in the United States as in the general population (39% vs 42%). Many patients are using herbs to treat their liver disease but are declining to discuss this use with their physician. C1 Vet Affairs Med Ctr, Div Gastroenterol Hepatol & Nutr, Washington, DC 20422 USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. Univ So Calif, Sch Med, Div Hepatol, Los Angeles, CA USA. Univ Iowa Hosp & Clin, Div Hepatol, Iowa City, IA 52242 USA. Vet Affairs Med Ctr, Div Gastroenterol, Long Beach, CA USA. New England Res Inst, Watertown, MA 02172 USA. NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Strader, DB (reprint author), Vet Affairs Med Ctr, Div Gastroenterol Hepatol & Nutr, 50 Irving St NW,151W, Washington, DC 20422 USA. NR 20 TC 82 Z9 83 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 BP 2391 EP 2397 AR PII S0002-9270(02)04350-2 DI 10.1016/S0002-9270(02)04350-2 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PJ UT WOS:000178229700038 PM 12358262 ER PT J AU Cash, BD Schoenfeld, PS Flood, AP Lieberman, DA AF Cash, BD Schoenfeld, PS Flood, AP Lieberman, DA TI Colorectal cancer screening in asymtpomatic, average risk females: Is age 50 the proper starting point? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NCI, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 334 BP S110 EP S110 DI 10.1016/S0002-9270(02)04806-2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400335 ER PT J AU Naz, S Giguere, CM Kohrman, DC Mitchem, KL Riazuddin, S Morell, RJ Ramesh, A Srisailpathy, S Deshmukh, D Riazuddin, S Griffith, AJ Friedman, TB Smith, RJH Wilcox, ER AF Naz, S Giguere, CM Kohrman, DC Mitchem, KL Riazuddin, S Morell, RJ Ramesh, A Srisailpathy, S Deshmukh, D Riazuddin, S Griffith, AJ Friedman, TB Smith, RJH Wilcox, ER TI Mutations in a novel gene, TMIE, are associated with hearing loss linked to the DFNB6 locus SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MYOSIN-VIIA GENE; USHER 1B SYNDROME; RECESSIVE DEAFNESS; DEFECTS; MAPS AB We have identified five different homozygous recessive mutations in a novel gene, TMIE (transmembrane inner ear expressed gene), in affected members of consanguineous families segregating severe-to-profound prelingual deafness, consistent with linkage to DFNB6. The mutations include an insertion, a deletion, and three missense mutations, and they indicate that loss of function of TMIE causes hearing loss in humans. TMIE encodes a protein with 156 amino acids and exhibits no significant nucleotide or deduced amino acid sequence similarity to any other gene. C1 Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, NIH, Rockville, MD 20850 USA. Natl Inst Deafness & Other Commun Disorders, Sect Gene Struct & Funct, Genet Mol Lab, NIH, Rockville, MD 20850 USA. Univ Iowa, Dept Otolaryngol, Mol Otolaryngol Res Labs, Iowa City, IA USA. Univ Iowa, Interdepartmental Genet Program, Iowa City, IA USA. Univ Michigan, Sch Med, Dept Human Genet, Kresge Hearing Res Inst,Dept Otolaryngol, Ann Arbor, MI USA. Univ Madras, Dept Genet, Madras, Tamil Nadu, India. Rotary Deaf Sch, Ichalkaranji, India. Univ Punjab, Ctr Excellence Mol Biol, Lahore, Pakistan. RP Wilcox, ER (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, NIH, 5 Res Court, Rockville, MD 20850 USA. RI naz, sadaf/F-4406-2015; OI Naz, Sadaf/0000-0002-1912-0235; Morell, Robert/0000-0003-1537-7356 FU NIDCD NIH HHS [R01-DC02842, 1 Z01 DC00035-04, R01 DC004410, 1 Z01 DC000064-01, Z01 DC000039, T32 DC000035, R01 DC002842, Z01 DC000064, R01-DC04410, 1 Z01 DC 0039-04] NR 15 TC 59 Z9 60 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 2002 VL 71 IS 3 BP 632 EP 636 DI 10.1086/342193 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 584VN UT WOS:000177489600017 PM 12145746 ER PT J AU Shields, T Gridley, G Moradi, T Adami, J Plato, N Dosemeci, M AF Shields, T Gridley, G Moradi, T Adami, J Plato, N Dosemeci, M TI Occupational exposures and the risk of ovarian cancer in Sweden SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE ovary; cancer; occupation; job exposure matrix; risk factors; relative risk ID EUROPEAN CASE-CONTROL; 24 US STATES; PHYSICAL-ACTIVITY; SOCIOECONOMIC-STATUS; POOLED ANALYSIS; FIELD EXPOSURE; WOMEN; MORTALITY; BREAST; INDUSTRY AB Background Studies of occupational exposures and ovarian cancer, often limited by few subjects or proportionate mortality data, have yielded inconsistent results. Methods Swedish women employed in 1960, 1970, or during both years were followed from 1971 to 1989 using census data linked to nationwide cancer and death registries. A total of 9,591 ovarian cancer cases were identified among 1,670,517 women. Poisson regression was used to estimate the relative risk of ovarian cancer in specific occupational groups and in women exposed to particular occupational exposures defined by job exposure matrices. We lacked data on reproductive factors. Results Jobs associated with elevated ovarian cancer rates in this and previous studies include dry cleaning, telegraph and telephone work, paper packaging, and graphic and printing work. In contrast to results of some previous studies, we found that hairdressers and beauticians were not at increased risk of ovarian cancer. Organic dusts, aromatic amines, aliphatic and aromatic hydrocarbons are suggested as specific etiologic agents. Conclusions In this large study, we have confirmed some results from smaller studies and identified some new relationships that need to be confirmed elsewhere. Published 2002 Wiley-Liss, Inc.(dagger) C1 NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Biostat Branch, Bethesda, MD 20892 USA. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. Karolinska Inst, Dept Clin Sci, Stockholm, Sweden. Karolinska Inst, Div Occupat Hlth, Stockholm, Sweden. NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. RP Shields, T (reprint author), NCI, Environm Epidemiol Branch, Execut Plaza S,Room 7055, Bethesda, MD 20892 USA. NR 51 TC 24 Z9 26 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD SEP PY 2002 VL 42 IS 3 BP 200 EP 213 DI 10.1002/ajim.10099 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 585AK UT WOS:000177500800004 PM 12210689 ER PT J AU Stehman-Breen, CO Levine, RJ Qian, C Morris, CD Catalano, PM Curet, LB Sibai, BM AF Stehman-Breen, CO Levine, RJ Qian, C Morris, CD Catalano, PM Curet, LB Sibai, BM TI Increased risk of preeclampsia among nulliparous pregnant women with idiopathic hematuria SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE preeclampsia; gestational hypertension; pregnancy; hematuria ID RENAL-DISEASE; HYPERTENSION; CALCIUM; TRIAL AB OBJECTIVE: Our purpose was to determine the risk of preeclampsia and gestational hypertension among nulliparous pregnant women with idiopathic hematuria. STUDY DESIGN: We conducted a prospective cohort study using data from the trial of Calcium for Preeclampsia Prevention (CPEP). Participants were followed up from screening and enrollment (gestational weeks 11-21) throughout pregnancy. Our analysis was limited to women who had been followed up to at least 20 weeks' gestation, had outcome information available, and were not suspected to have had urolithiasis. Surveillance for hematuria was conducted with dipsticks on clean-catch urine specimens obtained at research clinic visits. Idiopathic hematuria was defined as hematuria identified at regularly scheduled clinic visits in the absence of urinary tract infection and before the onset of labor. Logistic regression was used to estimate the risk of preeclampsia among women with hematuria compared with women without hematuria. RESULTS: Among the 4307 women available for analysis, 132 (3%) had idiopathic hematuria during pregnancy. Idiopathic hematuria was associated with an almost 2-fold increased odds for development of preeclampsia (adjusted odds ratio [aOR] = 1.89, 95% Cl 1.12-3.18) but not with increased odds of gestational hypertension (aOR = 0.78, 95% Cl 0.46-1.32). CONCLUSIONS: Idiopathic hematuria identified during pregnancy is associated with greater risk of preeclampsia but not gestational hypertension. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA 98108 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Allied Technol Grp, Rockville, MD USA. Oregon Hlth Sci Univ, Div Med Informat & Outcomes Res, Portland, OR 97201 USA. Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. Metrohlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. RP Stehman-Breen, CO (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Nephrol, 1660 S Columbian Way,Mailstop 111A, Seattle, WA 98108 USA. FU NICHD NIH HHS [N01-HD-1-3122, N01-HD-1-3125, N01-HD-1-3121, N01-HD-2-3154, N01-HD-1-3123, N01-HD-1-3124, N01-HD-1-3126, N01-HD-5-3246] NR 23 TC 8 Z9 8 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2002 VL 187 IS 3 BP 703 EP 708 DI 10.1067/mob.2002.125768 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 598BZ UT WOS:000178256400031 PM 12237651 ER PT J AU Hicks, A Potula, R Sui, YJ Villinger, F Pinson, D Adany, I Li, Z Long, C Cheney, P Marcario, J Novembre, F Mueller, N Kumar, A Major, E Narayan, O Buch, S AF Hicks, A Potula, R Sui, YJ Villinger, F Pinson, D Adany, I Li, Z Long, C Cheney, P Marcario, J Novembre, F Mueller, N Kumar, A Major, E Narayan, O Buch, S TI Neuropathogenesis of lentiviral infection in macaques - Roles of CXCR4 and CCR5 viruses and interleukin-4 in enhancing monocyte chemoattractant protein-1 production in macrophages SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; RHESUS MACAQUES; CEREBROSPINAL-FLUID; CHEMOTACTIC PROTEIN-1; CHEMOKINE RECEPTOR-2; DISEASE PROGRESSION; TISSUE MACROPHAGES; AIDS ENCEPHALITIS; HIV AB Neurological disease associated with lentiviral infection occurs mainly as a consequence of primary replication of the virus or a combination of the virus infection and replication of opportunistic pathogens in the central nervous system. Recent studies have shown that whereas the disease can be caused by CCR5 tropic viruses alone, its induction by CXCR4 (X4) tropic viruses occurred usually in association with infections caused by opportunistic pathogens and in the presence of a Th2 cytokine, interleukin (IL)-4.(1,2) Further, X4-mediated neurological disease developed preferentially in rhesus compared to pigtailed macaques. Because macrophages are the target cells for lentiviral infection in the brain and because macrophage chemoattractant protein (MCP)-1 is one of the major chemokines that is closely associated with acquired immune deficiency syndrome (AIDS) dementia, we tested for correlations between MCP-1 production and virus tropism in macrophages from the two species of macaques. The studies showed that the higher susceptibility of rhesus macaques to X4 virus-mediated encephalitis correlated with heightened production of virus and MCP-1 in cultured macrophages from this species and that these effects were further enhanced with treatment with IL-4. However, the latter effect was restricted to macrophages infected with X4 viruses. IL-4 may therefore be a basic requirement for X4 viruses to cause central nervous system disease. C1 Univ Kansas, Med Ctr, Dept Microbiol Immunol & Mol Genet, Marion Merrell Dow Lab Viral Pathogenesis, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66103 USA. Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Buch, S (reprint author), Univ Kansas, Med Ctr, Dept Microbiol Immunol & Mol Genet, Marion Merrell Dow Lab Viral Pathogenesis, 5000 Wahl Hall E,3901 Rainbow Blvd, Kansas City, KS 66160 USA. OI Buch, Shilpa/0000-0002-3103-6685 FU NCRR NIH HHS [RR-13152, RR-06753, R01 RR006753]; NIAID NIH HHS [AI-29382]; NIMH NIH HHS [MH-6296901]; NINDS NIH HHS [NS-32203] NR 41 TC 17 Z9 18 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2002 VL 161 IS 3 BP 813 EP 822 DI 10.1016/S0002-9440(10)64241-1 PG 10 WC Pathology SC Pathology GA 591BJ UT WOS:000177859600010 PM 12213709 ER PT J AU Fraser, D Wakefield, L Phillips, A AF Fraser, D Wakefield, L Phillips, A TI Independent regulation of transforming growth factor-beta 1 transcription and translation by glucose and platelet-derived growth factor SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PROXIMAL TUBULAR CELLS; SMOOTH-MUSCLE CELLS; STRUCTURAL-FUNCTIONAL RELATIONSHIPS; GROWTH-FACTOR-BETA-1 MESSENGER-RNA; EXPERIMENTAL DIABETIC NEPHROPATHY; LATENT TGF-BETA; ENDOTHELIAL-CELLS; TGF-BETA-1 SYNTHESIS; ACTIVATION; EXPRESSION AB Proximal tubular renal epithelial cells may contribute to the pathogenesis of renal interstitial fibrosis in diabetes by generation of cytokines such as transforming growth factor (TGF)-beta1. We have previously demonstrated that proximal tubular renal epithelial cell TGF-beta1 synthesis may be modulated by elevated glucose concentration and by cytokines such as platelet-derived growth factor (PDGF). The aim of the current study was to characterize the mechanism by which glucose and PDGF synergistically stimulate the generation of TGF-beta1. Addition of either 25 mmol/L of D-glucose or low-dose PDGF increased TGF-beta1 mRNA expression without stimulation of TGF-beta1 protein synthesis. In contrast sequential stimulation with 25 mmol/L of D-glucose for 48 hours followed by low-dose (25 ng/ml) PDGF led to a significant increase in TGF-beta1 synthesis. Elevated glucose concentration stimulated de novo gene transcription as assessed by stimulation of a TGF-beta1 promoter-luciferase construct. This led to induction of a poorly translated TGF-beta1 transcript determined by polysome analysis. PDGF at low dose did not influence TGF-beta1 transcription, but led to alteration in TGF-beta1 mRNA stability and translation. Without a previous glucose-induced increase in the amount of TGF-beta1 transcript, PDGF did not stimulate significant TGF-beta1 protein synthesis. At a high dose (100 ng/ml) PDGF stimulated TGF-beta1 synthesis independent of glucose concentration. This was associated with increased TGF-beta1 gene transcription and alteration in TGF-beta1 mRNA translational efficiency. In conclusion the data suggests that in diabetic nephropathy, the role of glucose is to lower the threshold at which a stimulus such as PDGF stimulates TGF-beta1 protein synthesis. The data also suggest that independent regulation of TGF-beta1 transcription and translation by glucose and PDGF account for their synergistic effect on TGF-beta1 protein synthesis. We hypothesize that the role of glucose in diabetic nephropathy is to prime the kidney for an injurious response to other stimuli. C1 Univ Wales Coll Med, Inst Nephrol, Cardiff CF14 4XN, S Glam, Wales. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Phillips, A (reprint author), Univ Wales Coll Med, Inst Nephrol, Heath Pk, Cardiff CF14 4XN, S Glam, Wales. NR 57 TC 51 Z9 58 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2002 VL 161 IS 3 BP 1039 EP 1049 DI 10.1016/S0002-9440(10)64265-4 PG 11 WC Pathology SC Pathology GA 591BJ UT WOS:000177859600034 PM 12213733 ER PT J AU Rosner, A Miyoshi, K Landesman-Bollag, E Xu, X Seldin, DC Moser, AR MacLeod, CL Shyamala, G Gillgrass, AE Cardiff, RD AF Rosner, A Miyoshi, K Landesman-Bollag, E Xu, X Seldin, DC Moser, AR MacLeod, CL Shyamala, G Gillgrass, AE Cardiff, RD TI Histological differences between ErbB/Ras and wnt pathway transgenic mammary tumors SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HAIR FOLLICLE MORPHOGENESIS; PROTEIN-KINASE CK2; I CLINICAL-TRIAL; BREAST-CANCER; GROWTH-FACTOR; BETA-CATENIN; EPITHELIAL-CELLS; MOUSE MODEL; PROGESTERONE-RECEPTOR; ACTIVATING MUTATIONS AB To study phenotype-genotype correlations, ErbB/Ras pathway tumors (transgenic for ErbB2, c-Neu, mutants of c-Neu, polyomavirus middle T antigene (PyV-mT), Ras, and bi-transgenic for ErbB2/Neu with ErbB3 and with progesterone receptor) from four different institutions were histopathologically compared with Wnt pathway tumors [transgenes Wnt1, Wnt10b, dominant-negative glycogen synthase kinase 3-beta, beta-Catenin, and spontaneous mutants of adenomatous polyposis coli gene (Apc)]. ErbB/Ras pathway tumors tend to form solid nodules consisting of poorly differentiated cells with abundant cytoplasm. ErbB/Ras pathway tumors also have scanty stroma and lack myoepithelial or squamous differentiation. In contrast, Wnt pathway tumors exhibit myoepithelial, acinar, or glandular differentiation, and, frequently, combinations of these. Squamous metaplasia is frequent and may include transdifferentiation to epidermal and pilar structures. Most Wnt pathway tumors form caricatures of elongated, branched ductules, and have well-developed stroma, inflammatory infiltrates, and pushing margins. Tumors transgenic for interacting genes such as protein kinase CK2alpha (casein kinase II), and the fibroblast growth factors (Fgf) Int2/Fgf3 or keratinocyte growth factor (Kgf/Fgf7) also have the Wnt pathway phenotype. Because the tumors from the ErbB/Ras and the Wnt pathway are so distinct and can be readily identified using routine hematoxylin and eosin sections, we suggest that pathway pathology is applicable in both basic and clinical cancer research. C1 Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Univ Tokushima, Sch Dent, Dept Biochem, Tokushima 770, Japan. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Wisconsin, Dept Human Oncol, Madison, WI USA. Univ Calif San Diego, Sch Med, Ctr Canc, Dept Med, La Jolla, CA 92093 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. McMaster Univ, Dept Med Sci, Hamilton, ON, Canada. RP Cardiff, RD (reprint author), Univ Calif Davis, Ctr Comparat Med, Cty Rd 98 & Hutchinson Dr, Davis, CA 95616 USA. FU NCI NIH HHS [P01 CA095616, CA64843, CA665401, CA81376]; NCRR NIH HHS [U42 RR014905, U42 RR14905]; NIEHS NIH HHS [ES11624, P01 ES011624] NR 71 TC 127 Z9 127 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2002 VL 161 IS 3 BP 1087 EP 1097 DI 10.1016/S0002-9440(10)64269-1 PG 11 WC Pathology SC Pathology GA 591BJ UT WOS:000177859600038 PM 12213737 ER PT J AU Bonner, JC AF Bonner, JC TI The epidermal growth factor receptor at the crossroads of airway remodeling SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Editorial Material ID EPITHELIAL-CELLS; PULMONARY FIBROSIS; MUCIN PRODUCTION; EXPRESSION; ACTIVATION C1 NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Bonner, JC (reprint author), NIEHS, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 23 TC 25 Z9 25 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD SEP PY 2002 VL 283 IS 3 BP L528 EP L530 DI 10.1152/ajplung.00126.2002 PG 3 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 582LU UT WOS:000177353100005 PM 12169571 ER PT J AU Veauvy, CM Wang, YX Walsh, PJ Perez-Pinzon, MA AF Veauvy, CM Wang, YX Walsh, PJ Perez-Pinzon, MA TI Comparison of the effects of ammonia on brain mitochondrial function in rats and gulf toadfish SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE hepatic encephalopathy; hyperammonemia; NADH; mitochondria; Opsanus beta; glutamine metabolism ID HYPERAMMONEMIC RATS; HEPATIC-ENCEPHALOPATHY; GLUTAMINE SYNTHESIS; HIPPOCAMPAL SLICES; METABOLISM; HYPEROXIDATION; INHIBITION; DYSFUNCTION; ANOXIA AB We compared the effect of hyperammonemia on NADH levels in brain slices and on the rate of oxygen consumption from isolated nonsynaptic brain mitochondria in ammonia-sensitive Wistar rats with that in ammonia-tolerant gulf toadfish (Opsanus beta). The NADH content was significantly decreased (12% less than control after 45 min with 1 mM NH4Cl) in rat brain slices, but it was not affected in brain slices from toadfish (with both 1 and 6 mM NH4Cl). The rates of oxygen consumption of different sets of enzymes of the electron transport chain (ETC; complexes I, II, III, and IV; II, III, and IV; and IV alone) were unaltered by hyperammonemic conditions in isolated nonsynaptic mitochondria from either rats or toadfish. These results lead us to conclude that the differing effects of ammonia on NADH levels in rat and toadfish brain slices must be due to aspects other than the direct effects of ammonia on enzymes of the ETC. Additionally, because these effects were seen in vitro, our studies enabled us to rule out the possibility that effects of ammonia on metabolism were via indirect systemic effects. These results are discussed in the context of current views on mechanisms of central nervous system damage in hyperammonemic states. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS,Marine & Freshwater Biomed Sci Ctr, Div Marine Biol & Fisheries, Miami, FL 33149 USA. Univ Miami, Sch Med, Dept Neurol & Neurosci, Miami, FL 33131 USA. Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada. RP Veauvy, CM (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS,Marine & Freshwater Biomed Sci Ctr, Div Marine Biol & Fisheries, 4600 Rickenbacker Causeway, Miami, FL 33149 USA. FU NIEHS NIH HHS [ES-11005, ES 05705]; NINDS NIH HHS [NS-05820] NR 29 TC 8 Z9 9 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 2002 VL 283 IS 3 BP R598 EP R603 DI 10.1152/ajpregu.00018.2002 PG 6 WC Physiology SC Physiology GA 584VY UT WOS:000177490500007 PM 12184993 ER PT J AU Yang, T Forrest, SJ Stine, N Endo, Y Pasumarthy, A Castrop, H Aller, S Forrest, JN Schnermann, J Briggs, J AF Yang, T Forrest, SJ Stine, N Endo, Y Pasumarthy, A Castrop, H Aller, S Forrest, JN Schnermann, J Briggs, J TI Cyclooxygenase cloning in dogfish shark, Squalus acanthias, and its role in rectal gland Cl secretion SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE vasoactive intestinal peptide; prostaglandins; shark rectal gland; NS-398; C-type natriuretic peptide; 5 '-rapid amplification of cDNA ends ID PROSTAGLANDIN-G/H SYNTHASE; COMPLEMENTARY-DNA; MOLECULAR-CLONING; MESSENGER-RNA; SPINY DOGFISH; NITRIC-OXIDE; EXPRESSION; CDNA; INHIBITION; TRANSPORT AB The present studies were carried out with the aims to determine the cDNA sequence for cyclooxygenase (COX) in an elasmobranch species and to study its role in regulation of chloride secretion in the perfused shark rectal gland (SRG). With the use of long primers (43 bp) derived from regions of homology between zebrafish and rainbow trout COX-2 genes, a 600-bp product was amplified from SRG and was found to be almost equally homologous to mammalian COX-1 and COX-2 (65%). The full-length cDNA sequence was obtained by 5'-RACE and by analyzing an EST clone generated by the EST Project of the Mt. Desert Island Biological Laboratory Marine DNA Sequencing Center. The longest open reading frame encodes a 593-amino acid protein that has 68 and 64% homology to mammalian COX-1 and COX-2, respectively. The gene and its protein product is designated as shark COX (sCOX). The key residues in the active site (Try(385), His(388), and Ser(530)) are conserved between the shark and mammalian COX. sCOX contains Val(523) that has been shown to be a key residue determining the sensitivity to COX-2-specific inhibitors including NS-398. The mRNA of sCOX, detected by RT-PCR, was found in all tissues tested, including rectal gland, kidney, spleen, gill, liver, brain, and heart, but not in fin. In the perfused SRG, vasoactive intestinal peptide (VIP) at 5 nM induced rapid and marked Cl- secretion (basal: <250 μeq.h(-1).g(-1); peak response: 3,108 +/- 479 μeq.h(-1).g(-1)). In the presence of 50 μM NS-398, both the peak response (2,131 +/- 307 μeq.h(-1).g(-1)) and the sustained response to VIP were significantly reduced. When NS-398 was removed, there was a prompt recovery of chloride secretion to control values. In conclusion, we have cloned the first COX in an elasmobranch species (sCOX) and shown that sCOX inhibition suppresses VIP-stimulated chloride secretion in the perfused SRG. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Yale Univ, Dept Med, New Haven, CT 06510 USA. Dartmouth Coll, Hanover, NH 03755 USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. RP Briggs, J (reprint author), NIDDK, NIH, Bldg 31,Rm 9A17,31 Ctr Dr MSC 2560, Bethesda, MD 20892 USA. RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU NIDDK NIH HHS [DK-34208]; NIEHS NIH HHS [P30-ES03828] NR 40 TC 18 Z9 19 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 2002 VL 283 IS 3 BP R631 EP R637 DI 10.1152/ajpregu.00743.2001 PG 7 WC Physiology SC Physiology GA 584VY UT WOS:000177490500011 PM 12184997 ER PT J AU Fee, E Brown, TM Lazarus, J Theerman, P AF Fee, E Brown, TM Lazarus, J Theerman, P TI Public health service dentist examines an Alaska native child, 1951 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article C1 Natl Lib Med, NIH, Hist Med Div, Bethesda, MD USA. Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2002 VL 92 IS 9 BP 1420 EP 1420 DI 10.2105/AJPH.92.9.1420 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 587UM UT WOS:000177661900014 PM 12197967 ER PT J AU Luoma, JB Pearson, JL AF Luoma, JB Pearson, JL TI Suicide and marital status in the United States, 1991-1996: Is widowhood a risk factor? SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID BEREAVEMENT; PERSPECTIVE; MORTALITY AB Objectives. This study examined whether marital status is associated with suicide rates among various age, sex, and racial groups, in particular with widowhood among young adults of both sexes. Methods. US national suicide mortality data were compiled for the years 19911996, and suicide rates were broken down by race, 5-year age groups, sex, and marital status. Results. Data on suicide rates indicated an approximately 17-fold increase among young widowed White men (aged 20-34 years), a 9-fold increase among young widowed African American men, and lesser increases among young widowed White women compared with their married counterparts. Conclusions. National data suggest that as many as 1 in 400 White and African American widowed men aged 20-35 years will die by suicide in any given year (compared with 1 in 9000 married men in the general population). C1 Natl Inst Mental Hlth, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Catholic Univ Amer, Washington, DC 20064 USA. RP Pearson, JL (reprint author), Natl Inst Mental Hlth, Div Serv & Intervent Res, 6001 Execut Blvd,Room 7160,MSC 9635, Bethesda, MD 20892 USA. OI Luoma, Jason/0000-0002-3601-7037 NR 26 TC 70 Z9 72 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2002 VL 92 IS 9 BP 1518 EP 1522 DI 10.2105/AJPH.92.9.1518 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 587UM UT WOS:000177661900033 PM 12197986 ER PT J AU Hauk, PJ Goleva, E Strickland, I Vottero, A Chrousos, GP Kisich, KO Leung, DYM AF Hauk, PJ Goleva, E Strickland, I Vottero, A Chrousos, GP Kisich, KO Leung, DYM TI Increased glucocorticoid receptor beta expression converts mouse hybridoma cells to a corticosteroid-insensitive phenotype SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID STEROID-RESISTANT ASTHMA; HELPER-FREE; HIGH-TITER; ISOFORM; BINDING; RETROVIRUSES; INHIBITION; ACTIVATION; MECHANISM; MICE AB Glucocorticoid (GC) insensitivity is a challenging clinical problem associated with many chronic inflammatory disorders and life-threatening disease progression. The molecular basis of GC insensitivity, however, is unknown. Alternative splicing of the GC receptor (GCR) pre-mRNA generates a second GCR, termed GCRP, which does not bind GC but antagonizes the transactivating activity of the classic GCR, termed GCRalpha. GC-insensitive conditions have been associated with increased GCRP expression. Whether or not increased GCRP expression can contribute to GC insensitivity, however, remains controversial. To more precisely demonstrate the effect of GCRbeta on steroid responsiveness, we virally transduced GCRbeta cDNA into mouse DO-11.10 hybridoma cells, as mice are known to be deficient in the GCRP gene. We demonstrate that viral transduction of GCRbeta cDNA into mouse hybridoma cells to induce stable expression of GCRbeta results in GC insensitivity of these cells. Furthermore, in such cells GCRalpha is complexed with GCRbeta. Such heterodimer formation may account for the reduced effectiveness of GC action in cells overexpressing GCRbeta. C1 Natl Jewish Med Res Ctr, Dept Pediat, Denver, CO 80206 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. RP Leung, DYM (reprint author), Natl Jewish Med Res Ctr, Dept Pediat, 1400 Jackson St,Room K926i, Denver, CO 80206 USA. FU NCRR NIH HHS [M01RR00051]; NHLBI NIH HHS [HL37260, HL34303, HL36577]; NIAMS NIH HHS [AR41256] NR 29 TC 46 Z9 50 U1 2 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD SEP PY 2002 VL 27 IS 3 BP 361 EP 367 DI 10.1165/rcmb.4861 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 590EZ UT WOS:000177806500012 PM 12204899 ER PT J AU Nicholson, SA Beasley, MB Brambilla, E Hasleton, PS Colby, TV Sheppard, MN Falk, R Travis, WD AF Nicholson, SA Beasley, MB Brambilla, E Hasleton, PS Colby, TV Sheppard, MN Falk, R Travis, WD TI Small cell lung carcinoma (SCLC) - A clinicopathologic study of 100 cases with surgical specimens SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE small cell lung carcinoma; pathology; histology; morphology; carcinoid; atypical carcinoid; large cell neuroendocrine carcinoma; pulmonary; neuroendocrine ID TRANSCRIPTION FACTOR-I; PULMONARY NEUROENDOCRINE TUMORS; HISTOPATHOLOGIC CLASSIFICATION; PROGNOSTIC-SIGNIFICANCE; CANCER; DIAGNOSIS; SURVIVAL; MANAGEMENT; EXPRESSION; SEPARATION AB Separation of small cell lung carcinoma (SCLC) from nonsmall cell lung carcinoma (NSCLC) is a critical distinction to be made in the diagnosis of lung cancer. However, the diagnosis of SCLC is most commonly made on small biopsies and cytologic specimens, and practicing pathologists may not be familiar with all its morphologic guises and frequent combination with NSCLC elements, which may be seen in larger specimens. Following the most recent WHO classification of lung tumors and with the hope of identifying prognostic markers, we examined in detail the histology of 100 surgical biopsies or resections with a diagnosis of SCLC from the AFIP and pathology panel of the International Association for the Study of Lung Cancer (IASLC). Multiple clinical and histologic features were studied by Kaplan-Meier analysis. Neuroendocrine architectural patterns, including nested and trabecular growth, with peripheral palisading and rosette formation were common in SCLC. Necrosis and apoptotic debris was prominent in all cases, but crush artifact was infrequent. Cell size in surgical biopsy specimens appears larger than in bronchoscopic biopsy specimens and occasional cells may show prominent nucleoli and vesicular nuclear chromatin, but this does not preclude the diagnosis of SCLC. A high percentage of cases (28%) showed combinations with NSCLC, with large cell carcinoma the most common, followed by adenocarcinoma and squamous cell carcinoma. Because of the frequency of a few scattered large cells in SCLC, we arbitrarily recommend that at least 10% of the tumor show large cell carcinoma before subclassification as combined SC/LC. However, combined SCLC is easily recognized if the additional component consists of other NSCLC subtypes such as adenocarcinoma or squamous cell carcinoma, so no percentage requirement is needed. Stage remained the only predictor of prognosis. C1 Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. CHU Grenoble, F-38043 Grenoble, France. Univ S Manchester Hosp, Manchester M20 8LR, Lancs, England. Mayo Clin Scottsdale, Scottsdale, AZ USA. Royal Brompton Hosp, London SW3 6LY, England. NCI, Environm Epidemiol Branch, NIH, Rockville, MD USA. RP Travis, WD (reprint author), Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Bldg 54,Rm M003B,6825 NW 16th St, Washington, DC 20306 USA. RI Brambilla, Elisabeth/L-8796-2013 NR 62 TC 171 Z9 181 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2002 VL 26 IS 9 BP 1184 EP 1197 DI 10.1097/01.PAS.0000022995.91977.CD PG 14 WC Pathology; Surgery SC Pathology; Surgery GA 588ZW UT WOS:000177733700009 PM 12218575 ER PT J AU Dubbert, PM Carithers, T Sumner, AE Barbour, KA Clark, BL Hall, JE Crook, ED AF Dubbert, PM Carithers, T Sumner, AE Barbour, KA Clark, BL Hall, JE Crook, ED TI Obesity, physical inactivity, and risk for cardiovascular disease SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE obesity; physical activity; cardiovascular disease; African americans ID CORONARY-HEART-DISEASE; TYPE-2 DIABETES-MELLITUS; NUTRITION EXAMINATION SURVEY; AFRICAN-AMERICAN WOMEN; 3RD NATIONAL-HEALTH; MIDDLE-AGED WOMEN; BODY-MASS INDEX; ATHEROSCLEROSIS RISK; UNITED-STATES; FOLLOW-UP AB Despite considerable progress in understanding disease mechanisms and risk factors, improved treatments, and public education efforts, cardiovascular disease (CVD) remains the leading cause of death in the United States. Obesity and physical inactivity, 2 important lifestyle-related risk factors for CVD, are prevalent in the southeastern United States and are becoming more prevalent in all racial groups and areas of the country. In reviewing these risk factors, we explored topics including prevalence and trends in population data; associated psychosocial and environmental factors; and some of the mechanisms through which these risk factors are thought to contribute to CVD. We identified significant, but as yet poorly understood, racial disparities in prevalence of obesity, low levels of physical activity, and correlates of these risk factors and examined important differences in the complex relationship between obesity, diabetes, and cardiovascular disease risk between African American and European American women. The Jackson Heart Study will provide important and unique information relevant to many unanswered questions about obesity, physical inactivity, and obesity in African Americans. C1 Univ Mississippi, Sch Med, Jackson, MS 39216 USA. GV Sonny Montgomery Vet Affairs Med Ctr, Jackson, MS USA. NIDDK, Bethesda, MD USA. Jackson State Univ, Jackson, MS 39217 USA. Wayne State Univ, Sch Med, Detroit, MI USA. John D Dingell Vet Affairs Med Ctr, Detroit, MI USA. RP Dubbert, PM (reprint author), VA Med Ctr 11M, 1500 E Woodrow Wilson Dr, Jackson, MS 39216 USA. EM patricia.dubbert@med.va.gov NR 97 TC 48 Z9 51 U1 3 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD SEP PY 2002 VL 324 IS 3 BP 116 EP 126 DI 10.1097/00000441-200209000-00002 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 593DW UT WOS:000177976800002 PM 12240709 ER PT J AU Kumon, Y Nakauchi, Y Suehiro, T Shiinoki, T Tanimoto, N Inoue, M Nakamura, T Hashimoto, K Sipe, JD AF Kumon, Y Nakauchi, Y Suehiro, T Shiinoki, T Tanimoto, N Inoue, M Nakamura, T Hashimoto, K Sipe, JD TI Proinflammatory cytokines but not acute phase serum amyloid A or C-reactive protein, downregulate paraoxonase 1 (PON1) expression by HepG2 cells SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Article DE atherosclerosis; inflammation; cytokine; HDL ID HIGH-DENSITY-LIPOPROTEIN; RHEUMATOID-ARTHRITIS; A PROTEIN; ATHEROSCLEROSIS; PLASMA; SAA AB The expression of paraoxonase(1) (PON1) during inflammation has been investigated in vitro. The alteration of steady state PON1 mRNA in HepG2 cells by interleukin-1,8 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), was investigated relative to acute-phase serum amyloid A (A-SAA) mRNA. PON1 mRNA expression by HepG2 cells was decreased within three hours of stimulation by IL-1beta or TNFalpha. Relative to PON1 mRNA expression, the pattern of steady state A-SAA mRNA expression was altered reciprocally and inversely by IL- 1beta. These findings suggested that the decrease in serum PON activity after abdominal surgery in our previous clinical study may he ascribed to a decrease in steady state PON1 mRNA expression by liver with proinflammatory cytokines. C1 Kochi Med Sch, Dept Internal Med 2, Nanko Ku, Kochi 7838505, Japan. NIH, Ctr Sci Review, IRG, Bethesda, MD 20892 USA. RP Kumon, Y (reprint author), Kochi Med Sch, Dept Internal Med 2, Nanko Ku, Kochi 7838505, Japan. NR 17 TC 45 Z9 49 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD SEP PY 2002 VL 9 IS 3 BP 160 EP 164 DI 10.3109/13506120209114817 PG 5 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 607LR UT WOS:000178793500002 PM 12408678 ER PT J AU Waibel, KH Regis, DP Uzel, G Rosenzweig, SD Holland, SM AF Waibel, KH Regis, DP Uzel, G Rosenzweig, SD Holland, SM TI Fever and leg pain in a 42-month-old SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA-RECEPTOR; MYCOBACTERIUM-AVIUM COMPLEX; SEVERE COMBINED IMMUNODEFICIENCY; INFECTION; SUSCEPTIBILITY; MUTATION; DISEASE; DEFICIENCY; MANAGEMENT; CHILDHOOD C1 NIH, Host Def Lab, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Dept Allergy & Immunol, Washington, DC 20307 USA. RP Holland, SM (reprint author), NIH, Host Def Lab, Bldg 10,Room 11N103,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. NR 31 TC 11 Z9 11 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD SEP PY 2002 VL 89 IS 3 BP 239 EP 243 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 595MH UT WOS:000178113000004 PM 12269642 ER PT J AU Albright, SV McCart, JA Libutti, SK Bartlett, DL Alexander, HR Sampson, ML Ruddel, ME Remaley, AT AF Albright, SV McCart, JA Libutti, SK Bartlett, DL Alexander, HR Sampson, ML Ruddel, ME Remaley, AT TI Rapid measurement of insulin using the Abbott IMx: application to the management of insulinoma SO ANNALS OF CLINICAL BIOCHEMISTRY LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; SURGICAL-MANAGEMENT AB Background Patients with multiple endocrine neoplasia (type 1) often present with multiple pancreatic endocrine tumours, such as insulinomas. A major difficulty in the surgical treatment of such patients is identifying which tumours are functionally active and therefore need to be resected for a cure. The objective of this study was to develop a rapid insulin assay that could be used intraoperatively for identifying insulinomas from pancreatic aspirates. Methods By reducing the incubation time and by increasing the sample volume, a rapid insulin assay was developed on the IMx analyser. This was used to measure insulin from tissue aspirates collected from suspected insulinomas under ultrasound guidance. Results The rapid insulin assay (y) could be performed in 14 min and showed a good correlation with the standard IMx (x) insulin assay (y = 0.808x + 0.04; r(2) = 0.986). Using the rapid insulin assay on pancreatic tissue aspirates, insulinomas could be readily distinguished from normal pancreatic tissue or from non-functional adenomas based on a marked increase in insulin content. Conclusion In summary, a new rapid assay for insulin is described that compares favourably to the standard IMx insulin assay and can potentially be used intraoperatively on pancreatic aspirates for identifying functionally active insulinomas. C1 NCI, Dept Lab Med, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Remaley, AT (reprint author), NCI, Dept Lab Med, NIH, Bethesda, MD 20892 USA. NR 6 TC 8 Z9 8 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 0004-5632 J9 ANN CLIN BIOCHEM JI Ann. Clin. Biochem. PD SEP PY 2002 VL 39 BP 513 EP 515 DI 10.1258/000456302320314548 PN 5 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 594UQ UT WOS:000178069800013 PM 12227859 ER PT J AU Dagvadorj, A Petersen, RB Lee, HS Cervenakova, L Shatunov, A Budka, H Brown, P Gambetti, P Goldfarb, LG AF Dagvadorj, A Petersen, RB Lee, HS Cervenakova, L Shatunov, A Budka, H Brown, P Gambetti, P Goldfarb, LG TI Spontaneous mutations in the prion protein gene causing transmissible spongiform encephalopathy SO ANNALS OF NEUROLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; FATAL FAMILIAL INSOMNIA; MICE AB We analyzed the prion protein gene (PRNP) region in patients with transmissible spongiform encephalopathy associated with the PRNP D178N mutation. The results suggest that the D178N chromosomes had independent origins in each affected pedigree or apparently sporadic case. A de novo spontaneous PRNP mutation was observed. We provide evidence that hereditary and apparently sporadic transmissible spongiform encephalopathy cases associated with the D178N mutation result from multiple recurrent mutational events. C1 NINDS, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA. Univ Cincinnati, Med Ctr, Dept Environm Hlth, Ctr Genome Informat, Cincinnati, OH 45267 USA. Amer Red Cross, Jerome H Holland Lab, Rockville, MD USA. Univ Vienna, Inst Neurol, Reference Ctr Human Prion Dis, Vienna, Austria. RP Goldfarb, LG (reprint author), NINDS, NIH, Bldg 10,Room 4B37,10 Ctr Dr,MSC 1361, Bethesda, MD 20892 USA. RI Petersen, Robert/B-5075-2011; Shatunov, Aleksey/E-6946-2011; OI Petersen, Robert/0000-0002-3154-0072; Budka, Herbert/0000-0002-1933-1577 NR 14 TC 16 Z9 16 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 2002 VL 52 IS 3 BP 355 EP 359 DI 10.1002/ana.10267 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 590JQ UT WOS:000177820100015 PM 12205650 ER PT J AU Zheng, G Al-Saleh, MF AF Zheng, G Al-Saleh, MF TI Modified maximum likelihood estimators based on ranked set samples SO ANNALS OF THE INSTITUTE OF STATISTICAL MATHEMATICS LA English DT Article DE asymptotic relative efficiency; estimating equation; judgment error; modified maximum likelihood equation; order statistics; ranked set sampling; robustness AB The maximum likelihood estimator (MLE) using a ranked set sample (RSS) usually has no closed expression because the maximum likelihood equation involves both hazard and inverse hazard functions, and may no longer be efficient when the judgment ranking is imperfect. In this paper, we consider a modified MLE (MMLE) using RSS for general parameters, which has the same expression as the MLE using a simple random sample (SRS), except that the SRS in the MLE is replaced by the RSS. The results show that, for the location parameter, the MMLE is always more efficient than the MLE using SRS, and for the scale parameter, the MMLE is at least as efficient as the MLE using SRS, when the same sample size is used. Under the perfect judgment ranking, numerical examples also show that the MMLE has good efficiency relative to the MLE based on RSS. When the judgment error is present, we conduct simulations to show that the MMLE is more robust than the MLE using RSS. C1 NHLBI, Rockledge Ctr 2, Off Biostat Res, Bethesda, MD 20892 USA. Sultan Qaboos Univ, Dept Math & Stat, Al Khoud, Oman. NR 26 TC 20 Z9 21 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0020-3157 J9 ANN I STAT MATH JI Ann. Inst. Stat. Math. PD SEP PY 2002 VL 54 IS 3 BP 641 EP 658 DI 10.1023/A:1022475413950 PG 18 WC Statistics & Probability SC Mathematics GA 605LJ UT WOS:000178679100014 ER PT J AU Shimizu, K Murata, T Okumura, K Manganiello, VC Tagawa, T AF Shimizu, K Murata, T Okumura, K Manganiello, VC Tagawa, T TI Expression and role of phosphodiesterase 3 in human squamous cell carcinoma KB cells SO ANTI-CANCER DRUGS LA English DT Article DE phosphodiesterase; phosphodiesterase inhibitor; squamous cell carcinoma ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; INHIBITED CAMP-PHOSPHODIESTERASE; MOLECULAR-CLONING; DIFFERENTIAL EXPRESSION; POTENTIAL TARGET; GENE FAMILY; PHASE-II; PROLIFERATION; LOCALIZATION; ISOFORMS AB Phosphodiesterase (PDE) 3s have been characterized in human squamous cell carcinoma KB cells. PDE3 activity was detected in homogenates of KB cells. PDE3A and 3B mRNAs were detected by RT-PCR in RNA from KB cells; the nucleotide sequences of the fragments were identical to those of human PDE3A and 3B. Immunoblotting with anti-PDE3 antibodies detected both PDE3A- and 3B-immunoreactive proteins in KB cells. The PDE3-specific inhibitor, cilostamide, inhibited the proliferation of KB cells. Our results indicate that PDE3s may be important regulators of the growth of KB cells. Therefore, PDE3 inhibitors may be potential new drugs for antiproliferative therapies in squamous cell carcinoma in the head and neck. [(C) 2002 Lippincott Williams Wilkins.] C1 Mie Univ, Fac Med, Dept Oral & Maxillofacial Surg, Tsu, Mie 5148507, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Shimizu, K (reprint author), Mie Univ, Fac Med, Dept Oral & Maxillofacial Surg, 2-174 Edobashi, Tsu, Mie 5148507, Japan. NR 33 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD SEP PY 2002 VL 13 IS 8 BP 875 EP 880 DI 10.1097/00001813-200209000-00014 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 598RK UT WOS:000178290200014 PM 12394274 ER PT J AU Yang, QF Shan, L Yoshimura, G Nakamura, M Nakamura, Y Suzuma, T Umemura, T Mori, I Sakurai, T Kakuda, K AF Yang, QF Shan, L Yoshimura, G Nakamura, M Nakamura, Y Suzuma, T Umemura, T Mori, I Sakurai, T Kakuda, K TI 5-Aza-2 '-deoxycytidine induces retinoic acid receptor beta 2 demethylation, cell cycle arrest and growth inhibition in breast carcinoma cells SO ANTICANCER RESEARCH LA English DT Article DE breast cancer; RARb2; 5-Aza-CdR; cell cycling; growth inhibition ID DNA METHYLATION; CANCER CELLS; PHASE-I; GENE; EXPRESSION; ISOTRETINOIN; PROMOTER; SITES AB Like all cancers, breast cancer is considered to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumor suppressor loss. More recently, CpG island hypermethylation is known to be associated with gene silencing in cancer, and these silenced genes can be reactivated by 5-aza-2'-deoxycytidine (5-Aza-CdR). Retinoic acid receptor beta2 gene is a tumor suppressor gene and the chemopreventive effects of retinoids are due to induction of RARbeta2. In this study, the effect of 5-Aza-CdR RARbeta2 restoration was investigated in the MRK-nu-1 human female breast cancer cell line. Changes of the RARbeta2 methylation status were assessed by methylation-specific PCR. Reverse transcription PCR was used to evaluate RARbbeta2 restoration. Cell cycling and growth inhibition were studied using flow cytometric analysis of DNA content and CellTiter 96 AQueous non-radioactive cell proliferation assay, respectively. 5-Aza-CdR treatment resulted in complete demethylation of the RARbeta2 gene. RARbeta2 restoration was accompanied by cell cycle arrest (increase in the G0/G1-and decrease in the S-and G2/M-phases) and time-dependent growth inhibition. In conclusion, RARbeta2 can be activated in vitro by 5-Aza-CdR, which may be one of the mechanisms for the tumor cell growth inhibition by 5-Aza-CdR. C1 Wakayama Med Univ, Affiliated Kohoku Hosp, Dept Surg, Wakayama 6497113, Japan. Wakayama Med Univ, Dept Pathol 2, Wakayama 6418509, Japan. Shandong Univ, Qilu Hosp, Dept Gen Surg, Jinan 250100, Shandong Prov, Peoples R China. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Yang, QF (reprint author), Wakayama Med Univ, Dept Pathol 2, 811-1 Kimiidera, Wakayama 6410012, Japan. RI Nakamura, Yasushi/J-5143-2014 NR 23 TC 28 Z9 39 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2002 VL 22 IS 5 BP 2753 EP 2756 PG 4 WC Oncology SC Oncology GA 630WB UT WOS:000180132200033 PM 12529992 ER PT J AU Strumberg, D Nitiss, JL Dong, JW Walker, J Nicklaus, MC Kohn, KW Heddle, JG Maxwell, A Seeber, S Pommier, Y AF Strumberg, D Nitiss, JL Dong, JW Walker, J Nicklaus, MC Kohn, KW Heddle, JG Maxwell, A Seeber, S Pommier, Y TI Importance of the fourth alpha-helix within the CAP homology domain of type II topoisomerase for DNA cleavage site recognition and quinolone action SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID GYRASE-A-PROTEIN; ESCHERICHIA-COLI; EUKARYOTIC TOPOISOMERASE; ENZYME-DNA; DRUG-INTERACTIONS; BINDING; YEAST; MECHANISM; MUTATION; INHIBITORS AB We report that point mutations causing alteration of the fourth alpha-helix (alpha4-helix) of the CAP homology domain of eukaryotic (Saccharomyces cerevisiae) type II topoisomerases (Ser(740)Trp, Gln(743) Pro, and Thr(744) Pro) change the selection of type II topoisomerase-mediated DNA cleavage sites promoted by Ca2+ or produced by etoposide, the fluoroquinolone CP-115,953, or mitoxantrone. By contrast, Thr(744)Ala substitution had minimal effect on Ca2+ and drug-stimulated DNA cleavage sites, indicating the selectivity of single amino acid substitutions within the alpha4-helix on type II topoisomerase-mediated DNA cleavage. The equivalent mutation in the gene for Escherichia coli gyrase causing Ser(83)Trp also changed the DNA cleavage pattern generated by Ca2+ or quinolones. Finally, Thr(144) Pro substitution in the yeast type II topoisomerase rendered the enzyme sensitive to antibacterial quinolones. This study shows that the alpha4-helix within the conserved CAP homology domain of type II topoisomerases is critical for selecting the sites of DNA cleavage. It also demonstrates that selective amino acid residues in the alpha4-helix are important in determining the activity and possibly the binding of quinolones to the topoisomerase II-DNA complexes. C1 Univ Essen Gesamthsch, Sch Med, W German Canc Ctr, Dept Internal Med & Med Oncol, D-45122 Essen, Germany. NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England. RP Strumberg, D (reprint author), Univ Essen Gesamthsch, Sch Med, Dept Internal Med Canc Res, Hufelandstr 55, D-45122 Essen, Germany. EM dirk.strumberg@uni-essen.de; pommier@nih.gov RI Nitiss, John/E-9974-2010; Heddle, Jonathan/H-4586-2014; Nicklaus, Marc/N-4183-2014; OI Nitiss, John/0000-0002-1013-4972; Nicklaus, Marc/0000-0002-4775-7030 FU NCI NIH HHS [CA21765, CA52814, P30 CA021765, R01 CA052814] NR 60 TC 11 Z9 13 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2002 VL 46 IS 9 BP 2735 EP 2746 DI 10.1128/AAC.46.9.2735-2746.2002 PG 12 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 585FQ UT WOS:000177515000002 PM 12183223 ER PT J AU Ma, L Jia, QY Kovacs, JA AF Ma, L Jia, QY Kovacs, JA TI Development of a yeast assay for rapid screening of inhibitors of human-derived Pneumocystis carinii dihydrofolate reductase SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DIHYDROPTEROATE SYNTHASE; PLASMODIUM-FALCIPARUM; IDENTIFICATION; ANTIFOLATE; EXPRESSION; POTENT; MODEL; DRUGS; GENE AB Human-derived Pneumocystis carinii dihydrofolate reductase (DHFR) was expressed in a Saccharomyces cerevisiae strain whose growth depends on complementation by this enzyme. We utilized a quantitative assay to measure the sensitivity of this yeast strain to DHFR inhibitors. This assay should be useful for identifying new inhibitors of human-derived P. carinii DHFR. C1 NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 15 TC 5 Z9 6 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2002 VL 46 IS 9 BP 3101 EP 3103 DI 10.1128/AAC.46.9.3101-3103.2002 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 585FQ UT WOS:000177515000062 PM 12183283 ER PT J AU Bada, HS Bauer, CR Shankaran, S Lester, B Wright, LL Das, A Poole, K Smeriglio, VL Finnegan, LP Maza, PL AF Bada, HS Bauer, CR Shankaran, S Lester, B Wright, LL Das, A Poole, K Smeriglio, VL Finnegan, LP Maza, PL TI Central and autonomic system signs with in utero drug exposure SO ARCHIVES OF DISEASE IN CHILDHOOD LA English DT Article ID NEONATAL WITHDRAWAL SYNDROME; INTRAUTERINE COCAINE EXPOSURE; MATERNAL COCAINE; NARCOTIC ADDICTION; IN-UTERO; NEUROBEHAVIORAL STATUS; NEWBORN-INFANTS; PREGNANCY; METHADONE; ABUSE AB Aims: To determine risk for central nervous system/autonomic nervous system (CNS/ANS) signs following in utero cocaine and opiate exposure. Methods: A multisite study was designed to determine outcomes of in utero cocaine and opiate exposure. A total of 11 811 maternal/infant dyads were enrolled. Drug exposed (EXP) infants were identified by maternal self report of cocaine or opiate use or by meconium testing. Of 1185 EXP, meconium analysis confirmed exposure in 717 to cocaine (CO) only, 100 to opiates (OP), and 92 to opiates plus cocaine (OP+CO); 276 had insufficient or no meconium to confirm maternal self report. Negative exposure history was confirmed in 7442 by meconium analysis and unconfirmed in 3184. Examiners masked to exposure status, assessed each enrolled infant. Using generalised estimating equations, adjusted odds ratios (OR) and 95% confidence intervals (Cl) were estimated for manifesting a constellation of CNS/ANS outcomes and for each sign associated with cocaine and opiate exposure. Results: Prevalence of CNS/ANS signs was low in CO, and highest in OP+CO. Signs were significantly related to one another. After controlling for confounders, CO was associated with increased risk of manifesting a constellation of CNS/ANS outcomes, OR (95% Cl): 1.7 (1.2 to 2.2), independent of OP effect, OR (95% Cl): 2.8 (2.1 to 3.7). OP+CO had additive effects, OR (95% Cl): 4.8 (2.9 to 7.9). Smoking also increased the risk for the constellation of CNS/ANS signs, OR (95% Cl) of 1.3 (1.04 to 1.55) and 1.4 (1.2 to 1.6), respectively, for use of less than half a pack per day and half a pack per day or more. Conclusion: Cocaine or opiate exposure increases the risk for manifesting a constellation of CNS/ANS outcomes. C1 Univ Kentucky, Dept Pediat, Lexington, KY 40506 USA. Miami Univ, Sch Med, Dept Pediat, Miami, FL USA. Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. Brown Univ, Sch Med, Dept Pediat, Women & Infants Hosp, Providence, RI USA. NICHD, Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIDA, Bethesda, MD 20892 USA. NIH, Off Res Womens Hlth, Bethesda, MD USA. ACYF, Washington, DC USA. RP Bada, HS (reprint author), 800 Rose St,Rm MS473, Lexington, KY 40536 USA. FU NICHD NIH HHS [U10 HD 21397, U10 HD 27856, U10 HD 27904, U01 HD 36790, U10 HD 21385] NR 68 TC 14 Z9 15 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-9888 J9 ARCH DIS CHILD JI Arch. Dis. Child. PD SEP PY 2002 VL 87 IS 2 SI SI BP F106 EP F112 DI 10.1136/fn.87.2.F106 PG 7 WC Pediatrics SC Pediatrics GA 589NN UT WOS:000177766300009 PM 12193516 ER PT J AU Hasin, DS Grant, DF AF Hasin, DS Grant, DF TI Major depression in 6050 former drinkers - Association with past alcohol dependence SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DSM-III-R; NATIONAL-COMORBIDITY-SURVEY; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; PLACEBO-CONTROLLED TRIAL; SUBSTANCE USE DISORDERS; PSYCHIATRIC-DISORDERS; CLINICAL IMPLICATIONS; IMIPRAMINE TREATMENT; MODERATE DRINKING AB Background: The association between alcoholism and major depression in the general population has been explained as misdiagnosed alcohol intoxication and withdrawal effects mistaken for depressive syndromes. To investigate whether this could account for the entire relationship, the association of past alcohol dependence with current major depression (ie, nonoverlapping time frames) was investigated in individuals who no longer drink or who drink very little. We conducted the study using data from the National Longitudinal Alcohol Epidemiologic Survey, a representative sample. Methods: Former drinkers who did not use drugs or smoke in the past year (n=6050) were divided into those with and without past DSM-IV alcohol dependence. These 2 groups were compared for the presence of current (last 12 months) DSM-IV major depression. The association between prior alcohol dependence and current major depression was tested with linear logistic regression, controlling for other variables. Results: Prior alcohol dependence increased the risk of current major depressive disorder more than 4-fold. This relationship was not attenuated by control variables. The majority of subjects with major depression last used substances 2 or more years prior to the interview, which eliminates acute intoxication or withdrawal effects as an explanation of their depressions. Conclusions: The strong, specific association between prior alcohol dependence and current or recent major depression in a nationally representative sample of former drinkers indicates that the association is not entirely an artifact of misdiagnosed intoxication and withdrawal effects. A better understanding of the nature of the relationship between the 2 disorders should be sought and will have important public health significance. C1 Columbia Univ, New York State Psychiat Inst, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. NIAAA, Div Biometry & Epidemiol, Bethesda, MD USA. RP Hasin, DS (reprint author), Columbia Univ, New York State Psychiat Inst, Mailman Sch Publ Hlth, Dept Epidemiol, 1051 Riverside Dr,Box 123, New York, NY 10032 USA. FU NIAAA NIH HHS [K02AA00161] NR 55 TC 149 Z9 152 U1 4 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2002 VL 59 IS 9 BP 794 EP 800 DI 10.1001/archpsyc.59.9.794 PG 7 WC Psychiatry SC Psychiatry GA 592JV UT WOS:000177935300003 PM 12215078 ER PT J AU Hortin, GL Carter, AB AF Hortin, GL Carter, AB CA Coll Amer Pathologists TI Intraoperative parathyroid hormone testing - Survey of testing program characteristics SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID SURGICAL-MANAGEMENT; NECK EXPLORATION; PRIMARY HYPERPARATHYROIDISM; SESTAMIBI SCINTIGRAPHY; PTH ASSAY; SURGERY; EVOLUTION; SUCCESS; SAMPLES; TUMORS AB Objective.-To examine the number and testing characteristics of laboratories that offer intraoperative testing of intact parathyroid hormone (PTH). Design.-Laboratories (n=355) that participated in 2001 in PTH proficiency testing with the College of American Pathologists Special Ligand Survey were surveyed about intraoperative PTH testing. Results.-Of the 320 laboratories that responded to the survey, 92 performed intraoperative PTH testing. Testing practices were divided nearly equally among laboratories that performed intraoperative PTH testing for all parathyroidectomies (40%), most but not all cases (31%), and less than half of cases (30%). Testing frequency usually was low, with about two thirds of laboratories reporting 5 or fewer cases per month. A surprising finding was that, although intraoperative PTH testing originally became widely practiced as a point-of-care test, 71% of laboratories performed testing in a central laboratory, 6% in satellite laboratories, and only 23% in operating suites. A survey of methods showed that 33% used the manual QuiCk-Intraoperative test, 47% used the automated Immulite Turbo intact PTH assay, and 20% used other methods. Conclusions-Intraoperative testing of intact PTH, although relatively new, has come into widespread practice during parathyroid surgery. Service delivery has evolved from a point-of-care model toward a central laboratory model, with this test serving as an illustrative example of factors that affect the balance between point-of-care and laboratory testing. C1 NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. E Carolina Univ, Brody Sch Med, Dept Pathol & Lab Med, Greenville, NC USA. RP Hortin, GL (reprint author), NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. RI Carter, Alexis/D-7843-2011 OI Carter, Alexis/0000-0002-0171-2216 NR 46 TC 14 Z9 14 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 2002 VL 126 IS 9 BP 1045 EP 1049 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 594UA UT WOS:000178068300007 PM 12204053 ER PT J AU Beasley, MB Franks, TJ Galvin, JR Gochuico, B Travis, WD AF Beasley, MB Franks, TJ Galvin, JR Gochuico, B Travis, WD TI Acute fibrinous and organizing pneumonia - A histologic pattern of lung injury and possible variant of diffuse alveolar damage SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; EOSINOPHILIC PNEUMONIA AB Context.-The histologic patterns of diffuse alveolar damage (DAD), bronchiolitis obliterans with organizing pneumonia (BOOP), and eosinophilic pneumonia (EP) are well-recognized histologic patterns of lung injury associated with an acute or subacute clinical presentation. We have recognized acute fibrinous and organizing pneumonia (AFOP) as a histologic pattern, which also occurs in this clinical setting but does not meet the classic histologic criteria for DAD, BOOP, or EP and may represent an underreported variant. Objectives.-To investigate the clinical significance of the AFOP histologic pattern and to explore its possible relationship to other disorders, including DAD and BOOR Design.-Open lung biopsy specimens and autopsy specimens were selected from the consultation files of the Armed Forces Institute of Pathology, which showed a dominant histologic pattern of intra-alveolar fibrin and organizing pneumonia. Varying amounts of organizing pneumonia, type 2 pneumocyte hyperplasia, edema, acute and chronic inflammation, and interstitial widening were seen. Cases with histologic patterns of classic DAD, BOOP, abscess formation, or eosinophilic pneumonia were excluded. To determine the clinical behavior of patients with this histologic finding, clinical and radiographic information and follow-up information were obtained. Statistical analysis was performed using Kaplan-Meier and chi(2) analysis. Results.-Seventeen patients (10 men, 7 women) with a mean age of 62 years (range, 33-78 years) had acute-onset symptoms of dyspnea (11), fever (6), cough (3), and hemoptysis (2). Associations believed to be clinically related to the lung disease included definitive or probable collagen vascular disease (3), amiodarone (1), sputum culture positive for Haemophilus influenza (1), lung culture positive for Acinetobacter sp. (1), lymphoma (1), hairspray (1), construction work (1), coal mining (1), and zoological work (1). Six patients had no identifiable origin or association. Follow-up revealed 2 clinical patterns of disease progression: a fulminate illness with rapid progression to death (n=9; mean survival, 0.1 year) and a more subacute illness, with recovery (n=8). Histologic analysis and initial symptoms did not correlate with eventual outcome, but 5 of the 5 patients who required mechanical ventilation died (P=.007). Conclusions.-Acute fibrinous and organizing pneumonia is a histologic pattern associated with a clinical picture of acute lung injury that differs from the classic histologic patterns of DAD, BOOP, or EP. Similar to these patterns of acute lung injury, the AFOP pattern can occur in an idiopathic setting or with a spectrum of clinical associations. The overall mortality rate is similar to DAD and therefore may represent a histologic variant; however, AFOP appears to have 2 distinct patterns of disease progression and outcome. The need for mechanical ventilation was the only parameter that correlated with prognosis. None of the patients with a subacute clinical course required mechanical ventilation. C1 Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. Armed Forces Inst Pathol, Dept Radiol Pathol, Washington, DC 20306 USA. NHLBI, Pulm Crit Care Med Branch, Washington, DC USA. RP Travis, WD (reprint author), Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, 6825 NW 16th St, Washington, DC 20306 USA. NR 13 TC 94 Z9 104 U1 0 U2 4 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 2002 VL 126 IS 9 BP 1064 EP 1070 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 594UA UT WOS:000178068300010 PM 12204055 ER PT J AU Corsi, A Riminucci, M Petrozza, V Collins, MT Natale, ME Cancrini, A Bianco, P AF Corsi, A Riminucci, M Petrozza, V Collins, MT Natale, ME Cancrini, A Bianco, P TI Incidentally detected giant oncocytoma arising in retroperitoneal heterotopic adrenal tissue SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID 3-BETA-HYDROXYSTEROID DEHYDROGENASE; ADRENOCORTICAL ONCOCYTOMA; NEOPLASMS AB A nonfunctional retroperitoneal oncocytoma incidentally discovered in a 40-year-old woman is described. The tumor, which was 17 cm in largest dimension, was completely separated from the kidneys and adrenal glands and consisted of nests of polygonal cells with large, granular, eosinophilic cytoplasm. Significant nuclear atypia, necrosis, and mitosis were absent. Ultrastructural analysis confirmed the oncocytic nature of the neoplastic cells. Since neoplastic cells were not immunoreactive for chromogranin and did not contain dense-core secretory granules, the diagnosis of oncocytic paraganglioma was excluded. Cells immunoreactive for 3beta-hydroxysteroid dehydrogenase, the enzyme catalyzing the conversions of pregnenolone to progesterone and dehydroepiandrosterone to androstenedione, were identified in the tumor, thus strongly indicating adrenocortical tissue origin. Multiple nests of 3beta-hydroxysteroid dehydrogenase-positive cells were detected in the loose retroperitoneal connective tissue. These findings strongly support the origin of the tumor from heterotopic retroperitoneal rests of the adrenal gland. To our knowledge, only 1 similar case has been described in the literature to date. C1 Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, Policlin Umberto I, I-00161 Rome, Italy. Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Univ Roma La Sapienza, Inst Surg 3, I-00161 Rome, Italy. RP Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, Policlin Umberto I, Viale Regina Elena 324, I-00161 Rome, Italy. EM p.bianco@flashnet.it RI Petrozza, Vincenzo/N-2424-2016 OI Petrozza, Vincenzo/0000-0001-9837-8690 NR 12 TC 18 Z9 18 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 2002 VL 126 IS 9 BP 1118 EP 1122 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 594UA UT WOS:000178068300021 PM 12204066 ER PT J AU Ruger, W Wilson, SE Waddoups, SL AF Ruger, W Wilson, SE Waddoups, SL TI Warfare and welfare: Military service, combat, and marital dissolution SO ARMED FORCES & SOCIETY LA English DT Article AB This article investigates the impact of military service on the duration of a veteran's first marriage,. a topic in the literature with both scant and highly contradictory conclusions. Our sample consisted of 3,800 males from the National Survey of Families and Households (1987-1994). Using hazard rate analysis, we estimate the impact of both combat and noncombat assignments on marital duration. Our statistical results imply: (1) self-reported participation in combat increases the hazard rate for marital dissolution by over 60 percent; (2) time- of marriage (whether before, during, or after the war) does not affect dissolution, except for wartime marriages during WWII, where the effect is strong; and (3) the effects of war differ significantly across the major U.S. wars; surprisingly, the strongest negative impact on duration occurs with the neglected Korean War veterans. C1 Brigham Young Univ, Dept Polit Sci, Provo, UT 84602 USA. Brandeis Univ, Waltham, MA 02254 USA. Natl Bur Econ Res, Cambridge, MA 02138 USA. NIA, Res Program, Bethesda, MD 20892 USA. RP Ruger, W (reprint author), Brigham Young Univ, Dept Polit Sci, 732 SWKT, Provo, UT 84602 USA. NR 38 TC 27 Z9 27 U1 0 U2 3 PU TRANSACTION PERIOD CONSORTIUM PI PISCATAWAY PA RUTGERS UNIV, DEPT 8010, 35 BERRUE CIRCLE, PISCATAWAY, NJ 08854-8042 USA SN 0095-327X J9 ARMED FORCES SOC JI Armed Forces Soc. PD FAL PY 2002 VL 29 IS 1 BP 85 EP + DI 10.1177/0095327X0202900105 PG 24 WC Political Science; Sociology SC Government & Law; Sociology GA 631QF UT WOS:000180177900004 ER PT J AU Aringer, M Hofmann, S Frucht, DM Min, C Centola, M Morinobu, A Visconti, R Haleem-Smith, H Kastner, DL Smolen, JS O'Shea, JJ AF Aringer, M Hofmann, S Frucht, DM Min, C Centola, M Morinobu, A Visconti, R Haleem-Smith, H Kastner, DL Smolen, JS O'Shea, JJ TI The transcription factor Ets-1 is essential for janus kinase 3 (Jak3) promoter activity SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Vienna, Dept Rheumatol Internal Med 3, Vienna, Austria. NIAMSD, Athrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S346 EP S346 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800913 ER PT J AU Chae, JJ Cheng, J Homarow, H Wood, G Raben, N Liu, PP Kastner, DL AF Chae, JJ Cheng, J Homarow, H Wood, G Raben, N Liu, PP Kastner, DL TI Mice deficient in pyrin, the FMF protein, show increased sensitivity to endotoxin through a new pathway regulating IL-1 activation and apoptosis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, Genet & Genom Branch, NIH, Bethesda, MD USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NIAMS, Arthrit & Rheumatism Branch, NIH, Bethesda, MD USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S371 EP S371 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800990 ER PT J AU Cooper, GS Lambe, MP Rallstrand, P Bjornadal, L AF Cooper, GS Lambe, MP Rallstrand, P Bjornadal, L TI Parity and the risk of scleroderma. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, Durham, NC USA. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. Karolinska Hosp, S-10401 Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S617 EP S617 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801694 ER PT J AU Cooper, GS Parks, CG Dooley, MA Treadwell, EL Gilkeson, GS St Clair, EW Archer, JD AF Cooper, GS Parks, CG Dooley, MA Treadwell, EL Gilkeson, GS St Clair, EW Archer, JD TI Occupational exposures and risk of systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, Durham, NC USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. ECU Sch Med, Greenville, NC USA. MUSC, Charleston, SC USA. Duke Univ, Med Ctr, Durham, NC USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S616 EP S616 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801691 ER PT J AU Diaz, A Richards, NW Kastner, DL Kunkel, SL Gumucio, DL AF Diaz, A Richards, NW Kastner, DL Kunkel, SL Gumucio, DL TI Transgenic mice expressing human pyrin exhibit a pro-apoptotic phenotype. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S379 EP S379 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801012 ER PT J AU Douglas, G Cooper, G Dooley, MA Gilkeson, G AF Douglas, G Cooper, G Dooley, MA Gilkeson, G TI Endothelial nitric oxide synthase polymorphisms in systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ N Carolina, Sch Med, Chapel Hill, NC USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S286 EP S286 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800743 ER PT J AU Gelber, AC Pillemer, SR Baum, BJ Wigley, FM Rosen, A Casciola-Rosen, LA AF Gelber, AC Pillemer, SR Baum, BJ Wigley, FM Rosen, A Casciola-Rosen, LA TI Distinct patterns of autoantibodies to centromere proteins in Sjogren's syndrome and scleroderma SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S129 EP S129 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800283 ER PT J AU Goldbach-Mansky, R Aksentijevich, I Chae, JJ Nowak, M Mallah, M Watford, W Hoffman, S Remmers, E Rozenzweig, S Rosenberg, H Stein, L Russo, R Goldsmith, D Dent, D Lovell, D Schikler, K Adams, B Moore, T Jones, J Mangra, N Lipnick, R Barron, K O'Shea, JJ Kastner, DL AF Goldbach-Mansky, R Aksentijevich, I Chae, JJ Nowak, M Mallah, M Watford, W Hoffman, S Remmers, E Rozenzweig, S Rosenberg, H Stein, L Russo, R Goldsmith, D Dent, D Lovell, D Schikler, K Adams, B Moore, T Jones, J Mangra, N Lipnick, R Barron, K O'Shea, JJ Kastner, DL TI Spontaneous mutations in CIAS1 cause neonatal onset multisystem inflammatory disease (NOMID). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, Genet & Genom Branch, NIH, Bethesda, MD USA. NIAMS, Immunol & Inflammat Branch, NIH, Bethesda, MD USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC 27514 USA. Hosp Pediat Juan P Garrahan, Buenos Aires, DF, Argentina. St Christophers Hosp Children, Philadelphia, PA 19133 USA. McMaster Univ, Hamilton, ON, Canada. Childrens Hosp, Ctr Med, Cincinnati, OH 45229 USA. Univ Louisville, Louisville, KY 40292 USA. Univ Michigan, Ann Arbor, MI 48109 USA. St Louis Univ, St Louis, MO 63103 USA. NIAID, Div Intramural Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S579 EP S579 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801587 ER PT J AU Goldbach-Mansky, RT Souto-Carneiro, MM Mahadevan, V Ettinger, R Carrero, H Wilson, M Lipsky, PE AF Goldbach-Mansky, RT Souto-Carneiro, MM Mahadevan, V Ettinger, R Carrero, H Wilson, M Lipsky, PE TI TNF blockade results in an increase of CD20+CD27+(memory) B cells in the peripheral circulation of rheumatoid arthritis (RA) patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S505 EP S505 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801380 ER PT J AU Goldbach-Mansky, RT Murphey, M Flemming, D Hill, S Morrison, K Wilson, M Philip, K Lipsky, PE Yao, L AF Goldbach-Mansky, RT Murphey, M Flemming, D Hill, S Morrison, K Wilson, M Philip, K Lipsky, PE Yao, L TI T2 weighted MRI may define "active" carpal bone erosions in patients with early rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Bethesda, MD USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NIAMSD, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S595 EP S595 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801631 ER PT J AU Guermazi, A Taouli, B Lynch, JA Li, J Peterfy, CG Kathryn, WY Kritchevsky, S Chen, Y Harris, T Lane, NE Genant, HK Nevitt, MC AF Guermazi, A Taouli, B Lynch, JA Li, J Peterfy, CG Kathryn, WY Kritchevsky, S Chen, Y Harris, T Lane, NE Genant, HK Nevitt, MC TI Prevalence of meniscus and ligament tears and their correlation with cartilage morphology and other MRI features in knee osteoarthritis (OA) in the elderly: The health ABC study. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Synarc Inc, San Francisco, CA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Tennessee, Memphis, TN USA. NIH, Bethesda, MD 20892 USA. RI Lynch, John/F-8209-2012 NR 0 TC 7 Z9 7 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S567 EP S567 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801552 ER PT J AU Hirsch, R Fryar, C Lawrence, R AF Hirsch, R Fryar, C Lawrence, R TI Chronic pain in adults in the United States. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Natl Ctr Hlth Stat, Hyattsville, MD USA. Natl Inst Musculoskeletal & Skin Dis, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S459 EP S459 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801245 ER PT J AU Hull, KM Aksentijevich, I Singh, H Dean, J Yarboro, C O'Shea, JJ Kastner, DL AF Hull, KM Aksentijevich, I Singh, H Dean, J Yarboro, C O'Shea, JJ Kastner, DL TI Efficacy of etanercet for the treatment of patients with TNF receptor-associated periodic syndrome (TRAPS). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, NIH, Bethesda, MD USA. NR 0 TC 5 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S378 EP S378 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801010 ER PT J AU Isenberg, DA Allen, E Farewell, V Ehrenstein, MR Cooper, R Hanna, M Lundberg, I Oddis, C Plotz, P Vencovsky, J Rider, L Miller, F AF Isenberg, DA Allen, E Farewell, V Ehrenstein, MR Cooper, R Hanna, M Lundberg, I Oddis, C Plotz, P Vencovsky, J Rider, L Miller, F TI Development of disease activity and damage indices for myositis: Further testing of four tools in adult onset patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 UCL, Int Myositis Dis Outcome Assessment Collaborat St, London, England. Inst Publ Hlth, Cambridge, England. Hope Hosp, Manchester, Lancs, England. Karolinska Inst, Stockholm, Sweden. Univ Pittsburgh, Pittsburgh, PA USA. NIAMS, NIH, Bethesda, MD USA. Inst Rheumatol, Prague, Czech Republic. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S488 EP S488 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801328 ER PT J AU Jawaheer, D Seldin, MF Amos, CI Wei, C Damle, A Xiao, XL Shigeta, R Monteiro, J Kem, M Criswell, LA Albani, S Nelson, L O Clegg, D Pope, R Schroeder, HW Bridges, L Pisetsky, DS Ward, R Kastner, DL Wilder, RL Pincus, T Callaghan, LF Flemming, D Wener, M Gregersen, PK AF Jawaheer, D Seldin, MF Amos, CI Wei, C Damle, A Xiao, XL Shigeta, R Monteiro, J Kem, M Criswell, LA Albani, S Nelson, L O Clegg, D Pope, R Schroeder, HW Bridges, L Pisetsky, DS Ward, R Kastner, DL Wilder, RL Pincus, T Callaghan, LF Flemming, D Wener, M Gregersen, PK TI A second genome-wide screen and a combined analysis of 512 multicase RA families supports linkage to multiple Non-HLA loci. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NS LIJ Res Inst, Manhasset, NY 98104 USA. UC Davis, Davis, CA 84112 USA. MDACC, Houston, TX 60611 USA. UC San Francisco, San Francisco, CA USA. UC San Diego, San Diego, CA 27706 USA. Fred Hutchinson Canc Res Ctr, Seattle OX1 2JD, WA USA. Univ Utah, Salt Lake City, UT USA. Northwestern Univ, Sch Med, Chicago, IL USA. Univ Alabama, Birmingham, AL USA. Duke Univ, Med Ctr, Durham, NC 27515 USA. Univ Oxford, Oxford, England. NIAMS, NIH, Bethesda, MD 98195 USA. MedImmune, Gaithersburg, MD USA. Vanderbilt Univ, Nashville, TN USA. Univ N Carolina, Chapel Hill, NC USA. Natl Naval Med Res Inst, Bethesda, MD USA. Univ Washington, Sch Med, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S391 EP S391 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801047 ER PT J AU Lam, AQ Hofmann, S Frank, S Agnello, D Zhou, YJ Youle, R O'Shea, JJ AF Lam, AQ Hofmann, S Frank, S Agnello, D Zhou, YJ Youle, R O'Shea, JJ TI Chaperone function of JAKs revisited: JAK3-Independent trafficking of the common gamma chain receptor subunit. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, HHMI, Bethesda, MD 20892 USA. NIAMS, MIIB, Bethesda, MD USA. NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S387 EP S387 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801035 ER PT J AU Lee, J Jang, JE Lipsky, PE AF Lee, J Jang, JE Lipsky, PE TI Immunoglobulin light chain repertoire in systemic lupus erythematosus: Role in emergence of autoreactive B cells in systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Ewha Womans Univ, Coll Med, Seoul 120750, South Korea. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S126 EP S126 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800275 ER PT J AU Lethbridge-Cejku, M Creamer, P Scott, WW Ling, SM Metter, J Hochberg, MC AF Lethbridge-Cejku, M Creamer, P Scott, WW Ling, SM Metter, J Hochberg, MC TI Weight loss is associated with reduced risk of incident radiographic knee osteoarthritis in men but not in women: Data from the Baltimore longitudinal study of aging. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Ctr Dis Control & Prevent, Atlanta, GA USA. Southmead Gen Hosp, Bristol, Avon, England. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIA, IRP, Baltimore, MD 21224 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S467 EP S467 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801267 ER PT J AU Levine, SM Raben, N Plotz, P Rosen, A Casciola-Rosen, L AF Levine, SM Raben, N Plotz, P Rosen, A Casciola-Rosen, L TI The granzyme B cleavage site in histidyl-tRNA synthetase is a critical component of its B cell epitope in myositis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S223 EP S223 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800551 ER PT J AU Ling, SM Metter, EJ Lethbridge-Cejku, M AF Ling, SM Metter, EJ Lethbridge-Cejku, M TI Age and gender modify the relationship between Osteoarthritis of the knee and bone density. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S466 EP S466 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801265 ER PT J AU Lodde, BM Leakan, RA Pillemer, SR AF Lodde, BM Leakan, RA Pillemer, SR TI Serum lipid levels in Sjogren's syndrome. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S369 EP S369 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800986 ER PT J AU McClain, MT Arbuckle, MR Heinlen, LD Rubertone, M Dennis, GJ Harley, JB James, JA AF McClain, MT Arbuckle, MR Heinlen, LD Rubertone, M Dennis, GJ Harley, JB James, JA TI The presence of Antiphospholipid antibodies prior to diagnosis of SLE signals early, rapid onset of disease with a more severe clinical course. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Jackson Found WRAMC, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S47 EP S47 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800041 ER PT J AU Moriguchi, M Gadina, M Tiffany, L Murphy, PM O'Shea, JJ AF Moriguchi, M Gadina, M Tiffany, L Murphy, PM O'Shea, JJ TI CXCL12 signaling is independent of Jak3. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S256 EP S256 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800648 ER PT J AU Morinobu, A O'Shea, JJ AF Morinobu, A O'Shea, JJ TI Historic acetylation of interferon-gamma and T-bet genes during Th1 cell differentiation. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, MIIB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S563 EP S563 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801541 ER PT J AU Nagaraju, K Zhao, P Hoffman, E Dwivedi, S Hall, J Tournadre, A Rosen, A AF Nagaraju, K Zhao, P Hoffman, E Dwivedi, S Hall, J Tournadre, A Rosen, A TI Innate and adaptive immune response genes are differentially expressed in normal post-pubertal male and female mice. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S619 EP S619 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801700 ER PT J AU Nevitt, M Felson, D Peterfy, C Wildy, K Ling, S Lane, N Newman, A Carbone, L Harris, T AF Nevitt, M Felson, D Peterfy, C Wildy, K Ling, S Lane, N Newman, A Carbone, L Harris, T TI Inflammation markers (CRP, TNF-a, IL-6) are not associated with radiographic or MRI findings of knee OA in the elderly: The Health ABC study. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 UCSF, San Francisco, CA USA. Boston Univ, Boston, MA 02215 USA. Synarc Inc, San Francisco, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Tennessee, Memphis, TN USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S372 EP S373 PG 2 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800995 ER PT J AU Pillemer, SR Brennan, M Sankar, V Leakan, RA Grisius, M Ligier, S Kok, MR Baum, BJ Fox, PC AF Pillemer, SR Brennan, M Sankar, V Leakan, RA Grisius, M Ligier, S Kok, MR Baum, BJ Fox, PC TI Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjogren's syndrome SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S370 EP S370 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800987 ER PT J AU Pillemer, SR Gelber, A Baum, BJ Casciola-Rosen, L Rosen, A AF Pillemer, SR Gelber, A Baum, BJ Casciola-Rosen, L Rosen, A TI CENP-C is a target of Autoantibodies in patients with primary Sjogren's syndrome, and is uniformly associated with antibodies to Ro and La. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S361 EP S361 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800958 ER PT J AU Radbruch, A Tykocinski, L Hajkova, P Stamm, T Soezeri, O Loehning, M Friedrich, B Hu-Li, J Pannetier, C Paul, WE Gruetz, G Walter, J AF Radbruch, A Tykocinski, L Hajkova, P Stamm, T Soezeri, O Loehning, M Friedrich, B Hu-Li, J Pannetier, C Paul, WE Gruetz, G Walter, J TI A GATA-3 binding site in the first intron of the interleukin-4 gene defines a critical element for the memory expression of interleukin-4 in Th lymphocytes. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Deutsch Rheuma Forschungszentrum Berlin, Berlin, Germany. Univ Saarland, D-6600 Saarbrucken, Germany. NIH, Bethesda, MD 20892 USA. Charite Berlin, Berlin, Germany. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S399 EP S399 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801070 ER PT J AU Rider, L Schiffenbauer, A Villalba, M Adams, E Joe, G Harris-Love, M James-Newton, L Hicks, J Pilkington, C Isenberg, D Lachenbruch, P Miller, F AF Rider, L Schiffenbauer, A Villalba, M Adams, E Joe, G Harris-Love, M James-Newton, L Hicks, J Pilkington, C Isenberg, D Lachenbruch, P Miller, F CA the JDM Disease Activity Coll TI Extramuscular disease activity is frequent in adult and juvenile idiopathic inflammatory myopathies (IIM) and does not correlate with other myositis activity measures. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, NIH, Bethesda, MD USA. US FDA, CDER, Rockville, MD 20857 USA. NIAID, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Inst Child Hlth, London, England. UCL, London, England. NR 0 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S612 EP S613 PG 2 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801681 ER PT J AU Rider, L Giannini, EH Lovell, D Isenberg, D Pilkington, C Cronin, M Feldman, B Finkel, R de la Torre, IG Huber, A James-Newton, L Kagen, L Lindsley, C Lundberg, I Malleson, P Oddis, C Pachman, L Passo, M Ravelli, A Reed, A Rennebohm, R Russman, B Rutkove, S Sherry, D Sivakumar, K Song, Y Targoff, I Vencovsky, J Villalba, M White, P Wortmann, R Ytterberg, S Harris-Love, M Joe, G Hicks, J Plotz, P Lachenbruch, P Miller, F AF Rider, L Giannini, EH Lovell, D Isenberg, D Pilkington, C Cronin, M Feldman, B Finkel, R de la Torre, IG Huber, A James-Newton, L Kagen, L Lindsley, C Lundberg, I Malleson, P Oddis, C Pachman, L Passo, M Ravelli, A Reed, A Rennebohm, R Russman, B Rutkove, S Sherry, D Sivakumar, K Song, Y Targoff, I Vencovsky, J Villalba, M White, P Wortmann, R Ytterberg, S Harris-Love, M Joe, G Hicks, J Plotz, P Lachenbruch, P Miller, F CA the International Myositis Outcom TI Defining clinically relevant change in core set activity measures for adult and juvenile idiopathic inflammatory mopathies (IIM). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S613 EP S613 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801682 ER PT J AU Rider, LG Schiffenbauer, AS Zito, M Lim, KL Ahmed, A Zemel, LS Rennebohm, RM Passo, MH Hicks, JE Lachenbruch, PA Heyes, MP Miller, FW AF Rider, LG Schiffenbauer, AS Zito, M Lim, KL Ahmed, A Zemel, LS Rennebohm, RM Passo, MH Hicks, JE Lachenbruch, PA Heyes, MP Miller, FW TI Neopterin and quinolinic acid are surrogate measures of disease activity in the juvenile idiopathic inflammatory myopathies. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, NIH, Bethesda, MD USA. NIMH, NIH, Bethesda, MD 20892 USA. Univ Glasgow, Glasgow Royal Infirm, Glasgow G31 2ER, Lanark, Scotland. Specialty Labs, Santa Monica, CA USA. Connecticut Childrens Med Ctr, Hartford, CT USA. Childrens Hosp, Columbus, OH 43205 USA. Childrens Hosp, Cincinnati, OH 45229 USA. NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S305 EP S305 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800799 ER PT J AU Sankar, V Kok, MR Baum, BJ Leakan, RA Pillemer, SR AF Sankar, V Kok, MR Baum, BJ Leakan, RA Pillemer, SR TI Risk factors for decline in exocrine function in Sjogren's syndrome. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S364 EP S364 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800969 ER PT J AU Segarra, M Vilardell, C Esparza, J Perales, M Serra, C Yamada, KM Cid, MC AF Segarra, M Vilardell, C Esparza, J Perales, M Serra, C Yamada, KM Cid, MC TI Signal transduction pathways involved in integrin-mediated MMP-2 and MMP-9 production by T lymphocytes. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Barcelona, Hosp Clin Barcelona, IDIBAPS, Dept Internal Med, E-08007 Barcelona, Spain. Univ Barcelona, Hosp Clin Barcelona, IDIBAPS, Dept Immunol, E-08007 Barcelona, Spain. NIDR, Craniofacial Dev & Regenerat Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S78 EP S78 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800137 ER PT J AU Segarra, M Vilardell, C Esparza, J Perales, M Serra, C Yamada, KM Cid, MC AF Segarra, M Vilardell, C Esparza, J Perales, M Serra, C Yamada, KM Cid, MC TI Signal transduction pathways involved in integrin-mediated MMP-2 and MMP-9 production by T lymphocytes SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Barcelona, IDIBAPS, Hosp Clin, Dept Internal Med, Barcelona, Spain. Univ Barcelona, IDIBAPS, Hosp Clin, Dept Immunol, Barcelona, Spain. NIDR, Craniofacioal Dev & Regenerat Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S34 EP S34 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800005 ER PT J AU Skapenko, A Lipsky, PE Kalden, JR Schulze-Koops, H AF Skapenko, A Lipsky, PE Kalden, JR Schulze-Koops, H TI Regulation of human Th1-mediated inflammation in vivo by in vitro generated Th2-effectors. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Erlangen Nurnberg, Erlangen, Germany. NIAMS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S484 EP S484 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801316 ER PT J AU Smith, JA Smith, S Whitcup, SM Suhler, E Clarke, G Thompson, D Robinson, M Barron, KS AF Smith, JA Smith, S Whitcup, SM Suhler, E Clarke, G Thompson, D Robinson, M Barron, KS TI The treatment of JRA-associated uveitis with etanercept. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NEI, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S482 EP S482 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801309 ER PT J AU Takada, K Arifayene, M Yarboro, CH Desta, Z Carrero, H Flockhart, DA Illei, GG AF Takada, K Arifayene, M Yarboro, CH Desta, Z Carrero, H Flockhart, DA Illei, GG TI Cytochrome p450 pharmacogenetics as a predictor of clinical response to pulse cyclophosphamide in lupus nephritis (LN). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S393 EP S393 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801053 ER PT J AU Takada, K Austin, HA Yarboro, CH Boumpas, DT Balow, JE Illei, GG AF Takada, K Austin, HA Yarboro, CH Boumpas, DT Balow, JE Illei, GG TI Prognostic value of achieving renal response within the first 6 months of pulse cyclophosphamide (CY) therapy: Implication for patient selection for immunoablative therapeutic trials. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Crete, Sch Med, Iraklion, Greece. NIDDK, Bethesda, MD USA. NIAMSD, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S292 EP S292 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800759 ER PT J AU Takada, K Bookbinder, S Furie, R Oddis, C Mojcik, C Bombara, M Plotz, P Kissel, J AF Takada, K Bookbinder, S Furie, R Oddis, C Mojcik, C Bombara, M Plotz, P Kissel, J TI A pilot study of eculizumab in patients with dermatomyositis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, NIH, Bethesda, MD USA. Ocala Rheumatol Res Ctr, Ocala, FL USA. N Shore Univ Hosp, Manhasset, NY USA. Univ Pittsburgh, Pittsburgh, PA USA. Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S489 EP S489 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801331 ER PT J AU Taouli, B Guermazi, A Zaim, S Peterfy, CG Mohr, A Felson, D Wildy, K Wang, BWE Lynch, JA Harris, T Fan, B Lane, NE Genant, HK Nevitt, MC AF Taouli, B Guermazi, A Zaim, S Peterfy, CG Mohr, A Felson, D Wildy, K Wang, BWE Lynch, JA Harris, T Fan, B Lane, NE Genant, HK Nevitt, MC TI Prevalence and correlates of knee cartilage defects, meniscal lesions and other abnormalities evaluated by MRI in a population sample of knees with normal x-rays: The Health ABC study. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 UCSF, San Francisco, CA USA. Synarc, San Francisco, CA USA. Boston Univ, Boston, MA 02215 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Tennessee, Memphis, TN USA. NIA, Bethesda, MD USA. RI Lynch, John/F-8209-2012 NR 0 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S148 EP S149 PG 2 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800340 ER PT J AU Velarde, MR Carrington, K Austin, J Mittleman, BB AF Velarde, MR Carrington, K Austin, J Mittleman, BB TI The NIAMS community health center: Addressing health disparities through research and patient care. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S610 EP S611 PG 2 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801675 ER PT J AU Wagner, CL Clair, EWS Han, CL Ford, J Schantz, A Maini, RN Lipsky, PE AF Wagner, CL Clair, EWS Han, CL Ford, J Schantz, A Maini, RN Lipsky, PE TI Effects of antibodies to infliximab on ACR response in patients with rheumatoid arthritis in the ATTRACT study SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Centocor Inc, ATTRACT Study Grp, Malvern, PA 19355 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Kennedy Inst, London, England. NIAMSD, Bethesda, MD 20892 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S132 EP S132 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800293 ER PT J AU Wong, JB Lipsky, PE Maini, R Patel, K van der Heijde, D AF Wong, JB Lipsky, PE Maini, R Patel, K van der Heijde, D CA ATTRACT Study Grp TI Rapid radiographic progession in rheumatoid arthritis and clinical and radiographic benefits from infliximab: Results from ATTRACT. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Natl Inst Hlth, Bethesda, MD USA. Kennedy Inst, Div Rheumatol, London W6 7DW, England. Centocor Inc, Malvern, PA USA. Univ Hosp, Maastricht, Netherlands. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S337 EP S337 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800887 ER PT J AU Berman, JJ AF Berman, JJ TI Confidentiality issues for medical data miners SO ARTIFICIAL INTELLIGENCE IN MEDICINE LA English DT Article DE data mining; confidentiality; security; encryption; HIPAA; IRB AB The first task in any medical data mining effort is ensuring patient confidentiality. In the past, most data mining efforts ensured confidentiality by the dubious policy of witholding their raw data from colleagues and the public. A cursory review of medical informatics literature in the past decade reveals that much of what we have "learned" consists of assertions derived from confidential datasets unavailable for anyone's review. Without access to the original data, it is impossible to validate or improve upon a researcher's conclusions. Without access to research data, we are asked to accept findings as an act of faith, rather than as a scientific conclusion. This special issue of Artificial Intelligence in Medicine is devoted to medical data mining. The medical data miner has an obligation to conduct valid research in a way that protects human subjects. Today, data miners have the technical tools to merge large data collections and to distribute queries over disparate databases. In order to include patient-related data in shared databases, data miners will need methods to anonymize and deidentify data. This article reviews the human subject risks associated with medical data mining. This article also describes some of the innovative computational remedies that will permit researchers to conduct research AND share their data without risk to patient or institution. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NCI, Pathol Informat Canc Diag Program, DCTD, NIH, Bethesda, MD 20892 USA. RP Berman, JJ (reprint author), NCI, Pathol Informat Canc Diag Program, DCTD, NIH, EPN Room 6028,6130 Execut Bldg, Bethesda, MD 20892 USA. NR 12 TC 36 Z9 36 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0933-3657 J9 ARTIF INTELL MED JI Artif. Intell. Med. PD SEP-OCT PY 2002 VL 26 IS 1-2 BP 25 EP 36 AR PII S0933-3657(02)00050-7 DI 10.1016/S0933-3657(02)00050-7 PG 12 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 597BJ UT WOS:000178201900002 PM 12234715 ER PT J AU Grimm, JW Shaham, Y Hope, BT AF Grimm, JW Shaham, Y Hope, BT TI Effect of cocaine and sucrose withdrawal period on extinction behavior, cue-induced reinstatement, and protein levels of the dopamine transporter and tyrosine hydroxylase in limbic and cortical areas in rats SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE cocaine withdrawal; craving; dopamine transporter; reinstatement; relapse; sucrose; tyrosine hydroxylase; rat ID MEDIAL PREFRONTAL CORTEX; MESSENGER-RNA LEVELS; NEUROCHEMICAL CHANGES; SEEKING BEHAVIOR; ANIMAL-MODEL; TIME-COURSE; BRAIN; ADDICTION; ABSTINENCE; REWARD AB Lever pressing during tests for resistance to extinction and cue-induced reinstatement of cocaine seeking in rats progressively increases over the first 2 months of withdrawal. In the present report, we investigated the generality of these findings in rats trained to self-administer sucrose, a non-drug reinforcer. We also examined whether the time-dependent changes in cocaine seeking correlate with the levels of the dopamine transporter (DAT) and tyrosine hydroxylase (TH) proteins in the amygdala, nucleus accumbens, prefrontal cortex and orbitofrontal cortex. Rats were trained to self-administer cocaine (0.5 mg/kg/i.v. infusion) or 10% sucrose (0.2 ml/infusion into a liquid drop receptacle) for 10 days (6 h/day); each reward delivery was paired with a tone+light cue. Tests for cocaine seeking were conducted following I or 15 reward-free days. On the test day, rats were initially tested for resistance to extinction during 6-7 60-min extinction sessions in the absence of the tone-light cue, until they reached the extinction criterion of less than 15 responses/60 min. Subsequently, rats were tested for cue-induced reinstatement during a 60-min session in which each lever press led to a contingent presentation of the tone-light cue. Lever pressing during the tests for reward seeking was significantly greater on day 15 than on day I following withdrawal from both cocaine and sucrose self-administration training. The levels of DAT, but not TH, were greater in the prefrontal cortex of cocaine-trained rats than in sucrose-trained rats on both days I and 15 of withdrawal. The levels of DAT and TH in other brain areas were not altered following withdrawal from cocaine or sucrose self-administration. These data suggest that the withdrawal period can modulate reward seeking of both drug and non-drug reinforcers, and that alterations in DAT and TH levels in the brain regions examined do not mediate this effect. (C) 2002 Lippincott Williams Wilkins. C1 Western Washington Univ, Dept Psychol, Bellingham, WA 98225 USA. NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD USA. RP Grimm, JW (reprint author), Western Washington Univ, Dept Psychol, 516 High St, Bellingham, WA 98225 USA. RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014 OI Hope, Bruce/0000-0001-5804-7061; FU Intramural NIH HHS [Z01 DA000434-08] NR 58 TC 68 Z9 68 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2002 VL 13 IS 5-6 BP 379 EP 388 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 608CU UT WOS:000178828200009 PM 12394414 ER PT J AU Elliot, EE AF Elliot, EE TI Cocaine sensitization in the mouse using a cumulative dosing regime SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE cocaine; context-dependent sensitization; locomotor activity; cumulative dosing; extinction; mouse ID INDUCED BEHAVIORAL SENSITIZATION; STRESS-INDUCED SENSITIZATION; INDEPENDENT SENSITIZATION; AMPHETAMINE; EXPRESSION; DOPAMINE; RATS; INDUCTION; RESPONSES; MORPHINE AB Many rodent models of cocaine sensitization use intermittent high doses of cocaine pretreatment followed by testing with a single moderate cocaine dose. The aim of the present study was to investigate the rate and extent of sensitization to the locomotor-stimulant effects of cocaine using multiple cocaine doses (5-40 mg/kg). Eight groups of male Swiss-Webster mice were pretreated with either single doses of cocaine (40 mg/kg) or saline in the home cage, or multiple doses in the test environment, for 4 days. On the fifth day they were tested for locomotor activity, following a single dose of saline and cumulative doses of cocaine (5-40 mg/kg at 10-minute intervals). All eight groups of mice developed context-dependent sensitization to the locomotor stimulant effects of cocaine. Subsequent testing, at 10-day intervals, revealed that sensitization was maximal after five test sessions of cumulative cocaine dosing, regardless of the pretreatment regime. The main determinant of the rate at which sensitization occurred was the frequency of cumulative cocaine dosing. However, both the potency and efficacy of cocaine were altered by different pretreatments associated with exposure to the locomotor activity chambers. This robust context-dependent sensitization was long lasting, and not abolished by a 5-day extinction procedure involving cumulative saline dosing in the locomotor activity chambers. In conclusion, cumulative dosing and its inherent handling, in combination with cocaine, induced marked sensitization not produced by cocaine alone. (C) 2002 Lippincott Williams Wilkins. C1 NIDA, Psychobiol Sect, IRP, Baltimore, MD USA. RP Elliot, EE (reprint author), Univ Adelaide, Dept Publ Hlth, Adelaide, SA 5005, Australia. NR 33 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2002 VL 13 IS 5-6 BP 407 EP 415 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 608CU UT WOS:000178828200012 PM 12394417 ER PT J AU Desai, RI Terry, P AF Desai, RI Terry, P TI Evidence of cross-tolerance between selective behavioural effects of nicotine and cocaine in mice SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract C1 NIDA, Psychobiol Sect, Medicat Discovery Res Branch, NIH, Baltimore, MD 21224 USA. Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2002 VL 13 IS 5-6 BP 481 EP 481 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 608CU UT WOS:000178828200032 ER PT J AU Katz, JL Desai, RI Terry, P AF Katz, JL Desai, RI Terry, P TI Comparison of the discriminative stimulus effects of SKF 38393 with those of other dopamine receptor agonists SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract C1 NIDA, Psychobiol Sect, Medicat Discovery Res Branch, NIH, Baltimore, MD 21224 USA. Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2002 VL 13 IS 5-6 BP 490 EP 491 PG 2 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 608CU UT WOS:000178828200055 ER PT J AU Shaham, Y AF Shaham, Y TI The drug withdrawal period and susceptibility to relapse to heroin and cocaine seeking SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract C1 NIDA, IRP, Behav Neurosci Branch, Baltimore, MD USA. NR 0 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2002 VL 13 IS 5-6 BP 503 EP 503 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 608CU UT WOS:000178828200082 ER PT J AU Shoaib, M Childs, E Hockemeyer, J Ferre, S Goldberg, SR AF Shoaib, M Childs, E Hockemeyer, J Ferre, S Goldberg, SR TI Potentiation of nicotine discrimination by caffeine and selective adenosine receptor antagonists SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract C1 Inst Psychiat, Sect Behav Pharmacol, London, England. Univ Bonn, D-53115 Bonn, Germany. NIDA, Preclin Pharmacol Sect, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2002 VL 13 IS 5-6 BP 503 EP 503 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 608CU UT WOS:000178828200083 ER PT J AU Goldberg, SR Munzar, P Justinova, Z Tanda, G AF Goldberg, SR Munzar, P Justinova, Z Tanda, G TI Drug-seeking behavior under a second-order schedule of thc self-administration in monkeys SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract C1 NIDA, Preclin Pharmacol Sect, NIH, Baltimore, MD 21224 USA. NIDA, Psychobiol Sect, NIH, Baltimore, MD 21224 USA. ALEXZA Mol Delivery Corp, Palo Alto, CA 94303 USA. RI Tanda, Gianluigi/B-3318-2009 OI Tanda, Gianluigi/0000-0001-9526-9878 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2002 VL 13 IS 5-6 BP 509 EP 510 PG 2 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 608CU UT WOS:000178828200098 ER PT J AU Mavromatis, BH Cheson, BD AF Mavromatis, BH Cheson, BD TI Pre- and post-treatment evaluation of non-Hodgkin's lymphoma SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE lymphoma; staging; response assessment; gallium scan; PET scan ID POSITRON-EMISSION-TOMOGRAPHY; BONE-MARROW INVOLVEMENT; HELICOBACTER-PYLORI INFECTION; MANTLE CELL LYMPHOMA; LOW-GRADE LYMPHOMA; COMPUTED-TOMOGRAPHY; MALIGNANT-LYMPHOMA; GASTRIC LYMPHOMA; FOLLOW-UP; COMBINATION CHEMOTHERAPY AB Once the diagnosis of a non-Hodgkin's lymphoma (NHL) has been established three critical steps in patient management must follow. The first is the pre-treatment evaluation and staging to identify prognostic factors (the subject of another chapter in this volume), impending problems, such as ureteral obstruction, spinal cord compression, biliary or vena caval obstruction. This assessment directs the best therapeutic approach, and also provides a baseline against which to assess response. The second step is the treatment itself. Third, conscientious follow-up after completion of therapy to monitor for disease recurrence as well as for long-term sequelae of therapy. `A careful history and physical examination are the most important components of patient evaluation. Whereas some evaluation procedures have become standard practice (e.g. chest radiographs, CT scans, gallium scan, blood chemistry and assessment of hepatic and renal function), the role of other studies is still being defined (e.g. PET scan). The increased use of systemic therapies has somewhat reduced the requirement for precise staging to determine treatment strategies, but will become more critical to identify early patients with resistant disease and those with minimal residual disease following treatment so that novel therapies can be introduced at that point. C1 NCI, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Cheson, BD (reprint author), NCI, Execut Plaza N,Rm 7026, Bethesda, MD 20892 USA. NR 64 TC 10 Z9 10 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD SEP PY 2002 VL 15 IS 3 BP 429 EP 447 DI 10.1053/beha.2002.0217 PG 19 WC Hematology SC Hematology GA 626FJ UT WOS:000179861300002 PM 12468398 ER PT J AU Holbrook, NJ Ikeyama, S AF Holbrook, NJ Ikeyama, S TI Age-related decline in cellular response to oxidative stress: links to growth factor signaling pathways with common defects SO BIOCHEMICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT Meeting on Cell Signaling Transcription and Translation as Therapeutic Targets CY JAN 30-FEB 02, 2002 CL LUXEMBOURG, GERMANY DE reactive oxygen species; aging; calorie restriction; mitogen-activated protein kinase; P13-K/Akt; proliferation; growth factor signaling ID ACTIVATED PROTEIN-KINASE; PHOSPHOLIPASE C-GAMMA; EXTENDED LIFE-SPAN; HYDROGEN-PEROXIDE; FACTOR RECEPTOR; T-CELLS; CALORIC RESTRICTION; REDUCED ASSOCIATION; REGULATED KINASES; INDUCED APOPTOSIS AB Accumulation of oxidative damage is believed to be a major contributor to the decline in physiologic function that characterizes mammalian aging, and recent studies suggest that how well you respond to acute oxidative stress is an important factor in determining longevity. Oxidant injury elicits a wide spectrum of responses ranging from proliferation to cell death. The particular outcome observed largely reflects the severity of the stress encountered and the relative degree of activation of various signal transduction pathways aimed at enhancing survival or inducing cell death. Herein we examine the relationship between pathways important in supporting cell survival in response to oxidant injury and those involved in regulating proliferation. We review evidence indicating that [Cuff. Opin. Cell Biol. 10 (1998) 248] common pathways are indeed involved in regulating these responses, and [Physiol. Rev. 82 (2002) 47] alterations in shared signaling events likely account for the age-related decline in the ability of cells to respond to both proliferative signals and oxidant stimuli. Published by Elsevier Science Inc. C1 Yale Univ, Sch Med, Dept Internal Med, Sect Geriatr, New Haven, CT 06520 USA. NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. RP Holbrook, NJ (reprint author), Yale Univ, Sch Med, Dept Internal Med, Sect Geriatr, POB 208025, New Haven, CT 06520 USA. NR 60 TC 63 Z9 66 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP PY 2002 VL 64 IS 5-6 BP 999 EP 1005 AR PII S0006-2952(02)01169-3 DI 10.1016/S0006-2952(02)01169-3 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 599XU UT WOS:000178361100033 PM 12213598 ER PT J AU Huang, KP Huang, FL AF Huang, KP Huang, FL TI Glutathionylation of proteins by glutathione disulfide S-oxide SO BIOCHEMICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT Meeting on Cell Signaling Transcription and Translation as Therapeutic Targets CY JAN 30-FEB 02, 2002 CL LUXEMBOURG, GERMANY DE glutathione disulfide S-oxide (glutathione thiosulfinate); glutathionylation; neurogranin; oxidative and nitrosative stress; S-nitrosoglutathione; signal transduction ID RAT-BRAIN NEUROGRANIN; NITRIC-OXIDE; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; SIGNAL-TRANSDUCTION; NITROSATIVE STRESS; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; NITROXYL ANION; KINASE-C; NITROSOTHIOLS AB Aqueous solution of S-nitrosoglutathione (GSNO) underwent spontaneous chemical transformation that generated several glutathione derivatives including glutathione sulfonic acid (GSO(3)H), glutathione disulfide S-oxide (GS(O)SG), glutathione disulfide S-dioxide, and glutathione disulfide. Surprisingly, GS(O)SG (also called glutathione thiosulfinate), which was not identified as a metabolite of GSNO previously, was one of the major products derived from GSNO. This compound was very reactive toward any thiol and the reaction product was a mixed disulfide. The rate of reaction of GS(O)SG with 5-mercapto-2-nitro-benzoate was nearly 20-fold faster than that of GSNO. The mechanism for the formation of GS(O)SG was believed to involve the sulfenic acid (GSOH) and thiosulfinamide (GS(O)NH2) intermediates; the former underwent self-condensation and the latter reacted with GSH to form GS(O)SG. Many reactive oxygen and nitrogen species were also capable of oxidizing GSH or GSSG to form GS(O)SG, which likely played a central role in integrating both the oxidative and nitrosative cellular responses through thionylation of thiols. Treatments of rat brain tissue slices with oxidants resulted in an enhanced thionylation of proteins with a concomitant increase in cellular level of GS(O)SG, suggesting that this compound might play a second messenger role for stimuli that produced a variety of oxidative species. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NICHHD, Endocrinol & Reprod Res Branch, Metab Regulat Sect, NIH, Bethesda, MD 20892 USA. RP Huang, KP (reprint author), NICHHD, Endocrinol & Reprod Res Branch, Metab Regulat Sect, NIH, Bldg 49,Room 6A36,49 Convent Dr MSC 4510, Bethesda, MD 20892 USA. NR 61 TC 74 Z9 75 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP PY 2002 VL 64 IS 5-6 BP 1049 EP 1056 AR PII S0006-2952(02)01175-9 DI 10.1016/S0006-2952(02)01175-9 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 599XU UT WOS:000178361100039 PM 12213604 ER PT J AU Schuler, B Pannell, LK AF Schuler, B Pannell, LK TI Specific Labeling of polypeptides at amino-terminal cysteine residues using Cy5-benzyl thioester SO BIOCONJUGATE CHEMISTRY LA English DT Article ID RESONANCE ENERGY-TRANSFER; NATIVE CHEMICAL LIGATION; FLUORESCENCE; PROTEINS; ESTERS; IGG AB Even for moderately sized proteins, the multiple occurrence of cysteine and lysine residues often prevents the specific labeling of polypeptides with a single probe. To increase specificity, a method was developed to convert the commonly available succinimidyl esters of fluorescent dyes into benzyl thioesters via trimethyl aluminum-activated benzyl mercaptan. The thioester can then be reacted very specifically with polypeptides containing an N-terminal cysteine residue, forming a stable amide bond, analogous to the native chemical ligation of peptide fragments. Both reaction steps are easy to perform and proceed to high yields. The practicability of the approach was demonstrated using the popular cyanine dye Cy5 and a soluble peptide, and it is expected to be applicable to a wide range of succinimidyl esters and both chemically and recombinantly synthesized proteins. The method should dramatically facilitate the preparation of proteins for experiments requiring exact positioning of labels, for instance, Forster resonance energy transfer studies. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Struct Mass Spectrometry Facil, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Schuler, B (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. RI Schuler, Benjamin/E-7342-2011 OI Schuler, Benjamin/0000-0002-5970-4251 NR 19 TC 31 Z9 34 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP-OCT PY 2002 VL 13 IS 5 BP 1039 EP 1043 DI 10.1021/bc025509t PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 595NF UT WOS:000178115100016 PM 12236786 ER PT J AU Wilbur, DS Chyan, MK Hamlin, DK Kegley, BB Nilsson, R Sandberg, BEB Brechbiel, M AF Wilbur, DS Chyan, MK Hamlin, DK Kegley, BB Nilsson, R Sandberg, BEB Brechbiel, M TI Trifunctional conjugation reagents. Reagents that contain a biotin and a radiometal chelation moiety for application to extracorporeal affinity adsorption of radiolabeled antibodies SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODY; WHOLE-BLOOD; CARCINOMA XENOGRAFTS; ANTIGEN EXPRESSION; DTPA LIGAND; AVIDIN; IMMUNOADSORPTION; STREPTAVIDIN; STABILITY; SERUM AB A method of removing radiolabeled monoclonal antibodies (mAbs) from blood using a device external to the body, termed extracorporeal affinity-adsorption (EAA), is being evaluated as a means of decreasing irradiation of noncancerous tissues in therapy protocols. The EAA device uses an avidin column to capture biotinylated-radiolabeled mAbs from circulated blood. In this investigation, three trifunctional reagents have been developed to minimize the potential deleterious effect on antigen binding brought about by the combination of radiolabeling and biotinylation of mAbs required in the EAA approach. The studies focused on radiolabeling with In-111 and Y-90, so the chelates CHX-A"-DTPA and DOTA, which form stable attachments to these radionuclides, were incorporated in the trifunctional reagents. The first trifunctional reagent prepared did not incorporate a group to block the biotin cleaving enzyme biotinidase, but the two subsequent reagents coupled aspartic acid to the biotin carboxylate for that purpose. All three reagents used 4,7,10-trioxa-1,13-tridecanediamine as water-soluble spacers between an aminoisophthalate core and the biotin or chelation group. The mAb conjugates were radioiodinated to evaluate cell binding as a function of substitution. Radioiodination was used so that a direct comparison with unmodified mAb could be made. Evaluation of the number of conjugates per antibody versus cell binding immunoreactivities indicated that minimizing the number of conjugates was best. Interestingly, a decrease of radioiodination yield as a function of the number of isothiocyanate containing conjugates per mAb was noted. The decreased yields were presumably due to the presence of thiourea functionality formed in the conjugation reaction. Radiolabeling with In-111 and Y-90 was facile at room temperature for conjugates containing the CHX-A", but elevated temperature (e.g., 45degreesC) was required to obtain good yields with the DOTA chelate. Stability of Y-90 labeled mAb in serum, and when challenged with 10 mM EDTA, was high. However, challenging the Y-90 labeled mAb with 10 mM DTPA demonstrated high stability for the DOTA containing conjugate, but low stability for the CHX-A" containing conjugate. Thus, the choice between these two chelating moieties might be made on requirements for facile and gentle labeling versus very high in vivo stability. Application of the trifunctional biotinylation reagents to the blood clearance of labeled antibodies in EAA is under investigation. The new reagents may also be useful for other applications. C1 Univ Washington, Dept Radiat Oncol, Seattle, WA 98103 USA. Mitra Med Technol, Lund, Sweden. NCI, Bethesda, MD 20892 USA. RP Wilbur, DS (reprint author), Univ Washington, Dept Radiat Oncol, 2121 N 35th St, Seattle, WA 98103 USA. RI Nilsson, Rune/C-1089-2013 OI Nilsson, Rune/0000-0001-8903-7384 NR 59 TC 18 Z9 19 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP-OCT PY 2002 VL 13 IS 5 BP 1079 EP 1092 DI 10.1021/bc025535r PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 595NF UT WOS:000178115100020 PM 12236790 ER PT J AU Chen, WZ Ravi, RG Kertesy, SB Dubyak, GR Jacobson, KA AF Chen, WZ Ravi, RG Kertesy, SB Dubyak, GR Jacobson, KA TI Functionalized congeners of tyrosine-based P2X(7) receptor antagonists: Probing multiple sites for linking and dimerization SO BIOCONJUGATE CHEMISTRY LA English DT Article ID ADENOSINE RECEPTORS; NUCLEOTIDE RECEPTOR; MOLECULAR PROBES; ACTIVATION; CELLS; IDENTIFICATION; NOMENCLATURE; EXPRESSION; SUBUNITS; CLONING AB Chemically funtionalized analogues of antagonists of the P2X(7) receptor, an ATP-gated cation channel, were synthesized as tools for biophysical studies of the receptor. These functionalized congeners were intended for use in chemical conjugation with retention of biological potency. The antagonists were L-tyrosine derivatives, related to [N-benzyloxycarbonyl-O-(4-arylsulfonyl)-L-tyrosyl]benzoylpiperazine (such as MRS2409, 2). The analogues were demonstrated to be antagonists in an assay of human P2X7 receptor function, consisting of inhibition of ATP-induced K+ efflux in HEK293 cells expressing the recombinant receptor. The analogues were of the general structure R-1-Tyr(OR2)-piperazinyl-R-3, in which three positions (R-1-R-3) were systematically varied in structure through introduction of chemically reactive groups. Each of the three positions was designed to incorporate a 3- or 4-nitrophenyl group. The nitro groups were reduced using NaBH4-copper(II) acetylacetonate to amines, which were either converted to the isothiocyanate groups, as potential affinity labels for the receptor, or acylated, as models for conjugation. An alternate route to N-alpha-3-aminobenzyloxycarbonyl functionalization was devised. The various positions of functionalization were compared for effects on biological potency, and the R-2 and R-3 positions were found to be most amenable to derivatization with retention of high potency. Four dimeric permutations of the antagonists were synthesized by coupling each of the isothiocyanate derivatives to either the precursor amine or to other amine congeners, Only dimers linked at the R-2-position were potent antagonists. In concentration-response studies, two derivatives, a 3-nitrobenzyloxycarbonyl derivative 18 and a 4-nitrotoluenesulfonate 26b, displayed IC50 values of roughly 100 nM as antagonists of P2X(7) receptor-mediated K+ flux. C1 NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [ZIA DK031127-03]; NIGMS NIH HHS [GM36387] NR 35 TC 14 Z9 14 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP-OCT PY 2002 VL 13 IS 5 BP 1100 EP 1111 DI 10.1021/bc020025i PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 595NF UT WOS:000178115100022 PM 12236792 ER PT J AU Kalinin, AE Kajava, AV Steinert, PM AF Kalinin, AE Kajava, AV Steinert, PM TI Epithelial barrier function: assembly and structural features of the cornified cell envelope SO BIOESSAYS LA English DT Review ID PROLINE-RICH PROTEINS; EPIDERMAL PERMEABILITY BARRIER; TRANSGLUTAMINASE CROSS-LINKING; STRATUM-CORNEUM; KERATINOCYTE TRANSGLUTAMINASE; TISSUE TRANSGLUTAMINASE; OMEGA-HYDROXYCERAMIDES; INCREASED EXPRESSION; INHERITED DISORDERS; LAMELLAR ICHTHYOSIS AB Terminally differentiating stratified squamous epithelial cells assemble a specialized protective barrier structure on their periphery termed the cornified cell envelope (CE). It is composed of numerous structural proteins that become cross-linked by several transglutaminase enzymes into an insoluble macromolecular assembly. Several proteins are involved in the initial stages of CE assembly, but only certain proteins from a choice of more than 20 different proteins are used in the final stages of CE reinforcement, apparently to meet tissue-specific requirements. In addition, a variable selection of proteins may be upregulated in response to genetic defects of one of the CE proteins or tissue injury, in an effort to maintain an effective barrier. Additionally, in the epidermis and hair fiber cuticle, a layer of lipids is covalently attached to the proteins, which provides essential water barrier properties. Here we describe our current understanding of CE structure, a possible mechanism of its assembly, and various disorders that cause a defective barrier. Published 2002 Wiley Periodicals, Inc.(dagger) C1 NIAMSD, Lab Skin Biol, NIH, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Ctr Mol Modeling, Bethesda, MD 20892 USA. RP Steinert, PM (reprint author), NIAMSD, Lab Skin Biol, NIH, 50 South Dr,Room 1523, Bethesda, MD 20892 USA. RI Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 NR 74 TC 266 Z9 273 U1 1 U2 17 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD SEP PY 2002 VL 24 IS 9 BP 789 EP 800 DI 10.1002/bies.10144 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 589FB UT WOS:000177747100005 PM 12210515 ER PT J AU Chen, YD Kamat, V Dougherty, ER Bittner, ML Meltzer, PS Trent, JM AF Chen, YD Kamat, V Dougherty, ER Bittner, ML Meltzer, PS Trent, JM TI Ratio statistics of gene expression levels and applications to microarray data analysis SO BIOINFORMATICS LA English DT Article ID DNA MICROARRAY; INFERENCE; PATTERNS AB Motivation: Expression-based analysis for large families of genes has recently become possible owing to the development of cDNA microarrays, which allow simultaneous measurement of transcript levels for thousands of genes. For each spot on a microarray, signals in two channels must be extracted from their backgrounds. This requires algorithms to extract signals arising from tagged mRNA hybridized to arrayed cDNA locations and algorithms to determine the significance of signal ratios. Results: This paper focuses on estimation of signal ratios from the two channels, and the significance of those ratios. The key issue is the determination of whether a ratio is significantly high or low in order to conclude whether the gene is upregulated or downregulated. The paper builds on an earlier study that involved a hypothesis test based on a ratio statistic under the supposition that the measured fluorescent intensities subsequent to image processing can be assumed to reflect the signal intensities. Here, a refined hypothesis test is considered in which the measured intensities forming the ratio are assumed to be combinations of signal and background. The new method involves a signal-to-noise ratio, and for a high signal-to-noise ratio the new test reduces (with close approximation) to the original test. The effect of low signal-to-noise ratio on the ratio statistics constitutes the main theme of the paper. Finally, and in this vein, a quality metric is formulated for spots. This measure can be used to decide whether or not a spot ratio should be deleted, or to adjust various measurements to reflect confidence in the quality of the measurement. C1 Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Texas A&M Univ, Dept Elect Engn, 3128 TAMU, College Stn, TX 77843 USA. EM e-dougherty@tamu.edu NR 16 TC 132 Z9 135 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD SEP PY 2002 VL 18 IS 9 BP 1207 EP 1215 DI 10.1093/bioinformatics/18.9.1207 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 593PM UT WOS:000178001400007 PM 12217912 ER PT J AU Park, Y Spouge, JL AF Park, Y Spouge, JL TI The correlation error and finite-size correction in an ungapped sequence alignment SO BIOINFORMATICS LA English DT Article ID STATISTICAL DISTRIBUTION; LOCAL SEQUENCE; PARTIAL-SUMS; PSI-BLAST; VALUES; SCORE; SIMILARITIES; DATABASES AB Motivation: The BLAST program for comparing two sequences assumes independent sequences in its random model. The resulting random alignment matrices have correlations across their diagonals. Analytic formulas for the BLAST p-value essentially neglect these correlations and are equivalent to a random model with independent diagonals. Progress on the independent diagonals model has been surprisingly rapid, but the practical magnitude of the correlations it neglects remains unknown. In addition, BLAST uses a finite-size correction that is particularly important when either of the sequences being compared is short. Several formulas for the finite-size correction have now been given, but the corresponding errors in the BLAST p-values have not been quantified. As the lengths of compared sequences tend to infinity, it is also theoretically unknown whether the neglected correlations vanish faster than the finite-size correction. Results: Because we required certain analytic formulas, our study restricted its computer experiments to ungapped sequence alignment. We expect some of our conclusions to extend qualitatively to gapped sequence alignment, however. With this caveat, the finite-size correction appeared to vanish faster than the neglected correlations. Although the finite-size correction underestimated the BLAST p-value, it improved the approximation substantially for all but very short sequences. In practice, the Altschul-Gish finite-size correction was superior to Spouge's. The independent diagonals model was always within a factor of 2 of the true BLAST p-value, although fitting p-value parameters from it probably is unwise. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Spouge, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 28 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD SEP PY 2002 VL 18 IS 9 BP 1236 EP 1242 DI 10.1093/bioinformatics/18.9.1236 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 593PM UT WOS:000178001400010 PM 12217915 ER PT J AU Gold, PW Drevets, WC Charney, DS AF Gold, PW Drevets, WC Charney, DS TI New insights into the role of cortisol and the glucocorticoid receptor in severe depression SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID CORTICOTROPIN-RELEASING HORMONE; MEDIAL PREFRONTAL CORTEX; RECURRENT MAJOR DEPRESSION; MESSENGER-RNA LEVELS; PARAVENTRICULAR NUCLEUS; MOOD DISORDERS; STRESS; CORTICOSTERONE; AMYGDALA; ANXIETY C1 NIMH, NIH, Clin Neuroendocrinol Branch, Intramural Res Program, Bethesda, MD 20852 USA. NIMH, NIH, Mood & Anxiety Disorders Program, Mol Imaging Branch TIA, Bethesda, MD 20852 USA. RP Gold, PW (reprint author), NIMH, NIH, Clin Neuroendocrinol Branch, Intramural Res Program, Bethesda, MD 20852 USA. NR 44 TC 130 Z9 135 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2002 VL 52 IS 5 BP 381 EP 385 AR PII S0006-3223(02)01480-4 DI 10.1016/S0006-3223(02)01480-4 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 593HN UT WOS:000177985100001 PM 12242053 ER PT J AU Bowley, MP Drevets, WC Ongur, D Price, JL AF Bowley, MP Drevets, WC Ongur, D Price, JL TI Low glial numbers in the amygdala in major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE major depressive disorder; bipolar disorder; amygdala; entorhinal cortex; glia; lithium; valproate ID PREFRONTAL CORTICAL PROJECTIONS; EMOTIONAL FACIAL EXPRESSIONS; BIPOLAR DISORDER; GLUTAMATE UPTAKE; MACAQUE MONKEYS; MOOD DISORDERS; STEREOLOGICAL METHODS; CORTEX; SCHIZOPHRENIA; BRAIN AB Background: Functional imaging studies implicate the prefrontal cortex and amygdala in major depressive disorder and bipolar disorder, and glial decreases have been reported in the prefrontal cortex. Here, glia and neurons were counted in the amygdala and entorhinal cortex in major depressive disorder, bipolar disorder, and control cases. Methods: Tissue blocks from major depressive disorder (7), bipolar disorder (10), and control (12) cases, equally divided between right and left, were cut into 50 mum sections and stained with the Nissl method. One major depressive disorder and all but two bipolar disorder cases had been treated with lithium or valproate. Neurons and glia were counted using stereological methods. Results: Glial density and the glia/neuron ratio were substantially reduced in the amygdala in major depressive disorder cases. The reduction was mainly accounted for by counts in the left hemisphere. No change was found in neurons. Average glia measures were not reduced in bipolar disorder cases; however, bipolar disorder cases not treated with lithium or valproate had significant glial reduction. Similar but smaller changes were found in the entorhinal cortex. Conclusions: Glia are reduced in the amygdala in major depressive disorder, especially on the left side. The results suggest that lithium and valproate may moderate the glial reduction. C1 Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Price, JL (reprint author), Washington Univ, Sch Med, Dept Anat & Neurobiol, 660 S Euclid Ave,Campus Box 8108, St Louis, MO 63110 USA. FU NIDCD NIH HHS [DC 00093]; NIMH NIH HHS [MH 01713] NR 64 TC 276 Z9 294 U1 5 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2002 VL 52 IS 5 BP 404 EP 412 AR PII S0006-3223(02)01404-X DI 10.1016/S0006-3223(02)01404-X PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 593HN UT WOS:000177985100004 PM 12242056 ER PT J AU Pompeia, C Freitas, JJS Kim, JS Zyngier, SB Curi, R AF Pompeia, C Freitas, JJS Kim, JS Zyngier, SB Curi, R TI Arachidonic acid cytotoxicity in leukocytes: implications of oxidative stress and eicosanoid synthesis SO BIOLOGY OF THE CELL LA English DT Article DE arachidonic acid; leukocytes; oxidative stress; apoptosis; necrosis; eicosanoids ID POLYUNSATURATED FATTY-ACIDS; PROTEIN-KINASE-C; LIPID BODIES; HL-60 CELLS; APOPTOSIS; MACROPHAGES; INDUCTION; N-3; DIFFERENTIATION; PROLIFERATION AB Arachidonic acid (AA)-induced cytotoxicity was evaluated in leukocytes: the human leukemia cell lines HL-60, Jurkat and Raji and in rat lymphocytes. Such cytotoxicity was dose- and time-dependent. At concentrations below 5 RM, AA was not toxic; at 10-400 muM, AA induced apoptosis and at concentrations beyond 400 muM, necrosis. The minimum exposure time to trigger cell death was of around I h, but the effect was increased by longer exposure times until 6-24 h. Apoptosis was morphologically characterized by a decrease in cell and nuclear volume, chromatin condensation and DNA fragmentation and the presence of lipid bodies, without changes in organelle integrity. Biochemically, AA-induced apoptosis was associated with internucleosomal fragmentation and caspase activation, evaluated by PARP cleavage and the use of a caspase inhibitor. Necrosis was characterized by increased cell volume, presence of loose chromatin, appearance of vacuoles, loss of membrane integrity and of the definition of organelles. The apoptotic effect of AA was studied as to oxidative-reductive imbalance and the participation of eicosanoids. Apoptotic AA treatment was accompanied by an increase in the quantity of thiobarbituric acid reactive substances (TBARS), low-level chemiluminescence and in the glutathione disulfide/reduced glutathione ratio, indicating oxidative stress. The addition of tocopherol, ascorbate, prostaglandin E, and lipoxygenase inhibitors delayed cell death, whereas the inhibition of cyclooxygenase promoted AA-induced cell death. Cell treatment with AA was accompanied by increased cellular production of LTB4. AA, therefore, is cytotoxic at physiological and supraphysiological concentrations, causing apoptosis and necrosis. Cell treatment with apoptotic concentrations of AA involves oxidative stress and changes in eicosanoid biosynthesis. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 NIDCD, NIH, Bethesda, MD 20892 USA. Univ Para State, Dept Physiol & Morphol Sci, Ctr Biol Sci, Belem, Para, Brazil. Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci 1, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Dept Physiol & Biophys, BR-05508 Sao Paulo, Brazil. RP Pompeia, C (reprint author), NIDCD, NIH, Room 4249,Bldg 50,50 South Dr, Bethesda, MD 20892 USA. RI Curi , Rui/C-9351-2012 NR 46 TC 54 Z9 56 U1 1 U2 4 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0248-4900 J9 BIOL CELL JI Biol. Cell PD SEP PY 2002 VL 94 IS 4-5 BP 251 EP 265 AR PII S0248-4900(02)01200-5 DI 10.1016/S0248-4900(02)01200-5 PG 15 WC Cell Biology SC Cell Biology GA 620VE UT WOS:000179552500005 PM 12489694 ER PT J AU Zhai, SP Sausville, E Figg, WD AF Zhai, SP Sausville, E Figg, WD TI A high-performance liquid chromatography method using ultraviolet detection for the quantitation of flavopiridol from human plasma SO BIOMEDICAL CHROMATOGRAPHY LA English DT Article ID DEPENDENT KINASE INHIBITOR AB Flavopiridol is an inhibitor of cyclin-dependent kinase, a key regulator of cell cycle, and is currently under clinical trials. We developed and validated an HPLC assay method for the quantitation of flavopiridol in human plasma samples. The sample preparation consisted of protein precipitation with acetonitrile. Separation was accomplished on a C-18 column and a C-18 precolumn insert utilizing a gradient profile consisting of ammonium acetate and methanol. Ultraviolet detection was set at 268 nm for flavopiridol and 323 nm for umbelliferone, the internal standard. The method was validated over flavopiridol concentration range of 0.025-3.0 mug/mL using 250 VL of plasma. The assay was linear over this concentration range with a coefficient of variation less than 10% for inter- and intra-assay. The retention times were around 6.2 min for umbelliferone and 9.8 min for flavopiridol. The recoveries of flavopiridol and umbelliferone were 88.6 +/- 1.0% and 97.1 +/- 3.7%, respectively. This method is suitable for quantifying flavopiridol in plasma samples and further characterizing the clinical pharmacology of this compound. Copyright (C) 2002 John Wiley Sons, Ltd. C1 NCI, Clin Pharmacol Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Sect, Ctr Canc Res, NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 6 TC 7 Z9 7 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0269-3879 J9 BIOMED CHROMATOGR JI Biomed. Chromatogr. PD SEP PY 2002 VL 16 IS 6 BP 379 EP 382 DI 10.1002/bmc.166 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 595YC UT WOS:000178135000003 PM 12228893 ER PT J AU Shih, JH Chatterjee, N AF Shih, JH Chatterjee, N TI Analysis of survival data from case-control family studies SO BIOMETRICS LA English DT Article DE age of onset; case-control family studies; copula models; correlated failure times; semiparametric models ID BREAST-CANCER RISK; LIFE-TABLES; ASSOCIATION; MODELS; DISTRIBUTIONS; ASHKENAZI; HISTORY; BRCA1; AGE AB In case-control family studies with survival endpoint; age of onset of diseases can be used to assess the familial aggregation of the disease and the relationship between the disease and genetic or environmental risk factors. Because of the retrospective nature of the case-control study, methods for analyzing prospectively collected correlated failure time data do not apply directly. In this article; we propose a semiparametric quasi-partial-likelihood approach to simultaneously estimate the effect of covariates on the age of onset and the association of ages of onset among family members that does not require specification of the baseline marginal distribution. We conducted a simulation study to evaluate the performance of the proposed approach and compare it with the existing semiparametric ones. Simulation results demonstrate that the proposed approach has better performance in terms of consistency and efficiency. We illustrate the methodology using a subset of data from the Washington Ashkenazi Study. C1 NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Shih, JH (reprint author), NCI, Div Canc Treatment & Diag, 6130 Execut Blvd, Bethesda, MD 20892 USA. NR 21 TC 20 Z9 20 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2002 VL 58 IS 3 BP 502 EP 509 DI 10.1111/j.0006-341X.2002.00502.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 680KF UT WOS:000182975800003 PM 12229984 ER PT J AU Albert, PS McShane, LM Korn, EL AF Albert, PS McShane, LM Korn, EL TI Design of a binary biomarker study from the results of a pilot study SO BIOMETRICS LA English DT Article DE binary data; biomarkers; correlated data; pilot studies; reproducibility studies; study design; variance components ID LINEAR MIXED MODELS AB Biomarkers are increasingly used in clinical and epidemiologic studies. Prior to these studies, small pilot studies are often conducted to assess the reproducibility of the biomarker. This article; discusses how the results of a pilot study can be used to design subsequent studies when the biomarker is a binary assessment. We consider situations in which the pilot study has two factors (e.g., laboratory and individual) that are either crossed or nested. We discuss how binary random-effects models can be used for estimating the sources of variation and how parameter estimates from these models can be used to appropriately design future studies. We also show that fitting a linear variance components model that ignores the binary nature of the data is a simple alternative method that results in nearly unbiased and moderately efficient estimators of important design parameters. We illustrate the methodology with data from a study assessing the reproducibility of p53 immunohistochemistry in bladder tumors. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), NCI, Biometr Res Branch, Execut Plaza N,Room 8136, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2002 VL 58 IS 3 BP 576 EP 585 DI 10.1111/j.0006-341X.2002.00576.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 680KF UT WOS:000182975800011 PM 12229992 ER PT J AU Albert, PS Follmann, DA Wang, SHA Suh, EB AF Albert, PS Follmann, DA Wang, SHA Suh, EB TI A latent autoregressive model for longitudinal binary data subject to informative missingness SO BIOMETRICS LA English DT Article DE informative missingness; longitudinal data; nonignorable missing data; repeated binary data ID EM ALGORITHM; LINEAR-MODEL; DROPOUT AB Longitudinal clinical trials often collect long sequences of binary data. Our application is a recent clinical trial in opiate addicts that examined the effect of a new treatment on repeated binary urine tests to assess opiate use over an extended follow-up. The dataset had two sources of missingness: dropout and intermittent missing observations. The primary endpoint of the study was comparing the marginal probability of a positive urine test over follow-up across treatment arms. We present a latent autoregressive model for longitudinal binary data subject to informative missingness. In this model, a Gaussian autoregressive process is shared between the binary response and missing-data processes, thereby inducing informative missingness. Our approach extends the work of others who have developed models that link the various processes through a shared random effect but do not allow for autocorrelation. We discuss parameter estimation using Monte Carlo EM and demonstrate through simulations that incorporating within-subject autocorrelation through a latent autoregressive process can be very important when longitudinal binary data is subject to informative missingness. We illustrate our new methodology using the opiate clinical trial data. C1 NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NR 20 TC 26 Z9 26 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2002 VL 58 IS 3 BP 631 EP 642 DI 10.1111/j.0006-341X.2002.00631.x PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 680KF UT WOS:000182975800017 PM 12229998 ER PT J AU Clegg, LX Gail, MH Feuer, EJ AF Clegg, LX Gail, MH Feuer, EJ TI Estimating the variance of disease-prevalence estimates from population-based registries SO BIOMETRICS LA English DT Article DE approximation; cancer registry; censoring; Kaplan-Meier estimator; Poisson distribution; prevalence estimation; variance and confidence interval for prevalence AB We propose a new Poisson method to estimate the variance for prevalence estimates obtained by the counting method described by Gail et al. (1999, Biometrics 55, 1137-1144) and to construct a confidence interval for the prevalence. We evaluate both the Poisson procedure and the procedure based on the bootstrap proposed by Gail et al. in simulated samples generated by resampling real data. These studies show that both variance estimators usually perform well and yield coverages of confidence intervals at nominal levels. When the number of disease survivors is very small; however, confidence intervals based on the Poisson method have supranominal coverage, whereas those based on the procedure of Gail et al. tend to have below-nominal coverage. For these reasons, we recommend the Poisson method, which also reduces the computational burden considerably. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Clegg, LX (reprint author), NCI, NIH, 6116 Execut Blvd,MSC 8316, Bethesda, MD 20892 USA. NR 6 TC 9 Z9 9 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2002 VL 58 IS 3 BP 684 EP 688 DI 10.1111/j.0006-341X.2002.00684.x PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 680KF UT WOS:000182975800024 PM 12230005 ER PT J AU Hall, WJ Liu, AY AF Hall, WJ Liu, AY TI Sequential tests and estimators after overrunning based on maximum-likelihood ordering SO BIOMETRIKA LA English DT Article DE Brownian motion; clinical trial; delayed observations; lagged data AB Often in sequential trials some additional data become available after a stopping boundary has been reached. A method for incorporating such information from overrunning is developed, based on a maximum-likelihood ordering of the sample space after overrunning. This yields a p-value for the primary test and a median-unbiased estimator and confidence intervals for the parameter under test. The context is that of observing a Brownian motion with drift, with either linear stopping boundaries in continuous time or discrete-time group-sequential boundaries. The methods apply to many clinical trials and are exemplified with data from a survival-analysis-based sequential clinical trial. C1 Univ Rochester, Med Ctr, Dept Biostat, Rochester, NY 14642 USA. NICHHD, Biometry & Math Stat Branch, Bethesda, MD 20892 USA. RP Hall, WJ (reprint author), Univ Rochester, Med Ctr, Dept Biostat, Rochester, NY 14642 USA. OI Liu, Aiyi/0000-0002-6618-5082 NR 8 TC 8 Z9 8 U1 1 U2 5 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON WC1E 6BT, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD SEP PY 2002 VL 89 IS 3 BP 699 EP 707 DI 10.1093/biomet/89.3.699 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 596EU UT WOS:000178151800016 ER PT J AU Matveev, V Sherman, A Zucker, RS AF Matveev, V Sherman, A Zucker, RS TI New and corrected simulations of synaptic facilitation SO BIOPHYSICAL JOURNAL LA English DT Article ID CALCIUM; CA2+; BINDING; BUFFERS C1 NIDDKD, Math Res Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Dept Cell & Mol Biol, Neurobiol Div, Berkeley, CA 94720 USA. RP Matveev, V (reprint author), 9190 Rockville Pike,Suite 350, Bethesda, MD 20892 USA. RI Zucker, Robert/J-9995-2012 FU NINDS NIH HHS [NS15114] NR 15 TC 45 Z9 46 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2002 VL 83 IS 3 BP 1368 EP 1373 PG 6 WC Biophysics SC Biophysics GA 589RQ UT WOS:000177774500012 PM 12202362 ER PT J AU Kumar, S Nussinov, R AF Kumar, S Nussinov, R TI Relationship between ion pair geometries and electrostatic strengths in proteins SO BIOPHYSICAL JOURNAL LA English DT Article ID MARITIMA GLUTAMATE-DEHYDROGENASE; IMMUNOGLOBULIN-BINDING DOMAIN; HIV-INACTIVATING PROTEIN; SALT BRIDGES; HYPERTHERMOPHILIC PROTEINS; DIELECTRIC-CONSTANTS; ENGINEERING ACTIVITY; CRYSTAL-STRUCTURE; LAMBDA-REPRESSOR; CYTOCHROME-C AB The electrostatic free energy contribution of an ion pair in a protein depends on two factors, geometrical orientation of the side-chain charged groups with respect to each other and the structural context of the ion pair in the protein. Conformers in NMR ensembles enable studies of the relationship between geometry and electrostatic strengths of ion pairs, because the protein structural contexts are highly similar across different conformers. We have studied this relationship using a dataset of 22 unique ion pairs in 14 NMR conformer ensembles for 11 nonhomologous proteins. In different NMR conformers, the ion pairs are classified as salt bridges, nitrogen-oxygen (N-O) bridges and longer-range ion pairs on the basis of geometrical criteria. In salt bridges, centroids of the side-chain charged groups and at least a pair of side-chain nitrogen and oxygen atoms of the ion-pairing residues are within a 4 Angstrom distance. In N-O bridges, at least a pair of the side-chain nitrogen and oxygen atoms of the ion-pairing residues are within 4 Angstrom distance, but the distance between the side-chain charged group centroids is greater than 4 Angstrom. In the longer-range ion pairs, the side-chain charged group centroids as well as the side-chain nitrogen and oxygen atoms are more than 4 Angstrom apart. Continuum electrostatic calculations indicate that most of the ion pairs have stabilizing electrostatic contributions when their side-chain charged group centroids are within 5 Angstrom distance. Hence, most (similar to92%) of the salt bridges and a majority (68%) of the N-O bridges are stabilizing. Most (similar to89%) of the destabilizing ion pairs are the longer-range ion pairs. In the NMR conformer ensembles, the electrostatic interaction between side-chain charged groups of the ion-pairing residues is the strongest for salt bridges, considerably weaker for N-O bridges, and the weakest for longer-range ion pairs. These results suggest empirical rules for stabilizing electrostatic interactions in proteins. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Kumar, S (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Lab Expt & Computat Biol, Bldg 469,Rm 151, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 64 TC 117 Z9 117 U1 1 U2 16 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2002 VL 83 IS 3 BP 1595 EP 1612 PG 18 WC Biophysics SC Biophysics GA 589RQ UT WOS:000177774500034 PM 12202384 ER PT J AU Kim, MK Jernigan, RL Chirikjian, GS AF Kim, MK Jernigan, RL Chirikjian, GS TI Efficient generation of feasible pathways for protein conformational transitions SO BIOPHYSICAL JOURNAL LA English DT Article ID NORMAL-MODES; REACTION PATHS; DYNAMICS; MOTIONS; FLUCTUATIONS; MOLECULES; SYSTEMS; NMR AB We develop a computationally efficient method to simulate the transition of a protein between two conformations. Our method is based on a coarse-grained elastic network model in which distances between spatially proximal amino acids are interpolated between the values specified by the two end conformations. The computational speed of this method depends strongly on the choice of cutoff distance used to define interactions as measured by the density of entries of the constant linking/contact matrix. To circumvent this problem we introduce the concept of using a cutoff based on a maximum number of nearest neighbors. This generates linking matrices that are both sparse and uniform, hence allowing for efficient computations that are independent of the arbitrariness of cutoff distance choices. Simulation results demonstrate that the method developed here reliably generates feasible intermediate conformations, because our method observes steric constraints and produces monotonic changes in virtual bond and torsion angles. Applications are readily made to large proteins, and we demonstrate our method on lactate dehydrogenase, citrate synthase, and lactoferrin. We also illustrate how this framework can be used to complement experimental techniques that partially observe protein motions. C1 Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21218 USA. NCI, Mol Struct Sect, Lab Expt & Computat Biol, CCR,NIH, Bethesda, MD 20892 USA. RP Chirikjian, GS (reprint author), Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21218 USA. RI Chirikjian, Gregory/A-3314-2010; Jernigan, Robert/A-5421-2012; kim, moon/H-2647-2012 NR 30 TC 108 Z9 109 U1 2 U2 8 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2002 VL 83 IS 3 BP 1620 EP 1630 PG 11 WC Biophysics SC Biophysics GA 589RQ UT WOS:000177774500036 PM 12202386 ER PT J AU Hu, P Zelen, M AF Hu, P Zelen, M TI Experimental design issues for the early detection of disease: novel designs SO BIOSTATISTICS LA English DT Article ID CANCER-SCREENING PROGRAMS; BREAST-CANCER; DEATH RATES; FOLLOW-UP; MORTALITY; MAMMOGRAPHY; TRIAL AB This paper investigates two experimental designs which have been used to evaluate the benefit of the early detection of breast cancer. They have some advantages over a classical design (the screening program versus usual medical care) in that subjects in a control group may benefit by participating in the study. We refer to the two experimental designs as the up-front (UFD) and close-out (COD) designs. The UFD consists of offering an initial exam to all participants. Then they can be randomized to a usual care group or a screening group receiving one or more special examinations. If the outcome of the initial examination is included in the analysis, then the study can answer the question of the benefit of an additional screening program after an initial examination. If the analysis excludes all the cases diagnosed at the initial examination, then the analysis evaluates the benefit of a screening program after elimination of the prevalent cases. These prevalent cases are most likely to be affected by length bias sampling and consequently will tend to have less aggressive disease and live longer. As a result, the UFD can answer two scientific questions. The COD consists of randomizing subjects to a usual care group and a screened group. However, the usual care group receives an examination which coincides at the time of the last exam in the study group. In this paper the power of these two designs have been evaluated. In both cases the power is severely reduced compared to the usual control group receiving no special exams. The power is a function of the sensitivity of the exam, the number and spacings of the exams given to the screened group as well as the sample size, disease incidence of the population and the survival distribution. The theoretical results on power are applied to the Canadian National Breast Cancer Study (ages 40-49) which used an UFD and the Stockholm Mammography Breast Cancer Screening Trial which utilized a COD. C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hu, P (reprint author), NCI, Biometry Res Grp, Bethesda, MD 20892 USA. NR 38 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD SEP PY 2002 VL 3 IS 3 BP 299 EP 313 DI 10.1093/biostatistics/3.3.299 PG 15 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 678YQ UT WOS:000182894600001 PM 12933599 ER PT J AU Zogakis, TG Costouros, NG Kruger, EA Forbes, S He, M Qian, M Feldman, AL Figg, WD Alexander, HR Liu, ET Kohn, EC Libutti, SK AF Zogakis, TG Costouros, NG Kruger, EA Forbes, S He, M Qian, M Feldman, AL Figg, WD Alexander, HR Liu, ET Kohn, EC Libutti, SK TI Microarray gene expression profiling of angiogenesis inhibitors using the rat aortic ring assay SO BIOTECHNIQUES LA English DT Article ID CARBOXYAMIDO-TRIAZOLE; CELL-LINES; GROWTH AB The rat aortic ring assay has been previously described as a useful ex vivo model for analyzing the biological activity of various inhibitors of angiogenesis. Rat aortic rings are exposed to antiangiogenic agents for a five-day incubation period. Then, the degree of microvessel outgrowth from the rings is analyzed and quantified. In contrast to most in vitro angiogenesis assays, the rat aortic ring model provides a unique microenvironment to evaluate the interaction of various cell types and biological factors for their influence on angiogenesis. Microarray analysis is an accepted method for the evaluation of gene expression profiles and can be used to better understand changes in gene expression that occur when rat aortic rings are exposed to a particular biological agent. Here we describe a method of using mieroarray technology to evaluate the modulation of gene expression in angiogenesis using the rat aortic ring assay. C1 NCI, Surg Branch, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, Bldg 10,Room 2B17,10 Ctr Dr, Bethesda, MD 20892 USA. RI Feldman, Andrew/D-5028-2012; Liu, Edison/C-4141-2008; Figg Sr, William/M-2411-2016 NR 10 TC 14 Z9 14 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 2002 VL 33 IS 3 BP 664 EP + PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 592XV UT WOS:000177962900028 PM 12238776 ER PT J AU Saunthararajah, Y Nakamura, R Nam, JM Robyn, J Loberiza, F Maciejewski, JP Simonis, T Molldrem, J Young, NS Barrett, JA AF Saunthararajah, Y Nakamura, R Nam, JM Robyn, J Loberiza, F Maciejewski, JP Simonis, T Molldrem, J Young, NS Barrett, JA TI HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome SO BLOOD LA English DT Article ID NECROSIS-FACTOR-ALPHA; HYPOCELLULAR BONE-MARROW; PRIMERS PCR-SSP; ANTITHYMOCYTE GLOBULIN; MEDIATED INHIBITION; INCREASED FREQUENCY; MONONUCLEAR-CELLS; CYCLOSPORINE; THERAPY; DISEASE AB The extent and importance of auto-immune mechanisms in myelodysplastic syndrome (MDS) and the role of immunosuppression in the treatment of this disease are not well defined. We report over-representation of HLA-DR2 and its serologic split HLA-DR15 in both MDS and aplastic anemia (AA). Four clinically and ethnically defined patient groups were analyzed. The HLA-DR15 antigen frequencies among North American white MDS patients (n = 72) and AA patients (n = 59), who received immunosuppressive treatment at the National Institutes of Health (NIH), were 36% and 42%, respectively. These antigen frequencies were significantly higher than that of the control population of 240 North American white NIH blood donors typed for HLA antigens by the same molecular technique (HLADR15, 21.3%, P = .01 for MDS, P <.001 for AA). Among North American white patients reported in the International Bone Marrow Transplant Registry (IBMTR), 30% of 341 MDS patients and 33% of 364 AA patients were positive for HLA-DR2. These antigen frequencies were higher than those reported for the general North American white population (HILA-DR2, 25.3%, P = .089 for MDS, P = .01 for AA). The DR15 and DR2 frequencies were significantly increased in MDS refractory anemia (RA) (P = .036 and P = .01, respectively) but not MDS refractory anemia with excess blasts. In the NIH MDS patients, HLA-DR15 was significantly associated with a clinically relevant response to antithymocyte globulin (ATG) or cyclosporine immunosuppression (multivariate analysis, P = .008). In MDS with RA, DR15 may be useful as a guide to pathophysiology, prognosis, and treatment. (C) 2002 by The American Society of Hematology. C1 NIH, HLA Lab, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Illinois, Chicago, IL USA. NHLBI, Bethesda, MD 20892 USA. Natl Canc Inst, Rockville, MD USA. Int Bone Marrow Transplant Registry, Milwaukee, WI USA. RP Barrett, JA (reprint author), NIH, HLA Lab, Dept Transfus Med, Bldg 10, Bethesda, MD 20892 USA. NR 38 TC 161 Z9 186 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2002 VL 100 IS 5 BP 1570 EP 1574 PG 5 WC Hematology SC Hematology GA 587WU UT WOS:000177667700011 PM 12176872 ER PT J AU Goedert, JJ Eyster, ME Lederman, MM Mandalaki, T de Moerloose, P White, GC Angiolillo, AL Luban, NLC Sherman, KE Manco-Johnson, M Preiss, L Leissinger, C Kessler, CM Cohen, AR DiMichele, D Hilgartner, MW Aledort, LM Kroner, BL Rosenberg, PS Hatzakis, A AF Goedert, JJ Eyster, ME Lederman, MM Mandalaki, T de Moerloose, P White, GC Angiolillo, AL Luban, NLC Sherman, KE Manco-Johnson, M Preiss, L Leissinger, C Kessler, CM Cohen, AR DiMichele, D Hilgartner, MW Aledort, LM Kroner, BL Rosenberg, PS Hatzakis, A CA Multictr Hemophelia Cohort Study TI End-stage liver disease in persons with hemophilia and transfusion-associated infections SO BLOOD LA English DT Article ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; NON-A-HEPATITIS; NON-B-HEPATITIS; VIRAL-HEPATITIS; NATURAL-HISTORY; HEPATOCELLULAR-CARCINOMA; CUMULATIVE INCIDENCE; HIV-INFECTION; FACTOR-VIII AB Many persons with hemophilia were infected with hepatitis C and B viruses (HCV, HBV) and HIV, but the consequences of these transfusion-acquired infections are poorly defined. We estimated the risk of HCV-related end-stage liver disease (ESLD) and the associations of age, HBV, and HIV with that risk. All 1816 HCV-seropositive hemophilic patients at 16 centers were followed for up to 16 years. Of these, 624 were HIV- and 1192 were HIV-coinfected; 135 had persistent HBV surface antigenemia, 1374 had resolved HBV infection, and 287 were HBV-uninfected. ESLD was defined as bleeding esophageal varices, hepatic encephalopathy, persistent ascites, or death excluding nonhepatic causes of these conditions. Competing risk models were used to estimate the annual hazard rate and cumulative incidence of ESLD. Proportional hazards models were used to estimate relative hazards of ESLD with covariates. ESLD developed in 127 of the HCV/HIV-coinfected participants, with an estimated 16-year cumulative incidence of 14.0% (95% confidence interval [CI], 11.6%-16.4%). Without HIV, 10 HCV-infected participants developed ESLD, for a significantly lower cumulative incidence of 2.6% (95% CI, 1.0%-4.3%, P <.0001). ESLD risk increased steeply with age in both groups. With HIV, ESLD risk was increased 8.1-fold (95% CI, 1.9-35.2) with HBV surface antigenemia, 2.1-fold (95% CI, 1.3-3.3) with fewer than 0.2 x 10(9)/L (200/muL) CD4(+) lymphocytes, and 1.04-fold (95% CI, 1.03-1.06) per year of age. Thus, HIV is associated with a markedly increased risk of HCV-related ESLD for persons with hemophilia, particularly with HBV infection, low CD4+ lymphocytes, or older age. (C) 2002 by The American Society of Hematology. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Penn State Univ, Sch Med, Milton S Hershey Med Ctr, University Pk, PA 16802 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Laikon Gen Hosp, Hemophilia Ctr, Reg Blood Transfus Ctr 2, Athens, Greece. Hop Cantonal Univ, Geneva, Switzerland. Univ N Carolina, Comprehens Hemophilia Ctr, Chapel Hill, NC USA. Childrens Hosp, Natl Med Ctr, Dept Hematol, Washington, DC 20010 USA. Univ Cincinnati, Med Ctr, Div Digest Dis, Cincinnati, OH 45221 USA. Univ Colorado, Mt States Reg Hemophilia & Thrombosis Program, Aurora, CO USA. Res Triangle Inst, Rockville, MD USA. Tulane Univ, Sch Med, Hematol Oncol Sect, New Orleans, LA USA. Georgetown Univ Hosp, Lombardi Canc Res Ctr, Washington, DC 20007 USA. Childrens Hosp, Dept Hematol, Philadelphia, PA 19104 USA. New York Presbyterian Hosp, Hemophilia Treatment Ctr, New York, NY USA. CUNY, Mt Sinai Med Ctr, Hemophilia Ctr, New York, NY USA. Univ Athens, Sch Med, Natl Retrovirus Reference Ctr, GR-11527 Athens, Greece. RP Goedert, JJ (reprint author), 6120 Execut Blvd,MSC 7248, Rockville, MD 20892 USA. FU NCI NIH HHS [N01-CP-33002] NR 37 TC 109 Z9 113 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2002 VL 100 IS 5 BP 1584 EP 1589 PG 6 WC Hematology SC Hematology GA 587WU UT WOS:000177667700014 PM 12176875 ER PT J AU Kuprash, DV Boitchenko, VE Yarovinsky, FO Rice, NR Nordheim, A Ruhlmann, A Nedospasov, SA AF Kuprash, DV Boitchenko, VE Yarovinsky, FO Rice, NR Nordheim, A Ruhlmann, A Nedospasov, SA TI Cyclosporin A blocks the expression of lymphotoxin alpha, but not lymphotoxin beta, in human peripheral blood mononuclear cells SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; SECONDARY LYMPHOID-TISSUES; T-CELL; SURFACE LYMPHOTOXIN; DEFICIENT MICE; MESSENGER-RNA; HETEROMERIC COMPLEX; CYTOKINE PRODUCTION; GENE-REGULATION AB The 2 lymphotoxin subunits LTalpha (also called tumor necrosis factor beta [TNF-beta]) and LTbeta belong to the family of TNF-related cytokines. They form either a soluble homotrimeric ligand (LTalpha(3)) that binds to and signals through CD120a/b (TNFRp55 and TNFRp75), or a membrane-associated heterotrimeric ligand (LTalpha(1)beta(2)) that binds to and signals through the LTbeta receptor (LTbetaR). In mice, LTbetaR signaling is critical for the maintenance of peripheral lymphoid tissues and optimal immune responses, and its down-regulation results in immunodeficiency. To determine the possible relationship between LT-mediated immunodeficiency and the immunosuppressive effects of cyclosporin A (CsA), we tested the effects of CsA on the expression of LTalpha and LTbeta in human peripheral blood mononuclear cells (PBMCs). When PBMCs were stimulated with phorbol myristate acetate/ionomycin or with anti- CD3/anti-CD28, the accumulation of LTalpha both at mRNA and protein levels was markedly inhibited by CsA. This inhibition is likely due to CsA's effect on the nuclear factor of activated T cell (NFAT) proteins binding to a novel NFAT-binding element at position -490 relative to LTalpha transcription start. LTbeta showed a distinct expression pattern and was insensitive to CsA. Thus, in addition to its effects on the expression of other TNF family members, such as TNFalpha, CD40-L, and CD95-L, CsA can block expression of surface LT complex by selectively inhibiting the expression of the LTalpha subunit. We propose that LT dysfunction and its downstream effects may contribute to immunosuppressive effects of CsA. (C) 2002 by The American Society of Hematology. C1 Russian Acad Sci, Engelhardt Inst Mol Biol, Lab Mol Immunol, Moscow 119991, Russia. Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia. Univ Tubingen, Inst Cell Biol, Dept Mol Biol, Tubingen, Germany. NCI, Div Basic Sci, Regulat Cell Growth Lab, Frederick, MD 21701 USA. NCI, Div Basic Sci, Mol Immunoregulat Lab, Frederick, MD 21701 USA. SAIC, Intramural Res Support Program, Frederick, MD USA. RP Nedospasov, SA (reprint author), Russian Acad Sci, Engelhardt Inst Mol Biol, Lab Mol Immunol, 32 Vavilov St, Moscow 119991, Russia. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; FU NCI NIH HHS [N01-CO-124000] NR 55 TC 16 Z9 17 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2002 VL 100 IS 5 BP 1721 EP 1727 PG 7 WC Hematology SC Hematology GA 587WU UT WOS:000177667700032 PM 12176893 ER PT J AU Szabolcs, P Reese, M Yancey, KB Hall, RP Kurtzberg, J AF Szabolcs, P Reese, M Yancey, KB Hall, RP Kurtzberg, J TI Case report - Combination treatment of bullous pemphigoid with anti-CD20 and anti-CD25 antibodies in a patient with chronic graft-versus-host disease SO BONE MARROW TRANSPLANTATION LA English DT Article DE transplantation; GVHD; bullous pemphigoid; rituximab; daclizumab ID MONOCLONAL-ANTIBODY; HEMOLYTIC-ANEMIA; RITUXIMAB; THROMBOCYTOPENIA; AUTOIMMUNE; RECEPTOR AB In this case report we describe a novel treatment with two chimeric monoclonal antibodies (MoAb) targeting the autoimmune B cell clone responsible for bullous pemphigoid (BP) as a manifestation of steroid refractory chronic graft-versus-host disease (GVHD) that developed after unrelated cord blood transplantation. Monitoring the BP-specific circulating antibodies and CD25-expressing activated T lymphocyte subset led us to combine anti-CD20 (Rituximab) mediated B cell ablation with anti-CD25 (Daclizumab) therapy to block CD4(+) T cell help. Complete clinical and serologic response was achieved within 4 weeks of initiation of therapy allowing global immunosuppression to be dramatically reduced. C1 Duke Univ, Med Ctr, Pediat Stem Cell Transplant Program, Dept Pediat, Durham, NC 27710 USA. NCI, Dermatol Branch, DCS, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Dermatol, Durham, NC USA. RP Szabolcs, P (reprint author), Duke Univ, Med Ctr, Pediat Stem Cell Transplant Program, Dept Pediat, Box 3350, Durham, NC 27710 USA. FU NHLBI NIH HHS [N01-HB-67141, N01-HB-67138]; PHS HHS [R01-A1-47258-01A1] NR 9 TC 51 Z9 53 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD SEP PY 2002 VL 30 IS 5 BP 327 EP 329 DI 10.1038/sj.bmt.1703654 PG 3 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 593TZ UT WOS:000178010800011 PM 12209356 ER PT J AU Wei, WL Norton, DD Wang, XT Kusiak, JW AF Wei, WL Norton, DD Wang, XT Kusiak, JW TI A beta 17-42 in Alzheimer's disease activates JNK and caspase-8 leading to neuronal apoptosis SO BRAIN LA English DT Article DE Alzheimer's disease; p3 peptide; apoptosis; caspase; JNK ID PROGRAMMED CELL-DEATH; AMYLOID PRECURSOR PROTEIN; C-JUN; CORTICAL-NEURONS; IN-VITRO; KINASE; PEPTIDE; EXPRESSION; BRAIN; P3 AB The p3 peptide [amyloid beta-peptide (Abeta) 17-40/42], derived by alpha- and gamma-secretase cleavage of the amyloid precursor protein (APP), is a major constituent of diffuse plaques in Alzheimer's disease and cerebellar pre-amyloid in Down's syndrome. However, the importance of p3 peptide accumulation in Alzheimer's disease and its toxic properties is not clear. Here, we demonstrate that treatment of cells with Abeta 17-42 leads to apoptosis in two human neuroblastoma cell lines, SH-SY5Y and IMR-32. Abeta 17-42 activated caspase-8 and caspase-3, induced poly(ADP-ribose) polymerase cleavage, but did not activate caspase-9. Selective caspase-8 and caspase-3 inhibitors completely blocked Abeta 17-42-induced neuronal death. Abeta 17-42 moderately activated c-Jun N-terminal kinase (JNK); however, overexpression of a dominant-negative mutant of SEK1, the upstream kinase of JNK, protected against Abeta 17-42 induced neuronal death. These results demonstrate that Abeta 17-42 induced neuronal apoptosis via a Fas-like/caspase-8 activation pathway. Our findings reveal the previously unrecognized toxic effect of Abeta 17-42. We propose that Abeta 17-42 constitutes an additional toxic peptide derived from APP proteolysis and may thus contribute to the neuronal cell loss characteristic of Alzheimer's disease. C1 NIA, Mol Neurobiol Unit, Cellular & Mol Biol Lab, Intramural Res Program,GRC,NIH, Baltimore, MD 21224 USA. RP Kusiak, JW (reprint author), NIA, Mol Neurobiol Unit, Cellular & Mol Biol Lab, Intramural Res Program,GRC,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wanliwei@hotmail.com; jk133r@nih.gov NR 38 TC 78 Z9 88 U1 0 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 2002 VL 125 BP 2036 EP 2043 DI 10.1093/brain/awf205 PN 9 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 585CE UT WOS:000177504900011 PM 12183349 ER PT J AU Jakovljevic, J Touillaud, MS Bondy, ML Singletary, SE Pillow, PC Chang, S AF Jakovljevic, J Touillaud, MS Bondy, ML Singletary, SE Pillow, PC Chang, S TI Dietary intake of selected fatty acids, cholesterol and carotenoids and estrogen receptor status in premenopausal breast cancer patients SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; carotenoids; diet; estrogen receptors; estrogen receptor status; fat ID HISTORY QUESTIONNAIRE; RISK-FACTORS; VITAMIN-A; HABITS; MICRONUTRIENTS; VEGETABLES; NUTRIENTS; RECORDS; FRUITS; WOMEN AB Although a wealth of research has focused on the influence of diet on breast cancer risk, the relationships between dietary factors and tumor characteristics of breast cancer, like estrogen receptor (ER) status, are not well characterized. In a case-case study, we evaluated self-reported dietary intake for five individual carotenoids, selected fatty acids, and cholesterol 1 year before diagnosis in 34 premenopausal breast cancer patients with ER-negative tumors and 86 premenopausal breast cancer patients with ER-positive tumors from The University of Texas M. D. Anderson Cancer Center. In multivariate logistic regression analysis adjusted for age, body mass index, and ethnicity, high intakes of linoleic acid were associated with more than a threefold greater risk of ER-negative disease than ER-positive disease (odds ratio (OR) = 3.48, 95% confidence interval (CI) = 1.42-8.54), whereas high cholesterol intake was associated with lower risk of ER-negative disease (OR = 0.35, 95% CI = 0.14-0.92). In a model evaluating carotenoids, selected fatty acids, and cholesterol together, the association with high intake of linoleic acid remained statistically significant (OR = 3.96, 95% CI = 1.53-10.25), while those for high intake of cholesterol (OR = 0.38, 95% CI = 0.14-1.03) and low intake of cryptoxanthin (OR = 0.43, 95% CI = 0.17-1.06) were of marginal significance. While no striking associations were observed for the intakes of total carotenoids, selected fatty acids, and cholesterol, our analysis revealed an association for the consumption of a specific fatty acid (i.e., linoleic acid), suggesting dietary influence of this factor on ER status in premenopausal breast cancer patients. However, larger studies are needed to clarify the role of micronutrients in ER status in breast cancer. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. RP Chang, S (reprint author), NCI, Off Prevent Oncol, Div Canc Prevent, 6120 Execut Blvd EPS,Suite T-41,MSC 7105, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA 70264, CA 56452] NR 41 TC 16 Z9 17 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 2002 VL 75 IS 1 BP 5 EP 14 DI 10.1023/A:1016588629495 PG 10 WC Oncology SC Oncology GA 578CM UT WOS:000177099900002 PM 12500930 ER PT J AU Danforth, DN Aloj, L Carrasquillo, JA Bacharach, SL Chow, C Zujewski, J Whatley, M Galen, B Merino, M Neumann, RD AF Danforth, DN Aloj, L Carrasquillo, JA Bacharach, SL Chow, C Zujewski, J Whatley, M Galen, B Merino, M Neumann, RD TI The role of F-18-FDG-PET in the local/regional evaluation of women with breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; F-18-fluorodeoxyglucose; imaging; local/regional tumor; monitoring response to chemotherapy; positron emission tomography; staging; tumors ID POSITRON-EMISSION-TOMOGRAPHY; LYMPH-NODE METASTASES; F-18 2-DEOXY-2-FLUORO-D-GLUCOSE; PREOPERATIVE CHEMOTHERAPY; FDG-PET; NEOADJUVANT CHEMOTHERAPY; SENTINEL NODE; CARCINOMA; FLUORODEOXYGLUCOSE; BIOPSY AB Purpose. In women with breast cancer, knowledge of the local/regional extent of the tumor is essential for staging, treatment planning, monitoring response to therapy, and follow-up. Positron emission tomography (PET) is an important imaging test which can detect tumor at multiple sites in women with breast cancer. We compared the ability of PET to provide a comprehensive view of the local/regional extent of tumor in women with stage I, II and stage III, IV breast cancer. Materials and methods. Forty-six women with breast cancer underwent PET using F-18-FDG. (18)FDG uptake in the breast primary tumor, associated skin, axillary and internal mammary lymph nodes, and the contralateral breast was determined qualitatively, and correlated with histologic, clinical and radiographic findings. Results. Twenty-four patients were premenopausal and 22 were postmenopausal, with the following distribution according to clinical stage: stage I - 2 patients, stage II - 16, stage III - 16, stage IV - 12 patients. Among stage I, II patients, the sensitivity for detection of the primary tumor was 83.3%, and for detection of axillary lymph node metastases was 42.9%. (1)8FDG-PET was negative for the breast skin, contralateral breast, and internal mammary lymph nodes in all stage I, II patients, in agreement with clinical and radiographic findings. Among 28 stage III, IV patients, the sensitivity of (18)FDG-PET for detection of the primary tumor was 90.5%, and for detection of axillary lymph node metastases 83.3%. Fourteen patients had clinically advanced changes in the skin, and the sensitivity of PET for detection of skin changes was 76.9%. (1)8FDG-PET was positive in the internal mammary lymph nodes in 25.0%, and negative in the contralateral breast in all patients with stage III, IV breast cancer. (18)FDG-PET was studied in 10 patients following neoadjuvant chemotherapy, and showed a strong correlation with clinical response, and with clinical and pathological findings post-treatment at multiple local/regional sites. Conclusion. (18)FDG-PET can provide a comprehensive image of local/regional tumor in women with breast cancer. (1)8FDG-PET may play a greater role in women with stage III, IV breast cancer because of increased sensitivity and the increased involvement of multiple local/regional sites with tumor. C1 NCI, Surg Branch, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. RP Danforth, DN (reprint author), NCI, Surg Branch, Bldg 10 Rm 2B38, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 32 TC 47 Z9 47 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 2002 VL 75 IS 2 BP 135 EP 146 DI 10.1023/A:1019664126220 PG 12 WC Oncology SC Oncology GA 582AD UT WOS:000177326800005 PM 12243506 ER PT J AU Chen, L Zhang, JC Tang, DC Fibach, E Rodgers, GP AF Chen, L Zhang, JC Tang, DC Fibach, E Rodgers, GP TI Influence of lineage-specific cytokines on commitment and asymmetric cell division of haematopoietic progenitor cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE self-renewal; differentiation; AC133(+) cells; EPO; G-CSF ID HEMATOPOIETIC STEM-CELLS; COLONY-STIMULATING FACTORS; IMMUNE-DEFICIENT MICE; UMBILICAL-CORD BLOOD; IN-VITRO; SELF-RENEWAL; DIFFERENTIATION; NOTCH; GENE; ERYTHROPOIETIN AB We examined the influence of cytokines on erythroid- and myeloid-lineage development of AC133(+) cells during primary and secondary cultures. Cells cultured for 14 d in liquid medium containing erythropoietin (EPO) were amplified 831-fold with 98.2% erythroid cells. A similar culture exposed to granulocyte colony-stimulating factor (G-CSF) grew 1350-fold with 97.4% myeloid cells. To assess whether the cells with EPO inducement could respond at this point to G-CSF signal, or vice versa, the EPO-stimulated population was re-grown with G-CSF, constituting 95.2% myeloid, of 5075-fold, cells after 14 d of re-culture. Conversely, reculture of the G-CSF-stimulated population with EPO resulted in a 4083-fold growth with 81.4% erythroid cells. Semisolid culture containing EPO orG-CSF showed that some individual colonies had self- renewal potential after 14 d culture and could be induced todevelop into a different lineage. Analysis of primitive markers, CD34 and Notch1, or lineage markers, EPO-R and CD13, by single-cell reverse transcription polymerase chain reaction showed that individual colonies of 2-16 cells contained at least one CD34-positive cell with expression ofNotch1 and co-expression of EPO-R and CD13 appeared on either CD34-positive or CD34-negative cells. In situ hybridization with the same cell surface markers in cell populations confirmed the asymmetric cell division and co-expression from single cell data. The study provides a useful model for the analysis of multipotential progenitor development, and indicates that progenitor cells co-express genes from different lineage pathways before commitment and that cytokines influence lineage commitment. C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Dept Haematol, IL-91120 Jerusalem, Israel. RP Rodgers, GP (reprint author), NIDDK, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N 119, Bethesda, MD 20892 USA. NR 40 TC 7 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2002 VL 118 IS 3 BP 847 EP 857 DI 10.1046/j.1365-2141.2002.03638.x PG 11 WC Hematology SC Hematology GA 584JH UT WOS:000177463100025 PM 12181058 ER PT J AU Wong, TY Hubbard, LD Klein, R Marino, EK Kronmal, R Sharrett, AR Siscovick, DS Burke, G Tielsch, JM AF Wong, TY Hubbard, LD Klein, R Marino, EK Kronmal, R Sharrett, AR Siscovick, DS Burke, G Tielsch, JM TI Retinal microvascular abnormalities and blood pressure in older people: the Cardiovascular Health Study SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ATHEROSCLEROSIS RISK; COMMUNITIES; RETINOPATHY; HYPERTENSION; STROKE; ADULTS AB Aim: To examine the relation between blood pressure and retinal microvascular abnormalities in older people. Methods: The Cardiovascular Health Study is a prospective cohort study conducted in four US communities initiated in 1989 to 1990. Blood pressure was measured according to standardised protocols at each examination. During the 1997-8 examination, retinal photographs were taken of 2405 people aged 69-97 years (2056 without diabetes and 349 with diabetes). Signs of focal microvascular abnormalities (focal arteriolar narrowing, arteriovenous nicking, and retinopothy) were evaluated from photographs according to standardised methods. To quantify generalised arteriolar narrowing, the photographs were digitised and diameters of individual arterioles were measured and summarised. Results: In non-diabetic people, elevated concurrent blood pressure taken at the time of retinal photography was strongly associated with presence of all retinal microvascular lesions. The multivariable adjusted odds ratios, comparing the highest to lowest quintile of concurrent systolic blood pressure, were 4.0 (95% confidence intervals (CI): 2.4 to 6.9, p test of trend<0.001) for focal arteriolar narrowing, 2.9 (95% CI: 1.6 to 5.3, p<0.001) for arteriovenous nicking, 2.8 (95% CI: 1.5 to 5.2, p<0.001) for retinopathy, and 2.1 (95% CI: 1.4 to 3.1, p<0.001) for generalised arteriolar narrowing. Generalised arteriolar narrowing and possibly arteriovenous nicking were also significantly associated with past blood pressure measured up to 8 years before retinal photography, even after adjustment for concurrent blood pressure. These associations were somewhat weaker in people with diabetes. Conclusions: Retinal microvascular abnormalities are related to elevated concurrent blood pressure in older people. Additionally, generalised retinal arteriolar narrowing and possibly orteriovenous nicking are related to previously elevated blood pressure, independent of concurrent blood pressure. These data suggest that retinal microvascular changes reflect severity and duration of hypertension. C1 Natl Univ Singapore, Dept Ophthalmol, Singapore 119260, Singapore. Singapore Eye Res Inst, Singapore, Singapore. Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. Univ Washington, Dept Biostat, CHS Coordinating Ctr, Seattle, WA 98195 USA. NHLBI, NIH, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Washington, Dept Med, Seattle, WA USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. RP Wong, TY (reprint author), Natl Univ Singapore, Dept Ophthalmol, 10 Kent Ridge Crescent, Singapore 119260, Singapore. FU NHLBI NIH HHS [HC-97-06] NR 36 TC 153 Z9 162 U1 0 U2 5 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD SEP PY 2002 VL 86 IS 9 BP 1007 EP 1013 DI 10.1136/bjo.86.9.1007 PG 7 WC Ophthalmology SC Ophthalmology GA 588TC UT WOS:000177715900017 PM 12185128 ER PT J AU Zhang, T Ng, P Caridha, D Leach, RA Asher, LV Novak, MJ Smith, WJ Zeichner, SL Chiang, PK AF Zhang, T Ng, P Caridha, D Leach, RA Asher, LV Novak, MJ Smith, WJ Zeichner, SL Chiang, PK TI Gene expressions in Jurkat cells poisoned by a sulphur mustard vesicant and the induction of apoptosis SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE sulphur mustard vesicant; 2-chloroethylethyl sulphide; apoptosis; caspases; microarray; Bcl; Akt; PDK ID PROTEIN-KINASE-B; SULFUR MUSTARD; 2-CHLOROETHYLETHYL SULFIDE; BAD PHOSPHORYLATION; C-MYC; ACTIVATION; TOXICOLOGY; NITROGEN; INVITRO; DEATH AB 1 The sulphur mustard vesicant 2-chloroethylethyl sulphide (CEES) induced apoptosis in Jurkat cells. 2 Akt (PKB), a pivotal protein kinase which can block apoptosis and promotes cell survival, was identified to be chiefly down-regulated in a dose-dependent manner following CEES treatment. Functional analysis showed that the attendant Akt activity was simultaneously reduced. 3 PDK1, an upstream effector of Akt, was also down-regulated following CEES exposure, but two other upstream effectors of Akt, PI3-K and PDK2, remained unchanged. 4 The phosphorylation of Akt at Ser(473) and Thr(308) was significantly decreased following CEES treatment, reflecting the suppressed kinase activity of both PDK1 and PDK2. 5 Concurrently, the anti-apoptotic genes, Bcl family, were down-regulated, in sharp contrast to the striking up-regulation of some death executioner genes, caspase 3, 6, and 8. 6 Based on these findings, a model of CEES-induced apoptosis was established. These results suggest that CEES attacked the Akt pathway, directly or indirectly, by inhibiting Akt transcription, translation, and post-translation modification. 7 Taken together, upon exposure to CEES, apoptosis was induced in Jurkat cells via the down-regulation of the survival factors that normally prevent the activation of the death executioner genes, the caspases. C1 Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD 20910 USA. NCI, NIH, Bethesda, MD 20892 USA. USA, Med Res Inst Chem Def, Aberdeen Proving Ground, MD 21010 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Chiang, PK (reprint author), Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD 20910 USA. NR 40 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 2002 VL 137 IS 2 BP 245 EP 252 DI 10.1038/sj.bjp.0704856 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 593NQ UT WOS:000177998700014 ER PT J AU Dewailly, E Furgal, C Knap, A Galvin, J Baden, D Bowen, B Depledge, M Duguay, L Fleming, L Ford, T Moser, F Owen, R Suk, WA Unluata, U AF Dewailly, E Furgal, C Knap, A Galvin, J Baden, D Bowen, B Depledge, M Duguay, L Fleming, L Ford, T Moser, F Owen, R Suk, WA Unluata, U TI Indicators of ocean and human health SO CANADIAN JOURNAL OF PUBLIC HEALTH-REVUE CANADIENNE DE SANTE PUBLIQUE LA English DT Article; Proceedings Paper CT Conference on Environmental Health Indicators CY OCT, 2000 CL QUEBEC CITY, CANADA ID POLYCHLORINATED-BIPHENYLS; EXPOSURE; METHYLMERCURY; CHILDREN; PCBS AB The interactions between humans and the ocean are significant, and necessitate more comprehensive study on an international scale. The world's oceans provide great health benefits to humans ranging from food and nutritional resources, to recreational opportunities and new treatments for human disease. However, recently, human health effects from exposure to substances present in the marine ecosystem such as synthetic organic chemicals (e.g., chlorobiphenyls, chlorinated dioxins and some industrial solvents), polycyclic aromatic hydrocarbons (PAHs), metals (both introduced and anthropogenic), marine toxins, and pathogens have been recorded and are of great concern. This paper reviews our state of knowledge of the interactions between oceans and human health and proposes indicators and a research strategy to investigate and monitor these relationships more closely. Four approaches to gathering information on indicators included here are: biomarkers; cellular pathology; physiological and behavioural responses; and changes in populations. All hold the potential to enhance our understanding of marine environmental quality and far-reaching effects on human health. Monitoring systems that include the rapid assessment of contaminants in the ecosystem and subsequent risk to human populations, with appropriate internationally distributed data bases, need to be developed and validated. Such tools would provide early detection of potential environmental threats, and enhance the ability to prevent human illness. C1 Univ Laval, Quebec City, PQ G1K 7P4, Canada. Bermuda Biol Stn Res Inc, St Georges, Bermuda. Univ N Carolina, Wilmington, NC 28401 USA. Univ Massachusetts, Boston, MA 02125 USA. Univ Plymouth, Plymouth PL4 8AA, Devon, England. Univ So Calif, Wrigley Inst, Los Angeles, CA 90089 USA. Univ Miami, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33152 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. US Dept State, Washington, DC 20520 USA. NIH, Res Triangle Pk, NC USA. UNESCO, Intergovt Oceanog Commiss, Paris, France. RP Furgal, C (reprint author), CHUQ, Publ Hlth Res Unit, Pavillon CHUL,2400 Rue Estimauville, Beauport, PQ G1E 7G9, Canada. FU NIEHS NIH HHS [P01 ES010594, P01 ES010594-02] NR 13 TC 2 Z9 2 U1 0 U2 7 PU CANADIAN PUBLIC HEALTH ASSOC PI OTTAWA PA 1565 CARLING AVE, SUITE 400, OTTAWA, ONTARIO K1Z 8R1, CANADA SN 0008-4263 J9 CAN J PUBLIC HEALTH JI Can. J. Public Health-Rev. Can. Sante Publ. PD SEP-OCT PY 2002 VL 93 SU 1 BP S34 EP S38 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 612GE UT WOS:000179065500007 PM 12425173 ER PT J AU Taylor, KL Shelby, R Kerner, J Redd, W Lynch, J AF Taylor, KL Shelby, R Kerner, J Redd, W Lynch, J TI Impact of undergoing prostate carcinoma screening on prostate carcinoma-related knowledge and distress SO CANCER LA English DT Article DE prostate carcinoma screening; informed consent; mass screening; prostate ID SHARED DECISION-MAKING; BREAST-CANCER; OVARIAN-CANCER; PSYCHIATRIC MORBIDITY; ANTIGEN TEST; RISK; MEN; BELIEFS; WOMEN; TRIAL AB BACKGROUND. Despite the ongoing controversy regarding the utility of prostate carcinoma (PCa) screening, the prevalence of asymptomatic men who participate in free PCa screening programs is on the rise. However, this increased awareness has not been associated with increased knowledge about the potential limitations of PCa creening. We conducted a prospective assessment to delineate men's motivations for undergoing screening and to determine the impact of screening on psychological distress and on men's knowledge about PCa screening. METHODS. We conducted two telephone interviews with a group of 136 men registered to undergo free PCa screening at two hospital-based sites. The first interview was conducted before screening and the second interview followed receipt of the screening results. Interviews assessed demographics and screening history, reasons for undergoing the current screening, cancer-related and general psychological distress, knowledge of risk factors for PCa, and knowledge of the benefits and limitations of screening. Only participants with normal screening results were included in these analyses. RESULTS. "Seeking peace of mind about prostate cancer" was rated as the most important reason for undergoing screening. PCa-related distress decreased following receipt of a negative result (P < 0.01). Stratified analyses indicated that this was particularly true among younger men and African American men (both PS < 0.001). Awareness of the benefits of screening was very high, but awareness of limitations was low, with fewer limitations reported following screening compared with prescreening (P < 0.01). Although awareness of the established risk factors improved following screening, controversial risk factors (i.e., those with limited empirical support) and factors that were unrelated to PCa risk were also rated as more important in the development of PCa than they were before screening (all Ps < 0.05). Therefore, the results may reflect that following screening, participants were simply more likely to endorse plausible risk factors, rather than actually reflecting an increase in participants' knowledge. CONCLUSIONS. These results suggest the importance of developing informed consent procedures and educational programs for the asymptomatic men who participate in free prostate screening programs each year, as the decision to be screened is being made without the benefit of a full understanding of the current state of medical knowledge about PCa screening. Until the definitive results of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial are available, improved patient education is needed to assist men in making screening decisions consistent with their own preferences. C1 Georgetown Univ, Lombardi Canc Ctr, Canc Control Program, Washington, DC 20007 USA. NCI, Div Canc Control & Populat Sci, Rockville, MD USA. Mt Sinai Sch Med, Ruttenberg Canc Ctr, New York, NY USA. Georgetown Univ, Med Ctr, Dept Surg, Div Adult Urol, Washington, DC 20007 USA. RP Taylor, KL (reprint author), Georgetown Univ, Lombardi Canc Ctr, Canc Control Program, 2233 Wisconsin Ave NW, Washington, DC 20007 USA. OI Kerner, Jon/0000-0002-8792-3830 FU NCI NIH HHS [K07 CA72645] NR 40 TC 27 Z9 27 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2002 VL 95 IS 5 BP 1037 EP 1044 DI 10.1002/cncr.10781 PG 8 WC Oncology SC Oncology GA 586VF UT WOS:000177606000013 PM 12209688 ER PT J AU Ballard-Barbash, R Blair, A Blair, SN Byers, T Hoffman-Goetz, L Lee, IM Troiano, R Westerlind, K AF Ballard-Barbash, R Blair, A Blair, SN Byers, T Hoffman-Goetz, L Lee, IM Troiano, R Westerlind, K CA Sci Program Comm TI Physical activity across the cancer continuum: Report of a workshop review of existing knowledge and innovative designs for future research SO CANCER LA English DT Article ID PROSTATE-CANCER; ASSOCIATIONS; PROGRESSION; PREVENTION C1 NCI, Appl Res Program, EPN 4005, Bethesda, MD 20892 USA. Cooper Inst, Dallas, TX USA. Univ Colorado, Denver, CO 80202 USA. Univ Waterloo, Waterloo, ON N2L 3G1, Canada. Harvard Univ, Boston, MA 02115 USA. AMC Canc Res Ctr, Denver, CO USA. RP Ballard-Barbash, R (reprint author), NCI, Appl Res Program, EPN 4005, 6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM rb59b@nih.gov OI Troiano, Richard/0000-0002-6807-989X NR 14 TC 16 Z9 16 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2002 VL 95 IS 5 BP 1134 EP 1143 DI 10.1002/cncr.10771 PG 10 WC Oncology SC Oncology GA 586VF UT WOS:000177606000026 ER PT J AU Leach, FS Koh, M Sharma, K McWilliams, G Talifero-Smith, L Codd, A Olea, R Elbahloul, O AF Leach, FS Koh, M Sharma, K McWilliams, G Talifero-Smith, L Codd, A Olea, R Elbahloul, O TI Mismatch repair gene mutations in renal cell carcinoma SO CANCER BIOLOGY & THERAPY LA English DT Article DE mismatch repair; hMLH 1; renal cell carcinoma; microsatellite instability ID NONPOLYPOSIS COLON-CANCER; MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; HOMOLOG; TUMORS; HMLH1; MICE; SUSCEPTIBILITY; INTERLEUKIN-2; NEPHRECTOMY AB We investigated the spectrum and genetic basis for mismatch repair (MMR) deficiency in renal cell carcinoma (RCC) by examining expression of four MMR genes important for hereditary and sporadic carcinogenesis. MMR deficiency was assessed using microsatellite instability (MSI) and genetic analyses of 25 cell lines derived from renal tumors. MMR gene alterations were detected using reverse transcription of RNA coupled with polymerase chain reaction (RT-PCR) and DNA sequencing. Three RCC lines with undetectable MLH1 were identified and investigated for MSI and inactivating mutations in the hMLH1 MMR gene. Genetic instability and hMLH1 mutations were identified in two RCC lines and their corresponding tumors. Genetic alterations affecting expression were limited to MLHI since other MMR proteins (MSH2, MSH6 and PMS2) were detectable in our RCC lines. Complete inactivation of MMR is apparently uncommon in RCC and occurs predominantly through inactivating mutations in the hMLH1 gene. C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Leach, FS (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 2B47, Bethesda, MD 20892 USA. NR 42 TC 18 Z9 18 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD SEP-OCT PY 2002 VL 1 IS 5 BP 530 EP 536 PG 7 WC Oncology SC Oncology GA 645TY UT WOS:000180996500016 PM 12496483 ER PT J AU Morin, PJ AF Morin, PJ TI Commentary - renal cell carcinoma - Taking care of business SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material ID MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; MISMATCH REPAIR; MUTATIONS; GENES; COLON C1 NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. RP Morin, PJ (reprint author), NIA, Cellular & Mol Biol Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD SEP-OCT PY 2002 VL 1 IS 5 BP 537 EP 538 PG 2 WC Oncology SC Oncology GA 645TY UT WOS:000180996500017 PM 12496484 ER PT J AU Malila, N Taylor, PR Virtanen, MJ Korhonen, P Huttunen, JK Albanes, D Virtamo, J AF Malila, N Taylor, PR Virtanen, MJ Korhonen, P Huttunen, JK Albanes, D Virtamo, J TI Effects of alpha-tocopherol and beta-carotene supplementation on gastric cancer incidence in male smokers (ATBC Study, Finland) SO CANCER CAUSES & CONTROL LA English DT Article DE beta-carotene; chemoprevention; randomized controlled trials; stomach neoplasms; vitamin E ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; RISK; POPULATION; CARCINOMA; DYSPLASIA; LINXIAN; CHINA AB Objectives: This study investigated the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of gastric cancer. Methods: A total of 29,133 male smokers, aged 50-69 years, participated in a placebo-controlled prevention trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in southwestern Finland between 1985 and 1993. The men were randomly assigned to receive alpha-tocopherol (50 mg/day) or beta-carotene (20 mg/day) supplementation in a 2 x 2 factorial design. We identified 126 gastric cancer cases during the median follow-up of six years. Of these, 122 were adenocarcinomas: 75 of intestinal type, 30 of diffuse type, and 17 of mixed type. Results: There was no significant effect for either supplementation on the overall incidence of gastric cancer: relative risk (RR) 1.21, 95% confidence interval (CI) 0.85-1.74 for alpha-tocopherol, and RR 1.26, 95% CI 0.88-1.80 for beta-carotene. Subgroup analyses by histologic type suggested an increased risk for beta-carotene on intestinal type cancers, RR 1.59, 95% CI 0.99-2.56. There were no differences across anatomic locations (cardia/noncardia) in the effects of alpha-tocopherol or beta-carotene supplementation. Conclusions: Our study found no overall preventive effect of long-term supplementation with alpha-tocopherol or beta-carotene on gastric cancer in middle-aged male smokers. C1 Natl Publ Hlth Inst, Helsinki, Finland. NCI, Bethesda, MD 20892 USA. RP Malila, N (reprint author), Finnish Canc Registry, Liisankatu 21 B, FIN-00170 Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 21 TC 44 Z9 47 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 2002 VL 13 IS 7 BP 617 EP 623 DI 10.1023/A:1019556227014 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 580FV UT WOS:000177225300004 PM 12296509 ER PT J AU Zheng, TZ Holford, TR Zahm, SH Owens, PH Boyle, P Zhang, YW Wise, JP Stephenson, LP Ali-Osman, F AF Zheng, TZ Holford, TR Zahm, SH Owens, PH Boyle, P Zhang, YW Wise, JP Stephenson, LP Ali-Osman, F TI Cigarette smoking, glutathione-S-transferase M1 and T1 genetic polymorphisms, and breast cancer risk (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE breast cancer; case-control; cigarette smoking; GSTM1; GSTT1 ID EPITHELIAL-CELLS; GSTT1 GENOTYPES; GSTM1; SUSCEPTIBILITY; LOCUS; P1; GSTP1; MU; TRANSFORMATION; ASSOCIATION AB Objective: It has been suggested that functional polymorphisms in genes encoding tobacco carcinogen-metabolizing enzymes may modify the relationship between tobacco smoking and breast cancer risk. We sought to determine if there is a gene-environment interaction between GSTM1 (GSTM1A and GSTM1B), and GSTT1 genotypes and cigarette smoking in the risk of breast cancer. Methods: Cases and controls were recruited in a case-control study conducted in Connecticut from 1994 to 1998. Cases were histologically confirmed, incident breast cancer patients, and controls were randomly selected from women histologically confirmed to be without breast cancer. A total of 338 cases and 345 controls were genotyped for GSTM1 and GSTT1. Results: None of the GSTM1 genotypes, either alone or in combination with cigarette smoking, was associated with breast cancer risk. There was, however, a significantly increased risk of breast cancer among postmenopausal women with a GSTT1 null genotype (OR = 1.9, 95% CI 1.2-2.9). There were also indications of increased risk of breast cancer associated with cigarette smoking for postmenopausal women with GSTT1-null genotype, especially for those who commenced smoking before age 18 (OR = 2.9, 95% CI 1.0-8.8). Conclusion: Women with a GSTT1-null genotype may have an increased breast cancer risk, especially postmenopausal women who started smoking at younger ages. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. European Inst Oncol, Dept Epidemiol & Biostat, Milan, Italy. Univ Texas, MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. RP Zheng, TZ (reprint author), 129 Church St,Suite 700, New Haven, CT 06510 USA. RI Boyle, Peter/A-4380-2014; Zahm, Shelia/B-5025-2015 OI Boyle, Peter/0000-0001-6251-0610; FU NCI NIH HHS [CA-62986, CA-81810] NR 48 TC 29 Z9 30 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 2002 VL 13 IS 7 BP 637 EP 645 DI 10.1023/A:1019500109267 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 580FV UT WOS:000177225300006 PM 12296511 ER PT J AU Chen, HL Ward, MH Tucker, KL Graubard, BI McComb, RD Potischman, NA Weisenburger, DD Heineman, EF AF Chen, HL Ward, MH Tucker, KL Graubard, BI McComb, RD Potischman, NA Weisenburger, DD Heineman, EF TI Diet and risk of adult glioma in eastern Nebraska, United States SO CANCER CAUSES & CONTROL LA English DT Article DE carotenoids; diet; glioma; N-nitroso compounds; phytochemicals ID SERUM-CHOLESTEROL CONCENTRATION; PRIMARY BRAIN-TUMORS; LOS-ANGELES-COUNTY; NORTHEAST CHINA; N-NITROSAMINES; CURED MEAT; INDICATORS; CALIFORNIA; ETIOLOGY; MENINGES AB Objective: To investigate potential associations between diet and adult glioma. Methods: We conducted a population-based case-control study of adult glioma in eastern Nebraska. Nutrient and food group intakes were estimated for 236 glioma cases and 449 controls using information obtained from a food-frequency questionnaire. Results: After adjusting for potential confounders, inverse associations with risk of adult glioma were observed for intakes of dark yellow vegetables (highest quartile versus lowest: OR = 0.6, p(t)rend = 0.03) and beans (OR = 0.4, p(t)rend = 0.0003), but no associations were seen for dietary sources of preformed nitrosamines or high-nitrate vegetables. Our nutrient analysis revealed significant inverse associations between risk of adult glioma and dietary intake of pro-vitamin A carotenoids (highest quartile versus lowest: OR = 0.5, p(t)rend = 0.005), alpha-carotene (OR = 0.5, p(t)rend = 0.01), beta-carotene (OR = 0.5, p(t)rend = 0.01), dietary fiber (OR = 0.6, p(t)rend = 0.048) and fiber from beans (OR = 0.5, p(t)rend = 0.0002). We observed no significant associations with risk of adult glioma for intakes of other nutrients or compounds including nitrate, nitrite, vitamin C, vitamin E, saturated fat, cholesterol, dietary fiber from grain products, or fiber from fruit and vegetables. Conclusion: Our study does not support the N-nitroso compound hypothesis, but suggests potential roles for carotenoids and possibly other phytochemicals in reducing risk of adult glioma. C1 Tufts Univ, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Ward, MH (reprint author), NCI, Occupat Epidemiol Branch, 6120 Execut Blvd,EPS-8104,MSC-7420, Bethesda, MD 20892 USA. RI Tucker, Katherine/A-4545-2010; OI Tucker, Katherine/0000-0001-7640-662X; Chen, Honglei/0000-0003-3446-7779 NR 42 TC 51 Z9 54 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 2002 VL 13 IS 7 BP 647 EP 655 DI 10.1023/A:1019527225197 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 580FV UT WOS:000177225300007 PM 12296512 ER PT J AU Mackall, CL Meltzer, PS Helman, LJ AF Mackall, CL Meltzer, PS Helman, LJ TI Focus on sarcomas SO CANCER CELL LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; TRAIL-INDUCED APOPTOSIS; SOFT-TISSUE SARCOMA; C-KIT; EWINGS-SARCOMA; GENE; EXPRESSION; ACTIVATION; MUTATIONS; SAFETY C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Helman, LJ (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 30 TC 52 Z9 52 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD SEP PY 2002 VL 2 IS 3 BP 175 EP 178 DI 10.1016/S1535-6108(02)00132-0 PG 4 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599UF UT WOS:000178353000005 PM 12242149 ER PT J AU Wacholder, S Chatterjee, N Hartge, P AF Wacholder, S Chatterjee, N Hartge, P TI Joint effect of genes and environment distorted by selection biases: Implications for hospital-based case-control studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DISEASE; DESIGNS; RISK AB The hospital-based case-control design enhances the response rates in studies that require the collection of biological samples from all of the participants. There are simple, established criteria for selecting controls so as to estimate the effect of a single factor without bias, but the analogous requirements for assessing an interaction are less clear. We derive these conditions by calculating the potential bias from selecting controls who were admitted for treatment of diseases related to either or both of the exposures of interest, designated as a gene variant (G) and an environmental agent (E). There is no bias in the estimate of the effect of E when G is associated with the control condition, whether causally or because of confounding. There is no bias in estimating multiplicative interaction between G and E for the disease of interest when there is no multiplicative G-E interaction for the control disease, even when the control condition is caused by G or E; if a mixture of several control diseases are used, however, the absence of G-E interaction in each individual disease does not ensure a lack of overall bias when controls are pooled. Hospital control designs are much less robust for assessing additive interaction. We conclude that the ideal control disease in a hospital-based study of gene-environment interaction is not caused by either G or E and that choosing controls from several conditions to act as a combined control group is a useful strategy. This formulation extends to the general problem of distortion of joint effects from selection biases or confounding. C1 NCI, Div Canc Epidemiol & Genet, NIH, EPS 8046, Bethesda, MD 20892 USA. RP Wacholder, S (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, EPS 8046, 6120 Execut Blvd, Bethesda, MD 20892 USA. NR 13 TC 41 Z9 41 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2002 VL 11 IS 9 BP 885 EP 889 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 592ZZ UT WOS:000177967900013 PM 12223433 ER PT J AU Stern, MC Umbach, DM Lunn, RM Taylor, JA AF Stern, MC Umbach, DM Lunn, RM Taylor, JA TI DNA repair gene XRCC3 codon 241 polymorphism, its interaction with smoking and XRCC1 polymorphisms, and bladder cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; STRAND BREAK REPAIR; RECOMBINATION; FREQUENCY; CELLS AB DNA repair efficiency varies among individuals, with reduced repair capacity as a risk factor for various cancers. This variability could be partly explained by allelic variants for different DNA repair genes. We examined the role of a common polymorphism in the XRCC3 gene (codon 241: threonine to methionine change) and bladder cancer risk. This gene plays a role in the homologous recombination pathway, which repairs double-strand breaks. The functional consequences of the XRCC3 codon 241 polymorphism are still unknown. We hypothesized that this polymorphism could affect repair of smoking-associated DNA damage and could thereby affect bladder cancer risk. We genotyped 233 bladder cancer cases and 209 controls who had been frequency matched to cases on age, sex, and ethnicity. We observed little evidence of a positive association between subjects who carried at least one copy of the codon 241 Met allele and bladder cancer (odds ratio: 1.3; 95% confidence interval: 0.9-1.9). Among heavy smokers, individuals with the Met allele had about twice the risk of those without it; however, a test of interaction was not statistically significant (P = 0.26). Previously, we observed in these subjects an association between bladder cancer risk and allelic variants of the XRCC1 gene, which is involved in the repair of base damage and single-strand breaks. In this study, we found some evidence for a gene-gene interaction between the XRCC1 codon 194 and XRCC3 codon 241 polymorphisms (P = 0.09) and some support for a possible gene-gene-smoking three-way interaction (P = 0.08). C1 NIEHS, Mol & Genet Epidemiol Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Genom Sect, Lab Computat Biol & Risk Anal, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Taylor, JA (reprint author), NIEHS, Mol & Genet Epidemiol Sect, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI taylor, jack/0000-0001-5303-6398 NR 22 TC 86 Z9 91 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2002 VL 11 IS 9 BP 939 EP 943 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 592ZZ UT WOS:000177967900023 PM 12223443 ER PT J AU Yao, L Pike, SE Pittaluga, S Cherney, B Gupta, G Jaffe, ES Tosato, G AF Yao, L Pike, SE Pittaluga, S Cherney, B Gupta, G Jaffe, ES Tosato, G TI Anti-tumor activities of the angiogenesis inhibitors interferon-inducible protein-10 and the calreticulin fragment vasostatin SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE angiogenesis; calreticulin; chemokine; endothelium; IP-10 ID X-C CHEMOKINE; IN-VIVO; GROWTH-FACTORS; ENDOGENOUS INHIBITOR; ENDOTHELIAL-CELLS; INTERLEUKIN-12; CANCER; REGRESSION; RECEPTOR; IP-10 AB Tumor growth depends upon an adequate supply of oxygen and nutrients achieved through angiogenesis and maintenance of an intact tumor vasculature. Therapy with individual agents that target new vessel formation or existing vessels has suppressed experimental tumor growth, but rarely resulted in the eradication of tumors. We therefore tested the combined anti-tumor activity of vasostatin and interferon-inducible protein-10 (IP-10), agents that differently target the tumor vasculature. Vasostatin, a selective and direct inhibitor of endothelial cell proliferation, significantly reduced Burkitt tumor growth and tumor vessel density. IP-10, an "angiotoxic" chemokine, caused vascular damage and focal necrosis in Burkitt tumors. When combined, vasostatin plus IP-10 reduced tumor growth more effectively than each agent alone, but complete tumor regression was not observed. Microscopically, these tumors displayed focal necrosis and reduction in vessel density. Combination therapy with the inhibitors of angiogenesis vasostatin and IP-10 is effective in reducing the rate of tumor growth but fails to induce tumor regression, suggesting that curative treatment may require supplemental drugs targeting directly the tumor cells. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res, Rockville, MD USA. RP Yao, L (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Room 12N226 MSC 1907,10 Ctr Dr, Bethesda, MD 20892 USA. NR 57 TC 32 Z9 36 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD SEP PY 2002 VL 51 IS 7 BP 358 EP 366 DI 10.1007/s00262-002-0294-2 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA 591GP UT WOS:000177871600002 PM 12192535 ER PT J AU Furuta, T Ueda, T Aune, G Sarasin, A Kraemer, KH Pommier, Y AF Furuta, T Ueda, T Aune, G Sarasin, A Kraemer, KH Pommier, Y TI Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells SO CANCER RESEARCH LA English DT Article ID CYCLOBUTANE PYRIMIDINE DIMERS; OVARIAN-CANCER; DNA-DAMAGE; GROUP-C; TRANSFORMATION; CHEMOTHERAPY; MECHANISMS; GENOME; TUMORS AB The resistance of tumor cells to chemotherapeutic agents, such as cisplatin, is an important problem to be solved in cancer chemotherapy. One of the mechanisms associated with cisplatin resistance is nucleotide excision repair (NER). There are two pathways in NER, transcription-coupled NER (TC-NER) and global genome NER (GG-NER). Here, we report that TC-NER-deficient cells [xeroderma pigmentosum group A (XP-A), XP-D, XP-F, XP-G, Cockayne syndrome group A (CS-A), and CS-B] are hypersensitive to cisplatin irrespective of their GG-NER status, and that gene complementation with XPA and XPD increases resistance to cisplatin. By contrast, XP-C cells with selective defect in GG-NER but with normal TC-NER have normal resistance to cisplatin. XPC complementation had no effect on cisplatin antiproliferative activity. We propose that one of the pathways related to cisplatin response is TC-NER, not GG-NER. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Inst Rech Canc, CNRS, UPR 2169, Lab Genet Instabil & Canc, F-94801 Villejuif, France. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 5068A, Bethesda, MD 20892 USA. RI Aune, Gregory/I-5895-2015 OI Aune, Gregory/0000-0002-2750-6461 FU Intramural NIH HHS [Z01 BC004517-31] NR 20 TC 207 Z9 218 U1 2 U2 15 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2002 VL 62 IS 17 BP 4899 EP 4902 PG 4 WC Oncology SC Oncology GA 591TW UT WOS:000177897200011 PM 12208738 ER PT J AU Volk, EL Farley, KM Wu, Y Li, F Robey, RW Schneider, E AF Volk, EL Farley, KM Wu, Y Li, F Robey, RW Schneider, E TI Overexpression of wild-type breast cancer resistance protein mediates methotrexate resistance SO CANCER RESEARCH LA English DT Article ID DIHYDROFOLATE-REDUCTASE GENE; REDUCED FOLATE CARRIER; ABC HALF-TRANSPORTER; CARCINOMA CELL-LINE; PLASMA-MEMBRANE VESICLES; MULTIDRUG-RESISTANCE; ANTIFOLATE RESISTANCE; L1210 CELLS; MITOXANTRONE RESISTANCE; DRUG ACCUMULATION AB Previously, we have reported that a multidrug-resistant, mitoxantrone (MX)-selected cell line, MCF7/MX, is highly cross-resistant to the antifolate methotrexate (MTX), because of enhanced ATP-dependent drug efflux (E. L. Volk et al., Cancer Res., 60: 3514-3521, 2000). These cells overexpress the breast cancer resistance protein (BCRP), and resistance to MTX as well as to MX was reversible by, the BCRP inhibitor, GF120918. These data indicated that BCRP causes the multidrug-resistance phenotype. To further examine the role of this transporter in MTX resistance, and in particular the role of amino acid 482, we analyzed a number of BCRP-overexpressing cell lines. MTX resistance correlated with BCRP expression in all of the cell lines expressing the wild-type transporter, which contains an Arg at position 482. In contrast, little or no cross-resistance was found in the MCF7/AdVp1000 and S1-M1-3.2 and S1-M1-80 cell lines, which contain acquired mutations at this position, R482T and R482G, respectively. Concomitantly, the greatest reduction in MTX accumulation was observed in the MCF7/MX cells (BCRPArg) as compared with cells expressing the Thr and Gly BCRP variants. Furthermore, the reduction in drug accumulation was sensitive to BCRP inhibition by, GF120918. In conclusion, we have demonstrated a novel role for BCRP as a mediator of MTX resistance and have provided further evidence for the importance of amino acid 482 in substrate specificity. C1 New York State Dept Hlth, Wadsworth Ctr, Biggs Labs, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY 12201 USA. SUNY Albany, Dept Biol, Albany, NY 12222 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Schneider, E (reprint author), New York State Dept Hlth, Wadsworth Ctr, Biggs Labs, Empire State Plaza, Albany, NY 12201 USA. FU NCI NIH HHS [CA72455] NR 51 TC 189 Z9 193 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2002 VL 62 IS 17 BP 5035 EP 5040 PG 6 WC Oncology SC Oncology GA 591TW UT WOS:000177897200031 PM 12208758 ER PT J AU Kass, ES Greiner, JW Kantor, JA Tsang, KY Guadagni, F Chen, Z Clark, B De Pascalis, R Schlom, J Van Waes, C AF Kass, ES Greiner, JW Kantor, JA Tsang, KY Guadagni, F Chen, Z Clark, B De Pascalis, R Schlom, J Van Waes, C TI Carcinoembryonic antigen as a target for specific antitumor immunotherapy of head and neck cancer SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; POLYMERASE CHAIN-REACTION; COSTIMULATORY MOLECULES; IMMUNE-RESPONSES; PHASE-I; DIFFERENTIAL EXPRESSION; PRESENTING CELLS; DENDRITIC CELLS; VACCINIA VIRUS; CEA LEVELS AB Human carcinoembryonic antigen (CEA) is an oncofetal glycoprotein overexpression of which by gastrointestinal carcinomas is well known. Expression of CEA in head and neck cancer (HNC) is not widely recognized. It is important to note that most of these studies used polyclonal antibodies that may have cross-reactivity with CEA-related antigens. Currently, CEA is being evaluated in preclinical and clinical studies as a target for specific immunotherapy against gastrointestinal adenocarcinomas that express the antigen. This study was conducted to evaluate CEA as a potential target for specific immunotherapy against HNC. Immunohistochemical analysis of tumor tissue from 69 cases of squamous cell carcinoma (SCC) of the head and neck using a CEA-specific monoclonal antibody (COL-1) showed the majority to be positive for CEA. Tumor cell lines derived from human HNC were screened for CEA transcripts using nested reverse transcription-PCR. Constitutive expression of CEA mRNA was detected in 7 of 10 HNC lines. CEA protein was detectable in lysates from all 7 of the lines by quantitative fluoroimmunometry. SDS-PAGE/Western blot analysis of cell lysates from these lines showed a COL-1 immunoreactive product with a molecular weight equivalent to that of CEA. Cell surface expression of CEA was low for the SCC lines; however, there was moderate to strong cytoplasmic staining intensity for all of the CEA(+) HNC lines by immunocytochemistry. Additional supportive evidence for CEA as a target was demonstrated by the presence of cytolytic activity of an HLA-A2-restricted/CEA-epitope-specific human CTL against a CEA-overexpressing HNC-derived SCC line. These results suggest that CEA may be considered as a possible target for specific vaccine-mediated immunotherapy against HNCs. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Surg Pathol Sect, Pathol Branch, NIH, Bethesda, MD 20892 USA. Regina Elena Inst Canc Res, Clin Pathol Lab, I-00144 Rome, Italy. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 8B09, Bethesda, MD 20892 USA. RI Guadagni, Fiorella/J-4432-2013 OI Guadagni, Fiorella/0000-0003-3652-0457 NR 61 TC 29 Z9 29 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2002 VL 62 IS 17 BP 5049 EP 5057 PG 9 WC Oncology SC Oncology GA 591TW UT WOS:000177897200033 PM 12208760 ER PT J AU Schmitz, J Reali, E Hodge, JW Patel, A Davis, G Schlom, J Greiner, JW AF Schmitz, J Reali, E Hodge, JW Patel, A Davis, G Schlom, J Greiner, JW TI Identification of an interferon-gamma-inducible carcinoembryonic antigen (CEA) CD8(+) T-cell epitope, which mediates tumor killing in CEA transgenic mice SO CANCER RESEARCH LA English DT Article ID RECOMBINANT VACCINIA VIRUS; ALTERED PEPTIDE LIGAND; STIMULATING FACTOR; COLORECTAL-CANCER; IMMUNE-RESPONSES; DNA VACCINE; PHASE-I; INDUCTION; FAS; IMMUNOTHERAPY AB This study describes a CD8(+) T-cell line specific for a MHC class E-restricted carcinoembryonic antigen (CEA) epitope, residues 526-533, isolated from CEA transgenic (CEA.Tg) mice immunized with a recombinant vaccinia-CEA vaccine. Incubation of splenocytes from the immune CEA.Tg mice with the CEA(526-533) peptide resulted in the outgrowth of low-avidity CD8(+) T cells, which produced IFN-gamma and mediated perforin-dependent tumor cell lysis. However, the CEA peptide-specific T cells killed CEA-expressing murine colorectal tumor cells only after pretreatment of the targets with marine IFN-gamma (muIFN-gamma), and lysis A as H-2D(b)-restricted and involved the Fas-FasL-mediated cytotoxic pathway. When the CEA peptide-specific T cells were used as in vivo effectors in adoptive T-cell transfer studies, muIFN-gamma treatment of the CEA.Tg mice was again required for T-cell-dependent growth suppression of CEA-expressing metastatic tumors. The results indicate that (a) vaccination of mice carrying the human CEA gene with recombinant vaccinia-CEA generates CEA epitope-specific, CD8-dependent CTL response, (b) CEA, a normal, tissue-specific antigen, can also serve as a target for antitumor immunity after the adoptive transfer of CEA peptide-specific T cells, and (c) muIFN-gamma might be an effective cancer vaccine adjuvant by virtue of its ability to augment the susceptibility of tumor targets to cell-mediated lysis. C1 NCI, Tumor Immunol & Biol Lab, CCR, NIH, Bethesda, MD 20892 USA. RP Greiner, JW (reprint author), NCI, Tumor Immunol & Biol Lab, CCR, NIH, Bldg 10,Room 8B09, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015; Reali, Eva/Q-1161-2016 OI Hodge, James/0000-0001-5282-3154; Reali, Eva/0000-0003-1900-1356 NR 42 TC 41 Z9 44 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2002 VL 62 IS 17 BP 5058 EP 5064 PG 7 WC Oncology SC Oncology GA 591TW UT WOS:000177897200034 PM 12208761 ER PT J AU Tao, LH Kramer, PM Wang, W Yang, S Lubet, RA Steele, VE Pereira, MA AF Tao, LH Kramer, PM Wang, W Yang, S Lubet, RA Steele, VE Pereira, MA TI Altered expression of c-myc, p16 and p27 in rat colon tumors and its reversal by short-term treatment with chemopreventive agents SO CARCINOGENESIS LA English DT Article ID ABERRANT CRYPT FOCI; FAMILIAL ADENOMATOUS POLYPOSIS; AZOXYMETHANE-INDUCED TUMORS; HUMAN COLORECTAL-CANCER; CELL-PROLIFERATION; DNA METHYLATION; PROGNOSTIC-SIGNIFICANCE; INDUCED REGRESSION; RECTAL ADENOMAS; CARCINOGENESIS AB Modulation of gene expression in tumors has the potential of being a surrogate end-point biomarker for chemoprevention. Thus, we determined the modulation by chemopreventive agents of the protein and mRNA expression of genes in rat colon tumors. Male F344 rats were administered three weekly injections of 15 mg/kg azoxymethane. Forty-seven weeks later, they received aspirin (600), calcium chloride (50 000), 2-(carboxyphenyl) retinamide (2-CPR, 315), alpha-difluoromethylornithine (DFMO, 3000), piroxicam (200), quercetin (33 600), 9-cis retinoic acid (9-cis RA, 30), rutin (3000), or sulindac (280) in their diet at the indicated mg/kg concentration for 7 days and were then killed. In colon tumors relative to the mucosa, the protein and mRNA levels of c-myc were increased, while the levels of p16 and p27 were decreased. Calcium chloride, DFMO, piroxicam and sulindac administered for 7 days decreased the mitotic index and reduced the protein and mRNA levels of c-myc in colon tumors. Calcium chloride, DFMO and piroxicam increased the protein and mRNA levels of p16 and along with sulindac increased the protein level of p27, but not its mRNA. The other agents failed to modulate both the mitotic index and the expression of the genes. The ability of the chemopreventive agents to prevent colon tumors was determined. Male F344 rats were administered three weekly injections of 15 mg/kg azoxymethane and 8 weeks later they were administered aspirin, 2-CPR, DFMO, piroxicam, 9-cis RA and rutin in their diet. The rats were killed 26 weeks after they started to receive the chemopreventive agents. The multiplicity of colon tumors was reduced by DFMO and piroxicam, increased by rutin and not affected by the other agents. Hence, agents that prevented colon cancer decreased the mitotic index and altered the expression of c-myc, p16 and p27 suggesting that modulation in the expression of these genes are potential biomarkers for chemopreventive activity. C1 Med Coll Ohio, Dept Pathol, HEB, Toledo, OH 43614 USA. NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Tao, LH (reprint author), Med Coll Ohio, Dept Pathol, HEB, Rm 202,3055 Arlington Ave, Toledo, OH 43614 USA. FU NCI NIH HHS [N01-CN-05123, N01-CN-75102] NR 43 TC 35 Z9 36 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2002 VL 23 IS 9 BP 1447 EP 1454 DI 10.1093/carcin/23.9.1447 PG 8 WC Oncology SC Oncology GA 586NT UT WOS:000177590600006 PM 12189186 ER PT J AU Rensen, SSM Thijssen, VLJL De Vries, CJ Doevendans, PA Detera-Wadleigh, SD Van Eys, GJJM AF Rensen, SSM Thijssen, VLJL De Vries, CJ Doevendans, PA Detera-Wadleigh, SD Van Eys, GJJM TI Expression of the smoothelin gene is mediated by alternative promoters SO CARDIOVASCULAR RESEARCH LA English DT Article DE contractile apparatus; gene expression; smooth muscle ID PROTEIN SECONDARY STRUCTURE; MUSCLE-CELLS; ACTIN; DIFFERENTIATION; IDENTIFICATION; CYTOSKELETAL; CONTRACTILE; CALPONIN; ISOFORM; FILAMENTS AB Objective: Two major isoforms of smoothelin have been reported, a 59-kDa smoothelin-A in visceral smooth muscle cells and a 110-kDa smoothelin-B in vascular smooth muscle cells. The present study was undertaken to investigate the expression of these smoothelin isoforms in different smooth muscle tissues and to determine how they are generated. Methods: Western blotting with a new, well-defined, smoothelin antibody was used to confirm the existence of two major smoothelin isoforms. Northern blotting, RT-PCR, primer extension and 5'RACE were applied to analyse the expression of these isoforms in human and mouse. Promoter reporter assays were carried out to establish the existence of a dual promoter system governing the expression pattern of the gene. Results: Antibody C6G confirmed the existence of two smoothelin proteins. Northern blotting showed that in vascular tissues a larger smoothelin transcript is generated than in visceral tissue. The cDNA of this larger smoothelin-B was cloned. Computer analysis of the open reading frame suggests an alpha-helical structure of 130 amino acids at the amino terminus of smoothelin-B. The smoothelin gene was cloned and sequenced. It comprises about 25 kb and contains 21 exons. The translational start of smoothelin-B is located in exon 2, whereas transcription and translation of the previously described smoothelin-A starts inside exon 10. Smoothelin-A and -B were demonstrated to be generated by two physically separated promoters. Splice variants within the calponin homology domain at the 3' end of the gene were found for both isoforms. Conclusions: Two major smoothelin isoforms are generated front a single gene by a dual promoter system in a tissue specific manner. Further variation in the smoothelin proteins is achieved by alternative splicing in the calponin homology domain. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Maastricht, Dept Genet & Cell Biol, Mol Genet Sect, NL-6200 MD Maastricht, Netherlands. Univ Amsterdam, Dept Biochem, NL-1066 CX Amsterdam, Netherlands. Univ Maastricht, Dept Cardiol, NL-6200 MD Maastricht, Netherlands. NIDCH, Genet Mol Lab, NIH, Bethesda, MD USA. RP Van Eys, GJJM (reprint author), Univ Maastricht, Dept Genet & Cell Biol, Mol Genet Sect, POB 616, NL-6200 MD Maastricht, Netherlands. RI Thijssen, Victor/B-2792-2009 OI Thijssen, Victor/0000-0002-6146-1842 NR 43 TC 42 Z9 45 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD SEP PY 2002 VL 55 IS 4 BP 850 EP 863 AR PII S0008-6363(02)00491-1 DI 10.1016/S0008-6363(02)00491-1 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 594CW UT WOS:000178032000018 PM 12176134 ER PT J AU Schomerus, C Laedtke, E Olcese, J Weller, JL Klein, DC Korf, HW AF Schomerus, C Laedtke, E Olcese, J Weller, JL Klein, DC Korf, HW TI Signal transduction and regulation of melatonin synthesis in bovine pinealocytes: impact of adrenergic, peptidergic and cholinergic stimuli SO CELL AND TISSUE RESEARCH LA English DT Article DE acetylcholine; arylalkylamine; N-acetyltransferase; biological rhythms; norepinephrine; PACAP; bovine ID SEROTONIN-N-ACETYLTRANSFERASE; CYCLASE-ACTIVATING POLYPEPTIDE; TRANSCRIPTION FACTOR CREB; PROTEIN KINASE-C; RAT PINEALOCYTES; ADENYLATE-CYCLASE; CYCLIC-AMP; PROTEASOMAL PROTEOLYSIS; DEPENDENT MECHANISM; GLAND AB Limited studies of the regulation of pineal melatonin biosynthesis in ungulates indicate that it differs considerably from that in rodents. Here we have investigated several signal transduction cascades and their impact on melatonin synthesis in bovine pinealocytes. Norepinephrine increased the intracellular calcium ion concentration ([Ca(2+)](i)) via alpha(1)-adrenergic receptors. Activation of beta-adrenergic receptors enhanced cAMP accumulation and rapidly elevated arylalkylamine N-acetyl-transferase (AANAT) activity and melatonin secretion. The beta-adrenergically evoked increases in AANAT activity were potentiated by alpha(1)-adrenergic stimulation, but this was not seen with cAMP or melatonin production. PACAP treatment caused small increases in cAMP, AANAT activity and melatonin biosynthesis, apparently in a subpopulation of cells. VIP and glutamate did not influence any of these parameters. Activation of nicotinic and muscarinic acetylcholine receptors increased [Ca(2+)](i), but did not alter cAMP levels, AANAT activity or melatonin production. Our study reveals that discrete differences in pineal signal transduction exist between the cow and rodent, and emphasizes the potential importance that the analysis of ungulate pinealocytes may play in understanding regulation of pineal melatonin biosynthesis in primates and man, whose melatonin-generating system appears to be more similar to that in ungulates than to that in rodents. C1 Univ Frankfurt, Inst Anat 2, Dr Senckenberg Anat, D-60590 Frankfurt, Germany. Univ Hamburg, Inst Hormon & Fortpflanzungsforschung, D-22529 Hamburg, Germany. NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Korf, HW (reprint author), Univ Frankfurt, Inst Anat 2, Dr Senckenberg Anat, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. EM korf@em.uni-frankfurt.de RI Olcese, James/A-6868-2009 NR 57 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD SEP PY 2002 VL 309 IS 3 BP 417 EP 428 DI 10.1007/s00441-002-0588-x PG 12 WC Cell Biology SC Cell Biology GA 595WY UT WOS:000178132600010 PM 12195298 ER PT J AU Camphausen, K AF Camphausen, Kevin TI Judah Folkman The Father of Modern Angiogenesis SO CELL CYCLE LA English DT Editorial Material C1 NCI, Radiat Oncol Branch, Radiat Oncol Sci Program, NIH, Bethesda, MD 20892 USA. RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, Radiat Oncol Sci Program, NIH, Bldg 10, Bethesda, MD 20892 USA. EM camphauk@mail.nih.gov NR 0 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD SEP-OCT PY 2002 VL 1 IS 5 BP 296 EP 297 DI 10.4161/cc.1.5.140 PG 2 WC Cell Biology SC Cell Biology GA V40PZ UT WOS:000209491800001 PM 12461285 ER PT J AU Brognard, J Dennis, PA AF Brognard, J Dennis, PA TI Variable apoptotic response of NSCLC cells to inhibition of the MEK/ERK pathway by small molecules or dominant negative mutants SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE ERK; kinase; apoptosis; chemotherapy; lung cancer ID ACTIVATED PROTEIN-KINASE; SIGNALING PATHWAY; CANCER; IDENTIFICATION; SURVIVAL; BLOCKADE; RECEPTOR; RAS; CYCLOOXYGENASE-2; PHOSPHORYLATION AB To evaluate the role of the MEK/ERK pathway in NSCLC survival, we analyzed NSCLC cell lines that differed in tumor histology and status of p53, Rb, and K-ras. Constitutive ERK1/2 activity was demonstrated in 17 of 19 cell lines by maintenance of ERK1/2 phosphorylation with serum deprivation. Phosphorylation of ERK1/2 correlated with phosphorylation of MEK1/2 and p90RSK, but was inversely correlated with phosphorylation of c-Raf at S259. With serum deprivation, the MEK inhibitors, PD98059 and U0126, inhibited ERK1/2 activity but did not increase apoptosis. PD98059 and U0126 induced cell cycle arrest in G(o)/G(i) in cells with the highest levels of ERK1/2 activity, which correlated with induction of p27 but not p21. To confirm the cytostatic response to MEK inhibitors, we performed transient transfections with dominant negative forms of MEK or ERK. Surprisingly, dominant negative MEK and ERK mutants increased apoptosis without affecting cell cycle or p27 levels. When combined with paclitaxel, MEK inhibitors had no effect on apoptosis. In contrast, dominant negative ERK2 potentiated paclitaxel-induced apoptosis. Our studies show that constitutive ERK1/2 activity in NSCLC cells promotes cellular survival and chemotherapeutic resistance. Moreover, our data are the first to demonstrate divergent cellular responses to inhibition of the MEK/ERK pathway by small molecule inhibitors or dominant negative mutants. C1 USN Med Oncol, NCI, Natl Naval Med Ctr, Bethesda, MD 20889 USA. NCI, Ctr Canc Res, Canc Therapeut Branch, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), USN Med Oncol, NCI, Natl Naval Med Ctr, Bldg 8,Rm 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 33 TC 68 Z9 70 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD SEP PY 2002 VL 9 IS 9 BP 893 EP 904 DI 10.1038/sj.cdd.4401054 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 586KN UT WOS:000177583300005 PM 12181740 ER PT J AU Kammouni, W Ramakrishna, G Sithanandam, G Smith, GT Fornwald, LW Masuda, A Takahashi, T Anderson, LM AF Kammouni, W Ramakrishna, G Sithanandam, G Smith, GT Fornwald, LW Masuda, A Takahashi, T Anderson, LM TI Increased K-ras protein and activity in mouse and human lung epithelial cells at confluence SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID GROWTH-FACTOR-II; FACTOR-BETA-RECEPTOR; HEPATOCYTE GROWTH; GENE-EXPRESSION; TUMOR SUPPRESSION; CARCINOMA CELLS; ACTIVATE RAF-1; UP-REGULATION; HUMAN CANCER; IGF-II AB Although K-ras is frequently mutated in lung adenocarcinomas, the normal function of K-ras p21 in lung is not known. In two mouse (E10 and C10) and one human (HPL1D) immortalized lung cell lines from peripheral epithelium, we have measured total K-ras p21 and active K-ras p21-GTP during cell proliferation and at growth arrest caused by confluence. In all three cell types, total K-ras p21 increased 2- to 4-fold at confluence, and active K-ras p21-GTP increased 10- to 200-fold. It was estimated that 0.03% of total K-ras p21 was in the active GTP-bound state at 50% confluence, compared with 1.4% at postconfluence. By contrast, stimulation of proliferation by serum-containing medium did not involve K-ras p21 activation, even though a rapid, marked activation of both Erk1/2 and Akt occurred. At confluence, large increases, up to 14-fold, were seen in Grb2/Sos1 complexes, which may activate K-ras p21. In sum, increased protein expression and activity of K-ras p21 are associated with growth arrest, not with proliferation, in mouse and human lung cell lines. C1 Natl Canc Inst Frederick, Lab Comparat Carcinogenesis, Ft Detrick, MD 21702 USA. SAIC Frederick Inc, Ft Detrick, MD 21702 USA. Aichi Canc Ctr, Res Inst, Div Mol Oncol, Nagoya, Aichi 4648681, Japan. RP Anderson, LM (reprint author), Natl Canc Inst Frederick, Lab Comparat Carcinogenesis, Bldg 538,Rm 205B, Ft Detrick, MD 21702 USA. RI Takahashi, Takashi/I-7262-2014 NR 67 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD SEP PY 2002 VL 13 IS 9 BP 441 EP 448 PG 8 WC Cell Biology SC Cell Biology GA 600FB UT WOS:000178379000005 PM 12354753 ER PT J AU Li, WP Pretner, E Shen, LY Drieu, K Papadopoulos, V AF Li, WP Pretner, E Shen, LY Drieu, K Papadopoulos, V TI Common gene targets of Ginkgo biloba extract (EGb 761) in human tumor cells: Relation to cell growth SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE gene expression; gene arrays; Ginkgo biloba; ginkgolide; breast; brain; liver cancer ID BENZODIAZEPINE-BINDING-SITES; HUMAN BREAST-CANCER; NF-KAPPA-B; PERIPHERAL BENZODIAZEPINE; COLONIC ADENOCARCINOMA; EXPRESSION ARRAYS; RECEPTOR LIGANDS; VIVO REGULATION; DNA-SYNTHESIS; PROLIFERATION AB The standardized extract of Ginkgo biloba leaves (EGb 761) has been shown to inhibit aggressive human breast cancer cell proliferation both in vitro and in vivo. These results were extended to human glioma and hepatoma cells in vitro suggesting that EGb 761 may have a more widespread application for tumor growth control. To understand the mechanism by which EGb 761 acts to inhibit cell proliferation, we investigated the effects of EGb 761 on human breast cancer, glioma and hepatoma cell transcriptomes by means of various large-scale DNA array techniques. The data presented focus on genes regulated by EGb 761 that are common to the three tumor cell types and for which the data were verified by two different types of DNA microarray and/or RNA (Northern) blot analysis and real-time quantitative PCR. These results could therefore help elucidate the mechanism of cytostatic action of EGb 761 and identify genes important for tumor growth. C1 Georgetown Univ, Med Ctr, Dept Cell Biol, Div Hormone Res, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Dept Pharmacol, Div Hormone Res, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Dept Neurosci, Div Hormone Res, Washington, DC 20057 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Inst Henri Beaufour Ipsen, Paris, France. RP Papadopoulos, V (reprint author), Georgetown Univ, Med Ctr, Dept Cell Biol, Div Hormone Res, Washington, DC 20057 USA. OI Papadopoulos, Vassilios/0000-0002-1183-8568 FU NCCIH NIH HHS [AT00359] NR 50 TC 15 Z9 16 U1 0 U2 1 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD SEP PY 2002 VL 48 IS 6 BP 655 EP 662 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 603HV UT WOS:000178554000009 PM 12396076 ER PT J AU Rajnavolgyi, E Benbernou, N Rethi, B Reynolds, D Young, HA Magocsi, M Muegge, K Durum, SK AF Rajnavolgyi, E Benbernou, N Rethi, B Reynolds, D Young, HA Magocsi, M Muegge, K Durum, SK TI IL-7 withdrawal induces a stress pathway activating p38 and Jun N-terminal kinases SO CELLULAR SIGNALLING LA English DT Article DE apoptosis; cell death; interlukin-7; jun; fos; MAP kinase; lymphocyte; stress ID RECEPTOR-DEFICIENT MICE; C-JUN; PROTEIN-KINASE; INTERLEUKIN-7 RECEPTOR; SIGNAL-TRANSDUCTION; T-CELLS; IN-VIVO; LYMPHOCYTE DEVELOPMENT; MURINE INTERLEUKIN-7; LOCUS ACCESSIBILITY AB IL-7 delivers survival signals to cells at an early stage in lymphoid development. In the absence of IL-7, pro-T cells undergo programmed cell death, which has previously been associated with a decline in Bcl-2 and translocation of Bax from cytosol to mitochondria. A new, earlier feature of IL-7 withdrawal was identified using an IL-7-dependent thymocyte line. We observed that withdrawal of IL-7 induced increased expression of jun and fos family member genes including c-jun, junB, junD, c-fos and fra2. This transient response peaked 3-4 h after IL-7 was withdrawn and resulted in increased DNA-binding activity of AP-1 and in a change in the composition of the Jun/Fos family dimers, shown by electrophoretic mobility shift and supershift assays. Induction of jun and fos genes and the increased DNA-binding activity of AP-1 were attributable to the phosphorylation-induced activation of the stress kinases p38 and JNK and were blocked by the chemical kinase inhibitors SB203580 and SB202190. The stress response contributed to cell death following IL-7 withdrawal as shown by blocking the activity of the stress (MAP) kinases or by blocking the production of c-Jun and c-Fos using antisense oligonucleotides. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Eotvos Lorand Univ, God, Hungary. Sci Applicat Int Corp, Frederick, MD USA. NCI, Expt Immunol Lab, Frederick, MD 21702 USA. Natl Inst Haematol & Immunol, Dept Isotope & Membrane Diagnost, Budapest, Hungary. RP Durum, SK (reprint author), NCI, Mol Immunoregulat Lab, Bldg 560,Room 31-71, Frederick, MD 21702 USA. EM durums@mail.ncifcrf.gov RI Rethi, Bence/C-5770-2013; Rajnavolgyi, Eva/D-4384-2013 OI Rethi, Bence/0000-0001-8220-5015; NR 60 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD SEP PY 2002 VL 14 IS 9 BP 761 EP 769 AR PII S0898-6568(02)00026-8 DI 10.1016/S0898-6568(02)00026-8 PG 9 WC Cell Biology SC Cell Biology GA 570KW UT WOS:000176658300005 PM 12034357 ER PT J AU O'Donnell, P Lewis, BL Weinberger, DR Lipska, BK AF O'Donnell, P Lewis, BL Weinberger, DR Lipska, BK TI Neonatal hippocampal damage alters electrophysiological properties of prefrontal cortical neurons in adult rats SO CEREBRAL CORTEX LA English DT Article ID VENTRAL TEGMENTAL AREA; D-1 DOPAMINE-RECEPTORS; NUCLEUS-ACCUMBENS; PYRAMIDAL NEURONS; IN-VIVO; STRIATAL DOPAMINE; SCHIZOPHRENIA; CORTEX; AFFERENTS; LESIONS AB A neonatal excitotoxic lesion of the ventral hippocampus in the rat produces a variety of behavioral and cellular changes that remain latent until early adulthood. These delayed effects resemble many phenomena observed in schizophrenia, a neuropsychiatric disorder of early adult onset in which abnormal development of the hippo-campus and prefrontal cortex has been postulated. Here we investigated the impact of this neonatal hippocampal lesion on the response of medial prefrontal cortical pyramidal neurons to specific afferent stimulation. Neonatal hippocampal damage altered the physiological responses of these neurons to electrical stimulation of midbrain dopaminergic-GABAergic projections, but not thalamic glutamatergic afferents. The lesion resulted in excessive firing of pyramidal neurons in response to mesocortical stimulation and this effect was not observed before adulthood or after similar hippocampal damage produced in adult rats. These data show that neonatal damage to the ventral hippocampus changes, in a developmentally specific manner, the nature of prefrontal cortical neuron responses to activation of projections from the ventral tegmental area, an effect that may explain the adverse impact of stress in schizophrenia. C1 Albany Med Coll, Ctr Neuropharmacol & Neurosci, Albany, NY 12208 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP O'Donnell, P (reprint author), Albany Med Coll MC136, Ctr Neuropharmacol & Neurosci, 47 New Scotland Ave, Albany, NY 12208 USA. RI Lipska, Barbara/E-4569-2017 FU NIMH NIH HHS [MH60131, MH57683] NR 47 TC 119 Z9 125 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2002 VL 12 IS 9 BP 975 EP 982 DI 10.1093/cercor/12.9.975 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 585CF UT WOS:000177505000009 PM 12183396 ER PT J AU Bertolino, A Roffman, JL Lipska, BK van Gelderen, P Olson, A Weinberger, DR AF Bertolino, A Roffman, JL Lipska, BK van Gelderen, P Olson, A Weinberger, DR TI Reduced N-Acetylaspartate in prefrontal cortex of adult rats with neonatal hippocampal damage SO CEREBRAL CORTEX LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; IN-VIVO; SCHIZOPHRENIC-PATIENTS; TEMPORAL-LOBE; METABOLITE CONCENTRATIONS; GLUTAMATE TRANSPORTER; EXCITOTOXIC LESIONS; STRIATAL DOPAMINE; HUMAN BRAIN; AMPHETAMINE AB Previous studies in animals suggested that neonatal lesions of the ventral hippocampus disrupt development of prefrontal cortex and its regulation of dopaminergic activity. In the present study, we assayed an in vivo chemical marker of neuronal integrity (proton magnetic resonance spectroscopy signal of N-acetylaspartate, NAA) in prefrontal cortex and striatum of rats with neonatal excitotoxic lesions of the ventral hippocampus. We also measured in post-mortem tissue expression of EAAC1 mRNA, a molecular marker of intrinsic neurons. In the cohort studied at juvenile age and again at young adulthood [postnatal day (PD) 37 and 71], we found selective reductions of NAA in the prefrontal cortex only at PD 71. Emergence of neuronal pathology was temporally associated with emergence of amphetamine-induced hyperlocomotion. Reduced prefrontal NAA was confirmed in the second cohort studied at an older age (PD 120). Expression of EAAC1 mRNA was significantly reduced in prefrontal cortex of the lesioned rats. No changes in NAA were found in the striatum in either cohort and cortical area size was not changed. These results suggest that early ventral hippocampal lesions produce developmental neuronal pathology in prefrontal cortex that is temporally associated with dysregulation of dopamine behaviors and is reminiscent of the temporal profile of the onset of schizophrenia. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. HHMI NIH Res Scholars Program, Bethesda, MD 20892 USA. NINDS, In Vivo NMR Ctr, NIH, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, 10 Ctr Dr,Room 4S235,MSC 1379, Bethesda, MD 20892 USA. EM weinberd@intra.nimh.nih.gov RI Bertolino, Alessandro/O-6352-2016 OI Bertolino, Alessandro/0000-0002-1251-1380 NR 65 TC 41 Z9 42 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2002 VL 12 IS 9 BP 983 EP 990 DI 10.1093/cercor/12.9.983 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 585CF UT WOS:000177505000010 PM 12183397 ER PT J AU Buters, JTM Mahadevan, B Quintanilla-Martinez, L Gonzalez, FJ Greim, H Baird, WM Luch, A AF Buters, JTM Mahadevan, B Quintanilla-Martinez, L Gonzalez, FJ Greim, H Baird, WM Luch, A TI Cytochrome p450 1B1 determines susceptibility to dibenzo[a,l]pyrene-induced tumor formation SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; CHINESE-HAMSTER CELLS; POTENT CARCINOGEN DIBENZOPYRENE; DNA ADDUCT FORMATION; RAT MAMMARY-GLAND; REGION 11,12-DIOL 13,14-EPOXIDES; GENE KNOCKOUT MICE; METABOLIC-ACTIVATION; FJORD-REGION; MOUSE SKIN AB Metabolic activation, DNA binding, and tumorigenicity of the carcinogenic polycyclic aromatic hydrocarbon dibenzo[a,l]pyrene (DB[a,l]P) catalyzed by murine cytochrome P450 (P450) enzymes were investigated. DNA binding of DB [a,l] P in human mammary carcinoma MCF-7 and human P450-expressing Chinese hamster V79 cell lines was previously shown to occur preferentially with metabolically generated fjord region DB[a,l]P-11,12-dihydrodiol 13,14-epoxides (DB[a,l]PDE). To elucidate different capabilities of murine P450 1A1 and 1B1 for metabolic activation of DB[a,l]P, V79 cell cultures stably expressing P450s 1A1 or 1B1 from mice were exposed to 10 or 100 nM DB[a,l]P. Both cell lines transformed DB[a,l]P to DNA binding intermediates. As with V79 cells expressing the corresponding human P450 enzyme [Luch et al. (1998) Chem. Res. Toxicol. 11, 686-695], murine P450 1B1-catalyzed metabolism and DNA binding proceeded exclusively through generation of fjord region DB[a,l]PDE. In addition, only DB [a,l] PDE-derived DNA adducts were found in V79 cells expressing P450 1A1 from mice. This is in contrast to our recent findings with V79 cells expressing P450 1A1 from humans or rats which catalyzed the formation of both highly polar DNA adducts as well as nonpolar DB[a,l]PDE-DNA adducts. To establish the role of P450 1B1 in DB[a,l]P-induced tumor formation in vivo, we treated P450 1B1-null and wild-type mice intragastrically and monitored survival rates and appearance of neoplasias in various organs. All wild-type mice (n = 17) used in this study developed at least one tumor at one site (tumor rate of 100%). In contrast, 5 of 13 P450 1B1-null mice were observed to be free from any tumor (tumor rate of 62%). The organ sites of tumor formation and the dignity of tumors were different between wild-type and P450 1B1-null mice. Wild-type mice were diagnosed with both benign and malignant tumors of the ovaries, lymphoid tissues, as well as with skin and endometrial hyperplasias, whereas P450 1B1-null mice developed only lung adenomas and endometrial hyperplasias. DNA binding studies using embryonic fibroblasts isolated from these animals provided further evidence that P450 1B1-catalyzed formation of fjord region DB[a,l]PDE-DNA adducts is the critical step in DB[a,l]P-mediated carcinogenesis in mice, and probably also in man. C1 Tech Univ Munich, Inst Toxikol & Umwelthyg, D-80636 Munich, Germany. GSF Forschungszentrum Umwelt & Gesundheit, Inst Pathol, D-85764 Oberschleissheim, Germany. Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. NCI, Div Basic Sci, Lab Metab, Bethesda, MD 20892 USA. RP Buters, JTM (reprint author), Tech Univ Munich, Ctr Allergy & Environm Munich, Biedersteinerstr 29, D-80802 Munich, Germany. RI Buters, Jeroen/G-5070-2011 FU NCI NIH HHS [CA28825, CA40228] NR 83 TC 67 Z9 70 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP PY 2002 VL 15 IS 9 BP 1127 EP 1135 DI 10.1021/tx020017q PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 595CN UT WOS:000178089400003 PM 12230405 ER PT J AU Lamb, ME Chuang, SS Wessels, H Broberg, AG Hwang, CP AF Lamb, ME Chuang, SS Wessels, H Broberg, AG Hwang, CP TI Emergence and construct validation of the big five factors in early childhood: A longitudinal analysis of their ontogeny in Sweden SO CHILD DEVELOPMENT LA English DT Article ID 5-FACTOR MODEL; PERSONALITY-DISORDERS; DIMENSIONS AB Researchers have shown that the five major dimensions of personality (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience) and two additional factors (irritability and positive activity) are evident from adolescence. This study attempted to replicate and extend these results in a longitudinal study of 102 Swedish children, followed from 2.3 to 15.2 years of age. Item analyses revealed consistently reliable irritability, conscientiousness, and positive activity factors, whereas the internal reliability of the extraversion, agreeableness, neuroticism, and openness to experience factors increased over time. Irritability and positive activity were not independent of the other factors. Scores on most of the personality factors were fairly stable over time. Over time, children became less extraverted, more agreeable, and more conscientious. Neuroticism and openness to experience increased in Phase III, although openness then decreased in Phase V. Validity of the original factors was demonstrated by correlations with independent assessments of the children's cognitive performance and adjustment to school. C1 NICHD, Sect Social & Emot Dev, Rockledge Ctr 1, Bethesda, MD 20892 USA. Univ Gothenburg, Gothenburg, Sweden. RP Lamb, ME (reprint author), NICHD, Sect Social & Emot Dev, Rockledge Ctr 1, Suite 8048,6705 Rockledge Dr, Bethesda, MD 20892 USA. NR 31 TC 58 Z9 59 U1 1 U2 7 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0009-3920 J9 CHILD DEV JI Child Dev. PD SEP-OCT PY 2002 VL 73 IS 5 BP 1517 EP 1524 DI 10.1111/1467-8624.00487 PG 8 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 598RX UT WOS:000178291200014 PM 12361316 ER PT J AU Alvarez, RD Huh, WK Khazaeli, MB Meredith, RF Partridge, EE Kilgore, LC Grizzle, WE Shen, S Austin, JM Barnes, MN Carey, D Schlom, J LoBuglio, AF AF Alvarez, RD Huh, WK Khazaeli, MB Meredith, RF Partridge, EE Kilgore, LC Grizzle, WE Shen, S Austin, JM Barnes, MN Carey, D Schlom, J LoBuglio, AF TI A phase I study of combined modality (90)Yttrium-CC49 intraperitoneal radioimmunotherapy for ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY CC49; CARCINOMA; ANTIGEN AB Purpose: The purpose of this study was to determine the feasibility and maximum tolerated dose of (90)Yttrium-CC49 (Y-90-CC49) as the radioimmunotherapy (RIT) component of an i.p. combined modality treatment for recurrent ovarian cancer. Experimental Design: A Phase I trial of Y-90-CC49 RIT was conducted in ovarian cancer patients who had persistent or recurrent intra-abdominal disease, had failed one or two prior chemotherapy regimens, and demonstrated TAG-72 expression. Patients were treated with a previously established combined modality treatment protocol of s.c. IFN alpha2b, i.p. paclitaxel, and increasing dosages of i.p. Y-90-CC49. Patients were monitored for toxicity, generation of human antimouse antibody response, and clinical efficacy. Results: Twenty eligible patients were treated per study specifications. All patients had been treated with debulking and paclitaxel/carboplatin-based chemotherapy at initial diagnosis. The patients included 11 patients with persistent disease at the time of second look laparotomy and 9 patients with delayed recurrence. Patients were treated with i.p. Y-90-CC49 given in combination with s.c. IFN alpha2b (dose of 3 x 10(6) units for a total of four doses) and i.p. paclitaxel (dose of 100 mg/m(2)). RIT treatment was associated with primarily hematological toxicity. The maximum tolerated dose of i.p. Y-90-CC49 was established at 24.2 MCi/m(2) in this combined regimen. Of nine patients with measurable disease, two had partial responses lasting 2 and 4 months. Of 11 patients with nonmeasurable disease, median time to progression was 6 months in 7 patients who recurred; 4 of these patients remain no evidence of disease at 9+, 18+, 19+, and 23+ months. Conclusions: (90)Yttrium-CC49-based RIT in combination with IFN alpha2b and i.p. paclitaxel is feasible and well tolerated at a dose of less than or equal to24.2 mCi/m(2). C1 Univ Alabama, Ctr Canc, Dept Obstet & Gynecol, Div Gynecol Oncol, Birmingham, AL 35233 USA. Univ Alabama, Ctr Canc, Dept Radiat Oncol, Birmingham, AL 35233 USA. Univ Alabama, Ctr Canc, Dept Pathol, Birmingham, AL 35233 USA. Univ Alabama, Ctr Canc, Dept Biostat, Birmingham, AL 35233 USA. Univ Alabama, Ctr Canc, Dept Med, Birmingham, AL 35233 USA. NCI, Bethesda, MD 20892 USA. RP Alvarez, RD (reprint author), Univ Alabama, Ctr Canc, Dept Obstet & Gynecol, Div Gynecol Oncol, 618 20th St S,OHB Room 538, Birmingham, AL 35233 USA. FU NCI NIH HHS [CM 87215, 1R01 CA OD6782801]; NCRR NIH HHS [M01 RR00032] NR 20 TC 68 Z9 69 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 2002 VL 8 IS 9 BP 2806 EP 2811 PG 6 WC Oncology SC Oncology GA 593JU UT WOS:000177988700009 PM 12231520 ER PT J AU Grove, AD Prabhu, VV Young, BL Lee, FC Kulpa, V Munson, PJ Kohn, EC AF Grove, AD Prabhu, VV Young, BL Lee, FC Kulpa, V Munson, PJ Kohn, EC TI Both protein activation and gene expression are involved in early vascular tube formation in vitro SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOGENOUS ESTROGEN METABOLITE; ENDOTHELIAL-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; INHIBITS ANGIOGENESIS; SIGNAL-TRANSDUCTION; TUMOR ANGIOGENESIS; IV COLLAGEN; CALDESMON; KINASE; PATHWAY AB Purpose: Gene expression and protein translation regulate and direct endothelial cell proliferation and differentiation. We initiated an unbiased global search for transcriptional changes occurring during endothelial cell vascular differentiation in vitro, focusing on genes not previously implicated in vascularization and angiogenesis. Experimental Design: cDNA and protein from human umbilical vein endothelial cells forming vascular tubes on the basement membrane surrogate, Matrigel, were collected and subjected to a global unbiased search for alterations in expression of genes not previously linked to angiogenesis. Results: Transcriptional inhibitors blocked vascular tube formation only when present within the first hour of incubation (P < 0.05). cDNA array analysis yielded 31 differentially regulated transcripts (of 5100 queried; false positive rate, 0.4%) from gene classes representing transcription, translational regulation, cell structure, and cell adhesion. mRNA levels of caldesmon, a cytoskeleton-associated protein not previously linked to angiogenesis, were markedly reduced during early tube formation. Caldesmon protein quantity was also markedly decreased as demonstrated by laser capture microdissection of tubule cells followed by immunoblotting. Strikingly, no significant changes in transcription of genes previously demonstrated to contribute to angiogenesis, invasion, or signal transduction contained on the array were observed. To investigate the possibility that posttranslational rather than transcriptional changes were involved in facilitating tube formation, we evaluated the activation status of two dominant signal pathways, RAS/mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT. A net 3-fold reduction in phospho-AKT and a 4-fold reduction in phospho-extracellular signal-regulated kinase-1/2 occurred in a transcription-independent fashion. Conclusions: These data suggest that both changes in gene expression and transcription-independent activation of signal transduction pathways may be involved in vascular tube formation. A combination of transcriptional and proteomic analysis has the potential to identify novel transcription-dependent and -independent molecular targets of angiogenesis. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), NCI, Pathol Lab, 10 Ctr Dr,MSC 1500,Bldg 10,Room 2A33, Bethesda, MD 20892 USA. NR 36 TC 21 Z9 22 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 2002 VL 8 IS 9 BP 3019 EP 3026 PG 8 WC Oncology SC Oncology GA 593JU UT WOS:000177988700038 PM 12231549 ER PT J AU Star, R Hostetter, T Hortin, GL AF Star, R Hostetter, T Hortin, GL TI New markers for kidney disease SO CLINICAL CHEMISTRY LA English DT Editorial Material ID RENAL-FUNCTION; SERUM C1 NIH, Dept Lab Med, Warren Magnusen Clin Ctr, Bethesda, MD 20892 USA. NIDDKD, Renal Diagnost & Therapeut Unit, Bethesda, MD 20892 USA. NIDDKD, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Dept Lab Med, Warren Magnusen Clin Ctr, Bldg 10,Room 2C-407,10 Ctr Dr, Bethesda, MD 20892 USA. NR 17 TC 24 Z9 32 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2002 VL 48 IS 9 BP 1375 EP 1376 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 586WF UT WOS:000177608600001 PM 12194910 ER PT J AU Kim, I Barnes, AJ Oyler, JM Schepers, R Joseph, RE Cone, EJ Lafko, D Moolchan, ET Huestis, MA AF Kim, I Barnes, AJ Oyler, JM Schepers, R Joseph, RE Cone, EJ Lafko, D Moolchan, ET Huestis, MA TI Plasma and oral fluid pharmacokinetics and pharmacodynamics after oral codeine administration SO CLINICAL CHEMISTRY LA English DT Article ID HUMAN-HAIR; HEALTHY-VOLUNTEERS; SALIVA; ABUSE; DRUGS; SINGLE; DISPOSITION; METABOLITES; HYDROXYLATORS; DEBRISOQUINE AB Background. The ease, noninvasiveness, and safety of oral fluid collection have increased the use of this alternative matrix for drugs-of-abuse testing; however, few controlled drug administration data are available to aid in the interpretation of oral fluid results. Methods: Single oral codeine doses (60 and 120 mg/70 kg) were administered to 19 volunteers. Oral fluid and plasma were analyzed for free codeine, norcodeine, morphine, and normorphine by solid-phase extraction combined with gas chromatography-mass spectrometry (SPE/GC-MS). Physiologic and subjective effects were examined. Results: Mean (SE) peak codeine concentrations were 214.2 +/- 27.6 and 474.3 +/- 77.0 mug/L in plasma and 638.4 +/- 64.4 and 1599.3 +/- 241.0 1 mug/L in oral fluid. The oral fluid-to-plasma ratio for codeine was relatively constant (similar to4) from 1 to 12 h. The mean half-life (t(1/2),) of codeine was 2.2 +/- 0.10 h in plasma and 2.2 +/- 0.16 h in oral fluid. Significant dose-related miosis and increases in sedation, psychotomimetic effect, and "high" occurred after the high dose. Mean codeine oral fluid detection time was 21 h with a 2.5 mug/l, cutoff, longer than that of plasma (12-16 K Detection times with the proposed Substance Abuse and Mental Health Services Administration cutoff (40 mug/L) were only 7 h. Norcodeine, but not morphine or normorphine, was quantified in both plasma and oral fluid. Conclusions: The disposition of codeine over time was similar in plasma and oral fluid, but because of high variability, oral fluid codeine concentrations did not reliably predict concurrent plasma concentrations. Oral fluid testing is a useful alternative matrix for monitoring codeine exposure with a detection window of 7-21 h for single doses, depending on cutoff concentrations. These controlled drug administration data should aid in the interpretation of oral fluid codeine results. (C) 2002 American Association for Clinical Chemistry. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Amgen Inc, Clin Affairs, Thousand Oaks, CA 91320 USA. ConeChem Res, Severna Pk, MD 21146 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 41 TC 57 Z9 59 U1 1 U2 11 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2002 VL 48 IS 9 BP 1486 EP 1496 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 586WF UT WOS:000177608600016 PM 12194925 ER PT J AU Xu, K Lipsky, RH Mangal, W Ferro, E Goldman, D AF Xu, K Lipsky, RH Mangal, W Ferro, E Goldman, D TI Single-nucleotide polymorphism allele frequencies determined by quantitative kinetic assay of pooled DNA SO CLINICAL CHEMISTRY LA English DT Letter ID LINKAGE DISEQUILIBRIUM; SAMPLES; DISEASE; ASSOCIATION; GENOME; GENES; LOCI; PCR C1 NIAAA, Neurogenet Lab, DICBR, NIH, Rockville, MD 20850 USA. RP Xu, K (reprint author), NIAAA, Neurogenet Lab, DICBR, NIH, 12420 Parklawn Dr,Pk 5 Bldg,Room 451,MSC 8110, Rockville, MD 20850 USA. RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lipsky, Robert/0000-0001-7753-1473 NR 16 TC 11 Z9 11 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2002 VL 48 IS 9 BP 1605 EP 1608 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 586WF UT WOS:000177608600039 PM 12194948 ER PT J AU Kumwenda, N Miotti, PG Taha, TE Broadhead, R Biggar, RJ Jackson, JB Melikian, G Semba, RD AF Kumwenda, N Miotti, PG Taha, TE Broadhead, R Biggar, RJ Jackson, JB Melikian, G Semba, RD TI Antenatal vitamin A supplementation increases birth weight and decreases anemia among infants born to human immunodeficiency virus-infected women in Malawi SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID TO-CHILD TRANSMISSION; BETA-CAROTENE SUPPLEMENTATION; RANDOMIZED TRIAL; A-DEFICIENCY; HIV-1 TRANSMISSION; VERTICAL TRANSMISSION; PREGNANCY OUTCOMES; GROWTH FAILURE; MORTALITY; ZIDOVUDINE AB Vitamin A is essential for immunity and growth. A controlled clinical that involved 697 human immunodeficiency virus (HIV)-infected pregnant women was conducted to determine whether vitamin A prevents anemia, low birth weight, growth failure, HIV transmission, and mortality. Women received daily doses of iron and folate, either alone or combined with vitamin A (3 mg retinol equivalent), from 18-28 weeks' gestation until delivery. In the vitamin A and control groups, respectively, the mean ( SE) birth weights were g 2895 +/- 31 g and 2805 +/- 32 g (P = .05), the proportions of low-birth-weight infants were 14.0% and 21.1% (P = .03), the proportions of anemic infants at 6 weeks postpartum were 23.4% and 40.6% (P < .001), and the respective cumulative proportions of infants who were HIV infected at 6 weeks and 24 months of age were 26.6% and 27.8% (P = .76) and 27.7% and 32.8% (P = .21). Receipt of vitamin A improved birth weight and neonatal growth and reduced anemia, but it did not affect perinatal HIV transmission. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol & Ophthalmol, Baltimore, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Pathol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIAID, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Univ Malawi, Coll Med, Dept Paediat & Child Hlth, Blantyre, Malawi. RP Semba, RD (reprint author), 550 N Broadway,Ste 700, Baltimore, MD 21205 USA. FU NIAID NIH HHS [AI-35173-117]; NICHD NIH HHS [HD-30042, HD-32247] NR 36 TC 75 Z9 77 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2002 VL 35 IS 5 BP 618 EP 624 DI 10.1086/342297 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 583VJ UT WOS:000177431000019 PM 12173139 ER PT J AU Lunning, MA Stetler-Stevenson, M Silberstein, PT Zenger, V Marti, GE AF Lunning, MA Stetler-Stevenson, M Silberstein, PT Zenger, V Marti, GE TI Spontaneous (pathological) splenic rupture in a blastic variant of mantle cell lymphoma: A case report and literature review SO CLINICAL LYMPHOMA LA English DT Article DE blastic transformation; chronic lymphocytic leukemia; splenomegaly; splenic infarct; cyclin D1 ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; INITIAL MANIFESTATION; SPLEEN; PHASE AB Spontaneous (pathological) splenic rupture (SPSR) in hematological malignancies is rare. This report describes a 71-year-old male diagnosed with mantle cell lymphoma-blastic variant (MCL-BV) who experienced an SPSR a few days before the initial diagnosis. The patient underwent a splenectomy and recovered without incident. Partial remission was seen following several cycles of CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone). However, relapse was rapid, with leukemic meningitis occurring several months later. It was successfully treated by intrathecal methotrexate and cranial spinal radiation. A progressive lymphocytosis developed, which responded to rituximab. Lymphadenopathy and skin involvement ensued, followed by pneumonia and death. The literature on SPSR in patients with MCL-BV and other lymphoproliferative disorders showed similar clinical and postoperative findings. Clinical presentation included Kehr's sign and acute abdominal pain. Postoperative findings included blood in the peritoneal cavity, multiple splenic hematomas, splenic infarcts, and splenic necrosis. Most strikingly, the majority of the patients reviewed appeared to have undergone some type of blastic transformation. One or any combination of these findings that has been noted above in addition to a bleeding diathesis could be the foundation to SPSR. We recommend consideration of splenic rupture in patients with a lymphoproliferative disorder coupled with rapid progression of marked or massive splenomegaly. C1 US FDA, CBER,Flow & Image Cytometry Sect, Lab Stem Cell Biol, Div Cell & Gene Therapies,NIH, Bethesda, MD 20892 USA. Mercy Canc Ctr, Mason City, IA USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), US FDA, CBER,Flow & Image Cytometry Sect, Lab Stem Cell Biol,, Div Cell & Gene Therapies,NIH, Bldg 29B,Room 2,NN08 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 31 TC 4 Z9 4 U1 1 U2 2 PU CANCER INFORMATION GROUP, LP PI DALLAS PA 3535 WORTH ST, SAMMONS TOWER, STE 4802, DALLAS, TX 75246 USA SN 1526-9655 J9 CLIN LYMPHOMA JI Clin. Lymphoma PD SEP PY 2002 VL 3 IS 2 BP 117 EP 120 DI 10.3816/CLM.2002.n.018 PG 4 WC Oncology SC Oncology GA 609RE UT WOS:000178917700008 PM 12435285 ER PT J AU Boroojerdi, B Meister, IG Foltys, H Sparing, R Cohen, LG Topper, R AF Boroojerdi, B Meister, IG Foltys, H Sparing, R Cohen, LG Topper, R TI Visual and motor cortex excitability: a transcranial magnetic stimulation study SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE transcranial magnetic stimulation; phosphene; phosphene threshold; motor threshold; visual cortex excitability ID PHOSPHENE THRESHOLDS; BRAIN; PERCEPTION; MIGRAINE; SITE AB Objectives: Phosphene thresholds (PTs) to transcranial magnetic stimulation over the occipital cortex and motor thresholds (MTs) have been used increasingly as measures of the excitability of the visual and motor cortex. MT has been utilized as a guide to the excitability of other, non-motor cortical areas such as dorsolateyal prefrontal cortex. The aims of this study were to compare the PTs to MTs; to assess their stability across sessions; and to investigate their relation to MTs. Methods: PTs and MTs were determined using focal transcranial magnetic stimulation over the visual and motor cortex. Results: PTs were shown to be significantly higher than MTs. Both PTs and MTs were stable across sessions. No correlation between PTs and MTs could be established. Conclusions: Phosphene threshold is a stable parameter of the visual cortex excitability. MTs were not related to the excitability of nonmotor cortical areas. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Klinikum, Neurol Klin, D-52074 Aachen, Germany. Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, NIH, Bethesda, MD USA. RP Boroojerdi, B (reprint author), Univ Klinikum, Neurol Klin, Pauwelsstr 30, D-52074 Aachen, Germany. RI Meister, Ingo/A-3642-2008 NR 21 TC 67 Z9 68 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD SEP PY 2002 VL 113 IS 9 BP 1501 EP 1504 AR PII S1388-2457(02)00198-0 DI 10.1016/S1388-2457(02)00198-0 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 591FW UT WOS:000177869900016 PM 12169333 ER PT J AU Bryant-Greenwood, P AF Bryant-Greenwood, P TI Molecular diagnostics in obstetrics and gynecology SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article ID FRAGILE-X-SYNDROME; POLYMERASE-CHAIN-REACTION; BREAST-CANCER; FACTOR-V; IN-SITU; EXPRESSION; HEMOCHROMATOSIS; OVEREXPRESSION; METHYLATION; CARCINOMA C1 NIH, Dept Pathol, Div Canc Biol, Bethesda, MD 20892 USA. RP Bryant-Greenwood, P (reprint author), 3539 Sheffield Manor Terrace,Apt 303, Silver Spring, MD 20904 USA. NR 27 TC 2 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD SEP PY 2002 VL 45 IS 3 BP 605 EP 621 DI 10.1097/01.GRF.0000024302.19473.05 PG 17 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 608DT UT WOS:000178830400003 PM 12370601 ER PT J AU Fischer, TL Pieper, JA Graff, DW Rodgers, JE Fischer, JD Parnell, KJ Goldstein, JA Greenwood, R Patterson, JH AF Fischer, TL Pieper, JA Graff, DW Rodgers, JE Fischer, JD Parnell, KJ Goldstein, JA Greenwood, R Patterson, JH TI Evaluation of potential losartan-phenytoin drug interactions in healthy volunteers SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID II RECEPTOR ANTAGONIST; HUMAN LIVER-MICROSOMES; RANDOMIZED TRIAL; HEART-FAILURE; IN-VITRO; TOLBUTAMIDE; METABOLITE; CYP2C9; PHARMACOKINETICS; 4-HYDROXYLATION AB Background: Phenytoin, a cytochrome P450 (CYP) 2C9 substrate, has a narrow therapeutic index and nonlinear pharmacokinetics. Therefore there is the potential for significant concentration-related adverse effects when phenytoin is coadministered with other CYP2C9 substrates. Losartan, an antihypertensive agent, is also a substrate for CYP2C9. Objective: Our objective was to assess the effects of losartan on the pharmacokinetics of phenytoin and the effects of phenytoin on the pharmacokinetics of losartan in a healthy population of volunteers. Methods: A prospective, randomized, 3-period crossover study was conducted in 16 healthy volunteers with phenytoin alone, phenytoin in combination with losartan, and losartan alone. Each treatment was given for 10 days with a 3-week washout period between treatments. On day 10, plasma concentrations of phenytoin and plasma and urine concentrations of losartan and its active carboxylic-acid metabolite E3174 were measured to determine steady-state pharmacokinetic parameters. Results: Coadministration of losartan had no effect on the pharmacokinetics of phenytoin. Coadministration of phenytoin increased the mean area under the concentration-time curve from time zero to 24 hours [AUC(0-24)] of losartan by 17% (355 +/- 220 ng . h/mL versus 427 +/- 177 ng . h/mL; P = .1), but this difference was not statistically significant. In the 14 CYP2C9*1/*1 subjects, the mean AUC(0-24) of losartan was increased by 29% (284 +/- 84 rig . h/mL versus 402 +/- 128 rig . h/mL; P = .008). Coadministration of phenytoin significantly reduced the AUC(0-24) of E3174 by 63% (1254 +/- 256 rig . h/mL versus 466 +/- 174 rig . h/mL; P = .0001) and the formation clearance of losartan to E3174 (1.91 +/- 0.8 mL/h per kilogram versus 0.62 +/- 0.4 mL/h per kilogram; P = .0001). Conclusions: Losartan, a CYP2C9 substrate, had no effect on the pharmacokinetics of phenytoin. However, phenytoin inhibited the CYP2C9-mediated conversion of losartan to E3174. C1 Univ N Carolina, Div Pharmacotherapy, Sch Pharm, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. Pharsight Corp, Mt View, CA USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Pieper, JA (reprint author), Univ N Carolina, Div Pharmacotherapy, Sch Pharm, CB7360,Beard Hall, Chapel Hill, NC 27599 USA. RI Goldstein, Joyce/A-6681-2012 FU NCRR NIH HHS [RR00046] NR 24 TC 21 Z9 21 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2002 VL 72 IS 3 BP 238 EP 246 DI 10.1067/mcp.2002.127945 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 597RY UT WOS:000178235600002 PM 12235444 ER PT J AU Dasmahapatra, AK Trewin, AL Hutz, RJ AF Dasmahapatra, AK Trewin, AL Hutz, RJ TI Estrous cycle-regulated expression of CYP1B1 mRNA in the rat ovary SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE CYP1A1; CYP 1131; ER-P; estrous cycle; ovary; granulosa cell; LH; TCDD ID POLYMERASE CHAIN-REACTION; RECEPTOR-BETA; MESSENGER-RNA; IN-VITRO; ADRENAL CYTOCHROME-P450; HYDROCARBON METABOLISM; GRANULOSA-CELLS; DOWN-REGULATION; REACTION ASSAY; INDUCTION AB CYP1B1, a member of the cytochrome P450 superfamily, is expressed constitutively in the steroidogenic tissues of mammals and is inducible by peptide hormones, cAMP and aromatic hydrocarbon receptor (AHR) ligands. The mechanism of induction of this cytochrome P450 is similar to that for CYP1A1, i.e. through the aromatic hydrocarbon receptor (AHR) signaling pathway. We have recently reported that CYP1B1, but not CYP1A1, is expressed in rat granulosa cells (GC) in the absence of any external stimulus. The induction of CYP1B1 mRNA in rat GC by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in vitro was followed by an increase in AHR and estrogen receptor (ER-P) RNA levels. Estrous cycle-dependent expression of AHR, AHR-nuclear translocator (ARNT) and ER-mRNAs in the rat ovary was reported. We suggest that CYP1B1 may play a major role in the regulation of rat ovarian function/cycle but until now this has been unexplored experimentally. The present study was therefore aimed at examining the expression of CYP1A1, CYP1B1 and ER-mRNA in rat ovarian tissues throughout the estrous cycle to establish any correlation in the expressions of these mRNAs in rat ovary. Total RNA was extracted from the ovary and liver of cycling adult rats and the mRNAs were analyzed using relative RT-PCR with gene-specific primers for the target mRNA and for RPL 19 or S16 primers as an internal control. The results indicated that in the ovary, CYP1B1 mRNA increased significantly on the evening of proestrus and dramatically decreased on the morning of estrus, while ER-mRNA remained unaltered throughout the estrous cycle. CYP1A1 mRNA in the ovary and both CYP1A1 and CYP1B1 mRNAs in the liver were undetectable. That the sudden decrease of ovarian CYP1B1 mRNA on the morning of estrus was not an effect of the LH surge was verified in vitro using our short-term GC culture model. GC prepared from rats super-stimulated with equine chorionic gonadotropin (eCG) were cultured for 6 h with or without LH and TCDD. It was observed that both CYP1A1 and CYP1B1 mRNAs were induced by TCDD with no apparent effect of LH. It is suggested that the high level of CYP1B1 mRNA expression on the evening of proestrus in rat ovary might be involved in metabolism of estrogens to catecholestrogen (a known effect of CYP1B1), and that expression is unaffected in GC by LH. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Wisconsin, Dept Biol Sci, NIEHS Marine & Freshwater Biomed Sci Ctr, Milwaukee, WI 53201 USA. RP Hutz, RJ (reprint author), Univ Wisconsin, Dept Biol Sci, NIEHS Marine & Freshwater Biomed Sci Ctr, 308 Lapham Hall,3209 N Maryland Ave, Milwaukee, WI 53201 USA. FU NIEHS NIH HHS [ES04184, ES08342] NR 25 TC 20 Z9 20 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1096-4959 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD SEP PY 2002 VL 133 IS 1 BP 127 EP 134 AR PII S1096-1959(02)00119-7 DI 10.1016/S1096-4959(02)00119-7 PG 8 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 610NK UT WOS:000178966500015 PM 12223220 ER PT J AU Gronenborn, AM AF Gronenborn, AM TI The importance of being ordered: improving NMR structures using residual dipolar couplings SO COMPTES RENDUS BIOLOGIES LA English DT Article DE NMR; alignment; anisotropy; liquid crystal; residual dipolar couplings; orientational constraints; protein structure determination ID LIQUID-CRYSTALLINE MEDIUM; MACROMOLECULAR STRUCTURE DETERMINATION; PROTEIN-STRUCTURE DETERMINATION; HIGH-RESOLUTION NMR; BIOLOGICAL MACROMOLECULES; ORIENTED MACROMOLECULES; STRUCTURE REFINEMENT; INDUCED ALIGNMENT; MAGNETIC-FIELD; NEMATIC PHASE AB Residual dipolar couplings arise from small degrees of alignment of molecules in a magnetic field. Most biomolecules lack sufficient intrinsic magnetic susceptibility anisotropies for practical purposes; however, alignment can be achieved using dilute aqueous phospholipid mixtures, colloidal suspensions of rod-shaped viruses, complex phases of surfactant systems and strained gels. The stability of the liquid crystalline phases varies with respect to temperature range, pH variation and time and is critically dependent on sample composition and experimental conditions. The magnitude of the residual dipolar couplings depends upon the degree of ordering and allows the determination of the corresponding inter-nuclear vectors with respect to the molecule's alignment frame. Inclusion of dipolar constraints into NMR structure calculations leads to improved precision and accuracy of the resulting structures, especially in cases where the information content provided by traditional NOE constraints is limited. In addition, rapid evaluation of backbone protein folds and determination of the relative orientations of individual components in multi-molecular complexes have become feasible. Dipolar coupling based strategies may well emerge as the most critical developments, in establishing NMR as a valuable and competitive methodology in the structural genomics initiative. To cite this article: A.M. Gronenborn, C. R. Biologies 325 (2002) 957-966. (C) 2002 Academie des sciences / Editions scientifiques et medicales Elsevier SAS. C1 NIH, NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA. RP Gronenborn, AM (reprint author), NIH, NIDDK, Chem Phys Lab, Bldg 5, Bethesda, MD 20892 USA. NR 45 TC 9 Z9 10 U1 0 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1631-0691 J9 CR BIOL JI C. R. Biol. PD SEP PY 2002 VL 325 IS 9 BP 957 EP 966 AR PII S1631069102018123/FLA DI 10.1016/S1631-0691(02)01512-3 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 620PG UT WOS:000179541300005 PM 12481689 ER PT J AU Quezado, ZMN Eichacker, PQ AF Quezado, ZMN Eichacker, PQ TI Prophylactic granulocyte colony-stimulating factor in the critically ill: Carefully balancing the benefits and risks SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE granulocyte-colony stimulating factor; inflammatory response; sepsis ID ESCHERICHIA-COLI PNEUMONIA; SEPTIC SHOCK; FACTOR FILGRASTIM; HOST-DEFENSE; RG-CSF; SEPSIS; HEMORRHAGE; MECHANISMS; THERAPY; TRIALS C1 NIH, Dept Anesthesia & Surg Serv, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Quezado, ZMN (reprint author), NIH, Dept Anesthesia & Surg Serv, Warren G Magnuson Clin Ctr, Bldg 10,Room 2C6245,10 Ctr Dr,MSC 1512, Bethesda, MD 20892 USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 27 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2002 VL 30 IS 9 BP 2162 EP 2164 DI 10.1097/01.CCM.0000026724.39340.AE PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 599XC UT WOS:000178359600044 PM 12352068 ER PT J AU Solomon, SR Tran, T Carter, C Donnelly, S Hensel, N Schindler, J Bahceci, E Ghetie, V Michalek, J Mavroudis, D Read, EJ Vitetta, E Barrett, AJ AF Solomon, SR Tran, T Carter, C Donnelly, S Hensel, N Schindler, J Bahceci, E Ghetie, V Michalek, J Mavroudis, D Read, EJ Vitetta, E Barrett, AJ TI Optimized clinical-scale culture conditions for ex vivo selective depletion of host-reactive donor lymphocytes: a strategy for GvHD prophylaxis in allogeneic PBSC transplantation SO CYTOTHERAPY LA English DT Article DE T-cell depletion; ex vivo cell culture; alloreactivity; expansion; allogeneic stem cell transplantation; graft-versus-host disease ID GRAFT-VERSUS-HOST; BONE-MARROW TRANSPLANTATION; ALLOREACTIVE T-CELLS; RICIN-A-CHAIN; MINOR HISTOCOMPATIBILITY ANTIGEN; CHRONIC MYELOID-LEUKEMIA; ADOPTIVE IMMUNOTHERAPY; DISEASE; RECEPTOR; IMMUNOTOXIN AB Background Ex vivo selective depletion (SD) is a strategy to prevent GvHD, in which host-reactive donor lymphocytes are selectively eliminated from a PBSC allograft while conserving useful donor immune function. Prior to testing this strategy in patients, our goal was to develop a clinical-scale SD process, which involves co-culture of donor lymphocytes and irradiated recipient cells, followed by the addition of an immunotoxin (IT) directed against the alpha-chain of the IL-2 receptor (CD25), expressed on activated donor T cells. Methods Stimulator cells were generated from immunomagnetically selected and expanded recipient T lymphocytes. Donor PBMCs from G-CSF-mobilized peripheral blood were co-cultured for 72 h with irradiated stimulator cells. Alloreactive T cells were targeted for elimination by the addition of the anti-CD25 IT, RFT5-SMPT-dgA, and the IT enhancer, NH4Cl. Results Stimulator-cell selection/expansion yielded > 2 x 10(10) highly enriched CD3(+) cells (98.9 +/- 2.2%). After SD, cell recovery was 68.5 +/- 23.3% and viability was 84.6 +/- 6.4%. This permitted a potential T-cell dose greater than or equal to1 x 10(8) CD3(+) cells kg(-1) to transplant recipients. Although SD donor lymphocytes retained little proliferative capacity against the original stimulator cells (2.6 +/- 0.6%), responses were conserved against third party cells (107.6 +/- 18.6%), the bacterial superantigen staphylococcus enterotoxin B (108.2 +/- 4.2%), and CMV Ag (72.1 +/- 3.8%). Discussion We have demonstrated that ex vivo SD is feasible in clinical-scale culture conditions. The ability of this strategy to prevent GvHD is the subject of an ongoing clinical trial, in which the SD lymphocyte product is transplanted in conjunction with a T cell-depleted PBSC allograft. C1 NHLBI, NIH, Hematol Branch, Stem Cell Allotransplantat Sect, Bethesda, MD 20892 USA. NIH, Cell Proc Sect, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Microbiol, Dallas, TX USA. RP Solomon, SR (reprint author), NHLBI, NIH, Hematol Branch, Stem Cell Allotransplantat Sect, 9000 Rockville Pike,MSC 1652,Bldg 10,Room 7C103, Bethesda, MD 20892 USA. NR 31 TC 48 Z9 48 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD SEP 1 PY 2002 VL 4 IS 5 BP 395 EP 406 DI 10.1080/146532402320775982 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 612LQ UT WOS:000179077500002 PM 12473206 ER PT J AU Barrett, J AF Barrett, J TI The basis of the alloimmune response SO CYTOTHERAPY LA English DT Article ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; MINOR HISTOCOMPATIBILITY ANTIGENS; REPERTOIRE C1 NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD SEP 1 PY 2002 VL 4 IS 5 BP 419 EP 422 DI 10.1080/146532402320776017 PG 4 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 612LQ UT WOS:000179077500004 PM 12473208 ER PT J AU Douek, DC AF Douek, DC TI The contribution of the thymus to immune reconstitution after hematopoietic stem-cell transplantation SO CYTOTHERAPY LA English DT Article ID BONE-MARROW TRANSPLANTATION; INTENSIVE CHEMOTHERAPY; AGE; RECOVERY; ADULTS C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Douek, DC (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Covent Dr, Bethesda, MD 20892 USA. NR 15 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD SEP 1 PY 2002 VL 4 IS 5 BP 425 EP 426 DI 10.1080/146532402320776035 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 612LQ UT WOS:000179077500006 PM 12473210 ER PT J AU Mackall, CL AF Mackall, CL TI Enhancing immune reconstitution after stem cell transplants with cytokines SO CYTOTHERAPY LA English DT Article C1 NCI, Pediat Branch, Bethesda, MD 20892 USA. RP Mackall, CL (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD SEP 1 PY 2002 VL 4 IS 5 BP 427 EP 428 DI 10.1080/146532402320776044 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 612LQ UT WOS:000179077500007 PM 12473211 ER PT J AU Fowler, D Hou, J Foley, J Hakim, F Odom, J Castro, K Carter, C Read, E Gea-Banacloche, J Kasten-Sportes, C Kwak, L Wilson, W Levine, B June, C Gress, R Bishop, M AF Fowler, D Hou, J Foley, J Hakim, F Odom, J Castro, K Carter, C Read, E Gea-Banacloche, J Kasten-Sportes, C Kwak, L Wilson, W Levine, B June, C Gress, R Bishop, M TI Phase I clinical trial of donor T-helper Type-2 cells after immunoablative, reduced intensity allogeneic PBSC transplant SO CYTOTHERAPY LA English DT Article ID VERSUS-HOST-DISEASE; BONE-MARROW TRANSPLANTATION; HEMATOLOGIC MALIGNANCIES; FOLLOW-UP; THERAPY; CHIMERISM; RESPONSES; REGIMEN; CD4(+) C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Penn, Ctr Canc, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Fowler, D (reprint author), NCI, Ctr Canc Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Levine, Bruce/D-1688-2009 NR 12 TC 14 Z9 14 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD SEP 1 PY 2002 VL 4 IS 5 BP 429 EP 430 DI 10.1080/146532402320776053 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 612LQ UT WOS:000179077500008 PM 12473212 ER PT J AU Warren, EH Tykodi, SS Murata, M Sandmaier, BM Storb, R Jaffee, E Childs, R Thompson, JA Greenberg, PD Riddell, SR AF Warren, EH Tykodi, SS Murata, M Sandmaier, BM Storb, R Jaffee, E Childs, R Thompson, JA Greenberg, PD Riddell, SR TI T-cell therapy targeting minor histocompatibility Ags for the treatment of leukemia and renal-cell carcinoma SO CYTOTHERAPY LA English DT Article C1 Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. RP Warren, EH (reprint author), Fred Hutchinson Canc Res Ctr, Program Immunol, Seattle, WA 98109 USA. RI Murata, Makoto/I-7370-2014 FU NCI NIH HHS [P01 CA078902] NR 3 TC 9 Z9 10 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD SEP 1 PY 2002 VL 4 IS 5 BP 441 EP 441 DI 10.1080/146532402320776116 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 612LQ UT WOS:000179077500014 PM 12473218 ER PT J AU Li, G Robinson, GW Lesche, R Martinez-Diaz, H Jiang, ZR Rozengurt, N Wagner, KU De-Chang, W Lane, TF Liu, X Hennighausen, L Wu, H AF Li, G Robinson, GW Lesche, R Martinez-Diaz, H Jiang, ZR Rozengurt, N Wagner, KU De-Chang, W Lane, TF Liu, X Hennighausen, L Wu, H TI Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland SO DEVELOPMENT LA English DT Article DE PTEN; mammary development; Cowden's disease; ductal growth; apoptosis ID TUMOR-SUPPRESSOR GENE; PROTEIN-KINASE-B; TRANSGENIC MICE; CELL-SURVIVAL; NEGATIVE REGULATION; GERMLINE MUTATIONS; COWDEN-SYNDROME; BREAST-CANCER; STEM-CELLS; PHOSPHATASE AB PTEN tumor suppressor is frequently mutated in human cancers, including breast cancers. Female patients with inherited PTEN mutations suffer from virginal hypertrophy of the breast with high risk of malignant transformation. However, the exact mechanisms of PTEN in controlling mammary gland development and tumorigenesis are unclear. In this study, we generated mice with a mammary-specific deletion of the Pten gene. Mutant mammary tissue displayed precocious lobulo-alveolar development, excessive ductal branching, delayed involution and severely reduced apoptosis. Pten null mammary epithelial cells were disregulated and hyperproliferative. Mutant females developed mammary tumors early in life. Similar phenotypes were observed in Pten-null mammary epithelia that had been transplanted into wild-type stroma, suggesting that PTEN plays an essential and cell-autonomous role in controlling the proliferation, differentiation and apoptosis of mammary epithelial cells. C1 Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Inst Radiat Med, Beijing, Peoples R China. RP Wu, H (reprint author), Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, 650 Circle Dr S, Los Angeles, CA 90095 USA. EM hwu@mednet.ucla.edu RI Wagner, Kay-Uwe/B-6044-2009; Robinson, Gertraud/I-2136-2012; LI, GANG/O-1409-2016 OI LI, GANG/0000-0003-3203-8567 FU NCI NIH HHS [P50CA86306, U01CA84128-03]; NINDS NIH HHS [NS38489] NR 50 TC 174 Z9 185 U1 1 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD SEP PY 2002 VL 129 IS 17 BP 4159 EP 4170 PG 12 WC Developmental Biology SC Developmental Biology GA 592WA UT WOS:000177958800018 PM 12163417 ER PT J AU Kudoh, T Wilson, SW Dawid, IB AF Kudoh, T Wilson, SW Dawid, IB TI Distinct roles for Fgf, Wnt and retinoic acid in posteriorizing the neural ectoderm SO DEVELOPMENT LA English DT Article DE Fgf; Wnt; retinoic acid; posteriorization; Cyp26; Raldh2; zebrafish ID CENTRAL-NERVOUS-SYSTEM; MIDBRAIN-HINDBRAIN BOUNDARY; FIBROBLAST-GROWTH-FACTOR; HOMEOBOX GENE; XENOPUS EMBRYOS; ZEBRAFISH; EXPRESSION; PATTERN; MOUSE; AXIS AB Early neural patterning in vertebrates involves signals that inhibit anterior (A) and promote posterior (P) positional values within the nascent neural plate. In this study, we have investigated the contributions of, and interactions between, retinoic acid (RA), Fgf and Wnt signals in the promotion of posterior fates in the ectoderm. We analyze expression and function of cyp26/P450RAI, a gene that encodes retinoic acid 4-hydroxylase, as a tool for investigating these events. Cyp26 is first expressed in the presumptive anterior neural ectoderm and the blastoderm margin at the late blastula. When the posterior neural gene hoxb1b is expressed during gastrulation, it shows a strikingly complementary pattern to cyp26. Using these two genes, as well as otx2 and meis3 as anterior and posterior markers, we show that Fgf and Wnt signals suppress expression of anterior genes, including cyp26. Overexpression of cyp26 suppresses posterior genes, suggesting that the anterior expression of cyp26 is important for restricting the expression of posterior genes. Consistent with this, knock-down of cyp26 by morpholino oligonucleotides leads to the anterior expansion of posterior genes. We further show that Fgf- and Wnt-dependent activation of posterior genes is mediated by RA, whereas suppression of anterior genes does not depend on RA signaling. Fgf and Wnt signals suppress cyp26 expression, while Cyp26 suppresses the RA signal. Thus, cyp26 has an important role in linking the Fgf, Wnt and RA signals to regulate AP patterning of the neural ectoderm in the late blastula to gastrula embryo in zebrafish. C1 UCL, Dept Anat & Dev Biol, London WC1E 6BT, England. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Kudoh, T (reprint author), UCL, Dept Anat & Dev Biol, Gower St, London WC1E 6BT, England. EM t.kudoh@ucl.ac.uk RI Wilson, Stephen/B-9404-2008; Zebrafish, UCL/A-3125-2009 OI Wilson, Stephen/0000-0002-8557-5940; NR 53 TC 187 Z9 188 U1 2 U2 26 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP PY 2002 VL 129 IS 18 BP 4335 EP 4346 PG 12 WC Developmental Biology SC Developmental Biology GA 602WT UT WOS:000178528000016 PM 12183385 ER PT J AU Shimizu, K Ishizuya-Oka, A Amano, T Yoshizato, K Ueda, S AF Shimizu, K Ishizuya-Oka, A Amano, T Yoshizato, K Ueda, S TI Isolation of connective-tissue-specific genes involved in Xenopus intestinal remodeling: thyroid hormone up-regulates Tolloid/BMP-1 expression SO DEVELOPMENT GENES AND EVOLUTION LA English DT Article DE Tolloid/BMP-1; thyroid hormone; intestinal remodeling; anteroposterior axis; Xenopus ID BONE MORPHOGENETIC PROTEIN-1; ADULT EPITHELIAL DEVELOPMENT; PROCOLLAGEN C-PROTEINASE; ACID-BINDING PROTEIN; AMPHIBIAN METAMORPHOSIS; CHORDIN; DROSOPHILA; EMBRYOS; ANTAGONIST; APOPTOSIS AB To clarify connective-tissue-specific genes involved in adult epithelial development during amphibian intestinal remodeling, we have isolated 16 cDNA clones derived from the anterior part of Xenopus laevis intestine cultured in vitro by using subtractive suppression hybridization. Among four genes identified, the expression of Xtld, a Xenopus homolog of Drosophila Tolloid closely related to bone morphogenic protein-1 (BMP-1), was most remarkably up-regulated during metamorphosis. To further explore the roles of Xtld in intestinal remodeling, we examined its developmental expression in the X. laevis intestine by in situ hybridization and northern blot analysis. Xtld mRNA first became detectable in the connective tissue just before the appearance of adult epithelial primordia. Subsequently, the level of Xtld mRNA reached a high in the connective tissue, concomitantly with adult epithelial development along the anteroposterior axis of the intestine. Thereafter, towards the completion of metamorphosis, the expression of Xtld mRNA was down-regulated. Thus, the expression profile of Xtld mRNA spatiotemporally correlates well with adult epithelial development in vivo. Furthermore, the present culture study has shown that thyroid hormone (TH) upregulates the expression of Xtld mRNA organ-autonomously in the anterior part of the intestine, but not in its posterior part, and that TH up-regulation of Xtld expression is not mediated by the epithelium. These results suggest that TH directly up-regulates Xtld expression in the connective tissue along the anteroposterior axis, which in turn plays important roles in adult epithelial development during amphibian intestinal remodeling. C1 Dokkyo Univ, Sch Med, Dept Histol & Neurobiol, Mibu, Tochigi 3210293, Japan. NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Hiroshima Univ, Fac Sci, Dept Biol, Dev Biol Lab, Hiroshima 7398526, Japan. RP Ishizuya-Oka, A (reprint author), Dokkyo Univ, Sch Med, Dept Histol & Neurobiol, Mibu, Tochigi 3210293, Japan. NR 34 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0949-944X J9 DEV GENES EVOL JI Dev. Genes Evol. PD SEP PY 2002 VL 212 IS 8 BP 357 EP 364 DI 10.1007/s00427-002-0250-3 PG 8 WC Cell Biology; Evolutionary Biology; Developmental Biology SC Cell Biology; Evolutionary Biology; Developmental Biology GA 598EB UT WOS:000178261500001 PM 12203091 ER PT J AU Gallego, MI Beachy, PA Hennighausen, L Robinson, GW AF Gallego, MI Beachy, PA Hennighausen, L Robinson, GW TI Differential requirements for Shh in mammary tissue and hair follicle morphogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE hedgehog; mammary gland; tissue interaction ID HEDGEHOG SIGNALING PATHWAY; MOUSE PATCHED GENE; SONIC-HEDGEHOG; GLAND DEVELOPMENT; MICE; CONSERVATION; INDUCTION; DEFECTS; MUTANTS; GROWTH AB Sonic Hedgehog (Shh) is a secreted morphogen that directs patterning and cellular differentiation through binding to its receptor Patched (Ptc). It is required for the development of skin-derived organs, such as hair, whiskers, and teeth. The mammary gland is a skin-derived organ that develops mainly during adult life in which Shh is expressed from puberty to lactation. We have investigated the role of Shh in mammary gland morphogenesis and differentiation by two transplantation approaches. Since Shh-null fetuses die at late embryogenesis, we transplanted Shh-null mammary anlagen into cleared fat pads and under the renal capsule of wild type host mice. Pregnancy-mediated functional differentiation of Shh-null mammary epithelium was indistinguishable from wild type transplants, while hair follicles derived from cotransplanted skin only developed in wild type transplants. Transplants of Ihh-null anlagen also developed normally. To assess the molecular consequences of Shh deletion in mammary tissue, we compared mRNA levels of patched 1, a target gene of Hedgehog signaling, in Shh-null and wild type mammary epithelial transplants. No reduction of Ptc1 transcripts was observed in Shh-null mammary tissues. Our results demonstrate that neither Shh nor Ihh is required for mammary gland morphogenesis and functional differentiation, suggesting that the two members of the Hedgehog family may have redundant function in activating the Ptc1 signaling pathway during mammary gland development. (C) 2002 Elsevier Science (USA). C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. RP Robinson, GW (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. EM traud1@nih.gov RI Robinson, Gertraud/I-2136-2012 NR 34 TC 34 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 1 PY 2002 VL 249 IS 1 BP 131 EP 139 DI 10.1006/dbio.2002.0761 PG 9 WC Developmental Biology SC Developmental Biology GA 592EW UT WOS:000177924600011 PM 12217324 ER PT J AU Horner, A Shum, L Ayres, JA Nonaka, K Nuckolls, GH AF Horner, A Shum, L Ayres, JA Nonaka, K Nuckolls, GH TI Fibroblast growth factor signaling regulates Dach1 expression during skeletal development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE endochondral ossification; transcription factor; cell cycle; growth plate; limb bud; patterning ID UBIQUITIN-CONJUGATING ENZYME; VERTEBRATE LIMB DEVELOPMENT; DROSOPHILA DACHSHUND; BONE-DEVELOPMENT; CHONDROCYTE DIFFERENTIATION; CELL-DIFFERENTIATION; EYE DEVELOPMENT; MOUSE DAC; IN-VITRO; CBFA1 AB Dach1 is a mouse homologue of the Drosophila dachshund gene, which is a key regulator of cell fate determination during eye, leg, and brain development in the fly. We have investigated the expression and growth factor regulation of Dach1 during pre- and postnatal skeletal development in the mouse limb to understand better the function of Dach1. Dach1 was expressed in the distal mesenchyme of the early embryonic mouse limb bud and subsequently became restricted to the tips of digital cartilages. Dach1 protein was localized to postmitotic, pre-hypertrophic, and early hypertrophic chondrocytes during the initiation of ossification centers, but Dach1 was not expressed in growth plates that exhibited extensive ossification. Dach1 colocalized with Runx2/Cbfa1 in chondrocytes but not in the forming bone collar or primary spongiosa. Dach1 also colocalized with cyclin-dependent kinase inhibitors p27 (Kip1) and p57 (Kip2) in chondrocytes of the growth plate and in the epiphysis before the formation of the secondary ossification center. Because fibroblast growth factors (FGF), bone morphogenetic proteins (BMP), and hedgehog molecules (Hh) regulate skeletal patterning of the limb bud and chondrocyte maturation in developing endochondral bones, we investigated the regulation of Dach1 by these growth and differentiation factors. Expression of Dach1 in 11 days postcoitus mouse limb buds in organ culture was up-regulated by implanting beads soaked in FGF1, 2,8, or 9 but not FGF10. BMP4-soaked beads down-regulated Dach1 expression, whereas Shh and bovine serum albumin had no effect. Furthermore, FGF4 or 8 could substitute for the apical ectodermal ridge in maintaining Dach1 expression in the limb buds. Immunolocalization of FGFR2 and FGFR3 revealed overlap with Dach1 expression during skeletal patterning and chondrocyte maturation. We conclude that Dach1 is a target gene of FGF signaling during limb skeletal development, and Dach1 may function as an intermediary in the FGF signaling pathway regulating cell proliferation or differentiation. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, Dev Biol Sect, NIH, Bethesda, MD 20892 USA. RP Nuckolls, GH (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, Dev Biol Sect, NIH, 6 Ctr Dr,Bldg 6,Room 324 MSC2745, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [Z01-AR41114] NR 62 TC 21 Z9 21 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD SEP PY 2002 VL 225 IS 1 BP 35 EP 45 DI 10.1002/dvdy.10132 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 590FD UT WOS:000177806900004 PM 12203718 ER PT J AU Zierler, K Andres, R AF Zierler, K Andres, R TI Muscle glucose uptake does not increase when only local arterial glucose concentration is increased SO DIABETES LA English DT Article AB Published models of mammalian whole-body glucose metabolism generally assume that glucose uptake is proportional to circulating glucose concentration at constant insulin concentration. One widely used model labels the increased whole-body glucose uptake seen,with increased venous glucose concentration as "glucose effectiveness." In 1956 and 1957, we found on average no change in forearm glucose uptake when we doubled, or more than doubled, local forearm arterial glucose concentration by close arterial infusion so that pancreatic arterial glucose concentration did not change. These experiments are being reported in extenso for the first time. Since that time, two other groups have found in glucose/insulin clamp experiments that whole-body glucose uptake was not proportional to hyperglycemic concentrations, although uptake did increase. It was hypothesized that perhaps some organs and tissues do increase uptake proportionally and other tissues not at all. Our results show that skeletal muscle is a tissue in which glucose uptake, at constant insulin, is not changed acutely by hyperglycemia; there is no forearm glucose effectiveness. We suppose that this constancy occurs because there are so few GLUTs on the sarcolemma surface in the basal state and that they are saturated even at euglycemia. We also report earlier experiments from 1954 to 1955 in which comparable hyperglycemia was reached by a large oral dose of glucose, with a 10-fold increase in glucose uptake. The arterial glucose time curve during hyperglycemia was 20-30 mg/dl higher than the forearm venous curve. C1 Johns Hopkins Univ, Sch Med, Dept Physiol & Med, Div Endocrinol & Metab, Baltimore, MD 21287 USA. NIA, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Zierler, K (reprint author), Johns Hopkins Univ, Sch Med, Dept Physiol & Med, Div Endocrinol & Metab, Suite 333,1830 E Monument St, Baltimore, MD 21287 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2002 VL 51 IS 9 BP 2698 EP 2702 DI 10.2337/diabetes.51.9.2698 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 588KX UT WOS:000177701600005 PM 12196461 ER PT J AU Colombo, C Cutson, JJ Yamauchi, T Vinson, C Kadowaki, T Gavrilova, O Reitman, ML AF Colombo, C Cutson, JJ Yamauchi, T Vinson, C Kadowaki, T Gavrilova, O Reitman, ML TI Transplantation of adipose tissue lacking leptin is unable to reverse the metabolic abnormalities associated with lipoatrophy SO DIABETES LA English DT Article ID INSULIN-RESISTANCE; DIABETES-MELLITUS; PANCREATIC-ISLETS; MICE; OBESITY; PROTEIN; MOUSE; GENE; LIPODYSTROPHY; ADIPONECTIN AB Severe adipose tissue deficiency (lipoatrophy) causes insulin-resistant diabetes, elevated serum triglyceride and fatty acid levels, and massive triglyceride deposition in the liver. In lipoatrophic A-ZIP/F-1 mice, transplantation of normal adipose tissue greatly improved these parameters, whereas 1 week of leptin infusion had more modest effects. In contrast, leptin infusion was strikingly more effective in the aP2-n sterol response element binding protein 1 lipoatrophic mouse. Here we show that a longer duration of leptin infusion further improves the metabolic status of the A-ZIP/F-1 mice and that genetic background does not make a major contribution to the effect of leptin on glucose and insulin levels. Adipose transplantation using leptin-deficient ob/ob fat had no effect on the phenotype of the A-ZIP/F-1 mice. Moreover, the presence of ob/ob adipose tissue did not enhance the effects of leptin infusion. Serum adiponectin levels were 2% of control levels in the A-ZIP/F-1 mouse and increased only twofold with adipose transplantation and not at all after leptin infusion, suggesting that adiponectin deficiency is not a major contributor to the diabetic phenotype. Taken together, these results suggest that sequestration of triglycerides into fat may not be enough to restore a nondiabetic phenotype and that leptin deficiency plays a major role in causing the metabolic complications of lipoatrophy. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Med, Dept Internal Med, Tokyo, Japan. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Reitman, ML (reprint author), Merck Res Labs, POB 2000,RY80M-213, Rahway, NJ 07065 USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 30 TC 71 Z9 77 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2002 VL 51 IS 9 BP 2727 EP 2733 DI 10.2337/diabetes.51.9.2727 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 588KX UT WOS:000177701600009 PM 12196465 ER PT J AU Corleto, VD Delle Fave, G Jensen, RT AF Corleto, VD Delle Fave, G Jensen, RT TI Molecular insights into gastrointestinal neuroendocrine tumours: importance and recent advances SO DIGESTIVE AND LIVER DISEASE LA English DT Review DE carcinoid; gastrinoma; Multiple Endocrine Neoplasia type-1; pancreatic endocrine turnour ID PANCREATIC ENDOCRINE TUMORS; COMPARATIVE GENOMIC HYBRIDIZATION; GROWTH-FACTOR-ALPHA; NEOPLASIA TYPE-1 GENE; STRAND CONFORMATION POLYMORPHISM; ZOLLINGER-ELLISON-SYNDROME; MIDGUT CARCINOID-TUMORS; SUPPRESSOR GENE; SPORADIC GASTRINOMAS; MEN1 GENE AB A subset of gastrointestinal neuroendocrine tumours [carcinoids and pancreatic endocrine tumours] show aggressive growth. Early identification of this subset is essential for management; however clinical, laboratory and histologic features frequently fail to achieve this. Currently, there is an increased understanding of the molecular pathogenesis/changes in neuroendocrine tumours and this may identify important prognostic factors and possibly, new treatments. Recent findings and progress in this area are briefly reviewed in this article. C1 NIDDK, DB, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Roma La Sapienza, Div Digest & Liver Dis, I-00185 Rome, Italy. RP Jensen, RT (reprint author), NIDDK, DB, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr,DR MSC 1804, Bethesda, MD 20892 USA. NR 149 TC 26 Z9 28 U1 0 U2 0 PU PACINI EDITORE PI PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE OSPEDALETTO, 56121 PISA, ITALY SN 1590-8658 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD SEP PY 2002 VL 34 IS 9 BP 668 EP 680 DI 10.1016/S1590-8658(02)80212-2 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 600KE UT WOS:000178388500013 PM 12405256 ER PT J AU Robert-Guroff, M AF Robert-Guroff, M TI HIV regulatory and accessory proteins: New targets for vaccine development SO DNA AND CELL BIOLOGY LA English DT Editorial Material C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. RP Robert-Guroff, M (reprint author), NCI, Basic Res Lab, Bethesda, MD 20892 USA. NR 6 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD SEP PY 2002 VL 21 IS 9 BP 597 EP 598 DI 10.1089/104454902760330129 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 598JA UT WOS:000178271500001 PM 12396601 ER PT J AU Hel, Z Tryniszewska, E Tsai, WP Johnson, JM Harrod, R Fullen, J Kalyanaraman, VS Altman, JD McNally, J Karpova, T Felber, BK Tartaglia, J Franchini, G AF Hel, Z Tryniszewska, E Tsai, WP Johnson, JM Harrod, R Fullen, J Kalyanaraman, VS Altman, JD McNally, J Karpova, T Felber, BK Tartaglia, J Franchini, G TI Design and in vivo immunogenicity of a polyvalent vaccine based on SIVmac regulatory genes SO DNA AND CELL BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTES; CELLULAR IMMUNE-RESPONSES; ANTIRETROVIRAL TREATMENT; DISEASE PROGRESSION; CD8(+) LYMPHOCYTES; CYNOMOLGUS MONKEYS; PRIMARY INFECTION; ESCAPE VARIANTS; IMPORTIN-BETA AB Most vaccine modalities for human immunodeficiency virus type 1 (HIV-1) tested for immunogenicity and efficacy in the SIVmac (simian immunodeficiency virus) macaque model do not include the viral regulatory proteins. Because viral regulatory proteins are expressed early during the virus life cycle and represent an additional source of antigens, their inclusion as a vaccine component may increase the overall virus-specific immune response in vaccinees. However, at least two of the early proteins, Tat and Nef, may be immunosuppressive, limiting their usefulness as components of an SIV vaccine. We have constructed a polyvalent chimeric protein in which the open reading frames for Tat and Nef have been reassorted and the nuclear localization sequence for Tat and Rev and the myristoylation site for Nef have been removed. The resulting DNA plasmid (pDNA-SIV-Retanef) (pDNA-SIV-RTN) encodes a protein of 55 kDa (Retanef) that localizes at the steady state in the cytoplasma of transfected cells. Both the DNA-SIV-RTN and the highly attenuated recombinant poxvirus vector NYVAC-SIV-RTN were demonstrated to be immunogenic in SIVmac251-infected macaques treated with ART as well as in naive macaques. An equivalent strategy may be used for the generation of polyvalent antigens encoding the regulatory proteins in a HIV-1 vaccine candidate. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. Med Acad Bialystok, Dept Paediat 3, Bialystok, Poland. Adv BioSci Labs Inc, Kensington, MD USA. Emory Univ, Yerkes Reg Primate Res Ctr, Vaccine Ctr, Atlanta, GA 30322 USA. NCI, Fluorescence Imaging Facil, Bethesda, MD 20892 USA. NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21701 USA. Aventis Pasteur, Toronto, ON, Canada. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. OI Hel, Zdenek/0000-0002-4923-4794 NR 55 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD SEP PY 2002 VL 21 IS 9 BP 619 EP 626 DI 10.1089/104454902760330156 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 598JA UT WOS:000178271500004 PM 12396604 ER PT J AU Patterson, LJ Malkevitch, N Zhao, J Peng, B Robert-Guroff, M AF Patterson, LJ Malkevitch, N Zhao, J Peng, B Robert-Guroff, M TI Potent, persistent cellular immune responses elicited by sequential immunization of rhesus macaques with Ad5 host range mutant recombinants encoding SIV Rev and SIV Nef SO DNA AND CELL BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; DISEASE PROGRESSION; TAT; PROTEIN; VACCINE; TYPE-1; CHALLENGE; AIDS; VARIANTS AB Vaccines incorporating multiple HIV components should elicit broad immunity and protection against a spectrum of HIV strains. Early regulatory and accessory gene products are attractive candidates for such vaccines. Here, immunogenicity studies on SIV Rev and Nef expressed in replication competent Adenovirus type 5 host range mutant vectors (Ad5hr) are summarized. Interferon-gamma (IFN-gamma)-secreting cells in response to Env and Rev peptides were enumerated by ELISPOT after two sequential immunizations of 55 macaques with Ad5hr-SIV env/rev. Responses to SIV Nef were assessed in 16 macaques also immunized with Ad5hr-SIV nef. Potent cellular immunity to both Rev and Nef was induced following the second Ad-recombinant immunization and persisted for at least 30 weeks. Persistent cellular immunity to SIV Env was also seen, with a mean of 700 IFN-gamma-secreting cells per million PBMC. Rev and Env responses were positively correlated. While greater responses to early gene products occur in natural infection, as immunogens Rev and Nef elicited the same number of IFN-gamma secreting cells as Env, after adjusting for differences in protein size. The same percentage of macaques also responded to Rev, Nef, and Env: 59, 63, and 64%, respectively. Overall, Ad5hr-SIVenv/rev and -SIVnef were highly effective immunogens. Their contribution to protective efficacy will be addressed in future studies. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP Robert-Guroff, M (reprint author), NCI, Basic Res Lab, NIH, 41 Lib Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA. NR 43 TC 16 Z9 16 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD SEP PY 2002 VL 21 IS 9 BP 627 EP 635 DI 10.1089/104454902760330165 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 598JA UT WOS:000178271500005 PM 12396605 ER PT J AU Betts, MR Yusim, K Koup, RA AF Betts, MR Yusim, K Koup, RA TI Optimal antigens for HIV vaccines based on CD8+T response, protein length, and sequence variability SO DNA AND CELL BIOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; IMMUNODEFICIENCY-VIRUS TYPE-1; CELLULAR IMMUNE-RESPONSES; INFECTION; VIREMIA; PROGRESSORS; CD4(+); CELLS; LOAD; CTL AB The identification of optimal antigens to include in an HIV vaccine designed to elicit a cellular immune response requires careful consideration of protein length, variability, and immunogenicity. Here, we have examined the relationship of these parameters in a cohort of HIV-infected subjects. We find that HIV Gag and Nef represent optimal antigens for the CD8+ T cell response, based on size, variability, and immunogenicity. Although the Env and Pol proteins have a poorer response to length (Pol) or variability (Env) ratio than Gag or Nef, they are still strong candidates for inclusion into an HIV vaccine, based on overall response frequency in the cohort. The accessory proteins Tat, Rev, Vif, Vpr, and Vpu in general all elicit very low CD8+ T cell responses, and this, in combination with their high variability, makes them less attractive as vaccine antigens. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Los Alamos Natl Lab, Los Alamos, NM USA. RP Koup, RA (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. NR 19 TC 15 Z9 17 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD SEP PY 2002 VL 21 IS 9 BP 665 EP 670 DI 10.1089/104454902760330200 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 598JA UT WOS:000178271500009 PM 12396609 ER PT J AU Chi-Fishman, G Sonies, BC AF Chi-Fishman, G Sonies, BC TI Effects of systematic bolus viscosity and volume changes on hyoid movement kinematics SO DYSPHAGIA LA English DT Article DE swallowing; deglutition; viscosity; volume; hyoid bone; kinematics; ultrasound; age; gender; deglutition disorders ID DIFFERENT AGES; NORMAL ADULTS; DYSPHAGIA; SWALLOW; MANAGEMENT; PRESSURE; DISEASE; MUSCLES AB Using ultrasonography with head and transducer stabilization, this study examined the effects of maximally controlled, systematic changes in bolus viscosity (thin juice-like, 7 cP; nectar-like, 243-260 cP; honey-like, 724-759 cP; spoon-thick, 2760-2819 cP) and volume (5, 10, 20, 30 cc) on hyoid kinematics in 31 healthy subjects (16 male, 15 female) in three age groups (20-39, 40-59, 60-79 years). Frame-by-frame hyoid displacements were tracked from digitized images of 612 swallows. Measures of movement durations, maximal amplitudes, total distances, and peak velocities were subjected to repeated measures multivariate analyses of variance with viscosity, volume, age, and gender as factors. Results showed that (1) spoon-thick swallows had the greatest preswallow gesture and total movement durations; (2) larger-volume swallows had significantly greater maximal amplitudes, forward peak velocity, and total vertical distance; (3) older subjects had longer start-to-max duration (though shorter preswallow gesture and total movement durations), greater maximal vertical amplitude, longer total vertical distance, and greater backward peak velocity than younger subjects; (4) males had greater values for all kinematic parameters except preswallow gesture, hyoid-at-max, and max-to-end durations. The results illustrate the importance of examining the interrelations among kinematic variables to better understand task accommodation and motor control strategies. The evidence also supports the concept of suprahyoid-infrahyoid functional adaptation and compensation in the healthy elderly. C1 NIH, Warren G Magnuson Clin Ctr, Dept Rehabil Med,Phys Disabil Branch, Ultrasound Imaging & Oral Pharyngeal Funct Lab, Bethesda, MD 20892 USA. RP Chi-Fishman, G (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Rehabil Med,Phys Disabil Branch, Ultrasound Imaging & Oral Pharyngeal Funct Lab, Rm 6S235,Bldg 10,OMF-PDB,RMD,CC,900 Rockville Pik, Bethesda, MD 20892 USA. NR 36 TC 39 Z9 43 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD FAL PY 2002 VL 17 IS 4 BP 278 EP 287 DI 10.1007/s00455-002-0070-3 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 599MF UT WOS:000178338000004 PM 12355143 ER PT J AU Chankvetadze, B Burjanadze, N Maynard, DM Bergander, K Bergenthal, D Blaschke, G AF Chankvetadze, B Burjanadze, N Maynard, DM Bergander, K Bergenthal, D Blaschke, G TI Comparative enantioseparations with native beta-cyclodextrin and heptakis-(2-O-methyl-3,6-di-O-sulfo)-beta-cyclodextrin in capillary electrophoresis SO ELECTROPHORESIS LA English DT Article DE beta-cyclodextrin; capillary electrophoresis; chiral recognition; enantioseparation; Heptakis-(2-0-methyl-3,6-di-O-sulfo)-o-cyclodextrin One-dimensional transverse rotating; frame nuclear Overhauser and exchange spectroscopy ID CHIRAL RESOLVING AGENTS; IONIZATION MASS-SPECTROMETRY; OPPOSITE MIGRATION ORDER; SINGLE-ISOMER; ELECTROKINETIC CHROMATOGRAPHY; NMR-SPECTROSCOPY; ENANTIOMERS; SELECTORS; SEPARATION; FAMILY AB Twenty-three cationic chiral analytes were resolved in capillary electrophoresis using native beta-cyclodextrin and single isomer heptakis-(2-O-methyl-3,6-di-O-sulfo)-beta-cycloclextrin as chiral selectors. For 12 of 16 chiral analytes resolved with both chiral selectors the enantiomer migration order was opposite. In selected cases the structure of cyclodextrin-analyte complexes in aqueous solution was investigated using one-dimensional transverse rotating frame nuclear Overhauser and exchange spectroscopy. It was found that in contrast to mainly inclusion-type complexes between chiral analytes and beta-cyclodextrin, external complexes are formed between the chiral analytes and structurally crowded, highly charged heptakis-(2-O-methyl-3,6-di-O-sulfo)-beta-cyclodextrin. C1 Univ Munster, Inst Pharmaceut & Med Chem, D-48149 Munster, Germany. Tbilisi State Univ, Sch Chem, Mol Recognit & Separat Sci Lab, GE-380086 Tbilisi, Rep of Georgia. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. Univ Munster, Inst Organ Chem, D-4400 Munster, Germany. RP Chankvetadze, B (reprint author), Univ Munster, Inst Pharmaceut & Med Chem, Hittorfstr 58-62, D-48149 Munster, Germany. NR 31 TC 39 Z9 39 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD SEP PY 2002 VL 23 IS 17 BP 3027 EP 3034 DI 10.1002/1522-2683(200209)23:17<3027::AID-ELPS3027>3.0.CO;2-V PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 596FT UT WOS:000178154100026 PM 12207312 ER PT J AU Issaq, HJ Conrads, TP Janini, GM Veenstra, TD AF Issaq, HJ Conrads, TP Janini, GM Veenstra, TD TI Methods for fractionation, separation and profiling of proteins and peptides SO ELECTROPHORESIS LA English DT Review DE fractionation; multidimensional separations; peptides; proteins; proteomics; review ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CAPILLARY ZONE ELECTROPHORESIS; CARCINOMA CELL-LINE; RESOLUTION 2-DIMENSIONAL ELECTROPHORESIS; FLIGHT MASS-SPECTROMETRY; CODED AFFINITY TAGS; GEL-ELECTROPHORESIS; PROTEOME ANALYSIS; COMPLEX-MIXTURES; PLASMA-PROTEINS AB In the last few years there has been an increased effort to develop technologies capable of identifying and quantifying large numbers of proteins expressed within a cell system (i.e., the proteome). The complexity of the mixtures being analyzed has made the development of effective fractionation and separation methods a critical component of this effort. This review highlights many of the protein and peptide fractionation and separation methods, such as electrophoresis and high-performance liquid chromatography (HPLC), which have experienced significant development over the past forty years. Modern instrumental strategies for the resolution of cell proteins, based on separations employing a single high-resolution or multidimensional approach, and the relative merits of each, will be discussed. The focus of this manuscript will be on the development of multidimensional separations such as two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), HPLC/HPLC, and HPLC-capillary electrophoresis and their application to the characterization of complex proteome mixtures. C1 NCI, SAIC Frederick Inc, Separat Technol Grp, Analyt Chem Lab, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, SAIC Frederick Inc, Separat Technol Grp, Analyt Chem Lab, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 90 TC 135 Z9 143 U1 6 U2 41 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD SEP PY 2002 VL 23 IS 17 BP 3048 EP 3061 DI 10.1002/1522-2683(200209)23:17<3048::AID-ELPS3048>3.0.CO;2-L PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 596FT UT WOS:000178154100029 PM 12207315 ER PT J AU Klee, CB Means, AR AF Klee, CB Means, AR TI Keeping up with calcium - Conference on calcium-binding proteins and calcium function in health and disease SO EMBO REPORTS LA English DT Editorial Material ID MICE LACKING; MUSCLE C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. NCI, Biochem Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Means, AR (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Box 3813, Durham, NC 27710 USA. NR 23 TC 11 Z9 12 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD SEP PY 2002 VL 3 IS 9 BP 823 EP 827 DI 10.1093/embo-reports/kvf182 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 595RN UT WOS:000178122700006 PM 12223462 ER PT J AU Humphreys, RC Bierie, B Zhao, L Raz, R Levy, D Hennighausen, L AF Humphreys, RC Bierie, B Zhao, L Raz, R Levy, D Hennighausen, L TI Deletion of Stat3 blocks mammary gland involution and extends functional competence of the secretory epithelium in the absence of lactogenic stimuli SO ENDOCRINOLOGY LA English DT Article ID CLUSTERIN GENE-EXPRESSION; PROGRAMMED CELL-DEATH; MATRIX METALLOPROTEINASES; ACCELERATED APOPTOSIS; SIGNAL TRANSDUCER; TISSUE INHIBITOR; TRANSGENIC MICE; STROMELYSIN-1; MORPHOGENESIS; ACTIVATION AB The transcription factor Stat3 is activated through tyrosine phosphorylation by many cytokines and is a fundamental mediator of their signals. In the mammary gland, Stat3 activity increases sharply shortly after weaning, and involution is delayed in mice, that contain a mutant Stat3 lacking 33 amino acids including the key tyrosine residue. We have now generated a more extensive mutation of Stat3 through the deletion of exons 15-21 in mammary epithelium. This resulted in the loss of 245 amino acids including the DNA binding and SH2 domains, and Stat3 protein was undetectable. Pregnancy-mediated mammary development and lactation were normal in these mice. Involution was delayed and, remarkably, Stat3-null mammary epithelium maintained its functional integrity and competence even 8 d after weaning, whereas control mammary tissue was rendered nonfunctional within 2 d. The lack of remodeling and functional stasis of the epithelium correlated with the disruption of proteinase activity. Our data demonstrate that mammary tissue can retain its functional competence in the absence of external lactogenic stimuli and demonstrate a delay in the initiation of the irreversible stage of involution. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. NYU Med Ctr, Dept Pathol, New York, NY 10091 USA. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Room 101, Bethesda, MD 20892 USA. EM hennighausen@nih.gov OI Levy, David/0000-0002-7320-7788 FU NIAID NIH HHS [AI28900] NR 36 TC 78 Z9 84 U1 4 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2002 VL 143 IS 9 BP 3641 EP 3650 DI 10.1210/en.2002-220224 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 586CY UT WOS:000177567800051 PM 12193580 ER PT J AU Shalev, A Pise-Masison, CA Radonovich, M Hoffmann, SC Hirshberg, B Brady, JN Harlan, DM AF Shalev, A Pise-Masison, CA Radonovich, M Hoffmann, SC Hirshberg, B Brady, JN Harlan, DM TI Oligonucleotide microarray analysis of intact human pancreatic islets: Identification of glucose-responsive genes and a highly regulated TGF beta signaling pathway SO ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; MORPHOGENETIC PROTEIN; EXPRESSION; CELLS; PROMOTER; MOUSE; AUTOIMMUNE; ACTIVATION; BINDING; MEMBER AB Human pancreatic islets are a major focus of diabetes research due to their key role in glucose homeostasis and their potential for transplantation in the treatment of type 1 diabetes. Currently, no comprehensive analysis of baseline or glucose-stimulated islet gene expression is available. Using oligonucleotide microarrays we analyzed isolated intact human islets incubated at low and high g.scose. We identified similar to6000 islet genes, several with clinical implications, as well as a number of glucose-regulated genes. Interestingly, two transforming growth factor beta (TGFbeta) superfamily members were highly regulated by glucose. One of them, PDF, was found to have a very high expression level compared to other TGFbeta superfamily members. Quantitative reverse transcriptase polymerase chain reaction confirmed these results and demonstrated that the highly expressed PDF was similar to10-fold down-regulated by glucose while other TGFbeta superfamily members and target genes were up-regulated. These results suggest that a highly regulated TGFbeta signaling cascade exists in human islets, and that PDF may play a central role in islet biology. Since TGFbeta is involved in differentiation and immune modulation, this novel pathway may link glucose metabolism, immune response and development of human islets. We report here the first gene expression profile of intact human islets. These and similar analyses will provide better understanding of human islet biology and enhance the development of novel diabetes therapies. C1 NIDDKD, Transplantat & Autoimmun Branch, NIH, Bethesda, MD 20889 USA. NIDDKD, Basic Res Labs, NIH, Bethesda, MD 20889 USA. RP Shalev, A (reprint author), NIDDKD, Transplantat & Autoimmun Branch, NIH, Bethesda, MD 20889 USA. NR 23 TC 126 Z9 128 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2002 VL 143 IS 9 BP 3695 EP 3698 DI 10.1210/en.2002-220564 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 586CY UT WOS:000177567800057 PM 12193586 ER PT J AU Knap, A Dewailly, E Furgal, C Galvin, J Baden, D Bowen, RE Depledge, M Duguay, L Fleming, LE Ford, T Moser, F Owen, R Suk, WA Unluata, U AF Knap, A Dewailly, E Furgal, C Galvin, J Baden, D Bowen, RE Depledge, M Duguay, L Fleming, LE Ford, T Moser, F Owen, R Suk, WA Unluata, U TI Indicators of ocean health and human health: Developing a research and monitoring framework SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE biologic effects; biomarkers; contamination; human health; indicators; ocean health ID HARMFUL ALGAL BLOOMS; IN-UTERO; EXPOSURE; METHYLMERCURY; CHILDREN; ORGANOCHLORINES; INUIT; POPULATION; PFIESTERIA; MERCURY AB We need to critically assess the present quality of the marine ecosystem, especially the connection between ecosystem change and threats to human health. In this article we review the current state of indicators to link changes in marine organisms with eventual effects to human health, identify research opportunities in the use of indicators of ocean and human health, and discuss how to establish collaborations between national and international governmental and private sector groups. We present a synthesis of the present state of understanding of the connection between ocean health and human health, a discussion of areas where resources are required, and a discussion of critical research needs and a template for future work in this field. To understand fully the interactions between ocean health and human health, programs should be organized around a "models-based" approach focusing on critical themes and attributes of marine environmental and public health risks. Given the extent and complex nature of ocean and human health issues, a program networking across geographic and disciplinary boundaries is essential. The overall goal of this approach would be the early detection of potential marine-based contaminants, the protection of marine ecosystems, the prevention of associated human illness, and by implication, the development of products to enhance human well-being. The tight connection between research and monitoring is essential to develop such an indicator-based effort. C1 Bermuda Biol Stn Res Inc, St Georges GE01, Bermuda. Univ Laval, Quebec City, PQ, Canada. Univ N Carolina, Dept Chem & Biol Sci, Wilmington, NC 28401 USA. Univ Massachusetts, Dept Environm Coastal & Ocean Sci, Boston, MA 02125 USA. Univ Plymouth, Dept Biol Sci, Plymouth PL4 8AA, Devon, England. Univ So Calif, Wrigley Inst, Los Angeles, CA USA. Univ Miami, Marine & Freshwater Biomed Sci Ctr, Natl Inst Environm Hlth Sci, Miami, FL 33152 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. US Dept State, Washington, DC 20520 USA. NIH, Res Triangle Pk, NC USA. UNESCO, Intergovt Oceanog Commiss, Paris, France. RP Knap, A (reprint author), Bermuda Biol Stn Res Inc, 17 Biol Lane, St Georges GE01, Bermuda. EM knap@bbsr.edu FU NIEHS NIH HHS [P01 ES010594-02, P01 ES010594] NR 50 TC 48 Z9 55 U1 3 U2 30 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2002 VL 110 IS 9 BP 839 EP 845 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 591RJ UT WOS:000177893800022 PM 12204815 ER PT J AU Suzukawa, K Weber, TJ Colburn, NH AF Suzukawa, K Weber, TJ Colburn, NH TI AP-1, NF kappa B, and ERK activation thresholds for promotion of neoplastic transformation in the mouse epidermal JB6 model SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE activator protein-1; epidermal growth factor; nuclear factor kappa B; serum-response element; 12-O-tetradecanoylphorbol-13-acetate; transformation; tumor necrosis factor-alpha ID NECROSIS-FACTOR-ALPHA; ANCHORAGE-INDEPENDENT GROWTH; INDUCED CELL-TRANSFORMATION; MAP KINASE PATHWAYS; HUMAN KERATINOCYTES; PROTEIN-1 ACTIVATION; C-JUN; INDUCED EXPRESSION; RESPONSE ELEMENT; TUMOR PROMOTION AB The promotion-sensitive mouse epidermal JB6 cells (done 41) have been used to identify the tumor-promoting activity of various compounds. Because treatment by tumor promoters [12-O-tetradecanoylphorbol-13-acetate (TPA), epidermal growth factor (EGF), or tumor necrosis factor alpha (TNFalpha)] transforms done 41 cells to anchorage-independent and tumorigenic phenotypes, they are considered to be undergoing late-stage tumor promotion. Here we address the question of how much activation of transformation-relevant transcription factors [activator protein-1 (AP-1), ternary complex factors (TCFs), or nuclear factor kappaB (NFkappaB)] is required for transformation response and how much tumor promoter produces significant risk of transformation. Stable transfectants harboring a reporter construct with an AP-1 response element, serum-response element (SRE), or NFkappaB response element were established. We examined the relationship between concentration of tumor promoters, key signaling events, and activation of the transcription factors. A concentration of >0.2 nM TPA or 0.12 ng/mL (0.02 nM) EGF produced a significant increase in transformation response as well as in extracellular signal-regulated protein kinase (ERK), SRE, or AP-1 activation. Treatment with >0.4 U/mL (2.35 pM) TNFalpha increased NFkappaB activity and transformation response in a dose-dependent manner. However, transformation response decreased at >33 U/mL TNFalpha due to a cytotoxic response. These findings suggest that the signaling pathway leading to the activation of ERK, TCF, and AP-1 proteins constitutes a major factor determining the risk of tumor promotion by TPA or EGF. Cell toxicity in addition to NFkappaB activation should be considered in predicting TNFalpha-induced transformation response. C1 NCI, Gene Regulat Sect, Basic Res Lab, Ft Detrick, MD 21702 USA. Pacific NW Natl Lab, Richland, WA 99352 USA. RP Colburn, NH (reprint author), NCI, Gene Regulat Sect, Basic Res Lab, Bldg 560,Room 21-89, Ft Detrick, MD 21702 USA. NR 41 TC 48 Z9 49 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2002 VL 110 IS 9 BP 865 EP 870 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 591RJ UT WOS:000177893800026 PM 12204819 ER PT J AU Sokol, RZ Wang, SX Wan, YJY Stanczyk, FZ Gentzschein, E Chapin, RE AF Sokol, RZ Wang, SX Wan, YJY Stanczyk, FZ Gentzschein, E Chapin, RE TI Long-term, low-dose lead exposure alters the gonadotropin-releasing hormone system in the male rat SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE gonadotropin-releasing hormone; hypothalamic-pituitary axis; lead acetate ID CENTRAL-NERVOUS-SYSTEM; REPRODUCTIVE TOXICITY; LUTEINIZING-HORMONE; MECHANISMS; SECRETION; NEUROTOXICITY; AXIS; BIOMARKERS; CADMIUM AB lead acetate for short periods of time induced changes in the hypothalamic gonadotropin-releasing hormone (GnRH) at the molecular level, but these changes were attenuated with increased concentration of exposure. The current study evaluated whether exposure to low levels of lead acetate over longer periods of time would produce a similar pattern of adaptation to toxicity at the molecular and biologic levels. Adult 100-day-old Sprague-Dawley male rats were dosed with 0, 0.025, 0.05, 0.1, and 0.3% lead acetate in water. Animals were killed after 1, 4, 8, and 16 weeks of treatment. Luteinzing hormone (LH) and GnRH levels were measured in serum, and lead levels were quantified in whole blood. Hypothalamic GnRH mRNA levels were also quantified. We found no significant differences in serum LH and GnRH among the groups of animals treated within each time period. A significant dose-related increase of GnRH mRNA concentrations with lead dosing occurred in animals treated for 1 week. Animals treated for more than 1 week also exhibited a significant increase in GnRH mRNA, but with an attenuation of the increase at the higher concentrations of lead with increased duration of exposure. We conclude that the signals within and between the hypothalamus and pituitary gland appear to be disrupted by long-term, low-dose lead exposure. C1 Univ So Calif, Dept Obstet & Gynecol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA USA. Harbor UCLA Med Ctr, Dept Pathol, Torrance, CA 90509 USA. NIEHS, Reprod Toxicol Grp, Res Triangle Pk, NC 27709 USA. RP Sokol, RZ (reprint author), Womens & Childrens Hosp, Room 8K9,1240 N Mission Rd, Los Angeles, CA 90033 USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [P30 ES07048, R01ES037649] NR 39 TC 25 Z9 25 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2002 VL 110 IS 9 BP 871 EP 874 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 591RJ UT WOS:000177893800027 PM 12204820 ER PT J AU Crain, EF Walter, M O'Connor, GT Mitchell, H Gruchalla, RS Kattan, M Malindzak, GS Enright, P Evans, R Morgan, W Stout, JW AF Crain, EF Walter, M O'Connor, GT Mitchell, H Gruchalla, RS Kattan, M Malindzak, GS Enright, P Evans, R Morgan, W Stout, JW TI Home and allergic characteristics of children with asthma in seven US urban communities and design of an environmental intervention: The Inner-City Asthma Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE environmental intervention; home environmental characteristics; inner-city children; pediatric asthma ID RISK-FACTORS; CHILDHOOD ASTHMA; PASSIVE SMOKING; VACUUM-CLEANERS; DOG ALLERGEN; EXPOSURE; SENSITIZATION; EFFICIENCY; MORBIDITY; HEALTH AB Most published environmental remediation interventions have been directed at single allergens and have employed demanding strategies; few have been performed in the homes of inner-city children disproportionately burdened by asthma. Our objective was a) to describe the allergen sensitivities, environmental tobacco smoke (ETS) exposure, and home environmental characteristics of a national sample of inner-city children with moderate to severe asthma and b) to develop and implement a multifaceted, home-based comprehensive intervention to reduce home allergens and ETS, tailored to the specific sensitization and exposure profiles of those children. Allergen skin testing and a home evaluation were performed to determine the presence of ETS and factors known to be associated with increased indoor allergen levels. Based on published remediation techniques, a home environmental intervention, organized into modules, each addressing one of five specific allergen groups or ETS, was designed. Of 994 allergic children from seven U.S. urban communities, 937 successfully completed baseline interviews and home allergen surveys and were enrolled. More than 50% of children had positive skin tests to three or more allergen groups. Cockroaches were reported in 58% of homes, wall-to-wall carpeting in the child's bedroom in 55%, a smoker in 48%, mice or rats in 40%, and furry pets in 28%. More than 60% of enrolled families received four or more modules, and between 94% and 98% of all modules were completed. We conclude that most inner-city children with moderate to severe asthma are sensitized to multiple indoor allergens and that environmental factors known to be associated with asthma severity are commonly present in their homes. The intervention developed for the Inner-City Asthma Study employs accepted methods to address an array of allergens and ETS exposure while ensuring that the intervention is tailored to the specific sensitization profiles and home characteristics of these children. C1 Albert Einstein Coll Med, Jacobi Med Ctr, Dept Pediat Emergency Med, Bronx, NY 10467 USA. Rho Inc, Chapel Hill, NC USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Texas, SW Med Sch, Dept Med, Dallas, TX 75230 USA. Mt Sinai Sch Med, Dept Pediat, New York, NY USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Arizona, Resp Sci Ctr, Tucson, AZ USA. Northwestern Univ, Sch Med, Dept Pediat, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. RP Crain, EF (reprint author), 1W20 Jacobi Hosp, 1400 Pelham Pkwy, Bronx, NY 10461 USA. OI O'Connor, George/0000-0002-6476-3926 FU NIAID NIH HHS [AI39785, AI-39769, AI-39901, AI-39902, AI-39776, AI-39900, AI39789, AI-39761] NR 39 TC 117 Z9 118 U1 3 U2 12 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2002 VL 110 IS 9 BP 939 EP 945 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 591RJ UT WOS:000177893800037 PM 12204830 ER PT J AU Rogan, WJ Weil, WB AF Rogan, WJ Weil, WB TI Duration of breast-feeding and PBBs SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter C1 NIEHS, Res Triangle Pk, NC 27709 USA. Michigan State Univ, E Lansing, MI 48824 USA. RP Rogan, WJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 5 TC 2 Z9 2 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2002 VL 110 IS 9 BP A503 EP A504 DI 10.1289/ehp.110-a503 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 591RJ UT WOS:000177893800006 PM 12269289 ER PT J AU Buck, GM Vena, JE Greizerstein, HB Weiner, JM McGuinness, B Mendola, P Kostyniak, PJ Swanson, M Bloom, MS Olson, JR AF Buck, GM Vena, JE Greizerstein, HB Weiner, JM McGuinness, B Mendola, P Kostyniak, PJ Swanson, M Bloom, MS Olson, JR TI PCB congeners and pesticides and female fecundity, New York State Angler Prospective Pregnancy Study SO ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE congener; fecundity; fish consumption; PCBs; pesticide; pregnancy; reproduction ID BIRTH-WEIGHT; TIME; EXPOSURE; RISK; CONSUMPTION; HEALTH; COHORT; FISH AB Consumption of PCB-contaminated sport fish from Lake Ontario has been reported to be associated with diminished female fecundity. To identify Polychlorinated biphenyl (PCB) congeners and other pesticides that might be associated with reduced fecundity, we followed 102 women aged 20-34 years attempting pregnancy who completed daily diaries for 12 at risk menstrual cycles. Fecundity referred to time-to-pregnancy (TTP) or the number of at risk menstrual cycles required for pregnancy. Blood specimens were obtained for 88 (86%) women and were analyzed using gas chromatography and electron capture for 66 PCB congeners and seven pesticides. Laboratory values were recovery, background and fat corrected prior to natural log transformation. Using stepwise discriminant analysis, congeners IUPAC #205 and #206 and hexaclorobenzene were significantly and positively associated with increasing TTP when women were categorized as becoming pregnant in the first or first three at risk menstrual cycles, respectively. Congeners #205 and #206 are reported to have anti) estrogenic structural activity. Published by Elsevier Science B.V. C1 SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. SUNY Buffalo, Dept Pharmacol & Toxicol, Buffalo, NY 14214 USA. RP Buck, GM (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B05, Rockville, MD 20852 USA. OI Mendola, Pauline/0000-0001-5330-2844; Bloom, Michael/0000-0002-0028-5494; Buck Louis, Germaine/0000-0002-1774-4490 NR 27 TC 10 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1382-6689 J9 ENVIRON TOXICOL PHAR JI Environ. Toxicol. Pharmacol. PD SEP PY 2002 VL 12 IS 2 BP 83 EP 92 AR PII S1382-6689(02)00026-1 DI 10.1016/S1382-6689(02)00026-1 PG 10 WC Environmental Sciences; Pharmacology & Pharmacy; Toxicology SC Environmental Sciences & Ecology; Pharmacology & Pharmacy; Toxicology GA 600DL UT WOS:000178375300004 PM 21782627 ER PT J AU Chatterjee, N Wacholder, S AF Chatterjee, N Wacholder, S TI Validation studies: Bias, efficiency, and exposure assessment SO EPIDEMIOLOGY LA English DT Editorial Material ID DISEASE; DESIGN C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Chatterjee, N (reprint author), 6120 Execut Blvd,EPS 8038, Bethesda, MD 20892 USA. NR 15 TC 6 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2002 VL 13 IS 5 BP 503 EP 506 DI 10.1097/01.EDE.0000022948.80077.AE PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 586CQ UT WOS:000177566700004 PM 12192218 ER PT J AU Ronckers, CM van Leeuwen, FE Hayes, RB Verduijn, PG Stovall, M Land, CE AF Ronckers, CM van Leeuwen, FE Hayes, RB Verduijn, PG Stovall, M Land, CE TI Cancer incidence after nasopharyngeal radium irradiation SO EPIDEMIOLOGY LA English DT Article DE cancer; radiation; head and neck ID FOLLOW-UP; POOLED ANALYSIS; UNITED-STATES; CHILDHOOD; MORTALITY; RADIATION; EXPOSURE; TUMORS; NETHERLANDS; COHORT AB Background. From 1940 until 1970, nasopharyngeal radium irradiation was used to treat children and military personnel suffering from Eustachian tube failure attributable to local lymphoid hyperplasia. Methods. We studied cancer incidence in a cohort of 4339 Dutch patients treated with nasopharyngeal radium irradiation, mostly in childhood, and 4104 frequency-matched non-exposed subjects. Average doses to the nasopharynx, pituitary gland, brain, and thyroid gland were 275, 10.9, 1.8, and 1.5 cGy, respectively. We assessed cancer incidence from cancer registry linkage (1989-1996), self-report including medical verification (1945-1988), and death certificates (1945-1996). Results. During 18-50 years of follow-up, four thyroid malignancies (standardized incidence ratio [SIR] = 2.8; 95% confidence interval [CI] 0.8-7.2) and five malignant brain tumors (SIR = 1.3; CI 0.4-3.1) were observed. Increased risks were observed for malignancies of lymphoproliferative and hematopoietic origin (SIR = 1.9; Cl = 1.2-2.8) and breast cancer (SIR = 1.5; CI = 1.1-2.1). Strong dose-response trends could not be demonstrated for any cancer outcome, although relative risk estimates were elevated in the highest-dose category for head and neck cancer and breast cancer. Conclusions. These data provide little evidence for a high excess risk of cancer associated with nasopharyngeal radium irradiation treatment as applied in the Netherlands. Inconsistent findings across studies and public concern warrant the continuing follow-up of available cohorts. C1 Reinaert Klin, Dept Ear Nose & Throat Med, Maastricht, Netherlands. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX USA. RP Ronckers, CM (reprint author), NCI, Radiat Epidemiol Branch, 6120 Execut Blvd,EPS 7049, Rockville, MD 20852 USA. OI Hayes, Richard/0000-0002-0918-661X FU NCI NIH HHS [N01-CP-33013] NR 41 TC 7 Z9 7 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2002 VL 13 IS 5 BP 552 EP 560 DI 10.1097/01.EDE.0000021464.28600.BE PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 586CQ UT WOS:000177566700011 PM 12192225 ER PT J AU Zheng, YL Li, BS Amin, ND Albers, W Pant, HC AF Zheng, YL Li, BS Amin, ND Albers, W Pant, HC TI A peptide derived from cyclin-dependent kinase activator (p35) specifically inhibits Cdk5 activity and phosphorylation of tau protein in transfected cells SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE Cdk5; p35; Cdk5 inhibitory peptide (CIP); Tau phosphorylation; Alzheimer's disease ID ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; NEUROFILAMENT; MICE; BRAIN; DEFECTS; NEURONS; DOMAIN; P25 AB Cyclin-dependent kinase-5 (Cdk5) is a serine/threonine kinase activated by its neuron-specific activator, p35, or its truncated form, p25. It has been proposed that the deregulation of Cdk5 activity by association with p25 in human brain tissue disrupts the neuronal cytoskeleton and may be involved in neurodegenerative diseases such as Alzheimer's disease. In this study, we demonstrate that a short peptide (amino acid residues 154-279; Cdk5 inhibitory peptide; CIP), derived from p35, specifically inhibits Cdk5 activity invitro and in HEK293 cells cotransfected with the peptideand Cdk5/p25, but had no effect on endogenous cdc2 kinaseactivity. Moreover, we demonstrate that the phosphorylation of tau in HEK293 cells, cotransfected with Cdk5/p25 and CIP, is effectively reduced. These results suggest that CIP specifically inhibits both Cdk5/p25 complex activity and the tau hyperphosphorylation induced by Cdk5/p25. The elucidation of the molecular basis of p25 activation and CIP inhibition of Cdk5 activity may provide insight into mechanisms underlying the pathology of Alzheimer's disease and contribute to therapeutic strategies. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Pant, HC (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Rm 4D04,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 31 TC 47 Z9 52 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD SEP PY 2002 VL 269 IS 18 BP 4427 EP 4434 DI 10.1046/j.1432-1033.2002.03133.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 593RN UT WOS:000178006100005 PM 12230554 ER PT J AU Schulze, TG Treichel, KC AF Schulze, TG Treichel, KC TI The European Federation of Psychiatric Trainees (EFPT) - an integral part of the European harmonisation of psychiatric education and practise SO EUROPEAN PSYCHIATRY LA English DT Article DE European Board of Psychiatry; trainee organisations; training in psychotherapy; examinations; psychiatric genetic research AB The European Federation of Psychiatric Trainees (EFPT) is the umbrella organisation for national European psychiatric trainees' organisations. It primarily aims at advancing and harmonising the quality of psychiatric education and practise. As a permanent observer member of the European Board of Psychiatry and the European Board of Child and Adolescent Psychiatry, the EFPT actively participates both in the development of educational guidelines and in the evaluation of psychiatric training institutions in Europe. Through its annually held European Forum for all Psychiatric Trainees the EFPT provides a unique opportunity for the exchange of training-related experiences and opinions on current developments in psychiatry. This is the first comprehensive overview of the history, goals, and political work of the EFPT, depicting its evolution from an informal meeting of psychiatric trainees to a recognised organisation representing over 10 000 young psychiatrists throughout Europe. (C) 2002 Editions scientifiques et medicales Elsevier SAS. C1 NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Univ Bonn, Dept Psychiat & Psychotherapy, D-5300 Bonn, Germany. Med & Soziales Zentrum GmbH, Dept Psychiat & Psychotherapy, Angermunde, Germany. RP Schulze, TG (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, Bldg 36,Rm 4C12 MSC 4095,36 Convent Dr, Bethesda, MD 20892 USA. RI Schulze, Thomas/H-2157-2013 NR 9 TC 11 Z9 11 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD SEP PY 2002 VL 17 IS 5 BP 300 EP 305 PG 6 WC Psychiatry SC Psychiatry GA 606DK UT WOS:000178718100012 PM 12510630 ER PT J AU La Paro, KM Olsen, K Pianta, RC AF La Paro, KM Olsen, K Pianta, RC TI Special education eligibility: Developmental precursors over the first three years of life SO EXCEPTIONAL CHILDREN LA English DT Article ID EARLY INTERVENTION; EARLY IDENTIFICATION; HOME-ENVIRONMENT; CHILDREN; RISK; PEDIATRICIANS; 3-YEAR-OLD; SCORES; SITES AB From the National Institute of Child Health and Development (NICHD) Study of Early Child Care sample, two groups of children at age 36 months were examined-children identified by medical professionals as needing special services and children eligible for special services based on developmental assessments. Demographic information, children behavioral functioning, mothers' psychological functioning, mother-child interactions, and quality of the home environment were examined. Early home environment and later behavior problems and children health problems significantly contributed to the prediction model for membership in the group identified by medical professionals. Early home environment and socioeconomic status (SES) significantly contributed to the prediction model for the group identified based on developmental assessments. Results have implications for efforts to screen and detect young children likely to benefit from special education services. C1 Univ Virginia, NICHD, Study Early Child Care, Charlottesville, VA 22908 USA. Univ Virginia, Natl Ctr Early Dev & Learning, Charlottesville, VA 22908 USA. RP La Paro, KM (reprint author), Univ Virginia, NICHD, Study Early Child Care, POB 800784, Charlottesville, VA 22908 USA. OI Pianta, Robert/0000-0002-6280-8051 NR 32 TC 4 Z9 4 U1 0 U2 2 PU COUNCIL EXCEPTIONAL CHILDREN PI RESTON PA 1920 ASSOCIATION DR, RESTON, VA 22091-1589 USA SN 0014-4029 J9 EXCEPT CHILDREN JI Except. Child. PD FAL PY 2002 VL 69 IS 1 BP 55 EP 66 PG 12 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 590AE UT WOS:000177794200004 ER PT J AU Cardenas, AM Arriagada, C Allen, DD Caviedes, R Cortes, JF Martin, J Couve, E Rapoport, SI Shimahara, T Cavides, P AF Cardenas, AM Arriagada, C Allen, DD Caviedes, R Cortes, JF Martin, J Couve, E Rapoport, SI Shimahara, T Cavides, P TI Cell lines derived from hippocampal neurons of the normal and trisomy 16 mouse fetus (a model for Down syndrome) exhibit neuronal markers, cholinergic function, and functional neurotransmitter receptors SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Down syndrome; trisomy 21; trisomy 16; calcium; glutamate; nicotine; acetylcholine; choline uptake; choline acetyltransferase; synaptophysin ID ROOT GANGLION NEURONS; ALZHEIMERS-DISEASE; ION CHANNELS; ANIMAL-MODEL; MUSCLE; MICE; DIFFERENTIATION; CHROMOSOME-21; ABNORMALITIES; CURRENTS AB We have established hippocampal cell lines from normal and trisonly, 16 fetal mice, a model of human trisomy 21. Both cell lines, named H1b (derived from a normal. Animal) and HTk (trisomic) possess neuronal markers by immunohistochemistry (enolase, synaptophysin, microtubule associated protein-2, and choline acetyltransferase) and lack glial markers (glial fibrillary Acidic protein And S-100). Also, we evaluated intracellular Ca2+ levels ([Ca2+](i)) in response to neurotransmitter Agonists, in cells loaded with the fluorescent Ca2+ indicators Indo-1 and Fluo-3. Both cell lines responded to glutamatergic stimuli induced by glutamate, N-methyl-D-aspartate, I-amino-2,3-dihydro-5methyl-3-oxo-4-isoxazole propanoic acid or kainate. Glutamate responses were only partially prevented by addition of 5 mM EGTA and the metabotropic glutamate receptor agonist, trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD), increased [Ca2+]i in both cell types. These results confirm the presence of glutamatergic metabotropic receptors. In glutamate-induced responses, HTk cells exhibited slower time-dependent decay kinetics than H1b cells. Cholinergic agonists (nicotine and muscarine) induced a rapid, transient increase in [Ca2+](i) in both cell types. Furthermore, some cells were sensitive to istamine and norepinephrine. All responses to the aforementioned agonists were prevented by addition of specific antagonists. We also studied incorporation and release of [H-3]choline in the cells, and observed no differences in uptake parameters. However, release induced by K+ and nicotine depolarization was greatly reduced in HTk cells. The results show that H1b and HTk cells retain neuronal characteristics and respond to specific neurotransmitter stimuli. The HTk differences could be related to neuronal pathophysiology in Down syndrome. (C) 2002 Elsevier Science (USA). C1 Univ Chile, Fac Med, Program Mol & Clin Pharmacol, ICBM, Santiago 7, Chile. Univ Chile, Fac Med, Morphol Program, ICBM, Santiago 7, Chile. Univ Valparaiso, Sch Med, Pharmacol Lab, Valparaiso, Chile. Univ Valparaiso, Valparaiso Ctr Cellular & Mol Neurosci, Valparaiso, Chile. Univ Valparaiso, Dept Biol, Valparaiso, Chile. Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX USA. NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. CNRS, NBCM, Gif Sur Yvette, France. Sansum Med Res Inst, Santa Barbara, CA USA. RP Cavides, P (reprint author), Univ Chile, Fac Med, Program Mol & Clin Pharmacol, ICBM, Casilla 70000, Santiago 7, Chile. EM pcaviede@machi.med.uchile.cl NR 32 TC 9 Z9 9 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD SEP PY 2002 VL 177 IS 1 BP 159 EP 170 DI 10.1006/exnr.2002.7957 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 598EY UT WOS:000178263600015 PM 12429219 ER PT J AU Ross, KC Waldman, BC Conejero-Goldberg, C Freed, W Coleman, JR AF Ross, KC Waldman, BC Conejero-Goldberg, C Freed, W Coleman, JR TI Transplantation of M213-2O cells with enhanced GAD(67) expression into the inferior colliculus alters audiogenic seizures SO EXPERIMENTAL NEUROLOGY LA English DT Article DE audiogenic seizures; GAD(67); cell lines; Epstein-Barr ID EPILEPSY-PRONE RAT; LARGE T-ANTIGEN; LONG-EVANS RAT; GABA; LINES; ALLELE AB The purpose of the present study was to examine the effects of GABA-producing cell transplants on audiogenic seizures (AGS). The M213-2O cell line was derived from fetal rat striatum and has GABAergic properties. This cell line was further modified to express human GADs, and produce elevated levels of GABA. The present study compares the effects of parent M213-2O cell transplants with those of GAD(67)-modified M213-2O cells in AGS-prone Long-Evans rats. Two weeks following implantation of engineered cells, latency to AGS-typical wild running was increased compared to nonimplanted subjects. Survival of the transplanted cells was confirmed by immunochemical labeling of GAD(67) and Epstein-Barr virus nuclear antigen. These findings support the use of GABA-producing cell lines to modify seizure activity. (C) 2002 Elsevier Science (USA). C1 Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA. Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. Univ S Carolina, Dept Pharmacol & Physiol, Columbia, SC 29208 USA. Natl Inst Drug Abuse, Baltimore, MD 21224 USA. RP Ross, KC (reprint author), Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA. NR 18 TC 15 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD SEP PY 2002 VL 177 IS 1 BP 338 EP 340 DI 10.1006/exnr.2002.7987 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 598EY UT WOS:000178263600033 PM 12429237 ER PT J AU Nagao, E Seydel, KB Dvorak, JA AF Nagao, E Seydel, KB Dvorak, JA TI Detergent-resistant erythrocyte membrane rafts are modified by a Plasmodium falciparum infection SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE malaria; plasmodium falciparum; lipid rafts; erythrocytes ID MALARIAL INFECTION; CHOLESTEROL; PROTEINS; FLOTILLIN-1; COMPONENTS; KNOBS; CELLS; RICH AB Detergent resistant membranes (DRMs) have been implicated in numerous cellular processes including signal transduction, membrane trafficking, and molecular sorting. Flotillins-1 and -2 have recently been shown to be large components of erythrocyte DRMs. In this study, we show that a Plasmodium wfalciparum infection disrupts the association of flotillins with erythrocyte DRMs. Flotillins are probably released from erythrocyte DRMs through the reduction of cholesterol and sphingomyelin levels during the course of a P. falciparum-infection. Although it is well known that a P. falciparum infection can modify the host erythrocyte membrane, this is the first report that P. falciparum can alter the DRM components of erythrocyte membranes. C1 NIAID, Lab Malaria & Vector Biol, NIH, Bethesda, MD 20892 USA. RP Dvorak, JA (reprint author), NIAID, Lab Malaria & Vector Biol, NIH, Bldg 4,Room 126,4 Ctr Dr MSC 0425, Bethesda, MD 20892 USA. NR 18 TC 31 Z9 33 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD SEP PY 2002 VL 102 IS 1 BP 57 EP 59 DI 10.1016/S0014-4894(02)00143-1 PG 3 WC Parasitology SC Parasitology GA 662NX UT WOS:000181954900007 PM 12615167 ER PT J AU Krasnova, IN Mccoy, MT Ladenheim, B Cadet, JL AF Krasnova, IN Mccoy, MT Ladenheim, B Cadet, JL TI CDNA array analysis of gene expression profiles in the striata of wild-type and Cu/Zn superoxide dismutase transgenic mice treated with neurotoxic doses of amphetamine SO FASEB JOURNAL LA English DT Article DE amphetamine; neurotoxicity; Cu/Zn SOD; striatum; gene expression analysis ID STRESS-INDUCED APOPTOSIS; METHAMPHETAMINE-INDUCED NEUROTOXICITY; PROGRAMMED CELL-DEATH; C-FOS; TRANSCRIPTION FACTORS; RAT STRIATUM; RECEPTOR ACTIVATION; OXIDATIVE STRESS; NERVOUS-SYSTEM; DNA-BINDING AB Amphetamine (AMPH) is a drug of abuse that causes the degeneration of striatal dopamine terminals in mammals. Superoxide radicals seem to participate in AMPH-induced damage because its toxicity is attenuated in Cu/Zn superoxide dismutase transgenic (SOD-tg) mice. To provide a detailed analysis of molecular changes associated with AMPH toxicity, we used cDNA arrays consisting of 1176 genes to detect differential changes in gene expression in the striata of wild-type and SOD-tg mice treated with neurotoxic doses of the drug. We found 42 genes that showed >1.8-fold changes in at least two consecutive time points during the course of the study and were differentially affected by AMPH in the two genotypes. Specifically, more transcription factors and genes involved in responses to injury/inflammation were affected in wild-type mice after AMPH administration. Some of these stimulant-induced superoxide-dependent alterations in gene expression might affect neuronal functions and promote neuronal damage. Other changes might help to provide some degree of protection against AMPH toxicity. These results support the view that the use of global array analysis of gene expression will help to identify novel molecular mediators of AMPH-induced neurodegeneration. C1 NIDA, Mol Neuropsychiat Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM JCADET@intra.nida.nih.gov NR 58 TC 18 Z9 18 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2002 VL 16 IS 11 BP 1379 EP 1388 DI 10.1096/fj.01-0796com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 601JC UT WOS:000178441800012 PM 12205029 ER PT J AU Zhang, J Meikle, S Grainger, DA Trumble, A AF Zhang, J Meikle, S Grainger, DA Trumble, A TI Multifetal pregnancy in older women and perinatal outcomes SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 14-19, 2002 CL NEW ORLEANS, LOUISIANA SP Soc Maternal Fetal Med DE multifetal pregnancy; twin; triplet; perinatal; infant mortality; old; age ID BIRTH CERTIFICATE DATA; DELAYED CHILDBEARING; FETAL DEATH; RISK; VALIDATION; PROGRAM AB Objective: To examine multifetal pregnancy in older women and permatal outcomes. Design: A cross-sectional study. Setting: A nationwide vital registry. Patient(s): A national population-based database that links the live birth, fetal, and infant death certificates reported of multiple gestations in the United States from 1995 to 1997. It includes 155,777 twin and 5,630 triplet pregnancies. Intervention(s): None. Main Outcome Measure(s): Very preterm birth (<33 weeks), very low birthweight (<1,500 a). and perinatal and infant deaths. Result(s): Compared with those with singleton pregnancies, women with multifetal gestation tended to be older, non-Hispanic white, better educated, married. and nulliparous and to have earlier and more frequent prenatal care. Pregnancies conceived by assisted reproductive technology accounted for an increasing number of multiple gestations in older women. In women with lower socioeconomic status, older age was associated with higher risks of poor perinatal outcomes in twin pregnancy (relative risks ranging from 1.0 to 1.9 with a dose-response pattern). However, in wdomen with higher socioeconomic status, older women did not have a higher risk of poor perinatal outcomes than younger women. Conclusion(s): The effect of older maternal age on perinatal outcomes in multifetal pregnancies may have been altered by assisted reproductive technology, frequent prenatal surveillance. and advanced neonatal care. (C) 2002 by American Society for Reproductive Medicine. C1 NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Univ Kansas, Div Reprod Endocrinol & Infertil, Wichita, KS 67214 USA. RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, NIH, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. NR 17 TC 54 Z9 58 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2002 VL 78 IS 3 BP 562 EP 568 AR PII S0015-0282(02)03272-7 DI 10.1016/S0015-0282(02)03272-7 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 596UP UT WOS:000178184900021 PM 12215334 ER PT J AU Catherino, WH Armstrong, A McKeeby, J Segars, JH Alvero, R Leondires, M AF Catherino, WH Armstrong, A McKeeby, J Segars, JH Alvero, R Leondires, M TI Pregnancy rates are negatively influenced by blood identified on the transfer catheter in patients undergoing blastocyst transfer. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 12-17, 2002 CL SEATTLE, WASHINGTON SP Amer Soc Reproduct Med C1 NICHD, NIH, Bethesda, MD USA. USUHS, NNMC, WRAMC, Combined Fed Program Reprod Endocrinol, Washington, DC USA. Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2002 VL 78 IS 3 SU 1 MA P420 BP S255 EP S255 DI 10.1016/S0015-0282(02)04080-3 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 597UP UT WOS:000178239400708 ER PT J AU Catherino, WH Levi, A Leondires, M Segars, JH Alvero, R McKeeby, J AF Catherino, WH Levi, A Leondires, M Segars, JH Alvero, R McKeeby, J TI The anthrax vaccine does not affect semen parameters, embryo quality, or pregnancy outcome in couples with a vaccinated male military service member. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 12-17, 2002 CL SEATTLE, WASHINGTON SP Amer Soc Reproduct Med C1 Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. NIH, Washington, DC USA. USUHS, Washington, DC USA. NNMC, Washington, DC USA. WRAMC, Combined Fed Program Reprod Endocrinol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2002 VL 78 IS 3 SU 1 MA O285 BP S108 EP S109 DI 10.1016/S0015-0282(02)03666-X PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 597UP UT WOS:000178239400286 ER PT J AU Catherino, WH Leondires, M McKeeby, J Cruess, D Segars, JH Armstrong, A AF Catherino, WH Leondires, M McKeeby, J Cruess, D Segars, JH Armstrong, A TI Prolonged ovarian stimulation in ART cycles does not improve clinical pregnancy rates in poor responders. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 12-17, 2002 CL SEATTLE, WASHINGTON SP Amer Soc Reproduct Med C1 NICHD, NIH, Bethesda, MD USA. USUHS, NNMC, WRAMC, Combined Fed Program Reprod Endocrinol, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. USUHS, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2002 VL 78 IS 3 SU 1 MA O127 BP S49 EP S49 DI 10.1016/S0015-0282(02)03508-2 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 597UP UT WOS:000178239400128 ER PT J AU Frattarelli, JL Levi, A Miller, BT Segars, JH AF Frattarelli, JL Levi, A Miller, BT Segars, JH TI Basal antral follicle number predicts IVF cycle pregnancy, cancellation, and ovarian responsiveness: A prospective study. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 12-17, 2002 CL SEATTLE, WASHINGTON SP Amer Soc Reproduct Med C1 Tripler Army Med Ctr, Honolulu, HI 96859 USA. Combined Fed Program Reprod Endocrinol, NIH, Bethesda, MD USA. Reprod Med Assoc New Jersey, Morristown, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2002 VL 78 IS 3 SU 1 MA O114 BP S44 EP S44 DI 10.1016/S0015-0282(02)03495-7 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 597UP UT WOS:000178239400115 ER PT J AU Gilles, J Creinin, MM Barnhart, KT Westhoff, C Frederick, MM Zang, J AF Gilles, J Creinin, MM Barnhart, KT Westhoff, C Frederick, MM Zang, J TI Wet versus dry intravaginal misoprostol application for treatment of early pregnancy failure. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 12-17, 2002 CL SEATTLE, WASHINGTON SP Amer Soc Reproduct Med C1 Univ Miami, Miami, FL 33152 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Columbia Univ, New York, NY USA. Clin Trials & Surveys Corp, Baltimore, MD USA. NIH, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2002 VL 78 IS 3 SU 1 MA O168 BP S64 EP S65 DI 10.1016/S0015-0282(02)03549-5 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 597UP UT WOS:000178239400169 ER PT J AU Materia, D Naik, D Hosid, S Levi, A Armstrong, A McKeeby, J AF Materia, D Naik, D Hosid, S Levi, A Armstrong, A McKeeby, J TI Frozen blastocyst embryo-transfer: The impact of the duration of estradiol induced endometrial stimulation on cycle outcome. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 12-17, 2002 CL SEATTLE, WASHINGTON SP Amer Soc Reproduct Med C1 ART Inst Washington Inc, Washington, DC USA. Combined Fed Program Reprod Endocrinol, WRAMC, NNMC, USUHS, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2002 VL 78 IS 3 SU 1 MA O189 BP S72 EP S72 DI 10.1016/S0015-0282(02)03570-7 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 597UP UT WOS:000178239400190 ER PT J AU Murdock, C Collins, M Robey, P Nieman, L AF Murdock, C Collins, M Robey, P Nieman, L TI Profound gonadotropin suppression in adult women with McCune-Albright syndrome. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 12-17, 2002 CL SEATTLE, WASHINGTON SP Amer Soc Reproduct Med C1 NIH, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2002 VL 78 IS 3 SU 1 MA O273 BP S103 EP S104 DI 10.1016/S0015-0282(02)03654-3 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 597UP UT WOS:000178239400274 ER PT J AU Nahari, CP Feldman, AL Sinaii, N Merino, MJ Stratton, P Nieman, LK AF Nahari, CP Feldman, AL Sinaii, N Merino, MJ Stratton, P Nieman, LK TI CD10 immunohistochemical staining enhances the pathological detection of endometriosis. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 12-17, 2002 CL SEATTLE, WASHINGTON SP Amer Soc Reproduct Med C1 NICHD, PREB, NIH, Bethesda, MD USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Feldman, Andrew/D-5028-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2002 VL 78 IS 3 SU 1 MA O234 BP S89 EP S90 DI 10.1016/S0015-0282(02)03615-4 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 597UP UT WOS:000178239400235 ER PT J AU Prupas, CS Mayecs, CM Tsibris, JCM Segars, JH Leppert, PC AF Prupas, CS Mayecs, CM Tsibris, JCM Segars, JH Leppert, PC TI Uterine leiomyomas are characterized by abnormal expression of Wnt signaling proteins and disordered collagen deposition. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 12-17, 2002 CL SEATTLE, WASHINGTON SP Amer Soc Reproduct Med C1 NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. Univ S Florida, Tampa, FL USA. NICHHD, Reprod Sci Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2002 VL 78 IS 3 SU 1 MA P164 BP S170 EP S170 DI 10.1016/S0015-0282(02)03847-5 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 597UP UT WOS:000178239400462 ER PT J AU Castellanos, FX Rapoport, JL AF Castellanos, FX Rapoport, JL TI Effects of caffeine on development and behavior in infancy and childhood: a review of the published literature SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE central nervous system stimulants; coffee; fetal development; vigilance; disruptive behavior disorders; attention deficit hyperactivity disorder ID SCHOOL-AGE-CHILDREN; DEATH-SYNDROME; PREGNANCY; ALCOHOL; COFFEE; CONSUMPTION; NICOTINE; EXPOSURE; NEWBORN; BOYS AB The Medline literature on the behavioral effects of caffeine in infants and children are reviewed. There has been little recent work in this area. Generally, caffeine is well tolerated in usual dietary amounts, and there is evidence that individuals differ in their susceptibility to caffeine-related adverse effects, which in turn may influence their consumption. Overall, the effects of caffeine in children seem to be modest and typically innocuous. (C) 2002 Published by Elsevier Science Ltd. C1 NIMH, NIH, Bethesda, MD 20814 USA. RP Castellanos, FX (reprint author), NIMH, NIH, Bethesda, MD 20814 USA. NR 35 TC 27 Z9 27 U1 3 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD SEP PY 2002 VL 40 IS 9 BP 1235 EP 1242 AR PII S0278-6915(02)00097-2 DI 10.1016/S0278-6915(02)00097-2 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 579VU UT WOS:000177183200003 PM 12204387 ER PT J AU Stadtman, ER AF Stadtman, ER TI Importance of individuality in oxidative stress and aging SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE aging; oxidative stress; protein carbonyls; proteasome; protein oxidation; protein degradation; free radical ID METHIONINE SULFOXIDE REDUCTASE; METAL-CATALYZED OXIDATION; CROSS-LINKED PROTEIN; RED BLOOD-CELLS; ESCHERICHIA-COLI; OXYGEN RADICALS; GLUTAMINE-SYNTHETASE; MULTICATALYTIC PROTEASE; DENATURED PROTEINS; ENZYMATIC-ACTIVITY AB Tight linkage between aging and oxidative stress is indicated by the observations that reactive oxygen species generated under various conditions of oxidative stress are able to oxidize nucleic acids, proteins, and lipids and that aging is associated with the accumulation of oxidized forms of cellular constituents, and also by the fact that there is an inverse relationship between the maximum life span of organisms and the age-related accumulation of oxidative damage. Nevertheless, validity of the oxidative stress hypothesis of aging is questioned by (i) the failure to establish a causal relationship between aging and oxidative damage and (ii) lack of a consistent correlation between the accumulation of oxidative damage and aging. The present discussion is focused on the complexity of the aging process and suggests that discrepancies between various studies in this area are likely due to the fact that aging is not a single process and that the lack of consistent experimental results is partly explained by individual variations. Even so, there is overwhelming support for a dominant role of oxidative stress in the aging of some individuals. (C) 2002 Elsevier Science Inc. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2140,50 South Dr,MSC-8012, Bethesda, MD 20892 USA. NR 104 TC 96 Z9 97 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 1 PY 2002 VL 33 IS 5 BP 597 EP 604 AR PII S0891-5849(02)00904-8 DI 10.1016/S0891-5849(02)00904-8 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 588BQ UT WOS:000177680900004 PM 12208345 ER PT J AU Cheng, HP Wang, SQ AF Cheng, HP Wang, SQ TI Calcium signaling between sarcolemmal calcium channels and ryanodine receptors in heart cells SO FRONTIERS IN BIOSCIENCE LA English DT Review DE Ca2+; ryanodine receptors; Ca2+ sparks; excitation-contraction coupling; Ca2+-induced Ca2+ release; local control theory; review ID RAT VENTRICULAR MYOCYTES; CA2+ RELEASE CHANNEL; RETICULUM LUMENAL CA2+; CARDIAC-MUSCLE-CELLS; SARCOPLASMIC-RETICULUM; SKELETAL-MUSCLE; LOCAL-CONTROL; SPATIAL NONUNIFORMITIES; INOSITOL TRISPHOSPHATE; NUMERICAL-SIMULATION AB Cardiac excitation-Ca2+ release coupling is, in essence, a tale of two molecules, sarcolemmal voltage-gated L-type Ca2+ channels (LCCs) and intracellular ryanodine receptors (RyRs), communicating via the Ca2+ induced Ca2+ release mechanism. Recent advances have provided a microscopic view of the intermolecular Ca2+ signaling between LCCs and RyRs. In a dyadic junction or a "couplon", LCCs open and close stochastically upon depolarization, delivering a train of high local Ca2+ pulses ("Ca2+ sparklets") to the RyRs in the abutting SR terminal cisternae. Stochastic activation of RyRs discharges "Ca2+ sparks" from different couplons, which summate into global Ca2+ transients. Hence, ignition of Ca2+ sparks by Ca2+ sparklets constitute elementary events of EC coupling. While the sparklet-spark coupling is of low fidelity (at 0 mV, about one out of 50 sparklets triggers a spark under physiological conditions), the high-gain amplification of CICR (similar to15 at 0 mV) is achieved because of the greater single-channel flux and open time of RyRs and multi-RyR origin of Ca2+ spark. The global stability of CICR is safeguarded by many factors acting in synergy, including physical separation of RyR clusters, sheer Ca2+ gradients around the channel pores, low intrinsic Ca2+ sensitivity of RyRs in vivo, and high cooperativity for the Ca2+ dependent spark activation. The local stability of CICR is insured because of strong, use-dependent inactivation of RyRs, that terminates Ca2+ sparks and confers persistent local SR refractoriness. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Cheng, HP (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 101 TC 25 Z9 36 U1 0 U2 5 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP PY 2002 VL 7 BP D1867 EP D1878 DI 10.2741/cheng PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 581PX UT WOS:000177303000002 PM 12161336 ER PT J AU Rudolph, JG White, S Sokolsky, C Bozak, D Mazzanti, C Lipsky, RH Goldman, D AF Rudolph, JG White, S Sokolsky, C Bozak, D Mazzanti, C Lipsky, RH Goldman, D TI Determination of melting temperature for variant detection using dHPLC: A comparison between an empirical approach and DNA melting prediction software SO GENETIC TESTING LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SINGLE-STRANDED CONFORMATION; BASE-PAIR MISMATCHES; GEL-ELECTROPHORESIS; MUTATION DETECTION; THERMODYNAMICS; STABILITY; SEQUENCE; POLYMORPHISMS; HYBRIDIZATION AB Detection of DNA sequence variants by the use of denaturing high-performance liquid chromatography (dHPLC) is a relatively new method (Underhill et al., 1997) and has distinct advantages over other methods such as single-strand conformation polymorphism (SSCP), direct sequencing, and DNA chip hybridization. The dHPLC-based single-nucleotide polymorphism (SNP) screening relies on different DNA thermodynamic properties between perfectly matched base pairs in homoduplex molecules and single base-pair mismatches in heteroduplex: DNAs. Separation of the two forms of duplex DNAs by dHPLC is based on ionic forces between the negatively charged DNA and the hydrophobic stationary phase, which consists of C-18 chains on PS-DVB (polystyrene-divinylbenzene) beads coated with a positively charged ion-pairing agent (TEAA, triethylammonium. acetate). Removal of the DNA from the TEAA-coated beads is dependent upon a mobile organic phase, in the form of a linear acetonitrile gradient. The major factor that influences the success of dHPLC to detect sequence variation is the thermal stability of the duplex DNA, which is determined by the melting temperature (TM50), where 50% of the DNA strand is single stranded and 50% is double stranded. The TM50 predicts the best probability of detecting a single base-pair change based on the altered thermodynamics it imparts to the DNA duplex. Generally, there are two ways to determine this melting temperature, either empirically or with the aid of predictive DNA melting analysis software. Such programs include the DNAMelt program located on the Stanford University DNA Sequencing and Technology Center website, MeltCalc(C) (Schutz and vonAhsen 1999), and WAVEMAKER(R), the proprietary melting analysis software provided with the Transgenomic WAVE(R) dHPLC system. The goal of the current study was to determine whether currently available predictive DNA melting programs could be used to increase efficiency and throughput of SNP detection. A wide range of amplicons, differing in both size and GC composition, were selected for analysis to simulate the broad spectrum of PCR products that may be encountered during a large-scale dHPLC screening project. C1 Transgenomic Inc, Gaithersburg, MD 20878 USA. NIAAA, Lab Neurogenet, NIH, Rockville, MD 20852 USA. RP Rudolph, JG (reprint author), Transgenomic Inc, 11 Firstfield Rd,Suite E, Gaithersburg, MD 20878 USA. RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lipsky, Robert/0000-0001-7753-1473 NR 23 TC 11 Z9 13 U1 1 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD FAL PY 2002 VL 6 IS 3 BP 169 EP 176 DI 10.1089/109065702761403324 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 616LC UT WOS:000179304400002 PM 12490056 ER PT J AU Hussey, J Lockhart, PJ Seltzer, W Wszolek, ZK Payami, H Hanson, M Gwinn-Hardy, K Farrer, M AF Hussey, J Lockhart, PJ Seltzer, W Wszolek, ZK Payami, H Hanson, M Gwinn-Hardy, K Farrer, M TI Accurate determination of ataxin-2 polyglutamine expansion in patients with intermediate-range repeats SO GENETIC TESTING LA English DT Article ID DOMINANT CEREBELLAR-ATAXIA; SPINOCEREBELLAR ATAXIA-2; TRINUCLEOTIDE REPEAT; SCA2 LOCUS; TYPE-2; AMPLIFICATION; INTERRUPTIONS; SEQUENCES; FAMILIES AB Spinocerebellar ataxia, type 2 (SCA2), results from an expansion of a stretch of polyglutamine repeats within the coding sequence of the ataxin-2 gene (ATX2), localized to chromosome 12q23-24. Recent studies have widened the clinical phenotype, notably for individuals with repeats of intermediate size, from 32 to 35 glutamine residues. This narrow range necessitates precise determination of repeat size. Diagnostic laboratories most often perform direct genotyping of ATX2 from polymerase chain-amplified patient DNA with subsequent sizing utilizing slab gel polyacrylamide gel electrophoresis (PAGE) or capillary electrophoresis. Using cloning and sequencing methods, we have constructed a ladder of ATX2 alleles of known size and sequence composition. This freely available size ladder will facilitate future quantification of expansions of the ATX2 locus. C1 Mayo Clin Jacksonville, Dept Neurosci, Jacksonville, FL 32224 USA. Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA. Athena Diagnost Inc, Worcester, MA 01605 USA. New York State Dept Hlth, David Axelrod Inst, Albany, NY 12208 USA. NINDS, Bethesda, MD 20892 USA. RP Farrer, M (reprint author), Mayo Clin Jacksonville, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. RI Lockhart, Paul/E-7753-2011 OI Lockhart, Paul/0000-0003-2531-8413 FU NINDS NIH HHS [NS40256] NR 15 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD FAL PY 2002 VL 6 IS 3 BP 217 EP 220 DI 10.1089/109065702761403397 PG 4 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 616LC UT WOS:000179304400009 PM 12490063 ER PT J AU Knebel, AR Hudgings, C AF Knebel, AR Hudgings, C TI End-of-life issues in genetic disorders: Literature and research directions SO GENETICS IN MEDICINE LA English DT Review DE death; dying; inheritance; end of life; genetic disorders ID MUSCULAR-DYSTROPHY; PALLIATIVE CARE; CYSTIC-FIBROSIS; DISEASE; EXERCISE AB Part I of this report summarizes findings from a literature search on end of life in people with genetic disorders. There is a paucity of research on this topic; thus this article includes descriptive studies, clinical reviews, and case presentations. Part II describes the proceedings of a workshop to discuss end-of-life issues in people with genetic disorders. The workshop brought together clinicians, researchers, and people living with genetic disorders to discuss this topic. The purpose of this article is to summarize the literature and workshop proceedings to provide directions for future investigation in this important area. C1 NINR, NIH, Bethesda, MD 20892 USA. RP Knebel, AR (reprint author), 31 Ctr Dr,MSC 2178,Bldg 31,Room 5B10, Bethesda, MD 20892 USA. NR 17 TC 3 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD SEP-OCT PY 2002 VL 4 IS 5 BP 366 EP 372 DI 10.1097/01.GIM.0000029039.86752.02 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 642GZ UT WOS:000180797000008 PM 12394350 ER PT J AU Rahman, L Bliskovski, V Reinhold, W Zajac-Kaye, M AF Rahman, L Bliskovski, V Reinhold, W Zajac-Kaye, M TI Alternative splicing of brain-specific PTB defines a tissue-specific isoform pattern that predicts distinct functional roles SO GENOMICS LA English DT Article ID TRACT-BINDING-PROTEIN; 3'-SPLICE-SITE SELECTION; P1 CLONING; IN-VIVO; POLYPYRIMIDINE; COMPLEX; REPRESSOR; ELEMENT; LIBRARY; INTRON AB Splicing of neural-specific exons is differentially regulated in neuronal and non-neuronal cells. The polypyrimidine tract binding protein (PTB) has been implicated as a negative regulator for exon splicing, whereas the brain-specific homolog of PTB, termed nPTB, promotes exon splicing exclusively in neurons. We have now isolated a novel mRNA splice variant of nPTB from non-neuronal cells. In contrast to the neural nPTB transcript, the expression of this novel isoform was absent from brain tissue and was generated in non-neuronal cells by alternative splicing to include five additional amino acid residues encoded by exon 9. In addition, we identified a brain-specific transcript containing a novel, alternatively spliced, internal exon 10. The exclusion of this 34-nucleotide exon 10 in non-neuronal tissues generates a premature termination codon and results in the truncation of the open reading frame. Our findings suggest that alternative splicing of nPTB has an important role in regulation of tissue-specific gene expression and thus in the functional activity of nPTB in neuronal and non-neuronal cells. C1 Natl Canc Inst, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zajac-Kaye, M (reprint author), Natl Canc Inst, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 30 TC 32 Z9 34 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 2002 VL 80 IS 3 BP 245 EP 249 DI 10.1006/geno.2002.6826 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 589RM UT WOS:000177774200001 PM 12213192 ER PT J AU Xu, ZP Dutra, A Stellrecht, CM Wu, CY Piatigorsky, J Saunders, GF AF Xu, ZP Dutra, A Stellrecht, CM Wu, CY Piatigorsky, J Saunders, GF TI Functional and structural characterization of the human gene BHLHB5, encoding a basic helix-loop-helix transcription factor SO GENOMICS LA English DT Article DE BHLHB5; bHLH; chromosome 8q13; chromosome 3qA3; genomic structure; brain-specific; Duane syndrome ID DEVELOPING NERVOUS-SYSTEM; ACHAETE-SCUTE HOMOLOG-1; NEGATIVE REGULATOR; SPINOCEREBELLAR ATAXIA; CHROMOSOME 8Q13; PROTEIN; DROSOPHILA; TWIST; EXPRESSION; NEURONS AB The genes encoding basic helix-loop-helix (bHLH) transcription factors have been implicated in many aspects of neural development, including cell growth, differentiation, and cell migration. Using both genomic and cDNA mouse and human clones encoding a neural-specific bHLH protein, human BHLHB5 was cloned and mapped to a region on chromosome 8q13 that segregates with Duane syndrome. Genomic sequence analysis of human BHLHB5 and mouse Bhlhb5 revealed that they contain a single exon encoding 381- and 355-amino-acid bHLH proteins, respectively. Multiple amino acid sequence alignments of the Bhlhb5 family members revealed several conserved motifs and an identical 147-amino-acid carboxy-terminal region that contains a 60-amino-acid bHLH domain. A 27-bp trinucleotide repeat (CAG)(9) encoding polyserine was found in human BHLHB5, but only one CAG was found at the corresponding position in the mouse Bhlhb5 and hamster BETA3 genes. Northern blot analysis of human BHLHB5 revealed brain-specific expression with the highest abundance in the cerebellum. Mouse Bhlhb5 can strongly repress a human PAX6 promoter. C1 Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20890 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20890 USA. Roswell Pk Canc Inst, Dept Human Genet, Buffalo, NY 14263 USA. RP Saunders, GF (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, 1515 Holcombe Blvd, Houston, TX 77030 USA. FU NEI NIH HHS [EY09675, EY10608] NR 50 TC 23 Z9 26 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 2002 VL 80 IS 3 BP 311 EP 318 DI 10.1006/geno.2002.6833 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 589RM UT WOS:000177774200010 PM 12213201 ER PT J AU Ameye, L Young, MF AF Ameye, L Young, MF TI Mice deficient in small leucine-rich proteoglycans: novel in vivo models for osteoporosis, osteoarthritis, Ehlers-Danlos syndrome, muscular dystrophy, and corneal diseases SO GLYCOBIOLOGY LA English DT Review DE biglycan; collagen; decorin; fibromodulin; lumican ID KERATAN SULFATE PROTEOGLYCAN; GROWTH-FACTOR-BETA; STATIONARY NIGHT BLINDNESS; TISSUE-SPECIFIC EXPRESSION; HUMAN FIBROMODULIN GENE; INTRON-EXON JUNCTIONS; REPEAT PROTEIN FAMILY; IN-SITU HYBRIDIZATION; 2 SMALL PROTEOGLYCANS; COMPLETE CDNA CLONING AB Small leucine-rich proteoglycans (SLRPs) are extracellular molecules that bind to TGFbetas and collagens and other matrix molecules. In vitro, SLRPs were shown to regulate collagen fibrillogenesis, a process essential in development, tissue repair, and metastasis. To better understand their functions in vivo, mice deficient in one or two of the four most prominent and widely expressed SLRPs (biglycan, decorin, fibromodulin, and lumican) were recently generated. All four SLRP deficiencies result in the formation of abnormal collagen fibrils. Taken together, the collagen phenotypes demonstrate a cooperative, sequential, timely orchestrated action of the SLRPs that altogether shape the architecture and mechanical properties of the collagen matrix. In addition, SLRP-deficient mice develop a wide array of diseases (osteoporosis, osteoarthritis, muscular dystrophy, Ehlers-Danlos syndrome, and corneal diseases), most of them resulting primarily from an abnormal collagen fibrillogenesis. The development of these diseases by SLRP-deficient mice suggests that mutations in SLRPs may be part of undiagnosed predisposing genetic factors for these diseases. Although the distinct phenotypes developed by the different singly deficient mice point to distinct in vivo function for each SLRP, the analysis of the double-deficient mice also demonstrates the existence of rescuing/compensation mechanisms, indicating some functional overlap within the SLRP family. C1 NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Young, MF (reprint author), NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30 Room 225, Bethesda, MD 20892 USA. NR 99 TC 131 Z9 133 U1 2 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD SEP PY 2002 VL 12 IS 9 BP 107R EP 116R DI 10.1093/glycob/cwf065 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 595RA UT WOS:000178121500001 PM 12213783 ER PT J AU Dawsey, SM Mark, SD Taylor, PR Limburg, PJ AF Dawsey, SM Mark, SD Taylor, PR Limburg, PJ TI Gastric cancer and H pylori SO GUT LA English DT Letter ID HELICOBACTER-PYLORI; GASTROESOPHAGEAL REFLUX; POPULATION; DISEASE C1 NCI, Bethesda, MD 20892 USA. RP Dawsey, SM (reprint author), NCI, 6116 Execut Blvd,Rm 705, Bethesda, MD 20892 USA. EM sd66g@nih.gov NR 8 TC 36 Z9 37 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 2002 VL 51 IS 3 BP 457 EP 458 DI 10.1136/gut.51.3.457 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 585DE UT WOS:000177507100037 PM 12171977 ER PT J AU Ruffini, PA Neelapu, SS Kwak, LW Biragyn, A AF Ruffini, PA Neelapu, SS Kwak, LW Biragyn, A TI Idiotypic vaccination for B-cell malignancies as a model for therapeutic cancer vaccines: from prototype protein to second generation vaccines SO HAEMATOLOGICA LA English DT Review DE B-cell malignancies; idiotype; vaccine; chemokines ID COLONY-STIMULATING FACTOR; PULSED DENDRITIC CELLS; SURFACE-IMMUNOGLOBULIN IDIOTYPE; CYTOTOXIC T-LYMPHOCYTES; NON-HODGKINS-LYMPHOMA; MULTIPLE-MYELOMA; ANTITUMOR IMMUNITY; INNATE IMMUNITY; DNA VACCINES; ADAPTIVE IMMUNITY AB Background and Objectives. Cancer vaccines are aimed at inducing tumor-specific immunity by immunizing patients with tumor cells or their antigenic components, known as tumor-associated antigens (TAA). Antigens which are either mutated or selectively or abundantly expressed in malignant, but not in normal, cells are considered as TAA. Each patient's B-cell malignancy is usually derived from a single expanded B-cell clone, which expresses an immunoglobulin (Ig) with a unique idiotype (Id, variable regions of Ig). Therefore, Id can be regarded as a TAA and a potential target in clinical vaccination approaches. Although use of tumor-derived Id as an immunogen to elicit antitumor immunity against B-cell malignancies is an attractive idea, the broader use of idiotypic vaccines has been hampered by the fact that autologous Id is not only a weakly immunogenic, self antigen, but is also patient-specific so that the vaccine must be individually prepared for each patient. In this review we will first summarize the latest data from the clinical tests of experimental idiotypic vaccines and discuss issues relevant to the clinical application of cancer vaccines in general; we will then critically review new trends and achievements in the development of the second generation vaccine formulations. Evidence and information sources. The authors of the present review are currently working in the field of B-cell tumor immunotherapy and have contributed original papers to peer-reviewed journals. The material analyzed in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. State of Art. The results from a number of experimental models and clinical trials have demonstrated that vaccination with tumor-derived Id can induce immune responses directed against the tumor. Idiotypic vaccines can be divided into two types, although both are at the experimental stage: traditional and second generation, based on the methods of production and vaccine delivery. Second generation vaccines utilizing genetically engineered protein and DNA formulations have, for the first time, opened up the possibility of streamlining production of simpler and effective custom-made idiotypic vaccines. The use of various adjuvants and exogenous carriers is being replaced by more potent genetic carders which target Id and various co-stimulatory molecules to professional antigen presenting cells (APC), particularly dendritic cells (DC). Perspectives. Id is the only widely accepted tumor marker and is a promising therapeutic target for immunotherapy of B-cell malignancies. It has been unequivocally established that Id vaccination of patients with follicular lymphoma administered when patients have minimal residual disease, has antitumor effect and potential to improve the clinical outcome. Consequently, the applicability of Id vaccines for other B-cell malignancies such as chronic lymphocytic leukemia, mantle cell lymphoma and multiple myeloma needs to be tested. Idiotypic vaccines should be tailored to target preferentially various subsets of immune cells, such as DCs, which would up take and properly process and present Id, activating both arms of the immune system, humoral and cellular. Moreover, the vaccine should induce the production of a milieu of inflammatory cytokines and lymphokines at the delivery site to elicit a T helper type 1 (Th1) immune response. Components of the inflammatory response can be used to target DCs in vivo, activating the so-called danger signal for circumventing the poor immunogenicity of self-tumor antigens. For example, chemotactic factors of innate immunity are able to deliver Id to APC and render this otherwise non-immunogenic antigen immunogenic. The strategies developed for Id vaccines can be used as a general strategy for eliciting T-cell immunity to other weakly immunogenic, clinically relevant self-tumor antigens. (C) 2002, Ferrata Storti Foundation. C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Frederick, MD 21702 USA. RP Biragyn, A (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bldg 567,Rm 207, Frederick, MD 21702 USA. EM arya@mail.ncifcrf.gov NR 110 TC 41 Z9 44 U1 0 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD SEP PY 2002 VL 87 IS 9 BP 989 EP 1001 PG 13 WC Hematology SC Hematology GA 595WT UT WOS:000178132100015 PM 12217812 ER PT J AU Diamondstone, LS Aledort, LM Goedert, JJ AF Diamondstone, LS Aledort, LM Goedert, JJ CA Multicentre Hemophilia Cohort Stud TI Factors predictive of death among HIV-uninfected persons with haemophilia and other congenital coagulation disorders SO HAEMOPHILIA LA English DT Article DE factor VIII inhibitors; haemophilia; hepatitis B virus; hepatitis C virus; mortality; prospective cohort study ID HEPATITIS-C VIRUS; NON-B-HEPATITIS; HUMAN-IMMUNODEFICIENCY-VIRUS; NON-A-HEPATITIS; UNITED-STATES; LONG-TERM; LIVER-DISEASE; HEMOPHILIA-A; NATURAL-HISTORY; LIFE EXPECTANCY AB Historically, the leading cause of death among persons with haemophilia and other congenital coagulation disorders was uncontrolled bleeding. Mortality was associated with severe deficiency of coagulation factors VIII or IX and especially with high-titre antifactor neutralizing antibodies (inhibitors). The catastrophic contamination of plasma donor pools with human immunodeficiency virus (HIV) resulted in acquired immunodeficiency syndrome replacing haemorrhage as the leading cause of death among persons with haemophilia. Rather little has been written, however, about mortality among those not infected with HIV. The objective of this study was to identify conditions associated with all-cause mortality among HIV-uninfected patients who were followed for a mean of 8.8 years in the Multicentre Hemophilia Cohort Study. Among the 364 children (mean age 8 years), there were four deaths; two related to cancer, one to trauma, and the fourth to haemorrhage, end-stage liver disease and sepsis. Among the 387 HIV-uninfected adults (mean age 35 years) there were 29 deaths, with haemorrhage the leading cause of death, followed by hepatic, stroke and cancer deaths. Prognostic factors for all-cause mortality among the adults included haemophilia Type A with neutralizing antibodies [age-adjusted relative rate (RR) 3.1, 95% confidence interval (CI) 1.4-6.9] and serologic evidence of both hepatitis B and C virus (RR 4.1, 95% CI 0.97-17.6). Although hepatitis C viral load was slightly lower in patients with hepatitis B virus surface antigenaemia, it was unrelated to vital status. We conclude that causes of death and prognostic factors for current HIV-uninfected haemophilia patients are similar to those noted before the HIV epidemic. Better understanding, prevention and control of neutralizing antibodies and hepatitis infections may substantially improve longevity for people with haemophilia. C1 Res Kitchen, San Francisco, CA USA. Mt Sinai Med Ctr, New York, NY 10029 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Goedert, JJ (reprint author), 6120 Execut Blvd,Room 8012, Rockville, MD 20892 USA. FU NCI NIH HHS [N01-CP-33002] NR 48 TC 13 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD SEP PY 2002 VL 8 IS 5 BP 660 EP 667 DI 10.1046/j.1365-2516.2002.00651.x PG 8 WC Hematology SC Hematology GA 588MC UT WOS:000177704400009 PM 12199676 ER PT J AU Stefan, N Stumvoll, M AF Stefan, N Stumvoll, M TI Adiponectin - Its role in metabolism and beyond SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE adiponectin; adipocytokines; glucose tolerance; insulin sensitivity; obesity peroxisome proliferator-activated receptor-gamma; thiazolidinediones; type 2 diabetes mellitus ID ADIPOSE-SPECIFIC PROTEIN; TUMOR-NECROSIS-FACTOR; INSULIN-RESISTANCE; GENE-EXPRESSION; OB/OB MICE; PLASMA-CONCENTRATIONS; DIABETES-MELLITUS; ADIPOCYTE; OBESITY; LEPTIN AB Adiponectin is a recently identified adipose tissue-derived protein (adipocytokine) with important metabolic effects. it is exclusively expressed in adipose tissue and released into the circulation. Adiponectin expression and/or secretion is increased by insulin like growth factor-1 and ionomycin, and decreased by tumor necrosis factor-alpha, glucocorticoids, beta-adrenergic agonists and cAMP. Data for insulin are somewhat inconclusive. Moreover, adiponectin expression and secretion are increased by activators of peroxisome proliferator-activated receptor (PPAR)-gamma. Besides inhibiting inflammatory pathways, recombinant adiponectin increases insulin sensitivity and improves glucose tolerance in various animal models. This insulin-sensitizing effect appears to be mostly attributable to enhanced suppression of glucose production, but beneficial effects on muscle cannot be excluded. In humans, plasma adiponectin concentrations exceed those of any other hormone by a thousand times; they decrease with obesity and are positively associated with whole-body insulin sensitivity. Therefore, low adiponectin may contribute to the decrease in whole-body insulin sensitivity that accompanies obesity. Furthermore, there is increasing evidence that genetic variants in the adiponectin gene itself and/or in genes encoding adiponectin-regulatory proteins - such as PPAR-gamma - may be associated with hypoadiponectinemia, insulin resistance and type 2 diabetes. This suggests that adiponectin may reflect PPAR-gamma activity in vivo. Finally, reversal or alleviation of hypoadiponectinemia may represent a target for development of drugs improving insulin sensitivity and glucose tolerance. C1 NIDDK, NIH, Clin Nutr & Metab Sect, Phoenix, AZ USA. Univ Tubingen, Med Klin, Abt Endokrinol Stoffwechsel & Pathobiochem, D-7400 Tubingen, Germany. RP Stumvoll, M (reprint author), NIH, Clin Diabet & Nutr Sect, 4212 N 16Th St,Rm 5-41, Phoenix, AZ 85016 USA. NR 59 TC 192 Z9 204 U1 1 U2 12 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD SEP PY 2002 VL 34 IS 9 BP 469 EP 474 DI 10.1055/s-2002-34785 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 608PT UT WOS:000178856100001 PM 12384822 ER PT J AU Horwitz, B Poeppel, D AF Horwitz, B Poeppel, D TI How can EEG/MEG and fMRI/PET data be combined? SO HUMAN BRAIN MAPPING LA English DT Editorial Material ID HUMAN BRAIN; MAGNETOENCEPHALOGRAPHY C1 NIDCD, Language Sect, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Linguist, Cognit Neurosci Language Lab, College Pk, MD 20742 USA. Univ Maryland, Dept Biol, Cognit Neurosci Language Lab, College Pk, MD 20742 USA. RP Horwitz, B (reprint author), NIDCD, Language Sect, NIH, Bldg 10,Rm 6C420,MSC 1591, Bethesda, MD 20892 USA. NR 18 TC 70 Z9 71 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2002 VL 17 IS 1 BP 1 EP 3 DI 10.1002/hbm.10057 PG 3 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 588NZ UT WOS:000177708700001 PM 12203682 ER PT J AU Tuschong, L Soenen, SL Blaese, RM Candotti, F Muul, LM AF Tuschong, L Soenen, SL Blaese, RM Candotti, F Muul, LM TI Immune response to fetal calf serum by two adenosine deaminase-deficient patients after T cell gene therapy SO HUMAN GENE THERAPY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; BOVINE SERUM; INFECTED PATIENTS; ANTIBODY; LYMPHOCYTES; TRANSPLANTATION; ALBUMIN AB The first approved clinical gene therapy trial for adenosine deaminase (ADA) deficiency employed autologous T cells grown in fetal calf serum (FCS)-supplemented medium and transduced with a retroviral vector (LASN) also produced in the presence of FCS. Ten years after their enrollment, both patients have circulating T cells containing vector DNA. However, whereas approximately 20% of the circulating T cells from patient 1 are still vector positive, less than 1% of patient 2's T cells have detectable vector. This difference appears to be not only a function of the original transduction efficiency and cell expansion capability in vitro, but also of the immune response that patient 2 developed to FCS components during the course of her treatment. In this study, serum samples from each patient were tested for antibodies to FCS by enzyme-linked immunosorbent assay and anti-FCS responses were demonstrated in both patients. Analysis of immunoglobulin classes revealed comparable levels of IgA and IgM anti-FCS titers. Patient 2, however, had significantly higher IgG responses to FCS than did patient 1. Investigation of the development of anti-FCS responses by IgG subclasses indicated that there was a different pattern in the development of IgG immunity to FCS between the two patients. In addition, significant antibody response to bovine lipoprotein was detected in patient 2, but not in patient 1 or in control samples. These findings suggest that the unique immune response mounted by patient 2 may have influenced the outcome of the gene transfer treatments in this patient. C1 NHGRI, Clin Gene Therapy Branch, Bethesda, MD 20892 USA. Fund Inherited Dis Res, Newtown, PA 18940 USA. NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Muul, LM (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9N252, Bethesda, MD 20892 USA. NR 24 TC 99 Z9 108 U1 0 U2 6 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP PY 2002 VL 13 IS 13 BP 1605 EP 1610 DI 10.1089/10430340260201699 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 588YX UT WOS:000177730800007 PM 12228015 ER PT J AU Tao, Q Huang, H Geiman, TM Lim, CY Fu, L Qiu, GH Robertson, KD AF Tao, Q Huang, H Geiman, TM Lim, CY Fu, L Qiu, GH Robertson, KD TI Defective de novo methylation of viral and cellular DNA sequences in ICF syndrome cells SO HUMAN MOLECULAR GENETICS LA English DT Article ID EPSTEIN-BARR-VIRUS; CPG ISLANDS; CYTOSINE-5 METHYLTRANSFERASES; CHROMOSOME INSTABILITY; IMMUNODEFICIENCY SYNDROME; MAMMALIAN DEVELOPMENT; ADVANCED REPLICATION; DENOVO METHYLATION; BURKITTS-LYMPHOMA; GENE-EXPRESSION AB ICF syndrome (immunodeficiency, centromere instability and facial anomalies) is a recessive human genetic disorder resulting from mutations in the DNA methyltransferase 3B (DNMT3B) gene. Patients with this disease exhibit numerous chromosomal abnormalities, including anomalous decondensation, pairing, separation and breakage, primarily involving the pericentromeric regions of chromosomes 1 and 16. Global levels of DNA methylation in ICF cells are only slightly reduced; however, certain repetitive sequences and genes on the inactive X chromosome of female ICF patients are significantly hypomethylated. In the present report, we analyze the molecular defect of de novo methylation in ICF cells in greater detail by making use of a model Epstein-Barr virus (EBV)-based system and three members of the unique cellular cancer-testis (C-T) gene family. Results with the EBV-based system indicate that de novo methylation of newly introduced viral sequences is defective in ICF syndrome. Limited de novo methylation capacity is retained in ICF cells, indicating that the mutations in DNMT3B are not complete loss-of-function mutations or that other DNMTs cooperate with DNMT3B. Analysis of three C-T genes (two on the X chromosome and one autosomal) revealed that loss of methylation from cellular gene sequences is heterogeneous, with both autosomal and X chromosome-based genes demonstrating sensitivity to mutations in DNMT3B. Aberrant hypomethylation at a number of loci examined correlated with altered gene expression levels. Lastly, no consistent changes in the protein levels of the DNA methyltransferases were noted when normal and ICF cell lines were compared. C1 NCI, Epigenet Gene Regulat & Canc Sect, NIH, Bethesda, MD 20892 USA. NUS, Clin Res Ctr MD11, Johns Hopkins Singapore, Tumor Virol Lab, Singapore 117597, Singapore. RP Robertson, KD (reprint author), NCI, Epigenet Gene Regulat & Canc Sect, NIH, Bldg 41,Room C306,41 Lib Dr, Bethesda, MD 20892 USA. RI QIU, GUO-HUA/B-5806-2011; Fu, Li/F-7182-2010 OI QIU, GUO-HUA/0000-0001-6202-4284; Fu, Li/0000-0003-2643-6278 FU NCI NIH HHS [CA84535-01] NR 65 TC 92 Z9 97 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 1 PY 2002 VL 11 IS 18 BP 2091 EP 2102 DI 10.1093/hmg/11.18.2091 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 586NU UT WOS:000177590700002 PM 12189161 ER PT J AU Sun, MS Pan, CJ Shieh, JJ Ghosh, A Chen, LY Mansfield, BC Ward, JM Byrne, BJ Chou, JY AF Sun, MS Pan, CJ Shieh, JJ Ghosh, A Chen, LY Mansfield, BC Ward, JM Byrne, BJ Chou, JY TI Sustained hepatic and renal glucose-6-phosphatase expression corrects glycogen storage disease type Ia in mice SO HUMAN MOLECULAR GENETICS LA English DT Article ID ADENOASSOCIATED VIRUS VECTORS; MEDIATED GENE-TRANSFER; VIRAL VECTORS; HEMOPHILIA-B; THERAPY; LIVER; MOUSE; TRANSDUCTION; MODEL AB Deficiency of glucose-6-phosphatase (G6Pase), a key enzyme in glucose homeostasis, causes glycogen storage disease type Ia (GSD-Ia), an autosomal recessive disorder characterized by growth retardation, hypoglycemia, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. G6Pase is an endoplasmic reticulum-associated transmembrane protein expressed primarily in the liver and the kidney. Therefore, enzyme replacement therapy is not feasible using current strategies, but somatic gene therapy, targeting G6Pase to the liver and the kidney, is an attractive possibility. Previously, we reported the development of a mouse model of G6Pase deficiency that closely mimics human GSD-Ia. Using neonatal GSD-Ia mice, we now demonstrate that a combined adeno virus and adeno-associated virus vector-mediated gene transfer leads to sustained G6Pase expression in both the liver and the kidney and corrects the murine GSD-Ia disease for at least 12 months. Our results suggest that human GSD-Ia would be treatable by gene therapy. C1 NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Off Lab Anim Sci, Frederick, MD 21702 USA. Univ Florida, Powell Gene Therapy Ctr, Gainesville, FL 32610 USA. Univ Florida, Dept Pediat & Mol Genet & Microbiol, Gainesville, FL 32610 USA. RP Chou, JY (reprint author), NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bldg 10,Room 9S241,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK5837] NR 38 TC 27 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 1 PY 2002 VL 11 IS 18 BP 2155 EP 2164 DI 10.1093/hmg/11.18.2155 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 586NU UT WOS:000177590700009 PM 12189168 ER PT J AU Amleh, A Dean, J AF Amleh, A Dean, J TI Mouse genetics provides insight into folliculogenesis, fertilization and early embryonic development SO HUMAN REPRODUCTION UPDATE LA English DT Review DE folliculogenesis; maternal factors; meiotic maturation; oogenesis; transgenesis ID PRIMORDIAL GERM-CELLS; BONE MORPHOGENETIC PROTEIN-15; ZONA-PELLUCIDA GLYCOPROTEIN; MATERNAL MESSENGER-RNAS; SPERM-EGG INTERACTION; GROWTH-DIFFERENTIATION FACTOR-9; FOLLICLE-STIMULATING-HORMONE; O-LINKED OLIGOSACCHARIDES; MEIOTIC MATURATION; CYTOPLASMIC POLYADENYLATION AB After colonization of the gonad, mouse female germ cells enter into the prophase of the first meiotic division as a mid-gestational hallmark of gender. Perinatally, oocytes interact with granulosa cells to form primordial follicles which, with cyclic periodicity, enter into a 3-week growth phase that culminates in meiotic maturation and ovulation. Successful fertilization in the oviduct results in the onset of embryogenesis. Genes expressed in oocytes encode maternal factors that control many of these developmental processes. The establishment of mouse models in which specific genes have been disrupted offers robust insights into molecular mechanisms that control oogenesis, folliculogenesis, fertilization and early embryogenesis. Although relatively few developmental circuits have been characterized in genetic detail, the ongoing revolution in mouse genetics holds great promise. These model systems provide novel information into the molecular basis of the pathways required for oocyte-specific processes as well as for interactions with the temporally changing environment of female germ cells. The similarities between the mouse and human genomes provide assurance that this knowledge will rapidly translate into a better understanding of human reproduction. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Amleh, A (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Room 3133,Bldg 50, Bethesda, MD 20892 USA. NR 102 TC 29 Z9 31 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1355-4786 J9 HUM REPROD UPDATE JI Hum. Reprod. Update PD SEP-OCT PY 2002 VL 8 IS 5 BP 395 EP 403 DI 10.1093/humupd/8.5.395 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 603PB UT WOS:000178567300001 PM 12398220 ER PT J AU Masilamani, S Turban, S Lockhart, H Beutler, K Packer, R Nielsen, J Knepper, M AF Masilamani, S Turban, S Lockhart, H Beutler, K Packer, R Nielsen, J Knepper, M TI Long-term angiotensin II infusion increases expression of proximal tubule Na-bicarbonate cotransporter (NBC1) SO HYPERTENSION LA English DT Meeting Abstract CT 56th Annual Fall Conference and Scientific Sessions of the Council-for-High-Blood-Pressure-Research in Associaton with the Council-on-Kidney-in-Cardiovascular-Disease CY SEP 25-28, 2002 CL ORLANDO, FLORIDA SP Council High Blood Pressure, Council Kidney Cardiovas Dis, Council Nutrition Phys Activ & Metab C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2002 VL 40 IS 3 MA P17 BP 398 EP 398 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 594LY UT WOS:000178052900130 ER PT J AU Svetkey, LP Simons-Morton, DG Proschan, MA Sacks, FM Conlin, PR Harsha, D Moore, TJ AF Svetkey, LP Simons-Morton, DG Proschan, MA Sacks, FM Conlin, PR Harsha, D Moore, TJ TI Blood pressure control with DASH diet and reduced sodium intake SO HYPERTENSION LA English DT Meeting Abstract CT 56th Annual Fall Conference and Scientific Sessions of the Council-for-High-Blood-Pressure-Research in Associaton with the Council-on-Kidney-in-Cardiovascular-Disease CY SEP 25-28, 2002 CL ORLANDO, FLORIDA SP Council High Blood Pressure, Council Kidney Cardiovas Dis, Council Nutrition Phys Activ & Metab C1 Duke Univ, Med Ctr, Durham, NC USA. NHLBI, NIH, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2002 VL 40 IS 3 MA P241 BP 437 EP 438 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 594LY UT WOS:000178052900346 ER PT J AU Tumanov, AV Kuprash, DV Lagarkova, MA Grivennikov, SI Abe, K Shakhov, AN Drutskaya, LN Stewart, CL Chervonsky, AV Nedospasov, SA AF Tumanov, AV Kuprash, DV Lagarkova, MA Grivennikov, SI Abe, K Shakhov, AN Drutskaya, LN Stewart, CL Chervonsky, AV Nedospasov, SA TI Distinct role of surface lymphotoxin expressed by B cells in the organization of secondary lymphoid tissues SO IMMUNITY LA English DT Article ID FOLLICULAR DENDRITIC CELLS; TUMOR-NECROSIS-FACTOR; BETA-DEFICIENT MICE; T-CELL; STROMAL CELLS; MOUSE SPLEEN; ABNORMAL-DEVELOPMENT; AFFINITY MATURATION; MONOCLONAL-ANTIBODY; GERMINAL-CENTERS AB In order to definitively ascertain the functional contribution of lymphotoxin (LT) expressed by B cells, we produced mice with the LTbeta gene deleted from B cells (B-LTbeta KO mice). In contrast to systemic LTbeta deletion, in B-LTbeta KO mice only splenic microarchitecture was affected, while lymph nodes and Peyer's patches (PP) were normal, except for PP's reduced size. Even though B-LTbeta KO spleens retained a small number of follicular dendritic cells (FDC) which appeared to be dependent on LPbeta produced by T cells, IgG responses to sheep red blood cells were markedly reduced. Thus, the organogenic function of B-LTbeta is almost entirely restricted to spleen, where it supports the correct lymphoid architecture that is critical for an effective humoral immune response. C1 VA Engelhardt Mol Biol Inst, Lab Mol Immunol, Moscow 119991, Russia. Belozersky Inst Physicochem Biol, Moscow 119991, Russia. NCI, Basic Res Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Nedospasov, SA (reprint author), VA Engelhardt Mol Biol Inst, Lab Mol Immunol, Moscow 119991, Russia. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016; OI Kuprash, Dmitry/0000-0002-1488-4148; Chervonsky, Alexander/0000-0001-7547-871X FU NCI NIH HHS [CA65795, N01-CO-12400] NR 67 TC 118 Z9 119 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2002 VL 17 IS 3 BP 239 EP 250 DI 10.1016/S1074-7613(02)00397-7 PG 12 WC Immunology SC Immunology GA 596KB UT WOS:000178163100002 PM 12354378 ER PT J AU Simons-Morton, BG AF Simons-Morton, BG TI Reducing young driver crash risk SO INJURY PREVENTION LA English DT Editorial Material C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Simons-Morton, BG (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,7B05, Bethesda, MD 20892 USA. NR 1 TC 9 Z9 10 U1 0 U2 1 PU B M J PUBLISHING INC PI SAN FRANCISCO PA 221 MAIN ST, PO BOX 7690, SAN FRANCISCO, CA 94120-7690 USA SN 1353-8047 J9 INJ PREV JI Inj. Prev. PD SEP PY 2002 VL 8 SU 2 BP 1 EP 2 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 656EX UT WOS:000181596800001 ER PT J AU Simons-Morton, BG Hartos, JL Leaf, WA AF Simons-Morton, BG Hartos, JL Leaf, WA TI Promoting parental management of teen driving SO INJURY PREVENTION LA English DT Article; Proceedings Paper CT Expert Conference on Young Drivers CY MAR 27-29, 2002 CL AIRLIE, VIRGINIA ID 16-AND 17-YEAR-OLD DRIVERS; YOUNG DRIVERS; 16-YEAR-OLD DRIVERS; CRASH INVOLVEMENT; RISK-TAKING; PASSENGERS; DRINKING; RESTRICTIONS; ATTITUDES; TEENAGERS AB Objective: Parenting may be an important protective factor against teen driving risk; however, parents do not limit teen driving as much as might be expected. The Checkpoint Program was designed to promote parental management of teen driving through the use of staged persuasive communications. Methods: Parent-teen dyads (n = 452) were recruited when teens received learner's permits and interviewed over the telephone at baseline, licensure, and three months post-licensure. After baseline, families were randomized to either the intervention group that received persuasive communications or to the comparison group that received general information about driving safety. Results: Both parents and teens in the intervention group reported significantly greater limits on teen driving at licensure and three months post-licensure. In multivariate analyses, intervention and baseline driving expectations had significant effects on driving limits at licensure. Intervention and driving limits established at licensure were associated with three month driving limits. Conclusion: The findings indicate that exposure to the Checkpoints Program increased parental limits on teen driving. C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Resusser Res Grp Inc, Trumbull, CT 06611 USA. RP Simons-Morton, BG (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,7B05, Bethesda, MD 20892 USA. NR 38 TC 38 Z9 38 U1 4 U2 5 PU B M J PUBLISHING INC PI SAN FRANCISCO PA 221 MAIN ST, PO BOX 7690, SAN FRANCISCO, CA 94120-7690 USA SN 1353-8047 J9 INJ PREV JI Inj. Prev. PD SEP PY 2002 VL 8 SU 2 BP 24 EP 30 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 656EX UT WOS:000181596800008 ER PT J AU Valenzuela, JG Pham, VM Garfield, MK Francischetti, IMB Ribeiro, JMC AF Valenzuela, JG Pham, VM Garfield, MK Francischetti, IMB Ribeiro, JMC TI Toward a description of the sialome of the adult female mosquito Aedes aegypti SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE salivary glands; proteome; electrophoresis; hematophagy ID YELLOW-FEVER MOSQUITO; REPEAT TRANSPOSABLE ELEMENTS; VECTOR ANOPHELES-GAMBIAE; SALIVARY-GLAND; LUTZOMYIA-LONGIPALPIS; INVERTEBRATE IMMUNITY; SECRETORY PROTEINS; RHODNIUS-PROLIXUS; HISTAMINE-BINDING; SIALOKININ-I AB To describe the set of mRNA and protein expressed in the salivary glands (sialome) of Aedes aegypti mosquitoes, we randomly sequenced a full-length cDNA library of this insect and performed Edman degradation of PVDF-transferred protein bands from salivary homogenates. We found 23 8 cDNA clusters which contained those coding for 10 of the 11 proteins found by aminoterminal degradation. All six previously described salivary proteins were found in this library. Full-length sequences of 32 novel cDNA sequences are reported, one of which is the product of a transposable element. Among the 31 novel protein sequences are 4 additional members of the D7 protein family; 4 novel members of the antigen 5 family (a protein family not reported in Aedes); a novel serpin; a novel member of the 30-kDa allergen of Ae. Aegypti; a secreted calreticulin; 2 proteins similar to mammalian angiopoietins; adenosine deaminase; purine hydrolase; lysozyme; a C-type lectin; 3 serine proteases, including one with high similarity to Bombyx prophenoloxidase, activating enzyme; 2 proteins related to invertebrate immunity; and several sequences that have no significant matches to known proteins. The possible role of these proteins in blood and sugar feeding by the mosquito is discussed. Published by Elsevier Science Ltd. C1 NIAID, Med Entomol Sect, Lab Parasit Dis, NIH, Bethesda, MD 20892 USA. NIAID, Res Technol Branch, Rockville, MD 20852 USA. RP Ribeiro, JMC (reprint author), NIAID, Med Entomol Sect, Lab Parasit Dis, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. OI Ribeiro, Jose/0000-0002-9107-0818 NR 67 TC 127 Z9 131 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD SEP PY 2002 VL 32 IS 9 BP 1101 EP 1122 AR PII S0965-1748(02)00047-4 DI 10.1016/S0965-1748(02)00047-4 PG 22 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 599XW UT WOS:000178361300016 PM 12213246 ER PT J AU Tchounwou, PB Yu, HT AF Tchounwou, Paul B. Yu, Hongtao TI Special Issue on Recent Advances in Environmental Health Research: Health Disparities, Toxicology and Carcinogenesis SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Editorial Material C1 [Tchounwou, Paul B.] Jackson State Univ, Mol Toxicol Res Lab, Jackson, MS 39217 USA. [Yu, Hongtao] Jackson State Univ, Chem Toxicol Biochem Lab, NIH, Ctr Environm Hlth,Sch Sci & Technol, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Mol Toxicol Res Lab, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD SEP PY 2002 VL 3 IS 9 BP 931 EP 933 DI 10.3390/i3090931 PG 3 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA V33IB UT WOS:000209011400001 ER PT J AU McNairy, SA AF McNairy, Sidney A., Jr. TI A Message from the Director SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Editorial Material C1 NIH, Div Res Infrastruct, Natl Ctr Res Resources, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP McNairy, SA (reprint author), NIH, Div Res Infrastruct, Natl Ctr Res Resources, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD SEP PY 2002 VL 3 IS 9 BP 934 EP 936 DI 10.3390/i3090934 PG 3 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA V33IB UT WOS:000209011400002 ER PT J AU Sutton, DJ Tchounwou, PB Ninashvili, N Shen, E AF Sutton, Dwayne J. Tchounwou, Paul B. Ninashvili, Nanuli Shen, Elaine TI Mercury Induces Cytotoxicity and Transcriptionally Activates Stress Genes in Human Liver Carcinoma (HepG(2)) Cells SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE Mercury; cytotoxicity; gene expression; HepG(2) cells AB Mercury is a non-essential element that exhibits a high degree of toxicity to humans and animals. Exposure to mercury has been associated with a significant number of adverse health effects including: cardiovascular disease, anemia, developmental abnormalities, neurobehavioral disorders, kidney and liver damage, and cancer in some cases. In several studies, the toxicity of mercury has been attributed to its high affinity to protein-containing sulfhydryl groups. However, little is known regarding the molecular mechanisms by which mercury exerts its toxicity, mutagenesis, and carcinogenesis. This research was therefore designed to assess the cellular and molecular responses of human liver carcinoma cells following exposure to mercury. Cytotoxicity was evaluated using the MTT-assay for cell viability, while the gene profile assay was performed to measure the transcriptional activation of stress genes in thirteen different recombinant cell lines generated from HepG2 cells. Cytotoxicity experiment yielded a LD50 value of 3.5 +/- 0.6 mu g/mL upon 48 hours of exposure, indicating that mercury is highly toxic. A dose response relationship was recorded with respect to both cytotoxicity and gene induction. Overall, nine out of the thirteen recombinant cell lines tested showed inductions to statistically significant levels (p<0.05). At 2.5 mu g/mL of mercury, the average fold inductions were 5.2 +/- 0.9, 21.4 +/- 3.9, 7.0 +/- 6.2, 6.8 +/- 1.1, 2.7 +/- 1.0, 4.5 +/- 2.0, 7.5 +/- 6.0, 2.2 +/- 0.7, and 2.5 +/- 0.3, for GSTYa, HMTIIA, c-fos, HSP70, CRE, p53RE, GADD153, GADD45, and GRP78, respectively. These results indicate the potential of mercury to undergo Phase II biotransformation in the liver (GSTYa), and to cause protein damage (HMTIIA, HSP70, and GRP78), cell proliferation (c-fos), metabolic perturbation (CRE), growth arrest and DNA damage (GADD153, GADD45), and apoptosis (p53RE). No significant inductions (p> 0.05) were observed for CYP1A1, XRE, NFkBRE, and RARE. C1 [Sutton, Dwayne J.; Tchounwou, Paul B.; Ninashvili, Nanuli] Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,Sch Sci & Technol, Jackson, MS 39217 USA. [Shen, Elaine] Xenometrix Inc, Xenometrix Res Lab, Boulder, CO 80301 USA. RP Sutton, DJ (reprint author), Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,Sch Sci & Technol, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU National Institutes of Health through the RCMI-Center for Environmental Health [1G12RR13459]; U.S. Department of Education through the Title III Graduate Education Program [PO31B990006] FX This research was financially supported in part by a grant from the National Institutes of Health (Grant No. 1G12RR13459), through the RCMI-Center for Environmental Health, and in part by a grant from the U.S. Department of Education (Grant No. PO31B990006), through the Title III Graduate Education Program. NR 70 TC 15 Z9 15 U1 0 U2 2 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD SEP PY 2002 VL 3 IS 9 BP 965 EP 984 DI 10.3390/i3090965 PG 20 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA V33IB UT WOS:000209011400005 ER PT J AU Dorsey, WC Tchounwou, PB Ishaque, AB Shen, E AF Dorsey, Waneene C. Tchounwou, Paul B. Ishaque, Ali B. Shen, Elaine TI Transcriptional Activation of Stress Genes and Cytotoxicity in Human Liver Carcinoma (HepG(2)) Cells Exposed to Pentachlorophenol SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE Pentachlorophenol; cytotoxicity; gene expression; HepG(2) cells AB Pentachlorophenol (PCP) is a biocidal chemical with several industrial, agricultural, and domestic applications. There is accumulating evidence indicating that PCP is highly toxic to humans, with major target organs including the lung, liver, kidneys, heart, and brain. Little is known regarding the molecular basis by which PCP induces toxicity, mutagenesis, and carcinogenesis. Therefore, this research was designed to assess the cellular and molecular responses of HepG(2) cells following exposure to PCP. The cytotoxicity experiment yielded a LD50 value of 23.4 +/- 9.7 mu g PCP/mL upon 48 hrs of exposure, indicating that PCP is acutely toxic. A dose-response relationship was recorded with respect to gene induction. For example, fold inductions of CYP1A1 were 1.0 +/- 0.0, 1.0 +/- 0.0, 1.3 +/- 0.5, 6.3 +/- 4.3, and 22.5 +/- 3.5 for 0, 6.2, 12.5, 25, and 50 mu g PCP/mL, respectively. Overall, five out of the thirteen recombinant cell lines tested showed inductions to statistically significant levels (p<0.05). At 50 mu g PCP/mL, the average fold inductions were 22.5 +/- 3.5, 52.8 +/- 2.5, 8.4 +/- 1.9, 6.16 +/- 2.4, and 12.5 +/- 6.8, for CYP1A1, XRE, HMTIIA, c-fos, and GADD153, respectively. These results indicate the potential of PCP to undergo Phase I biotransformation in the liver (CYP1A1, XRE), to cause cell proliferation (c-fos), growth arrest and DNA damage (GADD153), and to influence the toxicokinetics of metal ions (HMTIIA). Marginal inductions were recorded for HSP70, CRE, RARE, GADD45, and GRP78. Within the dose range (0-100 mu g/mL) tested, no significant inductions (p<0.05) were observed for GSTYa, NFkBRE, and p53RE. C1 [Dorsey, Waneene C.; Tchounwou, Paul B.; Ishaque, Ali B.] Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,Sch Sci & Technol, Jackson, MS 39217 USA. [Shen, Elaine] Xenometrix Inc, Xenometrix Res Lab, Boulder, CO 80301 USA. RP Dorsey, WC (reprint author), Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,Sch Sci & Technol, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU U. S. Department of Education through Title III Graduate Education [P031B990006-01] FX This research was financially supported by a grant from the U. S. Department of Education through Title III Graduate Education Grant No. P031B990006-01 to Jackson State University. We thank Dr. Abul Mohamed, Dean of the School of Science and Technology, for his technical support on this research project. NR 48 TC 4 Z9 4 U1 0 U2 1 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD SEP PY 2002 VL 3 IS 9 BP 992 EP 1007 DI 10.3390/i3090992 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA V33IB UT WOS:000209011400007 ER PT J AU Akiyama, Y Maruyama, K Watanabe, M Yamaguchi, K AF Akiyama, Y Maruyama, K Watanabe, M Yamaguchi, K TI Retroviral-mediated IL-12 gene transduction into human CD34(+) cell-derived dendritic cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE cord blood; CD34(+) cells; genetically modified dendritic cells; IL-12; cytotoxic T cell ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; CORD-BLOOD; PROGENITOR CELLS; IN-VITRO; LANGERHANS CELLS; TARGET-CELLS; FLT3 LIGAND; HIGH-LEVEL; TNF-ALPHA AB Genetically modified dendritic cells (DCs) with Th1 type cytokine genes are useful for activating anti-tumor immune response. We made human interleukin (IL)-12 p70 gene-transduced DCs generated from CD34(+) progenitor cells using a retrovirus system and investigated the function of IL-12-producing DCs. We used the pMX retroviral vector and made cytokine gene-containing viral vectors referred to as GFP pMX and hIL-12 pMX. Supernatants from BOSC23 cells transfected with GFP pMX and hIL-12 pMX were harvested and used for transfection of DC. Cord blood CD34(+) cells were incubated with supernatants containing retrovirus for 48 h with cytokines such as IL-3, IL-6, SCF, Flt3 ligand (FL), bFGF and IGF-I. The cells were cultured for 12 days in the presence of GM-CSF, SCF, FL, IL-4 and TNF-alpha to get mature DC-enriched population. Analysis of surface marker on DCs and allogeneic MLR assay were also performed. After a 14-day culture, 60-70% of cultured CD34(+) cells were DC marker (CD1a, DEC205) positive. The IL-12 p70 protein levels in supernatant of DC-GFP and DC-hIL-12 were 0.2 ng/ml and 53 ng/ml/5x10(5) DCs for 72 h, respectively. The addition of CH296 fibronectin fragment (FN) increased 3-fold IL-12 gene transduction efficiency into DCs. MLR assay showed that IL-12-producing DC exhibited more potent T cell growth-stimulating activity compared with GFP-DC. These results suggested that genetically modified CD34(+) cell-derived DCs with human IL-12 gene are fully efficient in T cell priming, and could be a good tool for effective cancer immunotherapy. C1 Natl Canc Ctr, Div Growth Factor, Chuo Ku, Tokyo, Japan. Natl Canc Inst, Expt Therapeut Sect, Expt Immunol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Akiyama, Y (reprint author), Natl Canc Ctr, Div Growth Factor, Chuo Ku, 5-1-1 Tsukiji, Tokyo, Japan. NR 32 TC 12 Z9 12 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD SEP PY 2002 VL 21 IS 3 BP 509 EP 514 PG 6 WC Oncology SC Oncology GA 582WX UT WOS:000177375100007 PM 12168093 ER PT J AU Coleman, CN Kelly, L Daly, NR Beard, C Kaplan, I Lamb, C Propert, K Manola, J AF Coleman, CN Kelly, L Daly, NR Beard, C Kaplan, I Lamb, C Propert, K Manola, J TI Phase III study of ibuprofen versus placebo for radiation-induced genitourinary side effects SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE nonsteroidal anti-inflammatory agents; cyclooxygenase inhibitors; ibuprofen; prostate cancer; radiation toxicity ID PROSTATE-CANCER CELLS; NF-KAPPA-B; CYCLOOXYGENASE-2 INHIBITOR; GAMMA-RADIATION; RADIOSENSITIVITY; ANGIOGENESIS; RADIOTHERAPY; ENHANCEMENT; PREVENTION; ACTIVATION AB Purpose: On the basis of our anecdotal clinical observations that nonsteroidal anti-inflammatory agents relieved dysuria during radiotherapy for patients with prostate cancer, we conducted a Phase III randomized trial of ibuprofen vs. placebo for patients who had an increase in acute urinary symptoms. Our in vitro and in vivo laboratory data with a higher concentration of ibuprofen than achievable in this study demonstrated radiosensitization. This study examined whether the inflammatory response within the prostate during radiotherapy would respond to the standard dose of ibuprofen as assessed by a symptom score. Methods and Materials: Patients were registered to the study and were followed weekly with a formal symptom assessment. A double-blind randomization to ibuprofen, 400 mg q.i.d., vs. placebo for 7 days was done at a time when the severity score increased. The symptom response was evaluated at the end of the week. Results: Between 1995 and 1998, 100 patients were entered, 28 did not have a sufficient change in symptom score to be randomized, and 19 were either unable to take ibuprofen or withdrew before randomization. Of the 53 patients randomized, 27 received placebo and 26 ibuprofen. No statistically significant differences were found between the placebo and ibuprofen groups between baseline and randomization or between randomization and the 1-week posttreatment assessment. Neither group had a change in symptom severity between randomization and the 1-week posttreatment evaluation. Conclusion: The standard anti-inflammatory dose of ibuprofen did not relieve the acute urinary or rectal symptoms during radiotherapy for prostate cancer. The nonsteroidal anti-inflammatory drugs are potential radiation sensitizers with the mechanism of action as yet unknown. Clinical trials of the cyclooxygenase inhibitors as radiation sensitizers should explore a range of doses and evaluate potential mechanisms of action, including cyclooxygenase inhibition and other non-cyclooxygenase mechanisms. (C) 2002 Elsevier Science Inc. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Coleman, CN (reprint author), NIH, Radiat Oncol Branch, Bldg 10,B3-B69, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA-42391] NR 24 TC 8 Z9 8 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2002 VL 54 IS 1 BP 191 EP 194 AR PII S0360-3016(02)02907-3 DI 10.1016/S0360-3016(02)02907-3 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 589VH UT WOS:000177780900024 PM 12182991 ER PT J AU Ma, X Dou, S Wright, JA Reich, RA Teeter, LD El Sahly, HM Awe, RJ Musser, JM Graviss, EA AF Ma, X Dou, S Wright, JA Reich, RA Teeter, LD El Sahly, HM Awe, RJ Musser, JM Graviss, EA TI 5 ' dinucleotide repeat polymorphism of NRAMP1 and susceptibility to tuberculosis among Caucasian patients in Houston, Texas SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE NRAMP1; polymorphism; tuberculosis; susceptibility ID HUMAN-IMMUNODEFICIENCY-VIRUS; NATURAL-RESISTANCE; MYCOBACTERIUM-TUBERCULOSIS; GENETIC SUSCEPTIBILITY; INTRACELLULAR PATHOGENS; MACROPHAGE PROTEIN; INFECTION; VARIANTS; LINKAGE; IDENTIFICATION AB SETTING: Houston Tuberculosis Initiative (HTI) and Baylor College of Medicine, Houston, Texas. OBJECTIVE: To further explore the association between the polymorphisms of NRAMP1 and human susceptibility/ resistance to tuberculosis (TB), specifically to determine whether the reported association shown for blacks and Asians holds true for Caucasian populations. DESIGN: In a case-control study, 135 adult Caucasian TB; patients and 108 adult Caucasian HIV-seronegative non-TB controls were analyzed for the association between the polymorphisms in NRAMP1 gene and clinical TB. RESULTS: Heterozygote at 5'(GT)(n), a dinucleotide repeat polymorphism in the promoter of NRAMP1, was observed at significantly higher frequencies among HIV-negative patients with pulmonary TB (41.6%; OR 2.02; 95%CI 1.11-3.64), extra-pulmonary TB (66.7%; OR 4.80; 95%CI 1.34-17.15), and HIV-seropositive TB patients (50%; OR 3.77; 95%CI 1.33-10.66) in comparison with the controls (27.8%). Homozygotes (GT)(10,10) were over-represented among HIV-positive TB patients (18.2%; OR 6.86; 95%CI 1.55-30.21) compared to the controls (5.5%). CONCLUSION: These findings suggest that the 5'(GT)(n) polymorphism of NRAMP1 modifies TB susceptibility in this Caucasian population, and could possibly be related to the site of infection among HIV-negative individuals and HIV-coinfected TB. C1 Baylor Coll Med, Dept Pathol 209E, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Graviss, EA (reprint author), Baylor Coll Med, Dept Pathol 209E, 1 Baylor Plaza, Houston, TX 77030 USA. FU NIAID NIH HHS [AI 41168, N01-AO-02738] NR 24 TC 48 Z9 50 U1 0 U2 2 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD SEP PY 2002 VL 6 IS 9 BP 818 EP 823 PG 6 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 591DR UT WOS:000177864900012 PM 12234138 ER PT J AU Broom, DC Jutkiewicz, EM Rice, KC Traynor, JR Woods, JH AF Broom, DC Jutkiewicz, EM Rice, KC Traynor, JR Woods, JH TI Behavioral effects of delta-opioid receptor agonists: Potential antidepressants? SO JAPANESE JOURNAL OF PHARMACOLOGY LA English DT Review DE delta-opioid agonist; forced swim assay; depression; enkephalin ID LEARNED HELPLESSNESS MODEL; FORCED SWIMMING TEST; ENDOGENOUS ENKEPHALINS; INDUCED SEIZURES; BW373U86; MICE; RAT; IMMUNOREACTIVITY; INVOLVEMENT; DEPRESSION AB The development of selective delta-opioid receptor agonists has revealed some very intriguing behavioral properties. delta-Opioid agonists have antinociceptive, scizuregenic and convulsive properties. A number of studies have identified a novel behavioral effect of delta-opioid-receptor agonists, implicating a role for the delta-opioid receptor in depression. Early clinical experiments demonstrated that exogenously administered opioid peptides had antidepressant activity in human patients. Also, enkephalinase inhibitors, which prevent the degradation of endogenous enkephalins, produced antidepressant-like effects mediated through the delta-opioid receptor in animal models of depression. More recently, the selective non-peptidic delta-opioid agonists SNC80 and (+)BW373U86 demonstrated antidepressant-like activity in the forced swim assay in rats. These studies propose that the delta-opioid receptor may provide a new therapeutic target for treating human depression. C1 Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Psychol, Ann Arbor, MI 48109 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Woods, JH (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. FU NIDA NIH HHS [DA00254]; NIGMS NIH HHS [GM07767] NR 35 TC 35 Z9 36 U1 1 U2 4 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 0021-5198 J9 JPN J PHARMACOL JI Jpn. J. Pharmacol. PD SEP PY 2002 VL 90 IS 1 BP 1 EP 6 DI 10.1254/jjp.90.1 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 596RU UT WOS:000178179900001 PM 12396021 ER PT J AU Griffith, AJ Szymko, YM Kaneshige, M Quinonez, RE Kaneshige, K Heintz, KA Mastroianni, MA Kelley, MW Cheng, SY AF Griffith, AJ Szymko, YM Kaneshige, M Quinonez, RE Kaneshige, K Heintz, KA Mastroianni, MA Kelley, MW Cheng, SY TI Knock-in mouse model for resistance to thyroid hormone (RTH): An RTH mutation in the thyroid hormone receptor beta gene disrupts cochlear morphogenesis SO JARO LA English DT Article DE deafness; genetic; hypothyroidism; hearing; organ of Corti; tectorial membrane ID HEARING-LOSS; AUDITORY FUNCTION; MICE; EXPRESSION; MECHANISMS; DELETION; STRAINS; ORGAN; CORTI AB Thyroid hormone and the beta isoform of its receptor, Trbeta, are essential for normal development of the mammalian auditory system. We have analyzed auditory system function and structure in a mouse strain with a targeted Thrb mutation, Thrb(PV), which leads to the loss of binding of thyroid hormone (T3) to the Trbeta protein. Heterozygosity for the orthologous human THRBPV mutation and other similar mutations in human THRB cause resistance to thyroid hormone (RTH), which is occasionally associated with mild sensorineural hearing impairment. Auditory brainstem response analysis of heterozygous Thrb(PV)/+ mice demonstrates that they develop normal hearing. In contrast, Thrb(PV)/Thrb(PV) mice have severe hearing impairment that is already present at 3 weeks of age. This hearing loss is associated with disruption of postnatal morphogenesis of the tectorial membrane and organ of Corti. Comparison with the previously described phenotype of a Thrb -/- knockout strain suggests that Thrb(PV) disrupts the function of other genes that are critical for development and/or maintenance of these structures. C1 NCI, Gene Regulat Sect, Mol Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Hearing Sect, Rockville, MD 20850 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Sect Gene Struct & Funct, Rockville, MD 20850 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Unit Dev Neurosci, Rockville, MD 20850 USA. RP Cheng, SY (reprint author), NCI, Gene Regulat Sect, Mol Biol Lab, Div Basic Sci, Bldg 37,Room 2D-24,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. FU NIDCD NIH HHS [Z01 DC 00054-01, Z01 DC 00055-01] NR 31 TC 40 Z9 41 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1525-3961 J9 JARO JI JARO PD SEP PY 2002 VL 3 IS 3 BP 279 EP 288 DI 10.1007/s101620010092 PG 10 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 600NR UT WOS:000178397700005 PM 12382103 ER PT J AU LeBeau, MA Christenson, RH Levine, B Darwin, WD Huestis, MA AF LeBeau, MA Christenson, RH Levine, B Darwin, WD Huestis, MA TI Intra- and interindividual variations in urinary concentrations of endogenous gamma-hydroxybutyrate SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID CHROMATOGRAPHY-MASS-SPECTROMETRY; BUTYROLACTONE GBL; ACID; GHB; RECOMMENDATIONS; EXCRETION; DRUG C1 Fed Bur Invest, FBI Lab, Chem Unit, Washington, DC 20535 USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. NIH, NIDA, IRP, Chem & Drug Metab, Baltimore, MD 21224 USA. RP LeBeau, MA (reprint author), Fed Bur Invest, FBI Lab, Chem Unit, Washington, DC 20535 USA. NR 27 TC 52 Z9 56 U1 2 U2 4 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD SEP PY 2002 VL 26 IS 6 BP 340 EP 346 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 587PC UT WOS:000177649500005 PM 12220015 ER PT J AU Groves, FD Issaq, H Fox, S Jeffrey, AM Whysner, J Zhang, L You, WC Fraumeni, JF AF Groves, FD Issaq, H Fox, S Jeffrey, AM Whysner, J Zhang, L You, WC Fraumeni, JF TI N-nitroso compounds and mutagens in Chinese fermented (sour) corn pancakes SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ESOPHAGEAL CANCER; HIGH-RISK; MYCOTOXINS; PRODUCTS; SHANDONG; SAMPLES; FISH AB Stomach cancer rates in rural Linqu County, Shandong Province, China, are exceptionally high. A previous case-control study revealed that the risk of stomach cancer was 30% higher among those who consumed sour (fermented) corn pancakes at least daily. A previous study of the sour pancakes reported volatile nitrosamines in most specimens, and almost half reportedly showed mutagenic activity. Few households currently consume sour pancakes, and the duration of fermentation has been shortened. We tested specimens of pancake batter and sour pancakes from Linqu County for mutagenic activity using the Ames test; for N-nitroso compounds (NOC) we used the Nitrolite-thermal energy analysis (TEA) method. Results of the Ames test were inconclusive: only 1 out of 15 cooked pancakes showed a positive mutagenic response, and all 15 batter specimens were negative; however, several batter specimens showed a weakly positive trend of mutagenicity with extract concentration. Our assay for total nitroso compounds was weakly positive in only 1 out of 15 specimens of sour pancake batter. That specimen was also tested by gas chromatography-TEA for nitrosaminciacids and volatile nitrosamines, but none were detected. It seems unlikely that the Chinese sour pancakes are significantly contaminated by NOC or other mutagens. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Ft Detrick, MD 21702 USA. Amer Hlth Fdn, Dept Pathol & Toxicol, Valhalla, NY 10595 USA. Beijing Inst Canc Res, Beijing 100036, Peoples R China. RP Groves, FD (reprint author), Med Univ S Carolina, Dept Biometry & Epidemiol, 135 Cannon St,Rm 302-H, Charleston, SC 29425 USA. FU NCI NIH HHS [N01-CP-05631, N01-CP-33041, N01-CP-156220, N01-CP-21009, N01-CP-95660] NR 18 TC 5 Z9 5 U1 1 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2002 VL 85 IS 5 BP 1052 EP 1056 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 598KB UT WOS:000178274000009 PM 12374403 ER PT J AU Hao, JJ Yarmolinsky, M AF Hao, JJ Yarmolinsky, M TI Effects of the P1 plasmid centromere on expression of P1 partition genes SO JOURNAL OF BACTERIOLOGY LA English DT Article ID INTEGRATION HOST FACTOR; HEAT-SHOCK PROTEINS; COLI F-PLASMID; ESCHERICHIA-COLI; PARB PROTEIN; BACILLUS-SUBTILIS; SOPB-PROTEIN; INTRACELLULAR-LOCALIZATION; PATTERN-FORMATION; CLONING VECTORS AB The partition operon of PI plasmid encodes two proteins, ParA and ParB, required for the faithful segregation of plasmid copies to daughter cells. The operon is followed by a centromere analog, parS, at which ParB binds. ParA, a weak ATPase, represses the par promoter most effectively in its ADP-bound form. ParB can recruit ParA to parS, stimulate its ATPase, and significantly stimulate the repression. We report here that parS also participates in the regulation of expression of the par genes. A single chromosomal parS was shown to augment repression of several copies of the par promoter by severalfold. The repression increase was sensitive to the levels of ParA and ParB and to their ratio. The increase may be attributable to a conformational change in ParA mediated by the parS-ParB complex, possibly acting catalytically. We also observed an in cis effect of parS which enhanced expression of parB, presumably due to a selective modulation of the mRNA level. Although ParB had been earlier found to spread into and silence genes flanking parS, silencing of the par operon by ParB spreading was not significant. Based upon analogies between partitioning and septum placement, we speculate that the regulatory switch controlled by the parS-ParB complex might be essential for partitioning itself. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Yarmolinsky, M (reprint author), NCI, Biochem Lab, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. NR 60 TC 23 Z9 23 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2002 VL 184 IS 17 BP 4857 EP 4867 DI 10.1128/JB.184.17.4857-4867.2002 PG 11 WC Microbiology SC Microbiology GA 583UN UT WOS:000177428700025 PM 12169611 ER PT J AU Gal, J Szvetnik, A Schnell, R Kalman, M AF Gal, J Szvetnik, A Schnell, R Kalman, M TI The metD D-methionine transporter locus of Escherichia coli is an ABC transporter gene cluster SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COMPLETE GENOME SEQUENCE; BINDING; PROTEIN; CLONING; ENZYMES; VECTORS; SYSTEMS; K-12 AB The metD D-methionine transporter locus of Escherichia coli was identified as the abc-yaeE-yaeC cluster (now renamed metNIQ genes). The abc open reading frame is preceded by tandem MET boxes bracketed by the -10 and -35 boxes of a promoter. The expression driven by this promoter is controlled by the MetJ repressor and the level of methionine. C1 Hungarian Acad Sci, Biol Res Ctr, Genet Inst, H-6701 Szeged, Hungary. Bay Zoltan Fdn Appl Res, Inst Biotechnol, H-6701 Szeged, Hungary. RP Gal, J (reprint author), NICHHD, Mol Genet Lab, NIH, 6 Ctr Dr,Bldg 6B,Room 3B-316, Bethesda, MD 20892 USA. NR 29 TC 28 Z9 32 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2002 VL 184 IS 17 BP 4930 EP 4932 DI 10.1128/JB.184.17.4930-4932.2002 PG 3 WC Microbiology SC Microbiology GA 583UN UT WOS:000177428700034 PM 12169620 ER PT J AU Campos-Olivas, R Louis, JM Clerot, D Gronenborn, B Gronenborn, AM AF Campos-Olivas, R Louis, JM Clerot, D Gronenborn, B Gronenborn, AM TI Letter to the Editor: H-1, C-13, and N-15 assignment of the N-terminal, catalytic domain of the replication initiation protein from the geminivirus TYLCV SO JOURNAL OF BIOMOLECULAR NMR LA English DT Letter DE DNA-binding; geminivirus; Rep; replication initiation; rolling circle ID DNA-REPLICATION; CELL-CYCLE; NMR C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Ctr Nacl Invest Oncol, Struct & Computat Biol Program, E-28029 Madrid, Spain. CNRS, Inst Sci Vegetales, F-91198 Gif Sur Yvette, France. RP Gronenborn, AM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. RI Campos-Olivas, Ramon/L-9173-2014 OI Campos-Olivas, Ramon/0000-0002-5743-2221 NR 10 TC 4 Z9 5 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD SEP PY 2002 VL 24 IS 1 BP 73 EP 74 DI 10.1023/A:1020664809314 PG 2 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 603GN UT WOS:000178550700009 PM 12449422 ER PT J AU Daumer, KM Taparowsky, EJ Hall, DJ Steinbeck, MJ AF Daumer, KM Taparowsky, EJ Hall, DJ Steinbeck, MJ TI Transcription from the tartrate-resistant acid phosphatase promoter is negatively regulated by the Myc oncoprotein SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE tartrate-resistant acid phosphatase; Myc; osteoclasts; initiator element; myelomonocytic cells; 1 alpha,25-dihydroxyvitamin D-3 ID C-MYC; DNA-BINDING; TRAP GENE; INDUCED-DIFFERENTIATION; HEMATOPOIETIC-CELLS; OSTEOCLAST; MAX; EXPRESSION; PROTEIN; BONE AB TRAP, a characteristic marker of osteoclast differentiation, is an enzyme that plays an active role in the process of bone resorption. Despite the importance of TRAP in osteoclast biology, the components involved in the transcriptional regulation of this gene are largely unknown. This study investigated the regulation of TRAP transcription by the Myc oncoprotein in three different cell types. A series of nested TRAP promoter deletion constructs were cotransfected into P388D(1) murine macrophages and C3H10T1/2 murine embryonic fibroblasts along with a backbone plasmid control or expression plasmids containing v-Myc, c-Myc, or an inactive v-Myc protein construct (Delta84/NLS). Both v-Myc and c-Myc negatively regulated transcription from the TRAP promoter in P388D(1) and C3H10T1/2 cells, 90% and 50%, respective to cell type and amount of endogenous Myc protein, and Delta84/NLS had no effect. The functional Myc-responsive element(s) within the TRAP promoter was localized to a region between -436 and +1 bp, which contains two putative Myc-inhibitory binding sites coincident with an initiator element (Inr) at -116 bp and -18 bp. Conversely, in the HD-11EM chicken v-Myc transformed preosteoclast cell line, the full-length TRAP promoter transcription was increased when endogenous v-Myc levels were decreased in response to pretreatment of these cells with 1alpha,25-dihydroxyvitamin D-3 [1alpha,25(OH)(2)D-3]. This report provides the first evidence of the specific regulation of TRAP at the transcriptional level by Myc, a transcription factor that is normally expressed at relatively high levels in preosteoclasts and other myelomonocytic cells and suggests that Myc plays an active role in suppressing the transcription of a mature osteoclast selective gene. C1 Thomas Jefferson Univ, Dept Orthoped Surg, Philadelphia, PA 19107 USA. Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Steinbeck, MJ (reprint author), Thomas Jefferson Univ, Dept Orthoped Surg, 1015 Walnut St,Room 324 Curtis, Philadelphia, PA 19107 USA. FU NCI NIH HHS [CA-67032]; NIAMS NIH HHS [AR-39740]; NIDCR NIH HHS [DE-11082, R29 DE011082] NR 43 TC 10 Z9 10 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 IS 9 BP 1701 EP 1709 DI 10.1359/jbmr.2002.17.9.1701 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 586ZN UT WOS:000177616200017 PM 12211441 ER PT J AU Thyagarajan, T Kulkarni, AB AF Thyagarajan, T Kulkarni, AB TI Transforming growth factor-beta 1 negatively regulates crystallin expression in teeth SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE transforming growth factor-beta; crystallins; dentin sialophosphoprotein; teeth; gene expression; stress proteins ID ALPHA-B-CRYSTALLIN; GAMMA-CRYSTALLINS; DELTA-CRYSTALLIN; BETA-CRYSTALLINS; LENS CRYSTALLINS; CELL ELONGATION; A-CRYSTALLIN; GENE FAMILY; MOUSE; DIFFERENTIATION AB Previously, we have reported that targeted overexpression of transforming growth factor (TGF) beta1 in the teeth of the transgenic mice (dTGF-beta1) results in a novel tooth phenotype phenomimicking the most prevalent tooth disorders in human. This phenotype was associated with discoloration and attrition of teeth due to defective mineralization. Here, we report a novel expression of crystallin family members in developing mouse teeth and its regulation by TGF-beta1 in these transgenic mice. alphaB- and beta-crystallins were found to be elevated in dTGF-beta1 mouse teeth, whereas gamma-crystallin (gammaB, gammaC, and gammaF), a marker of cell differentiation, was significantly reduced. Because crystallins are believed to be stress-related proteins, their expression in teeth implicates them in a similar role because teeth are constantly subjected to physical friction and temperature fluctuations. C1 Natl Inst Dent & Craniofacial Res, Funct Gen Unit, NIH, Bethesda, MD 20892 USA. RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Gen Unit, NIH, Bldg 30,Room 529,30 Convent Dr, Bethesda, MD 20892 USA. NR 34 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 IS 9 BP 1710 EP 1717 DI 10.1359/jbmr.2002.17.9.1710 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 586ZN UT WOS:000177616200018 PM 12211442 ER PT J AU Akintoye, SO Shi, S Brahim, J Collins, MT Robey, PQ AF Akintoye, SO Shi, S Brahim, J Collins, MT Robey, PQ TI Site-specific in vivo response to osteogenic induction by human bone marrow stromal stem cells of different embryonic origins SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU215 BP S340 EP S340 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800928 ER PT J AU Barnes, GL Hebert, K Hassan, MQ van Wijen, A Young, MF Lian, JB Stein, GS Gerstenfeld, LC AF Barnes, GL Hebert, K Hassan, MQ van Wijen, A Young, MF Lian, JB Stein, GS Gerstenfeld, LC TI Regulation of bone sialoprotein gene expression by the homeodomain proteins Msx2 and Dlx5. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Boston Univ, Med Ctr, Dept Orthopaed Surg, Boston, MA 02215 USA. Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Ctr Canc, Worcester, MA 01655 USA. NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M196 BP S439 EP S439 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801370 ER PT J AU Bastepe, M Weinstein, L Kronenberg, HM Juppner, H Chung, U AF Bastepe, M Weinstein, L Kronenberg, HM Juppner, H Chung, U TI In vivo role of stimulatory G protein (Gs) in cartilage development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 NIDDK, NIH, Bethesda, MD USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1065 BP S141 EP S141 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800066 ER PT J AU Bi, Y Chen, X Xu, T Iozzo, RV Young, MF AF Bi, Y Chen, X Xu, T Iozzo, RV Young, MF TI Biglycan and decorin have overlapping roles in the commitment, proliferation, differentiation, and survival of osteoblasts and their precursors. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1068 BP S141 EP S141 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800069 ER PT J AU Black, DM Rosen, CM Greenspan, S Ensrud, K Bilezikian, J Hue, T McGowan, J AF Black, DM Rosen, CM Greenspan, S Ensrud, K Bilezikian, J Hue, T McGowan, J TI Parathyroid hormone (PTH) and alendronate in the treatment of osteoporosis: PaTH trial update. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Maine, Bangor, ME 04401 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Minnesota, Minneapolis, MN USA. Columbia Univ, New York, NY USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU382 BP S378 EP S379 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801096 ER PT J AU Carbone, LD Tylavsky, FA Cauley, JA Harris, TB Bauer, DC Barrow, KD Kritchevsky, SB AF Carbone, LD Tylavsky, FA Cauley, JA Harris, TB Bauer, DC Barrow, KD Kritchevsky, SB TI The impact of cyclooxygenase selectivity on bone loss: The health ABC study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Univ Tennessee, Memphis, TN USA. Univ Pittsburgh, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. UCSF, Prevent Sci Grp, San Francisco, CA USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA F311 BP S204 EP S204 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800339 ER PT J AU Chen, X Xu, T Young, M AF Chen, X Xu, T Young, M TI Biglycan is essential for BMP-4 stimulated osteoblast differentiation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1067 BP S141 EP S141 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800068 ER PT J AU Chiusaroli, R Gu, H Baron, R Sanjay, A AF Chiusaroli, R Gu, H Baron, R Sanjay, A TI The functions of c-Cbl and Cbl-b are different in osteoclasts: Cbl-b deletion leads to increased osteoclast activity and osteopenia. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Yale Univ, Sch Med, New Haven, CT 06520 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1149 BP S160 EP S160 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800150 ER PT J AU Cummings, SR Harris, F Lang, T Harris, T Taaffe, D Tylavsky, F Cauley, JA Black, DM AF Cummings, SR Harris, F Lang, T Harris, T Taaffe, D Tylavsky, F Cauley, JA Black, DM TI QCT spine BMD, hip BMD, and risk of fractures in elderly black and white men and women. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Queensland, St Lucia, Qld, Australia. Univ Tennessee, Memphis, TN 38163 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1131 BP S156 EP S156 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800132 ER PT J AU Denhardt, DT Kazanecki, CC Fisher, LW Sorensen, ES AF Denhardt, DT Kazanecki, CC Fisher, LW Sorensen, ES TI Intracellular osteopontin may be required for OPN-null bone cells to respond to pulsatile fluid flow. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Rutgers State Univ, Piscataway, NJ USA. NIH, Csdb, Nidcr, Bethesda, MD 20892 USA. Univ Aarhus, Prot Chem Lab, Aarhus, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SA154 BP S241 EP S241 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800496 ER PT J AU Feng, JQ Ye, L Chen, D Huang, H Zhang, J Lu, Y Li, G Dallas, SL Harris, SE Bonewald, L Mishina, Y AF Feng, JQ Ye, L Chen, D Huang, H Zhang, J Lu, Y Li, G Dallas, SL Harris, SE Bonewald, L Mishina, Y TI Dmp1-deficient mice develop dwarfism, chondrodysplasia, and exhibit disorganized bone mineralization during postnatal development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Queens Univ Belfast, Belfast, Antrim, North Ireland. UTHCSA, San Antonio, TX USA. Univ Missouri, Sch Dent, Kansas City, MO USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1005 BP S127 EP S127 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800006 ER PT J AU Gronthos, S Chen, S Wang, CY Robey, PG Shi, S AF Gronthos, S Chen, S Wang, CY Robey, PG Shi, S TI Telomerase accelerates osteogenesis of bone marrow StromalStem cells by increasing proliferation and by up-regulation of CBFA1, osterix, and osteocalcin SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Univ Michigan, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA F218 BP S196 EP S196 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800302 ER PT J AU Hausler, KD Quinn, JMW Horwood, NJ Ellis, J Lengel, C Martin, TJ Rubin, JS Gillespie, MT AF Hausler, KD Quinn, JMW Horwood, NJ Ellis, J Lengel, C Martin, TJ Rubin, JS Gillespie, MT TI Secreted frizzled-related protein (sFRP-1) inhibits TNFalpha- or RANKL-dependent osteoclast formation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 St Vincents Inst Med Res, Melbourne, Vic, Australia. NCI, NIH, Bethesda, MD 20892 USA. RI Horwood, Nicole/B-4351-2009 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU257 BP S349 EP S349 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800971 ER PT J AU Horner, A Shum, L Ayres, JA Nuckolls, GH AF Horner, A Shum, L Ayres, JA Nuckolls, GH TI FGF signaling regulates Dach1 expression during limb skeletal development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 NIAMS, Biol & Orthopaed Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA F139 BP S190 EP S190 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800275 ER PT J AU Karadag, A Jain, A Fedarko, NS Fisher, LW AF Karadag, A Jain, A Fedarko, NS Fisher, LW TI Bone sialoprotein (BSP) promotes invasion by osteotropic cancer cells through an RGD dependant mechanism. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA F52 BP S182 EP S183 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800245 ER PT J AU Khadeer, MA Tang, Z Tenenhouse, HS Hernando, N Eiden, MV Gupta, A AF Khadeer, MA Tang, Z Tenenhouse, HS Hernando, N Eiden, MV Gupta, A TI Cellular distribution and protein interactions of Na-dependent phosphate transporters in the osteoclast. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Univ Maryland, Baltimore, MD 21201 USA. McGill Univ, Montreal, PQ, Canada. Univ Zurich, Inst Physiol, Zurich, Switzerland. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M37 BP S404 EP S404 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801212 ER PT J AU Klopot, A Hance, K Wang, L Barsony, J Fleet, JC AF Klopot, A Hance, K Wang, L Barsony, J Fleet, JC TI The effect of differentiation on nuclear vitamin D receptor (VDR) function in human intestinal cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Purdue Univ, W Lafayette, IN 47907 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M454 BP S497 EP S497 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801628 ER PT J AU Kundu, M Javed, A Yang, Y Nuckolls, G Muenke, M Lian, J Stein, G Liu, P AF Kundu, M Javed, A Yang, Y Nuckolls, G Muenke, M Lian, J Stein, G Liu, P TI Cbfb, a well-known, regulator of hematopoiesis, cooperates with Cbfa1 and plays a critical role in bone development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Dept Cell Biol, Worcester, MA 01605 USA. NIH, Human Genome Res Inst, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1004 BP S126 EP S126 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800005 ER PT J AU Lee, JS Ziran, N Chen, C Leet, AI Wientroub, S Robey, PG Collins, MT AF Lee, JS Ziran, N Chen, C Leet, AI Wientroub, S Robey, PG Collins, MT TI Onset of fibrous dysplastic lesions is related to the skeletal site of involvement. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 NIDCR, Craniofacial Skeletal Dis Branch, NIH, Bethesda, MD USA. Univ Rochester, Dept Orthoped Surg, Rochester, NY USA. Dana Childrens Hosp, Dept Ped Orthoped Surg, Tel Aviv, Israel. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU387 BP S380 EP S380 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801101 ER PT J AU Leet, AI Lee, JS Ziran, N Shi, S Kuznetsov, SA Robey, PG AF Leet, AI Lee, JS Ziran, N Shi, S Kuznetsov, SA Robey, PG TI Colony forming efficiency of circulating skeletal stem cells (CSSCs) and colony forming units-fibroblasts (CFU-Fs) during fracture and repair. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 NIH, CSDB, NIDER, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M226 BP S445 EP S445 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801400 ER PT J AU McGowan, JA Jackson, RD Cauley, JA LaCroix, AZ AF McGowan, JA Jackson, RD Cauley, JA LaCroix, AZ TI Calcium and vitamin D in the prevention of hip and other fractures: An update on the women's health initiative CaD trial. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Pittsburgh, Pittsburgh, PA USA. Ohio State Univ, Columbus, OH 43210 USA. NIAMSD, Bethesda, MD 20892 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M367 BP S477 EP S477 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801541 ER PT J AU Nielsen, KL Allen, MR Bloomfield, SA Timm, IA Chen, XD Young, MF Heegaard, A AF Nielsen, KL Allen, MR Bloomfield, SA Timm, IA Chen, XD Young, MF Heegaard, A TI Biglycan deficiency interferes with ovariectomy-induced bone loss. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Nord Biosci AS, Herlev, Denmark. Texas A&M Univ, Dept Hlth & Kinesiol, College Stn, TX 77843 USA. CCBR, Ballerup, Denmark. NIDCR, Craniofacial & Skeletal Dis Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1194 BP S170 EP S170 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800195 ER PT J AU Quinn, JMW Hausler, KD Gange, C Zhou, H Rubin, JS Martin, TJ Gillespie, MT AF Quinn, JMW Hausler, KD Gange, C Zhou, H Rubin, JS Martin, TJ Gillespie, MT TI Osteoclast progenitors stimulated by TGF-beta or by RANKL differ in their sensitivity to osteoclastogenesis inhibitors. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU243 BP S346 EP S346 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800957 ER PT J AU Riminucci, M Corsi, A Ippolito, E Robey, PG Bianco, P AF Riminucci, M Corsi, A Ippolito, E Robey, PG Bianco, P TI Fracture repair in fibrous dysplasia of bone: Evidence for local segregation and dynamic selection of disease genotype. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Univ Aquila, I-67100 Laquila, Italy. Univ Roma Tor Vergata, Rome, Italy. NIH, Nider, Csdb, Bethesda, MD 20892 USA. Univ Roma La Sapienza, Rome, Italy. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU386 BP S379 EP S379 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801100 ER PT J AU Shi, S Bianco, P Robey, PG Gronthos, S AF Shi, S Bianco, P Robey, PG Gronthos, S TI Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 NIDCR, NIH, Craniofacial & Skeletal Dis Branch, Bethesda, MD USA. Univ Roma La Sapienza, Dipartimento Med Sperimentale & Pathol, Rome, Italy. Inst Med & Vet Sci, Div Haematol, Adelaide, SA 5000, Australia. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M228 BP S446 EP S446 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801402 ER PT J AU Talmage, RV Lester, GE Mobley, HT Matthews, JL AF Talmage, RV Lester, GE Mobley, HT Matthews, JL TI Calcium homeostasis: A suggested role for bone surface proteins. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Univ N Carolina, Chapel Hill, NC USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Kilgore Coll, Longview, TX USA. Baylor Med Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M13 BP S399 EP S399 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801188 ER PT J AU Lakatta, EG Vinogradova, TM Bogdanov, KY AF Lakatta, EG Vinogradova, TM Bogdanov, KY TI beta-adrenergic stimulation modulation of heart rate via synchronization of ryanodine receptor Ca2+ release SO JOURNAL OF CARDIAC SURGERY LA English DT Article; Proceedings Paper CT 1st International Symposium on Cardiovascular Science CY NOV 23-24, 2001 CL CHINESE UNIV HONG KONG, HONG KONG, PEOPLES R CHINA HO CHINESE UNIV HONG KONG ID SINOATRIAL NODE CELLS; TOAD PACEMAKER CELLS; SARCOPLASMIC-RETICULUM; CALCIUM SPARKS; MYOCYTES; MECHANISMS; AUTOMATICITY; MUSCLE AB A robust "fight or flight response", largely mediated via acute beta-adrenergic receptor (beta-AR) stimulation to the heart to increase its beating rate and contractile performance, is an essential component of the vertebrate survival instinct. While it has long been recognized that activation of beta-AR increases the spontaneous beating rate of sinoatrial nodal cells (SANC), specific links between stimulation of beta-ARs and the resultant increase in firing rate have not been evaluated. Our recent studies(1,2) employed imaging of subcellular Ca2+ release coupled with recording of membrane potential or current in single, isolated cardiac SANC, to seek novel links between beta-AR stimulation and ryanodine receptor Ca2+ release and heart rate. An overview of these recent results, which provides novel insights into mechanisms of cardiac reserve that underlie the "fight or flight instinct, is presented here. C1 NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov NR 30 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD SEP-OCT PY 2002 VL 17 IS 5 BP 451 EP 461 PG 11 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 659ZX UT WOS:000181810300018 PM 12630548 ER PT J AU Zhou, J Pineyro, MA Wang, XL Doyle, ME Egan, JM AF Zhou, J Pineyro, MA Wang, XL Doyle, ME Egan, JM TI Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: Involvement of PDX-1 and HNF3 beta transcription factors SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; HOMEODOMAIN PROTEIN IDX-1; EPIDERMAL GROWTH-FACTOR; BETA-CELLS; BINDING PROTEIN; IN-VITRO; GENE-TRANSCRIPTION; MESSENGER-RNAS; INSULIN; EXPRESSION AB Exendin-4 (EX-4), a long acting agonist of GLP-1, induces an endocrine phenotype in Capan-1 cells. Under culture conditions which include serum, similar to10% of the cells contain insulin and glucagon. When exposed to EX-4 (0.1 nM, up to 5 days), the number of cells containing insulin and glucagon increased to similar to40%. Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX-4 treatment. We explored the sequence of activation of certain transcription factors, known to be essential for the beta cell phenotype: PDX-1, Beta2/NeuroD, and hepatocyte nuclear factor 3beta (HNF3 beta). Double immunostaining showed that PDX-1 coexisted with insulin and glucagon in EX-4-treated cells. Treatment caused an increase in PDX-1 protein levels by 24 11 and induced its nuclear translocation, Beta2/NeuroD protein levels also increased progressively over 24 h. HNF3beta protein level increased twofold as early as 6 h after EX-4 treatment. EMSA results indicated that EX-4 caused a 12-fold increase in HNF3beta binding to PDX-1 promoter area II. Beta2/NeuroD protein levels progressively increased after 24 h treatment. Differentiation to insulin-producing cells was also seen when Capan-1 cells were transfected with pdx-1, with 80% of these cells expressing insulin 3 days after transfection. PDX-1 antisense totally inhibited such conversion. During the differentiation of duct cells to endocrine cells,cAMP levels (EX-4 is a ligand for the GLP-1, G-protein coupled receptor) and MAP kinase activity increased. Our results indicate that EX-4 activates adenylyl cyclase and MAP kinase which, in turn, may lead to activation of transcription factors necessary for an endocrine phenotype, Published 2002 Wiley-Liss, Inc.(dagger) C1 NIA, Diabet Sect 23, NIH, Baltimore, MD 21224 USA. RP Egan, JM (reprint author), NIA, Diabet Sect 23, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 54 TC 72 Z9 81 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2002 VL 192 IS 3 BP 304 EP 314 DI 10.1002/jcp.10143 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 579PV UT WOS:000177187800007 PM 12124776 ER PT J AU Foster, JA Christopherson, PL Levine, RA AF Foster, JA Christopherson, PL Levine, RA TI GTP cyclohydrolase I induction in striatal astrocytes following intrastriatal kainic acid lesion SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Article DE dopamine; tyrosine hydroxylase; tetrahydrobiopterin (BH4); high performance liquid chromatography ID NITRIC-OXIDE SYNTHASE; TYROSINE-HYDROXYLASE; PARKINSONS-DISEASE; MESSENGER-RNA; TETRAHYDROBIOPTERIN BIOSYNTHESIS; GLIAL-CELLS; PC12 CELLS; DOPAMINE NEURONS; NIGRAL NEURONS; RAT-BRAIN AB The cause of premature death of dopamine neurons in patients with Parkinson's disease remains unknown. It is speculated that damaging reactive species resulting from the metabolism of dopamine, nitric oxide, and tetrahydrobiopterin (BH4) may be involved. GTP cyclohydrolase I (GCH1) is the first and rate-limiting enzyme in the synthesis of BH4, an essential cofactor for tyrosine hydroxylase and nitric oxide synthase in dopamine and nitric oxide production, respectively. Our studies have explored BH4 metabolism in the nigrostriatal system following intrastriatal kainic acid lesion. We have demonstrated that I week following kainic acid there was an increase in striatal GCH1 mRNA, protein, and activity. There was also an elevation of BH4 levels in the striatum. Part of the induction of GCH1 was localized in situ to astrocytes. Further, the striatal lesion caused death of both neurons and astrocytes in striatum, as shown by in situ end labeling. These novel observations suggest that the induction of GTP cyclohydrolase and BH4 in striatal astrocytes may be mediating death of striatal neuronal and non-neuronal cells. This work supports existing and emerging reports that demonstrate the importance of dopamine metabolism in neuronal death of the nigrostriatal system. (C) 2002 Elsevier Science B.V. All rights reserved. C1 William T Gossett Neurol Labs, Henry Ford Hlth Syst, Detroit, MI 48202 USA. Wayne State Univ, Dept Pharmaceut Sci, Detroit, MI USA. John D Dingell Vet Adm Med Ctr, Detroit, MI USA. RP Foster, JA (reprint author), NIMH, Bldg 36,Rm 2D-15,36 Convent Dr, Bethesda, MD 20892 USA. NR 36 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0891-0618 J9 J CHEM NEUROANAT JI J. Chem. Neuroanat. PD SEP PY 2002 VL 24 IS 3 BP 173 EP 179 AR PII S0891-0618(02)00044-3 DI 10.1016/S0891-0618(02)00044-3 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 603LU UT WOS:000178561800003 PM 12297263 ER PT J AU Pine, DS AF Pine, DS TI Treating children and adolescents with selective serotonin reuptake inhibitors: How long is appropriate? SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; CORTICOTROPIN-RELEASING FACTOR; MAJOR DEPRESSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; MENTAL-HEALTH-SERVICES; FOLLOW-UP; DOUBLE-BLIND; COMMUNITY SAMPLE; YOUNG-ADULTS; EPIDEMIOLOGIC SAMPLE AB This article addresses a key question on the use of selective serotonin reuptake inhibitors (SSRIs) among children and adolescents. As briefly reviewed, recent randomized controlled trials have established the safety and efficacy of SSRIs in the acute treatment of major depression and anxiety disorders among children and adolescents. Major questions emerge in light of these data concerning the potential risks and benefits of long-term SSRI use among children and adolescents who receive significant short-term benefits from SSRI treatment. The current review summarizes research on longitudinal outcomes, neuroscience, and psychopharmacology to formulate a set of preliminary recommendations on long-term SSRI use. A review of data in these areas supports three conclusions. First, for children who achieve marked reduction in anxiety or depressive symptoms on an SSRI, clinicians should consider recommending a medication-free trial. Second, when indicated, this medication-free,. trial should coincide with the first low-stress period occurring after 1 year of continual SSRI treatment. Third, SSRI treatment should be reinitiated in children who exhibit signs of relapse during this medication-free trial. C1 NIMH, Program Mood & Anxiety Disorders, Intramural Res Program, Bethesda, MD 20892 USA. RP Pine, DS (reprint author), NIMH, Program Mood & Anxiety Disorders, Intramural Res Program, Bldg 10,Room 4N-222,MSC 1381, Bethesda, MD 20892 USA. NR 73 TC 29 Z9 29 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FAL PY 2002 VL 12 IS 3 BP 189 EP 203 DI 10.1089/104454602760386888 PG 15 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 606LV UT WOS:000178736200003 PM 12427293 ER PT J AU Pollock, RA Carter, AS Avenevoli, S Dierker, LC Chazan-Cohen, R Merikangas, KR AF Pollock, RA Carter, AS Avenevoli, S Dierker, LC Chazan-Cohen, R Merikangas, KR TI Anxiety sensitivity in adolescents at risk for psychopathology SO JOURNAL OF CLINICAL CHILD AND ADOLESCENT PSYCHOLOGY LA English DT Article ID PANIC DISORDER; DIAGNOSTIC INTERVIEW; MAJOR DEPRESSION; CHILDREN; CHILDHOOD; COMORBIDITY; PARENTS; ATTACKS; INDEX; SCHIZOPHRENIA AB Examined the associations of adolescents' self-reported anxiety sensitivity with semi-structured, interview-based anxiety and depressive symptoms and anxiety disorders. The sample included 121 adolescents and their parents who participated in a larger epidemiological, high-risk family study of substance abuse and anxiety disorders (Merikangas, Dierker, & Szatmari, 1998). A series of hierarchical multiple regressions revealed the incremental validity of anxiety sensitivity, beyond the contribution of self-rated anxiety, to anxiety symptoms and comorbid anxiety disorders. Furthermore, familial risk for anxiety moderated the association between anxiety sensitivity and number of anxiety symptoms as well as number of comorbid anxiety disorders. Analyses of high- and low-risk groups demonstrated that the association between anxiety sensitivity and anxiety symptoms and disorders was evident in high-risk adolescents only. Although self-reported anxiety was associated with depressive symptoms, anxiety sensitivity was not. Results from this investigation further support the utility of assessing anxiety sensitivity in an adolescent population and suggest it as a trait marker of anxiety among at-risk individuals. C1 Massachusetts Gen Hosp, Dept Psychiat, Unit Psychiat & Neurodev Genet, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, VA New England Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Cambridge, MA 02138 USA. Univ Massachusetts, Boston, MA 02125 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. Wesleyan Univ, Dept Psychol, Middletown, CT 06459 USA. Adm Children Youth & Families, Commissioners Off Res & Evaluat, Washington, DC USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth Psychol, New Haven, CT 06520 USA. RP Pollock, RA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Unit Psychiat & Neurodev Genet, CNY Bldg 149,13th St,10th Floor, Charlestown, MA 02129 USA. FU NIDA NIH HHS [DA 00293] NR 50 TC 16 Z9 16 U1 1 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1537-4416 J9 J CLIN CHILD ADOLESC JI J. Clin. Child Adolesc. Psychol. PD SEP PY 2002 VL 31 IS 3 BP 343 EP 353 DI 10.1207/S15374424JCCP3103_06 PG 11 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 574VQ UT WOS:000176910600005 PM 12149972 ER PT J AU Ostir, GV Volpato, S Fried, LP Chaves, P Guralnik, JM AF Ostir, GV Volpato, S Fried, LP Chaves, P Guralnik, JM TI Reliability and sensitivity to change assessed for a summary measure of lower body function - Results from the Women's Health and Aging Study SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE aging; summary performance measure; reliability; sensitivity to change; disability ID LOWER-EXTREMITY FUNCTION; NONDISABLED OLDER PERSONS; SUBSEQUENT DISABILITY; PREDICTOR; CONSISTENCY; PERFORMANCE AB A summary performance measure comprised of a hierarchical balance task, a 4-meter walk, and five repetitive chair stands is increasingly being used as a predictor of independent living for older persons. The reliability and sensitivity to change of this summary performance measure have not been investigated, however. Because a measure can be reliable while being unresponsive to change, this study presents information on both the reliability and sensitivity to change for the Summary performance measure. This is a 3-year prospective cohort study of 1.002 moderately to severely disabled older women. Short- and long-term reliability was assessed by intraclass correlation coefficients (ICC). Sensitivity to change was assessed by slope differences for three age categories (65-74, 75-84, and greater than or equal to85) over six 6-month follow-Lip periods. Sensitivity to change was also assessed by summary performance change scores for those who did and did not suffer from one of four medical events [myocardial infarction (MI), stroke, hip fracture, or congestive heart failure (CHF)] at follow-up. The summary performance measure showed excellent reliability. Intraclass correlation coefficients ranged from 0.88 to 0.92 for measures made I week apart. The 6-month average intraclass correlation coefficient was 0.77 (range 0.72-0.79). The summary performance measure was also highly responsive to change. Subjects who suffered an incident MI, stroke, hip fracture, or CHF at follow-up were significantly more likely to have poorer summary performance change scores (-2.25) compared with those who did not have one of these medical events (-0.24). Additionally, subjects who suffered one of these events improved their summary performance scores in the following assessment period by 0.72. With increasing utilization of the summary performance measure by researchers and clinicians it is important that the measurement properties of this instrument are known. Our results show that the summary performance measure has excellent reliability and is highly sensitive to change. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Texas, Med Branch, Sealy Ctr Aging, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Internal Med, Galveston, TX 77555 USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. RP Ostir, GV (reprint author), Univ Texas, Med Branch, Sealy Ctr Aging, 301 Univ Blvd, Galveston, TX 77555 USA. RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 NR 13 TC 139 Z9 142 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD SEP PY 2002 VL 55 IS 9 BP 916 EP 921 AR PII S0895-4356(02)00436-5 DI 10.1016/S0895-4356(02)00436-5 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 600DH UT WOS:000178375000011 PM 12393080 ER PT J AU Bhoumik, A Huang, TG Ivanov, V Gangi, L Qiao, RF Woo, SLC Chen, SH Ronai, Z AF Bhoumik, A Huang, TG Ivanov, V Gangi, L Qiao, RF Woo, SLC Chen, SH Ronai, Z TI An ATF2-derived peptide sensitizes melanomas to apoptosis and inhibits their growth and metastasis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID C-JUN; MAMMALIAN-CELLS; FAMILY MEMBERS; IN-VIVO; KAPPA-B; EXPRESSION; ATF2; ACTIVATION; PROMOTER; GENE AB Melanomas are among the aggressive tumor types because of their notorious resistance to treatment and their high capacity to metastasize. ATF2 is among transcription factors implicated in the progression of melanoma and its resistance to treatment. Here we demonstrate that the expression of a peptide spanning amino acids 50-100 of ATF2 (ATF2(50-100)) reduces ATF2 transcriptional activities while increasing the expression and activity of c-jun. Altering the balance of Jun/ATF2 transcriptional activities sensitized melanoma cells to apoptosis, an effect that could be attenuated by inhibiting c-jun. Inhibition of ATF2 via RNA interference likewise increased c-jun expression and primed melanoma cells to undergo apoptosis. Growth and metastasis of SW1 and B16F10 mouse melanomas were inhibited by ATF2(50-100) to varying degrees up to a complete regression, depending on the mode (inducible, constitutive, or adenoviral delivery) of its expression. Thus, by attenuating ATF2 and inducing c-jun activity, ATF2(50-100) inhibits melanoma growth and metastasis. C1 CUNY Mt Sinai Sch Med, Ruttenberg Canc Ctr, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Carl C Icahn Inst Gene Therapy & Mol Med, New York, NY 10029 USA. NCI Sci Applicat Int Corp, Lab Mol Technol, Frederick, MD USA. RP Ronai, Z (reprint author), CUNY Mt Sinai Sch Med, Ruttenberg Canc Ctr, 1 Gustave L Levy Pl,Box 1130, New York, NY 10029 USA. RI Ivanov, Vladimir/A-3081-2008; OI Ivanov, Vladimir/0000-0002-2933-6339; RONAI, ZEEV/0000-0002-3859-0400 FU NCI NIH HHS [R01 CA078419, CA-59008, CA-78419] NR 32 TC 61 Z9 61 U1 1 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2002 VL 110 IS 5 BP 643 EP 650 DI 10.1172/JCI200216081 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 590LF UT WOS:000177823800011 PM 12208865 ER PT J AU Porter, FD AF Porter, FD TI Malformation syndromes due to inborn errors of cholesterol synthesis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LEMLI-OPITZ-SYNDROME; DOMINANT CHONDRODYSPLASIA PUNCTATA; ANTLEY-BIXLER-SYNDROME; ALZHEIMERS-DISEASE; MOUSE MODEL; 3-BETA-HYDROXYSTEROID DEHYDROGENASE; CHILD SYNDROME; BIOSYNTHESIS; MUTATIONS; GENE C1 NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD USA. RP Porter, FD (reprint author), NICHD, Heritable Disorders Branch, NIH, Bldg 10,Room 9S241,10 Ctr Dr, Bethesda, MD 20892 USA. NR 62 TC 70 Z9 71 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2002 VL 110 IS 6 BP 715 EP 724 DI 10.1172/JCI200216386 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 594VX UT WOS:000178073300001 PM 12235098 ER PT J AU Opitz, OG Harada, H Suliman, Y Rhoades, B Sharpless, NE Kent, R Kopelovich, L Nakagawa, H Rustgi, AK AF Opitz, OG Harada, H Suliman, Y Rhoades, B Sharpless, NE Kent, R Kopelovich, L Nakagawa, H Rustgi, AK TI A mouse model of human oral-esophageal cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; CYCLIN D1 OVEREXPRESSION; CIS-REGULATORY ELEMENT; SKIN TUMOR-DEVELOPMENT; TRANSGENIC MICE; TELOMERE DYSFUNCTION; HAPLO-INSUFFICIENT; P53; EXPRESSION; PROMOTER AB Squamous cancers of the oral cavity and esophagus are common worldwide, but no good genetically based animal model exists. A number of environmental factors as well as genetic alterations have been identified in these cancers, yet the specific combination of genetic events required for cancer progression remains unknown. The Epstein-Barr virus ED-L2 promoter (L2) can be used to target genes in a specific fashion to the oral-esophageal squamous epithelium. To that end, we generated L2-cyclin D 1 (L2D1(+)) mice and crossbred these with p53-deficient mice. Whereas L2D1(+) mice exhibit a histologic phenotype of oral-esophageal dysplasia, the combination of cyclin D1 expression and p53 deficiency results in invasive oral-esophageal cancer. The development of the precancerous lesions was significantly reversed by the application of sulindac in the drinking water of the L2D1(+)/p53(+/-) mice. Furthermore, cell lines derived from oral epithelia of L2D1(+)/p53(+/-) and L2D1(+)/p53(-/-) mice, but not control mice, formed tumors in athymic nude mice. These data demonstrate that L2D1(+)/p53(+/-) mice provide a well-defined, novel, and faithful model of oral-esophageal cancer, which allows for the testing of novel chemopreventive, diagnostic, and therapeutic approaches. C1 Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Ctr Res Inst, Philadelphia, PA 19104 USA. Univ Freiburg, Dept Med, D-7800 Freiburg, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. Natl Canc Inst, Div Canc Prevent, Bethesda, MD USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Rustgi, AK (reprint author), Univ Penn, Div Gastroenterol, 415 Curie Blvd, Philadelphia, PA 19104 USA. FU NCI NIH HHS [N01-CN-95031-72]; NIDCR NIH HHS [P01 DE-12467, P01 DE012467]; NIDDK NIH HHS [P30 DK-50306, P30 DK050306] NR 44 TC 64 Z9 67 U1 1 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2002 VL 110 IS 6 BP 761 EP 769 DI 10.1172/JCI200215324 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 594VX UT WOS:000178073300010 PM 12235107 ER PT J AU Yakar, S Rosen, CJ Beamer, WG Ackert-Bicknell, CL Wu, YP Liu, JL Ooi, GT Setser, J Frystyk, J Boisclair, YR LeRoith, D AF Yakar, S Rosen, CJ Beamer, WG Ackert-Bicknell, CL Wu, YP Liu, JL Ooi, GT Setser, J Frystyk, J Boisclair, YR LeRoith, D TI Circulating levels of IGF-1 directly regulate bone growth and density SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FACTOR-BINDING-PROTEINS; FACTOR-I; EPIPHYSEAL CHONDROCYTES; COLONY FORMATION; SUSPENSION-CULTURE; POSTNATAL-GROWTH; INBRED STRAINS; DNA-SYNTHESIS; INSULIN; HORMONE AB IGF-1 is a growth-promoting polypeptide that is essential for normal growth and development. In serum, the majority of the IGFs exist in a 150-kDa complex including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile subunit (ALS). This complex prolongs the half-life of serum IGFs and facilitates their endocrine actions. Liver IGF-1-deficient (LID) mice and ALS knockout (ALSKO) mice exhibited relatively normal growth and development, despite having 75% and 65% reductions in serum IGF-1 levels, respectively. Double gene disrupted mice were generated by crossing LID+ALSKO mice. These mice exhibited further reductions in serum IGF-1 levels and a significant reduction in linear growth. The proximal growth plates of the tibiae of LID+ALSKO mice were smaller in total height as well as in the height of the proliferative and hypertrophic zones of chondrocytes. There was also a 10% decrease in bone mineral density and a greater than 35% decrease in periosteal circumference and cortical thickness in these mice. IGF-1 treatment for 4 weeks restored the total height of the proximal growth plate of the tibia. Thus, the double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF-1 is necessary for normal bone growth and suggests that IGF-1, IGFBP-3, and ALS play a prominent role in the pathophysiology of osteoporosis. C1 NIDDK, Sect Cellular & Mol Physiol, Clin Endocrinol Branch, NIH, Bethesda, MD USA. Jackson Lab, Bar Harbor, ME 04609 USA. Royal Victoria Hosp, Dept Med, Montreal, PQ H3A 1A1, Canada. McGill Univ, Montreal, PQ H3A 1A1, Canada. Prince Henrys Inst Med Res, Clayton, Vic, Australia. Aarhus Univ Hosp, Inst Expt Clin Res, DK-8000 Aarhus, Denmark. Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. RP LeRoith, D (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Room 8D12,Bldg 10, Bethesda, MD 20892 USA. EM derek@helix.nih.gov FU NIDDK NIH HHS [DK-51624, R01 DK051624] NR 33 TC 478 Z9 498 U1 4 U2 25 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2002 VL 110 IS 6 BP 771 EP 781 DI 10.1172/JCI200215463 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 594VX UT WOS:000178073300011 PM 12235108 ER PT J AU Dupont, J Renou, JP Shani, M Hennighausen, L LeRoith, D AF Dupont, J Renou, JP Shani, M Hennighausen, L LeRoith, D TI PTEN overexpression suppresses proliferation and differentiation and enhances apoptosis of the mouse mammary epithelium SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BREAST-CANCER MODEL; GROWTH-FACTOR-I; TUMOR-SUPPRESSOR; TRANSGENIC MICE; GLAND DEVELOPMENT; CELL-SURVIVAL; TARGETED EXPRESSION; MAPK ACTIVATION; PROTEIN; RECEPTOR AB The phosphatase PTEN regulates growth, adhesion, and apoptosis, among many other cell processes. To investigate its role during mouse mammary gland development, we generated MK-PTEN, a transgenic mouse model in which human PTEN is overexpressed in ductal and alveolar mammary epithelium during puberty, pregnancy, lactation, and involution. No obvious phenotype was observed in mammary tissue of pubescent virgin mice. However, MK-PTEN females could not lactate normally, and similar to30% of pups died, with survivors exhibiting growth retardation. Transgenic offspring nursed by wild-type foster mothers, conversely, developed normally. This phenotype is consistent with a reduced number of alveolar epithelial cells due to a decrease in cell proliferation and an increase in apoptosis. Using mammary-enriched cDNA microarrays, we identified several genes that were preferentially expressed in MK-PTEN mammary tissue, including the IGF-binding protein-5 (Igfbp5) gene, and others whose expression was reduced, including the genes for c-Jun amino-terminal kinase. Secretory epithelial cell differentiation was impaired, as measured by the expression of specific milk protein genes. MK-PTEN mice also exhibited a 50% decrease in the phosphorylation state of Akt. Taken together, these results suggest that PTEN controls mammary gland development and, consequently, lactation. C1 NIDDK, Sect Mol & Cellular Physiol, Clin Endocrinol Branch, NIH, Bethesda, MD USA. NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD USA. RP LeRoith, D (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Room 8D12,Bldg 10, Bethesda, MD 20892 USA. NR 52 TC 60 Z9 62 U1 1 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2002 VL 110 IS 6 BP 815 EP 825 DI 10.1172/JCI200213829 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 594VX UT WOS:000178073300016 PM 12235113 ER PT J AU Espinel-Ingroff, A Fothergill, A Peter, J Rinaldi, MG Walsh, TJ AF Espinel-Ingroff, A Fothergill, A Peter, J Rinaldi, MG Walsh, TJ TI Testing conditions for determination of minimum fungicidal concentrations of new and established antifungal agents for Aspergillus spp.: NCCLS Collaborative Study SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IN-VITRO ACTIVITY; PERSISTENTLY GRANULOCYTOPENIC RABBITS; AMPHOTERICIN-B; PULMONARY ASPERGILLOSIS; INVASIVE ASPERGILLOSIS; FILAMENTOUS FUNGI; MURINE MODEL; ITRACONAZOLE; VORICONAZOLE; RESISTANCE AB Standard conditions are not available for evaluating the minimum fungicidal concentrations (MFCs) of antifungal agents. This multicenter collaborative study investigated the reproducibility in three laboratories of itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B MFCs for 15 selected isolates of Aspergillus spp. After MIC determinations for the 15 isolates in each center by the NCCLS M38-A broth microdilution method with four media, standard RPMI 1640 (RPMI), RPMI with 2% dextrose, antibiotic medium 3 (M3), and M3 with 2% dextrose, MFCs were determined for each isolate-medium-drug combination. MFCs were defined as the lowest drug dilutions that yielded <3 colonies (approximately 99 to 99.5% killing activity). The highest reproducibility (96 to 100%) was for amphotericin B MFCs with the four media. Although reproducibility was more variable and medium dependent for the azoles (91 to 98%), agreement was good to excellent for itraconazole, ravuconazole, and voriconazole MFCs with RPMI and M3 (93 to 98%). For posaconazole, the agreement was higher with M3 media (91 to 96%) than with RPMI media (91%). These data extend the refinement of testing guidelines for susceptibility testing of Aspergillus spp. and warrant consideration for introduction into future versions of the M38 document. The role of the MFC under these standardized testing conditions as a predictor of clinical outcome needs to be established in clinical trials. C1 Virginia Commonwealth Univ, Richmond, VA 23298 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NCI, Bethesda, MD 20892 USA. RP Espinel-Ingroff, A (reprint author), Virginia Commonwealth Univ, Med Coll Virginia Campus,1101 Marshall St,Sanger, Richmond, VA 23298 USA. NR 27 TC 82 Z9 87 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2002 VL 40 IS 9 BP 3204 EP 3208 DI 10.1128/JCM.40.9.3204-3208.2002 PG 5 WC Microbiology SC Microbiology GA 590NX UT WOS:000177829900015 PM 12202554 ER PT J AU Yang, S Lin, S Kelen, GD Quinn, TC Dick, JD Gaydos, CA Rothman, RE AF Yang, S Lin, S Kelen, GD Quinn, TC Dick, JD Gaydos, CA Rothman, RE TI Quantitative multiprobe PCR assay for simultaneous detection and identification to species level of bacterial pathogens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; DNA; AMPLIFICATION; SEPTICEMIA; DIAGNOSIS AB We describe a novel adaptation of the TaqMan PCR assay which potentially allows for highly sensitive detection of any eubacterial species with simultaneous species identification. Our system relies on a unique multiprobe design in which a single set of highly conserved sequences encoded by the 16S rRNA gene serves as the primer pair and is used in combination with both an internal highly conserved sequence, the universal probe, and an internal variable region, the species-specific probe. A pre-PCR ultrafiltration step effectively decontaminates or removes background DNA. The TaqMan system described reliabAly detected 14 common bacterial species with a detection limit of 50 fg. Further, highly sensitive and specific pathogen detection was demonstrated with a prototype species-specific probe designed to detect Staphylococcus aureus. This assay has broad potential in the clinical arena for rapid and specific diagnosis of infectious diseases. C1 Johns Hopkins Univ, Sch Med, Dept Emergency Med, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Rothman, RE (reprint author), Johns Hopkins Univ, Sch Med, Dept Emergency Med, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010; OI Rothman, Richard/0000-0002-1017-9505; Kelen, Gabor/0000-0002-3236-8286 FU NCRR NIH HHS [M01RR00052-39-5(S1), M01 RR000052] NR 17 TC 102 Z9 103 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2002 VL 40 IS 9 BP 3449 EP 3454 DI 10.1128/JCM.40.9.3449-3454.2002 PG 6 WC Microbiology SC Microbiology GA 590NX UT WOS:000177829900053 PM 12202592 ER PT J AU Shike, M Latkany, L Riedel, E Fleisher, M Schatzkin, A Lanza, E Corle, D Begg, CB AF Shike, M Latkany, L Riedel, E Fleisher, M Schatzkin, A Lanza, E Corle, D Begg, CB CA Polyp Prevention Trial Study Grp TI Lack of effect of a low-fat, high-fruit, -vegetable, and -fiber diet on serum prostate-specific antigen of men without prostate cancer: Results from a randomized trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MULTICENTER CLINICAL-TRIAL; LATENT CARCINOMA; MORTALITY; RISK; QUESTIONNAIRE; PREVENTION; PATTERNS; TRENDS AB Purpose: To determine whether a diet low in fat and high in fruits, vegetables, and fiber may be protective against prostate cancer by having an impact on serial levels of serum prostate-specific antigen (PSA). Methods: Six hundred eighty-nine men were randomized to the intervention arm and 661 to the control arm. The intervention group received intensive counseling to consume a diet low in fat and high in fiber, fruits, and vegetables. The control group received a standard brochure an a healthy diet. PSA in serum was measured at baseline and annually thereafter for 4 years, and newly diagnosed prostate cancers were recorded. Results: The individual PSA slope for each participant was calculated, and the distributions of slopes were compared between the two groups. There was no significant difference in distributions of the slopes (P =.99). The two groups were identical in the proportions of participants with elevated PSA at each time point. There was no difference in the PSA slopes between the two groups (P =.34) and in the,frequencies of elevated PSA values for those with elevated PSA at baseline. Incidence of prostate cancer during the 4 years was similar in the two groups (19 and 22 in the control and intervention arms, respectively). Conclusion: Dietary intervention over a 4-year period with reduced fat and increased consumption of fruits, vegetables, and fiber has no impact on serum PSA levels in men. The study also offers no evidence that this dietary intervention over a 4-year period affects the incidence of prostate cancer during the 4 years. (C) 2002 by American Society of Clinical Oncology. C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Bethesda, MD 20892 USA. RP Shike, M (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave,Box 224, New York, NY 10021 USA. FU NCI NIH HHS [N01-SC-05318] NR 38 TC 32 Z9 34 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2002 VL 20 IS 17 BP 3592 EP 3598 DI 10.1200/JCO.2002.01.040 PG 7 WC Oncology SC Oncology GA 596RB UT WOS:000178178100009 PM 12202659 ER PT J AU Bennett, CL Price, DK Kim, S Liu, D Jovanovic, BD Nathan, D Johnson, ME Montgomery, JS Cude, K Brockbank, JC Sartor, O Figg, WD AF Bennett, CL Price, DK Kim, S Liu, D Jovanovic, BD Nathan, D Johnson, ME Montgomery, JS Cude, K Brockbank, JC Sartor, O Figg, WD TI Racial variation in CAG repeat lengths within the androgen receptor gene among prostate cancer patients of lower socioeconomic status SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LINKAGE DISEQUILIBRIUM; FROZEN SERUM; RISK; POLYMORPHISM; RACE; MEN AB Purpose: To evaluate (1) whether there were racial differences in the androgen receptor gene CAG repeat length and in clinical or laboratory attributes of prostate cancer at the time of diagnosis, (2) whether there were differences in race, Gleason score, prostate-specific antigen (PSA) level, and stage at diagnosis by androgen receptor gene CAG repeat length; and (3) whether sociodemographic, clinical, and laboratory based factors might be associated with advanced-stage prostate cancer. To our knowledge, our study is the first to report on CAG repeat lengths in a cohort of prostate cancer patients, which includes large numbers of African-American men. Methods: CAG repeat lengths on the androgen receptor gene were evaluated for 151 African-American and 168 white veterans with prostate cancer. The chi(2) test, t test, and logistic regression analyses were used to evaluate the associations between CAG repeat lengths and race, stage, histologic grade, and PSA levels at diagnosis. Results: The mean age of the cohort at the time of diagnosis was 68.7 years. At presentation, 42.0% had stage D prostate cancer, 26.5% had Gleason scores of 8 to 10, and 53.0% had PSA levels greater than or equal to 10 ng/dL. Mean androgen receptor gene CAG repeat length for white veterans was 21.9 (SD, 3.5) versus 19.8 (SD, 3.2) for African-American veterans (P =.001). Men with shorter CAG repeats were more likely to have stage D prostate cancer (P =.09) but were not more likely to have a higher PSA concentration or Gleason score. Conclusion: In this cohort of men with prostate cancer, short CAG repeat length on the androgen receptor gene was associated with African-American race and possibly with higher stage but not with other clinical or pathologic findings. (C) 2002 by American Society of Clinical Oncology. C1 Dept Vet Affairs Med Ctr, MidW Ctr Hlth Serv Res & Dev, Chicago, IL USA. Chicago Vet Affairs Healthcare Syst, Lakeside Div, Chicago, IL USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Northwestern Univ, Dept Med, Div Hematol Oncol, Chicago, IL 60611 USA. Northwestern Univ, Dept Prevent Med, Div Biostat, Chicago, IL 60611 USA. Louisiana State Univ, Sch Med, Stanley Scott Canc Ctr, New Orleans, LA USA. Louisiana State Univ, Sch Med, Div Hematol Oncol, New Orleans, LA USA. NCI, Canc Therapeut Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Bennett, CL (reprint author), Vet Affairs Med Sci Bldg,400 E Ontario,Suite 204, Chicago, IL 60611 USA. RI Bennett, Charles/C-2050-2008; Figg Sr, William/M-2411-2016 FU NCI NIH HHS [P50-CA-09-03867] NR 24 TC 54 Z9 56 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2002 VL 20 IS 17 BP 3599 EP 3604 DI 10.1200/JCO.2002.11.085 PG 6 WC Oncology SC Oncology GA 596RB UT WOS:000178178100010 PM 12202660 ER PT J AU Singletary, SE Allred, C Ashley, P Bassett, LW Berry, D Bland, KI Borgen, PI Clark, CG Edge, SB Hayes, DF Hughes, LL Hutter, RVP Morrow, M Page, DL Recht, A Theriault, RL Thor, A Weaver, DL Wieand, HS Greene, FL AF Singletary, SE Allred, C Ashley, P Bassett, LW Berry, D Bland, KI Borgen, PI Clark, CG Edge, SB Hayes, DF Hughes, LL Hutter, RVP Morrow, M Page, DL Recht, A Theriault, RL Thor, A Weaver, DL Wieand, HS Greene, FL TI Revision of the American Joint Committee on Cancer staging system for breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID AXILLARY LYMPH-NODES; PATHOLOGICAL PROGNOSTIC FACTORS; FOLLOW-UP; PREOPERATIVE CHEMOTHERAPY; NEOADJUVANT CHEMOTHERAPY; ADJUVANT THERAPY; CARCINOMA; BIOPSY; SURVIVAL; METASTASES AB Purpose: To revise the American Joint Committee on Cancer staging system for breast carcinoma. Materials and Methods: A Breast Task Force submitted recommended changes and additions to the existing staging system that were (1) evidence-based and/or consistent with widespread clinical consensus about appropriate diagnostic and treatment standards and (2) useful for the uniform accrual of outcome information in national databases. Results: Major changes included the following: size-based discrimination between micrometastases and isolated tumor cells; identifiers to indicate usage of innovative technical approaches; classification of lymph node status by number of involved axillary lymph nodes, and new classifications for metastasis to the infraclavicular, internal mammary, and supraclavicular lymph nodes. Conclusion: This revised staging system will be officially adopted for use in tumor registries in January 2003. (C) 2002 by American Society of Clinical Oncology. C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Scott & White Mem Hosp & Clin, Temple, TX 76508 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Michigan, Ann Arbor, MI 48109 USA. WellStar Kennestone Hosp, Atlanta, GA USA. Int Union Canc, Livingston, NJ USA. Northwestern Univ, Chicago, IL 60611 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Univ Vermont, Burlington, VT USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. RP Singletary, SE (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, 1515 Holcombe Blvd,Box 444, Houston, TX 77030 USA. NR 48 TC 655 Z9 686 U1 4 U2 15 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2002 VL 20 IS 17 BP 3628 EP 3636 DI 10.1200/JCO.2002.02.026 PG 9 WC Oncology SC Oncology GA 596RB UT WOS:000178178100013 PM 12202663 ER PT J AU Higginson, IJ Costantini, M AF Higginson, IJ Costantini, M TI Communication in end-of-life cancer care: A comparison of team assessments in three European countries SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHYSICIAN-PATIENT COMMUNICATION; TERMINALLY ILL PATIENTS; PALLIATIVE CARE; FAMILY MEMBERS; PREFERENCES; EXPERIENCE; OUTCOMES; PAIN; INFORMATION; ATTITUDES AB Purpose: To compare team assessments of end-of-life communication in three European countries, and to identify factors associated with problematic communication. Patients and Methods: Three prospective cohort studies used similar standardized procedures, and included patients referred to palliative care services in the United Kingdom, Ireland, and Italy. Palliative team care staff assessed three components of communication in the last week of the patient's life-between the patient and family (or those close to them), between professionals and patient and family, and between professionals-using a validated measure. Univariate and multivariate, analyses explored the data and tested for relationships between possible explanatory variables and communication. Results: Data were collected on 1,326 patients, 416 in the United Kingdom, 411 in Ireland, and 499 in Italy. Mean age was 68 years (range, 19 to 95 years), 55% were male, and almost two thirds were married. Team members assessed that communication between patient and family was a moderate or severe problem in the last week of life for 30% to 40% of patients; 10% to 20% had moderate or severe problems recorded for the other two communication items. Problematic communication was associated with respiratory and breast cancers, a shorter time in care, and hospice death. It was also associated with greater spiritual need, need for care planning, and poorer patient,and family insight (Spearman's rho > 0.4), but not especially with pain and symptom control, in both univariate and multivariate analyses, both within countries and for all data combined. Conclusion: Severe communication problems were reported by team assessments in up to 40% of patients at the end of life. A multiprofessional approach is needed to recognize and improve this. (C) 2002 by American Society of Clinical Oncology. C1 Kings Coll London, Dept Palliat Care & Policy, Weston Educ Ctr, London SE5 9RJ, England. Natl Canc Inst, Unit Clin Epidemiol & Trials, Genoa, Italy. RP Higginson, IJ (reprint author), Kings Coll London, Dept Palliat Care & Policy, Weston Educ Ctr, Cutcombe Rd, London SE5 9RJ, England. EM irene.higginson@kcl.ac.uk RI costantini, massimo/G-1443-2012; OI costantini, massimo/0000-0002-5293-7079 NR 46 TC 38 Z9 38 U1 2 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2002 VL 20 IS 17 BP 3674 EP 3682 DI 10.1200/JCO.2002.11.008 PG 9 WC Oncology SC Oncology GA 596RB UT WOS:000178178100019 PM 12202669 ER PT J AU Krausz, KW Gelboin, HV AF Krausz, KW Gelboin, HV TI Specific inhibitory monoclonal antibodies to cytochrome P450 isoforms quantitate their role in the metabolism of a drug in human liver microsomes in vitro. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2002 VL 42 IS 9 MA 70 BP 1066 EP 1066 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586HR UT WOS:000177579000074 ER PT J AU Lu, Z Xu, Z AF Lu, Z Xu, Z TI Effects of saccular otolith removal on hearing sensitivity of the sleeper goby (Dormitator latifrons) SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article DE ear; fish; otolithic organ; saccule; sound localization ID ACOUSTIC PARTICLE MOTION; HAIR CELL ORIENTATION; TELEOST FISH; AUDITORY-SENSITIVITY; OPSANUS-TAU; EAR; DIRECTIONALITY; VOCALIZATION; GASBLADDER; AFFERENTS AB It is not known to what extent the entire saccule contributes to overall hearing sensitivity in any fish species. Here we report directional and frequency sensitivity in a teleost fish (Dormitator latifrons) and effects of unilateral and bilateral removal of saccular otoliths on its hearing sensitivity. The fish had different hearing thresholds in the horizontal (-54.4 to -50.3 dB re: 1 mum) and mid-sagittal (-58.6 to -53.1 dB) planes. At 100 Hz, unilateral otolith removal did not significantly change hearing sensitivity in the mid-sagittal plane, but caused selective reductions of auditory sensitivity by 3-7 dB in the azimuthal axes that are consistent with the longitudinal axis of the damaged saccule. Along the fish's longitudinal axis, unilateral otolith removal significantly decreased auditory sensitivity at 50 Hz and 400 Hz, but not at 100 Hz, 200 Hz, and 345 Hz. At 100 Hz, bilateral otolith removal resulted in robust hearing loss of 27-35 dB at different axes in both horizontal and mid-sagittal planes. Along the fish's longitudinal axis, the bilateral removal reduced auditory sensitivity by 13-27 dB at the different frequencies. Therefore, these results demonstrate that the saccule plays important roles in directional hearing and frequency responses. C1 Univ Miami, Dept Biol, Coral Gables, FL 33146 USA. Univ Miami, Program Neurosci, Miami, FL 33101 USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS Marine & Freshwater, Biomed Sci Ctr, Miami, FL 33149 USA. RP Lu, Z (reprint author), Univ Miami, Dept Biol, 1301 Mem Dr,Room 4, Coral Gables, FL 33146 USA. FU NIDCD NIH HHS [R29DC03275]; NIEHS NIH HHS [ES05705] NR 35 TC 21 Z9 22 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7594 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A -Neuroethol. Sens. Neural Behav. Physiol. PD SEP PY 2002 VL 188 IS 8 BP 595 EP 602 DI 10.1007/s00359-002-0334-6 PG 8 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA 608AH UT WOS:000178822600002 PM 12355235 ER PT J AU Murata, M Ohta, N Fujisawa, S Tsai, JY Sato, S Akagi, Y Takahashi, Y Neuenschwander, H Kador, PF AF Murata, M Ohta, N Fujisawa, S Tsai, JY Sato, S Akagi, Y Takahashi, Y Neuenschwander, H Kador, PF TI Selective pericyte degeneration in the retinal capillaries of galactose-fed dogs results from apoptosis linked to aldose reductase-catalyzed galactitol accumulation SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE retinal capillary; pericyte; endothelial cells; apoptosis; aldose reductase ID DIABETIC-RETINOPATHY; ENDOTHELIAL-CELLS; VESSEL CHANGES; MICROVASCULAR PERICYTES; MURAL CELLS; GLUCOSE; LOCALIZATION; PREVENTION; INHIBITORS; POLYOL AB Galactose-fed dogs develop retinal capillary changes similar to diabetic retinopathy with pericyte degeneration as the initial lesion. This is followed by the formation of microaneurysms, hemorrhages, and some areas of acellularity. To investigate the mechanisms for selective pericyte degeneration, retinal capillary pericytes and endothelial cells isolated from beagle dog retina were cultured for 2 weeks in Dulbecco's modified Eagle's medium (DMEM) containing 50 MM D-galactose. Apoptosis was detected in pericytes but not endothelial cells by in situ terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick end labelling (TUNEL) staining and the DNA fragmentation assay on agarose gel electrophoresis. This apoptosis was prevented by the addition of the aldose reductase inhibitor AL 1576 to the culture medium containing galactose. Apoptosis was not observed when pericytes were similarly cultured in control DMEM medium. These data support the premise that the selective degeneration of retinal capillary pericytes observed in galactose-fed dogs is linked to increased aldose reductase activity in these cells. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20892 USA. RP Kador, PF (reprint author), NEI, Lab Ocular Therapeut, NIH, Bldg 10,Room 10B11,10 Ctr Dr,MSC 1850, Bethesda, MD 20892 USA. NR 25 TC 24 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD SEP-OCT PY 2002 VL 16 IS 5 BP 363 EP 370 AR PII S1056-8727(01)00171-4 DI 10.1016/S1056-8727(01)00171-4 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592ND UT WOS:000177943000010 PM 12200082 ER PT J AU Valenzuela, JG Francischetti, IMB Pham, VM Garfield, MK Mather, TN Ribeiro, JMC AF Valenzuela, JG Francischetti, IMB Pham, VM Garfield, MK Mather, TN Ribeiro, JMC TI Exploring the sialome of the tick Ixodes scapularis SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE salivary gland; proteome; electrophoresis; hematophagy; Lyme's disease; tick; Ixodes scapularis ID CYSTEINE PROTEASE INHIBITOR; G BINDING-PROTEINS; RHIPICEPHALUS-APPENDICULATUS; AMBLYOMMA-VARIEGATUM; BOOPHILUS-MICROPLUS; HOST INTERACTIONS; IMMUNE-RESPONSE; SALIVARY-GLANDS; DAMMINI; FAMILY AB To attempt description of the set of mRNA and protein (sialome) expressed in the salivary glands of the tick Ixodes scapularis, we randomly sequenced 735 clones of a full-length salivary gland cDNA library of this arthropod and performed Edman degradation of protein bands from salivary gland homogenates (SGH) and saliva separated by SDS-PAGE. The sequences were grouped into 410 clusters, of which 383 are not associated with known L scapularis sequences. 15- and 17-protein bands from PAGE yielded amino-terminal information on the saliva and salivary gland gels, respectively. We attributed 19 of these sequences to translation products of the cDNA library. Full-length sequences were obtained for 87 clones. Among these protein sequences are several protease inhibitors of distinct classes, metalloproteases, novel proteins with histamine-binding domains, and several peptide families of unknown function displaying different conserved cysteine residues, many of which contain single Kunitz domains. This work provides information into the diversity of messages expressed in the salivary glands of L scapularis, describes novel sequences that may be responsible for known biological activites, indicates further biological activities that may be present in L scapularis saliva and identifies novel vaccine targets that may be used in Lyme disease prevention. C1 NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Rhode Isl, Ctr Vector Borne Dis, Kingston, RI 02881 USA. RP Ribeiro, JMC (reprint author), NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. OI Ribeiro, Jose/0000-0002-9107-0818 NR 60 TC 178 Z9 188 U1 1 U2 10 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD SEP PY 2002 VL 205 IS 18 BP 2843 EP 2864 PG 22 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 600MD UT WOS:000178393600009 PM 12177149 ER PT J AU Hoppin, JA Yucel, F Dosemeci, M Sandler, DP AF Hoppin, JA Yucel, F Dosemeci, M Sandler, DP TI Accuracy of self-reported pesticide use duration information from licensed pesticide applicators in the Agricultural Health Study SO JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE accuracy; farmers; pesticides; pesticide registration; questionnaire AB Epidemiologists frequently rely on self-reported information regarding a variety of exposures including smoking history, medication use, and occupational exposure because other sources of information are either unavailable or difficult to obtain. One way to evaluate the accuracy of self-reported information is through logic checks using other sources. To assess the quality of the self-reported pesticide product use history of 57,3 11 licensed pesticide applicators in the Agricultural Health Study (AHS), we compared the self-reported decade of first use and total years of use to the year the pesticide active ingredient was first registered for use. We obtained pesticide active ingredient registration information from the United States Environmental Protection Agency (USEPA) and other publicly available sources for the 52 pesticides on the AHS initial questionnaires administered from 1994 to 1997. Based on the registration year, we assessed 19 pesticides for potential inaccuracies regarding duration of use or decade of first use. When calculating potential total years of use, we did not consider the impact of chemicals being removed from the market, since the possibility for continued use existed. The majority of respondents provided plausible responses for both decade of first use and total duration of use. On average, 1% of the subjects overestimated total possible duration of use, ranging from less than 1% for carbofuran and chlorpyrifos to 5% for imazethapyr. Decade of first use was also reasonably reported, although more subject, did not report decade of first use than duration of use, with an average of 6% of subjects missing decade information for an individual chemical. For subjects who reported a decade of first use, 98% gave plausible responses on average, with overestimates highest for cyanazine, introduced in 1971 (6% reported earlier use), and chlorimuron ethyl, introduced in 1985 (7% reported earlier use). This analysis provided the opportunity to consider only one source of potential overreporting of exposure, and while underreporting may have also occurred, we cannot evaluate its role nor the balance between these potential inaccuracies, While we are unable to validate directly the accuracy of a respondent's use of pesticides, this analysis suggests that participants provide plausible information regarding their pesticide use. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. CODA Inc, Durham, NC USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, MD A3-05,POB 12223, Res Triangle Pk, NC 27709 USA. OI Sandler, Dale/0000-0002-6776-0018 NR 10 TC 95 Z9 97 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1053-4245 J9 J EXPO ANAL ENV EPID JI J. Expo. Anal. Environ. Epidemiol. PD SEP PY 2002 VL 12 IS 5 BP 313 EP 318 DI 10.1038/sj.jea.7500232 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 593WB UT WOS:000178016500002 PM 12198579 ER PT J AU Colt, JS Baris, D Clark, SF Ayotte, JD Ward, M Nuckols, JR Cantor, KP Silverman, DT Karagas, M AF Colt, JS Baris, D Clark, SF Ayotte, JD Ward, M Nuckols, JR Cantor, KP Silverman, DT Karagas, M TI Sampling private wells at past homes to estimate arsenic exposure: A methodologic study in New England SO JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE arsenic; drinking water; exposure assessment; private wells ID DRINKING-WATER SOURCE; BLADDER-CANCER; US POPULATION; RISK; MORTALITY; NITRATE; SKIN AB We are conducting a collaborative, population-based case-control study in Maine, New Hampshire. and Vermont to investigate the reasons for the elevated bladder cancer mortality in northern New England. Arsenic in drinking water is one of the primary exposures under investigation. To estimate subjects' lifetime exposure to waterborne arsenic, it will be necessary to obtain water samples from private wells that subjects used in the past. We conducted a methodologic study to assess the feasibility of locating and sampling from private wells at subjects' past residences. Ninety-eight New Hampshire residents (mean age 67 years) completed a questionnaire requesting the complete address, dates of occupancy. and drinking water sources for each home lived in since birth. An interviewer then asked subjects for more detailed information about each home to assist in a field search of past homes in the three-state study area of Maine. New Hampshire, and Vermont. Fifty-eight of the 98 subjects indicated that they had used a total of 103 private wells in 95 previous homes located in these three states. We conducted a field search to locate these 95 homes, visited town offices to find the properties on tax maps and obtain the current owners' names and addresses, attempted to obtain permission from the current owners to sample the wells. and collected water samples. In all. 48 (47%) of the 103 past wells in the study area were sampled successfully. The remaining wells were not sampled because the homes were not located (22%) or had been demolished (2%), permission to sample the wells was not obtained (17%), the wells had been destroyed (7%) or could not be found on the grounds of the residence (3%). or for other reasons (2%). Various approaches for improving the success rates for sampling water from private wells are discussed, as is the use of predictive modeling to impute exposures when sampling is not feasible. C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. US Geol Survey New Hampshire Vermont Dist, Pembroke, NH USA. Colorado State Univ, Environm Hlth Adv Syst Lab, Dept Environm Hlth, Ft Collins, CO USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Dartmouth Coll, Hanover, NH USA. RP Colt, JS (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8112, Bethesda, MD 20892 USA. EM coltj@mail.nih.gov NR 22 TC 8 Z9 8 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1053-4245 J9 J EXPO ANAL ENV EPID JI J. Expo. Anal. Environ. Epidemiol. PD SEP PY 2002 VL 12 IS 5 BP 329 EP 334 DI 10.1038/sj.jea.7500235 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 593WB UT WOS:000178016500004 PM 12198581 ER PT J AU Casper, LM Smith, KE AF Casper, LM Smith, KE TI Dispelling the myths - Self-care, class, and race SO JOURNAL OF FAMILY ISSUES LA English DT Article ID CHILDREN AB We use 1995 data from the Survey of Income and Program Participation to examine how race and class are related to self-care among children 5 to 13 years old. We find that contrary to popular belief, self-care is less common among minority and lower-class children. We also find that factors such as income and neighborhood safety are related to self-care and can attenuate the relationships observed between race, class, and self-care. Our analyses also indicate that variations in self-care by race, class, income level, and neighborhood safety are dependent on the age of the child, with a major transition in self-care occurring between the ages of 8 and 10. C1 NICHHD, Bethesda, MD 20892 USA. US Bur Census, Washington, DC 20233 USA. RP Casper, LM (reprint author), NICHHD, Bethesda, MD 20892 USA. NR 9 TC 12 Z9 12 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-513X J9 J FAM ISSUES JI J. Fam. Issues PD SEP PY 2002 VL 23 IS 6 BP 716 EP 727 DI 10.1177/0192513X02023006002 PG 12 WC Family Studies SC Family Studies GA 582HV UT WOS:000177345500002 ER PT J AU Goforth, PB Bertram, R Khan, FA Zhang, M Sherman, A Satin, LS AF Goforth, PB Bertram, R Khan, FA Zhang, M Sherman, A Satin, LS TI Calcium-activated K+ channels of mouse beta-cells are controlled by both store and cytoplasmic Ca2+: Experimental and theoretical studies SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE islets of Langerhans; KCa channels; ER; insulin; intracellular calcium ID PANCREATIC-ISLET-CELLS; BURSTING ELECTRICAL-ACTIVITY; ENDOPLASMIC-RETICULUM; B-CELLS; RYANODINE RECEPTOR; INTRACELLULAR ATP; EXCITABLE CELL; OSCILLATIONS; GLUCOSE; RELEASE AB A novel calcium-dependent potassium current (K-slow) that slowly activates in response to a simulated islet burst was identified recently in mouse pancreatic beta-cells (Gopel, S.O., T Kanno, S. Barg, L. Eliasson, J. Galvanovskis, E. Renstrom, and P. Rorsman. 1999. J. Gen. Physiol. 114:759-769). K-slow activation may help terminate the cyclic bursts of Ca2+-dependent action potentials that drive Ca2+ influx and insulin secretion in beta-cells. Here, we report that when [Ca2+](i) handling was disrupted by blocking Ca2+ uptake into the ER with two separate agents reported to block the sarco/endoplasmic calcium ATPase (SERCA), thapsigargin (1-5 muM) or insulin (200 nM), K-slow was transiently potentiated and then inhibited. K-slow amplitude could also be inhibited by increasing extracellular glucose concentration from 5 to 10 mM. The biphasic modulation of K-slow by SERCA blockers could not be explained by a minimal mathematical model in which [Ca2+], is divided between two compartments, the cytosol and the ER, and K-slow activation mirrors changes in cytosolic calcium induced by the burst protocol. However, the experimental findings were reproduced by a model in which K-slow activation is mediated by a localized pool of [Ca2+] in a subspace located between the ER and the plasma membrane. In this model the subspace [Ca2+] follows changes in cytosolic [Ca2+] but with a gradient that reflects Ca2+ efflux from the ER. Slow modulation of this gradient as the ER empties and fills may enhance the role of K-slow and [Ca2+] handling in influencing beta-cell electrical activity and insulin secretion. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Physiol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Med Endocrinol, Richmond, VA 23298 USA. Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Florida State Univ, Kasha Lab Biophys, Tallahassee, FL 32306 USA. NIDDKD, Math Res Branch, NIH, Bethesda, MD 20892 USA. RP Satin, LS (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, POB 980524, Richmond, VA 23298 USA. FU NIDDK NIH HHS [R01 DK046409, R01 DK-46409] NR 67 TC 40 Z9 40 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD SEP PY 2002 VL 120 IS 3 BP 307 EP 322 DI 10.1085/jgp.20028581 PG 16 WC Physiology SC Physiology GA 592FM UT WOS:000177926100003 PM 12198088 ER PT J AU Uphyrkina, O Miquelle, D Quigley, H Driscoll, C O'Brien, SJ AF Uphyrkina, O Miquelle, D Quigley, H Driscoll, C O'Brien, SJ TI Conservation genetics of the Far Eastern leopard (Panthera pardus orientalis) SO JOURNAL OF HEREDITY LA English DT Article ID MICROSATELLITES; CONSEQUENCES; DIVERSITY; KINSHIP; LIONS AB The Far Eastern or Amur leopard (Panthera pardus orientalis) survives today as a tiny relict population of 25-40 individuals in the Russian Far East. The population descends from a 19th-century northeastern Asian subspecies whose range extended over southeastern Russia, the Korean peninsula, and northeastern China. A molecular genetic survey of nuclear microsatellite and mitochondrial DNA (mtDNA) sequence variation validates subspecies distinctiveness but also reveals a markedly reduced level of genetic variation. The, amount of genetic diversity measured is the lowest among leopard subspecies and is comparable to the genetically depleted Florida panther and Asiatic lion populations. When considered in the context of nonphysiological perils that threaten small populations (e.g., chance mortality, poaching, climatic extremes, and infectious disease), the genetic and demographic data indicate a critically diminished wild population under severe threat of extinction. An established captive population of P. p. orientalis displays much higher diversity than the wild population sample, but nearly all captive individuals are derived from a history of genetic admixture with the adjacent Chinese subspecies, P. p. japonensis. The conservation management implications of potential restoration/augmentation of the wild population with immigrants from the captive population are discussed. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. Wildlife Conservat Soc, Bozeman, MT 59719 USA. NCI, SAIC, Frederick, MD 21702 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. OI Driscoll, Carlos/0000-0003-2392-505X NR 44 TC 29 Z9 35 U1 13 U2 98 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD SEP-OCT PY 2002 VL 93 IS 5 BP 303 EP 311 DI 10.1093/jhered/93.5.303 PG 9 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 635MJ UT WOS:000180402900001 PM 12547918 ER PT J AU Ito, Y Bustin, M AF Ito, Y Bustin, M TI Immunohistochemical localization of the nucleosome-binding protein HMGN3 in mouse brain SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE immunohistochemical expression; HMG proteins; chromatin; mouse brain; GFAP ID GROUP CHROMOSOMAL-PROTEINS; FIBRILLARY ACIDIC PROTEIN; THYROID-HORMONE; TRANSCRIPTION; GFAP AB HMGN3 (Trip7) is a member of the high-mobility group N (HMGN) nucleosome-binding protein family, which binds specifically to nucleosomes, reduces the compactness of the chromatin fiber, and enhances transcription from chromatin templates. By Western blotting and Northern blotting analysis, we showed that HMGN3 is expressed in a tissue-specific manner, with the strongest expression in mouse brain. Here we analyzed the expression of HMGN3 in various regions of the mouse brain by histological techniques. Enhanced expression of HMGN3 was observed in the lateral olfactory tract, anterior commissure, corpus callosum, internal capsule, fornix, stria medullans, optic tract, and axon bundles. The expression patterns of HMGN3 in the mouse brain was significantly different from that of the related protein HMGN2 and was very similar to that of the glial fibrillary acidic protein (GFAP). We suggest that HMGN3 might play a role in astrocyte function. C1 NCI, Prot Sect, Lab Metab, Div Basic Sci, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), Lawrence Berkeley Natl Lab, Div Life Sci, MS 74-157, Berkeley, CA 94720 USA. RI Bustin, Michael/G-6155-2015 NR 14 TC 12 Z9 13 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD SEP PY 2002 VL 50 IS 9 BP 1273 EP 1275 PG 3 WC Cell Biology SC Cell Biology GA 592ZV UT WOS:000177967500014 PM 12185205 ER PT J AU Borras, E Martin, R Judkowski, V Shukaliak, J Zhao, YD Rubio-Godoy, V Valmori, D Wilson, D Simon, R Houghten, R Pinilla, C AF Borras, E Martin, R Judkowski, V Shukaliak, J Zhao, YD Rubio-Godoy, V Valmori, D Wilson, D Simon, R Houghten, R Pinilla, C TI Findings on T cell specificity revealed by synthetic combinatorial libraries SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE positional scanning synthetic combinatorial libraries; biometrical analysis; protein database; T cell specificity ID PEPTIDE LIBRARIES; LYMPHOCYTE EPITOPE; MIMICRY EPITOPES; IDENTIFICATION; LIGANDS; ANTIGEN; ACID; GENERATION; DATABASES; SUPPORTS AB Combinatorial libraries and in particular positional scanning synthetic combinatorial libraries (PS-SCL) allow the study of T cell specificity. This is a systematic and unbiased approach that does not require any previous knowledge about the clones to be studied, neither their specificity nor they major histocompatibility complex (MHC) restriction. Two different types of T cell clone ligands can be identified: (1) peptides that do not necessarily correspond to proteins described in the databases, and (2) peptides that are fragments of natural proteins. In this paper, relevant examples of the application of PS-SCL and the deconvolution strategies followed to identify T cell epitopes for clones of known and unknown specificity will be reviewed. Also, important issues like the immunogenicity of such T cell ligands will be discussed. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Torrey Pines Inst Mol Studies & Mixture Sci Inc, San Diego, CA 92121 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. The Scripps Res Inst, La Jolla, CA 92037 USA. NCI, Nol Stat & Bioinformat Sect, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. Univ Lausanne Hosp, Ludwig Inst Canc Res, Div Clin Oncoimmunol, CH-1011 Lausanne, Switzerland. Mixture Sci Inc, San Diego, CA 92121 USA. RP Pinilla, C (reprint author), Torrey Pines Inst Mol Studies & Mixture Sci Inc, San Diego, CA 92121 USA. RI Valmori, Danila/K-2439-2015 NR 42 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD SEP 1 PY 2002 VL 267 IS 1 BP 81 EP 98 AR PII S0022-1759(02)00142-4 PG 18 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 584EE UT WOS:000177453600008 ER PT J AU Zhang, J Bardos, T Li, DD Gal, I Vermes, C Xu, JY Mikecz, K Finnegan, A Lipkowitz, S Glant, TT AF Zhang, J Bardos, T Li, DD Gal, I Vermes, C Xu, JY Mikecz, K Finnegan, A Lipkowitz, S Glant, TT TI Cutting edge: Regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NEGATIVE REGULATION; RING-TYPE; LIGASE; AUTOIMMUNITY; DEGRADATION; PATHWAY; COMPLEX; DOMAIN; ZAP-70; TCR AB Optimal T cell activation requires signaling through the TCR and CD28 costimulatory receptor. CD28 costimulation is believed to set the threshold for T cell activation. Recently, Cbl-b, a ubiquitin ligase, has been shown to negatively regulate CD28-dependent T cell activation. In this report, we show that CD28 costimulation selectively induces greater ubiquitination and degradation of Cbl-b in wild-type T cells than CD3 stimulation alone, and TCR-induced Cbl-b ubiquitination and degradation are significantly reduced in CD28-deficient T cells. Stimulation of CD28-deficient T cells with higher doses of anti-CD3 results in increased ubiquitination of Cbl-b, which correlates with enhanced T cell responses. Our results demonstrate that CD28 costimulation regulates the threshold for T cell activation, at least in part, by promoting Cbl-b ubiquitination and degradation. C1 Rush Med Coll, Sect Mol Med, Dept Orthoped Surg, Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Rush Med Coll, Rush Presbyterian St Lukes Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. Rush Med Coll, Rush Presbyterian St Lukes Med Ctr, Dept Biochem, Chicago, IL 60612 USA. Rush Med Coll, Rush Presbyterian St Lukes Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. NCI, Med Branch, Dept Genet, Bethesda, MD 20889 USA. RP Zhang, J (reprint author), Rush Med Coll, Sect Mol Med, Dept Orthoped Surg, Rush Presbyterian St Lukes Med Ctr, Cohn Res Bldg,Room 724,1735 W Harrison St, Chicago, IL 60612 USA. RI Zhang, Jian/A-2564-2008 FU NIAMS NIH HHS [AR47412, AR40310, AR45652] NR 24 TC 76 Z9 81 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2002 VL 169 IS 5 BP 2236 EP 2240 PG 5 WC Immunology SC Immunology GA 586PV UT WOS:000177594100002 PM 12193687 ER PT J AU Maki, W Morales, RE Carroll, VA Telford, WG Knibbs, RN Stoolman, LM Hwang, ST AF Maki, W Morales, RE Carroll, VA Telford, WG Knibbs, RN Stoolman, LM Hwang, ST TI CCR6 colocalizes with CD18 and enhances adhesion to activated endothelial cells in CCR6-transduced Jurkat T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CUTANEOUS LYMPHOCYTE ANTIGEN; NECROSIS-FACTOR-ALPHA; DIFFERENTIAL REGULATION; CHEMOKINE RECEPTOR-6; P-SELECTIN; BETA(1) INTEGRIN; DENDRITIC CELLS; FLOW CONDITIONS; CUTTING EDGE; IN-VITRO AB CCR6 is expressed by memory T cells (mTC) and is a requirement for efficient arrest of a subset of mTC to activated human dermal microvascular endothelial cells (HDMEC) under physiologic shear stress. We now address whether CCR6 alone is sufficient to induce arrest of a model T cell line (Jurkat) that shows low expression of all CCRs tested (CCR1-10). Herein, we transduced Jurkat (JK) T cells expressing fucosyltransferase VII with a chimeric chemokine receptor consisting of CCR6 fused to enhanced green fluorescent protein. In contrast to the starting JK lines, the resulting cell line (JK fucosyltransferase VII-CCR6) migrated 6-fold better to CCL20 in chernotaxis assays, arrested in response to CCL20 that was immobilized to plastic, and demonstrated a 2.5-fold increase in adhesion to activated HDMEC (p = 0.001). Adhesion was blocked by anti-CD18 mAb (p = 0.005) but not by anti-CD49d mAb (p = 0.3). After arrest on recombinant substrates, CCR6 clustered on the surface as detected by real-time observation of enhanced green fluorescent protein fluorescence. Dual-label confocal microscopy revealed that LFA-1 (CD18 and CD11a), but not CXCR4, colocalized with clustered CCR6 in the presence of immobilized CCL20. Thus, the functional expression of CCR6 is sufficient to provide the chemokine signaling necessary to induce arrest of a JK T cell line to activated HDMEC. Clustering of CCR6 and coassociation with critical integrins may serve to strengthen adhesion between T cells and activated endothelial cells. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Expt Therapeut & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. RP Hwang, ST (reprint author), NCI, Dermatol Branch, 10 Ctr Dr,Bldg 10,Room 12N246, Bethesda, MD 20892 USA. NR 34 TC 8 Z9 8 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2002 VL 169 IS 5 BP 2346 EP 2353 PG 8 WC Immunology SC Immunology GA 586PV UT WOS:000177594100015 PM 12193700 ER PT J AU Shi, GX Harrison, K Wilson, GL Moratz, C Kehrl, JH AF Shi, GX Harrison, K Wilson, GL Moratz, C Kehrl, JH TI RGS13 regulates germinal center B lymphocytes responsiveness to CXC chemokine ligand (CXCL)12 and CXCL13 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GTPASE-ACTIVATING PROTEINS; HETEROTRIMERIC G-PROTEINS; LYMPHOID ORGANS; ALPHA-SUBUNITS; FAMILY MEMBERS; CHEMOTAXIS; RECEPTORS; DOMAIN; GAIP; GENE AB Normal lymphoid tissue development and function depend upon directed cell migration. Providing guideposts for cell movement and positioning within lymphoid tissues, chemokines signal through cell surface receptors that couple to heterotrimeric G proteins, which are in turn subject to regulation by regulator of G protein signaling (RGS) proteins. In this study, we report that germinal center B lymphocytes and thymic epithelial cells strongly express one of the RGS family members, RGS13. Located between Rgs1 and Rgs2, Rgs13 spans 42 kb on mouse chromosome 1. Rgs13 encodes a 157-aa protein that shares 82% amino acid identity with its 159-aa human counterpart. In situ hybridization with sense and antisense probes localized Rgs13 expression to the germinal center regions of mouse spleens and Peyer's patches and to the thymus medulla. Affinity-purified RGS13 Abs detected RGS13-expressing cells in the light zone of the germinal center. RGS13 interacted with both Gialpha and Gqalpha and strongly impaired signaling through G(i)-linked signaling pathways, including signaling through the chemokine receptors CXCR4 and CXCR5. Prolonged CD40 signaling up-regulated RGS13 expression in human tonsil B lymphocytes. These results plus previous studies of RGS1 indicate the germinal center B cells use two RGS proteins, RGS1 and RGS13, to regulate their responsiveness to chemokines. C1 NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11B10,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Shi, GengXian/C-4660-2011; OI Kehrl, John/0000-0002-6526-159X NR 39 TC 77 Z9 78 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2002 VL 169 IS 5 BP 2507 EP 2515 PG 9 WC Immunology SC Immunology GA 586PV UT WOS:000177594100035 PM 12193720 ER PT J AU Wizel, B Starcher, BC Samten, B Chroneos, Z Barnes, PF Dzuris, J Higashimoto, Y Appella, E Sette, A AF Wizel, B Starcher, BC Samten, B Chroneos, Z Barnes, PF Dzuris, J Higashimoto, Y Appella, E Sette, A TI Multiple Chlamydia pneumoniae antigens prime CD8(+) Tc1 responses that inhibit intracellular growth of this vacuolar pathogen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; CYTOTOXIC T-LYMPHOCYTES; INCLUSION MEMBRANE; STRAIN TWAR; SEQUENCE-ANALYSIS; PRIMARY INFECTION; EPITHELIAL-CELLS; GAMMA-INTERFERON; GENOME SEQUENCES; CTL RESPONSES AB CD8(+) T cells play an essential role in immunity to Chlamydia pneumoniae (Cpn). However, the target Ags recognized by Cpn-specific CD8(+) T cells have not been identified, and the mechanisms by which this T cell subset contributes to protection remain unknown. In this work we demonstrate that Cpn infection primes a pathogen-specific CD8(+) T cell response in mice. Eighteen H-2(b) binding peptides representing sequences from 12 Cpn Ags sensitized target cells for MHC class I-restricted lysis by CD8(+) CTL generated from the spleens and lungs of infected mice. Peptide-specific IFN-gamma-secreting CD8(+) T cells were present in local and systemic compartments after primary infection, and these cells expanded after pathogen re-exposure. CD8(+) T cell lines to the 18 Cpn epitope-bearing peptides were cytotoxic, displayed a memory phenotype, and secreted IFN-gamma and TNF-alpha, but not IL-4. These CTL lines lysed Cpn-infected macrophages, and the lytic activity was inhibited by brefeldin A, indicating endogenous processing of CTL Ags. Finally, Cpn peptide-specific CD8(+) CTL suppressed chlamydial growth in vitro by direct lysis of infected cells and by secretion of IFN-gamma and other soluble factors. These studies provide information on the mechanisms by which CD8(+) CTL protect against Cpn, furnish the tools to investigate their possible role in immunopathology, and lay the foundation for future work to develop vaccines against acute and chronic Cpn infections. C1 Univ Texas Hlth Ctr, Dept Microbiol & Immunol, Ctr Pulm & Infect Dis Control, Tyler, TX 75708 USA. Univ Texas Hlth Ctr, Dept Biochem, Tyler, TX 75708 USA. Univ Texas Hlth Ctr, Dept Med, Tyler, TX 75708 USA. NCI, Bethesda, MD 20892 USA. Epiimmune Corp, San Diego, CA 92121 USA. RP Wizel, B (reprint author), Univ Texas Hlth Ctr, Dept Microbiol & Immunol, Ctr Pulm & Infect Dis Control, 11937 US Highway 271, Tyler, TX 75708 USA. OI Dzuris, John/0000-0002-0046-8426 FU NHLBI NIH HHS [R01 HL70641-01] NR 66 TC 47 Z9 50 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2002 VL 169 IS 5 BP 2524 EP 2535 PG 12 WC Immunology SC Immunology GA 586PV UT WOS:000177594100037 PM 12193722 ER PT J AU McDyer, JF Li, ZQ John, S Yu, X Wu, CY Ragheb, JA AF McDyer, JF Li, ZQ John, S Yu, X Wu, CY Ragheb, JA TI IL-2 receptor blockade inhibits late, but not early, IFN-gamma and CD40 ligand expression in human T cells: Disruption of both IL-12-dependent and -independent pathways of IFN-gamma production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD28 CO-STIMULATION; ANTI-TAC ANTIBODY; INTERLEUKIN-2 RECEPTOR; COSTIMULATORY MOLECULES; CYTOKINE PRODUCTION; ALLERGIC DISEASES; EFFECTOR FUNCTION; IMMUNE-RESPONSES; PROLIFERATION; AUTOIMMUNITY AB mAbs directed against the alpha-chain (Tac/CD25) of the IL-2R are an emerging therapy in both transplantation and autoimmune disease. However, the mechanisms underlying their therapeutic efficacy have not been fully elucidated. Therefore, we examined the affect of IL-2R blockade on Th1 and Th2 cytokine production from human PBMC. Addition of a humanized anti-Tac Ab (HAT) to activated PBMC cultures inhibited IFN-gamma production from CD4 and CD8 T cells by 80-90%. HAT partially inhibited production of TNF-alpha and completely inhibited production of IL-4, IL-5, and IL-10. Furthermore, IL-12, a central regulatory cytokine that induces IFN-gamma, was undetectable in treated cultures. As T cell-dependent induction of IL-12 is regulated via CD40/CD40 ligand (CD40L) interactions, we examined the affect of HAT on CD40L expression. We found CD40L expression to be biphasic with an early (6 h) peak that is CD28/IL-2-independent, but a later peak (48 h) being CD28/IL-2-dependent and inhibited by HAT. Similarly, IFN-gamma production at 6 h was CD28/IL-2-independent but CD28/IL-2-dependent and inhibited by HAT at 48 h. Nonetheless, addition of rCD40L or exogenous IL-12 to HAT-treated cultures could not restore IFN-gamma production. The IFN-gamma deficit in such cultures appears to be due to a direct inhibition by HAT of IL-12-independent IFN-gamma production from T cells rather than altered expression of either the IL-12Rbeta1 or IL-12Rbeta2 chains. These data demonstrate that IL-2 plays a critical role in the regulation of Th1 and Th2 responses and impacts both IL-12-dependent and -independent IFN-gamma production. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Ctr Clin, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Guys Kings & St Thomas Hosp, London, England. RP Ragheb, JA (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,MSC-1857, Bethesda, MD 20892 USA. NR 64 TC 58 Z9 59 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2002 VL 169 IS 5 BP 2736 EP 2746 PG 11 WC Immunology SC Immunology GA 586PV UT WOS:000177594100063 PM 12193748 ER PT J AU Nagorsen, D Monsurro, V Wang, E Marincola, FM AF Nagorsen, D Monsurro, V Wang, E Marincola, FM TI Characterization of CD8(-) HLA class I/epitope tetrameric complexes binding T cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE B-lymphocytes; HLA; T cell; tetramer ID LYMPHOCYTES; ANTIGEN; CYTOMEGALOVIRUS; EXPRESSION; FREQUENCY AB Antigen-specific M-expressing T cells play a crucial role in the host's defense against viral disease and malignancy. Epitope-specific CD8(+) T cell responses to malignant and viral disease can be accurately measured using tetramers (tHLA) of HLA class I molecules loaded with antigenic peptides. In addition, tHLA have been used to evaluate immune responses to antigen-specific immunization. tHLA bind specifically to complementary T-cell receptor (TCR) structures on the surface of T cells expressing the CD8 coreceptor. Surprisingly, however, CD8(-) cells binding tHLA are often observed. This study uses four-color flow cytometry to show that HLA-A*0201-tHLA-stained CD8- cells can be divided into two subsets: 87% represent B-lymphocytes (CD19(+), CD45RA(+), HLA-DR+, and CD20(+)), and 13% represent T-helper cells (CD3(+), CD4(+), CD45RA(+), and CD27(+)). This phenomenon is not HLA-restricted because it could be observed even in peripheral blood mononuclear cells (PBMC) from a non HLA-A*0201-expressing healthy donor. In addition, no T-cell receptor was detected on the B-lymphocytes. Retrospective enumeration of vaccine-induced CD8- tHLA(+) cells in 243 PBMC samples from 36 patients with melanoma undergoing peptide vaccination revealed that tHLA staining is not dependent on immunization status or the presence of CD8(+) tHLA(+) T cells. These findings, suggest that the nonspecific binding of tHLA to non-TCR-expressing T cells requires a careful interpretation of results and further steps in preparation of sample for tHLA-based sorting of epitope specific T cells. C1 NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C711,10 Ctr Dr, Bethesda, MD 20892 USA. NR 17 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD SEP-OCT PY 2002 VL 25 IS 5 BP 379 EP 384 DI 10.1097/01.CJI.0000025462.42534.B0 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 592GF UT WOS:000177927900001 PM 12218775 ER PT J AU Wang, SS Hildesheim, A Gao, XJ Schiffman, M Herrero, R Bratti, MC Sherman, ME Barnes, WA Greenberg, MD McGowan, L Mortel, R Schwartz, PE Zaino, RJ Glass, AG Burk, RD Karacki, P Carrington, M AF Wang, SS Hildesheim, A Gao, XJ Schiffman, M Herrero, R Bratti, MC Sherman, ME Barnes, WA Greenberg, MD McGowan, L Mortel, R Schwartz, PE Zaino, RJ Glass, AG Burk, RD Karacki, P Carrington, M TI Comprehensive analysis of human leukocyte antigen class I alleles and cervical neoplasia in 3 epidemiologic studies SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 19th International Papillomavirus Conference CY SEP 01-07, 2001 CL FLORIANOPLIS, BRAZIL ID MHC CLASS-I; HUMAN PAPILLOMAVIRUS TYPE-16; INTRAEPITHELIAL NEOPLASIA; CANCER; RISK; CARCINOMAS; ASSOCIATION; EXPRESSION; WOMEN; POLYMORPHISMS AB To comprehensively explore the relationship between human leukocyte antigen (HLA) class I alleles and cervical neoplasia, a subset of participants from 3 large US and Costa Rican cervix studies were typed for HLA class I alleles. Study subjects were women with cervical cancer or high-grade squamous epithelial lesions (HSILs; n=365) or low-grade squamous epithelial lesions (LSILs; n=275) or who were cytologically normal (control subjects; n=681). Allele-disease associations were assessed by logistic regression analysis. Consistent associations across all studies were observed for HLA-CW*0202 with a combined odds ratio of 0.53 (95% confidence interval [CI], 0.29-0.89) for cancer or HSILs and 0.58 (95% CI, 0.37-1.04) for LSILs, compared with control subjects and adjusted for study. This finding supports the hypothesis that a single allele may be sufficient to confer protection against cervical neoplasia. Given the relationship between HLA-C and its receptors on natural killer (NK) cells, a role is proposed for NK function in human papillomavirus infection and cervical neoplasia. C1 NCI, Interdisciplinary Studies Sect, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21701 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. George Washington Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC USA. George Washington Univ, Div Gynecol Oncol, Washington, DC USA. Univ Penn, Grad Hosp, Philadelphia, PA 19104 USA. Penn State Univ Hosp, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. Yale Univ, Sch Med, New Haven, CT USA. Kaiser Fdn, Inst Res, Oakland, CA USA. Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Epidemiol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Social Med, Bronx, NY 10467 USA. Proyecto Epidemiol, Guanacaste, Costa Rica. RP Wang, SS (reprint author), NCI, Interdisciplinary Studies Sect, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS MSC 7234, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA-78527, CO-12400, CP-21081, CP-31061] NR 28 TC 34 Z9 38 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2002 VL 186 IS 5 BP 598 EP 605 DI 10.1086/342295 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 582LR UT WOS:000177352900003 PM 12195346 ER PT J AU Gulick, RM Hu, XJ Fiscus, SA Fletcher, CV Haubrich, R Cheng, HL Acosta, E Lagakos, SW Swanstrom, R Freimuth, W Snyder, S Mills, C Fischl, M Pettinelli, C Katzenstein, D AF Gulick, RM Hu, XJ Fiscus, SA Fletcher, CV Haubrich, R Cheng, HL Acosta, E Lagakos, SW Swanstrom, R Freimuth, W Snyder, S Mills, C Fischl, M Pettinelli, C Katzenstein, D CA AIDS Clin Trials Grp Protocol 359 Team TI Durability of response to treatment among antiretroviral-experienced subjects: 48-week results from AIDS Clinical Trials Group Protocol 359 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 7th Conference on Retroviruses and Opportunistic Infections CY JAN 29-FEB 03, 2000 CL SAN FRANCISCO, CALIFORNIA ID RANDOMIZED CONTROLLED TRIAL; VIROLOGICAL FAILURE; ADEFOVIR DIPIVOXIL; TYPE-1 RNA; THERAPY; VIRUS; HIV-1; SAQUINAVIR; REGIMENS; NELFINAVIR AB The 24-week extension of AIDS Clinical Trials Group Protocol 359, a study of human immunodeficiency virus (HIV)-infected, indinavir-experienced patients, was designed to study the durability of "salvage" treatment regimens. Patients received saquinavir in combination with either ritonavir or nelfinavir and, in addition, delavirdine, adefovir, or both. Patients who demonstrated a virologic response at weeks 12-16 were eligible to continue therapy in the extension through week 48. Of the 105 eligible subjects who were enrolled in the extension, 86 (82%) completed 48 weeks, and 49 (57%) of those 86 had HIV RNA levels less than or equal to500 copies/mL at week 48. For these 86 subjects who completed 48 weeks, the median change in CD4 cell count from baseline was +72 cells/mm(3). Greater body weight, higher CD4 cell count, and greater degree of phenotypic susceptibility to indinavir and saquinavir at baseline were significantly associated with durable virologic suppression. These results show that some patients who experience treatment failure can demonstrate durable virologic and immunologic responses with salvage antiretroviral regimens. C1 Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Minnesota, Minneapolis, MN USA. Univ Calif San Diego, San Diego, CA 92103 USA. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. Univ Alabama, Birmingham, AL USA. Pharmacia & Upjohn Inc, Kalamazoo, MI 49001 USA. Social & Sci Syst, Silver Spring, MD USA. NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Miami, Sch Med, Miami, FL USA. RP Gulick, RM (reprint author), Cornell Univ, Weill Med Coll, Dept Med, Box 566,525 E 68th St, New York, NY 10021 USA. FU NIAID NIH HHS [AI-46386] NR 25 TC 10 Z9 10 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2002 VL 186 IS 5 BP 626 EP 633 DI 10.1086/342681 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 582LR UT WOS:000177352900006 PM 12195349 ER PT J AU Yang, QE Li, KG Mikovits, JA AF Yang, QE Li, KG Mikovits, JA TI Eradication of human immunodeficiency virus type 1-infected cells by a combination of antimetabolic cytotoxic chemotherapy and antiviral chemotherapy in vitro: A pilot study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW TRANSPLANTATION; ANTIRETROVIRAL THERAPY; PLASMA VIREMIA; REPLICATION; ZIDOVUDINE; INFECTION; HIV AB Although highly active antiretroviral therapy against human immunodeficiency virus (HIV) type 1 reduces the mortality of persons with acquired immunodeficiency syndrome, it does not eliminate HIV reservoirs. In this study, which used a 6-thioguanine (6-TG) resistant clone (4C6) of the MT-2 cell line as a model, the combination of 6-TG with both reverse-transcriptase (RT) inhibitor and protease inhibitor or 6-TG with a protease inhibitor alone completely eradicated HIV-1-carrying cells from the culture and protected uninfected 4C6 cells from HIV-1 infection. The combination of 6-TG and a RT inhibitor, azidothymidine, provided partial protection. Protection was extended to human peripheral blood mononuclear cells. These results suggest that adding a cytotoxic drug in combination antiviral chemotherapy may reduce the establishment of virus reservoirs and prevent virus spread. The clinical value of this and similar strategies should be further evaluated in HIV-infected patients. C1 NCI, Lab Antiviral Drug Mech, SAIC Frederick Inc, Frederick, MD 21702 USA. Mudanjiang Med Coll, Dept Med, Div Infect Dis, Mudanjiang, Peoples R China. RP Yang, QE (reprint author), NCI, Lab Antiviral Drug Mech, SAIC Frederick Inc, Bldg 439, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 15 TC 6 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2002 VL 186 IS 5 BP 706 EP 709 DI 10.1086/342049 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 582LR UT WOS:000177352900017 PM 12195360 ER PT J AU Reichelderfer, PS Kovacs, A Wright, DJ Landay, A Cu-Uvin, S Burns, DN Cohn, J Coombs, RW AF Reichelderfer, PS Kovacs, A Wright, DJ Landay, A Cu-Uvin, S Burns, DN Cohn, J Coombs, RW TI The menstrual cycle does not affect human immunodeficiency virus type 1 levels in vaginal secretions SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID FEMALE GENITAL-TRACT; RNA LEVELS; WOMEN; BLOOD C1 Univ Washington, Dept Lab Med, Seattle, WA 98104 USA. US Agcy Int Dev, Bishlek, Kyrgyzstan. NIH, Bethesda, MD 20892 USA. Westat Corp, Rockville, MD 20850 USA. Univ Calif Los Angeles, Maternal Child & Adolescent HIV Management & Res, Los Angeles, CA USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Miriam Hosp, Providence, RI 02906 USA. Wayne State Univ, Detroit, MI USA. Univ Washington, Dept Med, Seattle, WA 98104 USA. RP Coombs, RW (reprint author), Univ Washington, Dept Lab Med, Box 359690, Seattle, WA 98104 USA. FU NIAID NIH HHS [AI-27664, AI-30731]; NICHD NIH HHS [HD-33162] NR 9 TC 7 Z9 7 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2002 VL 186 IS 5 BP 726 EP 728 DI 10.1086/342051 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 582LR UT WOS:000177352900025 PM 12195368 ER PT J AU Koch, R Burton, B Hoganson, G Peterson, R Rhead, W Rouse, B Scott, R Wolff, J Stern, AM Guttler, F Nelson, M de la Cruz, F Coldwell, J Erbe, R Geraghty, MT Shear, C Thomas, J Azen, C AF Koch, R Burton, B Hoganson, G Peterson, R Rhead, W Rouse, B Scott, R Wolff, J Stern, AM Guttler, F Nelson, M de la Cruz, F Coldwell, J Erbe, R Geraghty, MT Shear, C Thomas, J Azen, C TI Phenylketonuria in adulthood: A collaborative study SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID PHENYLALANINE-HYDROXYLASE DEFICIENCY; MUTATIONS; PHENOTYPE AB During 1967-1983, the Maternal and Child Health Division of the Public Health Services funded a collaborative study of 211 newborn infants identified on newborn screening as having phenylketonuria (PKU). Subsequently, financial support was provided by the National Institute of Child Health and Human Development (NICHD). The infants were treated with a phenylalanine (Phe)-restricted diet to age 6 years and then randomized either to continue the diet or to discontinue dietary treatment altogether. One hundred and twenty-five of the 211 children were then followed until 10 years of age. In 1998, NICHD scheduled a Consensus Development Conference on Phenylketonuria and initiated a study to follow up the participants from the original Collaborative Study to evaluate their present medical, nutritional, psychological, and socioeconomic status. Fourteen of the original clinics (1967-1983) participated in the Follow-up Study effort. Each clinic director was provided with a list of PKU subjects who had completed the original study (1967-1983), and was asked to evaluate as many as possible using a uniform protocol and data collection forms. In a subset of cases, magnetic resonance imaging and spectroscopy (MRI/MRS) were performed to study brain Phe concentrations. The medical evaluations revealed that the subjects who maintained a phenylalanine-restricted diet reported fewer problems than the diet discontinuers, who had an increased rate of eczema, asthma, mental disorders, headache, hyperactivity and hypoactivity. Psychological data showed that lower intellectual and achievement test scores were associated with dietary discontinuation and with higher childhood and adult blood Phe concentrations. Abnormal MRI results were associated with higher brain Phe concentrations. Early dietary discontinuation for subjects with PKU is associated with poorer outcomes not only in intellectual ability, but also in achievement test scores and increased rates of medical and behavioural problems. C1 Univ So Calif, Childrens Hosp Los Angeles, Keck Sch Med, Dept Pediat,Div Med Genet,PKU Program 73, Los Angeles, CA 90027 USA. Dept Radiol, Los Angeles, CA USA. Childrens Mem Med Ctr, Chicago, IL USA. Univ Illinois, Dept Pediat, Chicago, IL USA. San Diego Reg Ctr, San Diego, CA USA. Univ Iowa, Div Med Genet, Iowa City, IA USA. Univ Texas, Med Branch, Childrens Hosp, Galveston, TX 77550 USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. Univ Wisconsin, Waisman Ctr Mental Retardat & Human Dev, Madison, WI 53706 USA. Univ Copenhagen, John F Kennedy Inst, Dept Inherited Metab Dis, Glostrup, Denmark. NICHHD, Bethesda, MD 20892 USA. Childrens Med Ctr, Tulsa, OK USA. Childrens Hosp, Div Genet, Buffalo, NY 14222 USA. Johns Hopkins Univ Hosp, Inst Genet, Baltimore, MD 21287 USA. Childrens Hosp, Denver, CO 80218 USA. RP Koch, R (reprint author), Univ So Calif, Childrens Hosp Los Angeles, Keck Sch Med, Dept Pediat,Div Med Genet,PKU Program 73, 4650 Sunset Blvd, Los Angeles, CA 90027 USA. FU NCRR NIH HHS [M01 RR-43 CDMAS]; NICHD NIH HHS [N01-HD-2-3148] NR 16 TC 87 Z9 87 U1 2 U2 14 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD SEP PY 2002 VL 25 IS 5 BP 333 EP 346 DI 10.1023/A:1020158631102 PG 14 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 593AN UT WOS:000177969200001 PM 12408183 ER PT J AU von Stebut, E Belkaid, Y Nguyen, B Wilson, M Sacks, DL Udey, MC AF von Stebut, E Belkaid, Y Nguyen, B Wilson, M Sacks, DL Udey, MC TI Skin-derived macrophages from Leishmania major-susceptible mice exhibit interleukin-12-and interferon-gamma-independent nitric oxide production and parasite killing after treatment with immunostimulatory DNA SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE CpG motif; cytokines; Leishmania; monocytes; macrophages; nitric oxide ID EXPERIMENTAL CUTANEOUS LEISHMANIASIS; TUMOR-NECROSIS-FACTOR; BACTERIAL-DNA; DENDRITIC CELLS; CPG-OLIGODEOXYNUCLEOTIDES; CUTTING EDGE; VISCERAL LEISHMANIASIS; MURINE MACROPHAGES; REACTIVE NITROGEN; IL-12 PRODUCTION AB Co-administration of CpG-containing immunostimulatory oligodeoxynucleotides and parasite antigen protects susceptible BALB/c mice from otherwise progressive infection with Leishmania major. Although the protective effect of CpG-containing immunostimulatory oligodeoxynucleotides is clearly dependent on endogenous interleukin-12 and interferon-gamma production, the source of these Th1-promoting cytokines in infected mice is unknown. In contrast to macrophages from Leishmania-resistant C57BL/6 mice, macrophages from susceptible BALB/c mice are hyporesponsive to stimulation with lipopolysaccharide and interferon-gamma. While studying interactions of various antigen-presenting cells with Leishmania, we found that BALB/c inflammatory skin macrophages, whether Leishmania-infected or uninfected, produced large amounts of interleukin-12 when treated with CpG-containing immunostimulatory oligodeoxynucleotides. Like lipopolysaccharide, CpG-containing immunostimulatory oligodeoxynucleotides induced production of interferon-gamma and release of nitric oxide by skin macrophages. Studies using skin macrophages from interleukin-12- and interferon-gamma-deficient BALB/c mice demonstrated that nitric oxide release was not dependent on interleukin-12 and interferon-gamma production. Approximately 44% and 27% of intracellular Leishmania major amastigotes were killed by infected skin macrophages within 72 h upon stimulation with CpG-containing immunostimulatory oligodeoxynucleotides and lipopolysaccharide, respectively. Parasite killing by macrophages was independent of endogenous interferon-gamma production, but was strongly enhanced by exogenous interferon-gamma. Parasite elimination was dependent on the induction of nitric oxide, however. In vivo, injection of CpG-containing immunostimulatory oligodeoxynucleotides into lesional skin reduced the parasite burden approximate to50-fold within the first 5 d of infection prior to full generation of a Th response. These results suggest that skin macrophages, constituting the principal reservoir of parasites in infected susceptible mice, produce Th1-promoting cytokines in response to CpG-containing immunostimulatory oligodeoxynucleotides. In addition, CpG-containing immunostimulatory oligodeoxynucleotides may also act locally on skin macrophages to facilitate Leishmania clearance by inducing nitric oxide production. C1 Univ Mainz, Dept Dermatol, D-55131 Mainz, Germany. NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA. NCI, Ctr Canc Res, Dermatol Branch, NIH, Bethesda, MD USA. RP von Stebut, E (reprint author), Univ Mainz, Dept Dermatol, Langenbeckstr 1, D-55131 Mainz, Germany. NR 51 TC 8 Z9 9 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2002 VL 119 IS 3 BP 621 EP 628 DI 10.1046/j.1523-1747.2002.01850.x PG 8 WC Dermatology SC Dermatology GA 592RV UT WOS:000177951400012 PM 12230504 ER PT J AU Sprecher, E Itin, P Whittock, NV McGrath, JA Meyer, R DiGiovanna, JJ Bale, SJ Uitto, J Richard, G AF Sprecher, E Itin, P Whittock, NV McGrath, JA Meyer, R DiGiovanna, JJ Bale, SJ Uitto, J Richard, G TI Refined mapping of Naegeli-Franceschetti-Jadassohn syndrome to a 6 cM interval on chromosome 17q11.2-q21 and investigation of candidate genes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE dermatoglyphics; ectodermal dysplasia; gene mapping; hyperpigmentation; palmoplantar keratoderma ID DERMATOPATHIA-PIGMENTOSA-RETICULARIS; GENOMIC ORGANIZATION; PROTEIN; FAMILY; 17Q21; AMPLIFICATION; HOMOLOG; GROWTH; CELLS; BRCA1 AB Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis are autosomal dominant ectodermal dysplasias characterized by the absence of dermatoglyphics, reticulate hyper-pigmentation of the skin, hypohidrosis, and heat intolerance. Palmoplantar keratoderma, nail dystrophy, and enamel defects are common in Naegeli-Franceschetti-Jadassohn syndrome, whereas diffuse alopecia is only seen in dermatopathia pigmentosa reticularis. We studied a large Swiss family with Naegeli-Franceschetti-Jadassohn syndrome originally described by Naegeli in 1927 and assessed linkage to chromosome 17q, which was proposed to harbor the Naegeli-Franceschetti-Jadassohn syndrome gene. Our results considerably narrow the Naegeli-Franceschetti-Jadassohn syndrome gene region from 27 cM to 6 cM flanked by D17S933 and D17S934 with a maximum multipoint LOD score of 2.7 at marker locus D17S800. In addition, we studied a small family with dermatopathia pigmentosa reticularis, and our linkage data suggest that dermatopathia pigmentosa reticularis may map to the same chromosomal region. The Naegeli-Franceschetti-Jadassohn syndrome critical interval spans approximately 5.4 Mb and contains a minimum of 45 distinct genes. We scrutinized 13 new prime candidates in addition to five genes previously examined, established the genomic organization of 10 of these genes, and excluded all of them by mutation analysis. Moreover, we identified a cDNA (KRT24) encoding a new keratin protein that bears high similarity to the type I keratins and displays a unique expression profile. No pathogenic mutations were identified in this novel gene either, however. In summary, our results substantially refine the Naegeli-Franceschetti-Jadassohn syndrome region and will aid in identifying a gene that is critical for ontogenesis of multiple ectodermal tissues. C1 Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Jefferson Inst Mol Med, Philadelphia, PA 19107 USA. Univ Basel, Dept Dermatol, Hosp Aarau, Basel, Switzerland. Guys Kings Coll & St Thomas Hosp Med Sch, St Thomas Hosp, Dept Cell & Mol Pathol, St Johns Inst Dermatol, London, England. NCI, NIH, Bethesda, MD 20892 USA. Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA. GeneDx, Rockville, MD USA. NIAMS, NIH, Bethesda, MD USA. RP Richard, G (reprint author), Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, 233 S 10th St,BLSB Suite 409, Philadelphia, PA 19107 USA. RI McGrath, John/D-6824-2012 OI McGrath, John/0000-0002-3708-9964 FU NIAMS NIH HHS [AR02141, AR38923] NR 30 TC 17 Z9 18 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2002 VL 119 IS 3 BP 692 EP 698 DI 10.1046/j.1523-1747.2002.01855.x PG 7 WC Dermatology SC Dermatology GA 592RV UT WOS:000177951400022 PM 12230514 ER PT J AU Lugassy, C Kleinman, HK Fernandez, PM Patierno, SR Webber, MM Ghanem, G Spatz, A Barnhill, RL AF Lugassy, C Kleinman, HK Fernandez, PM Patierno, SR Webber, MM Ghanem, G Spatz, A Barnhill, RL TI Human melanoma cell migration along capillary-like structures in vitro: A new dynamic model for studying extravascular migratory metastasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID IMMUNOHISTOCHEMICAL OBSERVATIONS; LAMININ; DIFFERENTIATION C1 George Washington Univ, Med Ctr, Dept Dermatol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Pharmacol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Program Mol & Cellular Oncol, Washington, DC 20037 USA. NIDCR, NIH, Bethesda, MD USA. Michigan State Univ, E Lansing, MI 48824 USA. Free Univ Brussels, Brussels, Belgium. Inst Gustave Roussy, Villejuif, France. RP Barnhill, RL (reprint author), George Washington Univ, Med Ctr, Dept Dermatol, Washington, DC 20037 USA. NR 10 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2002 VL 119 IS 3 BP 703 EP 704 DI 10.1046/j.1523-1747.2002.01857.x PG 2 WC Dermatology SC Dermatology GA 592RV UT WOS:000177951400025 PM 12230517 ER PT J AU Davis, AM Hull, SC Grady, C Wilfond, BS Henderson, GE AF Davis, AM Hull, SC Grady, C Wilfond, BS Henderson, GE TI The invisible hand in clinical research: The study coordinator's critical role in human subjects protection SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article; Proceedings Paper CT Annual Meeting on Public Responsibility in Medicine and Research (PRIM&R) CY DEC, 2001 CL BOSTON, MASSACHUSETTS ID NURSE C1 Univ N Carolina, Sch Med, Chapel Hill, NC 27515 USA. NHGRI, Bioeth Res Sect, Med Genet Branch, NIH, Bethesda, MD USA. NIH, Sect Human Subjects Res, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD USA. Georgetown Univ, Med Ctr, Ctr Clin Bioeth, Washington, DC 20057 USA. NHGRI, Bioeth Res Sect, Med Genet Branch, Bethesda, MD USA. RP Davis, AM (reprint author), Univ N Carolina, Sch Med, Chapel Hill, NC 27515 USA. OI Davis, Arlene/0000-0001-6486-0446 FU Intramural NIH HHS [Z99 HG999999]; NHGRI NIH HHS [R01 HG002087, R01HG02087] NR 32 TC 27 Z9 30 U1 2 U2 6 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, SUITE 1634, BOSTON, MA 02215 USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD FAL PY 2002 VL 30 IS 3 BP 411 EP 419 DI 10.1111/j.1748-720X.2002.tb00410.x PG 9 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 623MA UT WOS:000179706000008 PM 12497701 ER PT J AU Yang, D Chen, Q Gertz, B He, R Phulsuksombati, M Ye, RD Oppenheim, JJ AF Yang, D Chen, Q Gertz, B He, R Phulsuksombati, M Ye, RD Oppenheim, JJ TI Human dendritic cells express functional formyl peptide receptor-like-2 (FPRL2) throughout maturation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE chemotaxis; Ca2+ mobilization; maturation ID SERUM AMYLOID-A; N-FORMYLPEPTIDE RECEPTOR; LIPOXIN A(4) RECEPTOR; PROTEIN-COUPLED RECEPTOR; HUMAN PHAGOCYTIC-CELLS; REGIONAL LYMPH-NODES; VAL-D-MET; PHOSPHOINOSITIDE HYDROLYSIS; CHEMOATTRACTANT RECEPTORS; SUPEROXIDE GENERATION AB Immature and mature dendritic cells (iDC and mDC, respectively) migrate to different anatomical sites, e.g., sites of antigen (Ag) deposition and secondary lymphoid organs, respectively, to fulfill their roles in the induction of primary, Ag-specific immune responses. The trafficking pattern of iDC and mDC is based on their expression of functional chemotactic receptors and the in vivo sites expressing the corresponding ligands including chemokines and/or classical chemoattractants. In this study, we have evaluated the expression of the formyl peptide receptor like-2 (FPRL2) by human iDC and mDC. We show that iDC respond chemotactically and by Ca2+ mobilization to N-formyl-Met-Leu-Phe mid a recently identified synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), whereas mDC derived from the same donor only respond to WKYMVm. Furthermore, iDC and mDC express FPRL2 mRNA and protein. As mDC do not express any other members of the human FPR subfamily, FPRL2 expressed by DC must be functional and mediate the effect of WKYMVm on DC. Indeed, treatment of iDC and mDC with WKYMVm induces the internalization of FPRL2. Thus, human myeloid DC express functional FPRL2 and maintain its expression even after maturation, suggesting that the interaction of FPRL2 and its endogenous ligand(s) may be involved in regulating DC trafficking during Ag uptake and processing in the periphery as well as the T cell-stimulating phase of the immune responses. C1 NCI, CCR, LMI, NIH, Frederick, MD 21702 USA. Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL USA. RP Oppenheim, JJ (reprint author), NCI, CCR, LMI, NIH, Bldg 560,Room 21-89, Frederick, MD 21702 USA. RI Ye, Richard/O-5223-2016 OI Ye, Richard/0000-0002-2164-5620 NR 75 TC 43 Z9 46 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 2002 VL 72 IS 3 BP 598 EP 607 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 592GQ UT WOS:000177928900022 PM 12223529 ER PT J AU Ding, KY Gronenborn, AM AF Ding, KY Gronenborn, AM TI Sensitivity-enhanced E.COSY-type HSQC experiments for accurate measurements of one-bond N-15-H-1(N) and N-15-C-13 ' and two-bond C-13 '-H-1(N) residual dipolar couplings in proteins SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE residual dipolar couplings; E.COSY; proteins; structural genomics ID QUANTITATIVE J-CORRELATION; LIQUID-CRYSTALLINE PHASE; HIGH-RESOLUTION; NMR; SPECTROSCOPY; MACROMOLECULES; IMPROVEMENT; ALIGNMENT AB Novel E.COSY-type HSQC experiments are presented for the accurate measurement of one-bond N-15-H-1(N) and N-15-C-13' and two-bond C-13'-H-1(N) residual dipolar couplings in proteins. Compared with existing experiments, the (delta,J)-E.COSY experiments described here are composed of fewer pulses and the resulting spectra exhibit 1.4 times the sensitivity of coupled HSQC spectra. Since residual dipolar couplings play increasingly important roles in structural NMR, the proposed methods should find wide spread application for structure determination of proteins and other biological macromolecules. (C) 2002 Elsevier Science (USA). All rights reserved. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Gronenborn, AM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. NR 29 TC 16 Z9 16 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD SEP-OCT PY 2002 VL 158 IS 1-2 BP 173 EP 177 AR PII S1090-7807(02)00024-1 DI 10.1016/S1090-7807(02)00024-1 PG 5 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 619VE UT WOS:000179497500019 PM 12419684 ER PT J AU Slavotinek, AM Tifft, CJ AF Slavotinek, AM Tifft, CJ TI Fraser syndrome and cryptophthalmos: review of the diagnostic criteria and evidence for phenotypic modules in complex malformation syndromes SO JOURNAL OF MEDICAL GENETICS LA English DT Review ID BILATERAL RENAL AGENESIS; SYNDACTYLY SYNDROME; PULMONARY HYPERPLASIA; SURGICAL-CORRECTION; MURCS ASSOCIATION; ANOMALIES; MICROPHTHALMIA; MANIFESTATIONS; RECONSTRUCTION; ABNORMALITIES AB Fraser syndrome is characterised by cryptophthalmos, cutaneous syndactyly, malformations of the larynx and genitourinary tract, craniofacial dysmorphism, orofacial clefting, mental retardation, and musculoskeletal anomalies. The inheritance is autosomal recessive. No diagnostic cytogenetic abnormalities have been documented in affected patients, and no molecular genetic studies have been reported. We have reviewed 117 cases diagnosed as Fraser syndrome or cryptophthalmos published since the comprehensive review of Thomas et al in 1986 in order to validate the published diagnostic criteria and to delineate the phenotype associated with this syndrome. Our series showed more females (57/117) than males and consanguinity was present in 29/119 (24.8%). Eighty-eight patients satisfied the diagnostic criteria for Fraser syndrome.(75%). Cryptophthalmos was present in 103/117 (88%), syndactyly in 72/117 (61.5%), and ambiguous genitalia in 20/117 (17.1%). Ear malformations were recorded in 69/117 (59%), and renal agenesis in 53/117 (45.3%). Use of the published diagnostic criteria excluded several patients with cryptophthalmos and one or more physical feature(s) consistent with Fraser syndrome. The frequency of additional anomalies in our series was also higher than previously reported (for example, imperforate anus or anal stenosis were found in 34/117 (29%) compared with 2/124 (2%) in the series of Thomas et al (1986) and choanal stenosis or atresia was present in 7/117 (6%) compared to 0/124. These findings emphasise the clinical variability associated with Fraser syndrome and support genetic heterogeneity of the syndrome. We also noted patterns of anomalies (for example, bicornuate uterus with imperforate anus or anal stenosis and renal malformations) that are found in other syndromes and associations without cryptophthalmos, suggesting that common modifier genes may explain-some of the phenotypic variation in Fraser syndrome. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. RP Slavotinek, AM (reprint author), NHGRI, NIH, Bldg 49,Room 4B75,49 Convent Dr, Bethesda, MD 20892 USA. NR 96 TC 95 Z9 100 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 2002 VL 39 IS 9 BP 623 EP 633 DI 10.1136/jmg.39.9.623 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 593PE UT WOS:000178000700002 PM 12205104 ER PT J AU Gao, G Buskell, Z Seeff, L Tabor, E AF Gao, G Buskell, Z Seeff, L Tabor, E TI Drift in the hypervariable region of the hepatitis C virus during 27 years in two patients SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE hepatitis C virus; immune globulin; quasispecies ID TO-INFANT TRANSMISSION; NON-B HEPATITIS; IMMUNE-RESPONSE; NON-A; EVOLUTION; INFECTION; NEUTRALIZATION; CHIMPANZEES; MECHANISMS; PERSISTENT AB Serial serum samples were obtained over a 27-year period from a hepatitis C virus (HCV)-infected patient and from a nurse who appeared to become infected by this patient. The hypervariable region 1 (HVR1) and 5' noncoding region (5'NCR) of the HCV genome were amplified from each serum sample by polymerase chain reaction (PCR) and cloned. In the first serum specimen from the patient and the first two serum specimens from the nurse, most of the 20 clones from each serum sample had one common sequence in the HVR1 gene. All later serum samples contained a heterogeneous mixture of HCV quasispecies. The uniformity of the HVR1 sequence in the early samples and the emergence of greater diversity in later serum samples is consistent with the apparent transmission of HCV between the patient and nurse and the eventual emergence of other quasispecies as the virus replicated in the new host. In addition, the immune globulin given to the nurse may have been responsible for some of the HCV quasispecies changes observed in her serum. Published 2002 Wiley-Liss, Inc. C1 US FDA, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20852 USA. Vet Adm Med Ctr, Washington, DC 20422 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Tabor, E (reprint author), US FDA, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA. NR 22 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD SEP PY 2002 VL 68 IS 1 BP 60 EP 67 DI 10.1002/jmv.10170 PG 8 WC Virology SC Virology GA 579PX UT WOS:000177188000009 PM 12210431 ER PT J AU Crow, MT AF Crow, MT TI beta-adrenergic receptor signaling pathways mediating cell survival in cardiomyocytes: a role for PKC epsilon inhibition? SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Editorial Material ID RAT VENTRICULAR MYOCYTES; CARDIAC MYOCYTES; HEART-FAILURE; APOPTOSIS; ACTIVATION; MICE; NOREPINEPHRINE; OVEREXPRESSION; ANTAGONIST; EXPRESSION C1 Johns Hopkins Univ, Sch Med, Cardiovasc Sci Lab, Gerontol Res Ctr,NIA,NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21224 USA. RP Crow, MT (reprint author), Johns Hopkins Asthma & Allergy Ctr, Div Pulm & Crit Care Med, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM mcrow1@jhmi.edu NR 30 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 2002 VL 34 IS 9 BP 1121 EP 1125 DI 10.1006/jmcc.2002.2051 PG 5 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 604LL UT WOS:000178622500006 PM 12392884 ER PT J AU Ward, SM Gadbut, AP Tang, DJ Papageorge, AG Wu, LY Li, GD Barnett, JV Galper, JB AF Ward, SM Gadbut, AP Tang, DJ Papageorge, AG Wu, LY Li, GD Barnett, JV Galper, JB TI TGF beta regulates the expression of G alpha(i2) via an effect on the localization of Ras SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE TGF beta; parasympathetic response; G alpha(i2); Ras; atrial myocytes ID LOW-DENSITY LIPOPROTEINS; EMBRYONIC CHICK HEART; TRANSFORMING GROWTH-FACTOR-BETA-1; MUSCARINIC RECEPTORS; PROTEIN ISOPRENYLATION; GENE-EXPRESSION; GROWTH-FACTOR; ATRIAL CELLS; RESPONSIVENESS; FARNESYLATION AB The negative chronotropic response of the heart to parasympathetic stimulation is mediated via the interaction Of M-2 muscarinic receptors, Galpha(i2) and the G-protein coupled inward rectifying K+ channel, GIRK1. Here TGFbeta(1) is shown to decrease the expression of Galpha(i2) in cultured chick atrial cells in parallel with attenuation of the negative chronotropic response to parasympathetic stimulation. The response to the acetylcholine analogue. carbamylcholine, decreased from a 95 +/- 2%, (+/-SEM, n = 8) inhibition of beat rate in control cells to 1.8 +/- 2%, (+/- SEM. n = 8) in TGFbeta(1) treated cells. Data support the conclusion that TGFbeta regulation of Galpha(i2) expression was mediated via an effect on Ras. TGFbeta(1) inhibited Galpha(i2) promoter activity by 56 +/- 6% ( SEM, n = 4) compared to control. A dominant activating Ras mutant reversed the effect of TGFbeta on Galpha(i2) expression and stimulated Galpha(i2) promoter activity 1.7 fold above control. A dominant negative Ras mutant mimicked the effect of TGFbeta(1) on Galpha(i2) promoter activity. TGFbeta had no effect on the ratio of GDP/GTP bound Ras. but markedly decreased the level of membrane associated Ras and increased the level of cytoplasmic Ras compared to control. Furthermore, farnesol, a precursor to farnesylpyrophosphate, the substrate for the farnesylation of Ras, not only reversed TGFbeta(1) inhibition of Ras localization to the membrane, but also reversed TGFbeta(1) inhibition of Galpha(i2)-promoter activity. FTI-277, a specific inhibitor of the farnesylation of Ras, mimicked the effect of TGFbeta(1), on Ras localization and Galpha(i2) promoter activity. These data suggest a novel relationship between TGFbeta signaling, regulation of Ras function and the autonomic response of the heart. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Vanderbilt Univ, Med Ctr, Nashville, TN 37203 USA. RP Galper, JB (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Thorn Bldg,Rm 1209,75 Francis St, Boston, MA 02115 USA. EM galper@calvin.bwh.harvard.edu FU NHLBI NIH HHS [HL36014, R01 HL052922, HL08463, R01 HL052922-10] NR 31 TC 12 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 2002 VL 34 IS 9 BP 1217 EP 1226 DI 10.1006/jmcc.2002.7023 PG 10 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 604LL UT WOS:000178622500017 PM 12392895 ER PT J AU Krieg, RC Paweletz, CP AF Krieg, RC Paweletz, CP TI Proteome analysis in lymphangiogenesis SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Meeting Abstract C1 NCI, FDA, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD SEP PY 2002 VL 80 IS 9 BP B4 EP B4 PG 1 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 602KU UT WOS:000178505100018 ER PT J AU Rosenwald, A AF Rosenwald, A TI Computer-assisted interpretation of hybridized microarrays - Molecular profiling to predict survival in lymphoma SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Meeting Abstract C1 NCI, Metab Branch, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD SEP PY 2002 VL 80 IS 9 BP B6 EP B6 PG 1 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 602KU UT WOS:000178505100023 ER PT J AU Pettit, GR Ducki, S Tan, R Gardella, RS McMahon, JB Boyd, MR Pettit, GR Blumberg, PM Lewin, NE Doubek, DL Tackett, LP Williams, MD AF Pettit, GR Ducki, S Tan, R Gardella, RS McMahon, JB Boyd, MR Pettit, GR Blumberg, PM Lewin, NE Doubek, DL Tackett, LP Williams, MD TI Isolation and structure of pedilstatin from a Republic of Maldives Pedilanthus sp. SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID PROTEIN-KINASE-C; ANTINEOPLASTIC AGENTS; CYTOTOXIC CONSTITUENTS; TAXUS-CANADENSIS; PHORBOL ESTER; PHYLLANTHOSTATIN; SAPONIN; TAXANES; LIGNAN; DRUG AB A new cancer cell growth inhibitor designated pedilstatin (1) was isolated from a Republic of Maldives Pedilanthus sp. The structure was determined to be 13-O-acetyl-12-O-[2'Z,4'E-octadienoyl]-4alpha-deoxyphorbol on the basis of high-resolution mass spectral and 2D NMR assignments. Pedilstatin was found to significantly inhibit growth of the P388 lymphocytic leukemia cell line with an ED50 of 0.28 mug/mL, to afford, at concentrations of 2-5 muM, protection (to 80%) of human-derived lymphoblastoid CEM-SS cells from infection and cell-killing by HIV-1, and to show inhibition of protein kinase C with a K-i of 620 +/- 20 nM. C1 Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21702 USA. NCI, Mol Targets Drug Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. FU NCI NIH HHS [CA 44344-05-12, N01-CO-12400, R01 CA90441-01] NR 36 TC 16 Z9 19 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD SEP PY 2002 VL 65 IS 9 BP 1262 EP 1265 DI 10.1021/np020115b PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 598KJ UT WOS:000178274700007 PM 12350143 ER PT J AU Erickson, KL Gustafson, KR Pannell, LK Beutler, JA Boyd, MR AF Erickson, KL Gustafson, KR Pannell, LK Beutler, JA Boyd, MR TI New dimeric macrolide glycosides from the marine sponge Myriastra clavosa SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID DISCODERMIA-CALYX; PROTEIN PHOSPHATASE-1; CALLIPELTA SP; METABOLITES; INHIBITORS; DISCOVERY; BACTERIUM AB Clavosolides A-D (1-4), dimeric macrolides incorporating cyclopropyl, tetrahydropyranyl, and glycosidic ring systems, were isolated from the cytotoxic extract of a Philippines collection of the marine sponge Myriastra clavosa. The structures of the clavosolides, which occurred as only trace metabolites, were elucidated through extensive NMR spectroscopic analyses. Clavosolides A (1) and B (2) were recently reported metabolites from M. clavosa, while the unsymmetrical dimers clavosolides C (3) and D (4) had new structures. C1 NCI, Mol Targets Drug Discovery Program, Ctr Canc Res, Frederick, MD 21701 USA. RP Gustafson, KR (reprint author), NCI, Mol Targets Drug Discovery Program, Ctr Canc Res, Bldg 1052,Room 121, Frederick, MD 21701 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 23 TC 43 Z9 43 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD SEP PY 2002 VL 65 IS 9 BP 1303 EP 1306 DI 10.1021/np020193z PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 598KJ UT WOS:000178274700016 PM 12350152 ER PT J AU Lee, J Duan, W Mattson, MP AF Lee, J Duan, W Mattson, MP TI Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; caloric restriction; dentate gyrus; neurotrophic factor; stem cells ID NEURAL STEM-CELLS; BDNF MUTANT MICE; DENTATE GYRUS; ENRICHED ENVIRONMENT; MOUSE HIPPOCAMPUS; STRIATAL NEURONS; FACTOR-DEFICIENT; NT-3; INCREASES; RATS AB To determine the role of brain-derived neurotrophic factor (BDNF) in the enhancement of hippocampal neurogenesis resulting from dietary restriction (DR), heterozygous BDNF knockout (BDNF +/-) mice and wild-type mice were maintained for 3 months on DR or ad libitum (AL) diets. Mice were then injected with bromodeoxyuridine (BrdU) and killed either 1 day or 4 weeks later. Levels of BDNF protein in neurons throughout the hippocampus were decreased in BDNF +/- mice, but were increased by DR in wild-type mice and to a lesser amount in BDNF +/- mice. One day after BrdU injection the number of BrdU-labeled cells in the dentate gyrus of the hippocampus was significantly decreased in BDNF +/- mice maintained on the AL diet, suggesting that BDNF signaling is important for proliferation of neural stem cells. DR had no effect on the proliferation of neural stem cells in wild-type or BDNF +/- mice. Four weeks after BrdU injection, numbers of surviving labeled cells were decreased in BDNF +/- mice maintained on either AL or DR diets. DR significantly improved survival of newly generated cells in wild-type mice, and also improved their survival in BDNF +/- mice, albeit to a lesser extent. The majority of BrdU-labeled cells in the dentate gyrus exhibited a neuronal phenotype at the 4-week time point. The reduced neurogenesis in BDNF +/- mice was associated with a significant reduction in the volume of the dentate gyrus. These findings suggest that BDNF plays an important role in the regulation of the basal level of neurogenesis in dentate gyrus of adult mice, and that by promoting the survival of newly generated neurons BDNF contributes to the enhancement of neurogenesis induced by DR. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, GRC 4Fol,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012; Lee, Jaewon/N-9064-2013 NR 46 TC 510 Z9 532 U1 4 U2 24 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2002 VL 82 IS 6 BP 1367 EP 1375 DI 10.1046/j.1471-4159.2002.01085.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 589YW UT WOS:000177790000006 PM 12354284 ER PT J AU Brightman, MW AF Brightman, MW TI The brain's interstitial clefts and their glial walls SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; HEPARAN-SULFATE PROTEOGLYCAN; CEREBROSPINAL FLUID COMPARTMENTS; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; ADULT-RAT; PERLECAN; EXPRESSION; ASTROCYTES; RELEASE AB The heterogeneous contents of the CNS interstitial clefts and the configuration of their astrocytic walls may be regionally variable. Astrocytic processes of the glia limitans, in normal midbrain and in astroglial scars, form thin, parallel, concentric sheets comprising the walls of narrow interstitial clefts. There is a critical thickness of about 20 to 30 nm, below which astrocytic cell process or those of the fibroblast-like cells in the meninges, do not invaginate to form transcytotic vesicles. Large hydrophilic solutes cannot, therefore, pass across the thin portion of a cell process. Consequently, (a) the diffusion and convection paths of interstitial fluid and solutes are lengthened, (b) a solute will remain within the interstitial cleft between thin lamellae for a relatively long time and (c) if a ligand does bind to its receptor on the thin process's cell membrane, there can be no receptor-mediated transcytosis at that site. Interstitial clefts, themselves, vary in size, shape and content, including extracellular matrix and basal lamina. A common constituent of basal lamina and extracellular matrix, presumably including that at ependymal, astroglial and endothelial interfaces of the CNS, is heparan sulfate proteoglycans. As in other organs, these proteoglycans may store growth factors, growth inhibitors, cytokines and other modulators which can then be released enzymatically during, e.g., regeneration. Exogenous heparan sulfate proteoglycan might serve as a natural, intermittent-release matrix for delivery of trophic factors. C1 NIH, Neurobiol Lab, Bethesda, MD 20892 USA. RP Brightman, MW (reprint author), NIH, Neurobiol Lab, Bldg 36,Room 2A-21, Bethesda, MD 20892 USA. NR 44 TC 25 Z9 25 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD SEP-NOV PY 2002 VL 31 IS 8-9 BP 595 EP 603 DI 10.1023/A:1025783326667 PG 9 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 722QH UT WOS:000185387200004 PM 14501201 ER PT J AU Dosemeci, A Vinade, L Winters, CA Reese, TS Tao-Cheng, JH AF Dosemeci, A Vinade, L Winters, CA Reese, TS Tao-Cheng, JH TI Inhibition of phosphatase activity prolongs NMDA-induced modification of the postsynaptic density SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID PROTEIN-KINASE-II; TRANSIENT CEREBRAL-ISCHEMIA; DENDRITIC SPINES; TRANSLOCATION; RECEPTOR; AUTOPHOSPHORYLATION; LOCALIZATION; PLASTICITY; NEURONS; CAMKII AB NMDA-induced modification of postsynaptic densities (PSDs) was studied by immunoelectron microscopy. Treatment of cultured hippocampal neurons with NMDA for 2 min promotes a 2.3 fold thickening of the PSD and a 4 fold increase in PSD-associated CaMKII immunolabel. These changes are reversed 5 min after the removal of NMDA and Ca2+ from the medium. In addition, following NMDA treatment, PSDs exhibit a 7.5 fold increase in labeling with an antibody specific to the (Thr286) phospho-form of CaMKII, indicating that CaMKII translocated to the PSD is phosphorylated. When the phosphatase inhibitors, calyculin A or okadaic acid, are included in the medium, the NMDA-induced thickening of the PSD as well as the increase in PSD-associated CaMKII immunolabeling are largely maintained (75% and 88% of the peak values respectively) at 5 min after removal of NMDA and Ca2+ from the medium. These results imply that NMDA receptors can mediate activity-induced changes in the PSD and that phosphatases of type 1 and/or 2A are involved in the reversal of these changes. C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Marine Biol Lab, Woods Hole, MA 02543 USA. NINDS, EM Facil, NIH, Bethesda, MD 20892 USA. RP NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. EM tsr@codon.nih.gov NR 24 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD SEP-NOV PY 2002 VL 31 IS 8-9 BP 605 EP 612 DI 10.1023/A:1025735410738 PG 8 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 722QH UT WOS:000185387200005 PM 14501202 ER PT J AU Muraro, PA Kalbus, M Afshar, G McFarland, HF Martin, R AF Muraro, PA Kalbus, M Afshar, G McFarland, HF Martin, R TI T cell response to 2 ',3 '-cyclic nucleotide 3 '-phosphodiesterase (CNPase) in multiple sclerosis patients SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE 2 ',3 '-cyclic nucleotide 3 '-phosphodiesterase; myelin proteins; epitopes; multiple sclerosis ID MYELIN BASIC-PROTEIN; BINDING; IDENTIFICATION; LYMPHOCYTES; AUTOANTIGEN; REPERTOIRE; DISEASES AB T cell responses targeting myelin antigens are possibly involved in the pathogenesis of demyelinating diseases, such as multiple sclerosis (MS). Little is known about human T cell responses to 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), the third most abundant myelin protein. We examined the primary peripheral T cell response to CNPase and characterized CNPase-specific CD4+ long-term T cell lines (TCL) from MS patients and healthy donors. The strongest primary responses were found in two MS patients with very active disease and were directed against CNP(343-373). We identified immumodominant epitope clusters in the regions CNP(343-373) and (356-388) that were recognized in the context of MS-associated HLA-DR2 and DR4 molecules. These data provide the immunological basis for further investigation of CNPase as a potential target self-antigen in MS. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Tubingen, Sch Med, Dept Neurol, D-72076 Tubingen, Germany. RP Muraro, PA (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr Dr MSC1400, Bethesda, MD 20892 USA. OI Muraro, Paolo/0000-0002-3822-1218 NR 20 TC 21 Z9 21 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2002 VL 130 IS 1-2 BP 233 EP 242 AR PII S0165-5728(02)00229-1 DI 10.1016/S0165-5728(02)00229-1 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 599HX UT WOS:000178329200024 PM 12225906 ER PT J AU Sukhareva, M Smith, SV Maric, D Barker, JL AF Sukhareva, M Smith, SV Maric, D Barker, JL TI Functional properties of ryanodine receptors in hippocampal neurons change during early differentiation in culture SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INDUCED CALCIUM-RELEASE; CYCLIC ADP-RIBOSE; BULLFROG SYMPATHETIC NEURONS; CA2+ RELEASE; INTRACELLULAR CALCIUM; DEVELOPMENTAL-CHANGES; RAT-BRAIN; IMMUNOHISTOCHEMICAL LOCALIZATION; SUBCELLULAR-LOCALIZATION; CARDIAC DIHYDROPYRIDINE AB 6-((4,4-difluoro-5,7- dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl) amino) hexanoic acid ryanodine (BODIPY-ryanodine) binding and Ca2+ imaging were used to study the properties of ryanodine receptors (RyRs) and cytoplasmic Ca2+ (Ca-c(2+)) changes in neurons cultured from the embryonic rat hippocampus during the earliest stages of differentiation. Baseline Ca-c(2+) levels declined from 164 +/- 5 (SD) nM at early stages to 70 +/- 4 nM in differentiated neurons. Fluorescent BODIPY-ryanodine binding signals identified activated RyRs in somata, which were eliminated by removal of external Ca2+ or by blockage of Ca2+ entry through L-type but not N-type Ca2+ channels. The GABA synthesis inhibitor 3-mercaptopropionic acid completely abolished ryanodine binding. Caffeine or K+ depolarization inhibited the activity of RyRs at very early stages of differentiation but had stimulatory effects at later stages after a network of processes had formed. BayK-8644 stimulated RyRs throughout all regions of all differentiating cells. The results suggest that in differentiating embryonic hippocampal neurons the activity of RyRs is maintained via Ca2+ entering through L-type Ca2+ channels. The mode of activation of L-type voltage-gated Ca2+ channels with either membrane depolarization or specific pharmacological agents affects the coupled activity of RyRs differently as neurons differentiate processes and networks. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Sukhareva, M (reprint author), NINDS, Neurophysiol Lab, NIH, Bldg 36,Rm 2C19,36 Convent Dr, Bethesda, MD 20892 USA. NR 64 TC 12 Z9 12 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2002 VL 88 IS 3 BP 1077 EP 1087 DI 10.1152/jn.00557.2001 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 589MX UT WOS:000177764100001 PM 12205130 ER PT J AU Liu, QY Chang, YH Schaffner, AE Smith, SV Barker, JL AF Liu, QY Chang, YH Schaffner, AE Smith, SV Barker, JL TI Allopregnanolone activates GABA(A) receptor/Cl- channels in a multiphasic manner in embryonic rat hippocampal neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID NEUROACTIVE STEROIDS; NEUROSTEROID MODULATION; NERVOUS-SYSTEM; MECHANISM; CURRENTS; MASTOPARAN; ASTROCYTES; EXPRESSION; RELEASE; CELLS AB Although 3alpha-substituted metabolites of progesterone are well established to interact with GABA(A) receptor/Cl- channels, the nature of the interaction(s) remains uncertain. We used patch-clamp recording to study the interaction with GABA(A) receptor/Cl- channels expressed by embryonic hippocampal neurons differentiating in culture and nonneuronal cells transfected with GABA(A) receptor subunits. Allopregnanolone primarily induced multiphasic current responses in neurons, which were eliminated by bicuculline, an antagonist of GABA at GABA(A) receptor/Cl- channels. Similar multiphasic responses blocked by bicuculline were induced by allopregnanollone in nonneuronal cells transfected with alpha(1) and gamma(2) subunits, indicating that the steroid activation of GABA(A) receptor/Cl- channels occurred independently of GABA. Fluctuation analyses of current responses to allopregnanolone and GABA revealed underlying channel activities with similar estimated unitary properties. However, although both agonists activated Cl- channels with similar estimated short and long burst-length durations, most of those stimulated by the steroid were short, while most of those opened by GABA were long. Allopregnanolone potentiated GABA-evoked Cl- currents in nonneuronal cells transfected with alpha(1) and beta(2) or beta(3) subunits, which did not exhibit multiphasic responses to the steroid, indicating another, independent action of the steroid at activated receptors. Pertussis toxin treatment eliminated the low-amplitude current and attenuated the high-amplitude current induced by allopregnanolone in a reversible manner. Mastoparan, which activates G proteins directly, triggered a high-amplitude current after a delay, which was blocked by bicuculline. The results indicate that allopregnanolone interacts with GABA(A) receptor/Cl- channels expressed by embryonic hippocampal neurons in multiple ways, some of which are mediated by G proteins. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Barker, JL (reprint author), NINDS, Neurophysiol Lab, NIH, Bldg 36,Room 4A-21, Bethesda, MD 20892 USA. NR 31 TC 12 Z9 12 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2002 VL 88 IS 3 BP 1147 EP 1158 DI 10.1152/jn.00942.2001 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 589MX UT WOS:000177764100007 PM 12205136 ER PT J AU Lamar, M Lasarev, MR Libon, DJ AF Lamar, M Lasarev, MR Libon, DJ TI Determining levels of unawareness in dementia research SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the International-Neuropsychological-Society CY FEB 09-12, 2000 CL DENVER, COLORADO SP Int Neuropsychol Soc ID ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; AWARENESS; ANOSOGNOSIA; DEFICIT; DIAGNOSIS; SYMPTOMS; MODEL; STATE AB Clinical methods used to determine unawareness in dementia exist; however, their applicability to empirical research is limited. The authors present a statistically derived approach to determining unawareness that addresses these limitations. Dementia patients (n = 32) completed an awareness questionnaire. On an identical questionnaire, collateral sources (relatives or friends; n = 32) provided their best estimate of participants' abilities. The authors compared cluster analysis, the proposed empirical approach, to a currently used standard deviation cutoff score approach. Cluster analysis included all participants, displayed sound statistical properties, and was more sensitive to between-group differences in psychotic symptoms than standard deviation cutoff. Cluster analysis appears more appropriate for understanding the overall spectrum of unawareness in dementia research. C1 Drexel Univ, Neuropsychol Program, Philadelphia, PA 19104 USA. Crozer Chester Med Ctr, Neuropsychol Serv, Upland, PA USA. Oregon Hlth Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. MCP Hahnemann, Dept Psychiat, Philadelphia, PA USA. RP Lamar, M (reprint author), NIA, Lab Personal & Cognit, GRC, NIH, 5600 Nathan Shock Blvd, Baltimore, MD 21224 USA. OI Lasarev, Michael R/0000-0002-1896-2705 NR 21 TC 22 Z9 26 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2002 VL 14 IS 4 BP 430 EP 437 DI 10.1176/appi.neuropsych.14.4.430 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 611ZB UT WOS:000179047300006 PM 12426411 ER PT J AU Basheer, R Arrigoni, E Thatte, HS Greene, RW Ambudkar, IS McCarley, RW AF Basheer, R Arrigoni, E Thatte, HS Greene, RW Ambudkar, IS McCarley, RW TI Adenosine induces inositol 1,4,5-trisphosphate receptor-mediated mobilization of intracellular calcium stores in basal forebrain cholinergic neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE adenosine; cholinergic basal forebrain; A(1) adenosine receptor; intracellular calcium mobilization; inositol 1,4,5-trisphosphate receptor activation; sleep deprivation ID SLEEP-DEPRIVATION; PROLONGED WAKEFULNESS; HIPPOCAMPAL-NEURONS; RYANODINE RECEPTOR; PHOSPHOLIPASE-C; GENE-EXPRESSION; PROTEIN; RELEASE; BRAIN; RAT AB In the cholinergic basal forebrain, we found previously that the extracellular adenosine concentration increase that accompanies sleep deprivation, acting via the A(1) receptor, led to activation of the transcription factor nuclear factor-kappaB and to the upregulation of A(1) adenosine receptor mRNA. We thus began to examine intracellular signaling mechanisms. We report here that adenosine, acting in a dose-dependent manner and predominantly via A(1) receptors, stimulated IP3 receptor-regulated calcium release from intracellular stores. To the best of our knowledge, this calcium signaling pathway effect is a novel action of the G(i)-coupled A(1) adenosine receptor in neurons. Moreover, this calcium mobilization was not seen at all in noncholinergic neurons but was present in a large proportion of cholinergic neurons. These data suggest a potential role for a calcium-signaling pathway in adenosine-induced long-term effects of sleep deprivation and a key role for cholinergic neurons in this process. C1 Harvard Univ, Sch Med, Dept Psychiat, Vet Affairs Med Ctr, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Dept Neurol, Vet Affairs Med Ctr, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Dept Surg, Vet Affairs Med Ctr, W Roxbury, MA 02132 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Dallas Vet Affairs Med Ctr, Dallas, TX 75390 USA. NIDCR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. RP McCarley, RW (reprint author), Harvard Univ, Sch Med, 116A,940 Belmont St, Brockton, MA 02301 USA. RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [MH 39683] NR 58 TC 34 Z9 34 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 1 PY 2002 VL 22 IS 17 BP 7680 EP 7686 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 587CK UT WOS:000177622800040 PM 12196591 ER PT J AU Yamanaka, R Zullo, SA Ramsey, J Yajima, N Tsuchiya, N Tanaka, R Blaese, M Xanthopoulos, KG AF Yamanaka, R Zullo, SA Ramsey, J Yajima, N Tsuchiya, N Tanaka, R Blaese, M Xanthopoulos, KG TI Marked enhancement of antitumor immune responses in mouse brain tumor models by genetically modified dendritic cells producing Semliki Forest virus-mediated interleukin-12 SO JOURNAL OF NEUROSURGERY LA English DT Article DE dendritic cell; interleukin-12; Semliki Forest virus; gene therapy; brain neoplasm ID CYTOTOXIC T-LYMPHOCYTES; GENE-THERAPY; MURINE TUMORS; INTRATUMORAL INJECTION; INTRACRANIAL GLIOMAS; SINDBIS VIRUS; IN-VIVO; PEPTIDE; IL-12; RNA AB Object. The authors evaluated dendritic cell (DC)-based immunotherapy for malignant brain tumor to improve its therapeutic efficacy. Methods. Dendritic cells were isolated from bone marrow and pulsed with phosphate-buffered saline, Semliki Forest virus (SFV)-LacZ, retrovirus vector GCsap-interleukin (IL)-12, and SFV-IL-12, respectively, to treat mice bearing brain tumors of the B16 cell line. The results indicated that therapeutic immunization with DCs pulsed with SFV-IL-12 prolonged the survival of mice with established tumors. Semliki Forest virus induced apoptosis in DCs, which in turn facilitated the uptake of apoptotic cells by other DCs, thus providing a potential mechanism for enhanced immunogenicity. Conclusions. Therapy with DCs that have been pulsed with SFV-mediated IL-12 may be an excellent step in the development of new cancer vaccines. Intratumorally injected DCs that have been transiently transduced with IL-12 do not require pulsing of a source of tumor antigens to induce tumor regression. C1 Niigata Univ, Brain Res Inst, Dept Neurosurg, Niigata 9518585, Japan. NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD USA. RP Yamanaka, R (reprint author), Niigata Univ, Brain Res Inst, Dept Neurosurg, Asahimachi Dori 1-757, Niigata 9518585, Japan. NR 40 TC 38 Z9 42 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2002 VL 97 IS 3 BP 611 EP 618 DI 10.3171/jns.2002.97.3.0611 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 593JA UT WOS:000177986400016 PM 12296646 ER PT J AU Gewirtz, H Tawakol, A Bacharach, SL AF Gewirtz, H Tawakol, A Bacharach, SL TI Heterogeneity of myocardial blood flow and metabolism: Review of physiologic principles and implications for radionuclide imaging of the heart SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; SPATIAL HETEROGENEITY; PERFUSION-PRESSURE; CORONARY STENOSIS; PET/SPECT IMAGES; DOMESTIC SWINE; LEFT-VENTRICLE; CLOSED-CHEST; GATED SPECT; DOG HEARTS C1 Massachusetts Gen Hosp, Cardiac Unit, Dept Med, Boston, MA 02114 USA. NIH, Ctr Clin, Div Nucl Med, Bethesda, MD 20892 USA. RP Gewirtz, H (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Dept Med, Vincent Burnham 3,32 Blossom St, Boston, MA 02114 USA. NR 50 TC 7 Z9 7 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD SEP-OCT PY 2002 VL 9 IS 5 BP 534 EP 541 DI 10.1067/mnc.2002.125916 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 602JN UT WOS:000178502300012 PM 12360134 ER PT J AU Nesti, LJ Caterson, EJ Wang, M Chang, R Chapovsky, F Hoek, JB Tuan, RS AF Nesti, LJ Caterson, EJ Wang, M Chang, R Chapovsky, F Hoek, JB Tuan, RS TI TGF-beta 1 calcium signaling increases alpha 5 integrin expression in osteoblasts SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; COLLAGEN MESSENGER-RNA; FOCAL ADHESION KINASE; CELL-ADHESION; EXTRACELLULAR-MATRIX; SMAD PROTEINS; IN-VITRO; FIBRONECTIN; RECEPTORS; BONE AB TGF-beta1 is a potent osteoactive factor and exhibits a wide variety of effects on osteoblasts, most of which are mediated through receptor associated Smad proteins. We have recently reported a novel TGF-beta1 intracellular Ca2+ signaling pathway in osteoblasts, and found that this signaling is required for the TGF-beta1 mediated enhancement of osteoblast adhesion to substrate. Given that interaction between the extracellular matrix protein fibronectin and alpha5beta1 integrin on the cell surface is principally responsible for osteoblast substrate adhesion, we examined here whether the TGF-beta1 stimulated Ca2+ signal is involved in this pathway. Our results show that, in primary human osteoblasts, the TGF-beta1 induced intracellular Ca2+ signal is responsible, in part, for the stimulation of expression of alpha5 integrin, but not of beta1 integrin or fibronectin. Increased levels of alpha5 integrin protein and mRNA were seen as early as 12 h after TGF-beta1 treatment, but were inhibited by co-treatment of cells with nifedipine, a selective L-type Ca2+ channel blocker. TGF-beta1 treatment increased both fibronectin and beta1 integrin protein production within 48 h in a manner unaffected by co-treatment with nifedipine. Immunofluorescence observations revealed that TGF-beta1 treatment resulted in increased alpha5 integrin staining, and more prominent alpha5 integrin clustering, with increased co-localization with the actin cytoskeleton, effects that were blocked by co-treatment with nifedipine. The TGF-beta1 induced intracellular Ca2+ signal in human osteoblasts is thus an important mechanistic step in the regulation of alpha5 integrin expression, later contributing to enhanced cell adhesion. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. C1 Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. FU NIAAA NIH HHS [F30AA05516, AA08714, AA07186, AA07215]; NIAMS NIH HHS [AR44501]; NIDCR NIH HHS [DE11327, DE16864] NR 41 TC 19 Z9 19 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD SEP PY 2002 VL 20 IS 5 BP 1042 EP 1049 AR PII S0736-0266(02)00020-7 DI 10.1016/S0736-0266(02)00020-7 PG 8 WC Orthopedics SC Orthopedics GA 600GZ UT WOS:000178383400023 PM 12382972 ER PT J AU Noth, U Osyczka, AM Tuli, R Hickok, NJ Danielson, KG Tuan, RS AF Noth, U Osyczka, AM Tuli, R Hickok, NJ Danielson, KG Tuan, RS TI Multilineage mesenchymal differentiation potential of human trabecular bone-derived cells SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE trabecular bone; osteoblasts; mesenchymal progenitors; chondrogenesis; osteogenesis; adipogenesis ID MARROW STROMAL CELLS; CHICK EMBRYONIC CALVARIA; STEM-CELLS; IN-VITRO; MORPHOGENETIC PROTEIN-2; CHONDROGENIC DIFFERENTIATION; CALCIUM DEFICIENCY; OSTEOBLASTIC CELLS; GENE-EXPRESSION; INVITRO AB Explant cultures of adult human trabecular bone fragments give rise to osteoblastic cells that are known to express osteoblast-related genes and mineralize extracellular matrix. These osteoblastic cells have also been shown to undergo adipogenesis in vitro and chondrogenesis in vivo. Here we report the in vitro developmental potential of adult human osteoblastic cells (hOB) derived from explant cultures of collagenase-pretreated trabecular bone fragments. In addition to osteogenic and adipogenic differentiation, these cells are capable of chondrogenic differentiation in vitro in a manner similar to adult human bone marrow-derived mesenchymal progenitor cells. High-density pellet cultures of hOB maintained in chemically defined serum-free medium, supplemented with transforming growth factor-beta1, were composed of morphologically distinct, chondrocyte-like cells expressing mRNA transcripts of collagen types II, IX and X, and aggrecan. The cells within the high-density pellet cultures were surrounded by a sulfated proteoglycan-rich extracellular matrix that immunostained for collagen type II and proteoglycan link protein. Osteogenic differentiation of hOB was verified by an increased number of alkaline phosphatase-positive cells, that expressed osteoblast-related transcripts such as alkaline phosphatase, collagen type 1, osteopontin and osteocalcin, and formed mineralized matrix in monolayer cultures treated with ascorbate, beta-glycerophosphate, and bone morphogenetic protein-2. Adipogenic differentiation of hOB was determined by tHe appearance of intracellular lipid droplets, and expression of adipocyte-specific genes, Such as lipoprotein lipase and peroxisome proliferator-activated receptor gamma2, in monolayer cultures treated with dexamethasone, indomethacin, insulin and 3-isobtityl-1-methylxanthine. Taken together, these results show that cells derived from collagenase-treated adult human trabecular bone fragments have the potential to differentiate into multiple mesenchymal lineages in vitro. indicating their developmental plasticity and suggesting their mesenchymal progenitor nature. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, 50 South Dr,Room 1503,Bldg 50, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA 71602, R25 CA 69277]; NIAMS NIH HHS [AR 44501, AR 39740, AR 45181]; NIDCR NIH HHS [DE 11327, DE 12864] NR 70 TC 299 Z9 321 U1 1 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD SEP PY 2002 VL 20 IS 5 BP 1060 EP 1069 AR PII S0736-0266(02)00018-9 DI 10.1016/S0736-0266(02)00018-9 PG 10 WC Orthopedics SC Orthopedics GA 600GZ UT WOS:000178383400025 PM 12382974 ER PT J AU Chan, CC Koch, CA Kaiser-Kupfer, MI Parry, DM Gutmann, DH Zhuang, ZP Vortmeyer, AO AF Chan, CC Koch, CA Kaiser-Kupfer, MI Parry, DM Gutmann, DH Zhuang, ZP Vortmeyer, AO TI Loss of heterozygosity for the NF2 gene in retinal and optic nerve lesions of patients with neurofibromatosis 2 SO JOURNAL OF PATHOLOGY LA English DT Article DE retina; hamartoma; loss of heterozygosity; merlin; neurofibromatosis 2; optic nerve glioma; retinal dysplasia; Lisch nodule ID TUBEROUS SCLEROSIS COMPLEX; TUMOR-SUPPRESSOR; PIGMENT EPITHELIUM; COMBINED HAMARTOMA; LENS OPACITIES; TYPE-2 GENE; EXPRESSION; ABNORMALITIES; CHROMOSOME-22; ASSOCIATION AB Individuals affected with the neurofibromatosis 2 (NF2) cancer predisposition syndrome develop specific ocular lesions. To determine whether these lesions result from altered NF2 gene expression, microdissection and PCR were used to investigate 40 ocular lesions from seven eyes of four NF2 patients for LOH, with markers that flank the NF2 gene on chromosome 22q. NF2 protein (merlin) expression was also evaluated in these lesions, using immunohistochemistry. Retinal hamartoma was observed in an seven eyes, including one with combined pigment epithelial and retinal hamartoma (CPERH). Retinal tufts were present in four eyes (three patients), retinal dysplasia in two eyes (two patients), optic nerve neurofibroma in one eye, iris naevoid hyperplasia in two eyes (two patients) and pseudophakia in all eyes. Markers were informative in three patients (six eyes from three unrelated families). One patient was non-informative due to prolonged decalcification. All retinal and optic nerve, but not iris lesions, demonstrated consistent LOH for the NF2 gene. Merlin was not expressed in the retina, optic nerve, or iris lesions. These results suggest that inactivation of the NF2 gene is associated with the formation of a variety of retinal and optic nerve lesions in NF2 patients. Copyright (C) 2002 John Wiley Sons, Ltd. C1 NEI, NIH, Bethesda, MD 20892 USA. NICH, NIH, Bethesda, MD USA. NCI, DCEG, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Chan, CC (reprint author), NEI, NIH, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM ccc@helix.nih.gov RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 FU Intramural NIH HHS [Z01 EY000222-22] NR 47 TC 14 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 EI 1096-9896 J9 J PATHOL JI J. Pathol. PD SEP PY 2002 VL 198 IS 1 BP 14 EP 20 DI 10.1002/path.1174 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 591VZ UT WOS:000177902100003 PM 12210058 ER PT J AU Starc, TJ Lipshultz, SE Easley, KA Kaplan, S Bricker, JT Colan, SD Lai, WW Gersony, WM Sopko, G Moodie, DS Schluchter, MD AF Starc, TJ Lipshultz, SE Easley, KA Kaplan, S Bricker, JT Colan, SD Lai, WW Gersony, WM Sopko, G Moodie, DS Schluchter, MD CA Pediat Pulm Cardiovascular Complic TI Incidence of cardiac abnormalities in children with human immunodeficiency virus infection: The Prospective (PCHIV)-C-2-H-2 Study SO JOURNAL OF PEDIATRICS LA English DT Article ID LEFT-VENTRICULAR STRUCTURE; PEDIATRIC-PATIENTS; HIV-INFECTION; MULTICENTER; CARDIOMYOPATHY; MORTALITY; INFANTS; HEART; CONTRACTILITY; EXPERIENCE AB Objective: To describe the 5-year cumulative incidence of cardiac dysfunction in human immunodeficiency virus (HIV)infected children. Study design: We used a prospective cohort design, enrolling children at 10 hospitals. Group I included 205 vertically HIV-Infected children enrolled at a median age of 1.9 years. Group 11 consisted of 600 HIV-exposed children enrolled prenatally or as neonates, of whom 93 were ultimately HIV-Infected. The main outcome measures were echocardiographic indexes of left ventricular dysfunction. Results: In group 1, the 5-year cumulative incidence of left ventricular fractional shortening! 25% was 28.0%. The 5-year incidence of left ventricular end-diastolic dilatation was 21.7%, and heart failure and/or the use of cardiac medications 28.8%. The mortality rate I year after the diagnosis of heart failure was 52.5% [95% Cl, 30.5-74.5]. Within group II, the 5-year cumulative incidence of decreased fractional shortening was 10.7% in the HIV-Infected compared with 3.1% in the HIV-uninfected children (P =.01). Left ventricular dilation, heart failure, and/or the use of cardiac medications were more common in infected compared with uninfected children. Conclusions: During 5 years of follow-up, cardiac dysfunction occurred in 18% to 39% of HIV-Infected children and was associated with an increased risk of death. We recommend that HIV-infected children undergo routine echocardiographic surveillance, for cardiac abnormalities. C1 Columbia Univ, Presbyterian Hosp, Dept Pediat, Div Pediat Cardiol,Coll Phys & Surg, New York, NY USA. Mt Sinai Sch Med, Dept Pediat, Div Pediat Cardiol, New York, NY USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Pediat, Div Pediat Cardiol, Los Angeles Med Ctr, Los Angeles, CA 90024 USA. Cleveland Clin Fdn, Div Pediat Cardiol, Dept Biostat & Epidemiol, Cleveland, OH USA. Cleveland Clin Fdn, Div Pediat Cardiol, Dept Pediat, Cleveland, OH USA. Baylor Coll Med, Div Pediat Cardiol, Dept Pediat, Houston, TX 77030 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Starc, TJ (reprint author), Babies & Childrens Hosp, Columbia Presbyterian Med Ctr, 630 W 168th St,2 N,Room 260, New York, NY 10032 USA. RI Easley, Kirk/K-6910-2015 OI Easley, Kirk/0000-0003-4419-2617 FU NCRR NIH HHS [RR-00865, RR-00685, RR-00043, M01 RR000865, M01 RR000043, M01 RR000533, RR-00071, RR-00188, K01 RR000188, RR-00533, M01 RR000188, M01 RR000071, M01 RR002172, M01 RR000645, RR-02172, RR-00645]; NHLBI NIH HHS [N01-HR-96038, N01-HR-96041, N01 HR096037, N01 HR096043, N01-HR-96039, N01-HR-96042, N01-HR-96040] NR 30 TC 36 Z9 36 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2002 VL 141 IS 3 BP 327 EP 335 DI 10.1067/mpd.2002.126301 PG 9 WC Pediatrics SC Pediatrics GA 593EQ UT WOS:000177978500008 PM 12219051 ER PT J AU Carlo, WA Stark, AR Wright, LL Tyson, JE Papile, LA Shankaran, S Donovan, EF Oh, W Bauer, CR Saha, S Poole, WK Stoll, B AF Carlo, WA Stark, AR Wright, LL Tyson, JE Papile, LA Shankaran, S Donovan, EF Oh, W Bauer, CR Saha, S Poole, WK Stoll, B CA Natl Inst Child Hlth Human Dev Neo TI Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birth-weight infants SO JOURNAL OF PEDIATRICS LA English DT Article ID CHRONIC LUNG-DISEASE; RISK-FACTORS; INJURY; BAROTRAUMA; POPULATION; LAMBS; RABBITS; VOLUME; TRIAL; RATES AB Objective: To determine whether minimal ventilation decreases death or bronchopulmonary dysplasia (BPD). Study design: Infants with birth weight 501 g to 1000 g and mechanically ventilated before 12 hours were randomly assigned to minimal ventilation (partial pressure of carbon dioxide [PCO2] target >52 mm Hg) or routine ventilation (PCO2 target <48 mm Hg) and a tapered dexamethasone course or saline placebo for 10 days, using a 2 X 2 factorial design. The primary outcome was death or BPD at 36 weeks' postmenstrual age. Results: After enrollment of 220 patients, the trial was halted because of unanticipated nonrespiratory adverse events related to dexamethasone therapy. The relative risk for death or BPD at 36 weeks in the minimal versus routine ventilation groups was 0.93 (95% CI, 0.77-1.12; P =.43). Ventilator support at 36 weeks was 1% in the minimal versus 16% in the routine group (P <.01). Major morbidities and long-term outcome were comparable in both treatment groups. Conclusions: With the sample size studied, minimal ventilation did not reduce the incidence of death or BPD. The reduced ventilator support at 36 weeks in the minimal ventilation group warrants further study of this intervention. C1 Univ Alabama, Div Neonatol, Birmingham, AL 35233 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NICHHD, Rockville, MD USA. Univ Texas, Houston, TX USA. Univ New Mexico, Albuquerque, NM 87131 USA. Wayne State Univ, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Brown Univ, Women & Infants Hosp Rhode Isl, Providence, RI 02912 USA. Univ Miami, Coral Gables, FL 33124 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Emory Univ, Atlanta, GA 30322 USA. RP Carlo, WA (reprint author), Univ Alabama, Div Neonatol, 525 New Hillman Bldg,619 S 19th St, Birmingham, AL 35233 USA. FU NCRR NIH HHS [M01 RR02635, M01 RR00070, M01 RR00997, M01 RR02172, M01 RR06022, M01 RR08084]; NICHD NIH HHS [U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34167, U10 HD34216, U10 HD36790] NR 26 TC 81 Z9 85 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2002 VL 141 IS 3 BP 370 EP 375 DI 10.1067/mpd.2002.127507 PG 6 WC Pediatrics SC Pediatrics GA 593EQ UT WOS:000177978500014 PM 12219057 ER PT J AU Lung, FDT Tsai, JY Wei, SY Cheng, JW Chen, C Li, P Roller, PP AF Lung, FDT Tsai, JY Wei, SY Cheng, JW Chen, C Li, P Roller, PP TI Novel peptide inhibitors for Grb2 SH2 domain and their detection by surface plasmon resonance SO JOURNAL OF PEPTIDE RESEARCH LA English DT Article DE BIAcore X; Grb2; pepticles; Ras; SH2 domain; signal transduction pathway; surface plasmon resonance ID HIGH-AFFINITY; NONPHOSPHORYLATED INHIBITOR; LIGANDS; BINDING; REQUIREMENTS; ADAPTER; PROTEIN AB One of the critical intracellular signal transduction pathways involves the binding of the Grb2 SH2 domain to the phosphotyrosine (pTyr) motifs on growth factor receptors, such as epidermal growth factor receptor (EGFR) and erbB2, leading to downstream activation of the oncogenic Ras signaling pathway. Therefore, the Grb2 SH2 domain has been chosen as our target for the development of potential anticancer agents. As a continuation of our earlier work, herein we report the design and synthesis of new peptide analogs, and their inhibitory effect on the Grb2 SH2 domain using surface plasmon resonance (SPR) technology. These novel agents do not contain phosphotyrosine or phosphotyrosine mimics. Binding interactions between these peptides and the Grb2 SH2 domain were measured and analyzed using a BIAcore X instrument, which provides detailed information on the real-time detection of the binding interaction. The results of this study should provide important information for the further development of peptides or peptidomimetics with high affinity for the Grb2 SH2 domain. C1 China Med Coll, Dept Nutr, Taichung 404, Taiwan. Natl Tsing Hua Univ, Dept Life Sci, Div Struct Biol & Biomed Sci, Hsinchu 300, Taiwan. Acad Sinica, Inst Biomed Sci, Tokyo 115, Japan. NCI, Frederick Canc Res & Dev Ctr, Med Chem Lab, Frederick, MD 21702 USA. RP Lung, FDT (reprint author), China Med Coll, Dept Nutr, Taichung 404, Taiwan. NR 21 TC 11 Z9 11 U1 1 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-002X J9 J PEPT RES JI J. Pept. Res. PD SEP PY 2002 VL 60 IS 3 BP 143 EP 149 DI 10.1034/j.1399-3011.2002.02998.x PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 592RR UT WOS:000177951100001 PM 12213123 ER PT J AU Hyman, JJ Winn, DM Reid, BC AF Hyman, JJ Winn, DM Reid, BC TI The role of cigarette smoking in the association between periodontal disease and coronary heart disease SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE coronary disease/etiology; National Health and Nutrition Examination Survey III; periodontal diseases/complications; risk factors; smoking/adverse effects ID ACUTE MYOCARDIAL-INFARCTION; SELF-REPORTED HISTORY; CARDIOVASCULAR-DISEASE; DENTAL INFECTIONS; ATTACHMENT LOSS; RISK-FACTORS; ORAL HEALTH; POPULATION; ATHEROSCLEROSIS; SMOKERS AB Background: Cigarette smoking is a significant risk factor for both coronary heart disease and periodontal disease. The goal of this study was to better understand the role of smoking in the relationship between periodontal disease and heart attack history. Methods: The study population consisted of 5,285 participants in the Third National Health and Nutrition Examination Survey (NHANES) during 1988-1994 and who were age 40 years or older when examined. The data analysis employed logistic regression models and accounted for the complex sampling design used in NHANES. Results: After adjustment for potential confounders, we only found significant associations between periodontal loss of attachment (LOA) and heart attack history for smokers, with odds ratios and 95% confidence interval (CI) of 2.64 (1.48 to 4.71), 3.84 (1.22 to 12.10) and 5.87 (1.91 to 18.00) for those with 2.0 to 2.99, 3.0 to 3.99, and 4 mm or more mean LOA, respectively. When the analysis was stratified by smoking status and tertile of age at heart attack, the statistically significant associations were limited to smokers who had a heart attack between the ages of 25 and 50 years, with odds ratios and 95% CI associated with increasing mean LOA for this group of 3.29 (1.35 to 8.04), 7.32 (1.60 to 33.51), and 8.04 (1.91 to 18.00), respectively. Conclusions: These results suggest that cigarette smoking is a necessary cofactor in the relationship between periodontal disease and coronary heart disease, and the increase in risk appears to be age dependent. However, the key role played by smoking in the etiology of both periodontal and heart diseases makes it difficult to determine how much of the observed association resulted from periodontal disease. C1 NIDCR, Off Sci Policy & Anal, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Maryland, Sch Dent, Dept Oral Hlth Care Delivery, Baltimore, MD 21201 USA. RP Hyman, JJ (reprint author), NIDCR, Off Sci Policy & Anal, Room 3AN-38J,MSC 6401,45 Ctr Dr, Bethesda, MD 20892 USA. EM hymanj@email.nidr.nih.gov NR 45 TC 31 Z9 31 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 EI 1943-3670 J9 J PERIODONTOL JI J. Periodont. PD SEP PY 2002 VL 73 IS 9 BP 988 EP 994 DI 10.1902/jop.2002.73.9.988 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 593UJ UT WOS:000178011800003 PM 12296599 ER PT J AU Yono, M Takahashi, W Pouresmail, M Johnson, DR Foster, HE Weiss, RM Latifpour, J AF Yono, M Takahashi, W Pouresmail, M Johnson, DR Foster, HE Weiss, RM Latifpour, J TI Quantification of endothelins, their receptors, and endothelin-converting enzyme mRNAs in rat genitourinary tract using real-time RT-PCR SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Article DE endothelins; genitourinary tract; methods; rat; real-time RT-PCR ID SYBR GREEN-I; SMOOTH-MUSCLE; FUNCTIONAL EXPRESSION; HUMAN PROSTATE; VAS-DEFERENS; CLONING; CDNA; SUBTYPES; CELLS; TRANSCRIPTS AB Introduction: Quantification of mRNA expression is essential for the assessment of endothelin (ET) receptor-mediated mechanisms. Recently, a novel technique for the determination of mRNA expression, termed real-time reverse transcription polymerase chain reaction (RTPCR), has been developed. We therefore applied real-time PCR using SYBR Green I to quantify ET-1, ET-3, ET-converting enzyme-1 (ECE-1), and ETA and ETB receptor subtype mRNA expression in the rat genitourinary tract. Methods: The cDNA was synthesized by RT of RNA extracted from the rat bladder, ventral prostate, dorsolateral prostate, and vas deferens. All steps subsequent to the RT reaction were carried out by the thermal cycler/detector and computer-assisted programs processed a quantitative result. Results: Designing optimal primer sequences that minimized primer-dimer formation and adjusting annealing temperatures that prevented nonspecific product amplification have made it possible to identify a single peak in the melt curve and to obtain an appropriate standard curve for each gene transcript. In our experiments, input cDNA levels as low as 100 copies of the product could be detected. Discussion: We demonstrated that significant quantitative variations existed in the expression levels of ET-1, ET-3, ECE-1, and ETA and ETB receptor subtype mRNAs within a tissue and between different regions of the genitourinary tract and that the predominant expression of ETs and their receptor mRNAs in all tissues studied were ET-1 and the ETA receptor subtype, respectively. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Yale Univ, Sch Med, Urol Sect, New Haven, CT 06520 USA. Kumamoto Univ, Sch Med, Dept Urol, Kumamoto 860, Japan. NIAID, DAIT, Clin Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Latifpour, J (reprint author), Yale Univ, Sch Med, Urol Sect, 333 Cedar St,POB 208041, New Haven, CT 06520 USA. FU NIDDK NIH HHS [DK 38311, DK 42530] NR 36 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8719 J9 J PHARMACOL TOXICOL JI J. Pharmacol. Toxicol. Methods PD SEP-OCT PY 2002 VL 48 IS 2 BP 87 EP 95 DI 10.1016/S1056-8719(03)00022-4 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 720UB UT WOS:000185277400003 PM 14565565 ER PT J AU Perry, T Haughey, NJ Mattson, MP Egan, JM Greig, NH AF Perry, T Haughey, NJ Mattson, MP Egan, JM Greig, NH TI Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID FOREBRAIN CHOLINERGIC SYSTEM; NERVE GROWTH-FACTOR; RAT-BRAIN; BODY-WEIGHT; ALZHEIMERS-DISEASE; BINDING-SITES; RECEPTOR; EXPRESSION; MICE; IMMUNOLESIONS AB Glucagon-like peptide-1 (7-36)-amide (GLP-1) is an endogenous insulinotropic peptide that is secreted from the L cells of the gastrointestinal tract in response to food. It has potent effects on glucose-dependent insulin secretion, insulin gene expression, and pancreatic islet cell formation. In type 2 diabetes, GLP-1, by continuous infusion, can normalize blood glucose and is presently being tested in clinical trials as a therapy for this disease. More recently, GLP-1 has been found to have central nervous system (CNS) effects and to stimulate neurite outgrowth in cultured cells. We now report that GLP-1, and its longer-acting analog exendin-4, can completely protect cultured rat hippocampal neurons against glutamate-induced apoptosis. Extrapolating these effects to a well defined rodent model of neurodegeneration, GLP-1 and exendin-4 greatly reduced ibotenic acid-induced depletion of choline acetyltransferase immunoreactivity in basal forebrain cholinergic neurons. These findings identify a novel neuroprotective/neurotrophic function of GLP-1 and suggest that such peptides may have potential for halting or reversing neurodegenerative processes in CNS disorders, such as Alzheimer's disease, and in neuropathies associated with type 2 diabetes mellitus. C1 NIA, Sect Drug Design & Dev, Neurosci Lab, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. NIA, Sect Cellular & Mol Neurosci, Neurosci Lab, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. NIA, Diabet Sect, Clin Invest Lab, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Perry, T (reprint author), NIA, Sect Drug Design & Dev, Neurosci Lab, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 43 TC 185 Z9 203 U1 3 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2002 VL 302 IS 3 BP 881 EP 888 AR UNSP 37481/1001757 DI 10.1124/jpet.102.037481 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 584LB UT WOS:000177467100006 PM 12183643 ER PT J AU Liu, YX Qin, LY Wilson, BC An, LJ Hong, JS Liu, B AF Liu, YX Qin, LY Wilson, BC An, LJ Hong, JS Liu, B TI Inhibition by naloxone stereoisomers of beta-amyloid peptide (1-42)-induced superoxide production in microglia and degeneration of cortical and mesencephalic neurons SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ISCHEMIC-HEART-DISEASE; ALZHEIMERS-DISEASE; NITRIC-OXIDE; DOPAMINERGIC-NEURONS; INDUCED HYPERACTIVITY; ACTIVATED MICROGLIA; INFLAMMATORY DAMAGE; OPIATE ANTAGONISTS; SUBSTANTIA-NIGRA; CELL-DEATH AB Previously we reported that naloxone stereoisomers, in an opioid receptor-independent manner, attenuated the inflammation-mediated degeneration of dopaminergic neurons by inhibition of the activation of microglia, the resident immune cells in the brain. Recently we discovered that beta-amyloid peptide Abeta (1-42) exhibited enhanced neurotoxicity toward both cortical and mesencephalic neurons through the activation of microglia and production of superoxide. The purpose of this study was to determine whether naloxone isomers had any effect on Abeta (1-42)-induced neurodegeneration. Pretreatment of either cortical or mesencephalic neuron-glia cultures with 1 to 10 muM (-)-naloxone, prior to treatment for up to 11 days with 0.1 to 3 muM Abeta (1-42), afforded significant neuroprotection as judged by neurotransmitter uptake, immunocytochemical analysis, and cell counting. More importantly, (+)-naloxone, the ineffective enantiomer of (-)-naloxone in binding opioid receptors, was equally effective in affording neuroprotection. Mechanistically, inhibition of Abeta (1-42)- induced production of superoxide in microglia underlay the neuroprotective effect of naloxone stereoisomers. Moreover, neuroprotection and inhibition of Abeta (1-42)- induced superoxide production was also achieved with naloxone methiodide, a charged analog with quaternary amine, suggesting that the site of action for naloxone isomers is at the cell surface of microglia. These results demonstrated that naloxone isomers, through mechanisms unrelated to the opioid receptors, were capable of inhibiting Abeta(1-42)- induced microglial activation and degeneration of both cortical and mesencephalic neurons. Combined with our previous observations with inflammagen-induced neurodegeneration, naloxone analogs, especially (+)-naloxone, may have potential therapeutic efficacy for the treatment of Alzheimer's and Parkinson's disease. C1 Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Neuropharmacol Sect, NIH, Res Triangle Pk, NC 27709 USA. Dalian Univ Technol, Dept Bioengn, Dalian, Peoples R China. RP Liu, B (reprint author), Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Neuropharmacol Sect, NIH, MD F1-01,POB 12233, Res Triangle Pk, NC 27709 USA. RI liu, Bin/A-7695-2009 NR 62 TC 74 Z9 81 U1 0 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2002 VL 302 IS 3 BP 1212 EP 1219 AR UNSP 35956/1005694 DI 10.1124/jpet.102.035956 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 584LB UT WOS:000177467100045 PM 12183682 ER PT J AU Pandeya, SN Raja, AS Stables, JR AF Pandeya, SN Raja, AS Stables, JR TI Synthesis of isatin semicarbazones as novel anticonvulsants - role of hydrogen bonding SO JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES LA English DT Article ID POTENTIAL ANTICONVULSANTS AB Purpose: A series of substituted isatin semicarbazones and related bioisosteric hydrazones were designed and synthesised to meet the structural requirements essential for anticonvulsant properties. Methods: The structures of all synthesised compounds were confirmed by means of infrared, proton magnetic resonance spectroscopy and by elemental analyses. All compounds were evaluated for their anticonvulsant activity by maximal electroshock (MES), subcutaneous metrazol (ScMet) and subcutaneous strychnine (ScSty) induced seizure methods and their neurotoxic effects were determined by rotorod test. Results: A number of isatin semicarbazones exhibited significant protection after intraperitoneal administration at the dose of 100 and 300mg/kg. Some of them showed good anticonvulsant activity in MES test in rats after per oral administration at the dose of 30mg/kg. The bioisosteric hydrazone derivatives were inactive in all tests. Compound 6-chloroisatin-3- (4-bromophenyl)-semicarbazone has emerged as the most active analogue of the series showing good activity in all the three tests and was more active than phenytoin and valproic acid. Conclusions: The results evidenced the importance of hydrogen bonding and suggested a new pharmacophore model with four binding sites essential for anticonvulsant activity. C1 Banaras Hindu Univ, Inst Technol, Dept Pharmaceut, Varanasi 221005, Uttar Pradesh, India. Natl Inst Neurol Disorders & Stroke, Epilepsy Branch, NIH, Bethesda, MD USA. RP Pandeya, SN (reprint author), Banaras Hindu Univ, Inst Technol, Dept Pharmaceut, Varanasi 221005, Uttar Pradesh, India. NR 17 TC 6 Z9 6 U1 0 U2 5 PU CANADIAN SOC PHARMACEUTICAL SCIENCES PI EDMONTON PA 3118 DENTISTRY-PHARMACY CENTRE UNIV ALBERTA CAMPUS, EDMONTON, ALBERTA T6G2N8, CANADA SN 1482-1826 J9 J PHARM PHARM SCI JI J. Pharm. Pharm. Sci. PD SEP-DEC PY 2002 VL 5 IS 3 BP 275 EP 280 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 634FY UT WOS:000180330400009 ER PT J AU Stefan, K Kunesch, E Benecke, R Cohen, LG Classen, J AF Stefan, K Kunesch, E Benecke, R Cohen, LG Classen, J TI Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID LONG-TERM POTENTIATION; METHYL-D-ASPARTATE; MAGNETIC STIMULATION; INTRACORTICAL INHIBITION; NONOPIOID ANTITUSSIVES; HORIZONTAL CONNECTIONS; CORTICAL PLASTICITY; NEOCORTEX; DEXTROMETHORPHAN; INDUCTION AB Associative stimulation has been shown to enhance excitability in the human motor cortex (Stefan et al. 2000); however, little is known about the underlying mechanisms. An interventional paired associative stimulation (IPAS) was employed consisting of repetitive application of single afferent electric stimuli, delivered to the right median nerve, paired with single pulse transcranial magnetic stimulation (TMS) over the optimal site for activation of the abductor pollicis brevis muscle (APB) to generate approximately synchronous events in the primary motor cortex. Compared to baseline, motor evoked potentials (MEPs) induced by unconditioned, single TMS pulses increased after IPAS. By contrast, intracortical inhibition, assessed using (i) a suprathreshold test TMS pulse conditioned by a subthreshold TMS pulse delivered 3 ins before the test pulse, and (ii) a suprathreshold test TMS pulse conditioned by afferent median nerve stimulation delivered 25 ins before the TMS pulse, remained unchanged when assessed with appropriately matching test stimulus intensities. The increase of single-pulse TMS-evoked MEP amplitudes was blocked when IPAS was performed under the influence of dextromethorphan, an N-methyl-D-aspartate (NMDA) receptor antagonist known to block long-term potentiation (LTP). Further experiments employing the double-shock TMS protocol suggested that the afferent pulse, as one component of the IPAS protocol, induced disinhibition of the primary motor cortex at the time when the TMS pulse, as the other component of IPAS, was delivered. Together, these findings support the view that LTP-like mechanisms may underlie the cortical plasticity induced by IPAS. C1 Univ Wurzburg, Neurol Klin, Dept Neurol, Human Cort Pyhysiol & Motor Control Lab, D-97080 Wurzburg, Germany. Univ Rostock, Dept Neurol, D-18157 Rostock, Germany. NINDS, Human Cort Physiol Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Classen, J (reprint author), Univ Wurzburg, Neurol Klin, Dept Neurol, Human Cort Pyhysiol & Motor Control Lab, Josef Schneider Str 11, D-97080 Wurzburg, Germany. NR 42 TC 339 Z9 343 U1 2 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP 1 PY 2002 VL 543 IS 2 BP 699 EP 708 DI 10.1113/jphysiol.2002.023317 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 596VB UT WOS:000178186200026 PM 12205201 ER PT J AU Bateson, A Tenn, C Tanay, V Todd, K Hope, B Nakabeppu, Y AF Bateson, A Tenn, C Tanay, V Todd, K Hope, B Nakabeppu, Y TI Chronic exposure to benzodiazepine agonists produces a delayed but transient increase in FOSB gene products in rat striatum SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychopharmacology CY JUL 21-24, 2002 CL HARROGATE, ENGLAND C1 Univ Leeds, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England. Univ Alberta, Dept Pharmacol, Edmonton, AB T6G 2M7, Canada. Univ Alberta, Dept Psychiat, Edmonton, AB T6G 2M7, Canada. NINDS, MPS, NIH, Bethesda, MD 20892 USA. Kyushu Univ, Dept Biochem, Fukuoka 812, Japan. RI Hope, Bruce/A-9223-2010; Nakabeppu, Yusaku/A-8902-2011 OI Hope, Bruce/0000-0001-5804-7061; NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2002 VL 16 IS 3 SU S MA E7 BP A48 EP A48 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 595EN UT WOS:000178094000192 ER PT J AU Tohen, M Baker, RW Altshuler, L Zarate, CA Suppes, T Ketter, TA Risser, R Brown, E Luther, MF Gilmore, JA AF Tohen, M Baker, RW Altshuler, L Zarate, CA Suppes, T Ketter, TA Risser, R Brown, E Luther, MF Gilmore, JA TI Olanzapine versus divalproex sodium for bipolar mania: A 47-week study SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychopharmacology CY JUL 21-24, 2002 CL HARROGATE, ENGLAND C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NIMH, Bethesda, MD 20892 USA. Univ Texas, Dallas, TX 75230 USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2002 VL 16 IS 3 SU S MA D42 BP A46 EP A46 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 595EN UT WOS:000178094000182 ER PT J AU Gerard, HC Wang, Z Whittum-Hudson, JA El-Gabalawy, H Goldbach-Mansky, R Bardin, T Schumacher, HR Hudson, AP AF Gerard, HC Wang, Z Whittum-Hudson, JA El-Gabalawy, H Goldbach-Mansky, R Bardin, T Schumacher, HR Hudson, AP TI Cytokine and chemokine mRNA produced in synovial tissue chronically infected with Chlamydia trachomatis and C-pneumoniae SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE cytokines; synovial infection; Chlamydiae; transcription ID REACTIVE ARTHRITIS; GENE-EXPRESSION; UNDIFFERENTIATED OLIGOARTHRITIS; PERSISTENT INFECTION; DNA; PCR; TYPE-1; CELLS AB Objective. We used a highly quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay system to define the steady-state levels of mRNA encoding a large panel of soluble mediators of inflammation in synovial tissues from patients with chronic arthritis infected with Chlamydia trachomatis versus C pneumoniae. Methods. RNA/cDNA was prepared from synovial biopsies of 4 patients with chronic arthritis and joint infection with C. trachomatis, 6 with C. pneumoniae at that site, 3 uninfected healthy controls, and 3 patients with undifferentiated oligoarthritis (UO) who were PCR negative for all organisms assayed. Real-time RT-PCR was used to assess relative mRNA levels from 12 cytokine and 2 chemokine genes (IL-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-gamma, TNF-alpha, MCP-1, RANTES). Input loading was normalized to 18S rRNA. Data were obtained for each mRNA from each sample in triplicate in comparison to the same mRNA level in the controls. Results. In most C. trachomatis infected synovial tissue samples, high levels of IL-40 mRNA were present, with less mRNA for IL-8, IL-15, IFN-gamma, and TNF-alpha. Synovial tissues from chronic arthritis patients with synovial C pneumoniae showed significant levels, of mRNA solely for IL-8 and IL-18. All other cytokine messengers assessed in each sample from each patient group were at or near control level. One patient with C. pneumoniae showed a high transcript level for RANTES, and one patient with C trachomatis showed a high transcript level for MCP-1. No patient with UO showed elevated messenger level for any cytokines assayed, but RANTES mRNA was elevated in each. Conclusion. Our data suggest that while both C. trachomatis and C. pneumoniae have been associated with inflammatory joint disease, each elicits a somewhat different steady-state profile of mRNA encoding relevant cytokines and chemokines during chronic infection of synovial tissue. Precisely how these differing profiles relate to clinical aspects of synovial inflammation will require further study, but the observations confirm and extend data indicating potentially important differences in the pathobiology of these 2 bacterial species. C1 Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Internal Med, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Ophthalmol, Detroit, MI 48201 USA. DVA Med Ctr, Detroit, MI USA. NIAMS, Arthrit & Rheumatism Branch, NIH, Bethesda, MD USA. Hop Lariboisiere, Federat Rhumatol, F-75475 Paris, France. Univ Penn, Sch Med, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. RP Hudson, AP (reprint author), Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Gordon H Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. FU NIAID NIH HHS [AI-44055, AI-44493]; NIAMS NIH HHS [AR-42541, AR-47186] NR 39 TC 44 Z9 44 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 2002 VL 29 IS 9 BP 1827 EP 1835 PG 9 WC Rheumatology SC Rheumatology GA 590LX UT WOS:000177825300006 PM 12233874 ER PT J AU Pianta, RC AF Pianta, RC TI Untitled SO JOURNAL OF SCHOOL PSYCHOLOGY LA English DT Editorial Material C1 Univ Virginia, NICHD Study Early Child Care & Youth Dev, Charlottesville, VA 22908 USA. RP Pianta, RC (reprint author), Univ Virginia, NICHD Study Early Child Care & Youth Dev, POB 800784, Charlottesville, VA 22908 USA. OI Pianta, Robert/0000-0002-6280-8051 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-4405 J9 J SCHOOL PSYCHOL JI J. Sch. Psychol. PD SEP-OCT PY 2002 VL 40 IS 5 BP 369 EP 370 AR PII S0022-4405(02)00110-3 DI 10.1016/S0022-4405(02)00110-3 PG 2 WC Psychology, Educational SC Psychology GA 597DY UT WOS:000178207900001 ER PT J AU Berger, VW Ivanova, A AF Berger, VW Ivanova, A TI The bias of linear rank tests when testing for stochastic order in ordered categorical data SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE contingency table; envelope power function; exact conditional test; linear rank test ID CONTINGENCY-TABLES; ORDINAL DATA; INDEPENDENCE AB In many hypothesis testing problems, the alternative hypothesis is characterized by one or several restrictions arising from a natural ordering among the outcome levels. It is known that tests which ignore the ordering may lack adequate statistical power for the alternatives which are of the most interest. Considerably less, however, is known about developing tests which conform to a natural ordering. Stochastic order is an objective and compelling characterization of the superiority of one treatment over another. Consequently, testing for stochastic order is of considerable importance in applications involving the comparison of one treatment to another on the basis of ordered categorical data (e.g., in clinical trials). With few exceptions (that we identify), there is no optimal test for this problem, so it is reasonable to consider the class of tests that are simultaneously unbiased and admissible. There are known necessary and sufficient conditions for admissibility, but unbiasedness is more elusive. It is known that a necessary condition for unbiasedness is exactness conditionally on the margins. Further, one can construct a test which is both admissible and unbiased by repeatedly improving the trivially unbiased "ignore-the-data" test. This complicated approach, however, does not, in general, lead to a nested family of tests. We provide a new necessary condition for unbiasedness, and show that linear rank tests, which are widely used and locally most powerful, fail this condition for certain sets of margins. For such margins, linear rank tests are severely biased (with power as low as zero to detect certain alternatives of interest) and least stringent. Published by Elsevier Science B.V. C1 NCI, Biometry Res Grp, DCP, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC 27599 USA. NR 29 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD SEP 1 PY 2002 VL 107 IS 1-2 BP 237 EP 247 AR PII S0378-3758(02)00255-0 DI 10.1016/S0378-3758(02)00255-0 PG 11 WC Statistics & Probability SC Mathematics GA 594QJ UT WOS:000178061800015 ER PT J AU Enoch, MA White, KV Harris, CR Rohrbaugh, JW Goldman, D AF Enoch, MA White, KV Harris, CR Rohrbaugh, JW Goldman, D TI The relationship between two intermediate phenotypes for alcoholism: Low voltage alpha EEG and low P300 ERP amplitude SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID EVENT-RELATED POTENTIALS; THETA OSCILLATIONS; BRAIN POTENTIALS; AUDITORY-STIMULI; METABOLIC-RATE; GENETIC-BASIS; USE DISORDERS; RESPONSES; HERITABILITY; RISK AB Objective: There is considerable evidence that the amplitude of the heritable P300 event-related potential (ERP) is reduced in alcoholics and their alcohol-naive children. Low voltage alpha (LVA), a heritable resting electroencephalogram (EEG) trait present in 7-14% of the population, has been shown to be associated with alcoholism and anxiety disorders. A few studies have demonstrated a modest correlation between pre-stimulus alpha power and P300 amplitude. We aimed to test this finding in community volunteers, hypothesizing that LVA would be associated with low P300 amplitude. Method: Digitized resting EEG was recorded at the central parietal site (Pz) from 85 male and 113 female community volunteers (120 unrelated). ERPs were elicited at Pz by auditory and visual oddball paradigms. All participants were interviewed with the Schedule for Affective Disorders, Lifetime Version (SADS-L) and assigned blind-rated psychiatric diagnoses according to the American Psychiatric Association DSM-III-R criteria. Results: LVA participants (including alcoholics and nonalcoholics) had significantly lower auditory and visual P300 amplitudes. Absolute alpha power was modestly correlated with auditory and visual P300 amplitude and was associated with 9.4% and 4.6% of the variance, respectively Conclusions: The association between LVA and low P300 amplitude, two distinct electrophysiological traits, suggests that, at least in individuals with the LVA trait, some aspects of resting, unstimulated brain activity and activated brain function in the form of attentional response may be fundamentally related. C1 NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Rohrbaugh, JW (reprint author), NIAAA, Neurogenet Lab, 12420 Parklawn Dr,Pk 5 Bldg,Room 451,MSC 8110, Bethesda, MD 20892 USA. EM maenoch@niaaa.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 54 TC 15 Z9 17 U1 1 U2 1 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD SEP PY 2002 VL 63 IS 5 BP 509 EP 517 PG 9 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 600PZ UT WOS:000178401100001 PM 12380845 ER PT J AU Rawson, RA Stein, JB AF Rawson, RA Stein, JB TI Preface - Blending clinical practice and research: forging partnerships to enhance drug addiction treatment SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Editorial Material C1 Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90025 USA. Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Rawson, RA (reprint author), Univ Calif Los Angeles, Integrated Subst Abuse Programs, 11050 Santa Monica Blvd,Suite 100, Los Angeles, CA 90025 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD SEP PY 2002 VL 23 IS 2 BP 67 EP 68 AR PII S0740-5472(02)00268-4 DI 10.1016/S0740-5472(02)00268-4 PG 2 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 596BH UT WOS:000178143600001 ER PT J AU Hanson, GR Leshner, AI Tai, B AF Hanson, GR Leshner, AI Tai, B TI Introduction - I Putting drug abuse research to use in real-life settings SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Editorial Material C1 NIDA, Bethesda, MD 20892 USA. Amer Assoc Advancement Sci, Washington, DC 20005 USA. RP Tai, B (reprint author), NIDA, 6001 Execut Blvd,Room 4123, Bethesda, MD 20892 USA. NR 2 TC 57 Z9 57 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD SEP PY 2002 VL 23 IS 2 BP 69 EP 70 AR PII S0740-5472(02)00269-6 DI 10.1016/S0740-5472(02)00269-6 PG 2 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 596BH UT WOS:000178143600002 PM 12220602 ER PT J AU Kreek, MJ Vocci, FJ AF Kreek, MJ Vocci, FJ TI History and current status of opioid maintenance treatments: blending conference session SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Review DE heroin addiction; methadone maintenance treatments; HIV infection; drug-drug interactions; LAAM (levomethadyl acetate); buprenorphine; office-based pharmacotherapy ID ALPHA-ACETYLMETHADOL LAAM; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; INDUCED METHADONE WITHDRAWAL; GENERAL MEDICAL-PRACTICE; HEROIN-ADDICTS; FOLLOW-UP; DRUG-USERS; LEVOMETHADYL ACETATE; CONTROLLED-TRIAL; HEPATITIS-C AB Opiate addiction is a chronic, relapsing disorder. Left untreated, high morbidity and mortality rates are seen. Pharmacotherapies for this disorder using mu opiate agonists (methadone and levomethadyl acetate) and partial agonists have been developed in the last 40 years. Agonist pharmacotherapy with oral methadone for the treatment of opiate dependence was developed in clinical pharmacology studies at Rockefeller University by Dole, Nyswander, and Kreek. Further studies by this laboratory and others established that moderate to high dose treatment with methadone (80-120 mg) reduced or eliminated opiate use in outpatient settings with consequent reductions in morbidity and up to 4-fold reductions in mortality. Levomethadyl acetate (LAAM), a congener of methadone, is biotransformed to active metabolites responsible for its longer duration of action. The Federal Regulations regarding the dispensation of methadone and LAAM have recently been revised to facilitate the treatment of patients under a "medical maintenance" model, Future regulatory reform will likely involve the establishment of rules for "office based opioid treatment." (C) 2002 Elsevier Science Inc. All rights reserved. C1 NIDA, Div Treatment Res & Dev, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Lab Biol Addict Dis, New York, NY 10021 USA. Rockefeller Univ Hosp, New York, NY 10021 USA. RP Vocci, FJ (reprint author), NIDA, Div Treatment Res & Dev, NIH, Bethesda, MD 20892 USA. EM fv6k@nih.gov FU NCRR NIH HHS [M01-RR00102]; NIDA NIH HHS [DA K05-00049, DA P50-05130, DA R01-12848] NR 110 TC 67 Z9 69 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD SEP PY 2002 VL 23 IS 2 BP 93 EP 105 AR PII S0740-5472(02)00259-3 DI 10.1016/S0740-5472(02)00259-3 PG 13 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 596BH UT WOS:000178143600007 PM 12220607 ER PT J AU Burnett, TA Larson, CR AF Burnett, TA Larson, CR TI Early pitch-shift response is active in both steady and dynamic voice pitch control SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID VESTIBULOOCULAR REFLEX SUPPRESSION; FUNDAMENTAL-FREQUENCY; AUDITORY-FEEDBACK; PERTURBATION; MECHANISMS; HUMANS AB When air conducted auditory feedback pitch is experimentally shifted upward or downward during steady phonation, voice pitch changes in response. The first pitch change is an automatic deflection opposite in direction to the feedback shift. It appears to help stabilize voice pitch by counteracting unintended changes. But what happens during an intended pitch change? If the purpose of the first pitch-shift response is to stabilize voice pitch around a fixed target, it should be suppressed during voluntary pitch changes. Alternatively, if the pitch-shift response is a general process of voice control it should be modified during intended pitch changes to bring production in line with the desired output. Auditory feedback pitch was shifted during steady pitch and upward glissando vocalizations by thirty trained singers. Contrary to the "steady-specific" hypothesis. pitch-shift responses occurred during dynamic pitch vocalizations. Responses were comparable in direction, peak time, and slope, but had significantly longer latency and smaller magnitude than responses elicited during steady note phonation. Results indicate that the early pitch-shift response is a general component of voice control that serves to automatically bring phonation pitch into agreement with an intended target, whether that target is constant or changing in time. (C) 2002 Acoustical Society of America. C1 Northwestern Univ, Dept Commun Disorders, Evanston, IL 60208 USA. RP Burnett, TA (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM burnettt@ninds.nih.gov FU NIDCD NIH HHS [DC02764] NR 25 TC 47 Z9 48 U1 0 U2 0 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 2002 VL 112 IS 3 BP 1058 EP 1063 DI 10.1121/1.1487844 PN 1 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 593MZ UT WOS:000177996400029 PM 12243154 ER PT J AU Selbie, WS Gewalt, SL Ludlow, CL AF Selbie, WS Gewalt, SL Ludlow, CL TI Developing an anatomical model of the human laryngeal cartilages from magnetic resonance imaging SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID SPEECH PRODUCTION; PUBERTAL LARYNX; SECTIONS; IMAGES; MORPHOMETRICS; DIMENSIONS; FRAMEWORK; ASYMMETRY; MUSCLES; BRAIN AB The purpose of this work was to construct a three-dimensional anatomical framework of the cartilages of the human larynx. The framework included representative surface models of the four laryngeal cartilages and estimated attachment points for the intrinsic laryngeal muscles. High-resolution magnetic resonance imaging (MRI) was used to scan one female and four male human cadaveric larynges. The cartilages were segmented manually from the MRI volume for analysis. Two of these larynges were subsequently dissected and the landmark distances on the cartilages measured for comparison with the MRI measures and previous studies. The MRI measures were 8% smaller than the anatomical measures and 12% smaller than data reported in the literature. A laryngeal coordinate system was defined using the plane of symmetry of the cricoid cartilage. Measures of cricoid cartilage symmetry had less than 3% difference between the two sides for a series of measures. An algorithm for registering larynges that minimized the root-mean-square distance between the surface of a reference cricoid cartilage and the surfaces of nonisotropically scaled candidate cricoid cartilages was evaluated. This study provided an anatomical framework for registering different larynges to the same coordinate space. C1 NINDS, Med Neurol Branch, Laryngeal & Speech Sect, Bethesda, MD 20892 USA. Duke Univ, Dept Radiol, Ctr In Vivo Microscopy, Durham, NC 27710 USA. RP Selbie, WS (reprint author), NINDS, Med Neurol Branch, Laryngeal & Speech Sect, 10 Ctr Dr,MSC 1416, Bethesda, MD 20892 USA. OI Ludlow, Christy/0000-0002-2015-6171 FU NCRR NIH HHS [P41 RR05959]; NINDS NIH HHS [IZ01 NS02980-01] NR 51 TC 14 Z9 15 U1 0 U2 9 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 2002 VL 112 IS 3 BP 1077 EP 1090 DI 10.1121/1.1501586 PN 1 PG 14 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 593MZ UT WOS:000177996400031 PM 12243156 ER PT J AU Riddle, MA Ginsburg, GS Walkup, JT Labelarte, MJ Pine, DS Davies, M Greenhill, L Sweeney, M Klein, R Abikoff, H Hack, S Klee, B Bergman, L March, J Compton, S Robinson, J O'Hara, T Baker, S Ritz, L Roper, M AF Riddle, MA Ginsburg, GS Walkup, JT Labelarte, MJ Pine, DS Davies, M Greenhill, L Sweeney, M Klein, R Abikoff, H Hack, S Klee, B Bergman, L March, J Compton, S Robinson, J O'Hara, T Baker, S Ritz, L Roper, M CA Pediat Psychopharmacology Anxiety TI The Pediatric Anxiety Rating Scale (PARS): Development and psychometric properties SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE anxiety; children; adolescents; rating scales; assessment ID GLOBAL ASSESSMENT SCALE; RANDOMIZED CLINICAL-TRIAL; AFFECTIVE-DISORDERS; NORMAL-CHILDREN; K-SADS; RELIABILITY; VALIDITY; ADOLESCENTS; SCREEN; SCHIZOPHRENIA AB Objective: To describe the development and psychometric properties of the Pediatric Anxiety Rating Scale (PARS), a clinician-rated instrument for assessing the severity of anxiety symptoms associated with common DSM-IV anxiety disorders (social phobia, separation anxiety disorder, and generalized anxiety disorder) in children. Method: As part of a multisite study of the efficacy of fluvoxamine, 128 children (aged 6-17) and their parents were interviewed weekly with the PARS. Data from multiple raters on a subsample of children (using live and videotaped interviews) were used to evaluate interrater reliability. Internal consistency, test-retest reliability, and validity (convergent, divergent) also were evaluated. Results: The PARS showed high interrater reliability, adequate test-retest reliability, and fair internal consistency. Convergent and divergent validity were satisfactory. PARS scores were sensitive to treatment and paralleled change in other measures of anxiety symptoms and global improvement. Conclusions: The PARS is a useful clinician-rated instrument for assessing pediatric anxiety symptoms, severity, and impairment, particularly in treatment studies. Further study of the psychometric properties is warranted. C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. Columbia Univ, New York, NY 10027 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. NYU, New York, NY USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Duke Univ, Durham, NC 27706 USA. Nathan S Kline Inst Psychiat Res, New York, NY USA. NIMH, Bethesda, MD USA. RP Riddle, MA (reprint author), Johns Hopkins Childrens Ctr, Div Child & Adolescent Psychiat, Room 346,600 N Wolfe St, Baltimore, MD 21287 USA. NR 38 TC 10 Z9 11 U1 5 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2002 VL 41 IS 9 BP 1061 EP 1069 DI 10.1097/01.CHI.0000020259.43550.F4 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 586QY UT WOS:000177597000006 ER PT J AU DePaola, LG Mangan, D Mills, SE Costerton, W Barbeau, J Shearer, B Bartlett, J AF DePaola, LG Mangan, D Mills, SE Costerton, W Barbeau, J Shearer, B Bartlett, J TI A review of the science regarding dental unit waterlines SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID BACTERIAL-CONTAMINATION; MICROBIAL-CONTAMINATION; BIOFILMS; SYSTEMS; PREVALENCE; QUALITY AB Background: The National Institute of Dental and Craniofacial Research, or NIDCR; the American Dental Association, or ADA; and the Organization for Safety & Asepsis Procedures, or OSAP, sponsored a workshop on the topic of dental unit waterlines, or DUWLs, on Sept. 29, 2000, at the National Institutes of Health in Bethesda, Md. These organizations invited a group of experts from the ADA, NIDCR, OSAP, the U.S. Food and Drug Administration, the Centers for Disease Control and Prevention, and U.S. Department of Defense, academia and private industry to participate. Types of Studies Reviewed. The sponsors asked the participants to critically review the scientific literature on the subject in an attempt to determine the evidence basis for management of DUWL contamination and potential health risks, if any, in dental procedures. The ultimate goal of the workshop was to determine if a research agenda in the urea of DUWLs should be pursued and what questions such an agenda should involve. Results. The workshop yielded four questions that need to be addressed in future research: What is the safest and most effective agent(s)/device(s) for the achieving microbial levels of no more than 200 colony-forming units per milliliter, or CFU/mL, in the effluent dental water? How should these products be evaluated and by whom? What are the adverse health effects, if any, of chronic exposure to dental bioaerosol or to the agents introduced into the dental unit to treat the waterlines for both dental staff members and patients? How could these health issues be evaluated? Clinical Implications: Developing evidence-based parameters for the management of biofilm contamination that are efficacious and cost-effective will allow clinicians to meet in proposed ADA standard of no more than 200 CFU/mL of effluent water. C1 Univ Maryland, Coll Dent Surg, Sch Dent, Dept Diagnost Sci & Pathol, Baltimore, MD 21201 USA. NIDCR, Infect Dis Branch, NIH, Bethesda, MD 20892 USA. USAF, Washington, DC 20330 USA. Bolling AFB, Washington, DC USA. Montana State Univ, Ctr Biofilm Engn, Bozeman, MT 59717 USA. Univ Montreal, Fac Dent, Dept Stomatol, Montreal, PQ H3C 3J7, Canada. Bayer Corp, Sci Commun, West Haven, CT USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. RP DePaola, LG (reprint author), Univ Maryland, Coll Dent Surg, Sch Dent, Dept Diagnost Sci & Pathol, 666 W Baltimore St, Baltimore, MD 21201 USA. NR 37 TC 29 Z9 30 U1 0 U2 4 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 2002 VL 133 IS 9 BP 1199 EP 1206 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 595KK UT WOS:000178107900016 PM 12356251 ER PT J AU Leser, MS Yanovski, SZ Yanovski, JA AF Leser, MS Yanovski, SZ Yanovski, JA TI A low-fat intake and greater activity level are associated with lower weight regain 3 years after completing a very-low-calorie diet SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID PHYSICAL-ACTIVITY; OBESE SUBJECTS; UNITED-STATES; BODY-WEIGHT; MAINTENANCE; WOMEN; STRATEGIES; ADULTS; HEALTH; OVERWEIGHT AB Objective To examine the roles of diet, exercise, and lifestyle factors in determining long-term weight regain after weight loss with a very-low-calorie diet (VLCD). Subjects Twenty-seven of 38 women who lost weight with a VLCD. Design Graduates of a weight loss intervention study returned for follow-up 3 years after program completion. Percentage of initial weight loss that was regained was correlated with subjects' fat intake (assessed via 7-day food records and a Diet Habit Survey), energy intake (assessed via 7-day food records), activity level and lifestyle factors (assessed via questionnaires) that are supportive of weight loss maintenance. Statistical analyses performed Regression analysis was used to assess the relationship of weight regain with fat intake, activity level, and energy intake. Contingency table analysis was used to assess the association between weight regain and lifestyle factors. Results Subjects followed experienced a -20.7 kg +/-9.2 kg 19.2% +/-7%) (mean +/- standard deviation) weight change during the original VLCD program and a 13.9 kg +/- 11.3 kg (76.6% +/- 52.1%) weight change 3 years post-VLCD. Fat intake, assessed by a 7-day food diary, was positively correlated with weight regain at 3 years (r= 0.66, P=.0004). Less weight regain was also seen with a lower percent fat intake as reflected by a higher Diet Habit Survey score (r=0.55, P=.004). Women with the lowest tertile of reported fat intake (<25% of energy) from the Diet Habit Survey regained the least amount of weight (P=.05). Activity level was negatively correlated with weight regain (r= -0.53, P=.005). After correction for multiple comparisons, there was no association between total energy intake and weight regain. Lifestyle factors were also not associated with weight regain. Applications/conclusions Identifying strategies to maintain weight loss is crucial because of the negative health effects and increasing prevalence of obesity. For women who have lost weight on a VLCD, limiting dietary fat intake and maintaining physical activity are both important factors for the prevention of weight regain. To promote better weight loss outcomes, registered dietitians should help clients who have lost weight limit their fat intake to less than 30% of energy and encourage high activity levels. C1 NIH, Ctr Clin, Dept Nutr, Bethesda, MD 20892 USA. NIDDKD, Obes & Eating Disorders Program, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. NICHD, Unit Growth & Obes, Dev Endocrinol Branch, Bethesda, MD USA. US PHS, Washington, DC 20201 USA. RP Leser, MS (reprint author), NIH, Ctr Clin, Dept Nutr, Bldg 10,B1S234,10 Ctr Dr,MSC 1078, Bethesda, MD 20892 USA. NR 36 TC 27 Z9 27 U1 0 U2 2 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 2002 VL 102 IS 9 BP 1252 EP 1256 DI 10.1016/S0002-8223(02)90277-4 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 589ZJ UT WOS:000177791500014 PM 12792622 ER PT J AU Corti, MC Guralnik, JM Sartori, L Baggio, G Manzato, E Pezzotti, P Barbato, G Zambon, S Ferrucci, L Minervini, S Musacchio, E Crepaldi, G AF Corti, MC Guralnik, JM Sartori, L Baggio, G Manzato, E Pezzotti, P Barbato, G Zambon, S Ferrucci, L Minervini, S Musacchio, E Crepaldi, G TI The effect of cardiovascular and osteoarticular diseases on disability in older Italian men and women: Rationale, design, and sample characteristics of the Progetto Veneto Anziani (PROVA.) study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE disability; cardiovascular disease; arthritis; osteoporosis; epidemiology; aging ID ASSOCIATION; COMORBIDITY; MORTALITY; MOBILITY; HEALTH; RISK AB OBJECTIVES: Describe the methodology and preliminary results of the Progetto Veneto Anziani (PRO.V.A.) Study, an observational study of the Italian population aged 65 and older DESIGN: Cross-sectional cohort observation. SETTING: Northern Italy. PARTICIPANTS: Italians aged 65 and older, living in both the community and nursing homes. MEASUREMENTS: At baseline, participants were interviewed at their homes and subsequently examined by nurses and physicians at the two study clinics using an extensive battery of clinical, instrumental, biochemical, and physical performance tests. Hand, knee, hip, and chest x-rays and bone densitometry were performed in 92% of the participants, and 99% of the participants consented to blood drawing and deoxyribonucleic acid analyses. The physician who performed the physical examination determined disease presence based on several components of the interview and examination. A further, comprehensive determination was performed with standardized algorithms using all the information collected on each participant, including hospital records surveillance, standardized x-ray readings, and blood assays. In one of the study sites, a brain magnetic resonance imaging was performed in a subsample of the participants (820 persons). RESULTS: Overall response rate to the baseline clinic visit was 77% for men and 64% for women. Co-presence of at least one cardiovascular disease (CVD) and at least one osteoarticular disease (OAD) was identified in 10%, 22%, and 29% of men and 9%, 24%, and 40% of women aged 65 to 74, 75 to 84, and 85 and older, respectively. Overall, the mean number of coexisting chronic conditions was 4.8 for men and 2.4 for women. CONCLUSIONS: The PRO.V.A. study has the potential to provide an original contribution to clarify the mechanisms whereby diseases cause disability in older men and women; the particular focus on CVD and OADs will make it possible to comprehensively evaluate the development of disability as it relates to these two important conditions. C1 Camposampiero Hosp, Dept Med, Div Geriatr, I-35012 Padua, Italy. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Univ Padua, Sch Med, Dept Med & Surg Sci, I-35100 Padua, Italy. Azienda Osped, Div Internal Med, Padua, Italy. Ist Super Sanita, Epidemiol & Biostat Lab, I-00161 Rome, Italy. Ist Nazl Ric & Cura Gli Anziani, Dept Geriatr, Florence, Italy. RP Corti, MC (reprint author), Camposampiero Hosp, Dept Med, Div Geriatr, Via P Cosma 1, I-35012 Padua, Italy. NR 19 TC 53 Z9 53 U1 1 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2002 VL 50 IS 9 BP 1535 EP 1540 DI 10.1046/j.1532-5415.2002.50409.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 593AE UT WOS:000177968400009 PM 12383151 ER PT J AU Guralnik, JM Ferrucci, L AF Guralnik, JM Ferrucci, L TI Underestimation of disability occurrence in epidemiological studies of older people: Is research on disability still alive? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID FUNCTIONAL STATUS; RANDOMIZED TRIAL; SEX-DIFFERENCES; COMMUNITY; HEALTH; CARE; ADULTS; AGE; POPULATION; OUTCOMES C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. INRCA Geriatr dept, Lab Clin Epidemiol, Florence, Italy. RP Guralnik, JM (reprint author), NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NR 21 TC 33 Z9 33 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2002 VL 50 IS 9 BP 1599 EP 1601 DI 10.1046/j.1532-5415.2002.50421.x PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 593AE UT WOS:000177968400021 PM 12383164 ER PT J AU Cricco, M Simonsick, EM Foley, DJ AF Cricco, M Simonsick, EM Foley, DJ TI Insomnia and cognitive decline - Reply SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID BENZODIAZEPINES C1 NIA, Clin Invest Lab, Bethesda, MD 20892 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Cricco, M (reprint author), NIA, Clin Invest Lab, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2002 VL 50 IS 9 BP 1605 EP 1605 DI 10.1046/j.1532-5415.2002.50424.x PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 593AE UT WOS:000177968400027 ER PT J AU Shiota, T Jones, M Tsujino, H Qin, JX Zetts, AD Greenberg, NL Cardon, LA Panza, JA Thomas, JD AF Shiota, T Jones, M Tsujino, H Qin, JX Zetts, AD Greenberg, NL Cardon, LA Panza, JA Thomas, JD TI Quantitative analysis of aortic regurgitation: Real-time 3-dimensional and 2-dimensional color Doppler echocardiographic method - A clinical and a chronic animal study SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID OPERATIVE INTERVENTION; SYMPTOMATIC PATIENTS; VALVE-REPLACEMENT; VOLUME; VALIDATION; MODEL AB Background: For evaluating patients with aortic regurgitation (AR), regurgitant volumes, left ventricular (LV) stroke volumes (SV), and absolute LV volumes are valuable indices. Aim: The aim of this study was to validate the combination of real-time 3-dimensional echocardiography (3DE) and semiautomated digital color Doppler cardiac flow measurement (ACM) for quantifying absolute LV volumes, LVSV, and AR volumes using an animal model of chronic AR and to investigate its clinical applicability. Methods. In 8 sheep, a total of 26 hemodynamic states were obtained pharmacologically 20 weeks after the aortic valve noncoronary (n=4) or right coronary (n=4) leaflet was incised to produce AR. Reference standard LVSV and AR volume were determined using the electromagnetic flow method (EM). Simultaneous epicardial real-time 3DE studies were performed to obtain LV end-diastolic volumes (LVEDV), end-systolic volumes (LVESV), and LVSV by subtracting LVESV from LVEDV. Simultaneous ACM was performed to obtain LVSV and transmitral flows; AR volume was calculated by subtracting transmitral flow volume from LVSV. in a total of 19 patients with AR, real-time 3DE and ACM were used to obtain LVSVs and these were compared with each other. Results: A strong relationship was found between LVSV derived from EM and those from the real-time 3DE (r=0.93, P<.001, mean difference (3D-EM) = -1.0&PLUSMN;9.8 mL). A good relationship between LVSV and AR volumes derived from EM and those by ACM was found (r=0.88, P<.001). A good relationship between LVSV derived from real-time 3DE and that from ACM was observed (r=0.73, P<.01, mean difference = 2.5&PLUSMN;7.9 mL). In patients, a good relationship between LVSV obtained by real-time 3DE and ACM was found (r=0.90, P<.001, mean difference = 0.6+/-9.8 mL). Conclusion: The combination of ACM and real-time 3DE for quantifying LV volumes, LVSV, and AR volumes was validated by the chronic animal study and was shown to be clinically applicable. C1 Cleveland Clin Fdn, Dept Cardiol, Cleveland, OH 44195 USA. NHLBI, Lab Anim Surg & Med, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Shiota, T (reprint author), Cleveland Clin Fdn, Dept Cardiol F 15, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 16 TC 12 Z9 13 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD SEP PY 2002 VL 15 IS 9 BP 966 EP 971 DI 10.1067/mje.2002.120981 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 595QA UT WOS:000178119200017 PM 12221414 ER PT J AU Middleton, J AF Middleton, J TI Renal outcomes in the context of an acute GFR effect of dihydropyridine CCBs in the African American study of kidney disease (AASK). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 3A EP 3A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500012 ER PT J AU Srichai, MB Konieczkowski, M Barathan, S Khan, S Mundel, P Lee, S Bruggeman, L Schelling, JR Sedor, JR AF Srichai, MB Konieczkowski, M Barathan, S Khan, S Mundel, P Lee, S Bruggeman, L Schelling, JR Sedor, JR TI A novel WT1 co-regulator that shuttles between nucleus and plasma membrane. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 16A EP 17A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500078 ER PT J AU Yang, TX Paliege, A Mizel, D Huang, G Briggs, JP Schnermann, JB AF Yang, TX Paliege, A Mizel, D Huang, G Briggs, JP Schnermann, JB TI Interaction between COX-2 and NOSI in macula densa: Negative feedback in control of renin release. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 18A EP 19A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500089 ER PT J AU Cheng, O Zhang, XJ Usinger, W Molineaux, C Mannon, RB AF Cheng, O Zhang, XJ Usinger, W Molineaux, C Mannon, RB TI Connective tissue growth factor (CTGF): A novel effector of chronic allograft nephropathy (CAN). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. FibroGen, San Francisco, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 24A EP 24A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500115 ER PT J AU Athirakul, K Bradbury, AJ Ma, JX Graves, J Miller, L Quigley, R Coffman, TM Zeldin, DC AF Athirakul, K Bradbury, AJ Ma, JX Graves, J Miller, L Quigley, R Coffman, TM Zeldin, DC TI Cytochrome P450 Cyp2j5 regulates blood pressure and estrogen metabolism in female mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Duke Univ, Ctr Med, Durham, NC USA. NIEHS, NIH, Res Triangle Pk, NC USA. SW Texas State Univ, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 29A EP 29A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500142 ER PT J AU Yang, TX Huang, G Schnermann, JB Briggs, JP AF Yang, TX Huang, G Schnermann, JB Briggs, JP TI Severity of hypertension,and renal failure in COX-2 knockout mice is affected by genetic background and gender. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 29A EP 29A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500140 ER PT J AU Eggers, PW AF Eggers, PW TI Medicare expenditures following vascular access procedures. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 37A EP 37A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500181 ER PT J AU Eggers, PW Kimmel, PL AF Eggers, PW Kimmel, PL TI Is there an epidemic of HIV-associated nephropathy in the ESRD program? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 38A EP 38A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500185 ER PT J AU Green, GB Kim, J Winkler, CA Koziell, A Pollak, MR Kopp, JB Briggs, WA Dart, RA Korbet, SM Mokrzycki, M Kimmel, PL Schelling, JR Ahuja, TS Berns, JS Smith, MC Simon, EE Trachtman, H Shaw, AS AF Green, GB Kim, J Winkler, CA Koziell, A Pollak, MR Kopp, JB Briggs, WA Dart, RA Korbet, SM Mokrzycki, M Kimmel, PL Schelling, JR Ahuja, TS Berns, JS Smith, MC Simon, EE Trachtman, H Shaw, AS TI Genetic polymorphisms in CD2AP are common in patients with glomerular disease. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Washington Univ, Sch Med, St Louis, MO 63130 USA. NCI, Frederick, MD 21701 USA. Inst Child Hlth, London, England. Brigham & Womens Hosp, Boston, MA 02115 USA. NIDDK, Bethesda, MD USA. Johns Hopkins Med Ctr, Baltimore, MD USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. Northwestern Med Ctr, St Albans, VT 05478 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. George Washington Univ, Med Ctr, Washington, DC 20052 USA. Metrohlth Med Ctr, Cleveland, OH USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Grad Hosp Philadelphia, Philadelphia, PA 19146 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Tulane Univ Med Ctr Hosp & Clin, New Orleans, LA USA. Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 39A EP 39A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500190 ER PT J AU Grimm, DH Praetorius, HA Cai, Y Geng, L Zeltner, R Sweeney, W Avner, ED Somlo, S Spring, KR Caplan, MJ AF Grimm, DH Praetorius, HA Cai, Y Geng, L Zeltner, R Sweeney, W Avner, ED Somlo, S Spring, KR Caplan, MJ TI A role for polycystin-2 in the cilium mechanostimulation pathway. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Aarhus, Water & Salt Res Ctr, Brenstrupgaardsvej, Denmark. Yale Univ, New Haven, CT USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 47A EP 47A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500228 ER PT J AU Wall, SM Hassell, KA Royaux, IE Green, ED Chang, JY Shipley, GL Verlander, JW AF Wall, SM Hassell, KA Royaux, IE Green, ED Chang, JY Shipley, GL Verlander, JW TI Pendrin is predominantly expressed in the cortical collecting duct and connecting tubule of mouse kidney. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Florida, Gainesville, FL USA. Univ Texas, Sch Med, Houston, TX USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 64A EP 64A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500308 ER PT J AU Ecelbarger, CA Tian, Y Song, JA Knepper, MA Verbalis, JG AF Ecelbarger, CA Tian, Y Song, JA Knepper, MA Verbalis, JG TI Hypertonicity increases the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) and the gamma-subunit of ENaC in whole kidney. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. Georgetown Univ, Dept Med, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 67A EP 67A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500324 ER PT J AU Wang, WD Li, CL Kwon, TH Knepper, MA Frokiaer, J Nielsen, S AF Wang, WD Li, CL Kwon, TH Knepper, MA Frokiaer, J Nielsen, S TI Reduced expression of renal sodium transporters and increased urinary sodium excretion in rats with parathyroid hormone (PTH)-induced hypercalcemia. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Dongguk Univ, Dept Physiol, Kwangju, South Korea. Aarhus Univ, Water & Salt Res Ctr, Aarhus, Denmark. NR 0 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 67A EP 67A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500325 ER PT J AU Jung, JY Lim, SW Kim, WY Han, KH Cha, JH Knepper, MA Sands, JM Madsen, KM Kim, J AF Jung, JY Lim, SW Kim, WY Han, KH Cha, JH Knepper, MA Sands, JM Madsen, KM Kim, J TI Expression of urea transporters in hypokalemic mouse kidney. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Catholic Univ Korea, Seoul, South Korea. NIH, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 68A EP 68A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500331 ER PT J AU Lim, SW Kim, YH Lee, BS Cha, JH Sands, JM Knepper, MA Madsen, KM Kim, J AF Lim, SW Kim, YH Lee, BS Cha, JH Sands, JM Knepper, MA Madsen, KM Kim, J TI Hydration status affects subcellular localization of UT-A and UT-B in rat kidney. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Catholic Univ Korea, Seoul, South Korea. Emory Univ, Sch Med, Atlanta, GA 30322 USA. NIH, Bethesda, MD 20892 USA. Univ Florida, Gainesville, FL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 68A EP 68A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500330 ER PT J AU Stewart, GS Fenton, RA Smith, CP AF Stewart, GS Fenton, RA Smith, CP TI Differential expression of UT-A proteins in mouse kidney. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Manchester, Sch Biol Sci, Manchester, Lancs, England. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 69A EP 69A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500333 ER PT J AU Stewart, GS Fenton, RA Smith, CP AF Stewart, GS Fenton, RA Smith, CP TI Expression of UT-A urea transporters in mouse colonic crypts. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Manchester, Sch Biol Sci, Manchester, Lancs, England. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 69A EP 69A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500337 ER PT J AU Machado, MO Hirata, RD Riordan, GP Sellitti, DF Cusumano, AM Hirata, MH Hirszel, P Doi, SQ AF Machado, MO Hirata, RD Riordan, GP Sellitti, DF Cusumano, AM Hirata, MH Hirszel, P Doi, SQ TI Lipid deposition and HMG-CoA reductase, LDL-receptor and scavenger receptor mRNA renal expression is increased in the bGH mouse. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Univ Sao Paulo, Sch Pharm Sci, Sao Paulo, Brazil. CEMIC Sch Med, Buenos Aires, DF, Argentina. NIDCD, Sect Struct Cell Biol, NIH, Bethesda, MD USA. RI Hirata, Mario/C-9718-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 79A EP 80A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500388 ER PT J AU Qi, ZH Morrow, JD Hao, CM Zhao, M Langenbach, RL Breyer, MD AF Qi, ZH Morrow, JD Hao, CM Zhao, M Langenbach, RL Breyer, MD TI Tissue heterogeneity of Angiotensin II effects on prostaglandin (PG) synthesis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Vanderbilt Univ, Nashville, TN USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 82A EP 83A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500403 ER PT J AU Petermann, AT Hiromura, K Couser, WG Kopp, J Mundel, P Shankland, SJ AF Petermann, AT Hiromura, K Couser, WG Kopp, J Mundel, P Shankland, SJ TI Differential expression of D-type cyclins in podocytes in vitro and in vivo. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 90A EP 90A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500442 ER PT J AU Dmitrieva, NI Burg, MB AF Dmitrieva, NI Burg, MB TI High NaCl not only damages DNA, but inhibits DNA repair in renal inner medullary cells (mIMCD3). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI, LKEM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 95A EP 95A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500468 ER PT J AU Connaire, JJ Aronow, BJ Chmielewski, D Kopp, JB Rosenberg, ME AF Connaire, JJ Aronow, BJ Chmielewski, D Kopp, JB Rosenberg, ME TI Clusterin facilitates antibody-mediated mesangial cell injury. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA. Univ Minnesota, Minneapolis, MN USA. RI Aronow, Bruce/F-8438-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 97A EP 97A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500477 ER PT J AU Shi, G Jennings, JL Link, AJ Perantoni, A de Caestecker, MP AF Shi, G Jennings, JL Link, AJ Perantoni, A de Caestecker, MP TI Direct analysis of Cited1-interacting nuclear protein complexes suggests novel functions in the regulation of epithelial cell differentiation in the developing kidney. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Vanderbilt Univ, Sch Med, Div Nephrol, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Immunol & Microbiol, Nashville, TN 37212 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 103A EP 103A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500509 ER PT J AU Woroniecki, RP Susztak, K Bitzer, M Ju, WJ Cermak, L Kaskel, FJ Bottinger, EP AF Woroniecki, RP Susztak, K Bitzer, M Ju, WJ Cermak, L Kaskel, FJ Bottinger, EP TI Laser capture microdissection (LCM) and quantitative rt-PCR (qrt-PCR) for isolated glomerular and tubular gene expression profiling in a TGF-b1 Transgenic model of progressive glomerular sclerosis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Albert Einstein Coll Med, NIDDK, Ctr Biotechnol, Bronx, NY 10467 USA. Childrens Hosp Montefiore, Div Pediat Nephrol, Bronx, NY USA. RI Cermak, Lukas/N-2254-2016 OI Cermak, Lukas/0000-0002-8777-3692 NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 118A EP 119A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500587 ER PT J AU Kobayashi, H Kawamoto, S Jo, SK Brechbiel, MW Hu, XZ Yang, TX Schnermann, J Star, R AF Kobayashi, H Kawamoto, S Jo, SK Brechbiel, MW Hu, XZ Yang, TX Schnermann, J Star, R TI Functional kidney Imaging in mice using dendrimer based renal contrast agents. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NCI, DCS, ROB, NIH, Bethesda, MD 20892 USA. Johns Hopkins, Baltimore, MD USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 143A EP 143A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500706 ER PT J AU Yuen, PST Jo, SK Star, RA AF Yuen, PST Jo, SK Star, RA TI Differentiation of renal responses to volume depletion, ischemia-reperfusion, and mercuric chloride by gene expression analysis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 143A EP 144A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500708 ER PT J AU Fedorova, OV Agalakova, NI Lakatta, EG Shapiro, JI Bagrov, AY AF Fedorova, OV Agalakova, NI Lakatta, EG Shapiro, JI Bagrov, AY TI ATII mediates cross talk between two endogenous digitalis-like sodium pump ligands in Dahl hypertension. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIA, NIH, Bethesda, MD 20892 USA. Med Coll Ohio, Toledo, OH 43699 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 148A EP 148A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500729 ER PT J AU Schnermann, JB Hashimoto, S Bernstein, KE Briggs, JP AF Schnermann, JB Hashimoto, S Bernstein, KE Briggs, JP TI Vascular and proximal tubule function without tissue ACE - Studies in ACE.2 mice SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 148A EP 148A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500732 ER PT J AU Song, J Brown, KK Knepper, MA Verbalis, JG Ecelbarger, CA AF Song, J Brown, KK Knepper, MA Verbalis, JG Ecelbarger, CA TI Increased renal sodium transporter and channel subunit abundances in diabetic streptozotocin-treated rats. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Georgetown Univ, Dept Med, Washington, DC USA. GlaxoSmithKline Res, Dept Metab Dis, Res Triangle Pk, NC USA. NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 169A EP 169A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500836 ER PT J AU Gallon, L McDermott, DH Huong, TT Rubel, JR Kaufman, D Leventhal, J Milford, EL AF Gallon, L McDermott, DH Huong, TT Rubel, JR Kaufman, D Leventhal, J Milford, EL TI beta 3 integrin PlA1 homozygotes are at increased risk of acute rejection in human renal transplantation. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. NIAID, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 184A EP 184A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500910 ER PT J AU Abbott, KC Bucci, JR Cruess, D Taylor, AJ Agodoa, LY AF Abbott, KC Bucci, JR Cruess, D Taylor, AJ Agodoa, LY TI Graft loss and acute coronary syndromes after renal transplantation in the United States. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. Walter Reed Army Med Ctr, Serv Cardiol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 188A EP 188A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757500927 ER PT J AU Feldman, H Landis, JR Gaughan, C Joffe, M Xie, S Greene, T Franklin-Becker, E Kusek, J Beck, G Levey, A AF Feldman, H Landis, JR Gaughan, C Joffe, M Xie, S Greene, T Franklin-Becker, E Kusek, J Beck, G Levey, A CA CRIC Study Grp TI MDRD equations for measuring changes in GFR in longitudinal studies SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NE Med Ctr, Boston, MA USA. NIDDK, NIH, Bethesda, MD USA. RI Landis, J. Richard/A-9330-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 222A EP 222A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501088 ER PT J AU Kutner, NG Barnhart, H Zhang, R Pastan, S AF Kutner, NG Barnhart, H Zhang, R Pastan, S TI Quality of life assessment over time in DMMS wave 2 study patients: Staying on PD or HD vs. changing modality during the first year of therapy. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Emory Univ, Qual Life Rehabil Special Studies Ctr, USRDS, NIH,NIDDK, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 224A EP 224A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501099 ER PT J AU Dember, L Kaufman, J Beck, G Dixon, B Gassman, J Greene, T Himmelfarb, J Hunsicker, L Kusek, J Middleton, J Schwab, S Feldman, H AF Dember, L Kaufman, J Beck, G Dixon, B Gassman, J Greene, T Himmelfarb, J Hunsicker, L Kusek, J Middleton, J Schwab, S Feldman, H CA DAC Study Grp TI Dialysis access consortium (DAC) trial design: Clopidogrel prevention of early AV fistula thrombosis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Boston U, Boston, MA USA. Cleveland Clin, Cleveland, OH USA. U Iowa, Iowa City, IA USA. Maine Med Ctr, Portland, ME 04102 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Duke U, Durham, NC 27706 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 229A EP 229A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501121 ER PT J AU Dixon, BS Greene, T Beck, GJ Dember, LM Gassman, JJ Himmelfarb, J Hunsicker, LG Kaufman, J Kusek, JW Middleton, JP Schwab, SJ Feldman, HI AF Dixon, BS Greene, T Beck, GJ Dember, LM Gassman, JJ Himmelfarb, J Hunsicker, LG Kaufman, J Kusek, JW Middleton, JP Schwab, SJ Feldman, HI TI Dialysis access consortium (DAC) trial design: Sustained-release dipyridamole plus aspirin (D/A) to prevent graft failure. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Iowa, Iowa City, IA USA. Cleveland Clin, Cleveland, OH 44106 USA. Boston Univ, Boston, MA 02215 USA. Maine Med Ctr, Portland, ME 04102 USA. NIDDK, NIH, Bethesda, MD USA. SW Texas State Univ, Dallas, TX USA. Duke Univ, Durham, NC USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 232A EP 232A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501135 ER PT J AU Erlinger, TP Tarver-Carr, ME Powe, NR Appel, LJ Coresh, J Eberhardt, MS Brancati, FL AF Erlinger, TP Tarver-Carr, ME Powe, NR Appel, LJ Coresh, J Eberhardt, MS Brancati, FL TI Inflammation and the risk of chronic kidney disease in US adults. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NIH, Natl Ctr Hlth Stat, Hyattsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 261A EP 261A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501276 ER PT J AU Kwon, TH Nielsen, J Masilamani, S Hager, H Knepper, MA Frokiaer, J Nielsen, S AF Kwon, TH Nielsen, J Masilamani, S Hager, H Knepper, MA Frokiaer, J Nielsen, S TI Regulation of collecting duct AQP3 expression: Response to mineralocorticoid. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Aarhus, Water & Salt Res Ctr, Aarhus, Denmark. Dongguk Univ, Sch Med, Dept Physiol, Kyungju, South Korea. NHLBI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 272A EP 272A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501331 ER PT J AU Li, CL Wang, WD Kwon, TH Sardeli, C Knepper, MA Nielsen, S Frokiaer, J AF Li, CL Wang, WD Kwon, TH Sardeli, C Knepper, MA Nielsen, S Frokiaer, J TI alpha-MSH-treatment prevents downregulation of AQP1, AQP2 and AQP3 expression in rats with bilateral ureteral obstruction. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Aarhus, Water & Salt Res Ctr, Aarhus, Denmark. Dongguk Univ, Sch Med, Dept Physiol, Kyungji, South Korea. NHLBI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 272A EP 272A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501333 ER PT J AU Fernandez-Llama, P Fernandez-Varo, G Ros, J Arroyo, V Ballarin, J Barcelo, P Angelof, S Knepper, MA Jimenez, W AF Fernandez-Llama, P Fernandez-Varo, G Ros, J Arroyo, V Ballarin, J Barcelo, P Angelof, S Knepper, MA Jimenez, W TI Kidney abundance and urinary excretion of aquaporin-1 and NHE3 in rats with liver cirrhosis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Hosp Clin Barcelona, Barcelona, Spain. NHLBI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 273A EP 274A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501341 ER PT J AU Ferraris, JD Persaud, P Williams, CK Chen, Y Burg, MB AF Ferraris, JD Persaud, P Williams, CK Chen, Y Burg, MB TI Tonicity-induced increase of transactivating activity of TonEBP/OREBP. Role of PKA. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI, LKEM, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 275A EP 275A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501348 ER PT J AU Husted, RF Sigmund, RD Ageloff, S Knepper, MA Stokes, JB AF Husted, RF Sigmund, RD Ageloff, S Knepper, MA Stokes, JB TI Mechanisms of ENaC regulation by steroids, cAMP, and CFTR in H441 cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Iowa, Iowa City, IA 52242 USA. Vet Affairs Med Ctr, Iowa City, IA 52242 USA. NHLBI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 277A EP 278A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501362 ER PT J AU Nielsen, J Kwon, TW Toftgaard, A Knepper, MA Frokiaer, J Nielsen, S AF Nielsen, J Kwon, TW Toftgaard, A Knepper, MA Frokiaer, J Nielsen, S TI Regulation of ENaC in rats with lithium induced nephrogenic diabetes insipidus. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Aarhus, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark. NHLBI, Lab Kidney & Electrolyte Metab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 278A EP 278A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501367 ER PT J AU Uchida, S Yamashita, M Homma, H Kanda, Y Inokami, T Knepper, MA Nagase, M AF Uchida, S Yamashita, M Homma, H Kanda, Y Inokami, T Knepper, MA Nagase, M TI Hypercalciuric hypocalcemia in primary aldosteronism may be associated with upregulation of thiazide-sensitive NaCl cotransporter. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Teikyo Univ, Sch Med, Dept Internal Med, Tokyo, Tokyo, Japan. NHLBI, LKEM, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 282A EP 282A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501385 ER PT J AU Deng, JP Hu, XZ Yuen, PST Star, RA AF Deng, JP Hu, XZ Yuen, PST Star, RA TI Early mechanisms of action of alpha-MSH in ischemic kidney and lung injury. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD USA. RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 325A EP 325A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501605 ER PT J AU Muramatsu, Y Tsujie, M Kohda, Y Pham, B Perantoni, AO Zhao, H Jo, SK Yuen, PST Hu, XZ Star, RA AF Muramatsu, Y Tsujie, M Kohda, Y Pham, B Perantoni, AO Zhao, H Jo, SK Yuen, PST Hu, XZ Star, RA TI Early detection of cysteine-rich 61 protein (Cyr61, CCN1) in urine following renal ischemia reperfusion injury. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD USA. NCI, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21701 USA. RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 327A EP 327A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501615 ER PT J AU Ageloff, S Husted, RF Sigmund, RD Knepper, MA Stokes, JB AF Ageloff, S Husted, RF Sigmund, RD Knepper, MA Stokes, JB TI Renal Na transporter expression in Dahl salt-sensitive and resistant rats fed a high or low Na diet. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Iowa, Iowa City, IA USA. NHLBI, NIH, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Iowa City, IA 52242 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 330A EP 330A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501628 ER PT J AU Hashimoto, S Briggs, JP Schnermann, JB AF Hashimoto, S Briggs, JP Schnermann, JB TI Effect of carbonic anhydrase inhibition on glomerular filtration rate (GFR) and renal blood flow (RBF) in adenosine 1 receptor (A1AR) knockout mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 332A EP 332A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501642 ER PT J AU Yamada, K Goto, A Fijita, T Bagrov, A Fedorova, O AF Yamada, K Goto, A Fijita, T Bagrov, A Fedorova, O TI Contribution of maronobufagenin(MBG) to BP elevation in DOCA-saline hypertension. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. Tokyo Univ Hosp, Tokyo 113, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 332A EP 332A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501638 ER PT J AU Hansen, PB Huang, YN Yang, TX Mizel, D Briggs, J Schnermann, J AF Hansen, PB Huang, YN Yang, TX Mizel, D Briggs, J Schnermann, J TI Plasma renin in mice with one or two renin genes. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 335A EP 335A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501657 ER PT J AU Swanson, J Hale, D Cendales, L Kirk, A Mannon, RB AF Swanson, J Hale, D Cendales, L Kirk, A Mannon, RB TI Monitoring immunosuppression following kidney transplantation: Experience with the Cylex (TM) immune cell function assay SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Walter Reed Army Med Ctr, OTS, Washington, DC 20307 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 370A EP 370A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501824 ER PT J AU Shrivastav, S Kopp, JB AF Shrivastav, S Kopp, JB TI HIV-1 accessory protein Vpr suppresses mineralocorticoid receptor-mediated gene transcription. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 376A EP 377A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501856 ER PT J AU Kutner, NG Barnhart, H Zhang, R Pastan, S AF Kutner, NG Barnhart, H Zhang, R Pastan, S TI Baseline quality of life differs in patients who do and do not change dialysis modality in the first year: The DMMS Wave 2 Study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Emory Univ, NIDDK, NIH, USRDS,Qual Life Rehabil Spec Studies Ctr, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 403A EP 404A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501987 ER PT J AU Bucci, JR Oglesby, RJ Agodoa, LY Abbott, KC AF Bucci, JR Oglesby, RJ Agodoa, LY Abbott, KC TI Hospitalizations for total hip arthroplasty after renal transplantation in the United States. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Rheumatol Serv, Washington, DC 20307 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 405A EP 405A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757501993 ER PT J AU Leypoldt, JK Cheung, AK Deeter, RB Beddhu, S Goldfarb-Rumyantzev, AS Greene, T Depner, TA Kusek, JW AF Leypoldt, JK Cheung, AK Deeter, RB Beddhu, S Goldfarb-Rumyantzev, AS Greene, T Depner, TA Kusek, JW TI Equilibrated dialysis dose during short hemodialysis (HD) treatments. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Utah, Div Nephrol, Salt Lake City, UT USA. VASLCHCS, Renal Serv, Salt Lake City, UT USA. VASLCHCS, Res Serv, Salt Lake City, UT USA. Cleveland Clin Fdn, Dept Epidemiol & Biostat, Cleveland, OH 44195 USA. Univ Calif Davis, Div Nephrol, Sacramento, CA 95817 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 413A EP 413A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502032 ER PT J AU Allon, M Depner, TA AF Allon, M Depner, TA CA HEMO Study Grp TI Effect of hemodialysis dose and membrane on infectious outcomes: Results from the HEMO study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 421A EP 421A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502068 ER PT J AU Cheung, AK Levey, AS AF Cheung, AK Levey, AS CA HEMO Study Grp TI Effect of dialysis dose and membrane on cardiac outcomes: Results from the HEMO study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 421A EP 421A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502067 ER PT J AU Eknoyan, G Greene, T AF Eknoyan, G Greene, T CA HEMO Study Grp TI Primary results from the HEMO study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 421A EP 421A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502069 ER PT J AU Meyer, K Benz, R AF Meyer, K Benz, R CA HEMO Study Grp TI Quality of Life (QOL) outcomes in the HEMO study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 421A EP 422A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502071 ER PT J AU Rocco, M Dwyer, J AF Rocco, M Dwyer, J CA HEMO Study Grp TI Effect of dose and flux interventions on nutritional parameters. Results from the hemodialysis study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 421A EP 421A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502070 ER PT J AU Depner, TA Daugirdas, JT AF Depner, TA Daugirdas, JT CA HEMO Study Grp TI Does gender influence the effect of dialysis dose on mortality? Results of the HEMO study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 422A EP 422A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502072 ER PT J AU Lea, J Bakris, G Greene, T Hebert, L Lipkowitz, M Massry, A Middleton, J Miller, E Rostand, S Smith, W AF Lea, J Bakris, G Greene, T Hebert, L Lipkowitz, M Massry, A Middleton, J Miller, E Rostand, S Smith, W CA AASK Study Grp TI Association of baseline proteinuria and GFR with progression of kidney disease in the African American study of kidney disease (AASK). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 422A EP 422A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502073 ER PT J AU Miller, ER Appel, LJ Wang, S Bakris, GL Hebert, L Lipkowitz, M Massry, S Middleton, J Rostand, S Smith, W AF Miller, ER Appel, LJ Wang, S Bakris, GL Hebert, L Lipkowitz, M Massry, S Middleton, J Rostand, S Smith, W CA AASK Study Grp TI The effect of different blood pressure goals and antihypertensive drug regimes on change in proteinuria: Results from the African-American study of kidney disease. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 422A EP 422A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502074 ER PT J AU Appel, LJ Bakris, G Douglas-Baltimore, J Greene, T Kopple, J Massry, S Wang, XL AF Appel, LJ Bakris, G Douglas-Baltimore, J Greene, T Kopple, J Massry, S Wang, XL CA AASK Res Grp TI The relationship between achieved blood pressure (BP) and renal outcomes in the African American study of kidney disease (AASK). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 423A EP 423A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502076 ER PT J AU Lewis, J Greene, T Appel, L Contreras, G Dauglas, J Lash, J Toto, R Vanlente, F Wright, J AF Lewis, J Greene, T Appel, L Contreras, G Dauglas, J Lash, J Toto, R Vanlente, F Wright, J CA AASK Study Grp TI Effects of interventions on outcomes based on serum creatinine in the African American study of kidney disease (AASK). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 423A EP 423A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502077 ER PT J AU Kimmel, PL Argani, S Patel, SS Byrd-Holt, DD AF Kimmel, PL Argani, S Patel, SS Byrd-Holt, DD TI Anthropometric indiced, inflammation and urinary protein excretion in the NHANES III population. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, DKUHD, NIH, Bethesda, MD USA. VAMC, Dept Med, Washington, DC USA. George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. Social Sci Syst, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 424A EP 424A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502083 ER PT J AU Muntner, P He, J Vupputuri, S Coresh, J Batuman, V AF Muntner, P He, J Vupputuri, S Coresh, J Batuman, V TI Blood lead and chronic kidney disease in the general US population: Results from the Third National Health and Nutrition Examination Survey (NHANES III). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Tulane Univ, New Orleans, LA 70118 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 424A EP 424A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502084 ER PT J AU Cheung, AK Levin, NW AF Cheung, AK Levin, NW CA HEMO Study Grp TI Effect of high flux (HF) hemodialysis (HD) membranes on clinical outcomes: Results from the HEMO study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 432A EP 432A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502118 ER PT J AU Barisoni, L Racusen, LC Sinelkov, A Haas, M Kopp, JB AF Barisoni, L Racusen, LC Sinelkov, A Haas, M Kopp, JB TI Morphologic analysis of podocyte diseases: Role of activity and chronicity indices. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 451A EP 451A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502206 ER PT J AU Uhlig, K Wang, SR Beck, GJ Kusek, JW Marcovina, SM Greene, T Levey, AS Sarnak, MJ AF Uhlig, K Wang, SR Beck, GJ Kusek, JW Marcovina, SM Greene, T Levey, AS Sarnak, MJ TI Are lipoprotein(a) level and apoprotein(a) size risk factors for progression of non-diabetic kidney disease? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Tufts New England Med Ctr, Boston, MA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. NW Lipid Res Labs, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 465A EP 465A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502277 ER PT J AU Uhlig, K Wang, SR Beck, GJ Kusek, JW Marcovina, SM Greene, T Levey, AS Sarnak, MJ AF Uhlig, K Wang, SR Beck, GJ Kusek, JW Marcovina, SM Greene, T Levey, AS Sarnak, MJ TI Association of level of kidney function with lipoprotein(a) levels in non-diabetic kidney disease. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. NW Lipid Res Labs, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 467A EP 467A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502285 ER PT J AU Liu, J Cai, T Malhotra, D Bagrov, AY Fedorova, OV Xie, ZJ Shapiro, JI AF Liu, J Cai, T Malhotra, D Bagrov, AY Fedorova, OV Xie, ZJ Shapiro, JI TI Low concentrations of ouabain cause decreased transcellular Na transport and internalization of Na-K-ATPase in LLC-PK1 monolayers. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Med Coll Ohio, Toledo, OH USA. Natl Inst Aging, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 482A EP 482A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502359 ER PT J AU Da Silva, N Beaulieu, V Knepper, M Breton, S AF Da Silva, N Beaulieu, V Knepper, M Breton, S TI The SNARE proteins SNAP-23 and syntaxin 3 are expressed in epithelial cells of the epididymis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Program Membrane Biol, Charlestown, MA USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 486A EP 486A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502380 ER PT J AU Kwon, TH Nielsen, J Knepper, MA Frokiaer, J Nielsen, S AF Kwon, TH Nielsen, J Knepper, MA Frokiaer, J Nielsen, S TI Regulation of sodium transporters in the TAL of rat kidney: Response to angiotensin II (AII). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Dongguk Univ, Sch Med, Dept Physiol, Kyungju, South Korea. Univ Aarhus, Water & Salt Res Ctr, Aarhus, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 489A EP 489A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502395 ER PT J AU Li, CL Wang, WD Knepper, MA Nielsen, S Frokiaer, J AF Li, CL Wang, WD Knepper, MA Nielsen, S Frokiaer, J TI Altered expression of several major Na transporters in response to urinary tract obstruction in rats. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Univ Aarhus, Water & Salt Res Ctr, Aarhus, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 489A EP 489A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502398 ER PT J AU Kamijo, Y Hora, K Tanaka, N Kiyosawa, K Gonzalez, FJ Aoyama, T AF Kamijo, Y Hora, K Tanaka, N Kiyosawa, K Gonzalez, FJ Aoyama, T TI Novel function of peroxisome proliferator-activated, receptor a in glomerular filtrate reabsorption. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Shinshu Univ, Sch Med, Dept Aging Biochem, Matsumoto, Nagano 390, Japan. Shinshu Univ, Sch Med, Dept Internal Med 2, Matsumoto, Nagano 390, Japan. Shinshu Univ, Sch Med, Div Artificial Kidney, Matsumoto, Nagano 390, Japan. NCI, Lab Metab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 493A EP 493A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502416 ER PT J AU Chapman, AB Guay-Woodford, LM Grantham, JJ Torres, VE Kimmel, PL Hirschman, GH Miller, PJ Bae, T AF Chapman, AB Guay-Woodford, LM Grantham, JJ Torres, VE Kimmel, PL Hirschman, GH Miller, PJ Bae, T TI Magnetic resonance imaging (MRI) in early autosomal dominant polycystic kidney disease (ADPKD): Baseline characteristics of the Consortium for Radiographic Imaging Studies of Polycystic Kidney Disease (CRISP) cohort. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Emory Univ, Atlanta, GA 30322 USA. Univ Alabama, Birmingham, AL USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. NIDDK, NIH, Bethesda, MD USA. Washington Univ, St Louis, MO 63130 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 507A EP 507A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502486 ER PT J AU Priyadarshi, S Periyasamy, SM Malhotra, D Kennedy, D Bagrov, AY Fedorova, OV Xie, ZJ Shapiro, JI AF Priyadarshi, S Periyasamy, SM Malhotra, D Kennedy, D Bagrov, AY Fedorova, OV Xie, ZJ Shapiro, JI TI Marinobufagenin (MBG) and ouabain (O) cause increases in reactive oxygen species (ROS) and hypertrophy in adult rat cardiomyocytes. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Med Coll Ohio, Toledo, OH 43699 USA. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 512A EP 512A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502510 ER PT J AU Jo, SK Hu, XZ Aslankhav, A Star, RA AF Jo, SK Hu, XZ Aslankhav, A Star, RA TI Effect of dimethyl sulfoxide (DMSO) on mercuric chloride-induced acute renal failure in mice SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, MDB, NIH, Bethesda, MD 20892 USA. NIEHS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 545A EP 545A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502672 ER PT J AU Jo, SK Kobayashi, H Xu, XZ Koretsky, A Lizak, MJ Star, RA AF Jo, SK Kobayashi, H Xu, XZ Koretsky, A Lizak, MJ Star, RA TI Non-invasive detection of inflammation in rat ischemic acute renal failure by USPIO enhanced magnetic resonance imaging. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, MDB, NIH, Bethesda, MD 20892 USA. NCI, Dept Diagnost & Intervent Imagiol, NIH, Bethesda, MD 20892 USA. NINDS, Lab Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 551A EP 551A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502703 ER PT J AU Kaysen, G Dubin, J Muller, H Mitch, W Levin, N Rosales, L AF Kaysen, G Dubin, J Muller, H Mitch, W Levin, N Rosales, L CA Hemo Study Grp TI A sustained decrease in serum albumin (Salb) concentration is associated with the acute phase response and caused by decreased albumin synthesis (AlbSyn) in hemodialysis (HD) patients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Univ Calif Davis, Davis, CA 95616 USA. VA NCHCS, Mather, CA USA. Yale Univ, Div Biostat, New Haven, CT USA. Emory Univ, Atlanta, GA 30322 USA. Renal Res Inst, New York, NY USA. NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 584A EP 584A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502857 ER PT J AU Trespalacios, FC Taylor, AJ Agodoa, LY Bakris, GL Abbott, KC AF Trespalacios, FC Taylor, AJ Agodoa, LY Bakris, GL Abbott, KC TI Heart failure as an etiology for hospitalization in chronic dialysis patients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Serv Cardiol, Washington, DC 20307 USA. NIDDK, NIH, Bethesda, MD USA. Rush Presbyterian St Lukes Med Ctr, Dept Med, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 593A EP 593A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502903 ER PT J AU Trespalacios, FC Taylor, AJ Agodoa, LY Abbott, KC AF Trespalacios, FC Taylor, AJ Agodoa, LY Abbott, KC TI Incident acute coronary syndromes in chronic dialysis patients in the United States. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Serv Cardiol, Washington, DC 20307 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 594A EP 594A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757502906 ER PT J AU Stiles, KP Agodoa, LY Abbott, KC AF Stiles, KP Agodoa, LY Abbott, KC TI Renal cell carcinoma as a cause of end stage renal disease in the United States: Patient characteristics and survival. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. NIDDK, NIH, Bethesda, MD USA. Madigan Army Med Ctr, Serv Nephrol, Ft Lewis, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 624A EP 624A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503053 ER PT J AU Lemley, KV Boothroyd, DB Blouch, K Nelson, RG Lois, J Olshen, RA Myers, BD AF Lemley, KV Boothroyd, DB Blouch, K Nelson, RG Lois, J Olshen, RA Myers, BD TI Loss of GFR in type 2 diabetic Pima Indians with albuminuria detected at screening. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Stanford Univ, Stanford, CA 94305 USA. NIDDK, Epidemiol Clin Res Branch, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 645A EP 645A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503151 ER PT J AU Smith, DC Branton, MH Bynum, M Penzak, S Kopp, JB AF Smith, DC Branton, MH Bynum, M Penzak, S Kopp, JB TI A phase I/II trial of pirfenidone in idiopathic focal segmental glomerulosclerosis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 668A EP 669A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503266 ER PT J AU Winkler, C Thompson, M Iyengar, S Edwards, S Elston, R AF Winkler, C Thompson, M Iyengar, S Edwards, S Elston, R CA FIND Consortium TI Efficacy of establishing lymphoblastoid cell lines from ESRD patients as a renewable source of DNA. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD 20892 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 733A EP 733A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503581 ER PT J AU Praetorius, HA Frokiaer, J Praetorius, J Nielsen, S Spring, KR AF Praetorius, HA Frokiaer, J Praetorius, J Nielsen, S Spring, KR TI beta 1-integrin is expressed on the primary cilia of MDCK cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI, LKEM, Bethesda, MD 20892 USA. Univ Aarhus, Inst Expt Clin Res, Water & Salt Res Ctr, Aarhus, Denmark. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 739A EP 739A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503607 ER PT J AU Inoue, T Okada, H Kanno, Y Kobayashi, T Watanabe, Y Kikuta, K Kopp, JB Takigawa, M Nakamura, T Suzuki, H AF Inoue, T Okada, H Kanno, Y Kobayashi, T Watanabe, Y Kikuta, K Kopp, JB Takigawa, M Nakamura, T Suzuki, H TI Hepatocyte growth factor counteracts transforming growth factor-betal via attenuation of connective tissue growth factor induction and prevents renal fibrogenesis in 5/6 nephrectomized mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Saitama Med Coll, Iruma, Saitama, Japan. NIDDK, NIH, Bethesda, MD USA. Okayama Univ, Okayama, Japan. Osaka Univ, Dept Oncol, Suita, Osaka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 746A EP 747A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503648 ER PT J AU Miyaji, T Hu, XZ Star, RA AF Miyaji, T Hu, XZ Star, RA TI The effect of early and late fluid resuscitation in LPS-induced acute renal failure in aged mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 SU S BP 756A EP 756A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 589KL UT WOS:000177757503695 ER PT J AU Cheung, AK Yan, GF Greene, T Daugirdas, JT Dwyer, JT Levin, NW Ornt, DB Schulman, G Eknoyan, G AF Cheung, AK Yan, GF Greene, T Daugirdas, JT Dwyer, JT Levin, NW Ornt, DB Schulman, G Eknoyan, G CA Hemodialysis Study Grp TI Seasonal variations in clinical and laboratory variables among chronic hemodialysis patients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID BLOOD-PRESSURE; DIETARY-INTAKE; DISEASE; POPULATION; CHILDREN; YOUNG AB Seasonal variations in BP among chronic hemodialysis patients have been reported. It was hypothesized that other characteristics of these patients might also vary with the seasons. Twenty-one clinical and laboratory variables were examined for seasonal variations among 1445 patients enrolled in the Hemodialysis Study, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Mixed-effects models were applied to longitudinal changes (up to 45 mo) for individual patients for 19 of the 21 variables, which were measured at least twice each year, to determine the seasonal component of each variable. Seasonal variations in the other two variables, i.e., protein and energy intakes determined from annual dietary records, were assessed in cross-sectional comparisons of intakes of patients entering the study at different time points. Thirteen of the 21 variables examined demonstrated statistically significant (P < 0.01) seasonal components in their longitudinal variations. Predialysis blood urea nitrogen concentrations peaked in March, which coincided approximately with the peak protein catabolic rates, as well as protein and energy intakes (determined by dietary recall). Predialysis systolic and diastolic BP values were highest in winter and lowest in summer, corroborating previous reports. In addition, the lower predialysis BP values in summer were associated with higher outdoor temperatures and less interdialytic fluid gain. The mean predialysis hematocrit values were highest in July, which could not be attributed solely to the estimated changes in plasma volume. Seasonal variations in clinical and laboratory variables occur commonly among chronic hemodialysis patients. The reasons for most of these variations are not apparent and require further investigation. Nonetheless, failure to consider these variations might lead to biases in the interpretation of clinical studies. In addition, awareness of these variations might facilitate the interpretation of laboratory results and the clinical treatment of these patients. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Cheung, AK (reprint author), Univ Utah, Dialysis Program, 85 N Med Dr E,Room 201, Salt Lake City, UT 84112 USA. OI Dwyer, Johanna/0000-0002-0783-1769 NR 27 TC 34 Z9 38 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 IS 9 BP 2345 EP 2352 DI 10.1097/01.ASN.0000026611.07106.A7 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 588EA UT WOS:000177687000017 PM 12191979 ER PT J AU Tarver-Carr, ME Powe, NR Eberhardt, MS Laveist, TA Kington, RS Coresh, J Brancati, FL AF Tarver-Carr, ME Powe, NR Eberhardt, MS Laveist, TA Kington, RS Coresh, J Brancati, FL TI Excess risk of chronic kidney disease among African-American versus white subjects in the United States: A population-based study of potential explanatory factors SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; LOW-BIRTH-WEIGHT; NATIONAL DEATH INDEX; II DIABETES-MELLITUS; RACIAL-DIFFERENCES; SOCIOECONOMIC-STATUS; VITAL STATUS; BLACK; RACE; HYPERTENSION AB African Americans experience higher rates of chronic kidney disease (CKD) than do whites. It was hypothesized that racial differences in modifiable factors would account for much of the excess risk of CKD. A cohort study of 9082 African-American and white adults of age 30 to 74 yr, who participated in the Second National Health and Nutrition Examination Survey in 1976 to 1980 and were monitored for vital status through 1992 in the Second National Health and Nutrition Examination Survey Mortality Study, was conducted. Incident CKD was defined as treated CKD cases (ascertained by linkage to the Medicare Registry) and deaths related to kidney disease. The incidence of all-cause CKD was 2.7 times higher among African Americans, compared with whites. Adjustment for sociodemographic factors decreased the relative risk (RR) to 2.49, explaining 12% of the excess risk of CKD among African Americans. Further adjustment for lifestyle factors explained 24% of the excess risk, whereas adjustment for clinical factors alone explained 32%. Simultaneous adjustment for sociodemographic, lifestyle, and clinical factors attenuated the RR to 1.95 (95% confidence interval, 1.05 to 3.63), explaining 44% of the excess risk. Although the excess risk of CKD among African Americans was much greater among middle-age adults (30 to 59 yr of age; RR = 4.23, statistically significant) than among older adults (60 to 74 yr of age; RR = 1.27), indicating an interaction between race and age, the same patterns of explanatory factors were observed for the two age groups. Nearly one one-half of the excess risk of CKD among African-American adults can be explained on the basis of potentially modifiable risk factors; however, much of the excess risk remains unexplained. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Johns Hopkins Univ, Dept Sociol, Baltimore, MD 21218 USA. NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Brancati, FL (reprint author), Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St,Suite 2-600, Baltimore, MD 21205 USA. FU NIGMS NIH HHS [F31-GM20081] NR 59 TC 147 Z9 147 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 IS 9 BP 2363 EP 2370 DI 10.1097/01.ASN.0000026493.18542.6A PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 588EA UT WOS:000177687000019 PM 12191981 ER PT J AU Li, RM Branton, MH Tanawattanacharoen, S Falk, RA Jennette, JC Kopp, JB AF Li, RM Branton, MH Tanawattanacharoen, S Falk, RA Jennette, JC Kopp, JB TI Molecular identification of SV40 infection in human subjects and possible association with kidney disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; HUMAN BRAIN-TUMORS; LARGE T-ANTIGEN; SV40-LIKE SEQUENCES; REGULATORY REGION; SIMIAN VIRUS-40; DNA-SEQUENCES; SIMIAN-VIRUS-40; MESOTHELIOMA; CELLS AB Simian virus 40 (SV40), a monkey polyomavirus that is believed to have entered the human population through contaminated vaccines, is known to be renotropic in simians. If indeed SV40 is endemic within the human population, the route of transmission is unknown. It was therefore hypothesized that SV40 might be renotropic in humans and be detected more frequently in samples obtained from patients with kidney diseases. This study found that typical polyomavirus cytopathic effects (CPE) were present and SV40 T antigen was detected in CV-1 cells cultured with peripheral blood mononuclear cells (PBMC) or urinary cells obtained from patients with kidney disease and healthy volunteers. DNA sequences homologous to the SV40 viral regulatory genome were detected by PCR in urinary cells from 15 (41%) of 36 patients with focal segmental glomerulosclerosis (FSGS), 2 (10%) of 20 patients with other kidney diseases, and 1 (4%) of 22 healthy volunteers (FSGS compared with other glomerular disease, P < 0.02; FSGS compared with healthy volunteers, P = 0.003). SV40 viral regulatory region genome was detected from PBMC at similar frequencies in patients with FSGS (35%), other glomerular diseases (20%), and healthy volunteers (22%). SV40 genome was detected by PCR in kidney tissues from 17 (56%) of 30 of patients with FSGS and 4 (20%) of 20 patients with minimal change disease and membranous nephropathy (P < 0.01). Considerable genetic heterogeneity of the viral regulatory region was detected, which argues against laboratory contamination. SV40 genome was localized to renal tubular epithelial cell nuclei in renal biopsies of patients with FSGS by in situ hybridization. This study demonstrates for the first time that human kidney can serve as a reservoir for SV40 replication and that SV40 may contribute to the pathogenesis of kidney disease, particularly FSGS. C1 NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Univ N Carolina, Dept Pathol, Chapel Hill, NC USA. RP Kopp, JB (reprint author), NIDDKD, Kidney Dis Sect, NIH, 10-3N116, Bethesda, MD 20892 USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 33 TC 92 Z9 98 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2002 VL 13 IS 9 AR UNSP 1046-6673/1309-2320 DI 10.1097/01.ASN.0000028249.06596.CF PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 588EA UT WOS:000177687000014 PM 12191976 ER PT J AU Patterson, BH Dayton, CM Graubard, B AF Patterson, BH Dayton, CM Graubard, B TI Latent class analysis of complex sample survey data: Application to dietary data SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE categorical data; cluster sample; design effect; dietary propensity scores; jackknife; latent class model; sample weight ID INTAKE DISTRIBUTIONS; CONTINGENCY-TABLES; UNITED-STATES; CLASS MODELS; NUTRIENT; VALIDATION; DESIGN; FRUIT AB High fruit and vegetable intake is associated with decreased cancer risk. However, dietary recall data from national surveys suggest that, on any given day, intake falls below the recommended minima of three daily servings of vegetables and two daily servings of fruit. There is no single widely accepted measure of "usual" intake. One approach is to regard the distribution of intake as a mixture of "regular" (relatively frequent) and "nonregular" (relatively infrequent) consumers, using an indicator of whether an individual consumed the food of interest on the recall day. We use a new approach to summarizing dietary data, latent class analysis (LCA), to estimate "usual" intake of vegetables. The data consist of four 24-hour dietary recalls from the 1985 Continuing Survey of Intakes by Individuals collected from 1,028 women. Traditional LCA based on simple random sampling was extended to complex Survey data by introducing sample weights into the latent class estimation algorithm and by accounting for the complex sample design through the use of jackknife standard errors. A two-class model showed that 18% do not regularly consume vegetables, compared to an unweighted estimate of 33%. Simulations showed that ignoring sample weights resulted in biased parameter estimates and that jackknife variances were slightly conservative but provided satisfactory confidence interval coverage. Using a survey-wide estimate of the design effect for variance estimation is not accurate for LCA. The methods proposed in this article are readily implemented for the analysis of complex sample survey data. C1 NCI, Div Canc Prevent, Biometry Res Grp, Bethesda, MD 20892 USA. Univ Maryland, Dept Measurement Stat & Evaluat, College Pk, MD 20742 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Patterson, BH (reprint author), NCI, Div Canc Prevent, Biometry Res Grp, Bethesda, MD 20892 USA. NR 67 TC 34 Z9 35 U1 3 U2 12 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2002 VL 97 IS 459 BP 721 EP 729 DI 10.1198/016214502388618465 PG 9 WC Statistics & Probability SC Mathematics GA 593WY UT WOS:000178018500007 ER PT J AU Kaplan, N Morris, R AF Kaplan, N Morris, R TI Adjusting for population heterogeneity and misspecified haplotype frequencies when testing nonparametric null hypotheses in statistical genetics - Comment SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Editorial Material C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Kaplan, N (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2002 VL 97 IS 459 BP 753 EP 754 DI 10.1198/016214502388618546 PG 2 WC Statistics & Probability SC Mathematics GA 593WY UT WOS:000178018500015 ER PT J AU Cook, ED AF Cook, ED TI Selenium and vitamin E cancer prevention trial - This one's for us SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE cancer prevention; selenium; vitamin E; SELECT ID SUPPLEMENTATION C1 NCI, SELECT Minor & Med Underserved Subcomm, Bethesda, MD 20892 USA. RP Cook, ED (reprint author), NCI, SELECT Minor & Med Underserved Subcomm, Bethesda, MD 20892 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD SEP PY 2002 VL 94 IS 9 BP 856 EP 858 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 602WV UT WOS:000178528200013 PM 12392050 ER PT J AU Schaeffer, AJ Knauss, JS Landis, JR Propert, KJ Alexander, RB Litwin, MS Nickel, JC O'Leary, MP Nadler, RB Pontari, MA Shoskes, DA Zeitlin, SI Fowler, JE Mazurick, CA Kusek, JW Nyberg, LM AF Schaeffer, AJ Knauss, JS Landis, JR Propert, KJ Alexander, RB Litwin, MS Nickel, JC O'Leary, MP Nadler, RB Pontari, MA Shoskes, DA Zeitlin, SI Fowler, JE Mazurick, CA Kusek, JW Nyberg, LM CA Chronic Prostatitis Collaborative TI Leukocyte and bacterial counts do not correlate with severity of symptoms in men with chronic prostatitis: The National Institutes of Health chronic prostatitis cohort study SO JOURNAL OF UROLOGY LA English DT Article DE prostatitis; chronic disease; pelvic pain; leukocytes, bacteria ID NONBACTERIAL PROSTATITIS; INFLAMMATION; PREVALENCE; SEQUENCES; INDEX AB Purpose: We examine whether leukocytes and bacteria correlate with symptom severity in men with chronic prostatitis/chronic pelvic pain syndrome. Materials and Methods: All 488 men screened into the National Institutes of Health Chronic Prostatitis Cohort Study before close of recruitment on August 22, 2001 were selected for analysis. The National Institutes of Health Chronic Prostatitis Symptom Index, including subscores, were used to measure symptoms. Urethral inflammation was defined as white blood cell (WBC) counts of 1 or more (1+) in the first voided urine. Participants were classified as category IIIa based on WBC counts of 5 or more, or 10 or more (5+, 10+) in the expressed prostatic secretion, or 1+ or 5+ either in the post-expressed prostatic secretion urine (voided urine 3) or semen. Uropathogens were classified as localizing if the designated bacterial species were absent in voided urine 1 and voided urine 2 but present in expressed prostatic secretion, voided urine 3 or semen, or present in expressed prostatic secretion, voided urine 3 or semen at 2 log concentrations higher than at voided urine 1 or 2. Associations between symptoms, and inflammation and infection were investigated using generalized Mantel-Haenszel methods. Results: Of all participants 50% had urethral leukocytes and of 397 with expressed prostatic secretion samples 194 (49%) and 122 (31%) had 5+ or 10+ WBCs in expressed prostatic secretion, respectively. The prevalence of category IIIa ranged from 90% to 54%, depending on the composite set of cut points. None of the index measures were statistically different (p >0.10) for selected leukocytosis subgroups. Based on prostate and semen cultures, 37 of 488 men (8%) had at least 1 localizing uropathogen. None of the index measures were statistically different (p >0.10) for selected bacterial culture subgroups. Conclusions: Although men with chronic prostatitis routinely receive anti-inflammatory and antimicrobial therapy, we found that leukocytes and bacterial counts as we defined them do not correlate with severity of symptoms. These findings suggest that factors other than leukocytes and bacteria also contribute to symptoms associated with chronic pelvic pain syndrome. C1 Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, Philadelphia, PA 19104 USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Queens Univ, Dept Urol, Kingston, ON K7L 3N6, Canada. Cleveland Clin Florida, Weston, FL USA. Univ Mississippi, Jackson, MS 39216 USA. Univ Maryland, Baltimore, MD 21201 USA. NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Schaeffer, AJ (reprint author), Northwestern Univ, Sch Med, Dept Urol, Tarry 11-715,303 E Chicago Ave, Chicago, IL 60611 USA. RI Landis, J. Richard/A-9330-2010 FU NIDDK NIH HHS [R01 DK53734, R01 DK53730, R01 DK53732, R01 DK53736, R01 DK53746, R01 DK53752] NR 21 TC 103 Z9 155 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2002 VL 168 IS 3 BP 1048 EP 1053 AR UNSP 0022-5347/02/1683-1080/0 DI 10.1097/01.ju.0000024762.69326.df PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 585TA UT WOS:000177539600034 PM 12187220 ER EF