FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sharabi, Y Li, ST Dendi, R Holmes, C Goldstein, DS AF Sharabi, Y Li, ST Dendi, R Holmes, C Goldstein, DS TI Neurotransmitter specificity of sympathetic denervation in Parkinson's disease SO NEUROLOGY LA English DT Article ID DYSFUNCTION AB In PD, orthostatic hypotension reflects sympathetic noradrenergic denervation. The authors assessed sympathetic cholinergic innervation by the quantitative sudomotor axon reflex test (QSART) in 12 patients who had sympathetic neurocirculatory failure, markedly decreased cardiac 6-[F-18] fluorodopamine-derived radioactivity, and subnormal plasma norepinephrine increments during standing. All 12 had normal QSART results. The sympathetic nervous system lesion in PD involves loss of postganglionic catecholaminergic but not cholinergic nerves. C1 NINDS, Clin Neuroradiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neuroradiol Sect, NIH, Bldg 10 Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. NR 10 TC 18 Z9 20 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 25 PY 2003 VL 60 IS 6 BP 1036 EP 1039 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 679YB UT WOS:000182948600033 PM 12654979 ER PT J AU Hill, DA Gridley, G Cnattingius, S Mellemkjaer, L Linet, M Adami, HO Olsen, JH Nyren, O Fraumeni, JF AF Hill, DA Gridley, G Cnattingius, S Mellemkjaer, L Linet, M Adami, HO Olsen, JH Nyren, O Fraumeni, JF TI Mortality and cancer incidence among individuals with Down syndrome SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 92nd Annual Meeting of the American-Association-for-Cancer-Research CY MAR 24-28, 2001 CL NEW ORLEANS, LOUISIANA SP Amer Assoc Canc Res ID HELICOBACTER-PYLORI INFECTION; GERM-CELL TUMORS; COMPARATIVE GENOMIC HYBRIDIZATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; CEREBRAL AMYLOID ANGIOPATHY; MENTALLY-RETARDED PATIENTS; NEONATAL RISK-FACTORS; ALZHEIMERS-DISEASE; MYOCARDIAL-INFARCTION; MYELOID-LEUKEMIA AB Background: Individuals with Down syndrome (DS) have a predisposition to leukemia and possibly other cancers and excess mortality from other conditions, but information on the magnitude of risk associated with specific cancers or causes of death is sparse. Methods: Mortality experience and cancer incidence were evaluated in a combined cohort of 4872 individuals with a hospital discharge diagnosis of DS in Sweden (1965-1993) or Denmark (1977-1989) by linkage to national cancer and vital statistics registries. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were estimated by comparison with age, sex, and calendar-year expected values. Results: Individuals with DS had an increased risk of incident acute lymphocytic (SIR, 24.2; 95% confidence interval [CI], 15.2-36.6; n=22) and acute nonlymphocytic (SIR, 28.2; 95% CI 15.7-48.3; n = 14) leukemias. Risks f testicular cancer (SIR, 3.7; 95% CI, 1.0-9.4; n=4) and liver cancer (SIR, 6.0; 95% CI 1.2-17.5; n=3) were also elevated. individuals with DS also experienced elevated mortality attributed to stomach cancer (SMR, 6.4; 95% CI 1.7-16.4; n=4), dementia and Alzheimer disease (SMR, 54.1; 95% CI 27.9-94.4), epilepsy (SMR, 30.4; 95% CI 13.9-57.7), ischemic heart disease (SMR, 3.9; 95% CI 2.7-5.4), other heart disease (SMR, 16.5; 95% CI 11.0-3.7), cerebrovascular disease (SMR, 6.0; 95% CI 3.5-.6); infectious diseases (SMR, 12.0; 95% 6.0-21.4), and congenital anomalies (SMR, 25.8; 95% CI 21.0-31.4). Conclusions: Individuals with DS have a substantially increased risk of mortality due to specific causes and may have an elevated risk of other incident cancers in addition to leukemia. These results provide clues regarding chromosome 21 gene involvement in diseases that complicate DS and are important for disease detection and care of affected individuals. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. RP Hill, DA (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC 7238, Bethesda, MD 20892 USA. EM dhill@mail.nih.gov NR 62 TC 107 Z9 110 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 24 PY 2003 VL 163 IS 6 BP 705 EP 711 DI 10.1001/archinte.163.6.705 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 658JK UT WOS:000181717700012 PM 12639204 ER PT J AU Smothers, BA Yahr, HT Sinclair, MD AF Smothers, BA Yahr, HT Sinclair, MD TI Prevalence of current DSM-IV alcohol use disorders in short-stay, general hospital admissions, United States, 1994 SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID INTERVIEW SCHEDULE AUDADIS; PROBLEM DRINKERS; DRUG MODULES; ABUSE; DRINKING; SAMPLE; IDENTIFICATION; RELIABILITY; DEPENDENCE; SMOKING AB Background: This study provides, to our knowledge, the first national prevalence estimates of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-V), alcohol use disorders based on a structured, diagnostic instrument for inpatient admissions to US general hospitals. Existing prevalence estimates for inpatient admissions came from studies conducted in 1 or 2 hospitals and therefore do not support national inference. Methods: A multistage probability sample was designed to represent acute care admissions to nonfederal, short-stay, general hospitals in the contiguous United States; 2040 admissions (1613 males and 427 females) in 90 hospitals participated. Results: An estimated 1.8 million (95% confidence interval, 1.3-2.2 million) annual hospital admissions met the criteria for a current (ie, in the past 12 months) DSM-IV alcohol use disorder. Overall prevalence was estimated to be 7.4% (95% confidence interval, 5.6%-9.1%). Among current-drinking admissions, estimated prevalence was 24.0% (95% confidence interval, 18.7%-29.4%), and males and females had similar rates. Pairwise comparisons showed significant elevations in the prevalence of alcohol use disorders in current-drinking admissions who were younger, black, unmarried, of a lower socioeconomic status, on Medicaid or without health insurance, smokers, or drug users. Prevalence of alcohol use disorders was also significantly hihter in current-drinking admissions in hospitals that were government owned, had medical school affiliations, or had-a high number of emergency department visits per day. Conclusions: The prevalence of alcohol abuse or dependence in current-drinking admissions was substantial, suggesting that hospitalization offers a unique opportunity to identify alcohol use disorders. Further research is needed to determine factors that may be associated with significant pairwise results, especially for race or ethnicity. We recommend alcohol screening of all hospitalized drinkers, followed, as appropriate, by diagnostic evaluation and referral or intervention. C1 NIAAA, NIH, Bethesda, MD 20892 USA. Mathematica Policy Res, Princeton, NJ USA. RP Smothers, BA (reprint author), NIAAA, NIH, 6000 Execut Blvd,Suite 514, Bethesda, MD 20892 USA. EM bs86h@nih.gov FU AHRQ HHS [HHS100970018]; NIAAA NIH HHS [AA9705, N01AA90007]; SAMHSA HHS [N0AA82014] NR 41 TC 33 Z9 35 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 24 PY 2003 VL 163 IS 6 BP 713 EP 719 DI 10.1001/archinte.163.6.713 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 658JK UT WOS:000181717700013 PM 12639205 ER PT J AU Chan, KA Truman, A Gurwitz, JH Hurley, JS Martinson, B Platt, R Everhart, JE Moseley, RH Terrault, N Ackerson, L Selby, JV AF Chan, KA Truman, A Gurwitz, JH Hurley, JS Martinson, B Platt, R Everhart, JE Moseley, RH Terrault, N Ackerson, L Selby, JV TI A cohort study of the incidence of serious acute liver injury in diabetic patients treated with hypoglycemic agents SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 17th International Conference on Pharmacoepidemiology CY AUG 23-26, 2001 CL TORONTO, CANADA ID HEPATIC-FAILURE; TROGLITAZONE; HEPATOTOXICITY; DYSFUNCTION; PREVALENCE; DISEASE; HEALTH AB Background: The incidence of acute liver failure or serious liver injury in diabetic patients is needed to evaluate the safety of hypoglycemic drug therapy. Methods: We conducted a retrospective cohort study of 5 health maintenance organizations. Study patients were 171264 health plan members 19 years or older when they received oral hypoglycemic drugs or insulin between April 1, 1997, and June 30, 1999. We searched for hospital discharge diagnoses and procedures potentially indicative of acute liver injury and reviewed the full-text medical records. Acute liver failure was defined as acute liver disease and (1) hepatic encephalopathy, (2) prothrombin time prolongation greater than 3 seconds or international normalized ratio greater than 1.5, and (3) a total bilirubin level greater than 3.0 mg/dL (>51 mumol/L). Acute liver injury was diagnosed in individuals who did not meet I or more of the criteria for acute liver failure but had alanine transaminase or aspartate transaminase levels greater than 500 U/L. Results: We identified 35 cases of acute liver failure or injury not clearly attributable to a known cause other than use of hypoglycemic agents. The age- and sex-standardized incidence per 1000 person-years was 0.15 for insulin users, 0.08 for sulfonylurea users, 0.12 for metformin users, and 0.10 for troglitazone users. The incidence-was higher (on the order of 0.3 per. 1000) during the first 6 months of exposure to all hypoglycemic agents. Conclusions: Acute liver failure or injury not clearly attributable to other known causes occurred on the order of 1 per 10000 person-years among diabetic patients treated with oral hypoglycemic drugs or insulin. C1 Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94612 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Fallon Healthcare Syst, Worcester, MA USA. Meyers Primary Care Inst, Worcester, MA USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Lovelace Resp Res Inst, Albuquerque, NM USA. HealthPartners Res Fdn, Minneapolis, MN USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. NIDDKD, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. RP Selby, JV (reprint author), Kaiser Permanente Med Care Program, Div Res, 2000 Broadway, Oakland, CA 94612 USA. OI Chan, Kinwei/0000-0001-8161-1986 NR 33 TC 44 Z9 46 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 24 PY 2003 VL 163 IS 6 BP 728 EP 734 DI 10.1001/archinte.163.6.728 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 658JK UT WOS:000181717700015 PM 12639207 ER PT J AU Zhang, XC Pais, GCG Svarovskaia, ES Marchand, C Johnson, AA Karki, RG Nicklaus, MC Pathak, VK Pommier, Y Burke, TR AF Zhang, XC Pais, GCG Svarovskaia, ES Marchand, C Johnson, AA Karki, RG Nicklaus, MC Pathak, VK Pommier, Y Burke, TR TI Azido-containing aryl beta-diketo acid HIV-1 integrase inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID STRAND TRANSFER; REPLICATION; CELLS AB Aryl beta-diketo acids (ADK) comprise a general class of potent HIV-1 integrase (IN) inhibitors, which can exhibit selective inhibition of strand transfer reactions in extracellular recombinant IN assays and provide potent antiviral effects in HIV-infected cells. Recent studies have shown that polycyclic aryl or aryl rings bearing aryl-containing substituents are components of potent members of this class. Reported herein is the first use of azido functionality as an aryl replacement in beta-diketo acid IN inhibitors. The ability of azido-containing inhibitors to exhibit potent inhibition of IN and antiviral protection in HIV-infected cells, renders the azide group of potential value in the further development of ADK-based IN inhibitors. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 NCI, Med Chem Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, HIV Drug Reistance Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM tburke@helix.nih.gov RI Nicklaus, Marc/N-4183-2014; Burke, Terrence/N-2601-2014; OI Nicklaus, Marc/0000-0002-4775-7030 NR 22 TC 62 Z9 64 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAR 24 PY 2003 VL 13 IS 6 BP 1215 EP 1219 DI 10.1016/S0960-894X(03)00059-3 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 658HK UT WOS:000181715400051 PM 12643946 ER PT J AU Corthout, E Hallett, M Cowey, A AF Corthout, E Hallett, M Cowey, A TI Interference with vision by TMS over the occipital pole: a fourth period SO NEUROREPORT LA English DT Article DE occipital cortex; transcranial magnetic stimulation (TMS); vision ID TRANSCRANIAL MAGNETIC STIMULATION; EARLY VISUAL-CORTEX; AREAS V1; PERCEPTION; SUPPRESSION; TOPOGRAPHY; RESPONSES; V5 AB We investigated the effect of single-pulse transcranial magnetic stimulation (TMS) over the occipital pole on a forced-choice visual letter-identification task. Magnetic stimuli were applied on the midline but with the initial current directed pseudorandomly toward either left or right hemisphere; visual stimuli were presented randomly in either left or right hemifield; magnetic-visual stimulus onset asynchrony varied randomly between 12 values: -500 ms and from -50 ms to +50 ms in 10 ms steps. The data revealed the existence of a hitherto unknown fourth task-interfering TMS effect that was maximal at -10 ms and specific for magnetic stimulus polarity and visual stimulus location. This -10 ms effect cannot be explained by reflex blinking (as the -50 ms effect can) and direct disruption of letter-induced activity (as the +20 ms and +100 ms effects can), but it could be explained by direct disruption of pre-letter activity or indirect disruption of letter-induced activity. C1 Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Corthout, E (reprint author), Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England. EM erik.corthout@lincoln.ox.ac.uk NR 25 TC 25 Z9 25 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 24 PY 2003 VL 14 IS 4 BP 651 EP 655 DI 10.1097/00001756-200303240-00026 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 672ZP UT WOS:000182554200026 PM 12657905 ER PT J AU Gil-da-Costa, R Palleroni, A Hauser, MD Touchton, J Kelley, JP AF Gil-da-Costa, R Palleroni, A Hauser, MD Touchton, J Kelley, JP TI Rapid acquisition of an alarm response by a neotropical primate to a newly introduced avian predator SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE predator-prey arms races; playbacks; predator-assessment calls; evolutionary mechanisms; conservation biology ID ANTIPREDATOR RESPONSE; ALOUATTA-PALLIATA; HOWLER MONKEYS; CALLS; BEHAVIOR; SIGNALS; PANAMA; PREY AB Predation is an important selective pressure in natural ecosystems. Among non-human primates, relatively little is known about how predators hunt primate prey and how primates acquire adaptive responses to counteract predation. In this study we took advantage of the recent reintroduction of radio-tagged harpy eagles (Harpia harpyja) to Barro Colorado Island (BCI), Panama to explore how mantled howler monkeys (Alouatta palliata), one of their primary prey, acquire anti-predator defences. Based on the observation that harpies follow their prey prior to attack, and often call during this pursuit period, we broadcast harpy eagle calls to howlers on BCI as well as to a nearby control population with no harpy predation. Although harpies have been extinct from this area for 50-100 years, results indicate that BCI howlers rapidly acquired an adaptive anti-predator response to harpy calls, while showing no response to other avian vocalizations; howlers maintained this response several months after the removal of the eagles. These results not only show that non-human primates can rapidly acquire an alarm response to a newly introduced predator, but that they can detect and identify predators on the basis of acoustic cues alone. These findings have significant implications both for the role of learning mechanisms in the evolution of prey defence and for conservation strategies, suggesting that the use of 'probing' approaches, such as auditory playbacks, may highly enhance an a priori assessment of the impact of species reintroduction. C1 Harvard Univ, Dept Psychol, Primate Cognit Neurosci Lab, Cambridge, MA 02138 USA. Gulbenkian Inst Sci, Program Biol & Med, Lisbon, Portugal. Peregrine Fund, Neotrop Raptor Ctr, Panama City, Panama. RP Gil-da-Costa, R (reprint author), NIH, 10 Ctr Dr,MSC 1366,Bldg 10,Room 4C103, Bethesda, MD 20892 USA. EM rcosta@helix.nih.gov NR 31 TC 34 Z9 35 U1 5 U2 43 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 J9 P ROY SOC B-BIOL SCI JI Proc. R. Soc. B-Biol. Sci. PD MAR 22 PY 2003 VL 270 IS 1515 BP 605 EP 610 DI 10.1098/rspb.2002.2281 PG 6 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA 659HA UT WOS:000181769800008 PM 12769460 ER PT J AU Cabral, WA Mertts, MV Makareeva, E Colige, A Tekin, M Pandya, A Leikin, S Marin, JC AF Cabral, WA Mertts, MV Makareeva, E Colige, A Tekin, M Pandya, A Leikin, S Marin, JC TI Type I collagen triplet duplication mutation in lethal osteogenesis imperfecta shifts register of alpha chains throughout the helix and disrupts incorporation of mutant helices into fibrils and extracellular matrix SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DYE LABELING REAGENTS; N-PROTEINASE; PRO-ALPHA-1(I) CHAIN; SUCCINIMIDYL ESTERS; POINT MUTATION; PROCOLLAGEN; CLEAVAGE; DELETION; ALLELE; COL1A1 AB The majority of collagen mutations causing osteogenesis imperfecta (OI) are glycine substitutions that disrupt formation of the triple helix. A rare type of collagen mutation consists of a duplication or deletion of one or two Gly-X-Y triplets. These mutations shift the register of collagen chains with respect to each other in the helix but do not interrupt the triplet sequence, yet they have severe clinical consequences. We investigated the effect of shifting the register of the collagen helix by a single Gly-X-Y triplet on collagen assembly, stability, and incorporation into fibrils and matrix. These studies utilized a triplet duplication in COL1A1 exon 44 that occurred in the cDNA and gDNA of two siblings with lethal OI. The normal allele encodes three identical Gly-Ala-Hyp triplets at aa 868-876, whereas the mutant allele encodes four. The register shift delays helix formation, causing overmodification. Differential scanning calorimetry yielded a decrease in T-m of 2 degreesC for helices with one mutant chain and a 6 degreesC decrease in helices with two mutant chains. An in vitro binary co-processing assay of N-proteinase cleavage demonstrated that procollagen with the triplet duplication has slower N-propeptide cleavage than in normal controls or procollagen with proalpha1(I) G832S, G898S, or G997S substitutions, showing that the register shift persists through the entire helix. The register shift disrupts incorporation of mutant collagen into fibrils and matrix. Proband fibrils formed inefficiently in vitro and contained only normal helices and helices with a single mutant chain. Helices with two mutant chains and a significant portion of helices with one mutant chain did not form fibrils. In matrix deposited by proband fibroblasts, mutant chains were abundant in the immaturely cross-linked fraction but constituted a minor fraction of maturely cross-linked chains. The profound effects of shifting the collagen triplet register on chain interactions in the helix and on fibril formation correlate with the severe clinical consequences. C1 NICHD, Sect Connect Tissue Disorders, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NICHD, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA. Univ Liege, Connect Tissue Res Labs, Liege, Belgium. Virginia Commonwealth Univ, Med Coll Virginia, Dept Human Genet, Richmond, VA 23298 USA. RP Marin, JC (reprint author), NICHD, Sect Connect Tissue Disorders, Heritable Disorders Branch, NIH, Bldg 10,Rm 9S241,9000 Rockville Pike, Bethesda, MD 20892 USA. EM oidoc@helix.nih.gov RI Leikin, Sergey/A-5518-2008; Makareeva, Elena/F-5183-2011 OI Leikin, Sergey/0000-0001-7095-0739; NR 39 TC 18 Z9 20 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 21 PY 2003 VL 278 IS 12 BP 10006 EP 10012 DI 10.1074/jbc.M212523200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 659LE UT WOS:000181777500003 PM 12538651 ER PT J AU He, ML Zemkova, H Stojilkovic, SS AF He, ML Zemkova, H Stojilkovic, SS TI Dependence of purinergic P2X receptor activity on ectodomain structure SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C-TERMINAL DOMAIN; ATP-BINDING-SITE; MUTATIONAL ANALYSIS; GLUTAMATE-RECEPTOR; CRYSTAL-STRUCTURES; LIGAND-BINDING; PROTEIN-KINASE; ION CHANNELS; AMINO-ACIDS; DESENSITIZATION AB Purinergic receptors (P2XRs) activate and desensitize in response to the binding of extracellular nucleotides in a receptor- and ligand-specific manner, but the structural bases of their ligand preferences and channel kinetics have been incompletely characterized. Here we tested the hypothesis that affinity of agonists for binding domain accounts for a ligand-specific desensitization pattern. We generated chimeras using receptors with variable sensitivity to ATP in order: P2X(4)R > P2X(2a)R = P2X(2b)R much greater than P2X(7)R. Chimeras having the ectodomain Ile(66) - Tyr(310) sequence of P2X(2)R and Val(61) - Phe(313) sequence of P2X(7)R in the backbone of P2X(4)R were expressed but were non-functioning channels. P2X(2a) + X4R and P2X(2b) + X4R chimeras having the Val(66) - Tyr(315) ectodomain sequence of P2X(4)R in the backbones of P2X(2a)R and P2X(2b)R were functional and exhibited increased sensitivity to ligands as compared with both parental receptors. These chimeras also desensitized faster than parental receptors and in a ligand-nonspecific manner. However, like parental P2X(2)bR and P2X(2a)R, chimeric P2X(2b) + X4R desensitized more rapidly than P2X(2a) + X4R, and the rate of desensitization of P2X(2a) + X4R increased by substituting its Arg(371) - Pro(376) intracellular C-terminal sequence with the Glu(376) - Gly(381) sequence of P2X(4)R. These results indicate the relevance of interaction between the ectodomain and flanking regions around the transmembrane domains on ligand potency and receptor activation. Furthermore, the ligand potency positively correlates with the rate of receptor desensitization but does not affect the C-terminal-specific pattern of desensitization. C1 NICHD, ERRB, SCS, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHD, ERRB, SCS, NIH, Bldg 49,Rm 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov RI Zemkova, Hana/C-1844-2012 NR 44 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 21 PY 2003 VL 278 IS 12 BP 10182 EP 10188 DI 10.1074/jbc.M209094200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 659LE UT WOS:000181777500027 PM 12524445 ER PT J AU Staudinger, R Phogat, SK Xiao, XD Wang, XH Dimitrov, DS Zolla-Pazner, S AF Staudinger, R Phogat, SK Xiao, XD Wang, XH Dimitrov, DS Zolla-Pazner, S TI Evidence for CD4-enchanced signaling through the chemokine receptor CCR5 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIV-1; INFECTION; BINDING; FUSION; CD4; OLIGOMERIZATION; EXPRESSION; RETROVIRUS; CORECEPTOR; COMPONENT AB The chemokine receptor CCR5 is constitutively associated with the T cell co-receptor CD4 in plasma cell membranes, but the physiological role of this interaction has not been elucidated. Here we show that detergent-solubilized, purified CCR5 can directly associate with purified soluble fragments of the extracellular portion of CD4. We further demonstrate that the physical association of CCR5 and CD4 in membrane vesicles results in the formation of a receptor complex that exhibits macrophage inflammatory protein 1beta (MIP-1beta) binding properties that are distinct from CCR5. The affinity of the CD4-CCR5 complex for MIP-1beta was 3.5-fold lower than for CCR5, but the interaction of CD4 and CCR5 resulted in a receptor complex that exhibited enhanced G-protein signaling as compared with CCR5 alone. MIP1beta-induced G-protein activation was further increased by simultaneous stimulation of CD4 with its natural agonist, interleukin-16. Thus, the physical association of CD4 and CCR5 results in receptor cross-talk with allosteric CD4-dependent regulation of the binding and signaling properties of CCR5. Although the precise physiological role of the CD4 effects on CCR5-mediated signaling remains unknown, one can speculate that the cross-talk is a component of mechanisms involved in the fine tuning of immune system cell responses. C1 NYU, Sch Med, Dept Neurol, New York, NY 10016 USA. NCI, Lab Expt & Computat Biol, Frederick Canc Res & Dev Ctr, NIH, Ft Detrick, MD 21702 USA. NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NYU, Sch Med, Vet Affairs New York Harbor Healthcare Syst, New York, NY 10016 USA. RP Staudinger, R (reprint author), NYU, Sch Med, Dept Neurol, 550 1st Ave,NBV 7W11, New York, NY 10016 USA. EM robert.staudinger@med.nyu.edu FU NHLBI NIH HHS [HL59725]; NIAID NIH HHS [AI36085, AI27742] NR 29 TC 24 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 21 PY 2003 VL 278 IS 12 BP 10389 EP 10392 DI 10.1074/jbc.M212013200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 659LE UT WOS:000181777500054 PM 12531905 ER PT J AU Takahashi, S Saito, T Hisanaga, S Pant, HC Kulkarni, AB AF Takahashi, S Saito, T Hisanaga, S Pant, HC Kulkarni, AB TI Tau phosphorylation by cyclin-dependent kinase 5/p39 during brain development reduces its affinity for microtubules SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PAIRED HELICAL FILAMENTS; ALZHEIMER-LIKE STATE; CDK5 ACTIVATOR P35; PROTEIN-KINASE; NEURITE OUTGROWTH; RAT-BRAIN; ABNORMAL PHOSPHORYLATION; NEURONAL DIFFERENTIATION; CEREBELLAR MACRONEURONS; REGULATORY SUBUNIT AB The microtubule-associated protein tau is a developmentally regulated neuronal phosphoprotein. The phosphorylation of tau reduces its ability to bind and stabilize axonal microtubules during axonal growth. Although tau is phosphorylated by cyclin-dependent kinase 5 (Cdk5) in vitro, its in vivo roles remain unclear. Here, we show that tau is phosphorylated by Cdk5/p39 during brain development, resulting in a reduction of its affinity for microtubules. The activity of Cdk5 is tightly regulated by association with its neuronal activators, p35 or p39. The p35 and p39 expression levels were investigated in the developing mouse brain; the p39 expression level was higher in embryonic hind brain and spinal cord and in postnatal cerebral cortex, whereas that of p35 was most prominent in cerebral cortex at earlier stages of development. The ability of Cdk5 to phosphorylate tau was higher when in association with p39 than in association with p35. Tau phosphorylation at Ser-202 and Thr-205 was decreased in Cdk5-/- mouse brain but not in p35-/- mouse brain, suggesting that Cdk5/p39 is responsible for the in vivo phosphorylation of tau at these sites. Our data suggest that tau phosphorylation by Cdk5 may provide the neuronal microtubules with dynamic properties in a region-specific and developmentally regulated manner. C1 NIDCR, Funct Genom Unit, NIH, Bethesda, MD 20892 USA. Tokyo Metropolitan Univ, Dept Biol Sci, Grad Sch Sci, Hachioji, Tokyo 1920397, Japan. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Kulkarni, AB (reprint author), NIDCR, Funct Genom Unit, NIH, Bldg 30,Rm 527,30 Convent Dr, Bethesda, MD 20892 USA. EM ak40m@nih.gov NR 59 TC 51 Z9 59 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 21 PY 2003 VL 278 IS 12 BP 10506 EP 10515 DI 10.1074/jbc.M211964200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 659LE UT WOS:000181777500069 PM 12536148 ER PT J AU Tomso, DJ Bell, DA AF Tomso, DJ Bell, DA TI Sequence context at human single nucleotide polymorphisms: Overrepresentation of CpG dinucleotide at polymorphic sites and suppression of variation in CpG islands SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE CpG islands; single nucleotide polymorphisms; methylation; genomics; bioinformatics ID DNA METHYLATION; MUTATION AB Human polymorphisms originate as mutations, and the influence of context on mutagenesis should be reflected in the distribution of sequences surrounding single nucleotide polymorphisms (SNPs). We have performed a computational survey of nearly two million human SNPs to determine if sequence-dependent hotspots for polymorphism exist in the human genome. Here we show that sequences containing CpG dinucleotides, which occur at low frequencies in the human genome, are 6.7-fold more abundant at polymorphic sites than expected. In contrast, polymorphisms in CpG sequences located within CpG islands, important regulatory regions that modulate gene expression, are 6.8-fold less prevalent than expected. The distribution of polymorphic alleles at CpGs in CpG islands is also significantly different from that in non-island regions. These data strongly support a role for 5-methylcytosine deamination in the generation of human variation, and suggest that variation at CpGs in islands is suppressed. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Bell, DA (reprint author), NIEHS, Lab Computat Biol & Risk Anal, POB 12233,C3-03, Res Triangle Pk, NC 27709 USA. EM BELL1@niehs.nih.gov NR 15 TC 26 Z9 27 U1 0 U2 0 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 MAR 21 PY 2003 VL 327 IS 2 BP 303 EP 308 DI 10.1016/S0022-2836(03)00120-7 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 659YB UT WOS:000181805600001 PM 12628237 ER PT J AU Shibata, N Ishimaru, T Suzuki, E Kirk, KL AF Shibata, N Ishimaru, T Suzuki, E Kirk, KL TI Enantioselective fluorination mediated by N-fluoroammonium salts of cinchona alkaloids: First enantioselective synthesis of BMS-204352 (MaxiPost) SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ELECTROPHILIC ASYMMETRIC FLUORINATION; K POTASSIUM CHANNELS; AMMONIUM-SALTS; AGENT; 3-FLUOROOXINDOLES; 1,1-DIOXIDE; FLUORIDE; EPOXIDES; REAGENTS; OPENERS AB We have employed a cinchona alkaloid/Select-fluor-mediated enantioselective fluorination of the oxindole 2 to achieve the first enantioslective synthesis of BMS-204352 (MaxiPost, S-1), an effective opener of maxi-K channels. Fluorination occurred to produce S-1 with 84% ee using the bis-cinchona alkaloid (DHQ)(2)AQN. Recrystallization produced enantiomerically pure (>99% ee) product. Quinidine-mediated fluorination of 2 gave the (R)-antipode of 1 with 68% ee. C1 Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Toyama 9300194, Japan. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shibata, N (reprint author), Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Sugitani 2630, Toyama 9300194, Japan. EM nozshiba@ms.toyama-mpu.ac.jp NR 35 TC 82 Z9 82 U1 1 U2 17 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 MAR 21 PY 2003 VL 68 IS 6 BP 2494 EP 2497 DI 10.1021/jo026792s PG 4 WC Chemistry, Organic SC Chemistry GA 656YU UT WOS:000181639300062 PM 12636425 ER PT J AU Popescu, NC AF Popescu, NC TI Genetic alterations in cancer as a result of breakage at fragile sites SO CANCER LETTERS LA English DT Review DE fragile site; DNA replication; genomic DNA; oncogenic virus; gene alteration; oncogenes; tumor suppressor gene; chromosome translocations ID HUMAN HEPATOCELLULAR-CARCINOMA; HUMAN-PAPILLOMAVIRUS TYPE-16; COMPARATIVE GENOMIC HYBRIDIZATION; SISTER CHROMATID EXCHANGES; SELECTIVE GROWTH ADVANTAGE; VIRAL INTEGRATION SITES; B VIRUS INTEGRATION; EPSTEIN-BARR-VIRUS; TUMOR-CELL-LINES; C-MYC GENE AB The organization and replication of DNA render fragile sites (FSs) prone to breakage, recombination as well as becoming preferential targets for mutagens-carcinogens and integration. of oncogenic viruses. For many years, attempts to link FSs and cancer generated mostly circumstantial evidence. The discoveries that chromosome translocations, amplification of protooncogenes, deletion of tumor suppressor. genes, and integration of oncogenic viruses all result from the specific breakage of genomic DNA at FSs, however, have provided compelling support for such a link, further suggesting a causative role for FSs in cancer. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Mol Cytogenet Sect, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20814 USA. RP Popescu, NC (reprint author), NCI, Mol Cytogenet Sect, Expt Carcinogenesis Lab, Ctr Canc Res, Bldg 37,Room 36C05,37 Convent Dr,MSC 4258, Bethesda, MD 20814 USA. NR 135 TC 82 Z9 84 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAR 20 PY 2003 VL 192 IS 1 BP 1 EP 17 DI 10.1016/S0304-3835(02)00596-7 PG 17 WC Oncology SC Oncology GA 663VE UT WOS:000182026300001 PM 12637148 ER PT J AU Wei, XP Decker, JM Wang, SY Hui, HX Kappes, JC Wu, XY Salazar-Gonzalez, JF Salazar, MG Kilby, JM Saag, MS Komarova, NL Nowak, MA Hahn, BH Kwong, PD Shaw, GM AF Wei, XP Decker, JM Wang, SY Hui, HX Kappes, JC Wu, XY Salazar-Gonzalez, JF Salazar, MG Kilby, JM Saag, MS Komarova, NL Nowak, MA Hahn, BH Kwong, PD Shaw, GM TI Antibody neutralization and escape by HIV-1 SO NATURE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; PRIMARY INFECTION; TYPE-1; VARIANTS; GLYCOSYLATION; INDIVIDUALS; EMERGENCE; RESPONSES; RESIDUES AB Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear(1-6). To gain a better understanding of this role, we examined plasma from patients with acute HIV infection. Here we report the detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies. The viral inhibitory activity of Nab resulted in complete replacement of neutralization-sensitive virus by successive populations of resistant virus. Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation. This pattern of escape, and the exceptional density of HIV-1 envelope glycosylation generally(7,8) led us to postulate an evolving 'glycan shield' mechanism of neutralization escape whereby selected changes in glycan packing prevent Nab binding but not receptor binding. Direct support for this model was obtained by mutational substitution showing that Nab-selected alterations in glycosylation conferred escape from both autologous antibody and epitope-specific monoclonal antibodies. The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire. C1 Univ Alabama, Howard Hughes Med Inst, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Inst Adv Study, Princeton, NJ 08540 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Shaw, GM (reprint author), Univ Alabama, Howard Hughes Med Inst, 720 S 20th St,KAUL 816, Birmingham, AL 35294 USA. RI Nowak, Martin/A-6977-2008; OI Kilby, J. Michael/0000-0003-3222-1003 NR 30 TC 1410 Z9 1459 U1 9 U2 102 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 20 PY 2003 VL 422 IS 6929 BP 307 EP 312 DI 10.1038/nature01470 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 656XX UT WOS:000181637300039 PM 12646921 ER PT J AU Haviernik, P Schmidt, M Hu, XR Wolff, L AF Haviernik, P Schmidt, M Hu, XR Wolff, L TI Consistent inactivation of p19(Arf) but not p15(Ink4b) in murine myeloid cells transformed in vivo by deregulated c-Myc SO ONCOGENE LA English DT Article DE INK4; tumor suppressor; p15(Ink4b); p19(Arf); c-myc; myeloid leukemia ID ACUTE LYMPHOBLASTIC-LEUKEMIA; KINASE INHIBITOR P15(INK4B); CYCLIN-DEPENDENT KINASES; TUMOR-SUPPRESSOR GENE; RETINOBLASTOMA-PROTEIN; CDK INHIBITORS; GROWTH SUPPRESSION; BREAST-CANCER; INK4 FAMILY; TGF-BETA AB Cyclin-dependent kinase inhibitors p16(INK4a) and p-15(INK4b), encoded by the CDKN2A and B loci, play an important role in negative regulation of the cell cycle. Furthermore, p19(ARF) also encoded by the CDKN2A locus, has been shown to regulate positively the p53 pathway leading to growth arrest and apoptosis. All three genes have been inactivated in human tumors. In myeloid cells, p15(INK4b) mRNA is upregulated during cytokine-induced differentiation and/or growth arrest, and hypermethylation of the p15(INK4b) gene promoter region is a common event in acute myeloid leukemia. In the present study, we examined murine monocyte/macrophage tumors with deregulated c-myc for evidence of Ink4 gene inactivation. p15(Ink4b) mRNA and protein were detected in the majority of leukemias, and p16(Ink4a) mRNA and protein were highly expressed in two of them. pRb was in a hypophosphorylated state in most of the neoplasms indicating that the Cdk inhibitors that were expressed in the cells were functional. The observed expression of p15(Ink4b) is inconsistent with their proliferation state, although it might be expected to be expressed owing to the maturity of the cells. These data suggest, therefore, that deregulated c-Myc bypasses the pRb restriction point and cell cycle arrest in these tumors. An examination of p19(Arf) exons revealed deletions of the gene in up to 94% of the tumors. Since this gene shares exon 2 with p16(Ink4),, it is often difficult to determine which gene is the relevant tumor suppressor. However, the loss of only the p19(Arf)-specific exon 1beta was observed in a tumor that had normal p16(Ink4a), protein expression. In addition, the p19(Arf)-specific exon was deleted in another tumor that expressed a functional chimeric protein, p15Ex1-p16Ex2-3; it was demonstrated here that this fusion protein is capable of inducing G1 arrest. These data overall supports the hypothesis that the critical inactivation event in these hematopoietic neoplasms is elimination of p19(Arf), and not Ink4 function. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Wolff, L (reprint author), NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. NR 69 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 20 PY 2003 VL 22 IS 11 BP 1600 EP 1610 DI 10.1038/sj.onc.1206268 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 655YH UT WOS:000181580500002 PM 12642863 ER PT J AU Seker, H Rubbi, C Linke, SP Bowman, ED Garfield, S Hansen, L Borden, KLB Milner, J Harris, CC AF Seker, H Rubbi, C Linke, SP Bowman, ED Garfield, S Hansen, L Borden, KLB Milner, J Harris, CC TI UV-C-induced DNA damage leads to p53-dependent nuclear trafficking of PML SO ONCOGENE LA English DT Article DE P53; PML; DNA repair; BLM ID NUCLEOTIDE EXCISION-REPAIR; ACUTE PROMYELOCYTIC LEUKEMIA; BLOOM-SYNDROME; PREMATURE SENESCENCE; TUMOR SUPPRESSION; SYNDROME PROTEIN; MESSENGER-RNA; ONCOGENIC RAS; CELL-CYCLE; P53 AB The promyelocytic leukemia protein (PML) is a nuclear phosphoprotein that localizes to distinct domains in the nucleus, described as PML nuclear bodies (PML-NBs). Recent findings indicate that PML regulates the p53 response to oncogenic signals. Here, we define a p53-dependent role for PML in response to DNA damage. We exposed cells to ultraviolet light (UV-C) and imaged the nuclear distribution of PML, p53, and the BLM helicase by confocal microscopy. After DNA damage, PML partially relocated out of the PML-NBs, and colocalized with BLM and p53 at sites of DNA repair. In addition, using the isogenic HCT116 cell tines (p53+/+ and -/-), we show that the redistribution of PML was dependent on functional p53. Western analysis revealed that the level of PML protein remained unaltered after UV-C treatment. These results are consistent with the hypothesis that PML, in conjunction with p53 and BLM, contributes to the cellular response to UV-C-induced DNA damage and its repair. C1 NCI, Human Carcinogenesis Lab, CCR, NIH, Bethesda, MD 20892 USA. Univ York, Dept Biol, YCR Lab P53, York YO1 5DD, N Yorkshire, England. NCI, Expt Carcinogenesis Lab, CCR, NIH, Bethesda, MD 20892 USA. Creighton Univ, Sch Med, Dept Biomed Sci, Omaha, NE 68178 USA. Mt Sinai Sch Med, Dept Physiol & Biophys, Struct Biol Program, New York, NY 10029 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, CCR, NIH, 37 Convent Dr,Bldg 37,Room 2C05, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov NR 53 TC 32 Z9 35 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD MAR 20 PY 2003 VL 22 IS 11 BP 1620 EP 1628 DI 10.1038/sj.onc.1201640 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 655YH UT WOS:000181580500004 PM 12642865 ER PT J AU Bae, MA Rhee, H Song, BJ AF Bae, MA Rhee, H Song, BJ TI Troglitazone but not rosiglitazone induces G1 cell cycle arrest and apopiosis in human and rat hepatoma cell lines SO TOXICOLOGY LETTERS LA English DT Article DE troglitazone; rosiglitazone; p53; p21; cell cycle arrest; cyclin-dependent kinases; apoptosis ID ACTIVATED RECEPTOR-GAMMA; SMOOTH-MUSCLE CELLS; INHIBITS GROWTH; CARCINOMA CELLS; CANCER CELLS; PPAR-GAMMA; APOPTOSIS; THIAZOLIDINEDIONE; DIFFERENTIATION; P27(KIP1) AB Rosiglitazone (RSG), an agonist of peroxisome proliferator-activated receptor gamma (PPARgamma), induces minor toxicity in humans relative to another PPARgamma agonist, troglitazone (TRO). In contrast, recent reports suggest that RSG causes growth arrest and apoptosis of normal and cancerous cells. Therefore, in this study, we investigated the relative toxicities of TRO and RSG on three different hepatoma cell lines, and observed that TRO, but not RSG, was cytotoxic. Additionally, we studied the mechanism by which TRO induced damage to HepG2 hepatoma cells. Our results indicated that TRO increased the levels of p53, p27, and p21, while it reduced the levels of cyclin D1 and phospho-Rb in a time-dependent manner. Increased p27 and p21 levels coincided with reduced activities of cell cycle dependent kinases (cdk) such as cdk2- and cyclin A-protein kinases 24 h after TRO treatment. These results demonstrate that TRO, but not RSG, causes G1 arrest of hepatoma cells, most likely through changing the levels of cell cycle regulators. Furthermore, because RSG did not affect the levels of cell cycle regulators, TRO-mediated growth inhibition appears independent of PPARgamma activation. Published by Elsevier Science Ireland Ltd. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 12420 Parklawn Dr, Rockville, MD 20852 USA. EM bjs@mail.nih.gov NR 37 TC 40 Z9 42 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD MAR 20 PY 2003 VL 139 IS 1 BP 67 EP 75 DI 10.1016/S037842740200468X PG 9 WC Toxicology SC Toxicology GA 660RM UT WOS:000181846600007 PM 12595159 ER PT J AU Hayashi, T Su, TP AF Hayashi, T Su, TP TI Chronic [D-Ala(2), D-Leu(5)]enkephalin treatment increases the nerve growth factor in adult mouse brain SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE DADLE ([D-Ala(2), D-Leu(5)]enkephalin); NGF (nerve growth factor); GDNF (glia-derived neurotrophic factor) ID ENKEPHALIN BLOCKS; PEPTIDE; METHAMPHETAMINE; SURVIVAL AB The delta opioid peptide [D-Ala(2), D-Leu(5)]enkephalin (DADLE) has been shown to enhance the survival of dopaminergic neurons. Here, we found that chronic treatment with DADLE caused a significant increase in nerve growth factor (NGF) in the hippocampus and the midbrain of adult albino Swiss (CD-1) mice, but not in the striatum or frontal cortex. Glia-derived neurotrophic factor (GDNF) was not significantly affected. Thus, the neuroprotective action of DADLE may be mediated in part by NGF. (C) 2003 Elsevier Science B.V. All rights reserved. C1 NIDA, Cellular Pathobiol Unit, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA. RP Su, TP (reprint author), NIDA, Cellular Pathobiol Unit, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Hayashi, Teruo/A-9690-2008 NR 8 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAR 19 PY 2003 VL 464 IS 2-3 BP 237 EP 239 DI 10.1016/S0014-2999(03)01419-5 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 655EY UT WOS:000181539400021 PM 12620518 ER PT J AU Raman, VK Guttman, MA Pessanha, BS Dick, AJ Peters, DC McVeigh, ER Lederman, RJ AF Raman, VK Guttman, MA Pessanha, BS Dick, AJ Peters, DC McVeigh, ER Lederman, RJ TI Real-time magnetic resonance Imaging guidance for endograft delivery in a porcine model of abdominal aortic aneurysm SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 38A EP 39A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500167 ER PT J AU Begley, DA Mohiddin, SA Arai, AE Lin, JP Tripodi, D Fananapazir, L AF Begley, DA Mohiddin, SA Arai, AE Lin, JP Tripodi, D Fananapazir, L TI Insulin-like growth factor-1 attenuates myocardial hypertrophic response to sarcomeric mutations in human familial hypertrophic cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 144A EP 144A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500625 ER PT J AU Mohiddin, S Rowe, G Hathaway, L Leifer, E Leidy, N Biddle, S Marden, S Tripodi, D Fananapazir, L AF Mohiddin, S Rowe, G Hathaway, L Leifer, E Leidy, N Biddle, S Marden, S Tripodi, D Fananapazir, L TI Comparison of novel strategy therapies for obstructive hypertrophic cardiomyopathy: Relation of relief of left ventricular outflow obstruction to improved symptoms and health-related quality of life parameters SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 145A EP 145A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500626 ER PT J AU Sachdev, V Birdsall, CW Tripodi, D Ernst, I Fananapazir, L Plehn, JF AF Sachdev, V Birdsall, CW Tripodi, D Ernst, I Fananapazir, L Plehn, JF TI Left atrial volumetric remodeling predicts functional capacity in hypertrophic cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 145A EP 146A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500630 ER PT J AU McAreavey, D Moak, JP Tripodi, D Mohiddin, SA Wienhoff, RM Fananapazir, L AF McAreavey, D Moak, JP Tripodi, D Mohiddin, SA Wienhoff, RM Fananapazir, L TI Factors associated with increased risk of sudden death in young patients with hypertrophic cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 147A EP 147A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500637 ER PT J AU Mohiddin, SA Winkler, J Tripodi, D McAreavey, D Fananapazir, L AF Mohiddin, SA Winkler, J Tripodi, D McAreavey, D Fananapazir, L TI Progressive left ventricular impairment in hypertrophic cardiomyopathy patients is determined by functional location of mutation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 147A EP 147A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500636 ER PT J AU Gottdiener, JS Kitzman, DW Aurigemma, GP Arnold, AM Egher, CS Fowle, KM Hill, JC AF Gottdiener, JS Kitzman, DW Aurigemma, GP Arnold, AM Egher, CS Fowle, KM Hill, JC TI Left atrial volume is more strongly associated with prevalent congestive heart failure and predictive of incident congestive heart failure in the elderly than Doppler mitral inflow velocities or deceleration time SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 St Francis Hosp, Roslyn, NY USA. NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 148A EP 148A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500640 ER PT J AU Mohiddin, SA Cardoso, JP Lu, S Winkler, J Jha, S Horowits, R Fananapazir, L AF Mohiddin, SA Cardoso, JP Lu, S Winkler, J Jha, S Horowits, R Fananapazir, L TI Human nebulin-related anchoring protein a critical structural protein, sequence, genomic structure, tissue distribution, and association with cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 NHLBI, Bethesda, MD 20892 USA. NIAMSD, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 155A EP 155A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500672 ER PT J AU Gottdiener, JS Aurigemma, GP Kitzman, DW Arnold, AM Egher, CS Fowle, KM Hill, JC AF Gottdiener, JS Aurigemma, GP Kitzman, DW Arnold, AM Egher, CS Fowle, KM Hill, JC TI Diastolic left ventricular filling patterns in diastolic versus systolic congestive heart failure of the elderly the cardiovascular heart study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 NHLBI, Bethesda, MD 20892 USA. St Francis Hosp, Roslyn, NY 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 200A EP 200A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500862 ER PT J AU Wilson, PW D'Agostino, RB Sullivan, L Levy, D AF Wilson, PW D'Agostino, RB Sullivan, L Levy, D TI The impact of moderate elevations of blood pressure and low-density lipoprotein chlosterol on coronary heart disease risk SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Boston Univ, Boston, MA 02215 USA. NHLBI, Framingham, MA 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 267A EP 267A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501162 ER PT J AU Campia, U Sullivan, G Bryant, MB Quon, MJ Panza, JA AF Campia, U Sullivan, G Bryant, MB Quon, MJ Panza, JA TI Effects of insulin resistance on flow: Mediated dilation of conduit vessels SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 NHLBI, NIH, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 268A EP 268A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501168 ER PT J AU Arai, AE Sheikh, F Agyeman, KO Hoyt, R Sachdev, V Yu, XX San, H Metzger, M Dunbar, C Orlic, D AF Arai, AE Sheikh, F Agyeman, KO Hoyt, R Sachdev, V Yu, XX San, H Metzger, M Dunbar, C Orlic, D TI Lack of benefit from cytokine mobilized stein cell therapy for acute myocardial infarction in nonhuman primates SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Natl Inst Hlth, Bethesda, MD 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 371A EP 371A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501617 ER PT J AU Wang, HF Li, XK Jones, M Davies, CH Swanson, JC Rusk, RA Schindera, ST Zetts, AD Lie, GR Sahn, DJ AF Wang, HF Li, XK Jones, M Davies, CH Swanson, JC Rusk, RA Schindera, ST Zetts, AD Lie, GR Sahn, DJ TI Comparison of the left ventricle ejection fraction by separately quantifying normal and infarct myocardial cavity volume using three-dimensional tissue Doppler imaging: An in vivo sheep study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 407A EP 407A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501763 ER PT J AU Swanson, JC Davies, CH Hashimoto, I Rusk, RA Jones, M Zetts, AD Sahn, DJ AF Swanson, JC Davies, CH Hashimoto, I Rusk, RA Jones, M Zetts, AD Sahn, DJ TI Is tissue Doppler-based strain rate imaging superior to tissue Doppler imaging in compensating for lateral heart motion/translation? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Oregon Hlth & Sci Univ, Portland, OR USA. NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 418A EP 418A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501811 ER PT J AU Dilsizian, V Loredo, ML Jagoda, EM Eckelman, WC Shirani, J AF Dilsizian, V Loredo, ML Jagoda, EM Eckelman, WC Shirani, J TI Scintigraphic and immunohistochemical evidence for localization of angiotensin converting enzyme to myocytes in human ischemic cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Univ Maryland, Med Ctr, Baltimore, MD 21201 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 427A EP 427A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501850 ER PT J AU Dyke, CK Kellman, P Aletras, AH Arai, AE AF Dyke, CK Kellman, P Aletras, AH Arai, AE TI Pericardial effusion or epicardial fat? Improved discrimination with phase-sensitive inversion recovery magnetic resonance imaging SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 436A EP 436A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501889 ER PT J AU Li, XK Li, XN Davies, CH Jones, M Hashimoto, I Zetts, AD Mack, GK Rusk, RA Sahn, DJ AF Li, XK Li, XN Davies, CH Jones, M Hashimoto, I Zetts, AD Mack, GK Rusk, RA Sahn, DJ TI A semiautomatic tissue Doppler-based Tei index computation for evaluation of left ventricular function: A validation study in sheep with mitral regurgitation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 447A EP 447A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501936 ER PT J AU Swanson, JC Schindera, ST Jones, M Davies, CH Rusk, RA Sahn, DJ AF Swanson, JC Schindera, ST Jones, M Davies, CH Rusk, RA Sahn, DJ TI Assessment of the extent of ischemic aneurysm as defined by curved M-mode analysis of regional strain rate: An in vivo study in a chronic animal model SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 454A EP 454A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501966 ER PT J AU Hashimoto, I Li, XK Barber, BJ Hejmadi, B Jones, M Sahn, DJ AF Hashimoto, I Li, XK Barber, BJ Hejmadi, B Jones, M Sahn, DJ TI Quantitative assessment of regional peak myocardial acceleration during isovolumic contraction and relaxation time by tissue Doppler imaging SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 455A EP 455A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501972 ER PT J AU Hirsch, GA Ingkanisorn, WP Aletras, AH Kellman, P Arai, AE AF Hirsch, GA Ingkanisorn, WP Aletras, AH Kellman, P Arai, AE TI Infarct size needed to cause adverse left ventricular remodeling in humans: A magnetic resonance imaging study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 NHLBI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Hosp & Hlth Syst, Baltimore, MD 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 469A EP 469A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669502035 ER PT J AU Dick, AJ Guttman, MA Raman, VK Peters, DC Hill, JM Smith, S Scott, G McVeigh, ER Lederman, RJ AF Dick, AJ Guttman, MA Raman, VK Peters, DC Hill, JM Smith, S Scott, G McVeigh, ER Lederman, RJ TI Real-time magnetic resonance imaging for integrated identification, targeting, and injection of labeled stem cells to porcine myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 542A EP 542A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669502340 ER PT J AU Tosato, G AF Tosato, G TI Interferon-alpha is implicated in the transcriptional regulation of vascular endothelial growth factor SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID IN-VIVO; ANGIOGENESIS; INHIBITION; EXPRESSION; CELLS; THERAPY; CANCER; TUMORS; INVIVO; MUTANT C1 NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), NCI, Canc Res Ctr, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 31 TC 4 Z9 5 U1 0 U2 0 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 MAR 19 PY 2003 VL 95 IS 6 BP 420 EP 421 PG 2 WC Oncology SC Oncology GA 655NV UT WOS:000181559700002 PM 12644529 ER PT J AU Ballard-Barbash, R Barlow, WE Ernster, VL AF Ballard-Barbash, R Barlow, WE Ernster, VL CA Breast Canc Surveillance Consortiu TI Re: Detection of ductal carcinoma in situ in women undergoing screening mammography - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID BREAST; AGE C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA USA. Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Ballard-Barbash, R (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, EPN 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 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 MAR 19 PY 2003 VL 95 IS 6 BP 487 EP 488 PG 2 WC Oncology SC Oncology GA 655NV UT WOS:000181559700015 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI Re: Serum proteomic patterns for detection of prostate cancer - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Off Director, Ctr Biol Evaluat & Res, US FDA,Clin Proteom Program,NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, US FDA,Clin Proteom Program,NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), Bldg 29A,Rm 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 1 U2 1 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 MAR 19 PY 2003 VL 95 IS 6 BP 490 EP 491 PG 2 WC Oncology SC Oncology GA 655NV UT WOS:000181559700018 ER PT J AU Qin, SF Chock, PB AF Qin, SF Chock, PB TI Implication of phosphatidylinositol 3-kinase membrane recruitment in hydrogen peroxide-induced activation of PI3K and Akt SO BIOCHEMISTRY LA English DT Article ID B-CELL RECEPTOR; BRUTONS TYROSINE KINASE; SMOOTH-MUSCLE-CELLS; PHOSPHOINOSITIDE 3-KINASE; OXIDATIVE STRESS; SURVIVAL PATHWAY; ANGIOTENSIN-II; CROSS-LINKING; REDOX STRESS; PHOSPHORYLATION AB The effect of tyrosine phosphorylation of PI3K on its enzymatic activity is quite controversial, and the molecular mechanism by which ROS trigger PI3K membrane relocation is unclear. Therefore, we investigated the regulatory mechanism of hydrogen peroxide-induced PI3K activation in DT40 cells, utilizing genetic and pharmacological approaches. Our results revealed that hydrogen peroxide induced tyrosine phosphorylation of the p 110 but not the p85 subunit of PI3K in DT40 cells. This phosphorylation was intact in Btk- and Cbl-deficient DT40 cells, but was drastically suppressed in Lyn, Syk, or BCAP-deficient DT40 cells. Tyrosine phosphorylation of p I 10 did not alter its catalytic activity, and hydrogen peroxide stimulation did not cause an increase in the intrinsic PI3K activity; however, hydrogen peroxide stimulation did induce PI(3,4,5)P(3) accumulation and activate Akt. The activation of Akt, as monitored by its ability to phosphorylate GSK-3alpha/beta and by its S(473) phosphorylation, was strictly dependent on PI3K activity. Under our conditions, hydrogen peroxide-induced PI3K and Akt activation was independent of Lyn, Syk, Cbl, BCAP, or Ras when each was eliminated individually either by mutation or by a specific inhibitor. In comparison, Akt activation by B cell receptor cross-linking was dependent on BCAP. In addition, hydrogen peroxide treatment caused an increase in the amount of p85 PI3K associated with the particulate fraction. Together, these results indicate that the hydrogen peroxide-induced PI3K and Akt activation in DT40 cells was achieved through PI3K membrane recruitment to its substrate site, thereby enabling PI3K to maximize its catalytic efficiency. C1 NHLBI, LB, NIH, Bethesda, MD 20892 USA. RP Chock, PB (reprint author), NHLBI, LB, NIH, Bldg 50,Room 2134,50 S Dr,MSC-8012, Bethesda, MD 20892 USA. OI Qin, Suofu/0000-0002-3323-8846 NR 50 TC 70 Z9 72 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 18 PY 2003 VL 42 IS 10 BP 2995 EP 3003 DI 10.1021/bi0205911 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 655DD UT WOS:000181535300026 PM 12627965 ER PT J AU Rodrigues, CMP Sola, S Sharpe, JC Moura, JJG Steer, CJ AF Rodrigues, CMP Sola, S Sharpe, JC Moura, JJG Steer, CJ TI Tauroursodeoxycholic acid prevents Bax-induced membrane perturbation and cytochrome c release in isolated mitochondria SO BIOCHEMISTRY LA English DT Article ID PERMEABILITY TRANSITION PORE; CHANNEL-FORMING ACTIVITY; DEPENDENT ANION CHANNEL; RESONANCE SPIN-LABEL; URSODEOXYCHOLIC ACID; CELL-DEATH; CASPASE ACTIVATION; INDUCED APOPTOSIS; PROAPOPTOTIC BAX; ADENYLATE KINASE AB Bax is a potent pro-apoptotic member of the Bcl-2 protein family that localizes to the mitochondrial membrane during apoptosis. Tauroursodeoxycholic acid (TUDCA) modulates the apoptotic threshold, in part, by preventing Bax translocation both in vitro and in vivo. The mechanisms by which Bax induces and TUDCA inhibits release of cytochrome c are unclear. We show here that recombinant Bax protein induced cytochrome c release in isolated mitochondria without detectable swelling. Co-incubation with TUDCA prevented efflux of mitochondrial factors and proteolytic processing of caspases in cytosolic extracts. Spectroscopic analyses of mitochondria exposed to Bax revealed increased polarity and fluidity of the membrane lipid core as well as altered protein order, indicative of Bax binding, together with loss of spin-label paramagnetism, characteristic of oxidative damage. TUDCA markedly abrogated the Bax-induced membrane perturbation. In conclusion, our results indicate that Bax protein directly induces cytochrome c release from mitochondria through a mechanism that does not require the permeability transition. Rather, it is accompanied by changes in the organization of membrane lipids and proteins. TUDCA is a potent inhibitor of Bax association with mitochondria. Thus, TUDCA modulates apoptosis by suppressing mitochondrial membrane perturbation through pathways that are also independent of the mitochondrial permeability transition. C1 Univ Lisbon, Fac Pharm, Ctr Patogenese Mol, P-1600083 Lisbon, Portugal. Natl Inst Neurol Disorders & Stroke, Natl Inst Gen Med Sci, NIH, Bethesda, MD 20892 USA. Univ Nova Lisboa, Dept Chem, Fac Sci & Technol, P-2825114 Monte De Caparica, Portugal. Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Genet, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Cell Biol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Dev, Minneapolis, MN 55455 USA. RP Rodrigues, CMP (reprint author), Av Forcas Armadas, P-1600083 Lisbon, Portugal. EM cmprodrigues@ff.ul.pt RI Moura, Jose/D-6426-2013; Sola, Susana/M-5251-2013; REQUIMTE, SMB/M-5694-2013; Rodrigues, Cecilia/M-3572-2013; REQUIMTE, UCIBIO/N-9846-2013; iMed.ULisboa, iMed.ULisboa/C-6292-2014; iMed.ULisboa, CellFun /A-4244-2014 OI Moura, Jose/0000-0002-4726-2388; Sola, Susana/0000-0003-2036-797X; Rodrigues, Cecilia/0000-0002-4829-754X; NR 65 TC 59 Z9 59 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 18 PY 2003 VL 42 IS 10 BP 3070 EP 3080 DI 10.1021/bi026979d PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 655DD UT WOS:000181535300035 PM 12627974 ER PT J AU Price, SE Jappar, D Lorenzo, P Saavedra, JE Hrabie, JA Davies, KM AF Price, SE Jappar, D Lorenzo, P Saavedra, JE Hrabie, JA Davies, KM TI Micellar catalysis of nitric oxide dissociation from diazeniumdiolates SO LANGMUIR LA English DT Article ID CONTROLLED BIOLOGICAL RELEASE; QUANTITATIVE TREATMENT; INDICATOR EQUILIBRIA; ION-EXCHANGE; IN-VITRO; DONOR; SURFACTANTS; PHOSPHATE; NUCLEOPHILES; CHEMISTRY AB The effect of surfactant micelles on the acid-catalyzed dissociation of NO from diazeniumdiolate ions of structure (RRN)-R-1-N-2[N(O)NO](-) has been examined in phosphate-buffered solutions at 37 degreesC. The reaction behavior of zwitterionic substrates [2, R-1 = R-2 = H2N(CH2)(2); 3, R-1 = R-2 = H2N(CH2)(3); 4, R-1 = n-Pr, R-2 = H2N(CH2)(3); 5, R-1 = H2N(CH2)(3), R-2 = H2N(CH2)(3)NH(CH2)(4)] and anionic substrates [1, R-1 = R-2 = Et; 6, R-1 = R-2 = n-Pr] has been compared. All but DEANO (1) are catalyzed by anionic micelles of sodium dodecyl sulfate (SDS) but are unaffected by the presence of cationic cetyltrimethylammonium bromide or the zwitterionic surfactant 3-(N-dodecyl-N,N-dimethylammonio)-1-propanesulfonate (lauryl sulfobetaine). Catalysis by sodium decylphosphonate micelles has also been demonstrated for 2 (DETANO). The surfactant-mediated catalysis is discussed in terms of a distribution model with simultaneous reaction in the water and micellar pseudophases. Binding constants (K-s) for diazeniumdiolate association with the surfactant ;micelles have been obtained, and a comparison of second-order rate constants, k(2m) and k(2w), for their acid-catalyzed dissociation in the micellar and aqueous phases, respectively, has been made. For the zwitterionic polyamine diazeniumdiolates 2-5, the K-s values show good correlation with the number of positively charged nitrogen centers in the substrates, consistent with micellar association between protonated nitrogens in the zwitterions and the anionic headgroups of the micelle. The Coulombic interaction of zwitterionic substrates with SDS micelles is compared with the weak hydrophobic association which was found with the anionic diazeniumdiolate 6. C1 George Mason Univ, Dept Chem, Fairfax, VA 22030 USA. NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RP Davies, KM (reprint author), George Mason Univ, Dept Chem, 4400 Univ Dr, Fairfax, VA 22030 USA. NR 33 TC 14 Z9 14 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD MAR 18 PY 2003 VL 19 IS 6 BP 2096 EP 2102 DI 10.1021/la020889s PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 655PY UT WOS:000181562700033 ER PT J AU Koizumi, K Lintas, C Nirenberg, M Maeng, JS Ju, JH Mack, JW Gruschus, JM Odenwald, WF Ferretti, JA AF Koizumi, K Lintas, C Nirenberg, M Maeng, JS Ju, JH Mack, JW Gruschus, JM Odenwald, WF Ferretti, JA TI Mutations that affect the ability of the vnd/NK-2 homeoprotein to regulate gene expression: Transgenic alterations and tertiary structure SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Drosophila; neurobiology; protein-DNA binding; nuclear magnetic resonance ID CENTRAL-NERVOUS-SYSTEM; DNA-BINDING SPECIFICITY; NK-2 HOMEOBOX GENE; HOMEODOMAIN PROTEIN; COLUMN IDENTITY; FUSHI-TARAZU; DROSOPHILA; VND; TRANSCRIPTION; NEUROECTODERM AB The importance in downstream target regulation of tertiary structure and DNA binding specificity of the protein encoded by the vnd/NK-2 homeobox gene is analyzed. The ectopic expression patterns of WT and four mutant vnd/NK-2 genes are analyzed together with expression of two downstream target genes, ind and msh, which are down-regulated by vnd/NK-2. Three mutants are deletions of conserved regions (i.e., tinman motif, acidic motif, and NK-2 box), and the fourth, Y54M vnd/NK-2, corresponds to a single amino acid residue replacement in the homeodomain. Of the four ectopically expressed mutant genes examined, only the Y54M mutation inactivates the ability of the vnd/NK-2 homeodomain protein to repress ind and msh. The acidic motif deletion mutant slightly reduced the ability of the protein to repress ind and msh. By contrast, both tinman and NK-2 box deletion mutants behaved as functional vnd/NK-2 genes in their ability to repress ind and msh. The NMR-determined tertiary structures of the Y54M vnd/NK-2 homeodomain, both free and bound to DNA, are compared with the WT analog. The only structural difference observed for the mutant homeodomain is in the complex with DNA and involved closer interaction of the methionine-54 with A2, rather than with C3 of the (-) strand of the DNA. This subtle change in the homeodomain-DNA complex resulted in modifications of binding affinities to DNA. These changes resulting from a single amino acid residue replacement constitute the molecular basis for the phenotypic alterations observed on ectopic expression of the Y54M vnd/NK-2 gene during embryogenesis. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Dept Biochem & Mol Biol, Washington, DC 20059 USA. RP Ferretti, JA (reprint author), NHLBI, Biophys Chem Lab, NIH, 50 South Dr,MSC 8013,Bldg 50,Room 3517, Bethesda, MD 20892 USA. EM jafer@helix.nih.gov OI Lintas, Carla/0000-0003-1209-8554 FU NIGMS NIH HHS [GM 08016, S06 GM008016] NR 37 TC 19 Z9 19 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 2003 VL 100 IS 6 BP 3119 EP 3124 DI 10.1073/pnas.0438043100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 657PH UT WOS:000181675200028 PM 12626758 ER PT J AU Kanungo, J Kozmik, Z Swamynathan, SK Piatigorsky, J AF Kanungo, J Kozmik, Z Swamynathan, SK Piatigorsky, J TI Gelsolin is a dorsalizing factor in zebrafish SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACTIN-BINDING PROTEIN; LENS CRYSTALLINS; AMYLOIDOSIS; ORGANIZER; REQUIRES; CELLS; GENE; EXPRESSION; EVOLUTION; MOTILITY AB The gene for gelsolin (an actin-binding, cytoskeletal regulatory protein) was shown earlier to be specialized for high corneal expression in adult zebrafish. We show here that zebrafish gelsolin is required for proper dorsalization during embryogenesis. Inhibition of gelsolin expression by injecting fertilized eggs with a specific morpholino oligonucleotide resulted in a range of concentration-dependent ventralized phenotypes, including those lacking a brain and eyes. These were rescued by coinjection of zebrafish gelsolin or chordin (a known dorsalizing agent) mRNAs, or human gelsolin protein. Moreover, injection of gelsolin mRNA or human gelsolin protein by itself dorsalized the developing embryos, often resulting in axis duplication. Injection of the gelsolin-specific morpholino oligonucleotide enhanced the expression of Vent mRNA, a ventral marker downstream of bone morphogenetic proteins, whereas injection of gelsolin mRNA enhanced the expression of chordin and goosecoid mRNAs, both dorsal markers. Our results indicate that gelsolin also modulates embryonic dorsal/ventral pattern formation in zebrafish. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Piatigorsky, J (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bldg 6,Room 201,6 Ctr Dr, Bethesda, MD 20892 USA. EM joramp@nei.nih.gov RI Kozmik, Zbynek/G-3581-2014; Kozmik, Zbynek/I-8807-2014; OI Swamynathan, Shivalingappa/0000-0002-9158-1511 NR 37 TC 16 Z9 16 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 MAR 18 PY 2003 VL 100 IS 6 BP 3287 EP 3292 DI 10.1073/pnas.0634473100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 657PH UT WOS:000181675200056 PM 12629212 ER PT J AU Wiltshire, T Pletcher, MT Batalov, S Barnes, SW Tarantino, LM Cooke, MP Wu, H Smylie, K Santrosyan, A Copeland, NG Jenkins, NA Kalush, F Mural, RJ Glynne, RJ Kay, SA Adams, MD Fletcher, CF AF Wiltshire, T Pletcher, MT Batalov, S Barnes, SW Tarantino, LM Cooke, MP Wu, H Smylie, K Santrosyan, A Copeland, NG Jenkins, NA Kalush, F Mural, RJ Glynne, RJ Kay, SA Adams, MD Fletcher, CF TI Genome-wide single-nucleotide polymorphism analysis defines haplotype patterns in mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENETIC-MAP; DISCOVERY; DISEASE; COMPLEX; BLOCKS AB The nature and organization of polymorphisms, or differences, between genomes of individuals are of great interest, because these variations can be associated with or even underlie phenotypic traits, including disease susceptibility. To gain insight into the genetic and evolutionary factors influencing such biological variation, we have examined the arrangement (haplotype) of single-nucleotide polymorphisms across the genomes of eight inbred strains of mice. These analyses define blocks of high or low diversity, often extending across tens of megabases that are delineated by abrupt transitions. These observations provide a striking contrast to the haplotype structure of the human genome. C1 Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. Scripps Res Inst, San Diego, CA 92121 USA. Phenomix, San Diego, CA 92121 USA. Seqeunom Inc, San Diego, CA 92121 USA. NCI, Frederick, MD 21702 USA. Celera Genom, Rockville, MD 20850 USA. RP Wiltshire, T (reprint author), Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. EM timw@gnf.org RI Kay, Steve/F-6025-2011 OI Kay, Steve/0000-0002-0402-2878 NR 22 TC 181 Z9 188 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 2003 VL 100 IS 6 BP 3380 EP 3385 DI 10.1073/pnas.0130101100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 657PH UT WOS:000181675200073 PM 12612341 ER PT J AU Oh, S Berzofsky, JA Burke, DS Waldmann, TA Perera, LP AF Oh, S Berzofsky, JA Burke, DS Waldmann, TA Perera, LP TI Coadministration of HIV vaccine vectors with vaccinia viruses expressing IL-15 but not IL-2 induces long-lasting cellular immunity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CD8(+) T-CELLS; IN-VIVO; DNA VACCINES; INTERLEUKIN (IL)-2; TRANSGENIC MICE; LYMPHOCYTES-T; KILLER-CELLS; BETA-CHAIN; MEMORY; ANTIGEN AB Vaccine efficacy is determined largely by cellular and humoral immunity as well as long-lasting immunological memory. IL-2 and IL-15 were evaluated in vaccinia vectors expressing HIV gp160 for the establishment of an effective vaccine strategy. Both IL-2 and IL-15 in the vaccinia vector induced strong and long-lasting antibody-mediated immunity as well as a short-term cytotoxic T cell response against HIV gp120. In addition, IL-15 also supported robust CD8(+) T cell-mediated long-term immunity, whereas the CD8(+) T cell-mediated immunity induced by IL-2 was short-lived. Moreover, we found that the cytokine milieu at the time of priming had surprisingly persistent effects on the character of the memory CD8 T cells long afterward with respect to their fate, functional activities, cytokine receptor expression, and antigen-independent proliferation. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Johns Hopkins Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA. RP Berzofsky, JA (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, Ctr Canc Res,NIH, Bldg 10,Room 4B40, Bethesda, MD 20892 USA. EM berzofsk@helix.nih.gov; pereral@mail.nih.gov OI /0000-0002-5704-8094 NR 42 TC 129 Z9 142 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 2003 VL 100 IS 6 BP 3392 EP 3397 DI 10.1073/pnas.0630592100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 657PH UT WOS:000181675200075 PM 12626740 ER PT J AU Yamashita, T Hashiramoto, A Haluzik, M Mizukami, H Beck, S Norton, A Kono, M Tsuji, S Daniotti, JL Werth, N Sandhoff, R Sandhoff, K Proia, RL AF Yamashita, T Hashiramoto, A Haluzik, M Mizukami, H Beck, S Norton, A Kono, M Tsuji, S Daniotti, JL Werth, N Sandhoff, R Sandhoff, K Proia, RL TI Enhanced insulin sensitivity in mice lacking ganglioside GM3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LIPID RAFTS; PATHOGENESIS; ASSOCIATION; RESISTANCE; CAVEOLAE; RECEPTOR; MUSCLE; CELLS AB Gangliosides are sialic acid-containing glycosphingolipids that are present on all mammalian plasma membranes where they participate in recognition and signaling activities. We have established mutant mice that lack GM3 synthase (CMP-NeuAc:lactosylceramide alpha2,3-sialyltransferase; EC 2.4.99.-). These mutant mice were unable to synthesize GM3 ganglioside, a simple and widely distributed glycosphingolipid. The mutant mice were viable and appeared without major abnormalities but showed a heightened sensitivity to insulin. A basis for the increased insulin sensitivity in the mutant mice was found to be enhanced insulin receptor phosphorylation in skeletal muscle. Importantly, the mutant mice were protected from high-fat diet-induced insulin resistance. Our results show that GM3 ganglioside is a negative regulator of insulin signaling, making it a potential therapeutic target in type 2 diabetes. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Ochanomizu Univ, Glycosci Inst, Bunkyo Ku, Tokyo 1128610, Japan. Univ Nacl Cordoba, Fac Ciencias Quim, Dept Quim Biol, Ctr Invest Quim Biol Cordoba, RA-5000 Cordoba, Argentina. Univ Bonn, Kekule Inst Organ Chem & Biochem, D-53121 Bonn, Germany. Deutsch Krebsforschungszentrum, Abt Zellulare & Mol Pathol, D-69120 Heidelberg, Germany. RP Proia, RL (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10 Ctr Dr,MSC 1821,Bldg 10,Room 9N-314, Bethesda, MD 20892 USA. EM proia@nih.gov RI Beck, Shoshannah/A-8478-2011; Proia, Richard/A-7908-2012 NR 20 TC 285 Z9 295 U1 3 U2 8 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 MAR 18 PY 2003 VL 100 IS 6 BP 3445 EP 3449 DI 10.1073/pnas.0635898100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 657PH UT WOS:000181675200084 PM 12629211 ER PT J AU Park, J Murray, GJ Limaye, A Quirk, JM Gelderman, MP Brady, RO Qasba, P AF Park, J Murray, GJ Limaye, A Quirk, JM Gelderman, MP Brady, RO Qasba, P TI Long-term correction of globotriaosylceramide storage in Fabry mice by recombinant adeno-associated virus-mediated gene transfer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ALPHA-GALACTOSIDASE-A; ENZYME REPLACEMENT THERAPY; FUNCTIONAL CORRECTION; DEFICIENT MICE; DISEASE; EXPRESSION; VECTOR; PROMOTER; SECRETION; DRIVEN AB Fabry disease is an X-linked recessive inborn metabolic disorder characterized by systemic and vascular accumulation of globotriaosylceramide (Gb(3)) caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-gal A). The condition is associated with an increased morbidity and mortality due to renal failure, cardiac disease, and early onset of stroke. Hemizygous males are primarily affected clinically with variable expression in heterozygous females. Gene-therapy trials have been initiated recently in alpha-gal A knockout mouse models of Fabry disease by using a variety of viral vectors. In the present investigation we administered single i.v. injections of 1 x 10(10) genomes of recombinant adeno-associated virus (rAAV) encoding the human alpha-gal A gene driven by a modified chicken beta-actin (CAG) promoter to alpha-gal A knockout (Fabry) mice. Transgenic mice were analyzed for expression of alpha-gal A activity and Gb(3) levels in liver, kidney, heart, spleen, small intestine, lung, and brain. Administration of the rAAV-CAG-hAGA vector resulted in stable expression of alpha-gal A in organs of the Fabry mice for >6 months. alpha-Gal A activity in the organs became equal to or higher than that of wild-type mice. Accumulated Gb(3) in the liver, heart, and spleen was reduced to that of wild-type mice with lesser but significant reductions in kidney, lung, and small intestine. Injection of the rAAV-CAG-hAGA construct into skeletal muscle did not result in expression of alpha-gal A in it or in other tissues. This study provides a basis for a simple and efficient gene-therapy approach for patients with Fabry disease and is indicative of its potential for the treatment of other lysosomal storage disorders. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Qasba, P (reprint author), NHLBI, Div Blood Dis & Resources, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM qasbap@nhlbi.nih.gov NR 31 TC 59 Z9 64 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 2003 VL 100 IS 6 BP 3450 EP 3454 DI 10.1073/pnas.0537900100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 657PH UT WOS:000181675200085 PM 12624185 ER PT J AU Nagababu, E Chrest, FJ Rifkind, JM AF Nagababu, E Chrest, FJ Rifkind, JM TI Hydrogen-peroxide-induced heme degradation in red blood cells: the protective roles of catalase and glutathione peroxidase SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE red blood cell; hydrogen peroxide; heme degradation; fluorescence; glutathione peroxidase; catalase ID HUMAN ERYTHROCYTES; HEMOGLOBIN; MEMBRANE; OXIDATION; AUTOXIDATION; BINDING; DEFICIENCY; GENERATION; HEMOLYSIS; DISPOSAL AB Catalase and glutathione peroxidase (GSHPX) react with red cell hydrogen peroxide. A number of recent studies indicate that catalase is the primary enzyme responsible for protecting the red cell from hydrogen peroxide. We have used flow cytometry in intact cells as a sensitive measure of the hydrogen-peroxide-induced formation of fluorescent heme degradation products. Using this method, we have been able to delineate a unique role for GSHPX in protecting the red cell from hydrogen peroxide. For extracellular hydrogen peroxide, catalase completely protected the cells, while the ability of GSHPX to protect the cells was limited by the availability of glutathione. The effect of endogenously generated hydrogen peroxide in conjunction with hemoglobin autoxidation was investigated by in vitro incubation studies. These studies indicate that fluorescent products are not formed during incubation unless the glutathione is reduced to at least 40% of its initial value as a result of incubation or by reacting the glutathione with iodoacetamide. Reactive catalase only slows down the depletion of glutathione, but does not directly prevent the formation of these fluorescent products. The unique role of GSHPX is attributed to its ability to react with hydrogen peroxide generated in close proximity to the red cell membrane in conjunction with the autoxidation of membrane-bound hemoglobin. Published by Elsevier Science B.V. C1 NIA, Mol Dynam Sect, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, Flow Cytometry Unit, NIH, Baltimore, MD 21224 USA. RP Rifkind, JM (reprint author), NIA, Mol Dynam Sect, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 39 TC 76 Z9 80 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD MAR 17 PY 2003 VL 1620 IS 1-3 BP 211 EP 217 DI 10.1016/S0304-4165(02)00537-8 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 649VB UT WOS:000181227700026 PM 12595091 ER PT J AU Shih, SC Prag, G Francis, SA Sutanto, MA Hurley, JH Hicke, L AF Shih, SC Prag, G Francis, SA Sutanto, MA Hurley, JH Hicke, L TI A ubiquitin-binding motif required for intramolecular monoubiquitylation, the CUE domain SO EMBO JOURNAL LA English DT Article DE CUE domain; monoubiquitylation; Rsp5; ubiquitin-binding protein; Vps9 ID SACCHAROMYCES-CEREVISIAE; UBA DOMAIN; ENDOPLASMIC-RETICULUM; PROTEIN; DEGRADATION; SURFACE; YEAST; INTERACT; RECEPTOR; VECTORS AB Monoubiquitylation is a regulatory signal, like phosphorylation, that can alter the activity, location or structure of a protein. Monoubiquitin signals are likely to be recognized by ubiquitin-binding proteins that transmit the regulatory information conferred by monoubiquitylation. To identify monoubiquitin-binding proteins, we used a mutant ubiquitin that lacks the primary site of polyubiquitin chain formation as bait in a two-hybrid screen. The C-terminus of Vps9, a protein required in the yeast endocytic pathway, interacted specifically with monoubiquitin. The region required for monoubiquitin binding mapped to the Vps9 CUE domain, a sequence previously identified by database searches as similar to parts of the yeast Cue1 and mammalian Tollip proteins. We demonstrate that CUE domains bind directly to monoubiquitin and we have defined crucial interaction surfaces on both binding partners. The Vps9 CUE domain is required to promote monoubiquitylation of Vps9 by the Rsp5 hect domain ubiquitin ligase. Thus, we conclude that the CUE motif is an evolutionarily conserved monoubiquitin-binding domain that mediates intramolecular monoubiquitylation. C1 Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. NIDDKD, Mol Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, 2153 Sheridan Rd, Evanston, IL 60208 USA. EM l-hicke@northwestern.edu FU NHLBI NIH HHS [HL50121]; NIDDK NIH HHS [R01 DK053257, DK53257]; NIGMS NIH HHS [T32 GM008061, T32GM08061] NR 34 TC 190 Z9 198 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD MAR 17 PY 2003 VL 22 IS 6 BP 1273 EP 1281 DI 10.1093/emboj/cdg140 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 655HV UT WOS:000181546000005 PM 12628920 ER PT J AU Allende, ML Yamashita, T Proia, RL AF Allende, ML Yamashita, T Proia, RL TI G-protein coupled receptor S1P1 in endothelial cells directs vascular maturation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIDDK, GDDB, NIH, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1192 EP A1193 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902073 ER PT J AU Andreola, F Elizondo, G Calvisi, D Jakowlew, S Gonzalez, FJ De Luca, LM AF Andreola, F Elizondo, G Calvisi, D Jakowlew, S Gonzalez, FJ De Luca, LM TI Reversal of liver fibrosis in aryl hydrocarbon receptor knockout mice by vitamin A depletion SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, NIH, Bethesda, MD 20892 USA. Natl Canc Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1198 EP A1198 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902100 ER PT J AU Barros, SA Cannon, RE AF Barros, SA Cannon, RE TI Molecular structure and characterization of a novel murine ABC transporter, Abca13 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIEHS, Natl Ctr Toxicogenom, Canc Biol Grp, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1317 EP A1317 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902658 ER PT J AU Basu, NK Kole, L Mitra, PS Owens, IS AF Basu, NK Kole, L Mitra, PS Owens, IS TI Phosphorylation of bilirubin UDP-glucuronosyltransferase (UGT1A1) is required for activity and involves protein kinase c SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NICHD, HDB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1308 EP A1308 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902614 ER PT J AU Batra, A Ling, SM Spencer, RG Kasper, CE Galban, C Taub, D Abernethy, DR AF Batra, A Ling, SM Spencer, RG Kasper, CE Galban, C Taub, D Abernethy, DR TI Skeletal muscle atrophy induced by hind-limb unloading is associated with low muscle IL-6 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIA, Clin Invest Lab, Intramural Res Program, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. NIA, Intramural Res Program, Immunol Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A957 EP A957 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900958 ER PT J AU Bleicher, RJ Han, TY Liu, YY Wang, HT Gouaze, V Gottesman, M Bitterman, A Giuliano, AE Cabot, MC AF Bleicher, RJ Han, TY Liu, YY Wang, HT Gouaze, V Gottesman, M Bitterman, A Giuliano, AE Cabot, MC TI Enhanced ceramide glycosylation through upregulated gene expression in cancer cells selected for resistance to vinblastine and adriamycin SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 John Wayne Canc Inst, Dept Surg Oncol, Santa Monica, CA 90404 USA. Univ Calif Los Angeles, Los Angeles, CA USA. John Wayne Canc Inst, Breast Canc Res Program, Santa Monica, CA USA. NCI, Bethesda, MD 20892 USA. Carmel Hosp, Haifa, Israel. RI Gouaze-Andersson, Valerie/O-9180-2014 OI Gouaze-Andersson, Valerie/0000-0002-1797-515X NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1317 EP A1317 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902657 ER PT J AU Capelluto, DG Kutateladze, T Habas, R Finkielstein, C He, X Overduin, MJ AF Capelluto, DG Kutateladze, T Habas, R Finkielstein, C He, X Overduin, MJ TI DIX domain targets dishevelled to actin stress fibers and vesicular membranes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. NIH, Bethesda, MD 20892 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1027 EP A1027 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901298 ER PT J AU Carlson, BA Kumaraswamy, EA Su, D Lee, BJ Gladyshev, VN Hatfield, DL AF Carlson, BA Kumaraswamy, EA Su, D Lee, BJ Gladyshev, VN Hatfield, DL TI Targeted removal of the selenocysteine tRNA ([Ser]Sec) gene (Trsp) in mouse tissues SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, BRL, CCR, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68583 USA. LMG, SNU, Seoul, South Korea. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1096 EP A1096 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901620 ER PT J AU Cho, HY Reddy, SPM DeBiase, A Kleeberger, SR AF Cho, HY Reddy, SPM DeBiase, A Kleeberger, SR TI Microarray gene profiling of oxidative lung injury and NRF2 regulation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. George Washington Univ, Childrens Natl Med Ctr, Washington, DC USA. NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1254 EP A1254 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902362 ER PT J AU Cisneros, F Wilson, R Travlos, G Anderson, LM Branch, S AF Cisneros, F Wilson, R Travlos, G Anderson, LM Branch, S TI Susceptibility to postnatal growth retardation induced by 5-aza-2 '-deoxycytidine in utero: Gender specificity and correlation with reduced insulin-like growth factor SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 N Carolina State Univ, Raleigh, NC 27695 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A779 EP A779 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900118 ER PT J AU Davis, CD AF Davis, CD TI Deficient dietary selenium (Se) adversely affects putative risk factors for colon cancer susceptibility in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Nutrit Sci Res Grp, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1134 EP A1135 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901798 ER PT J AU Davis, CD Uthus, EO AF Davis, CD Uthus, EO TI Dietary selenium (Se) and folate affect dimethythydrazine (DMH)-induced aberrant crypt formation, global DNA methylation and one-carbon metabolism in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Nutrit Sci Res Grp, NIH, Bethesda, MD 20892 USA. USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1371 EP A1371 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902916 ER PT J AU Dyer, KD Rosenberg, HF AF Dyer, KD Rosenberg, HF TI Differential expression of mouse ribonuclease A family genes during pregnancy and development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIAID, Eosinophil Pathophysiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A835 EP A835 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900383 ER PT J AU Fenton, RA Ageloff, S Azadi, N Chou, CL Knepper, MA AF Fenton, RA Ageloff, S Azadi, N Chou, CL Knepper, MA TI Increased urea-transporter expression in IMCDs of Dahl salt-sensitive rat SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A933 EP A933 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900842 ER PT J AU Fischer, LM Koch, MA Stinchcombe, T Crowell, JA Zeisel, SH AF Fischer, LM Koch, MA Stinchcombe, T Crowell, JA Zeisel, SH TI Clinical characteristics of purified soy isoflavones: multiple dose administration to men with prostate neoplasia SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. RTI Int, Stat Res Div, Burlington, NC USA. Alamance Oncol Hematol Associates, Burlington, NC USA. NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1151 EP A1151 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901875 ER PT J AU Gallagher, D Kuznia, P Heshka, S Albu, J Heymsfield, S Goodpaster, B Visser, M Harris, T AF Gallagher, D Kuznia, P Heshka, S Albu, J Heymsfield, S Goodpaster, B Visser, M Harris, T TI Greater infiltration of adipose tissue in muscle of African-Americans-compared to Caucasians SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Columbia Univ, St Lukes Roosevelt Hosp, Obes Res Ctr, New York, NY 10025 USA. NIA, Geriatr Epidemiol Sect, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. VUMC, EMGO, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1205 EP A1205 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902131 ER PT J AU Gao, ZG Jacobson, KA AF Gao, ZG Jacobson, KA TI SCH-202676 allosterically modulates adenosine but not P2Y receptors SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1038 EP A1038 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901348 ER PT J AU Garvey, TL Khanna-Gupta, A Berliner, N Lekstrom-Himes, JA AF Garvey, TL Khanna-Gupta, A Berliner, N Lekstrom-Himes, JA TI Functional analysis of the alpha and beta promoters of C/EBP epsilon SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Sect Hematol, New Haven, CT USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A835 EP A835 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900381 ER PT J AU Giulian, GG Hwang, JC Bardo, AM Goldie, SN Krogmeier, JR Goldner, LS Merril, CR AF Giulian, GG Hwang, JC Bardo, AM Goldie, SN Krogmeier, JR Goldner, LS Merril, CR TI Analysis of the moving boundary in cross-gradient SDS-PAGE: a "triple point" SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIMH, HHS, NIH, Bethesda, MD 20892 USA. NIST, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A987 EP A987 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901102 ER PT J AU Gorman, MW Ogimoto, K Savage, MV Jacobson, KA Feigl, EO AF Gorman, MW Ogimoto, K Savage, MV Jacobson, KA Feigl, EO TI Nucleotide vasodilation in guinea pig hearts SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Washington, Seattle, WA 98195 USA. NIH, Bioorgan Chem Lab, Mol Recognit Sect, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1262 EP A1262 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902399 ER PT J AU Gray, MA Aziz, O Simmons, NL Boese, SH AF Gray, MA Aziz, O Simmons, NL Boese, SH TI Intracellular Ca2+ directly regulates the Ca2+ activated Cl conductance in mouse inner medullary collecting duct cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. NIEH NIH, Lab Signal Transduct, Res Triangle Pk, NC USA. Univ Potsdam, Inst Biochem Biol, Potsdam, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1224 EP A1224 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902220 ER PT J AU Hanauske-Abel, HM Lee, YB Wolff, EC Clement, PM Park, MH AF Hanauske-Abel, HM Lee, YB Wolff, EC Clement, PM Park, MH TI Deoxyhypusine hydroxylase, required for cell proliferation, is a 2-oxoacid-utilizing dioxygenase SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Natl Inst Dental & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A979 EP A980 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901065 ER PT J AU Hansen, PB Huang, YN Yang, TX Briggs, J Schnermann, J AF Hansen, PB Huang, YN Yang, TX Briggs, J Schnermann, J TI Vasoconstrictor mechanisms of adenosine in isolated perfused afferent arterioles of the mouse SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A920 EP A920 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900781 ER PT J AU Harris, TB Kuznia, P Heshka, S Albu, J Heymsfield, S Goodpaster, B Visser, M Gallagher, D AF Harris, TB Kuznia, P Heshka, S Albu, J Heymsfield, S Goodpaster, B Visser, M Gallagher, D TI Variation in muscle adipose tissue infiltration by weight and total adipose tissue in premenopausal women SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20895 USA. St Lukes Roosevelt Hosp, Dept Med, Obes Res Ctr, New York, NY USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. VUMC, EMGO, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1205 EP A1206 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902132 ER PT J AU Hendrix, MJC Seftor, EA Weiss, RM Kirschmann, DA Gruman, LM Hess, AR Lee, LMJ Margaryan, N Sherif, DD Schatteman, GC Quaranta, V Meltzer, PS Seftor, REB AF Hendrix, MJC Seftor, EA Weiss, RM Kirschmann, DA Gruman, LM Hess, AR Lee, LMJ Margaryan, N Sherif, DD Schatteman, GC Quaranta, V Meltzer, PS Seftor, REB TI Plasticity allows vasculogenic mimicry by melanoma tumor cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Iowa, Iowa City, IA 52242 USA. Scripps Res Inst, La Jolla, CA USA. Natl Genome Res Inst, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1165 EP A1165 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901940 ER PT J AU Hirayama, T Wada, A Moss, J AF Hirayama, T Wada, A Moss, J TI H-pylori VacA stimulates p38 and Erk1/2, but not JNK, phosphorylation in AZ-521 cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Nagasaki Univ, Inst Trop Med, Nagasaki 8528523, Japan. NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A793 EP A794 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900186 ER PT J AU Hollenback, D Bonham, L Coon, M Ball, A Pound, J Martin, T Morrison, DK White, T AF Hollenback, D Bonham, L Coon, M Ball, A Pound, J Martin, T Morrison, DK White, T TI lysoPhosphatidic acid acyltransferase-beta: A novel target for interruption of cellular signalling and induction of apoptosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Cell Therapeut Inc, Seattle, WA 98119 USA. NCI, Regulat Cell Growth Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1318 EP A1318 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902663 ER PT J AU Hur, GM Lin, Y Yang, QF Shen, HM Liu, ZG AF Hur, GM Lin, Y Yang, QF Shen, HM Liu, ZG TI Molecular mechanism of genotoxic stress-induced NF-kB activation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIH, Canc & Cell & Biol Branch, Bethesda, MD 20892 USA. RI SHEN, Han-Ming/B-5942-2011 OI SHEN, Han-Ming/0000-0001-7369-5227 NR 0 TC 4 Z9 4 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1015 EP A1015 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901240 ER PT J AU Itoh, M Chitnis, A AF Itoh, M Chitnis, A TI Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NICHD, NIH, LMG, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 4 U2 7 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 MAR 17 PY 2003 VL 17 IS 5 SU S BP A995 EP A995 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901143 ER PT J AU Jeong, SY Hsu, YT Lee, YJ Sharpe, J Motoshi Suzuki Youle, RJ AF Jeong, SY Hsu, YT Lee, YJ Sharpe, J Motoshi Suzuki Youle, RJ TI The role of the C-terminal membrane anchor domain of Bcl-XL in heterodimerization of Bcl-XL and Bax SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NINDS, SNB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1004 EP A1005 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901189 ER PT J AU Jones, T Hiol, A Osterhout, JL Waheed, AA Davey, PC Milligan, G Druey, KM AF Jones, T Hiol, A Osterhout, JL Waheed, AA Davey, PC Milligan, G Druey, KM TI Palmitoylation of a cysteine residue in the RGS box regulates RGS16 function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Glasgow, Dept Biochem & Mol Biol, Glasgow, Lanark, Scotland. RI Milligan, Graeme/F-9426-2011 OI Milligan, Graeme/0000-0002-6946-3519 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1341 EP A1341 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902773 ER PT J AU Jutkiewicz, EM Eller, EB Rice, KC Mosberg, HI Woods, JH AF Jutkiewicz, EM Eller, EB Rice, KC Mosberg, HI Woods, JH TI Antidepressant-like effects of an enkephalinase inhibitor alone and in combination with the delta-opioid agonist SNC80 in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. NIDDK, NIH, Bethesda, MD USA. Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1023 EP A1023 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901279 ER PT J AU Kono, M Sasaki, T Liu, YJ Wu, YP Mi, YD Yamashita, T Proia, RL AF Kono, M Sasaki, T Liu, YJ Wu, YP Mi, YD Yamashita, T Proia, RL TI G-protein coupled receptors S1P2 and S1P3 are required for proper vascular development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIH, GDDB, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1193 EP A1193 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902074 ER PT J AU Kwon, SY Badenhorst, P Novoselov, S Kryukov, GV Wei, Q Paterson, BM Carlson, BA Martin-Romero, FJ Lee, HS Gladyshev, VN Hatfield, DL Lee, BJ AF Kwon, SY Badenhorst, P Novoselov, S Kryukov, GV Wei, Q Paterson, BM Carlson, BA Martin-Romero, FJ Lee, HS Gladyshev, VN Hatfield, DL Lee, BJ TI Functional studies of drosophila selenoproteins: Selenophosphate synthetase 2 (SPS2), G-rich and BthD SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, BRL, CCR, NIH, Bethesda, MD 20892 USA. NCI, LMCB, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68583 USA. NCI, LB, NIH, Bethesda, MD 20892 USA. SNU, LMG, Seoul, South Korea. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1095 EP A1095 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901618 ER PT J AU Kwon, Y Bae, M Kim, WH Song, B AF Kwon, Y Bae, M Kim, WH Song, B TI Ethanol causes p53-deoendent cell cycle arrest and apoptosis of SK-N-SH neuroblastoma cells. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIAAA, LMBB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A978 EP A978 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901057 ER PT J AU Le, YY Gong, WH Dunlop, NM Zhou, Y Wang, JM AF Le, YY Gong, WH Dunlop, NM Zhou, Y Wang, JM TI Expression of functional formyl peptide receptors by human astrocytoma cell lines SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. SAIC, Mol Immunoregulat Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1346 EP A1346 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902796 ER PT J AU Li, CJ DePamphilis, ML AF Li, CJ DePamphilis, ML TI By ubiquitination and phosphorylation, the "ORC Cycle" regulating the initiation of DNA replication SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Anim & Nat Resources Inst, Growth Biol Lab, Beltsville, MD 20705 USA. NICHD, LMGR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A975 EP A975 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901045 ER PT J AU Liu, Y Shaw, S AF Liu, Y Shaw, S TI N-terminal extension of the kinase domain of PKC-theta and PKC-delta contributes to catalytic competence SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1308 EP A1308 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902615 ER PT J AU Lopez, ST Bulter, L Wayne, S Baumgartner, K Baumgartner, R Ballard-Barbash, R AF Lopez, ST Bulter, L Wayne, S Baumgartner, K Baumgartner, R Ballard-Barbash, R TI Changes in dietary intake after breast cancer diagnosis: The health, eating, activity, and lifestyle (HEAL) study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ New Mexico, Albuquerque, NM 87131 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A769 EP A769 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900069 ER PT J AU Lyles, J Cai, NS Cadet, JL AF Lyles, J Cai, NS Cadet, JL TI Changes in gene expression induced by prenatal 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) exposure SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Maryland, Baltimore, MD 21201 USA. Natl Inst Drug Abuse, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1213 EP A1213 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902167 ER PT J AU Malkinson, AM Zhang, F Pao, W Umphres, S Jakowlew, S Meyer, AM Nield, LD Miller, Y Takeda, K Fisher, J Gelfand, EW Mason, RJ AF Malkinson, AM Zhang, F Pao, W Umphres, S Jakowlew, S Meyer, AM Nield, LD Miller, Y Takeda, K Fisher, J Gelfand, EW Mason, RJ TI Surfactant apoprotein D serum levels are increased in mice bearing lung tumors SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Natl Jewish Hosp, Denver, CO USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dept Vet Affairs, Med Branch, Denver, CO USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1078 EP A1078 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901537 ER PT J AU Matsuyama, W Kamohara, H Galligan, C Faure, M Yoshimura, T AF Matsuyama, W Kamohara, H Galligan, C Faure, M Yoshimura, T TI Interaction of discoidin domain receptor 1 isoform b (DDR1b) with collagen activates p38 mitogen activated protein kinase and promotes differentiation of macrophages SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Kumamoto Univ, Sch Med, Dept Surg 2, Kumamoto 860, Japan. Sugen Inc, Dept Surg 2, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A795 EP A795 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900194 ER PT J AU McCann, NM Ferguson, P McVicar, D Johnston, JA AF McCann, NM Ferguson, P McVicar, D Johnston, JA TI SOCS3 binds to immune inhibitory receptors SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Queens Univ Belfast, Dept Immunol, Belfast BT9 7BL, Antrim, North Ireland. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1019 EP A1019 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901261 ER PT J AU McNutt, MC Smith, JL Freebern, WJ Haggerty, CM Gardner, K AF McNutt, MC Smith, JL Freebern, WJ Haggerty, CM Gardner, K TI Dynamic profiling of transcription: an integrated bioinformatics approach to gene regulation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1353 EP A1353 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902829 ER PT J AU Montano, I Smith, JL McNutt, MC Hoover, PJ Freebern, WJ Haggerty, CM Dzekunova, I Kawasaki, E Peterson, D Gardner, K AF Montano, I Smith, JL McNutt, MC Hoover, PJ Freebern, WJ Haggerty, CM Dzekunova, I Kawasaki, E Peterson, D Gardner, K TI Understanding signal transduction integration through. kinetic analysis of promoter occupancy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NCI, MicroArray Facil, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1352 EP A1353 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902828 ER PT J AU Notari, L Perruccio, E Smith, LEH Amaral, J Becerra, SP AF Notari, L Perruccio, E Smith, LEH Amaral, J Becerra, SP TI Pigment epithelium-derived factor, a substrate for matrix metalloproteinases MMP-2 and MMP-9 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NEI, NIH, Bethesda, MD 20892 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1330 EP A1330 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902719 ER PT J AU Paolocci, N Katori, T Belardi, D Tocchetti, CG Miranda, KM Wink, DA Kass, DA AF Paolocci, N Katori, T Belardi, D Tocchetti, CG Miranda, KM Wink, DA Kass, DA TI Nitroxyl anion improves contractile function and potentiates beta-adrenergic response in vivo congestive heart failure SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Johns Hopkins Med Inst, Div Cardiol, Dept Med, Baltimore, MD 21208 USA. NIH, Radiobiol Branch, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1252 EP A1252 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902349 ER PT J AU Patterson, BH Wastney, ME Combs, GF Brindak, M Veillon, C Taylor, PR Patterson, K Levander, OA AF Patterson, BH Wastney, ME Combs, GF Brindak, M Veillon, C Taylor, PR Patterson, K Levander, OA TI Selenium kinetics in humans: Simultaneous studies of Selenite and Selenomethionine SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, DCP, EPN, Bethesda, MD 20892 USA. Metab Modeling Serv Ltd, Hamilton, New Zealand. Cornell Univ, Ithaca, NY USA. USDA, Beltsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1136 EP A1136 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901803 ER PT J AU Shah, BH Catt, KJ AF Shah, BH Catt, KJ TI Dependence of GnRH-induced neuronal MAP kinase signaling on EGF receptor transactivation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NICHHD, ERRB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1019 EP A1019 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901258 ER PT J AU Shupp, JW Vandernoth, L Pontzer, CH Jett, M AF Shupp, JW Vandernoth, L Pontzer, CH Jett, M TI Protective effects of staphylococcal enterotoxin B transcytosis peptide SEB152-161 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Walter Reed Army Inst Res, Silver Spring, MD 20910 USA. NIH, NCCAM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1079 EP A1079 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901541 ER PT J AU Song, J Shi, M Knepper, MA Verbalis, JG Ecelbarger, CA AF Song, J Shi, M Knepper, MA Verbalis, JG Ecelbarger, CA TI Effect of dietary NaCl level on blood pressure and the abundance of renal sodium transport proteins in fructose-fed rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Georgetown Univ, Dept Med, Washington, DC 20057 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A933 EP A933 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900843 ER PT J AU Song, M Knepper, MA Verbalis, JG Ecelbarger, CA AF Song, M Knepper, MA Verbalis, JG Ecelbarger, CA TI Increased renal ENaC subunit abundances in streptozotocin (STZ)-induced diabetes. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Georgetown Univ, Med Ctr, Washington, DC 20057 USA. Natl Heart Lung & Blood Inst, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A915 EP A915 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900761 ER PT J AU Starke, DW Gallogly, MG Chock, PB Mieyal, JJ AF Starke, DW Gallogly, MG Chock, PB Mieyal, JJ TI Selective redox modulation of protein tyrosine phosphatase 1B activity: modeling intracellular events SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. NHLBI, Biochem Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1308 EP A1308 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902613 ER PT J AU Tiwari, S Wong, JM Heller, JA Blann, P Abernethy, DR Soldatov, NM AF Tiwari, S Wong, JM Heller, JA Blann, P Abernethy, DR Soldatov, NM TI Switch of calcium channel alpha(1c) subunit splice variant to exon-21 isoform in human aorta atherosclerotic plaque SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. Johns Hopkins Bayview MEd Ctr, Div Vasc Surg, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1049 EP A1049 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901401 ER PT J AU Tooze, JA Izmirlian, G Brown, C Perkins, S Hursting, S AF Tooze, JA Izmirlian, G Brown, C Perkins, S Hursting, S TI Armitage-doll analysis of diet : p53 gene dosage interactions in p53-deficient and wild-type mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1153 EP A1153 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901881 ER PT J AU Uhrenholt, TR Schjerning, J Norregaard, R Hansen, PB Jensen, BL Skott, O AF Uhrenholt, TR Schjerning, J Norregaard, R Hansen, PB Jensen, BL Skott, O TI Rapid inhibition of vasoconstriction in renal afferent arterioles by aldosterone SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ So Denmark, DK-5000 Odense C, Denmark. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A920 EP A920 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900783 ER PT J AU Waheed, AA Jones, TLZ AF Waheed, AA Jones, TLZ TI Hsp90 interactions and acylation target Galpha12 but not Galphal13 to lipid rafts SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1337 EP A1337 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902753 ER PT J AU Wang, H Bradbury, JA Blaisdell, JA Goldstein, JA Zeldin, DC AF Wang, H Bradbury, JA Blaisdell, JA Goldstein, JA Zeldin, DC TI Cloning, expression and characterization of three new murine CYP2Cs involved in fatty acid metabolism SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1325 EP A1325 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902694 ER PT J AU Wang, T Izmirlian, G Takahashi, Y Perkins, S Hursting, S AF Wang, T Izmirlian, G Takahashi, Y Perkins, S Hursting, S TI Microarray expression profiling of LNCaP prostate cancer cell gene expression following exposure to the soy isoflavone genistein SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 USDA, Beltsville Human Nutr Res Ctr, Phytonutrients Lab, Beltsville, MD 20705 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1372 EP A1372 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902919 ER PT J AU Wang, W Bird, TH Eiden, MV Anderson, WB AF Wang, W Bird, TH Eiden, MV Anderson, WB TI Regulation of Pit2 sodium-dependent phosphate transporter/amphotropic murine leukemia virus cell surface receptor function by cyclic AMP-dependent protein kinase SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, LCO, Bethesda, MD 20892 USA. NIMH, LCMR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1034 EP A1034 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901332 ER PT J AU Wek, RC Zhan, K Vattem, K Dever, TE Chen, JJ AF Wek, RC Zhan, K Vattem, K Dever, TE Chen, JJ TI Phosphorylation of eIF2 by HRI-related protein kinases is important for stress resistance in fisson yeast SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1259 EP A1259 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902383 ER PT J AU Yu, Q Leatherbury, L Spurney, C Wessels, A Lo, C AF Yu, Q Leatherbury, L Spurney, C Wessels, A Lo, C TI Large scale high throughput noninvasive screen for congenital cardiovascular anomalies in ENU mutagenized mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NHLBI, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1170 EP A1170 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901964 ER PT J AU Zhang, Y Dufau, ML AF Zhang, Y Dufau, ML TI Repression of transcription of the luteinizing hormone receptor gene: Interplay between nuclear orphan receptors and Sp1/Sp3 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1331 EP A1331 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902726 ER PT J AU Zhong, NX Moustafa, ME Rao, M Carlson, BA Feigenbaum, L Hatfield, DL AF Zhong, NX Moustafa, ME Rao, M Carlson, BA Feigenbaum, L Hatfield, DL TI Effects of the interactions of mutant and wild type selenocysteine (Sec) tRNA transgene products on selenoprotein biosynthesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, CCR, BRL, Bethesda, MD 20892 USA. FCRDC, SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1137 EP A1137 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901808 ER PT J AU Zhou, Y Bian, XW Gong, WH Zhang, X Le, YY Iribarren, P Sun, RH Wang, JM AF Zhou, Y Bian, XW Gong, WH Zhang, X Le, YY Iribarren, P Sun, RH Wang, JM TI Activation of formylpeptide receptor (FPR) in malignant astrocytoma cells promotes the production of vascular endothelial growth factor (VEGF) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Third Mil Med Univ, Mol Immunoregulat Lab, Chongqing, Peoples R China. SAIC, Mol Immunoregulat Lab, Frederick, MD USA. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. RI Zhang, Xia/B-8152-2008; Bian, Xiuwu/F-1569-2011; Bian, Xiu-wu/D-4736-2017 OI Zhang, Xia/0000-0002-9040-1486; Bian, Xiu-wu/0000-0003-4383-0197 NR 0 TC 0 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1346 EP A1346 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902797 ER PT J AU Chiaramonte, MG Mentink-Kane, M Jacobson, BA Cheever, AW Whitters, MJ Goad, MEP Wong, A Collins, M Donaldson, DD Grusby, MJ Wynn, TA AF Chiaramonte, MG Mentink-Kane, M Jacobson, BA Cheever, AW Whitters, MJ Goad, MEP Wong, A Collins, M Donaldson, DD Grusby, MJ Wynn, TA TI Regulation and function of the interleukin 13 receptor alpha 2 during a T helper cell type 2-dominant immune response SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE fibrosis; inflammation; liver; granuloma; mouse ID CRYPTOGENIC FIBROSING ALVEOLITIS; SCHISTOSOMA-MANSONI; GRANULOMA-FORMATION; HEPATIC-FIBROSIS; TH2 CELLS; IN-VIVO; MURINE SCHISTOSOMIASIS; CYTOKINE RESPONSES; IL-13 RECEPTOR; SIGNAL-TRANSDUCTION AB Highly polarized type 2 cytokine responses can be harmful and even lethal to the host if they are too vigorous or persist too long. Therefore, it is important to elucidate the mechanisms that down-regulate these reactions. Interleukin (IL)-13 has emerged as a central mediator of T helper cell (Th)2-dominant immune responses, exhibiting a diverse array of functional activities including regulation of airway hyperreactivity, resistance to nematode parasites, and tissue remodeling and fibrosis. Here, we show that IL-13 receptor (R)alpha2 is a critical down-regulatory factor of IL-13-mediated tissue fibrosis induced by the parasitic helminth Schistosoma mansoni. IL-13Ralpha2 expression was induced after the onset of the fibrotic response, IL-10, IL-13, and Stat6 dependent, and inhibited by the Th1-inducing adjuvant IL-12. Strikingly, schistosome-infected C57BL/6 and BALB/c IL-13Ralpha2-deficient mice showed a marked exacerbation in hepatic fibrosis, despite displaying no change in granuloma size, tissue eosinophilia, or mastocytosis. Fibrosis increased despite the fact that IL-13 levels decreased significantly in the liver and serum. Importantly, pathology was prevented when IL-13Ralpha2-deficient mice were treated with a soluble IL-13Ralpha2-Fc construct, formally demonstrating that their exacerbated fibrotic response was due to heightened IL-13 activity. Together, these studies illustrate the central role played by the IL-13Ralpha2 in the down-regulation of a chronic and pathogenic Th2-mediated immune response. C1 NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Wyeth Genet Inst, Andover, MA 01810 USA. Biomed Res Inst, Rockville, MD 20852 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bldg 50,Room 6154,MSC 8003, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 FU NIAID NIH HHS [AI4040171] NR 73 TC 186 Z9 194 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 17 PY 2003 VL 197 IS 6 BP 687 EP 701 DI 10.1084/jem.20020903 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 658WZ UT WOS:000181745200003 PM 12642601 ER PT J AU Daniels, JL Longnecker, MP Klebanoff, MA Gray, KA Brock, JW Zhou, HB Chen, Z Needham, LL AF Daniels, JL Longnecker, MP Klebanoff, MA Gray, KA Brock, JW Zhou, HB Chen, Z Needham, LL TI Prenatal exposure to low-level polychlorinated biphenyls in relation to mental and motor development at 8 months SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE infant; mental status schedule; motor skills; polychlorinated biphenyls; prenatal exposure delayed effects ID HUMAN-MILK; PCBS; ORGANOCHLORINES; NEUROTOXICITY; METAANALYSIS; CONGENERS; DDE AB The relation between exposure to low levels of polychlorinated biphenyls (PCBs), a class of persistent organic pollutants, and.cognitive and motor development in young children has been examined in several studies, and results have varied. The authors evaluated the association between prenatal exposure to PCBs and children's neurodevelopment using data from the Collaborative Perinatal Project. Pregnant women were enrolled from 1959 to 1965 from 12 sites. across the United States. PCBs were measured in maternal serum taken during pregnancy. To measure children's mental and psychomotor development at 8 months of age, the authors administered the Bayley Scales of Infant Development (means, 87 (standard deviation, 15) and 88 (standard deviation, 18), respectively). Overall, they did not observe a relation between prenatal PCB exposure and children's mental or psychomotor scores (n = 1,207; multivariate adjusted beta = 01 point per mug/liter increase of PCB, p = 0.71, and beta = 0.5, p = 0.14, respectively). The PCB-psychomotor score relation varied by study center (p < 0.05): The association was direct in some centers, inverse in others. This could not be attributed to variation in the timing or measurement of the child's neurodevelopment or analysis of PCBs because these were standardized across centers. The reasons for variation in results within this study and across other studies remain unclear. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. NIEHS, Chem Exposure & Mol Biol Branch, Res Triangle Pk, NC 27709 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Daniels, JL (reprint author), Univ N Carolina, Dept Epidemiol, CB 7435, Chapel Hill, NC 27599 USA. RI Needham, Larry/E-4930-2011; OI Longnecker, Matthew/0000-0001-6073-5322 NR 31 TC 53 Z9 53 U1 0 U2 4 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 MAR 15 PY 2003 VL 157 IS 6 BP 485 EP 492 DI 10.1093/aje/kwg010 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 656MM UT WOS:000181611600002 PM 12631537 ER PT J AU Garabrant, DH Lacey, JV Laing, TJ Gillespie, BW Mayes, MD Cooper, BC Schottenfeld, D AF Garabrant, DH Lacey, JV Laing, TJ Gillespie, BW Mayes, MD Cooper, BC Schottenfeld, D TI Scleroderma and solvent exposure among women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE occupational exposure; scleroderma, systemic; solvents; tetrachloroethylene; trichloroethanes; trichloroethylene ID PROGRESSIVE SYSTEMIC-SCLEROSIS; CONNECTIVE-TISSUE DISEASE; OCCUPATIONAL EXPOSURE; ORGANIC-SOLVENTS; VINYL-CHLORIDE; RISK-FACTORS; TRICHLOROETHYLENE AB Exposure to solvents has been reported to increase the risk of scleroderma. The authors investigated the relation between exposures to solvents in occupational and hobby settings and the development of scleroderma among women in a case-control study with population-based controls in Michigan (1980-1991) and Ohio (1980-1992). A total of 660 cases and 2,227 frequency-matched controls were interviewed by telephone. Diagnoses of scleroderma, were verified by medical records review. Paint thinners and removers were significantly associated with scleroderma both by self-report (odds ratio (OR) = 1.9, 95% confidence interval (Cl): 1.4, 2.6) and after expert review (OR = 2.0, 95% Cl: 1.5, 2.6). Other petroleum distillates (gasoline and mineral spirits) were not significantly associated with scleroderma after controlling for other correlated exposures in multivariable analyses. Trichloroethylene was associated with scleroderma both by self-report (OR = 2.0, 95% Cl: 0.8, 4.8) and after expert review (OR = 1.9, 95% Cl: 0.6, 6.6), but not significantly. Analyses by duration of exposure found that risk increased with, the duration of use of any of the solvents (OR = 1.01 /year of exposure, 95% Cl: 1.01, 1.02), but there was no evidence of increasing risk with increasing duration of exposure for any specific solvent studied. In summary, exposures to paint thinners and removers were associated with scleroderma in women but showed no evidence of increasing risk with increasing duration. Exposures to other specific chlorinated and nonchlorinated hydrocarbon solvents were not clearly associated with scleroderma. C1 Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Publ Hlth, Dept Environm & Ind Hlth, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. Univ Texas, Sch Med, Dept Internal Med, Houston, TX USA. RP Schottenfeld, D (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, 109 Observ St, Ann Arbor, MI 48109 USA. EM daschott@umich.edu FU NIAMS NIH HHS [5 P60 AR-20557]; OHS HRSA HHS [ST32 AR-07080] NR 45 TC 37 Z9 38 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 2003 VL 157 IS 6 BP 493 EP 500 DI 10.1093/aje/kwf223 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 656MM UT WOS:000181611600003 PM 12631538 ER PT J AU Slavotinek, A Poyser, L Wallace, A Martin, F Gaunt, L Kingston, H AF Slavotinek, A Poyser, L Wallace, A Martin, F Gaunt, L Kingston, H TI Two unique patients with trisomy 18 mosaicism and molecular marker studies SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE trisomy 18; trisomy 18 mosaicism; tetrasomy 18p ID NORMAL INTELLIGENCE; INSITU HYBRIDIZATION; PARENTAL ORIGIN; WOMAN; ISOCHROMOSOME-18P; NONDISJUNCTION; TETRASOMY-18P; DIAGNOSIS; GIRL; HYPOMELANOSIS AB We report two unusual patients with trisomy 18 mosaicism presenting with minor anomalies and failure to thrive in the first year of life. Chromosome analysis showed trisomy 18 in 30/30 peripheral blood lymphocytes in both children. Analysis of skin fibroblasts in the first child showed normal female chromosomes in 30/30 cells, and the fibroblast karyotype in the second child showed mosaicism for tetrasomy 18p, trisomy 18, and normal female chromosomes (karyotype 47,XX, +i(18)(p10)[47]/47,XX, +18[9]/46,XX[4]). Trisomy 18 commonly results from nondisjunction at maternal meiosis II (MII). Nondisjunction at maternal MII has also been postulated to be the initial step in the formation of tetrasomy 18p. In our second case, the additional chromosome 18 was the result of maternal nondisjunction at MII, consistent with this hypothesis. In the first case, nondisjunction at maternal meiosis I (MI) was responsible for the extra chromosome 18. (C) 2003 Wiley-Liss, Inc. C1 Univ Manchester, St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England. Univ Manchester, St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England. NIH, NHGRI, Bethesda, MD 20892 USA. RP Kingston, H (reprint author), Univ Manchester, St Marys Hosp, Dept Med Genet, Hathersage Rd, Manchester M13 0JH, Lancs, England. NR 41 TC 6 Z9 6 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAR 15 PY 2003 VL 117A IS 3 BP 282 EP 288 DI 10.1002/ajmg.a.10809 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 670HH UT WOS:000182401100013 PM 12599194 ER PT J AU Moslehi, R Kariminejad, MH Ghaffari, V Narod, S AF Moslehi, R Kariminejad, MH Ghaffari, V Narod, S TI Analysis of BRCA1 and BRCA2 mutations in an Iranian family with hereditary breast and ovarian cancer syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Letter ID GENETICS C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Univ Tehran, Tehran, Iran. Univ Tehran Med Sci, Tehran, Iran. Womens Coll Hosp, Ctr Res Women Hlth, Toronto, ON M5S 1B2, Canada. RP Moslehi, R (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7003,MSC 7236, Rockville, MD 20852 USA. EM moslehir@mail.nih.gov NR 3 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAR 15 PY 2003 VL 117A IS 3 BP 304 EP 305 DI 10.1002/ajmg.a.10031 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 670HH UT WOS:000182401100018 PM 12599199 ER PT J AU Walter, RE Beiser, A Givelber, RJ O'Connor, GT Gottlieb, DJ AF Walter, RE Beiser, A Givelber, RJ O'Connor, GT Gottlieb, DJ TI Association between glycemic state and lung function - The Framingham Heart Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE lung diseases; obstructive; diabetes mellitus; blood glucose; epidemiology; lung diseases ID OBSTRUCTIVE PULMONARY-DISEASE; DEPENDENT DIABETES-MELLITUS; NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; CIGARETTE-SMOKING; INFLAMMATORY MARKERS; ATHEROSCLEROSIS RISK; INSULIN-RESISTANCE; OLDER ADULTS; DECLINE AB Diabetes mellitus has been inconsistently associated with a reduced level of pulmonary function. To elucidate this association further, we analyzed the relationship of diabetes and of fasting blood glucose to the level of pulmonary function assessed by spirometry in the 3,254 members of the Framingham Offspring Cohort. Diabetes was defined as a fasting blood glucose of 126 mg/dl or more or pharmacologic treatment. Subjects were classified as current, former, or never smokers based on questionnaire responses. Predicted pulmonary function was determined from the coefficients of a regression of pulmonary function on age, sex, and body habitus in the 1,110 never smokers. Both the diagnosis of diabetes and a higher level of fasting blood glucose were associated with lower than predicted levels of pulmonary function. The adverse effect of diabetes and glycemic level on pulmonary function was stronger among ever smokers than never smokers, suggesting an interaction between the level of fasting glycemia and tobacco smoking. C1 Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Vet Adm Boston Hlth Care Syst, Boston, MA USA. RP Walter, RE (reprint author), Boston Univ, Sch Med, Ctr Pulm, R304,715 Albany St, Boston, MA 02118 USA. OI O'Connor, George/0000-0002-6476-3926 FU NHLBI NIH HHS [1 R03 HL 70289-01, 1R01 HL 49869-01, T32 HL 07035] NR 60 TC 110 Z9 118 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 15 PY 2003 VL 167 IS 6 BP 911 EP 916 DI 10.1164/rccm.2003022 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 653MA UT WOS:000181439100018 PM 12623860 ER PT J AU Eichacker, PQ Banks, SM Natanson, C AF Eichacker, PQ Banks, SM Natanson, C TI Tidal volumes in ARDS and meta-analysis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; SYNDROME TRIALS; METAANALYSIS C1 NIH, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 2 Z9 2 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 15 PY 2003 VL 167 IS 6 BP 933 EP 934 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 653MA UT WOS:000181439100023 ER PT J AU Eichacker, PQ Banks, SM Natanson, C AF Eichacker, PQ Banks, SM Natanson, C TI Tidal volumes in ARDS and meta-analysis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID RESPIRATORY-DISTRESS SYNDROME; VENTILATION STRATEGY; LUNG INJURY C1 NIH, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 15 PY 2003 VL 167 IS 6 BP 934 EP 935 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 653MA UT WOS:000181439100025 ER PT J AU Banks, SM Natanson, C Eichacker, PQ AF Banks, SM Natanson, C Eichacker, PQ TI Tidal volumes in ARDS and meta-analysis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Banks, SM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 15 PY 2003 VL 167 IS 6 BP 935 EP 936 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 653MA UT WOS:000181439100027 ER PT J AU Oleksiak, MF Wu, S Parker, C Qu, W Cox, R Zeldin, DC Stegeman, JJ AF Oleksiak, MF Wu, S Parker, C Qu, W Cox, R Zeldin, DC Stegeman, JJ TI Identification and regulation of a new vertebrate cytochrome P450 subfamily, the CYP2Ps, and functional characterization of CYP2P3, a conserved arachidonic acid epoxygenase/19-hydroxylase SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID MOLECULAR-CLONING; EPOXYEICOSATRIENOIC ACIDS; STENOTOMUS-CHRYSOPS; SMALL-INTESTINE; MARINE FISH; AMINO-ACID; EXPRESSION; METABOLITES; CELLS; OXYGENATION AB Three genes cloned from Fundulus heteroclitus (killifish) define a new P450 subfamily, CYP2P. Structurally, the CYP2Ps are related to fish CYP2Ns and mammalian CYP2Js. CYP2P transcripts are expressed predominantly in liver and intestine. CYP2P3 coexpressed with P450 oxidoreductase in a baculovirus system catalyzed benzphetamine-N-demethylation and arachidonic acid oxidation, forming 14,15-, 11,12-, and 8,9-epoxyeicosatrienoic acids and 19-hydroxyeicosatetraenoic acid. CYP2P3 regio- and enantioselectivities with arachidonic acid were remarkably similar to human CYP2J2 and rat CYP2J3. Epoxyeicosatrienoic acids and their corresponding hydration products, the dihydroxyeicosatrienoic acids, were detected in killifish liver and intestine, indicating metabolism of arachidonic acid by killifish P450s in vivo. Levels of these products in killifish intestine were higher than those in mammalian intestine. 12-O-Tetradecanoyl phorbol 13-acetate suppressed expression of CYP2P2 and CYP2P3 in killifish intestine; fasting itself suppressed expression of CYP2P2/3 but not CYP2P1. In rat intestine fasting similarly depressed the levels of CYP2J proteins. The CYP2Ps and the CYP2Js appear to be derived from a common ancestral gene, likely a fatty acid monooxygenase. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. RP Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. EM jstegeman@whoi.edu FU NIEHS NIH HHS [P42-ES07381] NR 57 TC 22 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 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR 15 PY 2003 VL 411 IS 2 BP 223 EP 234 DI 10.1016/S0003-9861(02)00734-8 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 658BN UT WOS:000181701900008 PM 12623071 ER PT J AU Jung, YJ Isaacs, JS Lee, SM Trepel, J Liu, ZG Neckers, L AF Jung, YJ Isaacs, JS Lee, SM Trepel, J Liu, ZG Neckers, L TI Hypoxia-inducible factor induction by tumour necrosis factor in normoxic cells requires receptor-interacting protein-dependent nuclear factor kappa B activation SO BIOCHEMICAL JOURNAL LA English DT Article DE hypoxia-inducible factor 1 alpha; nuclear factor kappa beta; receptor-interacting protein; tumour necrosis factor ID ENDOTHELIAL GROWTH-FACTOR; PROSTATE-CANCER CELLS; DEATH DOMAIN KINASE; FACTOR 1-ALPHA; TRANSCRIPTION FACTOR; GENE-EXPRESSION; TARGET GENES; NITRIC-OXIDE; FACTOR-ALPHA; DNA-BINDING AB Tumour necrosis factor alpha (TNF-alpha) binds to its receptor (TNFR1) and activates both death- and inflammation/survival-related signalling pathways. The inflammation and survival-related signalling cascade results in the activation of the transcription factor, nuclear factor kappaB (NF-kappaB) and requires recruitment of receptor-interacting protein (RIP) to TNFR I. The indispensable role of RIP in TNF-induced NF-kappaB activation has been demonstrated in RIP-/- mice and in cell lines derived from such mice. In the present study, we show that the TNF-alpha-induced accumulation of hypoxia-inducible factor 1alpha (HIF-1alpha) protein in normoxic cells is RIP-dependent. Exposing fibroblasts derived from RIP-/- mice to either cobalt or PMA resulted in an equivalent HIF-1alpha induction to that seen in RIP+/+ fibroblasts. In contrast, RIP-/- cells were unable to induce HIF-1alpha in response to TNF-alpha. Further, transient transfection of NIH 3T3 cells with an NF-kappaB super-repressor plasmid (an inhibitor of NF-kappaB activation) also prevented HIF-1alpha induction by TNF-alpha. Surprisingly, although HIF-1alpha mRNA levels remained unchanged after induction by TNF, induction of HIF-1alpha protein by the cytokine was completely blocked by pretreatment with the transcription inhibitors actinomycin D and 5,6-dichlorobenzimidazole riboside. Finally, TNF failed to induce both HIF1alpha, made resistant to von Hippel-Lindau (VHL), and wild-type HIF-1alpha transfected into VHL-/- cells. These results indicate that HIF-1alpha induction by TNF-alpha in normoxic cells is mediated by protein stabilization but is nonetheless uniquely dependent on NF-kappaB-driven transcription. Thus the results describe a novel mechanism of HIF-1alpha up-regulation and they identify HIF-1alpha as a unique component of the NF-kappaB-mediated inflammatory/ survival response. C1 NCI, Cell & Canc Biol Branch, CCR, Rockville, MD 20850 USA. NCI, Med Oncol Clin Res Unit, CCR, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Cell & Canc Biol Branch, CCR, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 60 TC 112 Z9 120 U1 0 U2 5 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 15 PY 2003 VL 370 BP 1011 EP 1017 DI 10.1042/BJ20021279 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 660GE UT WOS:000181824800030 PM 12479793 ER PT J AU Makrigiannakis, A Zoumakis, E Kalantaridou, S Mitsiades, N Margioris, A Chrousos, GP Gravanis, A AF Makrigiannakis, A Zoumakis, E Kalantaridou, S Mitsiades, N Margioris, A Chrousos, GP Gravanis, A TI Corticotropin-releasing hormone (CRH) and immunotolerance of the fetus SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE endometrium; CRH; implantation; FasL; decidualization; apoptosis ID ENDOMETRIAL STROMAL CELLS; EMBRYO IMPLANTATION; FAS LIGAND; EXPRESSION; RECEPTOR; DECIDUALIZATION; ANTIGEN; TISSUES; UTERUS; FETAL AB The hypothalamic neuropeptide corticotropin-releasing hormone (CRH) is produced by several tissues of the female reproductive system, including the endometrial glands and decidualized stroma, as well as the trophoblast, syncytiotrophoblast, and placental decidua. CRH is also secreted at inflammatory sites and possesses potent pro-inflammatory properties influencing both innate and acquired immune processes. Recent experimental findings show that uterine CRH participates in local immune phenomena associated with early pregnancy, such as differentiation of endometrial stroma to decidua and protection of the fetus from the maternal immune system. CRH induces the expression of apoptotic Fas ligand (FasL) on invasive extravillous trophoblast and maternal decidual cells at the fetal-maternal interface. Furthermore, CRH increases the apoptosis of activated T lymphocytes through FasL induction, participating in the processes of both implantation and early pregnancy tolerance. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Crete, Sch Med, Pharmacol Lab, Iraklion 71110, Greece. NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Makrigiannakis, A (reprint author), Univ Crete, Sch Med, Pharmacol Lab, Iraklion 71110, Greece. EM makrigia@med.uoc.gr NR 22 TC 19 Z9 21 U1 1 U2 2 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 MAR 15 PY 2003 VL 65 IS 6 BP 917 EP 921 AR PII S0006-2952(02)01547-2 DI 10.1016/S0006-2952(02)01547-2 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 659BX UT WOS:000181758300001 PM 12623122 ER PT J AU Kim, SG Soltysiak, KA Gao, ZG Chang, TS Chung, EJ Jacobson, KA AF Kim, SG Soltysiak, KA Gao, ZG Chang, TS Chung, EJ Jacobson, KA TI Tumor necrosis factor alpha-induced apoptosis in astrocytes is prevented by the activation of P2Y(6), but not P2Y(4) nucleotide receptors SO BIOCHEMICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Society-for-Neuroscience CY NOV 10-15, 2001 CL SAN DIEGO, CALIFORNIA SP Soc Neurosci DE apoptosis; pyrimidines; G protein-coupled receptor; phospholipase C; cell death; cytokines; TNF alpha; caspase; nucleotide receptor ID PROTEIN-KINASE-C; NF-KAPPA-B; ADENOSINE A(2) RECEPTORS; PURINERGIC RECEPTOR; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; EXPRESSION; ISCHEMIA; DEATH; ATP AB The physiological role of the uracil nucleotide-preferring P2Y(6) and P2Y(4) receptors is still unclear, although they are widely distributed in various tissues. In an effort to identify their biological functions, we found that activation by UDP of the rat P2Y(6) receptor expressed in 1321N1 human astrocytes significantly reduced cell death induced by tumor necrosis factor alpha (TNFalpha). This effect of UDP was not observed in non-transfected 1321N1 cells. Activation of the human P2Y(4) receptor expressed in 1321N1 cells by UTP did not elicit this protective effect, although both receptors were coupled to phospholipase C. The activation of P2Y(6) receptors prevented the activation of both caspase-3 and caspase-8 resulting from TNFalpha exposure. Even a brief (10-min) incubation with UDP protected the cells against TNFalpha-induced apoptosis. Interestingly, UDP did not protect the P2y(6)-1321N1 cells from death induced by other methods, i.e. oxidative stress induced by hydrogen peroxide and chemical ischemia. Therefore, it is suggested that P2Y(6) receptors interact rapidly with the TNFalpha-related intracellular signals to prevent apoptotic cell death. This is the first study to describe the cellular protective role of P2Y(6) nucleotide receptor activation. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Res Unit, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20] NR 51 TC 41 Z9 42 U1 0 U2 1 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 MAR 15 PY 2003 VL 65 IS 6 BP 923 EP 931 DI 10.1016/S0006-2952(02)01614-3 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 659BX UT WOS:000181758300002 PM 12623123 ER PT J AU Hariri, AR Mattay, VS Tessitore, A Fera, F Weinberger, DR AF Hariri, AR Mattay, VS Tessitore, A Fera, F Weinberger, DR TI Neocortical modulation of the amygdala response to fearful stimuli SO BIOLOGICAL PSYCHIATRY LA English DT Article DE emotion regulation; fear; prefrontal cortex; anterior cingulate cortex; amygdala; functional magnetic resonance imaging ID VENTROMEDIAL PREFRONTAL CORTEX; EMOTIONAL FACIAL EXPRESSIONS; ANTERIOR CINGULATE CORTEX; LONG-TERM DEPRESSION; BASOLATERAL AMYGDALA; ORBITOFRONTAL CORTEX; FUNCTIONAL MRI; IN-VIVO; MEMORY; CONNECTIONS AB Background: The cortical circuitry involved in conscious cognitive processes and the subcortical circuitry involved in fear responses have been extensively studied with neuroimaging, but their interactions remain largely unexplored. A recent functional magnetic resonance imaging (fMRI) study demonstrated that the engagement of the right prefrontal cortex during the cognitive evaluation of angry and fearful facial expressions is associated with an attenuation of the response of the amygdala to these same stimuli, providing evidence for a functional neural network for emotional regulation. Methods: In the current study, we have explored the generalizability of this functional network by using threatening and fearful non-face stimuli derived from the International Affective Picture System (IAPS), as well as the influence of this network on peripheral autonomic responses. Results: Similar to the earlier findings with facial expressions, blood oxygen level dependent fMRI revealed that whereas perceptual processing of IAPS stimuli was associated with a bilateral amygdala response, cognitive evaluation of these same stimuli was associated with attenuation of this amygdala response and a correlated increase in response of the right prefrontal cortex and the anterior cingulate cortex. Moreover, this pattern was reflected in changes in skin conductance. Conclusions: The current results further implicate the importance of neocortical regions, including the prefrontal and anterior cingulate cortices, in regulating emotional responses mediated by the amygdala through conscious evaluation and appraisal. (C) 2003 Society of Biological Psychiatry. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hariri, AR (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,Rm 3C108, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011 NR 38 TC 463 Z9 477 U1 4 U2 47 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 MAR 15 PY 2003 VL 53 IS 6 BP 494 EP 501 DI 10.1016/S0002-3223(03)01786-9 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 655TZ UT WOS:000181569900004 PM 12644354 ER PT J AU Kohen, R Neumaier, JF Hamblin, MW Edwards, E AF Kohen, R Neumaier, JF Hamblin, MW Edwards, E TI Congenitally learned helpless rats show abnormalities in intracellular signaling SO BIOLOGICAL PSYCHIATRY LA English DT Article DE depression; mood disorders; learned helplessness; animal models; gene expression; second messengers ID PROTEIN-KINASE-C; BIPOLAR AFFECTIVE-DISORDER; ELEMENT-BINDING PROTEIN; AMP-RESPONSIVE ELEMENT; CHRONIC ANTIDEPRESSANT TREATMENT; GLYCOGEN-SYNTHASE KINASE-3-BETA; RECURRENT MAJOR DEPRESSION; GENE-TRANSCRIPTION FACTOR; NEUROTROPHIC-FACTOR BDNF; MOOD-STABILIZING AGENTS AB Background: Affective disorders and the drugs used to treat them lead to changes in intracellular signaling. We used a genetic animal model to investigate to what extent changes in intracellular signal transduction confer a vulnerability to mood or anxiety disorders. Methods: Levels of gene expression in a selectively bred strain of rats with a high vulnerability to develop congenitally learned helplessness (cLH), a strain highly resistant to the same behavior (cNLH) and outbred Sprague-Dawley (SD) control animals were compared using quantitative reverse transcription polymerase chain reaction. Results: Congenitally learned helpless animals had a 24%-30% reduced expression of the cyclic adenosine monophosphate response element binding protein messenger ribonucleic acid (mRNA) in the hippocampus and a 40%-41% increased level of the antiapoptotic protein bcl-2 mRNA in the prefrontal cortex compared to cNLH and SD rats. Other significant changes included changes in the expression levels of the alpha catalytic subunit of protein kinase A, glycogen synthase kinase 3beta, and protein kinase C epsilon. Conclusions: Congenitally learned helpless animals show evidence of altered signal transduction and regulation of apoptosis compared to cNLH and SD control animals. (C) 2003 Society of Biological Psychiatry. C1 GRECC 182B, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Washington, DC USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NINDS, Bethesda, MD 20892 USA. RP Kohen, R (reprint author), GRECC 182B, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIMH NIH HHS [MH57049, MH63303] NR 77 TC 18 Z9 18 U1 3 U2 5 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 MAR 15 PY 2003 VL 53 IS 6 BP 520 EP 529 DI 10.1016/S0006-3223(03)01503-2 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 655TZ UT WOS:000181569900007 PM 12644357 ER PT J AU Hematti, P Sellers, SE Agricola, BA Metzger, ME Donahue, RE Dunbar, CE AF Hematti, P Sellers, SE Agricola, BA Metzger, ME Donahue, RE Dunbar, CE TI Retroviral transduction efficiency of G-CSF plus SCF-mobilized peripheral blood CD34(+) cells is superior to G-CSF or G-CSF+Flt3-L-mobilized cells in nonhuman primates SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC PROGENITOR CELLS; SEVERE COMBINED IMMUNODEFICIENCY; ADENOSINE-DEAMINASE DEFICIENCY; BREAST-CANCER PATIENTS; BONE-MARROW CELLS; EX-VIVO EXPANSION; STEM-CELL; GENE-TRANSFER; IN-VIVO AB Gene transfer experiments in nonhuman primates have been shown to be predictive of success in human clinical gene therapy trials. In most nonhuman primate studies, hematopoietic stem cells (HSCs) collected from the peripheral blood or bone marrow after administration of granulocyte colony-stimulating factor (G-PSF) + stem cell factor (SCF) have been used as targets, but this cytokine combination is not generally available for clinical use, and the optimum target cell population has not been systematically studied. In our current study We tested the retroviral transduction efficiency of rhesus macaque peripheral blood CD34(+) cells collected after administration of different cytokine mobilization regimens, directly comparing G-CSF+SCF versus G-CSF alone or G-CSF+Flt3-L in competitive repopulation assays. Vector supernatant was added daily for 96. hours in the presence of stimulatory cytokines. The transduction efficiency of HSCs as assessed by in vitro colony-forming assays was equivalent in all 5 animals tested, but the in vivo levels of mononuclear cell and granulocyte marking was higher at all time points derived from, target CD34(+) cells collected after G-CSF+SCF mobilization compared with target cells collected after G-CSF (n = 3) or G-CSF+Flt3-L (n = 2) mobilization. In 3 of the animals long-term marking levels of 5% to 25% were achieved, but originating only from the G-CSF+SCF-mobilized target cells. Transduction efficiency of HSCs collected by different mobilization regimens can vary significantly and is superior With G-CSF+SCF administration. The difference in transduction efficiency of HSCs collected from different sources should be considered whenever planning clinical gene therapy trials and should preferably be tested directly in comparative studies. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 54 TC 36 Z9 37 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 MAR 15 PY 2003 VL 101 IS 6 BP 2199 EP 2205 DI 10.1182/blood-2002-08-2663 PG 7 WC Hematology SC Hematology GA 653JT UT WOS:000181432600020 PM 12424191 ER PT J AU Fry, TJ Moniuszko, M Creekmore, S Donohue, SJ Douek, DC Giardina, S Hecht, TT Hill, BJ Komschlies, K Tomaszewski, J Franchini, G Mackall, CL AF Fry, TJ Moniuszko, M Creekmore, S Donohue, SJ Douek, DC Giardina, S Hecht, TT Hill, BJ Komschlies, K Tomaszewski, J Franchini, G Mackall, CL TI IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected nonhuman primates SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; IN-VIVO; INTERLEUKIN-7; NAIVE; PROLIFERATION; MEMORY; IMMUNODEFICIENCY; SURVIVAL; MICE; RECONSTITUTION AB Interleukin-7 (IL-7) is important for thymopoiesis in mice and humans because IL-7 receptor alpha (IL-7Ralpha) mutations result in a severe combined immunodeficiency phenotype with severe thymic hypoplasia. Recent evidence has indicated that IL-7 also plays an important role as a regulator of T-cell homeostasis. Here we report the immunologic effects of recombinant human IL-7 (rhIL-7) therapy in normal and simian immunodeficiency virus (SIV)infected nonhuman primates. Cynomolgus monkeys receiving 10 days of rhIL-7 showed substantial, reversible increases in T-cell numbers involving a dramatic expansion of both naive and normative phenotype CD4(+) and CD8(+) subsets. Although IL-7 is known to have thymopoietic effects in mice, we observed marked declines in the frequency and absolute number of T-cell receptor excision circle-positive (TREC+) cells in the peripheral blood and dramatic increases in the percentage of cycling T cells in the peripheral blood as measured by Ki-67 expression (baseline less than 5% to approximately 50% after 6 days of therapy) and ex vivo bromodeoxyuridine (BrdU) incorporation. Similarly, moderately CD4-depleted SIV-infected macaques treated with rhIL-7 also had significant increases in peripheral blood CD4(+) and CD8(+) T cells following rhIL-7 therapy. Thus, rhIL-7 induces dramatic alterations in peripheral T-cell homeostasis in both T-cell-replete and T-cell-depleted nonhuman primates. These results further implicate IL-7 as a promising immunorestorative agent but illustrate that a major component of its immunorestorative capacity reflects effects on mature cells. These results also raise the possibility that IL-7 therapy could be used to temporarily modulate T-cell cycling in vivo in the context of immunotherapies such as vaccination. C1 NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Anim Model & Retrovirus Vaccine Sect, Basic Res Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, Div Canc Therapy & Diag, Bethesda, MD 20892 USA. NCI, Toxicol & Pharmacol Branch, Div Canc Therapy & Diagnost, Bethesda, MD 20892 USA. NIAID, Vaccine Res Program, NIH, Bethesda, MD 20892 USA. SAIC, Biopharmaceut Dev Program, Frederick, MD USA. RP Fry, TJ (reprint author), Bldg 10,Rm 13N240,MSC 1928,10 Ctr Dr, Bethesda, MD 20892 USA. NR 39 TC 173 Z9 177 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2003 VL 101 IS 6 BP 2294 EP 2299 DI 10.1182/blood-2002-07-2297 PG 6 WC Hematology SC Hematology GA 653JT UT WOS:000181432600034 PM 12411295 ER PT J AU Chu, KC Tarone, RE Freeman, HP AF Chu, KC Tarone, RE Freeman, HP TI Trends in prostate cancer mortality among black men and white men in the United States SO CANCER LA English DT Article DE prostate cancer; incidence; survival; mortality; prostate specific antigen ID DEFINITIVE RADIOTHERAPY; INTERNATIONAL TRENDS; SURVEILLANCE SERIES; INTERPRETING TRENDS; HORMONAL-THERAPY; SURVIVAL RATES; BREAST-CANCER; BIRTH COHORT; NEW-MEXICO; CARCINOMA AB BACKGROUND. Prostate cancer mortality rates in the United States declined sharply after 1991 in white men and declined after 1992 in black men. The current study was conducted to investigate possible mechanisms for the declining prostate cancer mortality rates in the United States. METHODS. The authors examined and compared patterns of prostate cancer incidence, survival rates, and mortality rates among black men and white men in the United States using the 1969-1999 U.S. prostate cancer mortality rates and the 1975-1999 prostate cancer incidence, survival, and incidence-based mortality rates from the Surveillance, Epidemiology, and End Results (SEER) Program for the U.S. population. The SEER data represent approximately 10% of the U.S. population. RESULTS. Prostate cancer incidence and mortality rates showed transient increases after 1986, when the U.S. Food and Drug Administration approved the use of prostate specific antigen (PSA) testing. The age-adjusted prostate cancer mortality rates for men age 50-84 years, however, have dropped below the rate in 1986 since 1995 for white men and since 1997 for black men. In fact, for white men ages 50-79 years, the 1998 and 1999 rates were the lowest observed since 1950. Incidence-based mortality rates by disease stage revealed that the recent declines were due to declines in distant disease mortality. Moreover, the decrease in distant disease mortality was due to a decline in distant disease incidence, and not to improved survival of patients with distant disease. CONCLUSIONS. Similar incidence, survival, and mortality rate patterns are seen in black men and white men in the United States, although with differences in the timing and magnitude of recent rate decreases. Increased detection of prostate cancer before it becomes metastatic, possibly reflecting increased use of PSA testing after 1986, may explain much of the recent mortality decrease in both white men and black men. C1 NCI, Ctr Reduce Canc Hlth Dispart, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Etiol & Genet, Bethesda, MD 20892 USA. RP Chu, KC (reprint author), NCI, Ctr Reduce Canc Hlth Dispart, Bldg 6116 Execut Blvd,Room 6029,9000 Rockville Pi, Bethesda, MD 20892 USA. NR 40 TC 111 Z9 117 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2003 VL 97 IS 6 BP 1507 EP 1516 DI 10.1002/cncr.11212 PG 10 WC Oncology SC Oncology GA 652CL UT WOS:000181361900018 PM 12627516 ER PT J AU Swan, J Breen, N Coates, RJ Rimer, BK Lee, NC AF Swan, J Breen, N Coates, RJ Rimer, BK Lee, NC TI Progress in cancer screening practices in the United States - Results from the 2000 National Health Interview Survey SO CANCER LA English DT Article DE cancer screening; mammography; Pap; prostate specific antigen; colorectal screening; National Health Interview Survey ID PREVENTIVE SERVICES; COLORECTAL-CANCER; PROSTATE-CANCER; WOMEN; MAMMOGRAPHY; BREAST; CARE; PREDICTORS; GUIDELINES; RATIONALE AB BACKGROUND. Understanding differences in cancer screening among population groups in 2000 and successes or failures in reducing disparities over time among groups is important for planning a public health strategy to reduce or eliminate health disparities, a major goal of Healthy People 2010 national cancer screening objectives. In 2000, the new cancer control module added to the National Health Interview Survey (NHIS) collected more detailed information on cancer screening compared with previous surveys. METHODS. Data from the 2000 NHIS and earlier surveys were analyzed to discern patterns and trends in cancer screening practices, including Pap tests, mammography, prostate specific antigen (PSA) screening, and colorectal screening. The data are reported for population subgroups that were defined by a number of demographic and socioeconomic characteristics. RESULTS. Women who were least likely to have had a mammogram within the last 2 years were those with no usual source of health care (61%), women with no health insurance (67%), and women who immigrated to the United States within the last 10 years (61%). Results for Pap tests within the last 3 years were similar. Among both men and women, those least likely to have had a fecal occult blood test or endoscopy within the recommended screening interval had no usual source of care (14% for men and 18% for women), no health insurance (20% for men and 18% for women), or were recent immigrants (20% for men and 18% for women). An analysis of changes in test use since the 1987 survey indicates that the disparities are widening among groups with no usual source of care. CONCLUSIONS. No striking improvements have been observed for the groups with greatest need. Although screening use for most groups has increased since 1987, major disparities remain. Some groups, notably individuals with no usual source of care and the uninsured are falling further behind; and, according to the 2000 data, recent immigrants also experience a significant gap in screening utilization. More attention is needed to overcome screening barriers for these groups if the population benefits of cancer screening are to be achieved. C1 NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. RP Swan, J (reprint author), NCI, Div Canc Control & Populat Sci, NIH, 6116 Execut Blvd,Room 5033, Bethesda, MD 20892 USA. NR 37 TC 547 Z9 555 U1 2 U2 26 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2003 VL 97 IS 6 BP 1528 EP 1540 DI 10.1002/cncr.11208 PG 13 WC Oncology SC Oncology GA 652CL UT WOS:000181361900020 PM 12627518 ER PT J AU Bianco, C Strizzi, L Rehman, A Normanno, N Wechselberger, C Sun, YP Khan, N Hirota, M Adkins, H Williams, K Margolis, RU Sanicola, M Salomon, DS AF Bianco, C Strizzi, L Rehman, A Normanno, N Wechselberger, C Sun, YP Khan, N Hirota, M Adkins, H Williams, K Margolis, RU Sanicola, M Salomon, DS TI A nodal- and ALK4-independent signaling pathway activated by Cripto-1 through Glypican-1 and c-Src SO CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; PROTEIN; FAMILY; CANCER AB Human Cripto-1 (CR-1) is a member of the epidermal growth factor-Cripto FRL1 Cryptic family that has been shown to function as a core-ceptor with the type I Activin serine-threonine kinase receptor ALK4 for the transforming growth factor beta-related peptide Nodal. However, CR-1 can also activate the mitogen-activated protein kinase and Akt pathways independently of Nodal and ALK4 by an unknown mechanism. Here, we demonstrate that CR-1 specifically binds to Glypican-1, a membrane-associated heparan sulfate proteoglycan, and activates the tyrosine kinase c-Src, triggering the mitogen-activated protein kinase and Akt signaling pathways. Finally, an active Src kinase is necessary for CR-1 to induce in vitro transformation and migration in mouse mammary epithelial cells. C1 NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. Ist Fdn Pascale, Expt Oncol B Unit, I-80131 Naples, Italy. Upper Austrian Res GmbH Zentrum, A-4020 Linz, Austria. Biogen Inc, Cambridge, MA 02142 USA. NYU, Med Ctr, Dept Pharmacol, New York, NY 10016 USA. RP Salomon, DS (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, 10 Ctr Dr Bldg 10 5B39, Bethesda, MD 20892 USA. EM davetgfa@helix.nih.gov OI Normanno, Nicola/0000-0002-7158-2605 NR 21 TC 75 Z9 76 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2003 VL 63 IS 6 BP 1192 EP 1197 PG 6 WC Oncology SC Oncology GA 658BT UT WOS:000181702300009 PM 12649175 ER PT J AU Farley, J Smith, LM Darcy, KM Sobel, E O'Connor, D Henderson, B Morrison, LE Birrer, MJ AF Farley, J Smith, LM Darcy, KM Sobel, E O'Connor, D Henderson, B Morrison, LE Birrer, MJ TI Cyclin E expression is a significant predictor of survival in advanced, suboptimally debulked ovarian epithelial cancers: A Gynecologic Oncology Group study SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER; GENE AMPLIFICATION; P27(KIP1); OVEREXPRESSION; D1; ASSOCIATION; REGULATORS; CARCINOMA; INHIBITOR; TUMORS AB Cyclin E is a key regulator of the G(1)-S transition. Abnormalities in cyclin E expression have been related to survival in a variety of cancers. This study evaluated the prognostic relevance of cyclin E in human ovarian cancer. Immunohistochemical expression of cyclin E was evaluated in 139 advanced, suboptimally debulked epithelial ovarian cancer specimens from patients treated on Gynecologic Oncology Group protocol 111. High cyclin E protein expression (greater than or equal to 40% cyclin E positive tumor cells) was seen in 62 (45%) of the advanced, suboptimally debulked ovarian cancer patients. Expression of cyclin E was not associated with age, race, stage, grade, cell type, or amount of residual disease. High verses low cyclin E expression was associated with a shorter median survival (29 2 versus 35 +/- 3 months) and worse overall survival (P < 0.05). Univariate and multivariate regression analyses revealed that high relative to low cyclin E was associated with a 40-50% increase in the risk of death (hazard rate, P less than or equal to 0.05). Fluorescence in situ hybridization was used in a subset of 20 cases to examine cyclin E gene amplification. Eight of 10 cases with high cyclin E expression exhibited amplification of the cyclin E gene, whereas only 1 of 10 cases with low expression displayed gene amplification (P < 0.006). High cyclin E expression was an independent poor prognostic factor for patients with advanced ovarian cancer, and it was associated with amplification of the cyclin E gene. C1 NCI, Ctr Canc Res, Cell & Canc Biol Dept, Med Branch,Div Clin Sci, Rockville, MD 20850 USA. Tripler Army Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Honolulu, HI 96859 USA. Colorado State Univ, Dept Radiol Hlth Sci, Ft Collins, CO 80523 USA. Roswell Pk Canc Inst, Gynecol Oncol Grp Stat & Data Ctr, Buffalo, NY 14263 USA. Norton Healthcare Inc, Clin Pathol Associates, Louisville, KY 40207 USA. Vysis Inc, Downers Grove, IL 60515 USA. RP Birrer, MJ (reprint author), NCI, Ctr Canc Res, Cell & Canc Biol Dept, Med Branch,Div Clin Sci, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM birrerm@bprb.nci.nih.gov FU NCI NIH HHS [CA 27469, CA 37517] NR 30 TC 87 Z9 93 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2003 VL 63 IS 6 BP 1235 EP 1241 PG 7 WC Oncology SC Oncology GA 658BT UT WOS:000181702300016 PM 12649182 ER PT J AU Suh, N Roberts, AB Reffey, SB Miyazono, K Itoh, S ten Dijke, P Heiss, EH Place, AE Risingsong, R Williams, CR Honda, T Gribble, GW Sporn, MB AF Suh, N Roberts, AB Reffey, SB Miyazono, K Itoh, S ten Dijke, P Heiss, EH Place, AE Risingsong, R Williams, CR Honda, T Gribble, GW Sporn, MB TI Synthetic triterpenoids enhance transforming growth factor beta/Smad signaling SO CANCER RESEARCH LA English DT Article ID NITRIC-OXIDE PRODUCTION; TGF-BETA RECEPTOR; 2-CYANO-3,12-DIOXOOLEANA-1,9-DIEN-28-OIC ACID CDDO; ACTIVATOR INHIBITOR-1 PROMOTER; INFLAMMATORY-BOWEL-DISEASE; SMAD PROTEINS; TRANSCRIPTIONAL ACTIVATION; MOUSE MACROPHAGES; CARCINOMA-CELLS; LEUKEMIA-CELLS AB We have studied the effects of two new synthetic triterpenoids, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its derivative, 1-(2-cyano-3,12-dioxooleana-1,9-dien-28-oyl) imidazole (CDDO-Im), on transforming growth factor (TGF)-beta/Smad signaling. These agents, at nanomolar concentrations, increase the expression of TGF-beta-dependent genes, such as those for plasminogen activator inhibitor 1 and the type II TGF-beta receptor, and they synergize with TGF-beta in this regard. They prolong the activation of Smad2 induced by TGF-beta and markedly enhance the ability of Smad3 to activate a Smad binding element, CAGA-luciferase. In transfection assays, they reverse the inhibitory effects of Smad7. CDDO and CDDO-Im also enhance Smad signaling in the pathways of two other members of the TGF-beta superfamily, namely, activin and bone morphogenetic protein. Finally, these triterpenoids induce expression of the transcriptional coactivator p300-CBP-associated factor and synergize with TGF-beta in this regard. These are the first studies to report enhancement of Smad signaling by synthetic triterpenoids and should further their optimal use for applications in prevention or treatment of diseases in which there is aberrant function of TGF-beta. C1 Dartmouth Coll Sch Med, Dept Pharmacol, Hanover, NH 03755 USA. Dartmouth Coll, Hanover, NH 03755 USA. NCI, NIH, Bethesda, MD 20892 USA. Inst Canc Res, Tokyo 1708455, Japan. Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. RP Sporn, MB (reprint author), Dartmouth Coll Sch Med, Dept Pharmacol, Hanover, NH 03755 USA. EM michael.sporn@dartmouth.edu RI Heiss, Elke/B-6086-2015 OI Heiss, Elke/0000-0001-7618-5505 FU NCI NIH HHS [R01 CA78814] NR 66 TC 65 Z9 68 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2003 VL 63 IS 6 BP 1371 EP 1376 PG 6 WC Oncology SC Oncology GA 658BT UT WOS:000181702300035 PM 12649201 ER PT J AU Bray, M Wright, ME AF Bray, M Wright, ME TI Progressive vaccinia SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID SMALLPOX VACCINATION; INTERFERON-GAMMA; VIRUS; CIDOFOVIR; INFECTIONS; RESPONSES; DISEASE; MICE; HOST AB The resumption of smallpox vaccination for health care workers and other first responders has raised concern about the occurrence of complications in people with immunodeficiency disorders, including those infected with human immunodeficiency virus. During the era of universal vaccination, roughly 1 person per million vaccinees in the general population developed progressive vaccinia, which is characterized by the relentless outward spread of infection from the vaccination site and eventual dissemination to other areas on the body. Review of 56 cases reported in the English-language medical literature from 1893 through 1997 indicates that the condition occurred only in persons with severe cell-mediated immunodeficiency. Progressive vaccinia was found to be lethal in infants who completely lacked cellular immune function, but infection resolved in many adults with acquired immunodeficiency. Almost all cases were treated with vaccinia immune globulin, but its efficacy has never been tested in a placebo-controlled trial. Further research is needed to develop effective forms of therapy. C1 NIAID, Biodef Clin Res Branch, OCR, OD,NIH, Bethesda, MD 20892 USA. RP Bray, M (reprint author), NIAID, Biodef Clin Res Branch, OCR, OD,NIH, 6700A Rockledge Dr,Rm 5132, Bethesda, MD 20892 USA. NR 91 TC 60 Z9 63 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 MAR 15 PY 2003 VL 36 IS 6 BP 766 EP 774 DI 10.1086/374244 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 653RQ UT WOS:000181451200012 PM 12627361 ER PT J AU Miyoshi, N Sostaric, JZ Riesz, P AF Miyoshi, N Sostaric, JZ Riesz, P TI Correlation between sonochemistry of surfactant solutions and human leukemia cell killing by ultrasound and porphyrins SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE sonodynamic therapy; sonochemistry; ultrasound; surfactants; hydrophobicity; HL-60; HL-525; free radicals; cytolysis; porphyrin ID AQUEOUS-SOLUTIONS; IN-VITRO; ANALOG ATX-70; CAVITATION; ALCOHOL; DAMAGE; LYSIS; N,N-DIMETHYLFORMAMIDE; SONOLUMINESCENCE; ENHANCEMENT AB The synergistic effect of ultrasound and drugs on cells is known as sonodynamic therapy. The use of sonodynamic therapy for the potential clinical treatment of certain tumors is promising, however, the mechanism of sonodynamic therapy could be due to either sonomechanical and/or sonochemical effects on the cells. The aim of the current study is to determine the importance of the sonochemical mechanism for sonodynamic therapy. Sonochemical effects arise from the formation of radical species following collapse of cavitation bubbles. The synergistic effect of ultrasound (47 kHz) and analogues of a gallium-porphyrin derivative (ATX-70) on cytolysis of Human leukemia cells (HL-525 and HL-60) suspended in a cell culture medium were studied. Organic surfactants preferentially accumulate and subsequently decompose at the gas/solution interface of cavitation bubbles, producing secondary radicals that can diffuse to the bulk solution. The gallium porphyrin analogues used in the current study possess two n-alkyl side chains (ATX-C-x, where x = number of carbon atoms, ranging from x = 2 to x = 12). By varying the n-alkyl chain length, thereby modifying the surfactant properties of the ATX-Cx derivatives, cell killing in relation to the accumulation of ATX-C-x derivatives at the gas/solution interface of cavitation bubbles was determined. Following sonolysis in the presence of ATX-C-x, a strong correlation for the yield of carbon-centered radicals and cell killing was observed. These results support the hypothesis that a sonochemical mechanism is responsible for the synergistic effect of ultrasound and ATX-C-x on HL-525 and HL-60 cells. Published by Elsevier Science Inc. C1 NCI, CCR, RBB, NIH, Bethesda, MD 20892 USA. Fukui Med Univ, Dept Pathol, Fukui, Japan. RP Riesz, P (reprint author), NCI, CCR, RBB, NIH, Bldg 10,Rm B3-B69,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Sostaric, Joe/A-6033-2008 NR 41 TC 35 Z9 43 U1 0 U2 5 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 MAR 15 PY 2003 VL 34 IS 6 BP 710 EP 719 DI 10.1016/S0891-5849(02)01428-4 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 653RY UT WOS:000181451900009 PM 12633748 ER PT J AU Linares, E Nakao, LS Augusto, O Kadiiska, MB AF Linares, E Nakao, LS Augusto, O Kadiiska, MB TI EPR studies of in vivo radical production by lipopolysaccharide: Potential role of iron mobilized from iron-nitrosyl complexes SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE lipopolysaccharide; sepsis; free radicals; nitric oxide; redox-active iron; hydroxyl radical; EPR; spin trapping; Fenton chemistry ID NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; IN-VIVO; OXIDATIVE STRESS; RAT HEPATOCYTES; SEPSIS SYNDROME; CARBON-DIOXIDE; SEPTIC SHOCK; PEROXYNITRITE; METABOLISM AB Although oxidative stress has been implicated in the pathogenesis of sepsis, there is little evidence for the formation of radicals other than nitric oxide in its experimental models. Here we used low temperature EPR and EPR spin trapping to monitor nitric oxide and secondary radical formation in blood, liver, and bile samples from rats treated with a low lipopolysaccharide (LPS) dose (0.25 mg) and with dimethyl sulfoxide (DMSO) and the spin trap alpha-(4-pyridyl 1-oxide)-N-t-butylnitrone (POBN). The results showed that production of secondary radicals triggered by LPS is delayed in regard to maximum nitric oxide synthesis and is iron-dependent. One of the secondary produced radicals was identified as the hydroxyl radical. Its formation is proposed to occur because of the mobilization of redox-active iron required to repair the nitrosyl complexes produced by LPS. The results suggest that iron chelation may be a useful adjuvant therapy for treating sepsis. (C) 2003 Elsevier Science Inc. C1 Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05513970 Sao Paulo, Brazil. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Res Triangle Pk, NC USA. RP Augusto, O (reprint author), Univ Sao Paulo, Inst Quim, Dept Bioquim, Caixa Postal 26077, BR-05513970 Sao Paulo, Brazil. RI Augusto, Ohara/D-3839-2012; OI Augusto, Ohara/0000-0002-7220-4286; Linares, Edlaine/0000-0001-8164-3013 NR 56 TC 13 Z9 14 U1 0 U2 2 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 MAR 15 PY 2003 VL 34 IS 6 BP 766 EP 773 DI 10.1016/S0891-5849(02)01424-7 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 653RY UT WOS:000181451900014 PM 12633753 ER PT J AU Valasek, L Mathew, AA Shin, BS Nielsen, KH Szamecz, B Hinnebusch, AG AF Valasek, L Mathew, AA Shin, BS Nielsen, KH Szamecz, B Hinnebusch, AG TI The yeast eIF3 subunits TIF32/a, NIP1/c, and eIF5 make critical connections with the 40S ribosome in vivo SO GENES & DEVELOPMENT LA English DT Article DE eukaryotic translation initiation factor (eIf); multifactor complex (MFC); translational control; protein synthesis; 40S ribosome binding; TIF32/NIP1 ID HEPATITIS-C VIRUS; TRANSLATION INITIATION; SACCHAROMYCES-CEREVISIAE; MULTIFACTOR COMPLEX; START CODON; IN-VIVO; RNA; BINDING; PROTEIN; IDENTIFICATION AB Initiation factor 3 (eIF3) forms a multifactor complex (MFC) with eIF1, eIF2, and eIF5 that stimulates Met-tRNA(i)(Met) binding to 40S ribosomes and promotes scanning or AUG recognition. We have previously characterized MFC subcomplexes produced in vivo from affinity-tagged eIF3 subunits lacking discrete binding domains for other MFC components. Here we asked whether these subcomplexes can bind to 40S ribosomes in vivo. We found that the N-and C-terminal domains of NIP1/eIF3c, the N-and C-terminal domains of TIF32/eIF3a, and eIF5 have critical functions in 40S binding, with eIF5 and the TIF32-CTD performing redundant functions. The TIF32-CTD interacted in vitro with helices 16-18 of domain I in 18S rRNA, and the TIF32-NTD and NIP1 interacted with 40S protein RPSOA. These results suggest that eIF3 binds to the solvent side of the 40S subunit in a way that provides access to the interface side for the two eIF3 segments (NIP1-NTD and TIF32-CTD) that interact with eIF1, eIF5, and the eIF2/GTP/Met-tRNA(i)(Met) ternary complex. C1 NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RI Valasek, Leos/I-5743-2014 NR 32 TC 103 Z9 110 U1 2 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 15 PY 2003 VL 17 IS 6 BP 786 EP 799 DI 10.1101/gad.1065403 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 661MZ UT WOS:000181895500011 PM 12651896 ER PT J AU Moyer, SC Marzilli, LA Woods, AS Laiko, VV Doroshenko, VM Cotter, RJ AF Moyer, SC Marzilli, LA Woods, AS Laiko, VV Doroshenko, VM Cotter, RJ TI Atmospheric pressure matrix-assisted laser desorption/ionization.(AP MALDI) on a quadrupole ion trap mass spectrometer SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY LA English DT Article DE AP MALDI; time-of-flight; ITMS; tandem mass spectrometry; proteins; protein digests; acetylation; oligosaccharides; sulfation; phosphorylation ID DESORPTION IONIZATION; PROTEINS; DETECTOR; PEPTIDES AB A new atmospheric pressure ionization technique, atmospheric pressure matrix-assisted laser desorption/ionization (AP MALDI), was recently introduced by Laiko et al. [U.S. Patent 5,965,884; Abstracts of the 4th International Symposium on Mass Spectrometry in the Health and Life Sciences, San Francisco, CA, 25-29 August 1998; Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry, Proceedings of the 47th ASMS Conference on Mass Spectrometry and Allied Topics, Dallas, TX, 1999; Anal. Chem. 72 (2000) 652]. This source has been coupled to an orthogonal time-of-flight mass spectrometer [U.S. Patent 5,965,884; Abstracts of the 4th International Symposium on Mass Spectrometry in the Health and Life Sciences, San Francisco, CA, 25-29 August 1998; Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry, Proceedings of the 47th ASMS Conference on Mass Spectrometry and Allied Topics, Dallas, TX, 1999; Anal. Chem. 72 (2000) 652] and to an ion trap mass spectrometer (ITMS) [Anal. Chem. 72 (2000) 5239; Atmospheric Pressure MALDI/Ion Trap Mass Spectrometry, Proceedings of the 48th ASMS Conference on Mass Spectrometry and Allied Topics, Long Beach, CA, June 2000; An Atmospheric Pressure MALDI Probe for Use with ESI Source Interfaces, Proceedings of the 48th ASMS Conference on Mass Spectrometry and Allied Topics, Long Beach, CA, June 2000; Atmospheric Pressure Matrix-Assisted Laser Desorption Ionization, Proceedings of the 48th ASMS Conference on Mass Spectrometry and Allied Topics, Long Beach, CA, June 2000]. Here, we present the current status of the work involving the development of an AP MALDI source for an ITMS. In addition, we present recent work from our own laboratory to demonstrate the utility of this novel configuration. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA. NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Mass Technol, Burtonsville, MD 20866 USA. RP Cotter, RJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, B-7 Biophys Bldg,725 N Wolfe St, Baltimore, MD 21205 USA. NR 42 TC 40 Z9 41 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1387-3806 J9 INT J MASS SPECTROM JI Int. J. Mass Spectrom. PD MAR 15 PY 2003 VL 226 IS 1 BP 133 EP 150 AR PII S1387-3806(02)00972-7 DI 10.1016/S1387-3806(02)00972-7 PG 18 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 650NJ UT WOS:000181270000009 ER PT J AU Hirschfeld, S Ho, PTC Smith, M Pazdur, R AF Hirschfeld, S Ho, PTC Smith, M Pazdur, R TI Regulatory approvals of pediatric oncology drugs: Previous experience and new initiatives SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHILDHOOD LYMPHOCYTIC-LEUKEMIA; CHILDRENS-CANCER-GROUP; CYTOSINE-ARABINOSIDE; NEUROBLASTOMA; VM-26 AB Purpose: To review the Food and Drug Administration (FDA) experience with approvals of new drugs for pediatric oncology and to discuss new regulatory initiatives directed at pediatric oncology. Methods: A retrospective review of FDA archival documents and the published literature. Results: More than 100 drugs have been approved by the Division of Oncology Drug Products of the FDA for the treatment of malignancies. Only 15 have pediatric use information in their labeling, which is less than 50% of the drugs commonly used in the treatment of pediatric malignancies. In the past 20 years, there have been six submissions to the FDA for pediatric oncology indications. To illustrate principles of the approval process, each submission is discussed. Conclusion: Potential reasons for a lack of New Drug Application submissions for pediatric oncology include the small pediatric oncology market compared with the adult oncology market and perceived barriers to performing studies in children. Reasons for failure to approve pediatric indications include small numbers of patients, lack of appropriate controls, and failure to demonstrate patient benefit. Approval criteria include the use of controlled trials, prospective data collection, and disease-appropriate end points. Regulatory initiatives to promote pediatric therapeutic development and product labeling are discussed. J Clin Oncol 21:1066-1073. (C) 2003 by American Society of Clinical Oncology. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. GlaxoSmithKline, Philadelphia, PA USA. RP Hirschfeld, S (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD-150,1451 Rockville Pike, Rockville, MD 20852 USA. EM hirschfelds@cder.fda.gov RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 20 TC 26 Z9 26 U1 0 U2 0 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 MAR 15 PY 2003 VL 21 IS 6 BP 1066 EP 1073 DI 10.1200/JCO.2003.11.138 PG 8 WC Oncology SC Oncology GA 657QR UT WOS:000181678300017 PM 12637472 ER PT J AU Penson, DF Feng, ZD Kuniyuki, A McClerran, D Albertsen, PC Deapen, D Gilliland, F Hoffman, R Stephenson, RA Potosky, AL Stanford, JL AF Penson, DF Feng, ZD Kuniyuki, A McClerran, D Albertsen, PC Deapen, D Gilliland, F Hoffman, R Stephenson, RA Potosky, AL Stanford, JL TI General quality of life 2 years following treatment for prostate cancer: What influences outcomes? Results from the prostate cancer outcomes study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EXTERNAL-BEAM RADIATION; OF-LIFE; RADICAL PROSTATECTOMY; THERAPY; INCONTINENCE; MEN AB Purpose : The goal of this study was to determine the relationship between primary treatment, urinary dysfunction, sexual dysfunction, and general health-related quality of life (HROOL) in prostate cancer. Methods: A sample of men with newly diagnosed prostate cancer between 1994 and 1995 was randomly selected from six population-based Surveillance, Epidemiology, and End Results registries. A baseline survey was completed by 2,306 men within 6 to 12 months of diagnosis, and these men also completed a follow-up HROOL survey 2 years after diagnosis. Logistic regression models were used to determine whether primary treatment, urinary dysfunction, and sexual dysfunction were independently associated with general HROOL outcomes approximately 2 years after diagnosis as measured by the Medical Outcomes Study 36-item Short Form Health Survey. The magnitude of this effect was estimated using least square means models. Results: After adjustment for potential confounders, primary treatment was not associated with 2-year general HROOL outcomes in men with prostate cancer. Urinary function and bother were independently associated with worse general HROOL in all domains. Sexual function and bother were also independently associated with worse general HROOL, although the relationship was not as strong as in the urinary domains. Conclusion: Primary treatment is not associated with 2-year general HROOL outcomes in prostate cancer. Although both sexual and urinary function and bother are associated with quality of life, men who are more bothered by their urination or impotence are more likely to report worse quality of life. This implies that future research should be directed toward finding ways to improve treatment-related outcomes or help patients better cope with their posttreatment urinary or sexual dysfunction. C1 VAPSHCS, Urol Sect, Seattle, WA 98108 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Univ Connecticut, Sch Med, Div Urol, Farmington, CT USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Univ New Mexico, Sch Med, Dept Internal Med, Albuquerque, NM 87131 USA. Univ Utah, Sch Med, Dept Urol, Salt Lake City, UT USA. NCI, Div Canc Control & Populat Sci, Appl Res Branch, Bethesda, MD 20892 USA. RP Penson, DF (reprint author), VAPSHCS, Urol Sect, 112-UR,1660 S Columbian Way, Seattle, WA 98108 USA. EM penson@u.washington.edu FU NCI NIH HHS [N01-PC-67007, N01-PC-67000, N01-PC-67005, N01-PC-67006, N01-PC-67009, N01-PC-67010] NR 23 TC 121 Z9 128 U1 0 U2 4 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 MAR 15 PY 2003 VL 21 IS 6 BP 1147 EP 1154 DI 10.1200/JCO.2003.07.139 PG 8 WC Oncology SC Oncology GA 657QR UT WOS:000181678300028 PM 12637483 ER PT J AU Van Laethem, F Liang, XQ Andris, F Urbain, J Vandenbranden, M Ruysschaert, JM Resh, MD Stulnig, TM Leo, O AF Van Laethem, F Liang, XQ Andris, F Urbain, J Vandenbranden, M Ruysschaert, JM Resh, MD Stulnig, TM Leo, O TI Glucocorticoids alter the lipid and protein composition of membrane rafts of a murine T cell hybridoma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; GPI-ANCHORED PROTEINS; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; ANTIINFLAMMATORY ACTIONS; ENRICHED MICRODOMAINS; TYROSINE KINASE; LOCALIZATION; LYMPHOCYTES; ACTIVATION AB Glucocorticoids (GC) are widely used anti-inflammatory agents known to suppress T cell activation by interfering with the TCR activation cascade. The attenuation of early TCR signaling events by these compounds has been recently attributed to a selective displacement of key signaling proteins from membrane lipid rafts. In this study, we demonstrate that GC displace the acyl-bound adaptor proteins linker for activation of T cells and phosphoprotein associated with glycosphingolipid-enriched microdomains from lipid rafts of murine T cell hybridomas, possibly by inhibiting their palmitoylation status. Analysis of the lipid content of the membrane rafts revealed that GC treatment led to a significant decrease in palmitic acid content. Moreover, we found an overall decrease in the proportion of raft-associated saturated fatty acids. These changes were consistent with a decrease in fluorescence anisotropy of isolated lipid rafts, indicating an increase in their fluidity. These findings identify the mechanisms underlying the complex inhibitory effects of glucocorticoids on early TCR signaling and suggest that some of the inhibitory properties of GC on T cell responses may be related to their ability to affect the membrane lipid composition and the palmitoylation status of important signaling molecules. C1 Free Univ Brussels, Inst Biol & Med Mol, Physiol Anim Lab, Gosselies, Belgium. Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA. Free Univ Brussels, Lab Struct & Fonct Membranes Biol, Brussels, Belgium. Univ Vienna, Dept Internal Med 3, Vienna, Austria. RP Van Laethem, F (reprint author), NCI, Expt Immunol Branch, Bldg 10,Room 3N119, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM75966] NR 52 TC 27 Z9 30 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 MAR 15 PY 2003 VL 170 IS 6 BP 2932 EP 2939 PG 8 WC Immunology SC Immunology GA 653AF UT WOS:000181412500019 PM 12626544 ER PT J AU Baccam, M Woo, SY Vinson, C Bishop, GA AF Baccam, M Woo, SY Vinson, C Bishop, GA TI CD40-mediated transcriptional regulation of the IL-6 gene in B lymphocytes: Involvement of NF-kappa B, AP-1, and C/EBP SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; CROSS-LINKING CD40; CLASS-II MOLECULES; C-JUN PROMOTER; INTERLEUKIN-6 GENE; DNA-BINDING; EFFECTOR FUNCTIONS; EPITHELIAL-CELLS; CYCLIC-AMP; PHOSPHORYLATION AB Engagement of CD40 by its ligand CD154 induces IL-6 production by B lymphocytes. We previously reported that this IL-6 production is dependent upon binding of the adapter protein TNF receptor-associated factor 6 to the cytoplasmic domain of CD40, while binding of TNF receptor-associated factors 2 and 3 is dispensable, as is the activation-induced nuclear translocation of NF-kappaB. The present study was designed to characterize CD40-mediated transcriptional control of the IL-6 gene in B cells. CD40 engagement on B lymphocytes activated the IL-6 promoter, and mutations in the putative binding sites for AP-1 and C/EBP transcription factors reduced this activation. Interestingly, a mutation in the putative NF-kappaB binding site completely abrogated the basal promoter activity, thus also rendering the promoter unresponsive to CD40 stimulation, suggesting that this site is required for binding of NF-kappaB constitutively present in the nucleus of mature B cells. The expression of dominant negative Fos or C/EBPalpha proteins, which prevent binding of AP-1 or C/EBP complexes to DNA, also reduced CD40-mediated IL-6 gene expression. Furthermore, CD40 stimulation led to phosphorylation of c-Jun on its activation domain, implicating CD40-mediated Jun kinase activation in the transcriptional regulation of IL-6 production. C1 Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. Vet Affairs Med Ctr, Iowa City, IA 52242 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Bishop, GA (reprint author), Univ Iowa, Dept Microbiol, 3-570 Bowen Sci Bldg,51 Newton Rd, Iowa City, IA 52242 USA. FU NIAID NIH HHS [AI28847, AI49993] NR 53 TC 98 Z9 108 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2003 VL 170 IS 6 BP 3099 EP 3108 PG 10 WC Immunology SC Immunology GA 653AF UT WOS:000181412500041 PM 12626566 ER PT J AU Kobayashi, SD Voyich, JM Braughton, KR DeLeo, FR AF Kobayashi, SD Voyich, JM Braughton, KR DeLeo, FR TI Down-regulation of proinflammatory capacity during apoptosis in human polymorphonuclear leukocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; NF-KAPPA-B; HUMAN-NEUTROPHILS; PHOSPHOINOSITIDE 3-KINASE; DIFFERENTIAL EXPRESSION; AGING NEUTROPHILS; GENE-EXPRESSION; CELLS; CHEMOKINES; AKT AB Polymorphonuclear leukocytes (PMNs) are essential to innate immunity in humans and contribute significantly to inflammation. Although progress has been made, the molecular basis for termination of inflammation in humans is incompletely characterized. We used human oligonucleotide microarrays to identify genes encoding inflammatory mediators that were differentially regulated during the induction of apoptosis. One hundred thirty-three of 212 differentially expressed genes encoding proinflammatory factors, signal transduction mediators, adhesion molecules, and other proteins that facilitate the inflammatory response were down-regulated during the-induction of apoptosis following PMN phagocytosis. Among these, 42 genes encoded proteins critical to the inflammatory response, including receptors for IL-8beta, IL-10alpha, IL-13alpha1, IL-15alpha, IL-17, IL-18, C1q, low-density lipoprotein, IgG Fc (CD32), and formyl peptide, Toll-like receptor 6, platelet/endothelial cell adhesion molecule-1 (CD31), P-selectin (CD62), IL-1alpha, IL-16, and granulocyte chemoattractant protein-2 were down-regulated. Many of these genes were similarly down-regulated during Fas-mediated or camptothecin-induced apoptosis. We used flow cytometry to confirm that IL-8Rbeta (CXCR2) and IL-1a were significantly down-regulated during PMN apoptosis. We also discovered that 23 genes encoding phosphoinositide and calcium-mediated signal transduction components, which comprise complex pathways essential to the inflammatory response of host cells, were differentially regulated during PMN apoptosis. Importantly, our data demonstrate that PMNs down-regulate proinflammatory capacity at the level of gene expression during induction of apoptosis. These findings provide new insight into the molecular events that resolve inflammation following PMN activation in humans. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP DeLeo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. OI DeLeo, Frank/0000-0003-3150-2516 NR 48 TC 81 Z9 84 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2003 VL 170 IS 6 BP 3357 EP 3368 PG 12 WC Immunology SC Immunology GA 653AF UT WOS:000181412500071 PM 12626596 ER PT J AU Ackers, ML Parekh, B Evans, TG Berman, P Phillips, S Allen, M McDougal, JS AF Ackers, ML Parekh, B Evans, TG Berman, P Phillips, S Allen, M McDougal, JS TI Human immunodeficiency virus (HIV) seropositivity among uninfected HIV vaccine recipients SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 9th Conference on Retroviruses and Opportunistic Infection CY FEB 24-28, 2002 CL SEATTLE, WASHINGTON ID CLINICAL-TRIALS; EFFICACY TRIALS; RISK; DISCRIMINATION; PARTICIPATE; VOLUNTEERS; INFECTION; BLOOD; MEN AB Since 1987, >10,000 individuals worldwide have received immunizations with human immunodeficiency virus (HIV) preventive vaccine constructs. Many constructs elicit antibodies detected by standard serologic tests (enzyme immunoassays, rapid tests, and Western blots) and result in vaccine recipients' serum being identified as reactive and indicative of HIV infection. To determine the frequency of vaccine-induced HIV antibody among uninfected HIV vaccine trial participants and to identify factors associated with these results, serum samples from HIV-uninfected participants from selected United States phase I/II HIV-1 vaccine trials were tested with 6 serologic screening tests. Reactive specimens were tested by use of Western blot. Overall, 490 serum specimens from 461 vaccine recipients were tested; 100 (20.4%) reacted on at least 1 serologic test, and 65 (13%) were determined to be positive by Western blot. Canarypox or vaccinia vaccine recipients' serum with or without HIV envelope glycoprotein (gp120 or gp160) boosts accounted for all positive Western blot results; no positive Western blot results were obtained from gp120 subunit recipients. The potential for vaccine recipients being misclassified as HIV infected increased with vaccine complexity. C1 Ctr Dis Control & Prevent, HIV Vaccine Sect, Epidemiol Branch, Div HIV AIDS Prevent Surveillance & Epidemiol,Nat, Atlanta, GA USA. Ctr Dis Control & Prevent, HIV Immunol & Diagnost Branch, Div AIDS STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA USA. Univ Rochester, Rochester, NY USA. VaxGen, Brisbane, CA USA. NIAID, AIDS Vaccine Evaluat Grp, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Clin Res Branch, Div AIDS, NIH, Bethesda, MD 20892 USA. RP Ackers, ML (reprint author), Ctr Dis Control & Prevent, Off Commun, Natl Ctr HIV STD & TB Prevent, Mail Stop E-07, Atlanta, GA 30306 USA. OI Allen, Mary/0000-0001-8163-0714 NR 33 TC 30 Z9 31 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 MAR 15 PY 2003 VL 187 IS 6 BP 879 EP 886 DI 10.1086/368169 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 653RL UT WOS:000181450800001 PM 12660933 ER PT J AU Cao, H Kaleebu, P Hom, D Flores, J Agrawal, D Jones, N Serwanga, J Okello, M Walker, C Sheppard, H El-Habib, R Klein, M Mbidde, E Mugyenyi, P Walker, B Ellner, J Mugerwa, R AF Cao, H Kaleebu, P Hom, D Flores, J Agrawal, D Jones, N Serwanga, J Okello, M Walker, C Sheppard, H El-Habib, R Klein, M Mbidde, E Mugyenyi, P Walker, B Ellner, J Mugerwa, R CA HIV Network Prevention Trials TI Immunogenicity of a recombinant human immunodeficiency virus (HIV)-canarypox vaccine in HIV-Seronegative Ugandan volunteers: Results of the HIV Network for Prevention Trials 007 vaccine study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-LYMPHOCYTE RESPONSES; TYPE-1; AIDS; NEUTRALIZATION; CELLS; ANTIBODIES; ANTIGENS; IMMUNITY; AFRICA; GP120 AB In the first preventative human immunodeficiency virus (HIV) vaccine study to be carried out in Africa, 40 HIV-seronegative Ugandan volunteers were randomly assigned to receive a canarypox vector containing HIV-1 clade B (env and gag-pro) antigens (ALVAC-HIV; n=20), control vector containing the rabies virus glycoprotein gene (n=10), or saline placebo (n=10). Cytotoxic T lymphocyte activity against target cells expressing clade A, B, and D antigens was assessed using standard chromium-release and confirmatory interferon-gamma enzyme-linked immunospot (ELISPOT) assays. Neutralizing antibody responses to cell line-adapted strains and primary isolates in all 3 clades were also tested. Twenty percent of vaccine recipients generated detectable cytolytic responses to either Gag or Env, and 45% had vaccine-induced HIV-specific CD8(+) T cell responses, as measured by the ELISPOT assay. In contrast, only 5% of the control group had vaccine-specific responses. Neutralizing antibodies against primary and laboratory-adapted HIV-1 clade B strains were seen in 10% and 15% of vaccine recipients, respectively, but responses against clades A and D were not detected. Although the immunogenicity of this clade B-based vaccine was low, ALVAC-HIV elicited CD8(+) T cell responses with detectable cross-activity against clade A and D antigens in a significant proportion of vaccine recipients. C1 Calif Dept Hlth Serv, Viral & Rickettsial Dis Lab, Richmond, CA 94804 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Uganda Virus Res Inst Labs, Entebbe, Uganda. Joint Clin Res Ctr, Kampala, Uganda. Makerere Univ, Kampala, Uganda. Aventis Pasteur, Marcy Letoile, France. RP Cao, H (reprint author), Calif Dept Hlth Serv, Viral & Rickettsial Dis Lab, 850 Marina Bay Pkwy, Richmond, CA 94804 USA. NR 27 TC 50 Z9 52 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 MAR 15 PY 2003 VL 187 IS 6 BP 887 EP 895 DI 10.1086/368020 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 653RL UT WOS:000181450800002 PM 12660934 ER PT J AU Atkinson, J Edlin, BR Engels, EA Kral, AH Seal, K Gamache, CJ Whitby, D O'Brien, TR AF Atkinson, J Edlin, BR Engels, EA Kral, AH Seal, K Gamache, CJ Whitby, D O'Brien, TR TI Seroprevalence of human herpesvirus 8 among injection drug users in San Francisco SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 5th International Workshop on Kaposi-Sarcoma-Associated Herpesvirus and Related Agents CY AUG 07-11, 2002 CL KLOSTER IRSEE, GERMANY ID SARCOMA-ASSOCIATED HERPESVIRUS; BLOOD MONONUCLEAR-CELLS; KAPOSIS-SARCOMA; HUMAN-HERPESVIRUS-8 INFECTION; SEXUAL TRANSMISSION; DNA-SEQUENCES; PERIPHERAL-BLOOD; HOMOSEXUAL MEN; RISK-FACTORS; PREVALENCE AB The association between injection drug use and human herpesvirus 8 (HHV-8) was examined to investigate bloodborne transmission of the virus. In all, 1905 injection drug users (IDUs) enrolled in a cross-sectional study were tested for K8.1 antibodies to HHV-8 lytic antigen. Logistic regression was used to adjust for demographic and sexual behavior variables. HHV-8 seroprevalence was 10% among women, 10% among heterosexual men, and 23% among men who have sex with men. In adjusted analyses, HHV-8 seroprevalence increased with longer duration of injection drug use for each of these groups (P=.01, P=.03, and P=.049 for trend, respectively). HHV-8 infection is relatively common among IDUs in San Francisco, and longer duration of injection drug use is associated with an increase in the risk of HHV-8 infection that is not explained by sexual behavior or demographic differences. These results are consistent with the occurrence of bloodborne transmission of HHV-8 among IDUs. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Sci Applicat Int Corp, Viral Epidemiol Sect, Frederick, MD USA. Univ Calif San Francisco, Urban Hlth Study, San Francisco, CA 94143 USA. RP O'Brien, TR (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Rm 8016,MSC 7248, Rockville, MD 20852 USA. OI Edlin, Brian/0000-0001-8172-8797 FU NCI NIH HHS [N01-CO-12400] NR 31 TC 32 Z9 37 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 MAR 15 PY 2003 VL 187 IS 6 BP 974 EP 981 DI 10.1086/368332 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 653RL UT WOS:000181450800012 PM 12660944 ER PT J AU Akil, M Kolachana, BS Rothmond, DA Hyde, TM Weinberger, DR Kleinman, JE AF Akil, M Kolachana, BS Rothmond, DA Hyde, TM Weinberger, DR Kleinman, JE TI Catechol-O-methyltransferase genotype and dopamine regulation in the human brain SO JOURNAL OF NEUROSCIENCE LA English DT Article DE catechol-O-methyltransferase; dopamine; tyrosine hydroxylase; human; genotype; midbrain; psychosis; schizophrenia ID DORSOLATERAL PREFRONTAL CORTEX; VENTRAL TEGMENTAL AREA; HYDROXYLASE GENE-EXPRESSION; TRANSPORTER MESSENGER-RNA; CEREBRAL BLOOD-FLOW; TYROSINE-HYDROXYLASE; WORKING-MEMORY; STRIATAL DOPAMINE; SUBSTANTIA-NIGRA; PHYSIOLOGICAL DYSFUNCTION AB A functional polymorphism in the gene for catechol-O-methyltransferase ( COMT) has been shown to affect executive cognition and the physiology of the prefrontal cortex in humans, probably by affecting prefrontal dopamine signaling. The COMT valine allele, associated with relatively poor prefrontal function, is also a gene that may increase risk for schizophrenia. Although poor performance on executive cognitive tasks and abnormal prefrontal function are characteristics of schizophrenia, so is psychosis, which has been related to excessive presynaptic dopamine activity in the striatum. Studies in animals have shown that diminished prefrontal dopamine neurotransmission leads to upregulation of striatal dopamine activity. We measured tyrosine hydroxylase (TH) mRNA in mesencephalic dopamine neurons in human brain and found that the COMT valine allele is also associated with increased TH gene expression, especially in neuronal populations that project to the striatum. This indicates that COMT genotype is a heritable aspect of dopamine regulation and it further explicates the mechanism by which the COMT valine allele increases susceptibility for psychosis. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Akil, M (reprint author), 10 Ctr Dr,MSC1385, Bethesda, MD 20892 USA. EM akilm@intra.nimh.nih.gov NR 71 TC 231 Z9 237 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 15 PY 2003 VL 23 IS 6 BP 2008 EP 2013 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 659KY UT WOS:000181776900005 PM 12657658 ER PT J AU Perez, MA Field-Fote, EC Floeter, MK AF Perez, MA Field-Fote, EC Floeter, MK TI Patterned sensory stimulation induces plasticity in reciprocal Ia inhibition in humans SO JOURNAL OF NEUROSCIENCE LA English DT Article DE H-reflex; locomotion; transcranial magnetic stimulation; presynaptic inhibition; spinal cord; interneurons ID SPINAL-CORD INJURY; LONG-TERM POTENTIATION; HUMAN MOTOR CORTEX; LOCOMOTOR-ACTIVITY; MUSCLE AFFERENTS; ANKLE EXTENSORS; MECHANISMS; WALKING; CAT; DORSIFLEXION AB Training of spinal cord circuits using sensorimotor stimulation has been proposed as a strategy to improve movement after spinal injury. How sensory stimulation may lead to long-lasting changes is not well understood. We studied whether sensory stimulation might induce changes in the strength of a specific spinal interneuronal circuit: spinally mediated reciprocal Ia inhibition. In healthy humans, the strength of reciprocal inhibition between ankle flexor and extensor muscles was assessed before and after 30 min of peroneal nerve stimulation at motor threshold intensity. Three stimulation protocols were assessed: patterned nerve stimulation ( 10 pulses at 100 Hz every 1.5 sec), uniform nerve stimulation ( one pulse every 150 msec), and combined stimulation of the peroneal nerve and the motor cortex with transcranial magnetic stimulation. Short-latency reciprocal inhibition from ankle flexor to extensor muscles was measured by conditioning the soleus H-reflex with stimulation of the common peroneal nerve. The strength of the reciprocal inhibition was measured at baseline and for 20 min after each stimulation session. Patterned stimulation, with or without motor cortex stimulation, enhanced reciprocal inhibition for at least 5 min afterward. The uniform pattern of stimulation was ineffective. These results demonstrate the presence of short-term plasticity within spinal inhibitory circuits. We conclude that the pattern of sensory input is a crucial factor for inducing changes in the spinal circuit for reciprocal inhibition in humans. These findings may have implications for the use of repetitive patterned sensory stimulation in rehabilitative efforts to improve walking ability in patients with spinal injury. C1 NINDS, EMG Lab, NIH, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Dept Orthopaed & Rehabil, Div Phys Therapy, Miami, FL 33136 USA. Univ Miami, Sch Med, Miami Project Cure Paralysis, Miami, FL 33136 USA. RP Floeter, MK (reprint author), NINDS, EMG Lab, NIH, Bldg 10,Room 5C101,10 Ctr Dr,MSC 1404, Bethesda, MD 20892 USA. EM floeter@codon.nih.gov RI Field-Fote, Edelle/B-2143-2008 NR 46 TC 59 Z9 59 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 15 PY 2003 VL 23 IS 6 BP 2014 EP 2018 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 659KY UT WOS:000181776900006 PM 12657659 ER PT J AU Mathews, GC Diamond, JS AF Mathews, GC Diamond, JS TI Neuronal glutamate uptake contributes to GABA synthesis and inhibitory synaptic strength SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glutamate transporters; synaptic vesicles; GABA; metabolism; inhibition; hippocampus ID RAT HIPPOCAMPUS; PYRAMIDAL CELLS; GABAERGIC NEURONS; TRANSPORTER EAAC1; RECEPTOR SUBUNIT; MINI AMPLITUDE; D-ASPARTATE; TRANSMISSION; ASTROCYTES; SPILLOVER AB Neurons must maintain a supply of neurotransmitter in their presynaptic terminals to fill synaptic vesicles. GABA is taken up into inhibitory terminals by transporters or is synthesized from glutamate by glutamic acid decarboxylase. Here we report that glutamate transporters supply GABAergic terminals in the hippocampus with glutamate, which is then used to synthesize GABA for filling synaptic vesicles. Glutamate transporter antagonists reduced IPSC and miniature IPSC ( mIPSC) amplitudes, consistent with a reduction in the amount of GABA packaged into each synaptic vesicle. This reduction occurred rapidly and independently of synaptic activity, suggesting that modulation of vesicular GABA content does not require vesicle release and refilling. Raising extracellular glutamate levels increased mIPSC amplitudes by enhancing glutamate uptake and, consequently, GABA synthesis. These results indicate that neuronal glutamate transporters strengthen inhibitory synapses in response to extracellular glutamate. This modulation appears to occur under normal conditions and may constitute a negative feedback mechanism to combat hyperexcitability. C1 NINDS, Synapt Physiol Unit, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. RP Diamond, JS (reprint author), NINDS, Synapt Physiol Unit, NIH, 36 Convent Dr,Room 2C09, Bethesda, MD 20892 USA. EM diamondj@ninds.nih.gov RI Mathews, Gregory/A-9660-2009; Diamond, Jeffrey/C-1835-2015 OI Diamond, Jeffrey/0000-0002-1770-2629 NR 57 TC 111 Z9 115 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 15 PY 2003 VL 23 IS 6 BP 2040 EP 2048 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 659KY UT WOS:000181776900009 PM 12657662 ER PT J AU Wiener, MC Richmond, BJ AF Wiener, MC Richmond, BJ TI Decoding spike trains instant by instant using order statistics and the mixture-of-Poissons model SO JOURNAL OF NEUROSCIENCE LA English DT Article DE visual cortex; information; coding; modeling; statistics; timing ID MONKEY VISUAL-CORTEX; RESPONSE MODELS; NEURONAL RESPONSES; CODING STRATEGIES; CORTICAL-NEURONS; PLACE CELLS; INFORMATION; PATTERNS; OVERDISPERSION; HIPPOCAMPAL AB In the brain, spike trains are generated in time and presumably also interpreted as they unfold in time. Recent work (Oram et al., 1999; Baker and Lemon, 2000) suggests that in several areas of the monkey brain, individual spike times carry information because they reflect an underlying rate variation. Constructing a model based on this stochastic structure allows us to apply order statistics to decode spike trains instant by instant as spikes arrive or do not. Order statistics are time-consuming to compute in the general case. We demonstrate that data from neurons in primary visual cortex are well fit by a mixture of Poisson processes; in this special case, our computations are substantially faster. In these data, spike timing contributed information beyond that available from the spike count throughout the trial. At the end of the trial, a decoder based on the mixture-of-Poissons model correctly decoded about three times as many trials as expected by chance, compared with approximately twice as many as expected by chance using the spike count only. If our model perfectly described the spike trains, and enough data were available to estimate model parameters, then our Bayesian decoder would be optimal. For four-fifths of the sets of stimulus-elicited responses, the observed spike trains were consistent with the mixture-of-Poissons model. Most of the error in estimating stimulus probabilities is attributable to not having enough data to specify the parameters of the model rather than to misspecification of the model itself. C1 NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bldg 49,Room 1B-80, Bethesda, MD 20892 USA. EM bjr@ln.nimh.nih.gov NR 37 TC 27 Z9 29 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 15 PY 2003 VL 23 IS 6 BP 2394 EP 2406 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 659KY UT WOS:000181776900046 PM 12657699 ER PT J AU Velasco, I Velasco-Velazquez, MA Salazar, P Lajud, N Tapia, R AF Velasco, I Velasco-Velazquez, MA Salazar, P Lajud, N Tapia, R TI Influence of serum-free medium on the expression of glutamate transporters and the susceptibility to glutamate toxicity in cultured cortical neurons SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE glutamate toxicity; glutamate transporters; neuronal cultures; pyrrolidine dicarboxylate; serum-free medium ID RAT HIPPOCAMPAL-NEURONS; EXTRACELLULAR GLUTAMATE; CEREBRAL-CORTEX; L-GLUTAMATE TRANSPORT; NERVOUS-SYSTEM; IN-VIVO; GLT-1; NEUROTOXICITY; INHIBITION; DAMAGE AB The presence of glia and glial glutamate transporters seems to modify glutamate-mediated toxicity in neuronal cultures. In this work we cultured cortical cells in serum-containing medium and in a serum-free medium (Neurobasal medium + B27 supplement) and studied the expression of the glutamate transporters GLAST, GLT, and EAAC by immunocytochemistry and RT-PCR. The proportion of glial cells was below 10% in the Neurobasal medium and 46% in the serum-containing medium. Semiquantitative evaluation of the mRNA for the glutamate transporters showed similar amounts in cells grown in serum-free and serum-containing media. We detected immunoreactivity for the three transporters in both media, but EAAC was coexpressed with the neuronal marker MAP2, whereas GLAST and GLT predominated in nonneuronal cells. When the cultures were treated with glutamate for 15 min, the cultures in serum-containing medium showed a clear concentration-dependent neuronal death, whereas cells primed in this medium and switched to Neurobasal medium, as well as cells grown only in the latter, were less sensitive to glutamate concentrations up to 1 mM. A similar difference in the sensitivity to excitotoxicity was observed when the glutamate uptake inhibitor L-trans-2,4-pyrrolidine-dicarboxylate was applied during 6 hr, although the accumulation of extracellular glutamate was similar in the two media. We conclude that glutamate transporters with the culture conditions studied are sensitive to glutamate uptake inhibition and that Neurobasal/B27 medium protects cells against excitotoxicity. (C) 2003 Wiley-Liss, Inc. C1 Univ Nacl Autonoma Mexico, Dept Neurociencias, Inst Fisiol Celular, Mexico City, DF, Mexico. Univ Nacl Autonoma Mexico, Fac Med, Dept Farmacol, Mexico City, DF, Mexico. RP Velasco, I (reprint author), NINDS, Mol Biol Lab, NIH, 36 Convent Dr,Bldg 36,room 3C12, Bethesda, MD 20892 USA. RI Velasco-Velazquez, Marco/F-8779-2012; Velasco, Ivan/D-3593-2014; OI Velasco, Ivan/0000-0002-8953-6578; Velasco-Velazquez, Marco A./0000-0001-9717-0265 NR 35 TC 16 Z9 19 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR 15 PY 2003 VL 71 IS 6 BP 811 EP 818 DI 10.1002/jnr.10538 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 651PA UT WOS:000181327400008 PM 12605407 ER PT J AU Ghribi, O Herman, MM Savory, J AF Ghribi, O Herman, MM Savory, J TI Lithium inhibits A beta-induced stress in endoplasmic reticulum of rabbit hippocampus but does not prevent oxidative damage and tau phosphorylation SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE caspase 3; caspase 12; cytochrome c; GSK-3 beta; NF-kappa B ID GLYCOGEN-SYNTHASE KINASE-3-BETA; NF-KAPPA-B; ALZHEIMERS-DISEASE BRAIN; AMYLOID-INDUCED NEURODEGENERATION; ALUMINUM-INDUCED APOPTOSIS; INDUCED NEURONAL APOPTOSIS; PROTEIN KINASE-I; CASPASE-3 ACTIVATION; TRANSGENIC MICE; INDUCED NEUROTOXICITY AB The goal of this study was to assess the in vivo effect of Abeta on apoptosis pathways involving the endoplasmic reticulum and mitochondria, and its relationship to the induction of tau phosphorylation and DNA oxidative damage. In rabbits treated intracisternally with aggregated Abeta(1-42), clear evidence of endoplasmic reticulum stress was observed by the activation of caspase-12 and cleavage of caspase-3 in the endoplasmic reticulum. Mitochondrial injury was evident from the release of cytochrome c into the cytosol and the induction of oxidized mitochondrial DNA. Tau phosphorylation and nuclear translocation of NF-kappaB and GSK-3beta were also observed. Treatment with lithium, an inhibitor of GSK-3beta, inhibited caspase activation but did not prevent mitochondrial DNA damage or tau hyperphosphorylation, suggesting that the translocation of GSK-3beta may represent an upstream event that leads to caspase activation but is unrelated to tau hyperphosphorylation or mitochondrial DNA oxidative damage. We propose that treatment by lithium alone is not sufficient to protect against the multiple adverse effects of Abeta, and the use of agents that prevent oxidative DNA damage and tau hyperphosphorylation, together with lithium, may provide better protection from the neurotoxic effect of Abeta. (C) 2003 Wiley-Liss, Inc. C1 Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22908 USA. Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA. NIMH, IRP, NIH, Bethesda, MD USA. RP Savory, J (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Pathol, Box 800214, Charlottesville, VA 22908 USA. EM js2r@virginia.edu NR 63 TC 53 Z9 54 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR 15 PY 2003 VL 71 IS 6 BP 853 EP 862 DI 10.1002/jnr.10511 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 651PA UT WOS:000181327400013 PM 12605412 ER PT J AU Puccioni-Sohler, M Chimelli, L Mercon, M Goncalves, RR Pimenta, G Bianco, C Rios, M Jacobson, S AF Puccioni-Sohler, M Chimelli, L Mercon, M Goncalves, RR Pimenta, G Bianco, C Rios, M Jacobson, S TI Pathological and virological assessment of acute HTLV-1-associated myelopathy complicated with encephalopathy and systemic inflammation SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Symposium on NeuroVirology CY SEP 14-16, 2000 CL SAN FRANCISCO, CALIFORNIA SP NINDS, NIMH, Penn State Univ, Life Sci Consortium, Integrat Biosci Grad Program, Temple Univ, Coll Sci & Technol, Ctr Neurovirol & Canc Biol, Adv Biosci Resources, Inc, Pharmacia & Upjohn Inc DE HTLV-1; CSF; HTLV-1-associated myelopathy/tropical spastic paraparesis; HAM/TSP; quantitative PCR; viral load; HTLV-1 antibody index ID I-ASSOCIATED MYELOPATHY; CENTRAL-NERVOUS-SYSTEM; HAM/TSP; LOAD; DISEASE; CSF; DNA AB HTLV-I-associated myelopathy, also known as tropical spastic paraparesis (HAM/TSP), is a chronic inflammatory disease of the spinal cord. Acute cases are uncommon. We report the case of a 41-year-old woman with acute HAM/TSP complicated with encephalitis, an intense inflammatory reaction of the nervous system and lymphocytic infiltration of skeletal muscles, liver, salivary, adrenal and pituitary glands. The immunohistochemical studies of the lymphocytes surrounding blood vessels showed both B- and T-lymphocytes, in similar proportion, with both CD4- and CD8-positive cells. In addition, many perivascular and scattered macrophages were observed. Adult T-cell leukemia/lymphoma (ATL) was ruled out. The marrow aspirate was normal. Serial cerebrospinal fluid (CSF) analysis showed presence of HTLV-1 antibodies, but without intrathecal synthesis of specific antibodies. Determination of HTLV-1 viral loads demonstrated increased levels in the CSF relative to the peripheral blood and may be associated with widespread inflammation. The pathological and immunological findings may help understand the role of immune-reactive cells in the pathogenesis of HTLV-I-associated myelopathy. (C) 2002 Elsevier Science B.V. All rights reserved. C1 UFRJ, HUCFF, Clin Pathol Serv, CSF Lab,Dept Med, BR-22280030 Rio De Janeiro, Brazil. UFRJ, HUCFF, Dept Pathol, BR-22280030 Rio De Janeiro, Brazil. CSF Lab Neurolife, BR-22210010 Rio De Janeiro, Brazil. NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Amer Blood Ctr, Washington, DC 20005 USA. US FDA, Bethesda, MD 20817 USA. RP Puccioni-Sohler, M (reprint author), UFRJ, HUCFF, Clin Pathol Serv, CSF Lab,Dept Med, Rua Dezenove Fevereiro 185-705, BR-22280030 Rio De Janeiro, Brazil. NR 13 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD MAR 15 PY 2003 VL 207 IS 1-2 BP 87 EP 93 AR PII S0022-510X(02)00413-6 DI 10.1016/S0022-510X(02)00413-6 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 655CJ UT WOS:000181533500014 PM 12614936 ER PT J AU Swanson, SJ Hale, DA Mannon, RB Harlan, DM Kirk, AD AF Swanson, SJ Hale, DA Mannon, RB Harlan, DM Kirk, AD TI Kidney transplantation with rabbit antithymocyte globulin and sirolimus monotherapy - Reply SO LANCET LA English DT Letter ID REQUIREMENT; INDUCTION; TOLERANCE C1 NIDDKD, Transplantat & Autoimmun Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20307 USA. RP Kirk, AD (reprint author), NIDDKD, Transplantat & Autoimmun Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 NR 5 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 15 PY 2003 VL 361 IS 9361 BP 969 EP 970 DI 10.1016/S0140-6736(03)12753-5 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 658VP UT WOS:000181741600033 ER PT J AU Leem, SH Noskov, VN Park, JE Kim, SI Larionov, V Kouprina, N AF Leem, SH Noskov, VN Park, JE Kim, SI Larionov, V Kouprina, N TI Optimum conditions for selective isolation of genes from complex genomes by transformation-associated recombination cloning SO NUCLEIC ACIDS RESEARCH LA English DT Article ID YEAST ARTIFICIAL CHROMOSOMES; SACCHAROMYCES-CEREVISIAE; TAR CLONING; DNA; SEQUENCE; REGION; SYSTEM AB Transformation-associated recombination (TAR) cloning in yeast is used to isolate a desired chromosomal region or gene from a complex genome without construction of a genomic library. The technique involves homologous recombination during yeast spheroplast transformation between genomic DNA and a TAR vector containing short 5' and 3' gene-specific targeting hooks. Efficient gene capture requires a high yield of transformants, and we demonstrate here that the transformant yield increases similar to10-fold when the genomic DNA is sheared to 100-200 kb before being presented to the spheroplasts. Here we determine the most effective concentration of genomic DNA, and also show that the targeted sequences recombine much more efficiently with the vector's targeting hooks when they are located at the ends of the genomic DNA fragment. We demonstrate that the yield of gene-positive clones increases similar to20-fold after endonuclease digestion of genomic DNA, which caused double strand breaks near the targeted sequences. These findings have led to a greatly improved protocol. C1 NCI, Lab Biosyst & Canc, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Dong A Univ, Dept Biol, Pusan 604714, South Korea. Korea Basic Sci Inst, Proteome Anal Team, Taejon 305806, South Korea. RP Kouprina, N (reprint author), NCI, Lab Biosyst & Canc, Ctr Canc Res, NIH, Bldg 37,Room 5032, Bethesda, MD 20892 USA. NR 29 TC 22 Z9 24 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAR 15 PY 2003 VL 31 IS 6 AR e29 DI 10.1093/nar/gng029 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 655JE UT WOS:000181546900006 PM 12626728 ER PT J AU Nagatsugi, F Sasaki, S Miller, PS Seidman, MM AF Nagatsugi, F Sasaki, S Miller, PS Seidman, MM TI Site-specific mutagenesis by triple helix-forming oligonucleotides containing a reactive nucleoside analog SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SELECTIVE CROSS-LINKING; TARGETED GENE KNOCKOUT; SHUTTLE VECTOR PLASMID; MAMMALIAN-CELLS; SEQUENCE CONTEXT; DNA-POLYMERASES; 3RD STRAND; DUPLEX DNA; Y-FAMILY; CYTIDINE AB The specific recognition of homopurine-homo pyrimidine regions in duplex DNA by triplex-forming oligonucleotides (TFOs) provides an attractive strategy for genetic manipulation. Alkylation of nucleobases with functionalized TFOs would have the potential for site-directed mutagenesis. Recently, we demonstrated that a TFO bearing 2-amino-6-vinylpurine derivative, 1, achieves triplex-mediated reaction with high selectivity toward the cytosine of the G-C target site. In this report, we have investigated the use of this reagent to target mutations to a specific site in a shuttle vector plasmid, which replicates in mammalian cells. TFOs bearing 1 produced adducts at the complementary position of 1 and thereby introduced mutations at that site during replication/repair of the plasmid in mammalian cells. Reagents that produce covalent cytosine modifications are relatively rare. These TFOs enable the preparation of templates carrying targeted cytosine adducts for in vitro and in vivo studies. The ability to target mutations may prove useful as a tool for studying DNA repair, and as a technique for gene therapy and genetic engineering. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Kyushu Univ, Grad Sch Pharmaceut Sci, CREST,JST, Higashi Ku, Fukuoka 812, Japan. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. RP Seidman, MM (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. NR 49 TC 24 Z9 24 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAR 15 PY 2003 VL 31 IS 6 AR e31 DI 10.1093/nar/gng031 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 655JE UT WOS:000181546900008 PM 12626730 ER PT J AU Shannon-Weickert, C Wyatt, JE Lipska, BK Kleinman, JE Webster, MJ AF Shannon-Weickert, C Wyatt, JE Lipska, BK Kleinman, JE Webster, MJ TI Reduction of GAD-67 MRNA in the striatum of patients with schizophrenia and bipolar disorder SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 NIMH, CBDB, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 66 EP 66 DI 10.1016/S0920-9964(03)80583-2 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700198 ER PT J AU Weickert, TW Goldberg, TE Bigelow, LB Hyde, T Egan, MF Weinberger, DR AF Weickert, TW Goldberg, TE Bigelow, LB Hyde, T Egan, MF Weinberger, DR TI Language system abnormalities in patients with schizophrenia: Syntactic deficits are related to prefrontal function, thought disorder, and abnormal movement SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 NIMH, CBDB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 185 EP 185 DI 10.1016/S0920-9964(03)81085-X PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700557 ER PT J AU Gogtay, N Sporn, A Nicolson, R Classen, L Greenstein, D Giedd, JN Gochman, P Lenane, M Evans, A Rapoport, JL AF Gogtay, N Sporn, A Nicolson, R Classen, L Greenstein, D Giedd, JN Gochman, P Lenane, M Evans, A Rapoport, JL TI Progressive cortical gray matter loss in adolescence is specific to schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008; Giedd, Jay/A-3080-2008; Nicolson, Robert/E-4797-2011; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 196 EP 196 DI 10.1016/S0920-9964(03)81116-7 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700590 ER PT J AU Roberts, B Schooler, C Caplan, LJ AF Roberts, B Schooler, C Caplan, LJ TI Comparison of auditory and visually guided saccades and antisaccades in schizophrenic and control subjects SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 268 EP 268 DI 10.1016/S0920-9964(03)80418-8 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700797 ER PT J AU Sporn, AL Greenstein, D Gogtay, N Lenane, M Gochman, P Mattai, A Tossell, J Rapoport, JL AF Sporn, AL Greenstein, D Gogtay, N Lenane, M Gochman, P Mattai, A Tossell, J Rapoport, JL TI Predictors of two-year follow-up in children and adolescents with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 NIMH, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 304 EP 304 DI 10.1016/S0920-9964(03)80229-3 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700904 ER PT J AU Roth, BL Meltzer, HY Kroeze, WK Evans, JM Lopez, E AF Roth, BL Meltzer, HY Kroeze, WK Evans, JM Lopez, E TI Screening the 'receptorome' to discover novel proximal molecular targets of atypical antipsychotic drug actions SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 Case Western Reserve Univ, Sch Med, NIMH Psychoact Drug Screening Program, Cleveland, OH USA. RI Roth, Bryan/F-3928-2010; Meltzer, Herbert/E-8131-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 314 EP 315 DI 10.1016/S0920-9964(03)80261-X PG 2 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700936 ER PT J AU Justice, CM Miller, NH Marosy, B Zhang, J Wilson, AF AF Justice, CM Miller, NH Marosy, B Zhang, J Wilson, AF TI Familial idiopathic scoliosis - Evidence of an X-linked susceptibility locus SO SPINE LA English DT Article DE scoliosis; genetics; X chromosome ID PREVALENCE; GENETICS; TWINS AB Study Design. A genomic screen and statistical linkage analysis of a large sample of families with individuals having idiopathic scoliosis was performed. Objectives. To identify an X-linked susceptibility locus involved in the expression of familial idiopathic scoliosis. Summary of Background Data. A large sample of families with individuals having idiopathic scoliosis ( 202 families; 1198 individuals) were diagnosed through physical examination and radiographic criteria, and genomic screening and genetic linkage analyses were performed. Methods. Model-independent linkage analysis was used to screen genotyping data from 15 X-linked markers in 202 families ( 1198 individuals). Families were stratified based on the ratio of the likelihood of an X-linked dominant (XLD) inheritance model relative to that of an autosomal dominant (AD) model. Both model-independent and model- dependent linkage analyses were used to identify potential candidate regions. Results. When the entire set of families were analyzed with model- independent methods, no result was significant at the 0.05 level for any of the markers. However, when the families were stratified based on the ratio of the likelihood of the X-linked dominant to autosomal dominant mode of inheritance, results from model- dependent linkage analysis of 15% of the families most likely to have X-linked dominant inheritance showed six adjacent markers with positive lod score values and a maximum lod score of 1.69 (theta = 0.2) at marker GATA172D05. A lod score of 2.23 at this same marker was found in a single family with six affected individuals. Conclusion. The results suggest that a region on the X chromosome may be linked to the expression of familial idiopathic scoliosis in a subset of these families. C1 Johns Hopkins Univ, Baltimore, MD USA. NHGRI, Genomet Sect, NIH, Baltimore, MD USA. RP Miller, NH (reprint author), 610 N Caroline St, Baltimore, MD 21287 USA. EM nmillerb@jhmi.edu RI Wilson, Alexander/C-2320-2009 FU NCRR NIH HHS [1 P41 RR03655]; NHGRI NIH HHS [N01-HG-65403] NR 30 TC 79 Z9 95 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAR 15 PY 2003 VL 28 IS 6 BP 589 EP 594 DI 10.1097/00007632-200303150-00014 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 658FK UT WOS:000181710800013 PM 12642767 ER PT J AU Mazumdar, M Liu, AY AF Mazumdar, M Liu, AY TI Group sequential design for comparative diagnostic accuracy studies SO STATISTICS IN MEDICINE LA English DT Article DE receiver operating characteristic (ROC) analysis; area under the curve (AUC); Brownian motion ID SAMPLE-SIZE DETERMINATION; CLINICAL-TRIALS; COLORECTAL-CANCER; INFORMATION; RECURRENT; BOUNDARIES; CURVES; TESTS; PET AB In the field of diagnostic medicine, comparative clinical trials are necessary for assessing the utility of one diagnostic test over another. The area under the receiver operating characteristic (ROC) curve, commonly referred to as AUC, is a general measure of a test's inherent ability to distinguish between patients with and without a condition. Standardized AUC difference is the most frequently used statistic for comparing two diagnostic tests. In therapeutic comparative clinical trials with sequential patient entry, fixed sample design (FSD) is unjustified on ethical and economical grounds and group sequential design (GSD) is frequently used. In this paper, we argue that the same reasoning exists for the comparative clinical trials in diagnostic medicine and hence GSD should be utilized in this field for designing trials. Since computation of the stopping boundaries of GSD and data analysis after a group sequential test rely heavily on Brownian motion approximation, we derive the asymptotic distribution of the standardized AUC difference statistic and point out its resemblance to the Brownian motion. Boundary determination and sample size calculation are then illustrated through an example from a cancer clinical trial. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. RP Mazumdar, M (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave,Box 44, New York, NY 10021 USA. OI Liu, Aiyi/0000-0002-6618-5082 FU NCI NIH HHS [CA 80982, CA 82534] NR 34 TC 17 Z9 17 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 2003 VL 22 IS 5 BP 727 EP 739 DI 10.1002/sim.1386 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 649YW UT WOS:000181236400005 PM 12587102 ER PT J AU Chrapusta, SJ Egan, MF Wyatt, RJ Weinberger, DR Lipska, BK AF Chrapusta, SJ Egan, MF Wyatt, RJ Weinberger, DR Lipska, BK TI Neonatal ventral hippocampal damage modifies serum corticosterone and dopamine release responses to acute footshock in adult Sprague-Dawley rats SO SYNAPSE LA English DT Article DE schizophrenia; neurodevelopmental model; ibotenic acid; stress; 3-methoxytyramine; frontal cortex ID NUCLEUS-ACCUMBENS; PREFRONTAL CORTEX; PREPULSE INHIBITION; BILATERAL LESION; DORSAL STRIATUM; PRENATAL STRESS; FRONTAL-CORTEX; ANIMAL-MODEL; SCHIZOPHRENIA; GLUCOCORTICOIDS AB Rats with excitotoxic neonatal ventral hippocampal lesions (NVHL) manifest in early adulthood a variety of behavioral and neurochemical abnormalities mimicking those seen in patients with schizophrenia. Some of these aberrations implicate malfunction of the midbrain dopamine systems. We studied NVHL effects on dopamine release in the rat frontal cortex, nucleus accumbens, and striatum during acute stress caused by inescapable continuous footshock (0.45 mA). Serum total corticosterone and prolactin levels were used as peripheral indices of stress. As an indirect index of dopamine release, tissue 3-methoxytyramine levels attained in vivo 10 min after monoamine oxidase inhibition was assayed in rats sacrificed by instantaneous microwave fixation of the brain tissue. Nonshocked NVHL rats showed significantly less nucleus accumbens' 3-methoxytyramine accumulation than their sham counterparts. Frontal cortical 3-methoxytyramine levels rose similarly after 20-min footshock in both groups of rats, but while it normalized after 60-min footshock in the sham rats, it did not decrease in the NVHL rats. Nucleus accumbens' 3-methoxytyramine was significantly elevated after either 20-min or, 60-min footshock in both groups, whereas striatal 3-methoxytyramine was significantly elevated in the NVHL rats only. Serum corticosterone showed similar elevations in the sham and NVHL rats, but the patterns differed in that there was no attenuation after 60-min footshock in the latter. The lesion did not affect serum prolactin response. These data indicate that neonatal ventral hippocampal damage enhances and prolongs certain neural and neuroendocrine responses to acute physical stressor(s), and thus may affect adaptation and enhance detrimental effects of stress. C1 Polish Acad Sci, Med Res Ctr, Lab Expt Pharmacol, PL-02106 Warsaw, Poland. NIMH, Neuropsychiat Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Chrapusta, SJ (reprint author), Polish Acad Sci, Med Res Ctr, Lab Expt Pharmacol, 5 Pawinskiego St, PL-02106 Warsaw, Poland. EM chrapuss@medres.cmdik.pan.pl NR 70 TC 30 Z9 31 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-4476 EI 1098-2396 J9 SYNAPSE JI Synapse PD MAR 15 PY 2003 VL 47 IS 4 BP 270 EP 277 DI 10.1002/syn.10179 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 641BG UT WOS:000180723700005 PM 12539200 ER PT J AU Nadri, C Lipska, BK Kozlovsky, N Weinberger, DR Belmaker, RH Agam, G AF Nadri, C Lipska, BK Kozlovsky, N Weinberger, DR Belmaker, RH Agam, G TI Glycogen synthase kinase (GSK)-3 beta levels and activity in a neurodevelopmental rat model of schizophrenia SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE GSK-3; neurodevelopment; animal model; schizophrenia ID EXCITOTOXIC HIPPOCAMPAL DAMAGE; PREFRONTAL CORTEX; SOCIAL-BEHAVIOR; FRONTAL-CORTEX; IBOTENIC ACID; LITHIUM; EXPRESSION; PATHWAY; IMMUNOREACTIVITY; NEURONS AB We have previously reported reduced GSK-3beta protein levels and GSK-3 total (alpha+beta isoforms) activity in postmortem frontal cortex of schizophrenic patients. We now studied whether GSK-3beta is altered in the frontal cortex of rats with the neonatal excitotoxic hippocampal lesion used as a model of schizophrenia. Rats were infused with ibotenic acid (or artificial CSF in controls) bilaterally into the ventral hippocampus (VH) at postnatal day 7, then killed at postnatal day 35 (pre-puberty) or 56 (post-puberty). GSK-3beta protein levels were reduced in the frontal cortex of the lesioned rats as compared to sham animals; post-hoc comparisons revealed that the reduction was statistically significant at a pre-pubertal age. Total GSK-3 (alpha+beta) activity was not different between lesioned and sham rats at any age. These results demonstrate that reduced frontal cortical GSK-3beta levels may occur as a result of neonatal hippocampal damage and suggest that this animal model may be utilized to study the mechanism of GSK-3 reduction in schizophrenia, a disorder in which postmortem changes in GSK-3 were found. Published by Elsevier Science B.V. C1 Mental Hlth Ctr, Psychiat Res Unit, IL-84170 Beer Sheva, Israel. Ben Gurion Univ Negev, Fac Hlth Sci, Stanley Res Ctr, IL-84105 Beer Sheva, Israel. NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. RP Agam, G (reprint author), Mental Hlth Ctr, Psychiat Res Unit, POB 4600, IL-84170 Beer Sheva, Israel. NR 31 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD MAR 14 PY 2003 VL 141 IS 1-2 BP 33 EP 37 DI 10.1016/S0165-3806(02)00639-9 PG 5 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 662YD UT WOS:000181976200004 ER PT J AU Akahane, T Akahane, M Connor, CM Thorgeirsson, UP AF Akahane, T Akahane, M Connor, CM Thorgeirsson, UP TI Tissue inhibitor of metalloproteinase-1 suppresses endothelial cell migration through down-regulation of angiopoietin-1 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A688 EP A688 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733103242 ER PT J AU Akbar, M Calderon, ZM Kim, HY AF Akbar, M Calderon, ZM Kim, HY TI N-3 fatty acid deficiency increases neuronal apoptosis in a phosphatidylserine dependent manner SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIAAA, LMBB, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A170 EP A170 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100822 ER PT J AU Bromberg, S Twigger, S Nigam, R Hughes, A Mathis, J Lu, J Shimoyama, M Pasko, D Chen, CF Gopinathrao, G Dela Cruz, N Ginster, J Ramachandran, H Maglott, D Eppig, J Stahl, F Tonellato, P AF Bromberg, S Twigger, S Nigam, R Hughes, A Mathis, J Lu, J Shimoyama, M Pasko, D Chen, CF Gopinathrao, G Dela Cruz, N Ginster, J Ramachandran, H Maglott, D Eppig, J Stahl, F Tonellato, P TI Rat Genome Database: A comparative gemonics platform for rat, mouse and human SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Med Coll Wisconsin, Bioinformat Res Ctr, Milwaukee, WI 53226 USA. NIH, NCBI, Bethesda, MD 20892 USA. Jackson Lab, MGI, Bar Harbor, ME 04609 USA. Univ Gothenburg, RatMap, Gothenburg, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A491 EP A492 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102322 ER PT J AU Cai, Q Ferraris, JD Burg, MB AF Cai, Q Ferraris, JD Burg, MB TI Greater tolerance of renal medullary cells for a gradual increase in osmolality is associated with greater expression of osmo-protective genes. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A91 EP A91 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100440 ER PT J AU Chan, LMS Sweet, DH Walden, R Nigam, SK Beier, DR Miller, DS Pritchard, JB AF Chan, LMS Sweet, DH Walden, R Nigam, SK Beier, DR Miller, DS Pritchard, JB TI Mouse organic anion transporter 3 (Oat3 (Slc22a8)) is a dicarboxylate exchanger indirectly coupled to the sodium gradient SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. MUSC, Dept Pharm Sci, Charleston, SC USA. UCSD, Dept Cell & Mol Med, La Jolla, CA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A478 EP A478 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102259 ER PT J AU Chattopadhyay, MK Tabor, CW Tabor, H AF Chattopadhyay, MK Tabor, CW Tabor, H TI Oxidative stress causes death of polyamine-deficient Escherichia coli mutants SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIDDK, LBG, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A588 EP A588 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102772 ER PT J AU Chen, SY Samuel, W Fariss, RN Duncan, T Kutty, RK Wiggert, B AF Chen, SY Samuel, W Fariss, RN Duncan, T Kutty, RK Wiggert, B TI Differentiation of fenretinide treated human retinal pigment epithelial (RPE) cells into neuronal phenotype is associated with an increase in Hsp70 expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NEI, LRCMB, Bethesda, MD 20892 USA. NEI, LMOD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A590 EP A590 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102780 ER PT J AU Chen, Y Williams, CK Burg, MB Ferraris, JD AF Chen, Y Williams, CK Burg, MB Ferraris, JD TI Casein kinase I associates with TonEBP/OREBP and stimulates tonicity-induced increase in transactivating activity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NHLBI, LKEM, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A482 EP A483 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102281 ER PT J AU Chen, YP Ferguson, SS Negishi, M Goldstein, JA AF Chen, YP Ferguson, SS Negishi, M Goldstein, JA TI Identification of glucocorticoid receptor (GR) and constitutive androstane receptor (CAR) binding sites in the promoter of CYP2C19 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A240 EP A240 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101153 ER PT J AU Choi, MS Anderson, MA Zhang, ZJ Zimonjic, DB Popescu, N Mukherjee, AB AF Choi, MS Anderson, MA Zhang, ZJ Zimonjic, DB Popescu, N Mukherjee, AB TI Role of murine neutral/alkaline ceramidase in preventing ceramide-induced apoptosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NICHD, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Digene Corp, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A167 EP A167 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100805 ER PT J AU Choi, YH Park, SH Hockman, S Haluzik, M Gavrilova, O Degerman, E Manganiello, VC AF Choi, YH Park, SH Hockman, S Haluzik, M Gavrilova, O Degerman, E Manganiello, VC TI Insulin resistance in Phosphodiesterase 3B knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NIDDK, DB, NIH, Bethesda, MD 20892 USA. Lund Univ, CMB, Lund, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A593 EP A593 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102792 ER PT J AU DeLozier, TC Tang, J Rose, R Xi, T Mohrenweiser, HW Goldstein, JA AF DeLozier, TC Tang, J Rose, R Xi, T Mohrenweiser, HW Goldstein, JA TI Identification of human CYP2B6 single nucleotide polymorphisms in racially and ethnically diverse groups SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. Lawrence Livermore Natl Lab, Livermore, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A239 EP A239 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101150 ER PT J AU Desai, RI Kopajtic, T Newman, AH Katz, JL AF Desai, RI Kopajtic, T Newman, AH Katz, JL TI In vivo binding and behavioral effects of benztropine analogs SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIDA, Medicat Dev Div, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A204 EP A204 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100985 ER PT J AU Dixon, LB Virtanen, M Balder, E Rashidkhani, B AF Dixon, LB Virtanen, M Balder, E Rashidkhani, B CA DIETSCAN Grp TI Dietary patterns and colon and rectal cancers: Results from the DIETSCAN Project SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Bethesda, MD 20892 USA. NYU, New York, NY 10012 USA. Natl Publ Hlth Inst, Helsinki, Finland. TNO Nutr & Food Res, Zeist, Netherlands. Karolinska Inst, Stockholm, Sweden. Ist Nazl Studio & Cura Tumori, I-20133 Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A693 EP A693 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733103264 ER PT J AU Dobbins, DE Wilder, RL Remmers, EF AF Dobbins, DE Wilder, RL Remmers, EF TI An improved radiation hybrid map of the Cia3 region of rat chromosome 4 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. MedImmune Inc, Clin Dev, Gaithersburg, MD 20878 USA. NIAMS, Genet & Genom Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A492 EP A493 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102327 ER PT J AU Dunham, CL Weiss, JE Qin, LY Liu, B Hong, JS Cooper, CL AF Dunham, CL Weiss, JE Qin, LY Liu, B Hong, JS Cooper, CL TI Optimization of a mixed culture system for microglia and neurons using immortalized cell lines SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Truman State Univ, Div Sci, Kirksville, MO 63501 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A235 EP A236 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101132 ER PT J AU Freebern, WJ Haggerty, CM McNutt, MC Smith, JL Hoover, PJ Montano, I Gardner, K AF Freebern, WJ Haggerty, CM McNutt, MC Smith, JL Hoover, PJ Montano, I Gardner, K TI Profiling of transcriptional targets through a combinatorial approach SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A602 EP A603 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102839 ER PT J AU Freebern, WJ Hoover, PJ Smith, JL Haggerty, CM Gardner, K AF Freebern, WJ Hoover, PJ Smith, JL Haggerty, CM Gardner, K TI p73, an oncogene? SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A187 EP A187 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100905 ER PT J AU Fritz, A Solomon, KS Kudoh, T Mackereth, MD Dawid, IB AF Fritz, A Solomon, KS Kudoh, T Mackereth, MD Dawid, IB TI Early development of the otic placode in zebrafish SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Emory Univ, Dept Biol, Atlanta, GA 30322 USA. NICDH, Genet Mol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A380 EP A381 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101808 ER PT J AU Gelderman, MP Oliver, KL Yazdani, AT Murray, GJ Holtz, RB Brady, RO AF Gelderman, MP Oliver, KL Yazdani, AT Murray, GJ Holtz, RB Brady, RO TI Pre-clinical studies with plant-produced alpha-galactosidase A in the murine analog of Fabry disease SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NINDS, DMNB, NIH, Bethesda, MD 20892 USA. NINDS, DMNB, LSBC Corp, Vacaville, CA 95688 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A166 EP A166 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100799 ER PT J AU Goldstein, DS Brentzel, S Holmes, C Eldadah, B Sharabi, Y AF Goldstein, DS Brentzel, S Holmes, C Eldadah, B Sharabi, Y TI Association between supine hypertension and orthostatic hypotension in chronic autonomic failure SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A19 EP A20 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100096 ER PT J AU Goodman, MF Pham, P Schlacher, K Seitz, E O'Donnell, M Woodgate, R Cox, MM AF Goodman, MF Pham, P Schlacher, K Seitz, E O'Donnell, M Woodgate, R Cox, MM TI Biochemical basis of SOS mutagenesis in E. coli involving DNA polymerase V and two non-filamentous modes of RecA action SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ So Calif, Los Angeles, CA 90089 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. Univ Wisconsin, Madison, WI USA. NIH, Sect DNA Replicat Repair & Mutagenesis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A560 EP A560 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102633 ER PT J AU Haggerty, CM Freebern, WJ Smith, JL McNutt, MC Hoover, PJ Montano, I Gardner, K AF Haggerty, CM Freebern, WJ Smith, JL McNutt, MC Hoover, PJ Montano, I Gardner, K TI Profiling of transcriptional targets SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A675 EP A675 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733103180 ER PT J AU Hempel, N McManus, ME Negishi, M AF Hempel, N McManus, ME Negishi, M TI Gene regulation of human SULT1A sulfotransferases SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia. NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, Res Triangle Pk, NC 27709 USA. RI Hempel, Nadine/F-1700-2014 OI Hempel, Nadine/0000-0002-5574-8783 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A242 EP A242 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101160 ER PT J AU Hong, HHL Devereux, TR Moomaw, C Clayton, N Boorman, GA Dunnick, J Sills, RC AF Hong, HHL Devereux, TR Moomaw, C Clayton, N Boorman, GA Dunnick, J Sills, RC TI Genetic alterations in B-Catenin,P53 and K-ras genes and overexpression of cyclin D1 contribute to 0-nitrotoluene-induced large intestinal carcinogenesis in B6C3F1 mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIEHS, LEP, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, LMC, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, TOB, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A674 EP A674 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733103173 ER PT J AU Hoover, P Freebern, WJ Smith, JL McNutt, MC Gardner, K AF Hoover, P Freebern, WJ Smith, JL McNutt, MC Gardner, K TI p73: Revealing possible molecular mechanisms for a dominant negative and divergent role SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20877 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A672 EP A672 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733103166 ER PT J AU Jensen, A Praetorius, H Li, CL Knepper, MA Nielsen, S Frokiaer, J AF Jensen, A Praetorius, H Li, CL Knepper, MA Nielsen, S Frokiaer, J TI Candesartan prevents downregulation of AQP2, NaPi2 and BSC-1 and reduces polyuria after release of bilateral ureter obstruction in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Aarhus, Water & Salt Res Ctr, DK-8200 Aarhus, Denmark. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A483 EP A483 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102284 ER PT J AU Johnson, AC Rikiyama, T Oikawa, M Wilson, MA AF Johnson, AC Rikiyama, T Oikawa, M Wilson, MA TI GCF2 represses HIV-LTR transcription SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Lab Mol, Ctr Canc Res Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A186 EP A186 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100897 ER PT J AU Jozwiak, K Ravichandran, S Collins, JR Wainer, IW AF Jozwiak, K Ravichandran, S Collins, JR Wainer, IW TI Molecular interactions of alpha 3 beta 4 nicotinic acetylcholine receptor (nAChR) with its luminal non-competitive inhibitors: comparison of experimental chromatographic data with in silico docking studies SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIA, NIH, Baltimore, MD 21224 USA. NCI, SAIC Frederick, NIH, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A626 EP A626 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102950 ER PT J AU Kant, AK Graubard, BI AF Kant, AK Graubard, BI TI Weekly frequency of consuming commercially prepared meals by adult Americans: 1987-2000: Predictors and correlates SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 CUNY Queens Coll, Flushing, NY 11367 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A297 EP A297 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101414 ER PT J AU Katz, JL Libby, T Kopajtic, T Husbands, SM Newman, AH AF Katz, JL Libby, T Kopajtic, T Husbands, SM Newman, AH TI Behavioral effects of rimcazole analogues alone and in combination with cocaine SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RI Husbands, Stephen/D-5926-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A205 EP A206 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100992 ER PT J AU Kuznia, P Harris, T Heshka, S Albur, J Heymsfield, S Goodpaster, B Visser, M Gallagher, D AF Kuznia, P Harris, T Heshka, S Albur, J Heymsfield, S Goodpaster, B Visser, M Gallagher, D TI Thigh muscle adipose tissue infiltration versus total body SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIA, Geriatr Epidemiol Sect, Bethesda, MD 20892 USA. Columbia Univ, St Lukes Roosevelt Hosp, Obes Res Ctr, Inst Human Nutr, New York, NY USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. VUMC, EMGO, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A744 EP A744 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733103498 ER PT J AU Lamping, KG Wess, J Nuno, DW Faraci, FM AF Lamping, KG Wess, J Nuno, DW Faraci, FM TI Cholinergic receptors in the marine coronary circulation: Role of M2 and M3 muscarinic receptors in responses to acetylcholine SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Iowa, Dept Internal Med, Iowa City, IA 52246 USA. Vet Adm Med Ctr, Iowa City, IA 52246 USA. NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A507 EP A507 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102394 ER PT J AU Leak, LVLV Petricoin, EF Liotta, LA Jones, M AF Leak, LVLV Petricoin, EF Liotta, LA Jones, M TI Proteomic technologies to study lymphangiogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Howard Univ, Coll Med, Washington, DC 20059 USA. US FDA, Div Therapeut Prod, Bethesda, MD USA. NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A554 EP A554 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102606 ER PT J AU Lee, SJ Usmani, K Chanas, B Xi, T Mohrenweiser, H Goldstein, J AF Lee, SJ Usmani, K Chanas, B Xi, T Mohrenweiser, H Goldstein, J TI Identification and characterization of polymorphic variants of CYP3A5 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. Lawrence Livermore Natl Lab, Resequencing Grp, Livermore, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A240 EP A240 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101151 ER PT J AU Lee, SJ Usmani, K Chanas, B Xi, TN Mohrenweiser, H Goldstein, J AF Lee, SJ Usmani, K Chanas, B Xi, TN Mohrenweiser, H Goldstein, J TI Identification and characterization of poly morphic variants of CYP3A5 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. Lawrence Livermore Natl Lab, Resequencing Grp, Livermore, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A199 EP A199 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100961 ER PT J AU Liang, W Austin, S Hoang, Q Fishman, PH AF Liang, W Austin, S Hoang, Q Fishman, PH TI Insensitivity of the human beta(1)-adrenergic receptor (beta(1)AR) to agonist-mediated degradation: intracellular trafficking and role of the c-terminus SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NINDS, Bethesda, MD 20892 USA. Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A211 EP A211 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101016 ER PT J AU Lightfoot, JT Turner, MJ Lowe, AM Lindley, MTG Kleeberger, SR AF Lightfoot, JT Turner, MJ Lowe, AM Lindley, MTG Kleeberger, SR TI Genetic influence on daily physical activity level (PAL) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ N Carolina, Charlotte, NC 28223 USA. NIEHS, Pulm Pathobiol Lab, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A534 EP A534 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102512 ER PT J AU Lightfoot, JT Turner, MJ Jedlicka, A AF Lightfoot, JT Turner, MJ Jedlicka, A TI Genome scan for maximal aerobic capacity quantitative trait loci (QTL) in inbred mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ N Carolina, Charlotte, NC 28223 USA. Johns Hopkins Univ, Baltimore, MD USA. NIEHS, Pulm Pathobiol Lab, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A534 EP A534 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102511 ER PT J AU Lin, Y Wani, M Linu, ZG AF Lin, Y Wani, M Linu, ZG TI Tumor necrosis factor (TNF) signaling-independent activation of gene expression by TNFR-associated factor 2 (TRAF2): a potential mechanism of apoptosis regulation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Canc & Cell Biol Branch, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A194 EP A194 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100938 ER PT J AU Lowes, S Sykes, DB Pritchard, JB Miller, DS AF Lowes, S Sykes, DB Pritchard, JB Miller, DS TI Na+-dependent, Oat3-mediated organic anion uptake by rat choroid plexus (CP) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A477 EP A477 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102256 ER PT J AU Lozanoff, S Uyehara, CFT Ma, WB Himenes, M AF Lozanoff, S Uyehara, CFT Ma, WB Himenes, M TI Endothelin-1 and Na,K-ATPase expression and function in the kidney of mice with renal hypodysplasia and hypertension SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Hawaii, Sch Med, Honolulu, HI 96822 USA. Tripler Army Med Ctr, Honolulu, HI 96859 USA. NCI, Immunol Lab, Frederick, MD USA. Univ Hawaii, Lab Anim Serv, Honolulu, HI 96822 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A103 EP A103 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100497 ER PT J AU Masciarelli, S Liu, CY Park, SH Hockman, S Jin, C Conti, M Manganiello, V AF Masciarelli, S Liu, CY Park, SH Hockman, S Jin, C Conti, M Manganiello, V TI Cyclic nucleotide phosphodiesterase 3A (PDE3A) is essential for mouse oocyte maturation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NHLBI, NIH, Bethesda, MD 20892 USA. Stanford Univ, Med Ctr, Sch Med, Dept Gynecol & Obstet, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A588 EP A588 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102771 ER PT J AU Masereeuw, R Notenboom, S Kuik, LH Russel, FGM Miller, DS AF Masereeuw, R Notenboom, S Kuik, LH Russel, FGM Miller, DS TI Short-term gentamicin exposure to renal proximal tubule has long-term intracellular signaling consequences SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Med Ctr Nijmegen, Dept Pharmacol & Toxicol 233, NL-6500 HB Nijmegen, Netherlands. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014 OI Russel, Frans/0000-0002-7959-2314; NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A478 EP A479 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102262 ER PT J AU Matsumoto, RR Potelleret, FH Mack, AL Pouw, B Zhang, Y Bowen, WD AF Matsumoto, RR Potelleret, FH Mack, AL Pouw, B Zhang, Y Bowen, WD TI Attenuation of cocaine-induced convulsions by YZ-069 and four analogs: structure-activity comparisons in receptor binding and behavioral studies SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Oklahoma, Hlth Sci Ctr, Dept Pharmaceut Sci, Oklahoma City, OK 73190 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A206 EP A206 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100993 ER PT J AU Mc Loughlin, TJ Hornberger, TA Leszczynski, JK Bowen, PE Hwang, ES Hao, HL Moustafa, ME Carlson, BA Hatfield, DL Diamond, AM Esser, KA AF Mc Loughlin, TJ Hornberger, TA Leszczynski, JK Bowen, PE Hwang, ES Hao, HL Moustafa, ME Carlson, BA Hatfield, DL Diamond, AM Esser, KA TI Enhanced exercise-induced muscle adaptation in selenoprotein-deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Illinois, Chicago, IL 60608 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A439 EP A439 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102079 ER PT J AU McNutt, MC Smith, JL Gardner, K AF McNutt, MC Smith, JL Gardner, K TI Prospects in data mining: bioinformatic tools for gene regulatory pathway studies SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A388 EP A388 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101843 ER PT J AU Meng, JP Tsai-Morris, CH Dufau, ML AF Meng, JP Tsai-Morris, CH Dufau, ML TI Human prolactin receptor isoforms in breast cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NICHD, Sect Mol Endocrinol, ERRB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A449 EP A449 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102125 ER PT J AU Millen, AE Subar, AF AF Millen, AE Subar, AF TI Trends in use of vitamin and mineral supplements in the United States from 1987 to 2000 including usage of non-vitamin/non-mineral supplements in 2000: The 1987, 1992 and 2000 national health interview surveys (NHIS) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A711 EP A711 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733103347 ER PT J AU Morris, RG Chou, CL Knepper, MA AF Morris, RG Chou, CL Knepper, MA TI "Corticalization" of the inner medulla of aquaporin-1 null mice: studies in gene expression and transport SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A103 EP A103 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100495 ER PT J AU Movsesian, MA Krall, J Manganiello, VC AF Movsesian, MA Krall, J Manganiello, VC TI Role of PDE3A-136 in compartment-selective regulation of cAMP and cGMP-mediated signaling in cardiac and vascular myocytes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 VA Salt lake City Hlth Care Syst, Cardiol Sect, Salt Lake City, UT 84103 USA. Univ Utah, Salt Lake City, UT 84103 USA. NHLBI, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A605 EP A605 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102852 ER PT J AU Naya, T Shizukuda, Y Maledowicz, S Evans, TR AF Naya, T Shizukuda, Y Maledowicz, S Evans, TR TI GATA6 is expressed in adult cardiac myocytes: Its functional role on cardiac hypertrophy and contractile function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Illinois, Chicago, IL 60612 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A527 EP A527 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102480 ER PT J AU Nini, L Hiol, A Jones, TLZ AF Nini, L Hiol, A Jones, TLZ TI Candidates for the protein acyltransferase by in vitro expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Inst Nutr, Lab Chem & Applicated Biol, Marseille, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A170 EP A170 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100821 ER PT J AU Novoradovskaya, N Perou, C Whitfield, ML Basehore, S Pesich, R Aprelikova, O Fero, M Brown, PO Botstein, D Braman, J AF Novoradovskaya, N Perou, C Whitfield, ML Basehore, S Pesich, R Aprelikova, O Fero, M Brown, PO Botstein, D Braman, J TI Universal human, mouse & rat reference RNA as standards for microarray gene expression analysis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 STRATAGNE, R&D, La Jolla, CA 92037 USA. Univ N Carolina, Dept Genet, Chapel Hill, NC USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A78 EP A78 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100378 ER PT J AU Oriji, GK AF Oriji, GK TI Role of metoprolol, B1-adrenoceptor antagonist, thromboxane A2 and nitric oxide in CsA-induced hypertension SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NHLBI, NIH, Bethesda, MD 20892 USA. WPUNJ, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A111 EP A112 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100535 ER PT J AU Overduin, MJ Capelluto, D Finkielstein, C Kutateladze, TA Prestwich, G Ferguson, C He, X Habas, R Emr, SD AF Overduin, MJ Capelluto, D Finkielstein, C Kutateladze, TA Prestwich, G Ferguson, C He, X Habas, R Emr, SD TI Depth of FYVE domain membrane insertione and DIX domain's actin and vesicular localization SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. Echelon, Phosphoinositide Chem, Salt Lake City, UT USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. NIH, Bethesda, MD 20892 USA. UCSD, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A558 EP A558 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102625 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI FDA-NCI clinical proteomics progam: Applications at the bedside SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, FDA, Clin Proteom Program, Bethesda, MD 20892 USA. NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A380 EP A380 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101807 ER PT J AU Praetorius, HA Praetorius, J Frokiear, J Nielsen, S Spring, KR AF Praetorius, HA Praetorius, J Frokiear, J Nielsen, S Spring, KR TI Madin-Darby canine kidney cells express beta 1-integrin on their primary cilia SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Aarhus, Water & Salt Res Ctr, DK-8200 Aarhus, Denmark. NHLBI, LKEM, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A480 EP A480 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102270 ER PT J AU Praetorius, HA Frokiear, J Nielsen, S Spring, KR AF Praetorius, HA Frokiear, J Nielsen, S Spring, KR TI Bending the primary cilium of Madin-Darby, canine kidney cell opens Ca2+ sensitive, intermediate conductance K+ channels SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Aarhus, Water & Salt Res Ctr, DK-8200 Aarhus, Denmark. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A470 EP A470 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102221 ER PT J AU Prasad, VR Fisherr, TS Darden, T AF Prasad, VR Fisherr, TS Darden, T TI Substitutions at Phe61 of HIV-1 reverse transcriptase reveal a mechanistic basis for strand displacement DNA synthesis and a role for the fingers subdomain SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A599 EP A600 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102825 ER PT J AU Randazzo, PA Nie, ZZ Hirsch, D Yang, JS Hsu, VW AF Randazzo, PA Nie, ZZ Hirsch, D Yang, JS Hsu, VW TI The role of Arf GAPS in the generation of transport vesicles SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A366 EP A366 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101739 ER PT J AU Renfro, JL Villalobos, ARA Miller, DS Dehm, C AF Renfro, JL Villalobos, ARA Miller, DS Dehm, C TI Structural and biochemical changes in choroid plexus (CP) of Squalus acanthias in response to heat shock and zinc exposure SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Connecticut, Storrs, CT 06269 USA. Univ Rochester, Rochester, NY USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Mt Desert Isl Biol Lab, CMTS, Salsbury Cove, ME USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A75 EP A76 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100367 ER PT J AU Ricketts, SL Jahn, JE Carter, JC Theise, ND Conner, EA Thorgeirsson, SS Grisham, JW Coleman, WB AF Ricketts, SL Jahn, JE Carter, JC Theise, ND Conner, EA Thorgeirsson, SS Grisham, JW Coleman, WB TI Chromosome 11p11.2 allelotype in human hepatocellular carcinoma SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. NYU, Dept Pathol, New York, NY 10016 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A256 EP A256 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101226 ER PT J AU Roman, BL Pham, VN Vogel, AM Weinstein, BM AF Roman, BL Pham, VN Vogel, AM Weinstein, BM TI Mutations in kurzschluss cause aberrant aortic arch connections and compromise vascular and cardiac integrity in the zebrafish SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20007 USA. NICHD, Genet Mol Lab, NIH, Bethesda, MD USA. Artemis Pharmaceut, Tubingen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A351 EP A351 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101669 ER PT J AU Schwartz, EI Pinna, LA Maraia, RJ AF Schwartz, EI Pinna, LA Maraia, RJ TI Casein kinase 2 (CK2) phosphorylates the human La antigen in human cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NICHD, NIH, Bethesda, MD 20892 USA. Univ Padua, Dipartimento Chim Biol, Padua, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A190 EP A190 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100919 ER PT J AU Shimoyama, M Twigger, S Nigam, R Hughes, A Mathis, J Dela Cruz, N Lu, J Pasko, D Bromberg, S Chen, C Gopinathrao, G Ramachandran, H Hansen, C Critser, J Serikawa, T Rall, W Tonellato, P AF Shimoyama, M Twigger, S Nigam, R Hughes, A Mathis, J Dela Cruz, N Lu, J Pasko, D Bromberg, S Chen, C Gopinathrao, G Ramachandran, H Hansen, C Critser, J Serikawa, T Rall, W Tonellato, P TI Rat genome database - Disease model resource SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Med Coll Wisconsin, Bioinformat Res Ctr, Milwaukee, WI 53226 USA. NIH, Vet Resources Program, Bethesda, MD 20892 USA. Univ Missouri, Rat Resource & Res Ctr, Columbia, MO USA. Kyoto Univ, Inst Lab Anim, Kyoto, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A491 EP A491 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102321 ER PT J AU Shizukuda, Y Duque, K Buttrick, PM Larsen, P AF Shizukuda, Y Duque, K Buttrick, PM Larsen, P TI Transcriptional profiling of cultured adult rat cardiac myocytes: Analyses of DNA microarrays SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. Univ Illinois, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A79 EP A79 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100386 ER PT J AU Sweet, DH Chan, LMS Walden, R Yang, XP Miller, DS Pritchard, JB AF Sweet, DH Chan, LMS Walden, R Yang, XP Miller, DS Pritchard, JB TI Organic anion transporter 3 [Slc22a8] is a dicarboxylate exchanger indirectly coupled to the Na+ gradient SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A477 EP A478 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102258 ER PT J AU Tansey, JT Huml, AM Vogt, RA Davis, KE Jones, JM Fraser, KA Kimmel, AR Londos, C AF Tansey, JT Huml, AM Vogt, RA Davis, KE Jones, JM Fraser, KA Kimmel, AR Londos, C TI Protein kinase A-mediated phosphorylation of perilipin A regulates lipolysis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Otterbein Coll, Westerville, OH 43081 USA. NIDDK, LCDB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A593 EP A593 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102794 ER PT J AU Then, HT Nussenzweig, A Femandez-Capetillo, O Celeste, A AF Then, HT Nussenzweig, A Femandez-Capetillo, O Celeste, A TI DNA damage-induced G2/M checkpoint activation by historic H2AX and 53BP1 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A576 EP A577 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102713 ER PT J AU Torregrossa, MM Isgor, C Rice, KC Watson, S Woods, JH AF Torregrossa, MM Isgor, C Rice, KC Watson, S Woods, JH TI Stimulation of delta-opioid receptors increases BDNF mRNA expression in several brain regions SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Michigan, Neurosci Program, Ann Arbor, MI 48109 USA. Univ Michigan, Mental Hlth Res Inst, Ann Arbor, MI USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A203 EP A204 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100983 ER PT J AU Tsutsui, S Schnermann, J Power, C AF Tsutsui, S Schnermann, J Power, C TI Adenosine A1 receptor regulates inflammation at the severity of a murine model of multiple sclerosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Calgary, Calgary, AB T2N 4N1, Canada. NIDDK, NIH, Bethesda, MD USA. RI Power, Christopher/C-7181-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A657 EP A657 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733103095 ER PT J AU Turner, MJ Lightfoot, T Lindley, MT Lowe, AM Kleeberger, SR AF Turner, MJ Lightfoot, T Lindley, MT Lowe, AM Kleeberger, SR TI Genetic influence on age-related changes in daily physical activity level SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ N Carolina, Charlotte, NC 28223 USA. NIEHS, Pulm Pathobiol Lab, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A535 EP A535 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102515 ER PT J AU Wang, T Milner, M Kim, Y Milner, J AF Wang, T Milner, M Kim, Y Milner, J TI Effects of garlic-derived compound diallyl disulfide on prostate cancer cell LNCaP gene expression: cDNA microarray expression profiling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 USDA, Phytonutrients Lab, BHNRC, Beltsville, MD 20705 USA. NCI, Nutr Sci Res Grp, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A376 EP A376 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101787 ER PT J AU Wangemann, P White, EM Wu, T Albrecht, B Everett, LA Green, ED Marcus, DC AF Wangemann, P White, EM Wu, T Albrecht, B Everett, LA Green, ED Marcus, DC TI Pendrin-containing cochlear cells mediate DIDS-sensitive Cl-/OH- or formate(-) exchange and disruption of pendrin alters endocochlear pH homeostasis consistent with pendrin-mediated HCO3- secretion SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Kansas State Univ, Manhattan, KS 66506 USA. Univ Wurzburg, ENT Dept, Wurzburg, Germany. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A465 EP A465 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102198 ER PT J AU Weinstein, BM AF Weinstein, BM TI Imaging developing blood vessels in the zebrafish SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NICHD, LMG, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A345 EP A345 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101641 ER PT J AU Wolkowicz, MJ Shetty, J Westbrook, A Klotz, K Herr, J AF Wolkowicz, MJ Shetty, J Westbrook, A Klotz, K Herr, J TI Equatorial segment protein (ESP): An alloantigenic glycoprotein provides evidence for an equatorial segment subcompartment in acrosomal vesicle stage spermatids SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Virginia, Charlottesville, VA 22908 USA. NCBI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A356 EP A356 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101694 ER PT J AU Wu, JF Huang, KP Huang, FL AF Wu, JF Huang, KP Huang, FL TI Activations of group I metabotropic glutamate receptors and cholinergic muscarinic receptors elicit phosphorylation of neurogranin in the hippocampal slices SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NICHD, ERRB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A625 EP A625 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102946 ER PT J AU Wu, XH Rush, J Karaoglu, D Krasnewich, D Waechter, C Gilmore, R Lubinsky, M Freeze, H AF Wu, XH Rush, J Karaoglu, D Krasnewich, D Waechter, C Gilmore, R Lubinsky, M Freeze, H TI Deficiency of UDP-GlcNAc : dolichol phosphate N-acetyl-glucosamine-1 phosphate transferase causes a novel congenital disorder of glycosylation, type Ih SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Burnham Inst, Glycobiol Program, La Jolla, CA 92037 USA. Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY USA. Univ Massachusetts, Dept Mol Pharmacol & Biochem, Worcester, MA 01605 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Childres Hosp, GBD Ctr, Milwaukee, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A177 EP A177 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100853 ER PT J AU Ye, JP Gao, ZG Quon, M AF Ye, JP Gao, ZG Quon, M TI Role of IKK in regulation of insulin signaling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Pennington Biomed Res Ctr, Gene Regulat Lab, Baton Rouge, LA 70808 USA. NCCAM, Diabet Unit, NIH, Bethesda, MD USA. RI Quon, Michael/B-1970-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A592 EP A592 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102791 ER PT J AU Zhang, Z Ferraris, JD Brooks, HL Brisc, I Burg, MB AF Zhang, Z Ferraris, JD Brooks, HL Brisc, I Burg, MB TI TonEBP expression in tissues of normal and hypoosmotic rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 NHLBI, LKEM, NIH, Bethesda, MD 20892 USA. Univ Arizona, Dept Physiol, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A482 EP A482 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102279 ER PT J AU Zhao, XY Bradbury, JA Graves, J Zeldin, DC Imig, JD AF Zhao, XY Bradbury, JA Graves, J Zeldin, DC Imig, JD TI Hypertension is associated with an increased renal vascular reactivity to angiotensin II and endothelin in CYP2J5 null female mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Med Coll Georgia, Vasc Biol Ctr, Augusta, GA 30912 USA. Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA. NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A102 EP A102 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100492 ER PT J AU Mineo, C Yuhanna, IS Quon, MJ Shaul, PW AF Mineo, C Yuhanna, IS Quon, MJ Shaul, PW TI High density lipoprotein-induced endothelial nitric-oxide synthase activation is mediated by Akt and MAP kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FIBROBLAST GROWTH-FACTOR; ESTROGEN-RECEPTOR-ALPHA; SMOOTH-MUSCLE CELLS; PROTEIN-KINASE; SCAVENGER RECEPTOR; SHEAR-STRESS; CLASS-B; SIGNAL-TRANSDUCTION; DEPENDENT MANNER; PHOSPHORYLATION AB High density lipoprotein (HDL) activates endothelial nitric-oxide synthase (eNOS), leading to increased production of the antiatherogenic molecule NO. A variety of stimuli regulate eNOS activity through signaling pathways involving Akt kinase and/or mitogen-activated protein (MAP) kinase. In the present study, we investigated the role of kinase cascades in HDL-induced eNOS stimulation in cultured endothelial cells and COS M6 cells transfected with eNOS and the HDL receptor, scavenger receptor B-I. HDL (10-50 mug/ml, 20 min) caused eNOS phosphorylation at Ser-1179, and dominant negative Akt inhibited both HDL-mediated phosphorylation and activation of the enzyme. Phosphoinositide 3-kinase (P13 kinase) inhibition or dominant negative P13 kinase also blocked the phosphorylation and activation of eNOS by HDL. Studies with genistein and PP2 showed that the nonreceptor tyrosine kinase, Src, is an upstream stimulator of the P13 kinase-Akt pathway in this paradigm. In addition, HDL activated MAP kinase through P13 kinase, and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibition fully attenuated eNOS stimulation by HDL without affecting Akt or eNOS Ser-1179 phosphorylation. Conversely, dominant negative Akt did not alter HDL-induced MAP kinase activation. These results indicate that HDL stimulates eNOS through common upstream, Src-mediated signaling, which leads to parallel activation of Akt and MAP kinases and their resultant independent modulation of the enzyme. C1 Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX 75390 USA. NIH, Diabet Unit, Clin Invest Lab, NCCAM, Bethesda, MD 20892 USA. RP Mineo, C (reprint author), Univ Texas, SW Med Ctr, Dept Pediat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU NHLBI NIH HHS [HL 30276, HL 53546, HL 58888] NR 54 TC 235 Z9 245 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 14 PY 2003 VL 278 IS 11 BP 9142 EP 9149 DI 10.1074/jbc.M211394200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 654YF UT WOS:000181524000036 PM 12511559 ER PT J AU Huang, XL Pawliczak, R Yao, XL Cowan, MJ Gladwin, MT Walter, MJ Holtzman, MJ Madara, P Logun, C Shelhamer, JH AF Huang, XL Pawliczak, R Yao, XL Cowan, MJ Gladwin, MT Walter, MJ Holtzman, MJ Madara, P Logun, C Shelhamer, JH TI Interferon-gamma induces p11 gene and protein expression in human epithelial cells through interferon-gamma-activated sequences in the p11 promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOSOLIC PHOSPHOLIPASE A(2); ANNEXIN-II TETRAMER; INTERCELLULAR-ADHESION MOLECULE-1; HUMAN EPIDERMAL-KERATINOCYTES; CYTOKINE-INDUCED EXPRESSION; CALCIUM-BINDING PROTEINS; GROWTH-FACTOR-ALPHA; IFN-GAMMA; PROSTAGLANDIN GENERATION; PLASMINOGEN ACTIVATION AB The effect of interferon (IFN)-gamma on p11 expression was studied in two human epithelial cell lines (BEAS-2B and HeLa). Treatment with IFN-gamma resulted in increased steady-state levels of p11 mRNA and protein expression, with a time-dependent and dose-dependent effect. Transient transfection experiments of a reporter gene construct containing -1498 bp of the 5'-flanking region of the p11 promoter demonstrated that IFN-gamma induced p11 gene expression at the transcriptional level. These effects were inhibited at the promoter and protein levels by a specific JAK-2 kinase inhibitor, AG-490. Functional analysis of the p11 promoter indicates that two T-activated sequence elements (GAS) located at positions - 1219 and - 1090 are important for the induction of the p11 promoter by IFN-gamma. Transfection of mutated reporter constructs demonstrated that the mutation at the GAS-2 site (-1090) inhibited the p11 promoter activity, with a reduction of about similar to73% and mutation at the GAS-3 site (- 1219) eliminated about 26% of the p11 promoter activity. A STAT1 dominant negative mutant vector at Tyr-701 (JAK kinase phosphorylation site) blocked the effect of IFN-gamma on the p11 promoter activity. IFN-gamma induced a rapid tyrosine phosphorylation and nuclear translocation of STAT1 protein, which is involved in the binding to the GAS-2 site in the p11 promoter by EMSA analysis. These data suggest that IFN-gamma-induced p11 expression is mediated through the binding of STAT1 to GAS sites in the p11 promoter. Inhibition of p11 expression by inhibitory antisense RNAs (iRNA) treatment resulted in enhanced IFN-gamma and calcium ionophor-stimulated arachidonic acid release suggesting that at least in part IFN-gamma-stimulated p11 expression may serve a counterregulatory role. C1 NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Med Univ Lodz, Dept Clin Immunol & Allergy, PL-92213 Lodz, Poland. RP Shelhamer, JH (reprint author), NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bldg 10,Rm 7D43,10 Ctr Dr,MSC1662, Bethesda, MD 20892 USA. RI Pawliczak, Rafal/S-9649-2016; OI Pawliczak, Rafal/0000-0001-6784-453X NR 44 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 14 PY 2003 VL 278 IS 11 BP 9298 EP 9308 DI 10.1074/jbc.M212704200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 654YF UT WOS:000181524000055 PM 12645529 ER PT J AU Tian, LE Sayer, JM Kroth, H Kalena, G Jerina, DM Shuman, S AF Tian, LE Sayer, JM Kroth, H Kalena, G Jerina, DM Shuman, S TI Benzo[alpha]pyrene-dG adduct interference illuminates the interface of vaccinia topoisomerase with the DNA minor groove SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SITE-SPECIFIC INTERACTION; DIOL EPOXIDE; CLEAVAGE SITE; DUPLEX DNA; DEOXYGUANOSINE ADDUCTS; IB TOPOISOMERASE; EXONUCLEASE-III; STRAND CLEAVAGE; MECHANISM; COVALENT AB Vaccinia DNA topoisomerase forms a covalent DNA(3'-phosphotyrosyl)-enzyme intermediate at a pentapyrimidine target site 5'-C+5C+4C+3 T(+2)T(+1)pdown arrow in duplex DNA. The enzyme engages the target site within a C-shaped protein clamp. Here we mapped the interface of topoisomerase with the DNA minor groove by introducing chiral C-10 R and S 7,8-diol 9,10-epoxide adducts of benzo[a]pyrene (BP) at single N-2-deoxyguanosine (dG) positions within the nonscissile DNA strand. These trans opened BPdG adducts fit into the minor groove without perturbing helix conformation or base pairing, and the R and S diastereomers are oriented in opposite directions within the minor groove. We measured the effects of the BPdG adducts on the rate and extent of single-turnover DNA transesterification. We observed a sharp margin of interference effects, whereby +5 and -2 BPdG modifications were well tolerated but +4, +3, and -1 BPdG adducts were severely deleterious. Stereo-selective effects at the -1 nucleoside (the R isomer interfered, whereas the S isomer did not) delineated at high resolution the downstream border of the minor groove interface. BPdG inhibition of transesterification is likely caused by steric exclusion of constituents of the topoisomerase from the minor groove. We also applied the BPdG interference method to probe the interactions of exonuclease III with the minor groove. DNAs containing these BPdG adducts were protected from digestion by exonuclease III, which was consistently arrested at positions 2-4 nucleotides prior to the BP-modified guanosine. C1 Sloan Kettering Inst, Program Mol Biol, New York, NY 10021 USA. NIDDK, Bioorgan Chem Lab, DHHS, NIH, Bethesda, MD 20892 USA. RP Shuman, S (reprint author), Sloan Kettering Inst, Program Mol Biol, New York, NY 10021 USA. FU NIGMS NIH HHS [GM46330] NR 37 TC 16 Z9 16 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 14 PY 2003 VL 278 IS 11 BP 9905 EP 9911 DI 10.1074/jbc.M212468200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 654YF UT WOS:000181524000137 PM 12524450 ER PT J AU Oka, H Harada, KI Suzuki, M Fujii, K Iwaya, M Ito, Y Goto, T Matsumoto, H Ito, Y AF Oka, H Harada, KI Suzuki, M Fujii, K Iwaya, M Ito, Y Goto, T Matsumoto, H Ito, Y TI Purification of quinoline yellow components using high-speed counter-current chromatography by stepwise increasing the flow-rate of the mobile phase SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; flow-rate; quinotine yellow; dyes; sulfonates ID PEPTIDE SEPARATION; ALKALOIDS AB Quinoline yellow (Color Index No. 47005) consists of multiple components that show a large difference in their partition coefficients (K), ranging from 0.03 to 3.3 in the solvent system tert.-butyl methyl ether (MTBE)-1wbutanol-acetonitrile-aqueous 0.1 M trifluoroacetic acid (TFA). Consequently, it requires an excessively long elution time for the simultaneous separation of all components by the standard high-speed counter-current chromatography technique, which uses a constant flow-rate of the mobile phase. In order to overcome this problem, we increased the flow-rate of the mobile phase stepwise from 0.1 to 2.0 mL/min. Using this new procedure, six components (0.2-6.1 mg) were successfully isolated from 25 mg of a commercial quinoline yellow preparation in a single run using a two-phase solvent system composed of MTBE-1-butanol-acetonitrile-aqueous 0.1 M TFA (1:3:1:5, v/v). The purified components were analyzed by high-performance liquid chromatography, electrospray ionization mass spectrometry, and nuclear magnetic resonance spectroscopy. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagoya, Aichi 4628576, Japan. Meijo Univ, Fac Pharm, Nagoya, Aichi 4688503, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Oka, H (reprint author), Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagoya, Aichi 4628576, Japan. NR 16 TC 31 Z9 32 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAR 14 PY 2003 VL 989 IS 2 BP 249 EP 255 DI 10.1016/S0021-9673(03)00118-3 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 652JZ UT WOS:000181377200007 PM 12650257 ER PT J AU Cerritelli, ME Trus, BL Smith, CS Cheng, NQ Conway, JF Steven, AC AF Cerritelli, ME Trus, BL Smith, CS Cheng, NQ Conway, JF Steven, AC TI A second symmetry mismatch at the portal vertex of bacteriophage T7: 8-fold symmetry in the procapsid core SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE viral structural proteins; cryo-electron microscopy; bacteriophage morphogenesis; DNA packaging; image reconstruction ID HERPES-SIMPLEX VIRUS; CRYOELECTRON MICROSCOPY; DNA; PROTEIN; MACROMOLECULES; MATURATION; CAPSIDS; SYSTEM AB Like other bacteriophages, T7 has a singular vertex that is the site of a symmetry mismatch involving the portal/connector protein, a 12-fold ring at the vertex site which is also a 5-fold axis for the icosahedral capsid. In the mature virion, a 6-fold-symmetric tail extends outwards from the connector. T7 also has a cylindrical "core" that assembles on the inner surface of the connector during procapsid formation, is retained in the mature virion, and is required for infectivity. We have investigated the core structure by cryo-electron microscopy and image analysis of procapsids and find that it observes 8-fold symmetry. Stoichiometry data indicate that its major constituent is an octamer of gp15. Published by Elsevier Science Ltd. C1 NIAMSD, Struct Biol Lab, Bethesda, MD 20892 USA. NIH, Imaging Sci Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Inst Biol Struct JP Ebel, F-38027 Grenoble, France. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, Bldg 50,Room 1517,MSC 8025, Bethesda, MD 20892 USA. EM alasdair_steven@nih.gov RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 36 TC 29 Z9 30 U1 0 U2 0 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 MAR 14 PY 2003 VL 327 IS 1 BP 1 EP 6 DI 10.1016/S0022-2836(03)00117-7 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 657QP UT WOS:000181678100001 PM 12614603 ER PT J AU Asojo, OA Gulnik, SV Afonina, E Yu, B Ellman, JA Haque, TS Silva, AM AF Asojo, OA Gulnik, SV Afonina, E Yu, B Ellman, JA Haque, TS Silva, AM TI Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE crystal structure; aspartic protease; plasmepsin; Plasmodium falciparum; malaria ID HEMOGLOBIN DEGRADATION; COMBINATORIAL LIBRARY; CRYSTAL-STRUCTURES; CATHEPSIN-D; INHIBITORS; SPECIFICITY; REFINEMENT; MOLSCRIPT; PATHWAY; POTENT AB Malaria remains a human disease of global significance and a major cause of high infant mortality in endemic nations. Parasites of the genus Plasmodium cause the disease by degrading human hemoglobin as a source of amino acids for their growth and maturation. Hemoglobin degradation is initiated by aspartic proteases, termed plasmepsins, with a cleavage at the a-chain between residues Phe33 and Leu34. Plasmepsin II is one of the four catalytically active plasmepsins that has been identified in the food vacuole of Plasmodium falciparum. Novel crystal structures of uncomplexed plasmepsin II as well as the complex with a potent inhibitor have been refined with data extending to resolution limits of 1.9 Angstrom and 2.7 Angstrom, and to R factors of 17% and 18%, respectively. The inhibitor, N-(3-{(2-benzo[1,3]dioxol-5-yl-ethyl)[3-(1-methyl-3-oxo-1,3-dihydro-isoindol- 2-yl)-propionyl]-amino}-1-benzyl-2-(hydroxypropyl)-4-benzyloxy-3,5- dimethoxy-benzamide, belongs to a family of potent non-peptidic inhibitors that have large P1' groups. Such inhibitors could not be modeled into the binding cavity of the structure of plasmepsin II in complex with pepstatin A. Our structures reveal that the binding cavities of the new complex and uncomplexed plasmepsin II are considerably more open than that of the pepstatin A complex, allowing for larger heterocyclic groups in the P1', P2' and P2 positions. Both complexed and uncomplexed plasmepsin II crystallized in space group P2, with one monomer in the asymmetric unit. The structures show extensive interlocking of monomers around the crystallographic axis of symmetry, with areas in excess of 2300 Angstrom(2) buried at the interface, and a loop of one monomer interacting with the binding cavity of the 2-fold related monomer. Electron density for this loop is only fully ordered in the complexed structure. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 NCI, Struct Biochem Program, SAIC, Frederick, MD 21702 USA. Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. RP Silva, AM (reprint author), NCI, Struct Biochem Program, SAIC, Frederick, MD 21702 USA. EM asojo@ncifcrf.gov; abelardo.silva@sequoiapharma.com RI Ellman, Jonathan/C-7732-2013; Asojo, Oluwatoyin/C-2005-2012 OI Asojo, Oluwatoyin/0000-0002-4043-2700 FU NCI NIH HHS [N01 CO 74102] NR 36 TC 87 Z9 88 U1 0 U2 4 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 MAR 14 PY 2003 VL 327 IS 1 BP 173 EP 181 DI 10.1016/S0022-2836(03)00036-6 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 657QP UT WOS:000181678100014 PM 12614616 ER PT J AU Dellago, C Naor, MM Hummer, G AF Dellago, C Naor, MM Hummer, G TI Proton transport through water-filled carbon nanotubes SO PHYSICAL REVIEW LETTERS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; VALENCE-BOND MODEL; H+ CONDUCTION; CHANNEL; SOLVATION; WIRES AB Proton transfer along 1D chains of water molecules inside carbon nanotubes is studied by simulations. Ab initio molecular dynamics and an empirical valence bond model yield similar structures and time scales. The proton mobility along 1D water chains exceeds that in bulk water by a factor of 40, but is reduced if orientational defects are present. Excess protons interact with hydrogen-bonding defects through long-range electrostatics, resulting in coupled motion of protons and defects. C1 Univ Rochester, Dept Chem, Rochester, NY 14627 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Dellago, C (reprint author), Univ Vienna, Inst Expt Phys, Boltzmanngasse 5, A-1090 Vienna, Austria. RI Dellago, Christoph/E-1625-2011; Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 26 TC 226 Z9 230 U1 1 U2 50 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD MAR 14 PY 2003 VL 90 IS 10 AR 105902 DI 10.1103/PhysRevLett.90.105902 PG 4 WC Physics, Multidisciplinary SC Physics GA 656FE UT WOS:000181597500029 PM 12689010 ER PT J AU Derse, D Heidecker, G AF Derse, D Heidecker, G TI Forced entry - or does HTLV-I have the key? SO SCIENCE LA English DT Editorial Material ID T-CELLS; IMMUNOLOGICAL SYNAPSE; INFECTION C1 NCI, Basic Res Lab, Frederick, MD 21702 USA. RP Derse, D (reprint author), NCI, Basic Res Lab, Frederick, MD 21702 USA. NR 11 TC 10 Z9 15 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 14 PY 2003 VL 299 IS 5613 BP 1670 EP 1671 DI 10.1126/science.1083218 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 654WM UT WOS:000181519500022 PM 12637723 ER PT J AU Ransohoff, DF AF Ransohoff, DF TI Developing molecular biomarkers for cancer SO SCIENCE LA English DT Editorial Material ID DNA C1 Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Ransohoff, DF (reprint author), Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. NR 12 TC 54 Z9 62 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 14 PY 2003 VL 299 IS 5613 BP 1679 EP 1680 DI 10.1126/science.1083158 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 654WM UT WOS:000181519500027 PM 12637728 ER PT J AU Acharya, U Patel, S Koundakjian, E Nagashima, K Han, X Acharya, JK AF Acharya, U Patel, S Koundakjian, E Nagashima, K Han, X Acharya, JK TI Modulating sphingolipid biosynthetic pathway rescues photoreceptor degeneration SO SCIENCE LA English DT Article ID VISUAL-SYSTEM; DROSOPHILA; ARRESTIN; PROTEIN; ENDOCYTOSIS; RHODOPSIN; TRANSDUCTION; APOPTOSIS; DYNAMIN; ROLES AB Mutations in proteins of the Drosophila phototransduction cascade, a prototypic guanine nucleotide-binding protein-coupled receptor signaling system, lead to retinal degeneration and have been used as models to understand human degenerative disorders. Here, modulating the sphingolipid biosynthetic pathway rescued retinal degeneration in Drosophila mutants. Targeted expression of Drosophila neutral ceramidase rescued retinal degeneration in arrestin and phospholipase C mutants. Decreasing flux through the de novo sphingolipid biosynthetic pathway also suppressed degeneration in these mutants. Both genetic backgrounds modulated the endocytic machinery because they suppressed defects in a dynamin mutant. Suppression of degeneration in arrestin mutant flies expressing ceramidase correlated with a decrease in ceramide levels. Thus, enzymes of sphingolipid metabolism may be suitable targets in the therapeutic management of retinal degeneration. C1 NCI, Regulat Cell Growth Lab, Frederick, MD 21702 USA. Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. Sci Applicat Int Corp, Electron Microscopy Facil Image Anal Lab, Frederick, MD 21702 USA. Washington Univ, Sch Med, Dept Med, Div Bioorgan Chem & Mol Pharmacol, St Louis, MO 63110 USA. RP Acharya, JK (reprint author), NCI, Regulat Cell Growth Lab, Frederick, MD 21702 USA. NR 23 TC 89 Z9 91 U1 2 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 14 PY 2003 VL 299 IS 5613 BP 1740 EP 1743 DI 10.1126/science.1080549 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 654WM UT WOS:000181519500048 PM 12637747 ER PT J AU Straight, AF Cheung, A Limouze, J Chen, I Westwood, NJ Sellers, JR Mitchison, TJ AF Straight, AF Cheung, A Limouze, J Chen, I Westwood, NJ Sellers, JR Mitchison, TJ TI Dissecting temporal and spatial control of cytokinesis with a myosin II inhibitor SO SCIENCE LA English DT Article ID CONTRACTILE RING; PROTEIN-KINASE; MAMMALIAN-CELLS; CLEAVAGE FURROW; MITOTIC SPINDLE; MICROTUBULES; LOCALIZATION; PROTEOLYSIS; ANAPHASE; ANTIBODY AB Completion of cell division during cytokinesis requires temporally and spatially regulated communication from the microtubule cytoskeleton to the actin cytoskeleton and the cell membrane. We identified a specific inhibitor of nonmuscle myosin II, blebbistatin, that inhibited contraction of the cleavage furrow without disrupting mitosis or contractile ring assembly. Using blebbistatin and other drugs, we showed that exit from the cytokinetic phase of the cell cycle depends on ubiquitin-mediated proteolysis. Continuous signals from microtubules are required to maintain the position of the cleavage furrow, and these signals control the localization of myosin II independently of other furrow components. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Inst Chem & Cell Biol, Boston, MA 02115 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ St Andrews, Sch Chem, St Andrews KY16 9AJ, Fife, Scotland. RP Straight, AF (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 250 Longwood Ave, Boston, MA 02115 USA. OI Straight, Aaron/0000-0001-5885-7881 FU NIGMS NIH HHS [GM23928, GM62566] NR 32 TC 831 Z9 843 U1 3 U2 44 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 14 PY 2003 VL 299 IS 5613 BP 1743 EP 1747 DI 10.1126/science.1081412 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 654WM UT WOS:000181519500049 PM 12637748 ER PT J AU Hashimoto, R Fujimaki, K Jeong, MR Christ, L Chuang, DM AF Hashimoto, R Fujimaki, K Jeong, MR Christ, L Chuang, DM TI Lithium-induced inhibition of Src tyrosine kinase in rat cerebral cortical neurons: a role in neuroprotection against N-methyl-D-aspartate receptor-mediated excitotoxicity SO FEBS LETTERS LA English DT Article DE lithium; Src kinase; tyrosine phosphorylation; cerebral cortical neuron; bipolar disorder ID NMDA RECEPTORS; NR2B SUBUNIT; NEUROFILAMENT-L; CALCIUM INFLUX; PHOSPHORYLATION; FAMILY; PLASTICITY; EXPRESSION; SYSTEM AB The neuroprotective effects of lithium, a mood stabilizer, against glutamate-induced excitotoxicity in rat cortical neurons were associated with a decrease in Tyr1472 phosphorylation of the N-methyl-D-aspartate (NMDA) receptor NR2B subunit and a loss of receptor activity. Since this receptor tyrosine phosphorylation is mediated by the Src-family tyrosine kinases, we investigated the effects of lithium on the Src kinase activity. Levels of phosphorylated Src kinase at Tyr416, an index of Src activation, were reduced after treatment with LiCl (1 mM) for more than 3 days. Protein levels of Src-family kinases such as Src, Fyn, and Yes were unchanged by lithium treatment. The activities of cytosolic protein tyrosine kinase and protein phosphatase were also unchanged by lithium treatment, indicating the selectivity and the modulation. Moreover, the levels of postsynaptic densities (PSD) and SynGAP, the scaffolding proteins of the NMDA receptor complex, were unaltered by lithium. A Src kinase inhibitor, SU6656, and an NR2B antagonist, ifenprodil, partially blocked glutamate excitotoxicity. Our results suggest that lithium-induced inactivation of Src kinase contributes to this drug-induced NMDA receptor inhibition and neuroprotection against excitotoxicity. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bldg 10,Rm 4C-206,10 Ctr Dr MSC 1363, Bethesda, MD 20892 USA. RI Hashimoto, Ryota/P-8572-2014 OI Hashimoto, Ryota/0000-0002-5941-4238 NR 22 TC 49 Z9 60 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 13 PY 2003 VL 538 IS 1-3 BP 145 EP 148 DI 10.1016/S0014-5793(03)00167-4 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 655RV UT WOS:000181567200026 PM 12633868 ER PT J AU Lenz, P Bacot, SM Frazier-Jessen, MR Feldman, GM AF Lenz, P Bacot, SM Frazier-Jessen, MR Feldman, GM TI Nucleoporation of dendritic cells: efficient, gene transfer by electroporation into human monocyte-derived dendritic cells SO FEBS LETTERS LA English DT Article DE electroporation; dendritic cell; gene therapy; monocyte; nucleofection; green fluorescent protein ID CENTRIFUGAL ELUTRIATION CCE; ANTIGEN-PRESENTING CELLS; ADENOASSOCIATED VIRUS; ANTITUMOR IMMUNITY; MESSENGER-RNA; MEDIATED TRANSFECTION; NONVIRAL TRANSFECTION; ENRICHED FRACTIONS; TRANSDUCTION; RESPONSES AB Dendritic cells (DCs) are ideal accessory cells in the developing field of gene therapy. Although viral transfection of DO has become widespread, non-viral transfection of DCs has shown disappointing results. Recently, a new technique for transfecting primary cells has become available - the Amaxa Nucleofector(TM). Here, we describe the use of this device in the successful non-viral transfection of human monocyte-derived DCs. Using enhanced green fluorescent protein as a reporter gene DCs were transfectable with efficiencies approaching 60%, remaining responsive to lipopolysaccharide-stimulated cytokine production in short-term experiments (though long-term functional assays were hampered by loss of viability). Although these data demonstrate the ease and efficiency with which human monocyte-derived DCs can now be non-virally transfected, they also suggest the limitations of this technology due to the gradual loss of cell viability. The potential use of this system in the development of DC-based cell and gene therapies will be hampered until cell viability can be maintained. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 US FDA, Div Monclonal Antibodies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Feldman, GM (reprint author), US FDA, Div Monclonal Antibodies, Ctr Biol Evaluat & Res, HFM-564,Bldg 29A,Rm 3C24,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 44 TC 59 Z9 66 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 13 PY 2003 VL 538 IS 1-3 BP 149 EP 154 DI 10.1016/S0014-5793(03)00169-8 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 655RV UT WOS:000181567200027 PM 12633869 ER PT J AU Roberts, AB AF Roberts, AB TI Medicine - Smoke signals for lung disease SO NATURE LA English DT Editorial Material C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. NR 10 TC 10 Z9 10 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 13 PY 2003 VL 422 IS 6928 BP 130 EP 131 DI 10.1038/422130a PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 654HG UT WOS:000181488900030 PM 12634771 ER PT J AU Morris, DG Huang, XZ Kaminski, N Wang, YN Shapiro, SD Dolganov, G Glick, A Sheppard, D AF Morris, DG Huang, XZ Kaminski, N Wang, YN Shapiro, SD Dolganov, G Glick, A Sheppard, D TI Loss of integrin alpha v beta 6-mediated TGF-beta activation causes Mmp12-dependent emphysema SO NATURE LA English DT Article ID MACROPHAGE METALLOELASTASE; CYTOPLASMIC DOMAIN; LUNG INFLAMMATION; FOCAL CONTACTS; EXPRESSION; MICE; SUBUNIT; REVEALS; LOCALIZATION; INHIBITION AB Integrins are heterodimeric cell-surface proteins that regulate cell growth, migration and survival. We have shown previously that the epithelial-restricted integrin alphavbeta6 has another critical function; that is, it binds and activates latent transforming growth factor-beta (TGF-beta)(1,2). Through a global analysis of pulmonary gene expression in the lungs of mice lacking this integrin (Itgb6 null mice) we have identified a marked induction of macrophage metalloelastase (Mmp12)-a metalloproteinase that preferentially degrades elastin and has been implicated in the chronic lung disease emphysema(3). Here we report that Itgb6-null mice develop age-related emphysema that is completely abrogated either by transgenic expression of versions of the beta6 integrin subunit that support TGF-beta activation, or by the loss of Mmp12. Furthermore, we show that the effects of Itgb6 deletion are overcome by simultaneous transgenic expression of active TGF-beta1. We have uncovered a pathway in which the loss of integrin-mediated activation of latent TGF-beta causes age-dependent pulmonary emphysema through alterations of macrophage Mmp12 expression. Furthermore, we show that a functional alteration in the TGF-beta activation pathway affects susceptibility to this disease. C1 Univ Calif San Francisco, San Francisco Gen Hosp, Lung Biol Ctr, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Med, Div Pulm & Crit Care Med, Pittsburgh, PA 15261 USA. Brigham & Womens Hosp, Dept Med, Pulm & Crit Care Med Sect, Boston, MA 02115 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. RP Sheppard, D (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Lung Biol Ctr, Dept Med, San Francisco, CA 94143 USA. NR 27 TC 296 Z9 308 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 13 PY 2003 VL 422 IS 6928 BP 169 EP 173 DI 10.1038/nature01413 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 654HG UT WOS:000181488900046 PM 12634787 ER PT J AU Gear, RW Gordon, NC Miaskowski, C Paul, SM Heller, PH Levine, JD AF Gear, RW Gordon, NC Miaskowski, C Paul, SM Heller, PH Levine, JD TI Sexual dimorphism in very low dose nalbuphine postoperative analgesia SO NEUROSCIENCE LETTERS LA English DT Article DE kappa opioid; males; females; pain; sex; gender; humans ID MORPHINE ANALGESIA; SIGMA(1) RECEPTOR; OPIOID ANALGESIA; PENTAZOCINE; ANTAGONISM; SYSTEM AB In recent studies we demonstrated that the analgesic effect of the kappa-like opioids is significantly greater in women, that low dose nalbuphine (5 mg) produces profound anti-analgesia (i.e. enhances pain) in men, and that addition of a low dose of the non-selective opioid receptor antagonist naloxone (0.4 mg) to nalbuphine (5 mg) abolishes the sex difference and results in significantly enhanced analgesia in both sexes. To further delineate the dose-dependent analgesic and anti-analgesic effects of nalbuphine, the present study evaluated the effect of a lower dose of nalbuphine (2.5 mg), with and without naloxone, on dental postoperative pain. In women, nalbuphine alone induced modest, short duration analgesia, which was antagonized rather than enhanced by the addition of naloxone (0.4 mg). In men, this dose of nalbuphine alone did not produce analgesia or anti-analgesia, and naloxone (0.4 mg) did not alter the response to nalbuphine. Thus, the anti-analgesic effect of nalbuphine, present in both sexes at the 5 mg dose disappears at the lower dose of nalbuphine. In addition, the mild analgesia in women produced by this lower dose of nalbuphine is antagonized by naloxone. (C) 2003 Published by Elsevier Science Ireland Ltd. C1 Univ Calif San Francisco, NIH, Pain Ctr, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Kaiser Fdn Hosp, Hayward, CA 94545 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH, Pain Ctr, Dept Oral & Maxillofacial Surg, Box 0440,521 Parnassus Ave,Room C-522, San Francisco, CA 94143 USA. FU NINR NIH HHS [NR03923] NR 13 TC 27 Z9 27 U1 1 U2 1 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 MAR 13 PY 2003 VL 339 IS 1 BP 1 EP 4 DI 10.1016/S0304-3940(02)01438-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 652ZV UT WOS:000181411500001 PM 12618286 ER PT J AU Toyota, T Yamada, K Detera-Wadleigh, SD Yoshikawa, T AF Toyota, T Yamada, K Detera-Wadleigh, SD Yoshikawa, T TI Analysis of a cluster of polymorphisms in AKT1 gene in bipolar pedigrees: a family-based association study SO NEUROSCIENCE LETTERS LA English DT Article DE affective disorder; linkage; candidate gene; lithium; phosphoinositide signaling pathway; haplotype block; pedigree disequilibrium test ID HUMAN-GENOME; LITHIUM; DISORDER; LINKAGE; GROWTH AB We have previously performed a genome scan in 22 multiplex pedigrees with bipolar disorder and detected a moderate linkage signal on distal portion of chromosome 14q22-32. One of the large pedigrees displayed a parametric lod score > 3 at a marker on 14q23-32. Upon inspection of genes located in this region revealed AKT1, a kinase that activates a lithium-responsive cell-survival pathway. Because lithium is an effective mood stabilizer for bipolar disorder patients, AKT1 is an interesting candidate for further investigation. We screened the gene for possible mutations and detected 14 polymorphisms. Seven polymorphic sites were clustered in a small segment spanning exon 14 and downstream intron. Transmission of haplotypes constructed from this cluster showed a weak evidence of association between the AKT1 and bipolar disorder. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 RIKEN, Brain Sci Inst, Lab Mol Psychiat, Wako, Saitama 3510198, Japan. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Yoshikawa, T (reprint author), RIKEN, Brain Sci Inst, Lab Mol Psychiat, Wako, Saitama 3510198, Japan. NR 18 TC 25 Z9 25 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 MAR 13 PY 2003 VL 339 IS 1 BP 5 EP 8 DI 10.1016/S0304-3940(02)01428-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 652ZV UT WOS:000181411500002 PM 12618287 ER PT J AU Fruchter, O Dragu, R AF Fruchter, O Dragu, R TI A deadly examination SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. Rambam Med Ctr, IL-31096 Haifa, Israel. RP Fruchter, O (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 11 Z9 12 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 MAR 13 PY 2003 VL 348 IS 11 BP 1016 EP 1016 DI 10.1056/NEJMicm020803 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 653YT UT WOS:000181465200006 PM 12637611 ER PT J AU Metzger, H AF Metzger, H TI Two approaches to peanut allergy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID FC-EPSILON-RI; IGE C1 NIAMSD, Bethesda, MD 20892 USA. RP Metzger, H (reprint author), NIAMSD, Bethesda, MD 20892 USA. NR 14 TC 2 Z9 2 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 MAR 13 PY 2003 VL 348 IS 11 BP 1046 EP 1048 DI 10.1056/NEJMe030007 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 653YT UT WOS:000181465200010 PM 12637615 ER PT J AU Lloyd-Jones, DM Levy, D AF Lloyd-Jones, DM Levy, D TI C-reactive protein in the prediction of cardiovascular events SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Natl Heart Lung & Blood Inst Framingham, Heart Study, Framingham, MA 01702 USA. RP Lloyd-Jones, DM (reprint author), Natl Heart Lung & Blood Inst Framingham, Heart Study, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 2 TC 12 Z9 13 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 MAR 13 PY 2003 VL 348 IS 11 BP 1059 EP 1059 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 653YT UT WOS:000181465200016 PM 12637619 ER PT J AU Evans, MK Zonderman, AB Johnson, WR AF Evans, MK Zonderman, AB Johnson, WR TI C-reactive protein in the prediction of cardiovascular events SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID HEALTH C1 NIH, Baltimore, MD 21224 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Evans, MK (reprint author), NIH, Baltimore, MD 21224 USA. NR 4 TC 0 Z9 0 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 MAR 13 PY 2003 VL 348 IS 11 BP 1060 EP 1060 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 653YT UT WOS:000181465200018 ER PT J AU Do, TN Rosal, RV Drew, L Raffo, AJ Michl, J Pincus, MR Friedman, FK Petrylak, DP Cassai, N Szmulewicz, J Sidhu, G Fine, RL Brandt-Rauf, PW AF Do, TN Rosal, RV Drew, L Raffo, AJ Michl, J Pincus, MR Friedman, FK Petrylak, DP Cassai, N Szmulewicz, J Sidhu, G Fine, RL Brandt-Rauf, PW TI Preferential induction of necrosis in human breast cancer cells by a p53 peptide derived from the MDM2 binding site SO ONCOGENE LA English DT Article DE breast cancer; p53; MDM2; necrosis ID TUMOR-SUPPRESSOR GENE; C-TERMINAL PEPTIDE; IN-VIVO; INTRACELLULAR DELIVERY; MUTANT P53; ANTENNAPEDIA HOMEODOMAIN; PROTEIN TRANSDUCTION; CIRCULAR-DICHROISM; 3RD HELIX; DOMAIN AB p53 is the most frequently altered gene in human cancer and therefore represents an ideal target for cancer therapy. Several amino terminal p53-derived synthetic peptides were tested for their antiproliferative effects on breast cancer cell lines MDA-MB-468 (mutant p53), MCF-7 (overexpressed wild-type p53), and MDA-MB-157 (null p53). p53(15)Ant peptide representing the majority of the mouse double minute clone 2 binding site on p53 (amino acids 12-26) fused to the Drosophila carrier protein Antennapedia was the most effective. p53(15)Ant peptide induced rapid, nonapoptotic cell death resembling necrosis in all breast cancer cells; however, minimal cytotoxicity was observed in the nonmalignant breast epithelial cells MCF-10-2A and MCF-10F. Bioinformatic/biophysical analysis utilizing hydrophobic moment and secondary structure predictions as well as circular dichroism spectroscopy revealed an alpha-helical hydrophobic peptide structure with membrane disruptive potential. Based on these findings, p53(15)Ant peptide may be a novel peptide cancer therapeutic because it induces necrotic cell death and not apoptosis, which is uncommon in traditional cancer therapy. C1 Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Div Med Oncol, Expt Therapeut Program, New York, NY 10032 USA. Harbor VA Med Ctr, Dept Pathol & Lab Med, Manhasset, NY 10010 USA. Harbor VA Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA. NIH, Lab Metab, Bethesda, MD 20892 USA. RP Brandt-Rauf, PW (reprint author), Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY 10032 USA. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [CA 82528, R01 CA 42500]; NIOSH CDC HHS [OH 04192] NR 43 TC 54 Z9 61 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 13 PY 2003 VL 22 IS 10 BP 1431 EP 1444 DI 10.1038/sj.onc.1206258 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 652ZZ UT WOS:000181411900001 PM 12629507 ER PT J AU Qiang, YW Endo, Y Rubin, JS Rudikoff, S AF Qiang, YW Endo, Y Rubin, JS Rudikoff, S TI Wnt signaling in B-cell neoplasia SO ONCOGENE LA English DT Article DE Wnt; beta-catenin; myeloma; morphology; Rho ID MULTIPLE-MYELOMA; BETA-CATENIN; PROTEIN; RECEPTOR; PATHWAY; RHO; INTERLEUKIN-6; PROLIFERATION; TRANSDUCTION; WINGLESS AB Wnts comprise a family of secreted proteins that interact with receptors consisting of a Frizzled (Fz) family member alone or complexed with LDL receptor-related proteins (LRP5/6). Wnt signaling plays a crucial role in both development and differentiation, and activation of a 'canonical' Writ pathway resulting in P-catenin stabilization is associated with several types of human cancers. To date, little is known about potential Wnt signaling in mature lymphocytes or lymphoid neoplasia. Herein, we have analysed Wnt signaling in mature B cells (lymphomas) and plasma cells (multiple myeloma). Both Fz and LRP5/6 mRNAs were expressed in myeloma lines, but LRP5/6 were not observed in lymphomas. In myelomas, a canonical Wnt signaling pathway was activated following treatment with Wnt-3a as assessed by accumulation of beta-catenin, but beta-catenin levels actually decreased in lymphoma cells. Wnt-3a treatment further led to striking morphological changes in myeloma cells accompanied by rearrangement of the actin cytoskeleton. Morphological changes were associated with a second Wnt pathway dependent on Rho activation. These results suggest that Writ responsiveness is a stage-specific phenomenon in B-cell development and that the morphological changes associated with Wnt signaling may play a role in the motility and metastatic potential of myeloma cells. C1 NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rudikoff, S (reprint author), NCI, Cellular & Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. OI Qiang, Ya-Wei/0000-0002-2479-1412 NR 39 TC 108 Z9 114 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 13 PY 2003 VL 22 IS 10 BP 1536 EP 1545 DI 10.1038/sj.onc.1206239 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 652ZZ UT WOS:000181411900011 PM 12629517 ER PT J AU Vasan, RS Beiser, A D'Agostino, RB Levy, D Selhub, J Jacques, PF Rosenberg, IH Wilson, PWF AF Vasan, RS Beiser, A D'Agostino, RB Levy, D Selhub, J Jacques, PF Rosenberg, IH Wilson, PWF TI Plasma homocysteine and risk for congestive heart failure in adults without prior myocardial infarction SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CARDIOVASCULAR-DISEASE; HORDALAND HOMOCYSTEINE; FOLIC-ACID; CORONARY; HYPERHOMOCYSTEINEMIA; POPULATION; CLASSIFICATION; DETERMINANTS; DYSFUNCTION; FRAMINGHAM AB Context Elevated plasma homocysteine levels are associated with increased risk of vascular disease. It is unclear whether elevated homocysteine levels are a risk factor for congestive heart failure (CHF). Objective To study prospectively the-association between nonfasting plasma homocysteine and incidence of CHF. Design, Setting, and Participants Community-based prospective cohort study of 2491 adults (mean age 72 years, 1547 women) who participated in the Framingham Heart Study during the 1979-1982 and 1986-1990 examinations and were free of CHIF or prior myocardial infarction (recognized or unrecognized) at baseline. Main Outcome Measure incidence of a first episode of CHIF during an 8-year follow-up period. Results During follow-up, 156 subjects (88 women) developed CHF. In multivariable analyses controlling for established risk factors for CHF including the occurrence of myocardial infarction (recognized or unrecognized) during follow-up, plasma homocysteine levels higher than the sex-specific median value were associated with an adjusted hazards ratio,for heart failure of 1.93 in women (95% confidence interval, 1.19-3.14)and 1.84 in men (95% confidence interval, 1.06-3.17). The relation of plasma homocysteine levels to CHF risk was more continuous in women than in men. In analyses restricted to participants without any manifestation of coronary heart disease at baseline, the association of plasma homocysteine levels with risk of CHF was maintained in men and women. Conclusions An increased plasma homocysteine level independently predicts risk of the development of CHF in adults without prior myocardial infarction. Additional investigations are warranted to confirm these findings. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Endocrinol Sect, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Clin Epidemiol, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Tufts Univ, Jean Mayer US Dept Agr Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Site 2, Framingham, MA 01702 USA. OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01-HC-25195, 1K24 HL04334, R01 HL71039] NR 41 TC 136 Z9 149 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 12 PY 2003 VL 289 IS 10 BP 1251 EP 1257 DI 10.1001/jama.289.10.1251 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 653ZG UT WOS:000181466500026 PM 12633186 ER PT J AU Clore, GM Schwieters, CD AF Clore, GM Schwieters, CD TI Docking of protein-protein complexes on the basis of highly ambiguous intermolecular distance restraints derived from H-1(N)/N-15 chemical shift mapping and backbone N-15-H-1 residual dipolar couplings using conjoined rigid body/torsion angle dynamics SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PHOSPHORYL TRANSFER COMPLEX; SUGAR PHOSPHOTRANSFERASE SYSTEM; LIQUID-CRYSTALLINE MEDIUM; N-TERMINAL DOMAIN; NMR STRUCTURES; ACTIVE-SITE; ENZYME-I; RELATIVE ORIENTATION; STRUCTURE REFINEMENT; MOLECULAR-DYNAMICS AB A simple and reliable method for docking protein-protein complexes using H-1(N)/N-15 chemical shift mapping and backbone N-15-H-1 residual dipolar couplings is presented and illustrated with three complexes (EIN-HPr, IIA(Glc)-HPr, and IIA(Mtl)-HPr) of known structure. The H-1(N)/N-15 chemical shift mapping data are transformed into a set of highly ambiguous, intermolecular distance restraints (comprising between 400 and 3000 individual distances) with translational and some degree of orientational information content, while the dipolar couplings provide information on relative protein-protein orientation. The optimization protocol employs conjoined rigid body/torsion angle dynamics in simulated annealing calculations. The target function also comprises three nonbonded interactions terms: a van der Waals repulsion term to prevent atomic overlap, a radius of gyration term (Ergyr) to avoid expansion at the protein-protein interface, and a torsion angle database potential of mean force to bias interfacial side chain conformations toward physically allowed rotamers. For the EIN-HPr and IIA(Glc)-HPr complexes, all structures satisfying the experimental restraints (i.e., both the ambiguous intermolecular distance restraints and the dipolar couplings) converge to a single cluster with mean backbone coordinate accuracies of 0.7-1.5 Angstrom. For the IIA(Mtl)-HPr complex, twofold degeneracy remains, and the structures cluster into two distinct solutions differing by a 180 rotation about the z axis of the alignment tensor. The correct and incorrect solutions which have mean backbone coordinate accuracies of similar to0.5 and similar to10.5 Angstrom, respectively, can readily be distinguished using a variety of criteria: (a) examination of the overall H-1(N)/N-15 chemical shift perturbation map (because the incorrect cluster predicts the presence of residues at the interface that experience only minimal chemical shift perturbations; this information is readily incorporated into the calculations in the form of ambiguous intermolecular repulsion restraints); (b) back-calculation of dipolar couplings on the basis of molecular shape; or (c) the Ergyr distribution which, because of its global nature, directly reflects the interfacial packing quality. This methodology should be particularly useful for high throughput, NMR-based, structural proteomics. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 54 TC 94 Z9 97 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 12 PY 2003 VL 125 IS 10 BP 2902 EP 2912 DI 10.1021/ja028893d PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA 652YY UT WOS:000181409500037 PM 12617657 ER PT J AU Bokesch, HR O'Keefe, BR McKee, TC Pannell, LK Patterson, GML Gardella, RS Sowder, RC Turpin, J Watson, K Buckheit, RW Boyd, MR AF Bokesch, HR O'Keefe, BR McKee, TC Pannell, LK Patterson, GML Gardella, RS Sowder, RC Turpin, J Watson, K Buckheit, RW Boyd, MR TI A potent novel anti-HIV protein from the cultured cyanobacterium Scytonema varium SO BIOCHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYANOVIRIN-N; INACTIVATING PROTEIN; ANTIFREEZE PROTEINS; NATURAL-PRODUCTS; URTICA-DIOICA; CELL-FUSION; GREEN-ALGA; GLYCOPROTEIN; GP120 AB A new anti-HIV protein, scytovirin, was isolated from aqueous extracts of the cultured cyanobacterium Scytonema varium. The protein displayed potent anticytopathic activity against laboratory strains and primary isolates of HIV-1 with EC50 values ranging from 0.3 to 22 nM. Scytovirin binds to viral coat proteins gp120, gp160, and gp41 but not to cellular receptor CD4 or other tested proteins. This unique protein consists of a single 95-amino acid chain with significant internal sequence duplication and 10 cysteines forming five intrachain disulfide bonds. C1 Univ S Alabama, Coll Med, USA Canc Res Inst, Mobile, AL 36688 USA. So Res Inst, Frederick Res Ctr, Frederick, MD 21701 USA. SAIC Frederick, AIDS Vaccine Program, Frederick, MD 21702 USA. Univ Hawaii Manoa, Dept Chem, Honolulu, HI 96822 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. NCI, Mol Targets Discovery Program, Canc Res Ctr, Frederick, MD USA. RP Boyd, MR (reprint author), Univ S Alabama, Coll Med, USA Canc Res Inst, Mobile, AL 36688 USA. FU NCI NIH HHS [N01-CO-12400] NR 29 TC 81 Z9 86 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 11 PY 2003 VL 42 IS 9 BP 2578 EP 2584 DI 10.1021/bi0205698 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 652GV UT WOS:000181372200010 PM 12614152 ER PT J AU Ugur, O Onaran, HO Jones, TLZ AF Ugur, O Onaran, HO Jones, TLZ TI Partial rescue of functional interactions of a nonpalmitoylated mutant of the G-protein G alpha(s) by fusion to the beta-adrenergic receptor SO BIOCHEMISTRY LA English DT Article ID PLASMA-MEMBRANE LOCALIZATION; ADENYLYL-CYCLASE; TRANSFORMING ACTIVITY; THROMBIN RECEPTOR; LYMPHOMA-CELLS; ALPHA-SUBUNITS; AMINO-TERMINUS; GAMMA COMPLEX; PALMITOYLATION; ACYLATION AB Most heterotrimeric G-protein alpha subunits are posttranslationally modified by palmitoylation, a reversible process that is dynamically regulated. We analyzed the effects of Galpha(s) palmitoylation for its intracellular distribution and ability to couple to the beta-adrenergic receptor (betaAR) and stimulate adenylyl cyclase. Subcellular fractionation and immunofluorescence microscopy of stably transfected cyc(-) cells, which lack endogenous Galpha(s), showed that wild-type Galpha(s) was predominantly localized at the plasma membrane, but the mutant C3A-Galpha(s), which does not incorporate [H-3]palmitate, was mostly associated with intracellular membranes. In agreement with this mislocalization, C3A-Galpha(s), showed neither isoproterenol- or GTPgammaS-stimulated adenylyl cyclase activation nor GTPgammaS-sensitive high-affinity agonist binding, all of which were present in the wild-type Galpha(s) expressing cells. Fusion of C3A-Galpha(s) with the betaAR [betaAR-(C3A)Galpha(s)] partially rescued its ability to induce high-affinity agonist binding and to stimulate adenylyl cyclase activity after isoproterenol or GTPgammaS treatment. In comparison to results with the WT-Galpha(s) and betaAR (betaAR-Galpha(s)) fusion protein, the betaAR-(C3A)Galpha(s) fusion protein was about half as efficient at coupling to the receptor and effector. Chemical depalmitoylation by hydroxylamine of membranes expressing betaAR-Galpha(s) reduced the high-affinity agonist binding and adenylyl cyclase activation to a similar degree as that observed in betaAR-(C3A)Galpha(s) expressing membranes. Altogether, these findings indicate that palmitoylation ensured proper localization of Galpha(s), and facilitated bimolecular interactions of Galpha(s) with the betaAR and adenylyl cyclase. C1 Ankara Univ, Fac Med, Dept Pharmacol & Clin Pharmacol, TR-06100 Ankara, Turkey. Ankara Univ, Fac Med, Mol Biol & Technol Res & Dev Unit, TR-06100 Ankara, Turkey. Natl Inst Diabet & Digest Dis, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Ugur, O (reprint author), Ankara Univ, Fac Med, Dept Pharmacol & Clin Pharmacol, TR-06100 Ankara, Turkey. NR 47 TC 10 Z9 10 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 11 PY 2003 VL 42 IS 9 BP 2607 EP 2615 DI 10.1021/bi0236470i PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 652GV UT WOS:000181372200013 PM 12614155 ER PT J AU Toczek, MT Carson, RE Lang, L Ma, Y Spanaki, MV Der, MG Fazilat, S Kopylev, L Herscovitch, P Eckelman, WC Theodore, WH AF Toczek, MT Carson, RE Lang, L Ma, Y Spanaki, MV Der, MG Fazilat, S Kopylev, L Herscovitch, P Eckelman, WC Theodore, WH TI PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy SO NEUROLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; HUMAN BRAIN; PRONE RATS; EPILEPTIFORM ACTIVITY; PYRAMIDAL NEURONS; DENTATE GYRUS; CA1 NEURONS; BLOOD-FLOW; SEROTONIN; HIPPOCAMPUS AB Background: Activation of central serotonin (5-HT)(1A) receptors, found in high density in brainstem raphe, hippocampus, and temporal neocortex, exerts an anticonvulsant effect in various experimental seizure models. To test the hypothesis that 5-HT1A receptor binding is reduced in human epileptic foci, PET imaging was performed using the radioligand [F-18]trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl-ethyl]-N-(2-pyridyl)cyclohexanecarboxamide ([F-18]FCWAY), a selective 5-HT1A receptor antagonist, in patients with temporal lobe epilepsy and normal controls. Methods: MRI and PET were performed using [O-15]water and [F-18]FCWAY in 10 controls and in 12 patients with temporal lobe epilepsy confirmed on ictal video-EEG; patients also underwent [F-18]fluorodeoxyglucose PET. Using quantitative PET image analysis, regional values were obtained for [F-18]FCWAY volume of distribution (V), cerebral blood flow (CBF), and glucose cerebral metabolic rate (CMRglc). Hippocampal volume (HV) was also measured with MRI. [F-18]FCWAY V PET and MR measures were compared within patients and controls using paired t-tests; grouped comparisons were made with two sample t-tests. Results: Lower [F-18]FCWAY V was found ipsilateral than contralateral to the epileptic focus in inferior medial (IMT) and lateral (ILT) temporal regions of patients (ILT 47.4 +/- 6.1 vs 61.8 +/- 6.1, p < 0.01; IMT 52 +/- 4.6 vs 67.0 +/- 6.0, p < 0.01). [F-18]FCWAY V was 29% lower in raphe and 34% lower in the ipsilateral thalamic region of patients than controls. In ILT, mean [F-18]FCWAY V asymmetry index (AT) was significantly greater than mean CBF and mean CMRglc AI. Mean [F-18]FCWAY V AT in IMT was greater than mean HV AT, but the difference was not significant. Conclusion: These findings support the hypothesis of reduced serotonin receptor binding in temporal lobe epileptic foci. C1 NINDS, Clin Epilepsy Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. NINDS, Biostat Branch, NIH, Bethesda, MD 20892 USA. NIH, Positron Emiss Tomog Dept, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, Epilepsy Res Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5N250,MSC 1408, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 52 TC 141 Z9 142 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 11 PY 2003 VL 60 IS 5 BP 749 EP 756 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 679XY UT WOS:000182948300004 PM 12629228 ER PT J AU Hadley, DW Jenkins, J Dimond, E Nakahara, K Grogan, L Liewehr, DJ Steinberg, SM Kirsch, I AF Hadley, DW Jenkins, J Dimond, E Nakahara, K Grogan, L Liewehr, DJ Steinberg, SM Kirsch, I TI Genetic Counseling and testing in families with hereditary nonpolyposis colorectal cancer SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MISMATCH REPAIR GENES; BREAST-OVARIAN CANCER; COLON-CANCER; TUMOR SPECTRUM; MUTATIONS; HOMOLOG; SUSCEPTIBILITY; ATTITUDES; RELATIVES; GERMLINE AB Background: Genetic testing to refine cancer risk is available. However, little is known about factors affecting the uptake of testing for the most common hereditary colon cancer, hereditary nonpolyposis colorectal cancer. This study investigated attitudes, intentions, and uptake of genetic testing within newly identified families with hereditary nonpolyposis colorectal cancer. Methods: Cohort study conducted at the National Institutes of Health between April 15, 1996, and November 20, 1999. Data were collected through questionnaires before semistructured education sessions, individual counseling sessions, and the offer of genetic testing. Results: Of the 111 eligible first-degree relatives, 51% chose to participate in education and individual counseling sessions. Participation was associated with greater numbers of first-degree relatives with cancer; no association was found between participation and personal history of cancer. Before education and individual counseling sessions, 64% of participants had heard little about genetic testing for cancers; however, most (97%) stated intentions to pursue testing. Fifty-one percent identified learning about their children's risks as the most important reason to consider testing. Thirty-nine percent identified the potential effect on their health insurance as the most important reason to not undergo testing. Of the 111 eligible first-degree relatives, 51% chose to undergo genetic testing. Participants' intentions to pursue genetic testing were significantly affected by concerns regarding the ability to handle the emotional aspects of testing and the psychosocial effect on family members. Conclusions: Genetic counseling and testing offers the potential to focus cancer screening resources in individuals truly at increased risk, thereby reducing mortality and morbidity. Fears of discrimination and concerns about psychological and psychosocial issues may present barriers to the use of current cancer prevention strategies, including genetic counseling and testing. C1 NHGRI, Med Genet Branch, Genet Counseling Res Unit, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Genet Branch, Bethesda, MD USA. NCI, Biostat Data Management Sect, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Beaumont Hosp, Beaumont Hosp, Dept Med Oncol, Dublin 9, Ireland. RP Hadley, DW (reprint author), NHGRI, Med Genet Branch, Genet Counseling Res Unit, 10 Ctr Dr,MSC 1852,Bldg 10,Room 10C103, Bethesda, MD 20892 USA. EM dhadley@nhgri.nih.gov FU NHGRI NIH HHS [95-HG-0165] NR 37 TC 103 Z9 105 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 10 PY 2003 VL 163 IS 5 BP 573 EP 582 DI 10.1001/archinte.163.5.573 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 655PH UT WOS:000181561000008 PM 12622604 ER PT J AU Addadi, L Geva, M Kruth, HS AF Addadi, L Geva, M Kruth, HS TI Structural information about organized cholesterol domains from specific antibody recognition SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Review DE cholesterol-rich domain; antibody; molecular recognition; cell membrane; structure ID ATOMIC-FORCE MICROSCOPY; LOW-DENSITY LIPOPROTEIN; GPI-ANCHORED PROTEINS; PLASMA-MEMBRANE; MONOCLONAL-ANTIBODY; LIPID RAFTS; PHOSPHOLIPID MONOLAYERS; ANTIFREEZE PROTEIN; PERFRINGOLYSIN-O; CRYSTAL-SURFACES AB Cholesterol-rich domains have been observed to exist in cell membranes under physiological and pathological conditions. Their compositions and the microenvironment of their formation vary over a wide range. Very little information is however available on the molecular structure and organization of these domains. The techniques available to provide such structural information are reviewed here first. The possibility of using tailor-made antibodies as reporters of molecular organization in membranes is then considered. The concept of antibodies recognizing molecular organization rather than single molecular epitopes is established, reviewing the existing works on antibody and protein recognition of crystalline molecular arrays. The information that such antibodies could provide in cells is finally examined together with a proof of application. (C) 2003 Elsevier Science B.V All rights reserved. C1 Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. RP Addadi, L (reprint author), Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. NR 69 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD MAR 10 PY 2003 VL 1610 IS 2 BP 208 EP 216 DI 10.1016/S0005-2736(03)00019-1 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 662LV UT WOS:000181949000006 PM 12648775 ER PT J AU Lim, MH Kim, HO Moon, HR Lee, SJ Chun, MW Gao, ZG Melman, N Jacobson, KA Kim, JH Jeong, LS AF Lim, MH Kim, HO Moon, HR Lee, SJ Chun, MW Gao, ZG Melman, N Jacobson, KA Kim, JH Jeong, LS TI Design, synthesis and binding affinity of 3 '-fluoro analogues of Cl-IB-MECA as adenosine A(3) receptor ligands SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID RAT-BRAIN AB Several 3'-fluoro analogues, la, 1b, and le of selective and potent adenosine A(3) receptor agonist, Cl-IB-MECA were synthesized from D-xylose via highly regioselective opening of lyxo-epoxides, 8a and 811 with fluoride anion. Compared to the high binding affinity of Cl-IB-MECA to the A(3) adenosine receptor, the corresponding 3-fluoro derivative showed remarkably decreased binding affinity, indicating that 3'-hydroxyl group acts as hydrogen bonding acceptor, not hydrogen bonding donor like fluorine atom in binding to the A(3) adenosine receptor. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea. Seoul Natl Univ, Div Chem & Mol Engn, Seoul 151742, South Korea. Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Korea Inst Sci & Technol, Seoul 136791, South Korea. RP Jeong, LS (reprint author), Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 15 TC 20 Z9 20 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 MAR 10 PY 2003 VL 13 IS 5 BP 817 EP 820 DI 10.1016/S0960-894X(03)00027-1 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 655QG UT WOS:000181563500009 PM 12617898 ER PT J AU Li, P Peach, ML Zhang, MC Liu, HP Yang, DJ Nicklaus, M Roller, PP AF Li, P Peach, ML Zhang, MC Liu, HP Yang, DJ Nicklaus, M Roller, PP TI Structure-based design of thioether-bridged cyclic phosphopeptides binding to Grb2-SH2 domain SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PHOSPHOTYROSINE-CONTAINING PEPTIDE; SH2 DOMAIN; HIGH-AFFINITY; NONPHOSPHORYLATED INHIBITOR; REQUIREMENTS; ANTAGONIST; LIGANDS AB A series of phosphotyrosine containing cyclic peptides was designed and synthesized based upon the phage library derived cyclopeptide, G1TE. Considering the type-I beta-turn feature of peptidic ligand binding to Grb2 SH2 domain, we introduce alpha, alpha-disubstituted cyclic amino acid, Ach, into the 4th position of the cyclic peptide to induce a local right handed 3(10) helical conformation. In order to stabilize the favorable binding conformation, the bulky and hydrophobic amino acids, neopentylglycine (NPG) and phenylalanine, were introduced into the 8th and 2nd positions of the peptide ligand, respectively. To facilitate the sidechain of pTyr3 reaching into the phosphotyrosine binding pocket, a less bulky alanine was preferred in position 1. Based upon these global modifications, a highly potent peptide ligand 12 was discovered with an IC50 = 1.68 nM, evaluated by ELISA binding essay. Ligand 12 is at least 10(5) more potent than the lead peptide, termed G1TE. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. RP Roller, PP (reprint author), NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. OI Nicklaus, Marc/0000-0002-4775-7030 NR 15 TC 15 Z9 15 U1 0 U2 2 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 MAR 10 PY 2003 VL 13 IS 5 BP 895 EP 899 DI 10.1016/S0960-894X(03)00015-5 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 655QG UT WOS:000181563500027 PM 12617916 ER PT J AU Misra, RR Ratnasinghe, D Tangrea, JA Virtamo, J Andersen, MR Barrett, M Taylor, PR Albanes, D AF Misra, RR Ratnasinghe, D Tangrea, JA Virtamo, J Andersen, MR Barrett, M Taylor, PR Albanes, D TI Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer among male smokers in Finland SO CANCER LETTERS LA English DT Article DE alpha-tocopherol; beta-carotene; lung cancer; DNA repair; smoking ID LYS751GLN POLYMORPHISM; ALPHA-TOCOPHEROL; EXCISION-REPAIR; PREVENTION; POLYMERASE; ADDUCTS; SMOKING; BETA AB Associations between lung cancer risk and common polymorphisms in the DNA repair genes xeroderma pigmentosum complementation group D (XPD), X-ray repair cross-complementing group 1 (XRCC1), XRCC3 and apurinic/apyrimidinic endonuclease/redox factor 1 were examined within a randomized clinical trial designed to determine whether alpha-tocopherol, beta-carotene, or both would reduce cancer incidence among male smokers in Finland. We found no direct association between lung cancer risk and any of the DNA repair genotypes studied, however, the association between XPD codon 751 genotype and lung cancer was modified by alpha-tocopherol supplementation, and the association between XRCC1 codon 399 genotype and lung cancer was modified by the amount of smoking. Our results suggest that common alterations in single DNA repair genes are not major determinants of lung cancer susceptibility among smokers. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. New Chem Ent Inc, Thetagen Div, Bothell, WA USA. Informat Management Serv Inc, Silver Spring, MD 20904 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, FIN-00300 Helsinki, Finland. NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Misra, RR (reprint author), NCI, Canc Prevent Studies Branch, Ctr Canc Res, 6116 Execut Blvd,Suite 700, Bethesda, MD 20892 USA. EM misrar@ctep.nci.nih.gov RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01 CN45165] NR 23 TC 144 Z9 159 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAR 10 PY 2003 VL 191 IS 2 BP 171 EP 178 DI 10.1016/S0304-3835(02)00638-9 PG 8 WC Oncology SC Oncology GA 658GM UT WOS:000181713300006 PM 12618330 ER PT J AU Wu, CWH Kaas, JH AF Wu, CWH Kaas, JH TI Somatosensory cortex of prosimian galagos: Physiological recording, cytoarchitecture, and corticocortical connections of anterior parietal cortex and cortex of the lateral sulcus SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE primates; neocortex; motor cortex ID STREPSIRHINE PRIMATE GALAGO; IPSILATERAL CORTICAL CONNECTIONS; GRANULAR FRONTAL-CORTEX; MACAQUE MONKEYS; SOMATOTOPIC ORGANIZATION; BODY-SURFACE; SQUIRREL-MONKEYS; MARMOSET MONKEYS; M FASCICULARIS; OWL MONKEYS AB Compared with our growing understanding of the organization of somatosensory cortex in monkeys, little is known about prosimian primates, a major branch of primate evolution that diverged from anthropoid primates some 60 million years ago. Here we describe extensive results obtained from an African prosimian, Galago garnetti. Microelectrodes were used to record from large numbers of cortical sites in order to reveal regions of responsiveness to cutaneous stimuli and patterns of somatotopic organization. Injections of one to several. distinguishable tracers were placed at physiologically identified sites in four different cortical areas to label corticortical connections. Both types of results were related to cortical architecture. Three systematic representations of cutaneous receptors were revealed by the microelectrode recordings, S1 proper or area 3b, S2, and the parietal ventral area (PV), as described in monkeys. Strips of cortex rostral (presumptive area 3a) and caudal (presumptive area 1-2) to area 3b responded poorly to tactile stimuli in anesthetized galagos, but connection patterns with area 3b indicated that parallel somatosensory representations exist in both of these regions. Area 3b also interconnected somatotopically with areas S2 and PV. Areas S2 and PV had connections with areas 3a, 3b, 1-2, each other, other regions of the lateral sulcus, motor cortex (M1), cingulate cortex, frontal cortex, orbital cortex, and inferior parietal cortex. Connection patterns and recordings provided evidence for several additional fields in the lateral sulcus, including a retroinsular area (Ri), a parietal rostral area (PR), and a ventral somatosensory area (VS). Galagos appear to have retained an ancestoral preprimate arrangement of five basic areas (S1 proper, 3a, 1-2, S2, and PV). Some of the additional areas suggested for lateral parietal cortex may be primate specializations. C1 Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Kaas, JH (reprint author), Vanderbilt Univ, Dept Psychol, 301 Wilson Hall, Nashville, TN 37240 USA. EM jon.h.kaas@vanderbilt.edu FU NINDS NIH HHS [NS16446, R01 NS016446] NR 64 TC 55 Z9 56 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAR 10 PY 2003 VL 457 IS 3 BP 263 EP 292 DI 10.1002/cne.10542 PG 30 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 641UV UT WOS:000180766200004 PM 12541310 ER PT J AU Coombs, RW Reichelderfer, PS Landay, AL AF Coombs, RW Reichelderfer, PS Landay, AL TI Recent observations on HIV type-1 infection in the genital tract of men and women SO AIDS LA English DT Editorial Material DE AIDS; HIV-1; sexual transmission; genitalia; mucous membrane; male; female; cervix; semen; virus shedding ID HUMAN-IMMUNODEFICIENCY-VIRUS; LEUKOCYTE PROTEASE INHIBITOR; SEXUALLY-TRANSMITTED DISEASES; ACTIVE ANTIRETROVIRAL THERAPY; FEMALE REPRODUCTIVE-TRACT; VITAMIN-A-DEFICIENCY; HUMAN SEMINAL PLASMA; TIGHT EPITHELIAL BARRIERS; NECROSIS-FACTOR-ALPHA; HERPES-SIMPLEX VIRUS C1 Rush Presbyterian St Lukes Med Ctr, Dept Microbiol & Immunol, Chicago, IL 60612 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Landay, AL (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Microbiol & Immunol, 1653 W Congress Pkwy, Chicago, IL 60612 USA. FU NICHD NIH HHS [HD 40540-02, HD-33162, HD-40541-02]; PHS HHS [AL-27664] NR 284 TC 170 Z9 176 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 7 PY 2003 VL 17 IS 4 BP 455 EP 480 DI 10.1097/01.aids.0000042970.95433.f9 PG 26 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 653KT UT WOS:000181434900001 PM 12598766 ER PT J AU Rugeles, MT Trubey, CA Bedoya, VI Pinto, LA Oppenheim, JJ Rybak, SA Shearer, GM AF Rugeles, MT Trubey, CA Bedoya, VI Pinto, LA Oppenheim, JJ Rybak, SA Shearer, GM TI Ribonuclease is partly responsible for the HIV-1 inhibitory effect activated by HLA alloantigen recognition SO AIDS LA English DT Article DE AIDS; HIV; RNase; eosinophil-derived neurotoxin; alloantigen-stimulation; HIV-inhibitory factor ID CD8(+) T-CELLS; REVERSE TRANSCRIPTION; VIRUS-REPLICATION; TYPE-1; INFECTION AB Objective: This study was performed to determine whether ribonucleases (RNases) contribute to the soluble HIV-1 inhibitory activity that results from the recognition of HLA alloantigens. Design and methods: Supernatants from mixed lymphocyte reactions of peripheral blood mononuclear cells from healthy HLA-discordant individuals exhibited HIV-1 inhibitory activity (alloantigen-stimulated factors; ASF). These supernatants were tested for their sensitivity to heating (90degreesC for 3 min), and for the presence of three RNases belonging to the RNase A superfamily: eosinophil-clerived neurotoxin (EDN); RNase A; and angiogenin. Polyclonal antibodies specific for these RNases were used for Western blot analysis of the ASF, as well as for blocking the HIV-1 inhibitory activity of ASF. In addition, an RNase inhibitor (RI) was used to determine whether the anti-viral activity of ASIF was due to RNase activity. Results: HIV-1 inhibitory activity of ASF was: (i) resistant to heat treatment; (ii) blocked by 58% with an antibody specific for EDN, but not with antibodies against RNase A or angiogenin; and (iii) blocked by 65-100% with an RI. Moreover, Western blot analysis with an anti-EDN antibody detected EDN in the ASF. Conclusion: These findings indicate that the majority of the soluble HIV-1 inhibitory activity contained in the supernatants of mixed lymphocyte reactions is due to EDN or a closely related RNase. (C) 2003 Lippincott Williams Wilkins. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Antioquia, Medellin, Colombia. NCI, SAIC, Lab HPV, Frederick, MD 21701 USA. NCI, SAIC, Mol Immunoregulat Lab, Frederick, MD 21701 USA. NCI, SAIC, Dev Therapeut Program, Frederick, MD 21701 USA. RP Shearer, GM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Rm 4B-36, Bethesda, MD 20892 USA. FU PHS HHS [N01-C0-12400] NR 19 TC 52 Z9 55 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 7 PY 2003 VL 17 IS 4 BP 481 EP 486 DI 10.1097/01.aids.0000050850.71999.cd PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 653KT UT WOS:000181434900002 PM 12598767 ER PT J AU Lee, HK Takamiya, K Han, JS Man, HY Kim, CH Rumbaugh, G Yu, S Ding, L He, C Petralia, RS Wenthold, RJ Gallagher, M Huganir, RL AF Lee, HK Takamiya, K Han, JS Man, HY Kim, CH Rumbaugh, G Yu, S Ding, L He, C Petralia, RS Wenthold, RJ Gallagher, M Huganir, RL TI Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory SO CELL LA English DT Article ID LONG-TERM DEPRESSION; SELECTIVE GLUTAMATE RECEPTORS; DEPENDENT PROTEIN-KINASE; REGULATORY PHOSPHORYLATION; RAT-BRAIN; SYNAPSES; POTENTIATION; SITES; HIPPOCAMPUS; MICE AB Plasticity of the nervous system is dependent on mechanisms that regulate the strength of synaptic transmission. Excitatory synapses in the brain undergo long-term potentiation (LTP) and long-term depression (LTD), cellular models of learning and memory. Protein phosphorylation is required for the induction of many forms of synaptic plasticity, including LTP and LTD. However, the critical kinase substrates that mediate plasticity have not been identified. We previously reported that phosphorylation of the GluR1 subunit of AMPA receptors, which mediate rapid excitatory transmission in the brain, is modulated during LTP and LTD. To test if GluR1 phosphorylation is necessary for plasticity and learning and memory, we generated mice with knockin mutations in the GluR1 phosphorylation sites. The phosphomutant mice show deficits in LTD and LTP and have memory defects in spatial learning tasks. These results demonstrate that phosphorylation of GluR1 is critical for LTD and LTP expression and the retention of memories. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Howard Hughes Med Inst, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Psychol, Baltimore, MD 21218 USA. NIDCD, NIH, Bethesda, MD 20892 USA. RP Huganir, RL (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, Howard Hughes Med Inst, Baltimore, MD 21205 USA. OI Lee, Hey-Kyoung/0000-0002-5554-983X FU NIMH NIH HHS [R01 MH61108-02] NR 48 TC 416 Z9 444 U1 1 U2 31 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 7 PY 2003 VL 112 IS 5 BP 631 EP 643 DI 10.1016/S0092-8674(03)00122-3 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 653NW UT WOS:000181443600007 PM 12628184 ER PT J AU Klarmann, GJ Chen, X North, TW Preston, BD AF Klarmann, GJ Chen, X North, TW Preston, BD TI Incorporation of uracil into minus strand DNA affects the specificity of plus strand synthesis initiation during lentiviral reverse transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FELINE IMMUNODEFICIENCY VIRUS; POLYPURINE TRACT; IN-VITRO; REPAIR ENZYME; RNASE-H; REPLICATION; DUTPASE; SEQUENCE; RECOGNITION; BINDING AB Many retroviruses either encode dUTP pyrophosphatase (dUTPase) or package host-derived uracil DNA glycosylase as a means to limit the accumulation of uracil in DNA strands, suggesting that uracil is detrimental to one or more steps in the viral life cycle. In the present study, the effects of DNA uracilation on (-) strand DNA synthesis, RNase H activity, and (+) strand DNA synthesis were investigated in a cell-free system. This system uses the activities of purified human immunodeficiency virus type 1 (HIV-1) reverse transcriptase to convert single-stranded RNA to double-stranded DNA in a single reaction mixture. Substitution of dUTP for dTTP had no effect on (-) strand synthesis but significantly decreased yields of (+) strand DNA. Mapping of nascent (+) strand 5' ends revealed that this was due to decreased initiation from polypurine tracts with a concomitant increase in initiation at non-polypurine tract sites. Aberrant initiation correlated with a change in RNase H cleavage specificity when assayed on preformed RNA-DNA duplexes containing uracilated DNA, suggesting that appropriate "selection" of the (+) strand primer is affected. Collectively, these data suggest that accumulation of uracil in retroviral DNA may disrupt the viral life cycle by altering the specificity of (+) strand DNA synthesis initiation during reverse transcription. C1 Univ Utah, Dept Biochem, Salt Lake City, UT 84112 USA. Univ Utah, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA. Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. RP Klarmann, GJ (reprint author), NCI, HIV Drug Resistant Program, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [P30 CA42014]; NIAID NIH HHS [R01 AI38755, R01 AI34834, R01 AI28189] NR 54 TC 56 Z9 58 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 7 PY 2003 VL 278 IS 10 BP 7902 EP 7909 DI 10.1074/jbc.M207223200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 653ZK UT WOS:000181466800022 PM 12458216 ER PT J AU He, YY Huang, JL Ramirez, DC Chignell, CF AF He, YY Huang, JL Ramirez, DC Chignell, CF TI Role of reduced glutathione efflux in apoptosis of immortalized human keratinocytes induced by UVA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ULTRAVIOLET-B RADIATION; PLASMA-MEMBRANE PHOSPHATIDYLSERINE; CASPASE-INDEPENDENT PATHWAY; ACTIVATED PROTEIN-KINASE; CALCIUM-CHANNEL BLOCKERS; OXIDATIVE STRESS; BIOLOGICAL SAMPLES; MEDIATED APOPTOSIS; MALIGNANT-MELANOMA; DELAYED APOPTOSIS AB We have investigated the role played by GSH efflux in apoptosis of human HaCaT keratinocytes induced by UVA irradiation. UVA irradiation of HaCaT cells caused a rapid rise in GSH efflux across the intact cell membrane, followed by an increase in apoptosis. GSH efflux was stimulated by glucose and was reduced by the addition of exogenous GSH and intracellular GSH depletion by buthionine sulfoximine, suggesting that GSH transport is active and is influenced by the GSH concentration gradient across the cell membrane. Verapamil and cyclosporin A, blockers of the multidrug resistance-associated protein, decreased UVA-induced GSH efflux. GSH efflux occurred within 2 h of LTVA irradiation, suggesting that the stimulation of GSH efflux is due to an increase in the activity of pre-existing multidrug resistance-associated protein transporter carrier. Although inhibition of GSH efflux did not affect caspase activation and DNA fragmentation, it delayed the gradual increase in plasma membrane permeability and reduced phosphatidylserine translocation in HaCaT cells. It is therefore likely that upon LTVA irradiation, GSH efflux increased the intracellular oxidative stress without intervention of reactive oxygen species, thus resulting in more phosphatidylserine externalization and membrane rearrangement. These provide targets for macrophage recognition and phagocytosis and thus minimize the potential to invoke inflammation or neoplastic transformation. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP He, YY (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI RAMIREZ, DARIO/K-3312-2013 OI RAMIREZ, DARIO/0000-0001-6725-3326 NR 60 TC 63 Z9 67 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 7 PY 2003 VL 278 IS 10 BP 8058 EP 8064 DI 10.1074/jbc.M207781200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 653ZK UT WOS:000181466800041 PM 12502708 ER PT J AU Vullhorst, D Buonanno, A AF Vullhorst, D Buonanno, A TI Characterization of general transcription factor 3, a transcription factor involved in slow muscle-specific gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WILLIAMS-BEUREN-SYNDROME; SYNDROME CRITICAL REGION; TFII-I; FIBER-TYPE; TRANSGENIC MICE; DEPENDENT REGULATION; BINDING PROTEIN; SONIC HEDGEHOG; IDENTIFICATION; SEQUENCES AB General transcription factor 3 (GTF3) binds specifically to the bicoid-like motif of the troponin I-slow upstream enhancer. This motif is part of a sequence that restricts enhancer activity to slow muscle fibers. GTF3 contains multiple helix-loop-helix domains and an amino-terminal leucine zipper motif. Here we show that helix-loop-helix domain 4 is necessary and sufficient for binding the bicoid-like motif. Moreover, the affinity of this interaction is enhanced upon removal of amino-terminal sequences including domains 1 and 2, suggesting that an unmasking of the DNA binding surface may be a precondition for GTF3 to bind DNA in vivo. We have also investigated the interactions of six GTF3 splice variants of the mouse, three of which were identified in this study, with the troponin enhancer. The gamma-isoform lacking exon 23, and exons 26-28 that encode domain 6, interacted most avidly with the bicoid-like motif, the alpha- and beta- isoforms that include these exons fail to bind in gel retardation assays. We also show that GTF3 polypeptides associate with each other via the leucine zipper. We speculate that cells can generate a large number of GTF3 proteins with distinct DNA binding properties by alternative splicing and combinatorial association of GTF3 polypeptides. C1 NICHD, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Buonanno, A (reprint author), NICHD, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NR 45 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 7 PY 2003 VL 278 IS 10 BP 8370 EP 8379 DI 10.1074/jbc.M209361200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 653ZK UT WOS:000181466800082 PM 12475981 ER PT J AU Tansey, JT Huml, AM Vogt, R Davis, KE Jones, JM Fraser, KA Brasaemle, DL Kimmel, AR Londos, C AF Tansey, JT Huml, AM Vogt, R Davis, KE Jones, JM Fraser, KA Brasaemle, DL Kimmel, AR Londos, C TI Functional studies on native and mutated forms of perilipins - A role in protein kinase A-mediated lipolysis of triacylglycerols in Chinese hamster ovary cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HORMONE-SENSITIVE LIPASE; ACYL-COA SYNTHETASE; ADIPOCYTES; DROPLETS; STORAGE; OBESITY; BLOCKS; INHIBITION; INFECTION; TRIACSINS AB Perilipin A coats the lipid storage droplets in adipocytes and is polyphosphorylated by protein kinase A (PKA); the fact that PKA activates lipolysis in adipocytes suggests a role for perilipins in this process. To assess whether perilipins participate directly in PKA-mediated lipolysis, we have expressed constructs coding for native and mutated forms of the two major splice variants of the perilipin gene, perilipins A and B, in Chinese hamster ovary fibroblasts. Perilipins localize to lipid droplet surfaces and displace the adipose differentiation-related protein that normally coats the droplets in these cells. Perilipin A inhibits triacylglycerol hydrolysis by 87% when PKA is quiescent, but activation of PKA and phosphorylation of perilipin A engenders a 7-fold lipolytic activation. Mutation of PKA sites within the N-terminal region of perilipin abrogates the PKA-mediated lipolytic response. In contrast, perilipin B exerts only minimal protection against lipolysis and is unresponsive to PKA activation. Since Chinese hamster ovary cells contain no PKA-activated lipase, we conclude that the expression of perilipin A alone is sufficient to confer PKA-mediated lipolysis in these cells. Moreover, the data indicate that the unique C-terminal portion of perilipin A is responsible for its protection against lipolysis and that phosphorylation at the N-terminal PKA sites attenuates this protective effect. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Londos, C (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 50,Rm 3140, Bethesda, MD 20892 USA. OI Brasaemle, Dawn/0000-0002-8553-8285 NR 27 TC 151 Z9 154 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 7 PY 2003 VL 278 IS 10 BP 8401 EP 8406 DI 10.1074/jbc.M211005200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 653ZK UT WOS:000181466800086 PM 12477720 ER PT J AU Tian, LJ Coghill, LS MacDonald, SHF Armstrong, DL Shipston, MJ AF Tian, LJ Coghill, LS MacDonald, SHF Armstrong, DL Shipston, MJ TI Leucine zipper domain targets cAMP-dependent protein kinase to mammalian BK channels SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED POTASSIUM CHANNELS; SENSITIVE K+ CHANNEL; LARGE-CONDUCTANCE; CATALYTIC SUBUNIT; COILED COILS; CALCIUM; PHOSPHORYLATION; MODULATION; INTERACTS AB Large conductance, calcium- and voltage-activated potassium (BK) channels control excitability in many tissues and are regulated by several protein kinases and phosphatases that remain associated with the channels in cell-free patches of membrane. Here, we report the identification of a highly conserved, non-canonical, leucine zipper (LZ1) in the C terminus of mammalian BK channels that is required for cAMP-dependent protein kinase (PKA) to associate with the channel and regulate its activity. A synthetic polypeptide encompassing the central d position leucine residues in LZ1 blocks the regulation of recombinant mouse BK channels by endogenous PKA in HEK293 cells. In contrast, neither an alanine-substituted LZ1 peptide nor a peptide corresponding to another, more C-terminal putative leucine zipper LZ2, had any effect on regulation of the channels by endogenous PKA. Mutagenesis of the central two LZ1 d position leucines to alanine in the BK channel also eliminated regulation by endogenous PKA in HEK293 cells without altering the channel sensitivity to activation by voltage or by exogenous purified PKA. Inclusion of the STREX splice insert in the BK channel protein, which switches channel regulation by PKA from stimulation to inhibition, did not alter the requirement for an intact LZ1. Although PKA does not bind directly to the channel protein in vitro, mutation of LZ1 abolished co-immuno-precipitation of PKA and the respective BK channel splice variant from HEK293 cells. Furthermore, a 127-amino acid fusion protein encompassing the functional LZ1 domain co-immunoprecipitates a PKA-signaling complex from rat brain. Thus LZ1 is required for the association and regulation of mammalian BK channels by PKA, and other putative leucine zippers in the BK channel protein may provide anchoring for other regulatory enzyme complexes. C1 Univ Edinburgh, Sch Med, Div Biomed Sci, Membrane Biol Grp, Edinburgh EH8 9XD, Midlothian, Scotland. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Shipston, MJ (reprint author), Univ Edinburgh, Sch Med, Div Biomed Sci, Membrane Biol Grp, Hugh Robson Bldg, Edinburgh EH8 9XD, Midlothian, Scotland. RI Shipston, Mike/C-7309-2013 OI Shipston, Mike/0000-0001-7544-582X NR 36 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 7 PY 2003 VL 278 IS 10 BP 8669 EP 8677 DI 10.1074/jbc.M211661200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 653ZK UT WOS:000181466800119 PM 12509433 ER PT J AU Cen, O Gorska, MM Stafford, SJ Sur, S Alam, R AF Cen, O Gorska, MM Stafford, SJ Sur, S Alam, R TI Identification of UNC119 as a novel activator of SRC-type tyrosine kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C-SRC; SH2 DOMAIN; CRYSTAL-STRUCTURES; HUMAN EOSINOPHILS; T-LYMPHOCYTES; HRG4 UNC119; B-CELLS; LYN; CD45; PHOSPHORYLATION AB Lyn, an Src-type tyrosine kinase, is associated with the interleukin (IL)-5 receptor in eosinophils. The mechanism of its activation is unknown. Through yeast two-hybrid screening we have cloned and characterized a new signaling molecule, Unc119, that associates with IL-5Ralpha and Src family tyrosine kinases. Unc119 induces the catalytic activity of these kinases through interaction with Src homology 2 and 3 domains. IL-5 stimulation of eosinophils increases Unc119 association with Lyn and induces its catalytic activity. Lyn is important for eosinophil survival. Eosinophils that are transduced with Unc119 have increased Lyn activity and demonstrate prolonged survival in the absence of IL-5. Inhibition of Unc119 down-regulates eosinophil survival. To our knowledge Unc119 is the first receptor-associated activator of Src family tyrosine kinases. C1 NIAID, Div Allergy & Immunol, Res Ctr, Dept Internal Med, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. RP Alam, R (reprint author), Natl Jewish Med & Res Ctr, 1400 Jackson St, Denver, CO 80206 USA. FU NIAID NIH HHS [AI P01 46004, AI50179]; NIEHS NIH HHS [ES06676] NR 41 TC 37 Z9 39 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 7 PY 2003 VL 278 IS 10 BP 8837 EP 8845 DI 10.1074/jbc.M208261200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 653ZK UT WOS:000181466800140 PM 12496276 ER PT J AU Rogozin, IB Aravind, L Koonin, EV AF Rogozin, IB Aravind, L Koonin, EV TI Differential action of natural selection on the N and C-terminal domains of 2 '-5 ' oligoadenylate synthetases and the potential nuclease function of the C-terminal domain SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE 2 '-5 ' oligoadenylate synthetases; nuclease domain; positive selection; ATP-cone domain; nucleotidyltransferases ID CYTOPLASMIC POLY(A) POLYMERASE; INTERFERON-INDUCED 56-KDA; AMINO-ACID SITES; 2',5'-OLIGOADENYLATE SYNTHETASE; 2'-5'-OLIGOADENYLATE SYNTHETASE; DNA-POLYMERASE; NUCLEOTIDYLTRANSFERASE SUPERFAMILY; (2'-5')OLIGOADENYLATE SYNTHETASE; EVOLUTIONARY INFORMATION; POSITIVE SELECTION AB 2'-5' Oligoadenylate synthetases (OAS) are a family of enzymes, which are best known for their important role in interferon-dependent antiviral mechanisms, but are also involved in the regulation of apoptosis, cell growth and differentiation in vertebrates. These enzymes bind double-stranded RNA and catalyze the synthesis of 2'-5' oligoadenylates from ATR Several 2-5' oligoadenylate synthetase-like proteins, which lack the ability to synthesize 2'-5' A, have been recently identified in humans and mice; the functions of these inactivated OAS derivatives remain unknown. Examination of phylogenetic trees shows that OAS inactivation in mammals occurred on several independent occasions. Comparative sequence analysis of OAS, poly(A)-polymerases, TRF4/sigma-family polymerases, archaeal CCA-adding enzymes and uridilyltransferases from trypanosomes resulted in the identification of a C-terminal domain, which is conserved in all these enzymes and is distinct from the nucleotidyltransferase domain. Secondary structure prediction shows that this domain has a four-helix core, which is most closely related to the ATP-cone domain, a regulatory nucleotide-binding domain present in ribonucleotide reductases and several other enzymes and transcription regulators. These observations, taken together with the experimental evidence of nuclease activity in the TRF4/sigma-family of polymerases, suggest that the C-terminal domain of OAS and their homologs might have nuclease activity The putative nuclease domain is preferentially conserved in OAS derivatives that lack an active nucleotidyltransferase domain and, as indicated by the analysis of the ratio of synonymous to non-synonymous substitutions, appears to be subject to purifying selection in these proteins. In contrast, phylogenetic analysis provided evidence of episodic positive selection in the mouse OAS-like proteins with inactivated nucleotidyltransferase domains, which suggests that some of these proteins might have distinct antiviral functions. (C) 2003 Published by Elsevier Science Ltd. C1 NIH, Natl Ctr Biotechnol Information, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Information, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 86 TC 30 Z9 30 U1 0 U2 4 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 MAR 7 PY 2003 VL 326 IS 5 BP 1449 EP 1461 DI 10.1016/S0022-2836(03)00055-X PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 657ZZ UT WOS:000181698300013 PM 12595257 ER PT J AU Przybyl, AK Flippen-Anderson, JL Jacobson, AE Rice, KC AF Przybyl, AK Flippen-Anderson, JL Jacobson, AE Rice, KC TI Practical and high-yield syntheses of dihydromorphine from tetrahydrothebaine and efficient syntheses of (8S)-8-bromomorphide SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID CODEINE AB A practical method for the conversion of tetrahydrothebaine to dihydromorphine in 92% yield is described. The procedure should allow more efficient production of opium products and may be easily modified for large-scale synthesis. The conversion of codeine to (8S)-8-bromomorphide, a potentially valuable intermediate to 6-demethoxyoripavine and derivatives, is also described. The absolute configuration of (8S)-8-bromomorphide was determined by a single-crystal X-ray diffraction study of the hydrobromide salt. C1 NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. RP Rice, KC (reprint author), NIDDKD, Med Chem Lab, NIH, Bldg 8,Room B1-22,8 Ctr Dr,MSC 0815, Bethesda, MD 20892 USA. EM kr21@nih.gov NR 22 TC 6 Z9 6 U1 0 U2 3 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 MAR 7 PY 2003 VL 68 IS 5 BP 2010 EP 2013 DI 10.1021/jo0206871 PG 4 WC Chemistry, Organic SC Chemistry GA 651PV UT WOS:000181329900051 PM 12608825 ER PT J AU Ma, XQ Saksena, R Chernyak, A Kovac, P AF Ma, XQ Saksena, R Chernyak, A Kovac, P TI Neoglycoconjugates from synthetic tetra- and hexasaccharides that mimic the terminus of the O-PS of Vibrio cholerae O : 1, serotype Inaba SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID METHYL ALPHA-GLYCOSIDES; SQUARIC ACID DIESTER; ANTIGENIC DETERMINANTS; C-13-NMR SPECTRA; DIETHYL SQUARATE; BLOCK SYNTHESIS; OGAWA; POLYSACCHARIDE; PROTEINS; DISACCHARIDE AB A glycosyl acceptor and a glycosyl donor having the N-3-deoxy-L-glycero-tetronic acid side chain already attached have been prepared and used for the synthesis of the di- through to the hexasaccharide that mimic the upstream terminus of the O-specific polysaccharide of Vibrio cholerae O:1, serotype Inaba. The target tetra- and the hexasaccharide, which were obtained in the form of 5-methoxycarbonylpentyl glycosides, were linked,to BSA using squaric acid diester chemistry. The conjugation reactions were monitored by surface enhanced laser desorption ionization-time of flight mass spectrometry (SELDI-TOF MS). This allowed the progression of the conjugation of the synthetic oligosaccharides in a controlled way and termination of the reaction when the desired molar hapten/ BSA ratio had been reached, yielding neoglycoconjugates with predetermined carbohydrate/carrier ratios. The ability to monitor the conjugation by the SELDI-TOF MS technique made it possible to prepare, from one hapten in a one-pot reaction, several neoglycoconjugates having different, predetermined carbohydrate/carrier ratios. C1 NIDDK, LMC, NIH, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, LMC, NIH, Bethesda, MD 20892 USA. NR 28 TC 25 Z9 27 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PD MAR 7 PY 2003 VL 1 IS 5 BP 775 EP 784 DI 10.1039/b211660j PG 10 WC Chemistry, Organic SC Chemistry GA 659VP UT WOS:000181798400004 PM 12929359 ER PT J AU Libby, RT Smith, RS Savinova, OV Zabaleta, A Martin, JE Gonzalez, FJ John, SWM AF Libby, RT Smith, RS Savinova, OV Zabaleta, A Martin, JE Gonzalez, FJ John, SWM TI Modification of ocular defects in mouse developmental glaucoma models by tyrosinase SO SCIENCE LA English DT Article ID PRIMARY CONGENITAL GLAUCOMA; TRANSCRIPTION FACTOR GENE; FETAL DEVELOPMENT; ADRENERGIC CELLS; RETINOIC ACID; NEURAL CREST; PHENOTYPES; PROMOTER; NEURONS; CYP1B1 AB Mutations in the cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1) gene are a common cause of human primary congenital glaucoma (PCG). Here we show that Cyp1b1(-/-) mice have ocular drainage structure abnormalities resembling those reported in human PCG patients. Using Cyp1b1(-/-) mice, we identified the tyrosinase gene (Tyr) as a modifier of the drainage structure phenotype, with Tyr deficiency increasing the magnitude of dysgenesis. The severe dysgenesis in eyes lacking both CYP1B1 and TYR was alleviated by administration of the tyrosinase product dihydroxyphenylalanine (L-dopa). Tyr also modified the drainage structure dysgenesis in mice with a mutant Foxc1 gene, which is also involved in PCG. These experiments raise the possibility that a tyrosinase/L-dopa pathway modifies human PCG, which could open new therapeutic avenues. C1 Jackson Lab, Bar Harbor, ME 04609 USA. Howard Hughes Med Inst, Bar Harbor, ME 04609 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. RP John, SWM (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. OI Libby, Richard/0000-0003-2844-7632 FU NCI NIH HHS [CA34196] NR 28 TC 119 Z9 131 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 7 PY 2003 VL 299 IS 5612 BP 1578 EP 1581 DI 10.1126/science.1080095 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652EY UT WOS:000181367900039 PM 12624268 ER PT J AU Reynolds, JH Desimone, R AF Reynolds, JH Desimone, R TI Interacting roles of attention and visual salience in V4 SO NEURON LA English DT Article ID EXTRASTRIATE AREA V4; SELECTIVE ATTENTION; NEURAL MECHANISMS; RECEPTIVE-FIELD; MACAQUE MONKEY; SIMPLE CELLS; CORTEX; RESPONSES; MT; STIMULUS AB Attention increases the contrast gain of V4 neurons, causing them to respond to an attended stimulus as though its contrast had increased. When multiple stimuli appear within a neuron's receptive field (RF), the neuron responds primarily to the attended stimulus. This suggests that cortical cells may be "hard wired" to respond preferentially to the highest-contrast stimulus in their RF, and neural systems for attention capitalize on this mechanism by dynamically increasing the effective contrast of the stimulus that is task relevant. To test this, we varied the relative contrast of two stimuli within the recorded neurons' RFs, while the monkeys attended away to another location. Increasing the physical contrast of one stimulus caused V4 neurons to respond preferentially to that stimulus and reduced their responses to competing stimuli. When attention was directed to the lower-contrast stimulus, it partially overcame the influence of a competing, higher-contrast stimulus. C1 Salk Inst Biol Studies, Syst Neurobiol Lab, La Jolla, CA 92037 USA. NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Reynolds, JH (reprint author), Salk Inst Biol Studies, Syst Neurobiol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. NR 33 TC 220 Z9 222 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR 6 PY 2003 VL 37 IS 5 BP 853 EP 863 DI 10.1016/S0896-6273(03)00097-7 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 653TH UT WOS:000181452800014 PM 12628175 ER PT J AU Yanovski, JA Rose, SR Municchi, G Pescovitz, OH Hill, SC Cassorla, FG Cutler, GB AF Yanovski, JA Rose, SR Municchi, G Pescovitz, OH Hill, SC Cassorla, FG Cutler, GB TI Treatment with a luteinizing hormone-releasing hormone agonist in adolescents with short stature SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CENTRAL PRECOCIOUS PUBERTY; BONE-MINERAL DENSITY; IDIOPATHIC SHORT STATURE; NORMALLY TIMED PUBERTY; GH-DEFICIENT CHILDREN; SHORT NORMAL GIRLS; GROWTH-HORMONE; FINAL HEIGHT; ADULT HEIGHT; DELAYED PUBERTY AB Background: Treatment with a luteinizing hormone-releasing hormone (LHRH) agonist increases adult height in children with LHRH-dependent precocious puberty and is prescribed by some practitioners to augment height in short adolescents. We performed a randomized clinical trial to determine whether treatment with an LHRH agonist increases adult height in short adolescents with normally timed puberty. Methods: Fifty short adolescents (18 boys and 32 girls) with low predicted adult height (mean [+/-SD], 3.3+/-1.2 SD below the population mean) received either placebo (24 subjects) or an LHRH agonist (26 subjects). The mean (+/-SD) duration of treatment was 3.5+/-0.9 years in the LHRH-agonist group and 2.1+/-1.2 years in the placebo group (P<0.001). Adult height was measured when bone age exceeded 16 years in girls and 17 years in boys and when the rate of growth was less than 1.5 cm per year. Results: Forty-seven adolescents (94 percent) were followed until they attained adult height. At the time adult height was achieved, the subjects who had been treated with an LHRH agonist were older than those who had received placebo (20.5+/-2.1 years vs. 18.0+/-2.5 years, P=0.01) and were taller (standard-deviation score, -2.2+/-1.1 vs. -3.0+/-1.2; P=0.01). Analysis of covariance showed that LHRH-agonist treatment resulted in an increase of 0.6 (95 percent confidence interval, 0.2 to 0.9) in the standard-deviation score for height, or an increase of 4.2 cm (95 percent confidence interval, 1.7 to 6.7), over the initially predicted adult height (P=0.01). Treatment with an LHRH agonist resulted in significantly greater adult height than did placebo in boys and girls, in adolescents with idiopathic short stature, and in those who had a growth-limiting syndrome. The principal adverse event in the LHRH-agonist group was decreased accretion of bone mineral density (mean lumbar vertebral bone mineral density at the time adult height was achieved, 1.6+/-1.2 SD below the population mean, vs. 0.3+/-1.2 SD below the population mean in the placebo group; P<0.001). Conclusions: Treatment with an LHRH agonist for 3.5 years increases adult height by 0.6 SD in adolescents with very short stature but substantially decreases bone mineral density. Such treatment cannot be routinely recommended to augment height in adolescents with normally timed puberty. C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NICHHD, Sect Dev Endocrinol, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NIH, Diagnost Radiol Div, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NIH, 10 Ctr Dr,Bldg 10,Rm 10N262,MSC 1862, Bethesda, MD 20892 USA. OI Yanovski, Jack/0000-0001-8542-1637 FU NCRR NIH HHS [5M01 RR00997]; NICHD NIH HHS [Z01 HD-00610, Z01 HD-00641] NR 52 TC 71 Z9 77 U1 0 U2 2 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 MAR 6 PY 2003 VL 348 IS 10 BP 908 EP 917 DI 10.1056/NEJMoa013555 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 651UU UT WOS:000181341100006 PM 12621135 ER PT J AU Birenbaum, D Mattison, DR AF Birenbaum, D Mattison, DR TI Analgesics for the treatment of pain in children SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20852 USA. NIH, Bethesda, MD 20892 USA. RP Birenbaum, D (reprint author), US FDA, Rockville, MD 20852 USA. RI Mattison, Donald/C-2015-2009 NR 2 TC 1 Z9 1 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 MAR 6 PY 2003 VL 348 IS 10 BP 959 EP 960 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 651UU UT WOS:000181341100031 PM 12621144 ER PT J AU Vernon, EG Malik, K Reynolds, P Powlesland, R Dallosso, AR Jackson, S Henthorn, K Green, ED Brown, KW AF Vernon, EG Malik, K Reynolds, P Powlesland, R Dallosso, AR Jackson, S Henthorn, K Green, ED Brown, KW TI The parathyroid hormone-responsive B1 gene is interrupted by a t(1;7)(q42;p15) breakpoint associated with Wilms' tumour SO ONCOGENE LA English DT Article DE Wilms' tumour; chromosome 7; PTH-B1 gene ID SHORT ARM; HETEROZYGOSITY; TRANSLOCATION; CHROMOSOME-7; CELLS; LOCUS; IDENTIFICATION; ABNORMALITIES; MUTATIONS; ALLELES AB Wilms' tumour (WT) has a diverse and complex molecular aetiology, with several different loci identified by cytogenetic and molecular analyses. One such locus is on chromosome 7p, where cytogenetic abnormalities and loss of heterozygosity (LOH) indicate the presence of a Wilms' tumour suppressor gene. In order to isolate a candidate gene for this locus, we have characterized the breakpoint regions at a novel constitutional chromosome translocation (t(1;7)(q42;p15)), found in a child with WT and skeletal abnormalities. We identified two genes that were interrupted by the translocation: the parathyroid hormone-responsive B1 gene (PTH-B1) at 7p and obscurin at 1q. With no evidence for LOH at 1q42, we focused on the characterization of PTH-B1. We detected novel alternately spliced isoforms of PTH-B1, which were expressed in a wide range of adult and foetal tissues. Importantly, expression of two isoforms were disrupted in the WT of the t(1;7) patient. We also identified an additional splice isoform expressed only in 7p LOH tumours. The disruption of PTH-B1 by the t(1;7), together with aberrant splicing in sporadic WTs, suggests that PTH-B1 is a candidate for the 7p Wilms' tumour suppressor gene. C1 Univ Bristol, Sch Med Sci, Dept Pathol & Microbiol, CLIC Res Unit, Bristol BS8 1TD, Avon, England. MGH Canc Ctr, Boston, MA USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Brown, KW (reprint author), Univ Bristol, Sch Med Sci, Dept Pathol & Microbiol, CLIC Res Unit, Bristol BS8 1TD, Avon, England. RI dallosso, anthony/A-8335-2008; Brown, Keith/C-3355-2009; OI Brown, Keith/0000-0002-4258-5129; Dallosso, Anthony/0000-0002-1460-2550 NR 31 TC 23 Z9 25 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 6 PY 2003 VL 22 IS 9 BP 1371 EP 1380 DI 10.1038/sj.onc.1206332 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 652CA UT WOS:000181360900012 PM 12618763 ER PT J AU Resnick, SM Henderson, VW AF Resnick, SM Henderson, VW TI Estrogen replacement and risk of Alzheimer disease - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Epidemiol, Little Rock, AR 72205 USA. RP Resnick, SM (reprint author), NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 5 PY 2003 VL 289 IS 9 BP 1102 EP 1102 DI 10.1001/jama.289.9.1102-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 650XM UT WOS:000181289400016 ER PT J AU Rosenfeld, S Follmann, D Nunez, O Young, NS AF Rosenfeld, S Follmann, D Nunez, O Young, NS TI Antithymocyte globulin and cyclosporine for severe aplastic anemia - Association between hematologic response and long-term outcome SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; SAA WORKING PARTY; IMMUNOSUPPRESSIVE THERAPY; ANTILYMPHOCYTE GLOBULIN; PATHOPHYSIOLOGY; DISEASES; CHILDREN; FAILURE AB Context In most patients, aplastic anemia results from T-cell-mediated immune destruction of bone marrow. Aplastic anemia can be effectively treated by stem cell transplantation or immunosuppression. Objective To assess long-term outcomes after immunosuppressive therapy. Design, Setting, and Patients Cohort of 122 patients (31 were less than or equal to18 years and 91 were > 18 years) with severe aplastic anemia, as determined by bone marrow cellularity and blood cell count criteria, were enrolled in a single-arm interventional research protocol from 1991 to 1999 at a federal government research hospital. Interventions A dose of 40 mg/kg per day of antithymocyte globulin administered for 4 days, 10 to 12 mg/kg per day of cyclosporine for 6 months (adjusted for blood levels), and a short course of corticosteroids (1 mg/d of m ethyl prednisolone for about 2 weeks). Main Outcome Measures Survival, improvement of pancytopenia and transfusion-independence, relapse, and evolution to other hematologic diseases. Results Response rates were 60% at 3 months after initiation of treatment, 61% at 6 months, and 58% at 1 year. The blood cell counts of patients who responded no longer satisfied severity criteria and they were transfusion-independent. Overall actuarial survival at 7 years was 55%. Survival was associated with early satisfaction of response criteria (86% vs 40% at 5 years; P<.001) and by blood counts at 3 months (reticulocyte count or platelet count of >50 x 10(3)/muL predicted survival at 5 years of 90% [64/71] vs 42% [12/34] for patients with less robust recovery [P<.001 by log-rank test]). There were no deaths among responders more than 3 years after treatment. Relapse was common, but severe pancytopenia usually did not recur. Relapse did not influence survival. Thirteen patients showed evolution to other hematologic diseases, including monosomy 7. Conclusions Approximately half of patients with severe aplastic anemia treated with antithymocyte globulin and cyclosporine have durable recovery and excellent long-term survival. These outcomes were related to the quality of hematologic recovery. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Young, NS (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 32 TC 187 Z9 224 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 5 PY 2003 VL 289 IS 9 BP 1130 EP 1135 DI 10.1001/jama.289.9.1130 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 650XM UT WOS:000181289400029 PM 12622583 ER PT J AU Cheng, JC Matsen, CB Gonzales, FA Ye, W Greer, S Marquez, VE Jones, PA Selker, EU AF Cheng, JC Matsen, CB Gonzales, FA Ye, W Greer, S Marquez, VE Jones, PA Selker, EU TI Inhibition of DNA methylation and reactivation of silenced genes by zebularine SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TUMOR-SUPPRESSOR GENE; CYTOSINE METHYLATION; CYTIDINE DEAMINASE; CELL-LINES; 5-AZA-2'-DEOXYCYTIDINE; METHYLTRANSFERASE; 5-AZACYTIDINE; NEUROSPORA; EXPRESSION; MECHANISM AB Background: Gene silencing by abnormal methylation of promoter regions of regulatory genes is commonly associated with cancer. Silenced tumor suppressor genes are obvious targets for reactivation by methylation inhibitors such as 5-azacytidine (5-Aza-CR) and 5-aza-2'-deoxycytidine (5-Aza-CdR). However, both compounds are chemically unstable and toxic and neither can be given orally. We characterized a new demethylating agent, zebularine [1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one], which is a chemically stable cytidine analog. Methods: We tested the ability of zebularine to reactivate a silenced Neurospora crassa gene using a hygromycin gene reactivation assay. We then analyzed the ability of zebularine to inhibit DNA methylation in C3H 10T1/2 C18 (10T1/2) mouse embryo cells as assayed by induction of a myogenic phenotype and in T24 human bladder carcinoma cells, using the methylation-sensitive single nucleotide primer extension (Ms-SNuPE) assay. We also evaluated the effects of zebularine (administered orally or intraperitoneally) on growth of EJ6 human bladder carcinoma cells grown in BALB/c nu/nu mice (five mice per group) and the in vivo reactivation of a methylated p16 gene in these cells. All statistical tests were two-sided. Results: In N. crassa, zebularine inhibited DNA methylation and reactivated a gene previously silenced by methylation. Zebularine induced the myogenic phenotype in 10T1/2 cells, which is a phenomenon unique to DNA methylation inhibitors. Zebularine reactivated a silenced p16 gene and demethylated its promoter region in T24 bladder carcinoma cells in vitro and in tumors grown in mice. Zebularine was only slightly cytotoxic to T24 cells in vitro (1 mM zebularine for 48 hours decreased plating efficiency by 17% [95% confidence interval (CI) = 12.8% to 21.2%]) and to tumor-bearing mice (average maximal weight change in mice treated with 1000 mg/kg zebularine = 11% [95% CI = 4% to 19%]). Compared with those in control mice, tumor volumes were statistically significantly reduced in mice treated with high-dose zebularine administered by intraperitoneal injection (P<.001) or by oral gavage (P<.001). Conclusions: Zebularine is a stable DNA demethylating agent and the first drug in its class able to reactivate an epigenetically silenced gene by oral administration. C1 Univ So Calif, Norris Comprehens Canc Ctr & Hosp, Dept Biochem, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Norris Comprehens Canc Ctr & Hosp, Dept Biol Mol, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Norris Comprehens Canc Ctr & Hosp, Dept Urol, Keck Sch Med, Los Angeles, CA 90089 USA. Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA. Univ So Calif, Norris Comprehens Canc Ctr & Hosp, Dept Prevent Med, Los Angeles, CA 90089 USA. Univ Miami, Sch Med, Dept Microbiol & Immunol, Sylvester Canc Ctr, Miami, FL 33152 USA. Univ Miami, Sch Med, Dept Biochem & Mol Biol, Sylvester Canc Ctr, Miami, FL 33152 USA. Univ Miami, Sch Med, Dept Radiat Oncol, Sylvester Canc Ctr, Miami, FL 33152 USA. NCI, Med Chem Lab, Canc Res Ctr, Frederick, MD 21701 USA. RP Jones, PA (reprint author), Univ So Calif, Norris Comprehens Canc Ctr & Hosp, Dept Biochem, Keck Sch Med, 1441 Eastlake Ave, Los Angeles, CA 90089 USA. OI Matsen, Cindy/0000-0003-0179-5311 FU NCI NIH HHS [CA82422]; NIGMS NIH HHS [GM35690] NR 53 TC 301 Z9 326 U1 2 U2 30 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 MAR 5 PY 2003 VL 95 IS 5 BP 399 EP 409 PG 11 WC Oncology SC Oncology GA 650CJ UT WOS:000181244500012 PM 12618505 ER PT J AU Grumbach, MM Biller, BMK Braunstein, GD Campbell, KK Carney, JA Godley, PA Harris, EL Lee, JKT Oertel, YC Posner, MC Schlechte, JA Wieand, HS AF Grumbach, MM Biller, BMK Braunstein, GD Campbell, KK Carney, JA Godley, PA Harris, EL Lee, JKT Oertel, YC Posner, MC Schlechte, JA Wieand, HS TI Management of the clinically inapparent adrenal mass ("incidentaloma") SO ANNALS OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT State of the Science Conference CY FEB 04-06, 2002 CL BETHESDA, MARYLAND AB The National Institutes of Health Consensus Development Program convened surgeons, endocrinologists, pathologists, biostatisticians, radiologists, oncologists, and other health care professionals, as well as members of the general public, to address the causes, prevalence, and natural history of clinically inapparent adrenal masses, or "incidentalomas"; the appropriate evaluation and treatment of such masses; and directions for future research. Improvements in abdominal imaging techniques have increased detection of adrenal incidentalomas, and because the prevalence of these masses increases with age, appropriate management of adrenal tumors will be a growing challenge in our aging society. To address six predetermined questions, the 12-member nonfederal, nonadvocate state-of-the-science panel heard presentations from 21 experts in adrenal incidentalomas and consulted a systematic review of medical literature on the topic provided by the Agency for Healthcare Research and Quality and an extensive bibliography developed by the National Library of Medicine. The panel recommended a 1-mg dexamethasone suppression test and measurement of plasma-free metanephrines for all patients with an adrenal incidentaloma; additional measurement of serum potassium and plasma aldosterone concentration-plasma renin activity ratio for patients with hypertension; and surgery for patients with biochemical evidence of pheochromocytoma, patients with tumors greater than 6 cm, and patients with tumors greater than 4 cm who also meet other criteria. The panel also advocated a multidisciplinary approach to managing adrenal incidentalomas. The statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the federal government. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cushings Support & Res Fdn, Boston, MA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Mayo Clin, Rochester, MN USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27515 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Washington Hosp Ctr, Washington, DC 20010 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Iowa Hosp, Iowa City, IA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. RP Grumbach, MM (reprint author), NIH, Off Med Applicat Res, Bldg 31,Room 1B03,31 Ctr Dr MSC 2082, Bethesda, MD 20892 USA. NR 0 TC 436 Z9 456 U1 1 U2 15 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 MAR 4 PY 2003 VL 138 IS 5 BP 424 EP 429 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 650HJ UT WOS:000181257300009 PM 12614096 ER PT J AU Knowlton, JR Bubunenko, M Andrykovitch, M Guo, W Routzahn, KM Waugh, DS Court, DL Ji, XH AF Knowlton, JR Bubunenko, M Andrykovitch, M Guo, W Routzahn, KM Waugh, DS Court, DL Ji, XH TI A spring-loaded state of NusG in its functional cycle is suggested by X-ray crystallography and supported by site-directed mutants SO BIOCHEMISTRY LA English DT Article ID DEPENDENT TRANSCRIPTION TERMINATION; RNA-POLYMERASE-II; ESCHERICHIA-COLI; ELONGATION-FACTOR; IN-VIVO; TRANSLATION MACHINES; PHAGE-LAMBDA; N-PROTEIN; RHO; ANTITERMINATION AB Transcription factor NusG is present in all prokaryotes, and orthologous proteins have also been identified in yeast and humans. NusG contains a 27-residue KOW motif, found in ribosomal protein L24 where it interacts with rRNA. NusG in Escherichia coli (EcNusG) is an essential protein and functions as a regulator of Rho-dependent transcription termination, phage lambda N and rRNA transcription antitermination, and phage HK022 Nun termination. Relative to EcNusG, Aquifex aeolicus NusG (AaNusG). and several other bacterial NusG proteins contain a variable insertion sequence of similar to70 residues in the central region of the molecule. Recently, crystal structures of AaNusG in space groups P2(1) and I222 have been reported; the authors conclude that there are no conserved dimers among the contacting molecules in the crystals [Steiner, T., Kaiser, J. T., Marinkovic, S., Huber, R., and Wahl, M. C. (2002) EMBO J. 21, 4641-4653]. We have independently determined the structures of AaNusG also in two crystal forms, P2(1) and C222(1), and surprisingly found that AaNusG molecules form domain-swapped dimers in both crystals. Additionally, polymerization is also observed in the P2(1) crystal. A unique "ball-and-socket" junction dominates the intermolecular interactions within both oligomers. We believe that this interaction is a clue to the function of the molecule and propose a spring-loaded state in the functional cycle of NusG. The importance of the ball-and-socket junction for the function of NusG is supported by the functional analysis of site-directed mutants. C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Ji, XH (reprint author), NCI, Macromol Crystallog Lab, 1050 Boyles St,Bldg 539,POB B, Frederick, MD 21702 USA. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 NR 40 TC 36 Z9 37 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 4 PY 2003 VL 42 IS 8 BP 2275 EP 2281 DI 10.1021/bi0272508 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649EC UT WOS:000181193100003 PM 12600194 ER PT J AU Sasaki, N Murata, M Guo, YR Jo, SH Ohler, A Akao, M O'Rourke, B Xiao, RP Bolli, R Marban, E AF Sasaki, N Murata, M Guo, YR Jo, SH Ohler, A Akao, M O'Rourke, B Xiao, RP Bolli, R Marban, E TI MCC-134, a single pharmacophore, opens surface ATP-sensitive potassium channels, blocks mitochondrial ATP-sensitive potassium channels, and suppresses preconditioning SO CIRCULATION LA English DT Article DE ischemia; potassium; myocardial infarction ID CARDIAC MYOCYTES; K+ CHANNELS; CARDIOPROTECTION; ACTIVATION; AGENTS AB Background-MCC-134 (1-[4-(H-imidazol-1-yl)benzoyl]-N-methylcyclobutane-carbothioamide), a newly developed analog of aprikalim, opens surface smooth muscle-type ATP-sensitive potassium (K-ATP) channels but inhibits pancreatic K-ATP channels. However, the effects of MCC-134 on cardiac surface K-ATP channels and mitochondrial K-ATP (mitoK(ATP)) channels are unknown. A mixed agonist/blocker with differential effects on the two channel types would help to clarify the role of K-ATP channels in cardioprotection. Methods and Results-To index mitoK(ATP) channels, we measured mitochondrial flavoprotein fluorescence in rabbit ventricular myocytes. MCC-134 alone had little effect on basal flavoprotein fluorescence. However, MCC-134 inhibited diazoxide-induced flavoprotein oxidation in a dose-dependent manner (EC50=27 mumol/L). When ATP was included in the pipette solution, MCC-134 slowly activated surface K-ATP currents with some delay (>10 minutes). These results indicate that MCC-134 is a mitoK(ATP) channel inhibitor and a surface K-ATP channel opener in native cardiac cells. In cell-pelleting ischemia assays, coapplication of MCC-134 with diazoxide abolished the cardioprotective effect of diazoxide, whereas MCC-134 alone did not alter cell death. These results were reproducible in both rabbit and mouse myocytes. MCC-134 also attenuated the effect of ischemic preconditioning against myocardial infarction in mice, consistent with the results of cell-pelleting ischemia assays. Conclusions-A single drug, MCC-134, opens surface K-ATP channels but blocks mitoK(ATP) channels; the fact that this drug inhibits preconditioning reaffirms the primacy of mitoK(ATP) rather than surface K-ATP, channels in the mechanism of cardioprotection. C1 Johns Hopkins Univ, Inst Mol Cardiobiol, Lab, Baltimore, MD 21205 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Louisville, Div Cardiol, Expt Res Lab, Louisville, KY 40292 USA. Jewish Heart & Lung Inst, Louisville, KY USA. RP Marban, E (reprint author), Johns Hopkins Univ, Inst Mol Cardiobiol, Lab, 720 Rutland Ave Ross 844, Baltimore, MD 21205 USA. FU NHLBI NIH HHS [R37 HL055757, HL43151, R01 HL055757, R01 HL043151, R37 HL36957, R37 HL054598, R37 HL55757, R37 HL036957, R0I HL52598, R01 HL068088, HL68088] NR 21 TC 30 Z9 38 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 4 PY 2003 VL 107 IS 8 BP 1183 EP 1188 DI 10.1161/01.CIR.0000051457.64240.63 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653ZL UT WOS:000181466900018 PM 12615799 ER PT J AU Eizirik, E Yuhki, N Johnson, WE Menotti-Raymond, M Hannah, SS O'Brien, SJ AF Eizirik, E Yuhki, N Johnson, WE Menotti-Raymond, M Hannah, SS O'Brien, SJ TI Molecular genetics and evolution of melanism in the cat family SO CURRENT BIOLOGY LA English DT Article ID MOUSE AGOUTI LOCUS; COAT COLOR; MSH RECEPTOR; PIGMENTATION; MUTATIONS; EXTENSION; FELIDAE; GENES; PHENOTYPES; ALLELES AB Melanistic coat coloration occurs as a common polymorphism in 11 of 37 felid species and reaches high population frequency in some cases but never achieves complete fixation [1-3]. To investigate the genetic basis, adaptive significance, and evolutionary history of melanistic variants in the Felidae, we mapped, cloned, and sequenced the cat homologs of two putative candidate genes for melanism (ASIP [agouti] and MC1R) and identified three independent deletions associated with dark coloration in three different felid species. Association and transmission analyses revealed that a 2 bp deletion in the ASIP gene specifies black coloration in domestic cats, and two different "in-frame" deletions in the MC1R gene are implicated in melanism in jaguars and jaguarundis. Melanistic individuals from five other felid species did not carry any of these mutations, implying that there are at least four independent genetic origins for melanism in the cat family. The inferred multiple origins and independent historical elevation in population frequency of felid melanistic mutations suggest the occurrence of adaptive evolution of this visible phenotype in a group of related free-ranging species. C1 NCI, Lab Genom Divers, NIH, Frederick, MD 21702 USA. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. Nestle Purina PetCare Co, St Louis, MO 63164 USA. RP Eizirik, E (reprint author), NCI, Lab Genom Divers, NIH, Frederick, MD 21702 USA. EM eizrike@ncifcrf.gov; obrien@ncifcrf.gov RI Eizirik, Eduardo/K-8034-2012; Johnson, Warren/D-4149-2016 OI Eizirik, Eduardo/0000-0002-9658-0999; Johnson, Warren/0000-0002-5954-186X NR 23 TC 158 Z9 173 U1 18 U2 87 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 4 PY 2003 VL 13 IS 5 BP 448 EP 453 AR PII S0960-9822(02)00128-3 DI 10.1016/S0960-9822(03)00128-3 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 652PT UT WOS:000181388100030 PM 12620197 ER PT J AU Jackson, CL AF Jackson, CL TI Membrane traffic: Arl GTPases get a GRIP on the Golgi SO CURRENT BIOLOGY LA English DT Editorial Material ID COILED-COIL PROTEINS; EXCHANGE FACTOR; DOMAIN; VESICLES; EFFECTOR; YEAST; GENE C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Jackson, CL (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM cathyj@helix.nih.gov OI Jackson, Catherine/0000-0002-0843-145X NR 18 TC 26 Z9 27 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 4 PY 2003 VL 13 IS 5 BP R174 EP R176 AR PII S0960-9822(03)00116-7 DI 10.1016/S0960-9822(03)00116-7 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 652PT UT WOS:000181388100008 PM 12620205 ER PT J AU Yildirim, E Dietrich, A Birnbaumer, L AF Yildirim, E Dietrich, A Birnbaumer, L TI The mouse C-type transient receptor potential 2 (TRPC2) channel: Alternative splicing and calmodulin binding to its N terminus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cation channel; store-operated channel; gene structure; splice variants; pseudogene ID STORE DEPLETION; CATION CHANNEL; ENTRY CHANNEL; EXPRESSION; MICE; VARIANTS; CLONING; FAMILY AB Channels of the C-type transient receptor potential (TRPC) are involved in agonist-stimulated and capacitative calcium entry. There are seven TRPCs, all of which have a Ca2+-dependent calmodulin (CaM)-binding domain in their C termini. We now tested binding of CaM to TRPC N termini and show that only that of TRPC2 binds CaM in a Ca2+-dependent manner. Four TRPC2 cDNAs have been reported: a (also clone 14), b (also clone 17), alpha, and beta. Sequences responsible for CaM binding in TRPC2 a and b are absent from the alpha and beta isoforms. The a and 13 cDNAs of TRPC2 were reported as alternative forms, when recloning of TRPC2 a and b proved impossible. Here we analyzed total RNA samples from brain and testis for presence of TRPC2 a and b and describe the splicing patterns responsible for their formation, as well as those leading to the a and 6 forms of TRPC2. We re-assert existence of RNA encoding the TRPC2 a and b, encoded in 21 exons with an initiator ATG in exon 2 for TRPC2a and in exon 4 for TRCP2b. The analysis of alpha and beta TRPC2 cDNAs indicates that although the TRPC2beta mRNA may exist, the TRPC2alpha cDNA is derived from an incompletely processed TRPC2a mRNA: It includes in its presumed 5'-untranslated sequence, 713 nt of TRPC2a cDNA fused to 291 nt of an incompletely excised intron. While encoding an active channel in the mouse, the human TRPC2 appears to be a pseudogene. We searched for the human gene in the data bank and located approximately one-half of it in a chromosomal region syntenic to that of the mouse, with similar intron-exon structure. We conclude that the human TRPC2 gene may never have been an active gene because of incomplete ancestral duplication or, if it was complete at one point, that it became inactive upon loss of chromosomal sequences. C1 NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Birnbaumer, L (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. RI Dietrich, Alexander/G-8619-2013; OI Yildirim, Eda/0000-0002-4796-3854; Dietrich, Alexander/0000-0002-1168-8707 NR 21 TC 36 Z9 41 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2220 EP 2225 DI 10.1073/pnas.0438036100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000013 PM 12601176 ER PT J AU Chattopadhyay, MK Tabor, CW Tabor, H AF Chattopadhyay, MK Tabor, CW Tabor, H TI Polyamines protect Escherichia coli cells from the toxic effect of oxygen SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SUPEROXIDE-DISMUTASE; SPERMIDINE SYNTHASE; SINGLET OXYGEN; DNA DAMAGE; GENE; AUXOTROPHY; PUTRESCINE; RADICALS; PARAQUAT AB Wild-type Escherichia coli cells grow normally in 95% O-2/5% CO2. In contrast, cells that cannot make polyamines because of mutations in the biosynthetic pathway are rapidly killed by incubation in 95% O-2/5% CO2. Addition of polyarnines prevents the toxic effect of oxygen, permitting cell survival and optimal growth. Oxygen toxicity can also be prevented if the growth medium contains an amino acid mixture or if the polyamine-deficient cells contain a manganese-superoxide dismutase (Mn-SOD) plasmid. Partial protection is afforded by the addition of 0.4 M sucrose or 0.4 M sorbitol to the growth medium. We also report that concentrations of H2O2 that are nontoxic to wild-type cells or to mutant cells pretreated with polyamines kill polyamine-deficient cells. These results show that polyarnines are important in protecting cells from the toxic effects of oxygen. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Tabor, H (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 223, Bethesda, MD 20892 USA. NR 34 TC 103 Z9 109 U1 2 U2 7 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 MAR 4 PY 2003 VL 100 IS 5 BP 2261 EP 2265 DI 10.1073/pnas.2627990100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000020 PM 12591940 ER PT J AU Padilla, PI Chang, MJ Pacheco-Rodriguez, G Adamik, R Moss, J Vaughan, M AF Padilla, PI Chang, MJ Pacheco-Rodriguez, G Adamik, R Moss, J Vaughan, M TI Interaction of FK506-binding protein 13 with brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1): Effects of FK506 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ADP-RIBOSYLATION FACTOR; BINDING-PROTEIN; SEC7 DOMAIN; IMMUNOSUPPRESSIVE LIGANDS; ENDOPLASMIC-RETICULUM; MEMBRANE-TRANSPORT; CYCLOSPORINE-A; ARF; IMMUNOPHILINS; CALCINEURIN AB BIG1 and BIG2 are brefeldin A-inhibited guanine nucleotide-exchange proteins that activate ADP-ribosylation factors (ARI's), critical components of vesicular trafficking pathways. These proteins can exist in macromolecular complexes and move between Golgi membranes and cytosol. In the BIG1 molecule, a centrally located Sec7 domain is responsible for ARF activation, but functions of other regions are largely unknown. Yeast two-hybrid screens of a human placenta cDNA library with BIG1 cDNA constructs revealed specific interaction of the N-terminal region (amino acids 1-331) with FK506-binding protein 13 (FKBP13). The association was confirmed by immunoprecipitation of both endogenous BIG1 and FKBP13 from Jurkat T cells with antibodies against either one. Binding of BIG1, BIG2, and ARF to cell membranes in vitro was increased by guanosine 5'-[gamma-thioltriphosphate, and further increases were induced by FK506. Incubation of Jurkat T cells with FK506 increased binding of BIG1, BIG2, and ARIF to Golgi and other membranes in a time- and concentration-dependent manner, without effects on clathrin or gamma-adaptin binding. Binding of BIG1, BIG2, and ARF to membranes was also increased by L-732,531, an agonist structurally related to FK506, but was not increased by a related antagonist, L-685,818, nor by cyclosporin A or rapamycin. These findings are consistent with a role for FKBP13 and FK506 in vesicular trafficking, influencing ARF activity through their guanine nucleotide-exchange proteins. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Vaughan, M (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room 5N307,MSC 1434, Bethesda, MD 20892 USA. NR 34 TC 29 Z9 33 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 MAR 4 PY 2003 VL 100 IS 5 BP 2322 EP 2327 DI 10.1073/pnas.2628047100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000031 PM 12606707 ER PT J AU Hedenfalk, I Ringner, M Ben-Dor, A Yakhini, Z Chen, Y Chebil, G Ach, R Loman, N Olsson, H Meltzer, P Borg, A Trent, J AF Hedenfalk, I Ringner, M Ben-Dor, A Yakhini, Z Chen, Y Chebil, G Ach, R Loman, N Olsson, H Meltzer, P Borg, A Trent, J TI Molecular classification of familial non-BRCA1/BRCA2 breast cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENE-EXPRESSION PATTERNS; GERM-LINE MUTATIONS; COPY NUMBER; SUSCEPTIBILITY GENES; CHROMOSOME 8P12-P22; OVARIAN-CANCER; BRCA2; TUMORS; MICROARRAY; PROFILES AB In the decade since their discovery, the two major breast cancer susceptibility genes BRCA1 and BRCA2, have been shown conclusively to be involved in a significant fraction of families segregating breast and ovarian cancer. However, it has become equally clear that a large proportion of families segregating breast cancer alone are not caused by mutations in BRCA1 or BRCA2. Unfortunately, despite intensive effort, the identification of additional breast cancer predisposition genes has so far been unsuccessful, presumably because of genetic heterogeneity, low penetrance, or recessive/polygenic mechanisms. These non-BRCA1/2 breast cancer families (termed BRCAx families) comprise a histopathologically heterogeneous group, further supporting their origin from multiple genetic events. Accordingly, the identification of a method to successfully subdivide BRCAx families into recognizable groups could be of considerable value to further genetic analysis. We have previously shown that global gene expression analysis can identify unique and distinct expression profiles in breast tumors from BRCA1 and BRCA2 mutation carriers. Here we show that gene expression profiling can discover novel classes among BRCAx tumors, and differentiate them from BRCA1 and BRCA2 tumors. Moreover, microarray-based comparative genomic hybridization (CGH) to cDNA arrays revealed specific somatic genetic alterations within the BRCAx subgroups. These findings illustrate that, when gene expression-based classifications are used, BRCAx families can be grouped into homogeneous subsets, thereby potentially increasing the power of conventional genetic analysis. C1 Translat Genom Res Inst, Phoenix, AZ 85004 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Lund Hosp, Dept Oncol, SE-22100 Lund, Sweden. Agilent Labs, Palo Alto, CA 94303 USA. Helsingborg Hosp, Dept Pathol, SE-25187 Helsingborg, Sweden. RP Trent, J (reprint author), Translat Genom Res Inst, 400 N 5th St,Suite 1600, Phoenix, AZ 85004 USA. EM jtrent@tgen.org RI Ringner, Markus/G-3641-2011 OI Ringner, Markus/0000-0001-5469-8940 NR 41 TC 125 Z9 128 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2532 EP 2537 DI 10.1073/pnas.0533805100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000067 PM 12610208 ER PT J AU Panyi, G Bagdany, M Bodnar, A Vamosi, G Szentesi, G Jenei, A Matyus, L Varga, S Waldmann, TA Gaspar, R Damjanovich, S AF Panyi, G Bagdany, M Bodnar, A Vamosi, G Szentesi, G Jenei, A Matyus, L Varga, S Waldmann, TA Gaspar, R Damjanovich, S TI Colocalization and nonrandom distribution of Kv1.3 potassium channels and CD3 molecules in the plasma membrane of human T lymphocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN LYMPHOBLASTOID-CELLS; GATED K+ CHANNEL; HLA CLASS-I; IMMUNOLOGICAL SYNAPSE; LIPID RAFTS; NERVOUS-SYSTEM; RECEPTOR; ACTIVATION; LOCALIZATION; ASSOCIATION AB Distribution and lateral organization of Kv1.3 potassium channels and CD3 molecules were studied by using electron microscopy, confocal laser scanning microscopy, and fluorescence resonance energy transfer. Immunogold labeling and electron microscopy showed that the distribution of FLAG epitope-tagged Kv1.3 channels (Kv1.3/FLAG) significantly differs from the stochastic Poisson distribution in the plasma membrane of human T lymphoma cells. Confocal laser scanning microscopy images showed that Kv1.3/FLAG channels and CD3 molecules accumulated in largely overlapping membrane areas. The numerical analysis of crosscorrelation of the spatial intensity distributions yielded a high correlation coefficient (C = 0.64). A different hierarchical level of molecular proximity between Kv1.3/FLAG and CD3 proteins was reported by a high fluorescence resonance energy transfer efficiency (E = 51%). These findings implicate that reciprocal regulation of ion-channel activity, membrane potential, and the function of receptor complexes may contribute to the proper functioning of the immunological synapse. C1 Hungarian Acad Sci, Cell Biophys Res Grp, H-4012 Debrecen, Hungary. Univ Debrecen, Dept Biophys & Cell Biol, H-4012 Debrecen, Hungary. Univ Debrecen, Electron Microscopy Lab, Res Ctr Mol Med, Med & Hlth Sci Ctr, H-4012 Debrecen, Hungary. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Damjanovich, S (reprint author), Hungarian Acad Sci, Cell Biophys Res Grp, Nagyerdei Krt 98, H-4012 Debrecen, Hungary. EM dami@jaguar.dote.hu RI Vamosi, Gyorgy/C-9351-2009; Bodnar, Andrea/A-9286-2011; Damjanovich, Sandor/A-9284-2011; Panyi, Gyorgy/H-4406-2013 NR 32 TC 57 Z9 58 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2592 EP 2597 DI 10.1073/pnas.0438057100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000077 PM 12604782 ER PT J AU Boheler, KR Volkova, M Morrell, C Garg, R Zhu, Y Marguiles, K Seymour, AM Lakatta, EG AF Boheler, KR Volkova, M Morrell, C Garg, R Zhu, Y Marguiles, K Seymour, AM Lakatta, EG TI Sex- and age-dependent human transcriptome variability: Implications for chronic heart failure SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CDNA MICROARRAY; EXPRESSION; CARDIOMYOPATHY; LUMICAN; MUSCLE AB Heart failure (HF) is the end result of progressive and diverse biological adaptations within the diseased myocardium. We used cDNA microarrays and quantitative PCR to examine the transcriptomes of 38 left ventricles from failing and nonfailing human myocardium. After identification of a pool of putative HF-responsive candidate genes by microarrays on seven nonfailing and eight failing hearts, we used quantitative PCR and a general linear statistical model in a larger sample set (n = 34) to validate and examine the role of contributing biological variables (age and sex). We find that most HF-candidate genes (transcription factors, Cebpb, Npat; signaling molecules, Map2k3, Map4k5; extracellular matrix proteins, Lum, Cola1; and metabolic enzymes, Mars) demonstrated significant changes in gene expression; however, the majority of differences among samples depended on variables such as sex and age, and not on HF alone. Some HF-responsive gene products also demonstrated highly significant changes in expression as a function of age and/or sex, but independent of HF (Ngp1, Cd163, and Npat). These results emphasize the need to account for biological variables (HF, sex and age interactions) to elucidate genomic correlates that trigger molecular pathways responsible for the progression of HF syndromes. C1 NIA, Lab Cardiovasc Sci, Baltimore, MD 21224 USA. Univ Hull, Kingston Upon Hull HU6 7RX, N Humberside, England. Temple Univ, Sch Med, Philadelphia, PA 19140 USA. RP Boheler, KR (reprint author), NIA, Lab Cardiovasc Sci, Baltimore, MD 21224 USA. FU NIA NIH HHS [AG17022, R01 AG017022] NR 23 TC 66 Z9 70 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 MAR 4 PY 2003 VL 100 IS 5 BP 2754 EP 2759 DI 10.1073/pnas.0436564100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000105 PM 12601168 ER PT J AU Duan, WZ Guo, ZH Jiang, HY Ware, M Li, XJ Mattson, MP AF Duan, WZ Guo, ZH Jiang, HY Ware, M Li, XJ Mattson, MP TI Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis; diabetes; Huntington's disease; striatum ID STRIATAL PROJECTION NEURONS; NEUROTROPHIC FACTOR; 3-NITROPROPIONIC ACID; CALORIC-INTAKE; INTRANUCLEAR INCLUSIONS; PARKINSONS-DISEASE; CELLULAR TOXICITY; REPEAT EXPANSION; FOOD RESTRICTION; TRANSGENIC MICE AB In addition to neurological deficits, Huntington's disease (HD) patients and transgenic mice expressing mutant human huntingtin exhibit reduced levels of brain-derived neurotrophic factor, hyperglycemia, and tissue wasting. We show that the progression of neuropathological (formation of huntingtin inclusions and apoptotic protease activation), behavioral (motor dysfunction), and metabolic (glucose intolerance and tissue wasting) abnormalities in huntingtin mutant mice, an animal model of HD, are retarded when the mice are maintained on a dietary restriction (DR) feeding regimen resulting in an extension of their life span. DR increases levels of brain-derived neurotrophic factor and the protein chaperone heat-shock protein-70 in the striatum and cortex, which are depleted in HD mice fed a normal diet. The suppression of the pathogenic processes by DR in HD mice suggests that mutant huntingtin promotes neuronal degeneration by impairing cellular stress resistance, and that the body wasting in HD is driven by the neurodegenerative process. Our findings suggest a dietary intervention that may suppress the disease process and increase the life span of humans that carry the mutant huntingtin gene. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. NIA, Comparat Med Sect, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 56 TC 224 Z9 231 U1 2 U2 10 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 MAR 4 PY 2003 VL 100 IS 5 BP 2911 EP 2916 DI 10.1073/pnas.0536856100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000132 PM 12589027 ER PT J AU Erxleben, C Gomez-Alegria, C Darden, T Mori, Y Birnbaumer, L Armstrong, DL AF Erxleben, C Gomez-Alegria, C Darden, T Mori, Y Birnbaumer, L Armstrong, DL TI Modulation of cardiac Ca(V)1.2 channels by dihydropyridine and phosphatase inhibitor requires Ser-1142 in the domain III pore loop SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-KINASE-A; ACTIVATED CALCIUM CHANNELS; SMOOTH-MUSCLE CELLS; CA2+ CHANNELS; CYCLIC-AMP; GUANINE-NUCLEOTIDES; ALPHA(1) SUBUNIT; OKADAIC ACID; PHOSPHORYLATION; BINDING AB Dihydropyridine-sensitive, voltage-activated calcium channels respond to membrane depolarization with two distinct modes of activity: short bursts of very short openings (mode 1) or repetitive openings of much longer duration (mode 2). Here we show that both the dihydropyridine, BayK8644 (BayK), and the inhibitor of Ser/Thr protein phosphatases, okadaic acid, have identical effects on the gating of the recombinant cardiac calcium channel, Ca(V)1.2 (alpha(1)C). Each produced identical mode 2 gating in cell-attached patches, and each prevented rundown of channel activity when the membrane patch was excised into ATP-free solutions. These effects required Ser or Thr at position 1142 in the domain III pore loop between transmembrane segments S5 and S6, where dihydropyridines bind to the channel. Mutation of Ser-1142 to Ala or Cys produced channels with very low activity that could not be modulated by either BayK or okadaic acid. A molecular model of Ca(V)1.2 indicates that Ser-1142 is unlikely to be phosphorylated, and thus we conclude that BayK binding stabilizes mode 2 gating allosterically by either protecting a phospho Ser/Thr on the alpha(1)C subunit or mimicking phosphorylation at that site. C1 Natl Inst Physiol Sci, Okazaki, Aichi 444, Japan. NIEHS, Lab Signal Transduct & Struct Biol, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Armstrong, DL (reprint author), NIEHS, Labs Signal Transduct F205, POB 12233,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 47 TC 17 Z9 17 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2929 EP 2934 DI 10.1073/pnas.2628046100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000135 PM 12601159 ER PT J AU Krsmanovic, LZ Mores, N Navarro, CE Arora, KK Catt, KJ AF Krsmanovic, LZ Mores, N Navarro, CE Arora, KK Catt, KJ TI An agonist-induced switch in G protein coupling of the gonadotropin-releasing hormone receptor regulates pulsatile neuropeptide secretion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GREEN FLUORESCENT PROTEIN; EMBRYONIC OLFACTORY PLACODE; HYPOTHALAMIC NEURONS; AUTOCRINE REGULATION; INTRACELLULAR LOOP; TRANSGENIC MICE; RHESUS-MONKEY; NITRIC-OXIDE; CYCLIC-AMP; CALCIUM AB The pulsatile secretion of gonadotropin-releasing hormone (GnRH) from normal and immortalized hypothalamic GnRH neurons is highly calcium-dependent and is stimulated by cAMP. It is also influenced by agonist activation of the endogenous GnRH receptor (GnRH-R), which couples to G(q/11) as indicated by release of membrane-bound alpha(q/11) subunits and increased inositol phosphate/Ca2+ signaling. Conversely, GnRH antagonists increase membrane-associated alpha(q/11) subunits and abolish pulsatile GnRH secretion. GnRH also stimulates cAMP production but at high concentrations has a pertussis toxin-sensitive inhibitory effect, indicative of receptor coupling to G(i). Coupling of the agonist-activated GnRH-R to both G(s) and G(i) proteins was demonstrated by the ability of nanomolar GnRH concentrations to reduce membrane-associated alpha(s) and alpha(i3) levels and of higher concentrations to diminish alpha(i3) levels. Conversely, alpha(i3) was increased during GnRH antagonist and pertussis toxin treatment, with concomitant loss of pulsatile GnRH secretion. in cholera toxin-treated GnRH neurons, decreases in a, immunoreactivity and increases in cAMP production paralleled the responses to nanomolar GnRH concentrations. Treatment with cholera toxin and 8-bromo-cAMP amplified episodic GnRH pulses but did not affect their frequency. These findings suggest that an agonist concentration-dependent switch in coupling of the GnRH-R between specific G proteins modulates neuronal Ca2+ signaling via G(s)-cAMP stimulatory and G(i)-cAMP inhibitory mechanisms. Activation of G(i) may also inhibit GnRH neuronal function and episodic secretion by regulating membrane ion currents. This autocrine mechanism could serve as a timer to determine the frequency of pulsatile GnRH release by regulating Ca2+- and cAMP-dependent signaling and GnRH neuronal firing. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Catt, KJ (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A-36, Bethesda, MD 20892 USA. OI MORES, Nadia/0000-0002-4197-0914 NR 39 TC 94 Z9 97 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2969 EP 2974 DI 10.1073/pnas.05305708100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000142 PM 12591945 ER PT J AU Sengupta, S Linke, SP Pedeux, R Yang, Q Farnsworth, J Garfield, SH Valerie, K Shay, JW Ellis, NA Wasylyk, B Harris, CC AF Sengupta, S Linke, SP Pedeux, R Yang, Q Farnsworth, J Garfield, SH Valerie, K Shay, JW Ellis, NA Wasylyk, B Harris, CC TI BLM helicase-dependent transport of p53 to sites of stalled DNA replication forks modulates homologous recombination SO EMBO JOURNAL LA English DT Article DE DNA repair; nuclear trafficking; RAD51; sister chromatid exchange ID CHROMOSOME INSTABILITY SYNDROMES; SISTER-CHROMATID EXCHANGES; BLOOMS-SYNDROME PROTEIN; DOUBLE-STRAND BREAK; HOLLIDAY JUNCTIONS; FUNCTIONAL INTERACTION; MAMMALIAN-CELLS; HUMAN RAD51; REPAIR; COMPLEX AB Diverse functions, including DNA replication, recombination and repair, occur during S phase of the eukaryotic cell cycle. It has been proposed that p53 and BLM help regulate these functions. We show that p53 and BLM accumulated after hydroxyurea (HU) treatment, and physically associated and co-localized with each other and with RAD51 at sites of stalled DNA replication forks. HU-induced relocalization of BLM to RAD51 foci was p53 independent. However, BLM was required for efficient localization of either wild-type or mutated (Ser15Ala) p53 to these foci and for physical association of p53 with RAD51. Loss of BLM and p53 function synergistically enhanced homologous recombination frequency, indicating that they mediated the process by complementary pathways. Loss of p53 further enhanced the rate of spontaneous sister chromatid exchange (SCE) in Bloom syndrome (BS) cells, but not in their BLM-corrected counterpart, indicating that involvement of p53 in regulating spontaneous SCE is BLM dependent. These results indicate that p53 and BLM functionally interact during resolution of stalled DNA replication forks and provide insight into the mechanism of genomic fidelity maintenance by these nuclear proteins. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA. Mem Sloan Kettering Canc Ctr, Dept Human Genet, Lab Canc Susceptibil, New York, NY 10021 USA. ULP, Inst Genet & Biol Mol & Cellulaire, CNRS, INSERM, F-67404 Illkirch Graffenstaden, France. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. RI Shay, Jerry/F-7878-2011; OI Sengupta, Sagar/0000-0002-6365-1770 NR 43 TC 146 Z9 150 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 3 PY 2003 VL 22 IS 5 BP 1210 EP 1222 DI 10.1093/emboj/cdg114 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 652XN UT WOS:000181406300022 PM 12606585 ER PT J AU Kannouche, P de Henestrosa, ARF Coull, B Vidal, AE Gray, C Zicha, D Woodgate, R Lehmann, AR AF Kannouche, P de Henestrosa, ARF Coull, B Vidal, AE Gray, C Zicha, D Woodgate, R Lehmann, AR TI Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells SO EMBO JOURNAL LA English DT Article DE DNA polymerase; replication foci; UV light; xeroderma pigmentosum variants ID XERODERMA-PIGMENTOSUM VARIANT; PRONE LESION BYPASS; ERROR-PRONE; SACCHAROMYCES-CEREVISIAE; ULTRAVIOLET-RADIATION; TRANSLESION SYNTHESIS; EXCISION-REPAIR; GENE ENCODES; Y-FAMILY; POL-IOTA AB Y-family DNA polymerases can replicate past a variety of damaged bases in vitro but, with the exception of DNA polymerase eta (poleta), which is defective in xeroderma pigmentosum variants, there is little information on the functions of these polymerases in vivo. Here, we show that DNA polymerase iota (poliota), like poleta, associates with the replication machinery and accumulates at stalled replication forks following DNA-damaging treatment. We show that poleta and poliota foci form with identical kinetics and spatial distributions, suggesting that localization of these two polymerases is tightly co-ordinated within the nucleus. Furthermore, localization of poliota in replication foci is largely dependent on the presence of poleta. Using several different approaches, we demonstrate that poleta and poliota interact with each other physically and that the C-terminal 224 amino acids of poliota are sufficient for both the interaction with poleta and accumulation in replication foci. Our results provide strong evidence that poleta targets poliota to the replication machinery, where it may play a general role in maintaining genome integrity as well as participating in translesion DNA synthesis. C1 Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England. Canc Res UK London Res Inst, London WC2A 3PX, England. NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Lehmann, AR (reprint author), Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England. RI Zicha, Daniel/H-9310-2016 NR 37 TC 87 Z9 93 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 3 PY 2003 VL 22 IS 5 BP 1223 EP 1233 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 652XN UT WOS:000181406300023 PM 12606586 ER PT J AU Persico, AM Baldi, A Dell'Acqua, ML Moessner, R Murphy, DL Lesch, KP Keller, F AF Persico, AM Baldi, A Dell'Acqua, ML Moessner, R Murphy, DL Lesch, KP Keller, F TI Reduced programmed cell death in brains of serotonin transporter knockout mice SO NEUROREPORT LA English DT Article DE apoptosis; development; homologous recombination; knock-out; moroamine; naturally occurring cell death; programmed cell death; serotonin; serotonin transporter ID CRANIAL NEURAL CREST; APOPTOSIS; RAT; MIGRATION; RECEPTORS AB Serotonin (5-HT) is known to reduce apoptosis in vitro and in rodent models of brain ischemia. Modulation of programmed cell death during neural development was assessed in early postnatal brains of serotonin transporter (5-HTT) knockout mice, characterized by elevated extracellular 5-HT levels. The number of apoptotic cells visualized at postnatal day-1 (PI) by ISEL+ or TUNEL staining was significantly reduced in the striatum, thalamus/hypothalamus, cerebral cortex and hippocampus of 5-HTT knockout mice, compared to wild type and heterozygote mice, with differences displaying an increasing fronto-caudal gradient and regional specificity. These findings underscore 5-HT roles in the regulation of programmed cell death during brain development, and spur interest into pharmacological interventions aimed at relieving pathological apoptosis by potentiating serotoninergic neurotransmission. C1 Interdisciplinary Biomed Res Ctr, Lab Mol Psychiat & Neurogenet, I-00155 Rome, Italy. Interdisciplinary Biomed Res Ctr, Lab Dev Neurosci & Neuroplast, I-00155 Rome, Italy. Univ Naples 2, Dept Biochem, Sect Pathol, Naples, Italy. Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Persico, AM (reprint author), Interdisciplinary Biomed Res Ctr, Lab Mol Psychiat & Neurogenet, Univ Campus Biomed,Via Longoni 83, I-00155 Rome, Italy. RI Lesch, Klaus-Peter/J-4906-2013; OI Lesch, Klaus-Peter/0000-0001-8348-153X; Baldi, Alfonso/0000-0002-8693-3842 FU Telethon [E.1215] NR 23 TC 35 Z9 39 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 3 PY 2003 VL 14 IS 3 BP 341 EP 344 DI 10.1097/01.wnr.0000058244.21747.83 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 656ZW UT WOS:000181641800009 PM 12634480 ER PT J AU Adams, GP Shaller, C Garmestani, K Tesfaye, A Waldmann, TA Brechbiel, MW AF Adams, GP Shaller, C Garmestani, K Tesfaye, A Waldmann, TA Brechbiel, MW TI Alpha-emitting radioisotopes conjugated to anti-HER2/neu diabodies for the radioimmunotherapy of solid tumors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NCI, Radiat Oncol Branch, Inorgan & Radioimmune Chem Sect, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. EM gp_adams@fccc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 102-NUCL BP U265 EP U265 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001358 ER PT J AU Bethge, WA Wilbur, DS Hamlin, DK Santos, EB Brechbiel, MW Storb, R Sandmaier, BM AF Bethge, WA Wilbur, DS Hamlin, DK Santos, EB Brechbiel, MW Storb, R Sandmaier, BM TI Radioimmunotherapy with bismuth-213 as nonmyeloablative conditioning for marrow transplantation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98102 USA. Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. EM wbethge@fhcrc.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 80-NUCL BP U261 EP U261 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001336 ER PT J AU Bleckwenn, NA Bentley, WE Shiloach, J AF Bleckwenn, NA Bentley, WE Shiloach, J TI Expression of EGFP reporter protein with a recombinant vaccinia virus - Comparison of microcarrier and cell suspension based bioreactor systems. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA. Univ Maryland, UMBI, Ctr Biosyst Res, Dept Chem Engn, College Pk, MD 20742 USA. EM nb115q@nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 255-BIOT BP U225 EP U225 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800943 ER PT J AU Brechbiel, MW Milenic, DE Garmestani, K Abdulla, A Overstreet, T Flynn, J AF Brechbiel, MW Milenic, DE Garmestani, K Abdulla, A Overstreet, T Flynn, J TI Radioimmunotherapy of intraperitoneal disseminated disease: Preliminary evaluation of herceptin as a radio immunoconjugate. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NCI, NIH, Bethesda, MD 20892 USA. NIH, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 117-NUCL BP U267 EP U267 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001373 ER PT J AU Brooks, BR Stan, G Wu, XW AF Brooks, BR Stan, G Wu, XW TI Examining complex processes in macromolecular systems SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, College Pk, MD 20742 USA. Univ Georgia, Dept Chem, CCQC, Athens, GA 30602 USA. EM brbrooks@helix.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 289 BP U777 EP U777 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917803618 ER PT J AU Bulte, JWM Duncan, ID Frank, JA Douglas, T Kraitchman, DL AF Bulte, JWM Duncan, ID Frank, JA Douglas, T Kraitchman, DL TI Cellular magnetic resonance imaging using superparamagnetic nanoparticles. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. Univ Wisconsin, Dept Med Sci, Madison, WI 53706 USA. NIH, Expt Neuroimaging Sect, Bethesda, MD USA. Montana State Univ, Dept Chem & Biochem, Bozeman, MT USA. EM jwmbulte@mri.jhu.edu RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 197-IEC BP U982 EP U982 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917804617 ER PT J AU Choi, YS Comin, MJ Clifford, G Balzarini, J Marquez, VE AF Choi, YS Comin, MJ Clifford, G Balzarini, J Marquez, VE TI Asymmetric synthesis of a conformationally locked carboxylic analog of L-3 '-deoxythymine that mimics the South conformation: Biological implications and enzyme recognition. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. Rega Inst, Louvain, Belgium. EM marquezv@dc37a.nci.nih.gov RI Choi, Yongseok/F-8375-2012 OI Choi, Yongseok/0000-0002-3622-3439 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 119-MEDI BP U195 EP U195 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001042 ER PT J AU Dalal, NG Geva, J Fass, R Shiloach, J AF Dalal, NG Geva, J Fass, R Shiloach, J TI Dissolved oxygen affects the accumulation of recombinant clostridia peptide fragment in E.coli. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA. EM nd77k@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 278-BIOT BP U229 EP U229 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800966 ER PT J AU Dimitriadis, EK Horkay, F AF Dimitriadis, EK Horkay, F TI Measurement of the elastic modulus of thin gel layers by the atomic force microscope. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD 20892 USA. EM dimitria@helix.nih.gov; horkay@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 307-BIOT BP U233 EP U233 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800995 ER PT J AU Duan, DH AF Duan, DH TI Solid phase synthesis of diacylglycerol-lactones(DAG-lactones) in macrokans as a prelude to the synthesis of protein kinase c (PKC) isozyme-specific ligands by a combinatorial approach. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM duand@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 153-ORGN BP U304 EP U304 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001558 ER PT J AU Felder, CC McKinzie, DL Porter, A Gannon, KS Wess, J Bymaster, FP Nathanson, NM Hitchcock, SA AF Felder, CC McKinzie, DL Porter, A Gannon, KS Wess, J Bymaster, FP Nathanson, NM Hitchcock, SA TI Biochemical and behavioral studies using M1-M5 receptor knockout mice: Implications for development of a selective M1 receptor agonist clinical candidate. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 Eli Lilly & Co, Neurosci, Windlesham GU20 6PH, Surrey, England. NIDDK, Lab Bioinorgan Chem, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. EM Felder@Lilly.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 329-MEDI BP U232 EP U233 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001251 ER PT J AU Gorres, KL Louis, JM Clore, GM Bewley, CA AF Gorres, KL Louis, JM Clore, GM Bewley, CA TI Design and properties of stable trimeric coiled-coils derived from the N-helices of HIV-1 ENV GP41 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM gorr0023@mrs.umn.edu RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 864-CHED BP U485 EP U485 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917802170 ER PT J AU Heeger, S Moldenhauer, G Egerer, G Wesch, H Martin, S Nikula, T Apostolidis, C Brechbiel, MW Ho, AD Haas, R AF Heeger, S Moldenhauer, G Egerer, G Wesch, H Martin, S Nikula, T Apostolidis, C Brechbiel, MW Ho, AD Haas, R TI Alpha-radioimmunotherapy of B-lineage non-Hodgkin's lymphoma using 213Bi-labelled anti-CD19-and anti-CD20-CHX-A ''-DTPA conjugates. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 German Canc Res Ctr, Dept Mol Immunol, D-69120 Heidelberg, Germany. Univ Heidelberg Hosp, Heidelberg, Germany. German Canc Res Ctr, Dept Radiol, D-69120 Heidelberg, Germany. Commiss European Communities, Joint Res Ctr, Inst Transuranium Elements, Ispra, Italy. NCI, NIH, Bethesda, MD 20892 USA. Univ Duesseldorf, Dept Hematol Oncol & Clin Immunol, Dusseldorf, Germany. EM S.Heeger@DKFZ.de NR 0 TC 6 Z9 7 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 78-NUCL BP U261 EP U261 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001334 ER PT J AU Horkay, F Berman, AS Basser, PJ AF Horkay, F Berman, AS Basser, PJ TI New tissue micro-osmometer. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 NICHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 305-BIOT BP U233 EP U233 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800993 ER PT J AU Horkay, F Basser, PJ Hecht, AM Geissler, E AF Horkay, F Basser, PJ Hecht, AM Geissler, E TI Cross-linked polyacrylate hydrogels: Osmotic and neutron scattering properties. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, Grenoble, France. EM horkay@helix.nih.gov RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 2-POLY BP U532 EP U532 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918002699 ER PT J AU Hu, ZG Pandit, B Shi, JD Zink, J Sackett, DL Li, PK AF Hu, ZG Pandit, B Shi, JD Zink, J Sackett, DL Li, PK TI Thalidomide analogs with antiproliferative and antimicrotubule activities. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. NICHHD, Lab Integrat & Med Biophys, Bethesda, MD USA. Ohio State Univ, Dept Med Chem, Columbus, OH 43210 USA. EM Hu@dendrite.pharmacy.ohio-state.edu NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 126-MEDI BP U196 EP U197 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001049 ER PT J AU Ivanic, J AF Ivanic, J TI Occupation restricted multiple active space (ORMAS)-CI/SCF. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NCI, Adv Biomed Comp Ctr, SAIC Frecerick, Frederick, MD 21702 USA. EM jivanic@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 140-PHYS BP U454 EP U454 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918002318 ER PT J AU Jacobson, KA Kim, SK IJzerman, AP Gao, ZG AF Jacobson, KA Kim, SK IJzerman, AP Gao, ZG TI Allosteric modulation of A(3) adenosine receptors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. Leiden Amsterdam Ctr Drug Res, Leiden, Netherlands. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 316-MEDI BP U230 EP U230 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001238 ER PT J AU Karki, RG Nicklaus, MC AF Karki, RG Nicklaus, MC TI Insights into the binding modes of diketo acid HIV-1 integrase inhibitors-A molecular modeling study. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. EM rajeshri@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 36-MEDI BP U179 EP U179 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918000962 ER PT J AU Kim, P Shenoy, G Nguyen, QA Goodwin, M Dowd, CS Barry, CE AF Kim, P Shenoy, G Nguyen, QA Goodwin, M Dowd, CS Barry, CE TI Synthesis of racemic thiolactomycin (TLM) and its C(5) derivatives. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NIAID, TB Res Sect, NIH, Rockville, MD 20852 USA. EM pkim@niaid.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 288-ORGN BP U327 EP U328 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001693 ER PT J AU Kuznetsova, L Sturm, A Gupta, V Ojima, I AF Kuznetsova, L Sturm, A Gupta, V Ojima, I TI Taxane and taxoids as potential antiparasitic agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. NICHHD, Lab Integrat & Med Biophys, Bethesda, MD USA. Ohio State Univ, Dept Med Chem, Columbus, OH 43210 USA. EM lkuznets@ic.sunysb.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 125-MEDI BP U196 EP U196 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001048 ER PT J AU Lee, K Phan, J Wu, L Waugh, DS Zhang, ZY Burke, TR AF Lee, K Phan, J Wu, L Waugh, DS Zhang, ZY Burke, TR TI Tripeptide inhibitors of Yersinia protein-tyrosine phosphatase as potential leads for therapeutic development against plague ("black death"). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. NCI, Macromol Crystallog Lab, CCR, NIH, Frederick, MD 21702 USA. EM klee@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 50-MEDI BP U182 EP U182 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918000976 ER PT J AU Li, P Zhang, MC Peach, ML Yang, DJ Roller, PP AF Li, P Zhang, MC Peach, ML Yang, DJ Roller, PP TI Design and synthesis of potent Grb2-SH2 domain antagonists based upon phage library derived cyclic peptide G1TE. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NCI, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. EM pengli@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 100-MEDI BP U192 EP U192 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001025 ER PT J AU Luzzio, FA Ng, SSW Gutschow, M Hauschildt, S Weiss, M Teubert, U Kruger, E Mayorov, AV Eger, K Figg, WD AF Luzzio, FA Ng, SSW Gutschow, M Hauschildt, S Weiss, M Teubert, U Kruger, E Mayorov, AV Eger, K Figg, WD TI Antiangiogenic activity of N-substituted and tetrafluorinated thalidomide analogs. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 Univ Louisville, Dept Chem, Louisville, KY 40292 USA. NCI, Canc Therapeut Branch, Bethesda, MD 20892 USA. Univ Leipzig, Inst Pharm, Leipzig, Germany. EM faluzz0l@athena.louisville.edu RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 127-MEDI BP U197 EP U197 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001050 ER PT J AU Mattes, MJ Brechbiel, MW Michel, RB AF Mattes, MJ Brechbiel, MW Michel, RB TI Comparison of antibodies conjugated to 125-I, 111-In, 67-Ga or 131-I for single-cell kill. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 Ctr Mol Med & Immunol, Belleville, NJ 07109 USA. NIH, Bethesda, MD 20892 USA. EM mjmattes@gscancer.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 96-NUCL BP U264 EP U264 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001352 ER PT J AU Nicklaus, MC Ihlenfeldt, WD Voigt, JH Oellien, F AF Nicklaus, MC Ihlenfeldt, WD Voigt, JH Oellien, F TI Web-based tools for cheminformatics and drug design SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 NCI, Med Chem Lab, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. Univ Erlangen Nurnberg, Inst Organ Chem, Comp Chem Ctr, D-8520 Erlangen, Germany. EM mnl@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 034-CINF BP U554 EP U555 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917802647 ER PT J AU Nussinov, R AF Nussinov, R TI Integrating advanced algorithms to enhance docking and drug design. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 SAIC Frederick Inc, NCI, Basic Res Program, Frederick, MD 21702 USA. EM ruthn@ncisgi.ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 072-COMP BP U743 EP U743 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917803403 ER PT J AU Peach, ML Nicklaus, MC Blumberg, PM Marquez, VE AF Peach, ML Nicklaus, MC Blumberg, PM Marquez, VE TI Comparative modeling of C1 regulatory domains in the protein kinase C isozyme family. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 NCI, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. EM mpeach@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 188-COMP BP U761 EP U761 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917803517 ER PT J AU Rasaiah, JC AF Rasaiah, JC TI Hydrophobic and hydrophilic effects in confined systems. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 Univ Maine, Dept Chem, Orono, ME 04469 USA. Univ Maine, Dept Phys, Orono, ME 04469 USA. Warsaw Med Inst, Warsaw, Poland. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM rasaiah@maine.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 121-PHYS BP U451 EP U451 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918002301 ER PT J AU Rau, EH AF Rau, EH TI Mad as a hatter? The campaign for a mercury free NIH. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 NIH, Environm Protect Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM erau@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 10-CHAS BP U293 EP U293 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917801290 ER PT J AU Schenck, HA Cechova, S Pajewski, TN Ellena, J Cafiso, DS Stables, JP Brown, ML AF Schenck, HA Cechova, S Pajewski, TN Ellena, J Cafiso, DS Stables, JP Brown, ML TI Design, synthesis and discovery of hydroxyamides as orally available general anesthetics and anticonvulsants. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA. Univ Virginia, Dept Anesthesiol, Charlottesville, VA 22904 USA. NIH, Div Neurol Dis & Stroke, Bethesda, MD USA. EM has5w@virginia.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 213-MEDI BP U211 EP U211 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001135 ER PT J AU Shi, ZD Wei, CQ Gao, Y Lee, K Vasselli, J Zhang, MC Liu, HP Yang, DJ Linehan, M Burke, TR AF Shi, ZD Wei, CQ Gao, Y Lee, K Vasselli, J Zhang, MC Liu, HP Yang, DJ Linehan, M Burke, TR TI Design and synthesis of a novel macrocycle that exhibits high Grb2 SH2 domain-binding affinity. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. NCI, Urol Oncol Branch, CCR, NIH, Frederick, MD 21702 USA. Univ Michigan, Sch Med, Dept Hematol Oncol, Ann Arbor, MI 48109 USA. EM shiz@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 99-MEDI BP U191 EP U192 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001024 ER PT J AU Shi, ZD Wei, CQ Gao, Y Lee, K Vasselli, J Zhang, MC Liu, HP Yang, DJ Linehan, M Burke, TR AF Shi, ZD Wei, CQ Gao, Y Lee, K Vasselli, J Zhang, MC Liu, HP Yang, DJ Linehan, M Burke, TR TI Macrocyclization in the design of non phosphorus-containing GRB2 SH2 domain-binding ligands that exhibit high affinity in cell-based assays. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. NCI, Urol Oncol Branch, Canc Res Ctr, Frederick, MD 21702 USA. Univ Michigan, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. EM tburke@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 9-MEDI BP U174 EP U174 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918000935 ER PT J AU Showalter, BM Saavedra, JE Citro, ML Keefer, LK AF Showalter, BM Saavedra, JE Citro, ML Keefer, LK TI Synthesis and chemistry of diazeniumdiolate anions from hindered amines. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, BRP, SAIC Frederick Inc, Frederick, MD 21701 USA. EM bshowalter@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 282-MEDI BP U224 EP U224 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001204 ER PT J AU Sun, G Nicklaus, MC Marquez, VE AF Sun, G Nicklaus, MC Marquez, VE TI Theoretical study of the acidic hydrolysis of adendsine in aqueous solution by density functional theory. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 NCI, CCR, Med Chem Lab, Ft Detrick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 238-COMP BP U769 EP U769 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917803567 ER PT J AU Tekle, E Chock, BP AF Tekle, E Chock, BP TI Selective electroporation of a vesicle population in high frequency electric fields. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. EM ephrem@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 477-COLL BP U681 EP U681 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917803226 ER PT J AU Venkateswarlu, D Duke, RE Darden, T Pedersen, LG AF Venkateswarlu, D Duke, RE Darden, T Pedersen, LG TI Solution structural model for human extrinsic blood coagulation complex (TF.VIIA.X): Protein-protein docking and molecular dynamics refinement study. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 Univ N Carolina, Dept Chem, Chapel Hill, NC 27519 USA. NIEHS, Bethesda, MD USA. EM divi@email.unc.edu RI Pedersen, Lee/E-3405-2013; Venkateswarlu, Divi/K-1815-2014 OI Pedersen, Lee/0000-0003-1262-9861; Venkateswarlu, Divi/0000-0003-2481-7480 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 169-COMP BP U758 EP U758 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917803499 ER PT J AU Wang, SM Wang, RX Yang, CY Stuckey, J Tomita, Y Yang, DJ Li, P Rollers, PP Sun, HY Ding, K Wang, GP Tang, GZ Chen, JY Zhang, MC Nikolovska-Coleska, Z Cao, Y AF Wang, SM Wang, RX Yang, CY Stuckey, J Tomita, Y Yang, DJ Li, P Rollers, PP Sun, HY Ding, K Wang, GP Tang, GZ Chen, JY Zhang, MC Nikolovska-Coleska, Z Cao, Y TI Flexibility of anti-death protein BCL-XL and the significance for designing small molecule inhibitors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA. Georgetown Univ, Washington, DC 20057 USA. NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. EM shaomeng@umich.edu RI Ding, Ke/B-3257-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 131-COMP BP U752 EP U752 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917803462 ER PT J AU Waterhouse, DJ Saavedra, JE Wang, LY Buzard, GS Diwan, BA Singh, SV Davies, KM Citro, ML Ji, XH Shami, PJ Keefer, LK AF Waterhouse, DJ Saavedra, JE Wang, LY Buzard, GS Diwan, BA Singh, SV Davies, KM Citro, ML Ji, XH Shami, PJ Keefer, LK TI JS-K, a glutathione/glutathione S-transferase-activated nitric oxide (NO) donor of the diazeniumdiolate class with potent antineoplastic activity. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, BRP, SAIC Frederick Inc, Frederick, MD 21701 USA. Univ Utah, Dept Internal Med, Div Med Oncol, Salt Lake City, UT 84112 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15260 USA. SLC VA Med Ctr, Salt Lake City, UT USA. George Mason Univ, Dept Chem, Fairfax, VA 22030 USA. NCI, Biomol Struct Sect, Macromol Crystallog Lab, Frederick, MD 21701 USA. EM waterhoused@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 111-MEDI BP U194 EP U194 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001035 ER PT J AU Wesch, H Heeger, S Spicker, F Amelung, F Brechbiel, MW Moldenhauer, G Nikula, T AF Wesch, H Heeger, S Spicker, F Amelung, F Brechbiel, MW Moldenhauer, G Nikula, T TI Long term survival and toxicity in balb/c mice after systemic administration of alpha-emitters. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 German Canc Res Ctr, Dept Radiol, D-69120 Heidelberg, Germany. German Canc Res Ctr, Dept Mol Immunol, D-69120 Heidelberg, Germany. NCI, NIH, Bethesda, MD 20892 USA. EM H.Wesch@dkfz.de RI Amelung, Falk/J-9042-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 85-NUCL BP U262 EP U262 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001341 ER PT J AU Yergey, AL AF Yergey, AL TI Aspects of ideal mass spectrometric data for protein characterization. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 NICHHD, NIH, Sect Metab Anal & Mass Spectrometry, LCMB, Bethesda, MD 20892 USA. EM aly@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 279-ANYL BP U150 EP U151 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800685 ER PT J AU Zborowski, M Ostera, GR Moore, LR Milliron, S Chalmers, JJ Schechter, AN AF Zborowski, M Ostera, GR Moore, LR Milliron, S Chalmers, JJ Schechter, AN TI Magnetophoretic separation of red blood cells. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 Cleveland Clin Fdn, Dept Biomed Engn, Cleveland, OH 44195 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Toledo, Dept Bioengn, Toledo, OH 43606 USA. Ohio State Univ, Dept Chem Engn, Columbus, OH 43210 USA. EM zborow@bme.ri.ccf.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 260-IEC BP U991 EP U991 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917804678 ER PT J AU Zhang, Y Mukhin, AG Pavlova, OA Chefer, SI Vaupel, DB Brown, LL Hall, AW Kurian, V Horti, AG AF Zhang, Y Mukhin, AG Pavlova, OA Chefer, SI Vaupel, DB Brown, LL Hall, AW Kurian, V Horti, AG TI Synthesis, structure-activity relationship and pre-evaluation of heteryl derivatives of A-85380 as potential radiotracers for imaging of nicotinic acetylcholine receptors (nAChRs) in extrathalamic brain regions by positron emission tomography (PET). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM yizhang@intra.nida.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 225-MEDI BP U213 EP U213 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918001147 ER PT J AU Meinert, JA Blehar, MC Peindl, KS Neal-Barnett, A Wisner, KL AF Meinert, JA Blehar, MC Peindl, KS Neal-Barnett, A Wisner, KL TI Bridging the gap - Recruitment of African-American women into mental health research studies SO ACADEMIC PSYCHIATRY LA English DT Article ID CLINICAL-TRIALS; PREVENTION; COMMUNITY AB Objective: To develop a strategy for recruiting African-American women into a research study for pregnant women. Methods: With few exceptions, NIH-funded investigators must include women and minorities in clinical research. The authors used the recommendations provided in the Outreach Notebook for the NIH Guidelines on Inclusion of Women and Minorities as Subjects in Clinical Research as a guide to help them reach out to African-American women in the community. Results and Conclusions: The out-reach experience led to a conference for African-American women about mental health. On the basis of this experience, the authors formulated a five-pronged approach for recruitment of African-American women into their study. The NIH guidelines were useful for this purpose. (Academic Psychiatry 2003; 27:21-28). C1 Thomas Jefferson Univ, Dept Psychiat & Human Behav, Philadelphia, PA 19107 USA. Case Western Reserve Univ, Womens Mental HealthCARE, Cleveland, OH 44106 USA. NIMH, Womens Mental Hlth Program, Bethesda, MD 20892 USA. Kent State Univ, Kent, OH 44242 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Sch Med, Pittsburgh, PA 15213 USA. RP Peindl, KS (reprint author), Thomas Jefferson Univ, Dept Psychiat & Human Behav, 833 Chestnut St,Suite 210-E, Philadelphia, PA 19107 USA. FU NIMH NIH HHS [R01 MH60335] NR 18 TC 13 Z9 13 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD SPR PY 2003 VL 27 IS 1 BP 21 EP 28 DI 10.1176/appi.ap.27.1.21 PG 8 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 649NR UT WOS:000181215300004 PM 12824117 ER PT J AU Banumathi, S Dauter, M Dauter, Z AF Banumathi, S Dauter, M Dauter, Z TI Phasing at high resolution using Ta6Br12 cluster SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID ANGSTROM RESOLUTION; ISOMORPHOUS REPLACEMENT; PROTEIN CRYSTALLOGRAPHY; REFINEMENT; ASSEMBLIES; ENZYME AB The Ta6Br122+ cluster compound is known to be a powerful reagent for derivatization of crystals of large macromolecules at low resolution. The cluster is a regular octahedron of six Ta atoms with 12 bridging Br atoms at the edges of the octahedron. The cluster is compact, of approximately spherical shape, with a radius of about 6 Angstrom. Both tantalum and bromine display a significant anomalous diffraction signal at their absorption edges at 1.25 and 0.92 Angstrom, respectively. At resolutions lower than 5 Angstrom the tantalum cluster behaves as a super-atom and provides very large isomorphous and anomalous signals, which significantly diminish at about 4 Angstrom. However, beyond 3 Angstrom the individual Ta atoms can be resolved and the phasing power of the cluster increases again. The Ta6Br122+ cluster has been used for phasing four different proteins at high resolution. Ta6Br122+ appeared to be a mild derivatization reagent and, despite partial incorporation, led to a successful solution of crystal structures by the single-wavelength anomalous diffraction (SAD) approach. C1 SAIC Frederick Inc, Basic Res Program, Brookhaven Natl Lab, Upton, NY 11973 USA. NCI, Synchrotron Radiat Res Sect, Ctr Macromol Crystallog, Brookhaven Natl Lab, Upton, NY 11973 USA. RP Dauter, Z (reprint author), SAIC Frederick Inc, Basic Res Program, Brookhaven Natl Lab, Bldg 725A-X9, Upton, NY 11973 USA. NR 25 TC 17 Z9 17 U1 0 U2 1 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 MAR PY 2003 VL 59 BP 492 EP 498 DI 10.1107/S0907444903000064 PN 3 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 656LT UT WOS:000181609800011 PM 12595706 ER PT J AU Kim, MH Derewenda, U Devedjiev, Y Dauter, Z Derewenda, ZS AF Kim, MH Derewenda, U Devedjiev, Y Dauter, Z Derewenda, ZS TI Purification and crystallization of the N-terminal domain from the human doublecortin-like kinase SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID MICROTUBULE-ASSOCIATED PROTEIN; LISSENCEPHALY SYNDROME; NEURONAL MIGRATION; GENE; MUTATIONS; HETEROTOPIA; EXPRESSION; ENCODES; SUBUNIT; LIS1 AB The unique doublecortin-like tandem of two homologous domains is found in certain microtubule-associated proteins such as doublecortin (DCX) and doublecortin-like kinase (DCLK). It is responsible for interactions with tubulin/microtubules and regulates microtubule dynamics. Here, the expression and purification of the tandem from human DCLK (residues 49-280) and of the isolated domains (residues 49-154 and 176-280) and the successful crystallization of the N-terminal domain (N-DCLK) are reported. High-quality wildtype crystals were obtained and a complete native data set was collected to 1.5 Angstrom resolution. The crystals belong to space group C2, with unit-cell parameters a = 85.98, b = 29.62, c = 40.33 Angstrom, beta = 101.3degrees. Crystals of SeMet-substituted N-DCLK (Leu120Met) were also obtained, but they exhibit the symmetry of space group P2(1), with unit-cell parameters a = 38.81, b = 29.43, c = 40.1 Angstrom, beta = 115.7degrees. C1 Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. Univ Virginia, Ctr Canc, Charlottesville, VA 22908 USA. NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Brookhaven Natl Lab, Upton, NY 11973 USA. RP Derewenda, ZS (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, POB 800736, Charlottesville, VA 22908 USA. FU NINDS NIH HHS [NS36267] NR 18 TC 3 Z9 4 U1 0 U2 1 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 MAR PY 2003 VL 59 BP 502 EP 505 DI 10.1107/S0907444903000027 PN 3 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 656LT UT WOS:000181609800013 PM 12595708 ER PT J AU Darmanin, C Iwata, T Carper, DA Sparrow, LG Chung, RPT El-Kabbani, O AF Darmanin, C Iwata, T Carper, DA Sparrow, LG Chung, RPT El-Kabbani, O TI Expression, purification and preliminary crystallographic analysis of human sorbitol dehydrogenase SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID ALCOHOL DEHYDROGENASES; CRYSTAL-STRUCTURE; ACTIVE-SITE; BINDING; PATHWAY; ENZYME AB Human sorbitol dehydrogenase (SDH) was expressed in Escherichia coli BL21 cells and purified using ammonium sulfate precipitation and anion-exchange and dye-affinity chromatography. Purified SDH was crystallized from polyethylene glycol solutions using the hanging-drop vapour-diffusion method. X-ray data were collected to 2.75 Angstrom resolution. The crystals belong to the monoclinic C2 space group, with unit-cell parameters a = 145.9, b = 52.3, c = 169.0 Angstrom, beta = 101.8degrees. This is the first crystallization report of human sorbitol dehydrogenase. C1 Monash Univ, Victorian Coll Pharm, Dept Med Chem, Parkville, Vic 3052, Australia. Natl Tokyo Med Ctr, Meguro Ku, Tokyo 1528902, Japan. NEI, NIH, Bethesda, MD 20892 USA. CSIRO, Parkville, Vic 3052, Australia. RP El-Kabbani, O (reprint author), Monash Univ, Victorian Coll Pharm, Dept Med Chem, Parkville Campus, Parkville, Vic 3052, Australia. NR 20 TC 3 Z9 3 U1 0 U2 1 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 MAR PY 2003 VL 59 BP 558 EP 560 DI 10.1107/S0907444903000441 PN 3 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 656LT UT WOS:000181609800030 PM 12595725 ER PT J AU Epstein, DH Preston, KL AF Epstein, DH Preston, KL TI Does cannabis use predict poor outcome for heroin-dependent patients on maintenance treatment? Past findings and more evidence against SO ADDICTION LA English DT Review DE cannabis; methadone maintenance; treatment outcome ID ILLICIT DRUG-USE; METHADONE-MAINTENANCE; MARIJUANA USE; SUBSTANCE USE; RELIABILITY; ABSTINENCE; COMMUNITY; VALIDITY; ABUSE AB Aims To determine whether cannabinoid-positive urine specimens in heroin-dependent out-patients predict other drug use or impairments in psychosocial functioning, and whether such outcomes are better predicted by cannabis-use disorders than by cannabis use itself. Design Retrospective analyses of three clinical trials: each included a behavioral intervention (contingency management) for cocaine or heroin use during methadone maintenance. Trials lasted 25-29 weeks; follow-up evaluations occurred 3, 6 and 12 months post-treatment. For the present analyses, data were pooled across trials where appropriate. Setting Urban out-patient methadone clinic. Participants Four hundred and eight polydrug abusers meeting methadone-maintenance criteria. Measurements Participants were categorized as non-users, occasional users or frequent users of cannabis based on thrice-weekly qualitative urinalyses. Cannabis-use disorders were assessed with the Diagnostic Interview Schedule III-R. Outcome measures included proportion of cocaine- and opiate-positive urines and the Addiction Severity Index (at intake and follow-ups). Findings Cannabis use was not associated with retention, use of cocaine or heroin, or any other outcome measure during or after treatment. Our analyses had a power of 0.95 to detect an r(2) of 0.11 between cannabis use and heroin or cocaine use; the r(2) we detected was less than 0.03 and non-significant. A previous finding, that cannabis use predicted lapse to heroin use in heroin-abstinent patients, did not replicate in our sample. However, cannabis-use disorders were associated weakly with psychosocial problems at post-treatment follow-up. Conclusions Cannabinoid-positive urines need not be a major focus of clinical attention during treatment for opiate dependence, unless patients report symptoms of cannabis-use disorders. C1 NIDA, IRP, Treatment Sect, Clin Pharmacol & Therapeut Branch, Baltimore, MD 21224 USA. RP Epstein, DH (reprint author), NIDA, IRP, Treatment Sect, Clin Pharmacol & Therapeut Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS [Z99 DA999999] NR 28 TC 46 Z9 47 U1 0 U2 6 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 2003 VL 98 IS 3 BP 269 EP 279 DI 10.1046/j.1360-0443.2003.00310.x PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 650YF UT WOS:000181291700006 PM 12603227 ER PT J AU Winhusen, TM Somoza, EC Singal, B Kim, S Horn, PS Rotrosen, J AF Winhusen, TM Somoza, EC Singal, B Kim, S Horn, PS Rotrosen, J TI Measuring outcome in cocaine clinical trials: a comparison of sweat patches with urine toxicology and participant self-report SO ADDICTION LA English DT Article DE clinical trials; cocaine use measures; outcome measures in cocaine clinical trials; sweat patches ID DRUG-USE; METABOLITES; HEROIN; ABUSE AB Aims To evaluate the advantages of using a sweat patch (PharmCheck(TM)) for detecting cocaine abuse in cocaine-dependent patients participating in a clinical trial: The utility of the sweat patch was assessed from the following perspectives: the reliability and validity of quantitative sweat patch results, the possible degradation of cocaine to benzoylecgonine (BE) as a function of the length of time that a patch is worn, the completeness of the dataset yielded by thrice-weekly urine toxicology compared with thrice-weekly and weekly sweat patches, and the relative costs associated with sweat patch versus urine measures. Design Data were collected during a 10-week out-patient clinical trial in which participants wore two sweat patches, one applied every visit and one applied weekly. Urine samples were collected thrice weekly, as were self-reports of substance use. Setting A multi-site clinical trial conducted in Boston, Cincinnati and New York, USA. Participants Twenty-seven participants with comorbid diagnoses of cocaine dependence and adult attention deficit disorder completed the study. Measurements Sweat patch and urine samples were analyzed by standard methods for cocaine and cocaine metabolites. Findings Quantitative sweat patch measures had good reliability in that the correlation between the weekly and per-visit patches was 0.96 (P < 0.0001). The concurrent validity, as judged by the correlation between quantitative urine BE levels and either weekly (0.76, P<0.0001) or per-visit (0.73, P<0.0001) cocaine sweat patch levels was reasonable. The correlation between the self-report of cocaine use and these same two patches, however, was lower (0.40, P < 0.05 and 0.30, P < 0.05, respectively). The results revealed no significant degradation of cocaine to BE associated with wearing the patch for a longer time. Finally, the per-visit patch provided cocaine use data on 80.5% of all study days (a total of 70), while urine toxicology and the weekly patch provided 77.4% and 76.1%, respectively. Conclusions The present findings suggest that the PharmCheck(TM) patch might be an attractive alternative to urine toxicology for use as an outcome measure in cocaine clinical trials. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45220 USA. Vet Affairs Med Ctr, Cincinnati VAUC NIDA MDRU, Cincinnati, OH 45267 USA. Univ Cincinnati, Dept Math Sci, Cincinnati, OH 45221 USA. NYU, Sch Med, New York, NY USA. VHA New York Harbor Healthcare Syst, New York, NY USA. RP Winhusen, TM (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, 3210 Jefferson Ave, Cincinnati, OH 45220 USA. OI Winhusen, Theresa/0000-0002-3364-0739 FU NIDA NIH HHS [N01DA-7 8074, Y01 DA 50038-00] NR 15 TC 16 Z9 16 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 2003 VL 98 IS 3 BP 317 EP 324 DI 10.1046/j.1360-0443.2003.00311.x PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 650YF UT WOS:000181291700010 PM 12603231 ER PT J AU Teng, CT AF Teng, CT TI Regulation of lactoferrin gene expression SO AGRO FOOD INDUSTRY HI-TECH LA English DT Article ID EPIDERMAL GROWTH-FACTOR; MOLECULAR MECHANISM; RECEPTOR; ESTROGEN; MOUSE; PROMOTER; PROTEIN; ALPHA; COACTIVATORS; ELEMENTS C1 NIEHS, Reprod & Dev Toxicol Lab, Gene Regulat Sect, NIH, Res Triangle Pk, NC 27709 USA. NR 29 TC 1 Z9 1 U1 0 U2 0 PU TEKNOSCIENZE PUBL PI MILAN PA VIA AURELIO SAFFI 23, 20123 MILAN, ITALY SN 1722-6996 J9 AGRO FOOD IND HI TEC JI Agro Food Ind. Hi-Tech PD MAR-APR PY 2003 VL 14 IS 2 BP 40 EP 42 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 686TV UT WOS:000183337800007 ER PT J AU Grivel, JC Biancotto, A Ito, Y Lima, RG Margolis, LB AF Grivel, JC Biancotto, A Ito, Y Lima, RG Margolis, LB TI Bystander CD4(+) T lymphocytes survive in HIV-infected human lymphoid tissue SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELL DEPLETION; CROSS-LINKING; FAS LIGAND; EX-VIVO; APOPTOSIS; DEATH; MECHANISMS; ACTIVATION; HISTOCULTURES AB HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells. C1 NICHHD, Ctr Three Dimens Tissue Culture, NIH, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA. NICHHD, Ctr Three Dimens Tissue Culture, NIH, NASA, Bethesda, MD 20892 USA. RP Margolis, LB (reprint author), NICHHD, Ctr Three Dimens Tissue Culture, NIH, Lab Mol & Cellular Biophys, Bldg 10,Room 9D58,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 11 Z9 12 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 MAR PY 2003 VL 19 IS 3 BP 211 EP 216 DI 10.1089/088922203763315713 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 655KM UT WOS:000181551000006 PM 12689413 ER PT J AU DiBerardinis, LJ First, MW Party, E Smith, TC Warfield, CA Carpenter, JP Cook, JL Walters, DB Flynn, MR Galson, EL Greenley, PL Hitchings, DT Knutson, GW Price, JM Baum, JS Burton, JD Finucane, MD Ghidoni, DA Koenigsberg, J Lyons, M Memarzadeh, F Norton, DC Schuyler, G Zboralski, J Barkley, WE AF DiBerardinis, LJ First, MW Party, E Smith, TC Warfield, CA Carpenter, JP Cook, JL Walters, DB Flynn, MR Galson, EL Greenley, PL Hitchings, DT Knutson, GW Price, JM Baum, JS Burton, JD Finucane, MD Ghidoni, DA Koenigsberg, J Lyons, M Memarzadeh, F Norton, DC Schuyler, G Zboralski, J Barkley, WE TI Report of the Howard Hughes Medical Institute's workshop on the performance of laboratory chemical hoods SO AIHA JOURNAL LA English DT Article DE laboratory chemical hoods AB The Howard Hughes Medical Institute sponsored a workshop on laboratory chemical hoods on June 8, 9, and 10, 1998, that brought together 24 experts in the field of laboratory chemical hoods to critically assess the information known about hood performance. Workshop participants developed 31 consensus statements that reflect their collective views on the body of knowledge or lack thereof, for laboratory chemical hoods. The consensus statements fall into four broad categories: (1) hood selection, use, and operation; (2) hood and laboratory design issues; (3) ventilation system design issues; and (4) hood performance testing, The consensus statements include 26 statements on what is known and unknown about the performance of laboratory chemical hoods, 2 statements of definition, and 3 statements that reflect the participants' agreement not to agree. The brief commentary that follows each consensus statement provides guidance and recommendations. C1 MIT, Environm Hlth & Safety Off, Cambridge, MA 02139 USA. Harvard Univ, Sch Publ Hlth, Environm Sci & Engn Program, Boston, MA 02115 USA. Aventis CropSci NV, B-9000 Ghent, Belgium. Exposure Control Technol Inc, Cary, NC 27513 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. Kling Lindquist, Philadelphia, PA 19103 USA. EI, Durham, NC 27713 USA. KCP Inc, Raleigh, NC 27607 USA. Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. Galson Corp, Syracuse, NY 13214 USA. Hitchings Assoc, Indianapolis, IN 46268 USA. Knutson Ventilat Consulting Inc, Edina, MN 55410 USA. Northeastern Univ, Off Environm Hlth & Safety, Boston, MA 02115 USA. Hlth Educ & Res Assoc, St Louis, MO 63130 USA. IVE Inc, Bountiful, UT 84101 USA. Univ Penn, Philadelphia, PA 19104 USA. Baker Co, Sanford, ME 04073 USA. Aramark ServMaster Facil Serv, Madison, CT 06443 USA. NIH, Div Engn Serv, Bethesda, MD 20892 USA. Univ Michigan Hosp, Sch Med, Ann Arbor, MI 48109 USA. Rowan William Daveis & Irwin Inc, Guelph, ON N1K 1B8, Canada. Fisher Hamilton, Two Rivers, WI 54241 USA. RP DiBerardinis, LJ (reprint author), MIT, Environm Hlth & Safety Off, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 6 TC 3 Z9 3 U1 0 U2 1 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 USA SN 1529-8663 J9 AIHA J JI AIHA J. PD MAR-APR PY 2003 VL 64 IS 2 BP 228 EP 237 DI 10.1080/15428110308984812 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 666HR UT WOS:000182172200013 PM 12688847 ER PT J AU Terry, PD Rohan, TE Wolk, L AF Terry, PD Rohan, TE Wolk, L TI Intakes of fish and marine fatty acids and the risks of cancers of the breast and prostate and of other hormone-related cancers: a review of the epidemiologic evidence SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Review DE n-3 fatty acids; n-6 fatty acids; breast cancer; prostate cancer; endometrial cancer; ovarian cancer; hormone-dependent cancers; sex hormones; prostaglandins; eicosapentaenoic acid; docosahexaenoic acid ID SERUM ESTROGEN-LEVELS; EPITHELIAL OVARIAN-CANCER; MAMMARY-TUMOR GROWTH; DIETARY-FAT; ENDOMETRIAL CANCER; ADIPOSE-TISSUE; DOCOSAHEXAENOIC ACID; LIPID-PEROXIDATION; MEAT INTAKE; NEW-YORK AB Marine fatty acids, particularly the long-chain eicosapentaenoic and docosahexaenoic acids, have been consistently shown to inhibit the proliferation of breast and prostate cancer cell lines in vitro and to reduce the risk and progression of these tumors in animal experiments. However, whether a high consumption of marine fatty acids can reduce the risk of these cancers or other hormone-dependent cancers in human populations is unclear. Focusing primarily on the results of cohort and case-control studies, we reviewed the current epidemiologic literature on the intake of fish and marine fatty acids in relation to the major hormone-dependent cancers. Despite the many epidemiologic studies that have been published, the evidence from those studies remains unclear. Most of the studies did not show an association between fish consumption or marine fatty acid intake and the risk of hormone-related cancers. Future epidemiologic studies will probably benefit from the assessment of specific fatty acids in the diet, including eicosapentaenoic and docosahexaenoic acids, and of the ratio of these to n-6 fatty acids, dietary constituents that have not been examined individually very often. C1 Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA. Karolinska Inst, Dept Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. RP Terry, PD (reprint author), NIEHS, Epidemiol Branch, POB 12233 MD A3-05, Res Triangle Pk, NC 27709 USA. NR 136 TC 180 Z9 194 U1 1 U2 13 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 2003 VL 77 IS 3 BP 532 EP 543 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 649LT UT WOS:000181210600004 PM 12600840 ER PT J AU Pawlosky, RJ Hibbeln, JR Lin, YH Goodson, S Riggs, P Sebring, N Brown, GL Salem, N AF Pawlosky, RJ Hibbeln, JR Lin, YH Goodson, S Riggs, P Sebring, N Brown, GL Salem, N TI Effects of beef-and fish-based diets on the kinetics of n-3 fatty acid metabolism in human subjects SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE fatty acid kinetics; alpha-linolenic acid; n-3 fatty acids; docosahexaenoic acid; compartmental model; isotope tracer; fish diet ID ALPHA-LINOLENIC ACID; DOCOSAHEXAENOIC ACID; TERM INFANTS; GUINEA-PIG; BRAIN; DISEASE; RISK; RAT; FORMULA; PATHWAY AB Background: The quantity and type of dietary polyunsaturated fatty acids (PUFAs) can alter essential fatty acid metabolism in humans. Diets rich in 20- and 22-carbon PUFAs may inhibit desaturase expression or activity and decrease the synthesis of long-chain unsaturated fatty acids. Objective: It was theorized that the fat content of a fish-based diet would inhibit the kinetics of the in vivo metabolism of n-3 fatty acids compared with a beef-based diet. Design: A compartmental model was used to determine the coefficients of the kinetic rate constants from the plasma concentration time curves of pentadeuterated (d(5)) 18:3n-3, 20:5n-3, 22:5n-3, and 22:6n-3 of 10 subjects who subsisted on 3 diets with different long-chain PUFA contents. For 3 wk, subjects reported their food intake from their usual diets and then consumed a beef-based diet for 3 wk and then a fish-based diet for an additional 3 wk. Subjects consumed 1 g d(5)-18:3n-3 ethyl ester at weeks 3, 6, and 9. Blood was drawn over 168 h and the plasma analyzed for fatty acids. The coefficients of the kinetic constants of n-3 fatty acid metabolism and the percentage utilization of the substrates were determined. Results: Across all diets, < 1% of plasma 18:3n-3 was utilized for long-chain PUFA synthesis. There was a 70% reduction in the value of the rate constant coefficient that regulated transfer of the isotope from the 22:5n-3 compartment to 22:6n-3 when the fish-based diet was compared with the beef-based diet. The turnover rate of plasma d(5)-22:6n-3 also decreased. Conclusions: The primary effect of a fish-based diet on the kinetics of n-3 metabolism involves processes that inhibit the synthesis of 22:6n-3 from 22:5n-3. These processes may involve a system of feedback control mechanisms responsive to the plasma concentration of 22:6n-3 C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. USDA, Food Composit Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. NIAAA, Clin Studies Lab, NIH, Rockville, MD 20852 USA. NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA. RP Pawlosky, RJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Room 114,12420 Parklawn Dr, Rockville, MD 20852 USA. NR 24 TC 97 Z9 100 U1 1 U2 11 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 2003 VL 77 IS 3 BP 565 EP 572 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 649LT UT WOS:000181210600008 PM 12600844 ER PT J AU Lin, PH Proschan, MA Bray, GA Fernandez, CP Hoben, K Most-Windhauser, M Karanja, N Obarzanek, E AF Lin, PH Proschan, MA Bray, GA Fernandez, CP Hoben, K Most-Windhauser, M Karanja, N Obarzanek, E CA DASH Collaborative Res Grp TI Estimation of energy requirements in a controlled feeding trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE Harris-Benedict equation; FAO/WHO energy equation; stable weight; activity factor; controlled feeding study; clinical trial; clinical study ID DOUBLY LABELED WATER; PHYSICAL-ACTIVITY; BLOOD-PRESSURE; EXPENDITURE; RELIABILITY; VALIDATION; RECALL AB Background: Estimating energy requirements is a frequent task in clinical studies. Objective: We examined weight patterns of participants enrolled in a clinical trial and evaluated factors that may affect weight stabilization. The Harris-Benedict equation and the FAO/WHO equation, used in conjunction with physical activity levels estimated with the 7-d Physical Activity Recall, were compared for estimating energy expenditure. Design: This was a multicenter, randomized controlled feeding trial with participants of the Dietary Approaches to Stop Hypertension Trial. For 11 wk, the amount of food participants received was adjusted to maintain their body weights as close to their initial weights as possible. Change-point regression techniques were used to identify weight-stable periods. Factors related to achieving weight stabilization were examined with logistic regression. Results: A stable weight was achieved by 86% of the 448 participants during the run-in period and by 78% during the intervention period. Energy intake averaged 11 +/- 2.4 MJ/d (2628 +/- 578 kcal/d), with most participants (n = 270) requiring 9-13 MJ/d (2100-3100 kcal/d). The difference between predicted and observed intakes was highest at high estimated energy intakes, mainly because of high and probably incorrect estimates of the activity factor. Participants with lower energy intakes tended to need less adjustment of their energy intakes to maintain a stable weight than did participants with higher energy intakes. Conclusions: Weight stabilization is not affected by diet composition, sex, race, age, or baseline weight. Either the Harris-Benedict equation or the FAO/WHO equation can be used to estimate energy needs. Activity factors > 1.7 often lead to overestimation of energy needs. C1 Duke Univ, Med Ctr, Sarah W Stedman Ctr Nutr Studies, Durham, NC 27710 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Univ N Carolina, N Carolina Inst Publ Hlth, Chapel Hill, NC USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. RP Lin, PH (reprint author), Duke Univ, Med Ctr, Sarah W Stedman Ctr Nutr Studies, Box 3487, Durham, NC 27710 USA. FU NHLBI NIH HHS [U01-HL50968, U01-HL50972, U01-HL50977, U01-HL50981, U01-HL50982] NR 22 TC 26 Z9 28 U1 0 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 2003 VL 77 IS 3 BP 639 EP 645 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 649LT UT WOS:000181210600018 PM 12600854 ER PT J AU Poindexter, BB Ehrenkranz, RA Stoll, BJ Koch, MA Wright, LL Oh, W Papile, LA Bauer, CR Carlo, WA Donovan, EF Fanaroff, AA Korones, SB Laptook, AR Shankaran, S Stevenson, DK Tyson, JE Lemons, JA AF Poindexter, BB Ehrenkranz, RA Stoll, BJ Koch, MA Wright, LL Oh, W Papile, LA Bauer, CR Carlo, WA Donovan, EF Fanaroff, AA Korones, SB Laptook, AR Shankaran, S Stevenson, DK Tyson, JE Lemons, JA CA Natl Inst Child Hlth Human Dev Neo TI Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE glutamine; phenylalanine; tyrosine; extremely low-birth-weight; premature infants; low-birth-weight infants; parenteral nutrition; neonatology; neonatal care ID TYROSINE METABOLISM; PHENYLALANINE; NUTRITION; PREMATURE; MIXTURE; PATTERN; PROTEIN; GROWTH AB Background: Glutamine is one of the most abundant amino acids in both plasma and human milk and may be conditionally essential in premature infants. However, glutamine is not provided by standard intravenous amino acid solutions. Objective: We assessed the effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants receiving parenteral nutrition (PN). Design: A total of 141 infants with birth weights of 401-1000 g were randomly assigned to receive a standard intravenous amino acid solution that did not contain glutamine or an isonitrogenous amino acid solution with 20% of the total amino acids as glutamine. Blood samples were obtained just before initiation of study PN and again after the infants had received study PN (mean intake: 2.3 +/- 1.0 g amino acids . kg(-1) . d(-1)) for approximate to 10 d. Results: Infants randomly assigned to receive glutamine had mean plasma glutamine concentrations that increased significantly and were approximate to 30% higher than those in the control group in response to PN (425 +/- 182 and 332 +/- 148 mumol/L for the glutamine and control groups, respectively). There was no significant difference between the 2 groups in the relative change in plasma glutamate concentration between the baseline and PN samples. In both groups, there were significant decreases in plasma phenylalanine and tyrosine between the baseline and PN samples; the decrease in tyrosine was greater in the group that received glutamine. Conclusions: In extremely low-birth-weight infants, parenteral glutamine supplementation can increase plasma glutamine concentrations without apparent biochemical risk. Currently available amino acid solutions are likely to be suboptimal in their supply of phenylalanine, tyrosine, or both for these infants. C1 Indiana Univ, Indianapolis, IN 46204 USA. Yale Univ, New Haven, CT USA. Emory Univ, Atlanta, GA 30322 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NICHHD, Bethesda, MD 20892 USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ Miami, Coral Gables, FL 33124 USA. Univ Alabama, Birmingham, AL USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Tennessee, Memphis, TN USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Wayne State Univ, Detroit, MI USA. Stanford Univ, Stanford, CA 94305 USA. Univ Texas, Houston, TX USA. RP Poindexter, BB (reprint author), James Whitcomb Riley Hosp Children, 699 W Dr RR 208, Indianapolis, IN 46202 USA. FU NCRR NIH HHS [M01 RR 08084, M01 RR 00997, M01 RR 00070, M01 RR 00750, M01 RR 06022]; NICHD NIH HHS [U10 HD27881, U10 HD27856, U10 HD21364, U10 HD27871, U10 HD27853, U10 HD27880, U10 HD21397, U10 HD27904, U10 HD34216, U10 HD40689, U10 HD21415, U10 HD36790, HD 19089, U10 HD21385, U10 HD27851, U10 HD21373] NR 23 TC 36 Z9 43 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 2003 VL 77 IS 3 BP 737 EP 743 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 649LT UT WOS:000181210600034 PM 12600870 ER PT J AU Butler, LM Sinha, R Millikan, RC Martin, CF Newman, B Gammon, MD Ammerman, AS Sandler, RS AF Butler, LM Sinha, R Millikan, RC Martin, CF Newman, B Gammon, MD Ammerman, AS Sandler, RS TI Heterocyclic amines, meat intake, and association with colon cancer in a population-based study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE amines; case-control studies; colorectal neoplasms; meat; polycyclic hydrocarbons; aromatic ID POLYCYCLIC AROMATIC-HYDROCARBONS; N-NITROSO COMPOUNDS; FRIED BEEF PATTIES; COLORECTAL-CANCER; RED MEAT; PROSPECTIVE COHORT; DIETARY FIBER; UNITED-STATES; VARYING DEGREES; BREAST-CANCER AB The authors examined the association between colon cancer and meat intake categorized by level of doneness, cooking method, and estimated levels of heterocyclic amines (HCAs), benzo[a]pyrene, and mutagenicity. Data were collected as part of a population-based, case-control study of colon cancer in North Carolina between 1996 and 2000 that included 701 African-American (274 cases, 427 controls) and 957 White (346 cases, 611 controls) participants. Odds ratios were calculated by using unconditional logistic regression, comparing the fifth to the first quintile levels of intake or exposure. Intake of red meat was positively associated with colon cancer (odds ratio (OR)=2.0, 95% confidence interval (CI): 1.3, 3.2). Associations with meat intake by cooking method were strongest for pan-fried red meat (OR=2.0, 95% CI: 1.4, 3.0). Associations with meat intake by doneness were strongest for well-/very well done red meat (OR=1.7, 95% CI: 1.2, 2.5). The strongest association for individual HCAs was reported for 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) across all levels of exposure, with odds ratios of 1.8-2.0. Overall, sophisticated exposure measures were used to report modest, positive associations between red meat intake and colon cancer consistent with the hypothesis that HCAs may be among the etiologically relevant compounds in red meat. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Queensland Univ Technol, Sch Publ Hlth, Brisbane, Qld, Australia. Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. RP Butler, LM (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [R01-CA 66635]; NIDDK NIH HHS [P30 DK 34987, T32-DK07634] NR 72 TC 124 Z9 127 U1 1 U2 5 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 MAR 1 PY 2003 VL 157 IS 5 BP 434 EP 445 DI 10.1093/aje/kwf221 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 652ZN UT WOS:000181410900007 PM 12615608 ER PT J AU Li, DK Petitti, DB Willinger, M McMahon, R Odouli, R Vu, H Hoffman, HJ AF Li, DK Petitti, DB Willinger, M McMahon, R Odouli, R Vu, H Hoffman, HJ TI Infant sleeping position and the risk of sudden infant death syndrome in California, 1997-2000 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; infant; sleep; sudden infant death ID SUPINE SLEEP; PRONE; SIDS; HEALTH AB To assess the association between infant sleeping position and risk of sudden infant death syndrome (SIDS) in an ethnically diverse US population, the authors conducted a population-based case-control study in 11 counties in California from May 1997 through April 2000. The authors conducted in-person interviews with the mothers of 185 SIDS cases and 312 randomly selected race/ethnicity- and age-matched controls to collect information on sleeping positions. Infants who had last been put down to sleep in the prone or side position were at greater risk of SIDS than were infants who had last been put down on their backs (adjusted odds ratio (AOR)=2.6 (95% confidence interval (CI): 1.5, 4.5) and AOR=2.0 (95% CI: 1.2, 3.4) for the prone and side positions, respectively). The risk of SIDS was especially high for an unstable side position in which an infant was placed on its side and found prone (AOR=8.7, 95% CI: 3.3, 22.7). Infants who were usually placed on their backs to sleep but had last been put down in the prone or side position (an unaccustomed position) had a significantly high risk of SIDS (AOR=8.2 (95% CI: 2.6, 26.0) and AOR=6.9 (95% CI: 2.3, 20.6) for the prone and side positions, respectively). Infants placed in an unaccustomed prone or side sleeping position had a higher risk of SIDS than infants who were always placed prone or on the side. C1 Kaiser Permanente, Kaiser Fdn Res Inst, Div Res, Oakland, CA 94612 USA. Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. NICHHD, Pregnancy & Perinatol Branch, Ctr Res Mothers & Children, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Epidemiol & Biostat Program, Bethesda, MD USA. RP Li, DK (reprint author), Kaiser Permanente, Kaiser Fdn Res Inst, Div Res, 2000 Broadway, Oakland, CA 94612 USA. FU NICHD NIH HHS [N01-HD-5-3227] NR 28 TC 51 Z9 54 U1 0 U2 2 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 MAR 1 PY 2003 VL 157 IS 5 BP 446 EP 455 DI 10.1093/aje/kwf226 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 652ZN UT WOS:000181410900008 PM 12615609 ER PT J AU Tayebi, N Stubblefield, BK Park, JK Orvisky, E Walker, JM LaMarca, ME Sidransky, E AF Tayebi, N Stubblefield, BK Park, JK Orvisky, E Walker, JM LaMarca, ME Sidransky, E TI Reciprocal and nonreciprocal recombination at the glucocerebrosidase gene region: Implications for complexity in Gaucher disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CONGENITAL ADRENAL-HYPERPLASIA; FUSION GENE; PHENOTYPIC VARIATION; HUNTER-SYNDROME; MUTANT ALLELES; HUMAN GENOME; CYP21 GENE; HOT-SPOTS; IDS GENE; MUTATION AB Gaucher disease results from an autosomal recessive deficiency of the lysosomal enzyme glucocerebrosidase. The glucocerebrosidase gene is located in a gene-rich region of 1q21 that contains six genes and two pseudogenes within 75 kb. The presence of contiguous, highly homologous pseudogenes for both glucocerebrosidase and metaxin at the locus increases the likelihood of DNA rearrangements in this region. These recombinations can complicate genotyping in patients with Gaucher disease and contribute to the difficulty in interpreting genotype-phenotype correlations in this disorder. In the present study, DNA samples from 240 patients with Gaucher disease were examined using several complementary approaches to identify and characterize recombinant alleles, including direct sequencing, long-template polymerase chain reaction, polymorphic microsatellite repeats, and Southern blots. Among the 480 alleles studied, 59 recombinant alleles were identified, including 34 gene conversions, 18 fusions, and 7 downstream duplications. Twenty-two percent of the patients evaluated had at least one recombinant allele. Twenty-six recombinant alleles were found among 310 alleles from patients with type 1 disease, 18 among 74 alleles from patients with type 2 disease, and 15 among 96 alleles from patients with type 3 disease. Several patients carried two recombinations or mutations on the same allele. Generally, alleles resulting from nonreciprocal recombination (gene conversion) could be distinguished from those arising by reciprocal recombination (crossover and exchange), and the length of the converted sequence was determined. Homozygosity for a recombinant allele was associated with early lethality. Ten different sites of crossover and a shared pentamer motif sequence (CACCA) that could be a hotspot for recombination were identified. These findings contribute to a better understanding of genotype-phenotype relationships in Gaucher disease and may provide insights into the mechanisms of DNA rearrangement in other disorders. C1 NIMH, Clin Neurosci Branch, Sect Mol Neurogenet, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NIMH, Clin Neurosci Branch, Sect Mol Neurogenet, NIH, 49 Convent Dr MSC4405,49-B1EE16, Bethesda, MD 20892 USA. NR 78 TC 47 Z9 50 U1 0 U2 0 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 MAR PY 2003 VL 72 IS 3 BP 519 EP 534 DI 10.1086/367850 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 648LJ UT WOS:000181152600002 PM 12587096 ER PT J AU Sharabi, Y Scope, A Chorney, N Grotto, I Dagan, Y AF Sharabi, Y Scope, A Chorney, N Grotto, I Dagan, Y TI Diastolic blood pressure is the first to rise in association with early subclinical obstructive sleep apnea: Lessons from periodic examination screening SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE obstructive sleep apnea; blood pressure; screening; periodic examination ID HYPERTENSION; POPULATION; ADULTS; MEN AB Background: Obstructive sleep apnea syndrome (OSAS) is associated with long-term cardiovascular morbidity. Little is known about these relations at early stages. We conducted a case-control study in which we analyzed the clinical characteristics of young adults who underwent a periodic health examination and were screened for, and eventually found to experience, OSAS. Methods: We identified 121 subjects newly diagnosed in a sleep study as having OSAS, and 229 matched control subjects in which screening for OSAS was negative. All had a medical interview, physical examination, and routine laboratory tests. Results: Subjects who had OSAS had a higher, body mass index (3-kg/m(2) difference) and a higher diastolic blood pressure (4-mm Hg difference) value, without elevation in systolic blood pressure. There was no metabolic difference (lipids profile and fasting glucose levels) between groups. Conclusions: Diastolic blood pressure is higher early in the course of OSAS. Long term follow-up may determine effects of prevention and early intervention in OSAS and associated hypertension. (C) 2003 American Journal of Hypertension, Ltd. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Chaim Sheba Med Ctr, Period Examinat Ctr, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Sleep Disturbances Inst, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Israel Def Forces Med Corps, IL-52621 Tel Hashomer, Israel. RP Sharabi, Y (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr,Bldg 10,6N252, Bethesda, MD 20892 USA. RI Grotto, Itamar/F-2028-2012 NR 27 TC 30 Z9 44 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAR PY 2003 VL 16 IS 3 BP 236 EP 239 AR PII S0895-7061(02)03250-8 DI 10.1016/S0895-7061(02)03250-8 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 652KD UT WOS:000181377600011 PM 12620704 ER PT J AU Mikhelashvili-Browner, N Yousem, DM Wu, C Kraut, MA Vaughan, CL Oguz, KK Calhoun, VD AF Mikhelashvili-Browner, N Yousem, DM Wu, C Kraut, MA Vaughan, CL Oguz, KK Calhoun, VD TI Lack of sex effect on brain activity during a visuomotor response task: Functional MR imaging study SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CEREBRAL GLUCOSE-METABOLISM; REACTION-TIME; BLOOD-FLOW; MOTOR; STIMULATION; AGE; CORTEX AB BACKGROUND AND PURPOSE: As more individuals are enrolled in clinical functional MR imaging (fMRI) studies, an understanding of how sex may influence fMRI-measured brain activation is critical. METHODS: We used fixed- and random-effects models to study the influence of sex on fMRI patterns of brain activation during a simple visuomotor reaction time task in the group of 26 age-matched men and women. We evaluated the right visual, left visual, left primary motor, left supplementary motor, and left anterior cingulate areas. RESULTS: Volumes of activations did not significantly differ between the groups in any defined regions. Analysis of variance failed to show any significant correlations between sex and volumes of brain activation in any location studied. Mean percentage signal-intensity changes for all locations were similar between men and women. A two-way t test of brain activation in men and women, performed as a part of random-effects modeling, showed no significant difference at any site. CONCLUSION: Our results suggest that sex seems to have little influence on fMRI brain activation when we compared performance on the simple reaction-time task. The need to control for sex effects is not critical in the analysis of this task with fMRI. C1 Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol & Radiol Sci, Div Neuroradiol, Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA. Div Psychiat Neuroimaging, Baltimore, MD USA. NHLBI, Off Biostat Res, DECA, Bethesda, MD 20892 USA. Hacettepe Univ, Sch Med, Dept Radiol, Ankara, Turkey. RP Yousem, DM (reprint author), Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol & Radiol Sci, Div Neuroradiol, Dept Radiol & Radiol Sci, 600 N Wolfe St,Phipps B-112, Baltimore, MD 21205 USA. NR 28 TC 6 Z9 7 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2003 VL 24 IS 3 BP 488 EP 494 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 658WR UT WOS:000181744500034 PM 12637302 ER PT J AU Altekruse, SF Lacey, JV Brinton, LA Gravitt, PE Silverberg, SG Barnes, WA Greenberg, MD Hadjimichael, OC McGowan, L Mortel, R Schwartz, PE Hildesheim, A AF Altekruse, SF Lacey, JV Brinton, LA Gravitt, PE Silverberg, SG Barnes, WA Greenberg, MD Hadjimichael, OC McGowan, L Mortel, R Schwartz, PE Hildesheim, A TI Comparison of human papillomavirus genotypes, sexual, and reproductive risk factors of cervical adenocarcinoma and squamous cell carcinoma: Northeastern United States SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervical carcinoma; human papillomavirus; cervical adenocarcinoma; reproductive history ID UTERINE CERVIX; ENDOMETRIAL CANCER; RELIABILITY; SMOKING AB OBJECTIVE: Although human papillomavirus causes essentially all cervical carcinoma, cofactors may differ by cancer histologic type. We examined human papillomavirus genotypes and sexual and reproductive risk factors for cervical adenocarcinoma and squamous cell carcinoma. STUDY DESIGN: One hundred twenty-four women with adenocarcinoma, 139 women with squamous cell carcinoma, and 307 control subjects participated in this case-control study. Logistic regression analyses were performed to calculate odds ratios and Cls. RESULTS: Human papillomavirus 18 was associated most strongly with adenocarcinoma (odds ratio, 105; 95% Cl, 23-487). Human papillomavirus 16 was associated most strongly with squamous cell carcinoma (odds ratio, 30; 95% Cl, 12-77). More than three lifetime sexual partners was a risk factor for adenocarcinoma (odds ratio, 2.1; 95% Cl, 1.1-4.0) and squamous cell carcinoma (odds ratio, 3.0; 95% Cl, 1.6-5.9). Even being pregnant was associated inversely with adenocarcinoma (odds ratio, 0.4; 95% Cl, 0.2-0.8). Five or more pregnancies was associated with squamous cell carcinoma (odds ratio, 2.2; 95% Cl, 0.9-5.4). CONCLUSION: The relative importance of human papillomavirus genotypes 16 and 18 and the reproductive co-factor differences suggest distinct causes for cervical adenocarcinoma and squamous cell carcinoma. C1 NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Maryland, Dept Anat Pathol, Baltimore, MD 21201 USA. Georgetown Univ, Lombardi Canc Ctr, Washington, DC 20057 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. George Washington Univ, Div Gynecol Oncol, Washington, DC 20052 USA. Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. Univ Penn, Grad Hosp, Philadelphia, PA 19104 USA. RP Altekruse, SF (reprint author), NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA. EM altekrus@mail.nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 25 TC 54 Z9 64 U1 0 U2 2 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 MAR PY 2003 VL 188 IS 3 BP 657 EP 663 DI 10.1067/mob.2003.132 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 658XH UT WOS:000181746000010 PM 12634637 ER PT J AU Bytautiene, E Vedernikov, YP Saade, GR Romero, R Garfield, RE AF Bytautiene, E Vedernikov, YP Saade, GR Romero, R Garfield, RE TI Effect of histamine on phasic and tonic contractions of isolated uterine tissue from pregnant women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE histamine; histamine receptors; human myometrium; contractility; pregnancy ID ISOLATED MYOMETRIAL STRIPS; PROTEIN-KINASE-C; SMOOTH-MUSCLE; GUINEA-PIG; MAST-CELLS; RECEPTORS; MEDIATORS; OXYTOCIN; UTERUS AB OBJECTIVE: To enhance our understanding of the uterotonic effect of histamine, we compared the effects of histamine on spontaneous phasic and tonic contractile activity of uterine strips from term pregnant nonlaboring women. STUDY DESIGN: Longitudinal uterine strips were used from the lower uterine segment of term pregnant nonlaboring women undergoing elective cesarean. section. The concentration-response relationship to histamine (10(-8) to 10(-4) mol/L) was determined in spontaneously contracting strips or in strips contracted tonically witha protein kinase C activator (-)-indolactam V in the presence of H-1 receptor antagonist (S[+]-chlorpheniramine maleate), H-2 receptor antagonist (cimetidine), or solvent. RESULTS: Histamine increased spontaneous phasic myometrial contractions in a concentration-dependent manner. H-1, but not H-2, receptor antagonist significantly attenuated the response to histamine. Histamine significantly reduced tonic contractions of uterine strips induced by indolactam V. H histamine receptor antagonist abolished relaxation, whereas H-2 histamine receptor antagonist had no effect. CONCLUSION: Histamine increases spontaneous, but inhibits tonic, contractions of uterine strips from term pregnant nonlaboring women. Both effects are mediated through activation of H-1 receptors. C1 Univ Texas, Med Branch, Dept Obstet & Gynecol, Div Reprod Sci, Galveston, TX 77555 USA. NICHHD, Perinatol Res Branch, Bethesda, MD USA. RP Garfield, RE (reprint author), Univ Texas, Med Branch, Dept Obstet & Gynecol, Div Reprod Sci, 301 Univ Blvd,Rt J-62, Galveston, TX 77555 USA. EM rgarfiel@utmb.edu NR 26 TC 15 Z9 16 U1 0 U2 1 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 MAR PY 2003 VL 188 IS 3 BP 774 EP 778 DI 10.1067/mob.2003.162 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 658XH UT WOS:000181746000030 PM 12634656 ER PT J AU Hauth, JC MacPherson, C Carey, JC Klebanoff, MA Hillier, SL Ernest, JM Leveno, KJ Wapner, R Varner, M Trout, W Moawad, A Sibai, B AF Hauth, JC MacPherson, C Carey, JC Klebanoff, MA Hillier, SL Ernest, JM Leveno, KJ Wapner, R Varner, M Trout, W Moawad, A Sibai, B CA Natl Inst Child Hlth Human Dev Net TI Early pregnancy threshold vaginal pH and Gram stain scores. predictive of subsequent preterm birth in asymptomatic women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE early pregnancy vaginal pH/Gram stain; preterm birth ID BACTERIAL VAGINOSIS; INTRAAMNIOTIC INFECTION; CONTROLLED TRIAL; FLORA PATTERNS; METRONIDAZOLE; DELIVERY AB OBJECTIVE: The study was undertaken to identify early pregnancy vaginal markers predictive of subsequent preterm birth. STUDY DESIGN: In a multicenter Bacterial Vaginosis (BV) Trial, 21,554 women were screened with a vaginal pH and of these, two Populations were studied. These included 12,041 who had a pregnancy outcome in the database and 6838 women who had a vaginal pH of 4.5 or greater and a Gram stain score and a pregnancy outcome in the database. ColorpHast Indicator Strips were used to determine the vaginal pH and the Nugent criteria were used to determine a vaginal Gram stain score of 0 to 10. RESULTS: Delivery at <37, <35, or <32 weeks' gestation was similar for women with a vaginal pH of less than 4.4 or 4.7 (P not significant) but was increased in women with a pH of 5.0 (P =.04,.02,.03, respectively) or with a pH of 5.0 or greater (at each gestational age P < .0001). The effect of pH of 5.0 or greater was similar for women who had a spontaneous preterm birth at each gestational age (P < .0001) or birth weight of less than 2500 g or less than 1500 g (P < .0005.). Women with a vaginal pH of 4.5 or greater and a Gram stain score of 9 to 10 (compared with 0-8) had increased preterm births at <37, <35, and <32 weeks' gestation (P < .01), and birth weights less than 2500 g (P < .0001) or less than 1500 g (P < .01). Women whose vaginal pH was 5.0 or greater had a higher prevalence of vaginal fetal fibronectin 50 ng/mL (P < .0001), but the proportion of women with a vaginal fetal fibronectin 50 mg/mL did not differ by Gram stain score. CONCLUSION: Women with a vaginal pH of 5.0 or greater or a vaginal pH of 4.5 or greater and a Gram stain score of, 9 to 10 had significantly increased preterm births at <37, <35, and 32 weeks' gestation and/or a birth weight less than 2500 g or less than 1500g. C1 Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35249 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Univ Oklahoma, Dept Obstet & Gynecol, Oklahoma City, OK USA. NICHHD, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. Wake Forest Univ, Sch Med, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75235 USA. Thomas Jefferson Univ, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT 84112 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. RP Hauth, JC (reprint author), Univ Alabama, Dept Obstet & Gynecol, 619 19th St S,560 OHB, Birmingham, AL 35249 USA. RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU NIAID NIH HHS [AI 38514]; NICHD NIH HHS [U10 HD21410, U01 HD36801, U10 HD 27905, U10 HD 27917, U10 HD21414, U10 HD27860, U10 HD27861, U10 HD27869, U10 HD27883, U10 HD27889, U10 HD27915, U10 HD34116, U10 HD34122, U10 HD34136, U10 HD34208, U10 HD34210] NR 18 TC 47 Z9 47 U1 0 U2 1 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 MAR PY 2003 VL 188 IS 3 BP 831 EP 835 DI 10.1067/mob.2003.184 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 658XH UT WOS:000181746000040 PM 12634666 ER PT J AU Watts, DH Brown, ZA Money, D Selke, S Huang, ML Sacks, SL Corey, L AF Watts, DH Brown, ZA Money, D Selke, S Huang, ML Sacks, SL Corey, L TI A double-blind, randomized, placebo-controlled trial of acyclovir in late pregnancy for the reduction of herpes simplex virus shedding and cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE genital herpes; acyclovir; pregnancy ID POLYMERASE CHAIN-REACTION; RECURRENT GENITAL HERPES; INFECTION; TYPE-2; WOMEN; EXPOSURE; SUPPRESSION; TIME; DNA AB OBJECTIVE: The purpose of this study was to assess the efficacy of acyclovir in the reduction of herpes simplex virus culture and polymerase chain reaction positivity and cesarean delivery. STUDY DESIGN: Women with recurrent genital herpes simplex virus Were randomized to acyclovir 400 mg three times daily or placebo from 36 weeks of gestation until delivery. A subset of daily specimens for herpes simplex virus culture and DNA polymerase chain reaction was self-collected. Analyses used chi(2), Fisher exact, and Mann-Whitney U tests. RESULTS: Lesions occurred at delivery among 11 of 78 women (14%) who received placebo and 4 of 84 women (5%) who received acyclovir (P = .08). Herpes simplex virus culture and polymerase chain reaction positivity near delivery occurred in 7% and 34% women in the placebo group and 0 and 2% in the acyclovir group (P = .03 and < .01, respectively). Cesarean delivery for herpes simplex virus occurred in 8 of the women (10%) in the placebo group and in 3 of the women (4%) in the acyclovir group (P = .17). Despite reductions in herpes simplex virus detection, 6% of the women who received acyclovir had herpes simplex virus detected by polymerase chain reaction on >20% of days. Neonatal outcomes were similar between groups. CONCLUSION: Acyclovir significantly reduced, but did not eliminate, herpes simplex virus lesions and detection in late pregnancy. C1 Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Pharmacol & Therapeut, Vancouver, BC V5Z 1M9, Canada. Fred Hutchinson Canc Res Ctr, Viridae Clin Sci, Vancouver, BC, Canada. Fred Hutchinson Canc Res Ctr, Program Infect Dis, Vancouver, BC, Canada. RP Watts, DH (reprint author), NICHD, CRMC, Pediat Adolescent & Maternal AIDS Branch, NIH, 6100 Execut Blvd,Room 4B11, Bethesda, MD 20892 USA. FU NIAID NIH HHS [P01-AI30731] NR 25 TC 62 Z9 66 U1 0 U2 2 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 MAR PY 2003 VL 188 IS 3 BP 836 EP 843 DI 10.1067/mob.2003.185 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 658XH UT WOS:000181746000041 PM 12634667 ER PT J AU Jampol, LM Becker, KG AF Jampol, LM Becker, KG TI White spot syndromes of the retina: A hypothesis based on the common genetic hypothesis of autoimmune/inflammatory disease SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID OCCULT OUTER RETINOPATHY; PLACOID PIGMENT EPITHELIOPATHY; HEPATITIS-B VACCINE; MULTIFOCAL CHOROIDITIS; DOT SYNDROME; CHOROIDOPATHY; ENLARGEMENT; PANUVEITIS; LESIONS; AZOOR C1 Northwestern Univ, Dept Ophthalmol, Feinberg Sch Med, Chicago, IL 60611 USA. NIA, NIH, Baltimore, MD 21224 USA. RP Jampol, LM (reprint author), 645 N Michigan Ave,Ste 440, Chicago, IL 60611 USA. OI Becker, Kevin/0000-0002-6794-6656 NR 26 TC 48 Z9 55 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2003 VL 135 IS 3 BP 376 EP 379 AR PII S0002-9394(02)02088-3 DI 10.1016/S0002-9394(02)02088-3 PG 4 WC Ophthalmology SC Ophthalmology GA 650HT UT WOS:000181258100017 PM 12614757 ER PT J AU Bondjers, C Kalen, M Hellstrom, M Scheidl, SJ Abramsson, A Renner, O Lindahl, P Cho, HS Kehrl, J Betsholtz, C AF Bondjers, C Kalen, M Hellstrom, M Scheidl, SJ Abramsson, A Renner, O Lindahl, P Cho, HS Kehrl, J Betsholtz, C TI Transcription profiling of platelet-derived growth factor-B-deficient mouse embryos identifies RGS5 as a novel marker for pericytes and vascular smooth muscle cells SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PDGF BETA-RECEPTOR; MICE; ANGIOGENESIS; EXPRESSION; PROTEIN; ALVEOGENESIS; ABLATION; DEFECTS; GENE AB All blood capillaries consist of endothelial tubes surrounded by mural cells referred to as pericytes. The origin, recruitment, and function of the pericytes is poorly understood, but the importance of these cells is underscored by the severe cardiovascular defects in mice genetically devoid of factors regulating pericyte recruitment to embryonic vessels, and by the association between pericyte loss and microangiopathy in diabetes mellitus. A general problem in the study of pericytes is the shortage of markers for these cells. To identify new markers for pericytes, we have taken advantage of the platelet-derived growth factor (PDGF)-B knockout mouse model, in which developing blood vessels in the central nervous system are almost completely devoid of pericytes. Using cDNA microarrays, we analyzed the gene expression in PDGF-B null embryos in comparison with corresponding wild-type embryos and searched for downregulated genes. The most down-regulated gene present on our microarray was RGS5, a member of the RGS family of GTPase-activating proteins for G proteins. In situ hybridization identified RGS5 expression in brain pericytes, and in pericytes and vascular smooth muscle cells in certain other, but not all, locations. Absence of RGS5 expression in PDGF-B and PDGFRbeta-null embryos correlated with pericyte loss in these mice. Residual RGS5 expression in rare pericytes suggested that RGS5 is a pericyte marker expressed independently of PDGF-B/Rbeta signaling. With RGS5 as a proof-of-principle, our data demonstrate the usefulness of microarray analysis of mouse models for abnormal pericyte development in the identification of new pericyte-specific markers. C1 Univ Gothenburg, Sahlgrenska Acad, Dept Biochem Med, SE-40530 Gothenburg, Sweden. AngioGenet AB, Gothenburg, Sweden. Ctr Nacl Invest Oncol, Dept Expt Therapeut, Madrid, Spain. NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Betsholtz, C (reprint author), Univ Gothenburg, Sahlgrenska Acad, Dept Biochem Med, POB 440, SE-40530 Gothenburg, Sweden. RI Renner, Oliver/M-7002-2015; OI Renner, Oliver/0000-0002-4046-0517; Kehrl, John/0000-0002-6526-159X NR 35 TC 104 Z9 109 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 MAR PY 2003 VL 162 IS 3 BP 721 EP 729 DI 10.1016/S0002-9440(10)63868-0 PG 9 WC Pathology SC Pathology GA 649NN UT WOS:000181215000004 PM 12598306 ER PT J AU Barbieri, M Ferrucci, L Ragno, E Corsi, A Bandinelli, S Bonafe, M Olivieri, F Giovagnetti, S Franceschi, C Guralnik, JM Paolisso, G AF Barbieri, M Ferrucci, L Ragno, E Corsi, A Bandinelli, S Bonafe, M Olivieri, F Giovagnetti, S Franceschi, C Guralnik, JM Paolisso, G TI Chronic inflammation and the effect of IGF-I on muscle strength and power in older persons SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE muscle function; disability; aging; InCHIANTI Study; insulin-like growth factor I ID GROWTH-FACTOR-I; HOMEOSTASIS MODEL ASSESSMENT; SKELETAL-MUSCLE; INTERLEUKIN-6; IL-6; ASSOCIATION; DISABILITY; AGE; MOBILITY; GLUCOSE AB Deregulation of the inflammatory response plays a major role in the age-related decline of physical performance. The causal pathway leading from inflammation to disability has not been fully clarified, but several researches suggest that interleukin-6 (IL-6) causes a reduction of physical performance in elderly through its effect on muscle function. In vitro studies demonstrated that IL-6 inhibits the secretion of insulin-like growth factor I (IGF-1) and its biological activity, suggesting that the negative effect of IL-6 on muscle function might be mediated through IGF-I. We evaluated the joint effect of IGF-I and IL-6 on muscle function in a population-based sample of 526 persons with a wide age range (20-102 yr). After adjusting for potential confounders, such as age, sex, body mass index, IL-6 receptor, and IL-6 promoter polymorphism, IL-6, IGF-I, and their interaction were significant predictors of handgrip and muscle power. In analyses stratified by IL-6 tertiles, IGF-I was an independent predictor of muscle function only in subjects in the lowest IL-6 tertile, suggesting that the effect of IGF-I on muscle function depends on IL-6 levels. This mechanism may explain why IL-6 is a strong risk factor for disability. C1 Univ Naples 2, Dept Geriatr Med & Metab Dis, Div Med Interna 4, I-80138 Naples, Italy. Italian Natl Res Council, Aging Geriatr Dept, Lab Clin Epidemiol, I-50125 Florence, Italy. Univ Bologna, Dept Expt Pathol, I-40126 Bologna, Italy. Italian Natl Res Ctr Aging, I-60100 Ancona, Italy. NIA, Epidemiol Demog & Biometry Lab, Bethesda, MD 20814 USA. RP Paolisso, G (reprint author), Univ Naples 2, Dept Geriatr Med & Metab Dis, Div Med Interna 4, Piazza Miraglia 2, I-80138 Naples, Italy. RI Barbieri, Michelangela/K-2192-2016; Olivieri, Fabiola/K-6465-2016 OI Barbieri, Michelangela/0000-0002-9223-5792; Olivieri, Fabiola/0000-0002-9606-1144 NR 29 TC 142 Z9 147 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAR PY 2003 VL 284 IS 3 BP E481 EP E487 DI 10.1152/ajpendo.00319.2002 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 645RW UT WOS:000180993600004 PM 12419777 ER PT J AU Knepper, MA Saidel, GM Hascall, VC Dwyer, T AF Knepper, MA Saidel, GM Hascall, VC Dwyer, T TI Concentration of solutes in the renal inner medulla: interstitial hyaluronan as a mechano-osmotic transducer SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Review DE glycosaminoglycans; renal pelvis; vasopressin; hyaluronan ID THIN ASCENDING LIMB; COUNTERCURRENT MULTIPLICATION SYSTEM; CELL CHIP28 PROTEIN; COLLECTING DUCT; WATER TRANSPORT; COUNTERFLOW SYSTEM; SODIUM-CHLORIDE; HENLES LOOP; QUANTITATIVE-ANALYSIS; MATHEMATICAL-MODEL AB Although the concentrating process in the renal outer medulla is well understood, the concentrating mechanism in the renal inner medulla remains an enigma. The purposes of this review are fourfold. 1) We summarize a theoretical basis for classifying all possible steady-state inner medullary countercurrent concentrating mechanisms based on mass balance principles. 2) We review the major hypotheses that have been proposed to explain the axial osmolality gradient in the interstitium of the renal inner medulla. 3) We summarize and expand on the Schmidt-Nielsen hypothesis that the contractions of the renal pelvocalyceal wall may provide an important energy source for concentration in the inner medulla. 4) We discuss the special properties of hyaluronan, a glycosaminoglycan that is the chief component of a gel-like renal inner medullary interstitial matrix, which may allow it to function as a mechano-osmotic transducer, converting energy from the contractions of the pelvic wall to an axial osmolality gradient in the medulla. These considerations set the stage for renewed experimental investigation of the urinary concentrating process and a new generation of mathematical models of the renal concentrating mechanism, which treat the inner medullary interstitium as a viscoelastic system rather than a purely hydraulic system. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 43560 USA. Cleveland Clin Fdn, Dept Biomed Engn, Cleveland, OH 44195 USA. Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [HL-51971, Z01-HL-01282-KE] NR 95 TC 73 Z9 74 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 2003 VL 284 IS 3 BP F433 EP F446 DI 10.1152/ajprenal.00067.2002 PG 14 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 640JZ UT WOS:000180686900002 PM 12556362 ER PT J AU Leibenluft, E Charney, DS Towbin, KE Bhangoo, RK Pine, DS AF Leibenluft, E Charney, DS Towbin, KE Bhangoo, RK Pine, DS TI Defining clinical phenotypes of juvenile mania SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID EARLY ADOLESCENT BIPOLARITY; PREPUBERTAL CHILDREN; DIAGNOSTIC CRITERIA; AFFECTIVE-ILLNESS; DISORDER; SYMPTOMS; ADHD; RELIABILITY; SCHIZOPHRENIA; COMORBIDITY AB Objective: The authors suggest criteria for a range of narrow to broad phenotypes of bipolar disorder in children; differentiated according to the characteristics of the manic or hypomanic episodes, and present methods for validation of the criteria. Method: Relevant literature describing bipolar disorder in both children and adults was reviewed critically, and the input of experts was sought. Results: Areas of controversy include whether the diagnosis of bipolar disorder should require clearly demarcated affective episodes and, if so, of what duration, and whether specific hallmark symptoms of mania should be required for the diagnosis. The authors suggest a phenotypic system of juvenile mania consisting of a narrow phenotype, two intermediate phenotypes, and a broad phenotype. The narrow phenotype is exhibited by patients who meet the full DSM-IV diagnostic criteria for hypomania or mania, including the duration criterion, and also have hallmark symptoms of elevated mood or grandiosity. The intermediate phenotypes include 1) hypomania or mania not otherwise specified, in which the patient has clear episodes and hallmark symptoms, but the episodes are between 1 and 3 days in duration, and 2) irritable hypomania or mania, in which the patient has demarcated episodes with irritable, but not elevated, mood. The broad phenotype is exhibited by patients who have a chronic, nonepisodic illness that does not include the hallmark symptoms of mania but shares with the narrower phenotypes the symptoms of severe irritability and hyperarousal. Conclusions: The presence of distinct episodes and hallmark symptoms can be used to differentiate clinical phenotypes of juvenile mania. The utility and validity of this system can be tested in subsequent research. C1 NIMH, Mood & Anxiety Program, Bethesda, MD USA. RP Leibenluft, E (reprint author), 10 Ctr Dr,MSC 1255, Bethesda, MD 20892 USA. NR 43 TC 402 Z9 409 U1 1 U2 8 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2003 VL 160 IS 3 BP 430 EP 437 DI 10.1176/appi.ajp.160.3.430 PG 8 WC Psychiatry SC Psychiatry GA 655MX UT WOS:000181557600002 PM 12611821 ER PT J AU Bertolino, A Sciota, D Brudaglio, F Altamura, M Blasi, G Bellomo, A Antonucci, N Callicott, JH Goldberg, TE Scarabino, T Weinberger, DR Nardini, M AF Bertolino, A Sciota, D Brudaglio, F Altamura, M Blasi, G Bellomo, A Antonucci, N Callicott, JH Goldberg, TE Scarabino, T Weinberger, DR Nardini, M TI Working in memory deficits and levels of N-acetylaspartate patients with schizophreniform disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; DORSOLATERAL PREFRONTAL CORTEX; PROTON MR SPECTROSCOPY; NORMAL HUMAN BRAIN; ACETYL ASPARTATE; IN-VIVO; BIOCHEMICAL MARKERS; NEURONAL LOSS; FRONTAL-LOBE; WHITE-MATTER AB Objective: The authors used proton magnetic resonance spectroscopic imaging (H-1-MRSI) to assess potential reductions of N-acetylaspartate (a marker of neuronal integrity) in the hippocampal area and dorsolateral prefrontal cortex of patients with schizophreniform disorder. In addition, they assessed the relationship between N-acetylaspartate levels and working memory deficits. Method: Twenty-four patients with DSM-IV schizophreniform disorder and 24 healthy subjects were studied. Subjects underwent H-1-MRSI and were given the N-back working memory test. Results: The schizophreniform disorder patients had selective reductions of N-acetylaspartate ratios in the hippocampal area and the dorsolateral prefrontal cortex, and a positive correlation was seen between N-acetylaspartate ratios in the dorsolateral prefrontal cortex and performance during the 2-back working memory condition. Conclusions: Similar to findings reported in schizophrenia studies, N-acetylaspartate reductions in the hippocampal area and the dorsolateral prefrontal cortex were seen in patients with schizophreniform disorder. Moreover, the results support other evidence that neuronal pathology in the dorsolateral prefrontal cortex accounts for a proportion of working memory deficits already present at illness outset. C1 Univ Bari, Dipartimento Sci Neurol & Psichiat, Grp Neurosci Psichiat, Sezione Clin Malattie Mentali, I-70124 Bari, Italy. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. IRCCSS Casa Sollievo Sofferenza, Dept Neuroradiol, San Giovanni Rotondo, Italy. RP Bertolino, A (reprint author), Univ Bari, Dipartimento Sci Neurol & Psichiat, Grp Neurosci Psichiat, Sezione Clin Malattie Mentali, Giulio Cesare 9, I-70124 Bari, Italy. RI Callicott, Joseph/C-9102-2009; Bertolino, Alessandro/O-6352-2016 OI Callicott, Joseph/0000-0003-1298-3334; Bertolino, Alessandro/0000-0002-1251-1380 NR 36 TC 55 Z9 59 U1 1 U2 8 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2003 VL 160 IS 3 BP 483 EP 489 DI 10.1176/appi.ajp.160.3.483 PG 7 WC Psychiatry SC Psychiatry GA 655MX UT WOS:000181557600010 PM 12611829 ER PT J AU Nicolson, R Brookner, FB Lenane, M Gochman, P Ingraham, LJ Egan, MF Kendler, KS Pickar, D Weinberger, DR Rapoport, JL AF Nicolson, R Brookner, FB Lenane, M Gochman, P Ingraham, LJ Egan, MF Kendler, KS Pickar, D Weinberger, DR Rapoport, JL TI Parental schizophrenia spectrum disorders in childhood-onset and adult-onset schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 11-13, 2000 CL CHICAGO, ILLINOIS SP Soc Biol Psychiat ID ROSCOMMON FAMILY; PERSONALITY-DISORDERS; AGE; RELATIVES; SIBLINGS; RISK; CHILDREN AB Objective: Childhood onset of "adult" psychiatric disorders may be caused, in part, by more salient genetic risk. In this study, the rates of schizophrenia spectrum disorders among parents of patients with childhood-onset and adult-onset schizophrenia and parents of community comparison subjects were compared. Method: To assess the presence of axis I and axis 11 disorders associated with schizophrenia, parents of patients with childhood-onset schizophrenia (95 parents), patients with adult-onset schizophrenia (86 parents), and community comparison subjects (123 parents) were interviewed directly by using semistructured instruments. Information on 19 additional parents (parents of childhood-onset patients, N=2; parents of adult-onset patients, N=11; parents of community comparison subjects, N=6) was obtained by using a family history interview with the same instruments. Transcribed interviews were scored by a rater blind to group membership, and the morbid risks for schizophrenia spectrum disorders in the three groups were compared. Results: Parents of patients with childhood-onset schizophrenia had a significantly higher morbid risk of schizophrenia spectrum disorders (24.74%) than parents of patients with adult-onset schizophrenia (11.35%), and parents of both patient groups had a greater risk of schizophrenia spectrum disorders than did parents of comparison subjects (1.55%). Conclusions: Parents of patients with childhood-onset schizophrenia have a higher rate of schizophrenia spectrum disorders than parents of patients with adultonset illness. This is consistent with the hypothesis that a childhood onset of schizophrenia is due, at least in part, to a greater familial diathesis for the disorder. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. George Washington Univ, Dept Psychol, Washington, DC 20052 USA. Gabriel Pharma Inc, Rockville, MD USA. Virginia Commonwealth Univ Med Coll Virginia, Dept Psychiat, Richmond, VA USA. RP Rapoport, JL (reprint author), NIMH, Child Psychiat Branch, 3N202,10 Ctr Dr, Bethesda, MD 20892 USA. RI Nicolson, Robert/E-4797-2011 NR 28 TC 62 Z9 62 U1 1 U2 6 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2003 VL 160 IS 3 BP 490 EP 495 DI 10.1176/appi.ajp.160.3.490 PG 6 WC Psychiatry SC Psychiatry GA 655MX UT WOS:000181557600011 PM 12611830 ER PT J AU Vitiello, B Burnam, MA Bing, EG Beckman, R Shapiro, MF AF Vitiello, B Burnam, MA Bing, EG Beckman, R Shapiro, MF TI Use of psychotropic medications among HIV-infected patients in the United States SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NATIONAL PROBABILITY SAMPLES; PLACEBO-CONTROLLED TRIAL; LOW-PREVALENCE DISEASES; PRIMARY-CARE PHYSICIANS; QUALITY-OF-LIFE; ANTIDEPRESSANT TREATMENT; SERVICES UTILIZATION; DEPRESSIVE DISORDER; MENTAL-HEALTH; ADULTS AB Objective: This study describes the prevalence and pattern of use of psychotropic medications by HIV-positive patients receiving medical care in the United States and the search for possible predictors of use. Method: The HIV Cost and Services Utilization Study database was analyzed. From the estimated 231,400 HIV-positive patients in medical care in the contiguous United States, a probability sample of 2,864 adults who had paid at least one visit to their medical provider in early 1996 was selected. A representative group of 1,561 received the long form of the Composite International Diagnostic Interview and a questionnaire on psychotropic medications used during the previous 6 months; 1,489 patients (95.4%) completed the assessments. Results: An estimated 27.2% of HIV-positive patients took psychotropic medications in 1996. Antidepressants were the most commonly prescribed drug class (20.9% of patients), followed by anxiolytics (16.7%), antipsychotics (4.7%), and psychostimulants (3.0%). Among patients with major depression or dysthymia, 43.2% reported receiving antidepressants, and 34.3% reported receiving anxiolytics. Psychiatric comorbidity was associated with greater use of psychotropics. Use of psychotropics in general, and antidepressants in particular, was significantly lower among African Americans than whites or Hispanics. Among patients with mood disorders, 61.0% of whites, 51.4% of African Americans, and 66.7% of Hispanics reported use of antidepressant medications or some type of psychosocial intervention. Conclusions: Psychotropics were commonly used by HIV-positive patients in medical care. About half of the patients suffering from depressive disorders did not receive antidepressants. Psychotropic drug use was lower among African Americans than other ethnic groups. C1 NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RAND Corp, Santa Monica, CA USA. Charles R Drew Univ Med & Sci, Ctr AIDS Res Educ & Serv, Los Angeles, CA 90059 USA. RP Vitiello, B (reprint author), NIMH, Div Serv & Intervent Res, Room 7147,6001 Execut Blvd,MSC 9633, Bethesda, MD 20892 USA. FU AHRQ HHS [HS-08578]; NIMH NIH HHS [MH-00990] NR 39 TC 61 Z9 63 U1 0 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2003 VL 160 IS 3 BP 547 EP 554 DI 10.1176/appi.ajp.160.3.547 PG 8 WC Psychiatry SC Psychiatry GA 655MX UT WOS:000181557600018 PM 12611837 ER PT J AU Gogtay, N Sporn, A Clasen, LS Greenstein, D Giedd, JN Lenane, M Gochman, PA Zijdenbos, A Rapoport, JL AF Gogtay, N Sporn, A Clasen, LS Greenstein, D Giedd, JN Lenane, M Gochman, PA Zijdenbos, A Rapoport, JL TI Structural brain MRI abnormalities in healthy siblings of patients with childhood-onset schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID GRAY-MATTER; RELIABILITY; ADOLESCENCE; DISORDERS; INTERVIEW; AGE AB Objective: Childhood-onset schizophrenia shows progressive brain magnetic resonance imaging (MRI) changes during adolescence, which follow a back-to-front "wave." The authors' goal was to examine whether healthy siblings of patients with childhood-onset schizophrenia show structural brain abnormalities and the age-related pattern of abnormalities seen in patients with childhood-onset schizophrenia. Method: Anatomic brain MRI scans were obtained from 15 psychiatrically healthy full siblings of 15 patients with childhood-onset schizophrenia and from 32 matched community volunteers. Automated measures were used to compare total and regional brain volumes of the siblings and volunteers. Results: Siblings of patients with childhood-onset schizophrenia had smaller total cerebral volume and total, frontal, and parietal gray matter volumes than volunteers. When divided into younger and older groups, younger siblings had smaller parietal gray matter volumes and older siblings showed trends for smaller total and frontal gray matter volumes. Conclusions: Healthy siblings of patients with childhood-onset schizophrenia share brain MRI abnormalities with the patients that may follow a similar pattern of progression. Developmental brain abnormalities in childhood-onset schizophrenia may thus be genetic trait markers. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Montreal Neurol Inst, Montreal, PQ, Canada. RP Gogtay, N (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Rm 3N202, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008; Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 18 TC 43 Z9 44 U1 2 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2003 VL 160 IS 3 BP 569 EP 571 DI 10.1176/appi.ajp.160.3.569 PG 3 WC Psychiatry SC Psychiatry GA 655MX UT WOS:000181557600022 PM 12611841 ER PT J AU Vythilingam, M Chen, J Bremner, JD Mazure, CM Maciejewski, PK Nelson, JC AF Vythilingam, M Chen, J Bremner, JD Mazure, CM Maciejewski, PK Nelson, JC TI Psychotic depression and mortality SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DEXAMETHASONE SUPPRESSION TEST; LATE-LIFE DEPRESSION; MAJOR DEPRESSION; ANTIDEPRESSANTS; COMMUNITY; SUBTYPES; SYMPTOMS; DISEASE; RATES AB Objective: Major depressive disorder is associated with elevated mortality rates that increase with the severity of depression. The authors hypothesized that patients with psychotic depression would have higher mortality rates than patients with nonpsychotic depression. Method: Survival analytic techniques were used to compare the vital status of 61 patients with psychotic major depression with that of 59 patients with non psychotic major depression up to 15 years after hospital admission. Medical status was assessed with the Cumulative Illness Rating Scale. Dexamethasone suppression test (DST) data were available for 101 patients. Results: The mortality rate for subjects with psychotic depression was significantly greater than that for those with nonpsychotic depression, with 41% versus 20%, respectively, dying within 15 years after hospital admission. A proportional hazards model with age and medical status entered as covariates confirmed a significantly higher mortality rate in patients with psychotic depression (hazards ratio=2.31). A positive DST result was associated with psychotic depression but was not related to vital status. Conclusions: Patients with psychotic depression have a twofold greater risk of death than do patients with severe, nonpsychotic major depression. C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Vythilingam, M (reprint author), NIMH, 15K N Dr,Room 111,MSC 2670, Bethesda, MD 20892 USA. RI Bremner, James/B-1632-2013 NR 22 TC 71 Z9 74 U1 0 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2003 VL 160 IS 3 BP 574 EP 576 DI 10.1176/appi.ajp.160.3.574 PG 3 WC Psychiatry SC Psychiatry GA 655MX UT WOS:000181557600024 PM 12611843 ER PT J AU Sappol, M AF Sappol, M TI Science and spirituality - Response SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 Natl Lib Med, Bethesda, MD 20209 USA. RP Sappol, M (reprint author), Natl Lib Med, 8600 Rockville Pike,Bldg 38,Rm 1E-21, Bethesda, MD 20209 USA. NR 6 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 MAR PY 2003 VL 93 IS 3 BP 363 EP 364 DI 10.2105/AJPH.93.3.363-a PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 649KM UT WOS:000181207500004 ER PT J AU Fee, E Brown, TM Beatty, RL AF Fee, E Brown, TM Beatty, RL TI Early modern childbirth SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID POSITION C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), NIH, Hist Med Div, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 1 Z9 1 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 MAR PY 2003 VL 93 IS 3 BP 432 EP 432 DI 10.2105/AJPH.93.3.432 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 649KM UT WOS:000181207500020 PM 12604487 ER PT J AU Eichacker, PQ Banks, SM Natanson, C AF Eichacker, PQ Banks, SM Natanson, C TI Meta-analysis of tidal volumes in ARDS - From the authors SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; SYNDROME TRIALS; VENTILATION; MORTALITY C1 NIH, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 13 Z9 13 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 1 PY 2003 VL 167 IS 5 BP 798 EP 800 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 649FB UT WOS:000181195300024 ER PT J AU Sarntinoranont, M Rooney, F Ferrari, M AF Sarntinoranont, M Rooney, F Ferrari, M TI Interstitial stress and fluid pressure within a growing tumor SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE tumor; soft tissue mechanics; residual stress; poroelastic ID SOLID TUMORS; BLOOD-FLOW; GROWTH; HYPERTENSION; MACROMOLECULES; TRANSPORT; VASCULATURE; MECHANISMS; CONVECTION; PERFUSION AB A solid tumor is composed of a population of cells that is expanding as a result of cell division. With dense cell packing, the solid matrix of the interstitial tissue is subject to residual stress. In addition, elevated interstitial fluid pressure (IFP) has been reported by researchers for a number of solid tumors. These features were incorporated into a mathematical model that predicts the mechanical response of a solid tumor within its host environment. A theoretical framework accounting for volumetric expansion, transvascular exchange and extravascular transport of fluids was developed using poroelastic theory, and applied to a spherical, vascularized, alymphatic tumor undergoing small growth increments. Simulations of tumor IFP were similar to those predicted by Jain and Baxter (Ref. 23), showing elevated IFP that is driven by microvascular fluid pressure. Tumor growth, tissue stiffness, and IFP contribute to the compressive stresses predicted in the solid tumor interior. Tensile and compressive stresses were predicted in adjacent host tissues corresponding to radial and circumferential directions, respectively. An application of this model includes a solid stress-based framework for predicting regions of vascular collapse within the tumor interior. (C) 2003 Biomedical Engineering Society. [DOI: 10.1114/1.1554923]. C1 Univ Calif Berkeley, Dept Mech Engn, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Civil & Environm Engn, Berkeley, CA 94720 USA. RP Sarntinoranont, M (reprint author), NIH, Bldg 13,Rm 3N17, Bethesda, MD 20892 USA. EM sarntinm@mail.nih.gov NR 42 TC 61 Z9 65 U1 3 U2 15 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD MAR PY 2003 VL 31 IS 3 BP 327 EP 335 DI 10.1114/1.1554923 PG 9 WC Engineering, Biomedical SC Engineering GA 659ZC UT WOS:000181808400009 PM 12680730 ER PT J AU Gladen, BC Shkiryak-Nyzhnyk, ZA Chyslovska, N Zadorozhnaja, TD Little, RE AF Gladen, BC Shkiryak-Nyzhnyk, ZA Chyslovska, N Zadorozhnaja, TD Little, RE TI Persistent organochlorine compounds and birth weight SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE birth weight; hydrocarbons; chlorinated; insecticides; organochlorine; DDT; DDE; hexachlorobenzene; heptachlor epoxide; polychlorinated biphenyls ID DICHLORODIPHENYL DICHLOROETHENE DDE; POLYCHLORINATED-BIPHENYLS PCBS; HUMAN-MILK; GESTATIONAL-AGE; HEPTACHLOR EXPOSURE; PRETERM BIRTH; BREAST-MILK; PESTICIDES; WOMEN; LACTATION AB PURPOSE: To determine whether weight at birth is related to prenatal exposure to persistent organochlorine compounds. METHODS: Birth weight was obtained for 197 singleton infants drawn from the general population born in two cities in Ukraine in 1993 to 1994. Concentrations of seven organochlorine pesticides (p,p'-DDT, p,p'-DDE, beta-hexachlorocyclohexane, hexachlorobenzene, trans-nonachlor, oxychlordane, heptachlor epoxide) and 11 polychlorinated biphenyl congeners measured in maternal milk taken at four or five days after birth were used as an index of prenatal exposure. RESULTS: The greatest differences were seen for beta-hexachlorocyclohexane, with a pattern not suggestive of dose-response; infants in the lowest tertile were small, those in the central tertile were large, and those in the upper tertile were average. Adjustment for gestational age and other potential confounders had little effect on these patterns. Infants in the two upper tertiles for p,p'-DDE were larger than those in the lower tertile, with the effect being more striking after adjustment for gestational age. Adjustment for potential confounders made the pattern disappear. Other chemicals showed no convincing evidence of effects. CONCLUSIONS: Prenatal exposure to the chemicals studied, at concentrations currently seen in this population, does not impact weight at birth. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Inst Pediat Obstet & Gynecol, Kiev, Ukraine. RP Gladen, BC (reprint author), NIEHS, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM gladen@niehs.nih.gov NR 44 TC 65 Z9 66 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAR PY 2003 VL 13 IS 3 BP 151 EP 157 AR PII S1047-2797(02)00268-5 DI 10.1016/S1047-2797(02)00268-5 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 654ZC UT WOS:000181526000001 PM 12604157 ER PT J AU Longnecker, MP Zhou, H Klebanoff, MA Brock, JW AF Longnecker, MP Zhou, H Klebanoff, MA Brock, JW TI An unexpected distribution of sodium concentration in serum specimens stored for more than 30 years SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE sodium; blood; cohort studies; epidemiology; clinical chemistry; desiccation ID BREAST-CANCER; PREGNANCY; BIRTH; METABOLITE; PSYCHOSIS; WOMEN; RISK AB PURPOSE: Sera from over 50,000 pregnant women in the Collaborative Perinatal Project have been frozen at -20degreesC since 1959 to 1966, and with the health data on their offspring constitute a resource that is still actively used. In two studies using these specimens, we measured sodium concentration to assess desiccation. METHODS: Sodium was measured in over 5,000 specimens by two different methods. For 10 specimens with unusually low sodium values, a substudy was done to investigate the cause. RESULTS: High sodium levels (>140 mmol/L) were present in more than 20% of specimens, and levels were unusually low (<130 mmol/L) in more than 40% of specimens. The substudy showed that filtering the specimens increased sodium levels and that about 14% of the sodium was trapped in particulate matter. CONCLUSIONS: High sodium levels in these specimens were probably due to desiccation and possibly to leaching of sodium from the glass containers. Low sodium levels were probably caused by the particulate matter, which clogged the analytical sampling devices and also trapped sodium. In serum specimens that have been stored for long periods, use of routine laboratory procedures for analysis can yield erroneous results. Furthermore, measured analyte levels can be affected by more than just degradation and desiccation. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 22 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAR PY 2003 VL 13 IS 3 BP 178 EP 181 AR PII S1047-2797(02)00415-5 DI 10.1016/S1047-2797(02)00415-5 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 654ZC UT WOS:000181526000005 PM 12604161 ER PT J AU Theodore, WH AF Theodore, WH TI Implications of neuroimaging for the treatment of epilepsy SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID TEMPORAL-LOBE EPILEPSY; RESONANCE-IMAGING EVIDENCE; FEBRILE SEIZURES; HIPPOCAMPAL SCLEROSIS; MAGNETIC-RESONANCE; QUANTITATIVE MRI; LOBECTOMY PATIENTS; ONSET EPILEPSY; NEURONAL LOSS; LONG-TERM C1 NIH, Clin Epidemiol Sect, Bethesda, MD 20892 USA. RP Theodore, WH (reprint author), NIH, Clin Epidemiol Sect, Bldg 10, Bethesda, MD 20892 USA. NR 45 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAR PY 2003 VL 53 IS 3 BP 286 EP 288 DI 10.1002/ana.10516 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 649HB UT WOS:000181200400002 PM 12601695 ER PT J AU Rogawski, MA AF Rogawski, MA TI Progesterone, neurosteroids, and the hormonal basis of catamenial epilepsy SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID ANTICONVULSANT ACTIVITY; WITHDRAWAL; FINASTERIDE; RECEPTOR; WOMEN; 5-ALPHA-REDUCTASE; GANAXOLONE; MODEL; MICE C1 NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 24 TC 21 Z9 21 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAR PY 2003 VL 53 IS 3 BP 288 EP 291 DI 10.1002/ana.10534 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 649HB UT WOS:000181200400003 PM 12601696 ER PT J AU Johnson, CA McGarry, D Cook, JA Devasahayam, N Mitchell, JB Subramanian, S Krishna, MC AF Johnson, CA McGarry, D Cook, JA Devasahayam, N Mitchell, JB Subramanian, S Krishna, MC TI Maximum entropy reconstruction methods in electron paramagnetic resonance imaging SO ANNALS OF OPERATIONS RESEARCH LA English DT Article DE tomographic image reconstruction; electron paramagnetic resonance; maximum entropy; nonlinear optimization ID 3D RECONSTRUCTION; PET; ALGORITHM AB Electron Paramagnetic Resonance (EPR) is a spectroscopic technique that detects and characterizes molecules with unpaired electrons (i.e., free radicals). Unlike the closely related nuclear magnetic resonance (NMR) spectroscopy, EPR is still under development as an imaging modality. Athough a number of physical factors have hindered its development, EPR's potential is quite promising in a number of important application areas, including in vivo oximetry. EPR images are generally reconstructed using a tomographic imaging technique, of which filtered backprojection (FBP) is the most commonly used. We apply two iterative methods for maximum-entropy image reconstruction in EPR. The first is the multiplicative algebraic reconstruction technique ( MART), a well-known row-action method. We propose a second method, known as LSEnt (least-squares entropy), that maximizes entropy and performs regularization by maintaining a desired distance from the measurements. LSEnt is in part motivated by the barrier method of interior-point programming. We present studies in which images of two physical phantoms, reconstructed using FBP, MART, and LSEnt, are compared. The images reconstructed using MART and LSEnt have lower variance, better contrast recovery, subjectively better resolution, and reduced streaking artifact than those reconstructed using FBP. These results suggest that maximum-entropy reconstruction methods (particularly the more flexible LSEnt) may be critical in overcoming some of the physical challenges of EPR imaging. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Cook, JA (reprint author), NIH, Ctr Informat Technol, 12 S Dr,MSC 5624, Bethesda, MD 20892 USA. EM johnson@mail.nih.gov NR 33 TC 11 Z9 11 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0254-5330 J9 ANN OPER RES JI Ann. Oper. Res. PD MAR PY 2003 VL 119 IS 1-4 BP 101 EP 118 DI 10.1023/A:1022978322046 PG 18 WC Operations Research & Management Science SC Operations Research & Management Science GA 659GH UT WOS:000181768600006 ER PT J AU Barrientos, LG O'Keefe, BR Bray, M Anthony, S Gronenborn, AM Boyd, MR AF Barrientos, LG O'Keefe, BR Bray, M Anthony, S Gronenborn, AM Boyd, MR TI Cyanovirin-N binds to the viral surface glycoprotein, GP(1,2) and inhibits infectivity of Ebola virus SO ANTIVIRAL RESEARCH LA English DT Article DE cyanovirin-N; virucidal agent; HIV; Ebola filovirus; enveloped viruses ID HIV-INACTIVATING PROTEIN; VIRION GLYCOPROTEINS; ENVELOPED VIRUSES; GP120; IMMUNIZATION; THERAPY; VACCINE; FUSION; MICE; CD4 AB Ebola virus (Ebo) causes severe hemorrhagic fever and high mortality in humans. There are currently no effective therapies. Here, we have explored potential anti-Ebo activity of the human immunodeficiency virus (HIV)-inactivating protein cyanovirin-N (CV-N). CV-N is known to potently inhibit the infectivity of a broad spectrum of HIV strains at the level of viral entry. This involves CV-N binding to N-linked high-mannose oligossacharides on the viral glycoprotein gp120. The Ebola envelope contains somewhat similar oligosaccharide constituents, suggesting possible susceptibility to inhibition by CV-N. Our initial results revealed that CV-N had both in vitro and in vivo antiviral activity against the Zaire strain of the Ebola virus (Ebo-Z). Addition of CV-N to the cell culture medium at the time of Ebo-Z infection inhibited the development of viral cytopathic effects (CPEs). CV-N also delayed the death of Ebo-Z-infected mice, both when given as a series of daily subcutaneous injections and when the virus was incubated ex vivo together with CV-N before inoculation into the mice. Furthermore, similar to earlier results with HIV gp120, CV-N bound with considerable affinity to the Ebola surface envelope glycoprotein, GP(1,2). Competition experiments with free oligosaccharides were consistent with the view that carbohydrate-mediated CV-N/GP(1,2) interactions involve oligosaccharides residing on the Ebola viral envelope. Overall, these studies broaden the range of viruses known to be inhibited by CV-N, and further implicate carbohydrate moieties on viral surface proteins as common viral molecular targets for this novel protein. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ S Alabama, Coll Med, USA Canc Res Inst, Mobile, AL 36688 USA. NIDDK, Phys Chem Lab, NIH, Bethesda, MD USA. NCI, Mol Targets Drug Discovery Program, Ctr Canc Res, Frederick, MD 21701 USA. USA, Med Res Inst Infect Dis, Div Virol, Frederick, MD 21701 USA. CDCP, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Special Pathogens Branch, Atlanta, GA USA. RP Boyd, MR (reprint author), Univ S Alabama, Coll Med, USA Canc Res Inst, Mobile, AL 36688 USA. NR 32 TC 82 Z9 96 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAR PY 2003 VL 58 IS 1 BP 47 EP 56 AR PII S0166-3542(02)00183-3 DI 10.1016/S0166-3542(02)00183-3 PG 10 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 676LG UT WOS:000182753100005 PM 12719006 ER PT J AU Huang, RCC Li, Y Giza, PE Gnabre, JN Abd-Elazem, IS King, KY Hwu, JR AF Huang, RCC Li, Y Giza, PE Gnabre, JN Abd-Elazem, IS King, KY Hwu, JR TI Novel antiviral agent tetraglycylated nordihydroguaiaretic acid hydrochloride as a host-dependent viral inhibitor SO ANTIVIRAL RESEARCH LA English DT Article DE tetra-O-glycyl-nordihydroguaiaretic acid; G(4)N; human immunodeficiency virus; sp1; simian immunodeficiency virus ID LARREA-TRIDENTATA; TRANSCRIPTION; LIGNANS; POTENT; REPLICATION; NUCLEOSIDE; MUTATION; CELLS AB A water soluble derivative of nordihydroguaiaretic acid (NDGA), G(4)N (2), synthesized by reaction of NDGA (1) with N,N-dimethylglycine in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine and then with HCl(g) (Scheme 1), competes effectively with the DNA binding domain of recombinant Sp1 protein for binding to the human immunodeficiency virus (HIV) LTR as demonstrated by an electrophoretic mobility-shift assay (EMSA). By blocking Sp1 binding to the HIV LTR, G4N suppresses Sp1-regulated HIV Tat transactivation and replication in cultured cells with an IC50 of 12 muM similar to that of 3'-O-methyl-NDGA as we have previously reported. In addition simian immunodeficiency virus (SIV) replication was completely inhibited by G(4)N at 5.0 muM. G(4)N showed no toxic effect to 174 x CEM cells and H9 cells at 100 muM. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. NIAID, NIH, Bethesda, MD 20892 USA. Natl Tsing Hua Univ, Organosilicon & Synth Lab, Dept Chem, Hsinchu 30043, Taiwan. Acad Sinica, Inst Chem, Taipei 11529, Taiwan. RP Huang, RCC (reprint author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. FU NIDCR NIH HHS [1R01DE12165] NR 22 TC 15 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAR PY 2003 VL 58 IS 1 BP 57 EP 64 AR PII S0166-3542(02)00189-4 DI 10.1016/S0166-3542(02)00189-4 PG 8 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 676LG UT WOS:000182753100006 PM 12719007 ER PT J AU Lee, JK Sayers, TJ Back, TC Wigginton, JM Wiltrout, RH AF Lee, JK Sayers, TJ Back, TC Wigginton, JM Wiltrout, RH TI Lack of FasL-mediated killing leads to in vivo tumor promotion in mouse Lewis lung cancer SO APOPTOSIS LA English DT Article DE apoptosis; Fas; FasL; 3LL ID T-CELL PROLIFERATION; MURINE RENAL-CANCER; ANTI-FAS; IN-VIVO; GLIOMA-CELLS; DEATH FACTOR; APOPTOSIS; EXPRESSION; LIGAND; ACTIVATION AB Lewis lung carcinoma (3LL) cells were constitutively resistant to Fas-mediated apoptosis, but overexpression of Fas on 3LL cells allowed Fas-mediated apoptosis after crosslinking with agonist anti-Fas antibody (Jo2) in vitro. Surprisingly, Fas-overexpressing 3LL cells showed enhanced in vivo tumor progression, whereas no promotion of in vivo tumor growth was observed for dominant negative (DN) Fas-overexpressing 3LL transfectants in which the cytoplasmic death domain was deleted. In addition, the promotion of in vivo tumor growth by Fas-overexpression was reduced in gld (FasL-mutation) mice compared to normal mice. These data indicate that intact Fas/FasLcell signaling is required for the promotion of in vivo tumor growth by Fas overexpression in 3LL cells. In contrast to the efficient Fas-mediated killing induced in vitro by crosslinking with anti-Fas antibody, Fas-overexpressing 3LL cells were resistant in vitro to Fas-mediated apoptosis by activated T cells or transient FasL transfection. These data suggest that agonist anti-Fas antibody and natural FasL can transmit qualitatively different signals, and crosslinking of Fas with natural FasL on 3LL cells does not deliver the expected death signal. Thus, our results demonstrate that in some cases overexpression of Fas can result in a survival advantage for tumor cells in vivo. C1 Natl Inst Hlth, Natl Genome Res Inst, Seoul 122701, South Korea. NCI, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Frederick, MD 21702 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Lee, JK (reprint author), Natl Inst Hlth, Natl Genome Res Inst, 5 Nokbun Dong, Seoul 122701, South Korea. EM cookie_jklee@hotmail.com RI Sayers, Thomas/G-4859-2015 NR 37 TC 27 Z9 29 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD MAR PY 2003 VL 8 IS 2 BP 151 EP 160 DI 10.1023/A:1022918625509 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 659GF UT WOS:000181768400004 PM 12766475 ER PT J AU Judd, LL Akiskal, HS Schettler, PJ Coryell, W Endicott, J Maser, JD Solomon, DA Leon, AC Keller, MB AF Judd, LL Akiskal, HS Schettler, PJ Coryell, W Endicott, J Maser, JD Solomon, DA Leon, AC Keller, MB TI A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID BRANCH COLLABORATIVE PROGRAM; MAJOR DEPRESSIVE DISORDER; FOLLOW-UP; HYPOMANIA; UNIPOLAR; ILLNESS; PREVALENCE; PSYCHOBIOLOGY; PREDICTORS; STABILITY AB Background: This is the first prospective longitudinal study, to our knowledge, of the natural history of the weekly symptomatic status of bipolar 11 disorder (BP-II). Methods: Weekly affective symptom status ratings for 86 patients with BP-II were based on interviews conducted at 6- or 12-month intervals during a mean of 13.4 years of prospective follow-up. Percentage of weeks at each symptom severity level and the number of shifts in symptom status and polarity were examined. Predictors of chronicity for BP-II were evaluated using new chronicity measures. Chronicity was also analyzed in relation to the percentage of follow-up weeks with different types of somatic treatment. Results: Patients with BP-II were symptomatic 53.9% of all follow-up weeks: depressive symptoms (50.3% of weeks) dominated the course over hypomanic (1.3% of weeks) and cycling/mixed (2.3% of weeks) symptoms. Subsyndromal, minor depressive, and hypomanic symptoms combined were 3 times more common than major depressive symptoms. Longer intake episodes, a family history of affective disorders, and poor previous social functioning predicted greater chronicity. Prescribed somatic treatment did not correlate significantly with symptom chronicity. Patients with BP-II of brief (2-6 days) vs longer (greater than or equal to7 days) hypomanias were not significantly different on any measure. Conclusions: The longitudinal symptomatic course of BP-II is chronic and is dominated by depressive rather than hypomanic or cycling/mixed symptoms. Symptom severity fluctuates frequently within the same patient over time, involving primarily symptoms of minor and subsyndromal severity. Longitudinally, BP-II is expressed as a dimensional illness involving the full severity range of depressive and hypomanic symptoms. Hypomania of long or short duration in BP-II seems to be part of the same disease process. C1 Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. NIMH, Collaborat Program Psychobiol Depress Clin Studie, Bethesda, MD 20892 USA. Dept Vet Affairs, Psychiat Serv, San Diego Hlth Care Syst, San Diego, CA USA. Dept Vet Affairs, Psychol Serv, San Diego Hlth Care Syst, San Diego, CA USA. RP Judd, LL (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA. FU NIMH NIH HHS [R01 MH025478] NR 48 TC 661 Z9 672 U1 3 U2 36 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 MAR PY 2003 VL 60 IS 3 BP 261 EP 269 DI 10.1001/archpsyc.60.3.261 PG 9 WC Psychiatry SC Psychiatry GA 655UZ UT WOS:000181572200006 PM 12622659 ER PT J AU Christen, WG Manson, JE Glynn, RJ Gaziano, KM Sperduto, RD Buring, JE Hennekens, CH AF Christen, WG Manson, JE Glynn, RJ Gaziano, KM Sperduto, RD Buring, JE Hennekens, CH TI A randomized trial of beta carotene and age-related cataract in US physicians SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CIGARETTE-SMOKING; ALPHA-TOCOPHEROL; SERUM CAROTENOIDS; VITAMIN-A; NUTRIENT CONCENTRATIONS; CARDIOVASCULAR-DISEASE; PLASMA-CONCENTRATIONS; ANTIOXIDANT VITAMINS; ALCOHOL-CONSUMPTION; NUCLEAR CATARACT AB Objective: To examine the development of age-related cataract in a trial of beta carotene supplementation in men. Design: Randomized, double-masked, placebo-controlled trial. Methods: Male US physicians aged 40 to 84 years (n = 22071) were randomly assigned to receive eitherbeta carotene (50 mg on alternate days) or placebo for 12 years. Main Outcome Measures: Age-related cataract and extraction of age-related cataract, defined as an incident, age-related lens opacity, responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review. Results: There was no difference between the beta carotene and placebo groups in the overall incidence of cataract (998 cases vs 1017 cases;,relative risk [RR], 1.00; 95% confidence interval [CI], 0.91-1.09) or cataract ex-traction (584 vs 593; RR, 1.00; 95% CI, 0.89-1.12). In subgroup analyses, the effect of beta carotene supplementation appeared to be modified by smoking status at baseline (P = .02). Among current smokers, there were 108 cases of cataract in the beta carotene group and 133 in the placebo group (RR, 0.74; 95% CI, 0.57-0.95). Among current nonsmokers, there was no significant difference in the number of cases in the 2 treatment groups (884 vs 881; RR, 1.03; 95% CI, 0.94-1.13). The results for cataract extraction appeared to be similarly modified by baseline smoking status (P = .05). Conclusions: Randomized trial data from a large population of healthy men indicate no overall benefit or harm of 12 years of beta carotene supplementation on cataract or cataract extraction. However, among current smokers at baseline, beta carotene appeared to attenuate their excess risk of cataract by about one fourth. C1 Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Boston Healthcare Syst, Dept Vet Affairs, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. NEI, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33152 USA. RP Christen, WG (reprint author), Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E,3rd Floor, Boston, MA 02215 USA. FU NCI NIH HHS [CA 40360, CA 34944, R01 CA097193]; NEI NIH HHS [EY 06633]; NHLBI NIH HHS [HL 26490, HL 34595] NR 51 TC 41 Z9 43 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2003 VL 121 IS 3 BP 372 EP 378 PG 7 WC Ophthalmology SC Ophthalmology GA 653YP UT WOS:000181464900010 PM 12617708 ER PT J AU Cho-Chung, YS AF Cho-Chung, YS TI Antisense DNAs as targeted genetic medicine to treat cancer SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Article DE antisense; oligonucleotides; cancer; chemotherapy; gene expression; growth inhibition ID PROTEIN-KINASE-A; RI-ALPHA SUBUNIT; MIXED-BACKBONE OLIGONUCLEOTIDES; FIBROBLAST GROWTH-FACTOR; INHIBITS TUMOR-GROWTH; CYCLIC-AMP; REGULATORY SUBUNIT; IN-VIVO; OVARIAN-CANCER; BACTERIAL-DNA AB Nucleic acid therapies represent a direct genetic approach for cancer treatment. Such an approach takes advantage of mechanisms that activate genes known to confer a growth advantage to neoplastic cells. The ability to block the expression of these genes allows exploration of normal growth regulation. Progress in antisense technology has been rapid, and the traditional antisense inhibition of gene expression is now viewed on a genomic scale. This global view has led to a new vision in antisense technology, the elimination of nonspecific and undesirable side effects, and ultimately, the generation of more effective and less toxic nucleic acid medicines. Several antisense oligonucleotides are in clinical trials, are well tolerated, and are potentially active therapeutically. Antisense oligonucleotides are promising molecular medicines for treating human cancer in the near future. C1 NCI, Cellular Biochem Sect, BRL, CCR,NIH, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, BRL, CCR,NIH, Bldg 10,Room 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NCI NIH HHS [N02-BC-76212/C2700212] NR 87 TC 6 Z9 7 U1 0 U2 0 PU PHARMACEUTICAL SOCIETY KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD MAR PY 2003 VL 26 IS 3 BP 183 EP 191 DI 10.1007/BF02976827 PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 661AM UT WOS:000181869000001 PM 12723929 ER PT J AU Conforto, AB Marie, SKN Cohen, LG Scaff, M AF Conforto, AB Marie, SKN Cohen, LG Scaff, M TI Transcranial magnetic stimulation SO ARQUIVOS DE NEURO-PSIQUIATRIA LA Portuguese DT Article DE transcranial magnetical stimulation; neural plasticity; brain mapping ID HUMAN MOTOR CORTEX; CORTICAL EXCITABILITY; HUMAN BRAIN; REPRESENTATIONS; PLASTICITY; MECHANISMS; INDUCTION; EPILEPSY; STROKE; PULSE AB Transcranial magnetic stimulation (TMS) allows non-invasive study and modulation of cortical excitability in humans. Changes in cortical excitability in physiological and pathological conditions can be tracked by measurements such as motor threshold, motor evoked potentials, recruitment curves, intracortical facilitation and inhibition. The central motor conduction time can estimate neural transmission in central motor pathways. Changes in areas of representation in sensorimotor cortex can be studied with cortical mapping. Modulation of cortical processing can be used to evaluate different brain functions. Therapeutic use in depression, Parkinson's disease and epilepsy has raised great interest over the past decade. Noninvasive cortical. mapping may be achieved by combining TMS to other neurophysiological/neuroimaging techniques. TMS has great potential both as an investigational and as a therapeutical tool in Neurology and Psychiatry. C1 Univ Sao Paulo, Fac Med, Div Clin Neurol, BR-05403000 Sao Paulo, Brazil. Univ Sao Paulo, Fac Med, Div Clin Neurol, Hosp Clin, BR-05403000 Sao Paulo, Brazil. NINDS, Human Cort Physiol Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RI Marie, Suely/D-1870-2012 NR 32 TC 4 Z9 4 U1 0 U2 4 PU ASSOC ARQUIVOS DE NEURO- PSIQUIATRIA PI SAO PAULO SP PA PR AMADEU AMARAL 47/33, 01327-010 SAO PAULO SP, BRAZIL SN 0004-282X J9 ARQ NEURO-PSIQUIAT JI Arq. Neuro-Psiquiatr. PD MAR PY 2003 VL 61 IS 1 BP 146 EP 152 DI 10.1590/S0004-282X2003000100032 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 669DM UT WOS:000182336700032 PM 12715042 ER PT J AU Keaney, JF Larson, MG Vasan, RS Wilson, PWF Lipinska, I Corey, D Massaro, JM Sutherland, P Vita, JA Benjamin, EJ AF Keaney, JF Larson, MG Vasan, RS Wilson, PWF Lipinska, I Corey, D Massaro, JM Sutherland, P Vita, JA Benjamin, EJ TI Obesity and systemic oxidative stress - Clinical correlates of oxidative stress in the Framingham Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE oxidative stress; isoprostanes; diabetes; obesity; cardiovascular disease ID LOW-DENSITY-LIPOPROTEIN; HUMAN-BLOOD-PLASMA; LIPID-PEROXIDATION; IN-VIVO; DIABETES-MELLITUS; NAD(P)H OXIDASE; F-2-ISOPROSTANES; SUPEROXIDE; DISEASE; INSULIN AB Objective-To determine the clinical conditions associated with systemic oxidative stress in a community-based cohort. Information regarding cardiovascular risk factors associated with systemic oxidative stress has largely been derived from highly selected samples with advanced stages of vascular disease. Thus, it has been difficult to evaluate the relative contribution of each cardiovascular risk factor to systemic oxidative stress and to determine whether such risk factors act independently and are applicable to the general population. Methods and Results-We examined 2828 subjects from the Framingham Heart Study and measured urinary creatinine-indexed levels of 8- epi-PGF(2alpha) as a marker of systemic oxidative stress. Age- and sex-adjusted multivariable regression models were used to assess clinical correlates of oxidative stress. In age- and sex- adjusted models, increased urinary creatinine-indexed 8-epi- PGF(2alpha) levels were positively associated with female sex, hypertension treatment, smoking, diabetes, blood glucose, body mass index, and a history of cardiovascular disease. In contrast, age and total cholesterol were negatively correlated with urinary creatinine-indexed 8- epi-PGF(2alpha) levels. After adjustment for several covariates, decreasing age and total/HDL cholesterol ratio, sex, smoking, body mass index, blood glucose, and cardiovascular disease remained associated with urinary 8-epi-PGF(2alpha) levels. Conclusions-Smoking, diabetes, and body mass index were highly associated with systemic oxidative stress as determined by creatinine-indexed urinary 8-epi-PGF(2alpha) levels. The effect of body mass index was minimally affected by blood glucose, and diabetes and may suggest an important role of oxidative stress in the deleterious impact of obesity on cardiovascular disease. C1 Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Boston Univ, Sch Med, Evans Mem Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. NHLBI, Framingham Study, Framingham, MA USA. RP Keaney, JF (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, 715 Albany St,Rm W507, Boston, MA 02118 USA. OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [HL64753, HL04334, HL60886, HL71039, N01-HC-25195, N01-HV-28178]; NIDDK NIH HHS [DK55656] NR 41 TC 718 Z9 742 U1 2 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2003 VL 23 IS 3 BP 434 EP 439 DI 10.1161/01.ATV.0000058402.34138.11 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 655JY UT WOS:000181549400015 PM 12615693 ER PT J AU Goldbach-Mansky, R Woodburn, J Yao, L Lipsky, PE AF Goldbach-Mansky, R Woodburn, J Yao, L Lipsky, PE TI Magnetic resonance imaging in the evaluation of bone damage in rheumatoid arthritis: A more precise image or just a more expensive one? SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID INFLAMMATORY ARTHRITIS; FINGER JOINTS; EROSIONS; WRIST; RADIOGRAPHS C1 NIAMSD, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Goldbach-Mansky, R (reprint author), NIAMSD, NIH, Bldg 10,Room 9S205,10 Ctr Dr, Bethesda, MD 20892 USA. NR 18 TC 34 Z9 35 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 MAR PY 2003 VL 48 IS 3 BP 585 EP 589 DI 10.1002/art.10819 PG 5 WC Rheumatology SC Rheumatology GA 653LY UT WOS:000181438800001 PM 12632407 ER PT J AU Boumpas, DT Furie, R Manzi, S Illei, GG Wallace, DJ Balow, JE Vaishnaw, A AF Boumpas, DT Furie, R Manzi, S Illei, GG Wallace, DJ Balow, JE Vaishnaw, A CA BG9588 Lupus Nephritis Trial Grp TI A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID BONE-MARROW TRANSPLANTATION; CD40 LIGAND; ENDOTHELIAL-CELLS; CONTROLLED TRIAL; PULSE CYCLOPHOSPHAMIDE; MONOCLONAL-ANTIBODY; MURINE LUPUS; T-CELLS; IMMUNOSUPPRESSIVE THERAPY; MYCOPHENOLATE-MOFETIL AB Objective. CD40-CD40 ligand (CD40L) interactions play a significant role in the production of autoantibodies and tissue injury in lupus nephritis. We performed an open-label, multiple-dose study to evaluate the safety, efficacy, and pharmacokinetics of BG9588, a humanized anti-CD40L antibody, in patients with proliferative lupus nephritis. The primary outcome measure was 50% reduction in proteinuria without worsening of renal function. Methods. Twenty-eight patients with active proliferative lupus nephritis were scheduled to receive 20 mg/kg of BG9588 at biweekly intervals for the first 3 doses and at monthly intervals for 4 additional doses. Safety evaluations were performed on all patients. Eighteen patients receiving at least 3 doses were evaluated for efficacy. Results. The study was terminated prematurely because of thromboembolic events occurring in patients in this and other BG9588 protocols (2 myocardial infarctions in this study). Of the 18 patients for whom efficacy could be evaluated, 2 had a 50% reduction in proteinuria without worsening of renal function. Mean reductions of 38.9% (P < 0.005), 50.1% (P < 0.005), and 25.3% (P < 0.05) in anti-double-stranded DNA (anti-dsDNA) antibody titers were observed at 1, 2, and 3 months, respectively, after the last treatment. There-was a significant increase in serum C3 concentrations at 1 month after the last dose (P < 0.005), and hematuria disappeared in all 5 patients with significant hematuria at baseline. There were no statistically significant reductions in lymphocyte count or serum immunoglobulin, anticardiolipin antibody, or rubella IgG antibody concentrations after therapy. Conclusion. A short course of BG9588 treatment in patients with proliferative lupus nephritis reduces anti-dsDNA antibodies, increases C3 concentrations, and decreases hematuria, suggesting that the drug has immunomodulatory action. Additional studies will be needed to evaluate its long-term effects. C1 Univ Crete, Sch Med, Dept Internal Med, Div Rheumatol Allergy & Clin Immunol, Iraklion 71500, Greece. NIAMSD, DHHS, NIH, Bethesda, MD 20892 USA. N Shore Univ Hosp, Manhasset, NY USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NIDDK, NIH, Bethesda, MD USA. Biogen Inc, Cambridge, MA 02142 USA. RP Boumpas, DT (reprint author), Univ Crete, Sch Med, Dept Internal Med, Div Rheumatol Allergy & Clin Immunol, Iraklion 71500, Greece. FU NCRR NIH HHS [5M01/-RR-00056] NR 68 TC 299 Z9 315 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 MAR PY 2003 VL 48 IS 3 BP 719 EP 727 DI 10.1002/art.10856 PG 9 WC Rheumatology SC Rheumatology GA 653LY UT WOS:000181438800019 PM 12632425 ER PT J AU Moss, B AF Moss, B TI Pox virus virulence SO ASM NEWS LA English DT Letter C1 NIAD, Viral Dis Lab, NIH, Bethesda, MD USA. RP Moss, B (reprint author), NIAD, Viral Dis Lab, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0044-7897 J9 ASM NEWS JI ASM News PD MAR PY 2003 VL 69 IS 3 BP 107 EP 108 PG 2 WC Microbiology SC Microbiology GA 757HN UT WOS:000187557100003 ER PT J AU Dougherty, DM Mathias, CW Marsh, DM Greve, KW Bjork, JM Moeller, FG AF Dougherty, DM Mathias, CW Marsh, DM Greve, KW Bjork, JM Moeller, FG TI Commission error rates on a continuous performance test are related to deficits measured by the Benton visual retention test SO ASSESSMENT LA English DT Article DE Benton Visual Retention Test; Immediate and Delayed Memory Task; impulsivity; executive function; adolescents ID CHILD-BEHAVIOR CHECKLIST; PERSONALITY-DISORDER; IMPULSIVITY; RELIABILITY; ATTENTION; VALIDITY; ADOLESCENTS; AGGRESSION; IMMEDIATE; OFFENDERS AB This study is one in a series investigating the relationship between impulsive behavior on a Continuous Performance Test (i.e., the Immediate and Delayed Memory Task) and other cognitive deficits measured by clinical instruments. Forty-two adolescents were selected for two groups, controls and hospitalized patients with disruptive behavior disorders. Each adolescent completed the Immediate and Delayed Memory Task and the Benton Visual Retention Test. Our main findings were that, even when controlling for IQ, the Immediate and Delayed Memory Task commission errors were associated with adverse Benton performance, but only in the patient group. These results may be explained by a shared association between processes of impulsivity and other deficits of executive control that may interfere with successful performance of the Benton. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Neurobiol Res Lab & Clin, Houston, TX 77030 USA. Univ New Orleans, New Orleans, LA 70148 USA. NIAAA, Bethesda, MD USA. RP Dougherty, DM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Neurobiol Res Lab & Clin, 1300 Moursund St, Houston, TX 77030 USA. OI Bjork, James/0000-0003-0593-3291; Mathias, Charles/0000-0003-1902-673X FU NIMH NIH HHS [R01-MH63908] NR 46 TC 7 Z9 7 U1 3 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 J9 ASSESSMENT JI Assessment PD MAR PY 2003 VL 10 IS 1 BP 3 EP 12 DI 10.1177/1073191102250526 PG 10 WC Psychology, Clinical SC Psychology GA 663VX UT WOS:000182028000001 PM 12675379 ER PT J AU Thomas, TL Garland, FC Mole, D Cohen, BA Gudewicz, TM Spiro, RT Zahm, SH AF Thomas, TL Garland, FC Mole, D Cohen, BA Gudewicz, TM Spiro, RT Zahm, SH TI Health of US Navy submarine crew during periods of isolation SO AVIATION SPACE AND ENVIRONMENTAL MEDICINE LA English DT Article DE submarine; health; epidemiology; surveillance; isolated environment ID ASTRONAUT HEALTH; MORTALITY; RISK AB Background: An essential element in planning for long-term space missions is prediction of the medical support required. Medical data for analogous populations serving in isolated and/or contained environments are useful in predicting health risks for astronauts. Methods: This study evaluated the rates of health events that occurred among a highly screened, healthy military population during periods of isolation using a centralized database of medical encounter records from U.S. Navy submarines. The study population was composed of U.S. Navy officers and enlisted men deployed on 240 submarine patrols between 1 January 1997 and 30 September 2000. Results: A total of 1389 officers and 11,952 enlisted crew members served aboard participating submarines for 215,086 and 1,955,521 person-days at sea, respectively, during the study period. Officers had 214 initial visits to medical staff with 79 re-visits for the same condition during these patrols, while enlisted men had 3345 initial visits and 1549 re-visits. Among officers, the most common category of medical events was respiratory illnesses (primarily upper respiratory infections), followed by injury, musculoskeletal conditions, infectious diseases, symptoms and ill-defined conditions, and skin problems. Among enlisted men, the most common category of medical events was injury, followed by respiratory illnesses (upper respiratory infections), skin problems, symptoms and ill-defined conditions, digestive disorders, infectious conditions, sensory organ problems (ear infections and eye problems), and musculoskeletal conditions. Conclusions: Potential mission-impacting medical events reported were rare, i.e., among a crew of seven officers, only one medical event would be expected to occur during a 6-mo mission and result in 3/4 d or less of limited or no duty. Among a crew of seven enlisted men, about two medical events would be expected during a 6-mo mission and result in about I d of limited or no duty per medical event. C1 Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Div Epidemiol & Biostat, Bethesda, MD 20814 USA. RP Zahm, SH (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, EPS-8074,6120 Execut Blvd, Bethesda, MD 20892 USA. NR 11 TC 8 Z9 8 U1 0 U2 3 PU AEROSPACE MEDICAL ASSOC PI ALEXANDRIA PA 320 S HENRY ST, ALEXANDRIA, VA 22314-3579 USA SN 0095-6562 J9 AVIAT SPACE ENVIR MD JI Aviat. Space Environ. Med. PD MAR PY 2003 VL 74 IS 3 BP 260 EP 265 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Sport Sciences SC Public, Environmental & Occupational Health; General & Internal Medicine; Sport Sciences GA 652KF UT WOS:000181377800010 PM 12650274 ER PT J AU Maki, P Hogervorst, E AF Maki, P Hogervorst, E TI HRT and cognitive decline SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE hormone replacement therapy; oestrogens; progestogens; cognition; Alzheimer's disease ID ESTROGEN-REPLACEMENT THERAPY; SURGICALLY MENOPAUSAL WOMEN; CEREBRAL BLOOD-FLOW; HEALTHY POSTMENOPAUSAL WOMEN; DENDRITIC SPINE DENSITY; OLDER COMMUNITY WOMEN; ALZHEIMERS-DISEASE; HORMONE-REPLACEMENT; ELDERLY WOMEN; DOUBLE-BLIND AB It is biologically plausible that hormone replacement therapy (HRT) would be protective against cognitive decline and Alzheimer's disease (AD). We review observational and randomized trials to determine whether HRT might protect against cognitive decline in cognitively unimpaired and demented women. We also address issues of clinical relevance, including duration and type of treatment and patient characteristics, including type of menopause (surgical versus natural), age, education and menopausal symptoms. Differences in participant characteristics and testing methods limit the ability to draw conclusions across randomized studies of HRT in non-demented women. The available evidence suggests no detrimental effect of HRT on cognitive function and inconsistent benefits on verbal memory and reasoning, frontal functions and speeded attention. Meta-analyses of observational trials suggest that HRT protects against the development of AD, but randomized trials indicate no long-lasting benefit in patients with AD. Evidence is insufficient to recommend HRT to maintain cognitive function. C1 NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. Univ Oxford, OPTIMA, Radcliffe Infirm Trust,Dept Pharmacol, Oxford Project Invest Memory & Ageing, Oxford OX2 6HE, England. RP Maki, P (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Hogervorst, Eef/E-2579-2011 NR 95 TC 44 Z9 45 U1 3 U2 5 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-690X J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD MAR PY 2003 VL 17 IS 1 BP 105 EP 122 DI 10.1053/ybeem.2003.237 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 661NG UT WOS:000181896200008 PM 12763515 ER PT J AU Kreitman, RJ Pastan, I AF Kreitman, RJ Pastan, I TI Immunobiological treatments of hairy-cell leukaemia SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE immunotoxin; recombinant; Fv; BL22; LMB2; CD25; CD22; rituximab AB Hairy cell leukaemia (HCL) is extremely responsive to purine analogue theropy developed during the early 1990s, but some patients have emerged with resistance to purine analogues. For these patients, as well as for those with primarily refractory HCL, new treatments are necessary. Several new therapeutic options have been developed for the salvage treatment of HCL. These include recombinant immunotoxins and unlabelled monoclonal antibodies (mAbs). Recombinant immunotoxins are chimeric proteins in which the Fv portion of a mAb is fused to a 38 kDa fragment of Pseudomonas exotoxin A. Two recombinant immunotoxins, BL22 and LMB-2, targeting CD22 and CD25, respectively, have demonstrated efficacy in patients with HCL resistant to purine analogues. BL22 was reported to induce complete remissions (CRs) in the majority of patients with cladribine-resistant HCL; its clinical efficacy and safety profile are currently being further defined. The unlabelled mAb rituximab has also been reported to induce responses in the majority of HCL patients treated, and several Us have been observed. C1 NCI, Clin Immunotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Clin Immunotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 37,Room 5106, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov NR 81 TC 21 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD MAR PY 2003 VL 16 IS 1 BP 117 EP 133 DI 10.1053/ybeha.2003.255 PG 17 WC Hematology SC Hematology GA V41ZE UT WOS:000202837000011 PM 12670470 ER PT J AU Kobayashi, H Kawamoto, S Jo, SK Bryant, HL Brechbiel, MW Star, RA AF Kobayashi, H Kawamoto, S Jo, SK Bryant, HL Brechbiel, MW Star, RA TI Macromolecular MRI contrast agents with small dendrimers: Pharmacokinetic differences between sizes and cores SO BIOCONJUGATE CHEMISTRY LA English DT Article ID NEUTRON-CAPTURE THERAPY; POLYAMIDOAMINE DENDRIMER; MONOCLONAL-ANTIBODY; IN-VIVO; HIGH-GENERATION; ANGIOGRAPHY; LIVER; MICE; BIODISTRIBUTION; ENHANCEMENT AB Large macromolecular MRI contrast agents with albumin or dendrimer cores are useful for imaging blood vessels. However, their prolonged retention is a major limitation for clinical use. Although smaller dendrimer-based MRI contrast agents are more quickly excreted by the kidneys, they are also able to visualize vascular structures better than Gd-DTPA due to less extravasation. Additionally, unlike Gd-DTPA, they transiently accumulate in renal tubules and thus also can be used to visualize renal structural and functional damage. However, these dendrimer agents are retained in the body for a prolonged time. The purpose of this study was to obtain information from which a macromolecular dendrimer-based MRI contrast agents feasible for use in further clinical studies could be chosen. Six small dendrimer-based MRI contrast agents were synthesized, and their pharmacokinetics, whole-body retention, and dynamic MRI were evaluated in mice to determine an optimal agent in comparison to Gd-[DTPA]-dimeglumine. Diaminobutane (DAB) dendrimer-based agents cleared more rapidly from the body than polyamidoamine (PAMAM) dendrimer-based agents with the same numbers of branches. Smaller dendrimer conjugates were more rapidly excreted from the body than the larger dendrimer conjugates. Since PAMAM-G2, DAB-G3, and DAB-G2 dendrimer-based contrast agents showed relatively rapid excretion, these three conjugates might be acceptable for use in further clinical applications. C1 NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD USA. NIH, Warren Grant Magnuson Clin Ctr, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Metab Branch, Canc Res Ctr, NIH, Bldg 10,Room 4N109,10 Ctr Dr, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov NR 31 TC 196 Z9 204 U1 4 U2 42 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 MAR-APR PY 2003 VL 14 IS 2 BP 388 EP 394 DI 10.1021/bc025633c PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 658JW UT WOS:000181718700017 PM 12643749 ER PT J AU Onda, M Vincent, JJ Lee, B Pastan, I AF Onda, M Vincent, JJ Lee, B Pastan, I TI Mutants of immunotoxin anti-tac(dsFv)-PE38 with variable number of lysine residues as candidates for site-specific chemical modification. 1. Properties of mutant molecules SO BIOCONJUGATE CHEMISTRY LA English DT Article ID NONSPECIFIC ANIMAL TOXICITY; HAIRY-CELL LEUKEMIA; RECOMBINANT IMMUNOTOXIN; POLYETHYLENE-GLYCOL; PSEUDOMONAS EXOTOXIN; ANTITUMOR-ACTIVITY; HEMATOLOGIC MALIGNANCIES; ANTIBODY-RESPONSE; ISOELECTRIC POINT; FV AB Chemical modification of proteins with substances such as poly(ethylene glycol) can add useful properties to proteins. Currently PEGylation is done in a random manner utilizing amino residues dispersed throughout a protein. For proteins such as immunotoxins, which have several different functional domains, random modification leads to inactivation. To determine if we could produce an immunotoxin with a diminished number of lysine residues so that chemical modification could be restricted to certain regions of the protein, we chose the recombinant immunotoxin anti-Tac(dsFv)PE38 that has 13 lysine residues in the Fv portion and 3 in the toxin. We prepared a series of mutants with 0-12 lysines in the Fv and 0 or 3 in the toxin. Almost all of these molecules retain full biological activity. Our data indicate that replacement of lysine residues can be achieve without loss of biological potency. These molecules are a useful starting point to carry out site-specific PEGylation experiments. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM pasta@helix.nih.gov NR 32 TC 10 Z9 11 U1 1 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 MAR-APR PY 2003 VL 14 IS 2 BP 480 EP 487 DI 10.1021/bc020069r PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 658JW UT WOS:000181718700028 PM 12643760 ER PT J AU Stern, MD Anisimov, SV Boheler, KR AF Stern, MD Anisimov, SV Boheler, KR TI Can transcriptome size be estimated from SAGE catalogs? SO BIOINFORMATICS LA English DT Article ID CELLS AB Motivation: SAGE ((S) under bar erial (A) under bar nalysis of (G) under bar ene (E) under bar xpression) can be used to estimate the number of unique transcripts in a transcriptome. A simple estimator that corrects for sequencing and sampling errors was applied to a SAGE library (137 832 tags) obtained from mouse embryonic stem cells, and also to Monte Carlo simulated libraries generated using assumed distributions of 'true' expression levels consistent with the data. Results: When the corrected data themselves were taken as the underlying model of 'ground truth', the estimator converged to the 'true' value (53 535) only after counting 300 000 simulated tags, more than twice the number in the experiment. The SAGE data could also be well fit by a Monte Carlo model based on a truncated inverse-square distribution of expression levels, with 130 000 'true' transcripts and 10(6) samples needed for convergence. We conclude that the size of a transcriptome is ill-determined from SAGE libraries of even moderately large size. In order to obtain a valid estimate, one must sample a number of tags inversely proportional to the lowest abundance level, which is not known a priori. This constrains the design of SAGE experiments intended to determine biological complexity. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Stern, MD (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 8 TC 21 Z9 22 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 MAR 1 PY 2003 VL 19 IS 4 BP 443 EP 448 DI 10.1093/bioinformatics/btg018 PG 6 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 652ZL UT WOS:000181410700001 PM 12611798 ER PT J AU Marenco, S Weinberger, DR Schreurs, BG AF Marenco, S Weinberger, DR Schreurs, BG TI Single-cue delay and trace classical conditioning in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE eyeblink conditioning; schizophrenia; cerebellum; hippocampus; learning ID NICTITATING-MEMBRANE RESPONSE; CEREBELLAR INTERPOSITUS NUCLEUS; POSITRON-EMISSION TOMOGRAPHY; TEMPORAL-LOBE LESIONS; EYELID RESPONSES; INTERSTIMULUS-INTERVAL; WITHDRAWAL REFLEX; ACQUISITION; CORTEX; DISCRIMINATION AB Background: Classical conditioning provides a means of addressing mechanisms of learning and can therefore help understand the pathophysiology of memory alteration in schizophrenia. Methods: Single cue delay and trace eyeblink conditioning were used in patients with schizophrenia and matched normal control subjects to explore, respectively, cerebellar and hippocampal integrity during learning. We measured percent of conditioned (CRs) and unconditioned responses (URs), their amplitude, and onset and peak latencies. We also accounted for spontaneous blink rates and stimulus-induced responses before learning. Results: During delay conditioning, patients showed CRs with longer onset and peak latencies and improved efficiency compared to normal volunteers without there being differences between patients and normal control subjects in the percentage of CRs. During trace conditioning, neither group showed an increase in CRs as a function of conditioned stimulus-unconditioned stimulus pairings, in part because the level of spontaneous blink rates exceeded the level of CRs; however, patients with schizophrenia,showed increased responding 150-400 msec after the conditioned stimulus and in the last 100-150 msec before the unconditioned stimulus, whereas normal control subjects showed only the latter type of responses. The former type of response was more frequent in patients with schizophrenia even before either trace or delay conditioning. Conclusions: These results suggest integrity of cerebellar mechanisms underlying conditioning, although the altered timing of CRs in patients may indicate differences in the modulation of such responses. Both the greater CR onset latency during delay and the presence of early nonadaptive responses during trace are compatible with the pattern of responding seen in animals with hippocampal damage. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. W Virginia Univ, Sch Med, Dept Physiol & Pharmacol, Morgantown, WV 26506 USA. W Virginia Univ, Sch Med, Blanchette Rockefeller Neurosci Inst, Morgantown, WV 26506 USA. RP Marenco, S (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bldg 10,Room 4 S235,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Marenco, Stefano/A-2409-2008; OI Marenco, Stefano/0000-0002-2488-2365; Schreurs, Bernard/0000-0002-5776-0807 NR 71 TC 26 Z9 27 U1 1 U2 3 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 MAR 1 PY 2003 VL 53 IS 5 BP 390 EP 402 DI 10.1016/S0002-3223(03)01506-8 PG 13 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 649RA UT WOS:000181220700004 PM 12614992 ER PT J AU Hibbeln, JR Makino, KK Martin, CE Dickerson, F Boronow, J Fenton, WS AF Hibbeln, JR Makino, KK Martin, CE Dickerson, F Boronow, J Fenton, WS TI Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition among patients with schizophrenia or schizoaffective disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE smoking; schizophrenia; docosahexaenoic acid; eicosapentaenoic acid; arachidonic acid; omega-3 fatty acids ID MAGNETIC-RESONANCE SPECTROSCOPY; MEMBRANE PHOSPHOLIPID-METABOLISM; PURIFIED EICOSAPENTAENOIC ACID; FOOD FREQUENCY QUESTIONNAIRE; HIGH-ENERGY PHOSPHATE; DOCOSAHEXAENOIC ACID; LIPID-PEROXIDATION; FRONTAL-LOBE; CYTOSOLIC PHOSPHOLIPASE-A2; PSYCHIATRIC-PATIENTS AB Background: Prior reports of decreased levels of essential fatty acids among schizophrenic patients have generated several hypotheses proposing inherent abnormalities in phospholipid and fatty acid metabolism and have provided the basis for treatment trials; however, these essential fatty acid aberrations may be attributable to uncontrolled factors, such as smoking, rather than abnormalities inherent to schizophrenia. Methods: Erythrocyte fatty acid compositions were quantified in 72 medicated schizophrenic or schizoaffective patients both at baseline and after 16 weeks of supplementation with 3 g/day of either ethyl-eicosapentaenoic acid or placebo. Current smoking status, gender, dietary survey, and Montgomery Asburg Depression Rating Scale, Repeatable Battery for the Assessment of Neuropsychological Status, Abnormal Involuntary Movement Scale, and Positive and Negative Syndrome Scale scores were assessed. Results: Schizophrenic patients who smoked had lower baseline erythrocyte docosahexaenoic acid percent (2.98+/-.7 vs. 3.59 +/- 1.2, p <.005) and eicosapentaenoic acid (EPA) percent (.39 +/- .13 vs. .47 +/- .22, p <.05), compared with nonsmokers, with a significant gender interaction (p <.01) in multivariate analyses of variance. Baseline arachidonic acid did not differ. Smokers reported lower dietary intake (percent total fat) of linolenic acid (F = 10.1, p <.003) compared with nonsmokers. Nonsmoking women reported greater dietary intake of EPA compared with smoking men or nonsmokers of either gender. Conclusions: Smoking status, gender, and dietary intake significantly predicted erythrocyte polyunsaturated fatty acid status among schizophrenic patients. No evidence was found for subgroups of schizophrenia or relationships to specific symptom severity on the basis of erythrocyte fatty acids. Prior reports of abnormalities of essential fatty acid metabolism among schizophrenic patients may have been an artifact of patients' smoking behavior and differences in dietary intake of omega-3 fatty acids. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. NIMH, Off Director, NIH, Bethesda, MD 20892 USA. Sheppard & Enoch Pratt Hosp, Baltimore, MD 21204 USA. RP Hibbeln, JR (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 12420 Parklawn Dr,Pk 5,Room 150, Rockville, MD 20852 USA. NR 90 TC 83 Z9 84 U1 0 U2 0 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 MAR 1 PY 2003 VL 53 IS 5 BP 431 EP 441 DI 10.1016/S0002-3223(03)01549-4 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 649RA UT WOS:000181220700008 PM 12614996 ER PT J AU Bishop, MR Hou, JWS Wilson, WH Steinberg, SM Odom, J Castro, K Kasten-Sportes, C Gea-Banacloche, J Marchigiani, D Gress, R Fowler, DH AF Bishop, MR Hou, JWS Wilson, WH Steinberg, SM Odom, J Castro, K Kasten-Sportes, C Gea-Banacloche, J Marchigiani, D Gress, R Fowler, DH TI Establishment of early donor engraftment after reduced-intensity allogeneic hematopoietic stem cell transplantation to potentiate the graft-versus-lymphoma effect against refractory lymphomas SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE non-Hodgkin's lymphoma; allogeneic; reduced intensity; chimerism ID NON-HODGKINS-LYMPHOMA; BONE-MARROW TRANSPLANTATION; MALIGNANT-LYMPHOMA; DISEASE RESPONSE; MIXED CHIMERISM; HOST DISEASE; CHEMOTHERAPY; THERAPY; BLOOD; FLUDARABINE AB Reduced-intensity allogeneic hematopoietic stem cell transplantation (alloHSCT), which typically results in mixed chimerism initially after transplantation, has had limited efficacy in chemotherapy-refractory lymphomas. We hypothesized that the rapid establishment of complete donor chimerism would potentiate a graft-versus-lymphoma effect. Fifteen patients with chemotherapy-refractory lymphoma initially received induction with a conventional chemotherapy regimen (etoposide, prednisone, vincristine, cyclophosphamide, adriamycin, fludarabine [EPOCH-F]) to deplete host T cells and provide disease control prior to alloHSCT. Patients then received conditioning with fludarabine and cyclophosphamide followed by alloHSCT from HLA-matched siblings. Graft-versus-host disease prophylaxis consisted of cyclosporine alone. EPOCH-F resulted in 73 % of patients having partial responses or stable disease. EPOCH-F depleted host CD4(+) T cells from a median of 235 cells/muL to 56 cells/muL. Fourteen patients underwent alloHSCT, and all had >95% donor engraftment by day 14 after transplantation. The incidence of Grade II to III acute graft-versus-host disease was 71%. There were two therapy-related deaths. There were 8 partial responses and 3 complete responses (CRs) at day 28. Five additional CRs were observed at day 100 without withdrawal of cyclosporine or donor lymphocyte infusion. The rate of CRs for all 15 patients was 60%. The 1-year progression-free survival rate from time of study entry is 67% with only 1 relapse among 9 CRs. At a median potential follow-up of 28 months, the overall survival rate is 53%. These data demonstrate that a potent and durable graft-versus-lymphoma effect can occur against chemotherapy-refractory lymphomas and suggest that this effect may be associated with rapid, complete donor chimerism after reduced-intensity alloHSCT. (C) 2003 American Society for Blood and Marrow Transplantation. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Bishop, MR (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 44 TC 32 Z9 32 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2003 VL 9 IS 3 BP 162 EP 169 DI 10.1053/bbmt.2003.50008 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 661ZK UT WOS:000181920400003 PM 12652466 ER PT J AU Sackett, DL Chernomordik, V Krueger, S Nossal, R AF Sackett, DL Chernomordik, V Krueger, S Nossal, R TI Use of small-angle neutron scattering to study tubulin polymers SO BIOMACROMOLECULES LA English DT Article ID DEUTERIUM-OXIDE; X-RAY; MICROTUBULE POLYMERIZATION; LOW RESOLUTION; HEAVY-WATER; PROTEIN; INSTABILITY; DIFFRACTION; MICROSCOPY; ACTIVATION AB Small-angle neutron scattering has been used to examine taxol-stabilized microtubules and other tubulin samples in both H2O and D2O buffers. Measurements were made at pH/pD values between 6.0 and 7.8, and observed scattered intensities, I(Q), have been interpreted in terms of multicomponent models of microtubules and related tubulin polymers. A semiquantitative curve fitting procedure has been used to estimate the relative amounts of the supramolecular components of the samples. At both pH and pD 7.0 and above, the tubulin polymers are seen to be predominantly microtubules. Although in H2O buffer the polymer distribution is little changed as the pH varies, when pD is lowered the samples appear to contain an appreciable amount of sheetlike structures and the average microtubule protofilament number increases from ca. 12.5 at pD greater than or equal to approximate to7.0 to ca. 14 at pD approximate to6.0. Such structural change indicates that analysis of microtubule solutions based on H2O/D2O contrast variation must be performed with caution, especially at lower pH/pD. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Natl Inst Stand & Technol, NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. RP Nossal, R (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NR 45 TC 7 Z9 7 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD MAR-APR PY 2003 VL 4 IS 2 BP 461 EP 467 DI 10.1021/bm025760b PG 7 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 654KP UT WOS:000181496300036 PM 12625746 ER PT J AU Phillips, TM Smith, P AF Phillips, TM Smith, P TI Analysis of intracellular regulatory proteins by immunoaffinity capillary electrophoresis coupled with laser-induced fluorescence detection SO BIOMEDICAL CHROMATOGRAPHY LA English DT Article DE immunoaffinity capillary electrophoresis; laser-induced fluorescence; regulatory protein measurement; protein phosphorylation ID SIGNAL-TRANSDUCTION; CYTOKINES; DISEASE; CELLS; PATHOGENESIS; ACTIVATION; FLUIDS; KINASE AB Measurement of intracellular regulatory proteins is of great importance in many areas of biomedical research. In this communication we describe an antibody-based capillary electrophoresis system equipped with an on-line laser-induced fluorescence detector capable of measuring intracellular proteins in cultures as low as 100 cells. The system demonstrated a high degree of precision and accuracy, being capable of detecting the fluorochrome-labeled analytes of interest at concentration of approximately 0.5 pg. We have used this instrument to study concentrations of the intracellular regulatory proteins STAT-1 and STAT-3, following stimulation of lymphocyte cultures with the inflammatory cytokine, IL-6. Using a combination of four antibodies specific for either STAT-1 or STAT-3 in both their nonphosphorylated and phosphorylated forms, we were able to demonstrate the differential expression of these proteins over time. Copyright (C) 2003 John Wiley Sons, Ltd. C1 NIH, ORS, DBEPS, UAIR, Bethesda, MD 20892 USA. RP Phillips, TM (reprint author), NIH, ORS, DBEPS, UAIR, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 29 TC 26 Z9 26 U1 1 U2 3 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 MAR-APR PY 2003 VL 17 IS 2-3 BP 182 EP 187 DI 10.1002/bmc.240 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 673UT UT WOS:000182599200015 PM 12717808 ER PT J AU Haverkos, HW Soon, GX Steckley, SL Pickworth, W AF Haverkos, HW Soon, GX Steckley, SL Pickworth, W TI Cigarette smoking and cervical cancer: Part I: a meta-analysis SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Review DE cigarette smoking; cervical cancer; meta-analysis ID HUMAN-PAPILLOMAVIRUS INFECTION; ORAL-CONTRACEPTIVE USE; SIMPLEX VIRUS TYPE-2; HIGH-GRADE DYSPLASIA; RISK-FACTORS; INTRAEPITHELIAL NEOPLASIA; SEXUAL-BEHAVIOR; UTERINE CERVIX; CARCINOMA INSITU; UNITED-STATES AB Cancer of the cervix is the third most common cancer among women worldwide and its etiology is not clearly understood. Human papillomavirus can be found in approximately 95% of cervical cancers, but it does not appear to be necessary or sufficient to. induce malignancy. In 1977, Winkelstein suggested that cigarette smoking was a causative factor in the development of cervical cancer. We report a meta-analysis of cigarette smoking and cervical disease and conclude that the data support a role for cigarette smoking as a risk factor for cervical cancer. We propose a multifactorial hypothesis involving a virus-tar interaction as the etiology of cervical cancer. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 Walter Reed Army Med Ctr, Dept Med, Infect Dis Serv, Washington, DC 20307 USA. US FDA, Ctr Drug Evaluat & Res, Div Antiviral Drug Prod, Rockville, MD 20857 USA. NIDA, Baltimore, MD USA. RP Haverkos, HW (reprint author), Walter Reed Army Med Ctr, Dept Med, Infect Dis Serv, Washington, DC 20307 USA. NR 107 TC 43 Z9 46 U1 0 U2 7 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD MAR PY 2003 VL 57 IS 2 BP 67 EP 77 DI 10.1016/S0753-3322(02)00341-4 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 677BX UT WOS:000182788000001 PM 12854514 ER PT J AU Steckley, SL Pickworth, WB Haverkos, HW AF Steckley, SL Pickworth, WB Haverkos, HW TI Cigarette smoking and cervicalciancer: Part II: a geographic variability study SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Review DE cervical cancer; smoking; multifactorial ID HUMAN-PAPILLOMAVIRUS; CHLAMYDIA-TRACHOMATIS; CANCER AB Cigarette smoking is considered a causative factor in a variety of cancers. However, the role of smoking in cervical cancer is disputed, in part because women who smoke may have other risk factors for cervical cancer, particularly HPV infection. We reviewed cigarette smoking prevalence, cervical and lung cancer incidence, and gross domestic product (GDP) per capita in the US and 73 other countries. It appears that smoking may play a prominent role in cervical cancer in developing countries, but less of a role in other countries. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 NIDA, Addict Res Ctr, Intramural Res Program, NIH, Baltimore, MD USA. Walter Reed Army Med Ctr, Dept Med, Infect Dis Serv, Washington, DC 20307 USA. RP Pickworth, WB (reprint author), NIDA, Addict Res Ctr, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD USA. NR 16 TC 11 Z9 12 U1 0 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD MAR PY 2003 VL 57 IS 2 BP 78 EP 83 DI 10.1016/S0753-3322(02)00342-6 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 677BX UT WOS:000182788000002 PM 12842492 ER PT J AU Hetz, C Monardes, V Lisboa, P Munroe, D Leyton, L Quest, AFG AF Hetz, C Monardes, V Lisboa, P Munroe, D Leyton, L Quest, AFG TI Identification by transcription profiling in human colon carcinoma cells of genes regulated by tumor suppressor Caveolin-1 SO BIOMETALS LA English DT Editorial Material C1 Univ Chile, Fac Med, Inst Ciencias Biomed, Santiago, Chile. NCI, Microarray Lab, Mol Transfer Ctr, Bethesda, MD 20892 USA. RP Hetz, C (reprint author), Univ Chile, Fac Med, Inst Ciencias Biomed, Independencia 1027, Santiago, Chile. RI Hetz, Claudio/I-1900-2013 OI Hetz, Claudio/0000-0001-7724-1767 NR 0 TC 0 Z9 0 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0966-0844 J9 BIOMETALS JI Biometals PD MAR PY 2003 VL 16 IS 1 BP 233 EP 233 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 605HB UT WOS:000178671000030 ER PT J AU Dunson, DB Chulada, P Arbes, SJ AF Dunson, DB Chulada, P Arbes, SJ TI Bayesian modeling of time-varying and waning exposure effects SO BIOMETRICS LA English DT Article DE effect modifiers; exponential decay; exposure history; Gibbs sampling; piecewise polynomial; proportional hazards; time-dependent covariates; varying-coefficient model ID CENSORED SURVIVAL-DATA; REGRESSION-MODEL; COX REGRESSION; INFERENCE AB In epidemiologic studies, there is often interest in assessing the association between exposure history and disease incidence. For many diseases, incidence may depend not only on cumulative exposure, but also on the ages at which exposure occurred. This article proposes a flexible Bayesian approach for modeling age-varying and waning exposure effects. The Cox model is generalized to allow the hazard of disease to depend on an integral, across the exposed ages, of a piecewise polynomial function of age, multiplied by an exponential decay term. Linearity properties of the model facilitate posterior computation via a Gibbs sampler, which generalizes previous algorithms for Cox regression with time-dependent covariates. The approach is illustrated by an application to the study of protective effects of breastfeeding on incidence of childhood asthma. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pulm Pathol, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM dunson1@niehs.nih.gov NR 25 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2003 VL 59 IS 1 BP 83 EP 91 DI 10.1111/1541-0420.00010 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 663GG UT WOS:000181997400010 PM 12762444 ER PT J AU Chanturiya, A Yang, JP Scaria, P Stanek, J Frei, J Mett, H Woodle, M AF Chanturiya, A Yang, JP Scaria, P Stanek, J Frei, J Mett, H Woodle, M TI New cationic lipids form channel-like pores in phospholipid bilayers SO BIOPHYSICAL JOURNAL LA English DT Article ID GENE-TRANSFER; NASAL EPITHELIUM; CYSTIC-FIBROSIS; DNA; COMPLEXES; MECHANISM; LIPOSOMES; DELIVERY; MEMBRANES; EFFICACY AB Two representatives of a new class of cationic lipids were found to have high pore-forming activity in planar bilayer membranes. These molecules, called BHHD-TADC and BHTD-TADC, have qualitatively similar effects on phospholipid membranes. Addition of 2.5-5 muM of either of them to the membrane bathing solutions resulted in formation of long-lived anion-selective pores with conductance in the range 0.1-2 nS in 0.1 M KCl. Pore formation was found to be dependent on the potential applied to the membrane. When negative potential was applied to membrane at the side of addition, the rate of pore formation was much lower compared to when the positive potential was applied. Dependence of pore formation on compound concentration was highly nonlinear, indicating that this process requires assembly of molecules in the membrane. Addition of any of these compounds on both sides of the membrane increased the efficiency of pore formation by one to two orders of magnitude. Pore formation was strongly pH dependent. Although pores were formed with high efficiency at pH 6.5, only occasional fluctuations of membrane conductance were observed at pH 7.5. Possible mechanisms of new compounds biological activity are discussed. C1 Genet Therapy Inc, Gaithersburg, MD 20878 USA. Natl Inst Child Hlth & Human Dev, Lab Cellular & Biophys, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Intradigm Corp, Bethesda, MD 20817 USA. Novartis Pharma AG, Therapeut Area Oncol, CH-4002 Basel, Switzerland. RP Yang, JP (reprint author), Genet Therapy Inc, Gaithersburg, MD 20878 USA. NR 22 TC 10 Z9 10 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 2003 VL 84 IS 3 BP 1750 EP 1755 PG 6 WC Biophysics SC Biophysics GA 682ZY UT WOS:000183123000027 PM 12609876 ER PT J AU Zanuy, D Ma, BY Nussinov, R AF Zanuy, D Ma, BY Nussinov, R TI Short peptide amyloid organization: Stabilities and conformations of the islet amyloid peptide NFGAIL SO BIOPHYSICAL JOURNAL LA English DT Article ID SOLID-STATE NMR; BETA-SHEET; ALZHEIMERS-DISEASE; MOLECULAR-DYNAMICS; FIBRIL FORMATION; POLYPEPTIDE; FIBRILLOGENESIS; IDENTIFICATION; OLIGOMERS; PARALLEL AB Experimentally, short peptides have been shown to form amyloids similar to those of their parent proteins. Consequently, they present useful systems for studies of amyloid conformation. Here we simulate extensively the NFGAIL peptide, derived from the human islet amyloid polypeptide (residues 22-27). We simulate different possible strand/sheet organizations, from dinners to nonamers. Our simulations indicate that the most stable conformation is an antiparallel strand orientation within the sheets and parallel between sheets. Consistent with the alanine mutagenesis, we find that the driving force is the hydrophobic effect. Whereas the NFGAIL forms stable oligomers, the NAGAIL oligomer is unstable, and disintegrates very quickly after the beginning of the simulation. The simulations further identify a minimal seed size. Combined with our previous simulations of the prion-derived AGAAAAGA peptide, AAAAAAAA, and the Alzheimer Abeta fragments 16-22, 24-36,16-35, and 10-35, and the solid-state NMR data for Abeta fragments 16-22,10-35, and 1-40, some insight into the length and the sequence matching effects may be obtained. C1 NCI Frederick, Lab Expt & Computat Biol, Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. NCI Frederick, Lab Expt & Computat Biol, Intramural Res Support Program, Sci Applicat Int Corp, Ft Detrick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI Frederick, Lab Expt & Computat Biol, Canc Res & Dev Ctr, Bldg 469,Rm 151, Ft Detrick, MD 21702 USA. RI Ma, Buyong/F-9491-2011; Zanuy, David/G-3930-2014 OI Ma, Buyong/0000-0002-7383-719X; Zanuy, David/0000-0001-7704-2178 FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 33 TC 78 Z9 81 U1 2 U2 14 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 2003 VL 84 IS 3 BP 1884 EP 1894 PG 11 WC Biophysics SC Biophysics GA 682ZY UT WOS:000183123000041 PM 12609890 ER PT J AU Gebreyesus, KH Owens, RA AF Gebreyesus, KH Owens, RA TI Selective protection of restriction endonuclease sites SO BIOTECHNIQUES LA English DT Article ID CLONING; INFECTIVITY; SEQUENCE; DNA AB A difficulty that is encountered when attempting to insert a PCR-amplified product or DNA fragment of interest into a particular vector is the presence within the insert Of or more internal restriction endonuclease (RE) sites identical to those selected for the flanks of the insert. Our method circumvents this problem by partially protecting internal RE sites while flanking sites for the same RE are cleaved. The amplified product is first heat denatured in the presence of excess amounts of perfectly complementary oligonucleotides that can anneal to the flanks of the insert. The mixture is allowed to anneal and is subsequently digested with the appropriate endonucleases. This results in the cleavage of the flanking RE sites while digestion at the internal RE site is not efficient. The mixture is subsequently heat denatured and column purified to remove the oligonucleotides. The product is then allowed to anneal and can be used directly in a ligation reaction with the plasmid vector. This method facilitates the construction of recombinant molecules by creating desired flanks while preserving internal RE sites. C1 NIDDK, Mol & Cellular Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Owens, RA (reprint author), NIDDK, Mol & Cellular Biol Lab, NIH, Dept Hlth & Human Serv, Bldg 8,Rm 310,8 Ctr Dr MSC 0840, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 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 MAR PY 2003 VL 34 IS 3 BP 512 EP + PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 654AZ UT WOS:000181471500015 PM 12661157 ER PT J AU Simon, RM Dobbin, K AF Simon, RM Dobbin, K TI Experimental design of DNA microarray experiments SO BIOTECHNIQUES LA English DT Article ID MOLECULAR CLASSIFICATION; CLASS DISCOVERY; EXPRESSION C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Simon, RM (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike,MSC 7434, Bethesda, MD 20892 USA. NR 9 TC 27 Z9 29 U1 2 U2 6 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAR PY 2003 SU S BP 16 EP + PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 656EM UT WOS:000181595900003 ER PT J AU El Ouriaghli, F Fujiwara, H Melenhorst, JJ Sconocchia, G Hensel, N Barrett, AJ AF El Ouriaghli, F Fujiwara, H Melenhorst, JJ Sconocchia, G Hensel, N Barrett, AJ TI Neutrophil elastase enzymatically antagonizes the in vitro action of G-CSF: implications for the regulation of granulopoiesis SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; LEUKOCYTE ELASTASE; GROWTH-FACTOR; CATHEPSIN-G; IN-VITRO; GRANULOCYTE; INHIBITOR; LEUKEMIA; HEMATOPOIESIS; E-ALPHA-1-PI AB There is evidence that neutrophil production is a balance between the proliferative action of granulocyte-colony-stimulating factor (G-CSF) and a negative feedback from mature neutrophils (the chalone). Two neutrophil serine proteases; have been implicated in granulopoietic regulation: pro-proteinase 3 inhibits granulocyte macrophage-colony-forming unit (CFU-GM) growth, and elastase mutations cause cyclic and congenital neutropenia. We further studied the action of the neutrophil serine proteases (proteinase 3, elastase, azurocidin, and cathepsin G) on granulopoiesis in vitro. Elastase inhibited CFU-GM in methylcellulose culture. In serum-free suspension cultures of CD34(+) cells, elastase completely abrogated the proliferation induced by G-CSF but not that of GM-CSF or stem cell factor (SCF). The blocking effect of elastase was prevented by inhibition of its enzymatic activity with phenylmethylsulfonyl fluoride (PMSF) or heat treatment. When exposed to enzymatically active elastase, G-CSF, but not GM-CSF or SCF, was rapidly cleaved and rendered inactive. These results support a role for neutrophil elastase in providing negative feedback to granulopoiesis by direct antagonism of G-CSF. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 66 Z9 69 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 MAR 1 PY 2003 VL 101 IS 5 BP 1752 EP 1758 DI 10.1182/blood-2002-06-1734 PG 7 WC Hematology SC Hematology GA 648EE UT WOS:000181136200015 PM 12393522 ER PT J AU Warming, S Liu, P Suzuki, T Akagi, K Lindtner, S Pavlakis, GN Jenkins, NA Copeland, NG AF Warming, S Liu, P Suzuki, T Akagi, K Lindtner, S Pavlakis, GN Jenkins, NA Copeland, NG TI Evi3, a common retroviral integration site in murine B-cell lymphoma, encodes an EBFAZ-related Kruppel-like zinc finger protein SO BLOOD LA English DT Article ID DIFFERENTIATION; IDENTIFICATION; INITIATION; STRAINS; CLONING; LACKING; MODELS; ROAZ; E2A AB Retroviral insertional mutagenesis in inbred mouse strains provides a powerful method for cancer gene discovery. Here, we show that a common retroviral integration site (RIS) in AKXD B-cell lymphomas, termed Evi3, encodes at novel zinc finger protein with 30 Kruppel-like zinc finger repeats. Most integrations at Evi3 are located upstream of the first translated exon and result in 3' long-terminal repeat (LTR)-driven overexpression of Evi3. Evi3 is highly related to the early B-cell factor-associated zinc finder gene (Ebfaz), and all 30 zinc fingers found in Evi3 are conserved in EBFAZ. EBFAZ binds to and negatively regulates early B-cell factor (EBF) (also known as olfactory-1, OLF1), a basic helix-loop-helix (bHLH) transcription factor required for B-lineage commitment and the development of the olfactory epithelium. EBFAZ also binds to SMA- and MAD-related protein-1 (SMAD1) and SMAD4 in response to bone morphogenetic protein-2 (BMP2) signaling, which in turn activates the homeobox regulator of Xenopus mesoderm and neural development Xvent-2. Surprisingly, while Ebfaz and Evi3 are coexpressed in many tissues, and both proteins are nuclear, we could not detect Ebfaz expression in B cells by reverse transcriptase-polymerase chain reaction (RT-PCR), whereas Evi3 expression could be detected at all stages of B-cell development. Our results suggest that EVI3, like EBFAZ, is a multifunctional protein that participates in many signaling pathways via its multiple zinc fingers. Furthermore, our results suggest that EVI3, not EBFAZ, is the member of this protein family that interacts with and regulates EBF in B cells. C1 NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. NCI, Basic Res Lab, Frederick, MD 21702 USA. RP Copeland, NG (reprint author), NCI, Mouse Canc Genet Program, Bldg 539,Rm 229, Frederick, MD 21702 USA. NR 17 TC 46 Z9 49 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 MAR 1 PY 2003 VL 101 IS 5 BP 1934 EP 1940 DI 10.1182/blood-2002-08-2652 PG 7 WC Hematology SC Hematology GA 648EE UT WOS:000181136200041 PM 12393497 ER PT J AU Metayer, C Curtis, RE Vose, J Sobocinski, KA Horowitz, MM Bhatia, S Fay, JW Freytes, CO Goldstein, SC Herzig, RH Keating, A Miller, CB Nevill, TJ Pecora, AL Rizzo, JD Williams, SF Li, CY Travis, LB Weisdorf, DJ AF Metayer, C Curtis, RE Vose, J Sobocinski, KA Horowitz, MM Bhatia, S Fay, JW Freytes, CO Goldstein, SC Herzig, RH Keating, A Miller, CB Nevill, TJ Pecora, AL Rizzo, JD Williams, SF Li, CY Travis, LB Weisdorf, DJ TI Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: a multicenter case-control study SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; STEM-CELL TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; THERAPY-RELATED MYELODYSPLASIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; AUTOLOGOUS TRANSPLANTATION; SECONDARY LEUKEMIA; BEAM CHEMOTHERAPY; LATE COMPLICATION AB Although numerous reports indicate that patients receiving autotransplants for lymphoma are at increased risk for myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), the separate contributions of pretransplantation- and transplantation-related therapy are not well characterized. We conducted a case-control study of 56 patients with MDS/AML and 168 matched controls within a cohort of 2 739 patients receiving autotransplants for Hodgkin disease or non-Hodgkin lymphoma at 12 institutions (1989-1995). Detailed abstraction of medical records was undertaken to determine all pre- and post-transplantation therapy, and transplantation-related procedures. In multivariate analyses, risks of MDS/AML significantly increased with the intensity of pretransplantation chemotherapy with mechlorethamine (relative risks [RRs] = 2.0 and 4.3 for cumulative doses <50 mg/m(2) and a 50 mg/m(2) respectively; trend over dose categories, P = .04) or chlorambucil (RRs = 3.8 and 8.4 for duration <10 months or greater than or equal to10 months, respectively; trend, P = .009), compared With cyclophosphamide-based therapy. Transplantation-conditioning,regimens including total-body irradiation (TBI) at doses 12 Gy or less did not appear to elevate leukemia risk (FIR = 1.3; P = .48) compared with non-TBI regimens; however, a statistically significant increased risk was found for TBI doses of 13.2 Gy (RR = 4.6 P = .03). Peripheral blood stem cells were associated with a nonsignificant increased risk of MDS/AML (Rh = 1.8; P = .12) compared, With bone marrow grafts. Our data show that type and intensity of pretransplantation chemotherapy with alkylating agents are important risk factors of MDS/AML following autotransplantation. Transplantation-related factors may also modulate this risk; however, the apparent contribution of high-dose TBI requires confirmation. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. Med Coll Wisconsin, Autologous Blood & Bone Marrow Transplant Registr, Milwaukee, WI 53226 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Baylor Univ, Med Ctr, Dallas, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Louisville Hosp, Louisville, KY USA. Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. Johns Hopkins Oncol Ctr, Baltimore, MD USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Vancouver Gen Hosp, Vancouver, BC, Canada. Hackensack Univ, Med Ctr, Ctr Canc, Hackensack, NJ USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Mayo Clin, Rochester, MN USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP Curtis, RE (reprint author), NCI, Div Canc Epidemiol & Genet, Execut Plaza S,Rm 7042, Bethesda, MD 20892 USA. FU NCI NIH HHS [CP-21161, P01-CA-40053, U24-CA76518] NR 51 TC 106 Z9 110 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 MAR 1 PY 2003 VL 101 IS 5 BP 2015 EP 2023 DI 10.1182/blood-2002-04-1261 PG 9 WC Hematology SC Hematology GA 648EE UT WOS:000181136200054 PM 12393427 ER PT J AU Alter, BP Greene, MH Velazquez, I Rosenberg, PS AF Alter, BP Greene, MH Velazquez, I Rosenberg, PS TI Cancer in Fanconi anemia SO BLOOD LA English DT Letter C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA. RP Alter, BP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, 6120 Execut Blvd,Execut Plaza S 7020, Bethesda, MD 20892 USA. NR 5 TC 92 Z9 93 U1 0 U2 3 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 MAR 1 PY 2003 VL 101 IS 5 BP 2072 EP 2073 DI 10.1182/blood-2002-11-3597 PG 2 WC Hematology SC Hematology GA 648EE UT WOS:000181136200066 PM 12584146 ER PT J AU Kundu, M Liu, PP AF Kundu, M Liu, PP TI Cbf beta is involved in maturation of all lineages of hematopoietic cells during embryogenesis except erythroid SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article; Proceedings Paper CT Symposium on Transcriptional Regulation of RUNX Proteins in Development and Leukemia CY AUG 25-27, 2002 CL UNIV VIRGINIA, CHARLOTTESVILLE, VIRGINIA SP Leukemia & Lymphoma Soc HO UNIV VIRGINIA ID BINDING-FACTOR-BETA; FETAL LIVER HEMATOPOIESIS; FUSION GENE CBFB-MYH11; ACUTE MYELOID-LEUKEMIA; OSTEOBLAST DIFFERENTIATION; CLEIDOCRANIAL DYSPLASIA; BONE-DEVELOPMENT; STEM-CELLS; EXPRESSION; AML1 AB The transcription factor Cbfbeta forms a heterodimeric complex with members of the Runx family of proteins. Together, Cbfbeta and Runx I play a critical role in the establishment of definitive hematopoiesis in mouse embryos. Previously, we used a Cbfb-GFP "knock-in" mouse model to demonstrate that Cbfbeta is expressed in hematopoietic stem cells of the mouse fetal liver and aorta-gonad-mesonephros (Blood 100 (2002), 2449). We also examined the expression pattern of Cbfbeta in different lineages of adult hematopoietic cells and found that it is expressed uniformly in all lineages except B lymphocytes and erythroid cells. Cbfbeta expression decreases during maturation of B cells in the adult bone marrow, and is not expressed in nucleated erythroid precursors. Here, we examine the expression of Cbfbeta in various hematopoietic lineages, including myeloid, lymphoid, and erythroid during late stages of embryonic development, and compare it to the pattern observed in adults. We find that there are subtle differences in expression of Cbfbeta-GFP in embryonic hematopoietic cells compared to their adult counterparts, but that the overall pattern is the same. Our data complement recently published data on hematopoetic defects observed in transgenic Cbfb-null mouse embryos partially rescued by ectopic expression of Cbfb (Nature Genet. 32 (2002), 633; Nature Genet. 32 (2002), 645). and supports the emerging view that Cbfbeta and Runx proteins are required for normal maturation of hematopoietic cells as well as establishment of definitive hematopoiesis. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NHGRI, Oncogenesis & Dev Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Liu, PP (reprint author), NHGRI, Oncogenesis & Dev Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Bldg 49,Room 3A26, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 31 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2003 VL 30 IS 2 BP 164 EP 169 DI 10.1016/S1079-9796(03)00030-5 PG 6 WC Hematology SC Hematology GA 682CG UT WOS:000183072600004 PM 12732179 ER PT J AU Costa, P AF Costa, P TI A theoretical context for adult temperament SO BRAIN AND COGNITION LA English DT Meeting Abstract C1 NIA, Lab Personal & Cognit, Gerontol Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD MAR PY 2003 VL 51 IS 2 BP 160 EP 161 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 669PX UT WOS:000182360600005 ER PT J AU Ellis, CA Vos, MD Wickline, M Riley, C Vallecorsa, T Telford, WG Zujewski, J Clark, GJ AF Ellis, CA Vos, MD Wickline, M Riley, C Vallecorsa, T Telford, WG Zujewski, J Clark, GJ TI Tamoxifen and the farnesyl transferase inhibitor FTI-277 synergize to inhibit growth in estrogen receptor-positive breast tumor cell lines SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE apoptosis; breast; farnesyl transferase inhibitor; Ras; tamoxifen ID FARNESYLTRANSFERASE INHIBITORS; INDUCED APOPTOSIS; CANCER-CELLS; K-RAS; ANTIESTROGEN ACTION; TRANSFORMED-CELLS; CARCINOMA CELLS; TRANSGENIC MICE; PHASE-I; N-RAS AB Farnesyl transferase inhibitors (FTIs) serve to specifically inhibit farnesyl isoprenoid lipid modification of proteins. Although originally developed as anti-Ras oncoprotein drugs, it now appears that these compounds function independently of Ras. FTIs have been shown to inhibit transformation by a variety of mechanisms, including apoptosis involving cytochrome c release from mitochondria. Tamoxifen exhibits both anti-estrogenic and estrogenic properties and is widely used as an estrogen antagonist for the treatment of estrogen receptor (ER) positive human breast tumors. Tamoxifen can induce ER-dependent apoptosis in human breast tumor cells by a mechanism involving the Bcl2/mitochondrial arm of the apoptotic machinery. Since tamoxifen and FTIs may stimulate distinct components of the mitochondrial-based apoptotic machinery, we reasoned that their effects might be synergistic. Here we show that anti-estrogens and an FTI (FTI-277) synergize to inhibit cell growth and enhance cell death in ER positive, human breast tumor cell lines. However, the drugs exhibited only additive effects on an ER negative cell line. Analysis of treated ER positive T-47D cells demonstrated that a synergistic increase in apoptosis was induced, as measured by increased caspase 3 activity. Thus, tamoxifen and FTIs may synergize to promote apoptotic cell death in ER positive human breast tumor cells. C1 NCI, Dept Cell & Canc Biol, Rockville, MD 20850 USA. MB FABS Core, Bethesda, MD USA. RP Clark, GJ (reprint author), NCI, Dept Cell & Canc Biol, Room 307,9610 Med Ctr Dr, Rockville, MD 20850 USA. NR 52 TC 26 Z9 29 U1 0 U2 0 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 MAR PY 2003 VL 78 IS 1 BP 59 EP 67 DI 10.1023/A:1022105511409 PG 9 WC Oncology SC Oncology GA 639WD UT WOS:000180651700008 PM 12611458 ER PT J AU Bolan, CD Carter, CS Wesley, RA Yau, YY Barrett, AJ Childs, RW Read, EJ Leitman, SF AF Bolan, CD Carter, CS Wesley, RA Yau, YY Barrett, AJ Childs, RW Read, EJ Leitman, SF TI Prospective evaluation of cell kinetics, yields and donor experiences during a single large-volume apheresis versus two smaller volume consecutive day collections of allogeneic peripheral blood stem cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE allogeneic; large-volume leukapheresis; peripheral blood stem cells ID PROGENITOR CELLS; G-CSF; LEUKAPHERESIS PROCEDURES; CROSSOVER TRIAL; CD34+ CELLS; WHITE CELL; MOBILIZATION; TRANSPLANTATION; FILGRASTIM; SAFETY AB We report cell kinetics, yields and donation experiences of 20 demographically matched allogeneic peripheral blood stem cell (PBSC) donors who were prospectively assigned to undergo either a single 25 l or two consecutive daily 15 l (15 l x 2) apheresis procedures. Procedures were performed using prophylactic intravenous calcium administration after standard granulocyte colony-stimulating factor (GCSF) mobilization (10 mug/kg/d). Central line placements (two each), initial CD34 cell counts (0.077 vs 0.078 x 10(9) /l) and yields (7.9 vs 8.1 x 10(8) CD34 cells) were similar in the two groups; however, 25 l donors spent significantly less time both in the clinic (7.5 vs 10.8 h) and with central venous catheters in place (8.5 vs 29.5 h) than 15 l x 2 donors. End-procedure platelet counts were below 100 x 10(9)/l in one out of 10 25 l donors versus five out of 10 in 15 l x 2 donors (41%vs 53% mean decrease in platelet counts, P = 0.02). PBSC collection efficiency increased by 37% after 15 l of the 25-l volume had been processed, compared with no significant change during 15 l x 2 procedures. Results similar to these prospective findings were also observed in CD34 yields, symptoms and platelet counts in additional 25 l and 15 l procedures performed during the same period and evaluated retrospectively. This study indicates that a single 25-l apheresis procedure results in similar yields and symptoms, but less donor thrombocytopenia and inconvenience than two consecutive daily 15-l procedures. C1 NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Silver Spring, MD USA. NHLBI, Biostat Serv, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Bolan, CD (reprint author), NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 1C711,10 Ctr Dr,MSC 1184, Bethesda, MD 20892 USA. NR 28 TC 16 Z9 17 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 MAR PY 2003 VL 120 IS 5 BP 801 EP 807 DI 10.1046/j.1365-2141.2003.04157.x PG 7 WC Hematology SC Hematology GA 651PX UT WOS:000181330200012 PM 12614213 ER PT J AU Giedd, JN AF Giedd, JN TI The anatomy of mentalization: A view from developmental neuroimaging SO BULLETIN OF THE MENNINGER CLINIC LA English DT Article; Proceedings Paper CT Conference on Mentalization and Treatment Resistant Psychopathology CY JAN, 2003 CL TOPEKA, KANSAS ID DEFICIT-HYPERACTIVITY DISORDER; CORPUS-CALLOSUM MORPHOLOGY; MAGNETIC-RESONANCE IMAGES; QUANTITATIVE MRI; HUMAN BRAIN; CHRONIC-SCHIZOPHRENIA; TOURETTES-SYNDROME; PYRAMIDAL CELLS; RHESUS-MONKEY; AGES 4-18 AB The capacity for mentalization emerges from developmental changes in the physical structure of the brain. Although pediatric imaging studies have not directly addressed the process of mentalizing, general principles of brain development may shed light on the neurobiology of mentalization. Increases in white matter, which speeds communication between brain cells, growing complexity of neuronal networks suggested by gray matter changes, and environmentally sensitive plasticity are all essential aspects in a child's ability to mentalize and maintain the adaptive flexibility necessary for healthy transition into adulthood. C1 NIMH, Brain Imaging Unit, Child Psychiat Branch, NIH,US Dept HHS, Bethesda, MD 20892 USA. RP Giedd, JN (reprint author), NIMH, Brain Imaging Unit, Child Psychiat Branch, NIH,US Dept HHS, Bldg 10,Rm 6N240,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 43 TC 17 Z9 17 U1 1 U2 5 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0025-9284 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD SPR PY 2003 VL 67 IS 2 BP 132 EP 142 DI 10.1521/bumc.67.2.132.23445 PG 11 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 725LU UT WOS:000185545300004 PM 14604098 ER PT J AU Ford, LG Minasian, LM McCaskill-Stevens, W Pisano, ED Sullivan, D Smith, RA AF Ford, LG Minasian, LM McCaskill-Stevens, W Pisano, ED Sullivan, D Smith, RA TI Prevention and early detection clinical trials: Opportunities for primary care providers and their patients SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID PROSTATE-CANCER MORTALITY; FIELD DIGITAL MAMMOGRAPHY; BREAST-CANCER; LUNG-CANCER; RADICAL PROSTATECTOMY; POSTMENOPAUSAL WOMEN; REDUCING MORTALITY; RANDOMIZED TRIAL; UTERINE SARCOMA; TAMOXIFEN AB Enrollment into cancer prevention and early detection clinical trials represents a unique challenge compared with a diagnostic or treatment trial because it involves subjects without a diagnosis of cancer. This paper examines some of the barriers to participation in prevention and early detection trials and provides detailed information about two ongoing prevention and two ongoing early detection clinical trials open to enrollment as well as brief summaries of seven additional trials now open to enrollment. (C) American Cancer Society, 2003. C1 NCI, Div Canc Prevent, SELECT, Bethesda, MD 20892 USA. NCI, Community Oncol & Prevent Trials Res Grp, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, STAR, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. NCI, Div Canc Prevent, Biomed Imaging Program, Bethesda, MD 20892 USA. Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30329 USA. RP Ford, LG (reprint author), NCI, Div Canc Prevent, SELECT, Bethesda, MD 20892 USA. NR 43 TC 30 Z9 30 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAR-APR PY 2003 VL 53 IS 2 BP 82 EP 101 PG 20 WC Oncology SC Oncology GA 665DN UT WOS:000182104500003 PM 12691266 ER PT J AU Shavers, VL Harlan, LC Winn, D Davis, WW AF Shavers, VL Harlan, LC Winn, D Davis, WW TI Racial/ethnic patterns of care for cancers of the oral cavity, pharynx, larynx, sinuses, and salivary glands SO CANCER AND METASTASIS REVIEWS LA English DT Review DE race; ethnicity; cancer treatment; health disparities; head and neck cancer ID NECK-CANCER; HEAD; CARCINOMA; SURVIVAL; PRESERVATION; AMERICAN AB Background Among Americans, both incidence and mortality from cancers of the larynx, oral cavity, and pharynx are higher for African Americans than whites and for men than women. In addition, the 5-year survival rates for these sites are significantly lower for African Americans than whites for each disease stage, particularly among African American males. We examine racial/ethnic variation in tumor characteristics, treatment practices, and their relationship to survival for cancers of the oral cavity, pharynx, larynx, nasal cavity and salivary glands. Methods Eligible individuals were age 20 or older and newly diagnosed with a primary invasive cancer of the oral cavity (excluding the lip), pharynx, larynx, sinuses or salivary glands in 1997 reported to one of nine National Cancer Institute's Surveillance Epidemiology and End Results Registries (SEER). Persons meeting the eligibility criteria for each registry were first stratified by race/ethnic group and stage then selected by random sampling within strata. Results We found racial/ethnic differences in diagnoses at specific anatomic sites, disease stage and treatment. African Americans less frequently received a cancer directed treatment than both whites and Hispanics and when treated were generally less likely to receive cancer-directed surgery. In multivariate analysis, the receipt of any cancer directed treatment was significantly associated with race and age group. African Americans and Hispanics had poorer, but not significantly so, overall, but not cancer-specific, survival. Conclusion We found racial differences in the receipt of cancer treatment among patients diagnosed with selected head and neck cancers. We also found a less favorable distribution of stage for African Americans and Hispanics when compared with whites. The differences in stage we noted and the lower rates of oral cancer screening previously reported for these populations suggests that differential rates of early detection may contribute to racial differences in survival and mortality from cancers of the oral cavity and pharynx. Therefore, we conclude that more equitable receipt of cancer treatment along with preventive measures and earlier detection will help reduce racial/ethnic disparities in survival and mortality from cancers of the oral cavity, pharynx and larynx. C1 NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. RP Shavers, VL (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. NR 31 TC 73 Z9 73 U1 2 U2 7 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD MAR PY 2003 VL 22 IS 1 BP 25 EP 38 DI 10.1023/A:1022255800411 PG 14 WC Oncology SC Oncology GA 642LJ UT WOS:000180805600004 PM 12716034 ER PT J AU Anderson, WF Umar, A Brawley, OW AF Anderson, WF Umar, A Brawley, OW TI Colorectal carcinoma in black and white race SO CANCER AND METASTASIS REVIEWS LA English DT Review DE colorectal carcinoma; racial variations; chromosomal instability; microsatellite instability; genetic susceptibility polymorphisms; colorectal cancer screening ID FECAL OCCULT-BLOOD; METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM; MISMATCH-REPAIR GENES; LUNG-CANCER RISK; AFRICAN-AMERICANS; COLON-CANCER; LARGE-BOWEL; MICROSATELLITE INSTABILITY; UNITED-STATES; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE AB Worldwide, colorectal carcinoma (CRC) varies by race-ethnicity. The highest incidence occurs in whites of European descent. Rates in blacks of South Africa are much lower, but rise with migration to westernized countries, i.e. African Americans (blacks) in the US. In the US, CRC age-specific incidence rates increased dramatically with biologic aging for black and white men and women. For all ages, rates were slightly higher for black than for whites. Among whites, overall annual rates peaked in the 1980s then declined. Stage- and sub site-specific rate shifts suggested earlier detection of cancers through screening, particularly in the distal colon. Blacks have not experienced the same stage- and subsite temporal shifts, which were observed in whites. CRC racial differences have been attributed to biologic and/or non-biologic factors as well as to routine screening patterns. Racial variations demonstrate the need for a more comprehensive understanding of colorectal carcinogenesis, epidemiology, and colorectal screening patterns for low- and high-risk populations. C1 Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. NCI, Div Canc Prevent, Gastrointestinal Canc & Other Canc Res Grp, Bethesda, MD 20892 USA. RP Brawley, OW (reprint author), Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. NR 144 TC 37 Z9 39 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD MAR PY 2003 VL 22 IS 1 BP 67 EP 82 DI 10.1023/A:1022264002228 PG 16 WC Oncology SC Oncology GA 642LJ UT WOS:000180805600008 PM 12716038 ER PT J AU Durum, SK Aiello, FB AF Durum, SK Aiello, FB TI Interleukin-7 induces MUC1 SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE interleukin-7; MUC1; b-catenin; myeloma ID CELL-LINES; EXPRESSION; OVEREXPRESSION; ACTIVATION; RECEPTOR; GAMMA; GENE C1 NCI, Lab Mol Regulat, Ctr Canc Res, NIH, Frederick, MD 21701 USA. SAIC, Intramural Res Support Program, Frederick, MD USA. RP Durum, SK (reprint author), NCI, Lab Mol Regulat, Ctr Canc Res, NIH, Frederick, MD 21701 USA. NR 16 TC 4 Z9 4 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 MAR-APR PY 2003 VL 2 IS 2 BP 194 EP 195 PG 2 WC Oncology SC Oncology GA 688PU UT WOS:000183445200014 PM 12750562 ER PT J AU De Roos, AJ Stewart, PA Linet, MS Heineman, EF Dosemeci, M Wilcosky, T Shapiro, WR Selker, RG Fine, HA Black, PM Inskip, PD AF De Roos, AJ Stewart, PA Linet, MS Heineman, EF Dosemeci, M Wilcosky, T Shapiro, WR Selker, RG Fine, HA Black, PM Inskip, PD TI Occupation and the risk of adult glioma in the United States SO CANCER CAUSES & CONTROL LA English DT Article DE farming; glioma; industrial hygiene; occupation ID MAGNETIC-FIELD EXPOSURE; ELECTRIC UTILITY WORKERS; BRAIN CANCER MORTALITY; ELECTROMAGNETIC-FIELDS; TUMOR MORTALITY; NEW-ZEALAND; DEATH; SWEDEN; FARMERS; EMBALMERS AB Objective: Previous studies have observed increased glioma incidence associated with employment in the petroleum and electrical industries, and in farming. Several other occupations have also been associated with increased risk, but with inconsistent results. We evaluated associations between occupational title and glioma incidence in adults. Methods: Cases were 489 patients with glioma diagnosed from 1994 to 1998 at three United States hospitals. Controls were 799 patients admitted to the same hospitals for non-malignant conditions. An experienced industrial hygienist grouped occupations that were expected to have similar tasks and exposures. The risk of adult glioma was evaluated for those subjects who ever worked in an occupational group for at least six months, those who worked longer than five years in the occupation, and those with more than ten years latency since starting work in the occupation. Results: Several occupational groups were associated with increased glioma incidence for having ever worked in the occupation, including butchers and meat cutters (odds ratio [OR] = 2.4; 95% confidence limits [CL]: 1.0, 6.0), computer programmers and analysts (OR = 2.0; 95% CL: 1.0, 3.8), electricians (OR = 1.8; 95% CL: 0.8, 4.1), general farmers and farmworkers (OR = 2.5; 95% CL: 1.4, 4.7), inspectors, checkers, examiners, graders, and testers (OR = 1.5; 95% CL: 0.8, 2.7), investigators, examiners, adjustors, and appraisers (OR = 1.7; 95% CL: 0.8, 3.7), physicians and physician assistants (OR = 2.4; 95% CL: 0.8, 7.2), and store managers (OR = 1.6; 95% CL: 0.8, 3.1), whereas occupation as a childcare worker was associated with decreased glioma incidence (OR = 0.4; 95% CL: 0.2, 0.9). These associations generally persisted when the subjects worked longer than five years in the occupation, and for those with more than ten years latency since starting to work in the occupation. Conclusions: This is our first analysis of occupation and will guide future exposure-specific assessments. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. St Josephs Hosp, Barrow Neurol Inst, Phoenix, AZ USA. Western Penn Hosp, Pittsburgh, PA 15224 USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP De Roos, AJ (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 70 TC 32 Z9 35 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 MAR PY 2003 VL 14 IS 2 BP 139 EP 150 DI 10.1023/A:1023053916689 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 671CJ UT WOS:000182447400005 PM 12749719 ER PT J AU Althuis, MD Brogan, DD Coates, RJ Daling, JR Gammon, MD Malone, KE Schoenberg, JB Brinton, LA AF Althuis, MD Brogan, DD Coates, RJ Daling, JR Gammon, MD Malone, KE Schoenberg, JB Brinton, LA TI Breast cancers among very young premenopausal women (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE breast cancer; early onset; premenopausal; risk factors ID ESTROGEN-RECEPTOR STATUS; AGE 45 YEARS; RISK-FACTORS; PHYSICAL-ACTIVITY; MENSTRUAL FACTORS; COLLABORATIVE REANALYSIS; INDIVIDUAL DATA; WHITE WOMEN; CONTRACEPTIVES; PROGESTERONE AB Objective: To assess risk factors for breast cancer among very young compared to older premenopausal women. Methods: Between 1990 and 1992 a population-based case-control study conducted in Atlanta, GA, Seattle/Puget Sound, WA, and central NJ interviewed 3307 premenopausal women aged 20-54 years. Logistic regression models estimated adjusted relative risks (RR) and 95% confidence intervals (CI) for each of three 10-year age groups. Results: Among the youngest age group (< 35 years, n = 545), significant predictors of risk included African-American race (RR = 2.66; 95% CI 1.4-4.9) and recent use of oral contraceptives (RR = 2.26; 95% CI 1.4-3.6). Although these relationships were strongest for estrogen receptor-negative (ER-) tumors (RRs of 3.30 for race and 3.56 for recent oral contraceptive use), these associations were also apparent for young women with ER+ tumors. Delayed childbearing was a risk factor for ER+ tumors among the older premenopausal women (p(trend) < 0.01), but not for women < 35 years in whom early childbearing was associated with an increased risk, reflecting a short-term increase in risk immediately following a birth. Family history of early-onset breast cancer was more strongly associated with risk among women < 35 years (RR = 3.22) than those 45-54 years (RR = 1.51). Risk factors for premenopausal breast cancer not significantly modified by age at diagnosis included early age at menarche, low body mass index, and heavy alcohol consumption. Conclusion: These findings suggest the possibility that women who develop breast cancers at very young ages may be etiologically as well as clinically distinct. C1 NCI, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, Rockville, MD 20852 USA. Rollins Sch Publ Hlth, Atlanta, GA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ N Carolina, Chapel Hill, NC USA. New Jersey State Dept Hlth & Senior Serv, Trenton, NJ USA. RP Althuis, MD (reprint author), NCI, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, 6120 Execut Blvd,Rm 7084,EPS MSC 7234, Rockville, MD 20852 USA. EM althuism@mail.nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 55 TC 74 Z9 75 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2003 VL 14 IS 2 BP 151 EP 160 DI 10.1023/A:1023006000760 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 671CJ UT WOS:000182447400006 PM 12749720 ER PT J AU Wingo, PA Jamison, PM Hiatt, RA Weir, HK Gargiullo, PM Hutton, M Lee, NC Hall, HI AF Wingo, PA Jamison, PM Hiatt, RA Weir, HK Gargiullo, PM Hutton, M Lee, NC Hall, HI TI Building the infrastructure for nationwide cancer surveillance and control - a comparison between The National Program of Cancer Registries (NPCR) and The Surveillance, Epidemiology, and End Results (SEER) Program (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE cancer incidence; SEER; surveillance ID CONFIDENCE-INTERVALS; POPULATION; SYSTEM; RATES; US AB Objective: In preparation for jointly publishing official government cancer statistics, the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI) compared incidence rates from NCI's Surveillance Epidemiology and End Results (SEER) Program and CDC's National Program of Cancer Registries (NPCR). Methods: Data for 1999 covering 78% of the US population were obtained from SEER and selected NPCR registries that met high quality data criteria. Incidence rates (per 100,000 population) were age-adjusted to the 2000 US standard population, and 95% gamma confidence intervals were estimated. Results: NPCR rates for all sites combined were higher than SEER rates (males: NPCR 553.6, SEER 538.7; females: NPCR 420.8, SEER 412.5), but rates for specific cancer sites varied by registry program. Rates for colon cancer (males: NPCR 47.0, SEER 42.7; females: NPCR 36.5, SEER 33.8) and tobacco-related cancers were higher in NPCR than SEER. In contrast, NPCR rates were lower than SEER rates for cancers of the female breast (NPCR 134.0, SEER 135.9), prostate (NPCR 162.0, SEER 170.2), and melanoma as well as for cancers more common among Asians and Pacific Islanders (e.g., stomach cancer). Conclusions: Rate differences may arise from population differences in socio-demographic characteristics, screening use, health behaviors, exposure to cancer causing agents or registry operations factors. C1 Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Wingo, PA (reprint author), Ctr Dis Control & Prevent, 4770 Buford Highway NE,MS K-53, Chamblee, GA 30341 USA. NR 49 TC 78 Z9 81 U1 1 U2 2 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 MAR PY 2003 VL 14 IS 2 BP 175 EP 193 DI 10.1023/A:1023002322935 PG 19 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 671CJ UT WOS:000182447400009 PM 12749723 ER PT J AU Isaacs, JS Xu, WP Neckers, L AF Isaacs, JS Xu, WP Neckers, L TI Heat shock protein 90 as a molecular target for cancer therapeutics SO CANCER CELL LA English DT Article ID HIPPEL-LINDAU PROTEIN; BCR-ABL; ATPASE ACTIVITY; LEUKEMIA-CELLS; HSP90 COMPLEX; CHAPERONE; HYPOXIA; BINDING; HEAT-SHOCK-PROTEIN-90; GELDANAMYCIN C1 NCI, Ctr Canc Res, Cell & Canc Biol Branch, NIH, Rockville, MD 20850 USA. RP Neckers, L (reprint author), NCI, Ctr Canc Res, Cell & Canc Biol Branch, NIH, Rockville, MD 20850 USA. NR 40 TC 400 Z9 425 U1 2 U2 23 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR PY 2003 VL 3 IS 3 BP 213 EP 217 DI 10.1016/S1535-6108(03)00029-1 PG 5 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 662MP UT WOS:000181951400005 PM 12676580 ER PT J AU Mirsalis, JC Schindler-Horvat, J Hill, JR Green, CE Mitoma, C Tomaszewski, JE Tyson, CA Donohue, SJ AF Mirsalis, JC Schindler-Horvat, J Hill, JR Green, CE Mitoma, C Tomaszewski, JE Tyson, CA Donohue, SJ TI Toxicity of a quinocarmycin analog, DX-52-1, in rats and dogs in relation to clinical outcome SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE quinocarmycin analog DX-52-1; renal toxicity; bone marrow toxicity; gastrointestinal toxicity; Streptomyces melanovinaceus; species differences ID BIOLOGICAL EVALUATION; ANTITUMOR-ACTIVITY; CELL-LINES; KW2152; DERIVATIVES; AGENT; MICE AB Purpose: Quinocarmycin analog DX-52-1 is a cyanated derivative of quinocarmycin, a compound isolated from cultures of Streptomyces melanovinaceus. DX-52-1 was selected for preclinical development because it showed efficacy against melanoma cell lines in the NCI human tumor cell screen and melanoma xenografts in mice. This report describes studies in rats and dogs to determine the maximum tolerated dose (MTD) and identify dose-limiting toxicities (DLT) in each species in different regimens to establish a safe starting dose and potential target organs of DX-52-1 for phase I clinical trials. Methods: DX-52-1 was administered to Fischer 344 rats using repeated intravenous (i.v.) slow bolus injections following q3hx3 and q3hx3,q7dx3 regimens, and to beagle dogs using a single injection, 6-h continuous i.v. infusion (c.i.v.) and weekly 6-h c.i.v. for 3 weeks. Endpoints evaluated included clinical observations, body weights, hematology, serum clinical chemistry, and microscopic pathology of tissues. Results: The MTD of DX-52-1 was a total dose of 18 mg/m(2) body surface area for q3hx3 administration in rats and 30 mg/m(2) for a single c.i.v. administration in dogs. The total dose MTD for rats on a weekly (q3hx3,q7dx3) regimen was 54 mg/m(2), and for dogs on the weekly x3 (6-h c.i.v.) infusion was 60 mg/m(2). In rats, significant elevations in blood urea nitrogen and creatinine were observed together with acute renal tubular necrosis histologically. Modest increases in liver enzymes were also observed, as were decreases in reticulocytes that were unaccompanied by histologic changes in liver and bone marrow. In dogs, adverse signs included vomiting/retching, diarrhea, and transient hypothermia; also red blood cells, hemoglobin, hematocrit, and lymphocytes were decreased. Histologic evaluation of tissues from dogs revealed necrosis and cellular depletion of the bone marrow, and extensive damage to the entire gastrointestinal tract, including marked cellular necrosis of the mucosa and lymphoid necrosis of the gastrointestinal associated lymphoid tissue. Destruction of the mucosal lining of the intestinal tract was likely responsible for dehydration, toxemia, septicemia, and shock seen in moribund dogs. Conclusions: The MTD values were comparable between rats and dogs given roughly similar dose regimens (single dose or weekly) and both species tolerated a higher total dose with weekly administration. However, the principal target organ responsible for DLT in rats was the kidney, whereas in dogs, the most severe effects were on the gastrointestinal tract and bone marrow. Both renal and gastrointestinal toxicities were reported in patients after 6-h c.i.v. infusions in a limited phase I clinical trial, indicating that neither animal model alone was predictive of DX-52-1-induced toxicity in humans, and that both species were required to define human toxicity. C1 SRI Int, Toxicol Lab, Menlo Pk, CA 94025 USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Bethesda, MD 20892 USA. RP Mirsalis, JC (reprint author), SRI Int, Toxicol Lab, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA. FU NCI NIH HHS [N01-CM-37837] NR 21 TC 2 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2003 VL 51 IS 3 BP 193 EP 201 DI 10.1007/s00280-002-0553-0 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 671TF UT WOS:000182479600002 PM 12655436 ER PT J AU Komiya, T Fusetani, N Matsunaga, S Kubo, A Kaye, FJ Kelley, MJ Tamura, K Yoshida, M Fukuoka, M Nakagawa, K AF Komiya, T Fusetani, N Matsunaga, S Kubo, A Kaye, FJ Kelley, MJ Tamura, K Yoshida, M Fukuoka, M Nakagawa, K TI Ritterazine B, a new cytotoxic natural compound, induces apoptosis in cancer cells SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE ritterazine; cell cycle arrest; apoptosis; caspase ID TUNICATE RITTERELLA-TOKIOKA; 7-HYDROXYSTAUROSPORINE UCN-01; CYCLE ARREST; INHIBITOR; INDUCTION; ANALOG; ACTIN; AGENT; LINES AB Purpose: Ritterazine B, one of the ritterazine analogues extracted from Ritterella tokioka, has been shown to be chemically similar to cephalostatin 1, and among the ritterazine derivatives is the most cytotoxic to P388 murine leukemia cells. The objective of this study was to determine the cytotoxicity of ritterazine B to non-small-cell lung cancer (NSCLC) cells in vitro and its effects on the cell cycle and apoptosis. Methods: The cytotoxicity of ritterazine B against PC14 NSCLC cells was investigated using a 4-day MTT assay. Morphological changes in cells after exposure to this compound were evaluated by phase-contrast microscopy. The effects on the cell cycle of HL-60 leukemia cells and PC14 cells were elucidated by flow cytometry and an in vitro CDK/cyclin kinase assay. Induction of apoptosis in HL-60 cells was assessed using the TUNEL assay and Hoechst 33342 staining. In addition, molecules involved in apoptosis were evaluated by Western blotting. Results: Ritterazine B exerted strong cytotoxic effects against PC14 cells with a mean GI(50) of 75.1 nM. Cell cycle analysis showed that ritterazine B caused accumulation of HL-60 and PC14 cells at the G2/M checkpoint. Furthermore, ritterazine B-treated HL-60 cells became multinucleated, and at a concentration of 20 nM this resulted in the onset. of apoptosis. Neither cleavage of caspase target molecules nor phosphorylation of bcl-2 were observed in ritterazine B-treated HL-60 cells. Conclusions: These results indicate that ritterazine B might be a potent inducer of apoptosis acting via a novel antimitotic mechanism. C1 Kinki Univ, Sch Med, Div Med Oncol, Osakasayama, Osaka 5898511, Japan. Univ Tokyo, Marine Biochem Lab, Bunkyo Ku, Tokyo 113, Japan. NCI, Genet Branch, Ctr Canc Res, Natl Naval Med Ctr, Bethesda, MD 20889 USA. Duke Univ, Sch Med, Dept Med, Durham, NC 27705 USA. RP Komiya, T (reprint author), Kinki Univ, Sch Med, Div Med Oncol, 377-2 Ohnohigashi, Osakasayama, Osaka 5898511, Japan. RI kaye, frederic/E-2437-2011; OI Kelley, Michael/0000-0001-9523-6080 NR 21 TC 26 Z9 26 U1 2 U2 6 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2003 VL 51 IS 3 BP 202 EP 208 DI 10.1007/s00280-002-0558-8 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 671TF UT WOS:000182479600003 PM 12655437 ER PT J AU Chiu, BCH Ji, BT Dai, Q Gridley, G McLaughlin, JK Gao, YT Fraumeni, JF Chow, WH AF Chiu, BCH Ji, BT Dai, Q Gridley, G McLaughlin, JK Gao, YT Fraumeni, JF Chow, WH TI Dietary factors and risk of colon cancer in Shanghai, China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GRILLED RED MEAT; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; GASTROINTESTINAL CANCERS; NUTRITION TRANSITION; PROSPECTIVE COHORT; RECTAL-CANCER; WELL-DONE; EPIDEMIOLOGY; FIBER AB Colon cancer incidence rates have risen sharply in Shanghai, China, since the early 1970s, and diet may have contributed to the rising incidence. To clarify the role of dietary factors for colon cancer in Shanghai, we analyzed data from a population-based case-control study of 931 cases (462 males and 469 females) and 1552 controls (851 males and 701 females) ages 30-74 years in Shanghai, China, from 1990-1993. Subjects were interviewed in person for a detailed history of dietary practices and food preferences by using a food-frequency questionnaire. Colon cancer risk was estimated by odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, total energy, and other confounding factors. Risk for the highest versus the lowest quartile of intake was elevated for red meat (OR, 1.5; 95% CI, 1.0-2.1 for men and OR, 1.5; 95% CI, 1.0-2.2 for women), fish (OR, 1.7; 95% CI, 1.2-2.4 for men and OR, 1.2; 95% CI, 0.8-1.7 for women), and eggs (OR, 1.4; 95% CI, 1.0-1.9 for men and OR, 1.3; 95% CI, 0.9-1.9 for women), but was reduced for fresh fruit (OR, 0.7; 95% CI, 0.5-1.0 for men and OR, 0.6, 0.4-0.9 for women). High intake of preserved foods, whether animal or plant source, was associated with an excess risk of colon cancer (OR, 2.0; 95% CI, 1.5-2.9 for men and OR, 2.7; 95% CI, 1.9-3.8 for women). For dietary nutrients, risk generally declined with greater consumption of fiber and micronutrients common in fruit and vegetables, including vitamin C, carotene, and vitamin E. Intake of macronutrients in general was not significantly related to risk. Our findings suggest that diets high in fruit and antioxidant vitamins that are common in plant foods reduce the risk of colon cancer, whereas diets high in red meat, eggs, and preserved foods increase the risk. C1 Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Nebraska Med Ctr 984350, Omaha, NE 68198 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Shanghai Canc Inst, Shanghai, Peoples R China. Int Epidemiol Inst, Rockville, MD USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. RP Chiu, BCH (reprint author), Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Nebraska Med Ctr 984350, 600 S 42nd St, Omaha, NE 68198 USA. EM bchiu@unmc.edu NR 60 TC 93 Z9 96 U1 3 U2 26 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2003 VL 12 IS 3 BP 201 EP 208 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 658AC UT WOS:000181698600004 PM 12646508 ER PT J AU Chen, HL Miller, BA Giovannucci, E Hayes, RB AF Chen, HL Miller, BA Giovannucci, E Hayes, RB TI Height and the survival of prostate cancer patients SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UNITED-STATES; BODY-SIZE; RISK; MEN; ANTHROPOMETRY; MORTALITY; COHORT; BLACKS; WHITES AB We investigated the associations between height and other anthropometric factors and the survival of 584 prostate cancer patients, initially recruited for a population-based, case-control study. During a median of 6.6 years of follow-up, 129 prostate cancer deaths and 153 deaths because of other causes were identified. After adjusting for age, cancer stage, and grade, the relative risk and 95% confident intervals for prostate cancer death were 1.0 (reference), 0.9 (0.6-1.4), 0.5 (0.3-0.9), and 0.6 (0.31.0) for patients whose heights were <1.75 in, 1.75-1.79 in, 1.80-1.84 m, and &GE;1.85 in, respectively (P for trend = 0.01). Similar associations; were found in subgroup analyses by cancer stage, cancer grade, age, race, and occupation-based socioeconomic status. However, height was not associated with death because of other causes. In addition, no significant associations were found between body mass index or weight and either prostate cancer death or death because of other causes. Our results suggest that greater height may be associated with better survival of prostate cancer patients. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Chen, HL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Bldg 2,315,665 Huntington Ave, Boston, MA 02115 USA. EM hchen@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 NR 19 TC 9 Z9 10 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2003 VL 12 IS 3 BP 215 EP 218 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 658AC UT WOS:000181698600006 PM 12646510 ER PT J AU Inskip, PD Tarone, RE Brenner, AV Fine, HA Black, PM Shapiro, WR Selker, RG Linet, MS AF Inskip, PD Tarone, RE Brenner, AV Fine, HA Black, PM Shapiro, WR Selker, RG Linet, MS TI Handedness and risk of brain tumors in adults SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CEREBRAL LATERALIZATION; HISTORY; ASSOCIATION; PLASTICITY; ALLERGIES; DISEASE AB The objective of this study was to evaluate the relation between handedness, and the risk of malignant and benign brain tumors. Handedness has been hypothesized to serve as a behavioral marker of prenatal hormonal exposures or other factors that influence subsequent cancer risk. A case-control study was conducted at hospitals in three United States cities between 1994 and 1998. The cases were adult patients newly diagnosed with glioma (n = 489), meningioma (n = 197), or acoustic neuroma (n = 96), and the 799 frequency-matched controls were patients admitted to the same hospitals for a variety of nonmalignant conditions. Handedness was determined by interview. Unconditional logistic regression was used to estimate odds ratios (ORs) and calculate 95% confidence intervals (CIs). Persons who described themselves as left-handed or ambidextrous appeared to be at reduced risk of glioma relative to those who described themselves as right-handed (OR, 0.7; 95% CI, 0.5-0.9). The association was similar for men and women, and for left-sided and right-sided tumors. Neither meningioma (OR, 0.9; CI, 0.6-1.5) nor acoustic neuroma. (OR, 0.9; CI, 0.5-1.7) showed significant associations with handedness. These findings require confirmation but raise the possibility that early neurodevelopmental events or genetic factors related to handedness also influence the risk of glioma among adults. C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Neurooncol Branc, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. St Josephs Hosp, Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA. Med Ctr, Phoenix, AZ 85013 USA. Western Penn Hosp, Div Neurosurg, Pittsburgh, PA 15224 USA. RP Inskip, PD (reprint author), Execut Pl S,Room 7052,6120 Execut Blvd, Rockville, MD 20852 USA. NR 25 TC 11 Z9 12 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2003 VL 12 IS 3 BP 223 EP 225 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 658AC UT WOS:000181698600008 PM 12646512 ER PT J AU Christian, MC Trimble, EL AF Christian, MC Trimble, EL TI Increasing participation of physicians and patients from underrepresented racial and ethnic groups in National Cancer Institute sponsored clinical trials SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article; Proceedings Paper CT Symposium on Reducing the Unequal Burnden of Cancer CY OCT 18, 2001 CL BOSTON, MASSACHUSETTS ID RENAL-TRANSPLANTATION; ACCESS; DISPARITIES; GENDER; APPROPRIATE C1 NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. RP Christian, MC (reprint author), NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. NR 22 TC 31 Z9 31 U1 3 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2003 VL 12 IS 3 BP 277S EP 283S PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 658AC UT WOS:000181698600022 PM 12646527 ER PT J AU Pusztai, L Sotiriou, C Buchholz, TA Meric, F Symmans, WF Esteva, FJ Sahin, A Liu, ET Hortobagi, GN AF Pusztai, L Sotiriou, C Buchholz, TA Meric, F Symmans, WF Esteva, FJ Sahin, A Liu, ET Hortobagi, GN TI Molecular profiles of invasive mucinous and ductal carcinomas of the breast: a molecular case study SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID GENE-EXPRESSION PATTERNS; CANCERS; CELLS AB Expression profiling using cDNA microarrays have redefined the molecular classification of some cancers. The comprehensive genetic analysis also permits the identification of novel pathways that might determine subtle differences in tumor phenotype. Herein, we analyzed the tissues from a patient with bilateral cancer of different histologies in each breast (pure invasive mucinous and pure invasive ductal), thus providing a unique opportunity to assess the expression profiles determined by histology in an isogenic human background. Our results show that the mucinous phenotype is associated with the expression of immunostimulatory and inhibitory genes, consistent with the cellular infiltration of lymphocytes and with the expression of enzymes involved in mucin production. Moreover, the panel of matrix metallo-proteinases are distinctly different between the mucinous and the invasive tumors, suggesting that therapeutic targets to this class of compounds may need to be tailored for the varying histologies. Taken together, these data suggest that expression profiling can be used diagnostically to distinguish individual histologic subclassifications and may guide the selection of target therapeutics. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. NCI, Div Clin Sci, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. RP Pusztai, L (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. RI Liu, Edison/C-4141-2008 FU NCI NIH HHS [K23 CA82119] NR 15 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD MAR PY 2003 VL 141 IS 2 BP 148 EP 153 AR PII S0165-4608(02)00737-9 DI 10.1016/S0165-4608(02)00737-9 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 651PF UT WOS:000181328100009 PM 12606133 ER PT J AU Hu, ZL Bonifas, JM Aragon, G Kopelovich, L Liang, Y Ohta, S Israel, MA Bickers, DR Aszterbaum, M Epstein, EH AF Hu, ZL Bonifas, JM Aragon, G Kopelovich, L Liang, Y Ohta, S Israel, MA Bickers, DR Aszterbaum, M Epstein, EH TI Evidence for lack of enhanced hedgehog target gene expression in common extracutaneous tumors SO CANCER RESEARCH LA English DT Article ID BASAL-CELL CARCINOMA; CENTRAL-NERVOUS-SYSTEM; PRIMITIVE NEUROECTODERMAL TUMORS; DROSOPHILA PATCHED PTCH; HUMAN-MALIGNANT GLIOMAS; SOFT-TISSUE SARCOMAS; HUMAN HOMOLOG; SIGNALING PATHWAY; XERODERMA-PIGMENTOSUM; GORLIN SYNDROME AB Abnormal hedgehog signaling, most commonly caused by loss of PTCH1 inhibitor activity, drives tumorigenesis of basal cell carcinomas (BCCs). To assess whether other tumors also have abnormal hedgehog signaling, we have assayed RNA from common cancers at nine different sites for levels of expression of hedgehog target genes that are up-regulated uniformly in BCCs. We report here that such dysregulation appears not to be common in the types of non-BCC cancers studied, indicating that the molecular pathogenesis of BCCs, like their frequency and behavior, differs markedly from that of most other cancers. C1 Univ Alabama, Cooperat Human Tissue Network, Birmingham, AL 35294 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. San Francisco Gen Hosp, Dept Dermatol, San Francisco, CA 94110 USA. San Francisco Gen Hosp, Dept Neurol Surg, San Francisco, CA 94110 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94110 USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. Columbia Univ, Dept Dermatol, New York, NY 10032 USA. RP Epstein, EH (reprint author), San Francisco Gen Hosp, Dept Dermatol, Room 269,Bldg 100,1001 Potrero Ave, San Francisco, CA 94110 USA. FU NCI NIH HHS [CA 81888-01, CA44968] NR 56 TC 19 Z9 22 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2003 VL 63 IS 5 BP 923 EP 928 PG 6 WC Oncology SC Oncology GA 651PC UT WOS:000181327700006 PM 12615704 ER PT J AU Bauer, AK Faiola, B Abernethy, DJ Marchan, R Pluta, LJ Wong, VA Roberts, K Jaiswal, AK Gonzalez, FJ Butterworth, BE Borghoff, S Parkinson, H Everitt, J Recio, L AF Bauer, AK Faiola, B Abernethy, DJ Marchan, R Pluta, LJ Wong, VA Roberts, K Jaiswal, AK Gonzalez, FJ Butterworth, BE Borghoff, S Parkinson, H Everitt, J Recio, L TI Genetic susceptibility to benzene-induced toxicity: Role of NADPH: Quinone oxidoreductase-1 SO CANCER RESEARCH LA English DT Article ID BONE-MARROW; INHALED BENZENE; MICE; LEUKEMIA; EXPOSURE; P53; MECHANISM; WORKERS; NQO1; RISK AB Enzymes that activate and detoxify benzene are likely genetic determinants of benzene-induced toxicity. NAD(P)H: quinone oxidoreductase-1 (NQO1) detoxifies benzoquinones, proposed toxic metabolites of benzene. NQO1 deficiency in humans is associated with an increased risk of leukemia, specifically acute myelogenous leukemia, and benzene poisoning. We examined the importance of NQO1 in benzene-induced toxicity by hypothesizing that NQO1-deficient (NQO1-/-) mice are more sensitive to benzene than mice with wild-type NQO1 (NQO1+/+; 129/Sv background strain). Male and female NQO1-/- and NQO1+/+ mice were exposed to inhaled benzene (0, 10, 50, or 100 ppm) for 2 weeks, 6 h/day, 5 days/week. Micronucleated peripheral blood cells were counted to assess genotoxicity. Peripheral blood counts and bone marrow histology were used to assess hematotoxicity and myelotoxicity. p21 mRNA levels in bone marrow cells were used as determinants of DNA damage response. Female NQO1-/- mice were more sensitive (6-fold) to benzene-induced genotoxicity than the female NQO1+/+ mice. Female NQO1-/- mice had a 9-fold increase (100 versus 0 ppm) in micronucleated reticulocytes compared with a 3-fold increase in the female NQO1+/+ mice. However, the induced genotoxic response in male mice was similar between the two genotypes ( greater than or equal to10-fold increase at 100 ppm versus 0 ppm). Male and female NQO1-/- mice exhibited greater hematotoxicity than NQO1+/+ mice. p21 mRNA levels were induced significantly in male mice (> 10-fold) from both strains and female NQO1-/- mice (> 8-fold), which indicates an activated DNA damage response. These results indicate that NQO1 deficiency results in substantially greater benzene-induced toxicity. However, the specific patterns of toxicity differed between the male and female mice. C1 CIIT Ctr Hlth Res, Ctr Hlth Res, Res Triangle Pk, NC 27709 USA. Baylor Coll Med, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. RP Bauer, AK (reprint author), NIEHS, Pulm Pathobiol Lab, E214,Bldg 101,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM bauer1@niehs.nih.gov FU NIEHS NIH HHS [F32 ES011424-01, 1F32 ES11424-01, R01 ES07943] NR 43 TC 50 Z9 54 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2003 VL 63 IS 5 BP 929 EP 935 PG 7 WC Oncology SC Oncology GA 651PC UT WOS:000181327700007 PM 12615705 ER PT J AU Reinhold, WC Kouros-Mehr, H Kohn, KW Maunakea, AK Lababidi, S Roschke, A Stover, K Alexander, J Pantazis, P Miller, L Liu, E Kirsch, IR Urasaki, Y Pommier, Y Weinstein, JN AF Reinhold, WC Kouros-Mehr, H Kohn, KW Maunakea, AK Lababidi, S Roschke, A Stover, K Alexander, J Pantazis, P Miller, L Liu, E Kirsch, IR Urasaki, Y Pommier, Y Weinstein, JN TI Apoptotic susceptibility of cancer cells selected for camptothecin resistance: Gene expression profiling, functional analysis, and molecular interaction mapping SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; ENDOPLASMIC-RETICULUM STRESS; HUMAN PROSTATE-CANCER; DNA MISMATCH REPAIR; TOPOISOMERASE-I; C-JUN; TRANSCRIPTIONAL REGULATION; POTENTIATES APOPTOSIS; SENSITIZES CELLS; PROTEIN AB To study the molecular mechanisms by which drug resistance develops, we compared DU145 human prostate cancer cells with a subline selected for resistance to camptothecin. Differences in gene expression level were assessed by hybridizing the two cell types against each other using quadruplicate "Oncochip" cDNA microarrays that included 1648 cancer-related genes. Expression levels differing by a factor of > 1.5 were detected for 181 of the genes. These differences were judged statistically reliable on the basis of a stratum-adjusted Kruskal-Wallis test, after taking into account a dye-dependent variable. The 181 expression-altered genes included a larger than expected number of the "apoptosis-related" genes (P = 0.04). To assess whether this observation reflected a generalized resistance of RCO.1 to apoptosis, we exposed the cells to a range of stresses (cisplatin, staurosporine, UV, ionizing radiation, and serum starvation) and found greatly reduced apoptotic responses for RCO.1 (relative to DU145) using flow cytometric Annexin V and terminal deoxynucleotidyl transferase-mediated nick end labeling assays. We next examined the apoptosis-related genes in the context of a molecular interaction map and found expression differences in the direction "expected" on the basis of the apoptosis-resistance of RCO.1 for BAD, caspase-6, and genes that signal via the Akt pathway. Exposure of the cells to wortmannin, an inhibitor of the Akt effector phosphatidylinositol 3-kinase, provided functional support for involvement of the Akt pathway. However, closer examination of the molecular interaction map revealed a paradox: many of the expression differences observed for apoptosis-related genes were in the direction "contrary" to that expected given the resistance of RC0.1. The map indicated that most of these unexpected expression differences were associated with genes involved in the nuclear factor kappaB and transforming growth factor beta pathways. Overall, the patterns that emerged suggested a two-step model for the selection process that led to resistance in RCO.1 cells. The first hypothesized step would involve a decrease in apoptotic susceptibility through changes in the apoptosis-control machinery associated with the Bcl-2 and caspase gene families, and also in antiapoptotic pathways operating through Akt/PKB. The second step would involve changes in multifunctional upstream genes (including some genes in the nuclear factor kappaB and transforming growth factor beta pathways) that can facilitate apoptosis but that would also tend to contribute to cell proliferation in the presence of drug. Thus, we propose that a downstream blockade of apoptosis was "permissive" for the selection of upstream pathway changes that would otherwise have induced apoptosis. This model is analogous to one suggested previously for the relationship between oncogene function and apoptosis in carcinogenesis. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Miami, Coral Gables, FL 33146 USA. Natl Canc Inst, Ctr Adv Technol, Gaithersburg, MD 20874 USA. Fukui Med Univ, Dept Internal Med 1, Fukui 9101193, Japan. RP Reinhold, WC (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bldg 37,Room 5056, Bethesda, MD 20892 USA. RI Liu, Edison/C-4141-2008; Miller, Lance/A-5633-2009 NR 69 TC 43 Z9 48 U1 2 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 MAR 1 PY 2003 VL 63 IS 5 BP 1000 EP 1011 PG 12 WC Oncology SC Oncology GA 651PC UT WOS:000181327700017 PM 12615715 ER PT J AU Yang, XZ Merchant, MS Romero, ME Tsokos, M Wexler, LH Kontny, U Mackall, CL Thiele, CJ AF Yang, XZ Merchant, MS Romero, ME Tsokos, M Wexler, LH Kontny, U Mackall, CL Thiele, CJ TI Induction of caspase 8 by interferon gamma renders some neuroblastoma (NB) cells sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but reveals that a lack of membrane TR1/TR2 also contributes to TRAIL resistance in NB SO CANCER RESEARCH LA English DT Article ID HUMAN NEURO-BLASTOMA; GENE-EXPRESSION; RETINOIC ACID; CHILDHOOD NEUROBLASTOMAS; TUMORICIDAL ACTIVITY; DEATH RECEPTOR-5; DOWN-REGULATION; CANCER-PATIENTS; LEUKEMIA-CELLS; EWINGS-SARCOMA AB The resistance of neuroblastoma (NB) cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis has been attributed to a lack of caspase 8 expression. Here we demonstrate a clinically applicable molecular targeting strategy that not only increases caspase 8 expression ex vivo in NB cell lines but also in the tumor tissues of NB patients receiving IFN-gamma treatment. We identify the functional caspase 8 promoter, which is different from the methylated region reported previously, and show promoter activity is up-regulated by IFN-gamma through a IFN-gamma activation site-containing region. IFN-gamma also induces TRAIL expression in NB cell lines. However, the IFN-gamma restoration of caspase 8 in some NB cells revealed persistent TRAIL resistance in most NB cell lines examined. This additional lesion in the TRAIL path is because of a loss of cell membrane TRAIL receptors (TR1/TR2) not only in cell lines but in most of the NB tumor tissues evaluated. Restoration of TR2 expression by transfection enhances IFN-gamma-induced TRAIL sensitivity. Furthermore, we have found that we can improve TRAIL sensitivity in NB by reconstituting caspase 8 with IFN-gamma and TR2 with chemotherapeutic agents. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Univ Freiburg, Childrens Hosp, D-79106 Freiburg, Germany. RP Thiele, CJ (reprint author), NCI, Pediat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 13n240, Bethesda, MD 20892 USA. NR 50 TC 81 Z9 94 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2003 VL 63 IS 5 BP 1122 EP 1129 PG 8 WC Oncology SC Oncology GA 651PC UT WOS:000181327700033 PM 12615731 ER PT J AU Kim, JW Wang, XW AF Kim, JW Wang, XW TI Gene expression profiling of preneoplastic liver disease and liver cancer: a new era for improved early detection and treatment of these deadly diseases? SO CARCINOGENESIS LA English DT Editorial Material ID HUMAN HEPATOCELLULAR-CARCINOMA; HEPATOMA-CELL LINES; SUPPRESSION SUBTRACTIVE HYBRIDIZATION; LASER CAPTURE MICRODISSECTION; CDNA MICROARRAY ANALYSIS; CHRONIC HEPATITIS-B; GROWTH-FACTOR-BETA; DNA MICROARRAY; CLASS PREDICTION; SERIAL ANALYSIS AB Hepatocellular carcinoma (HCC) is a multi-step process associated with changes in gene expression. Currently, several technologies enable global gene expression profiling. The number of studies to probe global gene expression profiles of HCC or preneoplastic chronic liver diseases has increased exponentially in recent years. These studies have quickly provided rich information and some additional clues to the genesis of liver cancer. The application of gene expression profiling to preneoplastic liver diseases and HCC is growing in importance and practicality. In this commentary, we review the recent advances in the utilization of global gene expression profiling to liver cancer, which have provided new insight into the molecular mechanisms underlying the development of HCC. We have also discussed the problems related to these new technologies, as well as their contributions and implications. By recognizing the shortcomings, we can reassess our current approaches, which allow us to better design and analyze global gene expression-based experiments. These new approaches will undoubtedly contribute to a better understanding of hepatocarcinogenesis. C1 NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37,Room 2C25, Bethesda, MD 20892 USA. RI Wang, Xin/B-6162-2009 NR 81 TC 41 Z9 45 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2003 VL 24 IS 3 BP 363 EP 369 DI 10.1093/carcin/24.3.363 PG 7 WC Oncology SC Oncology GA 666AV UT WOS:000182154200002 PM 12663493 ER PT J AU Shibata, MA Kavanaugh, C Shibata, E Abe, H Nguyen, PM Otsuki, Y Trepel, JB Green, JE AF Shibata, MA Kavanaugh, C Shibata, E Abe, H Nguyen, PM Otsuki, Y Trepel, JB Green, JE TI Comparative effects of lovastatin on mammary and prostate oncogenesis in transgenic mouse models SO CARCINOGENESIS LA English DT Article ID LARGE T-ANTIGEN; LARGE-TUMOR-ANTIGEN; GROWTH IN-VITRO; CELL-CYCLE; COMPETITIVE INHIBITOR; MEVALONATE PATHWAY; INDUCED APOPTOSIS; BREAST-CANCER; KI-RAS; MICE AB The effects of lovastatin, a potent inhibitor of HMG CoA reductase, on experimental mammary and prostate oncogenesis, were studied in vitro and in vivo. Lovastatin inhibited cell growth in vitro in a dose-dependent manner for both mammary and prostate cancer cell lines, which was associated with p53-independent apoptosis. Flow cytometric analyses of lovastatin-treated mammary and prostate cancer cells demonstrated cell-cycle G(1) arrest, as well as decreases in S and G(2)/M fractions. p21(Waf1) and p27(Kip1) were induced by lovastatin in both types of cancer cells. Gene expression profiling of cells treated with lovastatin, however, was remarkable for a paucity of transcriptional changes induced by lovastatin. Treatment with lovastatin for 4 weeks did inhibit the formation of pre-neoplastic mammary intraepithelial neoplasias (MIN) in vivo, but not invasive carcinomas in the C3(1)/SV40 TAg transgenic model of mammary cancer. The decreased multiplicity of MIN lesions was associated with increased levels of apoptosis in these lesions. However, cell proliferation in the mammary lesions was not significantly different between lovastatin-treated and control mice 1 day after lovastatin treatment. In female mice treated with lovastatin for 12 weeks, there was a tendency for reduced tumor volume, which did not reach statistical significance. However, lovastatin did not suppress any lesion formation in the prostate of C3(1)/SV40 TAg transgenic male mice. Our results suggest that as lovastatin exerts an inhibitory effect on the development of early mammary lesions of mammary carcinogenesis, this compound may be useful for the chemoprevention of mammary cancer and might have utility as an adjuvant in breast cancer therapy. The chemopreventive effects of lovastatin in vivo, however, may be tissue-specific. C1 NCI, Lab Cell Regulat & Carcinogenesis, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Osaka Med Coll, Dept Anat & Biol, Osaka 5698686, Japan. RP Green, JE (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Div Basic Sci, NIH, Room C619,41 Lib Dr, Bethesda, MD 20892 USA. NR 40 TC 74 Z9 76 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2003 VL 24 IS 3 BP 453 EP 459 DI 10.1093/carcin/24.3.453 PG 7 WC Oncology SC Oncology GA 666AV UT WOS:000182154200013 PM 12663504 ER PT J AU Gago-Dominguez, M Bell, DA Watson, MA Yuan, JM Castelao, JE Hein, DW Chan, KK Coetzee, GA Ross, RK Yu, MC AF Gago-Dominguez, M Bell, DA Watson, MA Yuan, JM Castelao, JE Hein, DW Chan, KK Coetzee, GA Ross, RK Yu, MC TI Permanent hair dyes and bladder cancer: risk modification by cytochrome P4501A2 and N-acetyltransferases 1 and 2 SO CARCINOGENESIS LA English DT Article ID HUMAN HEPATIC MICROSOMES; LOWER URINARY-TRACT; CARCINOGENIC ARYLAMINES; ACETYLATION POLYMORPHISMS; METABOLIC OXIDATION; AROMATIC-AMINES; NAT1; ACTIVATION; SMOKING; SUSCEPTIBILITY AB We have previously reported permanent hair dye use to be a significant risk factor for bladder cancer in US women. We also have examined N-acetyltransferase-2 (NAT2) phenotype in relation to the hair dye-bladder cancer relationship, and found that the association is principally confined to NAT2 slow acetylators. In the present study, we assessed the possible modifying effects of a series of potential arylamine-metabolizing genotypes/phenotypes (GSTM1, GSTT1, GSTP1, NAT1, NAT2, CYP1A2) on the permanent hair dye-bladder cancer association, among female participants (159 cases, 164 controls) of the Los Angeles Bladder Cancer Study. Among NAT2 slow acetylators, exclusive permanent hair dye use was associated with a 2.9-fold increased risk of bladder cancer (95% CI = 1.2-7.5). The corresponding relative risk in NAT2 rapid acetylators was 1.3 (95% CI = 0.6-2.8). Frequency- and duration-related dose-response relationships confined to NAT2 slow acetylators were all positive and statistically significant. No such associations were noted among NAT2 rapid acetylators. Among CYP1A2 'slow' individuals, exclusive permanent hair dye use was associated with a 2.5-fold increased risk of bladder cancer (95% CI = 1.04-6.1). The corresponding risk in CYP1A2 'rapid' individuals was 1.3 (95% CI = 0.6-2.7). Frequency- and duration-related dose-response relationships confined to CYP1A2 'slow' individuals were all positive and statistically significant. No such associations were noted among CYP1A2 'rapid' individuals. Among lifelong non-smoking women, individuals exhibiting the non-NAT1*10 genotype showed a statistically significant increase in bladder cancer risk associated with exclusive permanent hair dye use (OR = 6.8, 95% CI = 1.7-27.4). The comparable OR in individuals with the NAT1*10 genotype was 1.0 (95% CI = 0.2-4.3). Similarly, all frequency- and duration-related dose-response relationships confined to individuals possessing the non-NAT1*10 genotype were positive and statistically significant. On the other hand, individuals of NAT1*10 genotype exhibited no such associations. C1 Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Gago-Dominguez, M (reprint author), Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, 1441 Eastlake Ave, Los Angeles, CA 90089 USA. RI Hein, David/A-9707-2008; OI Yuan, Jian-Min/0000-0002-4620-3108 FU NCI NIH HHS [P01 CA17054, R01 CA034627, R01 CA034627-17, R01 CA65726, R35CA53890]; NIEHS NIH HHS [P30 ES07048] NR 51 TC 94 Z9 96 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2003 VL 24 IS 3 BP 483 EP 489 DI 10.1093/carcin/24.3.483 PG 7 WC Oncology SC Oncology GA 666AV UT WOS:000182154200017 PM 12663508 ER PT J AU Kimura, S Kawabe, M Yu, AM Morishima, H Fernandez-Salguero, P Hammons, GJ Ward, JM Kadlubar, FF Gonzalez, FJ AF Kimura, S Kawabe, M Yu, AM Morishima, H Fernandez-Salguero, P Hammons, GJ Ward, JM Kadlubar, FF Gonzalez, FJ TI Carcinogenesis of the food mutagen PhIP in mice is independent of CYP1A2 SO CARCINOGENESIS LA English DT Article ID AROMATIC-AMINES; COLORECTAL-CANCER; AH RECEPTOR; METABOLISM; CAFFEINE; PHENOTYPES; INDUCTION; MOUSE; RISK AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant of the heterocyclic amines found in cooked meat. Based on in vitro studies with rats and humans, CYP1A2 is believed to be the primary enzyme responsible for N-2-hydroxylation, the initial step in the metabolic activation of PhIP. To determine whether CYP1A2 is the primary P450 responsible for metabolic activation of PhIP in mice that leads to tumor formation, neonatal Cyp1a2-null and wild-type mice were treated with similar to11 (low dose) and similar to22 (high dose) mg/kg PhIP at days 8 and 15, corresponding cumulatively to 600 and 1200 nmol PhIP, and analyzed at 19-21 months of age. Three major induced tumors were found; lymphomas and tumors in lung and liver. The incidence of lymphoma was higher in Cyp1a2-null females than wild-type females treated with low dose (600 nmol) PhIP whereas no significant differences were observed in other treatment groups of mice. Overall differences in incidences of lung adenoma/adenocarcinoma were in general not consistent among sexes, genotypes and PhIP doses used, although reduced incidences of lung tumors were found in Cyp1a2-null males with low dose (600 nmol) and null females with high dose (1200 nmol) PhIP. Higher incidences of hepatocellular adenoma were observed in Cyp1a2-null female and male mice as compared with wild-type mice. In vitro studies using Cyp1a2-null and wild-type mouse liver microsomes revealed that CYP1A2 is the major enzyme required for PhIP N2-hydroxylation in mouse, the initial metabolic activation of PhIP that is thought to lead to tumor formation. These in vivo and in vitro results suggest that although the metabolic activation of PhIP is carried out primarily by CYP1A2, an unknown pathway unrelated to CYP1A2 appears to be responsible for PhIP carcinogenesis in mouse when examined in the neonatal bioassay. In fact, CYP1A2 may even be protective against all transformation, especially in females. C1 NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Ctr Canc Res, Ft Detrick, MD 21702 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kimura, S (reprint author), NIH, Bldg 37,Room 2A19, Bethesda, MD 20892 USA. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 FU NCI NIH HHS [N01-CO-56000] NR 22 TC 32 Z9 34 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2003 VL 24 IS 3 BP 583 EP 587 DI 10.1093/carcin/24.3.583 PG 5 WC Oncology SC Oncology GA 666AV UT WOS:000182154200030 PM 12663521 ER PT J AU Yang, K Fan, KH Kurihara, N Shinozaki, H Rigas, B Augenlicht, L Kopelovich, L Edelmann, W AF Yang, K Fan, KH Kurihara, N Shinozaki, H Rigas, B Augenlicht, L Kopelovich, L Edelmann, W TI Regional response leading to tumorigenesis after sulindac in small and large intestine of mice with Apc mutations SO CARCINOGENESIS LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LONG-TERM TREATMENT; COLON-CANCER CELLS; COLORECTAL-CANCER; RECTAL-CANCER; INDUCED REGRESSION; INDUCED APOPTOSIS; TUMOR-FORMATION; FLAT ADENOMA AB Sulindac and other NSAIDs have been widely studied as potential chemopreventive agents for colon cancer. Shortterm studies have shown adenomatous polyps to regress in patients with familial adenomatous polyposis (FAP). In this study the effect of sulindac on cancer as an endpoint was evaluated in ApcMin mice, a preclinical model of FAP with an Apc mutation in codon 850 that leads to gastrointestinal adenomas and carcinomas. Three groups of mice were studied all of which were fed AIN-76A diet: one group was fed AIN-76A diet alone, a second group received sulindac 200 p.p.m. premixed in the diet and a third group received sulindac 180 p.p.m. added in drinking water. ApcMin mice were killed 9 weeks after feeding was initiated. Mice receiving sulindac developed fewer tumors in the intestine overall; the major decrease in tumor development after sulindac was seen in the small intestine regardless of route of administration. In the large intestine, however, sulindac significantly increased the incidence, multiplicity and volume of tumors in the colon of ApcMin mice, a regional response to sulindac differing from previous reports. Quantitative measurements of apoptosis, Bax and Bcl-x(L) protein expression in the ApcMin mice revealed the ratio of Bax/Bcl-x(L) expression and apoptosis increased in the small intestine but decreased in the cecum, consistent with the regional tumorigenesis observed after sulindac. These findings thus suggest involvement of Bax and apoptosis in tumors developing after sulindac treatment in this mouse model. C1 Rockefeller Univ, Strang Canc Res Lab, New York, NY 10021 USA. Amer Hlth Fdn, Valhalla, NY 10595 USA. Albert Einstein Coll Med, Bronx, NY 10461 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. RP Yang, K (reprint author), Rockefeller Univ, Strang Canc Res Lab, 1230 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [CN65031, R01-CA87559, U01-CA-84301] NR 61 TC 37 Z9 38 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2003 VL 24 IS 3 BP 605 EP 611 DI 10.1093/carcin/24.3.605 PG 7 WC Oncology SC Oncology GA 666AV UT WOS:000182154200033 PM 12663524 ER PT J AU Frolenkov, GI Mammano, F Kachar, B AF Frolenkov, GI Mammano, F Kachar, B TI Regulation of outer hair cell cytoskeletal stiffness by intracellular Ca2+: underlying mechanism and implications for cochlear mechanics SO CELL CALCIUM LA English DT Article DE cochlear amplifier; prestin; olivocohlear bundle; acetylcholine; intracellular calcium stores; slow motility ID GUINEA-PIG COCHLEA; MAMMALIAN COCHLEA; MOTOR PROTEIN; ACETYLCHOLINE; CALCIUM; MOTILITY; SLOW; ELECTROMOTILITY; GENERATION; INDICATORS AB Two Ca2+-dependent mechanisms have been proposed to regulate the mechanical properties of outer hair cells (OHCs), the sensory-motor receptors of the mammalian cochlea. One involves the efferent neurotransmitter, acetylcholine, decreasing OHC axial stiffness. The other depends on elevation of intracellular free Ca2+ concentration ([Ca2+](i)) resulting in OHC elongation, a process known as Ca2+-dependent slow motility. Here we provide evidence that both these phenomena share a common mechanism. In whole-cell patch-clamp conditions, a fast increase of [Ca2+](i) by UV-photolysis of caged Ca2+ or by extracellular application of Ca2+-ionophore, ionomycin, produced relatively slow (time constant similar to20 s) cell elongation. When OHCs were partially collapsed by applying minimal negative pressure through the patch pipette, elevation of the [Ca2+](i) up to millimole levels (estimated by Fura-2) was unable to restore the cylindrical shape of the OHC. Stiffness measurements with vibrating elastic probes showed that the increase of [Ca2+], causes a decrease of OHC axial stiffness, with time course similar to that of the Ca2+-dependent elongation, without developing any measurable force. We concluded that, contrary to a previous proposal, Ca2+-induced OHC elongation is unlikely to be driven by circumferential contraction of the lateral wall, but is more likely a passive mechanical reaction of the turgid OHC to Ca2+-induced decrease of axial stiffness. This may be the key phenomenon for controlling gain and operating point of the cochlear amplifier. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 NIDCD, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. Ist Nazl Fis Mat, Padua, Italy. Venetian Inst Mol Med, Padua, Italy. RP Frolenkov, GI (reprint author), NIDCD, Sect Struct Cell Biol, NIH, Bldg 50,Room 4346, Bethesda, MD 20892 USA. RI Mammano, Fabio/I-5064-2012; OI Mammano, Fabio/0000-0003-3751-1691; Frolenkov, Gregory/0000-0002-9810-5024 NR 41 TC 36 Z9 37 U1 1 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD MAR PY 2003 VL 33 IS 3 BP 185 EP 195 DI 10.1016/S0143-4160(02)00228-2 PG 11 WC Cell Biology SC Cell Biology GA 656JL UT WOS:000181604600004 PM 12600805 ER PT J AU Polster, BM Robertson, CL Bucci, CJ Suzuki, M Fiskum, G AF Polster, BM Robertson, CL Bucci, CJ Suzuki, M Fiskum, G TI Postnatal brain development and neural cell differentiation modulate mitochondrial Bax and BH3 peptide-induced cytochrome c release SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE Bax; BH3; cytochrome c; brain mitochondria; nerve growth factor; pheochromocytoma ID BCL-2 FAMILY MEMBERS; NERVE GROWTH-FACTOR; CEREBRAL HYPOXIA-ISCHEMIA; NEURONAL APOPTOSIS; FACTOR DEPRIVATION; GRANULE CELLS; DEATH; RAT; IMMATURE; PATHWAY AB dBax mediates cytochrome c release and apoptosis during neurodevelopment. Brain mitochondria that were isolated from 8-day, 17-day, and adult rats displayed decreasing levels of mitochondrial Bax. The amount of cytochrome c released from brain mitochondria by a peptide containing the BH3 cell death domain decreased with increasing age. However, approximately 60% of cytochrome c in adult brain mitochondria could be released by the BH3 peptide in the presence of exogenous human recombinant Bax. Mitochondrial Bax was downregulated in PC12S neural cells differentiated with nerve growth factor, and mitochondria isolated from these cells demonstrated decreased sensitivity to BH3-peptide-induced cytochrome c release. These results demonstrate that immature brain mitochondria and mitochondria from undifferentiated neural cells are particularly sensitive to cytochrome c release mediated by endogenous Bax and a BH3 death domain peptide. Postnatal developmental changes in mitochondrial Bax levels may contribute to the increased susceptibility of neurons to pathological apoptosis in immature animals. C1 Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Fiskum, G (reprint author), Univ Maryland, Sch Med, Dept Anesthesiol, MSTF 5-34,685 W Baltimore St, Baltimore, MD 21201 USA. FU NINDS NIH HHS [R01NS34152] NR 34 TC 28 Z9 32 U1 0 U2 3 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 MAR PY 2003 VL 10 IS 3 BP 365 EP 370 DI 10.1038/sj.cdd.4401158 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 674HZ UT WOS:000182632500010 PM 12700636 ER PT J AU Liu, XD Wen, FQ Kobayashi, T Abe, S Fang, QH Piek, E Bottinger, EP Roberts, AB Rennard, SI AF Liu, XD Wen, FQ Kobayashi, T Abe, S Fang, QH Piek, E Bottinger, EP Roberts, AB Rennard, SI TI Smad3 mediates the TGF-beta-induced contraction of type I collagen gels by mouse embryo fibroblasts SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE Smad; knockout mice; tissue remodeling ID MICE LACKING SMAD3; MATRIX CONTRACTION; DISRUPTION AB TGF-beta signals through TGF-beta receptors and Smad proteins. TGF-beta also augments fibroblast-mediated collagen gel contraction, an in vitro model of connective tissue remodeling. To investigate the importance of Smad2 or Smad3 in this augmentation process, embryo-derived fibroblasts from mice lacking expression of Smad2 or Smat/3 genes were cast into native type I collagen gels. Fibroblast-populated gels were then released into 0.2% FCS-DMEM alone or with recombinant human TGF-beta1, beta2, beta3, or recombinant rat PDGF-BB. Gel contraction was determined using an image analyzer. All three isoforms of TGF-beta significantly augmented contraction of collagen gets mediated by fibroblasts with genotypes of Smad2 knockout (S2KO), Smad2 wildtype (S2WT), and Smad3 wildtype (S3WT), but not Smad3 knockout (S3KO) mice. PDGF-BB augmented collagen gel contraction by all fibroblast types. These results suggest that expression of Smad3 but not Smad2 may be critical in TGF-beta augmentation of fibroblast-mediated collagen gel contraction. Thus, the Smad3 gene could be a target for blocking contraction of fibrotic tissue induced by TGF-beta. Cell Motil. Cytoskeleton 54:248-253, 2003. (C) 2003 Wiley-Liss, Inc. C1 Univ Nebraska, Nebraska Med Ctr 985125, Omaha, NE 68198 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Med, Div Nephrol, Bronx, NY 10467 USA. RP Rennard, SI (reprint author), Univ Nebraska, Nebraska Med Ctr 985125, Omaha, NE 68198 USA. FU NHLBI NIH HHS [R01-HL-64088] NR 23 TC 34 Z9 41 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 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD MAR PY 2003 VL 54 IS 3 BP 248 EP 253 DI 10.1002/cm.10098 PG 6 WC Cell Biology SC Cell Biology GA 651DP UT WOS:000181305400006 PM 12589683 ER PT J AU Grosenbach, DW Schlom, J Gritz, L Yafal, AG Hodge, JW AF Grosenbach, DW Schlom, J Gritz, L Yafal, AG Hodge, JW TI A recombinant vector expressing transgenes for four T-cell costimulatory molecules (OX40L, B7-1, ICAM-1, LFA-3) induces sustained CD4(+) and CD8(+) T-cell activation, protection from apoptosis, and enhanced cytokine production SO CELLULAR IMMUNOLOGY LA English DT Article DE costimulation; poxvirus; T-cell activation ID HIGH IL-4-PRODUCING EFFECTORS; GROWTH-FACTOR RECEPTOR; DENDRITIC CELLS; IN-VIVO; ANTITUMOR IMMUNITY; TUMOR-IMMUNITY; VACCINIA VIRUS; LIGAND; RESPONSES; ANTIGEN AB The role of OX40L on the activation of T cells was investigated using poxvirus vectors expressing OX40L alone or in combination with three other T-cell costimulatory molecules: B7-1, ICAM-1, and LFA-3. Poxvirus vector-infected cells were used to stimulate naive or activated CD4(+) and CD8(+) T cells. These studies demonstrate that (a) OX40L plays a role in sustaining the long-term proliferation of CD8+ T cells in addition to the known effect on CD4+ T cells following activation, (b) OX40L enhances the production of Th1 cytokines (IL-2, IFN-gamma, and TNF-alpha) from both CD4(+) and CD8(+) while no change in IL-4 expression was observed, and (c) the anti-apoptotic effect of OX40L on T cells is likely the result of sustained expression of anti-apoptotic genes while genes involved in apoptosis are inhibited. In addition, these are the first studies to demonstrate that the combined use of a vector driving the expression of OX40L with three other costimulatory molecules (B7-1, ICAM-1, and LFA-3) both enhances initial activation and then further potentiates sustained activation of naive and effector T cells. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Ther Biol Corp, Cambridge, MA 02142 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 36 TC 20 Z9 25 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAR PY 2003 VL 222 IS 1 BP 45 EP 57 DI 10.1016/S0008-8749(03)00080-7 PG 13 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 689UL UT WOS:000183511300005 PM 12798307 ER PT J AU Szabo, P Shen, S Telford, W Weksler, ME AF Szabo, P Shen, S Telford, W Weksler, ME TI Impaired rearrangement of IgH V to DJ segments in bone marrow Pro-B cells from old mice SO CELLULAR IMMUNOLOGY LA English DT Article ID SURROGATE LIGHT-CHAINS; SENESCENT BALB/C MICE; HISTONE ACETYLATION; V(D)J RECOMBINATION; HUMORAL IMMUNITY; AGE; EXPRESSION; REPERTOIRE; CHROMATIN; RECEPTOR AB There are fewer bone marrow Pre-B cells in old compared to young mice. We have demonstrated both decreased rearrangement of the V to DJ IgH gene segments and low levels of VH germline transcripts in Pro-B cells, the precursors of Pre-B cells, from old compared to young mice. However, there was no difference in the level of RAG-mRNA in purified Pro-B cells from old and young mice. Consistent with the prior reports that fewer bone marrow emigrants enter the peripheral B cell populations of old than young mice, we identified fewer transitional B cells in the blood, as well as the spleen, of old than young mice. Association of impaired IgH rearrangement with a decreased number of transitional B cells in old mice was supported by finding that the percentage and number of transitional B cells expressing rearranged IgH and IgL transgenes, which do not require rearrangement of their endogenous IgH gene segments, were comparable in old and young mice. In contrast, the percentage and number of transitional B cells in these Ig-transgenic mice, which escaped allelic exclusion and have rearranged endogenous IgH gene segments, showed an age-associated decline similar to that seen in wild type mice. These data are consistent with the view that impaired V to DJ rearrangement contributes to the decreased levels of bone marrow Pre-B cells as well as the decreased levels of transitional B cells in the periphery. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Cornell Univ, Weill Med Coll, Div Geriatr & Gerontol, New York, NY 10021 USA. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Weksler, ME (reprint author), Cornell Univ, Weill Med Coll, Div Geriatr & Gerontol, New York, NY 10021 USA. FU NIA NIH HHS [AG14669] NR 29 TC 31 Z9 31 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAR PY 2003 VL 222 IS 1 BP 78 EP 87 DI 10.1016/S0008-8749(03)00084-4 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 689UL UT WOS:000183511300008 PM 12798310 ER PT J AU Booth, BW Newcomb, DC McKane, SA Crews, AL Adler, KB Bonner, JC Martin, LD AF Booth, BW Newcomb, DC McKane, SA Crews, AL Adler, KB Bonner, JC Martin, LD TI Proliferation of the airway epithelium in asthma - Are inflammatory cells required? SO CHEST LA English DT Article; Proceedings Paper CT 45th Annual Thomas L Petty Aspen Lung Conference CY JUN 05-08, 2002 CL ASPEN, COLORADO C1 N Carolina State Univ, Coll Vet Med, Raleigh, NC 27606 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Martin, LD (reprint author), N Carolina State Univ, Coll Vet Med, 4700 Hillsborough St, Raleigh, NC 27606 USA. NR 0 TC 2 Z9 2 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2003 VL 123 IS 3 SU S BP 384S EP 385S DI 10.1378/chest.123.3_suppl.384S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 656QV UT WOS:000181619200029 PM 12628995 ER PT J AU Ingram, JL Rice, A Geisenhoffer, K Madtes, DK Bonner, JC AF Ingram, JL Rice, A Geisenhoffer, K Madtes, DK Bonner, JC TI Interleukin-13 stimulates the proliferation of lung myofibroblasts via a signal transducer and activator of transcription-6-dependent mechanism - A possible mechanism for the development of airway fibrosis in asthma SO CHEST LA English DT Article; Proceedings Paper CT 45th Annual Thomas L Petty Aspen Lung Conference CY JUN 05-08, 2002 CL ASPEN, COLORADO ID ALPHA-RECEPTOR; FIBROBLASTS C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Bonner, JC (reprint author), NIEHS, Pulm Pathobiol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 10 TC 17 Z9 20 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2003 VL 123 IS 3 SU S BP 422S EP 424S DI 10.1378/chest.123.3_suppl.422S PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 656QV UT WOS:000181619200044 PM 12629010 ER PT J AU Eden, E Hammel, J Rouhani, FN Brantly, ML Barker, AF Buist, AS Fallat, RJ Stoller, JK Crystal, RG Turino, GM AF Eden, E Hammel, J Rouhani, FN Brantly, ML Barker, AF Buist, AS Fallat, RJ Stoller, JK Crystal, RG Turino, GM CA alpha1-Antitrypsin Deficiency Regi TI Asthma features in severe alpha(1)-antitrypsin deficiency - Experience of the National Heart, Lung, and Blood Institute registry SO CHEST LA English DT Article DE alpha(1)-antitrypsin deficiency; asthma; lung disease, obstructive ID OBSTRUCTIVE PULMONARY-DISEASE; ALPHA-1-ANTITRYPSIN DEFICIENCY; SERUM IGE; BRONCHIAL-ASTHMA; ASSOCIATION; DECLINE; ATOPY; HYPERRESPONSIVENESS; BRONCHODILATOR; RESPONSIVENESS AB Study objectives: To describe asthma features in a cohort with alpha(1)-antitrypsin (AAT) deficiency, and determine the impact of asthma on FEV1 decline. Background: Asthma may be common in those with AAT deficiency, and may lead to accelerated airflow obstruction. Design: Analysis of data obtained from a 5-year, prospective National Heart, Lung, and Blood Institute registry. Setting: A multicenter registry consisting of 37 clinical centers, a central phenotyping laboratory, and a data analysis center. Participants: A cohort of 1,052 subjects with AAT deficiency. Measurements and results: Asthma was defined as reversible airflow obstruction, recurrent attacks of wheezing, and a reported diagnosis of asthma or allergy with or without an elevated serum IgE level. FEV1 decline was calculated by least-square means with adjustments for covariables. Asthma was present in 21% of the cohort and in 12.5% of those with a normal FEV1. Attacks of wheezing were reported in 66%, the first attack occurring at a mean+/-SD age of 31+/-16 years. Allergy and asthma was reported in 29% and 38%, respectively. An elevated IgE level occurred in 17% and was significantly associated with signs and symptoms of asthma and an allergy history. Unadjusted FEV1 decline was less in the group without asthma and a normal IgE level (-48.5 mL/yr) vs: the groups with asthma features (greater than or equal to64 mL/yr) [p=0.002]. Multivariable analysis showed that bronchodilator response, age, and smoking were significant predictors for FEV1 decline but not asthma. Conclusions: Symptoms and signs of asthma are common in AAT deficiency and may start at the age of most rapid FEV1 loss. Adjusting for other risk factors such as bronchodilator response, asthma as defined does not lead to an accelerated FEV1 decline. In AAT deficiency, augmentation therapy is not more effective in preventing the loss of lung function in those with asthma compared to those without. C1 St Lukes Roosevelt Hosp, James P Mara Ctr Lung Dis, New York, NY 10019 USA. Cognigen Corp, Buffalo, NY USA. NIH, Bethesda, MD 20892 USA. Univ Florida, Coll Med, Gainesville, FL USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Calif Pacific Med Ctr, San Francisco, CA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. New York Hosp, Cornell Med Ctr, New York, NY 10021 USA. RP Eden, E (reprint author), St Lukes Roosevelt Hosp, James P Mara Ctr Lung Dis, Room 3A-55,1000 10th Ave, New York, NY 10019 USA. FU NHLBI NIH HHS [N01-HR-86036] NR 25 TC 41 Z9 45 U1 0 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2003 VL 123 IS 3 BP 765 EP 771 DI 10.1378/chest.123.3.765 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 655DR UT WOS:000181536500025 PM 12628876 ER PT J AU Viscidi, RP Rollison, DEM Viscidi, E Clayman, B Rubalcaba, E Daniel, R Major, EO Shah, KV AF Viscidi, RP Rollison, DEM Viscidi, E Clayman, B Rubalcaba, E Daniel, R Major, EO Shah, KV TI Serological cross-reactivities between antibodies to simian virus 40, BK virus, and JC virus assessed by virus-like-particle-based enzyme immunoassays SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID HUMAN PLEURAL MESOTHELIOMA; SV40 CAPSID PROTEINS; DNA-SEQUENCES; INSECT CELLS; POLYOMAVIRUS-JC; SIMIAN-VIRUS-40; EXPRESSION; PREVALENCE; INFECTION; EXPOSURE AB Enzyme immunoassays (EIAs) for detection of serum antibodies to simian virus 40 (SV40), BK virus (BKV), and JC virus (JCV) were developed by using virus-like-particles (VLPs) produced in insect cells from recombinant baculoviruses expressing the VP1 protein of the respective virus. Rhesus macaque sera with neutralizing antibodies to SV40 showed a high level of reactivity in the SV40 VLP-based EIA, and these sera also showed lower levels of reactivity in the BKV and JCV VLP-based EIAs. Rhesus macaque sera negative for neutralizing antibodies to SV40 were negative in all three EIAs. Competitive binding assays showed that SV40 VLPs inhibited BKV reactivity. In rhesus macaque sera, high optical density (OD) values for antibodies to SV40 VLPs were correlated with high OD values for antibodies to BKV but not with high OD values for antibodies to JCV VLPs. Human sera with neutralizing antibodies to SV40 were more reactive to SV40 VLPs than human sera without neutralizing antibodies to SV40. The greater SV40 reactivities of human sera were correlated with greater reactivities to BKV VLPs but not JCV VLPs. These data suggest that cross-reactivity with BKV antibodies may account for part of the low-level SV40 reactivity seen in human sera. With their greater versatility and their suitability for large-scale testing, the VLP-based EIAs for SV40, BKV, and JCV are likely to contribute to a better understanding of the biology of these viruses. C1 NINDS, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Stanley Div Dev Neurovirol, Baltimore, MD 21205 USA. RP Viscidi, RP (reprint author), Johns Hopkins Univ Hosp, Blalock Bldg,Room 1105,600 N Wolfe St, Baltimore, MD 21287 USA. FU NIAID NIH HHS [R01-AI42058] NR 33 TC 104 Z9 107 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAR PY 2003 VL 10 IS 2 BP 278 EP 285 DI 10.1128/CDLI.10.2.278-285.2003 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 655RP UT WOS:000181566700014 PM 12626455 ER PT J AU Freidlin, B Breathnach, OS Johnson, BE AF Freidlin, B Breathnach, OS Johnson, BE TI A model to select regimens for phase III trials for patients with advanced-stage non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SOUTHWEST-ONCOLOGY-GROUP; TYROSINE KINASE INHIBITOR; MITOMYCIN-C FAM; RANDOMIZED TRIAL; COMBINATION CHEMOTHERAPY; CISPLATIN; VINDESINE; ETOPOSIDE; ADENOCARCINOMA; VINORELBINE AB Purpose: Historical data from pilot, Phase II, and Phase III studies for patients with advanced-stage non-small cell lung cancer (NSCLC) were used to evaluate a statistical model developed to provide assistance in selecting regimens from pilot studies for subsequent use in larger Phase III randomized studies. Experimental Design: Information from 33 Phase III trials for patients with advanced-stage NSCLC performed from 1973 and 1994 in the United States and Canada was collected. The data from antecedent pilot or Phase II and subsequent Phase III trials were analyzed using a predictive statistical model. This model uses the number of patients in the pilot/Phase II study, the median survival of patients in the pilot, and the number of deaths observed, to estimate the statistical likelihood that the pilot regimen will be shown superior to standard therapy in a subsequent Phase III trial. Results: Ten pilot/Phase II studies were identified that preceded eleven subsequent Phase III studies. The three pilot regimens associated with Phase III trials, revealing statistically significant longer survival, had an expected power of 0.69, 0.85, and 0.94 respectively. The regimens from the seven other pilot studies for which the median power expected was 0.38 (range, 0.07-0.80) showed no difference when compared with standard treatment in a Phase III trial. Conclusion: The use of the expected power model provides an important enhancement to the screening of new therapies. Regimens with an expected power of >0.55 may be good candidates for testing in Phase III trials. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. Univ Coll, Cork Univ Hosp, Dept Oncol, Cork, Ireland. Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 44 Binney St, Boston, MA 02115 USA. NR 40 TC 14 Z9 14 U1 0 U2 0 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 MAR PY 2003 VL 9 IS 3 BP 917 EP 922 PG 6 WC Oncology SC Oncology GA 653JA UT WOS:000181430400001 PM 12631588 ER PT J AU Davis, JM Navolanic, PM Weinstein-Oppenheimer, CR Steelman, LS Hu, W Konopleva, M Blagosklonny, MV McCubrey, JA AF Davis, JM Navolanic, PM Weinstein-Oppenheimer, CR Steelman, LS Hu, W Konopleva, M Blagosklonny, MV McCubrey, JA TI Raf-1 and Bcl-2 induce distinct and common pathways that contribute to breast cancer drug resistance SO CLINICAL CANCER RESEARCH LA English DT Article ID ABROGATE CYTOKINE DEPENDENCY; SIGNAL-TRANSDUCTION PATHWAY; MURINE HEMATOPOIETIC-CELLS; ELEMENT-BINDING PROTEIN; DIFFERENTIAL ABILITIES; PREVENT APOPTOSIS; DEREGULATED RAF; GENE FAMILY; TUMOR-CELLS; EXPRESSION AB Overexpression of Bcl-2 plays a role in the development of drug resistance in leukemia and other apoptosis-prone tumors. Raf isoforms are serine/threonine kinases that act as signal transducers in cascades initiated by many growth factors and mitogens. Raf isoform activation has been linked to drug resistance in leukemia. In this study we investigated effects of Bcl-2 and Raf-1 on doxorubicin-induced growth inhibition of MCF-7 breast cancer cells. In the absence of doxorubicin, overexpression of Bcl-2 or a constitutively active form of Raf-1 in MCF-7 cells did not affect proliferation rate. Overexpression of Bcl-2 increased resistance of MCF-7 cells to doxorubicin in 2-day, 5-day, and 8-week assays. Analysis of doxorubicin sensitivity of individual MCF/Bcl-2 clones showed that doxorubicin resistance was positively correlated with level of Bcl-2 overexpression. Overexpression of constitutively active Raf-1 also increased resistance to doxorubicin. Induction of Raf-1 activity in MCF-7 cells overexpressing Bcl-2 resulted in greater doxorubicin resistance than induction of Raf-1 activity in MCF-7 cells lacking Bcl-2 overexpression. Furthermore, levels of P-glycoprotein mRNA were increased in MCF-7 cells overexpressing a constitutively active Raf-1. MCF-7 cells overexpressing constitutively active Raf-1 were also more resistant to paclitaxel, which, like doxorubicin, is a substrate of P-glycoprotein. These observations suggest both independent and overlapping roles for Raf-1 and Bcl-2 oncogenes in the resistance to growth inhibition by doxorubicin. C1 E Carolina Univ, Brody Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA. E Carolina Univ, Brody Sch Med, Leo Jenkins Canc Ctr, Greenville, NC 27858 USA. Univ Valparaiso, Fac Farm, Dept Ciencias Farmaceut & Nutr, Valparaiso, Chile. Univ Texas, MD Anderson Canc Ctr, Sect Mol Hematol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Therapy Lab, Dept Blood & Bone Marrow Transplantat, Houston, TX 77030 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP McCubrey, JA (reprint author), E Carolina Univ, Brody Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA. EM mccubreyj@mail.ecu.edu OI McCubrey, James/0000-0001-6027-3156 FU NCI NIH HHS [R01 CA 512025, R01 CA 98195] NR 54 TC 81 Z9 87 U1 0 U2 1 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 MAR PY 2003 VL 9 IS 3 BP 1161 EP 1170 PG 10 WC Oncology SC Oncology GA 653JA UT WOS:000181430400035 PM 12631622 ER PT J AU Cho, YS Cho-Chung, YS AF Cho, YS Cho-Chung, YS TI Antisense protein kinase a RI alpha acts synergistically with hydroxycamptothecin to inhibit growth and induce apoptosis in human cancer cells: Molecular basis for combinatorial therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID TOPOISOMERASE-I INHIBITOR; CYCLIC-AMP; BREAST-CANCER; ANTITUMOR-ACTIVITY; MAMMALIAN-CELLS; FACTOR-RECEPTOR; OVARIAN-CANCER; TUMOR-GROWTH; SUBUNIT; PHOSPHORYLATION AB Purpose: The increased expression of RIalpha, the regulatory subunit of cyclic AMP (cAMP)-dependent protein kinase type I (PKA-I), has been correlated with cancer cell growth. An antisense oligonucleotide targeting the RIalpha subunit of PKA (antisense RIa) induces cell growth arrest, apoptosis, and differentiation in a variety of cancer cell lines in vitro and in tumors in vivo. This study investigated the utility of a combinatorial therapy consisting of the RNA-DNA second-generation RIa antisense HYB0165 (Gem231) and the cytotoxic drug hydroxycamptothecin (RCPT), which inhibits topoisomerase I. Experimental Design: LS-174T colon carcinoma and PC3M androgen-insensitive prostate cancer cells were used as experimental models. The antitumor and apoptotic activities of Gem231 and HCPT, singly and in combination, were measured by cell growth assay, synergism quotient, cell morphology, nuclear morphology, levels of PKA R and C subunits, anti- and proapoptotic proteins, and PKA activity ratio. Results: In a synergistic fashion, Gem231 and RCPT induced growth arrest, apoptosis, and changes in cell morphology; down-regulated RIalpha expression; down-regulated Bcl-2 and promoted its hyperphosphorylation; up-regulated the proapoptotic proteins Bax and Bad; and promoted hypophosphorylation of Bad. Antisense Gem231, but not HCPT, increased the PKA activity ratio, which measures the degree of PKA activation. Conclusion: The results showed that PKA-I activation by Gem231 and topoisomerase I inhibition by RCPT are responsible at the molecular level for the synergistic effects of tumor cell apoptosis and growth inhibition. These results demonstrated the molecular basis for the use of Gem231 and HCPT as combinatorial therapy to treat human cancer. C1 NCI, Cellular Biochem Sect, Basic Res Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Basic Res Lab, Ctr Canc Res,NIH, Bldg 10,Room 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 44 TC 21 Z9 25 U1 0 U2 1 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 MAR PY 2003 VL 9 IS 3 BP 1171 EP 1178 PG 8 WC Oncology SC Oncology GA 653JA UT WOS:000181430400036 PM 12631623 ER PT J AU Dufour, DR Talastas, M Fernandez, MDA Harris, B Strader, DB Seeff, LB AF Dufour, DR Talastas, M Fernandez, MDA Harris, B Strader, DB Seeff, LB TI Low-positive anti-hepatitis C virus enzyme immunoassay results: An important predictor of low likelihood of hepatitis C infection SO CLINICAL CHEMISTRY LA English DT Article ID RECOMBINANT IMMUNOBLOT ASSAY; NON-B HEPATITIS; TRANSFUSION-TRANSMITTED VIRUSES; LINKED-IMMUNOSORBENT-ASSAY; BLOOD-DONORS; NON-A; UNITED-STATES; DIAGNOSIS; ANTIBODIES; GENERATIONS AB Background: Tests for hepatitis C antibodies (anti-HCV enzyme immunoassays) are usually described as positive or negative. Several studies, mainly in blood donors, have found that specimens with low signal/cutoff NO ratios are commonly negative when tested with a recombinant immunoblot assay (RIBA) or for HCV RNA. Methods: We retrospectively reviewed 17 418 consecutive anti-HCV results from a screening program for high-risk veterans; 2986 (17.1%) samples were anti-HCV-positive, and 490 (16.4%) had S/C ratios less than or equal to3.7 (low positive). Additional tests were performed in 1814 anti-HCV-positive individuals. Results: RIBA was performed in 263 patients with low-positive anti-HCV; results were negative in 86%, indeterminate in 12%, and positive in 2%. Only 16 of 140 individuals (11%) with low-positive anti-HCV values were HCV RNA-positive, whereas HCV RNA was positive in 90% of 1435 individuals with high-positive anti-HCV values (P < 0.0001). Compared with those with high-positive anti-HCV, individuals with low-positive anti-HCV values were older (P < 0.0001) and were less likely to have risk factors for HCV (P < 0.0001 for most), multiple increased alanine aminotransferase (ALT) activity values (30% vs 81%; P < 0.0001), or positive antihepatitis B core antigen (19% vs 59%; P < 0.0002). Among 634 individuals with high anti-HCV titers and multiple increased ALT activity values, 95% were HCV RNA positive. Conclusions: The S/C ratio is important even in high-risk individuals; laboratories should report the S/C ratio along with anti-HCV EIA results and perform supplemental RIBA testing in those with low-positive values to avoid reporting false-positive results. (C) 2003 American Association for Clinical Chemistry. C1 Vet Affairs Med Ctr, Pathol & Lab Med Serv 113, Washington, DC 20422 USA. Vet Affairs Med Ctr, Med Serv, Washington, DC 20422 USA. NIDDKD, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20008 USA. RP Dufour, DR (reprint author), Vet Affairs Med Ctr, Pathol & Lab Med Serv 113, 50 Irving St NW, Washington, DC 20422 USA. NR 38 TC 44 Z9 48 U1 0 U2 5 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 MAR PY 2003 VL 49 IS 3 BP 479 EP 486 DI 10.1373/49.3.479 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 649EL UT WOS:000181193900016 PM 12600961 ER PT J AU Pinsky, PF Schoen, RE Weissfeld, JL Bresalier, RS Hayes, RB Gohagan, JK AF Pinsky, Paul F. Schoen, Robert E. Weissfeld, Joel L. Bresalier, Robert S. Hayes, Richard B. Gohagan, John K. CA Prostate Lung Colorectal Ovarian P TI Predictors of Advanced Proximal Neoplasia in Persons With Abnormal Screening Flexible Sigmoidoscopy SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article AB Background & Aims: The relationship between distal and proximal colonic findings is uncertain. Thus, there is no consensus on which findings on screening flexible sigmoidoscopy should trigger colonoscopy. Methods: We analyzed data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to assess the relationship between distal and proximal colonic findings. Results: A total of 8802 subjects had an abnormal baseline sigmoidoscopy and colonoscopy follow-up. Subjects with <10-mm single or multiple tubular adenomas had similar risks for advanced proximal neoplasia as subjects with hyperplastic polyps or other benign lesions (3%-5%). Subjects with large (>= 10 mm), villous, or severely dysplastic distal adenomas had similarly elevated risks for advanced proximal neoplasia (11%-12%). Multivariate logistic modeling showed a significantly increased risk for advanced proximal neoplasia associated with the presence of a large tubular (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.0-3.4) or villous distal adenoma (OR, 2.7; 95% CI, 2.1-3.5) but not with the presence of one (OR, 1.05; 95% CI, 0.8-1.3) or multiple (OR, 0.8; 95% CI, 0.5-1.2) <10-mm tubular distal adenomas. Conclusions: Among subjects with a polypoid lesion on screening flexible sigmoidoscopy, those with small tubular distal adenomas are at similar risk for advanced proximal neoplasia as those without distal adenomas. Subjects with a large, villous, or dysplastic distal adenoma are at increased risk. A strategy that encourages individuals with small tubular adenomas on sigmoidoscopy to undergo follow-up colonoscopy and excludes those with nonadenomatous lesions is of questionable validity, because both groups are at similar risk for advanced proximal neoplasia. C1 [Pinsky, Paul F.] NCI, Early Detect Res Grp, DCP, EPN,Div Canc Prevent,NIH, Bethesda, MD 20892 USA. [Hayes, Richard B.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Schoen, Robert E.; Weissfeld, Joel L.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Bresalier, Robert S.] Henry Ford Hlth Syst, Detroit, MI USA. RP Pinsky, PF (reprint author), NCI, Early Detect Res Grp, DCP, EPN,Div Canc Prevent,NIH, Room 3100,MSC 7346, Bethesda, MD 20892 USA. EM pinskyp@mail.nih.gov NR 24 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAR PY 2003 VL 1 IS 2 BP 103 EP 110 DI 10.1053/jcgh.2003.50017 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19KF UT WOS:000208070600006 PM 15017502 ER PT J AU Walker, JM Lwin, A Tayebi, N LaMarca, ME Orvisky, E Sidransky, E AF Walker, JM Lwin, A Tayebi, N LaMarca, ME Orvisky, E Sidransky, E TI Glucocerebrosidase mutation T369M appears to be another polymorphism SO CLINICAL GENETICS LA English DT Letter ID GAUCHER-DISEASE; IDENTIFICATION; GENE C1 NIMH, Sect Mol Neurogenet, NIH, Bethesda, MD 20892 USA. NHGRI, Human Genet Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NIMH, Sect Mol Neurogenet, NIH, 49 Convent Dr MSC 4405,49-B1EE16, Bethesda, MD 20892 USA. NR 7 TC 11 Z9 11 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD MAR PY 2003 VL 63 IS 3 BP 237 EP 238 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 666MY UT WOS:000182182100016 PM 12694238 ER PT J AU de Boer, AW Markowitz, N Lane, HC Saravolatz, LD Koletar, SL Donabedian, H Yoshizawa, C Duliege, AM Fyfe, G Mitsuyasu, RT AF de Boer, AW Markowitz, N Lane, HC Saravolatz, LD Koletar, SL Donabedian, H Yoshizawa, C Duliege, AM Fyfe, G Mitsuyasu, RT TI A randomized controlled trial evaluating the efficacy and safety of intermittent 3-, 4-, and 5-day cycles of intravenous recombinant human interleukin-2 combined with antiretroviral therapy (ART) versus ART alone in HIV-seropositive patients with 100-300 CD4(+) T cells SO CLINICAL IMMUNOLOGY LA English DT Article DE HIV; interleukin-2; CD4(+) T-cell count; viral load; safety; efficacy; AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; DOSE SUBCUTANEOUS INTERLEUKIN-2; INFECTED PATIENTS; TYPE-1; PLASMA; IMMUNOTHERAPY; LYMPHOCYTES; INCREASES; DISEASE; BURDEN AB The effect of length of therapy on the safety and efficacy profile of continuous intravenous (CIV) interleukin-2 (IL-2) in combination with antiretroviral therapy (ART) was evaluated in 81 HIV-seropositive patients with CD4(+) T-cell counts of 100-300/mm(3). Patients were randomized to CIV IL-2 (12 mIU/day) for 3, 4, or 5 days plus ART every 8 weeks for six cycles, or to ART alone. The mean percent increase in CD4(+) T-cell counts was 24.5% for IL-2 recipients compared with a mean percent decrease of 30.5% for control patients (P = 0.005). Increasing duration of CIV IL-2 therapy resulted in improved CD4(+) T-cell response. The most frequent clinical adverse events and laboratory abnormalities were predominantly of grade 1 or 2 severity. However, grade 3 or 4 events were reported in 57%, 60%, and 84% of the 3-, 4-, and 5-day CIV IL-2 patients, respectively. Serious adverse events, mainly due to the requirement of hospitalization, occurred in 20% of IL-2 recipients, compared with 10% of control patients. Viral load during the course of the study was not different among the treatment groups. IL-2 therapy in cycles of 5 days resulted in an optimal increase in CD4(+) T-cell counts and is the preferred cycle length for IL-2 therapy geared toward increasing CD4(+) T-cell numbers. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Chiron Corp, Clin Dev, Emeryville, CA 94608 USA. Henry Ford Hosp, Detroit, MI 48202 USA. NIAID, Bethesda, MD 20892 USA. Ohio State Univ Hosp, Columbus, OH 43210 USA. Med Coll Ohio, Toledo, OH 43699 USA. Univ Calif Los Angeles, Care Ctr, Los Angeles, CA 90024 USA. RP de Boer, AW (reprint author), Chiron Corp, Clin Dev, 4560 Horton St,M-S U-140, Emeryville, CA 94608 USA. NR 34 TC 17 Z9 17 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAR PY 2003 VL 106 IS 3 BP 188 EP 196 DI 10.1016/S1521-6616(02)00038-4 PG 9 WC Immunology SC Immunology GA 672DG UT WOS:000182505400004 PM 12706405 ER PT J AU Kottilil, S Malech, HL Gill, VJ Holland, SM AF Kottilil, S Malech, HL Gill, VJ Holland, SM TI Infections with Haemophilus species in chronic granulomatous disease: insights into the interaction of bacterial catalase and H2O2 production SO CLINICAL IMMUNOLOGY LA English DT Article DE chronic granulomatous disease; Haemophilus aphrophilus; Haemophilus paraphrophilus; catalase; hydrogen peroxide; reactive oxygen derivatives ID PARAPHROPHILUS; STREPTOCOCCUS; VIRULENCE AB Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes are incapable of generating bactericidal-reactive oxygen derivatives. Typically these patients are susceptible to life-threatening infections with catalase-producing organisms. Haemophilus species, particularly H. paraphrophilus, are not associated with CGD infections, because these organisms rarely if ever produce catalase. Haemophilus species are part of the indigenous oral microbial flora and, other than H. influenzae, are rarely recognized as pathogens. They are fastidious and require additional growth factors and capnophilic culture conditions for optimal growth and identification. Here we describe three cases of infection with non-H. influenzae (NHI) Haemophilus species in CGD patients. These organisms were catalase-negative and therefore not expected to be virulent in CGD patients, but they were also H2O2 production-negative, thereby negating the putative loss of virulence of being catalase-negative. These are the first reports of NHI Haemophilus species in CGD and reinforce the critical need for careful microbiologic evaluation of infections in CGD patients. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Clin Microbiol Serv, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N103,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. OI Malech, Harry/0000-0001-5874-5775 NR 27 TC 8 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAR PY 2003 VL 106 IS 3 BP 226 EP 230 DI 10.1016/S1521-6616(02)00048-7 PG 5 WC Immunology SC Immunology GA 672DG UT WOS:000182505400008 PM 12706409 ER PT J AU Lenz, P Thompson, CD Day, PM Bacot, SM Lowy, DR Schiller, JT AF Lenz, P Thompson, CD Day, PM Bacot, SM Lowy, DR Schiller, JT TI Interaction of papillomavirus virus-like particles with human myeloid antigen-presenting cells SO CLINICAL IMMUNOLOGY LA English DT Article DE papillomavirus; virus-like particles; dendritic cells; monocytes; macrophages; inflammatory cytokines; vaccine ID DENDRITIC CELLS; CERVICAL-CANCER; L1; AUTOANTIBODIES; IMMUNIZATION; INDUCTION; IMMUNITY; VACCINES; PROTEIN AB Papillomavirus-like particles (VLPs) are potent inducers of humoral and cellular immune responses, making them attractive candidates for noninfectious viral subunit vaccines. To further our understanding of how VLPs activate the immune system, we have investigated their interaction with human myeloid antigen-presenting cells. We found that VLPs bound, with increasing density, to the cell surface of human monocytes, macrophages, and monocyte-derived dendritic cells (DCs). Interestingly, there was a negative correlation between binding intensity and CD83 expression in DCs, suggesting that the main receptor for binding of VLPs may be downregulated during maturation. Exposure to VLPs resulted in acute phenotypic activation of monocytes and DCs. Furthermore, VLPs rapidly induced production of inflammatory cytokines in monocytes, macrophages, and DCs, as assessed by intracellular cytokine staining. For each cell type, the patterns of interleukin-1beta, interleukin-12, tumor necrosis factor-alpha, and interleukin-6 production were distinct from the pattern induced by lipopolysaccharide (LPS), a bacterial activator of myeloid antigen-presenting cells. Our results indicate that VLPs target multiple cells of the immune system, which helps to account for VLPs being so effective in priming humoral and cellular immune responses even in the absence of adjuvant. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD USA. RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, NIH, 37,Rm 4106,36 Convent Dr,MSC4040, Bethesda, MD 20892 USA. NR 19 TC 54 Z9 58 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAR PY 2003 VL 106 IS 3 BP 231 EP 237 DI 10.1016/S1521-6616(02)00039-6 PG 7 WC Immunology SC Immunology GA 672DG UT WOS:000182505400009 PM 12706410 ER PT J AU Sarlis, NJ Gourgiotis, L Guthrie, LC Galen, B Skarulis, MC Shawker, TH Patronas, NJ Reynolds, JC AF Sarlis, NJ Gourgiotis, L Guthrie, LC Galen, B Skarulis, MC Shawker, TH Patronas, NJ Reynolds, JC TI In-111 DTPA-octreotide scintigraphy for disease detection in metastatic thyroid cancer comparison with F-18FDG positron emission tomography and extensive conventional radiographic imaging SO CLINICAL NUCLEAR MEDICINE LA English DT Article DE computed tomography; magnetic resonance imaging; octreoscan; positron emission tomography; thyroid cancer ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; ELEVATED THYROGLOBULIN LEVELS; CARCINOMA CELL-LINES; FOLLOW-UP; FDG-PET; QUANTITATIVE ASSESSMENT; RADIONUCLIDE THERAPY; HUMAN TUMORS; I-131 SCAN; FLUORODEOXYGLUCOSE AB Purpose: The utility of In-111 DTPA octreotide scintigraphy (SRS) for disease detection in patients with metastatic thyroid carcinoma (TCA) remains controversial. The authors compared the sensitivity of In-111-based SRS, F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), and extensive conventional radiographic imaging (CRI) in this type of cancer. Methods: SRS, FDG PET, and CRI were performed concurrently in 21 patients (age, 56.4 +/- 12.9 years) who had aggressive TCA. Concordance rates % of lesion positivity among pairs of different techniques (A and B) were calculated as the ratio of the number of lesions positive with both techniques divided by the sum of the total number of lesions positive with technique A + total number of lesions positive with technique B, which was then multiplied by 200. Results: The combined use of CRI, FDG PET, and SRS resulted in the detection of 105 lesions, presumed to be due to metastatic deposits. Sensitivities for SRS and FDG-PET imaging were 49.5% and 67.6%, respectively. The lesion detection concordance rates were as follows: CRI versus FDG PET, 80.8%; CRI versus SRS, 74.2%; and FDG-PET versus SRS, 58.6%. Importantly, SRS detected five unexpected lesions, which were negative by both CRI and FDG-PET imaging. In two representative patients, a positive correlation (Spearman's rank = 0.71; P = 0.0576) existed between the percentage of lesional In-111 DTPA octreotide uptake and the standard uptake value in eight concordant lesions. Conclusion: Although SRS has only moderate sensitivity for disease detection in metastatic TCA, sometimes it can reveal lesions that otherwise would be undetectable by either CRI or FDG-PET imaging. C1 NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. RP Sarlis, NJ (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Endocrinol Neoplasia & Hormone Dis, 1515 Holcombe Blvd,Unit 435, Houston, TX 77030 USA. NR 58 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD MAR PY 2003 VL 28 IS 3 BP 208 EP 217 DI 10.1097/00003072-200303000-00008 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 648CD UT WOS:000181131500008 PM 12592128 ER PT J AU Perry, MB Premkumar, A Venzon, DJ Shawker, TH Gerber, LH AF Perry, MB Premkumar, A Venzon, DJ Shawker, TH Gerber, LH TI Ultrasound, magnetic resonance imaging, and posterior tibialis dysfunction SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TENDON DYSFUNCTION; DIAGNOSIS AB The authors studied posterior tibialis tendons in 31 subjects with posterior tibialis tendon pain to compare clinical findings with those of magnetic resonance imaging and ultrasound images. All subjects received clinical, ultrasound, and magnetic resonance imaging examinations using T1-weighted, T2-weighted, and enhanced magnetic resonance imaging, and high resolution ultrasound using power Doppler. Forty-four tendons in 25 women and six men with a mean age 43.3 years (range, 20-73 years) were studied. Magnetic resonance imaging tendon and peritendon enhancement are associated statistically with increasing pain intensity on resistance to testing. Ultrasound tendon and peritendon flow were associated with increasing pain intensity on resistance to testing. There is no statistically significant association between magnetic resonance imaging inhomogeneity and pain intensity on resistance to testing. Clinical and ultrasound examinations positively identify peritendinitis and tendonitis but not inhomogeneity (partial tear) of the posterior tibialis tendon. The magnetic resonance imaging is a more sensitive test for posterior tibialis tendon tear than either clinical or ultrasound evaluation. C1 NCI, Dept Rehabil Med, NIH, Bethesda, MD 20892 USA. NCI, Dept Radiol, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Perry, MB (reprint author), NCI, Dept Rehabil Med, NIH, 10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 17 TC 7 Z9 9 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAR PY 2003 IS 408 BP 225 EP 231 DI 10.1097/01.blo.0000053344.97749.ef PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 653LM UT WOS:000181436700030 PM 12616063 ER PT J AU Ricketts, MN Brown, P AF Ricketts, MN Brown, P TI Transmissible spongiform encephalopathy update and implications for blood safety SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; PLASMA DERIVATIVES; PRION DISEASES; VARIANT; RISK; TRANSFUSION; INFECTIVITY; SURVEILLANCE; COMPONENTS; VIRUS AB This article reviews the evidence regarding the risk of transmission of the human transmissible spongiform encephalopathies (TSEs) through transfusion and the implications for blood safety. At this time, the accumulated evidence does not support the implementation of measures targeted against the risk of transfusion transmission of sporadic, familial, or iatrogenic Creutzfeldt-Jakob disease (CJD). Evolving information about variant CJD (vCJD), however, suggests that policy makers need to consider implementing measures to protect against exposure to vCJD, if such measures themselves do not lead to decreased blood safety. Surveillance of TSEs and investigation of the risk of transfusion transmission must continue in order to provide further refinements in blood safety policy. C1 WHO, CH-1211 Geneva, Switzerland. NIH, Bethesda, MD 20892 USA. RP Ricketts, MN (reprint author), WHO, Room L412,Ave Appia, CH-1211 Geneva, Switzerland. NR 32 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2003 VL 23 IS 1 BP 129 EP + DI 10.1016/S0272-2712(02)00066-5 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 706XB UT WOS:000184479400007 PM 12733428 ER PT J AU Skowron, EA Holmes, SE Sabatelli, RM AF Skowron, EA Holmes, SE Sabatelli, RM TI Deconstructing differentiation: Self regulation, interdependent relating, and well-being in adulthood SO CONTEMPORARY FAMILY THERAPY LA English DT Article DE Bowen theory; differentiation of self; well-being; factor analysis ID INTERGENERATIONAL HIERARCHICAL BOUNDARY; PERSONAL AUTHORITY; FAMILY SYSTEM; INDIVIDUATION; TERMINATION; IDENTITY; MARRIAGE; PARENT AB This study examined underlying similarities between the Personal Authority in the Family System Questionnaire (PAFS; Bray, Williamson, & Malone, 1984a) and the Differentiation of Self Inventory (DSI; Skowron & Friedlander, 1998). Generalized least-squares factor analysis yielded two related factors, Self Regulation and Interdependent Relating, accounting for 60% of the variance in the solution. Greater Self Regulation-comprised of DSI scales characterized by less emotional reactivity and the ability to take an I position in relationships-and Interdependent Relating-marked by greater personal authority, intergenerational intimacy and less intergenerational fusion on the PAFS and less emotional cutoff on the DSI-predicted wellbeing among both women and men. Implications for family therapy and suggestions for future research are discussed. C1 Penn State Univ, University Pk, PA 16802 USA. Univ Connecticut, Sch Family Studies, Storrs, CT 06268 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Skowron, EA (reprint author), Penn State Univ, 327 Cedar Bldg, University Pk, PA 16802 USA. NR 48 TC 29 Z9 32 U1 2 U2 10 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0892-2764 J9 CONTEMP FAM THER JI Contemp. Fam. Ther. PD MAR PY 2003 VL 25 IS 1 BP 111 EP 129 DI 10.1023/A:1022514306491 PG 19 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 661PK UT WOS:000181898800007 ER PT J AU Panigada, M Berra, L Greco, G Stylianou, M Kolobow, T AF Panigada, M Berra, L Greco, G Stylianou, M Kolobow, T TI Bacterial colonization of the respiratory tract following tracheal intubation - Effect of gravity: An experimental study SO CRITICAL CARE MEDICINE LA English DT Article DE ventilator-associated pneumonia; tracheal tube orientation; mechanical ventilation; lung bacterial colonization; tracheal bacterial colonization; body rotation ID VENTILATOR-ASSOCIATED PNEUMONIA; GASTROESOPHAGEAL REFLUX; ARTIFICIAL-VENTILATION; MECHANICAL VENTILATION; BODY POSITION; ASPIRATION; PREVENTION; SUPINE; CARE AB Objective. To explore the role of the horizontal orientation of endotracheal tube and neck on bacterial colonization of the respiratory tract in anesthetized sheep on mechanical ventilation, without use of antibiotics. Design: Prospective animal study. Setting: National Institutes of Health research laboratory. Subjects: Anesthetized, paralyzed, and ventilated sheep. Interventions. Sheep were randomized into five groups and managed as follows: Group IS contained sheep that were not intubated and were immediately killed. Group HU4 contained six sheep that were mechanically ventilated for 4 hrs, with head and endotracheal tube elevated 30 degrees from horizontal. Group HU72 contained seven sheep that were prone, mechanically ventilated for 72 hrs, and managed the same as group HU4. Groups G and Gf each contained seven sheep that were prone on a lateral body rotation device, mechanically ventilated for 72 hrs, with neck and endotracheal tube horizontal. Group Gf received nasogastric enteral feeding. Measurements and Main Results. At the end of the study, sheep were examined postmortem, and a total of 11 tissue samples were taken from the trachea, the five lobar bronchi, and the five lobar parenchyma, for qualitative and quantitative culture. Group HU72 had significant decrease in Pao(2)/Fio(2) and heavy bacterial colonization in all sheep. Groups G and Gf retained excellent lung function; lung bacterial colonization was no different from the IS group. Conclusions, The horizontal orientation of the endotracheal tube and neck, through lateral body rotation, showed no altered airway colonization and maintained excellent gas exchange and lung function in our animal model. C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm & Cardiac Assist Devices, NIH, Bethesda, MD 20892 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Panigada, M (reprint author), NHLBI, PCCMB, NIH, 9000 Rockville Pike,Bldg 10,Rm 5D-07, Bethesda, MD 20892 USA. RI Panigada, Mauro/K-4650-2014 OI Panigada, Mauro/0000-0003-4841-9794 NR 28 TC 54 Z9 55 U1 0 U2 4 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 MAR PY 2003 VL 31 IS 3 BP 729 EP 737 DI 10.1097/01.CCM.0000049943.01252.E5 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 660RP UT WOS:000181846800010 PM 12626976 ER PT J AU Mandava, S Kolobow, T Vitale, G Foti, G Aprigliano, M Jones, M Muller, E AF Mandava, S Kolobow, T Vitale, G Foti, G Aprigliano, M Jones, M Muller, E TI Lethal systemic capillary leak syndrome associated with severe ventilator-induced lung injury: An experimental study SO CRITICAL CARE MEDICINE LA English DT Article DE lethal systemic capillary leak syndrome; ventilator-induced lung injury; multiple system organ failure; acute respiratory distress syndrome; respiratory rate; inspiratory time; peak inspiratory airway pressure ID RESPIRATORY-DISTRESS SYNDROME; END-EXPIRATORY PRESSURE; MECHANICAL VENTILATION; AIRWAY PRESSURE; ORGAN FAILURE; SURFACTANT; MODEL AB Objective., We report the evolution of severe ventilator-induced lung injury associated with lethal systemic capillary leak syndrome, when sheep were ventilated at a peak inspiratory pressure of 50 cm H2O, at a respiratory rate of 8 breaths(.)min(-1), with an inspiratory time of 2.5 secs. Design. A prospective laboratory animal study. Setting. Experimental animal research laboratory. Subjects. Mixed breed sheep. Interventions: Sheep were anesthetized, paralyzed, and mechanically ventilated. Measurements and Main Results. This sheep model was characterized by a rapidly evolving massive anasarca, hemoconcentration, cardiac dysfunction, multiple system organ failure, and severe ventilator-induced lung injury. Cardiovascular changes and profound hemoconcentration developed within 6 hrs from the start of mechanical ventilation, along with a major decline in pulmonary compliance and deterioration in arterial blood gases. When total static lung compliance decreased to 0.15 mL (cm H2O)(-1.)kg(-1) (7-30 hrs), the sheep were randomized to two groups. Group I received high (recruitive) positive end-expiratory pressure (9-20 cm H2O), adjusted as needed; group 11 received low (supportive) positive end-expiratory pressure (2-6 cm H2O). Sheep in both groups progressively deteriorated and died with cardiocirculatory failure and multiple system organ failure within 12-24 hrs from start of treatment. Conclusions., This model of lethal systemic capillary leak syndrome with multiple system organ failure differs greatly from our previous sheep model of acute ventilator-induced lung injury in which sheep were ventilated with a peak inspiratory pressure of 50 cm H2O, a respiratory rate of 4 breaths(.)min(-1), and an inspiratory time of 1.35 secs, without inducing capillary leak syndrome. The mere change of respiratory rate from 4 to 8 breaths(.)min(-1), with a near doubling of the inspiratory time to 2.5 secs, although maintaining eucapnia, resulted in lethal systemic capillary leak syndrome and multiple system organ failure with both gross and microscopic pathology of lungs greatly different from our previous model of mechanical ventilation-induced acute respiratory distress syndrome. C1 NHLBI, Pulm Crit Care Med Branch, Sect Pulm & Cardiac Assist Devices, NIH, Bethesda, MD 20892 USA. RP Kolobow, T (reprint author), NHLBI, Pulm Crit Care Med Branch, Sect Pulm & Cardiac Assist Devices, NIH, Bldg 10,Room 5D-07, Bethesda, MD 20892 USA. RI Foti, Giuseppe/K-8627-2016; OI foti, giuseppe/0000-0002-8698-2046 NR 24 TC 25 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2003 VL 31 IS 3 BP 885 EP 892 DI 10.1097/01.CCM.0000050294.04869.B8 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 660RP UT WOS:000181846800035 PM 12627001 ER PT J AU Horng, S Miller, FG AF Horng, S Miller, FG TI Ethical framework for the use of sham procedures in clinical trials SO CRITICAL CARE MEDICINE LA English DT Article DE randomized; controlled trial; placebo-controlled procedures; sham surgery; ethics ID TRANSMYOCARDIAL REVASCULARIZATION; REFRACTORY ANGINA; PLACEBO; SURGERY; DISEASE; LASER AB Ethical, professional, and financial considerations support the highest standards in demonstrating the safety and efficacy of new clinical interventions. Professional and regulatory mechanisms implemented to ensure that medical agents undergo a thorough process of systematic testing are lacking in the case of medical procedures. As a result, many procedures, including surgery, are rapidly introduced into the clinical setting without reliable evaluation of their efficacy. In many cases, a randomized, placebo-controlled procedure trial may be necessary to provide this data. We examine the major ethical objections to placebo-controlled procedure trials, including those involving sham surgery, and provide an ethical framework for assessing whether a placebo procedure is ethical to administer in the context of a clinical trial. A placebo-controlled trial of an invasive procedure can be ethically justified if: 1) there is a valuable, clinically relevant question to be answered by the research, 2) the placebo control is methodologically necessary to test the study hypothesis, 3) the risk of the placebo control itself has been minimized, 4) the risk of a placebo control does not exceed a threshold of acceptable research risk, 5) the risk of the placebo control is justified by valuable knowledge to be gained, and 6) the misleading involved in the administration of a placebo control is adequately disclosed and authorized during the informed consent process. C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. NR 33 TC 37 Z9 38 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 MAR PY 2003 VL 31 IS 3 SU S BP S126 EP S130 DI 10.1097/01.CCM.0000054906.49187.67 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 661XL UT WOS:000181915100003 PM 12626957 ER EF