FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wendler, D Emanuel, E AF Wendler, D Emanuel, E TI The debate over research on stored biological samples - What do sources think? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID GENETIC RESEARCH; INFORMED CONSENT; TISSUE AB Background: The debate over informed consent for research on stored biological samples has enormous scientific implications. Unfortunately, there are no data on individuals' attitudes regarding when their consent should be obtained for such research. Methods: Data were gathered using a telephone survey of 504 individuals living in the United States. Two cohorts were studied: (1) individuals who had participated in clinical research and contributed biological samples and (2) randomly selected Medicare recipients, Results: Of the respondents, 65.8% would require their consent for research on clinically derived, personally identified samples; 27.3% would require it for research on clinically derived samples that are "anonymized." For research-derived samples, 29.0% of the respondents would require their consent if the samples retain personal identifiers; 12.1% would require it if the samples are anonymized before the research is conducted. Also, 88.8% would want to be informed of results of uncertain clinical significance, and 91.9% would not impose greater safeguards on future research on a different disease. Conclusions: Current practice and policy recommendations regarding research using stored biological samples may be inconsistent with sources' preferences in several respects. In particular, it appears that most sources want to control whether their samples are used for research purposes, are not concerned with the particular disease that will be studied, and want to receive results of uncertain clinical significance. Follow-up research will be needed to assess the generalizability of the current data. C1 Warren G Magnuson Clin Ctr, Dept Clin Bioeth, NIH, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), Warren G Magnuson Clin Ctr, Dept Clin Bioeth, NIH, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. NR 15 TC 119 Z9 121 U1 0 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 JUL 8 PY 2002 VL 162 IS 13 BP 1457 EP 1462 DI 10.1001/archinte.162.13.1457 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 570AK UT WOS:000176635600008 PM 12090881 ER PT J AU Gopich, IV Szabo, A AF Gopich, IV Szabo, A TI Kinetics of reversible diffusion influenced reactions: The self-consistent relaxation time approximation SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID INTEGRAL ENCOUNTER THEORIES; MANY-PARTICLE TREATMENT; NON-MARKOVIAN THEORY; BIMOLECULAR REACTIONS; ARROW-C; MULTISTAGE REACTIONS; LIQUID SOLUTIONS; 3 DIMENSIONS; BINDING; SIMULATIONS AB The simplest general theory of the kinetics of reversible diffusion-influenced reactions that is exact both at short and long times for A+Breversible arrowC and A+Breversible arrowC+D is presented. The formalism is based on an approximate set of reaction-diffusion equations for the pair distribution functions which incorporate the influence of the chemical reaction by using effective rate constants that are determined self-consistently. For small deviations from equilibrium and contact reactivity, the relaxation function is given explicitly in the Laplace domain in terms of the Smoluchowski rate coefficient that describes the corresponding diffusion controlled irreversible reaction. Consequently, the kinetics can be easily obtained for arbitrary diffusion coefficients and equilibrium concentrations. (C) 2002 American Institute of Physics. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Gopich, IV (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012 NR 54 TC 67 Z9 67 U1 0 U2 13 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JUL 8 PY 2002 VL 117 IS 2 BP 507 EP 517 DI 10.1063/1.1482701 PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 566JR UT WOS:000176424800002 ER PT J AU Lindsay, RS Funahashi, T Hanson, RL Matsuzawa, Y Tanaka, S Tataranni, PA Knowler, WC Krakoff, J AF Lindsay, RS Funahashi, T Hanson, RL Matsuzawa, Y Tanaka, S Tataranni, PA Knowler, WC Krakoff, J TI Adiponectin and development of type 2 diabetes in the Pima Indian population SO LANCET LA English DT Article ID INSULIN-RESISTANCE; OBESITY; PROTEIN AB Adiponectin Is a collagen-like circulating protein secreted by adipocytes that Is proposed to mediate obesity-related resistance to Insulin. In a case-control series, we assessed the role of adiponectin in later development of type 2 diabetes In 70 patients who later developed type 2 diabetes and 70 controls, matched for body-mass index, age, and sex. Cases and controls were taken from the longitudinal study of health In the Pima Indian population. At baseline, the concentration of adiponectin was lower In cases than in controls (p=0.01) and Individuals with high concentrations of this protein were less likely to develop type 2 diabetes than those with low concentrations (incidence rate ratio 0.63 [95% CI 0.43-0.92]; p=0.02). C1 NIDDKD, NIH, Phoenix, AZ 85014 USA. Osaka Univ, Grad Sch Med, Dept Internal Med & Mol Sci, Osaka, Japan. RP Lindsay, RS (reprint author), NIDDKD, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 5 TC 709 Z9 771 U1 2 U2 11 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 6 PY 2002 VL 360 IS 9326 BP 57 EP 58 DI 10.1016/S0140-6736(02)09335-2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 569JR UT WOS:000176599700014 PM 12114044 ER PT J AU Larsson, M Fonteneau, JF Lirvall, M Haslett, P Lifson, JD Bhardwaj, N AF Larsson, M Fonteneau, JF Lirvall, M Haslett, P Lifson, JD Bhardwaj, N TI Activation of HIV-1 specific CD4 and CD8 T cells by human dendritic cells: roles for cross-presentation and non-infectious HIV-1 virus SO AIDS LA English DT Article DE HIV-1; dendritic cells; CD4 T cells; CD8 T cells; apoptosis; antigen presentation; immune response ID IMMUNODEFICIENCY-VIRUS; CLASS-I; ANTIGEN PRESENTATION; GENE-PRODUCTS; HUMAN SKIN; TYPE-1; RESPONSES; APOPTOSIS; INACTIVATION; INDIVIDUALS AB Background: The CD4 T cells in mucosal subepithelia are the first cells to become infected during sexual transmission of HIV-1. Dendritic cells (DC) are located in the same area and are known to play a central role in antiviral immune responses. However, extensive viral replication, syncytia formation and cell death follows the interaction between T cells and DC previously exposed to HIV-1. Despite this, anti-HIV responses are generated that control viremia following acute infection. Objective: The anti-HIV-1 cellular immune responses observed may be activated by sources other than productively infected DC. HIV-1 induces apoptosis both in cells it infects and in bystander cells. Furthermore, retroviral replication typically generates a predominance of defective particles. We tested whether DC exposed to antigen from either of these sources could elicit anti-HIV specific immune responses. Design and methods: Apoptotic or necrotic monocytes infected with vaccinia virus vectors encoding HIV antigens, a cell line with integrated HIV-1 and apoptotic CD4 T cells pulsed with non-infectious or infectious HIV-1 virus were used as sources of antigens to assess cross presentation by DC. Furthermore, direct DC presentation of antigen from non-infectious and infectious HIV-1 was examined. Results: We find that dead cells expressing HIV-1 antigens as well as non-infectious HIV-1 particles can be acquired and processed by DC, leading to the activation, differentiation and expansion of viral antigen-specific CD4 and CD8 T cells from seropositive individuals. Conclusions: These sources of antigens may be critical for the generation and maintenance of anti-HIV-1 immunity by DC. (C) 2002 Lippincott Williams Wilkins. C1 Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10021 USA. Linkoping Univ, Fac Hlth Sci, Dept Cell Biol, S-58183 Linkoping, Sweden. Natl Canc Inst Fredrick, SAIC, AIDS Vaccine Program, Retroviral Pathogenesis Lab, Frederick, MD USA. RP Larsson, M (reprint author), Rockefeller Univ, Cellular Physiol & Immunol Lab, 1230 York Ave, New York, NY 10021 USA. RI Jean-Francois, Fonteneau/L-4095-2015 OI Jean-Francois, Fonteneau/0000-0002-3284-8319 FU NCI NIH HHS [N01-CO-56000]; NCRR NIH HHS [M01-RR00102]; NIAID NIH HHS [AI 44628, AI 47742] NR 41 TC 82 Z9 84 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 5 PY 2002 VL 16 IS 10 BP 1319 EP 1329 DI 10.1097/00002030-200207050-00003 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 571LX UT WOS:000176719800003 PM 12131208 ER PT J AU Giomarelli, B Provvedi, R Meacci, F Maggi, T Medaglini, D Pozzi, G Mori, T McMahon, JB Gardella, R Boyd, MR AF Giomarelli, B Provvedi, R Meacci, F Maggi, T Medaglini, D Pozzi, G Mori, T McMahon, JB Gardella, R Boyd, MR TI The microbicide cyanovirin-N expressed on the surface of commensal bacterium Streptococcus gordonii captures HIV-1 SO AIDS LA English DT Article DE HIV; vaginal microbicides; cyanovirin-N; prevention of sexual transmission; Streptococcus gordonii; recombinant commensal bacteria; mucosal delivery ID VIRUS-INACTIVATING PROTEIN; GP120; BINDING; IMMUNIZATION; MICE; CYANOBACTERIUM; IMMUNOGENICITY; COLONIZATION; CD4 AB Objective: To explore the feasibility of expressing the potent HIV-inactivating protein, cyanovirin-N (CV-N), in the human commensal bacterium Streptococcus gordonii, as a possible approach for local delivery of CV-N to prevent sexual transmission of HIV-1. Design and methods: To express CV-N in S. gordonii, we used the host-vector system we had previously developed. CV-N was expressed as a fusion protein both attached to the bacterial surface and secreted in soluble form in the supernatant of liquid cultures. The soluble form of recombinant CV-N was tested for gp120-binding activity in an enzyme-linked immunosorbent assay, whereas S. gordonii strain expressing CV-N on the surface was analyzed in an in vitro HIV capturing assay. Results: Two recombinant S. gordonii strains secreting or displaying CV-N on the bacterial surface were constructed and the expression of CV-N was confirmed by immunoblot and flow-cytometric analysis. The secreted form of recombinant CV-N exhibited a concentration-dependent binding to the envelope glycoprotein gp120 of HIV-1, whereas CV-N displayed on the bacterial surface was able to capture HIV virions efficiently. Conclusion: The anti-HIV protein CV-N in S. gordonii was expressed in a biologically active form. This represents a first step in the development of a system to deliver and maintain an effective concentration of a microbicide in the vaginal mucosa. (C) 2002 Lippincott Williams Wilkins. C1 Univ Siena, LAMMB, Dept Biol Mol, Policlin Scotte, I-53100 Siena, Italy. Natl Canc Inst, Mol Targets Drug Discovery Program, NCI Ctr Canc Res, Frederick, MD USA. NCI, Sci Applicat Int Corp, Frederick, MD USA. RP Pozzi, G (reprint author), Univ Siena, LAMMB, Dept Biol Mol, Policlin Scotte, 1S Viale Bracci, I-53100 Siena, Italy. RI Provvedi, Roberta/I-8430-2012 FU NCI NIH HHS [N01-CO-12400] NR 26 TC 54 Z9 58 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 5 PY 2002 VL 16 IS 10 BP 1351 EP 1356 DI 10.1097/00002030-200207050-00006 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 571LX UT WOS:000176719800006 PM 12131211 ER PT J AU Voltattorni, CB Bertoldi, M Bianconi, S Deng, WP Wong, KL Kim, I Herbert, B Kirk, KL AF Voltattorni, CB Bertoldi, M Bianconi, S Deng, WP Wong, KL Kim, I Herbert, B Kirk, KL TI Behavior of fluorinated analogs of L-(3,4-dihydroxyphenyl)alanine and L-threo-(3,4-dihydroxyphenyl)serine as substrates for Dopa decarboxylase SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Dopa decarboxylase; fluorinated L-Dopa analogs; fluorinated threo-DOPS; pyridoxal 5 '-phosphate ID PARKINSONIAN-PATIENTS; L-THREO-3,4-DIHYDROXYPHENYLSERINE; METABOLISM; NOREPINEPHRINE; PRECURSOR; BRAIN; HUMANS; ASSAY; FLUID; ACID AB We have determined the kinetic parameters for Dopa decarboxylase (DDC) of three ring-fluorinated analogs of 3,4-dihydroxyphenylalanine (Dopa). The rank order of catalytic efficiency of decarboxylation (k(cat)/K-m) is Dopa > 6-F-Dopa > 2-F-Dopa > 5-F-Dopa. This rank is consistent with previous in vivo and in vitro studies which indicate that, of the fluorinated analogs, 6-F-Dopa has pharmacokinetics that are most suited for positron emission tomographic (PET) evaluation of dopamine function. The effectiveness of PET as a diagnostic tool, the convenient half-life of F-18 (110min) and the favorable pharmacokinetics of 6-[F-18]FDOPA have combined to make this an extremely valuable reagent to study dopaminergic activity. The reactions of the related fluorinated DOPS analogs show that, while 6-F-threo-3,4-(dihydroxyphenyl)serine (DOPS) is decarboxylated at approximately the same rate as the non-fluorinated substrate, 2-F-threo-DOPS is not converted into the corresponding amine. In both cases a Pictet-Spengler condensation with the pyridoxal 5'-phosphate (PLP) cofactor occurs to produce tetrahydroisoquinolines. Condensation of fluorinated catecholamines and catechol amino acids with endogenous aldehydes will be investigated as an approach to study possible mechanisms of L-Dopa-linked neurotoxicity. Published by Elsevier Science (USA). C1 Univ Verona, Fac Med & Chirurg, Sez Chim Biol, Dipartimento Sci Neurol & Visione, I-37100 Verona, Italy. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Voltattorni, CB (reprint author), Univ Verona, Fac Med & Chirurg, Sez Chim Biol, Dipartimento Sci Neurol & Visione, I-37100 Verona, Italy. OI Bianconi, Antonio/0000-0001-9795-3913 NR 34 TC 4 Z9 4 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 5 PY 2002 VL 295 IS 1 BP 107 EP 111 AR PII S0006-291X(02)00643-5 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 573EE UT WOS:000176815700019 ER PT J AU Lu, CB Chan, SL Fu, WM Mattson, MP AF Lu, CB Chan, SL Fu, WM Mattson, MP TI The lipid peroxidation product 4-hydroxynonenal facilitates opening of voltage-dependent Ca(2+)Channels in neurons by increasing protein tyrosine phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYLOID BETA-PEPTIDE; AMYOTROPHIC-LATERAL-SCLEROSIS; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; CALCIUM-CHANNEL; HIPPOCAMPAL-NEURONS; ARACHIDONIC-ACID; CA2+ CHANNELS; SUPEROXIDE-DISMUTASE; POSTSYNAPTIC CALCIUM AB Calcium influx through voltage-dependent calcium channels (VDCCs) mediates a variety of functions in neurons and other excitable cells, but excessive calcium influx through these channels can contribute to neuronal death in pathological settings. Oxyradical production and membrane lipid peroxidation occur in neurons in response to normal activity in neuronal circuits, whereas excessive lipid peroxidation is implicated in the pathogenesis of of neurodegenerative disorders. We now report on a specific mechanism whereby lipid peroxidation can modulate the activity of VDCCs. The lipid peroxidation product 4-hydroxy-2,3-nonenal (4HN) enhances dihydropyridine-sensitive whole-cell Ca2+ currents and increases depolarization-induced increases of intracellular Ca2+ levels in hippocampal neurons. Prolonged exposure to 4HN results in neuronal death which is prevented by treatment with glutathione an attenuated by the L-type Ca2+ channel blocker nimodipine. Tyrosine phosphorylation of alpha1 VDCC subunits is increased in neurons exposed to 4HN, and studies using inhibitors of tyrosine kinases and phosphatases indicate a requirement for tyrosine phosphorylation in the enhancement of VDCC activity in response to 4HN. Phosphorylation-mediated modulation of Ca2+ channel activity in response to lipid peroxidation may play important roles in the responses of neurons to oxidative stress in both physiological and pathological settings. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, GRC 4F01,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 68 TC 49 Z9 51 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 JUL 5 PY 2002 VL 277 IS 27 BP 24368 EP 24375 DI 10.1074/jbc.M201924200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 569PV UT WOS:000176611800053 PM 12006588 ER PT J AU Chou, CJ Haluzik, M Gregory, C Dietz, KR Vinson, C Gavrilova, O Reitman, ML AF Chou, CJ Haluzik, M Gregory, C Dietz, KR Vinson, C Gavrilova, O Reitman, ML TI WY14,643, a peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, improves hepatic and muscle steatosis and reverses insulin resistance in lipoatrophic A-ZIP/F-1 mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACID BETA-OXIDATION; ADIPOSE-TISSUE; DIABETES-MELLITUS; LIPOPROTEIN-LIPASE; SKELETAL-MUSCLE; LIPODYSTROPHY; LEPTIN; OBESITY; MOUSE; OVEREXPRESSION AB WY14,643 is a specific peroxisome proliferator-activated receptor a (PPARalpha) agonist with strong hypolipidemic effects. Here we have examined the effect of WY14,643 in the A-ZIP/F-1 mouse, a model of severe lipoatrophic diabetes. With I week of treatment, all doses of WY14,643 that were tested normalized serum triglyceride and fatty acid levels. Glucose and insulin levels also improved but only with high doses and longer treatment duration. WY14,643 reduced liver and muscle triglyceride content and increased levels of mRNA encoding fatty acid oxidation enzymes. In liver, the elevated lipogenic mRNA profile (including PPARgamma) in A-ZIP/F-1 mice remained unchanged. These results suggest that WY14,643 acts by increasing beta-oxidation rather by than decreasing lipogenesis or lipid uptake. Hyperinsulinemic euglycemic clamp studies indicated that WY14,643 treatment improved liver more than muscle insulin sensitivity and that hepatic mRNA levels of gluconeogenic enzymes were reduced. Combination treatment with both WY14,643 and a PPARgamma ligand, rosiglitazone, did not lower glucose levels more effectively than did treatment with WY14,643 alone. These data support the hypothesis that reducing intracellular triglycerides in non-adipose tissues improves insulin sensitivity and suggest that further investigation of the role of PPARa agonists in the treatment of lipoatrophic diabetes is warranted. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Reitman, ML (reprint author), Merck Res Labs, POB 2000,RY80M-213, Rahway, NJ 07065 USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 34 TC 133 Z9 139 U1 0 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 JUL 5 PY 2002 VL 277 IS 27 BP 24484 EP 24489 DI 10.1074/jbc.M202449200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 569PV UT WOS:000176611800068 PM 11994294 ER PT J AU Tian, LF Collins, C AF Tian, LF Collins, C TI Optimal trajectory planning of redundant manipulators in constrained workspace SO ELECTRONICS LETTERS LA English DT Article AB A novel genetic algorithm using a floating point representation is proposed to search for the optimal end-effector trajectory for a redundant manipulator. An evaluation function is defined based on the total displacement of the end-effector, the total angular displacement of all the joints, the uniformity of Cartesian and joint space velocities. C1 Univ Calif Riverside, Dept Mech Engn, Riverside, CA 92521 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Tian, LF (reprint author), Univ Calif Riverside, Dept Mech Engn, Riverside, CA 92521 USA. NR 3 TC 3 Z9 3 U1 0 U2 1 PU IEE-INST ELEC ENG PI HERTFORD PA MICHAEL FARADAY HOUSE SIX HILLS WAY STEVENAGE, HERTFORD SG1 2AY, ENGLAND SN 0013-5194 J9 ELECTRON LETT JI Electron. Lett. PD JUL 4 PY 2002 VL 38 IS 14 BP 762 EP 764 DI 10.1049/el:20020516 PG 3 WC Engineering, Electrical & Electronic SC Engineering GA 578CZ UT WOS:000177101000060 ER PT J AU Dimmock, JR Zello, GA Oloo, EO Quail, JW Kraatz, HB Perjesi, P Aradi, F Takacs-Novak, K Allen, TM Santos, CL Balzarini, J De Clercq, E Stables, JP AF Dimmock, JR Zello, GA Oloo, EO Quail, JW Kraatz, HB Perjesi, P Aradi, F Takacs-Novak, K Allen, TM Santos, CL Balzarini, J De Clercq, E Stables, JP TI Correlations between cytotoxicity and topography of some 2-arylidenebenzocycloalkanones determined by X-ray crystallography SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CHALCONES; DERIVATIVES; INHIBITION; PROGRAM; TUBULIN; ANALOGS; SYSTEM AB Three series of 2-arylidenebenzocycloalkanones 1-3 were prepared in order to compare the topography of the molecules with cytotoxicity. These compounds contain two aryl rings whose spatial relationships to each other were influenced by the size of the alicyclic ring and the nature of the substituents in the arylidene aryl rings. All compounds were evaluated against murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. From these results, 1l and 2c,l emerged as useful lead molecules and 1l was shown to significantly inhibit macromolecular DNA, RNA, and protein syntheses in L1210 cells. Various interatomic distances, bond angles, and a torsion angle of 19 representative compounds were determined by X-ray crystallography, and correlations between these data and the cytotoxicity were noted in nearly 40% of the cases examined. Structure-activity relationships revealed that in general, the steric properties of the groups in the arylidene aryl ring, as revealed by measurements of the molar refractivity values, contributed more to bioactivity than the electronic and hydrophobic properties of the aryl substituents. The compounds displayed little murine toxicity, which favors the decision to develop these molecules as cytotoxic and anticancer agents. C1 Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. Univ Saskatchewan, Dept Chem, Saskatoon, SK S7N 5C9, Canada. Univ Pecs, Dept Med Chem, Pecs, Hungary. Univ Pecs, Cent Res Lab, Pecs, Hungary. Semmelweis Univ, Dept Pharmaceut Chem, Budapest, Hungary. Univ Alberta, Dept Pharmacol, Edmonton, AB T6G 2H7, Canada. Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. NINDS, NIH, Bethesda, MD 20892 USA. RP Dimmock, JR (reprint author), Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. EM pal.perjesi@oak.pte.hu RI Kraatz, Heinz-Bernhard/D-2246-2014 OI Kraatz, Heinz-Bernhard/0000-0002-7149-0110 NR 25 TC 58 Z9 58 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 4 PY 2002 VL 45 IS 14 BP 3103 EP 3111 DI 10.1021/jm010559p PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 570NT UT WOS:000176664900022 PM 12086496 ER PT J AU Kim, JH Auerbach, JM Rodriguez-Gomez, JA Velasco, I Gavin, D Lumelsky, N Lee, SH Nguyen, J Sanchez-Pernaute, R Bankiewicz, K McKay, R AF Kim, JH Auerbach, JM Rodriguez-Gomez, JA Velasco, I Gavin, D Lumelsky, N Lee, SH Nguyen, J Sanchez-Pernaute, R Bankiewicz, K McKay, R TI Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease SO NATURE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NURR1-DEFICIENT MICE; ISTHMIC ORGANIZER; NEURAL PLATE; SPINAL-CORD; MUTANT MICE; IN-VITRO; DIFFERENTIATION; TRANSPLANTATION; EXPRESSION AB Parkinson's disease is a widespread condition caused by the loss of midbrain neurons that synthesize the neurotransmitter dopamine. Cells derived from the fetal midbrain can modify the course of the disease, but they are an inadequate source of dopamine-synthesizing neurons because their ability to generate these neurons is unstable. In contrast, embryonic stem (ES) cells proliferate extensively and can generate dopamine neurons. If ES cells are to become the basis for cell therapies, we must develop methods of enriching for the cell of interest and demonstrate that these cells show functions that will assist in treating the disease. Here we show that a highly enriched population of midbrain neural stem cells can be derived from mouse ES cells. The dopamine neurons generated by these stem cells show electrophysiological and behavioural properties expected of neurons from the midbrain. Our results encourage the use of ES cells in cell-replacement therapy for Parkinson's disease. C1 NINCDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP McKay, R (reprint author), NINCDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Kim, Jong-Hoon/F-2504-2013; Velasco, Ivan/D-3593-2014; Rodriguez-Gomez, Jose/C-8313-2015; Kim, Jong-Hoon/H-1476-2015 OI Velasco, Ivan/0000-0002-8953-6578; NR 43 TC 1041 Z9 1142 U1 21 U2 157 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 4 PY 2002 VL 418 IS 6893 BP 50 EP 56 DI 10.1038/nature00900 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 569JL UT WOS:000176599200034 PM 12077607 ER PT J AU Infante-Rivard, C Rivard, GE Yotov, WV Genin, E Guiguet, M Weinberg, C Gauthier, R Feoli-Fonseca, JC AF Infante-Rivard, C Rivard, GE Yotov, WV Genin, E Guiguet, M Weinberg, C Gauthier, R Feoli-Fonseca, JC TI Absence of association of thrombophilia polymorphisms with intrauterine growth restriction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; BIRTH-WEIGHT; VASCULAR-DISEASE; PROTHROMBIN GENE; COMMON MUTATION; RISK FACTOR; FETAL LOSS; HOMOCYSTEINE; THROMBOSIS; PREGNANCY AB Background: Previous data have demonstrated associations between thrombophilia polymorphisms in pregnant women and an increased risk of intrauterine growth restriction in their offspring, but this finding remains uncertain. Methods: We performed a hospital-based case-control study and a family-based study including 493 newborns with intrauterine growth restriction (defined by birth weight below the 10th percentile for gestational age and sex according to Canadian norms) and 472 controls (with birth weight at or above the 10th percentile). We determined the presence or absence in newborns and their parents of the following polymorphisms: methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, factor V Leiden G1691A, and prothrombin G20210A. Mothers were interviewed to obtain information on other risk factors for intrauterine growth restriction. Results: The risk of intrauterine growth restriction was not increased among mothers carrying a polymorphism associated with thrombophilia. In the case-control study, the odds ratios associated with two copies of the variant, after adjustment for newborn genotype and other risk factors, were 1.55 for MTHFR C677T (95 percent confidence interval, 0.83 to 2.90) and 0.49 for MTHFR A1298C (95 percent confidence interval, 0.25 to 0.93); heterozygotes for factor V Leiden had an odds ratio of 1.18 (95 percent confidence interval, 0.54 to 2.55), and heterozygotes for prothrombin G20210A had an odds ratio of 0.92 (95 percent confidence interval, 0.36 to 2.35). These polymorphisms in the newborn were not associated with an increased risk. Newborns who were homozygous for the MTHFR C677T variant had a decreased risk of intrauterine growth restriction (odds ratio after adjustment for mother's genotype and other confounders, 0.52 [95 percent confidence interval, 0.29 to 0.94]). The results of the family-based study supported those of the case-control study. Conclusions: Our findings do not indicate that there are associations between maternal or newborn polymorphisms associated with thrombophilia and an increased risk of intrauterine growth restriction. C1 McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A3, Canada. Univ Montreal, Hop St Justine, Ctr Hosp Univ Mere Enfant, Res Ctr, Montreal, PQ H3T 1C5, Canada. Univ Montreal, Hop St Justine, Ctr Hosp Univ Mere Enfant, Div Hematol & Oncol, Montreal, PQ H3T 1C5, Canada. Univ Montreal, Hop St Justine, Ctr Hosp Univ Mere Enfant, Dept Obstet, Montreal, PQ H3T 1C5, Canada. INSERM, U535, Paris, France. NIEHS, Res Triangle Pk, NC 27709 USA. RP Infante-Rivard, C (reprint author), McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, 1130 Pine Ave W, Montreal, PQ H3A 1A3, Canada. RI Genin, Emmanuelle/C-4974-2013 OI Genin, Emmanuelle/0000-0003-4117-2813 NR 30 TC 155 Z9 161 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 JUL 4 PY 2002 VL 347 IS 1 BP 19 EP 25 DI 10.1056/NEJM200207043470105 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 569HA UT WOS:000176594500004 PM 12097536 ER PT J AU Aerts, JLE Christiaens, MR Vandekerckhove, P AF Aerts, JLE Christiaens, MR Vandekerckhove, P TI Evaluation of progesterone receptor expression in eosinophils using real-time quantitative PCR SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE eosinophil; immune-suppressiom; progesterone receptors; quantitative PCR ID MEDROXYPROGESTERONE ACETATE; HUMAN-LYMPHOCYTES; PREGNANCY; ESTROGEN; MODULATION; LEUKEMIA; CELLS AB Progesterone has been shown in many instances to have immune-suppressant activities. Most of these activities have been investigated in the light of general immune suppression or with a focus on lymphocytes. However, many clinical and in vitro studies have shown that progesterone also has a suppressive effect on eosinophilia. This effect so far has not been thoroughly investigated. The purpose of this study was to evaluate whether the effect is mediated via the classical progesterone receptor (PR). We developed a new real-time quantitative PCR (RQ-PCR) for the analysis and quantification of expression of the classical PR. The test was first validated both on breast cancer cell lines and on breast cancer biopsies. Subsequently, when using eosinophils isolated from peripheral blood of healthy volunteers, we could not find evidence for the expression of PR. These data suggest that the effects of progesterone on eosinophils are not mediated by the classical PR. (C) 2002 Published by Elsevier Science B.V. C1 Univ Leuven, Univ Hosp Leuven, Expt Med Lab, Louvain, Belgium. Univ Leuven, Univ Hosp Leuven, Multidisciplinary Breast Ctr, Louvain, Belgium. RP Aerts, JLE (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B51,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Aerts, Joeri/J-6957-2014 OI Aerts, Joeri/0000-0002-9902-3696 NR 28 TC 9 Z9 13 U1 0 U2 1 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 JUL 3 PY 2002 VL 1571 IS 3 BP 167 EP 172 AR PII S0304-4165(02)00192-7 DI 10.1016/S0304-4165(02)00192-7 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 616JB UT WOS:000179299700001 PM 12090930 ER PT J AU Samuni, AM Krishna, MC DeGraff, W Russo, A Planalp, RP Brechbiel, MW Mitchell, JB AF Samuni, AM Krishna, MC DeGraff, W Russo, A Planalp, RP Brechbiel, MW Mitchell, JB TI Mechanisms underlying the cytotoxic effects of Tachpyr - a novel metal chelator SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE antioxidant; redox-activity; cytotoxicity; superoxide ID IRON OVERLOAD DISEASE; CELL-DEATH; DEFEROXAMINE; APOPTOSIS; THERAPY; DNA AB Tachpyr (N,N'N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane), a novel metal chelator, was previously shown to deplete intracellular iron and exert a cytotoxic effect on cultured bladder cancer cells. Tachpyr binds Fe(II) and readily reduces Fe(III). The iron(II)-Tachpyr chelate undergoes intramolecular oxidative dehydrogenation resulting in mono- and diimino Fe(II) complexes, The present study investigates the redox-activity of the Tachpyr-iron complex to better define the mechanism of Tachpyr's cytotoxicity. Tachpyr's mechanism of cytotoxicity was studied using cell-free solutions, isolated DNA, and cultured mammalian cells by employing UV-VIS spectrophotometry, oximetry, spin-trapping technique, and electron paramagnetic resonance (EPR) spectrometry. The results show that: (1) Tachpyr by itself after 24 h of incubation had a cytotoxic effect on cultured cells; (2) fully oxidized Tachpyr had no cytotoxic effects on cultured cells even after 24 h of incubation; (3) Tachpyr protected isolated DNA against H2O2-induced damage, but not against HX/XO-induced damage; and (4) Tachpyr-Fe(II) chelate slows down but does not block oxidation of Fe(II), allows O-2(.)-induced or Tachpyr-induced reduction of Fe(III), and consequently promotes production of (OH)-O-. through the Haber-Weiss reaction cycle, The results indicate that Tachpyr can protect cells against short-term, metal-mediated damage, However, upon prolonged incubation, Tachpyr exerts cytotoxic effects, Therefore, in addition to iron depletion, low-level oxidative stress, which in part occurs because of redox cycling of the coordinated iron ion, may contribute to the cytotoxic effects of Tachpyr. (C) 2002 Published by Elsevier Science B.V. C1 NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Rm B3B69,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 21 Z9 24 U1 0 U2 2 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 JUL 3 PY 2002 VL 1571 IS 3 BP 211 EP 218 AR PII S0304-4165(02)00218-0 DI 10.1016/S0304-4165(02)00218-0 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 616JB UT WOS:000179299700006 PM 12090935 ER PT J AU Wong, TY Klein, R Sharrett, AR Couper, DJ Klein, BEK Liao, DP Hubbard, LD Mosley, TH AF Wong, TY Klein, R Sharrett, AR Couper, DJ Klein, BEK Liao, DP Hubbard, LD Mosley, TH CA ARIC Investigators TI Cerebral white matter lesions, retinopathy, and incident clinical stroke SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RETINAL MICROVASCULAR ABNORMALITIES; CEREBROVASCULAR RISK-FACTORS; ATHEROSCLEROSIS RISK; BLOOD-PRESSURE; ELDERLY PEOPLE; SIGNAL HYPERINTENSITIES; CARDIOVASCULAR-DISEASE; SUBCORTICAL LESIONS; LEUKOARAIOSIS; COMMUNITIES AB Context White matter lesions (WMLs) detected on cerebral imaging scans have been hypothesized to have a microvascular etiology and to precede the development of clinical stroke. However, few clinical data are available to support these hypotheses. Objective To examine the relationship of WMLs, retinal microvascular abnormalities, and incident clinical stroke in healthy, middle-aged men and women. Design and Setting The Atherosclerosis Risk in Communities Study (ARIC), a prospective, population-based cohort study conducted in 4 US communities and initiated in 1987-1989. Participants A total of 1684 persons aged 51 to 72 years who had cerebral magnetic resonance imaging (MRI) and retinal photography at the third examination (1993-1995). Main Outcome Measures Odds of WMLs, defined by standardized methods from MRI, by presence or absence of specific retinal microvascular abnormality (eg, microaneurysm, retinal hemorrhage) on retinal photograph; incident clinical stroke, ascertained after a median follow-up of 47 years, according to presence or absence of WMLs and retinopathy. Results Persons with retinopathy were more likely to have WMLs than those without retinopathy (22.9% vs 9.9%; odds ratio, 2.5; 95% confidence interval [CI], 1.5-4.0, adjusted for age, sex, race, and vascular risk factors). The 5-year cumulative incidence of clinical stroke was higher in persons with vs without WMLs (6,8% vs 1.4%; adjusted relative risk [RR], 3.4; 95% CI, 1.5-7.7) and in persons with vs without retinopathy (8.0% vs 1.4%; adjusted RR, 4.9; 95% CI, 2.0-11.9). Persons with both WMLS and retinopathy had a significantly higher 5-year cumulative incidence of stroke than those without either WMLs or retinopathy (20.0% vs 1.4%; adjusted RR, 18.1; 95% CI, 5.9-55.4). Conclusions In this cohort, middle-aged persons with cerebral WMLs detected on MRI were more likely to have retinal microvascular abnormalities and to have an increased risk of clinical stroke than people without WMLs. The risk of stroke was higher when retinopathy was simultaneously present in persons with WMLs. C1 Natl Univ Singapore, Dept Ophthalmol, Singapore 119260, Singapore. Natl Univ Singapore, Singapore Natl Eye Ctr, Singapore 119260, Singapore. Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NHLBI, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. Penn State Univ, Coll Med, Dept Hlth Evaluat Sci, Hershey, PA USA. Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. RP Wong, TY (reprint author), Natl Univ Singapore, Dept Ophthalmol, 10 Kent Ridge Crescent, Singapore 119260, Singapore. FU NEI NIH HHS [EY013939]; NHLBI NIH HHS [N01-HC-55015, N01-HC-35125, N01-HC-35126, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022] NR 40 TC 291 Z9 298 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 3 PY 2002 VL 288 IS 1 BP 67 EP 74 DI 10.1001/jama.288.1.67 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 568YW UT WOS:000176573400021 PM 12090864 ER PT J AU Hedenfalk, IA AF Hedenfalk, IA TI Gene expression profiling of hereditary and sporadic ovarian cancers reveals unique BRCA1 and BRCA2 signatures SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER; MOLECULAR CLASSIFICATION; MESSENGER-RNA; PROMOTER; TUMORS; HYPERMETHYLATION; ADENOCARCINOMA; PREDICTION; CARCINOMAS; MUTATIONS C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Hedenfalk, IA (reprint author), NHGRI, Canc Genet Branch, NIH, 50 South Dr,MSC 8000, Bethesda, MD 20892 USA. NR 22 TC 14 Z9 14 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 JUL 3 PY 2002 VL 94 IS 13 BP 960 EP 961 PG 2 WC Oncology SC Oncology GA 569TG UT WOS:000176617900002 PM 12096075 ER PT J AU Etzioni, R Penson, DF Legler, JM di Tommaso, D Boer, R Gann, PH Feuer, EJ AF Etzioni, R Penson, DF Legler, JM di Tommaso, D Boer, R Gann, PH Feuer, EJ TI Overdiagnosis due to prostate-specific antigen screening: Lessons from US prostate cancer incidence trends SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TRANSURETHRAL RESECTION; HYPERPLASIA; MEN; MANAGEMENT; RATES; STRATEGIES; DIAGNOSIS; CARCINOMA; MORTALITY; PATTERNS AB Background: Overdiagnosis of clinically insignificant prostate cancer is considered a major potential drawback of prostate-specific antigen (PSA) screening. Quantitative estimates of the magnitude of this problem are, however, lacking. We estimated rates of prostate cancer overdiagnosis due to PSA testing that are consistent with the observed incidence of prostate cancer in the United States from 1988 through 1998. Overdiagnosis was defined as the detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. Methods: We developed a computer simulation model of PSA testing and subsequent prostate cancer diagnosis and death from prostate cancer among a hypothetical cohort of two million men who were 60-84 years old in 1988. Given values for the expected lead time-that is, the time by which the test advanced diagnosis-and the expected incidence of prostate cancer in the absence of PSA testing, the model projected the increase in population incidence of prostate cancer associated with PSA testing. By comparing the model-projected incidence with the observed incidence derived from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry data, we determined the lead times and corresponding overdiagnosis rates that were consistent with the observed data. Results: SEER data on prostate cancer incidence from 1988 through 1998 were consistent with overdiagnosis rates of approximately 29% for whites and 44% for blacks among men with prostate cancers detected by PSA screening. Conclusions: Among men with prostate cancer that would be detected only at autopsy, these rates correspond to overdiagnosis rates of, at most, 15% in whites and 37% in blacks. The observed trends in prostate cancer incidence are consistent with considerable overdiagnosis among PSA-detected cases. However, the results suggest that the majority of screen-detected cancers diagnosed between 1988 and 1998 would have presented clinically and that only a minority of cases found at autopsy would have been detected by PSA testing. C1 Fred Hutchinson Canc Res Ctr, Program Biostat, Seattle, WA 98104 USA. Vet Affairs Med Ctr, Seattle, WA 98108 USA. NCI, Div Canc Control & Populat Sci, Appl Res Branch, Canc Surveillance Res Program, Bethesda, MD 20892 USA. RAND Corp, Santa Monica, CA USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. RP Etzioni, R (reprint author), Fred Hutchinson Canc Res Ctr, Program Biostat, 1100 Fairview Ave N,MP 665, Seattle, WA 98104 USA. RI Boer, Rob/E-6473-2015 OI Boer, Rob/0000-0003-0680-001X FU NCI NIH HHS [R29CA70227, U01CA88160] NR 44 TC 533 Z9 544 U1 0 U2 15 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 JUL 3 PY 2002 VL 94 IS 13 BP 981 EP 990 PG 10 WC Oncology SC Oncology GA 569TG UT WOS:000176617900009 PM 12096083 ER PT J AU Jazaeri, AA Yee, CJ Sotiriou, C Brantley, KR Boyd, J Liu, ET AF Jazaeri, AA Yee, CJ Sotiriou, C Brantley, KR Boyd, J Liu, ET TI Gene expression profiles, of BRCA1-linked, BRCA2-linked, and sporadic ovarian cancers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID INVARIANT CHAIN EXPRESSION; CLASS-II TRANSACTIVATOR; PROMOTER HYPERMETHYLATION; BRCA1 MUTATION; GASTRIC-CANCER; BREAST; TUMORS; DNA; INACTIVATION; CARCINOMAS AB Background: Germline mutations in BRCA1 and BRCA2 are responsible for 5%-10% of epithelial ovarian cancers, but the molecular pathways affected by these mutations are unknown. We used complementary DNA (cDNA) microarrays to compare gene expression patterns in ovarian cancers associated with BRCA1 or BRCA2 mutations with gene expression patterns in sporadic epithelial ovarian cancers and to identify patterns common to both hereditary and sporadic tumors. Methods: Tumor samples from 61 patients with pathologically confirmed epithelial ovarian adenocarcinoma with matched clinicopathologic features were studied, including 18 with BRCA1 founder mutations, 16 with BRCA2 founder mutations, and 27 without either founder mutation (termed sporadic cancers). The cDNA microarrays contained 7651 sequence-verified features. Gene expression data were analyzed with a modified two-sided F test, with P<.0001 considered statistically significant. The expression level of six genes was also studied with reverse transcription-polymerase chain reaction. Results: The greatest contrast in gene expression was observed between tumors with BRCA1 mutations and those with BRCA2 mutations; 110 genes showed statistically significantly different expression levels (P<.0001). This group of genes could segregate sporadic tumors into two subgroups, "BRCA1-like"' and "BRCA2-like," suggesting that BRCA1-related and BRCA2-related pathways are also involved in sporadic ovarian cancers. Fifty-three genes were differentially expressed between tumors with BRCA1 mutations and sporadic tumors; six of the 53 mapped to Xp11.23 and were expressed at higher levels in tumors with BRCA1 mutations than in sporadic tumors. Compared with the immortalized ovarian surface epithelial cells used as reference, several interferon-inducible genes were overexpressed in the majority of tumors with a BRCA mutation and in sporadic tumors. Conclusions: Mutations in BRCA1 and BRCA2 may lead to carcinogenesis through distinct molecular pathways that also appear to be involved in sporadic cancers. Sporadic carcinogenic pathways may result from epigenetic aberrations of BRCA1 and BRCA2 or their downstream effectors. C1 NCI, Div Clin Sci, Gaithersburg, MD USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. RP Liu, ET (reprint author), Genome Inst Singapore, Capricorn Bldg,1 Sci Pk Rd,Sci Pk 2, Singapore 117604, Singapore. RI Jazaeri, Amir/A-2400-2008; Liu, Edison/C-4141-2008; Jazaeri, Amir/I-3458-2015 OI Jazaeri, Amir/0000-0003-4335-4151 FU NCI NIH HHS [U01CA88175] NR 45 TC 180 Z9 182 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 3 PY 2002 VL 94 IS 13 BP 990 EP 1000 PG 11 WC Oncology SC Oncology GA 569TG UT WOS:000176617900010 PM 12096084 ER PT J AU Lam, S MacAulay, C le Riche, JC Dyachkova, Y Coldman, A Guillaud, M Hawk, E Christen, MO Gazdar, AF AF Lam, S MacAulay, C le Riche, JC Dyachkova, Y Coldman, A Guillaud, M Hawk, E Christen, MO Gazdar, AF TI A randomized phase IIb trial of anethole dithiolethione in smokers with bronchial dysplasia SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID LUNG-CANCER; INTRAEPITHELIAL NEOPLASIA; SQUAMOUS METAPLASIA; FORMER SMOKERS; CHEMOPREVENTION; OLTIPRAZ; CARCINOMA; CARCINOGENESIS; TUMORIGENICITY; ISOTRETINOIN AB Background Results from preclinical studies have suggested that the organosulfur compound anethole dithiolethione (ADT) may be an effective chemopreventive agent for lung cancer. We conducted a phase IIb study to determine the effects of ADT in smokers with bronchial dysplasia. Methods: One hundred twelve current and former smokers with a smoking history of at least 30 pack-years and at least one site of bronchial dysplasia identified by an autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive placebo or ADT at 25 mg orally thrice daily for 6 months. Each subject then underwent a follow-up bronchoscopy-directed biopsy. We used changes in histopathologic grade and nuclear morphometry index (MI) as the primary and secondary end point biomarkers, respectively. Chisquare tests with continuity correction were used to compare response rates on a lesion- and person-specific basis between the two study groups. All statistical tests were two-sided. Results: One hundred one subjects had a follow-up bronchoscopy. In the lesion-specific analysis, progression rate of pre-existing dysplastic lesions by two or more grades and/or the appearance of new lesions was statistically significantly lower in the ADT group (8%) than in the placebo group (17%) (P<.001; difference = 9%, 95% confidence interval [CI] = 4% to 15%). In the person-specific analysis, the disease progression rate was statistically significantly lower in the ADT group (32%) than in the placebo group (59%) (P = .013; difference = 27%, 95% CI = 6% to 48%). The two treatment groups did not differ statistically significantly in terms of nuclear MI. Among individuals with an abnormal nuclear MI before treatment (29 in the ADT group and 25 in the placebo group), the progression rate in the ADT group (41%) was substantially lower than that in the placebo group (60%), although the difference was not statistically significant (P = .28; difference = 19%, 95% CI = -11% to 49%). Adverse events were mostly minor gastrointestinal symptoms that resolved with dose reduction or discontinuation of the medication. Conclusion: Our results suggest that, in smokers, ADT is a potentially efficacious chemoprevention agent for lung cancer. C1 British Columbia Canc Agcy, Dept Resp Med, Vancouver, BC V5Z 4E6, Canada. British Columbia Canc Agcy, Dept Canc Imaging, Vancouver, BC V5Z 4E6, Canada. British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. British Columbia Canc Agcy, Dept Populat Prevent Oncol, Vancouver, BC V5Z 4E6, Canada. Univ British Columbia, Vancouver, BC, Canada. NCI, Div Canc Prevent, Gastrointestinal & Other Canc Res Grp, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA. Solvay Pharma, Suresnes, France. RP Lam, S (reprint author), 2775 Heather St, Vancouver, BC V5Z 3J5, Canada. EM sclam@interchange.ubc.ca FU NCI NIH HHS [N01CN65030] NR 41 TC 104 Z9 107 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 3 PY 2002 VL 94 IS 13 BP 1001 EP 1009 PG 9 WC Oncology SC Oncology GA 569TG UT WOS:000176617900011 PM 12096085 ER PT J AU Walker, HC Lawrence, JJ McBain, CJ AF Walker, HC Lawrence, JJ McBain, CJ TI Activation of kinetically distinct synaptic conductances on inhibitory interneurons by electrotonically overlapping afferents SO NEURON LA English DT Article ID MOSSY FIBER SYNAPSES; TARGET-SPECIFIC EXPRESSION; RAT HIPPOCAMPUS; PYRAMIDAL CELLS; GLUTAMATE RECEPTORS; SUBUNIT COMPOSITION; AMPA RECEPTORS; TIME-COURSE; NEURONS; TRANSMISSION AB Mossy fiber (MF) and CA3 collateral (CL) axons activate common interneurons via synapses comprised of different AMPA receptors to provide feedforward and feedback inhibitory control of the CA3 hippocampal network. Because synapses potentially occur over variable electrotonic distances that distort somatically recorded synaptic currents, it is not known whether the underlying afferent-specific synaptic conductances are associated with different time courses. Using a somatic voltage jump technique to alter the driving force at the site of the synapse, we demonstrate that MF and CL synapses overlap in electrotonic location yet differ in conductance time course. Thus, afferent-specific conductance time courses allow single interneurons to differentially integrate feedforward and feedback information without the need to segregate distinct AMPA receptor subunits to different electrotonic domains. C1 NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. NR 50 TC 31 Z9 31 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUL 3 PY 2002 VL 35 IS 1 BP 161 EP 171 DI 10.1016/S0896-6273(02)00734-1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 569KP UT WOS:000176601800018 PM 12123616 ER PT J AU Chadwick, RS AF Chadwick, RS TI Axisymmetric indentation of a thin incompressible elastic layer SO SIAM JOURNAL ON APPLIED MATHEMATICS LA English DT Article DE mechanics of thin films; contact; Wiener-Hopf integral equations AB Axisymmetric indentation of an incompressible elastic layer by a frictionless rigid sphere is considered. Estimates of the contact radius and the force required to produce a given indentation are given when the thickness of the layer is mall compared to the contact radius. The elastic layer is either bonded to or slips along a rigid substrate. The estimates are obtained by asymptotically matching a lubrication-type expansion valid in the contact region to an edge layer expansion studied using the Wiener-Hopf technique. A substantially larger force is required to equally indent a bonded layer compared to a slipping layer. In the former case the force is inversely proportional to the cube of the layer thickness, rather than to the layer thickness itself, if the layer is free to slip. C1 Natl Inst Deafness & Other Commun Disorders, Sect Auditory Mechan, NIH, Bethesda, MD 20892 USA. RP Chadwick, RS (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Auditory Mechan, NIH, Bldg 10-Room 5D-49,10 Ctr Drive,MSC 1417, Bethesda, MD 20892 USA. NR 14 TC 40 Z9 40 U1 1 U2 16 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 0036-1399 J9 SIAM J APPL MATH JI SIAM J. Appl. Math. PD JUL 3 PY 2002 VL 62 IS 5 BP 1520 EP 1530 AR PII S0036139901388222 DI 10.1137/S0036139901388222 PG 11 WC Mathematics, Applied SC Mathematics GA 570UA UT WOS:000176675500004 ER PT J AU Miller, KD Masur, H Jones, EC Joe, GO Rick, ME Kelly, GG Mican, JM Liu, SY Gerber, LH Blackwelder, WC Falloon, J Davey, RT Polis, MA Walker, RE Lane, HC Kovacs, JA AF Miller, KD Masur, H Jones, EC Joe, GO Rick, ME Kelly, GG Mican, JM Liu, SY Gerber, LH Blackwelder, WC Falloon, J Davey, RT Polis, MA Walker, RE Lane, HC Kovacs, JA TI High prevalence of osteonecrosis of the femoral head in HIV-infected adults SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; SYSTEMIC LUPUS-ERYTHEMATOSUS; AVASCULAR NECROSIS; VENOUS THROMBOSIS; ANTIPHOSPHOLIPID ANTIBODIES; RENAL-TRANSPLANTATION; ARTERIAL-DISEASE; RISK-FACTORS; BONE AB Background: osteonecrosis has been reported to occur occasionally among HIV-infected patients. The diagnosis of symptomatic osteonecrosis of the hip in two of the authors' patients, together with reports from community physicians, raised a concern that the prevalence of osteonecrosis is increasing. Objective: To determine the prevalence of osteonecrosis of the hip in asymptomatic HIV-infected patients and to identify potential risk factors associated with osteonecrosis. Design: Survey and comparison study. Setting: The Clinical Center of the U.S. National Institutes of Health. Participants: 339 asymptomatic HIV-infected adults (of 364 asked to participate) and 118 age- and sex-matched HIV-negative volunteers enrolled between 1 June and 15 December 1999. Measurements: Osteonecrosis of the hip, as documented by magnetic resonance imaging. Data from clinic records and a patient questionnaire administered before magnetic resonance imaging were used in an analysis of risk factors. A subset of patients was evaluated for hypercoagulable state. Results: Fifteen (4.4% [95% Cl, 2.5% to 7.2%]) of 339 HIV-infected participants had osteonecrosis lesions on magnetic resonance imaging, and no HIV-negative participants had similar lesions. Among HIV-infected participants, osteonecrosis occurred more frequently in those who used systemic corticosteroids, lipid-lowering agents, or testosterone; those who exercised routinely by bodybuilding; and those who had detectable levels of anticardiolipin antibodies. Conclusions: Patients infected with HIV have an unexpectedly high occurrence of osteonecrosis of the hip. Although screening a-symptomatic patients is not warranted, HIV-infected patients with persistent groin or hip pain should be evaluated for this debilitating complication. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), NIH, Ctr Clin, Bldg 10,room 7D43,MSC1662, Bethesda, MD 20892 USA. OI Polis, Michael/0000-0002-9151-2268 NR 58 TC 111 Z9 121 U1 0 U2 2 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 JUL 2 PY 2002 VL 137 IS 1 BP 17 EP 24 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 569VA UT WOS:000176622000003 PM 12093241 ER PT J AU Kumar, S Nussinov, R AF Kumar, S Nussinov, R TI Close-range electrostatic interactions in proteins SO CHEMBIOCHEM LA English DT Review DE electrostatic interactions; flexibility; protein folding; protein structures; salt bridges ID MOLECULAR-DYNAMICS SIMULATION; CHARGE-CHARGE INTERACTIONS; HYDROPHOBIC FOLDING UNITS; THERMUS-THERMOPHILUS HB8; SIDE-CHAIN INTERACTIONS; SALT BRIDGES STABILIZE; BINDING FREE-ENERGIES; GCN4 LEUCINE-ZIPPER; ION-PAIRS; CYTOCHROME B(5) AB Two types of noncovalent bonding interactions are present in protein structures, specifics and nonspecific. Nonspecific interactions are mostly hydrophobic and van der Waals. Specific interactions are largely electrostatic. While the hydrophobic effect is the major driving force in protein folding, electrostatic interactions are important in protein folding, stability flexibility, and function. Here we review the role of close-range electrostatic interactions (salt bridges) and their networks in proteins. Salt bridges are formed by spatially proximal pairs of oppositely charged residues in native protein structures. Often salt-bridging residues are also close in the protein sequence and fall in the same secondary structural element, building block, autonomous folding unit, domain, or subunit, consistent with the hierarchical model for protein folding. Recent evidence also suggest that charges and polar residues in largely hydrophobic interfaces may act as hot spots for binding. Salt bridges are rarely found across protein parts which are joined by flexible hinges, a fact suggesting that salt bridges constrain flexibility and motion. While conventional chemical intuition expects that salt bridges contribute favorably to protein stability, recent computational and experimental evidence shows that salt bridges can be stabilizing or destabilizing. Due to systemic protein flexibility, reflected in small-scale side-chain and backbone atom motions, salt bridges and their stabilities fluctuate in proteins. At the same time, genome-wide, amino acid sequence composition, structural, and thermodynamic comparisons of thermophilic and mesophilic proteins indicate that significantly towards the thermophilic mesophilic protein stability differential. C1 NCI Frederick, Intramural Res Support Program, SAIC, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. NCI Frederick, Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Nussinov, R (reprint author), NCI Frederick, Intramural Res Support Program, SAIC, Bldg 469,Room 151, Frederick, MD 21702 USA. OI Kumar, Sandeep/0000-0003-2840-6398 FU NCI NIH HHS [N01-CO-56000] NR 158 TC 248 Z9 252 U1 6 U2 43 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI Chembiochem PD JUL 2 PY 2002 VL 3 IS 7 BP 604 EP 617 DI 10.1002/1439-7633(20020703)3:7<604::AID-CBIC604>3.0.CO;2-X PG 14 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 569WJ UT WOS:000176625200002 PM 12324994 ER PT J AU Del Parigi, A Chen, KW Salbe, AD Gautier, JF Ravussin, E Reiman, EM Tataranni, PA AF Del Parigi, A Chen, KW Salbe, AD Gautier, JF Ravussin, E Reiman, EM Tataranni, PA TI Tasting a liquid meal after a prolonged fast is associated with preferential activation of the left hemisphere SO NEUROREPORT LA English DT Article DE asymmetry; brain; PET; smell; taste ID POSITRON-EMISSION-TOMOGRAPHY; CEPHALIC PHASE; HUMANS; CORTEX; LATERALIZATION; PERCEPTION; AREAS AB We used positron emission tomographic scanning of the brain and measures of regional cerebral blood flow to investigate the response of 44 right-handed people to the oral administration of 2 ml of a liquid formula meal after a 36 h fast (and shortly before the administration of a satiating amount of the same meal). Several areas of the left hemisphere were significantly more activated than the contralateral, including the frontal operculum, ventral insula, and piriform cortex. In contrast with reports of right-hemisphere dominance in chemosensory perception in non-hungry individuals, our study reveals a preferential activation of the left hemisphere when people who are very hungry are briefly exposed to the chemical and physical properties of a liquid meal. This raises the possibility that the physiological context in which perception takes place (i.e. extreme vs moderate vs no hunger) may importantly affect the brain representation of chemosensory stimuli. C1 NIDDK, Obes Diabet & Energy Metab Unit, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Good Samaritan Reg Med Ctr, Positron Emiss Tomog Ctr, Phoenix, AZ USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Univ Arizona, Dept Psychiat, Tucson, AZ USA. RP Del Parigi, A (reprint author), NIDDK, Obes Diabet & Energy Metab Unit, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 NR 22 TC 24 Z9 24 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 JUL 2 PY 2002 VL 13 IS 9 BP 1141 EP 1145 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 587NV UT WOS:000177648700009 PM 12151757 ER PT J AU Corthout, E Hallett, M Cowey, A AF Corthout, E Hallett, M Cowey, A TI Early visual cortical processing suggested by transcranial magnetic stimulation SO NEUROREPORT LA English DT Article DE human; transcranial magnetic stimulation (TMS); vision ID CORTEX; CEREBELLUM; SUPPRESSION; PERCEPTION; EXCITABILITY; ATTENUATION; BRAIN AB Single-pulse transcranial magnetic stimulation (TMS) was applied to the occipital pole of healthy subjects while they performed a forced-choice visual letter-identification task. Pulses were applied on the midline but with a left-right asymmetric polarity; pulse application occurred at a variable delay after letter presentation onset; letters were presented in left or right hemifield. Averaging data over subjects and hemifields showed that performance attained local minima at 20 ms and 100 ms; averaging data over subjects and delays showed that performance was biased towards the same hemifield during both delay intervals; averaging data over subjects showed that the hemifield bias progressively decreased from 20 ms to 50 ms. The data are consistent with the possibility that also the earlier delay interval reflects visual cortical processing. 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. NR 20 TC 17 Z9 17 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 2 PY 2002 VL 13 IS 9 BP 1163 EP 1166 DI 10.1097/00001756-200207020-00018 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 587NV UT WOS:000177648700013 PM 12151761 ER PT J AU Spolski, RJ Alexander-Miller, MA Kuhn, RE AF Spolski, RJ Alexander-Miller, MA Kuhn, RE TI Suppressed cytotoxic T lymphocyte responses in experimental cysticercosis SO VETERINARY PARASITOLOGY LA English DT Article DE CTLs; cysticercosis; immunosuppression ID LARVAL TAENIA-CRASSICEPS; PEPTIDE; MICE AB Mitogen-induced T cell responses are suppressed in mice infected with larvae of Taenia crassiceps. The effects of experimental infection on specific T cell responses, however, have not been examined. In the present study, we demonstrate that larval-infected mice exhibit suppressed ability to develop anti-virus specific cytotoxic T lymphocyte (CTL) responses while maintaining apparently normal natural killer (NK) cell responsiveness. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Wake Forest Univ, Dept Biol, Winston Salem, NC 27109 USA. Wake Forest Univ, Dept Microbiol & Immunol, Winston Salem, NC 27103 USA. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Kuhn, RE (reprint author), Wake Forest Univ, Dept Biol, POB 7325, Winston Salem, NC 27109 USA. FU NIAID NIH HHS [AI 35730] NR 11 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4017 J9 VET PARASITOL JI Vet. Parasitol. PD JUL 2 PY 2002 VL 106 IS 4 BP 325 EP 330 AR PII S0304-4017(02)00105-X DI 10.1016/S0304-4017(02)00105-X PG 6 WC Parasitology; Veterinary Sciences SC Parasitology; Veterinary Sciences GA 570EW UT WOS:000176646800006 PM 12079738 ER PT J AU Seltzer, SE Sullivan, DC Hillman, BJ Staab, EV AF Seltzer, SE Sullivan, DC Hillman, BJ Staab, EV TI Factors affecting patient enrollment in radiology clinical trials: A case study of the American College of Radiology Imaging Network SO ACADEMIC RADIOLOGY LA English DT Article DE American College of Radiology; radiology and radiologists; research ID IMPROVEMENT AB Rationale and Objectives. This study was designed to identify factors that affect the enrollment of patients into American College of Radiology Imaging Network clinical trials. Materials and Methods. A quality improvement study was performed. Brainstorming produced an exhaustive list of factors that could affect the interest of sites in participating in American College of Radiology Imaging Network trials, as well as factors that could influence patient recruitment. Surveys, structured interviews, and benchmarking were used to validate and rank the importance of these factors. Results. Site participation was influenced mainly by the support of the department chair and the interest of the investigator. Patient recruitment was affected primarily by the ease of identifying candidates and the perceived experience level and skill of the support staff. Conclusion. Because radiologists do not control patient referrals for imaging tests, a premium must be placed on developing systems to maximize the identification and enrollment of candidates for clinical trials. Other factors considered critical to success in patient enrollment include the supportiveness of the departmental leadership, the experience and skill level of study personnel, and the availability of site-specific infrastructure to support the study. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. NCI, Biol Imaging Program, Bethesda, MD 20892 USA. Univ Virginia, Dept Radiol, Charlottesville, VA 22908 USA. RP Seltzer, SE (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JUL PY 2002 VL 9 IS 7 BP 862 EP 869 DI 10.1016/S1076-6332(03)80365-3 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 572LR UT WOS:000176776600020 PM 12139104 ER PT J AU Sun, PD Radaev, S Kattah, M AF Sun, PD Radaev, S Kattah, M TI Generating isomorphous heavy-atom derivatives by a quick-soak method. Part I: test cases SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID FC-GAMMA-RIII; CRYSTAL-STRUCTURE; DIFFRACTION AB Screening for heavy-atom derivatives remains a time-consuming and cumbersome process that often results in non-isomorphous derivatives whose phases cannot be combined. Using lysozyme and FcgammaRIII receptor crystals as test cases, an improved soaking method for the generation of conventional heavy-atom derivatives has been developed. The method is based on soaking crystals in heavy-atom compounds for a very brief time at near-saturation concentrations. Compared with the current heavy-atom soaking method, which often takes days to achieve a derivatization, the quick-soak method completes a derivatization within 10 min to 2 h. The bound heavy-atom sites display higher peak heights from quick soaks than from overnight soaks in all cases tested. The quick-soak derivatives also preserved native-like diffraction resolution and data quality that was better than the prolonged-soak derivatives. Furthermore, derivatives generated by brief soaks are more isomorphous to the native than those generated by overnight soaks. Short soaks not only increase the likelihood of success in heavy-atom screening by reducing the pitfalls associated with prolonged soaks, such as lack of isomorphism and overall lattice disorder, but also have the potential to transform a time-consuming derivative screening into an 'on-the-fly' real-time derivatization process. C1 NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIAID, Struct Biol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 10 TC 44 Z9 44 U1 0 U2 11 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 JUL PY 2002 VL 58 BP 1092 EP 1098 DI 10.1107/S0907444902006510 PN 7 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 564YW UT WOS:000176342000002 PM 12077427 ER PT J AU Sun, PD Radaev, S AF Sun, PD Radaev, S TI Generating isomorphous heavy-atom derivatives by a quick-soak method. Part II: phasing of new structures SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID RECEPTOR AB A quick-soak method has been applied to generate de novo heavy-atom phasing to solve two new protein structures, a type II transforming growth factor beta receptor (TBRII) and a natural killer cell receptor-ligand complex, NKG2D-ULBP3. In the case of TBRII, a crystal derivatized for only 10 min in saturated HgCl2 provided adequate phasing for structure determination. Comparison between HgCl2 derivatives generated by 10 min soaking and by 12 h soaking revealed similar phasing statistics. The shorter soak, however, resulted in a derivative more isomorphous to the native than the longer soak as judged by changes in the unit-cell parameter a upon derivatization as well as by the quality of a combined SIRAS electron-density map. In the case of the NKG2D-ULBP3 structure, all overnight soaks in heavy-atom solutions resulted in crystal lattice disorder and only the quick soaks preserved diffraction. Despite fragile lattice packing, the quick-soaked K2PtCl4 derivative was isomorphous with the native crystal and the electron-density map calculated from combined SIR and MAD phases is better than that calculated from MAD phases alone. Combined with mass-spectrometry-assisted solution heavy-atom derivative screening and the use of synchrotron radiation, the quick-soak derivatization has the potential to transform the time-consuming conventional heavy-atom search into a real-time 'on-the-fly' derivatization process that will benefit high-throughput structural genomics. C1 NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 11 TC 21 Z9 21 U1 0 U2 4 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 JUL PY 2002 VL 58 BP 1099 EP 1103 DI 10.1107/S0907444902006522 PN 7 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 564YW UT WOS:000176342000003 PM 12077428 ER PT J AU Boesen, CC Motyka, SA Patamawenu, A Sun, PD AF Boesen, CC Motyka, SA Patamawenu, A Sun, PD TI Crystallization and preliminary crystallographic studies of human TGF-beta type II receptor ligand-binding domain SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID CRYSTAL-STRUCTURE; TRANSFORMING GROWTH-FACTOR-BETA-2; SUPERFAMILY; KINASE; FOLD AB Three constructs (residues 15-136, 22-136 and 27-136) of the truncated extracellular domain of human transforming growth factor beta type II receptor (TBRII) were overexpressed in Escherichia coli. The constructs are referred to as TBRII(15-136), TBRII(22-136) and TBRII(27-136). The refolded receptors were purified using a combination of ion-exchange and size-exclusion chromatography. The purified receptors have an apparent molecular weight of 14 kDa as judged by size-exclusion chromatography. In the crystallization trials, TBRII(15-136) and TBRII(22-136) formed mostly crystal-like spheres but failed to produce data-quality crystals. TBRII(27-136) yielded large single crystals from hanging drops using the vapor-diffusion procedure with PEG 2000 or 4000 at pH 5.0. The crystals diffracted to 1.05 Angstrom [using the X9B beamline operated at lambda = 1.0092 Angstrom of the National Synchrotron Light Source (NSLS) at the Brookhaven National Laboratory] and belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 35.5, b = 40.7, c = 76.2 Angstrom. There was one molecule in the asymmetric unit, which corresponds to a solvent content of 42.1%. C1 NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NR 12 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUL PY 2002 VL 58 BP 1214 EP 1216 DI 10.1107/S0907444902007357 PN 7 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 564YW UT WOS:000176342000022 PM 12077447 ER PT J AU Yamada, KI Kuppusamy, P English, S Yoo, J Irie, A Subramanian, S Mitchell, JB Krishna, MC AF Yamada, KI Kuppusamy, P English, S Yoo, J Irie, A Subramanian, S Mitchell, JB Krishna, MC TI Feasibility and assessment of non-invasive in vivo redox status using electron paramagnetic resonance imaging SO ACTA RADIOLOGICA LA English DT Article DE tumor, redox status; thiols, nitroxides; electron paramagnetic resonance imaging; experimental ID NITROXIDE SPIN LABELS; IN-VIVO; FREE-RADICALS; MURINE TUMOR; SPECTROMETER; METABOLISM; OXYGENATION; SUPEROXIDE; REDUCTION; HYPOXIA AB Purpose: To test the feasibility of electron paramagnetic resonance imaging (EPRI) to provide non-invasive images of tissue redox status using redox-sensitive paramagnetic contrast agents. Material and Methods: Nitroxide free radicals were used as paramagnetic agents and a custom-built 300 MHz EPR spectrometer/imager was used for all studies. A phantom was constructed consisting of four tubes containing equal concentrations of a nitroxide. Varying concentrations of hypoxanthine/xanthine oxidase were added to each tube and reduction of the nitroxide was monitored by EPR as a function of time. Tumor-bearing mice were intravenously infused with a nitroxide and the corresponding reduction rate was monitored on a pixel-by-pixel basis using 2D EPR of the tumor-bearing leg and normal leg serving as control. For animal studies, nitroxides were injected intravenously (1.25 mmol/kg) and EPR projections were collected every 3 min after injection using a magnetic field gradient of 2.5 G/cm. The reduction rates of signal intensity on a pixel-by-pixel basis were calculated and plotted as a redox map. Redox maps were also collected from the mice treated with diethylmaleate (DEM), which depletes tissue thiols and alters the global redox status. Results: Redox maps obtained from the phantoms were in agreement with the intensity change in each of the tubes where the signals were decreasing as a function of the enzymatic activity, validating the ability of EPRI to accurately access changes in nitroxide reduction. Redox imaging capability of EPR was next evaluated in vivo . EPR images of the nitroxide distribution and reduction rates in tumor-bearing leg of mice exhibited more heterogeneity than in the normal tissue. Reduction rates were found to be significantly decreased in tumors of mice treated with DEM, consistent with the depletion of thiols and the consequent alteration of the redox status. Conclusion: Using redox-sensitive paramagnetic contrast agents, EPRI can non-invasively discriminate redox status differences between normal tissue and tumors. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, EPR Ctr, Baltimore, MD USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3B69, Bethesda, MD 20892 USA. RI Yamada, Ken-ichi/E-6318-2012 FU NCI NIH HHS [CA 78886] NR 21 TC 59 Z9 60 U1 0 U2 5 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0284-1851 J9 ACTA RADIOL JI Acta Radiol. PD JUL PY 2002 VL 43 IS 4 BP 433 EP 440 DI 10.1034/j.1600-0455.2002.430418.x PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 592QQ UT WOS:000177948700018 PM 12225490 ER PT J AU Shigematsu, R Chang, ML Yabushita, N Sakai, T Nakagaichi, M Nho, H Tanaka, K AF Shigematsu, R Chang, ML Yabushita, N Sakai, T Nakagaichi, M Nho, H Tanaka, K TI Dance-based aerobic exercise may improve indices of falling risk in older women SO AGE AND AGEING LA English DT Article DE balance; locomotion; agility ID FUNCTIONAL FITNESS; INJURY RATES; STRENGTH; WALKING; AGE AB Objective: to determine the effect of dance-based aerobic exercise on indices of falling in older women. Design: an exercise intervention trial with participants assigned either to an exercise group or to a control group. Setting: an exercise hall at a community centre for senior citizens. Participants: thirty-eight healthy women aged 72-87 years, living independently in the community. Intervention: twenty women performed dance-based aerobic exercise for 60 minutes, 3 days a week, for 12 weeks. The exercise included single-leg standing, squatting, marching, and heel touching; and targeted balance, strength, locomotion/agility, and motor processing. Main outcome measures: single-leg balance with eyes open/closed and functional reach as balance, hand-grip strength and keeping a half-squat position as strength, walking time around two cones and 3-minute walking distance as locomotion/agility, and hand-reaction time and foot tapping as motor processing. Results: at the pre-test, both exercise and control groups performed similarly in all tests. At the end of the intervention, the exercise group showed significantly greater single-leg balance with eyes closed, functional reach, and walking time around two cones. In contrast, there were no significant improvements in any of the test measures in the control group. Conclusions: dance-based aerobic exercise specifically designed for older women may improve selected components of balance and locomotion/agility, thereby attenuating risks of falling. C1 Japan Fdn Aging & Hlth, Aichi, Japan. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Tsukuba, Tsukuba, Ibaraki 305, Japan. Fdn Advancement Int Sci, Tsukuba, Ibaraki, Japan. Kyung Hee Univ, Coll Phys Educ, Kyonggi Do, South Korea. Univ Tsukuba, Inst Hlth & Sport Sci, Tsukuba, Ibaraki 305, Japan. Univ Tsukuba, Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki 305, Japan. RP Shigematsu, R (reprint author), Mie Univ, 1515 Kamihama, Tsu, Mie 5148507, Japan. NR 18 TC 79 Z9 84 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0002-0729 J9 AGE AGEING JI Age Ageing PD JUL PY 2002 VL 31 IS 4 BP 261 EP 266 DI 10.1093/ageing/31.4.261 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 580KE UT WOS:000177233100008 PM 12147563 ER PT J AU Rozzini, R Frisoni, GB Ferrucci, L Barbisoni, P Sabatini, T Ranieri, P Guralnik, JM Trabucchi, M AF Rozzini, R Frisoni, GB Ferrucci, L Barbisoni, P Sabatini, T Ranieri, P Guralnik, JM Trabucchi, M TI Geriatric Index of Comorbidity: validation and comparison with other measures of comorbidity SO AGE AND AGEING LA English DT Article DE comorbidity; functional status; Activity of Daily Living; performance test ID PHYSICAL PERFORMANCE-TEST; DAILY LIVING SCALES; OLDER ADULTS; DISABILITY; DISEASE; MORTALITY; HEALTH; REHABILITATION; POPULATION; MORBIDITY AB Background: the debate about measures of chronic comorbidity in the elderly is mainly due to the lack of consensus on pathogenetic models. Objective: the aim of the present study was to compare the concurrent validity of a number of measures of chronic comorbidity assuming different pathogenic models, versus disability in elderly patients. Setting: the Geriatric Evaluation and Rehabilitation Unit for subacute and disabled patients. Participants: 493 new and consecutive elderly patients (mean age 79 years, 71% females) admitted to the Geriatric Evaluation and Rehabilitation Unit. Measurements: we evaluated age, gender, cognitive status, depressive symptoms, functional status, somatic health, and nutritional status on admission. Functional status was assessed by the self- or proxy reported Katz's BADL scale and by the performance-based Reuben's Physical Performance Test. Somatic health was assessed as presence and severity of diseases according to standardized criteria. Comorbidity was measured as number of diseases, sum of disease severity, and with a composite score (Geriatric Index of Comorbidity) which takes into account both number of diseases and occurrence of very severe diseases. Mortality was assessed after 12 months. Results: specific diseases and their severity were found to be associated with disability measures. All measures of comorbidity were significantly correlated with disability, but only the Geriatric Index of Comorbidity was independently associated after adjustment for severity of individual diseases. In addition, increasing severity of comorbidity as defined by Geriatric Index of Comorbidity was associated with greater disability while this was not true for the other comorbidity measures (F statistics for the regression model including the Geriatric Index of Comorbidity=19.9). The Geriatric Index of Comorbidity, but not the other comorbidity measures, predicted mortality (relative risk of death 2.3, 95% confidence interval 1.7-3.1). Conclusion: the Geriatric Index of Comorbidity, a measure of comorbidity assuming that both number of diseases and occurrence of very severe diseases are determinants of health, has the greatest concurrent validity with disability and is the best predictor of mortality. C1 Geriatr Res Grp, I-25122 Brescia, Italy. Poliambulanza Hosp Brescia, Med Unit Acute Care Elderly, Brescia, Italy. IRCCS S Giovanni Dio, FBF, Lab Epidemiol & Neuroimaging, Brescia, Italy. I Fraticini Hosp, INRCA, Florence, Italy. NIA, Epidemiol & Demog & Biometry Program, Bethesda, MD 20892 USA. RP Rozzini, R (reprint author), Geriatr Res Grp, Via Romanino 1, I-25122 Brescia, Italy. RI Frisoni, Giovanni B/K-1360-2016 OI Frisoni, Giovanni B/0000-0002-6419-1753 NR 38 TC 98 Z9 105 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0002-0729 J9 AGE AGEING JI Age Ageing PD JUL PY 2002 VL 31 IS 4 BP 277 EP 285 DI 10.1093/ageing/31.4.277 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 580KE UT WOS:000177233100011 PM 12147566 ER PT J AU Pollard, RB Tierney, C Havlir, D Tebas, P Fox, L Smeaton, L Richman, D Friedland, GH AF Pollard, RB Tierney, C Havlir, D Tebas, P Fox, L Smeaton, L Richman, D Friedland, GH TI A phase II randomized study of the virologic and immunologic effect of zidovudine plus stavudine versus stavudine alone and zidovudine plus lamivudine in patients with > 300 CD4 cells who were antiretroviral naive (ACTG 298) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PHOSPHORYLATION IN-VITRO; COMBINATION THERAPY; CUBIC MILLIMETER; 2',3'-DIDEOXY-2',3'-DIDEHYDROTHYMIDINE; DIDANOSINE; COUNTS; TRIAL AB Before the development of multidrug regimens for treatment of patients with HIV infection single or dual nucleoside therapy was the standard of care. The present study was designed to examine the relative short (12-week) and long-term (48-week) activity of zidovudine (ZDV) vs stavudine (d4T) vs the combination in antiretroviral naive patients. The study was modified so that lamivudine (3TC) was added to ZDV after 12 weeks of monotherapy. A total of 129 subjects entered the study; however, not all were followed for 48 weeks as the study was terminated early due to changing standards of care. The median baseline viral load and CD4 cell count were 10,008 copies/ml and 407 cells/mm(3), respectively. There were no significant differences in the initial (12-week) change in viral load across the three arms. The viral load reduction at 48 weeks was greater in the ZDV/ZDV plus 3TC arm, with an average change of -0.91 log(10) copies/ml than in the d4T alone (-0.47 log(10) copies/ml) or d4T plus ZDV (-0.33 log(10) copies/ml), p = 0.03 and 0.02, respectively. There was a marginally significant increase in the CD4 cell count at Week 12 in the d4T arm as compared to the ZDV/ZDV plus 3TC arm. In general the treatments were well tolerated. The combination of d4T plus ZDV did not result in additional antiviral suppression as compared to either drug alone at 12 weeks and appeared to have less antiviral activity after Week 12. Based on this study and other data, combining d4T and ZDV is not recommended. C1 Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. NIH, Div AIDS, Bethesda, MD 20892 USA. VA Med Ctr, San Diego, CA 92103 USA. Yale Univ, Sch Med, New Haven, CT 06510 USA. RP Pollard, RB (reprint author), Univ Calif Davis, Med Ctr, Patient Support Serv Bldg,4150 V St,Suite G500, Sacramento, CA 95817 USA. RI Tebas, Pablo/A-7061-2008 NR 11 TC 4 Z9 4 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 JUL 1 PY 2002 VL 18 IS 10 BP 699 EP 704 DI 10.1089/088922202760072311 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 570TD UT WOS:000176673100003 PM 12167276 ER PT J AU Purohit, V Russo, D AF Purohit, V Russo, D TI Role of S-adenosyl-L-methionine in the treatment of alcoholic liver disease: introduction and summary of the symposium SO ALCOHOL LA English DT Article; Proceedings Paper CT Symposium on Role of S-Adenosyl-L-Methionine (SAMe) in the Treatment of Alcoholic Liver Disease CY SEP, 2001 CL BETHESDA, MARYLAND DE S-adenosyl-L-methionine (SAMe); alcoholic liver disease (ALD); oxidant stress; methylation; glutathione ID INJURY; RAT; ADENOSYLMETHIONINE; GLUTATHIONE; PROTECTS AB The National Institute on Alcohol Abuse and Alcoholism and the Office of Dietary Supplements, National Institutes of Health, sponsored a symposium on "Role of S-Adenosyl-L-Methionine (SAMe) in the Treatment of Alcoholic Liver Disease" in Bethesda, Maryland, September 2001. Alcoholic liver disease (ALD) is a major cause of illness and death in the United States. Oxidant stress plays a key role in pathogenesis of liver disease. S-Adenosyl-L-methionine, a dietary supplement, is the methyl donor for biochemical methylation reactions and a precursor of glutathione, the main hepatocellular antioxidant. S-Adenosyl-L-methionine has been shown to attenuate liver injury caused by alcohol and other hepatotoxins in some animal models. Understanding the mechanisms by which SAMe attenuates liver injury caused by alcohol may provide useful information for full-scale human clinical trials. For this symposium, seven speakers were invited to address the following issues: (1) impaired methionine metabolism in alcoholic liver injury; (2) regulation of liver function by SAMe; (3) folate deficiency, methionine metabolism, and alcoholic liver injury; (4) attenuating effect of SAMe on ALD ill experimental animals; (5) SAMe and mitochondrial glutathione depletion in ALD; (6) SAMe and cytokine production in liver injury; and (7) role of SAMe in the prevention of hepatocarcinogenesis. The presentations of this symposium support the suggestion that SAMe may have potential to treat ALD by (1) acting as a precursor of antioxidant glutathione, (2) repairing mitochondrial glutathione transport system, (3) attenuating toxic effects of proinflammatory cytokines, and (4) increasing DNA methylation. Further studies are required to evaluate the safety and effectiveness of SAMe treatment. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NIAAA, Biomed Res Branch, Div Basic Res, NIH, Bethesda, MD 20892 USA. RP Purohit, V (reprint author), NIAAA, Biomed Res Branch, Div Basic Res, NIH, 6000 Execut Blvd,Suite 402, Bethesda, MD 20892 USA. NR 10 TC 13 Z9 15 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUL PY 2002 VL 27 IS 3 BP 151 EP 154 AR PII S0741-8329(02)00232-X DI 10.1016/S0741-8329(02)00232-X PG 4 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 582HB UT WOS:000177343100001 PM 12163142 ER PT J AU Bashir, S Gibril, F Ojeaburu, JV Asgharian, B Entsuah, LK Ferraro, G Crafa, P Bordi, C Jensen, RT AF Bashir, S Gibril, F Ojeaburu, JV Asgharian, B Entsuah, LK Ferraro, G Crafa, P Bordi, C Jensen, RT TI Prospective study of the ability of histamine, serotonin or serum chromogranin A levels to identify gastric carcinoids in patients with gastrinomas SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; MULTIPLE ENDOCRINE NEOPLASIA; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; ENTEROCHROMAFFIN-LIKE CELLS; TERM OMEPRAZOLE TREATMENT; LONG-TERM; OXYNTIC MUCOSA; HYPERGASTRINEMIC PATIENTS; REFLUX ESOPHAGITIS; RAT STOMACH AB Background: Chronic hypergastrinaemia causes gastric enterochromaffin cell proliferation and carcinoid tumours. The only reliable means to diagnose enterochromaffin cell changes/carcinoids is by biopsy. Aim: To assess whether serum histamine, chromogranin A or serotonin and urinary N-methylimidazoleacetic acid or 5-hydroxyindoleacetic acid correlate with advanced enterochromaffin cell changes or gastric carcinoids in patients with gastrinomas. Methods: Consecutive patients (n =145) had the above assays and endoscopy with gastric biopsies. Results: Lower N-methylimidazoleacetic acid and chromogranin A levels (P< 0.0001) occurred in disease-free patients. In patients with active disease, the fasting serum gastrin levels correlated (P < 0.0001) with both chromogranin A and N-methylimidazoleacetic acid levels. Chromogranin A (P =0.005), but not N-methylimidazoleacetic acid, serotonin, 5-hydroxyindoleacetic acid or histamine levels, correlated with the enterochromaffin cell index. Carcinoids, but not advanced enterochromaffin cell changes only, were associated with higher chromogranin A and N-methylimidazoleacetic acid levels. Conclusions: Serum chromogranin A levels and urinary N -methylimidazoleacetic acid levels, but not serum histamine or serotonin or urinary 5-hydroxyindoleacetic acid, correlate with the presence of gastric carcinoids. However, no assay identified patients with advanced enterochromaffin cell changes only with high sensitivity/specificity. Thus, N -methylimidazoleacetic acid and chromogranin A levels are unable to identify patients with advanced changes in enterochromaffin cells and therefore neither can replace routine gastric biopsies. C1 NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Parma, Sect Anat Pathol, Dept Pathol & Lab Med, I-43100 Parma, Italy. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr DR MSC 1804, Bethesda, MD 20892 USA. NR 75 TC 23 Z9 25 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JUL PY 2002 VL 16 IS 7 BP 1367 EP 1382 DI 10.1046/j.1365-2036.2002.01249.x PG 16 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 577UU UT WOS:000177081200021 PM 12144588 ER PT J AU Wood, BJ Razavi, P AF Wood, BJ Razavi, P TI Virtual endoscopy: A promising new technology SO AMERICAN FAMILY PHYSICIAN LA English DT Article ID COLORECTAL-CANCER; CT COLONOGRAPHY; BARIUM ENEMA; COLONOSCOPY; CARCINOMA; COLON; BRONCHOSCOPY; MAMMOGRAPHY; POLYPS; SCREEN AB Growing evidence shows that early detection of cancer can substantially reduce mortality, necessitating screening programs that encourage patient compliance. Radiology is already established as a screening tool, as in mammography for breast cancer and ultrasonography for congenital anomalies. Advanced processing of helical computed tomographic data sets permits three-dimensional and virtual endoscopic models. Such models are noninvasive and require minimal patient preparation, making them ideal for screening. Virtual endoscopy has been used to evaluate the colon, bronchi, stomach, blood vessels, bladder, kidney, larynx, and paranasal sinuses. The most promising role for virtual endoscopy is in screening patients for colorectal cancer. The technique has also been used to evaluate the tracheobronchial tree for bronchogenic carcinoma. Three-dimensional and virtual endoscopy can screen, diagnose, evaluate and assist determination of surgical approach, and provide surveillance of certain malignancies. Copyright (C) 2002 American Academy of Family Physicians. C1 NIH, Ctr Clin, Special Procedures Div, Diagnost Radiol Dept, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wood, BJ (reprint author), NIH, Ctr Clin, Special Procedures Div, Diagnost Radiol Dept, Room 1C-660,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 27 TC 16 Z9 19 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD JUL 1 PY 2002 VL 66 IS 1 BP 107 EP 112 PG 6 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 571XV UT WOS:000176745200009 PM 12126025 ER PT J AU Gottdiener, JS Panza, JA Sutton, MS Bannon, P Kushner, H Weissman, NJ AF Gottdiener, JS Panza, JA Sutton, MS Bannon, P Kushner, H Weissman, NJ TI Testing the test: The reliability of echocardiography in the sequential assessment of valvular regurgitation SO AMERICAN HEART JOURNAL LA English DT Article ID LEFT-VENTRICULAR FUNCTION; AORTIC REGURGITATION; MITRAL REGURGITATION; ISOMETRIC-EXERCISE; POSTURAL CHANGES; DAY VARIABILITY; DOPPLER; DEXFENFLURAMINE; REGRESSION; REPRODUCIBILITY AB Background and Objective Substantial variability in serial echocardiographic qualitative assessment of valvular regurgitation may exist. Reader variability is generally well understood, but acquisition variability (portions of variability caused by equipment, sonographers, physiologic changes) has been less frequently assessed, particularly in combination with reader variability. We attempted to determine the relative contributions of acquisition and reader variability as components of total test-retest variability for aortic (AR) and mitral (MR) regurgitation. Methods Outpatient echocardiographic study was done at 2 clinical sites. Twenty-three predominantly obese middle-aged females had 3 echocardiograms, 2 performed 14 +/- 3 days apart and the third performed within I to 2 hours of the second. Triplets of echocardiograms were evaluated for change in grade of AR and MR. Medical history, anthropometrics, and blood pressures were obtained. Results Average intrareader variability (percentage of reads for which there is within-reader disagreement) was 5.6% for AR and 16.7% for MR. The average total test-retest variability (percentage of reads for which there is disagreement between visits) was 29.0% for AR and 24.6% for MR. The acquisition variability for AR was 23.4% +/- 7.7%; for MR, it was 7.9% +/- 10.2%. A significant predictor of change for AR/MR was the initial grade. Change in diastolic blood pressure was positively associated with change in AR and MR. Conclusions Intrareader agreement was substantial for AR and MR. Components of total test-retest variability found were reader, biological (change in diastolic blood pressure), and regression to the mean. Recommendations for clinical practice include monitoring blood pressure changes and understanding the confidence limits of the clinical test. Test-retest variability and its components should be considered in echocardiography and other diagnostic testing. C1 St Francis Hosp, Roslyn, NY 11576 USA. NHLBI, Bethesda, MD 20892 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Mercy Hosp, Pittsburgh, PA 15219 USA. BIOMED Comp Res Inst, Philadelphia, PA USA. Cardiovasc Res Inst, Washington, DC USA. RP Gottdiener, JS (reprint author), St Francis Hosp, Roslyn, NY 11576 USA. NR 30 TC 24 Z9 24 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 2002 VL 144 IS 1 BP 115 EP 121 DI 10.1067/mhj.2002.123139 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 573AV UT WOS:000176807900018 PM 12094197 ER PT J AU Bui, MN Arai, AE Hathaway, L Waclawiw, MA Csako, G Cannon, RO AF Bui, MN Arai, AE Hathaway, L Waclawiw, MA Csako, G Cannon, RO TI Effect of hormone replacement therapy on carotid arterial compliance in healthy postmenopausal women SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DISTENSIBILITY; INFLAMMATION; PROGESTERONE; ESTRADIOL; STIFFNESS; COLLAGEN; DENSITY; TRIAL; AGE AB Hormone replacement therapy for 3 months significantly improved carotid arterial compliance. determined by magnetic resonance imaging of the common carotid arteries and blood pressure measurements. in 22 healthy postmenopausal women compared with placebo period measurements in this randomized, double-blind, crossover trial. This effect was independent of changes in serum levels of lipids or markers of inflammation. C1 NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, Cardiac Energet Lab, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NIH, Dept Clin Pathol, Bldg 10,Room 7B15,10 Ctr Dr MSC 1650, Bethesda, MD 20892 USA. NR 18 TC 20 Z9 20 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 1 PY 2002 VL 90 IS 1 BP 82 EP + AR PII S0002-9149(02)02397-4 DI 10.1016/S0002-9149(02)02397-4 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 570AE UT WOS:000176635000023 PM 12088791 ER PT J AU Bazzano, LA He, J Ogden, LG Loria, CM Vupputuri, S Myers, L Whelton, PK AF Bazzano, LA He, J Ogden, LG Loria, CM Vupputuri, S Myers, L Whelton, PK TI Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE fruit; vegetables; ischemic heart disease; cerebrovascular disorders; mortality; cohort studies; NHANES I; National Health and Nutrition Examination Survey; cardiovascular disease ID CORONARY HEART-DISEASE; SERUM FOLATE; MORTALITY; STROKE; MEN; CONSUMPTION; REDUCE AB Background: Epidemiologic studies report inconsistent findings on the association of fruit and vegetable intake with the risk of cardiovascular disease. Objective: The objective was to examine the relation between fruit and vegetable intake and the risk of cardiovascular disease. Design: We studied 9608 adults aged 25-74 y participating in the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study and free of cardiovascular disease at the time of their baseline examination between 1971 and 1975. Fruit and vegetable intake at baseline was measured with a food-frequency questionnaire. The incidence of and mortabty from cardiovascular disease were obtained from medical records and death certificates. Results: Over an average of 19 y, 888 strokes (218 fatal), 1786 ischemic heart disease events (639 fatal), 1145 cardiovascular disease deaths, and 2530 all-cause deaths were documented. Consuming fruit and vegetables greater than or equal to3 times/d compared with <1 time/d was associated with a 27% lower stroke incidence [relative risk (RR): 0.73; 95% Cl: 0.57, 0.95; P for trend = 0.01), a 42% lower stroke mortality (0.58; 0.33, 1.02; P for trend = 0.05), a 24% lower ischemic heart disease mortality (0.76; 0.56, 1.03; P for trend = 0.07), a 27% lower cardiovascular disease mortality (0.73; 0.58, 0.92; P for trend = 0.008), and a 15% lower all-cause mortality (0.85; 0.72, 1.00; P for trend = 0.02) after adjustment for established cardiovascular disease risk factors, Conclusion: We showed an inverse association of fruit and vegetable intake with the risk of cardiovascular disease and all-cause mortality in the general US population. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat, New Orleans, LA 70112 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP He, J (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1430 Tulane Ave SL18, New Orleans, LA 70112 USA. FU NHLBI NIH HHS [R01HL60300, R03 HL61954] NR 28 TC 542 Z9 566 U1 7 U2 59 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 JUL PY 2002 VL 76 IS 1 BP 93 EP 99 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 565PK UT WOS:000176378500009 PM 12081821 ER PT J AU Althuis, MD Jordan, NE Ludington, EA Wittes, JT AF Althuis, MD Jordan, NE Ludington, EA Wittes, JT TI Glucose and insulin responses to dietary chromium supplements: a meta-analysis SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE chromium; dietary supplements; diabetes; insulin; glucose; hemoglobin; meta-analysis ID TOTAL PARENTERAL-NUTRITION; NICOTINIC-ACID; PICOLINATE SUPPLEMENTATION; DIABETES-MELLITUS; BODY-COMPOSITION; ELDERLY SUBJECTS; BLOOD-GLUCOSE; TOLERANCE; WOMEN; DEFICIENCY AB Background: Several authors, mostly on the basis of nonrandomized studies, have suggested dietary trivalent chromium supplementation as an attractive option for the management of type 2 diabetes and for glycemic control in persons at high risk of type 2 diabetes. Objective: The study aimed to determine the effect of chromium on glucose and insulin responses in healthy subjects and in individuals with glucose intolerance or type 2 diabetes. Design: The study design was a systematic review and meta-analysis of randomized clinical trials (RCTs). Results: The authors identified 20 reports of RCTs assessing the effect of chromium on glucose, insulin, or glycated hemoglobin (Hb A(1c)). This review summarizes data on 618 participants from the 15 trials that reported adequate data: 193 participants had type 2 diabetes and 425 were in good health or had impaired glucose tolerance. The meta-analysis showed no association between chromium and glucose or insulin concentrations among nondiabetic subjects. A study of 155 diabetic subjects in China showed that chromium reduced glucose and insulin concentrations; the combined data from the 38 diabetic subjects in the other studies did not. Three trials reported data on Hb A(1c): one study each of persons with type 2 diabetes, persons with impaired glucose tolerance, and healthy subjects. The study of diabetic subjects in China was the only one to report that chromium significantly reduced Hb A(ic). Conclusions: Data from RCTs show no effect of chromium on glucose or insulin concentrations in nondiabetic subjects. The data for persons with diabetes are inconclusive. RCTs in well-characterized, at-risk populations are necessary to determine the effects of chromium on glucose, insulin, and Hb A(1c). C1 Stat Collaborat Inc, Washington, DC USA. RP Althuis, MD (reprint author), NCI, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, 6120 Execut Blvd,Room 7184,EPS MSC 7234, Rockville, MD 20852 USA. NR 46 TC 131 Z9 136 U1 2 U2 17 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 JUL PY 2002 VL 76 IS 1 BP 148 EP 155 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 565PK UT WOS:000176378500016 PM 12081828 ER PT J AU Tucker, KL Chen, HL Hannan, MT Cupples, LA Wilson, PWF Felson, D Kiel, DP AF Tucker, KL Chen, HL Hannan, MT Cupples, LA Wilson, PWF Felson, D Kiel, DP TI Bone mineral density and dietary patterns in older adults: the Framingham Osteoporosis Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE bone mineral density; dietary patterns; fruit and vegetables; older adults; Framingham Osteoporosis Study ID FOOD-FREQUENCY QUESTIONNAIRE; BODY-MASS INDEX; ELDERLY MEN; POSTMENOPAUSAL WOMEN; HIP FRACTURE; ALCOHOL-CONSUMPTION; CLUSTER-ANALYSIS; RISK; HEALTH; PROTEIN AB Background: Several nutrients are known to affect bone mineral density (BMD). However, these nutrients occur together in foods and dietary patterns, and the overall effects of dietary choices are not well understood. Objective: We evaluated associations between dietary patterns and BMD in older adults. Design: Of the original Framingham Heart Study subjects, 907 aged 69-93 y completed food-frequency questionnaires as part of an osteoporosis study. We defined dietary patterns by cluster analysis. BMD was measured at the proximal right femur (femoral neck, trochanter, Ward's area) with a dual-photon absorptiometer and at the 33% radial shaft with a single-photon absorptiometer. We regressed BMD measures onto the cluster variable, adjusting for potential confounders. Results: Six dietary patterns were identified, with relatively Greater proportions of intake from meat, dairy, and bread; meat and sweet baked products; sweet baked products; alcohol; candy; and fruit, vegetables, and cereal. After adjustment for multiple comparisons, men in the last group had significantly (P = 0.05) greater BMD than did 2-4 other groups at the hip sites and the candy group at the radius. Men in the candy group had significantly (P < 0.05) lower BMD than did those in the fruit, vegetables, and cereal group for 3 of the 4 sites. Women in the candy group had significantly (P < 0.01) lower BMD than did all but one other group at the radius. Conclusions: Dietary pattern is associated with BMD. High fruit and vegetable intake appears to be protective in men. High candy consumption was associated with low BMD in both men and women. C1 Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NHLBI, Framingham MA Heart Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. RP Tucker, KL (reprint author), Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. RI Tucker, Katherine/A-4545-2010; OI Kiel, Douglas/0000-0001-8474-0310; Tucker, Katherine/0000-0001-7640-662X; Chen, Honglei/0000-0003-3446-7779 FU NHLBI NIH HHS [NHLBI N01-38038]; NIAMS NIH HHS [R01 AR/AG 41398, AR20613] NR 47 TC 137 Z9 144 U1 1 U2 12 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 JUL PY 2002 VL 76 IS 1 BP 245 EP 252 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 565PK UT WOS:000176378500030 PM 12081842 ER PT J AU Bazzano, LA He, J Ogden, LG Loria, CM Vupputuri, S Myers, L Whelton, PK AF Bazzano, LA He, J Ogden, LG Loria, CM Vupputuri, S Myers, L Whelton, PK TI Agreement on nutrient intake between the databases of the First National Health and Nutrition Examination Survey and the ESHA food processor SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; data collection; diet; nutrition surveys; nutritive value ID CORONARY HEART-DISEASE; DIETARY-FAT; RISK AB The objective of this study was to assess agreement on nutrient intake between the nutrient database of the First National Health and Nutrition Examination Survey (NHANES 1) and an up-to-date (December 1998) nutrient database, the ESHA Food Processor. Analysis was conducted among 11,303 NHANES I participants aged 2574 years in 1971-1975 who had undergone dietary assessment. A list of all unique foods consumed was obtained from a single 24-hour dietary recall questionnaire administered during the baseline NHANES I visit. Foods on the list were matched to foods in the ESHA Food Processor software. Agreement between participants' nutrient intakes as calculated with the NHANES I and ESHA nutrient databases was assessed using intraclass correlation analysis, linear regression analysis, and graphic methods. Intraclass correlation analysis demonstrated excellent concordance between most nutrient intakes, with coefficients above 0.95 for intakes of energy, carbohydrates, protein, cholesterol, and calcium; coefficients between 0.90 and 0.95 for intakes of total fat, saturated fat, potassium, and vitamin C; and coefficients of approximately 0.85 for intakes of sodium and vitamin A. Graphic methods and regression analyses also showed good-to-excellent correspondence for most nutrients. These findings support the validity of expanding existing nutrient intake databases to explore current hypotheses, provided that food formulation, enrichment, and fortification practices have not changed substantially over time. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat, New Orleans, LA USA. NHLBI, Bethesda, MD 20892 USA. RP He, J (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1430 Tulane Ave SL18, New Orleans, LA 70112 USA. FU NHLBI NIH HHS [R01 HL60300, R03 HL61954] NR 27 TC 18 Z9 19 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 JUL 1 PY 2002 VL 156 IS 1 BP 78 EP 85 DI 10.1093/aje/kwf003 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 569ED UT WOS:000176586900009 PM 12076891 ER PT J AU Conwell, Y Duberstein, PR Connor, K Eberly, S Cox, C Caine, ED AF Conwell, Y Duberstein, PR Connor, K Eberly, S Cox, C Caine, ED TI Access to firearms and risk for suicide in middle-aged and older adults SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID PSYCHOLOGICAL AUTOPSY; COMPLETED SUICIDE; ADOLESCENT SUICIDE; HOMICIDE; LEGISLATION; PREVENTION; VALIDITY; HANDGUNS; RATES AB Elderly white men are at the highest risk for suicide. Firearms arc, the most common method of suicide used by both men and women in later lift, and a greater proportion of older than younger suicide victims use a gun. This psychological autopsy study aimed to test hypotheses concerning the risk for suicide associated with access to and storage of firearms. Subjects included 86 suicide victims age 50 years of age and over and 86 community control subjects individually matched on age, sex, race, and county of residence. Presence of a firearm in the home was associated with increased risk for suicide, even after controlling for psychiatric illness. Elevated risk wets accounted for by access to handguns rather than long guns and was more pronounced in men than women. Among subjects who kept a gun in the home, storing the weapon loaded and unlocked were independent predictors of suicide. Findings support the potential benefit for suicide prevention of restricting access to handguns. Education programs for older persons, their families, and healthcare providers concerning the risks of having a gun in the home and reinforcement of rules for safe storage may contribute to reducing the rate of suicide in older people. C1 Univ Rochester, Sch Med, Ctr Study & Prevent Suicide, Rochester, NY 14642 USA. Univ Rochester, Ctr Study & Prevent Suicide, Sch Med, Dept Psychiat, Rochester, NY 14627 USA. NICHHD, Rochester, NY USA. Univ Rochester, Ctr Study & Prevent Suicide, Sch Med, Dept Biostat, Rochester, NY 14627 USA. RP Conwell, Y (reprint author), Univ Rochester, Sch Med, Ctr Study & Prevent Suicide, 300 Crittenden Blvd, Rochester, NY 14642 USA. FU NIMH NIH HHS [K24 MH01759, R01 MH54682] NR 47 TC 101 Z9 102 U1 2 U2 10 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUL-AUG PY 2002 VL 10 IS 4 BP 407 EP 416 DI 10.1176/appi.ajgp.10.4.407 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 571KR UT WOS:000176717000007 PM 12095900 ER PT J AU Cook, JM Pearson, JL Thompson, R Black, BS Rabins, PV AF Cook, JM Pearson, JL Thompson, R Black, BS Rabins, PV TI Suicidality in older African Americans - Findings from the EPOCH study SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID PUBLIC-HOUSING RESIDENTS; MENTAL-HEALTH-CARE; CAGE QUESTIONNAIRE; LIFE SATISFACTION; DEPRESSION; POPULATION; ALCOHOLISM; SYMPTOMS; IDEATION; PROGRAM AB The authors examined the current frequency of suicidality and associated characteristics in a sample of 835 African-American older adult residents of six urban public housing developments who consented to participate in an intervention trial of mobile outreach. The frequency of passive and active suicidal ideation was 2.5% and 1.4%, respectively Characteristics of individuals with both active and passive suicidality included elevated anxiety, social dysfunction, somatic symptoms, low social support, lack of a confidant, and low religiosity. Characteristics those with passive, but not active, ideation also included older age, lower levels of education, elevated depressive symptoms, poorer cognitive functioning, and having recently discussed emotional problems with a healthcare provider The characteristics of those reporting active, but not passive, ideation included having a history of mental health treatment and reporting no instrumental support. Multivariate analyses indicated that depression and religiosity were uniquely associated with passive suicidal ideation, and life satisfaction and religiosity were uniquely associated with active suicidal ideation. The authors discuss implications of these findings and offer suggestions for research and clinical practice. C1 Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. NIMH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Cook, JM (reprint author), Philadelphia VA Med Ctr, 116A,Univ & Woodland Aves, Philadelphia, PA 19104 USA. EM cook_j@mail.trc.upenn.edu RI Thompson, Richard/G-5408-2011 OI Thompson, Richard/0000-0003-0127-513X FU NIMH NIH HHS [MH 42412, MH 48673, MH P50 43703] NR 45 TC 34 Z9 34 U1 1 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUL-AUG PY 2002 VL 10 IS 4 BP 437 EP 446 DI 10.1176/appi.ajgp.10.4.437 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 571KR UT WOS:000176717000010 PM 12095903 ER PT J AU Weitz, CA Garruto, RM Chin, CT Liu, JC Liu, RL He, X AF Weitz, CA Garruto, RM Chin, CT Liu, JC Liu, RL He, X TI Lung function of Han Chinese born and raised near sea level and at high altitude in western China SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Article ID PRIMARY-SCHOOL CHILDREN; PULMONARY-FUNCTION; EUROPEAN ANCESTRY; AIR-POLLUTION; HEALTH-PROGRAM; DEVELOPMENTAL ADAPTATION; HYPOXIC ENVIRONMENT; CIGARETTE-SMOKING; CHEST MORPHOLOGY; FUNCTION GROWTH AB Forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), and FEV1/ FVC ratios were determined for 531 individuals of Han Chinese descent living at low altitude (250 m) near Beijing and for 592 individuals of Han descent who were born and raised at three high altitudes (3,200 m, 3,800 in, 4,300 m) in Qinghai Province, P.R.C. The study included males and females, ages 6-51 years. Thorax widths, depths, and circumferences of Han females and males born and raised at high altitude are similar to those of low-altitude Han. On the other hand, high-altitude children and adolescents have larger relative sitting heights, indicating greater thorax lengths. After adjusting for this variation in morphology, mean FVC values among 6-21 year-old Han at high altitude are only between 136 mL (for females) and 173 ml (for males) greater than those determined at low altitude but the differences are statistically significant and are maintained consistently throughout the growth period. These data indicate that growth at high altitude produces small-to-moderate increases in lung volumes (about 6%) relative to genetically similar groups growing up at low altitude. In addition, there is no evidence that lung volume growth is accelerated relative to morphological growth among Han children born and raised at high altitude. Adults, 22-51 years, also show greater FVC values at high altitude but the size of the increase relative to Han at low altitude is variable (3% in males and 11% in females). Greater lung function at high altitude is unlikely to result from increased activity or lower pollution, and thus appears to be primarily a result of development in a hypoxic environment. Differences in FVC and FEV1 at 3,200 m, 3,800 in, and 4,300 m are generally not significant, so that living at altitudes between 3,200 in and 4,300 m appears to have little additional effect on volumetric growth. (C) 2002 Wiley-Liss. Inc. C1 Temple Univ, Dept Anthropol, Philadelphia, PA 19122 USA. SUNY Binghamton, Binghamton, NY 13902 USA. NIH, Bethesda, MD 20891 USA. Beijing Med Univ, Maternal & Childrens Hosp, Beijing, Peoples R China. Qinghai Bur Publ Hlth, Dept Maternal & Child Hlth, Xining, Peoples R China. RP Weitz, CA (reprint author), Temple Univ, Dept Anthropol, 214 Gladfelter Hall, Philadelphia, PA 19122 USA. NR 60 TC 11 Z9 11 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PD JUL-AUG PY 2002 VL 14 IS 4 BP 494 EP 510 DI 10.1002/ajhb.10063 PG 17 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA 567PH UT WOS:000176492800011 PM 12112571 ER PT J AU Osier, MV Pakstis, AJ Soodyall, H Comas, D Goldman, D Odunsi, A Okonofua, F Parnas, J Schulz, LO Bertranpetit, J Bonne-Tamir, B Lu, RB Kidd, JR Kidd, KK AF Osier, MV Pakstis, AJ Soodyall, H Comas, D Goldman, D Odunsi, A Okonofua, F Parnas, J Schulz, LO Bertranpetit, J Bonne-Tamir, B Lu, RB Kidd, JR Kidd, KK TI A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID LIVER ALCOHOL-DEHYDROGENASE; COMMON DISEASE GENES; METABOLIZING GENES; IBERIAN PENINSULA; HUMAN GENOME; POLYMORPHISMS; ALLELE; LOCUS; MEN; POPULATIONS AB Variants of different Class I alcohol dehydrogenase (ADH) genes have been shown to be associated with an effect that is protective against alcoholism. Previous work from our laboratory has shown that the two sites showing the association are in linkage disequilibrium and has identified the ADH1B Arg47His site as causative, with the ADH1C Ile349Val site showing association only because of the disequilibrium. Here, we describe an initial study of the nature of linkage disequilibrium and genetic variation, in population samples from different regions of the world, in a larger segment of the ADH cluster (including the three Class I ADH genes and ADH7). Linkage disequilibrium across similar to40 kb of the Class I ADH cluster is moderate to strong in all population samples that we studied. We observed nominally significant pairwise linkage disequilibrium, in some populations, between the ADH7 site and some Class I ADH sites, at moderate values and at a molecular distance as great as 100 kb. Our data indicate (1) that most ADH-alcoholism association studies have failed to consider many sites in the ADH cluster that may harbor etiologically significant alleles and (2) that the relevance of the various ADH sites will be population dependent. Some individual sites in the Class I ADH cluster show values that are among F-st the highest seen among several dozen unlinked sites that were studied in the same subset of populations. The high values can be attributed to the discrepant frequencies of specific alleles in eastern Asia relative to those Fst in other regions of the world. These alleles are part of a single haplotype that exists at high (>65%) frequency only in the eastern-Asian samples. It seems unlikely that this haplotype, which is rare or unobserved in other populations, reached such high frequency because of random genetic drift alone. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. S African Inst Med Res, Human Genom Divers & Dis Res Unit, ZA-2000 Johannesburg, South Africa. Univ Witwatersrand, Johannesburg, South Africa. Univ Pompeu Fabra, Fac Ciencies Salut & Vida, Dept Ciencies Expt & Salut, Barcelona, Spain. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. Univ Benin, Fac Med, Dept Gynecol & Obstet, Benin, Nigeria. Univ Copenhagen, Hvidovre Hosp, Dept Psychiat, DK-2650 Hvidovre, Denmark. Univ Wisconsin, Milwaukee, WI 53201 USA. Tel Aviv Univ, Sackler Sch Med, Dept Genet, IL-69978 Tel Aviv, Israel. Natl Def Med Ctr, Triserv Gen Hosp, Dept Psychiat, Taipei, Taiwan. RP Kidd, KK (reprint author), Yale Univ, Sch Med, Dept Genet, SHM I-351333 Cedar St, New Haven, CT 06520 USA. RI Bertranpetit, Jaume/F-8550-2012; Comas, David/D-5382-2014; Goldman, David/F-9772-2010 OI Bertranpetit, Jaume/0000-0003-0100-0590; Comas, David/0000-0002-5075-0956; Goldman, David/0000-0002-1724-5405 FU NIAAA NIH HHS [AA09379, R01 AA009379] NR 45 TC 161 Z9 175 U1 1 U2 14 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 JUL PY 2002 VL 71 IS 1 BP 84 EP 99 DI 10.1086/341290 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 564GY UT WOS:000176307700009 PM 12050823 ER PT J AU Engel, LS Vaughan, TL Gammon, MD Chow, WH Risch, HA Dubrow, R Mayne, ST Rotterdam, H Schoenberg, JB Stanford, JL West, AB Blot, WJ Fraumeni, JF AF Engel, LS Vaughan, TL Gammon, MD Chow, WH Risch, HA Dubrow, R Mayne, ST Rotterdam, H Schoenberg, JB Stanford, JL West, AB Blot, WJ Fraumeni, JF TI Occupation and risk of esophageal and gastric cardia adenocarcinoma SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE occupational diseases; esophageal adenocarcinoma; gastric cardia adenocarcinoma ID DRY-CLEANING WORKERS; CANCER MORTALITY; UNITED-STATES; GASTROESOPHAGEAL REFLUX; GASTROINTESTINAL CANCER; STOMACH-CANCER; ORAL CAVITY; MEN; CARCINOMA; EXPOSURES AB Background Adenocarcinomas of the esophagus and gastric cardia have risen dramatically in incidence over the past few decades, however little research has been conducted on the occupational risk factors for these cancers. Methods In this population-based case-control study, lifetime job histories were compared between cases of esophageal adenocarcinoma (n = 283), gastric cardia adenocarcinoma (n = 259), and population controls (n = 689). Odds ratios (OR) and 95% confidence intervals (CI) for ever employment and by duration in various occupational and industrial categories were calculated using unconditional logistic regression. Results The risk of esophageal adenocarcinoma was elevated for persons ever employed in administrative support (OR = 1.5; 95% CI = 1.0-2.1); financial, insurance, and real estate (OR = 1.6; 95% CI = 1.0-2.4); and health services (OR = 2.2; 95% CI = 1.2-3.9). The risk of gastric cardia adenocarcinoma was increased among transportation workers (OR = 1.7; 95% CI = 1.1-2.6), as well as among carpenters (OR = 1.8; 95% CI = 0.9-3.9) and workers in the furniture manufacturing industry (OR = 2.4; 95% CI = 0.9-6.3). However, we observed few duration-response relations between length of employment in any category and cancer risk. Conclusions This study revealed associations of esophageal adenocarcinoma with employment in administrative support, health services, and a category of financial, insurance, and real estate industries, and of gastric cardia adenocarcinoma with transportation and certain woodworking occupations. Some of these findings may be due to the play of chance associated with the multiple comparisons made in this study. Our results suggest that, overall, workplace exposures play a minor role in the etiology and upward trend of esophageal and gastric cardia adenocarcinomas. Published 2002 Wiley-Liss, Inc.(dagger). C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. Yale Univ, Sch Med, Dept Epidemiol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Publ Hlth, New Haven, CT 06510 USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. New Jersey Dept Hlth & Senior Serv, Canc Epidemiol Serv, Trenton, NJ USA. Yale Univ, Dept Pathol, New Haven, CT USA. Int Epidemiol Inst, Rockville, MD USA. RP Engel, LS (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8113, Bethesda, MD 20892 USA. OI Engel, Lawrence/0000-0001-9268-4830 NR 48 TC 23 Z9 23 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 2002 VL 42 IS 1 BP 11 EP 22 DI 10.1002/ajim.10077 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 567XV UT WOS:000176513000002 PM 12111686 ER PT J AU Slavotinek, AM Dubovsky, E Dietz, HC Lacbawan, F AF Slavotinek, AM Dubovsky, E Dietz, HC Lacbawan, F TI Report of a child with aortic aneurysm, Orofacial clefting, hemangioma, upper sternal defect, and marfanoid features: Possible PHACE syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE PRACE spectrum; hemangiomas; sternal malformation; vascular dysplasia association; aortic dilatation and dissection ID SUPRAUMBILICAL MIDLINE RAPHE; FACIAL HEMANGIOMAS; INNOMINATE-ARTERY; COARCTATION; MALFORMATIONS; ASSOCIATION; ARCH; ANOMALIES; NECK AB We report a female patient who had a scalp hemangioma, a cleft uvula, an upper sternal defect, pectus excavatum, arachnodactyly, pes planus, and joint hypermobility. She had rupture of an aortic aneurysm after minor trauma at 11 years of age. At 17 years of age, elective repair of a dilated, ectatic aorta was complicated by cerebral ischemia. Other vascular abnormalities in the proband included an aneurysm of the left subclavian artery, atresia of the right carotid artery, and calcified cerebral aneurysms. We believe that the proband's physical anomalies are best described by the PHACE (posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities) phenotypic spectrum. This spectrum of physical anomalies also includes sternal clefting and hemagiomas as part of the sternal malformation/vascular dysplasia (SM/VD) association, as found in our patient, and the acronym PHACES has also been used. We consider that the PRACE phenotypic spectrum is likely to be broader than previously recognized and includes oro-facial clefting and aortic dilatation and rupture. Our patient also had skeletal anomalies that lead to consideration of Marfan syndrome as a diagnosis. It should be recognized that there is clinical overlap between PHACE syndrome and Marfan syndrome when aortic dilatation is present. We would also like to emphasize the minor nature of the cutaneous findings in our patient despite her severe vascular complications. This is in contrast to previous reports of large or multiple hemangiomas in PRACE syndrome. Published 2002 Wiley-Liss, Inc. C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Radiol, Washington, DC USA. Johns Hopkins Univ, Inst Med Genet, Howard Hughes Med Inst, Baltimore, MD USA. Childrens Natl Med Ctr, Dept Med Genet, Washington, DC USA. RP Slavotinek, AM (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [R01AR41135-09] NR 33 TC 21 Z9 22 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 1 PY 2002 VL 110 IS 3 BP 283 EP 288 DI 10.1002/ajmg.10455 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 563UG UT WOS:000176273900015 PM 12116239 ER PT J AU McInerney, JD Jenkins, J AF McInerney, JD Jenkins, J TI No threat to board certified geneticists and genetic counselors SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter C1 Natl Coalit Hlth Prof Educ Genet, Lutherville Timonium, MD USA. Natl Canc Inst, NIH, Bethesda, MD USA. Oncol Nursing Soc, Pittsburgh, PA USA. Core Competencies Working Grp, Natl Coalit Hlth Prof Educ Genet, Lutherville Timonium, MD USA. RP McInerney, JD (reprint author), 2360 W Joppa Rd Suite 320, Lutherville Timonium, MD 21093 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 1 PY 2002 VL 110 IS 3 BP 297 EP 297 DI 10.1002/ajmg.10386 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 563UG UT WOS:000176273900018 PM 12116242 ER PT J AU Schneider, DL Burke, L Wright, TC Spitzer, M Chatterjee, N Wacholder, S Herrero, R Bratti, MC Greenberg, MD Hildesheim, A Sherman, ME Morales, J Hutchinson, ML Alfaro, M Lorincz, A Schiffman, M AF Schneider, DL Burke, L Wright, TC Spitzer, M Chatterjee, N Wacholder, S Herrero, R Bratti, MC Greenberg, MD Hildesheim, A Sherman, ME Morales, J Hutchinson, ML Alfaro, M Lorincz, A Schiffman, M TI Can cervicography be improved? An evaluation with arbitrated cervicography interpretations SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervicography; cervical cancer; screening; cervical neoplasia ID COSTA-RICA; CERVICAL NEOPLASIA; POPULATION; WOMEN; CYTOLOGY; TRIAGE; CANCER; HPV AB OBJECTIVE: The purpose of this study was to estimate the optimal performance of cervicography. We compared an arbitrated cervigram classification with an arbitrated referent diagnosis of cervical neoplasia. STUDY DESIGN: From an initial group of 8460 women, a stratified sample of cervigrams from 3645 women and histologic information from 414 women underwent arbitration. Interobserver agreement was assessed for cervicography and the referent diagnosis. Sensitivity, specificity, and predictive values were estimated for initial and arbitrated cervicography results, compared with the initial and arbitrated referent diagnoses. RESULTS: For the detection of arbitrated high-grade lesions or cancer, arbitrated cervicography yielded an overall sensitivity of 63.9% and a specificity of 93.7%. Significantly higher sensitivity was associated with younger age and age-related visual characteristics. CONCLUSION: Optimization of the cervigram classification improved performance over a single interpretation in this population but suggested the limits of static visual screening. C1 US PHS, Div Immigrat Hlth Serv, Washington, DC 20536 USA. Beth Israel Med Ctr, Boston, MA USA. Columbia Univ, New York, NY USA. N Shore Hosp, Manhasset, NY USA. NCI, Stat Res & Applicat Sect, Bethesda, MD 20892 USA. NCI, Biostat Branch, Bethesda, MD 20892 USA. Minst Salud, Lyon, France. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA. NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. RP Schneider, DL (reprint author), US PHS, Div Immigrat Hlth Serv, 801 I St NW,Suite 910, Washington, DC 20536 USA. FU NCI NIH HHS [N01-CP-21081, N0 1-CP-31061] NR 15 TC 10 Z9 10 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2002 VL 187 IS 1 BP 15 EP 23 DI 10.1067/mob.2002.122848 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 576EA UT WOS:000176988800003 PM 12114883 ER PT J AU Shankaran, S Papile, LA Wright, LL Ehrenkranz, RA Mele, L Lemons, JA Korones, SB Stevenson, DK Donovan, EF Stoll, BJ Fanaroff, AA Oh, W Verter, J AF Shankaran, S Papile, LA Wright, LL Ehrenkranz, RA Mele, L Lemons, JA Korones, SB Stevenson, DK Donovan, EF Stoll, BJ Fanaroff, AA Oh, W Verter, J TI Neurodevelopmental outcome of premature infants after antenatal phenobarbital exposure SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE antenatal phenobarbital; neonatal; outcome ID BIRTH-WEIGHT INFANTS; INTRAVENTRICULAR HEMORRHAGE; INTRACRANIAL HEMORRHAGE; PREVENTION; THERAPY; NEWBORN; TRIAL; LESS AB OBJECTIVE: We previously demonstrated that antenatal phenobarbital does not decrease the risk of intracranial hemorrhage or early death in premature infants. The objective of the present study was to evaluate the impact of antenatal phenobarbital exposure on the neurodevelopmental outcome of premature infants born to women who were participating in the randomized clinical trial of antenatal phenobarbital exposure. STUDY DESIGN: Infants were evaluated at 18 to 22 months corrected age with a standard neurologic examination and the Bayley scales of infant development measuring the mental developmental index and the psychomotor developmental index. RESULTS: Of the 578 infants <34 weeks of gestational age who were born to women who were enrolled in the primary study, 7 infants died after discharge from the neonatal intensive care unit, and 135 infants were lost to follow-up. Infants who were lost to follow-up had a higher mean birth weight and gestational age and a lower maternal education, but the rates of intracranial hemorrhage were comparable to those infants who were evaluated. Among the infants who were evaluated (n = 436; 76%), the mean birth weight and gestational age, maternal education, and frequency and distribution of intracranial hemorrhage were similar in the antenatal phenobarbital exposed and placebo groups. Eighteen infants (8%) in the antenatal phenobarbital exposed group and 21 infants (11%) in the placebo group had cerebral palsy (P = not significant). There was no difference between the 2 groups in either the median Bayley II mental developmental index (85 in the antenatal phenobarbital and 86 in the placebo group) or the Psychomotor Developmental Index (91 in the antenatal phenobarbital and 91 in the placebo group). Infants with intracranial hemorrhage (23%) had significantly lower mental developmental index and psychomotor developmental index scores than infants with no intracranial hemorrhage, independent of antenatal phenobarbital exposure. In the total cohort of 436 infants, the presence of intracranial hemorrhage or periventricular leukomalacia was associated with lower mental developmental index and psychomotor developmental index scores; the presence of increasing birth weight, maternal education, and a complete course of antenatal steroids was associated with a higher mental developmental index score. CONCLUSION: Antenatal phenobarbital exposure did not favorably or adversely affect the neurodevelopmental outcome of premature infants at 18 to 22 months of age. C1 Wayne State Univ, Detroit, MI 48202 USA. Univ New Mexico, Albuquerque, NM 87131 USA. NICHHD, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT USA. George Washington Univ, Washington, DC USA. Indiana Univ, Indianapolis, IN 46204 USA. Univ Tennessee, Memphis, TN USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Cincinnati, Cincinnati, OH USA. Emory Univ, Atlanta, GA 30322 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Women & Infants Hosp Rhode Isl, Providence, RI USA. RP Shankaran, S (reprint author), Childrens Hosp Michigan, 3901 Beaubien Blvd, Detroit, MI 48201 USA. FU NCRR NIH HHS [M01 RR 00750, M01 RR 08084, M01 RR 00070, M01 RR 06022, M01 RR 00997]; NICHD NIH HHS [U10 HD27881, U10 HD27851, U01 HD19897, U10 HD 27904, U10 HD21364, U10 HD21385, U10 HD21415, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880] NR 25 TC 20 Z9 19 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2002 VL 187 IS 1 BP 171 EP 177 DI 10.1067/mob.2002.122445 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 576EA UT WOS:000176988800026 PM 12114906 ER PT J AU Silveira, C Belfort, R Muccioli, C Holland, GN Victora, CG Horta, BL Nussenblatt, RB AF Silveira, C Belfort, R Muccioli, C Holland, GN Victora, CG Horta, BL Nussenblatt, RB TI The effect of long-term intermittent trimethoprim/sulfamethoxazole treatment on recurrences of toxoplasmic retinochoroiditis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OCULAR TOXOPLASMOSIS; TRIMETHOPRIM-SULFAMETHOXAZOLE; CONGENITAL TOXOPLASMOSIS; GONDII INFECTION; SOUTHERN BRAZIL; AIDS AB PURPOSE: To determine the effect of long term intern mittent trimethoprim/sulfamethoxazole treatment on re currences of toxoplasmic retinochoroiditis. DESIGN: Prospective randomized open-labeled inter, ventional clinical trial. METHODS: A total of 124 patients with a history of recurrent toxoplasmic retinochoroiditis were randomized to treatment with one tablet of trimethoprim (160 mg)/ sulfamethoxazole (800 mg) (Bactrim F; Roche Pharmaceuticals, Ric de Janeiro, Brazil) every 3 days (61 patients) or to observation without treatment (63 patients) and were followed monthly for up to 20 consecutive months for clinical signs of disease recurrence. A recurrence was defined as a new focus of necrotizing retinochoroiditis with active inflammation either adjacent to or remote from preexisting retinochoroidal scars. RESULTS: Recurrences developed in four (6.6%) treated patients and in 15 (23.8%) controls (P = .01). Treatment was discontinued prematurely in four patients because of mild drug reactions. CONCLUSION: Long-term intermittent treatment with trimethoprim/sulfamethoxazole can reduce the rate of recurrent toxoplasmic retinochoroiditis. (C) 2002 by Elsevier Science Inc. All rights reserved. C1 Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil. Clin Silveira, Rio Grande Do Sul, Brazil. Univ Calif Los Angeles, Sch Med, Dept Ophthalmol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Ocular Inflammatory Dis Ctr, Los Angeles, CA 90024 USA. Fed Univ Pelotas, Pelotas, Brazil. Catholic Fed Univ, Pelotas, Brazil. NEI, NIH, Bethesda, MD 20892 USA. RP Belfort, R (reprint author), Rua Botucatu,822, BR-04023062 Sao Paulo, Brazil. RI Horta, Bernardo/A-7604-2008; Belfort Jr, Rubens/E-2252-2012; Muccioli, Cristina/C-3419-2013; Epidemiologicas, Centro de pesquisas /D-4561-2013; Victora, Cesar/D-4476-2013; OI Belfort Jr, Rubens/0000-0002-8422-3898; Victora, Cesar/0000-0002-2465-2180 NR 24 TC 82 Z9 86 U1 0 U2 4 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 JUL PY 2002 VL 134 IS 1 BP 41 EP 46 AR PII S0002-9394(02)01527-1 DI 10.1016/S0002-9394(02)01527-1 PG 6 WC Ophthalmology SC Ophthalmology GA 569QX UT WOS:000176614600006 PM 12095806 ER PT J AU Tsilou, E Csaky, K Rubin, BI Gahl, W Kaiser-Kupfer, M AF Tsilou, E Csaky, K Rubin, BI Gahl, W Kaiser-Kupfer, M TI Retinal visualization in an eye with corneal crystals using indocyanine green videoangiography SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report a patient in whom clear imaging of the retina, impossible with conventional methods, was obtained using indocyanine green (ICG) videoangiography. DESIGN: Interventional case report. METHODS: A 31-year,old patient with nephropathic cystinosis and complaints of decreased vision in the left eye underwent a complete ophthalmologic evaluation, including conventional photography, fluorescein angiography, and ICG videoangiography. RESULTS: With conventional methods (direct and indirect ophthalmoscopy, photography, and fluorescein angiography), the view of the left retina was obscured by densely packed corneal cystine crystals. During ICG angiography, clear imaging of the retina was obtained with near,infrared illumination. CONCLUSION: Indocyanine green videoangiography can be a useful tool in cases with cystinosis and other corneal opacities, where visualization and imaging of the retina are important but impossible with conventional methods. (C) 2002 by Elsevier Science Inc. All rights reserved. C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Tsilou, E (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, 10 Ctr Dr,MSC-1860,Bldg 10,Rm 10N226, Bethesda, MD 20892 USA. NR 3 TC 5 Z9 5 U1 0 U2 0 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 JUL PY 2002 VL 134 IS 1 BP 123 EP 125 DI 10.1016/S0002-9394(02)01508-8 PG 3 WC Ophthalmology SC Ophthalmology GA 569QX UT WOS:000176614600022 PM 12095822 ER PT J AU Shih, SC Robinson, GS Perruzzi, CA Calvo, A Desai, K Green, JE Ali, IU Smith, LEH Senger, DR AF Shih, SC Robinson, GS Perruzzi, CA Calvo, A Desai, K Green, JE Ali, IU Smith, LEH Senger, DR TI Molecular profiling of angiogenesis markers SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; BLOOD-VESSEL FORMATION; PROSTATE-CANCER; VASCULAR DEVELOPMENT; TUMOR ANGIOGENESIS; QUANTITATIVE PCR; EXPRESSION; VEGF; QUANTIFICATION AB The goal of this study was to develop a sensitive, simple, and widely applicable assay to measure copy numbers of specific mRNAs using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and identify a profile of gene expression closely associated with angiogenesis. We measured a panel of nine potential angiogenesis markers from a mouse transgenic model of prostate adenocarcinoma (TRAMP) and a mouse skin model of vascular endothelial growth factor (VEGF)-driven angiogenesis. In both models, expression of VEGF correlated with expression of mRNAs encoding other angiogenic cytokines (angiopoietin-1 and angiopoietin-2), endothelial cell receptor tyrosine kinases (Flt-1, KDR, Tie-1), and endothelial cell adhesion molecules (VE-cadherin, PECAM-1). Relative to control, in dermis highly stimulated by VEGF, the Ang-2 mRNA transcript numbers increased 35-fold, PECAM-1 and VE-cadherin increased 10-fold, Tie-1 increased 8-fold, KDR and Flt-1 each increased 4-fold, and Ang-1 increased 2-fold. All transcript numbers were correspondingly reduced in skin with less VEGF expression, indicating a relationship of each of these seven markers with VEGF. Thus, this study identifies a highly efficient method for precise quantification of a panel of seven specific mRNAs that correlate with VEGF expression and VEGF-induced neovascularization, and it provides evidence that real-time quantitative RT-PCR offers a highly sensitive strategy for monitoring angiogenesis. C1 Harvard Univ, Sch Med, Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Smith, LEH (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Ophthalmol, 300 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [N01-CN-85070-72]; NEI NIH HHS [R01 EY008670, EY 08670] NR 34 TC 96 Z9 100 U1 0 U2 5 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 JUL PY 2002 VL 161 IS 1 BP 35 EP 41 DI 10.1016/S0002-9440(10)64154-5 PG 7 WC Pathology SC Pathology GA 571LF UT WOS:000176718300006 PM 12107087 ER PT J AU Andersen, CL Monni, O Wagner, U Kononen, J Barlund, M Bucher, C Haas, P Nocito, A Bissig, H Sauter, G Kallioniemi, A AF Andersen, CL Monni, O Wagner, U Kononen, J Barlund, M Bucher, C Haas, P Nocito, A Bissig, H Sauter, G Kallioniemi, A TI High-throughput copy number analysis of 17q23 in 3520 tissue specimens by fluorescence in situ hybridization to tissue microarrays SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; SQUAMOUS-CELL CARCINOMA; BREAST-CANCER; CHROMOSOMAL IMBALANCES; DNA AMPLIFICATION; GENE-EXPRESSION; LOSSES; GAINS; KINASE; TUMORS AB The chromosomal region 17q23 has been shown to be commonly amplified in breast tumors, especially those with poor prognosis. in addition to breast cancer, studies by comparative genomic hybridization have implicated the involvement of 17q23 in other tumor types as well. Here we performed a large-scale survey on the distribution and frequency of the 17q23 copy number increases across different tumor types using fluorescence hi situ hybridization on tissue microarrays containing 4788 specimens. A total of 4429 tumor samples representing 166 different tumor categories and 359 normal tissue samples from 40 different tissue categories were analyzed. Successful hybridizations were observed in 3520 of the 4788 specimens (74%). Increased 17q23 copy number was detected in 15% of the evaluable specimens with tumors originating from the lung, mammary gland, and soft tissue being most frequently affected. Interestingly, high-level amplification was detected only in 2% of the tumors and was generally restricted to mammary tumors. in addition, we observed an association between the frequency of increased 17q23 copy number and tumor progression in various tumor types. These results indicate that increased 17q23 copy number occurs frequently in several different tumor types suggesting that increased dosage of genes in this region might play a role in development and progression of many tumor types. C1 Univ Tampere, Canc Genet Lab, Inst Med Technol, FIN-33014 Tampere, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Aarhus Univ Hosp, Dept Haematol, Cancercytogenet Lab, DK-8000 Aarhus, Denmark. Biomedicum Helsinki, Biomedicum Biochip Ctr, Helsinki, Finland. Tampere Univ Hosp, Tampere, Finland. Univ Basel, Basel, Switzerland. RP Kallioniemi, A (reprint author), Univ Tampere, Canc Genet Lab, Inst Med Technol, POB 607, FIN-33014 Tampere, Finland. EM anne.kallioniemi@uta.fi RI bucher, christoph/A-2520-2008; Andersen, Claus Lindbjerg/A-9217-2012; Andersen, Claus/C-1477-2017; OI Andersen, Claus Lindbjerg/0000-0002-7406-2103; Andersen, Claus/0000-0002-7406-2103; Kallioniemi, Anne/0000-0003-3552-8158 NR 30 TC 49 Z9 51 U1 0 U2 2 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 JUL PY 2002 VL 161 IS 1 BP 73 EP 79 DI 10.1016/S0002-9440(10)64158-2 PG 7 WC Pathology SC Pathology GA 571LF UT WOS:000176718300010 PM 12107091 ER PT J AU Spring, KR AF Spring, KR TI Claudins are the gatekeepers. Focus on "Claudins create charge-selective channels in the paracellular pathway between epithelial cells" SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Editorial Material C1 NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Spring, KR (reprint author), NIH, Kidney & Electrolyte Metab Lab, 10 Ctr Dr,MSC 1603,Bldg 10,Rm 6N260, Bethesda, MD 20892 USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 2002 VL 283 IS 1 BP C29 EP C30 DI 10.1152/ajpcell.00128.2002 PG 2 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 560EY UT WOS:000176070800002 PM 12055069 ER PT J AU Schnermann, J AF Schnermann, J TI Exercise SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Editorial Material ID HUMAN SKELETAL-MUSCLE; SOLEUS MUSCLE; DYNAMIC EXERCISE; COLD-EXPOSURE; NITRIC-OXIDE; BLOOD-FLOW; FORCE; RATS; K+; METABOLISM C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. NR 46 TC 1 Z9 1 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUL PY 2002 VL 283 IS 1 BP R2 EP R6 DI 10.1152/ajpregu.00146.2002 PG 5 WC Physiology SC Physiology GA 563LQ UT WOS:000176257500001 PM 12069926 ER PT J AU Schnermann, J AF Schnermann, J TI Adenosine mediates tubuloglomerular feedback SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Editorial Material ID MICE C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), NIDDKD, NIH, Bldg 10,Rm 4 D51,10 Ctr Dr MSC 1370, Bethesda, MD 20892 USA. NR 9 TC 21 Z9 21 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUL PY 2002 VL 283 IS 1 BP R276 EP R277 DI 10.1152/ajpregu.00072.2002 PG 2 WC Physiology SC Physiology GA 563LQ UT WOS:000176257500030 PM 12069955 ER PT J AU Leal-Pinto, E Cohen, BE Lipkowitz, MS Abramson, RG AF Leal-Pinto, E Cohen, BE Lipkowitz, MS Abramson, RG TI Functional analysis and molecular model of the human urate transporter/channel, hUAT SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE pyrazinoate; lactose; oxonate; glucose; adenosine; glycophorin A ID MICROVILLUS MEMBRANE-VESICLES; TRANSMEMBRANE ALPHA-HELICES; GALACTOSIDE-BINDING LECTIN; GLYCOPHORIN-A DIMERIZATION; URIC-ACID; AMINOHIPPURATE TRANSPORT; ADENOSINE RECEPTOR; CRYSTAL-STRUCTURE; GXXXG MOTIF; SEQUENCE AB Recombinant protein, designated hUAT, the human homologue of the rat urate transporter/channel (UAT), functions as a highly selective urate channel in lipid bilayers. Functional analysis indicates that hUAT activity, like UAT, is selectively blocked by oxonate from its cytosolic side, whereas pyrazinoate and adenosine selectively block from the channel's extracellular face. Importantly, hUAT is a galectin, a protein with two beta-galactoside binding domains that bind lactose. Lactose significantly increased hUAT open probability but only when added to the channel's extracellular side. This effect on open probability was mimicked by glucose, but not ribose, suggesting a role for extracellular glucose in regulating hUAT channel activity. These functional observations support a four-transmembrane-domain structural model of hUAT, as previously predicted from the primary structure of UAT. hUAT and UAT, however, are not functionally identical: hUAT has a significantly lower single-channel conductance and open probability is voltage independent. These differences suggest that evolutionary changes in specific amino acids in these highly homologous proteins are functionally relevant in defining these biophysical properties. C1 Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. NIAID, Div Extramural Act, NIH, Bethesda, MD 20892 USA. RP Abramson, RG (reprint author), Mt Sinai Sch Med, Dept Med, Div Nephrol, Box 1243,1 Gustave L Levy Pl, New York, NY 10029 USA. EM ruth.abramson@mssm.edu FU NIDDK NIH HHS [DK-52785, DK-57867] NR 80 TC 15 Z9 19 U1 0 U2 1 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 JUL PY 2002 VL 283 IS 1 BP F150 EP F163 DI 10.1152/ajprenal.00333.2001 PG 14 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 561KE UT WOS:000176138800017 PM 12060597 ER PT J AU Manning, J Beutler, K Knepper, MA Vehaskari, VM AF Manning, J Beutler, K Knepper, MA Vehaskari, VM TI Upregulation of renal BSC1 and TSC in prenatally programmed hypertension SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE sodium transport; thick ascending limb; distal convoluted tubule; essential hypertension; pressure natriuresis; bumetanide-sensitive sodium-potassium-2 chloride cotransporter; thiazide-sensitive sodium-chloride cotransporter ID THICK ASCENDING LIMB; NA-CL COTRANSPORTER; ADULT HYPERTENSION; BIRTH-WEIGHT; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; ALTERED EXPRESSION; RAT KIDNEYS; PROTEIN; GROWTH AB Prenatal factors, especially intrauterine growth retardation, have been shown to correlate with the risk of essential hypertension in adult life, but the mechanisms are unknown. An experimental model of prenatal programming of hypertension in the rat, induced by a maternal low-protein diet during pregnancy, was employed to study the role of renal Na reabsorption in the pathogenesis. The abundance of the apical Na transporter type III Na/H exchanger (NHE3), bumetanide-sensitive Na-K-2Cl cotransporter (BSC1), thiazide-sensitive Na-Cl cotransporter (TSC), and the amiloride-sensitive epithelial Na channel (ENaC) was determined by semiquantitative immunoblotting in kidneys from the offspring at 4 wk of age, before hypertension became manifest. There were no significant differences between the experimental and control rats in the abundance of NHE3 or any of the ENaC subunits. In contrast, the quantity of BSC1 in the experimental group was increased to 302% of control (P<0.001) and that of TSC to 157% of control (P<0.05). Determination of specific mRNA levels by ELISA-linked RT-PCR revealed a significantly increased BSC1 mRNA at 1 day (P<0.01), 4 wk (P<0.01), and 8 wk (P<0.001) of age, and a significantly increased TSC mRNA at 4 wk of age (P<0.05) in the experimental group. The results suggest that prenatal programming of hypertension involves transcriptional upregulation of Na transport in thick ascending limb and distal convoluted tubule. C1 Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Div Pediat Nephrol, New Orleans, LA 70118 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Vehaskari, VM (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Div Pediat Nephrol, 200 Henry Clay Ave, New Orleans, LA 70118 USA. EM Vvehas@lsuhsc.edu FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [1 R01-HL-66158, Z01-HL-01282-KE] NR 31 TC 113 Z9 115 U1 0 U2 3 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 JUL PY 2002 VL 283 IS 1 BP F202 EP F206 DI 10.1152/ajprenal.00358.2001 PG 5 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 561KE UT WOS:000176138800023 PM 12060603 ER PT J AU Kleinman, DV AF Kleinman, DV TI The guide to community preventive services - Oral health SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material C1 US PHS, Off Chief Dent Officer, Bethesda, MD USA. RP Kleinman, DV (reprint author), NIDCR, NIH, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2002 VL 23 SU S BP 1 EP 2 AR PII S0749-3797(02)00436-1 DI 10.1016/S0749-3797(02)00436-1 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 574JY UT WOS:000176886900001 PM 12091087 ER PT J AU Truman, BI Gooch, BF Sulemana, I Gift, HC Horowitz, AM Evans, CA Griffin, SO Carande-Kulis, VG AF Truman, BI Gooch, BF Sulemana, I Gift, HC Horowitz, AM Evans, CA Griffin, SO Carande-Kulis, VG CA Task Force Community Preventive Se TI Reviews of evidence on interventions to prevent dental caries, oral and pharyngeal cancers, and sports-related craniofacial injuries SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review DE cariostatic agents; community dentistry; community health planning; community health services; decision making; dental caries; evidence-based medicine; facial injuries; intervention studies; mouth protectors; oral health; oral and pharyngeal neoplasms; pit and fissure sealants; practice guidelines; preventive dentistry; preventive health services; public health dentistry; public health practice; review literature; tooth injuries ID GLASS-IONOMER CEMENT; FISSURE SEALANTS; WATER FLUORIDATION; UNITED-STATES; COST-EFFECTIVENESS; FOLLOW-UP; LONGITUDINAL EVALUATION; FOOTBALL PLAYERS; HEALTH PROMOTION; OCCLUSAL CARIES AB This report presents the results of systematic reviews of effectiveness, applicability, other positive and negative effects, economic evaluations, and barriers to use of selected population-based interventions intended to prevent or control dental caries, oral and pharyngeal cancers, and sports-related craniofacial injuries. The related systematic reviews are linked by a common conceptual approach. These reviews form the basis of recommendations by the Task Force on Community Preventive Services (the Task Force) about the use of these selected interventions. The Task Force recommendations are presented in this supplement(1). C1 Ctr Dis Control & Prevent, Community Guide Branch, Off Director,Div Oral Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. Ctr Dis Control & Prevent, Div Prevent Res & Analyt Methods, Epidemiol Program Off, Atlanta, GA 30341 USA. Brevard Coll, Div Social Sci, Brevard, NC USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Truman, BI (reprint author), Ctr Dis Control & Prevent, Community Guide Branch, Off Director,Div Oral Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway,MS-K73, Atlanta, GA 30341 USA. NR 210 TC 72 Z9 74 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2002 VL 23 SU S BP 21 EP 54 AR PII S0749-3797(02)00449-X DI 10.1016/S0749-3797(02)00449-X PG 34 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 574JY UT WOS:000176886900007 PM 12091093 ER PT J AU Gooch, BF Truman, BI Griffin, SO Kohn, WG Sulemana, I Gift, HC Horowitz, AM Evans, CA AF Gooch, BF Truman, BI Griffin, SO Kohn, WG Sulemana, I Gift, HC Horowitz, AM Evans, CA TI A comparison of selected evidence reviews and recommendations on interventions to prevent dental caries, oral and pharyngeal cancers, and sports-related craniofacial injuries SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE cariostatic agents; community dentistry; community health planning; community health services; decision making; dental caries; evidence-based medicine; facial injuries; fluoridation; intervention studies; meta-analysis; mouth protectors; oral health; pharyngeal neoplasms; pit and fissure sealants; practice guidelines; preventive dentistry; preventive health services; public health dentistry; public health practice; review literature; tooth injuries C1 Ctr Dis Control & Prevent, Div Oral Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Off Director, Atlanta, GA 30341 USA. Ctr Dis Control & Prevent, Div Prevent Res & Analyt Methods, Epidemiol Program Off, Atlanta, GA 30341 USA. Brevard Coll, Brevard, NC USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. RP Gooch, BF (reprint author), Ctr Dis Control & Prevent, Div Oral Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Off Director, MS F-10, Atlanta, GA 30341 USA. NR 10 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2002 VL 23 SU S BP 55 EP 80 AR PII S0749-3797(02)00450-6 DI 10.1016/S0749-3797(02)00450-6 PG 26 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 574JY UT WOS:000176886900008 PM 12091094 ER PT J AU Soltis, J Bernhards, D Donkin, H Newman, JD AF Soltis, J Bernhards, D Donkin, H Newman, JD TI Squirrel monkey chuck call: Vocal response to playback chucks based on acoustic structure and affiliative relationship with the caller SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE squirrel monkey; Saimiri; vocalization; communication; signal processing; affiliation ID SAIMIRI-SCIUREUS; CONTACT CALLS; VOCALIZATIONS; RECOGNITION; MODELS AB Adult female squirrel monkeys (genus Saimiri) that are socially familiar often exchange the chuck vocalization, which differs acoustically across individuals. We used behavioral observations, vocalization playback experiments, and analysis of the acoustic properties of vocalizations to investigate the effect of caller identity and acoustic structure on vocal response to playback chucks in two all-female social groups (n=10 females). Females were most likely to respond with a chuck to the playback chucks of their closely affiliated partners compared to those of nonaffiliated group members. This shows for the first time that the chuck stimulus alone is sufficient to elicit a chuck response from a female's affiliated partner. Additionally, females responded with a chuck mostly to familiar playback chucks from their own group and least to playbacks of silent controls. Unfamiliar playback chucks from the same species and a different squirrel monkey species elicited chuck responses intermediate between familiar chucks and silent controls. Post-hoc discriminant function analyses provide preliminary evidence that females are most likely to respond to unfamiliar chucks when those chucks are close in acoustic structure to familiar chucks from their own social group. These results provide a provisional explanation for error in the squirrel monkey signal processing system, in which unfamiliar chucks never heard before nevertheless elicit a chuck response if they are similar in acoustic structure to familiar group chucks. (C) 2002 Wiley-Liss, Inc. C1 NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD USA. RP Soltis, J (reprint author), NICHD, LCE, Comparat Ethol Lab, NIH, Box 529, Poolesville, MD 20837 USA. NR 25 TC 18 Z9 18 U1 2 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2002 VL 57 IS 3 BP 119 EP 130 DI 10.1002/ajp.10039 PG 12 WC Zoology SC Zoology GA 569PX UT WOS:000176612000002 PM 12111678 ER PT J AU Fee, E Brown, TM Lazarus, J Theerman, P AF Fee, E Brown, TM Lazarus, J Theerman, P TI The effects of the corset SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article C1 Natl Lib Med, Hist Med Div, NIH, Bethesda, MD USA. Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Bldg 38, Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 3 TC 0 Z9 0 U1 3 U2 4 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 JUL PY 2002 VL 92 IS 7 BP 1085 EP 1085 DI 10.2105/AJPH.92.7.1085 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 568AZ UT WOS:000176521400019 PM 12084685 ER PT J AU McBride, CM Bastian, LA Halabi, S Fish, L Lipkus, IM Bosworth, HB Rimer, BK Siegler, IC AF McBride, CM Bastian, LA Halabi, S Fish, L Lipkus, IM Bosworth, HB Rimer, BK Siegler, IC TI A tailored intervention to aid decisionmaking about hormone replacement therapy SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID RANDOMIZED TRIAL; BREAST-CANCER; SUPPORT; WOMEN C1 Ctr Comprehens Canc, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Vet Adm Med Ctr, Durham, NC USA. NCI, Div Canc Prevent & Control, Bethesda, MD USA. RP McBride, CM (reprint author), Duke Canc Prevent Detect & Control Res, DUMC Box 2949, Durham, NC 27710 USA. FU NCI NIH HHS [P01 CA072099, P01-CA-72099-05] NR 11 TC 29 Z9 29 U1 0 U2 1 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 JUL PY 2002 VL 92 IS 7 BP 1112 EP 1114 DI 10.2105/AJPH.92.7.1112 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 568AZ UT WOS:000176521400027 PM 12084693 ER PT J AU Singh, GK Siahpush, M AF Singh, GK Siahpush, M TI Increasing rural-urban gradients in US suicide mortality, 1970-1997 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UNITED-STATES; SOCIAL INTEGRATION; AUSTRALIA; DIFFERENTIALS; TRENDS; DEATHS; HEALTH; WALES AB Objectives. This study examined rural-urban gradients in US suicide mortality and the extent to which such gradients varied across time, sex, and age. Methods. Using a 10-category rural-urban continuum measure and 1970-1997 county mortality data, we estimated rural-urban differentials in suicide mortality over time by multiple regression and Poisson regression models. Results. Significant rural-urban gradients in age-adjusted male suicide mortality were found in each time period, indicating rising suicide rates with increasing levels of rurality. The gradient increased consistently, suggesting widening rural-urban differentials in male suicides over time. When controlled for geographic variation in divorce rate and ethnic composition, rural men, in each age cohort, had about twice the suicide rate of their most urban counterparts. Observed rural-urban differentials for women diminished overtime. In 1995 to 1997, the adjusted suicide rates for young and working-age women were 85% and 22% higher, respectively, in rural than in the most urban areas. Conclusions. The slope of the relationship between rural-urban continuum and suicide mortality varied substantially by time, sex, and age. Widening rural-urban disparities in suicide may reflect differential changes over time in key social integration indicators. C1 NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Anticanc Council Victoria, Canc Control Res Inst, VicHlth Ctr Tobacco Control, Carlton, Vic, Australia. RP Singh, GK (reprint author), NCI, Div Canc Control & Populat Sci, NIH, 6116 Execut Blvd,Suite 504,MSC 8316, Bethesda, MD 20892 USA. NR 31 TC 136 Z9 139 U1 3 U2 10 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 JUL PY 2002 VL 92 IS 7 BP 1161 EP 1167 DI 10.2105/AJPH.92.7.1161 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 568AZ UT WOS:000176521400036 PM 12084702 ER PT J AU Hoffmann, SC Stanley, EM Cox, ED DiMercurio, BS Koziol, DE Harlan, DM Kirk, AD Blair, PJ AF Hoffmann, SC Stanley, EM Cox, ED DiMercurio, BS Koziol, DE Harlan, DM Kirk, AD Blair, PJ TI Ethnicity greatly influences cytokine gene polymorphism distribution SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE allotransplantation; cytokines; polymorphisms renal ID KIDNEY-TRANSPLANT RECIPIENTS; RENAL-ALLOGRAFT SURVIVAL; INTERLEUKIN-10 GENE; AFRICAN-AMERICANS; INTERFERON-GAMMA; REJECTION; ASSOCIATION; EXPRESSION; BLACKS; IMMUNOSUPPRESSION AB Polymorphisms in the regulatory regions of cytokine genes are associated with high and low cytokine production and may modulate the magnitude of alloimmune responses following transplantation. Ethnicity influences allograft half-life and the incidence of acute and chronic rejection. We have questioned whether ethnic-based differences in renal allograft survival could be due in part to inheritance of cytokine polymorphisms. To address that question, we studied the inheritance patterns for polymorphisms in several cytokine genes (IL-2, IL-6, IL-10, TNF-alpha, TGF-beta, and IFN-gamma) within an ethnically diverse study population comprised of 216 Whites, 58 Blacks, 25 Hispanics, and 31 Asians. Polymorphisms were determined by allele-specific polymerase chain reaction and restriction fragment length analysis. We found striking differences in the distribution of cytokine polymorphisms among ethnic populations. Specifically, significant differences existed between Blacks and both Whites and Asians in the distribution of the polymorphic alleles for IL-2. Blacks, Hispanics and Asians demonstrated marked differences in the inheritance of IL-6 alleles and IL-10 genotypes that result in high expression when compared with Whites. Those of Asian descent exhibited an increase in IFN-gamma genotypes that result in low expression as compared to Whites. In contrast, we did not find significant ethnic-based differences in the inheritance of polymorphic alleles for TNF-a. Our results show that the inheritance of certain cytokine gene polymorphisms is strongly associated with ethnicity. These differences may contribute to the apparent influence of ethnicity on allograft outcome. C1 USN, Med Res Ctr, NIDDKD, Bethesda, MD 20889 USA. Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20889 USA. RP Blair, PJ (reprint author), USN, Med Res Ctr, NIDDKD, Bethesda, MD 20889 USA. RI Kirk, Allan/B-6905-2012 NR 47 TC 207 Z9 222 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUL PY 2002 VL 2 IS 6 BP 560 EP 567 DI 10.1034/j.1600-6143.2002.20611.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 568QF UT WOS:000176553200011 PM 12118901 ER PT J AU Obiakor, H Sehgal, D Dasso, JF Bonner, RF Malekafzali, A Mage, RG AF Obiakor, H Sehgal, D Dasso, JF Bonner, RF Malekafzali, A Mage, RG TI A comparison of hydraulic and laser capture microdissection methods for collection of single B cells, PCR, and sequencing of antibody VDJ SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE B cells; single-cell PCR; immunoglobulin VDJ; microdissection ID POLYMERASE-CHAIN-REACTION; SPLENIC GERMINAL-CENTERS; GENE CONVERSION; V-H; T-CELLS; HYPERMUTATION; DIVERSIFICATION; REPERTOIRE; RABBITS AB During the development of B lymphocytes, a series of gene rearrangements assemble the sequences that encode immunoglobulin heavy and light chains (VDJ). Earlier studies of VDJ sequence diversification during expansion of cells in splenic or appendix germinal centers used hydraulic micromanipulation (HM) to collect single B cells for PCR amplification of rearranged antibody heavy and light chain genes. PCR products were directly sequenced without a cloning step. Hydraulic micromanipulation is a very tedious method. Once capability to collect single cells by laser capture microdissection (LCM) was developed, we modified previous tissue staining and fixation methods so that we could collect cells from a given stained tissue section by HM and LCM and directly compare our success rates using these two methods. Cells were alkaline lysed and after two rounds of nested PCR products were recovered and directly sequenced. Because each rearrangement of genomic DNA that occurs to form the immunoglobulin heavy-chain-encoding sequence in developing B cells is unique, this system allowed us to verify our success rate in recovering single lymphocytes from tissue sections and amplifying a single allele. The methods developed have now made LCM an efficient alternative to HM for the collection of single B cells. (C) 2002 Elsevier Science (USA). C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11 N 31,10 Ctr Dr,MSC-1892, Bethesda, MD 20892 USA. RI Bonner, Robert/C-6783-2015 NR 13 TC 13 Z9 14 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUL 1 PY 2002 VL 306 IS 1 BP 55 EP 62 DI 10.1006/abio.2002.5671 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 568CE UT WOS:000176524200008 PM 12069414 ER PT J AU Chiu, BCH Weisenburger, DD Cantor, KP Zahm, SH Holmes, F Burmeister, LF Blair, A AF Chiu, BCH Weisenburger, DD Cantor, KP Zahm, SH Holmes, F Burmeister, LF Blair, A TI Alcohol consumption, family history of hematolymphoproliferative cancer, and the risk of non-Hodgkin's lymphoma in men SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE alcohol; family history; lymphoma; non-Hodgkin's lymphoma ID LEUKEMIA; DISEASE; MALIGNANCIES; AGGREGATION; TOBACCO AB PURPOSE: To investigate the association between alcohol consumption and the risk of non-Hodgkin's lymphoma (NHL) and to examine whether the association is modified by a family history of hematolymphoproliferative cancer (HLPC). METHODS: Data on white men from two population-based case-control studies of NHL conducted in Iowa/Minnesota and Kansas were pooled for this analysis. Information on alcohol consumption, family history of HLPC, and other factors was obtained by interviewing 792 cases and 2193 controls or, if deceased, their next-of-kin. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIS). RESULTS: There was no clear association between NHL and the use of alcohol, beer, hard liquor, or wine. The relationship, however, may differ according to a family history of HLPC. Alcohol use was not associated with the risk of NHL in men without a family history of HLPC (ORs = 0.8 and 0.9 for men consuming alcohol less than or equal to median and > median, respectively), the presence of a family history in the absence of alcohol use was associated with a slightly increased risk (OR = 1.4; 95% Cl 0.8-2.5), whereas risks of NHL among men with a positive family history were 2.1 (CI 1.0-4.7) for men consuming alcohol less than or equal to median (13.7 g/day) and 2.8 (1.3-5.9) for men consuming alcohol greater than median. CONCLUSIONS: The present data found no clear association between alcohol consumption and the risk of NHL among men without a family history of HLPC, whereas alcohol intake was associated an elevated risk in men with a positive family history. The finding of effect modification of the alcohol-NHL association by a family history of HLPC is novel and requires confirmation. Ann Epidemiol 2002;12:309-315. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Nebraska, Med Ctr, Dept Prevent & Socirtal Med, Nebraska Med Ctr 984350, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66103 USA. Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA USA. RP Chiu, BCH (reprint author), Univ Nebraska, Med Ctr, Dept Prevent & Socirtal Med, Nebraska Med Ctr 984350, Omaha, NE 68198 USA. RI Zahm, Shelia/B-5025-2015 NR 36 TC 28 Z9 28 U1 0 U2 1 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 JUL PY 2002 VL 12 IS 5 BP 309 EP 315 AR PII S1047-2797(01)00259-9 DI 10.1016/S1047-2797(01)00259-9 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 561ZX UT WOS:000176173900005 PM 12062917 ER PT J AU Zywicke, HA van Gelderen, P Connor, JR Burdo, JR Garrick, MD Dolan, KG Frank, JA Bulte, JWM AF Zywicke, HA van Gelderen, P Connor, JR Burdo, JR Garrick, MD Dolan, KG Frank, JA Bulte, JWM TI Microscopic R2*mapping of reduced brain iron in the belgrade rat SO ANNALS OF NEUROLOGY LA English DT Article ID RESTLESS LEGS SYNDROME; DIFFERENT FIELD STRENGTHS; RETICULOCYTES; TRANSFERRIN; TRANSPORT; FERRITIN; MRI AB R2* mapping has recently been used to detect iron overload in patients with movement disorders. We demonstrate here that this technique can also be used to detect reduced brain iron, as in the case of a missense mutation in the iron-transporting protein divalent metal transporter 1. Surprisingly, we found that the same brain regions are affected (ie, the globus pallidus, substantia nigra, and cerebellar dentate nucleus); this suggests a much more extensive role for these structures in regulating overall brain iron homeostasis. Therefore, for the clinical monitoring of movement disorders for which normal brain iron homeostasis (either overload or reduction) may be implicated, R2* mapping appears to be well-suited. C1 NINCDS, Lab Diagnost Radiol Res, Ctr Clin, NIH, Bethesda, MD 20892 USA. NINCDS, Lab Adv Magnet Resonance Imaging, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Neurosci & Anat, Hershey, PA USA. SUNY Buffalo, Dept Biochem, Buffalo, NY 14214 USA. RP Bulte, JWM (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol, 217 Traylor Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 20 TC 19 Z9 22 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 2002 VL 52 IS 1 BP 102 EP 105 DI 10.1002/ana.10216 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 566WT UT WOS:000176451800017 PM 12112055 ER PT J AU Aune, GJ Furuta, T Pommier, Y AF Aune, GJ Furuta, T Pommier, Y TI Ecteinascidin 743: a novel anticancer drug with a unique mechanism of action SO ANTI-CANCER DRUGS LA English DT Review DE cancer chemotherapy; DNA alkylation; DNA binding; DNA repair; minor groove binder; transcription ID NUCLEOTIDE-EXCISION-REPAIR; MINOR-GROOVE; TOPOISOMERASE-I; CELL-LINES; DEOXYRIBONUCLEIC-ACID; CARIBBEAN TUNICATE; DNA INTERACTIONS; SOLID TUMORS; GUANINE N2; PHASE-I AB Ecteinascidin 743 (Et743) is an interesting compound in phase II/III clinical trials. Its chemistry is complex, its mechanism of action is original and it is active in human cancers, such as sarcomas refractory to conventional chemotherapy. The present review describes the discovery of the drug, its specific interactions with DNA and its reversible alkylation mechanism with guanine N-2 in the DNA minor groove. Et743 is a selective transcription inhibitor, which has the unique characteristic of poisoning transcription-coupled nucleotide excision repair. Understanding the molecular pharmacology of Et743 should help in deciding which patients should receive Et743 treatments and which agents should be most useful in association. [(C) 2002 Lippincott Williams Wilkins]. C1 NCI, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Ctr Canc Res, Mol Pharmacol Lab, bldg 37,Rm 5068, Bethesda, MD 20892 USA. RI Aune, Gregory/I-5895-2015 OI Aune, Gregory/0000-0002-2750-6461 NR 56 TC 95 Z9 98 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JUL PY 2002 VL 13 IS 6 BP 545 EP 555 DI 10.1097/00001813-200207000-00001 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 583DE UT WOS:000177390000001 PM 12172500 ER PT J AU Gil-Lamaignere, C Roilides, E Mosquera, J Maloukou, A Walsh, TJ AF Gil-Lamaignere, C Roilides, E Mosquera, J Maloukou, A Walsh, TJ TI Antifungal Triazoles and polymorphonuclear leukocytes synergize to cause increased hyphal damage to Scedosporium prolificans and Scedosporium apiospermum SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID COLONY-STIMULATING FACTOR; ASPERGILLUS-FUMIGATUS; INFLATUM INFECTION; AMPHOTERICIN-B; PSEUDALLESCHERIA-BOYDII; HUMAN-NEUTROPHILS; CANDIDA-ALBICANS; ITRACONAZOLE; VORICONAZOLE; INVITRO AB Scedosporium prolificans and Scedosporium apiospermum (Pseudallescheria boydii) cause pulmonary and disseminated infections refractory to most currently used antifungal agents in immunocompromised patients. We therefore investigated the potential antifungal activities of the triazoles itraconazole (ITC), voriconazole (VRC), and posaconazole (PSC) in combination with human polymorphonuclear leukocytes (PMNs) against the hyphae of these fungal pathogens. A colorimetric assay with (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]2H-tetrazolium-5-carboxanilide) sodium salt was used for the measurement of hyphal damage as an indicator of antifungal activity. We found that the newer triazoles VRC and PSC displayed synergistic effects with PMNs against S. prolificans hyphae after 24 h (P < 0.05), whereas the effect of ITC in combination with PMNs was additive (P < 0.01). All three triazoles displayed additive antifungal activities in combination with PMNs against S. apiospermum hyphae (P < 0.05). The synergistic or additive effects that these triazoles exhibited, combined with the antifungal activities of human PMNs, may have important therapeutic implications for the management of infections due to S. prolificans and S. apiospermum. C1 NCI, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. Aristotle Univ Thessaloniki, Hippokration Hosp, Pediat Dept 3, GR-54642 Thessaloniki, Greece. Univ Manchester, Hope Hosp, Dept Med, Salford M6 8HD, Lancs, England. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, NIH, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. RI Gil-Lamaignere, Cristina/A-3866-2013 NR 38 TC 38 Z9 39 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2002 VL 46 IS 7 BP 2234 EP 2237 DI 10.1128/AAC.46.7.2234-2237.2002 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 565ND UT WOS:000176375600024 PM 12069979 ER PT J AU Zalah, L Huleihel, M Manor, E Konson, A Ford, H Marquez, VE Johns, DG Agbaria, R AF Zalah, L Huleihel, M Manor, E Konson, A Ford, H Marquez, VE Johns, DG Agbaria, R TI Metabolic pathways of N-methanocarbathymidine, a novel antiviral agent, in native and herpes simplex virus type 1 infected Vero cells SO ANTIVIRAL RESEARCH LA English DT Article DE herpes simplex virus; herpes simplex thymidine kinase; N-methanocarbathymidine; ganciclovir; phosphorylation; plaque forming unit ID THYMIDINE KINASE GENE; DNA-POLYMERASE; 9-(1,3-DIHYDROXY-2-PROPOXYMETHYL)GUANINE TRIPHOSPHATE; CYTOSTATIC ACTIVITY; NUCLEOSIDE ANALOGS; IN-VITRO; INHIBITION; PHOSPHORYLATION; GANCICLOVIR; ACYCLOVIR AB N-Methanocarbathymidine ((N)-MCT), a thymidine analog incorporating a pseudosugar with a fixed Northern conformation, exhibits potent antiherpetic activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). This study contrasts the metabolic pathway of (N)-MCT and the well-known antiherpetic agent ganciclovir (GCV) in HSV-1-infected and uninfected Vero cells. Treatment of HSV-1 infected Vero cells immediately after viral infection with (N)-MCT profoundly inhibited the development of HSV-1 infection. Using standard plaque reduction assay to measure viral infection, (N)-MCT showed a potency greater than that of ganciclovir (GCV), the IC(50)s were 0.02 and 0.25 muM for (N)-MCT and GCV, respectively. (N)-MCT showed no cytotoxic effect on uninfected Vero cells (CC50 > 100 muM). Dose and time dependence studies showed high levels of (N)-MCT-triphosphate ((N)-MCT-TP), and GCV-triphosphate (GCV-TP) in HSV-1-infected cells incubated with (N)-MCT or GCV, respectively. In contrast, uninfected cells incubated with (N)-MCT showed elevated levels of (N)-MCT-monophosphate only, while low levels of mono, di- and triphosphates of GCV were found following incubation with GCV. Although the accumulation rate of (N)-MCT and GCV phosphates in HSV-1-infected cells were similar, the decay rate of (N)-MCT-TP was slower than that of GCV-TP. These results suggest that: (1) the antiviral activity of (N)-MCT against herpes viruses is mediated through its triphosphate metabolite; (2) in contrast to GCV, the diphosphorylation of (N)-MCT in HSV-1- infected cells is the rate limiting step; (3) (N)-MCT-TP accumulates rapidly and has a long half-life in HSV-1-infected cells; and (4) HSV-tk catalyzed the mono, and diphosphorylation of (N)-MCT while monophosphorylating GCV only. These results provide a biochemical rational for the highly selective and effective inhibition of HSV-1 by (N)-MCT. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Inst Appl Biosci, IL-84105 Beer Sheva, Israel. NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Agbaria, R (reprint author), Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel. RI HULEIHEL, MAHMOUD/F-1837-2012 NR 36 TC 34 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUL PY 2002 VL 55 IS 1 BP 63 EP 75 AR PII S0166-3542(02)00010-4 DI 10.1016/S0166-3542(02)00010-4 PG 13 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 572GV UT WOS:000176766500006 PM 12076752 ER PT J AU Morrey, JD Smee, DF Sidwell, RW Tseng, C AF Morrey, JD Smee, DF Sidwell, RW Tseng, C TI Identification of active antiviral compounds against a New York isolate of West Nile virus SO ANTIVIRAL RESEARCH LA English DT Article DE West Nile virus; ribavirin; antiviral; flavivirus; 6-azauridine ID ARGENTINE HEMORRHAGIC-FEVER; RIBAVIRIN; INHIBITION; RNA; REPLICATION; NUCLEOSIDE; CYTIDINE; INVITRO; ANALOG; HERPES AB The recent West Nile virus (WNV) outbreak in the United States has increased the need to identify effective therapies for this disease. A chemotherapeutic approach may be a reasonable strategy because the virus infection is typically not chronic and antiviral drugs have been identified to be effective in vitro against other flaviviruses. A panel of 34 substances was tested against infection of a recent New York isolate of WNV in Vero cells and active compounds were also evaluated in MA-104 cells. Some of these compounds were also evaluated in Vero cells against the 1937 Uganda isolate of the WNV. Six compounds were identified to be effective against virus-induced CPE with 50% effective concentrations (EC50) less than 10 mug/ml and with a selectivity index (SI) of greater than 10. Known inhibitors of orotidine monophosphate decarboxylase and inosine monophosphate dehydrogenase involved in the synthesis of GTP, UTP, and TTP were most effective. The compounds 6-azauridine, 6-azauridine triacetate, cyclopententyleytosine (CPE-C), mycophenolic acid and pyrazofurin appeared to have the greatest activities against the New York isolate, followed by 2-thio-6-azauridine. Anti-WNV activity of 6-azauridine was confirmed by virus yield reduction assay when the assay was performed 2 days after initial infection in Vero cells. The neutral red assay mean EC50 of ribavirin was only 106 mug/ml with a mean SI of 9.4 against the New York isolate and only slightly more effective against the Uganda isolate. There were some differences in the drug sensitivities of the New York and Uganda isolates, but when comparisons were made by categorizing drugs according to their modes of action, similarities of activities between the two isolates were identified. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Utah State Univ, Dept Anim Dairy & Vet Sci, Inst Antiviral Res, Logan, UT 84322 USA. NIAID, Virol Branch, NIH, Bethesda, MD 20892 USA. RP Morrey, JD (reprint author), Utah State Univ, Dept Anim Dairy & Vet Sci, Inst Antiviral Res, Logan, UT 84322 USA. FU NIAID NIH HHS [N01-AI65291] NR 37 TC 113 Z9 119 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUL PY 2002 VL 55 IS 1 BP 107 EP 116 AR PII S0166-3542(02)00013-X DI 10.1016/S0166-3542(02)00013-X PG 10 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 572GV UT WOS:000176766500009 PM 12076755 ER PT J AU Wieking, K Knockaert, M Leost, M Zaharevitz, DW Meijer, L Kunick, C AF Wieking, K Knockaert, M Leost, M Zaharevitz, DW Meijer, L Kunick, C TI Synthesis of paullones with aminoalkyl side chains SO ARCHIV DER PHARMAZIE LA English DT Article DE antitumor activity; benzazepinones; cyclin-dependent kinases; inhibitors; paullones ID CYCLIN-DEPENDENT KINASES; TUMOR-CELL-LINES; INHIBITORS; TARGETS; CANCER; SCREEN AB Paullones 3 and 4 with aminoalkyl side chains in 2- or 3-position were synthesized as derivatives of kenpaullone 1. Both 3 and 4 showed the characteristic CDK1-inhibitory activity of the paullones and a modest antiproliferative activity on cultured human tumor cell lines. Hence, 3 and 4 appear to be suitable tools for affinity studies directed to find additional intracellular paullone targets. C1 Univ Hamburg, Inst Pharm, D-20146 Hamburg, Germany. CNRS, Biol Stn, F-29682 Roscoff, France. NCI, Rockville, MD 20893 USA. RP Kunick, C (reprint author), Univ Hamburg, Inst Pharm, Bundesstr 45, D-20146 Hamburg, Germany. NR 17 TC 19 Z9 20 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0365-6233 J9 ARCH PHARM JI Arch. Pharm. PD JUL PY 2002 VL 335 IS 7 BP 311 EP 317 DI 10.1002/1521-4184(200209)335:7<311::AID-ARDP311>3.0.CO;2-F PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 596BR UT WOS:000178176500001 PM 12207280 ER PT J AU Rapoport, SI Bosetti, F AF Rapoport, SI Bosetti, F TI Do lithium and anticonvulsants target the brain arachidonic acid cascade in bipolar disorder? SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CYTOSOLIC PHOSPHOLIPASE A(2); RAT-BRAIN; SIGNAL-TRANSDUCTION; FATTY-ACIDS; DOCOSAHEXAENOIC ACID; TREATMENT DECREASES; CEREBRAL-CORTEX; NERVOUS-SYSTEM; CELL-LINE AB Background: Lithium and certain anticonvulsants, including carbamazepine and valproic acid, are effective antimanic drugs for treating bipolar disorder, but their mechanisms of action remain uncertain. Experimental Observations: Feeding rats lithium chloride for 6 weeks, to produce a brain lithium concentration of 0.7 mM, reduced arachidonic acid turnover within brain phospholipids by 75%. The effect was highly specific, as turnover rates of docosahexaenoic acid and palmitic acid were unaffected. Arachidonate turnover in rat brain also was reduced by long-term valproic acid administration. Lithium's reduction of arachidonate turnover corresponded to its down-regulating gene expression and enzyme activity of cytosolic phospholipase A(2) an enzyme that selectively liberates arachidonic but not docosahexaenoic acid from phospholipids. Lithium also reduced the brain protein level and activity of cyclooxygenase 2, as well as the brain concentration of prostaglandin E-2, an arachidonate metabolite produced via cyclooxygenase 2. Conclusions: These results give rise to the hypothesis that lithium and antimanic anticonvulsants act by targeting parts of the "arachidonic acid cascade," which may be functionally hyperactive in mania. Thus, drugs that target enzyme in the cascade, such as cyclooxygenase 2 inhibitors, might be candidate treatments for mania. Also, in view of competition between arachidonic and docosahexaenoic acids in a number Of functional processes, docosahexaenoic acid or its precursors would be expected to be therapeutic. Neither of these predictions is evident from other current hypotheses for the antimanic action of lithium and anticonvulsant drugs. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 10,Room 6N202, Bethesda, MD 20892 USA. NR 88 TC 132 Z9 136 U1 0 U2 2 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 JUL PY 2002 VL 59 IS 7 BP 592 EP 596 DI 10.1001/archpsyc.59.7.592 PG 5 WC Psychiatry SC Psychiatry GA 571KG UT WOS:000176716100001 PM 12090811 ER PT J AU Neumeister, A Konstantinidis, A Stastny, J Schwarz, MJ Vitouch, O Willeit, M Praschak-Rieder, N Zach, J de Zwaan, M Bondy, B Ackenheil, M Kasper, S AF Neumeister, A Konstantinidis, A Stastny, J Schwarz, MJ Vitouch, O Willeit, M Praschak-Rieder, N Zach, J de Zwaan, M Bondy, B Ackenheil, M Kasper, S TI Association between serotonin transporter gene promoter polymorphism (5HTTLPR) and behavioral responses to tryptophan depletion in healthy women with and without family history of depression SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 03-05, 2001 CL NEW ORLEANS, LOUISIANA SP Soc Biolog Psychiatry ID TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE; ONSET ALZHEIMERS-DISEASE; MAJOR AFFECTIVE-DISORDER; ANXIETY-RELATED TRAITS; NEUTRAL AMINO-ACIDS; FACE-TO-FACE; FUNCTIONAL POLYMORPHISM; INTRAVENOUS TRYPTOPHAN; DOPAMINE-D4 RECEPTOR; PLASMA TRYPTOPHAN AB Background: Evidence suggests that serotonin transporter gene promoter polymorphism (5HTTLPR)-dependent low transcriptional activity of the human serotonin transporter gene may be a genetic susceptibility factor for depression. We studied the behavioral responses to tryptophan depletion (TD) in healthy women with and without a first-degree family history of depression and examined the relationship to 5HTTLPR alleles. Methods: Twenty-four healthy women with a negative family history of depression and 21 women with a positive family history of depression were genotyped for the polymorphism of the 5HTTLPR and then entered a double-blind, placebo-con trolled, randomized crossover TD study. The effects of these interventions were assessed with measures of depression and plasma tryptophan levels. Results: The TD induced a robust decrease of plasma tryptophan levels in all women irrespective of family history of depression or 5HTTLPR genotypes. The s/s genotype of the 5HTTLPR was associated with an increased risk of developing depressive symptoms during TD irrespective of family history. In contrast, individuals with the l/l genotype did not develop depressive symptoms, irrespective of family history. Finally, s/l subjects without family history showed a mood response that was intermedia e between the s/s and l/l subjects, while s/l subjects with a family history of depression showed the same depressiogenic effect of TD as seen in the s/s subjects. Conclusions: The results of the present study suggest that the s-allele of the 5HTTLPR and a positive family history of depression are additive risk factors for the development of depression during TD. C1 NIMH, NIH, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. Univ Vienna, Dept Gen Psychiat, Vienna, Austria. Univ Munich, Hosp Psychiat, Dept Neurochem, Munich, Germany. Max Planck Inst Human Dev, Berlin, Germany. RP Neumeister, A (reprint author), NIMH, NIH, Mood & Anxiety Disorders Res Program, North Dr,Bldg 15K,Room 200, Bethesda, MD 20892 USA. NR 79 TC 159 Z9 161 U1 6 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 2002 VL 59 IS 7 BP 613 EP 620 DI 10.1001/archpsyc.59.7.613 PG 8 WC Psychiatry SC Psychiatry GA 571KG UT WOS:000176716100004 PM 12090814 ER PT J AU Kupfer, DJ Hyman, SE Schatzberg, AF Pincus, HA Reynolds, CF AF Kupfer, DJ Hyman, SE Schatzberg, AF Pincus, HA Reynolds, CF TI Recruiting and retaining future generations of physician scientists in mental health SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 09-14, 2000 CL SAN JUAN, PUERTO RICO SP Amer Coll Neuropsychopharmacol ID CLINICAL-RESEARCH; PSYCHIATRY C1 Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. NIMH, Bethesda, MD 20892 USA. RP Kupfer, DJ (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [R25 MH-60473, MH-52247, MH-30915] NR 9 TC 60 Z9 62 U1 1 U2 4 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 JUL PY 2002 VL 59 IS 7 BP 657 EP 660 DI 10.1001/archpsyc.59.7.657 PG 4 WC Psychiatry SC Psychiatry GA 571KG UT WOS:000176716100009 PM 12090819 ER PT J AU Nadareishvili, ZG Rothwell, PM Beletsky, V Pagniello, A Norris, JW AF Nadareishvili, ZG Rothwell, PM Beletsky, V Pagniello, A Norris, JW TI Long-term risk of stroke and other vascular events in patients with asymptomatic carotid artery stenosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID NATURAL-HISTORY; ENDARTERECTOMY; DISEASE; MODERATE; TORONTO; COSTS AB Context: The annual risk of ischemic stroke in patients with asymptomatic carotid artery stenosis is about 2% during the short-term (2-3 years), but the long-term risks of stroke and other vascular events are unknown, although they may affect surgical decision making. Objective: To evaluate the long-term risk of stroke and other vascular events in patients with asymptomatic carotid artery stenosis. Design: Cohort study with a median follow-up of 10 years (range, 5-18 years). Setting: The teaching hospital of the University of Toronto, Toronto, Ontario. Patients: From the initial cohort of 500 patients, 106 patients with asymptomatic carotid artery stenosis were selected because they had completed at least 5 years of follow-up. Main Outcome Measures: Ipsilateral stroke, myocardial infarction, and nonstroke vascular death. Results: The 10- and 15-year actuarial risks of ipsilateral stroke were 5.7% (95% confidence interval [CI], 0%-12%) and 8.7% (95% CI, 1%-17%), respectively, in patients with 0% to 49% internal carotid artery stenosis, and 9.3% (95% CI, 1%-18%) and 16.6% (95% CI, 1%-32%) in patients with 50% to 99% internal carotid artery stenosis. The 10- and 15-year risks of myocardial infarction and nonstroke vascular death were 10.1% (95% CI, 4%-16%) and 24.0% (95% CI, 14%-34%). Age (P=.02), diabetes mellitus (P=.02), and internal carotid artery stenosis of 50% or more (P=.04) were predictive of increased risks of myocardial infarction and nonstroke vascular death. Internal carotid artery stenosis of 50% or more did predict the risk of ipsilateral stroke (P=.003) when all 181 asymptomatic carotid arteries were included. Conclusions: The annual stroke risk in patients with asymptornatic carotid artery stenosis was low and remained stable during long-term follow-up. Any benefit from carotid surgery is therefore unlikely to increase significantly with long-term follow-up. The high long-term risks of myocardial infarction and nonstroke vascular death suggest that prevention strategies should concentrate on coronary risk more than stroke risk. C1 Univ Toronto, Sunnybrook & Womens Coll, Hlth Sci Ctr, Stroke Res Unit, Toronto, ON, Canada. Radcliffe Infirm, Dept Clin Neurol, Stroke Prevent Res Unit, Oxford OX2 6HE, England. RP Nadareishvili, ZG (reprint author), NINDS, Stroke Branch, NIH, 36 Convent Dr,Bldg 36,4A03, Bethesda, MD 20892 USA. NR 21 TC 61 Z9 69 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 2002 VL 59 IS 7 BP 1162 EP 1166 DI 10.1001/archneur.59.7.1162 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 571JP UT WOS:000176714500013 PM 12117365 ER PT J AU Balsamo, LM Xu, B Grandin, CB Petrella, JR Braniecki, SH Elliott, TK Gaillard, WD AF Balsamo, LM Xu, B Grandin, CB Petrella, JR Braniecki, SH Elliott, TK Gaillard, WD TI A functional magnetic resonance Imaging study of left hemisphere language dominance in children SO ARCHIVES OF NEUROLOGY LA English DT Article ID SENTENCE COMPREHENSION; CORTICAL LOCALIZATION; PREFRONTAL CORTEX; BRAIN ACTIVATION; SPEECH STIMULI; WADA TEST; MRI; FMRI; LATERALIZATION; APHASIA AB Background: Functional magnetic resonance imaging is a noninvasive method of assessing language dominance in a pediatric population. Objective: To determine the pattern of receptive language lateralization in healthy children. Design: We used functional magnetic resonance imaging to assess an auditory language task in 11 children (7 girls, 4 boys; mean age, 8.5 years). Participants alternately rested and listened to descriptors of nouns presented auditorily, naming the object described silently. Asymmetry indices ([left - right)/(left + right)]) were calculated for a priori-determined regions of interest. Results: The results showed strong activation bilaterally, with greater activation on the left in the superior and middle temporal gyri. Other areas of activation included the cuneus, the left inferior temporal gyrus, the prefrontal area, and the left fusiform and lingual gyri. Regions of interest analysis of individual scans showed additional activation in the left frontal lobe. Asymmetry indices showed strong left lateralization of the inferior frontal gyrus, middle frontal gyrus, and the Wernicke region. Conclusions: Hemispheric lateralization was clearly demonstrated in 8 children. As in adults, left hemisphere lateralization of receptive language is present at age 8 years. C1 Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. NINDS, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. American Univ, Washington, DC 20016 USA. RP Gaillard, WD (reprint author), Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave NW, Washington, DC 20010 USA. FU NINDS NIH HHS [K08-NS1663] NR 59 TC 73 Z9 76 U1 9 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 2002 VL 59 IS 7 BP 1168 EP 1174 DI 10.1001/archneur.59.7.1168 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 571JP UT WOS:000176714500014 PM 12117366 ER PT J AU Enzer, I Dunn, G Jacobsson, L Bennett, PH Knowler, WC Silman, A AF Enzer, I Dunn, G Jacobsson, L Bennett, PH Knowler, WC Silman, A TI An epidemiologic study of trends in prevalence of rheumatoid factor seropositivity in Pima Indians - Evidence of a decline due to both secular and birth-cohort influences SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ARTHRITIS; PROGRESSION; PERIOD AB Objective. Previous population studies have suggested that both rheumatoid factor (RF) production and rheumatoid arthritis (RA) may be declining in occurrence, and. both secular and birth-cohort influences have been implicated. Since Pima Indians have a very high incidence of RA and also have shown recent evidence or a decline in RA, this study evaluated the relative contributions of age, secular, and birth-cohort influences on RF seropositivity in the Pima Indian population. Methods. RF data, as assayed by both the bentonite flocculation test (BFT) and the sheep cell agglutination test (SCAT), were available on 5,345 Pima Indians born between 1886 and 1975, who were surveyed at biennial intervals between 1966 and 1995. An age-period-cohort analysis was conducted using data on 18,295 examinations undertaken during the period of study. Results. There was a decline in the proportion of positive test results for RF (titer greater than or equal to1:32) by both BFT and SCAT, in both male and female subjects from 1966-1975 to the later decades of the study (1976-1985 and 1986-1995). Across all periods, by both assays, the crude proportion of positive titers increased with increasing age of the subjects. There was a very clear birth-cohort effect: the highest likelihood of seropositivity was in those individuals born around the end of the nineteenth century, with continuing decline in seropositivity up to the most recent birth cohort. A logistic regression analysis, adjusting for Pima heritage and sex, demonstrated a substantially greater influence of birth cohort than of calendar year on the frequency of RF positivity. Conclusion. In the Pima Indian population, environmental influences in early life are important predictors of the lifelong likelihood of RF positivity. This may have implications for understanding the epidemiology and etiology of RA. C1 Univ Manchester, Sch Med, ARC Epidemiol Res Unit, Manchester M13 9PT, Lancs, England. Malmo Univ Hosp, Malmo, Sweden. NIH, Phoenix, AZ USA. RP Silman, A (reprint author), Univ Manchester, Sch Med, ARC Epidemiol Res Unit, Stopford Bldg, Manchester M13 9PT, Lancs, England. NR 23 TC 21 Z9 22 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 JUL PY 2002 VL 46 IS 7 BP 1729 EP 1734 DI 10.1002/art.10360 PG 6 WC Rheumatology SC Rheumatology GA 572KK UT WOS:000176773200005 PM 12124855 ER PT J AU Tao, XL Younger, J Fan, FZ Wang, B Lipsky, PE AF Tao, XL Younger, J Fan, FZ Wang, B Lipsky, PE TI Benefit of an extract of Tripterygium wilfordii Hook F in patients with rheumatoid arthritis - A double-blind, placebo-controlled study SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ETHYL-ACETATE EXTRACT; CHINESE HERBAL REMEDY; T2 AB Objective. To examine the safety and efficacy of an extract of Tripterygium wilfordii Hook F (TWHF) in the treatment of patients with rheumatoid arthritis (RA). Methods. An ethanol/ethyl acetate extract from the roots or TWHF was prepared and used in a prospective, double-blind, placebo-controlled study in patients with longstanding RA in whom conventional therapy had failed. Patients were randomly assigned to receive either placebo or low-dose (180 mg/day) or high-dose (360 mg/day) extract for 20 weeks, followed by an open-label extension period. Clinical responses were defined as 20% improvement in disease activity according to the American College of Rheumatology criteria. Side effects were actively queried and recorded at each visit. Results. A total of 35 patients were enrolled in the trial; 21 patients completed the 20-week study. One patient from each group withdrew because of side effects. Twelve, 10, and 10 patients in the placebo, low-dose, and high-dose groups, respectively, completed at least 4 weeks of treatment. Of these patients, 8 and 4 in the high-dose and low-dose groups, but none in the placebo group, met criteria for clinical response. Four, 4, and 7 patients in the placebo, low-dose, and high-dose groups, respectively, were enrolled in the open-label extension; of these, 2, 4, and 5 patients, respectively, met criteria for clinical response. The most common side effect was diarrhea, which caused I patient in the high-dose group to withdraw from the trial. No patients withdrew because of adverse events during the open-label extension. Conclusion. The ethanol/ethyl acetate extract of TWHF shows therapeutic benefit in patients with treatment-refractory RA. At therapeutic dosages, the TWHF extract was well tolerated by most patients in this study. C1 NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Harold C Simmons Arthrit Ctr, Dallas, TX USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMSD, Autoimmun Branch, NIH, Bldg 10,Room 9N228,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 32 TC 180 Z9 195 U1 0 U2 11 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 JUL PY 2002 VL 46 IS 7 BP 1735 EP 1743 DI 10.1002/art.10411 PG 9 WC Rheumatology SC Rheumatology GA 572KK UT WOS:000176773200006 PM 12124856 ER PT J AU Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS AF Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS TI Hormonal and reproductive risk factors for development of systemic lupus erythematosus - Results of a population-based, case-control study SO ARTHRITIS AND RHEUMATISM LA English DT Article ID PREMATURE OVARIAN FAILURE; AUTOIMMUNE-DISEASE; MATERNAL BLOOD; BREAST-CANCER; ORAL-CONTRACEPTIVES; GENDER DIFFERENCES; REVISED CRITERIA; SERUM PROLACTIN; INTERVIEW DATA; HYPERPROLACTINEMIA AB Objective. Estrogen and prolactin may accelerate the progression of murine systemic lupus erythematosus (SLE). In humans, 85% of lupus patients are women, which also suggests the importance of hormonal factors in disease pathogenesis. The purpose of this study was to examine hormonal and reproductive risk factors for lupus among women. Methods. This population-based, case-control study included 240 female SLE patients diagnosed between January 1, 1995 and July 31, 1999 who fulfilled the American College of Rheumatology classification criteria. Female controls (n=321) were identified through driver's license records. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) as measures of association, adjusting for age, state, race, and education. Analyses were limited to exposures before diagnosis. Results. Breast-feeding was associated with a decreased risk of developing SLE (OR 0.6, 95% CI 0.4-0.9), with a statistically significant trend for number of babies breast-fed and total weeks of breast-feeding. There were no associations with number of pregnancies or live births. Natural menopause occurred earlier in women with subsequent development of SLE compared with controls (P<0.001). There was little association between SLE and current use or duration of use of hormone replacement therapy or oral contraceptives, and no association with previous use of fertility drugs. Conclusion. We found little evidence that estrogen- or prolactin-related exposures are associated with an increased risk of lupus. The reduced risk observed among women who had breast-fed one or more babies should be examined in other studies. Early natural menopause, rather than decreasing risk of SLE because of reduced estrogen exposure, may be a marker of susceptibility to development of SLE. C1 NIEHS, Epidemiol Branch A3 05, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Chapel Hill, NC USA. E Carolina Univ, Sch Med, Greenville, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch A3 05, POB 12233, Res Triangle Pk, NC 27709 USA. NR 54 TC 94 Z9 102 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 2002 VL 46 IS 7 BP 1830 EP 1839 DI 10.1002/art.10365 PG 10 WC Rheumatology SC Rheumatology GA 572KK UT WOS:000176773200017 PM 12124867 ER PT J AU Parks, CG Cooper, GS Nylander-French, LA Sanderson, WT Dement, JM Cohen, PL Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS Hoppin, JA Savitz, DA AF Parks, CG Cooper, GS Nylander-French, LA Sanderson, WT Dement, JM Cohen, PL Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS Hoppin, JA Savitz, DA TI Occupational exposure to crystalline silica and risk of systemic lupus erythematosus - A population-based, case-control study in the southeastern United States SO ARTHRITIS AND RHEUMATISM LA English DT Article ID TOBACCO GLYCOPROTEIN TGP; STAGE RENAL-DISEASE; INDUCED APOPTOSIS; REVISED CRITERIA; IN-VIVO; CANCER; DUST; SCLERODERMA; SMOKING; WORKERS AB Objective. Crystalline silica may act as an immune adjuvant to increase inflammation and antibody production, and findings of occupational cohort studies suggest that silica exposure may be a risk factor for systemic lupus erythematosus (SLE). We undertook this population-based study to examine the association between occupational silica exposure and SLE in the southeastern US. Methods. SLE patients (n = 265; diagnosed between January 1, 1995 and July 31, 1999) were recruited from 4 university rheumatology practices and 30 community-based rheumatologists in 60 contiguous counties. Controls (n = 355), frequency-matched to patients by age, sex, and state of residence, were randomly selected from driver's license registries. The mean age of the patients at diagnosis was 39 years; 91% were women and 60% were African American. Detailed occupational and farming histories were collected by in-person interviews. Silica exposure was determined through blinded assessment of job histories by 3 industrial hygienists, and potential medium- or high-level exposures were confirmed through followup telephone interviews. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression. Results. More patients (19%) than controls (8%) had a history of medium- or high-level silica exposure from farming or trades. We observed an association between silica and SLE (medium exposure OR 2.1 [95% CI 1.1-4.0], high exposure OR 4.6 [95% CI 1.4-15.4]) that was seen in separate analyses by sex, race, and at different levels of education. Conclusion. These results suggest that crystalline silica exposure may promote the development of SLE in some individuals. Additional research is recommended in other populations, using study designs that minimize potential selection bias and maximize the quality of exposure assessment. C1 NIEHS, Epidemiol Branch, Durham, NC 27709 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. NIOSH, Cincinnati, OH 45226 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. E Carolina Univ, Sch Med, Greenville, NC USA. Vet Adm Med Ctr, Charleston, SC 29403 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Parks, CG (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Durham, NC 27709 USA. OI Parks, Christine/0000-0002-5734-3456 NR 56 TC 80 Z9 82 U1 3 U2 5 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 JUL PY 2002 VL 46 IS 7 BP 1840 EP 1850 DI 10.1002/art.10368 PG 11 WC Rheumatology SC Rheumatology GA 572KK UT WOS:000176773200018 PM 12124868 ER PT J AU Shamim, EA Rider, LG Pandey, JP O'Hanlon, TP Jara, LJ Samayoa, EA Burgos-Vargas, R Vazquez-Mellado, J Alcocer-Varela, J Salazar-Paramo, M Kutzbach, AG Malley, JD Targoff, IN Garcia-De La Torre, I Miller, FW AF Shamim, EA Rider, LG Pandey, JP O'Hanlon, TP Jara, LJ Samayoa, EA Burgos-Vargas, R Vazquez-Mellado, J Alcocer-Varela, J Salazar-Paramo, M Kutzbach, AG Malley, JD Targoff, IN Garcia-De La Torre, I Miller, FW TI Differences in idiopathic inflammatory myopathy phenotypes and genotypes between Mesoamerican Mestizos and North American Caucasians - Ethnogeographic influences in the genetics and clinical expression of myositis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INCLUSION-BODY MYOSITIS; CLASS-II ALLELES; JUVENILE DERMATOMYOSITIS; RHEUMATOID-ARTHRITIS; ETHNIC-GROUPS; AUTOANTIBODIES; ASSOCIATION; DISEASES; ONSET; IMMUNOGENETICS AB Objective. As part of a larger, worldwide study of the ethnogeography of myositis, we evaluated the clinical, serologic, and immunogenetic features of Mestizo (Mexican and Guatemalan) and North American Cancasian patients with idiopathic inflammatory myopathy (IIM). Methods. Clinical manifestations, autoantibodies, HLA-DRB1 and DQA1 alleles, and immunoglobulin Gm/Km allotypes were compared between 138 Mestizos with IIM and 287 Caucasians with IIM, using the same classification criteria and standardized questionnaires. Results. IIM in Mestizo patients was characterized by a higher proportion of dermatomyositis (69% of adult Mestizos versus 35% of adult Caucasians; P < 0.001) and anti-Mi-2 autoantibodies (30% versus 7% of adults, respectively, and 32% versus 4% of children, respectively; P < 0.01). Genetic risk factors also differed in these populations. Whereas Mestizos had no HLA risk factors for IIM, HLA-DRBI*0301, the linked allele DQA1*0501, and DRB1 alleles sharing the first hypervariable region motif (EYSTS13)-E-9 were major risk factors in Caucasian patients with IIM. Furthermore, different HLA-DRB1 and DQA1 alleles were associated with anti-Mi-2 autoantibodies (DRB1*04 and DQA1*03 in Mestizos and DRB1*07 and DQA1*02 in Caucasians). Immunoglobulin gamma-chain allotypes Gm(1), Gm(17) (odds ratio for both 11.3, P = 0.008), and Gm(21) (odds ratio 7.3, P = 0.005) and kappa-chain allotype Km(3) (odds ratio 7.3, P = 0.005) were risk factors for IIM in Mestizos; however, no Gull or Km allotypes were risk or protective factors in Caucasians. In addition, Gull and Km phenotypes were unique risk factors (Gm 1,3,17 5,13,21 and Gm 1,17 23 21 and Km 3,3) or protective factors (Km 1,1) for the development of myositis and anti-Mi-2 autoantibodies (Gm 1,2,3,17 23 5,13,21) in adult Mestizos. Conclusion. IIM in Mesoamerican Mestizos differs from IIM in North American Caucasians in the frequency of phenotypic features and in the immune-response genes predisposing to and protecting from myositis and anti-Mi-2 autoantibodies at 4 chromosomal loci. These and other data suggest the likelihood that the expression of IIM is modulated by different genes and environmental exposures around the world. C1 NIEHS, Environm Autoimmun Grp, Off Clin Res, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Med Univ S Carolina, Charleston, SC 29425 USA. Hosp Especialidades Ctr Med La Raza, Mexico City, DF, Mexico. Hosp Gen San Juan de Dios, Ssn Juan De Dios, Guatemala. Univ Nacl Autonoma Mexico, Mexico City 04510, DF, Mexico. Hosp Gen Mexico City, Mexico City, DF, Mexico. Inst Nacl Nutr Salvador Zubiran, Mexico City 14000, DF, Mexico. Univ Guadalajara, Guadalajara 44430, Jalisco, Mexico. Hosp Especialidades Ctr Med La Raza, Ctr Med Occidente, Inst Mexicano Seura Social, Unidad Invest Med & Epidemiol, Guadalajara, Jalisco, Mexico. Univ Francisco Marrequin, Guatemala City, Guatemala. NIH, Ctr Informat Technol, Bethesda, MD USA. Univ Oklahoma, Med Sci Ctr, Vet Affairs Med Ctr, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Hosp Gen Occidente Secretaria Salud, Guadalajara, Jalisco, Mexico. RP Shamim, EA (reprint author), NIEHS, Environm Autoimmun Grp, Off Clin Res, NIH, 9 Mem Dr,Room 1W101,MSC 0958, Bethesda, MD 20892 USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 42 TC 49 Z9 52 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 JUL PY 2002 VL 46 IS 7 BP 1885 EP 1893 DI 10.1002/art.10358 PG 9 WC Rheumatology SC Rheumatology GA 572KK UT WOS:000176773200023 PM 12124873 ER PT J AU Calvert, RJ Ramakrishna, G Tepper, S Diwan, BA Anderson, LM Kritchevsky, D AF Calvert, RJ Ramakrishna, G Tepper, S Diwan, BA Anderson, LM Kritchevsky, D TI Alterations in membrane-bound and cytoplasmic K-ras protein levels in mouse lung induced by treatment with lovastatin, cholestyramine, or niacin: effects are highly mouse strain dependent SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE cholesterol; lovastatin; cholestyramine; niacin; mouse lung; K-ras ID A/J MICE; TUMORS; CHOLESTEROL; EXPRESSION; REDUCTASE; CANCER; RATS; LOCALIZATION; INHIBITION; RODENT AB Agents that either increase (cholestyramine, CS) or decrease (lovastatin, Lov) de novo peripheral cholesterol synthesis may increase (CS) or decrease (Lov) ras protein membrane localization by altering protein prenylation, and potentially have pro- or anti-carcinogenic effects. Male A/J, Swiss, and C57/BL6 mice were treated with 2 or 4% CS, 1% dietary niacin, or 25 mg/kg of Lov three times per week (Lov-3X) or five times per week (Lov-5X). After 3 weeks, serum cholesterol and triglycerides were determined enzymatically. Membrane and cytoplasmic K-ras proteins in lung were determined by immunoprecipitation followed by western blotting with a K-ras specific antibody. Results confirmed the hypothesis only in isolated instances. A/J mice had a significant 30% increase in cytoplasmic K-ras and a 40% decrease in membrane K-ras from Lov treatment, as predicted. C57/BL6 mice had a significant 77% increase in membrane K-ras, as expected from CS feeding. At variance with the hypothesis, Swiss mice had increased levels (3-28%) of membrane K-ras with all treatments (including Lov), and C57/BL6 mice treated with Lov had a 58-78% increase in cytoplasmic K-ras without any reduction in the levels of membrane K-ras. Niacin, predicted to have no effect on ras membrane localization, decreased cytoplasmic K-ras in A/J mice, increased both membrane and cytoplasmic K-ras in Swiss mice, and had no effect in C57/BL6 mice. Results may have differed from those predicted because of strain-dependent differences in response to the cholesterol-lowering agents. A difference in response among the mouse strains suggests that individual genetic differences may alter the effect of hypocholesterolemic agents on K-ras membrane localization, and potentially the risk of ras-dependent cancer. Published by Elsevier Science Inc. C1 US FDA, Div Res & Appl Technol, Off Nutr Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. NCI, SAIC, Frederick, MD 21702 USA. RP Calvert, RJ (reprint author), US FDA, Div Res & Appl Technol, Off Nutr Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 22 TC 3 Z9 3 U1 0 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 JUL 1 PY 2002 VL 64 IS 1 BP 41 EP 48 AR PII S0006-2952(02)01077-8 DI 10.1016/S0006-2952(02)01077-8 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 578JJ UT WOS:000177113400005 PM 12106604 ER PT J AU Mandler, R Kobayashi, H Davis, MY Waldmann, TA Brechbiel, MW AF Mandler, R Kobayashi, H Davis, MY Waldmann, TA Brechbiel, MW TI Modifications in synthesis strategy improve the yield and efficacy of geldanamycin-herceptin immunoconjugates SO BIOCONJUGATE CHEMISTRY LA English DT Article ID BREAST-CANCER; ANTIPROLIFERATIVE ACTIVITY; IN-VIVO; THERAPY; DERIVATIVES; EXPRESSION; ANTIBODY; ONCOGENE AB Geldanamycin (GA) was modified with N-tert-butyloxycarbonyl-1,3-diaminopropane to introduce a latent primary amine. After deprotection, this primary amine provided a site for introduction of a maleimide group that enabled linkage to proteins. This maleimido derivative of geldanamycin (GMB-APA-GA) was linked to the monoclonal antibody Herceptin after the antibody had been modified with Traut's reagent to introduce thiol groups. By this sequence, a new immunoconjugate (H:APA-GA) was generated that showed greater antiproliferative activity than the previously reported analogous immunoconjugate created with a 1,4-diaminobutane spacer derivative of geldanamycin to form an immunoconjugate, H:ABA-GA. Both immunoconjugates inhibited in vitro the growth of MDA-361/DYT2 cells, a cell line overexpressing the HER2 antigen, while Herceptin alone was ineffective. However, H:APA-GA showed better efficacy than H:ABA-GA (IC50 = 0.2 vs 0.58 mg/mL and cell doubling time > 12 vs 6 days, respectively). Results of the in vivo therapy experiments in a xenograft model were consistent with the in vitro findings. Treatment with Herceptin prolonged the survival of the tumor-bearing mice when compared with the control group, but H:ABA-GA and H:APA-GA were each more efficacious than unmodified Herceptin. However, unlike H:ABA-GA, the immunoconjugate H:APA-GA caused stable tumor regression (in 25% of the recipients), showing a qualitative improvement with potential clinical relevance. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Metab Branch, NIH, 10 Ctr Dr,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. NR 25 TC 10 Z9 11 U1 1 U2 8 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 JUL-AUG PY 2002 VL 13 IS 4 BP 786 EP 791 DI 10.1021/bc010124g PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 574VF UT WOS:000176909700012 PM 12121134 ER PT J AU Morgan, GJ Davies, FE Linet, M AF Morgan, GJ Davies, FE Linet, M TI Myeloma aetiology and epidemiology SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Review DE myeloma; epidemiology; genetics ID ATOMIC-BOMB SURVIVORS; PETROLEUM DISTRIBUTION WORKERS; CHRONIC ANTIGENIC-STIMULATION; SWEDISH AGRICULTURAL-WORKERS; HAIR-COLORING PRODUCTS; NON-HODGKINS-LYMPHOMA; NECROSIS-FACTOR-ALPHA; LONG-TERM EXPOSURE; X-RAY WORKERS; MULTIPLE-MYELOMA AB Recently there have been substantial improvements in our understanding of the biology of myeloma. These findings have important implications for aetiological studies aimed at defining the causative factors for myeloma. Myeloma is closely related to monoclonal gammopathy of unknown significance (MGUS), which is now recognized to be very common in the older population. The epidemiology of these conditions is presented and discussed in the context of the genetic factors governing both the risk of developing MGUS or of transformation to myeloma. Biological studies support a role for aberrant class switch recombination early in the natural history of myeloma suggesting that factors in the environment may interact with this mechanism to increase myeloma risk. Case-control and cohort studies have identified several known and suspected environmental exposures. These exposures include high doses of ionizing radiation, and occupational exposure in the farming and petrochemical industries. The data supporting these associations are presented and discussed in the context of the molecular mechanisms underlying these exposures. In particular DNA damage occurring as a consequence could readily interact with the class switch recombination process to increase the risk of chromosomal translocations, oncogene deregulation and malignant transformation. A further hypothesis, which has been extensively investigated, is the role of chronic immune/antigenic stimulation and the risk of myeloma. This concept is difficult to explain in the context of our current immunological concepts. The data supporting the association and how molecular epidemiological studies using genetic variants in cytokine genes are allowing us to revisit this concept are discussed in detail. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 Univ Leeds, Acad Unit Haematol & Oncol, Leeds, W Yorkshire, England. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Morgan, GJ (reprint author), Univ Leeds, Acad Unit Haematol & Oncol, Leeds, W Yorkshire, England. NR 221 TC 46 Z9 48 U1 4 U2 16 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 JUL PY 2002 VL 56 IS 5 BP 223 EP 234 DI 10.1016/S0753-3322(02)00194-4 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 586GG UT WOS:000177575800002 PM 12199621 ER PT J AU Wang, SQ Song, LS Xu, L Meissner, G Lakatta, EG Rios, E Stern, MD Cheng, H AF Wang, SQ Song, LS Xu, L Meissner, G Lakatta, EG Rios, E Stern, MD Cheng, H TI Thermodynamically irreversible gating of ryanodine receptors in situ revealed by stereotyped duration of release in Ca2+ sparks SO BIOPHYSICAL JOURNAL LA English DT Article ID RAT VENTRICULAR MYOCYTES; CALCIUM-INDUCED RELEASE; RETICULUM LUMENAL CA2+; SKELETAL-MUSCLE; SARCOPLASMIC-RETICULUM; CARDIAC-MUSCLE; AMPLITUDE DISTRIBUTION; VOLTAGE-DEPENDENCE; ELEMENTARY EVENTS; CHANNEL AB For a single or a group of Markov channels gating reversibly, distributions of open and closed times should be the sum of positively weighted decaying exponentials. Violation of this microscopic reversibility has been demonstrated previously on a number of occasions at the single channel level, and has been attributed to possible channel coupling to external sources of free energy. Here we show that distribution of durations of Ca2+ release underlying Ca2+ sparks in intact cardiac myocytes exhibits a prominent mode at similar to8 ms. Analysis of the cycle time for repetitive sparks at hyperactive sites revealed no intervals briefer than similar to35 ms and a mode at similar to90 ms. These results indicate that, regardless of whether Ca2+ sparks are single-channel or multi-channel in origin, they are generated by thermodynamically irreversible stochastic processes. In contrast, data from planar lipid bilayer experiments were consistent with reversible gating of RyR under asymmetric cis (4 muM) and trans Ca2+ (10 mM), Suggesting that the irreversibility for Ca2+ spark genesis may reside at a supramolecular level. Modeling suggests that Ca2+-induced Ca2+ release among adjacent RyRs may couple the external energy derived from Ca2+ gradients across the SR to RyR gating in situ, and drive the irreversible generation of Ca2+ sparks. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Rush Univ, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA. RP Cheng, H (reprint author), NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RI Song, Long-Sheng/D-5899-2012 NR 50 TC 35 Z9 37 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 2002 VL 83 IS 1 BP 242 EP 251 PG 10 WC Biophysics SC Biophysics GA 566UC UT WOS:000176445800022 PM 12080116 ER PT J AU Davis, JS Satorius, CL Epstein, ND AF Davis, JS Satorius, CL Epstein, ND TI Kinetic effects of myosin regulatory light chain phosphorylation on skeletal muscle contraction SO BIOPHYSICAL JOURNAL LA English DT Article ID HUXLEY-SIMMONS PHASE-2; FORCE GENERATION; PHOSPHATE RELEASE; 2,3-BUTANEDIONE MONOXIME; TEMPERATURE-JUMP; STRIATED-MUSCLE; THICK FILAMENTS; FIBERS; ACTIN; TENSION AB Kinetic analysis of contracting fast and slow rabbit muscle fibers in the presence of the tension inhibitor 2,3-butanedione monoxime suggests that regulatory light chain (RLC) phosphorylation up-regulates the flux of weakly attached cross-bridges entering the contractile cycle by increasing the actin-catalyzed release of phosphate from myosin. This step appears to be separate from earlier Ca2+ regulated steps. Small step-stretches of single skinned fibers were used to study the effect of phosphorylation on fiber mechanics. Subdivision of the resultant tension transients into the Huxley-Simmons phases 1, 2(fast), 2(slow), 3, and 4 reveals that phosphorylation reduces the normalized amplitude of the delayed rise in tension (stretch activation response) by decreasing the amplitudes of phase 3 and, to a lesser extent, phase 2(slow). In slow fibers, the RLC P1 isoform phosphorylates at least 4-fold faster than the P2 isoform, complicating the role of RLC phosphorylation in heart and slow muscle. We discuss the functional relevance of the regulation of stretch activation by RLC phosphorylation for cardiac and other oscillating muscles and speculate how the interaction of the two heads of myosin could account for the inverse effect of Ca2+ levels on isometric tension and rate of force redevelopment (k(TR)). C1 NHLBI, Mol Physiol Sect, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Davis, JS (reprint author), NHLBI, Mol Physiol Sect, Mol Cardiol Lab, NIH, Bldg 10,10 Ctr Dr,MSC,Room 8N202, Bethesda, MD 20892 USA. NR 47 TC 44 Z9 44 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 JUL PY 2002 VL 83 IS 1 BP 359 EP 370 PG 12 WC Biophysics SC Biophysics GA 566UC UT WOS:000176445800032 PM 12080126 ER PT J AU Katagiri, Y Ingham, KC AF Katagiri, Y Ingham, KC TI Enhanced production of green fluorescent fusion proteins in a baculovirus expression system by addition of secretion signal SO BIOTECHNIQUES LA English DT Article ID INSECT CELLS; FIBRONECTIN; MARKER C1 Amer Red Cross, Holland Lab, Rockville, MD USA. RP Katagiri, Y (reprint author), NHLBI, NIH, Bldg 10,Room 8C106,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL21791] NR 10 TC 6 Z9 6 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 JUL PY 2002 VL 33 IS 1 BP 24 EP 26 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 575UC UT WOS:000176966000001 PM 12139250 ER PT J AU Smith, RH Afione, SA Kotin, RM AF Smith, RH Afione, SA Kotin, RM TI Transposase-mediated construction of an integrated adeno-associated virus type 5 helper plasmid SO BIOTECHNIQUES LA English DT Article ID ADENOASSOCIATED VIRUS; GENE-TRANSFER; NERVOUS-SYSTEM; VECTORS; PURIFICATION; SEROTYPE-5; GENERATION; DELIVERY; CLONING AB Adeno-associated viruses (AAVs) are replication-defective parvoviruses that require helper virus functions for efficient productive replication. The AAVs are currently premier candidates as vectors for human gene therapy applications hi particular, much recent interest has been expressed concerning recombinant AAV serotype 5 (rAAV 5) vectors, as they appear to utilize cellular receptors distinct from those of the prototypical AAV serotype (AAV-2) and have been reported to have transduction properties in vivo that differ significantly from those of the prototype. One of the most popular current methods, for the production of rAAVs involves co-transfection of human 293 cells with three plasmids: (i) art adenovirus (Ad)-derived helper plasmid containing Ad genes required for-AAV replication. (ii) an AAV-derived plasmid encoding complementing AAV genes (i.e., the viral rep and cap genes), and (iii) a target plasmid containing a transgene of interest flanked by AAV inverted terminal repeats (ITRs) that confer packaging and replication capabilities upon the ITR-flanked heterologous DNA. Here we describe novel plasmid reagents designed,for convenient and efficient production of rAAV-5. An integrated helper plasmid containing all Ad genes required for the efficient production of recombinant AAV, as well as the complementing AAV genes on the same plasmid backbone, was constructed via transposase-mediated insertion into an Ad helper plasmid of a transposable element containing the AAV-5 rep and cap genes linked to a selectable marker. This simple strategy can be used in the rapid and efficient construction of integrated helper plasmids derived from any reported AAV serotype for which a molecular clone exists. C1 NHLBI, LBG, NIH, Bethesda, MD 20892 USA. RP Kotin, RM (reprint author), NHLBI, LBG, NIH, Bldg 10,Rm 7D18, Bethesda, MD 20892 USA. RI kotin, robert/B-8954-2008 NR 19 TC 11 Z9 11 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUL PY 2002 VL 33 IS 1 BP 204 EP + PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 575UC UT WOS:000176966000026 PM 12139247 ER PT J AU Tsai, EJ Malech, HL Kirby, MR Hsu, AP Seidel, NE Porada, CD Zanjani, ED Bodine, DM Puck, JM AF Tsai, EJ Malech, HL Kirby, MR Hsu, AP Seidel, NE Porada, CD Zanjani, ED Bodine, DM Puck, JM TI Retroviral transduction of IL2RG into CD34(+) cells from X-linked severe combined immunodeficiency patients permits human T- and B-cell development in sheep chimeras SO BLOOD LA English DT Article ID APE LEUKEMIA-VIRUS; RECEPTOR-GAMMA-CHAIN; MEDIATED GENE-TRANSFER; BLOOD STEM-CELLS; BONE-MARROW TRANSPLANTATION; MOBILIZED PERIPHERAL-BLOOD; HUMAN HEMATOPOIETIC-CELLS; HIGH-LEVEL EXPRESSION; LONG-TERM CULTURES; HUMAN CORD-BLOOD AB X-linked severe combined immunodeficiency (XSCID) is caused by mutations of the common gamma chain of cytokine receptors, gamma(c). Because bone marrow transplantation (BMT) for XSCID does not provide complete immune reconstitution for many patients and because of the natural selective advantage conferred on lymphoid progenitors by the expression of normal gamma(c), XSCID is a good candidate disease for therapeutic retroviral gene transfer to hematopoietic stem cells. We studied XSCID patients who have persistent defects in B-cell and/or combined B- and T-cell function despite having received T cell-depleted haploidentical BMT. We compared transduction of autologous B-cell lines and granulocyte colony-stimulating factor-mobilized peripheral CD34(+) cells from these patients using an MFGS retrovirus vector containing the gamma(c) gene IL2RG pseudotyped with amphotropic, gibbon ape leukemia virus, or RD114 envelopes. Transduced B-cell lines and peripheral CD34(+) cells demonstrated provirus integration and new cell-surface gamma(c) expression. The chimeric sheep model was exploited to test development of XSCID CD34(+) cells into mature myeloid and lymphoid lineages. Transduced and untransduced XSCID CD34(+) cells injected into developing sheep fetuses gave rise to myeloid cells. However, only transduced gamma(c)(+) progenitors from XSCID patients developed into T and B cells. These results suggest that gene transfer to autologous peripheral CD34(+) cells using MFGS-gc retrovirus may benefit XSCID patients with persistent T- and B-cell deficits despite prior BMT. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Natl Inst Hlth, Res Scholar Program, Bethesda, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Nevada, Sch Med, Reno, NV 89557 USA. RP Puck, JM (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bldg 49,Rm 4A14,49 Convent Dr, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL40722, HL46566, HL39875] NR 55 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2002 VL 100 IS 1 BP 72 EP 79 DI 10.1182/blood.V100.1.72 PG 8 WC Hematology SC Hematology GA 567GQ UT WOS:000176477400012 PM 12070011 ER PT J AU Novak, EK Gautam, R Reddington, M Collinson, LM Copeland, NG Jenkins, NA McGarry, MP Swank, RT AF Novak, EK Gautam, R Reddington, M Collinson, LM Copeland, NG Jenkins, NA McGarry, MP Swank, RT TI The regulation of platelet-dense granules by Rab27a in the ashen mouse, a model of Hermansky-Pudlak and Griscelli syndromes, is granule-specific and dependent on genetic background SO BLOOD LA English DT Article ID STORAGE POOL DEFICIENCY; MOLECULAR MECHANISMS; INHERITED ABNORMALITIES; MULTIVESICULAR BODIES; BLOOD-PLATELETS; ALPHA-GRANULES; PIGMENT MUTANT; MAST-CELLS; EXOCYTOSIS; PROTEINS AB The ashen (ash) mouse, a model for Hermansky-Pudlak syndrome (HPS) and for a subset of patients with Griscelli syndrome, presents with hypopigmentation, prolonged bleeding times, and platelet storage pool deficiency due to a mutation which abrogates expression of the Rab27a protein. Platelets of mice with the ashen mutation on the C3H/HeSnJ inbred strain background have greatly reduced amounts of dense granule components such as serotonin and adenine nucleotides though near-normal numbers of dense granules as enumerated by the dense granule-specific fluorescent dye mepacrine. Thus, essentially normal numbers of platelet dense granules are produced but the granule interiors are abnormal. Collagen-mediated aggregation of mutant platelets is significantly depressed. No abnormalities in the concentrations or secretory rates of 2 other major platelet granules, lysosomes and alpha granules, were apparent. Similarly, no platelet ultrastructural alterations other than those involving dense granules were detected. Therefore, Rab27a regulates the synthesis and secretion of only one major platelet organelle, the dense granule. There were likewise no mutant effects on levels or secretion of lysosomal enzymes of several other tissues. Together with other recent analyses of the ashen mouse, these results suggest a close relationship between platelet dense granules, melanosomes of melanocytes and secretory lysosomes of cytotoxic T lymphocytes, all mediated by Rab27a. Surprisingly, the effects of the ashen mutation on platelet-dense granule components, platelet aggregation, and bleeding times were highly dependent on genetic background. This suggests that bleeding tendencies may likewise vary among patients with Griscelli syndrome and HPS with Rab27a mutations. C1 Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA. Univ London Imperial Coll Sci Technol & Med, London, England. NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. Mayo Clin, Dept Biochem & Mol Biol, Scottsdale, AZ USA. RP Swank, RT (reprint author), Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Carlton & Elm St, Buffalo, NY 14263 USA. FU NCI NIH HHS [CA 16056]; NEI NIH HHS [EY12104]; NHLBI NIH HHS [HL31698, HL51480] NR 67 TC 40 Z9 40 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 JUL 1 PY 2002 VL 100 IS 1 BP 128 EP 135 DI 10.1182/blood.V100.1.128 PG 8 WC Hematology SC Hematology GA 567GQ UT WOS:000176477400018 PM 12070017 ER PT J AU Risitano, AM Kook, H Zeng, WH Chen, GB Young, NS Maciejewski, JP AF Risitano, AM Kook, H Zeng, WH Chen, GB Young, NS Maciejewski, JP TI Oligoclonal and polyclonal CD4 and CD8 lymphocytes in aplastic anemia and paroxysmal nocturnal hemoglobinuria measured by V beta CDR3 spectratyping and flow cytometry SO BLOOD LA English DT Article ID T-CELL REPERTOIRE; VERSUS-HOST DISEASE; BONE-MARROW; PERIPHERAL-BLOOD; IN-VIVO; ANTITHYMOCYTE GLOBULIN; INTERFERON-GAMMA; GENE USAGE; RECEPTOR; ANTIGEN AB We have hypothesized that in aplastic anemia (AA) the presence of antigen-specific T cells is reflected by their contribution to the expansion of a particular variable beta chain (Vbeta) subfamily and also by clonal CDR3 skewing. To determine the role of disease-specific "signature" T-cell clones in AA, we studied preferential Vbeta usage by flow cytometry and analyzed Vbeta-CDR3 regions for the presence of oligoclonality. We first established the contribution of each Vbeta family to the total CD4(+) and CD8(+) lymphocyte pool; in AA and paroxysmal nocturnal hemoglobinuria, a seemingly random overrepresentation of different VP families was observed. On average, we found expansion in 3 (of 22 examined) Vbeta families per patient. When the contribution of individual Vbeta families to the effector pool was examined, more striking Vbeta skewing was found. Vbeta-CDR3 size distribution was analyzed for the expanded Vbeta families in isolated CD4(+) and CD8(+) populations; underrepresented Vbeta families displayed more pronounced CDR3 skewing. Expanded CD4(+)Vbeta subfamilies showed mostly a polyclonal CDR3 size distribution with only 38% of skewing in expanded Vbeta families. In contrast, within overrepresented CD8(+)Vbeta types, marked CDR3 skewing (82%) was seen, consistent with nonrandom expansion of specific CD8(+) T-cell clones. No preferential expansion of particular Vbeta families was observed, in relation to HLA-type. In patients examined after immunosuppressive therapy, an abnormal Vbeta-distribution pattern was retained, but the degree of expansion of individual Vbeta was lower. As Vbeta skewing may correlate with relative Vbeta size, oligoclonality in combination with numerical Vbeta expansion can be applied to recognition of disease-specific T-cell receptors. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Maciejewski, JP (reprint author), Taussig Canc Ctr, Expt Hematol & Hematopoiesis Div, R40,9500 Euclid Ave, Cleveland, OH 44195 USA. NR 46 TC 76 Z9 86 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 JUL 1 PY 2002 VL 100 IS 1 BP 178 EP 183 DI 10.1182/blood-2002-01-0236 PG 6 WC Hematology SC Hematology GA 567GQ UT WOS:000176477400026 PM 12070025 ER PT J AU Zhang, ML Yao, ZS Garmestani, K Axworthy, DB Zhang, Z Mallett, RW Theodore, LJ Goldman, CK Brechbiel, MW Carrasquillo, JA Waldmann, TA AF Zhang, ML Yao, ZS Garmestani, K Axworthy, DB Zhang, Z Mallett, RW Theodore, LJ Goldman, CK Brechbiel, MW Carrasquillo, JA Waldmann, TA TI Pretargeting radioinimunotherapy of a murine model of adult T-cell leukemia with the alpha-emitting radionuclide, bismuth 213 SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; MONOCLONAL-ANTIBODY; INTERLEUKIN-2 RECEPTOR; CANCER XENOGRAFTS; COLON-CANCER; RADIOIMMUNOTHERAPY; STREPTAVIDIN; THERAPY; BIOTIN; AVIDIN AB We used a pretargeting technique to treat a nonobese diabetic/severe combined immunodeficient murine model of human adult T-cell leukemia with an anti-Tac antibody-streptavidin (HAT-SA) conjugate, which recognizes CD25, followed by bismuth 213 (Bi-213)-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)biotin. In the 3-step pretargeting radioimmunotherapy protocol, HAT-SA (140 or 400 mug) was administered intravenously (i.v.) to bind to the interleukin 2 receptor alpha (IL-2Ralpha; CD25)-expressing tumor cells. After 24 hours, 100 mug of a synthetic clearing agent was administered i.v. to remove unbound circulating HAT-SA conjugate from the circulation. Four hours later, Bi-213-DOTA-biotin was administered i.v. for therapy. Tumor growth was significantly inhibited in 3 trials by using 250 muCi (9.25 MBq) of Bi-213-DOTA-biotin with a pretargeting technique as monitored by serum levels of soluble IL-2Ralpha and/or human beta-2-microglobulin (P<.05, t test) and by survival of tumor-bearing mice in the treatment groups (P<.02, log rank test) as compared with the control groups. No prolongation of survival was observed with a nonspecific antibody-SA conjugate or in the absence of the radionuclide. Additionally, no prolongation of survival resulted from administration of Bi-213 directly linked to intact HAT. Furthermore, there was no prolongation of survival when the beta-emitting radionuclide yttrium 90 instead of the alpha-emitting radionuclide Bi-213 was used. The pretargeting approach with Bi-213 inhibited tumor growth more effectively than did immunotherapy with unmodified HAT. The best results were obtained with combination therapy that involved Bi-213-DOTA-biotin with a pretargeting technique supplemented by 4 weekly doses of HAT. The findings of this study support the use of this combination approach in a clinical trial in patients with IL-2Ralpha-expressing leukemias. C1 NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Dept Nucl Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NeoRx Corp, Seattle, WA 98119 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Canc Res Ctr, NIH, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 42 TC 75 Z9 77 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 JUL 1 PY 2002 VL 100 IS 1 BP 208 EP 216 DI 10.1182/blood-2002-01-0107 PG 9 WC Hematology SC Hematology GA 567GQ UT WOS:000176477400030 PM 12070029 ER PT J AU Szocinski, JL Khaled, AR Hixon, J Halverson, D Funakoshi, S Fanslow, WC Boyd, A Taub, DD Durum, SK Siegall, CB Longo, DL Murphy, WJ AF Szocinski, JL Khaled, AR Hixon, J Halverson, D Funakoshi, S Fanslow, WC Boyd, A Taub, DD Durum, SK Siegall, CB Longo, DL Murphy, WJ TI Activation-induced cell death of aggressive histology lymphomas by CD40 stimulation: induction of bax SO BLOOD LA English DT Article ID IN-VITRO; B-CELLS; GROWTH-FACTOR; BCL-2 FAMILY; LIGAND; PROLIFERATION; INHIBITION; APOPTOSIS; RECEPTOR; ANTIGEN AB CD40 is present on both normal and neoplastic B-lineage cells. CD40 stimulation of normal B cells has been shown to promote normal growth and differentiation, whereas aggressive histology B lymphomas are growth inhibited. The inhibition of neoplastic B-cell growth is believed to occur via activation-induced cell death in which stimuli that typically promote the growth of normal cells prevent the growth of their neoplastic counterparts. We show here that CD40 stimulation using either a soluble recombinant human CD40 ligand (srhCD40L) or anti-CD40 monoclonal antibody resulted in apoptosis of human Burkitt lymphoma cell lines. Additional studies examining the mechanism of CD40-mediated death revealed an increase in bax messenger RNA with a subsequent increase in Bax protein in the mitochondria of the treated cells. In vitro exposure of the cells to bax antisense oligonucleotides resulted in a significant decline in Bax protein levels and partial protection from CD40-mediated death, indicating that induction of Bax was at least one mechanism underlying this inhibitory effect of CD40 stimulation on lymphomas. When immunodeficient mice bearing Burkitt lymphoma were treated with srhCD40L, significant increases in survival were observed indicating a direct antitumor effect as a result of CD40 stimulation in vivo. Overall, these results demonstrate that CD40 ligation of aggressive histology B-lymphoma cells results in inhibition both in vitro and in vivo and thus may be of potential clinical use in their treatment. C1 NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Lab Leukocyte Biol, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NIA, Immunol Lab, Baltimore, MD 21224 USA. Immunex Corp, Seattle, WA USA. Hood Coll, Dept Biol, Frederick, MD 21701 USA. Seattle Genet, Bothell, WA USA. RP Murphy, WJ (reprint author), NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bldg 567,Rm 210, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 37 TC 41 Z9 42 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2002 VL 100 IS 1 BP 217 EP 223 DI 10.1182/blood.V100.1.217 PG 7 WC Hematology SC Hematology GA 567GQ UT WOS:000176477400031 PM 12070030 ER PT J AU Kogan, SC Ward, JM Anver, MR Berman, JJ Brayton, C Cardiff, RD Carter, JS de Coronado, S Downing, JR Fredrickson, TN Haines, DC Harris, AW Harris, NL Hiai, H Jaffe, ES MacLennan, ICM Pandolfi, PP Pattengale, PK Perkins, AS Simpson, RM Tuttle, MS Wong, JF Morse, HC AF Kogan, SC Ward, JM Anver, MR Berman, JJ Brayton, C Cardiff, RD Carter, JS de Coronado, S Downing, JR Fredrickson, TN Haines, DC Harris, AW Harris, NL Hiai, H Jaffe, ES MacLennan, ICM Pandolfi, PP Pattengale, PK Perkins, AS Simpson, RM Tuttle, MS Wong, JF Morse, HC TI Bethesda proposals for classification of nonlymphoid hematopoietic neoplasms in mice SO BLOOD LA English DT Article ID MYELOID-LEUKEMIA AB The hematopathology subcommittee of the Mouse Models of Human Cancers Consortium recognized the need for a classification of murine hematopoietic neoplasms that would allow investigators to diagnose lesions as well-defined entities according to accepted criteria. Pathologists and investigators worked cooperatively to develop proposals for the classification of lymphoid and nonlymphoid hematopoietic neoplasms. It is proposed here that nonlymphoid hematopoietic neoplasms of mice be classified in 4 broad categories: nonlymphoid leukemias, nonlymphoid hematopoietic sarcomas, myeloid dysplasias, and myeloid proliferations (nonreactive). Criteria for diagnosis and subclassification of these lesions include peripheral blood findings, cytologic features of hematopoietic tissues, histopathology, immunophenotyping, genetic features, and clinical course. Differences between murine and human lesions are reflected in the terminology and methods used for classification. This classification will be of particular value to investigators seeking to develop, use, and communicate about mouse models of human hematopoietic neoplasms. C1 Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Apelon Inc, Alameda, CA USA. Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. Univ Calif Davis, Dept Pathol, Davis, CA 95616 USA. Childrens Hosp Los Angeles, Dept Pathol, Los Angeles, CA 90027 USA. Baylor Coll Med, Ctr Comparat Med, Houston, TX 77030 USA. Kyoto Univ, Grad Sch Med, Dept Pathol & Biol Dis, Kyoto, Japan. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Cornell Univ, Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. Cornell Univ, Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. NCI, Canc Diag Program, Ctr Bioinformat, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, Bethesda, MD 20892 USA. NCI, Tumor Pathol Sect, Frederick, MD 21701 USA. NCI, SAIC, Frederick, MD 21701 USA. NIAID, Infect Dis Pathogenesis Branch, Rockville, MD USA. St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. Univ Birmingham, Sch Med, MRC, Ctr Immune Regulat, Birmingham, W Midlands, England. Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic, Australia. Yale Univ, Dept Pathol, New Haven, CT 06510 USA. RP Kogan, SC (reprint author), Univ Calif San Francisco, Ctr Comprehens Canc, 2340 Sutter St,Rm N-361,Box 0128, San Francisco, CA 94143 USA. EM skogan@cc.ucsf.edu OI Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [CA75986, CA84221, N01-CO-56000] NR 16 TC 267 Z9 273 U1 1 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 JUL 1 PY 2002 VL 100 IS 1 BP 238 EP 245 DI 10.1182/blood.V100.1.238 PG 8 WC Hematology SC Hematology GA 567GQ UT WOS:000176477400034 PM 12070033 ER PT J AU Morse, HC Anver, MR Fredrickson, TN Haines, DC Harris, AW Harris, NL Jaffe, ES Kogan, SC MacLennan, ICM Pattengale, PK Ward, JM AF Morse, HC Anver, MR Fredrickson, TN Haines, DC Harris, AW Harris, NL Jaffe, ES Kogan, SC MacLennan, ICM Pattengale, PK Ward, JM TI Bethesda proposals for classification of lymphoid neoplasms in mice SO BLOOD LA English DT Article ID B-CELL LYMPHOMAS; MARGINAL ZONE; C57BL/6 MICE; IMMUNODEFICIENCY SYNDROME; NATURAL-KILLER; MURINE AIDS; T-CELLS; LEUKEMIA; MOUSE; MODEL AB A consensus system for classification of mouse lymphoid neoplasms according to their histopathologic and genetic features has been an elusive target for investigators involved in understanding the pathogenesis of spontaneous cancers or modeling human hematopoietic diseases in mice. An international panel of scientists with expertise in mouse and human hematopathology joined with the hematopathology subcommittee of the Mouse Models for Human Cancers Consortium to develop criteria for definition and classification of these diseases together with a standardized nomenclature. The fundamental elements contributing to the scheme are clinical features, morphology, immunophenotype, and genetic characteristics. The resulting classification has numerous parallels to the World Health Organization classification of human lymphoid tumors while recognizing differences that may be species specific. The classification should facilitate communications about mouse models of human lymphoid diseases. C1 NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Histotechnol Lab, SAIC Frederick, NIH, Frederick, MD 21701 USA. NCI, Vet & Tumor Pathl Sect, Ctr Canc Res, NIH, Frederick, MD 21701 USA. Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Birmingham, Sch Med, Birmingham, W Midlands, England. RP Morse, HC (reprint author), 7 Ctr Dr,Rm 7-304,MSC 0760, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [N01-CO56000] NR 46 TC 228 Z9 233 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 JUL 1 PY 2002 VL 100 IS 1 BP 246 EP 258 DI 10.1182/blood.V100.1.246 PG 13 WC Hematology SC Hematology GA 567GQ UT WOS:000176477400035 PM 12070034 ER PT J AU Sandmaier, BM Bethge, WA Wilbur, DS Hamlin, DK Santos, EB Brechbiel, MW Fisher, DR Storb, R AF Sandmaier, BM Bethge, WA Wilbur, DS Hamlin, DK Santos, EB Brechbiel, MW Fisher, DR Storb, R TI Bismuth 213-labeled anti-CD45 radioimmunoconjugate to condition dogs for nonmyeloablative allogeneic marrow grafts SO BLOOD LA English DT Article ID TOTAL-BODY IRRADIATION; HEPATIC VENOOCCLUSIVE DISEASE; STEM-CELL TRANSPLANTATION; COMPLEXES IN-VIVO; MONOCLONAL-ANTIBODY; MYELODYSPLASTIC SYNDROME; EMITTING RADIONUCLIDES; LABELED-ANTIBODY; SOLID TUMORS; CANINE MODEL AB To lower treatment-related Mortality and toxicity of conventional marrow transplantation, a nonmyeloablative regimen using 200 cGy total-body irradiation (TBI) and mycophenolate mofetil (MMF) combined with cyclosporine (CSP) for postgrafting immunosuppression was developed. To circumvent possible toxic effects of external-beam gamma irradiation, strategies for targeted radiation therapy were investigated. We tested whether the short-lived (half-life, 46 minutes) alpha-emitter bismuth 213 (Bi-213) conjugated to an anti-CD45 monoclonal antibody (MAb) could replace 200 cGy TBI and selectively target hematopoietic tissues in a canine model of nonmyeloablative DLA-identical marrow transplantation. Biodistribution studies using iodine 123-labeled anti-CD45 mAb showed uptake in blood, marrow, lymph nodes, spleen, and liver. In a dose-escalation study, 7 dogs treated with the Bi-213-anti-CD45 conjugate (Bi-213 dose, 0.1-5.9 mCi/kg [3.7-218 MBq/kg]) without marrow grafts had no toxic effects other than a mild, reversible suppression of blood counts. On the basis of these studies, 3 dogs were treated with 0.5 mg/kg Bi-213-labeled anti-CD45 mAb (Bi-213 doses, 3.6, 4.6, and 8.8 mCi/kg [133, 170, and 326 MBq/kg]) given in 6 injections 3 and 2 days before grafting of marrow from DLA-identical littermates. The dogs also received MMF (10 mg/kg subcutaneously twice daily the day of transplantation until day 27 afterward) and CSP (15 mg/kg orally twice daily the day before transplantation until 35 days afterward). The therapy was well tolerated except for transient elevations in levels of transaminases in 3 dogs, followed by, in one dog, ascites. All dogs had prompt engraftment and achieved stable mixed hematopoietic chimerism, with donor contributions ranging from 30% to 70% after more than 27 weeks of follow-up. These results will form the basis for additional studies in animals and later the design of clinical trials using Bi-213 as a nonmyeloablative conditioning regimen with minimal toxicity. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. NCI, NIH, Bethesda, MD 20892 USA. Pacific NW Natl Lab, Richland, WA 99352 USA. RP Sandmaier, BM (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. FU NCI NIH HHS [CA78902, P01 CA078902, CA15704]; NHLBI NIH HHS [HL36444] NR 68 TC 50 Z9 53 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 JUL 1 PY 2002 VL 100 IS 1 BP 318 EP 326 DI 10.1182/blood-2001-12-0322 PG 9 WC Hematology SC Hematology GA 567GQ UT WOS:000176477400044 PM 12070043 ER PT J AU Holada, K Simak, J Risitano, AM Maciejewski, J Young, NS Vostal, JG AF Holada, K Simak, J Risitano, AM Maciejewski, J Young, NS Vostal, JG TI Activated platelets of patients with paroxysmal nocturnal hemoglobinuria express cellular prion protein SO BLOOD LA English DT Article ID TRANSMEMBRANE FORM; ANCHORED PROTEINS; APLASTIC-ANEMIA; FLOW-CYTOMETRY; BLOOD-CELLS; DISEASES; FAILURE AB Cellular prion protein (PrPc) is a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein that contains a putative membrane-spanning section. Patients with paroxysmal nocturnal hemoglobinuria (PNH) lack GPI proteins on the surface of somatically mutated hematopoietic stem cell and its progeny. Platelet expression of PrPc was studied in 8 PNH patients. Resting PNH (CD55(-)) platelets were devoid of surface PrPc, but activation of platelets resulted in the surface expression of PrPc. Expressed PrPc was detected by 2 monoclonal antibodies (mAbs) against the N-terminal part of the molecule but not by mAb 6H4, which binds at the C-terminus beyond the membrane-spanning section. However, 6H4 detected PrPc on Western blots of PNH platelets, demonstrating that the lack of 6H4 binding was not caused by PrPc truncation. Our results indicate that in the absence of GPI anchor, PrPc can be expressed intracellularly and up-regulated on the platelet membrane, likely in a transmembrane form with the C-terminal part of the molecule inserted into the cytoplasm. C1 US FDA, Lab Cellular Hematol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Vostal, JG (reprint author), US FDA, Lab Cellular Hematol, Div Hematol, Ctr Biol Evaluat & Res, Bldg 29,Room 323,HFM-335,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 22 TC 17 Z9 18 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 JUL 1 PY 2002 VL 100 IS 1 BP 341 EP 343 DI 10.1182/blood.V100.1.341 PG 3 WC Hematology SC Hematology GA 567GQ UT WOS:000176477400047 PM 12070046 ER PT J AU Nash, HA AF Nash, HA TI In vivo genetics of anaesthetic action SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE anaesthetics, volatile; Caenorhabditis elegans; Danio rerio; Drosophila melanogaster, genetic factors; ions, ion channels; membrane, ABC transporters; membrane, stomatin; membrane, syntaxin; Mus musculus ID VOLATILE GENERAL-ANESTHETICS; MEYER-OVERTON RULE; CAENORHABDITIS-ELEGANS; DROSOPHILA-MELANOGASTER; GABA(A) RECEPTOR; A RECEPTOR; ION CHANNELS; SYNAPTIC TRANSMISSION; MOUSE HIPPOCAMPUS; KNOCKOUT MICE C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Nash, HA (reprint author), NIMH, Mol Biol Lab, Bldg 36 Room 1B08,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 98 TC 20 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JUL PY 2002 VL 89 IS 1 BP 143 EP 155 DI 10.1093/bja/aef159 PG 13 WC Anesthesiology SC Anesthesiology GA 573JE UT WOS:000176825400013 PM 12173226 ER PT J AU Falk, RT Fears, TR Hoover, RN Pike, MC Wu, AH Nomura, AMY Kolonel, LN West, DW Ziegler, RG AF Falk, RT Fears, TR Hoover, RN Pike, MC Wu, AH Nomura, AMY Kolonel, LN West, DW Ziegler, RG TI Does place of birth influence endogenous hormone levels in Asian-American women? SO BRITISH JOURNAL OF CANCER LA English DT Article DE Asian-American; oestrogen; androgen; breast cancer; migration ID BREAST-CANCER RISK; LONG-TERM TREATMENT; ONE-YEAR PERIOD; POSTMENOPAUSAL WOMEN; JAPANESE WOMEN; NORMAL BRITISH; ESTRONE SULFATE; DEHYDROEPIANDROSTERONE-SULFATE; PLASMA DEHYDROEPIANDROSTERONE; INTERLABORATORY CONCORDANCE AB In 1983-87, we conducted a population-based case-control study of breast cancer in Asian women living in California and Hawaii, in which migration history (a composite of the subject's place of birth, usual residence in Asia (urban/rural), length of time living in the West, and grandparents' place of birth) was associated with a six-fold risk gradient that paralleled the historical differences in incidence rates between the US and Asian countries. This provided the opportunity to determine whether endogenous hormones vary with migration history in Asian-American women. Plasma obtained from 316 premenopausal and 177 naturally premenopausal study controls was measured for levels of estrone (EI), estradiol (E2), estrone sulphate (EIS), androstenedione (A), testosterone (T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), progesterone (PROG) and sex hormone-binding globulin (SHBG), Levels of the oestrogens and sex hormone-binding globulin did not differ significantly between Asian- and Westem-born women, although among premenopausal women, those least westernised had the lowest levels of El, E2, and EIS. Androgen levels, particularly DHEA, were lower in women born in the West. Among premenopausal women, age-adjusted geometric mean levels of DHEA were 16.5 and 13.8 nmol l(-1) in Asian- and Western-born women respectively; in postmenopausal women these values were 1 1.8 and 9.2 nmol l(-1), (P<0.001) respectively. Among postmenopausal women, androgens tended to be highest among the least westernised women and declined as the degree of westernisation increased. Our findings suggest that aspects of hormone metabolism play a role in population differences in breast cancer incidence. (C) 2002 Cancer Research UK. C1 NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA. Univ Hawaii, Program Epidemiol, Canc Res Ctr Hawaii, Honolulu, HI 96817 USA. No Calif Canc Ctr, Union City, CA 94587 USA. RP Falk, RT (reprint author), NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd MSC-7234,Suite 7070, Bethesda, MD 20892 USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 53 TC 18 Z9 18 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL 1 PY 2002 VL 87 IS 1 BP 54 EP 60 DI 10.1038/sj.bjc.6600339 PG 7 WC Oncology SC Oncology GA 574FQ UT WOS:000176878400010 PM 12085256 ER PT J AU Shelby, RA Taylor, KL Kerner, JF Coleman, E Blum, D AF Shelby, RA Taylor, KL Kerner, JF Coleman, E Blum, D TI The role of community-based and philanthropic organizations in meeting cancer patient and caregiver needs SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID CARE NEEDS; PALLIATIVE CARE; UNMET NEEDS; FOLLOW-UP; FAMILIES; HOME; DETERMINANTS; PENNSYLVANIA; PREVENTION; DISEASE AB We examined information from community-based and philanthropic organizations to document the cancer-related services that are currently available, establish which services are still needed, and determine who utilizes these formal support networks. In Phase 1, 32 of 41 eligible organizations participated in a survey conducted from December 1999 to March 2000. The most common mission focus among participating organizations was information/referral-centered. The most common services provided were referrals to information resources and provision of cancer-related information, Only two of the organizations in Phase 1 provided client demographic information and both indicated that client populations were predominantly white, female, and over age 40, Phase 11 of the study involved analyzing patient data from Cancer Care, Inc., a national service organization for cancer patients. Between 1983 and 1997, there were 2,714 prostate cancer patients and 9,451 breast cancer patients included in the Cancer Care database. Their most commonly reported problems were related to personal adjustment to illness, financial, home care, and transportation needs. There were significant differences in problems reported depending upon age and disease status. In addition, the results of this study support the idea that those at highest risk for developing and dying of cancer are the least likely to utilize formal support networks, Further, a gap in service provision for assistance with practical needs (e.g., transportation, home care, child care, psychosocial support) was identified. Due to the increasing use of outpatient care for cancer patients, a greater demand for practical assistance can be expected in the future. The availability of practical services will need to be increased in order to effectively meet cancer patient needs. C1 Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Div Canc Control, Washington, DC 20007 USA. NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD USA. Canc Care Inc, New York, NY USA. RP Shelby, RA (reprint author), Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. FU NCI NIH HHS [K07-CA72645] NR 54 TC 34 Z9 35 U1 1 U2 2 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 JUL-AUG PY 2002 VL 52 IS 4 BP 229 EP 246 PG 18 WC Oncology SC Oncology GA 574QY UT WOS:000176902100004 PM 12139234 ER PT J AU Elkahloun, AG Gaudet, J Robinson, GS Sgroi, DC AF Elkahloun, AG Gaudet, J Robinson, GS Sgroi, DC TI In situ gene expression analysis of cancer using loser capture microdissection, Microarrays and real time quantitative PCR SO CANCER BIOLOGY & THERAPY LA English DT Review DE laser capture microdissection; gene expression; microarrays; real-time quantitative PCR ID BREAST-CANCER; MOLECULAR ANALYSIS; CDNA MICROARRAYS; EPITHELIAL-CELLS; MESSENGER-RNA; LASER; CARCINOMA; PATTERNS; HYBRIDIZATION; PROFILES AB The simultaneous development of laser capture microdissection (LCM) and high-throughput mRNA analysis platforms has provided a significant technological advance in the world of cancer biology. The combination of such technologies provides a unique and powerful opportunity to directly assess the in situ molecular genetic events that are associated with initiation and progression of human malignancies. Despite these technological advances, the integration of LCM with high-throughput gene expression analysis has been met with various challenges. The goal of this review is to highlight some of the obstacles that we have faced and continue to face as we try to optimally apply LCM to in situ gene expression analysis. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Pharmacia Corp, St Louis, MO 63198 USA. RP Sgroi, DC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Charlestown Navy Yard, Boston, MA 02129 USA. NR 36 TC 22 Z9 23 U1 0 U2 1 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 JUL-AUG PY 2002 VL 1 IS 4 BP 354 EP 358 PG 5 WC Oncology SC Oncology GA 645TW UT WOS:000180996300006 PM 12432245 ER PT J AU Velasco, A Albert, PS Rosenberg, H Martinez, C Leach, FS AF Velasco, A Albert, PS Rosenberg, H Martinez, C Leach, FS TI Clinicopathologic implications of hMSH2 gene expression and microsatellite instability in prostate cancer SO CANCER BIOLOGY & THERAPY LA English DT Article DE hMSH2 gene expression; microsatellite instability; prostate cancer; mismatch repair ID NONPOLYPOSIS COLORECTAL-CANCER; DNA MISMATCH REPAIR; CARCINOMA; MORTALITY; DEFECTS; STAGE; PROGRESSION; DIAGNOSIS; MUTATIONS; SURVIVAL AB Human mismatch repair (MMR) genes encode highly conserved interacting proteins that correct replication errors predisposing to hereditary gastrointestinal and genitourinary malignancies. We previously investigated expression of the prototype MMR gene hMSH2 in normal, benign prostatic hyperplasia and malignant prostate tissues (Velasco et al., Cancer 94:690-699, 2002). An association was detected between reduced. hMSH2 staining and favorable outcome as determined by undetectable serum prostate specific antigen (PSA) after radical prostatectomy. We now investigate the association between clinicopathological variables and hMSH2 expression or microsatellite instability (MSI). A statistically significant association was found between tumors exhibiting MSI (MSI+ tumors) and lower preoperative serum PSA values, smaller tumor volumes and lower frequency of surgical specimens with extracapsular extension of tumor. No statistically of significant association (P value less than or equal to 0.05) was found between hMSH2 staining and these clinicopathologic variables. Based on our analysis, we conclude that MMR deficiency has important clinicopathologic implications in prostate cancer. Furthermore, specific MMR genes may have different effects on prostate cancer biology. C1 Catholic Univ Chile, Dept Urol, Santiago, Chile. Catholic Univ Chile, Dept Pathol, Santiago, Chile. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Leach, FS (reprint author), Scott Dept Urol, 6560 Fannin St,Suite 2100, Houston, TX 77030 USA. NR 43 TC 13 Z9 13 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 JUL-AUG PY 2002 VL 1 IS 4 BP 362 EP 367 PG 6 WC Oncology SC Oncology GA 645TW UT WOS:000180996300008 PM 12432247 ER PT J AU Blagosklonny, MV Darzynkiewicz, Z Figg, WD AF Blagosklonny, MV Darzynkiewicz, Z Figg, WD TI Flavopiridol inversely affects p21(WAF1/CIP1) and p53 and protects p21-sensitive cells from paclitaxel SO CANCER BIOLOGY & THERAPY LA English DT Article DE flavopiridol; paclitaxel; p53; p21 ID BREAST-CANCER CELLS; DEPENDENT KINASE MODULATORS; INHIBITOR-INDUCED APOPTOSIS; CARCINOMA CELLS; LEUKEMIA-CELLS; GROWTH ARREST; PHORBOL ESTER; CYCLE ARREST; CHECKPOINT; AGENTS AB Resting cells are relatively resistant to microtubule-active drugs including paclitaxel (PTX). By causing p53-mediated arrest, pretreatment with low concentrations of doxorubicin (DOX) protected HCT116 cells from the cytotoxicity caused by PTX. Unlike DOX, flavopiridol (FL) did not protect HCT116 cells. Low concentrations of FL (50 nM) induced p21 but not p53. High concentrations of FL (500 nM) decreased levels of p21 and Mdm-2 but dramatically induced p53. Thus, FL reciprocally affects p21 and p53. In LNCaP, a prostate cancer cell line which is highly sensitive to p21-induced growth arrest (p21-sensitive), low concentrations of FL (50 nM) induced p21 (without induction of p53) and caused G1 and G2 arrest. This precluded mitotic arrest, Bcl-2 and Raf-1 phosphorylation, and diminished cell death caused by PTX. In contrast, FL did not protect PC3M, arrest-resitant and highly aggressive prostate cancer cells. Like LNCaP, HL60 and SKBr3 cells are known to be p21-sensitive. As predicted, low concentrations of FL antagonized PTX-mediated cytotoxicity in HL60 and SKBr3 cell lines. In summary, only low concentrations of FL can induce p21, and, in turn, only p21-sensitive cells are protected from PTX. C1 New York Med Coll, Branch Canc Res Inst, Hawthorne, NY 10532 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Blagosklonny, MV (reprint author), New York Med Coll, Branch Canc Res Inst, 19 Bradhurst Ave, Hawthorne, NY 10532 USA. RI Figg Sr, William/M-2411-2016; OI Darzynkiewicz, Zbigniew/0000-0002-2040-7081 FU NCI NIH HHS [R01 CA028704, R01 CA028704-25] NR 56 TC 23 Z9 23 U1 0 U2 1 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 JUL-AUG PY 2002 VL 1 IS 4 BP 420 EP 425 PG 6 WC Oncology SC Oncology GA 645TW UT WOS:000180996300020 PM 12432259 ER PT J AU Pollock, PM Meltzer, PS AF Pollock, PM Meltzer, PS TI A genome-based strategy uncovers frequent BRAF mutations in melanoma SO CANCER CELL LA English DT Article ID TUMOR-SUPPRESSOR; GENE; RAS; MELANOCYTES C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Pollock, PM (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NR 11 TC 90 Z9 93 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUL PY 2002 VL 2 IS 1 BP 5 EP 7 DI 10.1016/S1535-6108(02)00089-2 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599UA UT WOS:000178352500003 PM 12150818 ER PT J AU Kawakami, K Kawakami, M Husain, SR Puri, RK AF Kawakami, K Kawakami, M Husain, SR Puri, RK TI Targeting interleukin-4 receptors for effective pancreatic cancer therapy SO CANCER RESEARCH LA English DT Article ID PSEUDOMONAS EXOTOXIN; MONOCLONAL-ANTIBODY; COLORECTAL-CANCER; CARCINOMA-CELLS; MANAGEMENT; PROTEIN; 4-TOXIN; TOXIN AB We demonstrate that pancreatic cancer tissues express receptors for interleukin (IL)-4 in situ at high density. Using the approach of selective receptor targeting, we have tested the efficacy of a recombinant cytotoxin IL4-Pseudomonas exotoxin A, which is composed of a targeting moiety (IL-4) and a mutated form of Pseudomonas exotoxin. Our results demonstrate that this molecule exerts vigorous antitumor activity against human pancreatic tumors implanted s.c. in immunodeficient animals. Sixty percent of animals treated with intratumoral injections of IL4-Pseudomonas exotoxin A experienced complete disappearance of established tumors. Animals with pancreatic tumors implanted orthotopically exhibited prolonged survival that was significantly greater by comparison with untreated animals. Thus, IL-4 receptor-targeted cytotoxin represents a potent agent that may provide an effective therapy for pancreatic cancer. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therap, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therap, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 20 TC 32 Z9 33 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 JUL 1 PY 2002 VL 62 IS 13 BP 3575 EP 3580 PG 6 WC Oncology SC Oncology GA 569BL UT WOS:000176579500001 PM 12097255 ER PT J AU Wang, E Miller, LD Ohnmacht, GA Mocellin, S Perez-Diaz, A Petersen, D Zhao, YD Simon, R Powell, JI Asaki, E Alexander, HR Duray, PH Herlyn, M Restifo, NP Liu, ET Rosenberg, SA Marincola, FM AF Wang, E Miller, LD Ohnmacht, GA Mocellin, S Perez-Diaz, A Petersen, D Zhao, YD Simon, R Powell, JI Asaki, E Alexander, HR Duray, PH Herlyn, M Restifo, NP Liu, ET Rosenberg, SA Marincola, FM TI Prospective molecular profiling of melanoma metastases suggests classifiers of immune responsiveness SO CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; RESPONSES; CELLS; IRF-1 AB We amplified RNAs from 63 tine needle aspiration (FNA) samples from 37 s.c. melanoma metastases from 25 patients undergoing immunotherapy for hybridization to a 6108-gene human cDNA chip. By prospectively following the history of the lesions, we could correlate transcript patterns with clinical outcome. Cluster analysis revealed a tight relationship among autologous synchronously sampled tumors compared with unrelated lesions (average Pearson's r = 0.83 and 0.7, respectively, P < 0.0003). As reported previously, two subgroups of metastatic melanoma lesions were identified that, however, had no predictive correlation with clinical outcome. Ranking of gene expression data from pretreatment samples identified similar to30 genes predictive of clinical response (P < 0.001). Analysis of their annotations denoted that approximately half of them were related to T-cell regulation, suggesting that immune responsiveness might be predetermined by a tumor microenvironment conducive to immune recognition. C1 NCI, Ctr Clin, Immunogenet Sect, Dept Transfus Med,NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. NCI, Ctr Informat Technol, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, NIH, Gaithersburg, MD 20877 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. RP Marincola, FM (reprint author), NCI, Ctr Clin, Immunogenet Sect, Dept Transfus Med,NIH, Bldg 10,Room 1C711,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; Liu, Edison/C-4141-2008; Miller, Lance/A-5633-2009; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 20 TC 193 Z9 198 U1 1 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 JUL 1 PY 2002 VL 62 IS 13 BP 3581 EP 3586 PG 6 WC Oncology SC Oncology GA 569BL UT WOS:000176579500002 PM 12097256 ER PT J AU Zeng, G Li, Y El-Gamil, M Sidney, J Sette, A Wang, RF Rosenberg, SA Robbins, PF AF Zeng, G Li, Y El-Gamil, M Sidney, J Sette, A Wang, RF Rosenberg, SA Robbins, PF TI Generation of NY-ESO-1-specific CD4+and CD8+T cells by a single peptide with dual MHC class I and class II specificities: A new strategy for vaccine design SO CANCER RESEARCH LA English DT Article ID TESTIS ANTIGEN NY-ESO-1; CD4(+) T-CELLS; METASTATIC MELANOMA; IMMUNE-RESPONSE; DENDRITIC CELLS; EPITOPES; IDENTIFICATION; LYMPHOCYTES; INDUCTION; MOLECULES AB The existence of overlapping CD8+ and CD4+ T-cell epitopes within certain tumor antigens provides an opportunity to test the hypothesis that relatively short peptides could be used to generate both CD8+ and CD4+ T cells against tumor. In this report, T-cell responses to a fragment of the tumor antigen NY-ESO-1 that contained an HLA-DP4-restricted helper T cell epitope as well as an HLA-A2-restricted cytotoxic T cell epitope were analyzed. One peptide, ESO:157-170 (SLLMWITQCFLPVF) was recognized by both NY-ESO-1-reactive CD8+ and CD4+ T-cell clones. Both CD4+ and CD8+ T cells were efficiently generated from the peripheral blood of multiple melanoma patients after is vitro stimulations using ESO:157-170. Dual-specific peptides containing both cytotoxic T-cell and helper T-cell epitopes may represent an attractive strategy of vaccine design aimed at generating tumor-reactive CD4+ and CD8+ T cells. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Epimmune Inc, San Diego, CA 92121 USA. Baylor Coll Med, Ctr Gene & Cell Therapy, Houston, TX 77030 USA. RP Zeng, G (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC003811-33] NR 26 TC 82 Z9 88 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2002 VL 62 IS 13 BP 3630 EP 3635 PG 6 WC Oncology SC Oncology GA 569BL UT WOS:000176579500011 PM 12097265 ER PT J AU Kim, IY Seong, DW Kim, BC Lee, DK Remaley, AT Leach, F Morton, RA Kim, SJ AF Kim, IY Seong, DW Kim, BC Lee, DK Remaley, AT Leach, F Morton, RA Kim, SJ TI Raloxifene, a selective estrogen receptor modulator, induces apoptosis in androgen-responsive human prostate cancer cell line LNCaP through an androgen-independent pathway SO CANCER RESEARCH LA English DT Article ID POSTMENOPAUSAL WOMEN; TRIAL; BETA; EXPRESSION; LIGAND; DEATH; RISK AB Raloxifene, a selective estrogen receptor (ER) modulator, is a mixed estrogen agonist/antagonist that has been shown to prevent osteoporosis and breast cancer in women. Because the prostate contains a high level of ER-beta, the present study investigated the effect of raloxifene in the androgen-sensitive human prostate cancer cell line LNCaP. Previously, it has been demonstrated that LNCaP cells express ER-beta but not ER-alpha and that tamoxifene induces apoptosis in these cells. After treatment with raloxifene, a dramatic increase in cell death occurred in a dose-dependent manner (10(-9) to 10(-6) M range). Using the terminal deoxynucleotidyl transferase-mediated nick end labeling apoptotic assay, we demonstrated that the nuclear fragmentation was due to apoptosis. The dramatic change in cellular morphology after treatment with raloxifene was no longer observed when cells were pretreated with a pan-caspase inhibitor, Z-VAD-FMK, and a specific caspase-9 inhibitor, Z-LEHD-FMK. Furthermore, immunoblot demonstrated an activation of caspase-9 in LNCaP cells. Because LNCaP cells contain a mutated androgen receptor that allows cellular proliferation in the presence of antiandrogens, prostate-specific antigen assay and transfection with a reporter construct containing luciferase gene under the control of androgen response element (PARE) were carried out. The results demonstrated that raloxifene does not significantly alter androgen receptor activity in LNCaP cells. Taken together, these results demonstrate that raloxifene, a selective ER modulator, induces apoptosis in the androgen-sensitive human prostate cancer cell line LNCaP through an androgen-independent pathway. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. RP Kim, SJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room C629,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 50 Z9 52 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2002 VL 62 IS 13 BP 3649 EP 3653 PG 5 WC Oncology SC Oncology GA 569BL UT WOS:000176579500015 PM 12097269 ER PT J AU Ciolino, HP MacDonald, CJ Yeh, GC AF Ciolino, HP MacDonald, CJ Yeh, GC TI Inhibition of carcinogen-activating enzymes by 16 alpha-fluoro-5-androsten-17-one SO CANCER RESEARCH LA English DT Article ID ARYL-HYDROCARBON RECEPTOR; DEHYDROEPIANDROSTERONE DHEA; BREAST-CANCER; SPONTANEOUS TUMORIGENESIS; MAMMARY-CARCINOMA; MICE; RAT; DNA; CELLS; CHEMOPREVENTION AB In the present study, we examined the effect of a synthetic analogue of the chemopreventive hormone dehydroepiandrosterone, 16alpha-fluoro-5-androsten-17-one, also known as fluasterone, on the activity and expression of carcinogen-activating enzymes in MCF-7 cells. The increase in cytochrome P450 (CYP) 1A1 and 1B1 activity, as measured by ethoxyresorufin-O-deethylase activity, in cells treated with the carcinogens dimethylbenzanthracene (DMBA) or 2,3,5,7-tetrachlorodibenzopdioxin (TCDD), was inhibited by cotreatment with fluasterone. However, treatment of the cells with fluasterone after induction with DMBA or TCDD failed to decrease enzyme activity, indicating that inhibition was not the result of direct enzyme inhibition. Therefore, we examined the effect of fluasterone on gene expression at the mRNA level. Both DMBA and TCDD caused a dramatic increase in the amount of CYP1A1 and CYP1B1 mRNA, the two major isoforms involved in carcinogen activation in these cells. In cells cotreated with fluasterone, however, there was a dose-dependent decrease in CYP1A1 and CYP1B1 mRNA. Fluasterone also inhibited the basal level of CYP1A1 mRNA but not CYP1B1. Fluasterone inhibited the rate of CYP1A1 promoter-controlled transcription, indicating that it affects the transcriptional regulation of the gene. Actinomycin D chase experiments showed that fluasterone also caused an increase in the degradation of CYP1A1 mRNA, while leaving CYP1B1 mRNA unaffected. These results indicate that fluasterone inhibits the increase in the expression of CYP1A1 normally caused by exposure to carcinogens by both transcriptional and post-transcriptional mechanisms and that CYP1B1 expression is not susceptible to the same post-transcriptional mechanism. C1 NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Cellular Def & Carcinogenesis Sect,NIH, Frederick, MD 21702 USA. RP Ciolino, HP (reprint author), NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Cellular Def & Carcinogenesis Sect,NIH, Bldg 560,Room 12-05, Frederick, MD 21702 USA. NR 37 TC 9 Z9 9 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 JUL 1 PY 2002 VL 62 IS 13 BP 3685 EP 3690 PG 6 WC Oncology SC Oncology GA 569BL UT WOS:000176579500021 PM 12097275 ER PT J AU Goebel, SU Iwamoto, M Raffeld, M Gibril, F Hou, W Serrano, J Jensen, RT AF Goebel, SU Iwamoto, M Raffeld, M Gibril, F Hou, W Serrano, J Jensen, RT TI HER-2/neu expression and gene amplification in gastrinomas: Correlations with tumor biology, growth, and aggressiveness SO CANCER RESEARCH LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; COMPARATIVE GENOMIC HYBRIDIZATION; PANCREATIC ENDOCRINE TUMORS; PAPILLARY THYROID CARCINOMAS; POLYMERASE-CHAIN-REACTION; HUMAN-BREAST-CANCER; C-ERBB-2 PROTEIN EXPRESSION; EPITHELIAL OVARIAN-CANCER; HUMAN PITUITARY-TUMORS; PROGNOSTIC VALUE AB A proportion of gastrointestinal neuroendocrine tumors are aggressive; however, little is known of molecular determinants of their growth, and molecular studies have identified no useful prognostic factors. Overexpression of HER-2/neu is common in some nonendocrine tumors, frequently correlates with increased tumor aggressiveness, and can be used as a basis of treatment with trastuzumab. Little is known of its expression in malignant pancreatic endocrine tumors. In the present study HER-2/neu gene amplification and expression was determined in 43 gastrinomas from different patients. Results were correlated with clinical, laboratory, and tumor characteristics including tumor growth. HER-2/neu gene amplification was assessed by differential PCR, mRNA levels assessed by quantitative PCR, and protein by immunohistochemistry. Fourteen percent of patients had HER-2/neu gene amplification in tumors compared with levels in their WBCs. HER-2/neu mRNA varied over a 700-fold range. However, only 3% exceeded levels seen in normal pancreas, and immunohistochemistry did not show protein overexpression in any tumor (n = 10). HER-2/neu mRNA levels were significantly higher (P = 0.032) in tumors associated with liver metastases but not with tumor location or size. These results show that HER-2/neu amplification/overexpression does not seem to play a role in the molecular pathogenesis of most gastrinomas, as suggested in a previous study, involving small numbers of cases. However, mild gene amplification occurs in a subset, and overexpression is associated with aggressiveness. Therefore, HER-2/neu levels could have prognostic significance as well as identify a patient subset with gastrinomas who might benefit from trastuzumab treatment. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. NR 92 TC 45 Z9 47 U1 0 U2 1 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 JUL 1 PY 2002 VL 62 IS 13 BP 3702 EP 3710 PG 9 WC Oncology SC Oncology GA 569BL UT WOS:000176579500024 PM 12097278 ER PT J AU Pereira, MA Li, YZ Gunning, WT Kramer, PM Al-Yaqoub, F Lubet, RA Steele, VE Szabo, E Tao, LH AF Pereira, MA Li, YZ Gunning, WT Kramer, PM Al-Yaqoub, F Lubet, RA Steele, VE Szabo, E Tao, LH TI Prevention of mouse lung tumors by budesonide and its modulation of biomarkers SO CARCINOGENESIS LA English DT Article ID DEPENDENT KINASE INHIBITOR; CELL NUCLEAR ANTIGEN; FEMALE A/J MICE; ARCHIVAL RODENT TISSUES; PULMONARY CARCINOGENESIS; PROGNOSTIC-SIGNIFICANCE; C/EBP-ALPHA; CANCER; CHEMOPREVENTION; PROLIFERATION AB Chemopreventive drugs have the potential to decrease the morbidity and mortality of lung cancer. The development of these drugs could be expedited by the application of surrogate end-point biomarkers that demonstrate chemopreventive efficacy. In this study, the ability of budesonide to prevent lung tumors in mice was characterized further and its effects on biomarkers were determined. Lung tumors were induced in female strain A mice by vinyl carbamate (16 mg/kg) administered once weekly for 2 consecutive weeks. Four weeks later the mice started to receive 0.6, 1.2 or 2.4 mg/kg budesonide continually in the diet until killed at week 20. Budesonide caused a dose-dependent decrease in the multiplicity of lung tumors of 25, 58 and 82%, respectively. Budesonide (2.4 mg/kg diet) administered starting at weeks 4, 10 or 16, decreased tumor multiplicity by 82, 66 and 30% at week 20. Administering 2.4 mg/kg budesonide at weeks 4-20 or 20-35 and killing the mice at week 35 did not significantly decrease the yield of tumors, although both treatment regimens did decrease the size of the tumors and the progression of adenomas to carcinomas. Thus, budesonide delayed the appearance of lung tumors and decreased their growth and progression to carcinomas. To determine the effect of limited exposure to budesonide on biomarkers, it was administered for only 7 days prior to death at week 35. Budesonide decreased the proliferating cell nuclear antigen labeling in lung adenomas, carcinomas, parenchyma and bronchial airways by 87.6, 59.0, 41.1 and 25.4%, respectively. Budesonide treatment also increased the protein level of the p21 and p27 genes and increased the mRNA level of p21. Thus, short-term treatment with budesonide modulated biological and molecular end-points in lung tumors that might be developed further as biomarkers for its clinical chemopreventive efficacy in the lung. C1 Med Coll Ohio, HEB, Dept Pathol, Toledo, OH 43614 USA. NCI, Div Canc Chemoprevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Pereira, MA (reprint author), Med Coll Ohio, HEB, Dept Pathol, Room 200F,3055 Arlington Ave, Toledo, OH 43614 USA. RI Gunning, William/E-4681-2010 FU NCI NIH HHS [N01 CN 95107] NR 35 TC 48 Z9 48 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 JUL PY 2002 VL 23 IS 7 BP 1185 EP 1192 DI 10.1093/carcin/23.7.1185 PG 8 WC Oncology SC Oncology GA 574VR UT WOS:000176910700013 PM 12117777 ER PT J AU Kang, Y Ozbun, LL Angdisen, J Moody, TW Prentice, M Diwan, BA Jakowlew, SB AF Kang, Y Ozbun, LL Angdisen, J Moody, TW Prentice, M Diwan, BA Jakowlew, SB TI Altered expression of G1/S regulatory genes occurs early and frequently in lung carcinogenesis in transforming growth factor-beta 1 heterozygous mice SO CARCINOGENESIS LA English DT Article ID CYCLIN D1 OVEREXPRESSION; SQUAMOUS-CELL CARCINOMA; LASER CAPTURE MICRODISSECTION; TGF-BETA; TUMOR-SUPPRESSOR; II RECEPTOR; NONSMALL CELL; CANCER-CELLS; MOUSE; INHIBITION AB We developed the AJBL6 transforming growth factor-beta 1 (TGF-beta1) heterozygous (HT) mouse by mating A/J mice with C57BL/6 TGF-beta1 HT mice that shows increased carcinogen-induced lung lesions with decreased latency to examine progressive events in lung tumorigenesis. Mouse cDNA macroarrays were used to identify cell cycle genes that are differentially regulated in ethyl carbamate-induced lung adenocarcinomas compared with normal lung tissue in AJBL6 TGF-beta1 HT mice using probes that were generated from tissues isolated using laser capture microdissection. While expression of the genes for cyclin D1, CDK4, and E2F1 increased in lung adenocarcinomas relative to normal lung, expression of p15(Ink4b), p16(Ink4a), p21(Cip1), p27(Kip1), p57(Kip2), and pRb genes decreased in comparison. Competitive RT-PCR showed that the levels of cyclin D1 and CDK4 mRNAs were 2- and 3-fold higher, respectively, in lung adenocarcinomas than in normal lung, while the mRNAs for p15(Ink4b), p16(Ink4a), p21(Cip1), p27(Kip1), and pRb were 3- to 4-fold lower in adenocarcinomas than in normal lung, thus validating the macroarray findings. Competitive RT-PCR of microdissected lesions also showed that the levels of cyclin D1 and CDK4 mRNAs increased significantly, while the mRNAs for p15(Ink4b) and p27(Kip1) decreased significantly as lung tumorigenesis progressed. Immunohistochemical staining for cyclin D1 and CDK4 showed staining in >80% of nuclei in adenocarcinomas compared with fewer than 20% of nuclei staining positively in normal lung. In contrast, while >60% of normal lung cells showed immunostaining for p15(Ink4b), p16(Ink4a), p21(Cip1), p27(Kip1), and pRb, staining for these proteins decreased in hyperplasias, adenomas, and adenocarcinomas. These data show that multiple components of the cyclin D1/CDK4/p16(Ink4a)/pRb signaling pathway are frequently altered early in lung lesions of AJBL6 TGF-beta1 HT mice that are induced by ethyl carbamate as a function of progressive lung carcinogenesis, suggesting that components of this pathway may be potential targets for gene therapy. C1 NCI, Cell & Canc Biol Branch, Rockville, MD 20850 USA. SAIC Frederick, Intramural Support Program, Frederick, MD 21702 USA. RP Jakowlew, SB (reprint author), NCI, Cell & Canc Biol Branch, Rockville, MD 20850 USA. NR 63 TC 16 Z9 19 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 2002 VL 23 IS 7 BP 1217 EP 1227 DI 10.1093/carcin/23.7.1217 PG 11 WC Oncology SC Oncology GA 574VR UT WOS:000176910700017 PM 12117781 ER PT J AU Natesan, A Geetha, L Zatz, M AF Natesan, A Geetha, L Zatz, M TI Rhythm and soul in the avian pineal SO CELL AND TISSUE RESEARCH LA English DT Review DE pineal; melatonin; cireadian rhythms; entrainment; AA-NAT; phototransduction; birds ID SEROTONIN N-ACETYLTRANSFERASE; ACTIVATED PROTEIN-KINASE; CHICK PINEAL; CIRCADIAN CLOCK; MELATONIN RHYTHM; PHOTOENDOCRINE TRANSDUCTION; MESSENGER-RNA; MAP KINASE; SUPRACHIASMATIC NUCLEUS; MOLECULAR ANALYSIS AB The avian pineal gland, like that of mammals, displays a striking circadian rhythm in the synthesis and release of the hormone melatonin. However, the pineal gland plays a more prominent role in avian circadian organization and differs from that in mammals in several ways. One important difference is that the pineal gland in birds is relatively autonomous. In addition to making melatonin, the avian pineal contains photoreceptors and a circadian clock (thus, an entire circadian system) within itself. Furthermore, avian pineals retain their circadian properties in organ or dispersed cell culture, making biochemical components of regulatory pathways accessible. Avian pinealocytes are directly photosensitive, and novel candidates for the unidentified photopigments involved in the regulation of clock function and melatonin production, including melanopsin, pinopsin. iodopsin, and the cryptochromes, are being evaluated. Transduction pathways and second messengers that may be involved in acute and entraining effects, including cyclic nucleotides, calcium fluxes, and protein kinases, have been, and continue to be, examined. Moreover, several clock genes similar to those found in Drosophila and mouse are expressed, and their dynamics and interactions are being studied. Finally, the bases for acute and clock regulation of the key enzyme in melatonin synthesis, arylalkylamine N-acetyltransferase (AA-NAT), are described. The ability to study entrainment, the oscillator itself, and a physiological output in the same tissue at the same time makes the avian pineal gland an excellent model to study the bases and regulation of circadian rhythms. C1 NIMH, Sect Biochem Pharmacol, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Natesan, A (reprint author), NIMH, Sect Biochem Pharmacol, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. NR 97 TC 46 Z9 50 U1 1 U2 7 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD JUL PY 2002 VL 309 IS 1 SI SI BP 35 EP 45 DI 10.1007/s00441-002-0571-6 PG 11 WC Cell Biology SC Cell Biology GA 574QL UT WOS:000176901000005 PM 12111535 ER PT J AU Ganguly, S Coon, SL Klein, DC AF Ganguly, S Coon, SL Klein, DC TI Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation SO CELL AND TISSUE RESEARCH LA English DT Review DE pineal gland; melatonin; arylalkylamine N-acetyltransferase; circadian; second messenger; signal transduction ID ARYLALKYLAMINE N-ACETYLTRANSFERASE; PROTEIN KINASE-C; HYDROXYINDOLE-O-METHYLTRANSFERASE; PARAVENTRICULAR NUCLEUS AREA; BETA-ADRENERGIC STIMULATION; CYCLIC-AMP RESPONSE; RAT PINEALOCYTES; SUPRACHIASMATIC NUCLEUS; PROTEASOMAL PROTEOLYSIS; CIRCADIAN EXPRESSION AB The large daily rhythm in circulating melatonin levels is a highly conserved feature of vertebrate physiology: high values always occur at night. The dynamics of the rhythm are controlled by the next-to-last enzyme in melatonin synthesis (serotonin --> N-acetylserotonin --> melatonin), arylalkylamine N-acetyltransferase (AANAT), the "melatonin rhythm enzyme". In vertebrate biology, AANAT plays a unique time-keeping role as the molecular interface between the environment and the hormonal signal of time, melatonin. This chapter describes the mammalian AANAT regulatory system, which includes the retina, neural structures, transsynaptic processes, and molecular events. In addition, special attention is paid to the functional characteristics of the systems which insure that the nocturnal increase in melatonin is an accurate and reliable indicator of the duration of the night, and why the melatonin rhythm is the most reliable output signal of the Mind's Clock. C1 NICHHD, NIH, Sect Neuroendocrinol, Dev Neurobiol Lab, Bethesda, MD 20892 USA. RP Klein, DC (reprint author), NICHHD, NIH, Sect Neuroendocrinol, Dev Neurobiol Lab, Bethesda, MD 20892 USA. NR 109 TC 148 Z9 153 U1 1 U2 17 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD JUL PY 2002 VL 309 IS 1 SI SI BP 127 EP 137 DI 10.1007/s00441-002-0579-y PG 11 WC Cell Biology SC Cell Biology GA 574QL UT WOS:000176901000013 PM 12111543 ER PT J AU Agarwal, R Cohen-Fix, O AF Agarwal, Ritu Cohen-Fix, Orna TI Mitotic Regulation The Fine Tuning of Separase Activity SO CELL CYCLE LA English DT Review DE Anaphase; Securin; Sister chromatid; separation AB Mitotic progression requires the dissolution of cohesion between sister chromatids. Cohesion is dissolved by an essential protease known as separase. Separase is highly conserved throughout evolution and is subjected to multiple levels of regulation. Here we discuss recent studies that unravel several key mechanisms for regulating separase activity. C1 [Agarwal, Ritu; Cohen-Fix, Orna] NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD USA. RP Cohen-Fix, O (reprint author), 8 Ctr Dr,Bldg 8,Room 319, Bethesda, MD 20892 USA. EM ornacf@helix.nih.gov NR 24 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD JUL-AUG PY 2002 VL 1 IS 4 BP 253 EP 255 DI 10.4161/cc.1.4.133 PG 3 WC Cell Biology SC Cell Biology GA V40PY UT WOS:000209491700006 ER PT J AU Lavigne, MC Murphy, PM Leto, TL Gao, JL AF Lavigne, MC Murphy, PM Leto, TL Gao, JL TI The N-formylpeptide receptor (FPR) and a second G(i)-coupled receptor mediate fMet-Leu-Phe-stimulated activation of NADPH oxidase in murine neutrophils SO CELLULAR IMMUNOLOGY LA English DT Article DE fMLF receptors; gene knockout; superoxide; signal transduction; G protein-coupled receptor ID FORMYL PEPTIDE RECEPTOR; PROTEIN-COUPLED RECEPTOR; INTERLEUKIN-8 RECEPTORS; SIGNAL-TRANSDUCTION; RESPIRATORY BURST; PHAGOCYTIC-CELLS; CHEMOTAXIS; CYTOSKELETON; PI3K-GAMMA; IL-8R1 AB N-Formylypeptides such as fMet-Leu-Phe (fMLF) potently induce superoxide production through NADPH oxidase activation. The receptors that mediate this response have not been defined. Here, we provide definitive proof using a mouse model that formyl peptide receptor (FPR) is a receptor, but not the only receptor, that mediates fMLF-induced oxidase activation. In wild-type (FPR+/+) mouse neutrophils, superoxide production is dependent on the concentration of fMLF with an EC50 of similar to5 muM and a peak at similar to50 muM. In contrast, FPR-deficierit (FPR-/-) mouse neutrophils produced markedly less superoxide with an EC50 of similar to50 muM and a peak at similar to200 muM. Yet, FPR+/+ and FPR-/- neutrophils showed similar oxidase activation kinetics and G(i) protein-dependent pharmacological sensitivities. These results suggested that a second receptor, likely FPR2, mediates superoxide production at high concentrations of fMLF. This less sensitive second pathway may permit continued oxidant generation in response to formyl peptides when FPR is desensitized in high concentrations of the chemotactic gradient. (C) 2002 Elsevier Science (USA). All rights reserved. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Gao, JL (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Rm 11N111, Bethesda, MD 20892 USA. NR 33 TC 18 Z9 19 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUL-AUG PY 2002 VL 218 IS 1-2 BP 7 EP 12 AR PII S0008-8749(02)00564-6 DI 10.1016/S0008-8749(02)00564-6 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 627XQ UT WOS:000179962300002 PM 12470609 ER PT J AU Eckert, MA Leonard, CM Molloy, EA Blumenthal, J Zijdenbos, A Giedd, JN AF Eckert, MA Leonard, CM Molloy, EA Blumenthal, J Zijdenbos, A Giedd, JN TI The epigenesis of planum temporale asymmetry in twins SO CEREBRAL CORTEX LA English DT Article ID MONOZYGOTIC TWINS; TRANSFUSION SYNDROME; SITUS-INVERSUS; HEMISPHERIC-ASYMMETRY; LANGUAGE IMPAIRMENT; BRAIN ASYMMETRIES; CEREBRAL-CORTEX; CROSSED APHASIA; CHILDREN; DYSLEXIA AB Variation in hemispheric asymmetry of the planum temporale (PT) has been related to verbal ability. The degree to which genetic and environmental factors mediate PT asymmetry is not known. This study examined the heritability for planar asymmetry in 12 dizygotic (DZ) and 27 monozygotic (MZ) male twin pairs who were between 6 and 16 years of age. There was weak but positive evidence for heritability of planar asymmetry. Co-twin similarity for planar asymmetry and Sylvian fissure morphology increased when excluding twins discordant for writing hand and when excluding twins exhibiting birth weight differences >20% from the analyses. Birth weight differences were also related to twin differences in total cerebral volume, but not central sulcus asymmetry. These results suggest that exogenous perinatal factors affect the epigenesis of planar asymmetry development. C1 Univ Florida, McKnight Brain Inst, Dept Neurosci, Gainesville, FL 32610 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. RP Eckert, MA (reprint author), Univ Florida, McKnight Brain Inst, Dept Neurosci, POB 100244, Gainesville, FL 32610 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 FU NIDCD NIH HHS [F32 DC00393-1, R03 DC005364-01A1, R03 DC005364] NR 63 TC 32 Z9 33 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUL PY 2002 VL 12 IS 7 BP 749 EP 755 DI 10.1093/cercor/12.7.749 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 562YT UT WOS:000176227100007 PM 12050086 ER PT J AU Davatzikos, C Resnick, SM AF Davatzikos, C Resnick, SM TI Degenerative age changes in white matter connectivity visualized in vivo using magnetic resonance imaging SO CEREBRAL CORTEX LA English DT Article ID ALZHEIMERS-DISEASE; TEXTURE ANALYSIS; BRAIN IMAGES; IN-VIVO; DEFORMATIONS; MRI; REGISTRATION; MORPHOMETRY; HIPPOCAMPUS; ATROPHY AB Age effects on the signal characteristics of white matter (WM) were examined via magnetic resonance imaging (MRI). Global and local patterns of WM degeneration were demonstrated using a new image analysis methodology. Significant cross-sectional and longitudinal age effects were found in the WM, primarily in the left hemisphere. Importantly, signal changes, which likely reflect WM demyelination, and changes in water, protein and mineral content of tissue, were unrelated to volumetric changes. Thus, measures of tissue characteristics provide unique and complementary information to widely used measures of brain atrophy. Moreover, signal measurements displayed stronger associations with age and can potentially be more sensitive than volumetric measures as indicators of preclinical disease, because they reflect changes in the underlying tissue composition. To our knowledge, our study is the first documentation of longitudinal age- and region-dependent changes in magnetic resonance signal characteristics of WM fibers, reflecting underlying degenerative effects of aging. C1 Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21287 USA. NIA, Lab Personal & Cognit, Baltimore, MD USA. RP Davatzikos, C (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol, JHOC 3230,601 N Caroline St, Baltimore, MD 21287 USA. FU NIA NIH HHS [AG-93-07, R01-AG14971] NR 31 TC 52 Z9 55 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUL PY 2002 VL 12 IS 7 BP 767 EP 771 DI 10.1093/cercor/12.7.767 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 562YT UT WOS:000176227100009 PM 12050088 ER PT J AU Wray, S AF Wray, S TI Molecular mechanisms for migration of placodally derived GnRH neurons SO CHEMICAL SENSES LA English DT Article ID HORMONE-RELEASING HORMONE; EXPRESSION; PERIPHERIN; SYSTEM; CELLS AB Gonadotropin-releasing hormone (GnRH) neurons, critical for reproduction, are derived from the nasal placode and migrate into the brain along nasal axons. GnRH neurons appear to diverge from olfactory sensory cells during early stages of nasal placode differentiation. However, GnRH neurons rely on olfactory/vomeronasal axons as their pathway to the central nervous system (CNS). A novel factor, termed nasal embryonic luteinizing hormone-releasing hormone factor (NELF), was discovered in a differential screen of migrating versus nonmigrating GnRH neurons. NELF is expressed in olfactory sensory cells and GnRH cells in nasal areas. Antisense experiments demonstrated that knock-down of NELF decreased olfactory axon outgrowth and GnRH neuronal migration. These results indicate that NELF plays a role as a guidance molecule for olfactory axon projections and migration of GnRH cells. We hypothesize that NELF acts via a homophilic interaction and that NELF expression is critical for reproduction by insuring that GnRH cells reach the CNS. Furthermore, down-regulation of NELF on GnRH cells as they enter the telencephalon may allow GnRH cells to distinguish a different pathway(s) in the CNS (from those leading to olfactory regions) and thereby facilitate establishment of the appropriate adult-like GnRH distribution. C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, Bldg 36,Room 5A-25, Bethesda, MD 20892 USA. OI wray, susan/0000-0001-7670-3915 NR 13 TC 19 Z9 20 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD JUL PY 2002 VL 27 IS 6 BP 569 EP 572 DI 10.1093/chemse/27.6.569 PG 4 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 577HN UT WOS:000177055600010 PM 12142333 ER PT J AU Marcus, PM AF Marcus, PM TI Lung cancer screening, once again SO CHEST LA English DT Editorial Material ID ACTION PROJECT C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Marcus, PM (reprint author), 6130 Execut Blvd,Suite 3131, Bethesda, MD 20892 USA. NR 14 TC 1 Z9 1 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2002 VL 122 IS 1 BP 3 EP 4 DI 10.1378/chest.122.1.3 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 575CG UT WOS:000176927900002 PM 12114327 ER PT J AU Stoller, JK Rouhani, F Brantly, M Shahin, S Dweik, RA Stocks, JA Clausen, J Campbell, E Norton, F AF Stoller, JK Rouhani, F Brantly, M Shahin, S Dweik, RA Stocks, JA Clausen, J Campbell, E Norton, F TI Biochemical efficacy and safety of a new pooled human plasma alpha(1)-antitrypsin, respitin SO CHEST LA English DT Article DE alpha(1)-antitrypsin deficiency; antiprotease; efficacy; safety ID AUGMENTATION THERAPY; DEFICIENCY; ELASTASE; INHIBITOR; DESMOSINE; EMPHYSEMA; DILUTION; COMPLEX; LAVAGE; URINE AB Background: Augmentation therapy with pooled human plasma-derived alpha(1)-antitrypsin (AAT) has been shown to have biochemical efficacy in restoring serum AAT levels above the protective threshold. Also, clinical efficacy has been suggested. Objective: To evaluate the bioequivalence of a new solvent detergent-treated preparation of pooled human plasma-derived AAT (proposed name Respitin; Alpha Therapeutic Corporation; Los Angeles, CA) to the commercially available preparation (Prolastin; Bayer Corporation; West Haven, CT), we conducted a randomized controlled trial. Methods: Eligible subjects were adults (>18 years of age) who had never smoked or were ex-smokers, had severe deficiency of AAT, and had fixed airflow obstruction (ie, postbroncholdilator FEV1 of 30 to 80% of predicted values and/or diffusing capacity of the lung for carbon monoxide [DLCO] Of < 70% of predicted values with evidence of emphysema on a CT scan). Of the, 28 subjects recruited, 26 completed the 12-week comparison. Participants were randomized to receive Respitin (60 mg/kg once weekly; 14 subjects) or Prolastin (60 mg/kg once weekly; 14 subjects), and recipients of Prolastin then crossed over to receive Respitin thereafter for the 24-week duration of the study. Results: The primary efficacy criteria were satisfied for equivalence to comparator (ie, the ratio of mean trough serum levels for Respitin/Prolastin at weeks 8 to 11 exceeded the efficacy, Criterion [0.905; p = 0.0206] as did the slope of the mean trough level over weeks 11 to 23 [- 0.003 μmol. per week]). In Respitin recipients, the trough serum antineutrophil elastase capacity at week 7 and at weeks 8 to 11 was also equivalent to the comparator, as was the rise in AAT levels in epithelial lining fluid from baseline to week 7. The levels of urinary elastin degradation products showed little appreciable change for > 24 weeks, and no difference between compared groups was shown through week 12. Adverse events were similarly infrequent in compared groups. Finally, neither spirometry measurements nor DLCO showed a significant change through 24 weeks. Conclusions: We conclude that this new solvent detergent-treated pooled human plasma-derived AAT (Respitin) demonstrates biochemical equivalence to Prolastin and that this new drug is well-tolerated. C1 Cleveland Clin Fdn, Dept Pulm & Crit Care Med, Cleveland, OH 44195 USA. NHLBI, Pulm Crit Care Branch, NIH, Bethesda, MD 20892 USA. Univ Florida, Coll Med, Gainesville, FL USA. Alpha Therapeut Corp, Los Angeles, CA USA. Univ Texas Hlth Ctr, Tyler, TX USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. RP Stoller, JK (reprint author), Cleveland Clin Fdn, Dept Pulm & Crit Care Med, A 90,9500 Euclid Ave, Cleveland, OH 44195 USA. NR 20 TC 43 Z9 45 U1 2 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 JUL PY 2002 VL 122 IS 1 BP 66 EP 74 DI 10.1378/chest.122.1.66 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 575CG UT WOS:000176927900014 PM 12114340 ER PT J AU Bhangoo, RK Leibenluft, E AF Bhangoo, RK Leibenluft, E TI Affective neuroscience and the study of normal and abnormal emotion regulation SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID FRONTAL BRAIN ASYMMETRY; VAGAL TONE; BIOLOGICAL SUBSTRATE; AFFECTIVE RESPONSES; AFFECTIVE STYLE; DEPRESSION; INFANTS; INHIBITION; ACTIVATION; MECHANISMS AB This article introduces the basic concepts of affective neuroscience and demonstrates how they can be applied to research on the normal development of the regulation of emotion. The discussion focuses on the biologic mechanisms mediating emotional processes and the regulation of emotion. The development of such mechanisms is influenced by endogenous and environmental factors. The most important environmental influences are the relationships with caregivers. This article describes techniques that call be used to identify the neural circuitry underlying the regulation of emotions and to study how such circuitry functions differently in patients with bipolar and other mood disorders than in control subjects. In particular, this article highlights research techniques of relevance to the study of childhood bipolar disorder. C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. RP Bhangoo, RK (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, Room 4N-208,NIMH Bldg 10,10 Ctr Dr,MCS 1255, Bethesda, MD 20892 USA. EM bhangoor@intra.nimh.nih.gov NR 49 TC 6 Z9 6 U1 10 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JUL PY 2002 VL 11 IS 3 BP 519 EP + AR PII S1056-4993(02)00007-X DI 10.1016/S1056-4993(02)00007-X PG 15 WC Psychiatry SC Psychiatry GA 588QC UT WOS:000177711300007 PM 12222081 ER PT J AU Seong, SY AF Seong, SY TI Microimmunoassay using a protein chip: Optimizing conditions for protein immobilization SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID OLIGONUCLEOTIDE; STREPTAVIDIN; MICROCHIPS; ARRAYS; DNA AB Optimizing conditions for the microarraying of protein antigens onto glass slides were studied. Various vendors, surface functional groups, buffers, and fixatives were evaluated to enhance protein binding. A total of 125 pg of human immunoglobulin was detectable with this assay system, suggesting that protein microarray can be applied for routine immunodiagnosis. C1 Seoul Natl Univ, Coll Med, Dept Microbiol & Immunol, Seoul 110799, South Korea. Seoul Natl Univ, Med Res Ctr, Inst Endem Dis, Seoul 110799, South Korea. RP Seong, SY (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, 4 Ctr Dr,Bldg 4,Room 111, Bethesda, MD 20892 USA. RI Seong, Seung Yong /J-2764-2012 NR 15 TC 22 Z9 25 U1 0 U2 3 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 JUL PY 2002 VL 9 IS 4 BP 927 EP 930 DI 10.1128/CDLI.9.4.927-930.2002 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 575CW UT WOS:000176929600033 PM 12093699 ER PT J AU Ozen, S Balci, B Ozkara, S Ozcan, A Yilmaz, E Besbas, N Ozguc, M Kastner, DL Bakkaloglu, A AF Ozen, S Balci, B Ozkara, S Ozcan, A Yilmaz, E Besbas, N Ozguc, M Kastner, DL Bakkaloglu, A TI Is there a heterozygote advantage for familial Mediterranean fever carriers against tuberculosis infections: Speculations remain? SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Letter ID POPULATION; FREQUENCY; MUTATION C1 Hacettepe Univ, Fac Med, Dept Pediat Nephrol & Rheumatol, TR-06100 Ankara, Turkey. Hacettepe Univ, Fac Med, Dept Biol Mol, TR-06100 Ankara, Turkey. Ataturk Chest Dis & Surg Ctr, Ankara, Turkey. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Ozen, S (reprint author), Hacettepe Univ, Fac Med, Dept Pediat Nephrol & Rheumatol, TR-06100 Ankara, Turkey. RI YILMAZ, ENGIN/I-8278-2013; PEYNIRCIOGLU, BANU/I-8337-2013 NR 6 TC 18 Z9 18 U1 0 U2 1 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD JUL-AUG PY 2002 VL 20 IS 4 SU 26 BP S57 EP S58 PG 2 WC Rheumatology SC Rheumatology GA 597HQ UT WOS:000178216500015 PM 12371639 ER PT J AU Fehm, T Sagalowsky, A Clifford, E Beitsch, P Saboorian, H Euhus, D Meng, SD Morrison, L Tucker, T Lane, N Ghadimi, BM Heselmeyer-Haddad, K Ried, T Rao, C Uhr, J AF Fehm, T Sagalowsky, A Clifford, E Beitsch, P Saboorian, H Euhus, D Meng, SD Morrison, L Tucker, T Lane, N Ghadimi, BM Heselmeyer-Haddad, K Ried, T Rao, C Uhr, J TI Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant SO CLINICAL CANCER RESEARCH LA English DT Article ID IN-SITU HYBRIDIZATION; POLYMERASE-CHAIN-REACTION; COLORECTAL-CANCER PATIENTS; METASTATIC BREAST-CANCER; MICROMETASTATIC TUMOR-CELLS; BONE-MARROW; PERIPHERAL-BLOOD; INTERPHASE CYTOGENETICS; PROSTATE-CANCER; DNA-PLOIDY AB Purpose: Numerous studies of circulating epithelial cells (CECs) have been described in cancer patients, and genetic abnormalities have been well documented. However, with one exception in colorectal cancer, there has been no report of matching the genetic abnormalities in the CECs with the primary tumor. The purpose of this investigation was to determine (a) whether CECs in patients including those with early tumors are aneusomic and (b) whether their aneusomic patterns match those from the primary tumor, indicating common clonality. Experimental Design: Thirty-one cancer patients had CECs identified by immunofluorescence staining using a monoclonal anti-cytokeratin antibody. Their CECs were analyzed by enumerator DNA probes for chromosomes 1, 3, 4, 7, 8, 11, or 17 by dual or tricolor fluorescence in situ hybridization. Touch preparations of the primary tumor tissue were available from 17 of 31 patients and hybridized with the same set of probes used to genotype the CECs. Results: The number of CECs from each patient ranged from 1-92 cells/cytospin. CECs showed abnormal copy numbers for at least one of the probes in 25 of 31 patients. Touch preparations from the primary tumors of 13 patients with aneusomic CECs were available. The pattern of aneusomy matched a clone in the primary tumor in 10 patients. Conclusions: We conclude that the vast majority of CECs in breast, kidney, prostate, and colon cancer patients are aneusomic and derived from the primary tumor. C1 Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Urol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Surg, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Oncol, Dallas, TX 75390 USA. NCI, Bethesda, MD 20892 USA. Vysis Inc, Downers Grove, IL 60515 USA. Immunicon Corp, Huntingdon, PA 19006 USA. RP Uhr, J (reprint author), Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, 600 Harry Hines Blvd,NB 9-210, Dallas, TX 75390 USA. RI Chinthalapally, Rao/B-3633-2010 FU NCI NIH HHS [CA 78303] NR 64 TC 201 Z9 214 U1 0 U2 12 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 JUL PY 2002 VL 8 IS 7 BP 2073 EP 2084 PG 12 WC Oncology SC Oncology GA 571VR UT WOS:000176740300008 PM 12114406 ER PT J AU Cragg, LH Andreeff, M Feldman, E Roberts, J Murgo, A Winning, M Tombes, MB Roboz, G Kramer, L Grant, S AF Cragg, LH Andreeff, M Feldman, E Roberts, J Murgo, A Winning, M Tombes, MB Roboz, G Kramer, L Grant, S TI Phase I trial and correlative laboratory studies of bryostatin I (NSC 339555) and high-dose 1-B-D-arabinofuranosylcytosine in patients with refractory acute leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ARA-C; CYTOSINE-ARABINOSIDE; CELL-LINES; INDUCED APOPTOSIS; PHARMACOLOGICAL INHIBITORS; DIFFERENTIATION; INDUCTION AB A Phase I trial has been conducted in patients with refractory/relapsed acute leukemia in which escalating doses of the protein kinase C (PKC) activator and down-regulator bryostatin 1 (NSC399555), administered as a 24-h continuous infusion on days 1 and 11, were given immediately before and after a split course of high-dose 1-beta-D-arabinofuranosylcytosine (HiDAC; 1.5 g/m(2) every 12 h x 4) administered on days 2 and 3, and 9 and 10. The bryostatin 1 maximally tolerated dose (MTD) was identified as 50 mug/m(2), with myalgias representing the major dose-limiting toxicity (DLT). Other DLTs included prolonged neutropenia and thrombocytopenia, and hepatotoxicity. Of the 23 patients who completed their course of therapy and were fully evaluable for response, the large majority of whom had unfavorable prognostic characteristics, 4 complete remissions (CRs) were obtained. An additional 3 patients were treated at a 3 g/m(2) ara-C (1-beta-n-arabinofuranosylcytosine) dose level to determine whether this HiDAC dose could be administered in conjunction with bryostatin 1. All 3 of these patients experienced DLT, and this dose was considered above the MTD. However, one of the latter patients, who was heavily pretreated, also achieved a CR that persisted 5+ months without maintenance. Finally, 1 patient post-HiDAC and autologous bone marrow transplantation achieved a 5+ month leukemia-free survival although she did not meet the criteria for a CR because of persistent transfusion requirements. Correlative laboratory studies performed on blasts from 9 patients revealed that in vivo administration of bryostatin I resulted in variable effects on total blast PKC activity, including decreases in 4 samples, increases in 2, and no change in 3. Previous in vivo bryostatin 1 exposure also exerted disparate effects on the extent of apoptosis observed in blasts exposed to ara-C ex vivo, although increases were noted in a subset of patient samples. Interestingly, in vivo administration of bryostatin 1 by itself induced lethality in some patient specimens. No clear relationship between the in vivo effects of bryostatin 1 on blast PKC activity and the extent of ara-C-related apoptosis that occurred ex vivo was apparent. Together, these findings demonstrate that bryostatin 1 can be safely administered as a continuous infusion before and after a split course of HiDAC in patients with refractory leukemia, and identify the bryostatin 1 MTD as 50 mug/m(2) when given by this schedule. Furthermore, the achievement of several CRs in the setting of a Phase I trial in which many patients had particularly high-risk features (e.g., short initial remission, previous HiDAC or autologous bone marrow transplantation, and multiple previous salvage regimens) suggests that this regimen has activity in acute leukemia and warrants additional investigation. C1 Virginia Commonwealth Univ, Med Coll Virginia, Div Hematol Oncol, Richmond, VA 23284 USA. Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. Univ Texas, SW Med Ctr, MD Anderson Canc Ctr, Houston, TX 75390 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Grant, S (reprint author), Virginia Commonwealth Univ Med Coll Virginia, MCV Stn Box 230, Richmond, VA 23298 USA. FU NCI NIH HHS [CA92950, CA63753, CA77141] NR 50 TC 25 Z9 27 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 JUL PY 2002 VL 8 IS 7 BP 2123 EP 2133 PG 11 WC Oncology SC Oncology GA 571VR UT WOS:000176740300014 PM 12114412 ER PT J AU Grem, JL Harold, N Keith, B Chen, AP Kao, V Takimoto, CH Hamilton, JM Pang, J Pace, M Jasser, GB Quinn, MG Monahan, BP AF Grem, JL Harold, N Keith, B Chen, AP Kao, V Takimoto, CH Hamilton, JM Pang, J Pace, M Jasser, GB Quinn, MG Monahan, BP TI A phase I Pharmacologic and pharmacodynamic study of pyrazoloacridine given as a weekly 24-hour continuous intravenous infusion in adult cancer patients SO CLINICAL CANCER RESEARCH LA English DT Article ID RENAL-CELL CARCINOMA; SOLID TUMORS; NSC-366140; TRIAL; PD115934; PHARMACOKINETICS; MURINE; VITRO; AGENT; MICE AB Purpose: Pyrazoloacridine (PZA) is an investigational nucleic acid binding agent that inhibits the activity of topoisomerases I and II through a mechanism distinct from other topoisomerase poisons. PZA shows schedule-independent cytotoxicity against tumor cells, whereas host toxicity is greater with shorter infusions. We assessed the clinical toxicities and pharmacologic effects of PZA given as a 24-h i.v. infusion weekly for 3 of 4 weeks. Experimental Design: Thirty-two adult patients with solid tumors received PZA at five dose levels (100-351 mg/m(2)). Plasma samples were obtained at the end of the PZA infusion at all of the dose levels, with extended sampling in a cohort treated at the recommended dose. Results: Dose-limiting granulocytopenia and mucositis occurred in 2 of 6 patients at 351 mg/m(2), but lower doses were well tolerated. No responses were seen, but 28% had stable disease for greater than or equal to3 months. Plasma levels strongly correlated with the degree of granulocytopenia. Extended pharmacokinetics in 7 patients treated with 281 mg/m(2) indicated the following averages: maximum plasma level, 1.6 muM; area under the plasma concentration-time curve, 56 muM.h; terminal half-life, 27 h; urinary recovery, 17% over 72 h. DNA fragmentation in post-PZA bone marrow mononuclear cells was seen in 9 of 28 samples (all at greater than or equal to281 mg/m(2)). Conclusions: Unlike other schedules of PZA, neurotoxicity and thrombocytopenia were not problematic with a weekly 24-h infusion of PZA. The recommended Phase II dose is 281 mg/m(2), which was well tolerated. Both end of infusion plasma levels and presence of DNA damage correlated with granulocyte toxicity. C1 NCI, Natl Naval Med Ctr, Bethesda, MD 20889 USA. Natl Naval Med Res Inst, Dept Radiol, Bethesda, MD 20889 USA. RP Grem, JL (reprint author), NCI, Natl Naval Med Ctr, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. EM gremj@mail.nih.gov NR 26 TC 7 Z9 7 U1 0 U2 4 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 JUL PY 2002 VL 8 IS 7 BP 2149 EP 2156 PG 8 WC Oncology SC Oncology GA 571VR UT WOS:000176740300017 PM 12114415 ER PT J AU Peghini, PL Iwamoto, M Raffeld, M Chen, YJ Goebel, SU Serrano, J Jensen, RT AF Peghini, PL Iwamoto, M Raffeld, M Chen, YJ Goebel, SU Serrano, J Jensen, RT TI Overexpression of epidermal growth factor and hepatocyte growth factor receptors in a proportion of gastrinomas correlates with aggressive growth and lower curability SO CLINICAL CANCER RESEARCH LA English DT Review ID ZOLLINGER-ELLISON-SYNDROME; FACTOR SCATTER FACTOR; HUMAN PANCREATIC-CANCER; ENDOCRINE NEOPLASIA TYPE-1; TUMOR-SUPPRESSOR GENE; C-MET PROTOONCOGENE; HUMAN HEPATOCELLULAR-CARCINOMA; PAPILLARY THYROID CARCINOMAS; LYMPH-NODE METASTASIS; CELL LUNG CARCINOMAS AB Purpose: Growth factor receptor expression and activation, particularly for epidermal growth factor (EGF) and hepatocyte growth factor (HGF), in many endocrine and nonendocrine tumors is important in determining tumor recurrence, growth, and aggressiveness. Whether this is true of neuroendocrine tumors such as gastrinomas is unclear. Experimental Design: To address this question, we analyzed the extent of EGFR and HGFR expression in gastrinomas from 38 patients with Zollinger-Ellison syndrome and correlated it with clinical and tumor characteristics. EGFR (n = 38) and HGFR (n = 22) mRNA levels were determined by competitive PCR, and immunohistochemistry was performed on a subset. Results: In each of the gastrinomas studied, detectable levels of EGFR and HGFR mRNA were present. Low levels of EGFR protein expression were detected in 40% of gastrinomas and HGFR protein expression in 90%. EGFR mRNA expression varied by 1050-fold and HGFR by 375-fold. Eighteen percent of gastrinomas overexpressed EGFR mRNA and 14% overexpressed HGFR mRNA, compared with normal pancreas. Maximal EGFR and HGFR mRNA levels were 4- and 1.2-fold increased and correlated with the presence of liver metastases (P = 0.034) and decreased long-term curability (P = 0.027) but not tumor location, size, or tumor functional characteristics. Conclusions: These above results indicate that Furthermore, each is overexpressed in a minority (15-20%) of the gastrinomas, and the overexpression correlates with aggressive growth and lower curability. C1 NIDDKD, NIH, Digest Dis Branch, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, NIH, Digest Dis Branch, Bldg 10,Room 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. NR 119 TC 55 Z9 58 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 JUL PY 2002 VL 8 IS 7 BP 2273 EP 2285 PG 13 WC Oncology SC Oncology GA 571VR UT WOS:000176740300033 PM 12114431 ER PT J AU Nagata, S Onda, M Numata, Y Santora, K Beers, R Kreitman, RJ Pastan, I AF Nagata, S Onda, M Numata, Y Santora, K Beers, R Kreitman, RJ Pastan, I TI Novel anti-CD30 recombinant immunotoxins containing disulfide-stabilized Fv fragments SO CLINICAL CANCER RESEARCH LA English DT Article ID LARGE-CELL LYMPHOMA; A-CHAIN IMMUNOTOXINS; TRUNCATED PSEUDOMONAS EXOTOXIN; DISSEMINATED HODGKIN TUMORS; VESICULAR STOMATITIS-VIRUS; DNA-IMMUNIZED MICE; ANTITUMOR-ACTIVITY; SINGLE-CHAIN; IN-VITRO; COMPLETE REGRESSION AB Purpose: To develop a novel targeting reagent to CD30 expressed on Hodgkin's disease and anaplastic large cell lymphoma, we made a panel of recombinant immunotoxins specific for CD30 using Fvs of newly produced anti-CD30 monoclonal antibodies (MAbs) and a M-r 38,000 truncated mutant of Pseudomonas exotoxin. Experimental Design: A group of MAbs against CD30 was produced and characterized for their reactivity and epitopes. Recombinant immunotoxins were made using the Fv genes cloned from the hybridomas. Their cytotoxic activities were examined on various CD30-positive cell lines. Results: Six MAbs were produced. All reacted with recombinant soluble CD30 and to a CD30-Fc fusion protein, and bound to native CD30 expressed on Hodgkin's lymphoma-derived cell lines. The epitopes of the six MAbs were classified into two groups by a mutual competition assay for the binding to CD30 on cells. Sequencing the cDNAs revealed that all of the variable chains are unique except one valiable light that is shared by two MAbs. We made four disulfide stabilized Fv-based recombinant immunotoxins, in which the valiable heavy, which is genetically fused with truncated mutant of Pseudomonas exotoxin, forms a disulfide bond with the valiable light. The purified immunotoxins bound to recombinant soluble CD30 immobilized on a biosensor chip with K(d)s of 4-400 ant. Fluorescence-activated cell sorter analysis confirmed their specific binding. In vitro cytotoxicity tests showed that the immunotoxins specifically kill a variety of CD30-positive lymphoma cell lines as well as CD30-transfected A431 cells. The IC50 ranged from 0.3 to 100 ng/ml. Conclusions: Four anti-CD30 disulfide stabilized Fv immunotoxins were successfully produced. Two of these showed good cytotoxic activity to various CD30-positive cell lines. These newly produced immunotoxins should be additionally evaluated for the treatment of CD30-positive lymphomas. C1 NCI, NIH, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, NIH, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr MSC 4264,Bldg 37,Room 5106, Bethesda, MD 20892 USA. NR 47 TC 29 Z9 30 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 JUL PY 2002 VL 8 IS 7 BP 2345 EP 2355 PG 11 WC Oncology SC Oncology GA 571VR UT WOS:000176740300041 PM 12114439 ER PT J AU Dai, J Shen, RQ Sumitomo, M Stahl, R Navarro, D Gershengorn, MC Nanus, DM AF Dai, J Shen, RQ Sumitomo, M Stahl, R Navarro, D Gershengorn, MC Nanus, DM TI Synergistic activation of the androgen receptor by bombesin and low-dose androgen SO CLINICAL CANCER RESEARCH LA English DT Article ID INDEPENDENT PROSTATE-CANCER; SIGNAL-TRANSDUCTION PATHWAYS; FOCAL ADHESION KINASE; CELL-LINES; NEUTRAL ENDOPEPTIDASE; GROWTH; GENE; PROGRESSION; EXPRESSION; MECHANISMS AB Purpose: Neuropeptide growth factors such as bombesin are implicated in progression to androgen-independent prostate cancer (PC). We examined the impact of bombesin on androgen receptor (AR)-mediated gene expression. Experimental Design: The AR together with the AR-responsive probasin ARR(3)tk-luc or PSA-pPUE-ELB-luc promoter was cotransfected into Swiss 3T3 and PC-3 cells, both of which express high-affinity bombesin receptors; the cells were incubated with bombesin (0-50 nM) and dihydrotestosterone (DHT; 0-10 nM), and luciferase activities were measured. DHT increased transcription similar to40-fold at doses of 1 and 10 nm but had no effect at 10 pm. Bombesin alone, or with 1 or 10 nM DHT, did not further increase transcription. However, 5 nm bombesin and 10 pm DHT, doses that by themselves had no effect, resulted in a similar to20 fold increase in transcription (P < 0.005). This synergistic effect was blocked by bombesin receptor antagonists and recombinant neutral endopeptidase, which hydrolyzes bombesin. Bombesin and DHT together also increased binding of nuclear extracts from PC-3 cells transfected with AR to a consensus androgen response element in mobility shift assays and increased the level of secreted prostate-specific antigen in LNCaP cell supernatant compared with DHT or bombesin alone. Immunoprecipitation of AR from P-32-labeled LNCaP cells revealed that 5 nm bombesin + 10 pm DHT induced AR phosphorylation comparable with 1 nM DHT, whereas bombesin or 10 pM DHT alone did not. Conclusions: These data indicate that bombesin can synergize with low (castrate) levels of DHT to induce AR-mediated transcription and suggest that neuropeptides promote AR-mediated signaling in androgen-independent prostate cancer. C1 Cornell Univ, Weill Med Coll, Dept Urol, Urol Oncol Res Lab, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Div Hematol & Med Oncol, New York, NY 10021 USA. NIH, Bethesda, MD 20892 USA. RP Nanus, DM (reprint author), Cornell Univ, Weill Med Coll, Dept Urol, Urol Oncol Res Lab, 525 E 68th St, New York, NY 10021 USA. FU NCI NIH HHS [CA 80240] NR 35 TC 32 Z9 32 U1 1 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 JUL PY 2002 VL 8 IS 7 BP 2399 EP 2405 PG 7 WC Oncology SC Oncology GA 571VR UT WOS:000176740300047 PM 12114445 ER PT J AU Khanna, C Prehn, J Hayden, D Cassaday, RD Caylor, J Jacob, S Bose, SM Hong, SH Hewitt, SM Helman, LJ AF Khanna, C Prehn, J Hayden, D Cassaday, RD Caylor, J Jacob, S Bose, SM Hong, SH Hewitt, SM Helman, LJ TI A randomized controlled trial of octreotide pamoate long-acting release and carboplatin versus carboplatin alone in dogs with naturally occurring osteosarcoma: Evaluation of insulin-like growth factor suppression and chemotherapy SO CLINICAL CANCER RESEARCH LA English DT Article ID FACTOR-I RECEPTOR; SOMATOSTATIN ANALOG; INHIBITION; APOPTOSIS; CELLS AB Purpose: The purpose of this research was to determine whether insulin-like growth factor (IGF) suppression, using a long-acting analogue of somatostatin (OncoLAR, octreotide pamoate long-acting release), will decrease chemotherapy resistance by eliminating an important survival signal to osteosarcoma (OSA) cells in a relevant naturally occurring cancer model. Experimental Design: We conducted a randomized, blinded, placebo-controlled preclinical study in pet dogs with naturally occurring OSA. The study compared primary tumor necrosis and apoptosis, and survival of pet dogs receiving OncoLAR and carboplatin chemotherapy compared with dogs receiving placebo and carboplatin. Results: Dogs receiving OncoLAR had suppression of serum IGF levels by similar to43% without toxicity. No differences in primary tumor necrosis, apoptosis, tumor IGF mRNA expression, or survival were seen between the dogs receiving OncoLAR plus chemotherapy compared with OncoLAR alone. Conclusion: The suppression of IGF levels by the extent and/or duration achieved in the trial was not sufficient to improve chemotherapy-related antitumor effects in pet dogs with OSA. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Tissue Array Project, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Coll Vet Med, St Paul, MN 55113 USA. RP Khanna, C (reprint author), NCI, Pediat Oncol Branch, NIH, Room 10,13N240,10 Ctr Dr, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 21 TC 39 Z9 42 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 JUL PY 2002 VL 8 IS 7 BP 2406 EP 2412 PG 7 WC Oncology SC Oncology GA 571VR UT WOS:000176740300048 PM 12114446 ER PT J AU Egorin, MJ Zuhowski, EG McCully, CM Blaney, SM Kerr, JZ Berg, SL Balis, FM AF Egorin, MJ Zuhowski, EG McCully, CM Blaney, SM Kerr, JZ Berg, SL Balis, FM TI Pharmacokinetics of intrathecal gemcitabine in nonhuman primates SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; PHASE-II TRIAL; SINGLE-AGENT GEMCITABINE; NON-HODGKINS-LYMPHOMA; CEREBROSPINAL-FLUID; NEOPLASTIC MENINGITIS; UROTHELIAL CANCER; RANDOMIZED TRIAL; PANCREAS CANCER; OVARIAN-CANCER AB Purpose: Gemcitabine is an excellent candidate for regional therapy. We quantified cerebrospinal fluid (CSF) and plasma concentrations of gemcitabine and its inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU), in nonhuman primates given intrathecal gemcitabine. Experimental Design: Three nonhuman primates received 5 mg of gemcitabine via lateral ventricle. CSF was sampled from the fourth ventricle in all of the animals and the lumbar space in one, and one had plasma sampled. One animal had ventricular CSF sampled after receiving 5 mg intralumbar gemcitabine. Gemcitabine and dFdU were measured by high-performance liquid chromatography. Three additional animals had 5 mg intralumbar gemcitabine administered weekly for 4 weeks and were monitored for toxicity. Results: At 37 C in vitro, gemcitabine was stable in CSF. Ventricular delivery of gemcitabine produced peak ventricular CSF gemcitabine concentrations of 297 +/- 105 mug/ml. After 6 h, the concentrations were <0.03 mug/ml. Intrathecal gemcitabine was rapidly and extensively converted to dFdU. CSF dFdU concentrations increased to 82 mug/ml at 1 h and then declined to very low values by 24 h. After intraventricular administration, CSF gemcitabine and dFdU area(s) under the curve (AUC) were 251 +/- 85 and 249 +/- 88 mug/ml x h. Intralumbar gemcitabine produced lower ventricular CSF gemcitabine and dFdU concentrations than did intraventricular gemcitabine. The plasma gemcitabine AUC associated with 5 mg of intraventricular gemcitabine was 2 mg/ml x h, which was >200-fold lower than the CSF gemcitabine AUC in the same animal. Transient CSF pleocytosis was the only toxicity observed. Conclusions: Our results demonstrate a large pharmacokinetic advantage of intrathecal gemcitabine and support a planned Phase I clinical trial of this dosing strategy. C1 Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Div Hematol Oncol, Dept Med, Pittsburgh, PA 15213 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Texas Childrens Ctr, Houston, TX 77030 USA. RP Egorin, MJ (reprint author), Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, E1040 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. NR 44 TC 16 Z9 16 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 JUL PY 2002 VL 8 IS 7 BP 2437 EP 2442 PG 6 WC Oncology SC Oncology GA 571VR UT WOS:000176740300052 PM 12114450 ER PT J AU Bleesing, JJH Brown, MR Novicio, C Guarraia, D Dale, JK Straus, SE Fleisher, TA AF Bleesing, JJH Brown, MR Novicio, C Guarraia, D Dale, JK Straus, SE Fleisher, TA TI A composite picture of TcR alpha/beta(+) CD4(-)CD8(-) T cells (alpha/beta-DNTCs) in humans with autoimmune lymphoproliferative syndrome SO CLINICAL IMMUNOLOGY LA English DT Article DE human; T lymphocytes; apoptosis; autoimmunity; cell surface molecules; CD45; O-glycans; lymphoproliferation ID CXC CHEMOKINE RECEPTOR-5; O-GLYCAN BIOSYNTHESIS; MRL-LPR MICE; LPR/LPR MICE; LYMPHOCYTE APOPTOSIS; MUTATIONS; DISEASE; MEMORY; GENE; EXPRESSION AB The discovery of an unusual T-cell subset characterized by the expression of the alpha/beta T-cell receptor without expression of either CD4 or CD8 [alpha/beta-double-negative T cells (alpha/beta-DNTCs)] provided critical insights in the evaluation of a "new" lymphoproliferative disorder known as autoimmune lymphoproliferative syndrome (ALPS). ALPS is a disorder of defective Fas-mediated lymphocyte apoptosis, manifested by accumulation of alpha/beta-DNTCs and other lymphocyte subsets, leading to lymphadenopathy and splenomegaly, autoimmunity, and an increased risk of lymphoma. The expanded population of alpha/beta-DNTCs from ALPS patients has a remarkable uniform phenotype that is for the most part similar to alpha/beta-DNTCs from mice with defective Fas (lpr) or Fas ligand (gld). This is in contrast to the minor alpha/beta-DNTC compartment in healthy individuals that contains multiple, immunophenotypically distinct subpopulations. Current data indicate that alpha/beta-DNTCs from ALPS patients are derived from cytotoxic CD8(+) T cells, chronically activated in vivo but anergic in vitro. Their anergic state may be related to persistent modifications of O-linked carbohydrates on cell surface molecules, such as CD43 and CD45, as well as to the increased presence of interleukin-10. Although largely consistent with a model of (linear) CD8(+) cytotoxic T-cell differentiation, the expression patterns of certain surface molecules, such as CD27 and CD28, are not consistent with this model. This may be the result of the perturbed homeostasis of lymphocytes in ALPS, thereby revealing pathways of differentiation and immunophenotypes, including phenotypes pertaining to cell surface glycosylation that are hidden from view in healthy individuals. (C) 2002 Elsevier Science (USA). C1 Univ Arkansas, Childrens Hosp, Res Inst, Little Rock, AR 72202 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Bleesing, JJH (reprint author), Univ Arkansas, Childrens Hosp, Res Inst, 1120 Marshall St,Slot 512-13, Little Rock, AR 72202 USA. NR 68 TC 46 Z9 47 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 JUL PY 2002 VL 104 IS 1 BP 21 EP 30 DI 10.1006/clim.2002.5225 PG 10 WC Immunology SC Immunology GA 582GL UT WOS:000177341400003 PM 12139944 ER PT J AU Goldman, FD Vibhakar, R Puck, JM Straus, SE Ballas, ZK Hollenback, C Loew, T Thompson, A Song, KJ Cook, RT AF Goldman, FD Vibhakar, R Puck, JM Straus, SE Ballas, ZK Hollenback, C Loew, T Thompson, A Song, KJ Cook, RT TI Aberrant T-cell antigen receptor-mediated responses in autoimmune lymphoproliferative syndrome SO CLINICAL IMMUNOLOGY LA English DT Article DE autoimmune lymphoproliferative syndrome; T-cell antigen receptor; CD4; signal transduction; Fas receptor; cytokines ID FAS GENE; APOPTOSIS; EXPRESSION; LYMPHOCYTES; ACTIVATION; MUTATIONS; DISEASE; CALCIUM; SUBSETS AB Autoimmune Lymphoproliferative Syndrome (ALPS) is a disorder of defective lymphocyte apoptosis due to mutations of the Fas receptor and other molecules in the Fas signaling pathway. In addition to accumulation of CD4(-) CD8(-) double-negative (DN) T cells, many patients display a dysregulated cytokine pattern with dysfunctional T cells, suggesting Fas defects may impact pathways of T-cell activation/differentiation. Here, we report two novel mutations in the Fas receptor resulting in an ALPS phenotype. Utilizing flow cytometry, we found anti-CD3 activated CD4(+) T cells from these patients were incapable of fully upregulating activation markers (CD25, CD69, and CD40L) or producing interferon-gamma and IL-2. Additionally, DN T cells were unable to transduce proximal T-cell antigen receptor signals or produce cytokines. Furthermore, DN T cells overexpressed CD57 and phenotypically resembled end-stage effector cells. As DN T cells were essentially anergic, the clinical manifestations of autoimmunity are more likely to be a consequence of aberrant cytokine secretion within the CD4(+) T-cell subpopulation. (C) 2002 Elsevier Science (USA). C1 Univ Iowa Hosp & Clin, Dept Pediat, Iowa City, IA 52242 USA. Univ Iowa Hosp & Clin, Dept Med, Iowa City, IA 52242 USA. Univ Iowa Hosp & Clin, Dept Pathol, Iowa City, IA 52242 USA. NIAID, Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. Dept Vet Affairs Med Ctr, Iowa City, IA 52242 USA. RP Goldman, FD (reprint author), Univ Iowa Hosp & Clin, Dept Pediat, 200 Hawkins Dr, Iowa City, IA 52242 USA. FU NCI NIH HHS [R01 CA 84137-01]; NIAAA NIH HHS [AA09598] NR 25 TC 14 Z9 14 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 JUL PY 2002 VL 104 IS 1 BP 31 EP 39 DI 10.1006/clim.2002.5249 PG 9 WC Immunology SC Immunology GA 582GL UT WOS:000177341400004 PM 12139945 ER PT J AU Jirapongsananuruk, O Niemela, JE Malech, HL Fleisher, TA AF Jirapongsananuruk, O Niemela, JE Malech, HL Fleisher, TA TI CYBB mutation analysis in X-linked chronic granulomatous disease SO CLINICAL IMMUNOLOGY LA English DT Article DE chronic granulomatous disease; CGD; CYBB; gp91(phox); mutation analysis; DNA sequencing; phagocyte defect ID GP91-PHOX; GENE; OXIDASE AB Chronic granulomatous disease (CGD) results from mutations of phagocyte NADPH oxidase. Seventy percent are X-linked (X-)CGD with absent or defective gp91(phox) protein encoded by the CYBB gene. A subset of X-CGD patients demonstrates partial oxidase activity and/or varied levels of the gp91(phox) protein. Definitive genotypic diagnosis in these unusual patients requires mutation analysis. Typically, CYBB mutation analysis has relied on initial screening of cDNA by single-stranded conformation polymorphism analysis, followed by selective sequencing. We report a fluorescent, automated method for CYBB mutation analysis using genomic DNA that provides more rapid and reliable results. Moreover, the use of genomic DNA in this approach allows mutation detection in the mRNA coding region, promoter/enhancer region, and intronic sequences flanking splice junctions and does not require mRNA preparation. The PCR conditions were optimized for each exon, including those with A+T-rich regions. We analyzed DNA from two unusual X-CGD patients and established the genetic basis for their phenotype. We also sequenced 100 normal X chromosomes to establish wild-type consensus sequences and identify polymorphisms. (C) 2002 Elsevier Science (USA). C1 NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Fleisher, TA (reprint author), NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 2C-306,10 Ctr Dr MSC 1508, Bethesda, MD 20892 USA. OI Malech, Harry/0000-0001-5874-5775; Niemela, Julie/0000-0003-4197-3792 NR 13 TC 17 Z9 20 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUL PY 2002 VL 104 IS 1 BP 73 EP 76 DI 10.1006/clim.2002.5230 PG 4 WC Immunology SC Immunology GA 582GL UT WOS:000177341400009 PM 12139950 ER PT J AU Clark, CG Diamond, LS AF Clark, CG Diamond, LS TI Methods for cultivation of luminal parasitic protists of clinical importance SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID ENTAMOEBA-HISTOLYTICA SCHAUDINN; GIARDIA-LAMBLIA; BLASTOCYSTIS-HOMINIS; AXENIC CULTIVATION; CLONAL GROWTH; TRICHOMONAS-VAGINALIS; DIENTAMOEBA-FRAGILIS; GENETIC DIVERSITY; DISPAR BRUMPT; SERUM-FREE AB Cultivation of luminal protistan parasites has a long history. In this review we discuss the methods and media that are most widely used for the establishment and maintenance of the following organisms in culture: Entamoeba histolytica, Giardia intestinalis, Trichomonas vaginalis, Dientamoeba fragilis, Blastocystis hominis, and Balantidium coli. While cultivation is of limited importance in the diagnostic laboratory, it is essential to most research laboratories, and it is toward the latter that this review is primarily aimed. C1 Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England. NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Clark, CG (reprint author), Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, Keppel St, London WC1E 7HT, England. EM graham.clark@lshtm.ac.uk RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 NR 72 TC 195 Z9 212 U1 3 U2 22 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 EI 1098-6618 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD JUL PY 2002 VL 15 IS 3 BP 329 EP + DI 10.1128/CMR.15.3.329-341.2002 PG 14 WC Microbiology SC Microbiology GA 572TP UT WOS:000176791300002 PM 12097242 ER PT J AU Heegaard, ED Brown, KE AF Heegaard, ED Brown, KE TI Human parvovirus B19 SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID RED-CELL APLASIA; POLYMERASE-CHAIN-REACTION; IDIOPATHIC THROMBOCYTOPENIC PURPURA; HEMATOPOIETIC PROGENITOR CELLS; ACUTE LYMPHOCYTIC-LEUKEMIA; ERYTHROCYTE-P-ANTIGEN; B19-ASSOCIATED HEMOPHAGOCYTIC SYNDROME; MIMICKING MYELODYSPLASTIC SYNDROME; ACTIVE ANTIRETROVIRAL THERAPY; ACUTE LYMPHOBLASTIC-LEUKEMIA AB Parvovirus B19 (B19) was discovered in 1974 and is the only member of the family Parvoviridae known to be pathogenic in humans. Despite the inability to propagate the virus in cell cultures, much has been learned about the pathophysiology of this virus, including the identification of the cellular receptor (P antigen), and the control of the virus by the immune system. B19 is widespread, and manifestations of infection vary with the immunologic and hematologic status of the host. In healthy immunocompetent individuals B19 is the cause of erythema infectiosum and, particularly in adults, acute symmetric polyarthropathy. Due to the tropism of B19 to erythroid progenitor cells, infection in individuals with an underlying hemolytic disorder causes transient aplastic crisis. In the immunocompromised host persistent B19 infection is manifested as pure red cell aplasia and chronic anemia. Likewise, the immature immune response of the fetus may render it susceptible to infection, leading to fetal death in utero, hydrops fetalis, or development of congenital anemia. B19 has also been suggested as the causative agent in a variety of clinical syndromes, but given the common nature, causality is often difficult to infer. Diagnosis is primarily based on detection of specific antibodies by enzyme-linked immunosorbent assay or detection of viral DNA by dot blot hybridization or PCR. Treatment of persistent infection with immunoglobulin reduces the viral load and results in a marked resolution of anemia. Vaccine phase I trials show promising results. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Hosp State Copenhagen, Rigshosp, Dept Clin Microbiol, Copenhagen, Denmark. RP Brown, KE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C218,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 335 TC 294 Z9 327 U1 2 U2 24 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD JUL PY 2002 VL 15 IS 3 BP 485 EP + DI 10.1128/CMR.15.3.485-505.2002 PG 22 WC Microbiology SC Microbiology GA 572TP UT WOS:000176791300013 PM 12097253 ER PT J AU Abbott, KC Hypolite, IO Agodoa, LY AF Abbott, KC Hypolite, IO Agodoa, LY TI Sickle cell nephropathy at end-stage renal disease in the United States: patient characteristics and survival SO CLINICAL NEPHROLOGY LA English DT Article ID RISK-FACTORS; TRANSPLANTATION; MORTALITY; FAILURE; DEATH AB Background: The patient characteristics, including age at presentation to end-stage renal disease (ESRD) and mortality associated with sickle cell nephropathy (SCN) have not been characterized for a national sample of patients. Methods: 375,152 patients in the United States Renal Data System were initiated on ESRD therapy between January 1, 1992 and June 30, 1997 and analyzed in an historical cohort study of SCN. Results: Of the study population, 397 (0.11%) had SCN, of whom 93% were African-American. The mean age at presentation to ESRD was 40.68 +/- 14.00 years. SCN patients also had an independently increased risk of mortality (hazard ratio 1.52, 95% CI: 1.27-1.82) even after adjustment for placement on the renal transplant waiting list, diabetes, hematocrit, creatinine, and body mass index. However, when receipt of renal transplantation was also included in the model, SCN was no longer significant (p = 0.51, HR = 1.10, 95% CI: 0.82-1.48). SCN patients were much less likely to be placed on the renal transplant waiting list or receive renal transplants in comparison to age and race matched controls, and results of survival analysis were similar in this model. Conclusions: SCN patients were much less likely to be listed for or receive renal transplantation than other comparable patients with ESRD. SCN patients were at independently increased of mortality compared with other patients with ESRD, including those with diabetes, but this increased risk did not persist when models adjusted for their low rates of renal transplantation. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDDK, Off Minor Hlth Res Coordinat, NIH, Bethesda, MD USA. NIDDK, NIH, Bethesda, MD USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 16 TC 31 Z9 32 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD JUL PY 2002 VL 58 IS 1 BP 9 EP 15 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 570TX UT WOS:000176675100002 PM 12141416 ER PT J AU Wassermann, EM AF Wassermann, EM TI Variation in the response to transcranial magnetic brain stimulation in the general population SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE motor evoked potentials; individual differences; motor cortex ID MOTOR CORTEX EXCITABILITY; INTRACORTICAL INHIBITION; CORTICAL EXCITABILITY; FACILITATION; THRESHOLD; DISORDER; DISTANCE; HUMANS; COIL; AGE AB Objectives: The aim of this study is to describe the variability and other characteristics of the motor evoked potential (MEP) to transcranial magnetic stimulation (TMS) in a large database. Methods: One hundred fifty one subjects, including 17 sib pairs, free of neurological or psychiatric disease and on no neuroactive medications were studied with uniform techniques. Nineteen were studied on 3 occasions. Measures included MEP threshold (N = 141) during rest and voluntary muscle activation and the response to paired TMS (subthreshold conditioning stimulus) at interstimulus intervals (ISIS) of 3, 4, 10, and 15 ins (N = 53). Results: There was a large variability in all the measures. Approximately 40-50% of this appeared to come from within-subjects variation or experimental error. The MEP threshold data were skewed downward, but normalized with log transformation. The paired-pulse ratios (conditioned/unconditioned MEP) were normally distributed except those from the 3 ms ISI which had no lower tail and could not be normalized. There were subjects showing inhibition and others showing facilitation at all ISIs. There were no correlations in any of the data with age or sex, but MEP thresholds were highly correlated within sibs. Conclusions: These data should be useful for planning, analyzing, and interpreting TMS studies in healthy and patient populations. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NINDS, Brain Stimulat Unit, NIH, Bethesda, MD 20892 USA. RP Wassermann, EM (reprint author), 10 Ctr Dr MSC 1430, Bethesda, MD USA. NR 19 TC 222 Z9 222 U1 1 U2 15 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JUL PY 2002 VL 113 IS 7 BP 1165 EP 1171 AR PII S1388-2457(02)00144-X DI 10.1016/S1388-2457(02)00144-X PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 572QJ UT WOS:000176786200024 PM 12088713 ER PT J AU Khan, AA Brahim, JS Rowan, JS Dionne, RA AF Khan, AA Brahim, JS Rowan, JS Dionne, RA TI In vivo selectivity of a selective cyclooxygenase 2 inhibitor in the oral surgery model SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GASTROINTESTINAL TOXICITY; RHEUMATOID-ARTHRITIS; PROSTAGLANDIN; GLUCOCORTICOIDS; EXPRESSION; TISSUE; DRUGS; PAIN AB Objective: Prostanoids formed by cyclooxygenase play an important role in pain and the induction of inflammation. It is generally believed that COX-I is constitutively expressed, whereas COX-2 is primarily inducible during inflammation. This study examined the in vivo selectivity of celecoxib, a COX-2 inhibitor, and evaluated whether estimates of selectivity that are based on in vitro and ex vivo analyses are reliable indicators of in vivo selectivity. Methods. Subjects (103 outpatients undergoing surgical removal of two impacted mandibular third molars) received either 200 mg celecoxib, 600 mg ibuprofen, or placebo 8 hours before surgery and a second dose I hour before surgery. After surgery, microdialysis probes were placed in the surgical sites for collection of inflammatory transudate. Samples were collected every 20 minutes and pain intensity was estimated concurrently with a visual analog scale and a categorical rating scale for up to 4 hours after surgery. Results: A significant analgesic effect (P < .01, compared with placebo) was shown for both drugs, with the efficacy of celecoxib being intermediate between ibuprofen and placebo. A similar relationship was observed for the suppression of prostaglandin E, (a product of both isoforms) at time points consistent with COX-2 expression (P < .001). Ibuprofen consistently suppressed thromboxane B, (a product of COX-1) levels at all time points (P < .05), whereas the effect of celecoxib did not differ from that of placebo. Conclusions. The suppression of products of COX-2 coincident with pain suppression and the absence of COX-1 inhibition suggest that celecoxib is a relatively selective COX-2 inhibitor in vivo. C1 NIDCR, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Dent, Dept Oral & Craniofacial Biol Sci, Baltimore, MD USA. RP Dionne, RA (reprint author), NIDCR, NIH, 10 Ctr Dr,Rm 1N-117, Bethesda, MD 20892 USA. FU NIDCR NIH HHS [T32DE07309] NR 20 TC 38 Z9 38 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 2002 VL 72 IS 1 BP 44 EP 49 DI 10.1067/mcp.2002.125560 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 584HU UT WOS:000177461800005 PM 12152003 ER PT J AU Black, P Max, MB Desjardins, P Ardia, A Pallotta, T AF Black, P Max, MB Desjardins, P Ardia, A Pallotta, T TI A randomized, double-blind, placebo-controlled comparison of the analgesic efficacy, onset of action, and tolerability of ibuprofen arginate and ibuprofen in postoperative dental pain SO CLINICAL THERAPEUTICS LA English DT Article DE dental pain; pain management; ibuprofen; onset; clinical trial ID INTRAMUSCULAR KETOROLAC; ARGININE; SURGERY; MANAGEMENT; DURATION; SODIUM; MODEL AB Background: Because of its enhanced pharmacokinetic characteristics, ibuprofen arginate might be expected to provide faster pain relief than standard ibuprofen formulations in patients experiencing acute pain. Objective: This study assessed the analgesic efficacy, speed of onset, and tolerability of ibuprofen arginate compared with a commercially available form of ibuprofen in patients with postoperative dental pain. Methods: Patients were randomized to receive ibuprofen arginate 200 or 400 mg, ibuprofen 200 or 400 mg, or placebo in this multicenter, double-blind, double-dummy, parallel-group trial. Patients were observed for 6 hours after administration of a single dose of study medication. A repeated-dose, open-label phase followed. Pain intensity and pain relief were measured using traditional verbal descriptor scales; onset of analgesia was assessed using 2 stopwatches to measure the time to achievement of specific pain relief criteria. Results: A total of 498 patients (219 men, 279 women; mean age, 21.5 years) participated in this study. Baseline pain was moderate in 388 patients (78%) and severe in 110 patients (22%). Meaningful pain relief was reached after a median of 29 and 28 minutes with ibuprofen arginate 200 and 400 mg, respectively, and after 52 and 44 minutes with ibuprofen 200 and 400 mg, respectively (all, P < 0.05). The percentages of patients who achieved meaningful pain relief within the first hour after treatment were 77.6% and 83.7% for ibuprofen arginate 200 and 400 mg, respectively, 61.0% and 63.0% for ibuprofen 200 and 400 mg, respectively, and 39.8% for placebo. The differences between ibuprofen arginate and ibuprofen were statistically significant (both doses, P < 0.05). Significantly greater numbers of patients achieved meaningful pain relief with ibuprofen arginate 400 mg compared with placebo from 20 minutes through 6 hours and with ibuprofen arginate 200 mg from 30 minutes through 6 hours (P < 0.05). Compared with placebo, a greater number of patients achieved meaningful pain relief with ibuprofen 400 mg from 45 minutes through 6 hours; with ibuprofen 200 mg, the corresponding interval was from 1 through 6 hours. After the first hour, pain reduction was similar for the similar doses of the 2 ibuprofen preparations. Median remedication times with both doses of ibuprofen arginate were similar to those with both doses of ibuprofen, ranging from 4.0 to 5.2 hours. Adverse-event profiles were similar between the 2 active medications. Conclusions: Ibuprofen arginate was effective in this population of patients experiencing moderate to severe pain after surgical extraction of &GE;1 impacted third molar, with 16 to 24 minutes' faster time to meaningful pain relief than with ibuprofen. The 2 formulations had similar tolerability profiles. C1 Scirex Corp Inc, Austin, TX 78705 USA. NIDCR, NIH, Bethesda, MD USA. Zambon Grp SpA, Bresso, Italy. RP Desjardins, P (reprint author), Scirex Corp Inc, 3200 Red River,Suite 300, Austin, TX 78705 USA. NR 28 TC 31 Z9 32 U1 0 U2 11 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD JUL PY 2002 VL 24 IS 7 BP 1072 EP 1089 DI 10.1016/S0149-2918(02)80020-0 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 581MQ UT WOS:000177296500005 PM 12182253 ER PT J AU Bedford, JJ Burg, MB Peters, E Smith, RAJ Leader, JP AF Bedford, JJ Burg, MB Peters, E Smith, RAJ Leader, JP TI Putative osmolytes in the kidney of the Australian brush-tailed possum, Trichosurus vulpecula SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE methylamines; osmolytes; possum; kidney; marsupial ID ORGANIC OSMOLYTES; MEDULLA; RESONANCE; SOLUTES; TISSUES; BETAINE AB The Australian brush-tailed possum, Trichosurus vulpecula, is capable of producing a moderately concentrated urine, at least up to 1300 mOsm 1(-1). Kidneys of adult animals fed in captivity on a normal diet with ready access to water were analysed. The inner medullary regions were found to have moderately high concentrations of sodium (outer medulla, 367 +/- 37; inner medulla 975 +/- 93 mmol kg(-1) dry wt.), chloride (outer medulla 240 21; inner medulla 701 +/- 23 mmol kg(-1) dry wt.) and urea (outer medulla, 252 +/- 62; inner medulla, 714 +/- 69 mmol kg(-1) protein). When the animals were fed on a 'wet diet', amounts of these substances in the outer medulla and cortex were reduced, although with the exception of urea these changes were not significant. There were highly significant changes in amounts of Na+, Cl- and urea in the inner medulla (Na+, 566 +/- 7; Cl-, 422 +/- 9 mmol kg(-1) dry wt.; urea 393 +/- 84 mmol kg(-1) protein). Likewise, the inner medulla of animals fed a 'dry diet' with limited access to water showed highly significant increases in the same substances (Na+, 1213 +/- 167; Cl-, 974 +/- 137 mmol kg-' dry wt.; urea, 1672 +/- 98 mmol kg-' protein). Inositol was found in the outer medulla (224 +/- 90 mmol kg(-1) protein) and inner medulla (282 mmol kg(-1) protein) as was sorbitol (outer medulla, 62 +/- 20; inner medulla, 274 +/- 72 mmol kg(-1) protein). Both these polyols were reduced in amount in renal tissue from 'wet diet' animals, and increased in 'dry diet' animals, but the changes were not statistically significant. The methylamines, betaine and glycerophosphorylcholine (GPC), showed a similar pattern, but both were significantly elevated in the inner medulla of 'dry diet' animals (betaine 154 +/- 57 to 315 +/- 29 mmol kg(-1) protein; GPC 35 +/- 7 to 47 +/- 10 mmol kg(-1) protein). it was concluded that in this marsupial the concentrating mechanism probably functions in a similar way to that in higher mammals, and that the mechanism of osmoprotection of the medulla of the kidney involves the same osmolytes. However, the high ratio of betaine to GPC in the inner medulla resembles the situation in the avian kidney. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Otago, Dept Physiol, Dunedin, New Zealand. Univ Otago, Dept Chem, Dunedin, New Zealand. NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Leader, JP (reprint author), Univ Otago, Dept Physiol, POB 913, Dunedin, New Zealand. NR 36 TC 2 Z9 2 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1096-4959 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD JUL PY 2002 VL 132 IS 3 BP 635 EP 644 AR PII S1096-4959(02)00078-7 DI 10.1016/S1096-4959(02)00078-7 PG 10 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 576WP UT WOS:000177030300014 PM 12091109 ER PT J AU James, SL AF James, SL TI Support for parasitology research at the National Institute of Allergy and Infectious Diseases SO COMPARATIVE PARASITOLOGY LA English DT Article; Proceedings Paper CT 676th Meeting of the Helminthological-Society-of-Washington CY 2001 CL WASHINGTON, D.C. SP Helminthol Soc Washington C1 NIAID, Parasitol & Int Programs Branch, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. RP James, SL (reprint author), NIAID, Parasitol & Int Programs Branch, Div Microbiol & Infect Dis, NIH, 6700B Rockledge Dr,Room 3101, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HELMINTHOLOGICAL SOC WASHINGTON PI LAWRENCE PA C/O ALLEN PRESS INC, 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 1525-2647 J9 COMP PARASITOL JI Comp. Parasitol. PD JUL PY 2002 VL 69 IS 2 BP 120 EP 123 DI 10.1654/1525-2647(2002)069[0120:SFPRAT]2.0.CO;2 PG 4 WC Parasitology; Zoology SC Parasitology; Zoology GA 579RQ UT WOS:000177192000003 ER PT J AU Larizza, A Makalowski, W Pesole, G Saccone, C AF Larizza, A Makalowski, W Pesole, G Saccone, C TI Evolutionary dynamics of mammalian mRNA untranslated regions by comparative analysis of orthologous human, artiodactyl and rodent gene pairs SO COMPUTERS & CHEMISTRY LA English DT Article DE UTR; evolution; mammalia; orthologous genes; substitution rate; repeats ID EUKARYOTIC MESSENGER-RNAS; PROTEIN-CODING GENES; NONSYNONYMOUS SUBSTITUTIONS; SYNONYMOUS SUBSTITUTION; ACID COMPOSITION; HUMAN GENOME; RATES; TRANSLATION; SEQUENCES; MOUSE AB Most evolutionary studies based on molecular data refer to the portion of genomes encoding for proteins. Today, however, more and more attention is paid to the so-called 'non-coding' regions, which constitute a notable portion of the metazoan nuclear genome. Among them, the untranslated regions of messenger RNAs (mRNA UTRs) are particularly important, as they are involved in the regulation of gene expression, controlling translation efficiency as well as mRNA localization and stability. Up to now, only few studies have focused on the analysis of the compositional and structural features of UTRs, or carried out to investigate quantitatively their evolutionary dynamics. For this reason we have carried out an inter-order study on the evolutionary rate of 5' and 3' UTRs with respect to the corresponding coding region in 93 triplets of orthologous genes (selected through a phylogenetic approach, for a total of 645 625 nt) belonging to Primates (Homo sapiens), Artiodactyla (Bos taunts) and Rodentia (Mus spp.). Our study, that considered only likely orthologous genes, has revealed interesting features on the evolution of these regions concerning nucleotide substitution rate and indels and repetitive element distribution. UTRs from different genes showed a remarkable heterogeneity in the evolutionary dynamics, with some homologous so highly divergent to prevent their alignment, and other rather conserved, at least in some regions; most divergent sequence pairs were excluded from our analysis. The comparison between the nucleotide substitution rates calculated for 5' and 3' UTRs with those calculated on synonymous coding position allowed us to verify and measure the existence of functional constraints acting upon the UTRs of different genes which have shown, in many cases, a positive selection driven evolutionary dynamics. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Milan, Dipartimento Fisiol & Biochim Gen, I-20133 Milan, Italy. Univ Bari, Dipartmento Biochim & Biol Mol, I-70126 Bari, Italy. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Pesole, G (reprint author), Univ Milan, Dipartimento Fisiol & Biochim Gen, Via Celoria 26, I-20133 Milan, Italy. EM graziano.pesole@unimi.it RI Pesole, Graziano/C-1408-2009; Pesole, Graziano/E-9051-2014; Makalowski, Wojciech/I-2843-2016 OI Pesole, Graziano/0000-0003-3663-0859; Pesole, Graziano/0000-0003-3663-0859; NR 34 TC 20 Z9 21 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0097-8485 J9 COMPUT CHEM JI Comput. Chem. PD JUL PY 2002 VL 26 IS 5 SI SI BP 479 EP 490 AR PII S0097-8485(02)00009-8 DI 10.1016/S0097-8485(02)00009-8 PG 12 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 575CK UT WOS:000176928300008 PM 12144177 ER PT J AU Levine, SJ AF Levine, SJ TI Fas-mediated alveolar epithelial cell apoptosis in acute lung injury: Friend or foe? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE acute lung injury; acute respiratory distress syndrome; diffuse alveolar damage; apoptosis; cell death; Fas; Fas ligand ID RESPIRATORY-DISTRESS SYNDROME; IN-VIVO; DEATH; HYPERPLASIA; RESOLUTION; EXPRESSION; DAMAGE; MICE; RAT C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 17 TC 1 Z9 1 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 JUL PY 2002 VL 30 IS 7 BP 1667 EP 1668 DI 10.1097/00003246-200207000-00053 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 573PY UT WOS:000176841100053 PM 12131005 ER PT J AU Rolla, H Grey, M Schmidt, CL Niegemann, E Brendel, M Henriques, JAP AF Rolla, H Grey, M Schmidt, CL Niegemann, E Brendel, M Henriques, JAP TI Mutant pso8-1 of Saccharomyces cerevisiae, sensitive to photoactivated psoralens, UV radiation, and chemical mutagens, contains a rad6 missense mutant allele SO CURRENT GENETICS LA English DT Article DE yeast; psoralen sensitivity; RAD6; nitrosoguanidine ID UBIQUITIN-CONJUGATING ENZYME; DNA-REPAIR GENES; YEAST; PROTEIN; MUTATION; GLUTATHIONE; DEFICIENT; DAMAGE; LINKS AB A novel mutant isolate of Saccharomyces cerevisiae, sensitive to photoactivated mono- and bi-functional psoralens, to UV at 254 nm (UVC), and to nitrosoguanidine, was found to complement the photoactivated psoralen-sensitivity phenotype conferred by the pso1-pso7 mutations and was therefore named pso8-1. A constructed pso8-1 rad4-4 double mutant was super-sensitive to UVC, thus indicating a synergistic interaction of the two mutant alleles. Molecular cloning via complementation of the pso8 mutant's sensitivity phenotype and genetic studies revealed that pso8 is allelic to RAD6. While a pso8-1 mutant had low mutagen-induced mutability, homoallelic diploids showed nearly wild-type sporulation. Sequence analysis of the mutant allele showed pso8-1 to contain a novel, hitherto undescribed T-->C transition in nucleotide position 191, leading to a substitution by leucine of a highly conserved proline at position 64, Rad6-[P64L], which may have severe consequences for the tertiary structure (and hence binding to Rad18p) of the mutant protein. C1 UFRGS, Ctr Biotechnol, Dept Biofis, Porto Alegre, RS, Brazil. Univ Frankfurt, Inst Mikrobiol, D-60590 Frankfurt, Germany. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Frankfurt, Kinderklin 3, D-60590 Frankfurt, Germany. RP Henriques, JAP (reprint author), UFRGS, Ctr Biotechnol, Dept Biofis, Av Bento Goncalves 9500, Porto Alegre, RS, Brazil. NR 31 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0172-8083 J9 CURR GENET JI Curr. Genet. PD JUL PY 2002 VL 41 IS 4 BP 217 EP 223 DI 10.1007/s00294-002-0295-x PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 589BL UT WOS:000177738100004 PM 12172962 ER PT J AU Le Roith, D Kim, H Fernandez, AM Accili, D AF Le Roith, D Kim, H Fernandez, AM Accili, D TI Inactivation of muscle insulin and IGF-I receptors and insulin responsiveness SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Article DE glucose uptake; skeletal muscle; glucose transporters; insulin receptors; IGF-I receptors ID SKELETAL-MUSCLE; GLUCOSE-TRANSPORT; GLUT4 OVEREXPRESSION; TARGETED DISRUPTION; PROTEIN-KINASE; MICE LACKING; DB/DB MICE; RESISTANCE; TISSUE; KNOCKOUT AB Purpose of review This review will outline the recent advances in the area of insulin-stimulated skeletal muscle glucose uptake and its effect on whole body glucose homeostasis, using gene-deletion and transgenic mouse models. Recent findings Insulin resistance is often the first abnormality detected in cases of type 2 diabetes, and is seen at the level of the peripheral tissues especially muscle. Both the insulin receptor and the insulin-like growth factor I receptor are capable of stimulating glucose uptake into skeletal muscle. One model involves the gene deletion of muscle glucose transport protein 4, which leads to severe insulin resistance and hyperglycemia, and a second model using a transgenic approach abrogates the function of the insulin-like growth factor I receptor and the insulin receptor resulting in severe insulin resistance and progression to diabetes. Both models demonstrate that abrogation of the insulin-like growth factor I receptor and the insulin receptor or a common signalling pathway must be inhibited to cause sufficient insulin resistance to lead to type 2 diabetes; with either glucotoxicity or lipotoxicity being involved in the progression from severe to resistance to full-blown type 2 diabetes. Summary Thus, abrogation of insulin-stimulated glucose uptake in skeletal muscle, at least in mice, may lead to severe insulin resistance and diabetes. C1 NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA. Columbia Univ, Ctr Diabet, New York, NY USA. RP Le Roith, D (reprint author), NIH, Clin Endocrinol Branch, Room 8D12,Bldg 10,MSC 1758, Bethesda, MD 20892 USA. NR 31 TC 17 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD JUL PY 2002 VL 5 IS 4 BP 371 EP 375 DI 10.1097/00075197-200207000-00004 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 573CK UT WOS:000176811600004 PM 12107371 ER PT J AU Tisdale, JF Dunbar, CE AF Tisdale, JF Dunbar, CE TI Plasticity and hematopoiesis: Circe's transforming potion? SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID BONE-MARROW CELLS; NEURAL STEM-CELLS; ENDOTHELIAL PROGENITOR CELLS; IN-VIVO; STROMAL CELLS; MYOCARDIAL-INFARCTION; ISCHEMIC MYOCARDIUM; PANCREATIC-ISLETS; MESANGIAL CELLS; CARDIAC-MUSCLE AB It has long been believed that mammalian stem cells are irreversibly committed to the individual tissue in which they reside; however, several recent studies have challenged this assertion and suggest a remarkable plasticity of stem cells derived from various adult tissues. Hematopoietic stem cells have been central to this paradigm shift, and in this review, the authors discuss the recent advances in this rapidly growing field. Although several exciting findings in rodents have already led to clinical trials in humans, true stem cell plasticity has not rigorously been established in most, if not all, studies to date, and a number of issues remain unresolved. Large animal models should prove invaluable to the progress of the field. (C) 2002 Lippincott Williams Wilkins, Inc. C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Tisdale, JF (reprint author), NIDDK, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N116,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 56 TC 4 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JUL PY 2002 VL 9 IS 4 BP 268 EP 273 DI 10.1097/00062752-200207000-00002 PG 6 WC Hematology SC Hematology GA 573FQ UT WOS:000176819000002 PM 12042699 ER PT J AU Chesi, M Bergsagel, PL Kuehl, WM AF Chesi, M Bergsagel, PL Kuehl, WM TI The enigma of ectopic expression of FGFR3 in multiple myeloma: a critical initiating event or just a target for mutational activation during tumor progression SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; T(4-14)(P16.3-Q32) CHROMOSOMAL TRANSLOCATION; IN-SITU HYBRIDIZATION; FACTOR RECEPTOR-3; K-RAS; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; PROTEIN-KINASE; GENE-MUTATIONS; N-RAS AB The t(4;14)(p16.3;q32) translocation that occurs uniquely in a subset of multiple myeloma tumors results in ectopic expression of wild-type FGFR3 and enhanced expression of MMSET, a gene that is homologous to the MLL gene that is involved in acute myeloid leukemias. Wild-type FGFR3 appears to be weakly transforming in a hematopoietic murine model, whereas FGFR3 that contains kinase-activating mutations is strongly transforming in NIH3T3 cells and the hematopoietic model. The subsequent acquisition of FGFR3 kinase-activating mutations in some tumors with t(4;14) translocations confirms a role for FGFR3 in tumor progression. However, it remains to be proven if and how dysiregulation of FGFR3 or MMSET mediates an early oncogenic process in multiple myeloma. (C) 2002 Lippincott Williams Wilkins, Inc. C1 Cornell Univ, Weill Med Coll, New York, NY USA. NCI, Canc Res Ctr, Genet Branch, Bethesda, MD 20892 USA. RP Kuehl, WM (reprint author), Naval Hosp, Genet Branch, Bldg 8,Room 5101, Bethesda, MD 20889 USA. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NCI NIH HHS [K01-CA74265] NR 34 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JUL PY 2002 VL 9 IS 4 BP 288 EP 293 DI 10.1097/00062752-200207000-00005 PG 6 WC Hematology SC Hematology GA 573FQ UT WOS:000176819000005 PM 12042702 ER PT J AU Davis, RE Staudt, LM AF Davis, RE Staudt, LM TI Molecular diagnosis of lymphoid malignancies by gene expression profiling SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NF-KAPPA-B; CELL LYMPHOMA; MUTATION; CANCER; PHENOTYPE AB Gene expression profiling using DNA microarrays has great potential to improve the understanding, diagnosis, and management of lymphomas, leukemias, and other malignancies. Gene expression profiling studies of diffuse large B-cell lymphoma (DLBCL) have shown that this diagnostic category encompasses at least two molecularly distinct diseases, differing in differentiation stage (cell of origin), oncogenic mechanisms, and clinical outcome. Gene expression profiling revealed that the antiapoptotic NF-kappaB pathway is constitutively active in one DLBCL subgroup, termed activated B cell-like DLBCL, and subsequent studies validated NF-kappaB as a therapeutic target in this type of lymphoma. DNA microarray studies of chronic lymphocytic leukemia (CLL) have led to a gene expression-based predictor that identifies two subtypes of CLL that differ with respect to clinical course and presence of immunoglobulin gene mutations in the CLL cells. These findings underscore the value of gene expression profiling in defining subtypes within the lymphoid malignancies that are molecularly and clinically distinct and argue that this genomic technology should become an integral part of prospective clinical trials. (C) 2002 Lippincott Williams Wilkins, Inc. C1 NCI, Ctr Canc Res, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Ctr Canc Res, Metab Branch, NIH, Bldg 10,Rm 4N114,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 23 TC 44 Z9 47 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JUL PY 2002 VL 9 IS 4 BP 333 EP 338 DI 10.1097/00062752-200207000-00011 PG 6 WC Hematology SC Hematology GA 573FQ UT WOS:000176819000011 PM 12042708 ER PT J AU Lawson, ND Vogel, AM Weinstein, BM AF Lawson, ND Vogel, AM Weinstein, BM TI sonic hedgehog and vascular endothelial growth factor act upstream of the notch pathway during arterial endothelial differentiation SO DEVELOPMENTAL CELL LA English DT Article ID DANIO-RERIO; ZEBRAFISH EMBRYOS; FACTOR VEGF; CARDIOVASCULAR DEVELOPMENT; VENOUS DIFFERENTIATION; SIGNAL-TRANSDUCTION; ANGIOGENIC GROWTH; SMOOTH-MUSCLE; EXPRESSION; MUTATIONS AB The appearance of molecular differences between arterial and venous endothelial cells before circulation suggests that genetic factors determine these cell types. We find that vascular endothelial growth factor (vegf) acts downstream of sonic hedgehog (shh) and upstream of the Notch pathway to determine arterial cell fate. Loss of Vegf or Shh results in loss of arterial identity, while exogenous expression of these factors causes ectopic expression of arterial markers. Microinjection of vegf mRNA into embryos lacking Shh activity can rescue arterial differentiation. Finally, activation of the Notch pathway in the absence of Vegf signaling can rescue arterial marker gene expression. These studies reveal a complex signaling cascade responsible for establishing arterial cell fate and suggest differential effects of Vegf on developing endothelial cells. C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Weinstein, BM (reprint author), NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. FU NICHD NIH HHS [Z01 HD 01011] NR 50 TC 488 Z9 508 U1 2 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUL PY 2002 VL 3 IS 1 BP 127 EP 136 DI 10.1016/S1534-5807(02)00198-3 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 572HY UT WOS:000176769500015 PM 12110173 ER PT J AU Guard, HJ Newman, JD Roberts, RL AF Guard, HJ Newman, JD Roberts, RL TI Morphine administration selectively facilitates social play in common marmosets SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE common marmosets; social play behavior; opiates; morphine; naloxone; juveniles ID OPIOID RECEPTOR-BINDING; JUVENILE RATS; SEPARATION-DISTRESS; BETA-ENDORPHIN; BEHAVIOR; NALOXONE; BRAIN; DEPRIVATION; ATTACHMENT; NOREPINEPHRINE AB Common marmosets (Callithrix jacchus) form extended families, and several cohorts of young may reside together Play is shown extensively among the offspring. We hypothesized that opiate activity modulates social play, and predicted that administration of morphine (0.5 mg/kg) would facilitate social play, whereas pretreatment with naloxone (0.5 mg/kg) would block morphine's effects. Morphine administration was associated with significantly increased socialplay, and the effect of morphine was attributable to the focal subject, since play initiated by others was unaffected by treatment. Non-social categories of play, such as object manipulation and locomotor play, and affiliative behaviors, such as time spent huddled, were it unaffected by treatment. Twittering and play face, behaviors used by young during play, also increased after morphine administration. Pretreatment with naloxone blocked morphine's effects. Total activity was significantly increased by morphine administration. We conclude that social play is specifically facilitated by opiate activation, whereas other categories of play behavior and social behavior were unaffected by morphine. Thus, social play represents a distinct category of social behavior in juvenile common marmosets with regulatory processes that are unique from other types of social behavior. Published (C) 2002 Wiley Periodicals, Inc. C1 NICHHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. RP Roberts, RL (reprint author), NICHHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. NR 64 TC 14 Z9 14 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD JUL PY 2002 VL 41 IS 1 BP 37 EP 49 DI 10.1002/dev.10043 PG 13 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA 566VY UT WOS:000176450000004 PM 12115289 ER PT J AU Haluzik, M Dietz, KR Kim, JK Marcus-Samuels, B Shulman, GI Gavrilova, O Reitman, ML AF Haluzik, M Dietz, KR Kim, JK Marcus-Samuels, B Shulman, GI Gavrilova, O Reitman, ML TI Adrenalectomy improves diabetes in A-ZIP/F-1 lipoatrophic mice by increasing both liver and muscle insulin sensitivity SO DIABETES LA English DT Article ID SKELETAL-MUSCLE; ADIPOSE-TISSUE; HEPATIC GLUCONEOGENESIS; HYPOTHALAMIC OBESITY; NEUROPEPTIDE-Y; RNA LEVELS; LEPTIN; RESISTANCE; RAT; METABOLISM AB The virtually fatless A-ZIP/F-1 mouse is profoundly insulin resistant, diabetic, and a good model for humans with severe generalized lipoatrophy. Like a number of other mouse models of diabetes, the A-ZIP/F-1 mouse has elevated serum corticosterone levels. Leptin infusion lowers the corticosterone levels, suggesting that leptin deficiency contributes to the hypercorticosteronemic state. To test the hypothesis that the increased glucocorticoids contribute to the diabetes and insulin resistance, we examined the. effect of adrenalectomy on A-ZIP/F-1 mice. Adrenalectomy significantly decreased the blood glucose, serum insulin, and glycated hemoglobin levels. Hyperinsulinemic-euglycemic clamps were performed to characterize the changes in whole-body and tissue insulin sensitivity. The adrenalectomized A-ZIP/F-1 mice displayed a marked improvement in insulin-induced suppression of endogenous glucose production, indicating increased hepatic insulin sensitivity. Adrenalectomy also increased muscle glucose uptake and glycogen synthesis. These results suggest that the chronically increased serum corticosterone levels contribute to the diabetes of the A-ZIP/F-1 mice and that removal of the glucocorticoid excess improves the insulin sensitivity in both muscle and liver. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. RP Haluzik, M (reprint author), NIDDK, Diabet Branch, NIH, Bldg 10,Room 8N-250,10 Ctr Dr, Bethesda, MD 20892 USA. RI Reitman, Marc/B-4448-2013; OI Reitman, Marc/0000-0002-0426-9475; Dietz, Kelly/0000-0003-3670-2912 FU NIDDK NIH HHS [U24 DK-59635, R01 DK040936, R01 DK-40936] NR 46 TC 31 Z9 31 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2002 VL 51 IS 7 BP 2113 EP 2118 DI 10.2337/diabetes.51.7.2113 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 569RP UT WOS:000176616200016 PM 12086940 ER PT J AU Hirshberg, B Montgomery, S Wysoki, MG Xu, H Tadaki, D Lee, J Hines, K Gaglia, J Patterson, N Leconte, J Hale, D Chang, R Kirk, AD Harlan, DM AF Hirshberg, B Montgomery, S Wysoki, MG Xu, H Tadaki, D Lee, J Hines, K Gaglia, J Patterson, N Leconte, J Hale, D Chang, R Kirk, AD Harlan, DM TI Pancreatic islet transplantation using the nonhuman primate (rhesus) model predicts that the portal vein is superior to the celiac artery as the islet infusion site SO DIABETES LA English DT Article ID LONG-TERM SURVIVAL; DIABETES-MELLITUS; HUMANIZED ANTI-CD154; BLOOD-FLOW; IN-VITRO; ALLOGRAFTS; DISEASE; VIVO; RAT AB We've established a nonhuman primate islet allotransplant model to address questions such as whether transplanting islets into the gut's arterial system would more safely and as effectively support long-term islet allograft survival compared with the traditional portal vein approach. We reasoned that islets make up <2% of pancreatic cell mass but consume an estimated 20% of arterial blood flow, suggesting an advantage for the arterial site. Access to the arterial system is also easier and safer than the portal system. Pancreatectomized rhesus macaques were transplanted with allogeneic islets infused into either the portal vein (n = 6) or the celiac artery (n = 4). To prevent rejection, primates were given daclizumab, tacrolimus, and rapamycin. In five of six portal vein experiments, animals achieved normoglycemia without exogenous insulin. In contrast, none of the animals given intra-arterial islets showed even transient insulin independence (P = 0.048). Two of the latter animals received a second islet transplant, this time to the portal system, and both achieved insulin independence. Thus, intraportal islet transplantation under conventional immunosuppression is feasible in primates and can result in long-term insulin independence when adequate immunosuppression is maintained. Arterial islet injection, however, does not appear to be a viable islet transplantation technique. C1 NIDDK, Navy Transplantat & Autoimmun Branch, Bethesda, MD 20889 USA. Yale Univ, Dept Radiol, New Haven, CT USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. RP Hirshberg, B (reprint author), NIDDK, Navy Transplantat & Autoimmun Branch, 10 Ctr Dr,Bldg 10,Rm 11S219, Bethesda, MD 20889 USA. RI Kirk, Allan/B-6905-2012 NR 23 TC 29 Z9 32 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2002 VL 51 IS 7 BP 2135 EP 2140 DI 10.2337/diabetes.51.7.2135 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 569RP UT WOS:000176616200019 PM 12086943 ER PT J AU Preston, KL Umbricht, A Epstein, DH AF Preston, KL Umbricht, A Epstein, DH TI Abstinence reinforcement maintenance contingency and one-year follow-up SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE methadone; contingency management; abstinence reinforcement ID ILLICIT DRUG-USE; METHADONE-MAINTENANCE; COCAINE ABSTINENCE; HEROIN USE; BEHAVIORAL-APPROACH; DEPENDENCE; PSYCHOTHERAPY; ADDICTION; DELIVERY; PROGRAM AB Background: Relapse to drug use is often seen when contingencies designed to reduce drug use are discontinued. This paper reports on a stepdown maintenance contingency and 1-year follow-up in110 patients who were maintained on methadone (50 or 70 mg/day) and who had completed a contingency management trial targeted to decreasing their opiate use. In the prior study (induction phase, 8 weeks) participants received vouchers for each opiate-negative urine screen or noncontingently. Methods: In this study (maintenance phase, 12 weeks), participants were rerandomized to receive vouchers and take-home methadone doses contingent on providing opiate-negative urine specimens (N = 55) or noncontingently (N = 55). Since participants had been rerandomized from induction-phase contingencies, most study data were analyzed as if from a 2 x 2 (induction x maintenance) design. Follow-up interviews were conducted at 3, 6, and 12 months after study participation. Results: Patients who received the maintenance contingency following an 8-week induction contingency had better outcomes than those who received noncontingent incentives in either the maintenance or induction phases of the trial. Good outcome at follow-up was predicted by enrollment in methadone maintenance after the study. Significantly more participants in the maintenance contingency group transferred directly to another methadone program. Conclusion: These findings support the therapeutic value of extending the duration of contingency management and long-term methadone maintenance. Published by Elsevier Science Ireland Ltd. C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Preston, KL (reprint author), NIDA, Intramural Res Program, 5500 Nathan Schock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 45 TC 25 Z9 25 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUL 1 PY 2002 VL 67 IS 2 BP 125 EP 137 AR PII S0376-8716(02)00023-6 DI 10.1016/S0376-8716(02)00023-6 PG 13 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 576TW UT WOS:000177022600003 PM 12095662 ER PT J AU Cornish, JW Herman, BH Ehrman, RN Robbins, SJ Childress, AR Bead, V Esmonde, CA Martz, K Poole, S Caruso, FS O'Brien, CP AF Cornish, JW Herman, BH Ehrman, RN Robbins, SJ Childress, AR Bead, V Esmonde, CA Martz, K Poole, S Caruso, FS O'Brien, CP TI A randomized, double-blind, placebo-controlled safety study of high-dose dextromethorphan in methadone-maintained male inpatients SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE heroin dependence; dextromethorphan; NMDA; methadone; addiction; pharmacotherapy ID NMDA RECEPTOR ANTAGONISTS; CONDITIONING FACTORS; OPIATE WITHDRAWAL; OPIOID TOLERANCE; MORPHINE; DRUG; PREFERENCE; ADDICTION; MK-801; MICE AB The NMDA antagonist dextromethorphan hydrobromide (DM) may be useful in the treatment of opioid dependence, particularly as a means of reducing tolerance to methadone during replacement therapy. As a prelude to clinical efficacy studies, a randomized, double-blind, placebo-controlled study examined the safety of DM in combination with methadone in inpatient, opiate-dependent volunteers. Male participants received daily methadone (50-70 mg/day) and either DM (n = 10) or placebo (n = 5) during the 12-day active medication phase of the study. DM participants received doses of 120, 240, and 480 mg/day in increasing order (4 days each). DM at high doses caused mild elevations of heart rate, blood pressure, temperature, and plasma bromide. However, none of these effects was clinically significant. DM caused no significant changes in respiration, pupil diameter, or subjective drug effects measured by standard scales. Participants in the DM group reported many more adverse events than did subjects on placebo (173 vs. 21), but these effects were not clinically serious. The most commonly reported side effects were sleepiness and drowsiness. Several participants reported intoxicating effects at the highest dose. Overall, DM was well-tolerated by the methadone-maintained opiate-dependent subjects studied here. These results support the further exploration of DM as an adjunct medication during methadone replacement therapy. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NIDA, Div Treatment Res & Dev, Bethesda, MD 20892 USA. Arcadia Univ, Glenside, PA 19038 USA. Ridgeview Stat, Bluemont, VA 20135 USA. ENDO Pharmaceut Inc, Chadds Ford, PA 19317 USA. RP Cornish, JW (reprint author), Univ Penn, Dept Psychiat, Ctr Studies Addict, 3535 Market St,4th Floor, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [P60-DA-05186] NR 23 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUL 1 PY 2002 VL 67 IS 2 BP 177 EP 183 AR PII S0376-8716(02)00025-X DI 10.1016/S0376-8716(02)00025-X PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 576TW UT WOS:000177022600008 PM 12095667 ER PT J AU Lahiri, DK Farlow, MR Greig, NH Sambamurti, K AF Lahiri, DK Farlow, MR Greig, NH Sambamurti, K TI Current drug targets for Alzheimer's disease treatment SO DRUG DEVELOPMENT RESEARCH LA English DT Review DE Alzheimer's disease; amyloid; anticholinesterases; APP gene; cholesterol; cholinergic agents; cholinomimetic drugs; clonepezil; estrogen; exelon; galantamine; microtubule-associated protein; NSAIDs; oxidative damage; phenserine; vaccine ID AMYLOID PRECURSOR PROTEIN; TERMINAL FRAGMENT-GAMMA; TRANSGENIC MOUSE MODEL; BETA-SECRETASE; A-BETA; MOLECULAR-GENETICS; PROMOTER ACTIVITY; OXIDATIVE DAMAGE; MESSENGER-RNA; CHOLINESTERASE-INHIBITORS AB Alzheimer's disease (AD), the most common form of dementia among the elderly, is a progressive, degenerative disorder of the brain with a loss of memory and cognition. A defining characteristic of AD is the deposition of amyloid fibrils and neurofibrillary tangles in the brain of afflicted individuals. Biochemically, they are mainly composed of beta-amyloid protein (AD) and phosphorylated tau proteins, respectively. There is also a loss of the presynaptic markers of the cholinergic system, such as acetylcholine, in the brain areas related to memory and learning. The biochemical pathways leading to AD are presently unknown and are a subject of intensive study with current theories favoring a hypothesis where AD aggregates to toxic forms that induce tau phosphorylation and aggregation. It is believed that this ultimately leads to dysfunction and death of cholinergic neurons, and compensation for this loss had been the primary focus of first generation therapeutic agents. The amyloid and tau hypotheses have lead to a focus on amyloid and tau as therapeutic targets. The current therapeutic goals are to reduce amyloid levels, prevention of amyloid aggregation/toxicity and tau phosphorylation/aggregation. AD has a heterogeneous etiology with a large percentage termed sporadic AD arising from unknown causes and a smaller fraction of early onset familial AD (FAD) caused by mutations in several genes, such as the beta-amyloid precursor protein (APP) and presenilins (PS1, PS2). Other genes, such as apolipoprotein E (APOE), are considered to be risk factors for AD. Several proteins, such as APP, APOE, BACE (P-amyloid cleaving enzyme), PS1/2, secretases, and tau play important roles in the pathology of AD. Therefore, attempts are being made to develop new inhibitors for BACE, PS-1 and gamma-secretase for treatment of AD. There is also a significant advancement in understanding the function of cholinesterase (ChE) in the brain and the use of ChE inhibitors in AD. The mechanism of a new generation of acetyl- and butyrylChE inhibitors is being studied and tested in human clinical trials for AD. Other strategies, such as vaccination, anti-inflammatory agents, cholesterol-lowering agents, anti-oxidants and hormone therapy, are also being studied for treating or slowing the progression of AD. Developments of early diagnostic tools based on quantitative biochemical markers will be useful to better follow the course of the disease and to evaluate different therapeutic strategies. In the present review, we attempt to critically examine recent trends in AD research from neurochemical to clinical areas. We analyze various neurobiological mechanisms that provide the basis of new targets for AD drug development. These current research efforts should lead to a deeper understanding of the pathobiochemical processes that occur in the AD brain to effectively diagnose and prevent their occurrence. C1 Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. NIA, Neurosci Lab, Drug Design & Dev Sect, Baltimore, MD 21224 USA. Mayo Clin, Dept Neurosci, Jacksonville, FL USA. RP Lahiri, DK (reprint author), Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Rm PR-313,791 Union Dr, Indianapolis, IN 46202 USA. NR 124 TC 115 Z9 120 U1 2 U2 24 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JUL PY 2002 VL 56 IS 3 BP 267 EP 281 DI 10.1002/ddr.10081 PG 15 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 601KQ UT WOS:000178445300001 ER PT J AU Gold, B AF Gold, B TI Counseling molecular diagnostics SO DRUG DISCOVERY TODAY LA English DT Editorial Material C1 NCI, Lab Genom Divers, Human Genet Sect, Frederick, MD 21702 USA. RP Gold, B (reprint author), NCI, Lab Genom Divers, Human Genet Sect, Bldg 560,Room 11-85, Frederick, MD 21702 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD JUL 1 PY 2002 VL 7 IS 13 BP 687 EP 689 AR PII S1359-6446(02)02312-7 DI 10.1016/S1359-6446(02)02312-7 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 569RT UT WOS:000176616500001 PM 12110216 ER PT J AU Radko, SP Chrambach, A AF Radko, SP Chrambach, A TI Separation and characterization of sub-mu m- and mu m-sized particles by capillary zone electrophoresis SO ELECTROPHORESIS LA English DT Review DE capillary zone electrophoresis; microparticles; review ID COMMON COLD VIRUS; RED-BLOOD-CELLS; INDUCED FLUORESCENCE DETECTION; HUMAN RHINOVIRUS SEROTYPE-2; LATEX-PARTICLES; COLLOIDAL PARTICLES; SURFACE-PROPERTIES; POLYSTYRENE LATEX; CHEMILUMINESCENCE DETECTION; ELECTROKINETIC BEHAVIOR AB The analytical separation and characterization of particles in the size range of sub-gm and pm diameters by capillary zone electrophoresis (CZE) has been reviewed. The theoretical basis, on which the mobility can be interpreted to provide information regarding characteristics of particle surface, has shortly been presented. Particular emphasis was put on the model dependence of that interpretation and the need in most applications to forego the classical idealized model of spherical particles with "smooth" surfaces and to apply more realistic models, which take the "hairy" surface of real particles into account. Some highlights of the literature on the CZE of polystyrene latex microspheres, organic and inorganic colloids, lipoprotein particles, viruses, liposomes, biological membrane vesicles, and biological cells have been discussed. Also summarized are the reports on the particle size dependence of mobility and peak broadening in CZE and on electrophoretic behavior of rodlike particles and particle aggregates. Finally, the effects of neutral polymers in the background electrolyte on particle mobility and peak width are reviewed. C1 NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Russian Acad Med Sci, Med Genet Res Ctr, Dept Biotechnol, Moscow, Russia. RP Chrambach, A (reprint author), NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. NR 125 TC 105 Z9 107 U1 2 U2 31 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 2002 VL 23 IS 13 BP 1957 EP 1972 DI 10.1002/1522-2683(200207)23:13<1957::AID-ELPS1957>3.0.CO;2-I PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 581MZ UT WOS:000177297400002 PM 12210247 ER PT J AU Cretich, M Stastna, M Chrambach, A Chiari, M AF Cretich, M Stastna, M Chrambach, A Chiari, M TI Decreased protein peak asymmetry and width due to static capillary coating with hydrophilic derivatives of polydimethylacrylamide SO ELECTROPHORESIS LA English DT Article DE capillary coating; capillary zone electrophoresis ID ZONE-ELECTROPHORESIS; PERFORMANCE; POLYMER AB We have recently described [1] a fast and simple method for the "adsorbed static" coating of capillaries in capillary zone electrophoresis (CZE) with epoxy-poly(dimethylacrylamide) (EPDMA). Protein CZE peaks in the EPDMA-coated capillaries exhibited a peak asymmetry similar to that obtained in capillaries with "covalent static" coating of polyacrylamide, suggesting a similar degree of adsorption of the protein onto the coating [2]. Instability of such coating at very low ionic strength and its stripping from the capillary in the presence of sodium dodecyl sulfate (SDS) also indicated a hydrophilic bonding of EPDMA to the silanol surface of the capillary, while its stripping in the CZE of "carboxylate-modified" polystyrene suggested a competition between carboxylate and EPDMA for the hydrophilic bonds to silanol. To test those propositions, a number of EPDMA-derived coating agents with increased hydrophilicity were synthesized. Of a number of the hydrophilic coating agents tested (Table 1) only two, 2% hydrolyzed EPDMA (HPDMA) hydrolyzed in sulfuric acid to effect the conversion of the epoxy groups to diols (Table 1, No. 38), and 20% EPDMA(Table 1, No. 44) exhibited for representative proteins a decreased peak asymmetry and width while the stability of the suppression of electroosmotic flow (EOF), and the stability of mobility in consecutive CZE runs was reduced relative to EPDMA. Coating agents which were more highly hydrophilic than those two (Table 1, No. 49) or less hydrophilic than 2% EPDMA (Table 1, Nos. 57, 53, 46) provided no stable static coating. C1 NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. CNR, Inst Mol Recognit Chem, I-20133 Milan, Italy. RP Chrambach, A (reprint author), NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. RI Stastna, Miroslava/G-9266-2014; OI Cretich, Marina/0000-0001-8251-5275; Chiari, Marcella/0000-0002-4670-1430 NR 7 TC 17 Z9 18 U1 1 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 2002 VL 23 IS 14 BP 2274 EP 2278 AR UNSP EL 4988 DI 10.1002/1522-2683(200207)23:14<2274::AID-ELPS2274>3.0.CO;2-Y PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 582EP UT WOS:000177337000017 PM 12210233 ER PT J AU Deterding, LJ Cutalo, JM Khaledi, M Tomer, KB AF Deterding, LJ Cutalo, JM Khaledi, M Tomer, KB TI Separation and characterization of human high-density apolipoproteins using a nonaqueous modifier in capillary electrophoresis-mass spectrometry SO ELECTROPHORESIS LA English DT Article DE apolipoproteins; capillary electrophoresis; high-density lipoproteins; mass spectrometry; tandem mass spectrometry ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CORONARY-ARTERY DISEASE; A-I; PLASMA APOLIPOPROTEINS; GEL-ELECTROPHORESIS; LIPOPROTEINS; SERUM; ISOTACHOPHORESIS; ISOFORMS; PROTEINS AB The separation and characterization of human apolipoproteins and their isoforms was investigated using capillary electrophoresis (CE) in combination with mass spectrometry (MS). The focus of these analyses was the major protein constituents of plasma high-density lipoproteins, apolipoprotein A-I and A-II. Using aqueous buffers in CE, no separation between apolipoprotein A-I and A-II was observed. With the addition of 10-20% acetonitrile, however, the two species could be separated. Furthermore, multiple peaks for each of the apolipoprotein species were observed under these CE conditions. In order to identify and characterize the components, these separations were then coupled with online mass spectrometric detection (CE-MS). Our CE-MS results suggest that the multiple components observed in the acetonitrile-containing CE separation appear to be oxidized forms of the proteins in addition to native forms of the apolipoprotein A-I and A-II. These data are in agreement with previous reports that the methionine residues of the high-density lipoproteins (HDLs) are sensitive to oxidation, which in turn, alters their lipid binding characteristics and secondary structure. In addition to oxidized forms of the proteins, apolipoprotein A-II contained additional components, which varied in mass by 128 Da. The structural differences between these components were determined by proteolytic digestion and tandem MS. Using these techniques, we determined that these components were due to truncation of the C-terminal glutamine amino acid residue on apolipoprotein A-II. These results demonstrate that CE in combination with MS is a promising technique for screening and characterizing isomers of plasma apolipoproteins. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA. RP Deterding, LJ (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr,POB 12233,MD F0-03, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 57 TC 19 Z9 20 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 2002 VL 23 IS 14 BP 2296 EP 2305 AR UNSP EL 4977 DI 10.1002/1522-2683(200207)23:14<2296::AID-ELPS2296>3.0.CO;2-I PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 582EP UT WOS:000177337000020 PM 12210236 ER PT J AU Boehm, M Yoshimoto, T Crook, MF Nallamshetty, S True, A Nabel, GJ Nabel, EG AF Boehm, M Yoshimoto, T Crook, MF Nallamshetty, S True, A Nabel, GJ Nabel, EG TI A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression SO EMBO JOURNAL LA English DT Article DE cell cycle; hKIS; p27(Kip1); phosphorylation; serine ID RNA-RECOGNITION MOTIF; INHIBITOR P27(KIP1); UBIQUITIN-LIGASE; S-PHASE; PROTEIN; P27; DEGRADATION; EXPRESSION; STATHMIN; COMPLEX AB The cyclin-dependent kinase inhibitor, p27(Kip1), which regulates cell cycle progression, is controlled by its subcellular localization and subsequent degradation. p27(Kip1) is phosphorylated on serine 10 (S10) and threonine 187 (T187). Although the role of T187 and its phosphorylation by Cdks is well-known, the kinase that phosphorylates S10 and its effect on cell proliferation has not been defined. Here, we identify the kinase responsible for S10 phosphorylation as human kinase interacting stathmin (hKIS) and show that it regulates cell cycle progression. hKIS is a nuclear protein that binds the C-terminal domain of p27(Kip1) and phosphorylates it on S10 in vitro and in vivo, promoting its nuclear export to the cytoplasm. hKIS is activated by mitogens during G(0)/G(1), and expression of hKIS overcomes growth arrest induced by p27(Kip1). Depletion of KIS using small interfering RNA (siRNA) inhibits S10 phosphorylation and enhances growth arrest. p27(-/-) cells treated with KIS siRNA grow and progress to S/G(2) similar to control treated cells, implicating p27(Kip1) as the critical target for KIS. Through phosphorylation of p27(Kip1) on S10, hKIS regulates cell cycle progression in response to mitogens. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 37 TC 203 Z9 213 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 1 PY 2002 VL 21 IS 13 BP 3390 EP 3401 DI 10.1093/emboj/cdf343 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 572PL UT WOS:000176784100018 PM 12093740 ER PT J AU Braddock, DT Baber, JL Levens, D Clore, GM AF Braddock, DT Baber, JL Levens, D Clore, GM TI Molecular basis of sequence-specific single-stranded DNA recognition by KH domains: solution structure of a complex between hnRNP KKH3 and single-stranded DNA SO EMBO JOURNAL LA English DT Article DE hnRNP K; KH domains; NMR; sequence-specific ssDNA recognition; solution structure ID NUCLEAR RIBONUCLEOPROTEIN-K; RESIDUAL DIPOLAR COUPLINGS; C-MYC; STRUCTURE REFINEMENT; TRANSCRIPTION FACTOR; CHEMICAL-SHIFT; PROTEIN; RNA; BINDING; NMR AB To elucidate the basis of sequence-specific single-stranded (ss) DNA recognition by K homology (KH) domains, we have solved the solution structure of a complex between the KH3 domain of the transcriptional regulator heterogeneous nuclear ribonucleoprotein K (hnRNP K) and a 10mer ssDNA. We show that hnRNP K KH3 specifically recognizes a tetrad of sequence 5'd-TCCC. The complex is stabilized by a dense network of methyl-oxygen hydrogen bonds involving the methyl groups of three isoleucine residues and the O2 and N3 atoms of the two central cytosine bases. Comparison with the recently solved structure of a specific protein-ssDNA complex involving the KH3 and KH4 domains of the far upstream element (FUSE) binding protein FBP suggests that the amino acid located five residues N-terminal of the invariant GXXG motif, which is characteristic of all KH domains, plays a crucial role in discrimination of the first two bases of the tetrad. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, 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; Levens, David/C-9216-2009 OI Clore, G. Marius/0000-0003-3809-1027; Levens, David/0000-0002-7616-922X NR 42 TC 87 Z9 90 U1 1 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 JUL 1 PY 2002 VL 21 IS 13 BP 3476 EP 3485 DI 10.1093/emboj/cdf352 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 572PL UT WOS:000176784100026 PM 12093748 ER PT J AU Skelding, Z Sarnovsky, R Craig, NL AF Skelding, Z Sarnovsky, R Craig, NL TI Formation of a nucleoprotein complex containing Tn7 and its target DNA regulates transposition initiation SO EMBO JOURNAL LA English DT Article DE DNA-protein complex; DNA transposition; enzyme activation; Tn7; transposase ID SITE-SPECIFIC RECOMBINATION; OF-FUNCTION MUTANTS; MU-DNA; TN7-ENCODED PROTEINS; SYNAPTIC COMPLEX; STRAND TRANSFER; SYSTEM; ATP; TRANSCRIPTION; INTERMEDIATE AB Tn7 insertion into its specific target site, attTn7, is mediated by the proteins TnsA, TnsB, TnsC and TnsD. The double-strand breaks that separate Tn7 from the donor DNA require the Tns proteins, the transposon and an attTn7 target DNA, suggesting that a prerequisite for transposition is the formation of a nucleoprotein complex containing TnsABC+D, and these DNAs. Here, we identify a TnsABC+D transposon-attTn7 complex, and demonstrate that it is a transposition intermediate. We demonstrate that an interaction between TnsB, the transposase subunit that binds to the transposon ends, and TnsC, the target DNA-binding protein that controls the activity of the transposase, is essential for assembly of the TnsABC+D transposon-attTn7 complex. We also show that certain TnsB residues are required for recombination because they mediate a TnsB-TnsC interaction critical to formation of the TnsABC+D transpo son-attTn7 complex. We demonstrate that TnsA, the other transposase subunit, which also interacts with TnsC, greatly stabilizes the TnsABC+D transpo son-attTn7 complex. Thus multiple interactions between the transposase subunits, TnsA and TnsB, and the target-binding transposase activator, TnsC, control Tn7 transposition. C1 Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Dept Genet & Mol Biol, Baltimore, MD 21205 USA. NCI, Bethesda, MD 20892 USA. RP Craig, NL (reprint author), Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Dept Genet & Mol Biol, Baltimore, MD 21205 USA. FU NCI NIH HHS [P01 CA16519-28] NR 33 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 1 PY 2002 VL 21 IS 13 BP 3494 EP 3504 DI 10.1093/emboj/cdf347 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 572PL UT WOS:000176784100028 PM 12093750 ER PT J AU LeDuc, JW Damon, I Meegan, JM Relman, DA Huggins, J Jahrling, PB AF LeDuc, JW Damon, I Meegan, JM Relman, DA Huggins, J Jahrling, PB TI Smallpox research activities: US Interagency collaboration, 2001 SO EMERGING INFECTIOUS DISEASES LA English DT Article C1 Ctr Dis Control & Prevent, Atlanta, GA 30332 USA. NIH, Bethesda, MD 20892 USA. Stanford Univ, Stanford, CA 94305 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. RP LeDuc, JW (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30332 USA. NR 9 TC 47 Z9 49 U1 0 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUL PY 2002 VL 8 IS 7 BP 743 EP 745 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 565XE UT WOS:000176394200022 PM 12095449 ER PT J AU Yu, JA Pacak, K AF Yu, JA Pacak, K TI Management of malignant pheochromocytoma SO ENDOCRINOLOGIST LA English DT Review ID ENDOCRINE NEOPLASIA TYPE-2; I-131 MIBG SCINTIGRAPHY; NEUROENDOCRINE TUMORS; METASTATIC PHEOCHROMOCYTOMA; METAIODOBENZYLGUANIDINE I-131-MIBG; I-123 METAIODOBENZYLGUANIDINE; OCTREOTIDE SCINTIGRAPHY; ARTERIAL EMBOLIZATION; PLASMA METANEPHRINES; INCREASED EXPRESSION AB Pheochromotocytoma is a rare but lifer threatening tumor of chromaffin cells characterized by excesssive production of catecholamines. Malignant pheochromocytoma is established by the development of distant metastases in non,chromaffin cell sites. The pathogenesis of sporadic pheochromocytomas is largely unknown, and specific genetic markers that distinguish benign from malignant tumors remain unidentified. Extra-adrenal involvement and large tumor size are major features suggestive of future malignant potential. In some cases, increased dopamine excretion and its metabolites are associated with malignant pheochromocytoma. Nuclear imaging techniques, such as metaiodobenzylguanidine (MIBG) scintigraphy, somatostatin receptor scintigraphy, and positron emission tomography (PET) scanning play important roles in localizing metastatic lesions. In selected patients, radical resection of primary and metastatic tumors is the treatment of choice, either with curative or palliative intention. Pharmacological blockade of the effects of catecholamine excess is critical in preoperative care and long-term management of malignant pheochromocytoma. Therapy with iodine (1) 131-MIBG is the treatment of choice when unresectable MIBG positive lesions are present. The usefulness of yttrium (y) 99-labeled somatostatin analogs is still undergoing study. Chemotherapy is reserved for patients with progressive disease who do not respond to other therapies, and external beam radiation is indicated for patients with local symptoms caused by tumor invasion. Future advances in clinical management of malignant pheochromocytoma depend on the development of specific predictors for malignancy and effective novel treatments. C1 NICHHD, PREB, NIH, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHD, PREB, NIH, Bldg 10,Room 9D42,10 Ctr Dr,MSC 1583, Bethesda, MD 20892 USA. NR 84 TC 6 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD JUL-AUG PY 2002 VL 12 IS 4 BP 291 EP 299 DI 10.1097/01.ten.0000022705.62247.fb PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 575FH UT WOS:000176935900007 ER PT J AU Sharifi, N Reuss, AE Wray, S AF Sharifi, N Reuss, AE Wray, S TI Prenatal LHRH neurons in nasal explant cultures express estrogen receptor beta transcript SO ENDOCRINOLOGY LA English DT Article ID HORMONE-RELEASING HORMONE; EMBRYONIC OLFACTORY PLACODE; MESSENGER-RIBONUCLEIC-ACID; GENE-EXPRESSION; RHESUS-MONKEY; GNRH NEURONS; RAT-BRAIN; MIGRATION; IMMUNOREACTIVITY; MAINTENANCE AB Sex steroids influence LHRH neuronal activity, exerting a negative or positive feedback action, depending on the reproductive state of the animal. Recent evidence indicates that LHRH neurons possess the estrogen receptor beta (ERbeta) subtype postnatally, suggesting that estrogen may act, in part, directly on LHRH neurons. In this study, we identified ERbeta transcript in prenatal LHRH neurons as a function of age. Single-cell cDNA pools were made from LHRH neurons maintained for 7, 14, and 28 d in vitro (div). Screening of the cDNA pools by PCR with ERP-specific primers revealed ERbeta-positive LHRH neurons at all three ages. However, the number of LHRH cells coexpressing ERbeta transcript decreased dramatically between 14 (6110) and 28 div (1/10). None of the LHRH cells were positive for ERalpha transcript. These results indicate that developing LHRH neurons express the transcript for ERbeta and suggest that continued expression of ERbeta is either a characteristic of LHRH neurons that may require cues from the central nervous system and/or periphery or predetermined to be maintained in a subpopulation of LHRH neurons. C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, Bldg 36,Room 5A-21, Bethesda, MD 20892 USA. NR 31 TC 46 Z9 48 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2002 VL 143 IS 7 BP 2503 EP 2507 DI 10.1210/en.143.7.2503 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 568PE UT WOS:000176550400008 PM 12072381 ER PT J AU Shalev, A Blair, PJ Hoffmann, SC Hirshberg, B Peculis, BA Harlan, DM AF Shalev, A Blair, PJ Hoffmann, SC Hirshberg, B Peculis, BA Harlan, DM TI A proinsulin gene splice variant with increased translation efficiency is expressed in human pancreatic islets SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RNA; 5'-UNTRANSLATED REGIONS; INSULIN GENE; BIOSYNTHESIS; CARCINOMAS; SEQUENCE AB As glucose-induced insulin expression is mainly regulated at the translational level, and such regulation often involves the W-untranslated region (5'UTR), we examined the human proinsulin gene 5'UTR. RT-PCR and sequencing demonstrated that a proinsulin splice variant (SPV) generated from a cryptic 5'-splice site and retaining the first 26 bp of intron I was present in human pancreatic islets from normal donors. The expression of this SPV was metabolically regulated, as shown by quantitative real-time RT-PCR, revealing a more than 10-fold increase in the SPV in isolated human islets incubated at 16.7 mm compared with 1.67 mm glucose. In vitro wheat-germ translation and in vivo transfection studies demonstrated that the altered 5'UTR of the SPV increased translation. The SPV yielded 4-fold more in vitro translated preproinsulin protein than the native proinsulin mRNA, and the SPV 5'UTR inserted upstream from a luciferase reporter gene resulted in a more than 6-fold higher luciferase activity, suggesting enhanced translation in vivo. Retention of the 26 bp changed the proposed secondary RNA structure of the SPV, which may facilitate ribosomal binding and explain the increase in translation efficiency. These results suggest a novel mechanism by which metabolic changes can modulate the expression of 5'UTR SPVs and thereby regulate translation efficiency. C1 NIDDKD, Transplantat & Autoimmun Branch, NIH, AFFRI, Bethesda, MD 20889 USA. NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20889 USA. RP Shalev, A (reprint author), NIDDKD, Transplantat & Autoimmun Branch, NIH, AFFRI, Bldg 43,Room 3222,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 19 TC 43 Z9 43 U1 4 U2 5 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2002 VL 143 IS 7 BP 2541 EP 2547 DI 10.1210/en.143.7.2541 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 568PE UT WOS:000176550400013 PM 12072386 ER PT J AU Carter, LA Tabor, MB Bonner, JC Bonner, LA AF Carter, LA Tabor, MB Bonner, JC Bonner, LA TI Mitogen-activated protein kinase activation by oxidative and bacterial stress in an amphibian cell culture model SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE amphibian decline; endotoxins; environmental stress; mitogen-activated protein kinase; reactive oxygen species; Xenopus ID SOLAR UV-B; POPULATION DECLINES; MALFORMED FROGS; MAP KINASE; RADIATION; MISSISSIPPI; PESTICIDES; INDUCTION; SURVIVAL; RECEPTOR AB The decline of many amphibian species could be caused by their susceptibility to environmental pollutants that cause cellular stress and cell death. A variety of intracellular signal transduction pathways are activated by environmental stress factors, which result in cell death. Mitogen-activated protein kinases are intracellular signaling molecules that include the extracellular signal-regulated kinases (ERK-1 and ERK-2), We used cultured Xenopus tadpole cells (XTC-2 cells) to investigate the activation of ERK by oxidative or bacterial stress, two environmental factors that could contribute to pollution in aquatic systems. We exposed XTC-2 cell monolayers to hydrogen peroxide or bacterial lipopolysaccharide and measured ERK activation by Western blotting using antibodies raised against phosphorylated ERK-1 and ERK-2. Only ERK-2 was detected in XTC-2 cells. Both hydrogen peroxide and lipopolysaccharide caused ERK-2 phosphorylation in a time- and concentration-dependent manner. Hydrogen peroxide caused a 20- to 30-fold increase in ERK-2 activation that peaked 30 min after treatment, and lipopolysaccharide induced a 5- to 10-fold increase in ERK-2 activation that peaked 60 min after treatment. PD98059, an inhibitor of the ERK pathway, reduced the cytotoxic response of XTC-2 cells to hydrogen peroxide or lipopolysaccharide. These data suggest that ERK-2 is an intracellular target of oxidative and bacterial stress in amphibians that mediates, at least in part, the cytotoxic response to hydrogen peroxide or lipopolysaccharide. Moreover, the Xenopus (XTC-2) cell culture system could serve as a useful model to identify agents that might threaten amphibian populations and human health. C1 Peace Coll, Raleigh, NC 27604 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Bonner, LA (reprint author), Peace Coll, Pressly Bldg,15 E Peace St, Raleigh, NC 27604 USA. NR 34 TC 2 Z9 2 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 2002 VL 110 IS 7 BP 641 EP 645 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 585VZ UT WOS:000177546400023 PM 12117640 ER PT J AU Alfaro-Moreno, E Martinez, L Garcia-Cuellar, C Bonner, JC Murray, JC Rosas, I Rosales, SPD Osornio-Vargas, AR AF Alfaro-Moreno, E Martinez, L Garcia-Cuellar, C Bonner, JC Murray, JC Rosas, I Rosales, SPD Osornio-Vargas, AR TI Biologic effects induced in vitro by PM10 from three different zones of Mexico City SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE apoptosis; cytotoxicity; DNA breakage; E-selectin; IL-6; Mexico City; particle composition; PGE(2); PM10; TNF alpha ID PARTICULATE AIR-POLLUTION; ALVEOLAR MACROPHAGES; COARSE PARTICLES; MORTALITY; EXPRESSION; APOPTOSIS; FINE; INDUCTION; MONOCYTES; OUTDOOR AB Exposure to urban airborne particles is associated with an increase in morbidity and mortality. There is little experimental evidence of the mechanisms involved and the role of particle composition. We assessed cytotoxicity (crystal violet assay), apoptosis [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) or annexin V assay], DNA breakage (comet assay), and production of proinflammatory mediators [tumor necrosis factor alpha (TNFalpha), interleukin 6 (IL-6), prostaglandin E-2 (PGE(2))] (enzyme-linked immunosorbent assay), and E-selectin (flow cytometry) in cell lines exposed to particulate matter < 10 μm in size (PM10) obtained from the northern, central, and southern zones of Mexico City. Particle concentrations ranged from 2.5 to 160 μg/cm(2). We used epithelial, endothelial, fibroblastic, and monocytic cells and assessed DNA damage in Balb-c cells, TNFα and IL-6 production in mouse monocytes, and PGE(2) in rat lung fibroblasts. We determined the expression of E-selectin in human endothelial cells and evaluated the cytotoxic potential of the PM10 samples in all cell types. PM10 from all three zones of Mexico City caused cell death, DNA breakage, and apoptosis, with particles from the north and central zones being the most toxic. All of these PM10 samples induced secretion of proinflammatory molecules, and particles from the central zone were the most potent. Endothelial cells exposed to PM10 from the three zones expressed similar E-selectin levels. Mexico City PM10 induced biologic effects dependent on the zone of origin, which could be caused by differences in the mixture or size distribution within particle samples. Our data suggest that particle composition as well as particle size should be considered in assessing the adverse effects of airborne particulate pollution. C1 Inst Nacl Cancerol, Subdirecc Invest Basica, Mexico City 14000, DF, Mexico. Univ Nacl Autonoma Mexico, Ctr Ciencias Atmosfera, Mexico City 04510, DF, Mexico. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Univ Nottingham, Nottingham NG7 2RD, England. Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico. RP Osornio-Vargas, AR (reprint author), Inst Nacl Cancerol, Subdirecc Invest Basica, Av San Fernando 22, Mexico City 14000, DF, Mexico. RI Osornio Vargas, Alvaro/D-4012-2009; Osornio Vargas, Alvaro/B-4645-2010 OI Osornio Vargas, Alvaro/0000-0001-8287-7102 NR 37 TC 111 Z9 112 U1 3 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 2002 VL 110 IS 7 BP 715 EP 720 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 585VZ UT WOS:000177546400032 PM 12117649 ER PT J AU Goldfarb, LG AF Goldfarb, LG TI Genetics and infectious disease: Convergence at the prion SO EPIDEMIOLOGY LA English DT Editorial Material ID CREUTZFELDT-JAKOB-DISEASE; KURU; VARIANT; GENOTYPE; NEUROPATHOLOGY; EPIDEMIC; VCJD; UK C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Goldfarb, LG (reprint author), NINDS, NIH, Bldg 10,Room 4B37,10 Ctr Dr,MSC 1361, Bethesda, MD 20892 USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 BP 379 EP 381 DI 10.1097/01.EDE.0000016931.03319.3D PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600003 PM 12094090 ER PT J AU Martin, SA Harlow, SD Sowers, F Longnecker, MP Garabrant, D Shore, DL Sandler, DP AF Martin, SA Harlow, SD Sowers, F Longnecker, MP Garabrant, D Shore, DL Sandler, DP TI DDT metabolite and androgens in African-American farmers SO EPIDEMIOLOGY LA English DT Article DE anti-androgen; androgens; hypogonadism; blacks; farmers; pesticide exposure; DDT; DDE ID TESTOSTERONE LEVELS; HUMAN-SERUM; RECEPTOR; WOMEN; MEN; FLUTAMIDE; P,P'-DDE; MALES AB Background. The ubiquitous dichlorodiphenyltrichloroethane (DDT) metabolite 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) is an androgen receptor antagonist. Data on potential antiandrogenic activity of DDE in humans are limited. Methods. The relations between concentrations of plasma DE and several serum androgens (total testosterone, bioavailable testosterone, 5alpha-dihydrotestosterone, and free androgen index) were examined in 137 North Carolina black male farmers, using multiple linear regression. Results. Participants ranged in age form 30 to 88 years (mean = 62 years). Most had farmed for about 30 years and 27% reported having used DDT. The median DDE level was 7.7 mug per liter (1213 mug per kg lipid), slightly higher than in other recent studies. Overall, concentrations of DDE and androgens were unrelated. Total testosterone decreased 2% (95% confidence limits [CL] = -9%, 5%) per increase in interquartile distance of lipid-adjusted DDE. The percentage change in other hormones was similarly negligible. However, among those whose DDE level was in the top tenth percentile, compared with all others, total testosterone and free androgen index were lower by 23% (CL = -40%, 1%) and 22% (CL = -41%, 4%) respectively. Plasma androgen levels decreased with age, a relation that has previously been studies only in whites. Conclusions. Studies of more highly exposed populations may be needed to evaluate effects, if any, of DDE. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Westat Corp, Durham, NC USA. RP Sandler, DP (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. OI Longnecker, Matthew/0000-0001-6073-5322; Sandler, Dale/0000-0002-6776-0018 NR 28 TC 40 Z9 41 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 BP 454 EP 458 DI 10.1097/01.EDE.0000016382.31505.66 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600014 PM 12094101 ER PT J AU Alavanja, MCR Samanic, C Dosemeci, M Tarone, R Lynch, C Lubin, J Thomas, K Coble, J Sandler, D Blair, A AF Alavanja, MCR Samanic, C Dosemeci, M Tarone, R Lynch, C Lubin, J Thomas, K Coble, J Sandler, D Blair, A TI Prostate cancer risk in the agricultural health cohort SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Univ Iowa, Iowa City, IA 52242 USA. US EPA, Washington, DC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 887 BP S240 EP S240 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600819 ER PT J AU Allen, R Gondy, G Mage, D Stewart, P Coble, J Blair, A AF Allen, R Gondy, G Mage, D Stewart, P Coble, J Blair, A TI Evaluating potential for occupational pesticide exposure in the NHANES-III SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 US EPA, Washington, DC 20460 USA. Temple Univ, ISR, Philadelphia, PA 19122 USA. NCI, Occupat Studies Branch, Philadelphia, PA 19122 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 842 BP S230 EP S230 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600775 ER PT J AU Bell, EM Vermeulen, R Tollerud, DJ Rothman, N Blair, A AF Bell, EM Vermeulen, R Tollerud, DJ Rothman, N Blair, A TI Immune response in pesticide applicators exposed to 2,4-dichlorophenoxyacetic acid SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Med Coll Penn & Hahnemann Univ, Philadelphia, PA USA. RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 905 BP S243 EP S243 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600837 ER PT J AU Blair, A AF Blair, A TI Use of biomonitoring and questionnaire data in assessment of pesticide exposures for studies of chronic diseases among farmers and their families SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 073 BP S93 EP S93 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600088 ER PT J AU Buck, GM Tee, PG Fitzgerald, E Vana, JE McGuinness, B Weiner, JM AF Buck, GM Tee, PG Fitzgerald, E Vana, JE McGuinness, B Weiner, JM TI Maternal consumption of contaminated sport fist and infant gestation and birth size, New York state angler cohort study SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NICHHD, New York State Dept Hlth, New York, NY USA. SUNY Buffalo, Buffalo, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 938 BP S249 EP S249 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600866 ER PT J AU Camann, DE Yau, AY Colt, JS AF Camann, DE Yau, AY Colt, JS TI Distributions and quality of acidic pesticide measurements in bag dust from four areas of USA SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. SW Res Inst, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 636 BP S193 EP S194 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600593 ER PT J AU Cantor, KP AF Cantor, KP TI Disinfection byproducts, estimates of exposure, and cancer risk: A brief review SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 164 BP S108 EP S109 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600165 ER PT J AU Castano-Vinyals, G Cantor, K Villanueva, CM Tardon, A Serra, C Closas, GR Carrato, A Malats, N Real, P Silverman, D Rothman, N Dosemeci, M Kogevinas, M AF Castano-Vinyals, G Cantor, K Villanueva, CM Tardon, A Serra, C Closas, GR Carrato, A Malats, N Real, P Silverman, D Rothman, N Dosemeci, M Kogevinas, M TI Socioeconomic status and consumption of bottled water SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Inst Municipal Invest Med, Resp & Environm Hlth Res Unit, E-08003 Barcelona, Spain. NCI, Occupat Epidemiol Branch, Rockville, MD USA. Univ Oviedo, Oviedo, Spain. UPF, Barcelona, Spain. UMH, Elche, Spain. RI Serra, C/E-6879-2014; Kogevinas, Manolis/C-3918-2017 OI Serra, C/0000-0001-8337-8356; NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 174 BP S110 EP S111 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600175 ER PT J AU Curwin, BC Sanderson, WT Reynolds, SJ Ward, EM Alavanja, MCR AF Curwin, BC Sanderson, WT Reynolds, SJ Ward, EM Alavanja, MCR TI Pesticide contamination inside farm and non-farm homes and vehicles SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Colorado State Univ, Dept Environm Hlth, Ft Collins, CO 80523 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 642 BP S195 EP S195 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600599 ER PT J AU De Roos, AJ Stewart, PA Linet, MS Inskip, PD AF De Roos, AJ Stewart, PA Linet, MS Inskip, PD TI Occupation and the risk of adult glioma in the United States SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Div Canc Epidemiol & Genet, NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 811 BP S224 EP S224 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600744 ER PT J AU De Roos, AJ Vermeulen, R Blair, A Hildesheim, A Pinto, L Gillette, PP Lynch, CF Allen, RH Alavanja, MC AF De Roos, AJ Vermeulen, R Blair, A Hildesheim, A Pinto, L Gillette, PP Lynch, CF Allen, RH Alavanja, MC TI Study of immune effects in corn farmers within the agricultural health study SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 US EPA, Res Triangle Pk, NC 27711 USA. Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA. NCI, HPV Monitoring Lab, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 331 BP S137 EP S137 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600310 ER PT J AU Engel, LS Vaughan, TL Gammon, MD Chow, WH Risch, HA Dubrow, R Mayne, ST Rotterdam, H Schoenberg, JB Stanford, JL West, AB Blot, WJ Fraumeni, JF AF Engel, LS Vaughan, TL Gammon, MD Chow, WH Risch, HA Dubrow, R Mayne, ST Rotterdam, H Schoenberg, JB Stanford, JL West, AB Blot, WJ Fraumeni, JF TI Occupation and risk of esophageal and gastric cardia adenocarcinoma SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27515 USA. Yale Univ, Sch Med, Dept Epidemiol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Publ Hlth, New Haven, CT 06510 USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10027 USA. New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. Yale Univ, Dept Pathol, New Haven, CT USA. Int Epidemiol Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 470 BP S163 EP S163 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600441 ER PT J AU Hoppin, JA Umbach, DM London, SJ Alavanja, MCR Sandler, DP AF Hoppin, JA Umbach, DM London, SJ Alavanja, MCR Sandler, DP TI Wheeze risk associated with animal production among farmers in the agricultural health study: Interactions with atopy, asthma, and smoking SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 434 BP S157 EP S157 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600409 ER PT J AU Hoppin, JA Arcury, TA Quandt, SA Rao, P Doran, AM AF Hoppin, JA Arcury, TA Quandt, SA Rao, P Doran, AM TI Reporting pesticide exposure results to participants: Issues and observations SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 301 BP S133 EP S133 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600285 ER PT J AU Kamel, F Rowland, AS Anger, WK Baird, DD Gladen, BC Moreno, T Park, LP Stallone, L Sandler, DP AF Kamel, F Rowland, AS Anger, WK Baird, DD Gladen, BC Moreno, T Park, LP Stallone, L Sandler, DP TI Neurobehavioral performance and work experience in Florida farmworkers SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ New Mexico, Albuquerque, NM 87131 USA. NIEHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 337 BP S138 EP S138 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600316 ER PT J AU Lynberg, M Ashley, D Mendola, P Nuckols, JR Cantor, K Blount, B Singer, P Wilkes, C Backer, L Langlois, P AF Lynberg, M Ashley, D Mendola, P Nuckols, JR Cantor, K Blount, B Singer, P Wilkes, C Backer, L Langlois, P TI An integrated research agenda to evaluate tap water disinfection byproducts and human health: Part II SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC USA. Colorado State Univ, Dept Environm Hlth, Ft Collins, CO 80523 USA. NCI, Bethesda, MD 20892 USA. Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27515 USA. Wilkes Technol Inc, Bethesda, MD USA. Texas Dept Hlth, Austin, TX 78756 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 167 BP S109 EP S109 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600168 ER PT J AU Lynberg, M Ashley, M Mendola, P Nuckols, JR Cantor, K Blount, B Singer, P Wilkes, C Backer, L Langlois, P AF Lynberg, M Ashley, M Mendola, P Nuckols, JR Cantor, K Blount, B Singer, P Wilkes, C Backer, L Langlois, P TI An integrated research agenda to evaluate tap water disinfection byproducts and human health: Part 1 SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC USA. Colorado State Univ, Dept Environm Hlth, Ft Collins, CO 80523 USA. NCI, Bethesda, MD 20892 USA. Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27515 USA. Wilkes Technol Inc, Bethesda, MD USA. Texas Dept Hlth, Austin, TX 78756 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 165 BP S109 EP S109 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600166 ER PT J AU Melnick, R Boorman, G Hooth, M AF Melnick, R Boorman, G Hooth, M TI Studies on drinking water disinfection byproducts by the National Toxicology Program SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 181 BP S112 EP S112 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600182 ER PT J AU Miller, RS Nuckols, JR Gunier, RB Hertz, A Ward, MH Reynolds, P AF Miller, RS Nuckols, JR Gunier, RB Hertz, A Ward, MH Reynolds, P TI Linking the California pesticide use reporting database with spatial land use data for exposure assessment SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Colorado State Univ, Ft Collins, CO 80523 USA. NCI, Bethesda, MD 20892 USA. Calif Dept Hlth Serv, Sacramento, CA 95814 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 732 BP S210 EP S211 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600677 ER PT J AU Nuckols, JR Small, L Maxwell, SM Miller, RS Ward, MH AF Nuckols, JR Small, L Maxwell, SM Miller, RS Ward, MH TI A geographical information system (GIS)-based exposure metric for estimating nitrate in drinking water supplies SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Colorado State Univ, Ft Collins, CO 80523 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 729 BP S210 EP S210 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600674 ER PT J AU Peters, A Klot, S Heier, M Trentinalglia, I Cyrys, J Hauptmann, M Wichmann, HE Loewel, H AF Peters, A Klot, S Heier, M Trentinalglia, I Cyrys, J Hauptmann, M Wichmann, HE Loewel, H TI Particulate air pollution and the onset of nonfatal myocardial infarction SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 GSF, Inst Epidemiol, Neuherberg, Germany. NCI, Bethesda, MD 20892 USA. RI Cyrys, Josef/B-5359-2014 NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 862 BP S234 EP S235 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600795 ER PT J AU Samanic, C Hoppin, JA Lubin, JA Blair, A Alavanja, MCR AF Samanic, C Hoppin, JA Lubin, JA Blair, A Alavanja, MCR TI Factor analysis of pesticide use patterns among pesticide applicators in the agricultural health study SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 912 BP S244 EP S244 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600844 ER PT J AU Schonwalder, C AF Schonwalder, C TI State of the art: Joining toxicology and epidemiology for better risk assessment SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 042 BP S88 EP S89 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600063 ER PT J AU Thomas, K Sheldon, L Gordon, S Jones, M Reynolds, S Raymer, J Akland, G Dosemeci, M Alavanja, M AF Thomas, K Sheldon, L Gordon, S Jones, M Reynolds, S Raymer, J Akland, G Dosemeci, M Alavanja, M TI Interim results from the Agricultural Health Study/Pesticide Exposure Study SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 US EPA, Natl Exposure Res Lab, Res Triangle Pk, NC USA. Battelle Mem Inst, Columbus, OH 43201 USA. Univ Iowa, Iowa City, IA 52242 USA. Colorado State Univ, Ft Collins, CO 80523 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 076 BP S94 EP S94 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600091 ER PT J AU Thorne, PS Kulhankova, K Yin, M Cohn, R Friedman, W Zeldin, DC AF Thorne, PS Kulhankova, K Yin, M Cohn, R Friedman, W Zeldin, DC TI Endotoxin in household dust is associated with resident, housing, and demographic characteristics SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 ASI, Res Triangle Pk, NC USA. HUD, OHHLHC, Washington, DC USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Univ Iowa, Iowa City, IA 52242 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 433 BP S157 EP S157 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600408 ER PT J AU Villanueva, CM Cantor, K Grimalt, J Tardon, A Castano-Vinyals, G Closas, GR Serra, C Carrato, A Malats, N Silverman, D Rothman, N Dosemeci, M Kogevinas, M AF Villanueva, CM Cantor, K Grimalt, J Tardon, A Castano-Vinyals, G Closas, GR Serra, C Carrato, A Malats, N Silverman, D Rothman, N Dosemeci, M Kogevinas, M TI Error in ascertaining chlorination status of drinking water due to omitting workplace water sources SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Municipal Inst Med Res, Resp & Environm Hlth Res Unit, IMIM, Barcelona, Spain. NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. CSIC, Barcelona, Spain. Univ Oviedo, Oviedo, Spain. UPF, Barcelona, Spain. UMH, Elche, Spain. RI Grimalt, Joan/E-2073-2011; Serra, C/E-6879-2014; Kogevinas, Manolis/C-3918-2017 OI Grimalt, Joan/0000-0002-7391-5768; Serra, C/0000-0001-8337-8356; NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 173 BP S110 EP S110 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600174 ER PT J AU Villanueva, CM Cantor, KP Cordier, S Jaakkola, J King, WD Lynch, CF Porru, S Kogevinas, M AF Villanueva, CM Cantor, KP Cordier, S Jaakkola, J King, WD Lynch, CF Porru, S Kogevinas, M TI Pooled analysis of case-control studies on bladder cancer and chlorination by-products SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Inst Municipal Invest Med, E-08003 Barcelona, Spain. NCI, Bethesda, MD 20892 USA. INSERM, Rennes, France. Univ Helsinki, Helsinki, Finland. Queens Univ, Kingston, ON K7L 3N6, Canada. Univ Iowa, Iowa City, IA USA. Univ Brescia, Brescia, Italy. RI Grimalt, Joan/E-2073-2011; Cordier, Sylvaine/F-7919-2013; Kogevinas, Manolis/C-3918-2017 OI Grimalt, Joan/0000-0002-7391-5768; NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 152 BP S106 EP S106 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600153 ER PT J AU Ward, MH Nuckols, JR Giglierano, J Wolter, C Miller, RS Colt, JS Camann, D Hartge, P AF Ward, MH Nuckols, JR Giglierano, J Wolter, C Miller, RS Colt, JS Camann, D Hartge, P TI Proximity to crops and residential exposure to agricultural pesticides in Iowa SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. SW Res Inst, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 728 BP S210 EP S210 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600673 ER PT J AU Weed, DL AF Weed, DL TI The precautionary principle and the philosophy of public health SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 055 BP S90 EP S91 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600074 ER PT J AU Yau, AY Camann, DE Ward, MH AF Yau, AY Camann, DE Ward, MH TI Analytical method for determining dinitroaniline, phenolic and chloroacetamide herbicides in house dust SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. SW Res Inst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 638 BP S194 EP S194 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600595 ER PT J AU Vasan, RS Levy, D AF Vasan, RS Levy, D TI Rates of progression to hypertension among nonhypertensive subjects: implications for blood pressure screening SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID COHORT; MEN C1 Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. RP Vasan, RS (reprint author), Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. OI Ramachandran, Vasan/0000-0001-7357-5970 NR 18 TC 7 Z9 7 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUL PY 2002 VL 23 IS 14 BP 1067 EP 1070 DI 10.1053/euhj.2002.3223 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 578CV UT WOS:000177100600001 PM 12090739 ER PT J AU Scheffer, GL Flens, MJ Hageman, S Izquierdo, MA Shoemaker, RH Scheper, RJ AF Scheffer, GL Flens, MJ Hageman, S Izquierdo, MA Shoemaker, RH Scheper, RJ TI Expression of the vascular endothelial cell protein C receptor in epithelial tumour cells SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE multidrug resistance; LMR-42 monoclonal antibody; expression cloning; endothelial cell protein C receptor; anticoagulation ID RESISTANCE-ASSOCIATED PROTEINS; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; VAULT PROTEIN; LINES; CANCER; OVEREXPRESSION; GENE; IDENTIFICATION; TRANSPORTER AB The rat monoclonal antibody LMR-42 has previously been shown to react with an external epitope of a plasma membrane protein with a M, of approximately 55,000 that was upregulated in multidrug-resistant (MDR) tumour cells. Here, we report the isolation of the cDNA encoding the LMR-42 antigen from the MDR human fibrosarcoma cell line HT1080/DR4 and the lung cancer cell line GLC4/ADR by expression cloning, Sequence analysis showed that the LMR-42 antigen is identical to the endothelial cell protein C receptor (EPCR). Using the LMR-42 Mab for cytochemical analyses of a disease-oriented panel of 45 non-drug selected tumour cell lines of the National Cancer Institute (NCI), we found high EPCR expression in 47% of the primary tumour cell lines, including melanomas, renal- and colon carcinomas. In a small panel of human tumours, occasionally very high EPCR expression was detected in endothelial vessels, but expression in the tumour cells was a rare event. The functional significance of overexpression of EPCR on both primary and drug-selected tumour cells is still unclear. As the protein is related to MHC class I molecules and shares no characteristics with any of the currently known transporter proteins, EPCR is not expected to play a causal role in the resistant phenotype of the MDR tumour cells. Nevertheless, exposure of tumour cells to cytostatic drugs may frequently lead to EPCR overexpression. Since EPCR is known to play a pivotal role in preventing blood coagulation through binding of (activated) protein C. it might endow tumour cells. both of mesenchymal and epithelial derivations, with increased growth potential by local anti-coagulant activity. (C) 2002 Published by Elsevier Science Ltd. C1 Free Univ Amsterdam, Med Ctr, Dept Pathol, NL-1081 HV Amsterdam, Netherlands. Catalan Inst Oncol, Dept Oncol, Barcelona, Spain. NCI, Therapeut Program, Screening Technol Branch, Frederick, MD 21701 USA. RP Scheper, RJ (reprint author), Free Univ Amsterdam, Med Ctr, Dept Pathol, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. NR 37 TC 27 Z9 29 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2002 VL 38 IS 11 BP 1535 EP 1542 AR PII S0959-8049(02)00108-9 DI 10.1016/S0959-8049(02)00108-9 PG 8 WC Oncology SC Oncology GA 577QK UT WOS:000177072900017 PM 12110501 ER PT J AU Malila, N Virtamo, J Virtanen, M Pietinen, P Albanes, D Teppo, L AF Malila, N Virtamo, J Virtanen, M Pietinen, P Albanes, D Teppo, L TI Dietary and serum alpha-tocopherol, beta-carotene and retinol, and risk for colorectal cancer in male smokers SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE colorectal neoplasms; antioxidants; diet; plasma; vitamin E; beta-carotene; cohort studies ID COLON-CANCER; VITAMIN-E; NUTRITIONAL FACTORS; FIBER INTAKE; TRIAL; NUTRIENTS; WOMEN; IOWA AB Objective: To study the association between dietary and serum antioxidant vitamins and carotenoids and risk for colorectal cancer in male smokers. Design: A prospective cohort study within a randomised, double-blind, placebo-controlled trial testing supplementation with alpha-tocopherol (50 mg/day), beta-carotene (20 mg/day) or both in preventing cancer. Subjects and methods: Participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study with complete dietary data and serum samples available from baseline. These included 26 951 middle-aged male smokers among whom 184 colorectal cancer cases were diagnosed during By of follow-up. Relative risks were calculated with Cox proportional hazards models adjusting for trial supplementation, age, body mass index, serum cholesterol, cigarettes smoked per day and physical activity. Results: There was no significant association between dietary vitamin C or E, alpha-or gamma-tocopherol, retinol, alpha- or beta-carotene, lycopene or lutein+zeaxanthin and risk for colorectal cancer. Serum alpha-tocopherol, beta-carotene or retinol was also not associated with the risk, neither did the season when baseline blood was drawn modify the relationship between serum beta-carotene and colorectal cancer risk. Conclusions: Our data support the results from previous studies in which no association between dietary antioxidant vitamins and carotenoids and risk for colorectal cancer has been observed. Likewise, no association between baseline serum antioxidant concentrations and colorectal cancer risk was evident. Sponsorship: The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was supported by a contract with the US National Cancer Institute (N01-CN-45165). C1 Finnish Canc Registry, FIN-00170 Helsinki, Finland. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NCI, Bethesda, MD 20892 USA. RP Malila, N (reprint author), Finnish Canc Registry, Liisankatu 21 B, FIN-00170 Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 37 TC 46 Z9 48 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD JUL PY 2002 VL 56 IS 7 BP 615 EP 621 DI 10.1038/sj.ejcn.1601366 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 575TA UT WOS:000176963200008 PM 12080400 ER PT J AU Kveberg, L Bryceson, Y Inngjerdingen, M Rolstad, B Maghazachi, AA AF Kveberg, L Bryceson, Y Inngjerdingen, M Rolstad, B Maghazachi, AA TI Sphingosine 1 phosphate induces the chemotaxis of human natural killer cells. Role for heterotrimeric G proteins and phosphoinositide 3 kinases SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE NK cell; sphingolipid; chemotaxis; G protein; P13 kinase ID 1-PHOSPHATE RECEPTORS EDG-1; HUMAN ENDOTHELIAL-CELLS; COUPLED RECEPTOR; LYSOPHOSPHATIDIC ACID; NK CELLS; SIGNALING PATHWAYS; MOLECULAR-CLONING; CHEMOKINE RECEPTORS; BETA-GAMMA; SPHINGOSINE-1-PHOSPHATE AB We have examined the effect of sphingolipids on the chemotaxis of human natural killer (NK) cells. Messenger RNA for Edg-1, Edg-6 and Edg-8 but not Edg-3, are expressed in these cells. Sphingosine 1 phosphate (SPP), dihydro SPP (DHSPP) or the CC chemokine RANTES (CCL5), but not sphingosine induces the chemotaxis of these cells. Pertussis toxin inhibits the chemotaxis induced by these ligands. Permeabilization of INK cells with streptolysin 0 (SLO) and introduction of blocking antibodies to the heterotrimeric G proteins, showed that Galpha(i2), Galpha(s), Galpha(q/11) or Galpha(13) mediate the chemotaxis of SPP, whereas Galpha(i2), Galpha(o) or Galpha(q/11) mediate the chemotaxis of DHSPR Galpha(i2), Galpha(o), Galpha(s), Galpha(q/11), Galpha(z) or Galpha(12) mediates RANTES-induced INK cell chemotaxis. Further analysis showed that phosphoinositide 3 kinase (PI3K) inhibitors wortmannin and LY294002 inhibit NK cell chemotaxis induced by SPP, DHSPP or RANTES. Blocking antibody to PI3Kgamma inhibits the chemotaxis induced by the three ligands, whereas anti-PI3Kbeta was without effect. In contrast, SPP and DHSPP recruit PI3Kbeta isozyme into NK cell membranes, suggesting that although this isoform is not involved in chemotaxis, it is activated by these phospholipids. C1 Univ Oslo, Dept Anat, N-0317 Oslo, Norway. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Maghazachi, AA (reprint author), Univ Oslo, Dept Anat, POB 1105, N-0317 Oslo, Norway. NR 48 TC 55 Z9 55 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2002 VL 32 IS 7 BP 1856 EP 1864 DI 10.1002/1521-4141(200207)32:7<1856::AID-IMMU1856>3.0.CO;2-B PG 9 WC Immunology SC Immunology GA 573WL UT WOS:000176855000006 PM 12115604 ER PT J AU Lobito, AA Yang, BZ Lopes, MF Miagkov, A Adams, RN Palardy, GR Johnson, MM McFarland, HI Recher, M Drachman, DB Lenardo, MJ AF Lobito, AA Yang, BZ Lopes, MF Miagkov, A Adams, RN Palardy, GR Johnson, MM McFarland, HI Recher, M Drachman, DB Lenardo, MJ TI T cell receptor transgenic mice recognizing the immunodominant epitope of the Torpedo californica acetylcholine receptor SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE myasthenia gravis; experimental autoimmune myasthenia gravis; B cell; antibody; TCR transgenic ID AUTOIMMUNE MYASTHENIA-GRAVIS; ALPHA-SUBUNIT; SYNTHETIC PEPTIDES; EXTRACELLULAR PART; ANTIGENIC SITES; LYMPHOCYTE-T; ANTIBODY; DISEASE; CHAIN; DEGRADATION AB Myasthenia gravis (MG) is an autoimmune disease caused by T cell-dependent antibody-mediated reduction of acetylcholine receptors (AChR) at the neuromuscular junction. Immunization of animals with Torpedo californica AChR (TAChR) results in an experimental model of MG. We used the variable regions of alpha and beta T cell receptor (TCR) genes recognizing an immunodominant peptide containing amino acids 146-162 from the alpha subunit of TAChR presented in the context of I-A(b) to generate TCR-transgenic mice. We found that the transgenic TCR was strongly positively selected and that transgenic T cells proliferated robustly to the immunodominant peptide and TAChR. Unexpectedly, there was a variable paucity of B cells in the blood and spleen from transgenic mice, which averaged about 16% of peripheral blood lymphocytes, compared to 55% in wild-type B6 mice. Unselected transgenic mice immunized with TAChR exhibited weak anti-TAChR antibody responses. However, transgenic mice selected to have relatively higher B cell numbers produced anti-TAChR titers equal to B6 mice and a predominance of Th1-induced antibody isotypes were observed in certain experiments. The incidence and severity of clinical disease was variable following immunizations. These mice should be useful for studying the pathogenesis and treatment of MG. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Neuromuscular Lab, Dept Neurol, Baltimore, MD USA. Univ Zurich Hosp, Dept Pathol, Inst Expt Immunol, CH-8091 Zurich, Switzerland. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Rm 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. RI lopes, marcela/E-2201-2012; McFarland, Hugh/K-1503-2016 OI lopes, marcela/0000-0002-4508-0505; McFarland, Hugh/0000-0002-3322-038X FU NINDS NIH HHS [NS07368, 1R01NS7205] NR 61 TC 3 Z9 3 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2002 VL 32 IS 7 BP 2055 EP 2067 DI 10.1002/1521-4141(200207)32:7<2055::AID-IMMU2055>3.0.CO;2-Q PG 13 WC Immunology SC Immunology GA 573WL UT WOS:000176855000029 PM 12115627 ER PT J AU Kiyatkin, EA Brown, PL Wise, RA AF Kiyatkin, EA Brown, PL Wise, RA TI Brain temperature fluctuation: a reflection of functional neural activation SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE arousal; metabolism; rats; stress; thermorecording in behaving animals ID RATS; HYPERTHERMIA AB Although it is known that relatively large increases in local brain temperature can occur during behaviour and in response to various novel, stressful and emotionally arousing environmental stimuli, the source of this heat is not clearly established. To clarify this issue, we monitored the temperature in three brain structures (dorsal and ventral striatum, cerebellum) and in arterial blood at the level of the abdominal aorta in freely moving rats exposed to several environmental challenges ranging from traditional stressors to simple sensory stimuli (cage change, tail pinch, exposure to another male rat, a female rat, a mouse or an unexpected sound). We found that brain temperature was consistently higher than arterial blood temperature, and that brain temperature increased prior to, and to a greater extent than, the increase in blood temperature evoked by each test challenge. Thus, the local metabolic consequences of widely correlated neural activity appear to be the primary source of increases in brain temperature and a driving force behind the associated changes in body temperature. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Wise, Roy/A-6465-2012 NR 23 TC 83 Z9 84 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUL PY 2002 VL 16 IS 1 BP 164 EP 168 DI 10.1046/j.1460-9568.2002.02066.x PG 5 WC Neurosciences SC Neurosciences & Neurology GA 579WC UT WOS:000177199900018 PM 12153543 ER PT J AU Schmidt, K AF Schmidt, K TI Can ROI methodology/normalised tissue activities be used instead of absolute blood flow measurements in the brain? Against SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Editorial Material ID SLEEP; SPET C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Schmidt, K (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,Rm 1A-07,36 Convent Dr, Bethesda, MD 20892 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD JUL PY 2002 VL 29 IS 7 BP 953 EP 956 DI 10.1007/s00259-002-0838-x PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 576JT UT WOS:000177001600017 PM 12212548 ER PT J AU Makino, M Okazaki I Kasai, S Nishi, N Bougaeva, M Weeks, BS Otaka, A Nielsen, PK Yamada, Y Nomizu, M AF Makino, M Okazaki, I Kasai, S Nishi, N Bougaeva, M Weeks, BS Otaka, A Nielsen, PK Yamada, Y Nomizu, M TI Identification of cell binding sites in the laminin alpha 5-chain G domain SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; TERMINAL GLOBULAR DOMAIN; ALPHA-1 CHAIN; NEURITE OUTGROWTH; SYNTHETIC PEPTIDES; INTEGRIN ALPHA-3-BETA-1; BASEMENT-MEMBRANE; MOLECULAR-CLONING; LUNG-CARCINOMA; GAMMA-1 CHAIN AB The laminins consist of at least 11 polypeptides (5 alpha-chains, 3 beta-chains, and 3 gamma-chains) specific to basement membranes. Here we investigate the biological activity associated with the G domain of the newly identified laminin alpha5-chain using 113 overlapping synthetic peptides (positions 2679-3635). Using HT-1080 cells, 21 peptides showed attachment activity either on peptide-coated tissue culture plates or to peptide-conjugated Sepharose beads. Heparin inhibited cell attachment to 16 peptides, while ethylenediaminetetraacetic acid exhibited no inhibitory activity. Peptides A5G-27, A5G-65, and A5G-71 showed the strongest cell attachment, with the minimum active core sequences of the peptides being GIIFFL, HQNMGSVN-VSV, and YLQFVG, respectively. Furthermore, these 16 peptides were tested for their ability to stimulate neurite outgrowth in the PC12 cells. MG-3, 5- A5G-71, A5G-73, A5G-81, and A5G-101 were the I peptides of the 16 that demonstrated the ability to promote neurite outgrowth. These results demonstrate that synthetic peptides with a5-chain G domain primary amino acid sequences possess some of the same biological activities attributable to the whole laminin and the a5-chain G domain. Therefore, these peptides may be useful in the investigation of laminin-receptor interactions and possibly mechanisms of laminin signal transduction. (C) 2002 Elsevier Science (USA). C1 Hokkaido Univ, Grad Sch Environm Earth Sci, Kita Ku, Sapporo, Hokkaido 0600810, Japan. Adelphi Univ, Dept Biol, Div Math & Sci, Garden City, NY 11530 USA. Kyoto Univ, Grad Sch Pharmaceut Sci, Kyoto 6068501, Japan. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Nomizu, M (reprint author), Hokkaido Univ, Grad Sch Environm Earth Sci, Kita Ku, Kita 10 Nishi 5, Sapporo, Hokkaido 0600810, Japan. EM nomizu@ees.hokudai.ac.jp NR 52 TC 29 Z9 29 U1 1 U2 2 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 1 PY 2002 VL 277 IS 1 BP 95 EP 106 DI 10.1006/excr.2002.5540 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 567NL UT WOS:000176490800008 PM 12061820 ER PT J AU Du, Y Campbell, JL Nalbant, D Youn, HY Bass, ACH Cobos, E Tsai, S Keller, JR Williams, SC AF Du, Y Campbell, JL Nalbant, D Youn, HY Bass, ACH Cobos, E Tsai, S Keller, JR Williams, SC TI Mapping gene expression patterns during myeloid differentiation using the EML hematopoietic progenitor cell line SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; BINDING-PROTEIN-EPSILON; TRANSCRIPTION FACTORS; MURINE HOMOLOG; STEM-CELLS; GRANULOCYTIC DIFFERENTIATION; 4-JOINTED GENE; RETINOIC ACID; MESSENGER-RNA; IN-VITRO AB Objective. The detailed examination of the molecular events that control the early stages of myeloid differentiation has been hampered by the relative scarcity of hematopoietic stem cells and the lack of suitable cell line models. In this study, we examined the expression of several myeloid and nonmyeloid genes in the murine EML hematopoietic stem cell line. Methods. Expression patterns for 19 different genes were examined by Northern blotting and RT-PCR in RNA samples from EML, a variety of other immortalized cell lines, and purified murine hematopoietic stem cells. Representational difference analysis (RDA) was performed to identify differentially expressed genes in EML. Results. Expression patterns of genes encoding transcription factors (four members of the C/EBP family, GATA-1, GATA-2, PU.1, CBFbeta, SCL, and c-myb) in EML were examined and were consistent with the proposed functions of these proteins in hematopoietic differentiation. Expression levels of three markers of terminal myeloid differentiation (neutrophil elastase, proteinase 3, and Mac-1) were highest in EML cells at the later stages of differentiation. In a search for genes that were differentially expressed in EML cells during myeloid differentiation, six cDNAs were isolated. These included three known genes (lysozyme, histidine decarboxylase, and tryptophan hydroxylase) and three novel genes. Conclusion. Expression patterns of known genes in differentiating EML cells accurately reflected their expected expression patterns based on previous studies. The identification of three novel genes, two of which encode proteins that may act as regulators of hematopoietic differentiation, suggests that EML is a useful model system for the molecular analysis of hematopoietic differentiation. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Biochem, Lubbock, TX 79430 USA. UMC, SW Canc Ctr, Lubbock, TX USA. Univ Utah, Sch Med, Dept Med, Div Hematol, Salt Lake City, UT USA. NCI, IRSP SAIC Inc, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Williams, SC (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Biochem, 3601 4th St, Lubbock, TX 79430 USA. OI Youn, Hyewon/0000-0003-1006-2689 FU NCI NIH HHS [N01-CO-5600] NR 50 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2002 VL 30 IS 7 BP 649 EP 658 AR PII S0301-472X(02)00817-2 DI 10.1016/S0301-472X(02)00817-2 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 576ZC UT WOS:000177036200005 PM 12135661 ER PT J AU Chen, GB Kirby, M Zeng, WH Young, NS Maciejewski, JP AF Chen, GB Kirby, M Zeng, WH Young, NS Maciejewski, JP TI Superior growth of glycophosphatidy linositol-anchored protein-deficient progenitor cells in vitro is due to the higher apoptotic rate of progenitors with normal phenotype in vivo SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; PIG-A GENE; DECAY-ACCELERATING FACTOR; APLASTIC-ANEMIA; STEM-CELLS; SOMATIC MUTATIONS; TARGET-CELLS; HEMATOPOIESIS; RESISTANCE; EXPRESSION AB Objective. Recently, phenotypically normal CD34 cells from the marrow of patients with paroxysmal nocturnal hemoglobinuria (PNH) were reported to show impaired growth and elevated Fas receptor expression as compared to glycophosphatidylinositol-anchored protein (GPI-AP)-deficient CD34 cells and CD34 cells from normal individuals. These results are consistent with the theory that PNH cells have an intrinsic growth advantage, but their superior expansion in vitro could also be the outcome of selective extrinsic pressure in vivo. Material and Methods. Growth characteristics, competitive features, and susceptibility to apoptosis of sorted normal or GPI-AP-deficient CD34(+) cells derived from PNH patients were assessed in suspension and methylcellulose cultures. Results. When we directly compared the growth of patients' CD34 cells, separated based on expression of GPI-AP CD55 and CD59, in most of the patients studied, mutant CD34 cells showed higher progeny production and outgrew phenotypically normal CD34 cells derived from PNH patients in mixing experiments. However, their proliferation rate did not exceed that of control CD34 cells. To determine whether deficient growth of phenotypically normal CD34 cells in PNH was secondary to a pre-existing in vivo insult, we determined the fraction of apoptotic cells within fresh normal and PNH CD34 cells. Normal CD34 cells from PNH patients showed a high proportion of apoptotic cells and higher Fas expression, while GPI-AP-deficient and control CD34 cells showed similar, low rates of apoptosis. After correction for pre-existing apoptosis, the proliferation potential of normal and PNH CD34 cells was similar. Conclusions. These results strongly suggest that clonal expansion of GPI-AP-deficient progenitor cells from PNH patients is due to their selection in the hostile marrow environment of the patient. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Maciejewski, JP (reprint author), Taussig Canc Ctr R40, Expt Hematol & Hematopoiesis Sect, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 41 TC 33 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2002 VL 30 IS 7 BP 774 EP 782 AR PII S0301-472X(02)00811-1 DI 10.1016/S0301-472X(02)00811-1 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 576ZC UT WOS:000177036200020 PM 12135676 ER PT J AU Gary, DS Getchell, TV Getchell, ML Mattson, MP AF Gary, DS Getchell, TV Getchell, ML Mattson, MP TI Olfactory bulbectomy protects hippocampal pyramidal neurons against excitotoxic death SO EXPERIMENTAL NEUROLOGY LA English DT Article DE apoptosis; epilepsy; glutamate; kainic acid; learning and memory; olfaction ID DIETARY RESTRICTION; DENTATE GYRUS; RAT-BRAIN; INCREASES; DISEASE; DAMAGE; SYSTEM; CELLS AB The olfactory system is functionally linked to the hippocampus, and odors can modify the activity of hippocampal neurons. Because hippocampal neurons are selectively vulnerable to death in several prominent neurodegenerative conditions, we tested the hypothesis that activity in olfactory pathways can modify the sensitivity of hippocampal neurons to excitotoxic damage. We report that rats subjected to olfactory bulbectomy exhibit a decrease in the vulnerability of hippocampal pyramidal neurons to excitotoxic injury. Four-month-old male Sprague-Dawley rats were subjected to bilateral olfactory bulbectomy or a sham operation. Three months later the rats were given a unilateral infusion of kainic acid in the dorsal hippocampus and were euthanized 24 h later. There was a threefold increase in the number of CA3 neurons that survived kainic acid administration in the bulbectomized rats compared to sham-operated rats. These findings provide the first evidence that olfactory input affects the vulnerability of neurons to excitotoxic death. (C) 2002 Elsevier Science (USA). C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. RP Gary, DS (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 19 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 2002 VL 176 IS 1 BP 266 EP 268 DI 10.1006/exnr.2002.7925 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 574VV UT WOS:000176911000028 PM 12093105 ER PT J AU Liu, F Schaphorst, KL Verin, AD Jacobs, K Birukova, A Day, RM Bogatcheva, N Bottaro, DP Garcia, JGN AF Liu, F Schaphorst, KL Verin, AD Jacobs, K Birukova, A Day, RM Bogatcheva, N Bottaro, DP Garcia, JGN TI Hepatocyte growth factor enhances endothelial cell barrier function and cortical cytoskeletal rearrangement: potential role of glycogen synthase kinase-3 beta SO FASEB JOURNAL LA English DT Article DE beta-catenin; MAP kinases; endothelial permeability; cytoskeleton; transendothelial electrical resistance ID C-MET RECEPTOR; PROTEIN-KINASE-C; SCATTER FACTOR; VASCULAR-PERMEABILITY; TYROSINE PHOSPHORYLATION; INTERCELLULAR-JUNCTIONS; DIFFERENTIAL REGULATION; BIOLOGICAL RESPONSES; EPITHELIAL-CELLS; HGF/SF RECEPTOR AB The stabilization of endothelial cell (EC) barrier function within newly formed capillaries is a critical feature of angiogenesis. We examined human lung EC barrier regulation elicited by hepatocyte growth factor (HGF), a recognized angiogenic factor and EC chemoattractant. HGF rapidly and dose-dependently elevated transendothelial electrical resistance (TER) of EC monolayers (>50% increase at 100 ng/ml), with immunofluorescence microscopic evidence of both cytoplasmic actin stress fiber dissolution and strong augmentation of the cortical actin ring. HGF rapidly stimulated phosphatidylinositol 3'-kinase, ERK, p38 mitogen-activated protein kinase, and protein kinase C activities. Pharmacological inhibitor studies demonstrated each pathway to be intimately involved in HGF-induced increases in TER, cortical actin thickening, and phosphorylation of the Ser/Thr glycogen synthase kinase-3beta (GSK-3beta), a potential target for the HGF barrier-promoting response. GSK-3beta phosphorylation was strongly correlated with reductions in both HGF-induced TER and enhanced beta-catenin immunoreactivity observed at cell-cell junctions. Our data suggest a model in which HGF-mediated EC cytoskeletal rearrangement and barrier enhancement depend critically on the activation of a complex kinase cascade that converges at GSK-3beta to increase the availability of beta-catenin, thereby enhancing endothelial junctional integrity and vascular barrier function. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. NCI, Bethesda, MD 20892 USA. RP Liu, F (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. RI Garcia, Joe/E-8862-2010; Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 FU NHLBI NIH HHS [HL 03666, HL 50533, HL 58064, HL 69340] NR 65 TC 121 Z9 123 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 2002 VL 16 IS 9 BP 950 EP 962 DI 10.1096/fj.01-0870com PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 590HH UT WOS:000177813100026 PM 12087056 ER PT J AU Tsibris, JCM Segars, J Coppola, D Mane, S Wilbanks, GD O'Brien, WF Spellacy, WN AF Tsibris, JCM Segars, J Coppola, D Mane, S Wilbanks, GD O'Brien, WF Spellacy, WN TI Insights from gene arrays on the development and growth regulation of uterine leiomyomata SO FERTILITY AND STERILITY LA English DT Article DE c-kit; dlk; genomic imprinting; mast cells; myometrium; PPAR gamma; retinoic acid; RNA editing; RXR alpha; stem cell factor ID STEM-CELL FACTOR; ACTIVATED RECEPTOR-GAMMA; HUMAN MYOMETRIUM; MESSENGER-RNA; MAST-CELLS; C-KIT; INTERSTITIAL-CELLS; ESTROGEN-RECEPTOR; BODY-SIZE; FACTOR-II AB Objective: To use microarray analysis as an unbiased approach to identify genes involved in the induction and growth of uterine leiomyomata. Design: Screen by arrays for up to 12.000 genes in leiomyoma (L) and control myometrium (M) from nine patients. Setting: University research laboratories. Patient(s): Nine patients in the follicular and luteal phases of the menstrual cycle. Intervention (s): mRNA from L and M was converted to biotin-labeled cRNA and hybridized to cDNA oligonucleotide sequences on the arrays. Main Outcome Measure(s): Greater than two-fold change in gene expression between leiomyoma and matched myometrium. Result(s): Prominent among the 67 genes overexpressed in L relative to M were dlk or Pref-1, doublecortin, JM27, ionotropic glutamate receptor subunit 2, apolipoprotein E3. IGF2, semaphorin F, myelin proteolipid protein. MEST, frizzled, CRABP 11, stromelysin-3, and TGFbeta3. The genes dlk, IGF2, and MEST are paternally expressed imprinted genes, and the others are involved in tissue differentiation and growth. Prominent among the 78 genes down-regulated in L relative to M were alcohol dehydrogenases tryptase, dermatopontin, thrombospondin. coxsackievirus receptor, nur77, and c-kit. Conclusion(s): Arrays offer large-scale screening of mRNA expression, which will help us differentiate between the genes and metabolic pathways necessary for leiomyoma growth and those regulating myometrial contractions. C1 Univ S Florida, Dept Obstet & Gynecol, Tampa, FL 33606 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. NICHHD, Bethesda, MD 20892 USA. Univ S Florida, Dept Pathol, Tampa, FL 33606 USA. H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL USA. H Lee Moffit Canc Ctr & Res Inst, Microarray Core Facil, Tampa, FL USA. RP Tsibris, JCM (reprint author), Univ S Florida, Dept Obstet & Gynecol, 4 Columbia Dr,Room 524, Tampa, FL 33606 USA. FU Intramural NIH HHS [Z99 HD999999] NR 59 TC 133 Z9 140 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 2002 VL 78 IS 1 BP 114 EP 121 AR PII S0015-0282(02)03191-6 DI 10.1016/S0015-0282(02)03191-6 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 569MK UT WOS:000176606000019 PM 12095500 ER PT J AU Prakash, O Mason, A Luftig, RB Bautista, AP AF Prakash, O Mason, A Luftig, RB Bautista, AP TI Hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infections in alcoholics SO FRONTIERS IN BIOSCIENCE LA English DT Review DE HCV; HIV; alcoholic liver disease; viral hepatitis; cirrhosis; hepatocellular carcinoma; inflammatory cells; chemokines; review ID INJECTION-DRUG USERS; TRANSFORMING GROWTH FACTOR-BETA-1; LIVER FIBROSIS PROGRESSION; CYTOTOXIC T-LYMPHOCYTES; TUMOR-NECROSIS-FACTOR; TRANSFUSION-ASSOCIATED HEPATITIS; ACETALDEHYDE-MODIFIED EPITOPES; NON-B HEPATITIS; HEPATOCELLULAR-CARCINOMA; CORE PROTEIN AB Approximately 400,000 individuals in the United States are co-infected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) and it is likely that almost one in two of these subjects consumes alcohol. The majority of these patients suffer an accelerated course of liver disease as manifested by the onset of cirrhosis within 5 to 10 years of developing HCV infection, as well as an increased risk of developing hepatocellular carcinoma (HCC). It is thought that chronic alcohol abuse mediates liver damage as a result of increased production of free radicals and proinflammatory cytokines. In the setting of chronic HCV infection, alcohol ingestion has an additional effect of diminishing immune clearance and increasing viral burden to hasten the onset of cirrhosis and HCC. Likewise, chronic HCV and HIV-1 co-infection results in a net increase in HCV burden; higher prevalence rates of HCV transmission to sexual partners and offspring, as well as an accelerated progression to end stage liver disease as compared to individuals with HCV infection alone. Thus, the synergistic effects of alcohol abuse and HIV-1 greatly impact on the morbidity and mortality for patients with HCV coinfection. Ultimately, this cumulative disease process will require far more aggressive management with abstinence and counseling for alcohol abuse; highly active antiretroviral therapy (HAART) for HIV infection and combination anti-viral therapy for HCV infection to stem the rapid progression to end stage liver disease. C1 Alton Ochsner Med Fdn & Ochsner Clin, Oncol Mol Lab, New Orleans, LA 70121 USA. Alton Ochsner Med Fdn & Ochsner Clin, Sect Gastroenterol & Hepatol, New Orleans, LA 70121 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA USA. NIH, Ctr Sci Review, Bethesda, MD 20892 USA. RP Prakash, O (reprint author), Alton Ochsner Med Fdn & Ochsner Clin, Mol Oncol Res Lab, 1516 Jefferson Highway, New Orleans, LA 70121 USA. FU NIAAA NIH HHS [P50 AA 09803, R01 AA 08846] NR 189 TC 19 Z9 19 U1 1 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JUL PY 2002 VL 7 BP E286 EP E300 DI 10.2741/prakash PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 569BY UT WOS:000176581200012 PM 12086918 ER PT J AU Wray, S AF Wray, S TI Development of gonadotropin-releasing hormone-1 neurons SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Review ID CELL-ADHESION MOLECULE; EMBRYONIC OLFACTORY PLACODE; TRANSCRIPTION FACTOR AP-2; MIGRATING LHRH NEURONS; MEDIAL BASAL HYPOTHALAMUS; CHICK-EMBRYO; RHESUS-MONKEY; IMMUNOREACTIVE NEURONS; DEVELOPING MOUSE; NASAL-PLACODE AB Gonadotropin releasing hormone-1 (GnRH-1) neurons, critical for reproduction, are derived from the nasal placode and migrate into the brain during prenatal development. Once within the brain, GnRH-1 cells become integral components of the CNS-pituitary-gonadal axis, essential for reproductive maturation and maintenance of reproductive function in adults. This review focuses on the lineage and development of the GnRH-1 neuroendocrine system. Although the migration of these cells from nose to brain has been well documented in a variety of species, many questions remain concerning the molecules and cues directing GnRH-1 cell differentiation, migration, axon targeting, and establishment and control of GnRH-1 secretion. These processes most likely involve multiple and redundant cues because if these mechanisms fail, reproduction dysfunction will ensue and guarantee that this defect does not remain in the gene pool. C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, Bldg 36,Room 5A-21, Bethesda, MD 20892 USA. OI wray, susan/0000-0001-7670-3915 NR 109 TC 94 Z9 94 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD JUL PY 2002 VL 23 IS 3 BP 292 EP 316 AR PII S0091-3022(02)00001-8 DI 10.1016/S0091-3022(02)00001-8 PG 25 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 583FF UT WOS:000177395400003 PM 12127307 ER PT J AU Peghini, PL Annibale, B Azzoni, C Milione, M Corleto, VD Gibril, F Venzon, DJ Delle Fave, G Bordi, C Jensen, RT AF Peghini, PL Annibale, B Azzoni, C Milione, M Corleto, VD Gibril, F Venzon, DJ Delle Fave, G Bordi, C Jensen, RT TI Effect of chronic hypergastrinemia on human enterochromaffin-like cells: Insights from patients with sporadic gastrinomas SO GASTROENTEROLOGY LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; TERM OMEPRAZOLE TREATMENT; PANCREATIC ENDOCRINE TUMORS; ACID SUPPRESSIVE THERAPY; ATROPHIC BODY GASTRITIS; HISTAMINE H-2 BLOCKADE; HORMONE ALPHA-SUBUNIT; TREATED LONG-TERM; OXYNTIC MUCOSA; HELICOBACTER-PYLORI AB Background & Aims: The effect of chronic hypergastrinemia alone on gastric enterochromaffin-like (ECL) cells in humans is largely unknown because in the common chronic hypergastrinemic states (atrophic gastritis, chronic proton pump inhibitor use), it is not possible to separate the effect of hypergastrinemia and other factors, such as gastritis or atrophy. Studies of patients with sporadic Zollinger-Ellison syndrome (ZES) allow this separation. Methods: In 106 patients with ZES, gastric biopsies were taken, and the qualitative ECL cell pattern/grade and the (x-subunit of human chorionic gonadotropin (ot-hCG) expression were determined. Results: In patients with active disease, 99% had ECL hyperplasia and abnormal alpha-hCG staining. Fifty percent had advanced changes in both of these, with 7% having dysplasia and 0% having carcinoids. Advanced ECL cell and (alpha-hCG changes were most affected by the level of hypergastrinemia. For ECL cell changes, even mild hypergastrinemia had an effect. Advanced ECL change was also affected by the duration of drug treatment, cure status, and presence of atrophic gastritis, but not by sex or previous vagotomy. The (alpha-hCG expression independently predicted dysplasia. Conclusions: In humans, chronic hypergastrinemia alone causes advanced ECL cell change and abnormal expression of mucosal (alpha-hCG. No threshold for this effect was detected, as reported by some, and in contrast to animal studies, sex and vagal tone did not play a major role. The long-term risk of developing gastric carcinoids with chronic hypergastrinemia is low in patients with sporadic gastrinomas (at least 100 times less than in patients with multiple endocrine neoplasia type :1 with ZES) for at least 15-20 years. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20889 USA. Univ Roma La Sapienza, Div Digest & Liver Dis, Rome, Italy. Univ Parma, Sect Anat Pathol, Dept Pathol & Lab Med, Parma, Italy. Natl Canc Inst, Biostat & Data Management Sect, NIH, Bethesda, MD USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20889 USA. RI Venzon, David/B-3078-2008; Milione, Massimo/B-8644-2017 OI Milione, Massimo/0000-0002-1202-139X NR 85 TC 81 Z9 84 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2002 VL 123 IS 1 BP 68 EP 85 DI 10.1053/gast.2002.34231 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 570VD UT WOS:000176678600012 PM 12105835 ER PT J AU Katon, W Gonzales, J AF Katon, W Gonzales, J TI Primary care and treatment of depression: a response to the NIMH "White Papers" SO GENERAL HOSPITAL PSYCHIATRY LA English DT Editorial Material ID CHRONIC ILLNESS; RANDOMIZED TRIAL; INTERVENTION; MANAGEMENT; QUALITY; NURSE C1 Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Katon, W (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JUL-AUG PY 2002 VL 24 IS 4 BP 194 EP 196 AR PII S0163-8343(02)00199-8 DI 10.1016/S0163-8343(02)00199-8 PG 3 WC Psychiatry SC Psychiatry GA 570VP UT WOS:000176679900001 PM 12100829 ER PT J AU Kuznetsov, VA Knott, GD Bonner, RF AF Kuznetsov, VA Knott, GD Bonner, RF TI General statistics of stochastic process of gene expression in eukaryotic cells SO GENETICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SERIAL ANALYSIS; MESSENGER-RNA; GENOME; TRANSCRIPTION; NETWORKS; OCCURS; SCALE; DNA AB Thousands of genes are expressed at such very low levels (less than or equal to1 copy per cell) that global gene expression analysis of rarer transcripts remains problematic. Ambiguity in identification of rarer transcripts creates considerable uncertainty in fundamental questions such as the total number of genes expressed in an organism and the biological significance of rarer transcripts. Knowing the distribution of the true number of genes expressed at each level and the corresponding gene expression level probability function (GELPF) could help resolve these uncertainties. We found that all observed large-scale gene expression data sets in yeast, mouse, and human cells follow a Pareto-like distribution model skewed by many low-abundance transcripts. A novel stochastic model of the gene expression process predicts the universality of the GELPF both across different cell types within a multicellular organism and across different organisms. This model allows us to predict the frequency distribution of all gene expression levels within a single cell and to estimate the number of expressed genes in a single cell and in a population of cells. A random "basal" transcription mechanism for protein-coding genes in all or almost all eukaryotic cell types is predicted. This fundamental mechanism might enhance the expression of rarely expressed genes and, thus, provide a basic level of phenotypic diversity, adaptability, and random monoallelic expression in cell populations. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Civilized Software, Silver Spring, MD 20906 USA. RP Kuznetsov, VA (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bldg 13,Rm 3W16, Bethesda, MD 20892 USA. EM vk28u@nih.gov RI Bonner, Robert/C-6783-2015 NR 40 TC 100 Z9 108 U1 0 U2 2 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUL PY 2002 VL 161 IS 3 BP 1321 EP 1332 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 579RW UT WOS:000177192500033 PM 12136033 ER PT J AU Oliver, B AF Oliver, B TI Fly factory SO GENOME RESEARCH LA English DT Editorial Material ID DROSOPHILA-MELANOGASTER; LARVAL CUTICLE; ZYGOTIC LOCI; CHROMOSOME; PATTERN C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Washington, DC 20392 USA. RP Oliver, B (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Washington, DC 20392 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2002 VL 12 IS 7 BP 1017 EP 1018 DI 10.1101/gr.295602 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 569LR UT WOS:000176604300002 PM 12097337 ER PT J AU Lespinet, O Wolf, YI Koonin, EV Aravind, L AF Lespinet, O Wolf, YI Koonin, EV Aravind, L TI The role of lineage-specific gene family expansion in the evolution of eukaryotes SO GENOME RESEARCH LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; COMPARATIVE GENOMICS; PROTEIN SEQUENCES; DOMAINS; CYTOCHROME-P450; SUPERFAMILY; INFORMATION; ARABIDOPSIS; DIVERGENCE; MECHANISMS AB A computational procedure was developed for systematic detection of lineage-specific expansions (LSEs) of protein families in sequenced genomes and applied to obtain a census of LSEs in five eukaryotic species, the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the green plant Arabidopsis thaliana. A significant fraction of the proteins encoded in each of these genomes, up to 80% in A thailana, belong to LSEs. Many paralogous gene families in each of the analyzed species are almost entirely comprised of LSEs, indicating that their diversification occurred after the divergence of the major lineages of the eukaryotic crown group. The LSEs show readily discernible patterns of protein functions. The functional categories most prone to LSE are structural proteins, enzymes involved in ail organism's response to pathogens and environmental stress, and various components of signaling pathways responsible for specificity, including ubiquitin ligase E3 subunits and transcription factors. The functions of several previously uncharacterized, vastly expanded protein families were predicted through in-depth protein sequence analysis, for example, small-molecule kinases and methylases that are expanded independently ill the fly and in the nematode. The functions of several other major LSEs remain mysterious; these protein families are attractive targets for experimental discovery of novel, lineage-specific functions in eukaryotes. LSEs seem to be one of the principal means of adaptation and one of the most important sources of organizational and regulatory diversity in crown-group eukaryotes. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Lespinet, Olivier/C-1235-2008 OI Lespinet, Olivier/0000-0002-4961-7461 NR 55 TC 239 Z9 251 U1 2 U2 19 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2002 VL 12 IS 7 BP 1048 EP 1059 DI 10.1101/gr.174302 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 569LR UT WOS:000176604300006 PM 12097341 ER PT J AU Iseli, C Stevenson, BJ de Souza, SJ Samaia, HB Camargo, AA Buetow, KH Strausberg, RL Simpson, AJG Bucher, P Jongeneel, CV AF Iseli, C Stevenson, BJ de Souza, SJ Samaia, HB Camargo, AA Buetow, KH Strausberg, RL Simpson, AJG Bucher, P Jongeneel, CV TI Long-range heterogeneity at the 3 ' ends of human mRNAs SO GENOME RESEARCH LA English DT Article ID ALTERNATIVE POLYADENYLATION; MESSENGER-RNA; DNA-SEQUENCE; 3'-UNTRANSLATED REGION; HUMAN TRANSCRIPTOME; GENE-EXPRESSION; SITES; IDENTIFICATION; GENOME; INDEX AB The publication of a draft of the human genome and of large collections of transcribed sequences has made it possible to study the complex relationship between the transcriptome and the genome. In the work presented here, we have focused on mapping mRNA 3' ends onto the genome by use of the raw data generated by the expressed sequence tag (EST) sequencing projects. We Find that at least half of the human genes encode multiple transcripts whose polyadenylation is driven by multiple signals. The corresponding transcript 3' ends are spread over distances in the kilobase range. This finding has profound implications for Our understanding of gene expression regulation and of the diversity of human transcripts, for the design of cDNA microarray probes, and for the interpretation of gene expression profiling experiments. C1 NCI, Bethesda, MD 20892 USA. RI Jongeneel, Cornelis/B-2135-2012; Camargo, Anamaria/E-9388-2012; Brentani, Helena/G-6839-2011 OI Camargo, Anamaria/0000-0002-6076-9597; Brentani, Helena/0000-0001-5192-4682 NR 23 TC 59 Z9 62 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2002 VL 12 IS 7 BP 1068 EP 1074 DI 10.1101/gr.62002 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 569LR UT WOS:000176604300008 PM 12097343 ER PT J AU Xie, JP Cai, T Zhang, HL Lan, MS Notkins, AL AF Xie, JP Cai, T Zhang, HL Lan, MS Notkins, AL TI The zinc-finger transcription factor INSM1 is expressed during embryo development and interacts with the cbl-associated protein SO GENOMICS LA English DT Article DE zinc fingers; nuclear protein; mouse chromosome 2; intronless gene; embryo development; CAP ID PROLINE-RICH PEPTIDES; BINDING-PROTEIN; HUMAN SORBIN; SH3 DOMAINS; FAMILY; GENE; IA-1; CELL; DROSOPHILA; REPRESSION AB Here we describe the isolation and characterization of the mouse homolog of the human zinc-finger transcription factor INSM1 (IA-1) and identify an interacting protein. A 2.9-kb cDNA with an open reading frame of 1563 nucleotides, corresponding to a translated protein of 521 amino acids, was isolated from a mouse PTC-1 cDNA library. Mouse INSM1 was found to be 86% identical to human INSM1 and both proteins contain proline-rich regions and multiple zinc-finger DNA-binding motifs. Sequencing of mouse Insm1 genomic DNA revealed that it is an intronless gene. Chromosomal mapping localized Insm1 to chromosome 2. Northern blot analysis showed that mouse Insm1 expression begins at 10.5 days in the embryo, decreases after 13.5 days, and is barely detected at 18.5 days. In mouse brain, Insm1 is strongly expressed for 2 weeks after birth but shows little or no expression thereafter. Transfection of cells with GFP-tagged INSM1 revealed that INSM1 is expressed exclusively in the nucleus. We identified proteins that interacted with INSM1 by the yeast two-hybrid system and the binding of one of them, Cbl-associated protein (CAP), to INSM1 was confirmed by in vitro pull-down experiments, nuclear colocalization, and co-immunoprecipitation assays. Further studies showed that both INSM1 and CAP proteins were present in the nucleus of insulinoma cells and that endogenous INSM1 protein was co-precipitated with antibody to CAP. These findings raise the possibility that during embryo development CAP may enter the nucleus through its own nuclear localization signal or by binding to INSM1. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, Expt Med Sect, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Hlth Sci Ctr, Childrens Hosp, Res Inst Children, New Orleans, LA 70112 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA 70112 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA 70112 USA. RP Notkins, AL (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, Expt Med Sect, NIH, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [R01 DK061436] NR 31 TC 26 Z9 30 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUL PY 2002 VL 80 IS 1 BP 54 EP 61 DI 10.1006/geno.2002.6800 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 567QH UT WOS:000176495300010 PM 12079283 ER PT J AU Holtzclaw, LA Pandhit, S Bare, DJ Mignery, GA Russell, JT AF Holtzclaw, LA Pandhit, S Bare, DJ Mignery, GA Russell, JT TI Astrocytes in adult rat brain express type 2 inositol 1,4,5-trisphosphate receptors SO GLIA LA English DT Article DE IP(3)R2; astrocytes; immunohistochemistry ID ENDOPLASMIC-RETICULUM PROTEINS; SINGLE-CHANNEL FUNCTION; CENTRAL-NERVOUS-SYSTEM; CA2+ RELEASE SITES; CALCIUM WAVES; IMMUNOHISTOCHEMICAL LOCALIZATION; TRISPHOSPHATE RECEPTORS; IN-SITU; CULTURED ASTROCYTES; MOUSE BRAIN AB Astrocytes respond to neuronal activity by propagating Ca2+ waves elicited through the inositol 1,4,5-trisphosphate pathway. We have previously shown that wave propagation is supported by specialized Ca2+ release sites, where a number of proteins, including inositol 1,4,5-trisphosphate receptors (IP3R), occur together in patches. The specific IP3R isoform expressed by astrocytes in situ in rat brain is unknown, In the present report, we use isoform-specific antibodies to localize immunohistochemically the IP3R subtype expressed in astrocytes in rat brain sections. Astrocytes were identified using antibodies against the astrocyte-specific markers, S-100beta, or GFAP. Dual indirect immunohistochemistry showed that astrocytes in all regions of adult rat brain express only IP(3)R2. High-resolution analysis showed that hippocampal astrocytes are endowed with a highly branched network of processes that bear fine hair-like extensions containing punctate patches of lP(3)R2 staining in intimate contact with synapses. Such an organization is reminiscent of signaling microdomains found in cultured glial cells. Similarly, Bergmann glial cell processes in the cerebellum also contained fine hair-like processes containing IP(3)R2 staining. The IP(3)R2-containing fine terminal branches of astrocyte processes in both brain regions were found juxtaposed to presynaptic terminals containing synaptophysin as well as PSD 95-containing postsynaptic densities. Corpus callosum astrocytes had an elongated morphology with IP(3)R2 studded processes extending along fiber tracts. Our data suggest that PLC-mediated Ca2+ signaling in astrocytes in rat brain occurs predominantly through IP(3)R2 ion channels. Furthermore, the anatomical arrangement of the terminal astrocytic branches containing IP3R2 ensheathing synapses is ideal for supporting glial monitoring of neuronal activity. C1 NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. Loyola Univ, Dept Physiol, Maywood, IL 60153 USA. RP Russell, JT (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bldg 49,Room 5A-78, Bethesda, MD 20892 USA. OI Bare, Dan/0000-0002-3365-4401 NR 54 TC 55 Z9 56 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD JUL PY 2002 VL 39 IS 1 BP 69 EP 84 DI 10.1002/glia.10085 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 566BE UT WOS:000176406200008 PM 12112377 ER PT J AU Boeggeman, E Qasba, PK AF Boeggeman, E Qasba, PK TI Studies on the metal binding sites in the catalytic domain of beta 1,4-galactosyltransferase SO GLYCOBIOLOGY LA English DT Article DE aspartate motifs; bovine beta 4Gal-T1; catalytic domain; metal-binding sites; substrate binding ID BETA-4-GALACTOSYLTRANSFERASE GENE FAMILY; N-ACETYLGLUCOSAMINE; ALPHA-LACTALBUMIN; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; BOVINE BETA-1,4-GALACTOSYLTRANSFERASE; UDP-GALACTOSE; 2 FORMS; GALACTOSYLTRANSFERASE; CLONING AB The catalytic domain of bovine beta1,4-galactosyltransferase (beta4Gal-T1) has been shown to have two metal binding sites, each with a distinct binding affinity. Site I binds Mn2+ with high affinity and does not bind Ca2+, whereas site II binds a variety of metal ions, including Ca2+. The catalytic region of beta4Gal-T1 has DXD motifs, associated with metal binding in glycosyltransferases, in two separate sequences: (DYDYNCFVFSDVD254)-Y-242 (region I) and W(312)GWGGEDDD(320) (region II). Recently, the crystal structure of beta4Gal-T1 bound with UDP, Mn2+, and alpha-lactalbumin was determined in our laboratory. It shows that in the primary metal binding site of beta4Gal-T1, the Mn2+ ion, is coordinated to five ligands, two supplied by the phosphates of the sugar nucleotide and the other three by Asp254, His347, and Met344. The residue Asp254 in the (DVD254)-V-252 sequence in region I is the only residue that is coordinated to the Min(2+) ion. Region II forms a loop structure and contains the (EDDD320)-D-317 sequence in which residues Asp318 and Asp319 are directly involved in GlcNAc binding. This study, using site-directed mutagenesis, kinetic, and binding affinity analysis, shows that Asp254 and His347 are strong metal ligands, whereas Met344, which coordinates less strongly, can be substituted by alanine or glutamine. Specifically, substitution of Met344 to Gln has a less severe effect on the catalysis driven by Co2+. Glu317 and Asp320 mutants, when partially activated by Mn2+ binding to the primary site, can be further activated by Co2+ or inhibited by Ca2+, an effect that is the opposite of what is observed with the wild-type enzyme. C1 NCI CCR, Struct Glycobiol Sect, Frederick, MD 21702 USA. NCI CCR, Intramural Res Support Program, SAIC, Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Qasba, PK (reprint author), NCI CCR, Struct Glycobiol Sect, Bldg 469,Room 221, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 48 TC 35 Z9 37 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD JUL PY 2002 VL 12 IS 7 BP 395 EP 407 DI 10.1093/glycob/cwf045 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578XC UT WOS:000177145500002 PM 12122021 ER PT J AU Trimble, CL Kosary, C Trimble, EL AF Trimble, CL Kosary, C Trimble, EL TI Long-term survival and patterns of care in women with ovarian tumors of low malignant potential SO GYNECOLOGIC ONCOLOGY LA English DT Article ID SEROUS BORDERLINE TUMORS; PERITONEAL IMPLANTS; CARCINOMA; ORIGIN AB Objectives. The objectives of this study were to ascertain long-term survival and patterns of care among women diagnosed with ovarian tumors of low malignant potential (LMP) in a population-based data set. Methods. Using the NCI's Surveillance, Epidemiology, and End Results (SEER) database, we identified 2818 women diagnosed with ovarian tumors of low malignant potential between 1988 and 1997. Results. By FIGO stage, 10-year relative survival was as follows: stage I, 99%; stage II, 98%; stage 111, 96%; and stage IV 77%. One-quarter of women with stage I disease underwent partial or unilateral oophorectomy only, while women with more advanced disease commonly underwent omentectomy, unilateral or bilateral oophorectomy, and hysterectomy. Adjuvant chemotherapy was given to about 30% of women with stage III and IV disease. Radiation therapy was rarely used. We observed no significant changes in primary surgery or adjuvant treatment over time. Conclusions. The diagnosis of an ovarian tumor of LMP conveys a relatively benign prognosis. Conservative surgery should be considered in younger women with early-stage disease. There are insufficient data to support a role for adjuvant chemotherapy for women with advanced disease. (C) 2002 Elsevier Science (USA). C1 NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Dept Gynecol & Obstet, Baltimore, MD 21287 USA. RP Trimble, CL (reprint author), NCI, 6130 Execut Blvd,Suite 7025,MSC 7436, Bethesda, MD 20892 USA. NR 16 TC 84 Z9 91 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2002 VL 86 IS 1 BP 34 EP 37 DI 10.1006/gyno.2002.6711 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 573JU UT WOS:000176826900007 PM 12079297 ER PT J AU Houle, CD Ding, XY Foley, JF Afshari, CA Barrett, JC Davis, BJ AF Houle, CD Ding, XY Foley, JF Afshari, CA Barrett, JC Davis, BJ TI Loss of expression and altered localization of KAI1 and CD9 protein are associated with epithelial ovarian cancer progression SO GYNECOLOGIC ONCOLOGY LA English DT Article DE CD82; E-cadherin; N-cadherin; ovarian epithelial cancer; cell adhesion ID METASTASIS SUPPRESSOR GENE; E-CADHERIN EXPRESSION; PROSTATE-CANCER; N-CADHERIN; TRANSMEMBRANE-4 SUPERFAMILY; KAI1/CD82 EXPRESSION; ADHESION MOLECULES; PANCREATIC-CANCER; CELLS; MRP-1/CD9 AB Objective. Impairment of cell adhesion plays a vital role in tumor progression. E- and N-cadherin, CD9, and KAI1 are all adhesion molecules that have been implicated in the progression of several different tumor types. To help explain the potential role these adhesion molecules have in ovarian cancer, comparisons were made between expression patterns in normal ovary and various grades of primary and metastatic epithelial ovarian cancers. Methods. Thirty-two primary and 8 metastatic human ovarian epithelial carcinomas and 18 samples of normal ovarian tissue were examined for adhesion molecule expression using immunohistochemistry. Results. KAI1 and CD9 revealed an inverse relationship between tumor grade and expression levels, characterized by high expression in low-grade tumors and low expression in high-grade tumors and metastases. KAI1 and CD9 also demonstrated a shift in cellular localization from the membrane in grade 1 tumors to the cytoplasm in grade 3 tumors. N-cadherin expression showed a positive trend between expression levels and tumor grade. E-cadherin expression varied little between different tumor grades and metastases. Inclusion cysts (n = 6) and surface invaginations often strongly expressed KAI1, CD9, and E-cadherin. KAI1 expression was variable in ovarian follicles and corpora lutea depending on their stage of development. Conclusions. Although sample size is limited, these findings suggest that progression of ovarian epithelial carcinomas is associated with down-regulation and altered cellular localization of KAI1 and CD9. In addition, variable KAI1 expression during follicular and luteal development suggests that it has a physiological function in the ovary. Further investigation will be needed to see if it is also regulated this way during progression of ovarian cancers. (C) 2002 Elsevier Science (USA). C1 NIEHS, Lab Womens Hlth, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NCI, Lab Biosyst & Canc, Canc Res Ctr, Bethesda, MD 20892 USA. RP Davis, BJ (reprint author), NIEHS, Lab Womens Hlth, Res Triangle Pk, NC 27709 USA. NR 31 TC 55 Z9 66 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2002 VL 86 IS 1 BP 69 EP 78 DI 10.1006/gyno.2002.6729 PG 10 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 573JU UT WOS:000176826900013 PM 12079303 ER PT J AU Pileri, SA Grogan, TM Harris, NL Banks, P Campo, E Chan, JKC Favera, RD Delsol, G De Wolf-Peeters, C Falini, B Gascoyne, RD Gaulard, P Gatter, KC Isaacson, PG Jaffe, ES Kluin, P Knowles, DM Mason, DY Mori, S Muller-Hermelink, HK Piris, MA Ralfkiaer, E Stein, H Su, IJ Warnke, RA Weiss, LM AF Pileri, SA Grogan, TM Harris, NL Banks, P Campo, E Chan, JKC Favera, RD Delsol, G De Wolf-Peeters, C Falini, B Gascoyne, RD Gaulard, P Gatter, KC Isaacson, PG Jaffe, ES Kluin, P Knowles, DM Mason, DY Mori, S Muller-Hermelink, HK Piris, MA Ralfkiaer, E Stein, H Su, IJ Warnke, RA Weiss, LM TI Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases SO HISTOPATHOLOGY LA English DT Review DE dendritic cell neoplasms; histiocytic sarcoma; malignant histiocytosis; Langerhans cell tumour and sarcoma; interdigitating dendritic cell sarcoma; follicular dendritic cell sarcoma; mononuclear-phagocytic system; reticuloendothelial system; dendritic cell; malignant lymphoma; immunohistochemistry ID PLASMACYTOID T-CELLS; EPSTEIN-BARR-VIRUS; CHRONIC MYELOPROLIFERATIVE DISORDERS; MACROPHAGE DIFFERENTIATION ANTIGEN; INTERDIGITATING RETICULUM CELLS; PARAFFIN WAX SECTIONS; IN-SITU HYBRIDIZATION; REED-STERNBERG CELLS; MALIGNANT HISTIOCYTOSIS; MONOCLONAL-ANTIBODIES AB Neoplasms of histiocytes and dendritic cells are rare, and their phenotypic and biological definition is incomplete. Seeking to identify antigens detectable in paraffin-embedded sections that might allow a more complete, rational immunophenotypic classification of histiocytic/dendritic cell neoplasms, the International Lymphoma Study Group (ILSG) stained 61 tumours of suspected histiocytic/dendritic cell type with a panel of 15 antibodies including those reactive with histiocytes (CD68, lysozyme (LYS)), Langerhans cells (CD1a), follicular dendritic cells (FDC: CD21, CD35) and S100 protein. This analysis revealed that 57 cases (93%) fit into four major immunophenotypic groups (one histiocytic and three dendritic cell types) utilizing six markers: CD68, LYS, CD1a, S100, CD21, and CD35. The four (7%) unclassified cases were further classifiable into the above four groups using additional morphological and ultrastructural features. The four groups then included: (i) histiocytic sarcoma (n =18) with the following phenotype: CD68 (100%), LYS (94%), CD1a (0%), S100 (33%), CD21/35 (0%). The median age was 46 years. Presentation was predominantly extranodal (72%) with high mortality (58% dead of disease (DOD)). Three had systemic involvement consistent with `malignant histiocytosis'; (ii) Langerhans cell tumour (LCT) (n =26) which expressed: CD68 (96%), LYS (42%), CD1a (100%), S100 (100%), CD21/35 (0%). There were two morphological variants: cytologically typical (n =17) designated LCT; and cytologically malignant (n =9) designated Langerhans cell sarcoma (LCS). The LCS were often not easily recognized morphologically as LC-derived, but were diagnosed based on CD1a staining. LCT and LCS differed in median age (33 versus 41 years), male:female ratio (3.7:1 versus 1:2), and death rate (31% versus 50% DOD). Four LCT patients had systemic involvement typical of Letterer-Siwe disease; (iii) follicular dendritic cell tumour/sarcoma (FDCT) (n =13) which expressed: CD68 (54%), LYS (8%), CD1a (0%), S100 (16%), FDC markers CD21/35 (100%), EMA (40%). These patients were adults (median age 65 years) with predominantly localized nodal disease (75%) and low mortality (9% DOD); (iv) interdigitating dendritic cell tumour/sarcoma (IDCT) (n =4) which expressed: CD68 (50%), LYS (25%), CD1a (0%), S100 (100%), CD21/35 (0%). The patients were adults (median 71 years) with localized nodal disease (75%) without mortality (0% DOD). In conclusion, definitive immunophenotypic classification of histiocytic and accessory cell neoplasms into four categories was possible in 93% of the cases using six antigens detected in paraffin-embedded sections. Exceptional cases (7%) were resolvable when added morphological and ultrastructural features were considered. We propose a classification combining immunophenotype and morphology with five categories, including Langerhans cell sarcoma. This simplified scheme is practical for everyday diagnostic use and should provide a framework for additional investigation of these unusual neoplasms. C1 Univ Arizona, Hlth Sci Ctr, Coll Med, Dept Pathol, Tucson, AZ 85724 USA. Univ Bologna, Serv Pathol Anat & Hematopathol, I-40126 Bologna, Italy. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Clin Hosp, Serv Anat Pathol, Barcelona, Spain. Queen Elizabeth Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. Columbia Univ, Dept Pathol, New York, NY USA. Toulouse Univ, Cent Lab Pathol Anat, Toulouse, France. Univ Louvain, Dept Pathol, Louvain, Belgium. Univ Perugia, Inst Haematol, I-06100 Perugia, Italy. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Hop Henri Mondor, Dept Pathol, F-94010 Creteil, France. Univ Oxford, Dept Cellular Sci, Oxford, England. UCL, Dept Histopathol, London, England. NCI, Bethesda, MD 20892 USA. Univ Gottingen, Dept Pathol, D-3400 Gottingen, Germany. Cornell Univ, Dept Pathol, New York, NY USA. Univ Tokyo, Dept Pathol, Tokyo, Japan. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. Virgen Salud Hosp, Serv Anat Pathol, Toledo, Spain. Univ Copenhagen, Dept Pathol, Herlev, Denmark. Benjamin Franklin Univ, Inst Pathol, Berlin, Germany. Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. Natl Cheng Kung Univ Hosp, Dept Pathol, Tainan, Taiwan. City Hope Natl Med Ctr, Div Pathol, Duarte, CA 91010 USA. RP Grogan, TM (reprint author), Univ Arizona, Hlth Sci Ctr, Coll Med, Dept Pathol, 1501 N Campbell Ave,POB 245043, Tucson, AZ 85724 USA. EM pileri@almadns.unibo.it; TMGrogan@U.Arizona.edu RI Su, Ih-Jen/B-2655-2010; OI Piris, Miguel A/0000-0001-5839-3634; Campo, elias/0000-0001-9850-9793 FU NCI NIH HHS [CA32102-18, CA34233] NR 88 TC 319 Z9 363 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD JUL PY 2002 VL 41 IS 1 BP 1 EP 29 DI 10.1046/j.1365-2559.2002.01418.x PG 29 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 571XW UT WOS:000176745300001 PM 12121233 ER PT J AU Roth, GS Handy, AM Mattison, JA Tilmont, EM Ingram, DK Lane, MA AF Roth, GS Handy, AM Mattison, JA Tilmont, EM Ingram, DK Lane, MA TI Effects of dietary caloric restriction and aging on thyroid hormones of rhesus monkeys SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE primate; thyroxin; triiodothyronine; dietary restriction ID FOOD RESTRICTION; PRIMATES AB Plasma levels of thyroid hormones - triiodothyronine (T-3), thyroxin T-4), and thyroid-stimulating hormone (TSH) were measured in male and female rhesus monkeys (Macaca mulatta) fed either ad libitum or a 30% calorie-restricted (CR) diet (males for 11 years; females for 6 years). The same hormones were measured in another group of young male rhesus monkeys during adaptation to the 30% CR regimen. Both long- and shorter-term CR diet lowered total T-3 in plasma of the monkeys. The effect appeared to be greater in younger monkeys than in older counter-parts. No effects of CR diet were detected for either free or total T-4, although unlike T-3, levels of this hormone decreased with age. TSH levels also decreased with age, and were increased by longterm CR diet in older monkeys only. No consistent effects of shorter-term CR diet were observed for TSH. In the light of the effects of the thyroid axis on overall metabolism, these results suggest a possible mechanism by which CR diets may elicit their well-known beneficial 'anti-aging' effects in mammals. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Roth, GS (reprint author), NIA, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 19 TC 30 Z9 31 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUL PY 2002 VL 34 IS 7 BP 378 EP 382 DI 10.1055/s-2002-33469 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 585GJ UT WOS:000177516800006 PM 12189585 ER PT J AU Sevostianov, A Horwitz, B Nechaev, V Williams, R Fromm, S Braun, AR AF Sevostianov, A Horwitz, B Nechaev, V Williams, R Fromm, S Braun, AR TI fMRI study comparing names versus pictures of objects SO HUMAN BRAIN MAPPING LA English DT Article DE brain; human; fMRI; working memory; visual processing; central executive; prefrontal cortex; one-back task; semantics ID WORKING-MEMORY; FRONTAL LOBES; NEURAL SYSTEMS; TERM-MEMORY; PET-RCBF; WORD; ACTIVATION; MODELS; COMPONENT; PATHWAY AB We performed an fMRI one-back recognition study aimed at distinguishing the semantic versus perceptual aspects of how objects and their written forms are processed. There were three types of visually presented items: pictures (schematic drawings of objects); words identifying these objects; and a mixed condition in which pictures were interleaved with words. A semantic decision about object identity was required when pictures were interleaved with words. This condition, contrasted with the other two, invoked a larger signal in Multiple areas, including frontal cortex, bilateral occipitotemporal cortex, and the right middle temporal gyrus. We propose that the left occipitotemporal and right temporal activations are indicative of the neural substrate mediating picture-word conversions, whereas the frontal activations reflect the coordinating functions of the central executive. Published 2002 Wiley-Liss, Inc. C1 NIDCD, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Human Brain, St Petersburg 196140, Russia. RP Horwitz, B (reprint author), NIDCD, Language Sect, Voice Speech & Language Branch, NIH, Bldg 10,Rm 6C420,MSC 1591,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 31 Z9 31 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUL PY 2002 VL 16 IS 3 BP 168 EP 175 DI 10.1002/hbm.10037 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 569TU UT WOS:000176619000004 PM 12112770 ER PT J AU Bornstein, MH AF Bornstein, MH TI Toward a multiculture, multiage, multimethod science SO HUMAN DEVELOPMENT LA English DT Article DE development; cross-cultural developmental research methodology; language ID INFANTS AB Historically, developmental investigators have tended to assess phenomena of interest in one way at one age in one culture. In this essay, I explore some rationales and advantages for a multiculture, multiage, multimethod science. Copyright (C) 2002 S. Karger AG, Basel. C1 NICHHD, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. NR 16 TC 16 Z9 16 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0018-716X J9 HUM DEV JI Hum. Dev. PD JUL-AUG PY 2002 VL 45 IS 4 BP 257 EP 263 DI 10.1159/000064986 PG 7 WC Psychology, Developmental SC Psychology GA 581EU UT WOS:000177278800007 ER PT J AU Kaludov, N Handelman, B Chiorini, JA AF Kaludov, N Handelman, B Chiorini, JA TI Scalable purification of adeno-associated virus type 2, 4, or 5 using ion-exchange chromatography SO HUMAN GENE THERAPY LA English DT Article ID RECOMBINANT ADENOASSOCIATED VIRUS; GENE-TRANSFER; VECTORS; TRANSDUCTION; EXPRESSION; PERSISTENT; CLONING; CELLS; AAV5; MICE AB The availability of high-titer, high-purity, adeno-associated virus type 2 (AAV2) stocks has dramatically increased our understanding of this virus and its utility as a gene transfer vector. Current methods of purification take advantage of the stable interaction of AAV2 with heparin sulfate. This affinity chromatography, however, is not useful for purifying AAV4 and AAV5, because these serotypes lack heparin-binding activity. We have developed simple ion exchange high-performance liquid chromatography (HPLC) method for purifying different AAV serotypes that does not rely on the affinity of the viruses for heparin. The protocol is fast, efficient, and yields highly infectious material. Analysis of the highly purified virus indicated that more than 90% of the particles contained genomes and were more active than virus purified by cesium chloride (CsCl) gradient purification. This procedure is scalable and can easily be streamlined for large-scale production of recombinant adeno-associated virus (rAAV), regardless of the serotype. Ultimately, the new purification method will further the characterization of rAAV of different serotypes as vectors for gene therapy applications. C1 Natl Inst Dent & Cranialfacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Chiorini, JA (reprint author), NIH, 10-1N113,10 Ctr Dr MSC 1190, Bethesda, MD 20902 USA. NR 16 TC 94 Z9 97 U1 0 U2 7 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL PY 2002 VL 13 IS 10 BP 1235 EP 1243 DI 10.1089/104303402320139014 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 569UH UT WOS:000176620300010 PM 12133276 ER PT J AU Malyarchuk, BA Rogozin, IB Berikov, VB Derenko, MV AF Malyarchuk, BA Rogozin, IB Berikov, VB Derenko, MV TI Analysis of phylogenetically reconstructed mutational spectra in human mitochondrial DNA control region SO HUMAN GENETICS LA English DT Article ID MTDNA CONTROL REGION; SUBSTITUTION RATE VARIATION; MAJOR NONCODING REGION; NUCLEOTIDE SUBSTITUTION; HYPERVARIABLE SEGMENT; AFRICAN POPULATIONS; BASE SUBSTITUTION; HOT-SPOTS; SEQUENCES; SITES AB Analysis of mutations in mitochondrial DNA is an important issue in population and evolutionary genetics. To study spontaneous base substitutions in human mitochondrial DNA we reconstructed the mutational spectra of the hypervariable segments I and 11 (HVS I and 11) using published data on polymorphisms from various human populations. An excess of pyrimidine transitions was found both in HVS I and 11 regions. By means of classification analysis numerous mutational hotspots were revealed in these spectra. Context analysis of hotspots revealed a complex influence of neighboring bases on mutagenesis in the HVS I region. Further statistical analysis suggested that a transient misalignment dislocation mutagenesis operating in monotonous runs of nucleotides play an important role for generating base substitutions in mitochondrial DNA and define context properties of mtDNA. Our results suggest that dislocation mutagenesis in HVS I and 11 is a fingerprint of errors produced by DNA polymerase gamma in the course of human mitochondrial DNA replication. C1 Russian Acad Sci, Inst Biol Problems North, Magadan 685000, Russia. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. NIH, NLM, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Russian Acad Sci, Inst Math, Novosibirsk 630090, Russia. RP Malyarchuk, BA (reprint author), Russian Acad Sci, Inst Biol Problems North, Portovaya Str 18, Magadan 685000, Russia. OI Berikov, Vladimir/0000-0002-5207-9764 NR 59 TC 42 Z9 48 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUL PY 2002 VL 111 IS 1 BP 46 EP 53 DI 10.1007/s00439-002-0740-4 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 580CX UT WOS:000177218000007 PM 12136235 ER PT J AU Martin-Touaux, E Puech, JP Chateau, D Emiliani, C Kremer, EJ Raben, N Tancini, B Orlacchio, A Kahn, A Poenaru, L AF Martin-Touaux, E Puech, JP Chateau, D Emiliani, C Kremer, EJ Raben, N Tancini, B Orlacchio, A Kahn, A Poenaru, L TI Muscle as a putative producer of acid alpha-glucosidase for glycogenosis type II gene therapy SO HUMAN MOLECULAR GENETICS LA English DT Article ID DISEASE TYPE-II; ADENOVIRUS-MEDIATED TRANSFER; SKELETAL-MUSCLE; IN-VIVO; INTRACELLULAR-TRANSPORT; PROTEIN TRANSDUCTION; ENZYME REPLACEMENT; CLINICAL-TRIAL; KNOCKOUT MICE; FABRY-DISEASE AB Glycogenosis type II (GSD II) is a lysosomal disorder affecting skeletal and cardiac muscle. In the infantile form of the disease, patients display cardiac impairment, which is fatal before 2 years of life. Patients with juvenile or adult forms can present diaphragm involvement leading to respiratory failure. The enzymatic defect in GSD II results from mutations in the acid alpha-glucosidase (GAA) gene, which encodes a 76 kDa protein involved in intralysosomal glycogen hydrolysis. We previously reported the use of an adenovirus vector expressing GAA (AdGAA) for the transduction of myoblasts and myotubes cultures from GSD II patients. Transduced cells secreted GAA in the medium, and GAA was internalized by receptor-mediated capture, allowing glycogen hydrolysis in untransduced cells. In this study, using a GSD II mouse model, we evaluated the feasibility of GSD II gene therapy using muscle as a secretary organ. Adenovirus vector encoding AdGAA was injected in the gastrocnemius of neonates. We detected a strong expression of GAA in the injected muscle, secretion into plasma, and uptake by peripheral skeletal muscle and the heart. Moreover, glycogen content was decreased in these tissues. Electron microscopy demonstrated the disappearance of destruction foci, normally present in untreated mice. We thus demonstrate for the first time that muscle can be considered as a safe and easily accessible organ for GSD II gene therapy. C1 Inst Cochin Genet Mol, INSERM, U567, Dept Genet Dev & Pathol Mol, F-75014 Paris, France. Univ Paris 05, Paris, France. Hop La Pitie Salpetriere, INSERM, U153, Paris, France. Univ Perugia, Dipartimento Sci Biochim & Biotecnol Mol, I-06100 Perugia, Italy. Genethon 3, CNRS, URA 1923, Evry, France. NIH, Bethesda, MD 20892 USA. RP Martin-Touaux, E (reprint author), Inst Cochin Genet Mol, INSERM, U567, Dept Genet Dev & Pathol Mol, F-75014 Paris, France. RI Kremer, Eric /D-3734-2013; Tancini, Brunella/F-6467-2014; Emiliani, Carla/G-3738-2010 OI Tancini, Brunella/0000-0001-9070-5765; Emiliani, Carla/0000-0002-6368-1515 NR 40 TC 26 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL 1 PY 2002 VL 11 IS 14 BP 1637 EP 1645 DI 10.1093/hmg/11.14.1637 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 569MN UT WOS:000176606300006 PM 12075008 ER PT J AU Dunson, DB Colombo, B AF Dunson, DB Colombo, B TI TwoDay Algorithm in predicting fertile time - Reply SO HUMAN REPRODUCTION LA English DT Letter C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Univ Padua, Dept Stat, Padua, Italy. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, MD A3-03, Res Triangle Pk, NC 27709 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUL PY 2002 VL 17 IS 7 BP 1925 EP 1926 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 572QG UT WOS:000176786000044 ER PT J AU Thayer, JF AF Thayer, JF TI Progress in the analysis of heart-rate variability SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Editorial Material C1 NIA, LPC, GRC, Baltimore, MD 21224 USA. RP Thayer, JF (reprint author), NIA, LPC, GRC, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD JUL-AUG PY 2002 VL 21 IS 4 BP 22 EP 23 DI 10.1109/MEMB.2002.1032634 PG 2 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 590QQ UT WOS:000177833900005 PM 12222112 ER PT J AU Thayer, JF Siegle, GI AF Thayer, JF Siegle, GI TI Neurovisceral integration in cardiac and emotional regulation SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID HEART-RATE-VARIABILITY; PREFRONTAL CORTEX; MODULATION; BEHAVIOR; PERSPECTIVE; MECHANISMS; ANXIETY; SYSTEM; EEG C1 NIA, LPC, GRC, Baltimore, MD 21224 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Thayer, JF (reprint author), NIA, LPC, GRC, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 42 TC 52 Z9 53 U1 0 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD JUL-AUG PY 2002 VL 21 IS 4 BP 24 EP 29 DI 10.1109/MEMB.2002.1032635 PG 6 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 590QQ UT WOS:000177833900006 PM 12222113 ER PT J AU Sollers, JJ Sanford, TA Nabors-Oberg, R Anderson, CA Thayer, JF AF Sollers, JJ Sanford, TA Nabors-Oberg, R Anderson, CA Thayer, JF TI Examining changes in HRV in response to varying ambient temperature SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID HEART-RATE-VARIABILITY; MODULATION; HUMANS C1 NIA, Gerontol Res Ctr, NIH,Lab Personal & Cognit, Emot & Quantitat Psychophysiol Unit, Baltimore, MD 21224 USA. Univ Missouri, Columbia, MO 65211 USA. Iowa State Univ, Ames, IA 50011 USA. RP Sollers, JJ (reprint author), NIA, Gerontol Res Ctr, NIH,Lab Personal & Cognit, Emot & Quantitat Psychophysiol Unit, 2C15,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Anderson, Craig/I-6447-2012 OI Anderson, Craig/0000-0001-6353-0023 FU NIAAA NIH HHS [1F31 AA13673-01] NR 8 TC 12 Z9 12 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD JUL-AUG PY 2002 VL 21 IS 4 BP 30 EP 34 DI 10.1109/MEMB.2002.1032636 PG 5 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 590QQ UT WOS:000177833900007 PM 12222114 ER PT J AU Thayer, JF Sollers, JJ Ruiz-Padial, E Vila, J AF Thayer, JF Sollers, JJ Ruiz-Padial, E Vila, J TI Estimating respiratory frequency from autoregressive spectral analysis of heart period SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID RATE-VARIABILITY C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, Lab Personal & Cognit, Emot & Quantitat Psychophyusiol Unit, Baltimore, MD 21224 USA. Univ Jaen, Jaen, Spain. Univ Granada, E-18071 Granada, Spain. RP Sollers, JJ (reprint author), NIA, Gerontol Res Ctr, NIH, 2C15,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Vila, Jaime/F-9719-2010; Ruiz Padial, Elisabeth/G-8962-2011 OI Vila, Jaime/0000-0002-1767-8606; NR 16 TC 44 Z9 44 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD JUL-AUG PY 2002 VL 21 IS 4 BP 41 EP 45 DI 10.1109/MEMB.2002.1032638 PG 5 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 590QQ UT WOS:000177833900009 PM 12222116 ER PT J AU Nabors-Oberg, RE Niaura, RS Sollers, JJ Thayer, JF AF Nabors-Oberg, RE Niaura, RS Sollers, JJ Thayer, JF TI The effects of controlled smoking on heart period variability SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID CIGARETTE-SMOKING; BLOOD-PRESSURE; CESSATION; NICOTINE; MODULATION; ANXIETY C1 NIA, LPC, GRC, Baltimore, MD 21224 USA. Univ Missouri, Columbia, MO USA. Brown Univ, Providence, RI 02912 USA. RP Thayer, JF (reprint author), NIA, LPC, GRC, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NHLBI NIH HHS [HL32318]; NICHD NIH HHS [5 T32 HDO7460-0] NR 30 TC 13 Z9 13 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD JUL-AUG PY 2002 VL 21 IS 4 BP 65 EP 70 DI 10.1109/MEMB.2002.1032641 PG 6 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 590QQ UT WOS:000177833900012 PM 12222119 ER PT J AU Wang, X Wang, JTL Shasha, D Shapiro, BA Rigoutsos, I Zhang, KZ AF Wang, X Wang, JTL Shasha, D Shapiro, BA Rigoutsos, I Zhang, KZ TI Finding patterns in three-dimensional graphs: Algorithms and applications to scientific data mining SO IEEE TRANSACTIONS ON KNOWLEDGE AND DATA ENGINEERING LA English DT Article DE KDD; classification and clustering; data mining; geometric hashing; structural pattern discovery; biochemistry; medicine ID KNOWLEDGE DISCOVERY; DATABASES; PROTEINS; MOTIFS; SEARCH AB This paper presents a method for finding patterns in 3D graphs. Each node in a graph is an undecomposable or atomic unit and has a label. Edges are links between the atomic units. Patterns are rigid substructures that may occur in a graph after allowing for an arbitrary number of whole-structure rotations and translations as well as a small number (specified by the user) of edit operations in the patterns or in the graph. (When a pattern appears in a graph only after the graph has been modified, we call that appearance "approximate occurrence.") The edit operations include relabeling a node, deleting a node and inserting a node. The proposed method is based on the geometric hashing technique, which hashes node-triplets of the graphs into a 3D table and compresses the label-triplets in the table. To demonstrate the utility of our algorithms, we discuss two applications of them in scientific data mining. First, we apply the method to locating frequently occurring motifs in two families of proteins pertaining to RNA-directed DNA Polymerase and Thymidylate Synthase and use the motifs to classify the proteins. Then, we apply the method to clustering chemical compounds pertaining to aromatic, bicyclicalkanes, and photosynthesis. Experimental results indicate the good performance of our algorithms and high recall and precision rates for both classification and clustering. C1 Calif State Univ Fullerton, Dept Comp Sci, Fullerton, CA 92834 USA. New Jersey Inst Technol, Dept Comp & Informat Sci, Newark, NJ 07102 USA. NYU, Courant Inst Math Sci, Dept Comp Sci, New York, NY 10012 USA. Natl Canc Inst, Lab Expt & Computat Biol, Div Basic Sci, Frederick, MD 21702 USA. IBM Corp, Thomas J Watson Res Ctr, Yorktown Hts, NY 10598 USA. Univ Western Ontario, Dept Comp Sci, London, ON N6A 5B7, Canada. RP Calif State Univ Fullerton, Dept Comp Sci, Fullerton, CA 92834 USA. EM wang@ecs.fullerton.edu; jason@cis.njit.edu; shasha@cs.nyu.edu; bshapiro@ncifcrf.gov; rigoutso@us.ibm.com; kzhang@csd.uwo.ca NR 36 TC 21 Z9 21 U1 2 U2 6 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1041-4347 EI 1558-2191 J9 IEEE T KNOWL DATA EN JI IEEE Trans. Knowl. Data Eng. PD JUL-AUG PY 2002 VL 14 IS 4 BP 731 EP 749 DI 10.1109/TKDE.2002.1019211 PG 19 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 570HU UT WOS:000176653500004 ER PT J AU Shaffer, AL Lin, KI Kuo, TC Yu, X Hurt, EM Rosenwald, A Giltnane, JM Yang, LM Zhao, H Calame, K Staudt, LM AF Shaffer, AL Lin, KI Kuo, TC Yu, X Hurt, EM Rosenwald, A Giltnane, JM Yang, LM Zhao, H Calame, K Staudt, LM TI Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program SO IMMUNITY LA English DT Article ID GERMINAL-CENTER FORMATION; TRANSCRIPTION FACTOR BSAP; C-MYC; SWITCH RECOMBINATION; ANTIGEN RECEPTOR; TARGET GENES; TERMINAL DIFFERENTIATION; TYROSINE KINASE; IN-VIVO; SPI-B AB Blimp-1, a transcriptional repressor, drives the terminal differentiation of B cells to plasma cells. Using DNA microarrays, we found that introduction of Blimp-1 into B cells blocked expression of a remarkably large set of genes, while a much smaller number was induced. Blimp-1 initiated this cascade of gene expression changes by directly repressing genes encoding several transcription factors, including Spi-B and Id3, that regulate signaling by the B cell receptor. Blimp-1 also inhibited immunoglobulin class switching by blocking expression of AID, Ku70, Ku86, DNA-PKcs, and STAT6. These findings suggest that Blimp-1 promotes plasmacytic differentiation by extinguishing gene expression important for B cell receptor signaling, germinal center B cell function, and proliferation while allowing expression of important plasma cell genes such as XBP-1. C1 Columbia Univ Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA. RP Calame, K (reprint author), Columbia Univ Coll Phys & Surg, Dept Microbiol, 701 W 168th St, New York, NY 10032 USA. RI Lin, KUO-I /C-6928-2009; Giltnane, Jennifer/D-2584-2013 FU NIAID NIH HHS [AI43576]; NIGMS NIH HHS [GM29361] NR 69 TC 532 Z9 543 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2002 VL 17 IS 1 BP 51 EP 62 DI 10.1016/S1074-7613(02)00335-7 PG 12 WC Immunology SC Immunology GA 579PR UT WOS:000177187500006 PM 12150891 ER PT J AU Metzger, H AF Metzger, H TI Molecular versatility of antibodies SO IMMUNOLOGICAL REVIEWS LA English DT Review ID BASOPHILIC LEUKEMIA-CELLS; AFFINITY IGE RECEPTOR; FC-EPSILON-RI; RAT MAST-CELLS; IMMUNOGLOBULIN-E RECEPTORS; HISTAMINE-RELEASE; ALPHA-SUBUNIT; LYN KINASE; TRANSFECTED CELLS; PHASE-SEPARATION AB As immunology developed into a discrete discipline, the principal experimental efforts were directed towards uncovering the molecular basis of the specificity exhibited by antibodies and the mechanism by which antigens induced their production. Less attention was given to how antibodies carry out some of their effector functions, although this subject presents an interesting protein-chemical and evolutionary problem; that is, how does a family of proteins that can bind a virtually infinite variety of ligands, many of which the species producing that protein has never encountered, reproducibly initiate an appropriate response? The experimental data persuasively suggested that aggregation of the antibody was a necessary and likely sufficient initiating event, but this only begged the question: how does aggregation induce a response? I used the IgE:mast cell system as a paradigm to investigate this subject. Data from our own group and from many others led to a molecular model that appears to explain how a cell 'senses' that antigen has reacted with the IgE. The model is directly applicable to one of the fundamental questions cited above, i.e. the mechanism by which antigens induce the production of antibodies. Although the model is conceptually simple, incorporating the actual molecular events into a quantitatively accurate scheme represents an enormous challenge. C1 NIAMS, Sect Chem Immunol, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Metzger, H (reprint author), NIAMS, Sect Chem Immunol, Arthrit & Rheumatism Branch, NIH, 9N-228,10 Ctr Dr,MSC 1820, Bethesda, MD 20892 USA. NR 121 TC 10 Z9 11 U1 1 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUL PY 2002 VL 185 BP 186 EP 205 DI 10.1034/j.1600-065X.2002.18516.x PG 20 WC Immunology SC Immunology GA 586MZ UT WOS:000177588900016 PM 12190931 ER PT J AU Carabeo, RA Grieshaber, SS Fischer, E Hackstadt, T AF Carabeo, RA Grieshaber, SS Fischer, E Hackstadt, T TI Chlamydia trachomatis induces remodeling of the actin cytoskeleton during attachment and entry into HeLa cells SO INFECTION AND IMMUNITY LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; CRYPTOSPORIDIUM-PARVUM INFECTION; OUTER-MEMBRANE PROTEIN; FIBROBLASTS L-CELLS; EPITHELIAL-CELLS; SHIGELLA-FLEXNERI; HOST-CELLS; III SECRETION; PHOSPHOINOSITIDE 3-KINASE; INTRACELLULAR PARASITISM AB To elucidate the host cell machinery utilized by Chlamydia trachomatis to invade epithelial cells, we examined the role of the actin cytoskeleton in the internalization of chlamydial elementary bodies (EBs). Treatment of HeLa cells with cytochalasin D markedly inhibited the internalization of C trachomatis serovar L2 and D Ells. Association of EBs with HeLa cells induced localized actin polymerization at the site of attachment, as visualized by either phalloidin staining of fixed cells or the active recruitment of GFP-actin in viable infected cells. The recruitment of actin to the specific site of attachment was accompanied by dramatic changes in the morphology of cell surface microvilli. Ultrastructural studies revealed a transient microvillar hypertrophy that was dependent upon C trachomatis attachment, mediated by structural components on the EBs, and cytochalasin D sensitive. In addition, a mutant CHO cell line that does not support entry of C. trachomatis serovar L2 did not display such microvillar hypertrophy following exposure to L2 Ells, which is in contrast to infection with serovar D, to which it is susceptible. We propose that C. trachomatis entry is facilitated by an active actin remodeling process that is induced by the attachment of this pathogen, resulting in distinct microvillar reorganization throughout the cell surface and the formation of a pedestal-like structure at the immediate site of attachment and entry. C1 NIAID, Rocky Mt Labs, Hosp Parasite Interact Sect, Intracellular Parasites Lab,NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Rocky Mt Microscopy Brnach, NIH, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Rocky Mt Labs, Hosp Parasite Interact Sect, Intracellular Parasites Lab,NIH, Hamilton, MT 59840 USA. NR 62 TC 94 Z9 96 U1 2 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2002 VL 70 IS 7 BP 3793 EP 3803 DI 10.1128/IAI.70.7.3793-3803.2002 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 564ET UT WOS:000176302600057 PM 12065523 ER PT J AU Fields, KA Fischer, E Hackstadt, T AF Fields, KA Fischer, E Hackstadt, T TI Inhibition of fusion of Chlamydia trachomatis inclusions at 32 degrees C correlates with restricted export of IncA SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; HOST-CELL; GENE-EXPRESSION; INFECTED-CELLS; PURIFICATION; SECRETION AB Chlamydia trachomatis is an obligate intracellular bacterium that develops within a parasitophorous vacuole termed an inclusion. The inclusion is nonfusogenic with lysosomes but intercepts lipids from a host cell exocytic pathway. Initiation of chlamydial development is concurrent with modification of the inclusion membrane by a set of C. trachomatis-encoded proteins collectively designated Incs. One of these Incs, IncA, is functionally associated with the homotypic fusion of inclusions. Inclusions also do not fuse when cultures are multiply infected with C. trachomatis and cultivated at 32degreesC. We obtained evidence linking these experimental Observations by characterizing IncA localization in 32degreesC cultures. Analysis of inclusions by light and transmission electron microscopy confirmed that HeLa cells infected with multiple C. trachomatis elementaty bodies and cultivated at 32degreesC for 24 h contained multiple, independent inclusions. Reverse transcriptase PCR and immunoblot analyses of C. trachomatis-infected HeLa cells demonstrated the presence of IncA at 24 h in 32degreesC cultures. When parallel cultures were probed with IncA-specific antibodies in indirect immunofluorescence assays, IncA was detectable in intracellular chlamydiae but not within the inclusion membrane. In addition, analysis of purified reticulate bodies from 37 and 32degreesC cultures showed that bacterium-associated pools of IncA are enriched in cultures grown at 32degreesC. Microscopic observation of infected cells revealed that some vacuoles had fused by 48 h postinfection, and this finding was correlated with the detection of IncA in inclusion membranes by immunofluorescence microscopy. The data are consistent with a requirement for IncA in fusions of C. trachomatis inclusions and suggest that the effect of incubation at 32degreesC is manifested by restricted export of IncA to the inclusion membrane. C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Host Parasite Interact Sect, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Microscopy Branch, Hamilton, MT 59840 USA. RP NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Host Parasite Interact Sect, Hamilton, MT 59840 USA. EM Ted_Hackstadt@NIH.GOV NR 28 TC 29 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2002 VL 70 IS 7 BP 3816 EP 3823 DI 10.1128/IAI.70.7.3816-3823.2002 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 564ET UT WOS:000176302600059 PM 12065525 ER PT J AU Herron, LL Chakravarty, R Dwan, C Fitzgerald, JR Musser, JM Retzel, E Kapur, V AF Herron, LL Chakravarty, R Dwan, C Fitzgerald, JR Musser, JM Retzel, E Kapur, V TI Genome sequence survey identifies unique sequences and key virulence genes with unusual rates of amino acid substitution in bovine Staphylococcus aureus SO INFECTION AND IMMUNITY LA English DT Article ID MOLECULAR POPULATION; EXPRESSION; COWS AB Staphylococcus aureus is a major cause of mastitis in bovine and other ruminant species. We here present the results of a comparative genomic analysis between a bovine mastitis-associated clone, RF122, and the recently sequenced human-associated clones, Mu50 and N315, of Staphylococcus aureus. A shotgun sequence survey of similar to10% of the RF122 genome identified numerous unique sequences and those with elevated rates of nonsynonymous substitution. Taken together, these analyses show that there are notable differences in the genomes of bovine mastitis-associated and human clones of S. aureus and provide a framework for the identification of specific factors associated with host specificity in this major human and animal pathogen. C1 Univ Minnesota, Dept Vet Pathobiol, St Paul, MN 55108 USA. Univ Minnesota, Biomed Genom Ctr, St Paul, MN 55108 USA. Univ Minnesota, Computat Biol Ctr, Minneapolis, MN 55455 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Kapur, V (reprint author), Univ Minnesota, Dept Vet Pathobiol, 205 Vet Sci,1971 Commonwealth Ave, St Paul, MN 55108 USA. RI Kapur, Vivek/F-7610-2013; OI Kapur, Vivek/0000-0002-9648-0138 FU NIGMS NIH HHS [GM08347, T32 GM008347] NR 15 TC 38 Z9 39 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2002 VL 70 IS 7 BP 3978 EP 3981 DI 10.1128/IAI.70.7.3978-3981.2002 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 564ET UT WOS:000176302600082 PM 12065548 ER PT J AU Groll, AN Walsh, TJ AF Groll, AN Walsh, TJ TI Invasive fungal infections in the neutropenic cancer patient: Current approaches and future strategies SO INFECTIONS IN MEDICINE LA English DT Article DE mycoses; cancer; transplantation; antifungal agents ID BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; B COLLOIDAL DISPERSION; AMPHOTERICIN-B; HEPATOSPLENIC CANDIDIASIS; PULMONARY ASPERGILLOSIS; FLUCONAZOLE PROPHYLAXIS; IMMUNOCOMPROMISED PATIENTS; ANTIFUNGAL THERAPY AB Invasive fungal infections are important causes of morbidity and mortality in cancer patients with prolonged neutropenia following dose-intensive chemotherapy or hematopoietic stem cell transplantation. Recent epidemiologic trends indicate a shift toward infections by Aspergillus species, non-albicans Candida species, and previously uncommon fungal pathogens that have decreased susceptibility to current antifungal agents, In the last decade, much progress has been made in establishing disease definitions and paradigms for antifungal intervention and in the design and conduct of interventional clinical trials. This article reviews current approaches to prevention and treatment of opportunistic fungal infections in neutropenic patients and discusses novel approaches to antifungal chemotherapy and supportive measures. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Munster, Dept Pediat Hematol Oncol, D-4400 Munster, Germany. RP Groll, AN (reprint author), NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 61 TC 2 Z9 2 U1 0 U2 1 PU SCP COMMUNICATIONS INC PI NEW YORK PA 134 W 29TH ST, NEW YORK, NY 10001-5304 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD JUL PY 2002 VL 19 IS 7 BP 326 EP 334 PG 9 WC Infectious Diseases SC Infectious Diseases GA 572YW UT WOS:000176803400010 ER PT J AU de Lima, MFR Ferreira, CAS de Freitas, DRJ Valenzuela, JG Masuda, A AF de Lima, MFR Ferreira, CAS de Freitas, DRJ Valenzuela, JG Masuda, A TI Cloning and partial characterization of a Boophilus microplus (Acari : Ixodidae) glutathione S-transferase SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Boophilus microplus; glutathione S-transferase; ectoparasites; cDNA cloning ID ASPARTIC PROTEINASE PRECURSOR; MOLECULAR-CLONING; CATTLE TICK; METARHIZIUM-ANISOPLIAE; PROTECTIVE ANTIGEN; CATALYTIC ACTIVITY; MESSENGER-RNA; IN-VITRO; RESISTANCE; EXPRESSION AB A cDNA of glutathione S-transferase (GST) was isolated from a cDNA library of salivary glands of Boophilus microplus. The recombinant protein was purified by glutathione affinity chromatography and assayed upon the chromogenic substrate CDNB. The 864 bp cloned fragment was sequenced and showed an open reading frame coding for a protein of 220 amino acids. Expression of the GST gene was tested by RT-PCR in tick tissues and larvae mRNA. Comparison of the deduced amino acid sequence with GSTs from other species revealed that the enzyme is closely related to the mammalian class mu GSTs. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Fed Rio Grande do Sul, Ctr Biotecnol Estado Rio Grande Sul, BR-91501970 Porto Alegre, RS, Brazil. Univ Fed Rio Grande do Sul, Dept Bioquim, BR-91501970 Porto Alegre, RS, Brazil. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Fed Rio Grande do Sul, Dept Mol Biol & Biotecnol, BR-91501970 Porto Alegre, RS, Brazil. RP Univ Fed Rio Grande do Sul, Ctr Biotecnol Estado Rio Grande Sul, CP 15005,Campus Vale, BR-91501970 Porto Alegre, RS, Brazil. EM aoi@dna.cbiot.ufrgs.br RI Ferreira, Carlos /J-3672-2015; Freitas, Daniela/B-2879-2014 OI Ferreira, Carlos /0000-0002-3727-5097; Freitas, Daniela/0000-0002-5632-0332 NR 51 TC 27 Z9 27 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 EI 1879-0240 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD JUL PY 2002 VL 32 IS 7 BP 747 EP 754 AR PII S0965-1748(01)00157-6 DI 10.1016/S0965-1748(01)00157-6 PG 8 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 566TP UT WOS:000176444600005 PM 12044491 ER PT J AU Zhang, X Young, HA AF Zhang, X Young, HA TI PPAR and immune system - what do we know? SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Review DE fatty acids; NK cells; nuclear hormone receptor; Th1/Th2 differentiation; transcription ID ACTIVATED RECEPTOR-GAMMA; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CREB-BINDING PROTEIN; NF-KAPPA-B; KINASE-MEDIATED PHOSPHORYLATION; CELLS IN-VIVO; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); GENE-EXPRESSION; CYCLOPENTENONE PROSTAGLANDINS; TRANSCRIPTION FACTOR AB Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear steroid receptor superfamily. Originally, the receptors were identified as critical controllers for several key enzymes that catalyze the oxidation of fatty acids. PPARs consist of three members: PPAR-alpha, PPAR-beta/delta, and PPAR-gamma. Among them, PPAR-gamma is essential for controlling thermogenesis and adipocyte differentiation. The ligands for PPAR-gamma include 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2))-a metabolite from the prostaglandin synthesis pathway, and "glitazones "-drugs utilized in the treatment of patients with diabetes. The precursors for prostaglandins are fatty acids consumed from diet and these precursors have long been postulated to have a regulatory role in immune functions. Emerging evidence indicates that PPAR-gamma and its ligands are indeed important for the modulation of immune and inflammatory reactions. In this review, we will spotlight the molecular mechanisms of receptor/ligand function and how they may regulate immune and inflammatory reactions. We also propose that PPAR-gamma and its endogenous ligands are participating factors for Type 1 /Type 2 T and NK cell differentiation and development. Deciphering the mechanism of action of PPAR-gamma and its ligands may lead to a new therapeutic regiment for treatment of diseases involving dysfunction of the immune system. (C) 2002 Elsevier Science B.V All rights reserved. C1 NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Zhang, X (reprint author), NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RI Zhang, Xia/B-8152-2008 OI Zhang, Xia/0000-0002-9040-1486 FU Intramural NIH HHS [Z01 BC009283-23] NR 116 TC 52 Z9 59 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD JUL PY 2002 VL 2 IS 8 BP 1029 EP 1044 AR PII S1567-5769(02)00057-7 DI 10.1016/S1567-5769(02)00057-7 PG 16 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 596RM UT WOS:000178179300001 PM 12349941 ER PT J AU Papageorgiou, T Stratakis, CA AF Papageorgiou, T Stratakis, CA TI Ovarian tumors associated with multiple endocrine neoplasias and related syndromes (Carney complex, Peutz-Jeghers syndrome, von Hippel-Lindau disease, Cowden's disease) SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Review DE Carney complex; Cowden disease; genetics; multiple endocrine neoplasias; ovarian cancer; ovarian tumors; Peutz-Jeghers syndrome ID SEX CORD TUMOR; CERVICAL ADENOMA-MALIGNUM; FEMALE GENITAL-TRACT; SERTOLI-CELL TUMOR; PROTEIN-KINASE-A; ANNULAR TUBULES; HIRSCHSPRUNG-DISEASE; RET PROTOONCOGENE; SUPPRESSOR GENE; GERMLINE MUTATIONS AB Despite the relatively high prevalence of ovarian cancer (1% of American women will develop this disease in their lifetime) and recent developments in its molecular genetic understanding (several proto-oncogenes, such as AKT2 and cKRAS , and tumor suppressor genes, such as BRCA1 and BRCA2 , have been implicated), little is known about the presence of ovarian tumors and cancer in women already diagnosed with other familial multiple tumor syndromes. In this review, we focus on the possible association of ovarian tumors with multiple endocrine neoplasias (MENs) and their related syndromes, such as Carney complex (CNC), Peutz-Jeghers syndrome (PJS), von Hippel-Lindau disease (VHLD), and Cowden's disease (CD). These conditions recently have been molecularly elucidated, and some of the genes responsible for them (including STK11/LKB1 and PTEN , the genes responsible for PJS and CD, respectively) have already been investigated in series of sporadic ovarian lesions, mostly carcinomas. A brief description of each disease is followed by a literature search for affected patients with ovarian tumors; we review our own experience with CNC patients and ovarian tumors. An association between PJS and CNC and ovarian neoplasms seems likely; carcinoids of the ovary may occur in patients with MEN 1. Only few patients with CD and VHLD have any ovarian pathology, but PTEN , the CD gene has been investigated in sporadic ovarian tumors. The aim of the present report is to alert clinicians who care for patients with MENs, CNC, PJS, VHLD, CD, and other syndromes for possible associations between various types of ovarian tumors and these conditions. C1 NICHD, Unit Genet & Endocrinol, DEB, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Unit Genet & Endocrinol, DEB, NIH, Bldg 10,Room 10 N262,10 Ctr Dr MSC1862, Bethesda, MD 20892 USA. NR 112 TC 29 Z9 33 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD JUL-AUG PY 2002 VL 12 IS 4 BP 337 EP 347 DI 10.1046/j.1525-1438.2002.01147.x PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 577WQ UT WOS:000177085900004 PM 12144681 ER PT J AU Dyagil, I Adam, M Beebe, GW Burch, JD Gaidukova, SN Gluzman, D Gudzenko, N Klimenko, V Peterson, L Reiss, RF Finch, SC AF Dyagil, I Adam, M Beebe, GW Burch, JD Gaidukova, SN Gluzman, D Gudzenko, N Klimenko, V Peterson, L Reiss, RF Finch, SC TI Histologic verification of leukemia, myelodysplasia, and multiple myeloma diagnoses in patients in Ukraine, 1987-1998 SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Ukraine; leukemia; multiple myeloma; myelodysplasia ID RADIATION RISKS 1986-1995; CHERNOBYL ACCIDENT; PROGNOSTIC FACTORS; EMERGENCY WORKERS; CANCER MORTALITY; THYROID-CANCER; BOMB SURVIVORS; FOLLOW-UP; CLASSIFICATION; RADIOTHERAPY AB In preparation for a possible large epidemiological study of radiation-related leukemia in Chernobyl clean-up workers of Ukraine, histologic evaluation of 62 cases of leukemia and related disorders was conducted by a panel of expert hematologists and hematopathologists from the United States, France, and Ukraine. All cases were randomly selected from a surrogate population of men in the general population of 6 regions of Ukraine who were between the ages of 20 and 60 years in 1986 and were reported to have developed leukemia, myelodysplasia, or multiple myeloma between the years 1987 and 1998. The hematologists and hematopathologists on the panel were in agreement with one another and with the previously reported diagnoses and classifications of about 90% of the cases of acute and chronic leukemia in the study. These results suggest that strong reliance can be placed on the clinical diagnoses of acute and chronic forms of leukemia and multiple myeloma that have occurred in Ukrainian Chernobyl clean-up workers providing that the diagnoses are supported by records of the patients having had adequate histologic bone marrow studies. The number of cases in this study with the diagnosis of myelodysplasia, however, was too small to draw firm conclusions. C1 Res Ctr Radiat Med, Kiev, Ukraine. Hosp Enfants Armand Trousseau, Paris, France. NCI, NIH, Bethesda, MD 20892 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Med Acad Postgrad Med Educ, Kiev, Ukraine. RE Kavetsky Inst Expt Pathol, Kiev, Ukraine. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. RP Finch, SC (reprint author), Cooper Hlth Syst, 1 Cooper Plaza, Camden, NJ 08103 USA. NR 40 TC 9 Z9 11 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD JUL PY 2002 VL 76 IS 1 BP 55 EP 60 DI 10.1007/BF02982719 PG 6 WC Hematology SC Hematology GA 573YC UT WOS:000176859400008 PM 12138896 ER PT J AU Vicennati, V Vottero, A Friedman, C Papanicolaou, DA AF Vicennati, V Vottero, A Friedman, C Papanicolaou, DA TI Hormonal regulation of interleukin-6 production in human adipocytes SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE interleukin-6; adipocyte; insulin; cortisol ID C-REACTIVE PROTEIN; OB GENE-EXPRESSION; FREE FATTY-ACIDS; DAYTIME SLEEPINESS; INSULIN-RESISTANCE; UNSTABLE ANGINA; PRIMARY CULTURE; ADIPOSE-TISSUE; LEPTIN; OBESITY AB OBJECTIVE: To elucidate the hormonal regulation of interleukin-6 (IL-6) production by human adipose tissue and its relation to leptin. DESIGN: In vitro study. Human adipocytes were incubated with dexamethasone (with or without RU486), norepinephrine and epinephrine (with or without propranolol), or insulin. MEASUREMENTS: IL-6 and leptin secretion by human adipocytes. RESULTS: A gradual increase in IL-6 secretion by adipocytes during differentiation was observed. A positive correlation was found between basal IL-6 release and both glycerol 3-phosphate dehydrogenase activity-a marker of adipocyte differentiation-and leptin release. Dexamethasone decreased IL-6 secretion and increased leptin secretion in a dose-dependent manner. Both catecholamines increased IL-6 and leptin secretion. The effects of dexamethasone and catecholamines on IL-6 and leptin were abrogated by RU486 and propranolol, respectively. Incubation with insulin resulted in a dose-dependent stimulation of IL-6 and leptin secretion. CONCLUSION: IL-6 is produced by human adipocytes and is a potential marker of adipocyte differentiation. Furthermore it is a hormonally regulated cytokine, suppressed by glucocorticoids, and stimulated by catecholamines and insulin in physiological concentrations. C1 Emory Univ, Dept Med, Div Endocrinol, Atlanta, GA 30322 USA. Univ Bologna, S Orsola Hosp, Endocrine Unit, Bologna, Italy. NICHHD, Pediat & Reprod Endocrinol branch, NIH, Bethesda, MD 20892 USA. RP Papanicolaou, DA (reprint author), Emory Univ, Dept Med, Div Endocrinol, Room 1307 W wing WMRB,1639 Pierce Dr, Atlanta, GA 30322 USA. OI Vicennati, Valentina/0000-0002-0026-137X NR 31 TC 71 Z9 79 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JUL PY 2002 VL 26 IS 7 BP 905 EP 911 DI 10.1038/sj.ijo.0802035 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 565BK UT WOS:000176348100003 PM 12080442 ER PT J AU Ellsworth, DL Coady, SA Chen, W Srinivasan, SR Elkasabany, A Gustat, J Boerwinkle, E Berenson, GS AF Ellsworth, DL Coady, SA Chen, W Srinivasan, SR Elkasabany, A Gustat, J Boerwinkle, E Berenson, GS TI Influence of the beta 2-adrenergic receptor Arg16Gly polymorphism on longitudinal changes in obesity from childhood through young adulthood in a biracial cohort: the Bogalusa Heart Study SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE obesity; BMI; weight gain; genetics; adrenergic receptor; children ID HUMAN ADIPOSE-TISSUE; BETA(2)-ADRENOCEPTOR GENE; CHILDREN; OVERWEIGHT; GLN27GLU; TRENDS; ADOLESCENTS; PREVALENCE; WEIGHT; IMPACT AB BACKGROUND: The beta2-adrenergic receptor (ADRB2) plays a major role in regulating energy expenditure by stimulating lipid metabolism in human adipose tissue. Polymorphisms in the ADRB2 gene have been associated with obesity and various weight-related traits in cross-sectional studies of adults, but little is known about the effects of the ADRB2 gene on childhood obesity or the propensity to gain weight over time. OBJECTIVE: To assess the effects of a polymorphism in codon 16 (Arg16-->Gly) of the ADRB2 gene, which has been associated with a decrease in beta2-receptor density and efficiency, on longitudinal changes in obesity from childhood to young adulthood in a biracial cohort. DESIGN: Seven cross-sectional screenings of children and five cross-sectional screenings of young adults who were previously examined as children produced longitudinal data from childhood to young adulthood. METHODS: Height, weight and subscapular and triceps skinfolds were measured by trained examiners following identical protocols over the course of the study. Gender- and age-stratified analyses using random coefficients models were used to examine longitudinal genetic effects on obesity in 1151 African-American and Caucasian males and females who attended an average of six examinations over a 24y period from childhood to young adulthood. RESULTS: Age-stratified analyses showed no clear genetic relationships with changes in obesity measures over time in females, but an age-dependent association was observed in males, where the relationship between the Arg16Gly polymorphism and obesity became stronger with age. In males who were 4-9y of age at the beginning of the study in 1973, body mass index (BMI) was 4% higher in Gly/Gly and Arg/Gly males compared to those with Arg/Arg by 26y of age. Subscapular skinfold measurements in Gly/Gly males became significantly different from Arg/Arg males (20% higher) by age 20. In the oldest male cohort (10-14 y of age in 1973), BMI increased at a significantly greater rate (0.4%/y) in males carrying the Glyl 6 form of the receptor relative to Arg/Arg males. BMI was significantly different between homozygous genotypes by approximately 26y of age, and reached 8% higher in Gly/Gly males by age 32. Subscapular skinfolds also increased at a significantly greater rate (2%/y) in Gly/Gly males compared to Arg/Arg males, becoming significantly different (27%) by approximately 22 y of age and reaching a maximum difference of 50% by age 32. CONCLUSIONS: Our data suggest that the beta2-adrenergic receptor is associated with the propensity to gain weight from childhood to young adulthood in males. An increased understanding of genetic influences on the development of obesity may improve the effectiveness of interventions designed to reduce excess body weight and help define the role of genetic factors in diabetes and cardiovascular disease. C1 NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Tulane Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. Tulane Sch Publ Hlth & Trop Med, Ctr Cardiovasc Hlth, New Orleans, LA USA. Univ Texas, Houston Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. Univ Texas, Houston Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. RP Berenson, GS (reprint author), Tulane Ctr Cardiovasc Hlth, 1440 Canal St,Suite 2140, New Orleans, LA 70112 USA. FU NHLBI NIH HHS [HL38844] NR 36 TC 47 Z9 51 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JUL PY 2002 VL 26 IS 7 BP 928 EP 937 DI 10.1038/sj.ijo.0802020 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 565BK UT WOS:000176348100006 PM 12080445 ER PT J AU Snijder, MB Visser, M Dekker, JM Seidell, JC Fuerst, T Tylavsky, F Cauley, J Lang, T Nevitt, M Harris, TB AF Snijder, MB Visser, M Dekker, JM Seidell, JC Fuerst, T Tylavsky, F Cauley, J Lang, T Nevitt, M Harris, TB TI The prediction of visceral fat by dual-energy X-ray absorptiometry in the elderly: a comparison with computed tomography and anthropometry SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE DXA; visceral fat; elderly; body composition; fat distribution ID ABDOMINAL SAGITTAL DIAMETER; SOFT-TISSUE COMPOSITION; BODY-COMPOSITION; ADIPOSE-TISSUE; WAIST CIRCUMFERENCE; INTRAABDOMINAL FAT; CARDIOVASCULAR RISK; LIPID-METABOLISM; OLDER MEN; OBESE MEN AB INTRODUCTION: Effective methods for assessing visceral fat are important to investigate the role of visceral fat for the increased health risks in obesity. Techniques for direct measurement of soft tissue composition such as CT or MRI are expensive, time-consuming or require a relatively high radiation dose. Simple anthropometric methods, such as waist-to-hip ratio, waist circumference or sagittal diameter are widely used. However, these methods cannot differentiate between visceral and subcutaneous fat and are less accurate. The aim of the present study is to investigate whether the dual-energy X-ray absorptiometry (DXA) method, possibly combined with anthropometry, offers a good alternative to CT for the prediction of visceral fat in the elderly. METHODS: Subjects were participants in the Health ABC-study, a cohort study of black and white men and women aged 70 79, investigating the effect of weight-related health conditions on disablement. Total body fat and trunk fat were measured by DXA using a Hologic QDR 1500. A 10 mm CT scan at the L4 - L5 level was acquired to measure visceral fat and total abdominal fat. Weight, height, sagittal diameter and waist circumference were measured using standard methods. Fat in a manually defined DXA subregion (4 cm slice at the top of iliac crest) at the abdomen was calculated in a sub-group of participants (n = 150; 50% male; 45.3% Afro-American/54.7% Caucasian, age 70 - 79 y). This subregion, the standard trunk region and total fat were used as indicators of visceral fat. RESULTS: Total abdominal fat by DXA (subregion) was strongly correlated with total abdominal fat by CT (r ranging from 0.87 in white men to 0.98 in black women). The DXA subregion underestimated total abdominal fat by 10% compared to the CT slice. The underestimation by DXA was seen especially in people with less abdominal fat. The association of visceral fat by CT with the DXA subregion (r= 0.66, 0.78, 0.79 and 0.65 for white and black men and women, respectively) was comparable with the association of the CT measure with the sagittal diameter (r=0.74, 0.70, 0.84 and 0.68). Combining DXA measurements with anthropometry gave only limited improvement for the prediction of visceral fat by CT compared to univariate models (maximal increase of r(2) 4%). CONCLUSION: DXA is a good alternative to CT for predicting total abdominal fat in an elderly population. For the prediction of visceral fat the sagittal diameter, which has a practical advantage compared to DXA, is just as effective. C1 Vrije Univ Amsterdam, Inst Res Extramural Med, NL-1081 BT Amsterdam, Netherlands. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Natl Inst Publ Hlth & Environm Protect, Dept Epidemiol, NL-3720 BA Bilthoven, Netherlands. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. RP Snijder, MB (reprint author), Vrije Univ Amsterdam, Inst Res Extramural Med, Van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. RI Lang, Thomas/B-2685-2012; seidell, jacob/N-7427-2013; Cauley, Jane/N-4836-2015 OI Lang, Thomas/0000-0002-3720-8038; Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 38 TC 141 Z9 148 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JUL PY 2002 VL 26 IS 7 BP 984 EP 993 DI 10.1038/sj.ijo.0801968 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 565BK UT WOS:000176348100015 PM 12080454 ER PT J AU Huff, J AF Huff, J TI IARC monographs, industry influence, and upgrading, downgrading, and under-grading chemicals - A personal point of view SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE International Agency for Research on; Cancer; public health; worker health; scientific integrity; IARC monographs; carcinogenicity; industry; standards; primary prevention; National Toxicology Program ID INDUCED HEPATOCYTE PROLIFERATION; RISK ASSESSMENT; CARCINOGENESIS BIOASSAYS; LIVER CARCINOGENESIS; LABORATORY-ANIMALS; FIBROUS GLASS; CANCER; 1,3-BUTADIENE; MECHANISMS; EXPOSURE AB The first IARC Monographs Volume was distributed in 1972, and over the 23 years through 1993, under the leadership of Dr Lorenzo Tomatis, 59 IARC Monographs were completed. During 1977-1979 the author was privileged to lead the program for Volumes 15-22, and participated in the pioneering development of the LARC Preamble and Categories of Evidence. During this era other Chiefs of the IARC Monographs included Claus Agthe, Harri Vainio, Antero Aitio, and Julian Wilbourn. Since then (starting with Volume 62: 1995), a new attitude seems to have pervaded the IARC Monographs program, resulting in an increasing influence of or partiality for industry and a diminishing dedication to public and occupational health and safety concerns, and for primary prevention. Some of this attitude comes from an apparent misguided scientific zest prematurely to endorse purported or hypothetical mechanisms of chemical carcinogenesis or modes of action of chemicals causing cancer in experimental animals' These speculations are in turn used cavalierly to discount the value of experimental evidence for predicting probable carcinogenicity to humans. Most often this is accomplished by opining that the mechanism(s) of carcinogenicity in animals would not be operative in humans. End of explanation. Examples whereby the IARC has recently "down-graded" or "under-graded" the available evidence of carcinogenicity include: acrylonitrile; atrazine; benzidine-based dyes; 1,3-butadiene, dichloromethane (methylene chloride); di(2-ethylhexyl) phthalate; glass wool insulation, MtBE [methyl tertiary butyl ether]; ochratoxin A; saccharin; sunlamps and sunbeds (use of); trichloroethylene; sulfamethazine; and others more inclusively mentioned in the text and tables. Further impeding or compromising public health, chemicals causing site-specific cancers in animals attendant with calculi/precipitate in the urinary bladder, goiter and thyroid gland, kidney and alpha-2mu globulin, peroxisome proliferation and liver tumors, and cell proliferation in general have led the LARC to discount these carcinogenic effects. To stem this tide at the IARC, new leadership, with more objectivity mid public health perspective, is needed. C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 63 TC 46 Z9 46 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JUL-SEP PY 2002 VL 8 IS 3 BP 249 EP 270 PG 22 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 595DN UT WOS:000178091700010 PM 12358081 ER PT J AU Axelson, O Castleman, B Epstein, S Franco, G Giannasi, F Grandjean, P Greenberg, M Hooper, K Huff, J Jacobson, M Joshi, TK Kulkarni, GK LaDou, J Mazaheri, M Mekonnen, Y Melnick, R Mirabelli, D Ofrin, R Partanen, T Pott, F Sass, J Soskolne, CL Suplido, ML Terracini, B Tomatis, L Ungvary, G Watterson, A Wesseling, C Yassi, A AF Axelson, O Castleman, B Epstein, S Franco, G Giannasi, F Grandjean, P Greenberg, M Hooper, K Huff, J Jacobson, M Joshi, TK Kulkarni, GK LaDou, J Mazaheri, M Mekonnen, Y Melnick, R Mirabelli, D Ofrin, R Partanen, T Pott, F Sass, J Soskolne, CL Suplido, ML Terracini, B Tomatis, L Ungvary, G Watterson, A Wesseling, C Yassi, A TI Letter to Dr. Gro Harlem Brundtland, Director-General, WHO SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Letter C1 Linkoping Univ, Div Environm & Occupat Med, Linkoping, Sweden. Univ Illinois, Chicago, IL 60680 USA. Univ Modena, I-41100 Modena, Italy. Univ So Denmark, Odense, Denmark. Labor Inspectorate, Sao Paulo, Brazil. NIEHS, Bethesda, MD USA. Univ Tehran Med Sci, Dept Occupat Med, Tehran, Iran. Univ Addis Ababa, Addis Ababa, Ethiopia. San Giovanni Battista Hosp, Canc Epidemiol Unit, Turin, Italy. Univ Turin, Dept Biomed Sci & Human Oncol, I-10124 Turin, Italy. Univ Philippines, Open Univ, Fac Hlth Sci, Quezon City 1101, Philippines. Univ Dusseldorf, Dept Expt Hyg, D-4000 Dusseldorf, Germany. Univ Alberta, Dept Publ Hlth Sci, Edmonton, AB, Canada. NIOSH, Budapest, Hungary. Univ Stirling, Occupat & Environm Hlth Res Grp, Stirling FK9 4LA, Scotland. Occupat Hlth & Safety Agcy Healthcare, Vancouver, BC, Canada. RP Axelson, O (reprint author), Linkoping Univ, Div Environm & Occupat Med, Linkoping, Sweden. EM olav.axelson@ymk.liu.se; bcastle@bcpl.net; epstein@uic.edu; franco@unimo.it; giannasi@telnet.com.br; pgrand@health.sdu.dk; gillmorris.greenberg@btinternet.com; kim_hooper@hotmail.com; huffl@niehs.nih.gov; mjacobson@cspinet.org; joshitk@vsnl.com; GK.Kulkarni@kwa2.siemens.co.in; joeladou@aol.com; maria_mazaheri@yahoo.com; yalemtsehay@yahoo.com; melnickr@niehs.nih.gov; dario.mirabelli@cpo.it; timo_partanen@yahoo.com; 0217153853-0001@t-online.de; jsass@nrdc.org; colin.soskolne@ualberta.ca; mlsuplido@pacific.net.ph; terracini@etabeta.it; lomatis@hotmail.com; ncph@fjokk.hu; a.e.watterson@stir.ac.uk; cwesseli@una.ac.cr; annaleey@aol.com NR 4 TC 8 Z9 8 U1 0 U2 0 PU HAMILTON HARDY PUBL INC PI ATTLEBORO PA 8 N MAIN ST, STE 404A, ATTLEBORO, MA 02703 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JUL-SEP PY 2002 VL 8 IS 3 BP 271 EP 273 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 595DN UT WOS:000178091700011 PM 12358082 ER PT J AU Jacobson, MF Clapp, R Legator, M Lijinsky, W Reuber, MD Kleihues, P AF Jacobson, MF Clapp, R Legator, M Lijinsky, W Reuber, MD Kleihues, P TI Letter to Dr. Gro Harlem Brundtland, Director-General, WHO SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Letter C1 Boston Univ, Dept Environm Hlth, Boston, MA 02215 USA. Univ Texas, Med Branch, Div Environm Epidemiol, Galveston, TX 77550 USA. NCI, Chem Carcinogenesis Program, Frederick Canc Res Ctr, Frederick, MD 21701 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JUL-SEP PY 2002 VL 8 IS 3 BP 279 EP 280 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 595DN UT WOS:000178091700013 PM 12358084 ER PT J AU Melnick, RL AF Melnick, RL TI The IARC evaluation of di(2-ethylhexyl)phthalate (DEHP): A flawed decision based on an untested hypothesis SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTOR; ACYL-COA OXIDASE; PEROXISOME PROLIFERATORS; PPAR-ALPHA; RAT HEPATOCYTES; KUPFFER CELLS; DNA-SYNTHESIS; EXPRESSION; LIVER; MECHANISM C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Melnick, RL (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 24 TC 14 Z9 14 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JUL-SEP PY 2002 VL 8 IS 3 BP 284 EP 286 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 595DN UT WOS:000178091700015 PM 12358086 ER PT J AU Haxby, JV Gobbini, MI AF Haxby, JV Gobbini, MI TI Human neural systems for face perception and social communication SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 2002 VL 45 IS 1-2 BP 56 EP 57 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 578AP UT WOS:000177095500141 ER PT J AU Pietrini, P Furey, ML Ricciardi, E Gobbini, MI Guazzelli, M Haxby, JV AF Pietrini, P Furey, ML Ricciardi, E Gobbini, MI Guazzelli, M Haxby, JV TI Seeing with one's hands: Supramodal cortical organization of perception in the human brain revealed by fMRI SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NIMH, Bethesda, MD 20892 USA. Univ Pisa, I-56100 Pisa, Italy. 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 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 2002 VL 45 IS 1-2 BP 56 EP 56 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 578AP UT WOS:000177095500140 ER PT J AU Furey, ML AF Furey, ML TI Temporal features of selective visual attention SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIMH, NIH, Bethesda, MD 20892 USA. Univ Pisa, I-56100 Pisa, Italy. 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 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 2002 VL 45 IS 1-2 BP 57 EP 57 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 578AP UT WOS:000177095500142 ER PT J AU Misra, RR Hursting, SD Perkins, SN Sathyamoorthy, N Mirsalis, JC Riccio, ES Crowell, JA AF Misra, RR Hursting, SD Perkins, SN Sathyamoorthy, N Mirsalis, JC Riccio, ES Crowell, JA TI Genotoxicity and carcinogenicity studies of soy isoflavones SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE carcinogenicity; chemoprevention; genistein; genotoxicity; soy isoflavones ID HUMAN PROSTATE CARCINOMA; TOPOISOMERASE-II; IN-VITRO; SPONTANEOUS TUMORIGENESIS; GLAND DIFFERENTIATION; MAMMARY TUMORIGENESIS; GENISTEIN EXPOSURE; DIETARY GENISTEIN; MATERNAL EXPOSURE; INFANT LEUKEMIA AB The potential cancer preventive efficacy of soy isoflavones is being investigated in preclinical and phase 1 clinical studies sponsored by the U. S. National Cancer Institute. Although 90-day oral toxicity studies with PTI G-2535 (an investigational soy isoflavone drug product) in rats and dogs, as well as teratology studies, indicated no signs of toxicity, there remains a mechanistic concern associated with the ability of isoflavones (i.e., genistein) to inhibit topoisomerase, possibly leading to DNA strand breaks. The present report describes results from two in vitro genotoxicity studies, one in vivo genotoxicity study, and a single carcinogenicity study conducted in p53 knockout mice. Bacterial mutagenesis experiments using six tester strains without metabolic activation revealed no evidence that PTI G-2535 was mutagenic. In similar experiments with exogenous metabolic activation there were statistically significant increases in revertants, but less than twofold, in a single (Salmonella typhimurium TA100) tester strain. Mouse lymphoma cell mutagenesis experiments conducted with and without metabolic activation revealed statistically significant increases in mutation frequency at PTI G-2535 concentrations, 0.8 and 12 mug/ml, respectively; such increases were dose related and increases in the frequency of both small and large colonies were observed. A statistically significant increase in the frequency of micronucleated polychromatic erythrocytes was also seen 24 hours after treatment in male, but not female, mice who received 500 and 1000 mg/kg body weight PTI G-2535; however, such increases were small, were not dose related, and were not observed 48 hours after treatment. In contrast, dietary genistein had no effect on survival, weight gain, or the incidence or types of tumors that developed in cancer-prone rodents lacking the p53 tumor suppressor gene, p53 knockout mice. The apparent risk/benefit of isoflavone ingestion may ultimately depend on the dose and developmental timing of exposure. C1 NCI, Chemoprevent Agent Dev Res Grp, Div Canc Prevent, EPN 2117, Bethesda, MD 20892 USA. NCI, Off Prevent Oncol, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Basic Res Lab, Ctr Canc Res, Bethesda, MD 20892 USA. SRI Int, Menlo Pk, CA 94025 USA. RP Crowell, JA (reprint author), NCI, Chemoprevent Agent Dev Res Grp, Div Canc Prevent, EPN 2117, 6130 Execut Blvd, Bethesda, MD 20892 USA. NR 45 TC 19 Z9 21 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JUL PY 2002 VL 21 IS 4 BP 277 EP 285 DI 10.1080/10915810290096441 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 579HX UT WOS:000177173500003 PM 12171629 ER PT J AU Ham, DI Gentleman, S Chan, CC McDowell, JH Redmond, TM Gery, I AF Ham, DI Gentleman, S Chan, CC McDowell, JH Redmond, TM Gery, I TI RPE65 is highly uveitogenic in rats SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; MACULAR DEGENERATION; BINDING PROTEIN; MICROSOMAL PROTEIN; MESSENGER-RNA; LEWIS RATS; S-ANTIGEN; UVEITIS; DISEASE AB PURPOSE. To examine the hypothesis that RPE65, a protein specific to the retinal pigment epithelium, is uveitogenic in rats. METHODS. Rats of four inbred strains (Lewis, Brown Norway, Fischer, and SHR) were immunized with native or recombinant bovine RPE65, or with S-antigen (S-Ag), emulsified with complete Freund adjuvant, and treated simultaneously with killed Bordetella pertussis bacteria, as indicated. Development of ocular changes was examined and scored both clinically and histologically. RESULTS. Lewis rats immunized with RPE65 showed development of acute and severe inflammatory eye disease that affected most ocular tissues. The minimum uveitogenic dose of RPE65 was similar to that of S-Ag (1 mug per rat), but the changes induced by RPE65 at higher dose ranges were less severe than those induced by S-Ag. Concurrent treatment of the RPE65-immunized rats with B. Pertussis bacteria was not critical for disease induction, but enhanced dramatically the pathogenic reaction. Unlike the results with several other retinal proteins, no pinealitis was detected in rats immunized with RPE65. Fischer (F344) rats resembled Lewis rats in being similarly affected by RPE65 or S-Ag. In contrast, Brown Norway (W,T) rats developed severe disease when immunized with RPE65, but showed minimal changes in response to S-Ag. SHR rats responded poorly to disease induced by RPE65, and S-Ag-induced disease failed to develop. CONCLUSIONS. RPE65 is highly uveitogenic in rats, thus suggesting that this molecule could be involved in pathogenic autoimmunity in the human eye. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Dept Ophthalmol, Seoul, South Korea. Univ Florida, Dept Ophthalmol, Gainesville, FL USA. RP Gery, I (reprint author), NEI, Immunol Lab, NIH, Bldg 10,10 Ctr Dr,Room 10N112, Bethesda, MD 20892 USA. EM igery@helix.nih.gov OI Redmond, T. Michael/0000-0002-1813-5291 NR 38 TC 15 Z9 15 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2002 VL 43 IS 7 BP 2258 EP 2263 PG 6 WC Ophthalmology SC Ophthalmology GA 567JU UT WOS:000176482300030 PM 12091425 ER PT J AU Kondo, M Sieving, PA AF Kondo, M Sieving, PA TI Post-photoreceptoral activity dominates primate photopic 32-Hz ERG for sine-, square-, and pulsed stimuli SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID STATIONARY NIGHT BLINDNESS; HUMAN CONE ELECTRORETINOGRAM; FLICKER ELECTRORETINOGRAM; SINUSOIDAL EXCITATION; RETINITIS-PIGMENTOSA; ADAPTATION; MUTATIONS; AMPLITUDE; COMPONENT; NEURONS AB PURPOSE. To evaluate the relative contributions of photoreceptors and postphotoreceptoral activity to the primate 32-Hz flicker electroretinogram (ERG) elicited by sine-wave, square-wave, and pulse stlimuli. METHODS. Flicker 32-Hz ERGS were evoked from four adult rhesus (Macaca mulatta) monkeys using sine-wave, square-wave, and 4-ms pulse trains and xenon photostrobe flicker stimuli. All stimuli had time-averaged luminance of 2.11 log cd/m(2) and were presented on a 1.63-log cd/m(2) white background. Intravitreal injections of DL-2-amino-4-phosphonobutyric acid (APB) and cis-2,3-piperidinedicarboxylic acid (PDA) were given to block activity of ON- and OFF-bipolar cells, respectively. RESULTS. Flicker harmonic analysis showed that the fundamental frequency component provided nearly 75% of the sine-wave and square-wave ERGS versus 63% for 4-ms pulse stimuli and only 49% for strobe flicker. Strobe-flicker responses contained the greatest contribution from higher harmonic components. Removing the ON component with APB increased the fundamental component's amplitudes by more than 30% with sine-wave and square-wave ERGS but had a lesser effect on responses to 4-ms pulses and strobe flicker. When cone responses were isolated by synaptic blockade with APB+PDA, the fundamental component's amplitude was reduced to less than 20% of control for all four stimuli. Postsynaptic ON and OFF components were characterized by amplitude and phase vectors, and sine-wave and square-wave stimuli gave a large phase difference (138degrees) between ON and OFF components, which resulted in greater response self-cancellation than with the 4-ms pulse train (121degrees phase difference) or for strobe flicker (118degrees). CONCLUSIONS. The major decrease in flicker responses after photoreceptor synaptic blockade implicates a major contribution from postphotoreceptoral activity to the fundamental flicker component, regardless of the stimulus type. Sine-wave and square-wave stimuli produced larger phase differences between ON- and OFF-pathway components, thereby causing more complete self-cancellation of postphotoreceptoral contributions and revealing slightly greater relative contribution directly from cone photoreceptors with these stimuli than with pulsed stimuli. The direct cone contribution was always small, however, and the clinical point is that 32-Hz flicker ERG amplitudes do not provide an unambiguous assessment of direct cone photoreceptor contribution with any of these stimuli. C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. Nagoya Univ, Sch Med, Dept Ophthalmol, Nagoya, Aichi 466, Japan. RP Sieving, PA (reprint author), NEI, NIH, Bldg 31,Room 6A03,31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY07003, R01-EY06094] NR 29 TC 36 Z9 37 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2002 VL 43 IS 7 BP 2500 EP 2507 PG 8 WC Ophthalmology SC Ophthalmology GA 567JU UT WOS:000176482300061 PM 12091456 ER PT J AU Stadtman, ER AF Stadtman, ER TI How I became a biochemist SO IUBMB LIFE LA English DT Biographical-Item C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2140,50 South Dr,MSC 8012, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD JUL PY 2002 VL 54 IS 1 BP 39 EP 40 DI 10.1080/15216540290106477 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 594YG UT WOS:000178079600009 PM 12387575 ER PT J AU Semaan, S Des Jarlais, DC Sogolow, E Johnson, WD Hedges, LV Ramirez, G Flores, SA Norman, L Sweat, MD Needle, R AF Semaan, S Des Jarlais, DC Sogolow, E Johnson, WD Hedges, LV Ramirez, G Flores, SA Norman, L Sweat, MD Needle, R TI A meta-analysis of the effect of HIV prevention interventions on the sex behaviors of drug users in the United States SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 13th International AIDS Conference CY JUL 09-14, 2000 CL DURBAN, SOUTH AFRICA DE HIV infection; AIDS; HIV risk behavior; sex behavior; injection drug users; drug users; substance abuse; meta-analysis ID HIGH-RISK POPULATIONS; CRACK COCAINE USE; INJECTION-DRUG; CONDOM USE; AIDS EDUCATION; PRELIMINARY OUTCOMES; NATIONAL SAMPLE; ABUSE TREATMENT; WOMEN; REDUCTION AB We examined the effectiveness of 33 U.S.-based HIV intervention studies in reducing the sexual risk behaviors of drug users by reducing unprotected sex or increasing the use of male condoms. The studies, identified as of June 1998, through the HIV/AIDS Prevention Research Synthesis project, were published in 1988 or later, measured behavioral or biologic outcomes, used experimental designs or certain quasi-experimental designs, and reported sufficient data for calculating an effect size for sexual risk reduction. Of the 33 studies, 94% recruited injection drug users; 21% recruited crack users. The mean age of participants was 36 years. Almost all studies were randomized (94%), provided another HIV intervention to the comparison groups (91%), and evaluated behavioral interventions (91%). On average, interventions were conducted in 5 sessions (total, 10 hours) during 4.5 months. Interventions compared with no interventions were strong and significant (k = 3; odds ratio [OR], 0.60; 95% confidence interval [CI], 0.43-0.85). Interventions compared with other HIV interventions showed a modest additional benefit (k = 30; OR, 0.91; 95% CI, 0.81-1.03). When we extrapolated our result (an OR of 0.60) to a population with a 72% prevalence of risk behavior, the proportion of drug users who reduced their risk behaviors was 12.6% greater in the intervention groups than in the comparison groups. Our meta-analysis shows that interventions can lead to sexual risk reduction among drug users and justifies providing interventions to drug users. Developing interventions with stronger effects to further reduce sexual risk behaviors among drug users must remain a high priority. C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. Univ Chicago, Dept Educ, Chicago, IL 60637 USA. Univ Chicago, Dept Psychol, Chicago, IL 60637 USA. Univ Chicago, Dept Sociol, Chicago, IL 60637 USA. Univ Chicago, Harris Grad Sch Publ Policy Studies, Chicago, IL 60637 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. Univ W Indies, Kingston 7, Jamaica. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21218 USA. NIDA, Rockville, MD USA. RP Semaan, S (reprint author), Ctr Dis Control & Prevent, Mail Stop E-02,1600 Clifton Rd, Atlanta, GA 30333 USA. EM ssemaan@cdc.gov NR 106 TC 100 Z9 103 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD JUL 1 PY 2002 VL 30 SU 1 BP S73 EP S93 DI 10.1097/01.QAI.0000017613.32101.90 PG 21 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 577AH UT WOS:000177039000008 ER PT J AU Post, RM Leverich, GS Fergus, E Miller, R Luckenbaugh, D AF Post, RM Leverich, GS Fergus, E Miller, R Luckenbaugh, D TI Parental attitudes towards early intervention in children at high risk for affective disorders SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; mania; childhood; early intervention ID BIPOLAR AFFECTIVE-DISORDER; MAJOR AFFECTIVE-DISORDER; ONSET; MANIA; AGE; PSYCHOSIS; CHILDHOOD; FAMILY AB Background: Parents volunteered to complete surveys on attitudes toward treatment intervention in children at a theoretically high (20-30%) or very high (70%) risk for affective disorders because of an assumed uni-lineal or bi-lineal family history of bipolar illness. Methods: Questions focused on examining at what ages and stage of symptom and syndrome evolution parents would wish their child to begin treatment with different types of therapeutic approaches and clinical trial designs. Sixty percent of the respondents had a personal history of unipolar or bipolar affective disorders. Results: In 156 completed surveys, 83% of parents favored acute medication intervention and 67% favored long-term medication treatment for those children at very high risk at or before the development of severe symptoms (i.e. even prior to meeting full diagnostic thresholds). On the average, parents indicated that they would enter their child in a trial of: two types of psychotherapy at a point in illness evolution between moderate and severe symptoms, two types of open medications between severe symptoms and a definite diagnosis, two blind medications at a definite diagnosis, and a blind trial of placebo and medication after a definite diagnosis but before multiple recurrences of the illness. Parents, primarily on the basis of perceived safety, would allow their children to use medications that have been found to be effective in adults. Limitations: In addition to a number of methodological limitations, responders to the survey were self-selected. Conclusions: The results indicate a willingness on the part of most parents to treat a child at high risk for affective illness early in the course of symptom evolution, even prior to a full syndromic illness or diagnosis. This and other parental views of the risk-benefit and ethical dimensions of early intervention may be helpful in the initiation and design of studies aimed at assessing the efficacy of early interventions in childhood-onset bipolar illness and its prodromes. (C) 2002 Elsevier Science BY All rights reserved. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Rm 3S239,10 Ctr Dr,MSC-1272, Bethesda, MD 20892 USA. NR 28 TC 7 Z9 7 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUL PY 2002 VL 70 IS 2 BP 117 EP 124 AR PII S0165-0327(01)00299-3 DI 10.1016/S0165-0327(01)00299-3 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 580FC UT WOS:000177223600002 PM 12117623 ER PT J AU Rotrosen, D Matthews, JB Bluestone, JA AF Rotrosen, D Matthews, JB Bluestone, JA TI The immune tolerance network: A new paradigm for developing tolerance-inducing therapies SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE immune tolerance; costimulation; anergy; autoimmunity; transplantation; asthma; allergy ID DONOR BONE-MARROW; RENAL-ALLOGRAFT REJECTION; ANTIGEN-PRESENTING CELLS; TRANSPLANTATION TOLERANCE; PHASE-I; CHIMERISM; IMMUNOSUPPRESSION; IMMUNOTHERAPY; PROLIFERATION; MECHANISMS AB Immune tolerance therapies are designed to reprogram immune cells in a highly specific fashion to eliminate pathogenic responses while preserving protective immunity. A concept that has tantalized immunologists for decades, the development of tolerance-inducing therapies, would revolutionize the management of a wide range of chronic and often debilitating diseases by obviating the need for lifelong immunosuppressive regimens. The advances of the past decade have provided a more detailed understanding of the molecular events associated with T-cell recognition and activation. Building on these advances, immunologists have demonstrated the feasibility of various tolerance-inducing approaches in small- and large-animal models of autoimmunity, allergy, and transplant graft rejection. Unprecedented opportunities to test these approaches in a variety of human diseases have now emerged. To capitalize on these advances, the National Institutes of Health recently established the Immune Tolerance Network (ITN), an international consortium of more than 70 basic and clinical immunologists dedicated to the evaluation of novel tolerance-inducing therapies and associated studies of immunologic mechanisms. By using a unique interactive approach to accelerate the development of clinical tolerance therapies, the ITN is partnering with the biotechnology and pharmaceutical industries to examine innovative tolerogenic approaches in a range of allergic and autoimmune diseases and to prevent graft rejection after transplantation. Two years since its inception, the ITN now has approximately 2 dozen clinical trials or tolerance assays studies ongoing or in later stages of protocol development. This report summarizes the rationale for emphasizing clinical research on immune tolerance and highlights the progress of the ITN. C1 Univ Calif San Francisco, Dept Med, Immune Tolerance Network, San Francisco, CA USA. NIAID, Bethesda, MD 20892 USA. RP Rotrosen, D (reprint author), 6700-B Rockledge Dr,Room 5142,MSC 7640, Bethesda, MD 20817 USA. NR 29 TC 23 Z9 23 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2002 VL 110 IS 1 BP 17 EP 23 DI 10.1067/mai.2002.124258 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 574CF UT WOS:000176870300002 PM 12110811 ER PT J AU Luccioli, S Brody, DT Hasan, S Keane-Myers, A Prussin, C Metcalfe, DD AF Luccioli, S Brody, DT Hasan, S Keane-Myers, A Prussin, C Metcalfe, DD TI IgE(+), Kit(-), I-A/I-E- myeloid cells are the initial source of IL-4 after antigen challenge in a mouse model of allergic pulmonary inflammation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE mast cells; basophils; asthma; IL-4; IgE; Fc receptors ID EOSINOPHILIC AIRWAY INFLAMMATION; CD4(+) T-CELLS; FC-EPSILON-RI; MURINE MODEL; MAST-CELLS; SCHISTOSOMA-MANSONI; PERIPHERAL-BLOOD; DEFICIENT MICE; ASTHMA; INTERLEUKIN-4 AB Background: IL-4 is generated within hours after antigen lung challenge and influences events that take place early in the induction of pulmonary inflammation. However, the cells responsible for this early IL-4 production in the lung are unknown. Objectives: We sought to characterize the initial inflammatory events in the lung after antigen challenge and to identify cells responsible for producing 11-4 at early time points. Methods: Mice were sensitized with ovalbumin or passive IgE and challenged intranasally. Histologic measures of inflammation were used, and lung tissue cytokine production was analyzed by means of RT-PCR. Cells producing IL-4 were characterized by means of in situ hybridization and flow cytometry. Results: IL-4 mRNA was detectable 100 minutes after challenge in sensitized animals. Blockade of this early IL-4 down-regulated vascular cell adhesion molecule I mRNA expression and attenuated the early recruitment of eusinophils to the lung. CD4-depleted and mast cell-deficient mice both expressed early IL-4. Cellular analysis revealed the presence of IL-4 protein at 100 minutes exclusively in IgE myeloid cells that did not express CD3, Kit, or I-AA-E. Moreover, IL-4 production induced by means of passive IgE sensitization and abrogated in FcR gamma-chain-deficient mice supports the conclusion that this IL-4 production is dependent on IgE/gamma-chain interaction. Conclusion: IL-4 production by an IgE/gamma-chain-dependent mechanism occurs rapidly after allergen challenge. At these early time points, IL-4 is produced by a myeloid cell with the characteristics of a mouse basophil (IgE(+), Kit(-), I-A/I-E-). These data thus suggest that strategies targeting basophils should be considered in the treatment of early lung inflammation. C1 NIAID, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. RP Luccioli, S (reprint author), NIAID, Lab Allerg Dis, NIH, Twinbrook 2,Room 203,12441 Parklawn Dr, Rockville, MD 20852 USA. OI Prussin, Calman/0000-0002-3917-3326 NR 44 TC 36 Z9 36 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2002 VL 110 IS 1 BP 117 EP 124 DI 10.1067/mai.2002.125828 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 574CF UT WOS:000176870300022 PM 12110830 ER PT J AU Rosenkrands, I Slayden, RA Crawford, J Aagaard, C Barry, BE Andersen, P AF Rosenkrands, I Slayden, RA Crawford, J Aagaard, C Barry, BE Andersen, P TI Hypoxic response of Mycobacterium tuberculosis studied by metabolic labeling and proteome analysis of cellular and extracellular proteins SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ALPHA-CRYSTALLIN; CULTURE FILTRATE; BOVIS BCG; ALANINE DEHYDROGENASE; IDENTIFICATION; MACROPHAGES; GROWTH; EXPRESSION; GENOMICS; DORMANCY AB The events involved in the establishment of a latent infection with Mycobacterium tuberculosis are not fully understood, but hypoxic conditions are generally believed to be the environment encountered by the pathogen in the central part of the granuloma. The present study was undertaken to provide insight into M. tuberculosis protein expression in in vitro latency models where oxygen is depleted. The response of M. tuberculosis to low-oxygen conditions was investigated in both cellular and extracellular proteins by metabolic labeling, two-dimensional electrophoresis, and protein signature peptide analysis by liquid chromatography-mass spectrometry. By peptide mass fingerprinting and immunodetection, five proteins more abundant under low-oxygen conditions were identified from several lysates of M. tuberculosis: Rv0569, Rv2031c (HspX), Rv2623, Rv2626c, and Rv3841 (BfrB). In M. tuberculosis culture filtrates, two additional proteins, Rv0363c (Fba) and Rv2780 (Aid), were found in increased amounts under oxygen limitation. These results extend our understanding; of the hypoxic response in M. tuberculosis and potentially provide important insights into the physiology of the latent bacilli. C1 Statens Serum Inst, Dept TB Immunol, DK-2300 Copenhagen S, Denmark. MDS Protana, Odense, Denmark. NIAID, TB Res Sect, Rockville, MD USA. RP Rosenkrands, I (reprint author), Statens Serum Inst, Dept TB Immunol, 5 Artillerivej, DK-2300 Copenhagen S, Denmark. RI Slayden, Richard/O-8626-2016 OI Slayden, Richard/0000-0001-6857-7277 FU Intramural NIH HHS [Z01 AI000783-11] NR 31 TC 111 Z9 133 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2002 VL 184 IS 13 BP 3485 EP 3491 DI 10.1128/JB.184.13.3485-3491.2002 PG 7 WC Microbiology SC Microbiology GA 563CQ UT WOS:000176237400009 PM 12057942 ER PT J AU Pande, S Makela, A Dove, SL Nickels, BE Hochschild, A Hinton, DM AF Pande, S Makela, A Dove, SL Nickels, BE Hochschild, A Hinton, DM TI The bacteriophage T4 transcription activator MotA interacts with the far-C-terminal region of the sigma(70) subunit of Escherichia coli RNA polymerase SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; MIDDLE PROMOTER; ASIA PROTEIN; PROKARYOTIC TRANSCRIPTION; SIGMA-70 SUBUNIT; GENE-EXPRESSION; BINDING-PROTEIN; DNA; RECOGNITION; CONTACTS AB Transcription from bacteriophage T4 middle promoters uses Escherichia coli RNA polymerase together with the T4 transcriptional activator MotA and the T4 coactivator AsiA. AsiA binds tightly within the C-terminal portion of the sigma(70) subunit of RNA polymerase, while MotA binds to the 9-bp MotA box motif, which is centered at -30, and also interacts with sigma(70). We show here that the N-terminal half of MotA (MotA(NTD)), which is thought to include the activation domain, interacts with the C-terminal region of sigma(70) in an E. coli two-hybrid assay. Replacement of the C-terminal 17 residues of sigma(70) with comparable sigma(38) residues abolishes the interaction with MotA(NTD) in this assay, as does the introduction of the amino acid substitution R608C. Furthermore, in vitro transcription experiments indicate that a polymerase reconstituted with a sigma(70) that lacks C-terminal amino acids 604 to 613 or 608 to 613 is defective for MotA-dependent activation. We also show that a proteolyzed fragment of MotA that contains the C-terminal half (MotA(CTD)) binds DNA with a K-D(app) that is similar to that of full-length MotA. Our results support a model for MotA-dependent activation in which protein-protein contact between DNA-bound MotA and the far-C-terminal region of sigma(70) helps to substitute functionally for an interaction between sigma(70) and a promoter -35 element. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Hinton, DM (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, Bldg 8,Room 2A-13, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM44025, R01 GM044025] NR 63 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2002 VL 184 IS 14 BP 3957 EP 3964 DI 10.1128/JB.184.14.3957-3964.2002 PG 8 WC Microbiology SC Microbiology GA 569CH UT WOS:000176582200024 PM 12081968 ER PT J AU Chernomordik, V Hattery, DW Gannot, I Zaccanti, G Gandjbakhche, A AF Chernomordik, V Hattery, DW Gannot, I Zaccanti, G Gandjbakhche, A TI Analytical calculation of the mean time spent by photons inside an absorptive inclusion embedded in a highly scattering medium SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE optical imaging; photon migration; time of flight; differential absorption ID RESOLVED TRANSILLUMINATION EXPERIMENTS; ABNORMALITIES; MEDICINE; CONTRAST; DOMAIN; MODEL AB The mean time spent by photons inside a nonlocalized optically abnormal embedded inclusion has been derived analytically. The accuracy of the results has been tested against Monte Carlo and experimental data. We show that for quantification of the absorption coefficient of absorptive inclusions, a corrective factor that takes into account the size of the inclusion is needed. This finding suggests that perturbation methods derived for very small inclusions which are used in inverse algorithms require a corrective factor to adequately quantify the differential absorption coefficient of nonlocalized targets embedded in optically turbid media. (C) 2002 Society of Photo-Optical Instrumentation Engineers. C1 NICHD, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Fac Engn, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. Univ Florence, I-50019 Florence, Italy. INFM, Dipartimento Fis, I-50019 Florence, Italy. RP Chernomordik, V (reprint author), NICHD, NIH, Bldg 12A,Rm 2041,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 14 TC 6 Z9 6 U1 0 U2 1 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL PY 2002 VL 7 IS 3 BP 486 EP 492 DI 10.1117/1.1481900 PG 7 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 584RR UT WOS:000177482700027 PM 12175301 ER PT J AU Marriott, SJ Lemoine, FJ Jeang, KT AF Marriott, SJ Lemoine, FJ Jeang, KT TI Damaged DNA and miscounted chromosomes: Human T cell leukemia virus type I tax oncoprotein and genetic lesions in transformed cells SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Review DE HTLV-1; tax; transformation; genome stability ID TRANSACTIVATION FUNCTION; GENOMIC INSTABILITY; MITOTIC CHECKPOINT; HUMAN CANCERS; P53; PROTEIN; HTLV-1; REPAIR; MODEL; LYMPHOMA AB Genetic instability is a recurring theme in human cancers. Although the molecular mechanisms mediating this effect commonly observed in transformed cells are not completely understood, it has been proposed to involve either the loss of DNA repair capabilities or the loss of chromosomal stability. The transforming retrovirus human T cell leukemia virus type I (HTLV-I) encodes a viral oncoprotein Tax, which is believed to cause the genomic instability characteristic of HTLV-I-infected cells. This review focuses on the ability of HTLV-I Tax to disrupt the cellular processes of DNA repair and chromosomal segregation. The consequences of these effects as well as the evolutionary advantage this may provide to HTLV-I are discussed. Copyright (C) 2002 National Science Council, ROC and S. KargerAG, Basel. C1 Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Program Cell & Mol Biol, Houston, TX 77030 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Marriott, SJ (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, 1 Baylor Plaza, Houston, TX 77030 USA. RI Jeang, Kuan-Teh/A-2424-2008 FU NCI NIH HHS [CA-55684, CA-77371] NR 72 TC 43 Z9 43 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD JUL-AUG PY 2002 VL 9 IS 4 BP 292 EP 298 DI 10.1159/000064998 PG 7 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 577MH UT WOS:000177064300001 PM 12145525 ER PT J AU Chen, GJ Jeng, CH Lin, SZ Tsai, SH Wang, Y Chiang, YH AF Chen, GJ Jeng, CH Lin, SZ Tsai, SH Wang, Y Chiang, YH TI Fetal striatal transplants restore electrophysiological sensitivity to dopamine in the lesioned striatum of rats with experimental Huntington's disease SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE Huntington's disease; neural transplantation; dopamine; regeneration; electrophysiology; striatum ID QUINOLINIC ACID LESIONS; CAUDATE-PUTAMEN; GRAFTS; NEURONS; RECEPTORS; TISSUE; MODEL; D1; LOCALIZATION; INCREASE AB Dopamine (DA), a major neurotransmitter used in the striatum, is involved in movement disorders such as Parkinson's disease and Huntington's chorea. With the loss of neurons in the striatum of patients with Huntington's disease (HID), there is an associated downregulation of DA receptors, which may alter DA-mediated responses. In the present study, DA-mediated electrophysiological depression was studied in animals with quinolinic acid (QA)-induced experimental HD. QA was directly applied to the right striatum of adult female Sprague-Dawley rats. Animals receiving QA developed ipsilateral rotation after the application of apomorphine. Fetal striatal tissue transplants grafted 1 month after lesioning attenuated apomorphine-induced rotation. Six months after lesioning, the animals were anesthetized with urethane for electrophysiological study. DA, applied directly to neurons by pressure microejection, inhibited spontaneous single-unit activity in the striatal neurons of nonlesioned, lesioned and lesioned/grafted rats. QA lesioning reduced responses to DA in the striatal neurons. The dose of DA required to inhibit striatal neuron activity in the lesioned rats was significantly increased compared to that in the nonlesioned rats. Transplantation of fetal striatal tissue restored the electrophysiological sensitivity to DA in the lesioned striatum. The dose of DA used to suppress striatal neuron activity was reduced after grafting. Immunohistostaining showed survival of gamma-aminobutyric acid neurons at the graft site. Tyrosine hydroxylase-positive terminals were found innervating the striatal grafts. In conclusion, our data demonstrate that fetal striatal transplants restore electrophysiological sensitivity to DA in the lesioned striatum of animals with experimental HD. Copyright (C) 2002 National Science Council, ROC and S. Karger AG, Basel. C1 Natl Def Med Ctr, Tri Serv Gen Hosp, Dept Neurol Surg, Taipei 114, Taiwan. Natl Def Med Ctr, Dept Pharmacol, Taipei 114, Taiwan. Taipei Med Univ, Inst Injury Prevent & Control, Taipei, Taiwan. NIDA, Baltimore, MD USA. RP Chiang, YH (reprint author), Natl Def Med Ctr, Tri Serv Gen Hosp, Dept Neurol Surg, 325 Cheng Kung Rd,Sec 2, Taipei 114, Taiwan. NR 29 TC 17 Z9 18 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD JUL-AUG PY 2002 VL 9 IS 4 BP 303 EP 310 PG 8 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 577MH UT WOS:000177064300003 PM 12145527 ER PT J AU Schwieters, CD Clore, GM AF Schwieters, CD Clore, GM TI Reweighted atomic densities to represent ensembles of NMR structures SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article ID 3-DIMENSIONAL STRUCTURES; MOLECULAR-DYNAMICS; NUCLEIC-ACIDS; PROTEINS; SPECTROSCOPY; GEOMETRY; VMD AB A reweighted atomic probability density is introduced as a means of representing ensembles of NMR structures in a simple, concise and informative manner. This density is shown to give a better visual representation of molecular structure information than an unweighted density, and should provide a useful interactive graphics tool during the course of iterative NMR structure refinement. The approach is illustrated using several examples. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIH, Computat Biosci & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Schwieters, CD (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 16 TC 57 Z9 58 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JUL PY 2002 VL 23 IS 3 BP 221 EP 225 DI 10.1023/A:1019875223132 PG 5 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 586MD UT WOS:000177587000006 PM 12238594 ER PT J AU Corsi, A Xu, T Chen, XD Boyde, A Liang, J Mankani, M Sommer, B Iozzo, RV Eichstetter, I Robey, PG Bianco, P Young, MF AF Corsi, A Xu, T Chen, XD Boyde, A Liang, J Mankani, M Sommer, B Iozzo, RV Eichstetter, I Robey, PG Bianco, P Young, MF TI Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers-Danlos-like changes in bone and other connective tissues SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE decorin; biglycan; collagen fibrils; double-knockout; Ehlers-Danlos ID MEAN ATOMIC-NUMBER; FIBRILLOGENESIS INVITRO; SKIN FRAGILITY; CORE PROTEIN; I COLLAGEN; PROTEOGLYCANS; LUMICAN; FIBROMODULIN; BIOSYNTHESIS; FIBROBLASTS AB Decorin (dcn) and biglycan (bgn), two members of the family of small leucine-rich proteoglycans (SLRPs), are the predominant proteoglycans expressed in skin and bone, respectively. Targeted disruption of the dcn gene results in skin laxity and fragility, whereas disruption of the bgn gene results in reduced skeletal growth and bone mass leading to generalized osteopenia, particularly in older animals. Here, we report that bgn deficiency leads to structural abnormality in collagen fibrils in bone, dermis, and tendon, and to a "subclinical" cutaneous phenotype with thinning of the dermis but without overt skin fragility. A comparative ultrastructural study of different tissues from bgn- and dcn-deficient mice revealed that bgn and dcn deficiency have similar effects on collagen fibril structure in the dermis but not in bone. Ultrastructural and phenotypic analysis of newly generated bgn/dcn double-knockout (KO) mice revealed that the effects of dcn and bgn deficiency are additive in the dermis and synergistic in bone. Severe skin fragility and marked osteopenia characterize the phenotype of double-KO animals in which progeroid changes are observed also in the skin. Ultrastructural analysis of bone collagen fibrils in bone of double-KO mice reveals a complete loss of the basic fibril geometry with the emergence of marked "serrated fibril" morphology. The phenotype of the double-KO animal mimics directly the rare progeroid variant of human Ehlers-Danlos syndrome (EDS), in which skin fragility, progeroid changes in the skin (reduced hypodermis), and osteopenia concur as a result of impaired glycosaminoglycan (GAG) linking to bgn and dcn core proteins. Our data show that changes in collagen fibril morphology reminiscent of those occurring in the varied spectrum of human EDS are induced by both bgn deficiency and dcn deficiency in mice. The effects of an individual SLRP deficiency are tissue specific, and the expression of a gross phenotype depends on multiple variables including level of expression of individual SLRPs in different tissues and synergisms between different SLRPs (and likely other macromolecules) in determining matrix structure and functional properties. C1 NICSD, Craniofacial & Skeletal Dis Branch, Mol Biol Bones & Teeth Unit, NIH, Bethesda, MD 20892 USA. Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. UCL, Dept Anat & Dev Biol, London WC1E 6BT, England. Thomas Jefferson Univ, Jefferson Med Coll, Dept Path Anat & Cell Biol, Philadelphia, PA 19107 USA. Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00185 Rome, Italy. RP Young, MF (reprint author), NICSD, Craniofacial & Skeletal Dis Branch, Mol Biol Bones & Teeth Unit, NIH, Bldg 30,Room 225,MSC 4320, Bethesda, MD 20892 USA. RI CAI, RONG/I-7095-2013; Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; Iozzo, Renato/0000-0002-5908-5112 NR 41 TC 218 Z9 224 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 2002 VL 17 IS 7 BP 1180 EP 1189 DI 10.1359/jbmr.2002.17.7.1180 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 566KL UT WOS:000176427200007 PM 12102052 ER PT J AU Xing, LP Bushnell, TP Carlson, L Tai, ZX Tondravi, M Siebenlist, U Young, F Boyce, BF AF Xing, LP Bushnell, TP Carlson, L Tai, ZX Tondravi, M Siebenlist, U Young, F Boyce, BF TI NF-kappa B p50 and p52 expression is not required for RANK-expressing osteoclast progenitor formation but is essential for RANK- and cytokine-mediated osteoclastogenesis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE NF-kappa B; osteoclast; RANKL; RANK ID DIFFERENTIATION FACTOR; TRANSCRIPTION FACTOR; BONE-RESORPTION; TNF-ALPHA; IN-VIVO; OSTEOPROTEGERIN LIGAND; ESTROGEN DEFICIENCY; MATURE OSTEOCLASTS; APOPTOSIS; RECEPTOR AB Expression of RANKL by stromal cells and of RANK and both NF-kappaB p50 and p52 by osteoclast precursors is essential for osteoclast formation. To examine further the role of RANKL, RANK, and NF-kappaB signaling in this process, we used NF-kappaB p50(-/-);p52(-/-) double knockout (dKO) and wild-type (WT) mice. Osteoclasts formed in cocultures of WT osteoblasts with splenocytes from WT mice but not from dKO mice, a finding unchanged by addition of RANKL and macrophage colony-stimulating factor (M-CSF). NF-kappaB dKO splenocytes formed more colony-forming unit granulocyte macrophage (CFU-GM) colonies than WT cells, but no osteoclasts were formed from dKO CFU-GM colonies. RANKL increased the number of CFU-GM colonies twofold in WT cultures but not in dKO cultures. Fluorescence-activated cell sorting (FACS) analysis of splenocytes from NF-kappaB dKO mice revealed a two-to threefold increase in the percentage of CD11b (Mac-1) and RANK double-positive cells compared with WT controls. Treatment of NF-kappaB dKO splenocytes with interleukin (IL)-1, TNF-alpha, M-CSF, GM-CSF, and IL-6 plus soluble IL-6 receptor did not rescue the osteoclast defect. No increase in apoptosis was observed in cells of the osteoclast lineage in NF-kappaB dKO or p50(-/-);p52(+/-) (3/4KO) mice. Thus, NF-kappaB p50 and p52 expression is not required for formation of RANK-expressing osteoclast progenitors but is essential for RANK-expressing osteoclast precursors to differentiate into TRAP(+) osteoclasts in response to RANKL and other osteoclastogenic cytokines. C1 Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA. Univ Rochester, Med Ctr, Dept Hematol Oncol, Rochester, NY 14642 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Bethesda, MD USA. RP Boyce, BF (reprint author), Univ Rochester, Med Ctr, Dept Pathol & Lab Med, 601 Elmwood Ave,Box 626, Rochester, NY 14642 USA. FU NIAMS NIH HHS [AR 43510] NR 52 TC 98 Z9 106 U1 2 U2 6 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 2002 VL 17 IS 7 BP 1200 EP 1210 DI 10.1359/jbmr.2002.17.7.1200 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 566KL UT WOS:000176427200009 PM 12096833 ER PT J AU Young, MF AF Young, MF TI Small leucine rich proteoglycans: Essential for the structure and function of mineralized tissue SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 2002 VL 17 IS 7 MA IS9 BP 1321 EP 1321 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 566KL UT WOS:000176427200030 ER PT J AU Martindale, JL Holbrook, NJ AF Martindale, JL Holbrook, NJ TI Cellular response to oxidative stress: Signaling for suicide and survival SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; EPIDERMAL GROWTH-FACTOR; HEAT-SHOCK-PROTEIN; PEROXIDE-INDUCED APOPTOSIS; PHOSPHOLIPASE C-GAMMA; MANGANESE SUPEROXIDE-DISMUTASE; TUMOR-SUPPRESSOR P53; HYDROGEN-PEROXIDE; ATAXIA-TELANGIECTASIA AB Reactive oxygen species (ROS), whether produced endogenously as a consequence of normal cell functions or derived from external sources, pose a constant threat to cells living in an aerobic environment as they can result in severe damage to DNA, protein, and lipids. The importance of oxidative damage to the pathogenesis of many diseases as well as to degenerative processes of aging has becoming increasingly apparent over the past few years. Cells contain a number of antioxidant defenses to minimize fluctuations in ROS, but ROS generation often exceeds the cell's antioxidant capacity, resulting in a condition termed oxidative stress. Host survival depends upon the ability of cells and tissues to adapt to or resist the stress, and repair or remove damaged molecules or cells. Numerous stress response mechanisms have evolved for these purposes, and they are rapidly activated in response to oxidative insults. Some of the pathways are preferentially linked to enhanced survival, while others are more frequently associated with cell death. Still others have been implicated in both extremes depending on the particular circumstances. In this review, we discuss the various signaling pathways known to be activated in response to oxidative stress in mammalian cells, the mechanisms leading to their activation, and their roles in influencing cell survival. These pathways constitute important avenues for therapeutic interventions aimed at limiting oxidative damage or attenuating its sequelae. Published 2002 Wiley-Liss, Inc. C1 Yale Univ, Sch Med, Dept Internal Med, Sect Geriatr, New Haven, CT 06520 USA. NIA, Cellular & Mol Biol Lab, Cell Stress & Aging Sect, Baltimore, MD 21224 USA. RP Holbrook, NJ (reprint author), Yale Univ, Sch Med, Dept Internal Med, Sect Geriatr, 333 Cedar St,POB 208309, New Haven, CT 06520 USA. RI Bell, Tiffany/F-4403-2010 NR 209 TC 1269 Z9 1330 U1 32 U2 190 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 2002 VL 192 IS 1 BP 1 EP 15 DI 10.1002/jcp.10119 PG 15 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 559NJ UT WOS:000176032000001 PM 12115731 ER PT J AU Charmandari, E Eisenhofer, G Mehlinger, SL Carlson, A Wesley, R Keil, MF Chrousos, GP New, MI Merke, DP AF Charmandari, E Eisenhofer, G Mehlinger, SL Carlson, A Wesley, R Keil, MF Chrousos, GP New, MI Merke, DP TI Adrenomedullary function may predict phenotype and genotype in classic 21-hydroxylase deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CONGENITAL ADRENAL-HYPERPLASIA; GENE CONVERSION; STEROID 21-HYDROXYLATION; DISEASE MANIFESTATION; LIQUID-CHROMATOGRAPHY; MOLECULAR GENOTYPE; CYCLIC-AMP; EXPRESSION; MUTATIONS; CATECHOLAMINES AB Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by decreased synthesis of glucocorticoids and mineralocorticoids, adrenal hyperandrogenism, and impaired development and function of the adrenal medulla. Although genotype can usually predict phenotype, genotype-phenotype discordance has been described. We investigated the association between adrenomedullary function, disease severity, and genotype in 37 children [22 males and 15 females; age range, 4.7-14.9 yr; 28 salt-wasting (SW) and 9 simple virilizing (SV) CAH] with classic 21-hydroxylase deficiency. Plasma and 24-h urinary catecholamines and their metabolites, and the 21-hydroxylase genotype were determined in all patients. The disease-causing mutations were divided into 4 groups (Null, A, B, and C) according to in vitro 21-hydroxylase activity as previously described. Genotype groups Null (n = 9) and A (n = 15) were predicted to result in SW CAH, group B (n = 8) was predicted to have the SV phenotype, and group C (n = 1) was predicted to have nonclassic CAH. A fifth group, D (n = 4), included patients in whom mutations were detected in only 1 allele. Plasma total metanephrine (420.1 +/- 60.0 vs. 657.7 +/- 67.8 pg/ml; P = 0.04) and free metanephrine (13.4 +/- 1.7 vs. 24.0 +/- 4.1 pg/ml; P = 0.008) concentrations were significantly lower in children with SW CAH than in those with the SV form of the disease. Plasma free metanephrine concentrations best predicted phenotype, with accuracy similar to that of genotype. Concordance rates between genotype and phenotype were higher in the most severely affected patients (Null, 88.9%; A, 93.3%; B, 75%; plasma free metanephrine, <18.5 pg/ml: SW, 92%). The plasma free metanephrine concentration correlated with the expected 21-hydroxylase activity based on genotype, and there was a significant trend for free metanephrine concentrations across the three genotype groups (P < 0.0001). Our findings indicate that measurement of adrenomedullary function, best assessed by the free metanephrine concentration, is a useful biomarker of disease severity in 21-hydroxylase deficiency. Molecular genotype and plasma free metanephrine concentration predict phenotype with similar accuracy. Both methods are more accurate in the most severe forms of the disease. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Cornell Univ, Med Ctr, Presbyterian Hosp, Dept Pediat, New York, NY 10021 USA. RP Charmandari, E (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RI Charmandari, Evangelia/B-6701-2011 NR 49 TC 32 Z9 32 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2002 VL 87 IS 7 BP 3031 EP 3037 DI 10.1210/jc.87.7.3031 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 578GU UT WOS:000177109700006 PM 12107196 ER PT J AU Oral, EA Ruiz, E Andewelt, A Sebring, N Wagner, AJ Depaoli, AM Gorden, P AF Oral, EA Ruiz, E Andewelt, A Sebring, N Wagner, AJ Depaoli, AM Gorden, P TI Effect of leptin replacement on pituitary hormone regulation in patients with severe lipodystrophy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FAMILIAL PARTIAL LIPODYSTROPHY; POLYCYSTIC-OVARY-SYNDROME; ADIPOSE-TISSUE; ONSET; DEFICIENCY; MUTATION; PUBERTY; HUMANS; DYSFUNCTION; PATTERN AB Leptin is important in regulating energy homeostasis. Severe lipodystrophy is associated with leptin deficiency and insulin resistance, hypertriglyceridemia, and hepatic steatosis. Leptin deficiency is also associated with abnormalities of the pituitary hormones in rodent models and patients with congenital absence of leptin. We inquired whether similar abnormalities are seen in patients with lipodystrophy and whether replacement of leptin will make an impact on the regulation of pituitary hormones. Seven female patients (aged 15-42 yr, all diabetic) with lipodystrophy and serum leptin levels less than 4 mg/liter were treated with recombinant methionyl-human leptin (recombinant leptin) in physiological doses in an open-labeled study. The following parameters were evaluated before and at 4 months of leptin treatment: menstrual history, pelvic ultrasonogram, LHRH, TRH, and CRH tests. While on recombinant leptin, mean serum leptin concentration increased from 1.3 +/- 0.3 mg/liter to 11.1 +/- 2.5 mg/liter. Only one of five patients who had intact reproductive systems was cycling normally before leptin therapy, and all five had normal menses by the fourth month of leptin therapy. Serum E2 concentrations increased (110 +/- 44 pmol/liter vs. 546 +/- 247 pmolAiter, P = 0.002), serum T concentrations decreased (3.5 +/- 3.0 nmol/liter vs. 1.3 +/- 0.7 nmol/liter, P = 0.055), and the attenuated LH response to LHRH was corrected with therapy. Serum T(3) and free T(4) were in the normal range before leptin therapy and did not change. However, serum TSH concentrations fell from 2.2 +/- 1.1 muU/ml to 1.2 +/- 0.7 muU/ml (P < 0.001). The percent increase in TSH following TRH administration was similar before (560%) and at 4 months (580%) of leptin therapy. The mean nonstimulated ACTH and cortisol concentrations were, respectively, 6.0 +/- 3.4 pmoL/liter and 680 +/- 280 nmol/liter before leptin and did not change after 4 months of therapy (4.2 +/- 1.2 pmol/liter, P = 0.11 and 453 142 nmolAiter, P = 0.13, respectively). The ACTH and cortisol responses to CRH stimulation were normal both before and after therapy. Leptin replacement improved menstrual abnormalities and low E2 levels and corrected the attenuated LH response to LHRH in a group of young women with lipodystrophy and leptin deficiency. These results add to the growing body of evidence that metabolic signals such as leptin play a role in neuroendocrine regulation. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Gorden, P (reprint author), NIDDKD, Diabet Branch, NIH, Bldg 10,Room 8S235A, Bethesda, MD 20892 USA. EM phillip_gorden@nih.gov OI Oral, Elif/0000-0002-9171-1144 NR 28 TC 71 Z9 77 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2002 VL 87 IS 7 BP 3110 EP 3117 DI 10.1210/jc.87.7.3110 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 578GU UT WOS:000177109700020 PM 12107209 ER PT J AU Charmandari, E Calis, KA Keil, MF Mohassel, MR Remaley, A Merke, DP AF Charmandari, E Calis, KA Keil, MF Mohassel, MR Remaley, A Merke, DP TI Flutamide decreases cortisol clearance in patients with congenital adrenal hyperplasia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID 21-HYDROXYLASE DEFICIENCY; METABOLISM AB Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency is characterized by a defect in cortisol and aldosterone secretion and adrenal hyperandrogenism. Current treatment is to provide adequate glucocorticoid and mineralocorticoid substitution to prevent adrenal crises and to suppress excess adrenal androgen secretion. Satisfactory adrenocorticaI suppression often requires supraphysiological doses of hydrocortisone, which may produce an unacceptable degree of hypercortisolism. A new four-drug treatment regimen of flutamide, testolactone, reduced hydrocortisone dose, and 9alpha-fludrocortisone has been shown to achieve normal growth and development after 2 yr of therapy and may, therefore, represent a potential alternative approach to the treatment of children with classic congenital adrenal hyperplasia. We investigated the effect of flutamide and testolactone, and flutamide alone, on cortisol clearance by performing clearance studies twice in 13 children (6 males and 7 females; age range, 7.0-14.5 yr) with classic 21-hydroxylase deficiency. All studies were conducted at least 3 months after institution of the four-drug treatment regimen. In eight patients (group 1), the first cortisol clearance study was performed on the four-drug regimen, and the second study was performed after a 48-h washout period off flutamide and testolactone. In five patients (group 2), the first study was conducted 1 wk after discontinuation of testolactone and while patients were receiving flutamide, hydrocortisone and 9alpha-fludrocortisone, and the second study was performed after a 48-h washout period off flutamide. Oral hydrocortisone was held on the day of the clearance studies, and all patients received a continuous infusion of hydrocortisone (0.6 mg/m(2.)h) from 1800 h to 0200 h, with cortisol concentrations measured once hourly. In addition, an in vitro study was conducted to exclude the possibility of an analytical interference of flutamide, 2-hydroxyflutamide, and testolactone with the serum cortisol immunoassay. Total body cortisol clearance was significantly lower during treatment with the four-drug regimen than during treatment with hydrocortisone and 9a-fludrocortisone (153.5 +/- 26.8 vs.355.4 +/- 65.8 ml/min; P = 0.001). Similar results were obtained comparing flutamide, hydrocortisone, and 9alpha-fludrocortisone therapy to hydrocortisone and 9a-fludrocortisone therapy (155.8 +/- 26.5 vs. 281.8 +/- 96.2 ml/min; P = 0.037). The in vitro study indicated that an interference with the serum cortisol immunoassay was unlikely. These findings indicate that the addition of flutamide and testolactone to the treatment regimen of hydrocortisone and 9a-fludrocortisone decreases cortisol clearance in patients with classic 21-hydroxylase deficiency, and this effect seems to be due to flutamide. Glucocorticoid replacement doses should be reduced when flutamide is added to the treatment regimen of patients receiving hydrocortisone. C1 NICHHD, Pediat & Reproduct Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. RP Charmandari, E (reprint author), NICHHD, Pediat & Reproduct Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Suite 9D42, Bethesda, MD 20892 USA. RI Charmandari, Evangelia/B-6701-2011 NR 19 TC 7 Z9 7 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2002 VL 87 IS 7 BP 3197 EP 3200 DI 10.1210/jc.87.7.3197 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 578GU UT WOS:000177109700033 PM 12107224 ER PT J AU Mihailescu, D Shore-Freedman, E Mukani, S Lubin, J Ron, E Schneider, AB AF Mihailescu, D Shore-Freedman, E Mukani, S Lubin, J Ron, E Schneider, AB TI Multiple neoplasms in an irradiated cohort: Pattern of occurrence and relationship to thyroid cancer outcome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DOSE-RESPONSE RELATIONSHIPS; RADIATION; CARCINOMA; CHILDHOOD; CHILDREN; HEAD; NECK; SUSCEPTIBILITY; ADOLESCENTS; ACCIDENT AB We have examined the pattern of four radiation-related neo-plasms in a radiation-exposed cohort of 2795 patients. They had received conventional radiation treatments for benign conditions in the head and neck area when they were children. At the end of follow-up, 350 thyroid cancers, 108 benign and malignant salivary tumors, 87 neural tumors, and 70 cases of hyperparathyroidism had occurred. In 492 individuals (17.6% of the cohort), there were single tumors, and in 60 individuals (2.1%, there were multiple tumors. Because this was an apparent excess of multiple tumors, we tested the hypothesis that the excess arose, at least in part, from variation in radiation susceptibility in the cohort. To analyze this, we developed a method to account for differences in length of follow-up and known risk factors, such as age at radiation exposure, radiation dose, and gender. This analysis showed that the excess concordance of neoplasms could be explained by known risk factors, thereby suggesting that susceptibility factors did not play a role in the development of multiple tumors. Of the 350 thyroid cancers, 50 occurred in subjects with other radiation-related neoplasms. Therefore, we tested an additional hypothesis, that the presence of these other neoplasms was related to the clinical behavior of the thyroid cancer. Using thyroid cancer recurrence as the end point, we did not observe a relationship with the presence of other neo-plasms. In summary, we demonstrated an excess of concordance of radiation-related neoplasms that could be explained by known risk factors, and we found that thyroid cancer behavior was not related to the occurrence of multiple tumors. C1 Univ Illinois, Coll Med, Sect Endocrinol & Metab, Chicago, IL 60612 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Schneider, AB (reprint author), Univ Illinois, Coll Med, Sect Endocrinol & Metab, 1819 W Polk St,MC 640, Chicago, IL 60612 USA. EM abschnei@uic.edu OI Shore-Freedman, Eileen/0000-0001-6194-1814 FU NCI NIH HHS [R01 CA 21518]; NCRR NIH HHS [M01 RR 13987] NR 20 TC 19 Z9 21 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2002 VL 87 IS 7 BP 3236 EP 3241 DI 10.1210/jc.87.7.3236 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 578GU UT WOS:000177109700039 PM 12107231 ER PT J AU Yoshida, A Taniguchi, S Hisatome, I Royaux, IE Green, ED Kohn, LD Suzuki, K AF Yoshida, A Taniguchi, S Hisatome, I Royaux, IE Green, ED Kohn, LD Suzuki, K TI Pendrin is an iodide-specific apical porter responsible for iodide efflux from thyroid cells SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FRTL-5 CELLS; SYNDROME GENE; FOLLICULAR THYROGLOBULIN; EXPRESSION; PDS; SYMPORTER; TRANSPORT; CHANNEL; TRANSCRIPTION; TISSUES AB The Pendred syndrome gene encodes a 780-amino acid putative transmembrane protein (pendrin) that is expressed in the apical membrane of thyroid follicular cells. Although pendrin was shown to transport iodide and chloride using Xenopus laevis oocytes and Sf9 insect cells, there is no report using mammalian cells to study its role in thyroid function. We show here, using COS-7 cells and Chinese hamster ovary cells transfected with expression vectors encoding sodium iodide symporter or human Pendred syndrome gene cDNA and by comparison with studies using rat thyroid FRTL-5 cells, that pendrin is an iodide-specific transporter in mammalian cells and is responsible for iodide efflux in the thyroid. C1 Tottori Univ, Fac Med, Dept Internal Med 1, Yonago, Tottori 6838504, Japan. NIDDKD, NIH, Genome Technol Branch, NHGRI, Bethesda, MD 20892 USA. NIDDKD, NIH, Cell Regulat Sect, Metab Dis Branch, Bethesda, MD 20892 USA. Ohio Univ, Sch Osteopath Med, Athens, OH 45701 USA. Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA. Natl Inst Infect Dis, Dept Microbiol, Leprosy Res Ctr, Tokyo 1890002, Japan. RP Yoshida, A (reprint author), Tottori Univ, Fac Med, Dept Internal Med 1, Nishimachi 36-1, Yonago, Tottori 6838504, Japan. EM ayoshida@bronzc.ocn.ne.jp NR 33 TC 94 Z9 99 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2002 VL 87 IS 7 BP 3356 EP 3361 DI 10.1210/jc.87.7.3356 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 578GU UT WOS:000177109700057 PM 12107249 ER PT J AU Patel, JN Coppack, SW Goldstein, DS Miles, JM Eisenhofer, G AF Patel, JN Coppack, SW Goldstein, DS Miles, JM Eisenhofer, G TI Norepinephrine spillover from human adipose tissue before and after a 72-hour fast SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SHORT-TERM; IN-VIVO; LIPOLYSIS; INSULIN; METABOLISM; SUPPRESSION; STARVATION; GLYCEROL; KINETICS; TURNOVER AB Adipose tissue lipolysis is at least in part stimulated by the sympathetic nervous system (SNS). Although there is a generalized decrease in SNS activity with fasting, the rate of lipolysis during fasting increases. The aim of this study was to determine whether there is an association between activation of sympathetic nerves innervating adipose tissue and the increase in lipolysis seen during fasting in humans. We used the isotope dilution technique to measure regional norepinephrine spillover from abdominal se adipose tissue from seven healthy subjects before and after a 72-h fast. Our results showed a significant increase in adipose tissue spillover of norepinephrine (mean +/- SEM, 0.40 +/- 0.09 vs. 1.08 +/- 0.18 pmol (.)100 g(-1.)min(-1), P < 0.05) and arterial norepinephrine concentrations (0.92 +/- 0.10 vs. 1.23 +/- 0.08 nmol-liter(-1), P < 0.05) after the fast with no significant change in total body norepinephrine spillover, forearm norepinephrine spillover, epinephrine concentrations, or energy expenditure. We show for the first time, in humans, a selective regional increase in adipose tissue norepinephrine spillover in response to a 72-h fast and suggest that the SNS may play a greater role in the regulation of lipid metabolism during fasting than previously thought. C1 Natl Inst Neurol Disorders & Stroke, NIH, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. St Bartholomews & Royal London Sch Med, London E1 1BB, England. Mayo Clin, Endocrine Res Unit, Rochester, MN 55905 USA. RP Coppack, SW (reprint author), Royal London Hosp, Dept Diabet & Metab Med, 5th Floor Alexandra Wing, London E1 1BB, England. EM s.w.coppack@mds.qmw.ac.uk FU NIDDK NIH HHS [DK 38092] NR 34 TC 27 Z9 27 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2002 VL 87 IS 7 BP 3373 EP 3377 DI 10.1210/jc.87.7.3373 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 578GU UT WOS:000177109700060 PM 12107252 ER PT J AU Murphy, BR Collins, PL AF Murphy, BR Collins, PL TI Live-attenuated virus vaccines for respiratory syncytial and parainfluenza viruses: applications of reverse genetics SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CANDIDATE VACCINE; HEMAGGLUTININ-NEURAMINIDASE; TEMPERATURE SENSITIVITY; TYPE-3 VACCINE; SUBGROUP-A; GLYCOPROTEINS; MUTATIONS; CHILDREN; PROTEIN; INFANTS C1 NIAID, Resp Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Murphy, BR (reprint author), NIAID, Resp Viruses Sect, Infect Dis Lab, NIH, Bldg 50,Room 6517,50 South Dr MSC 8007, Bethesda, MD 20892 USA. NR 35 TC 57 Z9 59 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2002 VL 110 IS 1 BP 21 EP 27 DI 10.1172/JCI200216077 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 570NV UT WOS:000176665100004 PM 12093883 ER PT J AU Qi, ZH Hao, CM Langenbach, RI Breyer, RM Redha, R Morrow, JD Breyer, MD AF Qi, ZH Hao, CM Langenbach, RI Breyer, RM Redha, R Morrow, JD Breyer, MD TI Opposite effects of cyclooxygenase-1 and-2 activity on the pressor response to angiotensin II SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INTRARENAL BLOOD-FLOW; PROSTAGLANDIN E-2; ARACHIDONIC-ACID; MACULA DENSA; PULMONARY-HYPERTENSION; SELECTIVE-INHIBITION; INTERSTITIAL-CELLS; RENIN SECRETION; GENE DISRUPTION; MESSENGER-RNA AB Therapeutic use of cyclooxygenase-inhibiting (COX-inhibiting) nonsteroidal antiinflammatory drugs (NSAIDs) is often complicated by renal side effects including hypertension and edema. The present studies were undertaken to elucidate the roles of COX 1 and COX2 in regulating blood pressure and renal function. COX2 inhibitors or gene knockout dramatically augment the pressor effect of angiotensin II (Ang II). Unexpectedly, after a brief increase, the pressor effect of Ang II was abolished by COX1 deficiency (either inhibitor or knockout). Ang II infusion also reduced medullary blood flow in COX2-deficient but not in control or COX1-deficient animals, suggesting synthesis of COX2-dependent vasodilators in the renal medulla. Consistent with this, Ang II failed to stimulate renal medullary prostaglandin E2 and prostaglandin I-2 production in COX2-deficient animals. Ang II infusion normally promotes natriuresis and diuresis, but COX2 deficiency blocked this effect. Thus, COX1 and COX2 exert opposite effects on systemic blood pressure and renal function. COX2 inhibitors reduce renal medullary blood flow, decrease urine flow, and enhance the pressor effect of Ang II. In contrast, the pressor effect of Ang II is blunted by COX 1 inhibition. These results suggest that, rather than having similar cardiovascular effects, the activities of COX 1 and COX2 are functionally antagonistic. C1 Vet Adm Med Ctr, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Med, Div Nephrol, Nashville, TN 37212 USA. NIEHS, Lab Expt Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37212 USA. RP Breyer, MD (reprint author), Vet Adm Med Ctr, F-427 ACRE Bldg, Nashville, TN 37212 USA. FU NCI NIH HHS [CA 77839, P01 CA077839]; NIDDK NIH HHS [R01 DK048831, DK 48831, R01 DK037097, R01-DK-37097]; NIGMS NIH HHS [GM 15431, P01 GM015431, P50 GM015431] NR 66 TC 170 Z9 174 U1 1 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2002 VL 110 IS 1 BP 61 EP 69 DI 10.1172/JCI200214752 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 570NV UT WOS:000176665100010 PM 12093889 ER PT J AU Leppla, SH Robbins, JB Schneerson, R Shiloach, J AF Leppla, SH Robbins, JB Schneerson, R Shiloach, J TI Development of an improved vaccine for anthrax SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TOXIN PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; LETHAL FACTOR; INHALATIONAL ANTHRAX; PLASMID; ANTIBODIES; CHALLENGE; VIRULENCE; EFFICACY; BINDING C1 NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. RP Leppla, SH (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 303,30 Convent Dr, Bethesda, MD 20892 USA. NR 34 TC 86 Z9 91 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2002 VL 110 IS 2 BP 141 EP 144 DI 10.1172/JCI200216204 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 574DF UT WOS:000176872600001 PM 12122102 ER PT J AU Chizhikov, V Wagner, M Ivshina, A Hoshino, Y Kapikian, AZ Chumakov, K AF Chizhikov, V Wagner, M Ivshina, A Hoshino, Y Kapikian, AZ Chumakov, K TI Detection and genotyping of human group A rotaviruses by oligonucleotide microarray hybridization SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; DNA; EXPRESSION; MICROCHIPS; IDENTIFICATION; IMMOBILIZATION; SEROTYPES; SEQUENCE; ARRAYS; GEL AB A rapid and reliable method for the identification of five clinically relevant G genotypes (G1 to G4 and G9) of human rotaviruses based on oligonucleotide microarray hybridization has been developed. The genotype-specific oligonucleotides immobilized on the surface of glass slides were selected to bind to the multiple target regions within the VP7 gene that are highly conserved among individual rotavirus genotypes. Rotavirus cDNA was amplified in a PCR with primers common to all group A rotaviruses. A second round of nested PCR amplification was performed in the presence of indodicarbocyanine-dCTP and another pair of degenerate primers also broadly specific for all genotypes. The use of one primer containing 5'-biotin allowed us to prepare fluorescently labeled single-stranded hybridization probe by binding of another strand to magnetic beads. The identification of rotavirus genotype was based on hybridization with several individual genotype-specific oligonucleotides. This approach combines the high sensitivity of PCR with the selectivity of DNA-DNA hybridization. The specificity of oligonucleotide microchip hybridization was evaluated by testing 20 coded rotavirus isolates from different geographic areas for which genotypes were previously determined by conventional methods. Analysis of the coded specimens showed that this microarray-based method is capable of unambiguous identification of all rotavirus strains. Because of the presence of random mutations, each individual virus isolate produced a unique hybridization pattern capable of distinguishing different isolates of the same genotype and, therefore, subgenotype differentiation. This strain information indicates one of several advantages that microarray technology has over conventional PCR techniques. C1 US FDA, Ctr Biol Evaluat & Res, Lab Method Dev, Kensington, MD 20895 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Chizhikov, V (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Method Dev, HFM-470,1401 Rockville Pike, Rockville, MD 20852 USA. NR 26 TC 137 Z9 164 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2002 VL 40 IS 7 BP 2398 EP 2407 DI 10.1128/JCM.40.7.2398-2407.2002 PG 10 WC Microbiology SC Microbiology GA 569MH UT WOS:000176605800014 PM 12089254 ER PT J AU Marques, AR Martin, DS Philipp, MT AF Marques, AR Martin, DS Philipp, MT TI Evaluation of the C6 peptide enzyme-linked immunosorbent assay for individuals vaccinated with the recombinant OspA vaccine SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IMMUNODOMINANT CONSERVED REGION; BORRELIA-BURGDORFERI VLSE; LYME-DISEASE; INVARIABLE REGION; SERODIAGNOSIS; DISCRIMINATION AB The C6 enzyme-linked immunosorbent assay (ELISA), based on a peptide (C6) that reproduces the sequence of invariable region 6 of VlsE, the antigenic variation protein of Borrelia burgdorferi, has been shown to be a sensitive and specific test for the serologic diagnosis of Lyme disease. We now report that none of 29 uninfected individuals vaccinated with the recombinant OspA vaccine had an antibody response to the C6 peptide. The C6 peptide ELISA can be used to diagnose Lyme disease in patients who have received the OspA vaccine. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, Tulane Reg Primate Res Ctr, Covington, LA USA. RP Marques, AR (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. FU NCRR NIH HHS [P51 RR000164, RR00164] NR 16 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2002 VL 40 IS 7 BP 2591 EP 2593 DI 10.1128/JCM.40.7.2591-2593.2002 PG 3 WC Microbiology SC Microbiology GA 569MH UT WOS:000176605800041 PM 12089281 ER PT J AU Xu, M Chan, Y Fischer, SH Remaley, AT AF Xu, M Chan, Y Fischer, SH Remaley, AT TI Improvement of AMPLICOR human immunodeficiency virus type 1 viral load test (version 1.5) by addition of a coprecipitant during the RNA isolation step SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PCR AB The effect of the addition of a coprecipitant during the RNA isolation step on the analytical performance of the COBAS AMPLICOR human immunodeficiency virus type 1 (HIV-1) Monitor (version 1.5; Roche) viral load test was tested. Thirty-six specimens including patient samples, positive control samples, and negative control samples were processed in the presence and absence of the Pellet Paint coprecipitant. Specimens processed without the coprecipitant had lower RNA yields, as evidenced by a lower signal for the quantitation standard (QS). In addition, the results for all samples processed with the coprecipitant were acceptable on the basis of the optical density (ODreading for the QS, whereas the result for one specimen processed without the coprecipitant was unacceptable on the basis of the OD reading for the QS, which required the assay to be repeated. Furthermore, the use of the coprecipitant improved the overall precision of the assay. C1 NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Remaley, AT (reprint author), NIH, Dept Lab Med, Bldg 10,Rm 2C-433,10 Ctr Dr, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2002 VL 40 IS 7 BP 2616 EP 2617 DI 10.1128/JCM.40.7.2616-2617.2002 PG 2 WC Microbiology SC Microbiology GA 569MH UT WOS:000176605800048 PM 12089288 ER PT J AU Tanaka, H Wakisaka, A Ogasa, H Kawai, S Liang, CT AF Tanaka, H Wakisaka, A Ogasa, H Kawai, S Liang, CT TI Effect of IGF-I and PDGF administered in vivo on the expression of osteoblast-related genes in old rats SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; BONE-FORMATION; MESSENGER-RNA; ALKALINE-PHOSPHATASE; COLLAGEN-SYNTHESIS; CELL REPLICATION; FACTOR-BETA; PROTEINS; HORMONE; DNA AB In order to establish the cellular basis for using growth factors as possible therapeutic agents for the age-dependent deficit in bone formation activity, we examined the individual and combined effects of IGF-I and/or platelet-derived growth factor (PDGF) on the gene expression of osteoblast-related markers in male rats. The expression of osteoblast markers was examined in the femurs of adult and old rats following marrow ablation, which amplifies gene expression activity. The mRNA levels of collagen(alpha1) (I) (COLI), alkaline phosphatase (AP), osteopontin (OP) and osteocalcin (OC) were significantly lower in the old as compared with the adult rats. To determine whether growth factors can abolish the age-related deficits in mRNA expression in old bone, PDGF and/or IGF-I were infused directly into the right femur for 5 days following marrow ablation. The contralateral femur was infused with vehicle only and used as a control. PDGF stimulated the expression of OP mRNA in both adult and old rats, whereas COLI, AP and OC mRNAs were not affected. IGF-I infusion did not have a significant effect on mRNA expression in adult rats. In contrast, treatment with IGF-I significantly enhanced the mRNA levels of COLI, AP and OP in old rats. To examine whether the combination of both factors could affect the expression of osteoblast markers synergistically, PDGF and IGF-I were infused together. In adult bones, the combined treatment with PDGF and IGF-I caused a slight increase in the level of OP gene expression but no change in AP, OC or COLI genes. Although neither IGF-I nor PDGF alone was effective in stimulating the expression of OC, the combined treatment in old bones enhanced OC expression significantly. The expression of COLI, AP and OP was also stimulated, but the stimulation was no different from that of IGF-I alone. In PDGF plus IGF-I treatment with a high dose, no dose-response effects were observed. Within the limits of the present study, it is suggested that IGF-I and, to a much lesser extent, PDGF may partially restore the deficit in the expression of osteoblast markers in old bones, and that the combination of both factors is slightly better than IGF-I alone in stimulating OC expression. C1 Yamaguchi Univ, Sch Med, Dept Orthoped Surg, Yamaguchi 7558505, Japan. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Natl Hlth Res Inst, Taipei 115, Taiwan. RP Tanaka, H (reprint author), Yamaguchi Univ, Sch Med, Dept Orthoped Surg, 1-1-1 Minamikogushi, Yamaguchi 7558505, Japan. NR 35 TC 34 Z9 40 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JUL PY 2002 VL 174 IS 1 AR UNSP 0022-0795/02/0174-063 DI 10.1677/joe.0.1740063 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 575LU UT WOS:000176948400008 PM 12098664 ER PT J AU Wang, SL Banno, Y Nozawa, Y AF Wang, SL Banno, Y Nozawa, Y TI Two forms of membrane-bound sphingosine kinase in Tetrahymena and activity changes during growth and the cell cycle SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE cell proliferation; sphingosine kinase; sphingosine-1-phosphate; synchronous cell division ID AIRWAY SMOOTH-MUSCLE; MOLECULAR-CLONING; FUNCTIONAL-CHARACTERIZATION; LYSOPHOSPHATIDIC ACID; DEPENDENT EXPRESSION; SIGNAL-TRANSDUCTION; G-PROTEIN; SPHINGOSINE-1-PHOSPHATE; 1-PHOSPHATE; RECEPTOR AB Sphingosine kinase is responsible for the formation of sphingosine-l-phosphate, a sphingolipid mediator with important roles in numerous physiological processes. The sphingosine kinase activity of Tetrahymena pyriformis was recovered predominantly in the particulate fraction and it could be solubilised in 1% beta-octylglucoside. Anion-exchange chromatography resolved the beta-octylglucoside-solubilised sphingosine kinase activity into two peaks corresponding to proteins of Mr 140,000 and 80,000 respectively, as determined by subsequent size exclusion chromatography on Superdex 200. N,N-dimethylsphingosine did not inhibit the sphingosine kinase activity in either fraction, whereas D,L-threo-dihydrosphingosine inhibited sphingosine phosphorylation by the Mr 80,000 kinase but had no effect on the Mr 140,000 kinase activity. The activities also showed different stimulatory responses to Triton X-100 or NaCl. Overall, the results suggest the existence in Tetrahymena of two distinct membrane-associated sphingosine kinases. The kinase activity determined at the different culture stages showed a transient elevation at the mid-logarithmic phase. Further, the sphingosine kinase activity was examined during the synchronous cell division induced by cyclic heat treatments in T. pyriformis. We report for the first time that the sphingosine kinase activity greatly increased at 30 to 45 min after the end of heat treatment prior to the synchronous cell division (75 min), suggesting that the activity changes were associated with the cell cycle and that the up-regulated sphingosine kinase activity would be required for the initiation of the oncoming synchronous cell division in Tetrahymena cells. C1 Gifu Univ, Sch Med, Dept Biochem, Gifu 5008705, Japan. Gifu Int Inst Biotechnol, Kanigun 5050116, Japan. Inst Appl Biochem, Kanigun 5050116, Japan. RP Nozawa, Y (reprint author), NCI, Basic Res Lab, Canc Res Ctr, Bldg 37,Room 2D05, Bethesda, MD 20892 USA. NR 48 TC 5 Z9 5 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD JUL-AUG PY 2002 VL 49 IS 4 BP 305 EP 311 DI 10.1111/j.1550-7408.2002.tb00374.x PG 7 WC Microbiology SC Microbiology GA 584GA UT WOS:000177457800006 PM 12188220 ER PT J AU Hoelzel, AR Fleischer, RC Campagna, C Le Boeuf, BJ Alvord, G AF Hoelzel, AR Fleischer, RC Campagna, C Le Boeuf, BJ Alvord, G TI Impact of a population bottleneck on symmetry and genetic diversity in the northern elephant seal SO JOURNAL OF EVOLUTIONARY BIOLOGY LA English DT Article DE bottleneck; fluctuating asymmetry; genetic diversity; marine mammal ID FLUCTUATING ASYMMETRY; VARIABILITY; GHOST; MICE AB The northern elephant seal (NES) suffered a severe population bottleneck towards the end of the nineteenth century. Theoretical expectations for the impact of population bottlenecks include the loss of genetic diversity and a loss of fitness (e.g. through a disruption of developmental stability); however, there are few direct demonstrations in natural populations. Here, we report on the comparison of archive samples collected prior to and following the NES population bottleneck. Measures of genetic diversity show a loss of variation consistent with expectations and suggest a strong disruption in the pattern of allele frequencies following the bottleneck. Measures of bilateral characters show an increase in fluctuating asymmetry. C1 Univ Durham, Dept Biol Sci, Durham DH1 3LE, England. Smithsonian Inst, Natl Zool Pk, Dept Zool Res, Washington, DC 20008 USA. Consejo Nacl Invest Cient & Tecn, Ctr Nacl Patagonico, RA-9120 Puerto Madryn, Chubut, Argentina. Univ Calif Santa Cruz, Dept Biol, Santa Cruz, CA 95064 USA. NCI, Data Management Serv Inc, FCRDC, Frederick, MD 21702 USA. RP Hoelzel, AR (reprint author), Univ Durham, Dept Biol Sci, South Rd, Durham DH1 3LE, England. OI Campagna, Claudio/0000-0002-7971-5062 NR 51 TC 66 Z9 68 U1 4 U2 52 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1010-061X J9 J EVOLUTION BIOL JI J. Evol. Biol. PD JUL PY 2002 VL 15 IS 4 BP 567 EP 575 DI 10.1046/j.1420-9101.2002.00419.x PG 9 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 564NE UT WOS:000176319800008 ER PT J AU Breier, JI Gray, LC Fletcher, JM Foorman, B Klaas, P AF Breier, JI Gray, LC Fletcher, JM Foorman, B Klaas, P TI Perception of speech and nonspeech stimuli by children with and without reading disability and attention deficit hyperactivity disorder SO JOURNAL OF EXPERIMENTAL CHILD PSYCHOLOGY LA English DT Article DE dyslexia; attention deficit hyperactivity disorder; speech perception; phonetics ID VARIABLE-DIFFERENCE MODEL; SHORT-TERM-MEMORY; DEVELOPMENTAL APHASIA; DYSLEXIC-CHILDREN; DEFICIT/HYPERACTIVITY DISORDER; PHONOLOGICAL AWARENESS; LANGUAGE IMPAIRMENT; PROCESSING DEFICITS; AUDITORY-PERCEPTION; CAUSAL CONNECTION AB The auditory temporal deficit hypothesis predicts that children with reading disability (RD) will exhibit deficits in the perception of speech and nonspeech acoustic stimuli in discrimination and temporal ordering tasks when the interstimulus interval (ISI) is short, Initial studies testing this hypothesis did not account for the potential presence of attention deficit hyperactivity disorder (ADHD). Temporal order judgment and discrimination tasks were administered to children with (1) RD/no-ADHD (n = 38), (2) ADHD (n = 29) (3) RD and ADHD (RD/ADHD: n = 32), and (4) no impairment (NI: n 43). Contrary to predictions, children with RD showed no specific sensitivity to ISI and performed worse relative to children without RD on speech but not nonspeech tasks. Relationships between perceptual tasks and phonological processing measures were stronger and more consistent for speech than nonspeech stimuli. These results were independent of the presence of ADHD and suggest that children with RD have a deficit in phoneme perception that correlates with reading and phonological processing ability. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Neurosurg, Vivian L Smith Ctr Neurol Res, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Dept Otolaryngol, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Dept Pediat, Houston, TX 77030 USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. Med Illness Counselling Ctr, Bethesda, MD USA. RP Breier, JI (reprint author), Univ Texas, Hlth Sci Ctr, Dept Neurosurg, Vivian L Smith Ctr Neurol Res, Houston, TX 77030 USA. FU NICHD NIH HHS [R01 HD35938] NR 77 TC 40 Z9 42 U1 8 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-0965 J9 J EXP CHILD PSYCHOL JI J. Exp. Child Psychol. PD JUL PY 2002 VL 82 IS 3 BP 226 EP 250 AR PII S0022-0965(02)00005-X DI 10.1016/S0022-0965(02)00005-X PG 25 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 572ME UT WOS:000176777900003 PM 12093108 ER PT J AU Yasuda, T Tezuka, T Maeda, A Inazu, T Yamanashi, Y Gu, H Kurosaki, T Yamamoto, T AF Yasuda, T Tezuka, T Maeda, A Inazu, T Yamanashi, Y Gu, H Kurosaki, T Yamamoto, T TI Cbl-b positively regulates Btk-mediated activation of phospholipase C-gamma 2 in B cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE BCR; Cbl family; calcium; GEMs; adaptor protein ID RECEPTOR SIGNAL-TRANSDUCTION; PROTEIN-TYROSINE KINASES; ANTIGEN RECEPTOR; C-CBL; NEGATIVE REGULATOR; BINDING-PROTEIN; LIPID RAFTS; T-CELLS; PHOSPHORYLATION; BLNK AB Genetic studies have revealed that Cbl-b plays a negative role in the antigen receptor-mediated proliferation of lymphocytes. However, we show that Cbl-b-deficient DT40 B cells display reduced phospholipase C (PLC)-gamma2 activation and Ca2+ mobilization upon B cell receptor (BCR) stimulation. In addition, the overexpression of Cbl-b in WEHI-231 mouse B cells resulted in the augmentation of BCR-induced Ca2+ mobilization. Cbl-b interacted with PLC-gamma2 and helped the association of PLC-gamma2 with Bruton's tyrosine kinase (Btk), as well as B cell linker protein (BLNK). Cbl-b was indispensable for Btk-dependent sustained increase in intracellular Ca2+. Both NH2-terminal tyrosine kinase-binding domain and COOH-terminal half region of Cbl-b were essential for its association with PLC-gamma2 and the regulation of Ca2+ mobilization. These results demonstrate that Cbl-b positively regulates BCR-mediated Ca2+ signaling, most likely by influencing the Btk/BLNK/PLC-gamma2 complex formation. C1 Univ Tokyo, Inst Med Sci, Dept Oncol, Minato Ku, Tokyo 1088639, Japan. Kansai Med Univ, Dept Mol Genet, Inst Liver Res, Moriguchi, Osaka 5708506, Japan. NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA. Tokyo Med & Dent Univ, Med Res Inst, Dept Cell Regulat, Bunkyo Ku, Tokyo 1138510, Japan. RP Yamamoto, T (reprint author), Univ Tokyo, Inst Med Sci, Dept Oncol, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. RI Kurosaki, Tomohiro/D-1306-2009 OI Kurosaki, Tomohiro/0000-0002-6352-304X NR 56 TC 36 Z9 38 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 2002 VL 196 IS 1 BP 51 EP 63 DI 10.1084/jem.20020068 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 569TJ UT WOS:000176618100005 PM 12093870 ER PT J AU Lippincott-Schwartz, J AF Lippincott-Schwartz, J TI Analysis of intracellular trafficking pathways and protein dynamics within living cells SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 NICHD, Cell Biol & Metab Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2002 VL 120 IS 1 MA 5 BP 2A EP 2A PG 1 WC Physiology SC Physiology GA 569LD UT WOS:000176603100015 ER PT J AU Smith, GH Vonderhaar, BK AF Smith, GH Vonderhaar, BK TI Re: Immunocytochemical demonstration of caseins in mouse mammary glands SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Letter ID EPITHELIAL-CELLS; VIRGIN MICE; DIFFERENTIATION; EXPRESSION; PROLACTIN; COLLAGEN; TISSUES C1 NCI, Mammary Biol Grp, Basic Res Lab, Ctr Canc Res, Bethesda, MD USA. RP Smith, GH (reprint author), Bldg 10,Room 5B56,9000 Rockville Pike, Bethesda, MD USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUL PY 2002 VL 50 IS 7 BP 997 EP 998 PG 2 WC Cell Biology SC Cell Biology GA 566WF UT WOS:000176450700014 PM 12094781 ER PT J AU Faunce, DE Stein-Streilein, J AF Faunce, DE Stein-Streilein, J TI NKT cell-derived RANTES recruits APCs and CD8(+) T cells to the spleen during the generation of regulatory T cells in tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTORS; SYSTEMIC TOLERANCE; EXPRESSION; LYMPHOCYTES; ACTIVATION; RESPONSES; ALPHA; BETA; MICE AB The induction of peripheral tolerance via immune privileged sites such as the eye requires splenic colocalization of NKT cells and CD1d(+) tolerogenic F4/80(+) APCs, both of which are needed for the generation of CD8(+)-regulatory T (Tr) cells. Whereas tolerogenic APCs secrete the chemokine macrophage-inflammatory protein-2 for the purpose of recruiting NKT cells, the signals responsible for recruiting potential Tr cells and additional APCs to the spleen are not known. Here we examined the ability of CD1d-stimulated NKT cells to produce chemokines that can recruit other cells needed for tolerance. Our results show that NKT cells stimulated by either CD1d-transfected fibroblasts in vitro or CD1d(+) tolerogenic APCs both in vivo and ex vivo produced RANTES in a CD1d-dependent manner. The requirement for RANTES in tolerance was demonstrated by studies in which RANTES blockade in vivo prevented not only APC accumulation in the spleen but also the generation of CD8(+) Tr cells that suppress Th1 immunity. Thus, CD1d-restricted NKT cells provide critical signals for orchestrating the accumulation of cells needed for tolerance induction. These data expand our current knowledge of RANTES beyond its role in Th1 immune responses to show its importance in tolerance induction and add a novel aspect to our understanding of the role of NKT cells in tolerance. Understanding the precise mechanisms involved in tolerance induction may lead to more effective therapeutic strategies for autoimmunity and graft rejection. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, NEI, Training Program Mol Bases Eye Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pulm & Crit Care,Dept Med, Boston, MA 02115 USA. RP Stein-Streilein, J (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NEI NIH HHS [EY07021-01, EY11983-01, EY13306] NR 28 TC 83 Z9 88 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 JUL 1 PY 2002 VL 169 IS 1 BP 31 EP 38 PG 8 WC Immunology SC Immunology GA 565GA UT WOS:000176360400006 PM 12077225 ER PT J AU Provenzano, M Mocellin, S Bettinotti, M Preuss, J Monsurro, V Marincola, FM Stroncek, D AF Provenzano, M Mocellin, S Bettinotti, M Preuss, J Monsurro, V Marincola, FM Stroncek, D TI Identification of immune dominant cytomegalovirus epitopes using quantitative real-time polymerase chain reactions to measure interferon-gamma production by peptide-stimulated peripheral blood mononuclear cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE cytomegalovirus; immune therapy; cytotoxic T lymphocytes; transplantation; cytokines; major histocompatibility complex ID MARROW-TRANSPLANT RECIPIENTS; CYTOTOXIC T-LYMPHOCYTES; ALLOGENEIC BONE-MARROW; MATRIX PROTEIN PP65; ADOPTIVE TRANSFER; RECONSTITUTION; MELANOMA; ANTIGEN; CLONES; VIRUS AB The identification of HLA restricted immune dominant cytotoxic T cell (CTL) epitopes limits immune therapy. Cytomegalovirus (CMV) disease remains a significant cause of morbidity after allogeneic stem cell transplantation. Adoptive immune therapy using CTLs stimulated with immune dominant CMV pp65 peptides may be effective in preventing CMV disease, but immune dominant CMV peptides have been identified for only a few HLA class I molecules. The purpose of this study was to use a novel molecular system to establish a rapid and precise method to identify new HLA-restricted CMV epitopes. Cytomegalovirus pp65 peptides expected to bind to the HLA-24 molecule were identified with a computer algorithm. Five candidate peptides were screened by direct ex Vivo stimulation of peripheral blood mononuclear cells (PBMCs) from CMV-seropositive HLA-A*2402 individuals, and quantitative real time PCR (qRT-PCR) was used to evaluate CTL responses by measuring interferon-gamma (IFN-gamma) transcripts. One of the five candidate peptides. pp65(341-50) (QYDPVAALFF), induced significant quantities of IFN-gamma mRNA production after 3 hours. PBMCs from CMV-seropositive HLA-A*2402 individuals sensitized in vitro with pp65(341-350) also recognized CMV-infected targets. In conclusion, the measurement of IFN-gamma mRNA by qRT-PCR can be used to detect CTL responses 3 hours after peptide stimulation of a small quantity of PBMCs. This method has an advantage over other methods used to identify immune dominant epitopes in that it does not require in vitro expansion of CTLs with cytokines or virally infected targets. As a result, this method measures naturally induced immune reactions. C1 NCI, Warren G Magnuson Clin Ctr, Dept Transfus Med, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Pathol, Bethesda, MD 20892 USA. RP Stroncek, D (reprint author), NCI, Warren G Magnuson Clin Ctr, Dept Transfus Med, NIH, Bldg 10-1C711, Bethesda, MD 20892 USA. NR 30 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2002 VL 25 IS 4 BP 342 EP 351 DI 10.1097/01.CJI.0000022030.33645.24 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 578GL UT WOS:000177109000006 PM 12142557 ER PT J AU Meijer, SL Dols, A Urba, WJ Hu, HM Smith, JW Vetto, J Wood, W Doran, T Chu, Y Sayaharuban, P Alvord, WG Fox, BA AF Meijer, SL Dols, A Urba, WJ Hu, HM Smith, JW Vetto, J Wood, W Doran, T Chu, Y Sayaharuban, P Alvord, WG Fox, BA TI Adoptive cellular therapy with tumor vaccine draining lymph node lymphocytes after vaccination with HLA-B7/beta(2)-microglobulin gene-modified autologous tumor cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE adoptive immunotherapy; tumor vaccine; melanoma; renal cell cancer ID T-CELLS; IMMUNOTHERAPY; INTERLEUKIN-2; CANCER; EXPRESSION; GENERATION; TOXICITY; MELANOMA; TYPE-1; DNA AB Adoptive immunotherapy with anti-CD3-expanded lymphocytes from lymph nodes draining alloantigen gene-modified autologous tumor vaccines is an effective treatment of poorly immunogenic murine tumors. This phase I/II study was performed to determine the feasibility and toxicity of combining ex vivo gene transfer of autologous tumor cells and adoptive immunotherapy with anti-CD3-expanded tumor vaccine draining lymph node lymphocytes (TVDLN) in patients with metastatic melanoma and renal cell cancer (RCC). To facilitate the generation of tumor-specific lymphocytes in the TVDLN, autologous tumor cells were modified by gene transfer ex vivo to express the alloantigen HLA-B7, a modification that has the potential to enhance the immunogenicity of the tumor cells. After vaccination with gene-modified tumor cells, patients' lymph nodes were harvested; TVDLN lymphocytes were activated and expanded ex vivo with anti-CD3 and interleukin-2 (IL-2), and adoptively transferred to patients in combination with systemic IL-2. Twenty patients, nine with melanoma and I I with RCC were treated. Tumor was harvested successfully in all 20 patients. Ex vivo gene transfer was performed using lipofection with a lipid: DNA plasmid complex containing the genes for HLA-B7 and beta2-microglobulin. The mean expression of HLA-B7 by autologous tumor cells after gene transfer was 4.53% (range 0.3%-12.1%). Lymph nodes were harvested from all 20 patients with a mean of 53 x 107 and 60 x 107 cells obtained from the gene-modified and unmodified tumor vaccine sites, respectively. Successful expansion of adequate TVDLN was accomplished in 19 of 20 harvests of unmodified vaccines and in 18 of 20 gene-modified vaccines. No major toxicities were noted after vaccination with autologous tumor cells or adoptive transfer of ex vivo activated TVDLN lymphocytes. Typical IL-2-related toxicities were observed in all patients. No objective tumor regressions were observed. MHC class I restricted, tumor-specific cytokine secretion was observed in lymphocytes from TVDLN and the peripheral blood of vaccinated patients. C1 Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Portland, OR 97213 USA. Providence Portland Med Ctr, Earle A Chiles Res Inst, Lab Mol & Tumor Immunol, Portland, OR 97213 USA. Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Oregon Canc Ctr, Portland Vet Affairs Med Ctr, Dept Surg, Portland, OR 97201 USA. Frederick Canc Res Facil, Comp Serv, Frederick, MD USA. Frederick Canc Res Facil, Stat Serv, Frederick, MD USA. RP Fox, BA (reprint author), Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, 4805 NE Glisan St, Portland, OR 97213 USA. FU NCI NIH HHS [R21 CA76078] NR 20 TC 21 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2002 VL 25 IS 4 BP 359 EP 372 DI 10.1097/01.CJI.0000018062.31201.75 PG 14 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 578GL UT WOS:000177109000008 PM 12142559 ER PT J AU Domachowske, JB Bonville, CA Easton, AJ Rosenberg, HF AF Domachowske, JB Bonville, CA Easton, AJ Rosenberg, HF TI Differential expression of proinflammatory cytokine genes in vivo in response to pathogenic and nonpathogenic pneumovirus infections SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; MACROPHAGE-INFLAMMATORY PROTEIN-1-ALPHA; PNEUMONIA VIRUS; HOST-DEFENSE; OLIGONUCLEOTIDE ARRAYS; ANTIVIRAL RESPONSES; MICE; PROTEINS; SEQUENCE; MOUSE AB Pneumonia virus of mice (PVM; Paramyxoviridae, subfamily Pneumovirinae) is an important pathogen for the study of physiologically relevant acute inflammatory responses in rodent hosts. In contrast to the severe symptomatology observed in response to infection with PVM strain J3666, infection with strain 15 resulted in few clinical symptoms, limited cellular inflammatory response, and no production of macrophage inflammatory protein-1alpha or monocyte chemoattractant peptide (MCP)-1. Microarray analysis of transcripts from lung tissue indicates that PVM J3666 infection promotes up-regulation of specific proinflammatory genes, most notably interferon (IFN)-1beta, IFN response genes, and chemokines MCP-1, MCP-3, RANTES (regulated on activation, normally T cell-expressed and secreted), and eotaxin. Of these, only RANTES expression increased in response to infection with strain 15, with no increased expression of IFN or IFN response genes, despite ongoing viral replication. These results suggest that pneumovirus replication alone is insufficient to promote antiviral inflammation and that evaluation of the more divergent strain-specific pneumovirus proteins may provide some intriguing leads toward the molecular basis of this differential response. C1 SUNY, Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England. RP Domachowske, JB (reprint author), SUNY, Upstate Med Univ, Dept Pediat, 750 E Adams St, Syracuse, NY 13210 USA. EM domachoj@upstate.edu NR 32 TC 44 Z9 45 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 1 PY 2002 VL 186 IS 1 BP 8 EP 14 DI 10.1086/341082 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 564GZ UT WOS:000176307800002 PM 12089656 ER PT J AU Makar, TK Wilt, S Dong, ZY Fishman, P Mouradian, MM Dhib-Jalbut, S AF Makar, TK Wilt, S Dong, ZY Fishman, P Mouradian, MM Dhib-Jalbut, S TI IFN-beta gene transfer into the central nervous system using bone marrow cells as a delivery system SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; COLLAGEN-INDUCED ARTHRITIS; INTERFERON-BETA; MULTIPLE-SCLEROSIS; HEMATOPOIETIC-CELLS; UP-REGULATION; ADULT MICE; IN-VIVO; EXPRESSION; THERAPY AB The peripheral delivery of interferon-beta (IFN-beta) for the treatment of central nervous system (CNS) diseases is only partially effective because of the blood-brain barrier (BBB). To circumvent this problem, we evaluated the feasibility of genetically altering bone marrow cells ex vivo and using them as vehicles to transfer the IFN-beta cDNA into the mouse CNS. An IFN-beta retroviral expression vector (pLXSN-IFNbeta) was used to stably transfect PA317 cells. The supernatant from these producer cells, which expressed IFN-beta mRNA and protein, were used to infect bone marrow cells. When transplanted into irradiated mice, IFN-beta-engineered marrow cells accessed the CNS and expressed IFN-beta mRNA and protein. Marrow cells transduced with a control neomycin vector entered the brain and expressed the neomycin but not the IFN-beta gene. In the CNS, IFN-beta delivered by marrow cells induced the mRNA expression of 2',5'-oligoadenylate synthetase (2',5'-OAS), indicating biologic activity. Our findings demonstrating that bone marrow cells can serve as a delivery system for IFN-beta cDNA into the CNS could have implications for the treatment of neurologic disorders, such as multiple sclerosis (MS), viral encephalitis, and brain tumors. C1 Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA. Dept Vet Affairs, Baltimore, MD 21201 USA. Maryland VA Med Ctr, Dept Vet Affairs Med Ctr, Res Serv, Baltimore, MD 21201 USA. Univ Texas, Dept Cell Biol, Houston, TX USA. NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Dhib-Jalbut, S (reprint author), Univ Maryland Hosp, Dept Neurol, Room N4W46,22 S Greene St, Baltimore, MD 21201 USA. OI Mouradian, M. Maral/0000-0002-9937-412X FU PHS HHS [K-24-02082] NR 42 TC 14 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD JUL PY 2002 VL 22 IS 7 BP 783 EP 791 DI 10.1089/107999002320271378 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 575VQ UT WOS:000176969500006 PM 12184916 ER PT J AU Lei, T Nguyen, D Nguyen, J Moss, J Darling, T AF Lei, T Nguyen, D Nguyen, J Moss, J Darling, T TI Increased expression of platelet-derived growth factor A and pleiotrophin in tuberous sclerosis skin tumors SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. NHLBI, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 012 BP 209 EP 209 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100013 ER PT J AU Sugaya, M Watanabe, T Atkins, A Aquilino, E Jaffe, E Feigenbaum, L Blauvelt, A AF Sugaya, M Watanabe, T Atkins, A Aquilino, E Jaffe, E Feigenbaum, L Blauvelt, A TI Transgenes expressed under the control of the VEGFR-3 promoter are selectively expressed by lymphatic endothelial cells of transgenic mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Pathol Branch, Bethesda, MD 20892 USA. NCI, SAIC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 010 BP 209 EP 209 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100012 ER PT J AU Darling, TN Wang, J Takeuchi, F Lei, T Pack, S Zhuang, Z Moss, J AF Darling, TN Wang, J Takeuchi, F Lei, T Pack, S Zhuang, Z Moss, J TI Allelic deletion of the TSC2 gene in tuberous sclerosis skin tumors and cultured stromal cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. NINDS, Mol Pathogenesis Unit, SNB, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 043 BP 215 EP 215 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100044 ER PT J AU Athar, M Russo, J Kim, AL Zhang, H Tang, X Aszterbaum, M Kopelovich, L Epstein, EH Bickers, DR AF Athar, M Russo, J Kim, AL Zhang, H Tang, X Aszterbaum, M Kopelovich, L Epstein, EH Bickers, DR TI Innovative model for accelerated induction of cutaneous basal cell carcinomas: ptch+/- heterozygous knockout mice over-expressing ornithine decarboxylase SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Columbia Univ, Coll Phys & Surg, New York, NY USA. NCI, Div Chemoprevent, Bethesda, MD 20892 USA. UCSF, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 051 BP 216 EP 216 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100051 ER PT J AU Watanabe, T Sugaya, M Atkins, A Aquilino, E Blauvelt, A AF Watanabe, T Sugaya, M Atkins, A Aquilino, E Blauvelt, A TI The Kaposi's sarcoma-associated herpesvirus gene LANA immortalizes primary human umbilical vein endothelial cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 069 BP 219 EP 219 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100069 ER PT J AU Hwang, ST Maki, W Fang, H Murakami, T AF Hwang, ST Maki, W Fang, H Murakami, T TI Chemokine receptors alter metastastic pathways in B16 murine melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 080 BP 221 EP 221 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100083 ER PT J AU Tang, X Athar, M Kim, AL Kopelovich, L Epstein, EH Bickers, DR AF Tang, X Athar, M Kim, AL Kopelovich, L Epstein, EH Bickers, DR TI Novel approach to cancer chemoprevention: Inhibition of sonic hedgehog (shh) signaling by cyclopamine (CPN) abrogates ultraviolet B-induced basal cell carcinomas (BCCs) in ptch+/- heterozygous mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Columbia Univ, Coll Phys & Surg, New York, NY USA. NCI, Div Chemoprevent, Bethesda, MD 20892 USA. UCSF, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 084 BP 221 EP 221 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100085 ER PT J AU Toro, JR Liewehr, D Sorbara, L Raffeld, M Steinberg, S Jaffe, E AF Toro, JR Liewehr, D Sorbara, L Raffeld, M Steinberg, S Jaffe, E TI Gamma delta T cells: A novel marker associated with decreased survival in cutaneous peripheral T cell lymphoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 079 BP 221 EP 221 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100080 ER PT J AU Kraemer, KH Khan, SG Shahlavi, T Busch, DB Ueda, T Inui, H Emmert, S Muniz-Medina, V Baker, CC Gozukara, E Slor, H Metin, A Albert, RB Ziffer, DW Coleman, DM DiGiovanna, JJ AF Kraemer, KH Khan, SG Shahlavi, T Busch, DB Ueda, T Inui, H Emmert, S Muniz-Medina, V Baker, CC Gozukara, E Slor, H Metin, A Albert, RB Ziffer, DW Coleman, DM DiGiovanna, JJ TI Spectrum of mutations in 25 xeroderma pigmentosum complementation group C patients from the United States, Turkey and Israel SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, BRI, Bethesda, MD 20892 USA. AFIP, Toxicol, Washington, DC USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. Yuzuncu YlU, Derm, Van, Turkey. Brown Med Sch, Providence, RI USA. Inonu U, Biochem, Malatya, Turkey. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 085 BP 222 EP 222 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100086 ER PT J AU DiGiovanna, J Ueda, T Inui, H Busch, DB Pittelkow, MR Sanders, E Price, V Lehmann, AR Kraemer, KH AF DiGiovanna, J Ueda, T Inui, H Busch, DB Pittelkow, MR Sanders, E Price, V Lehmann, AR Kraemer, KH TI Trichothiodystrophy with and without xeroderma pigmentusum SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, BRL, Bethesda, MD 20892 USA. AFIP, Toxicol, Washington, DC USA. Mayo Clin, Rochester, MN USA. Univ Alabama, Birmingham, AL USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Sussex, GDSC, Brighton, E Sussex, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 093 BP 223 EP 223 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100093 ER PT J AU Liu, X Cooley, M Hartley, S Bhogte, E Glick, A AF Liu, X Cooley, M Hartley, S Bhogte, E Glick, A TI Overexpression of Smad7 cooperates with a ras oncogene to cause hyperproliferation and malignant conversion of primary mouse keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Cellular Carcinogenesis & Tumor Promot, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 098 BP 224 EP 224 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100101 ER PT J AU Chernyavsky, A Arredondo, J Nguyen, V Ndoye, A Zia, S Wess, J Grando, S AF Chernyavsky, A Arredondo, J Nguyen, V Ndoye, A Zia, S Wess, J Grando, S TI Molecular mechanisms of stimulatory effect of M4 muscarinic acetylcholine receptor on keratinocyte migration SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Calif Davis, Davis, CA 95616 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 108 BP 225 EP 225 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100109 ER PT J AU Ehrlich, A Borris, D Tejura, K Steinberg, S Fojo, T Figg, W Detmar, M Turner, M Blauvelt, A AF Ehrlich, A Borris, D Tejura, K Steinberg, S Fojo, T Figg, W Detmar, M Turner, M Blauvelt, A TI Intravenous micellar paclitaxel improves severe psoriasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 171 BP 236 EP 236 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100171 ER PT J AU Terunuma, A Jackson, KL Kapoor, V Telford, WG Vogel, JC AF Terunuma, A Jackson, KL Kapoor, V Telford, WG Vogel, JC TI Side population cells in the human epidermis: A novel candidate for keratinocyte stem cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 269 BP 252 EP 252 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100268 ER PT J AU Zouboulis, CC Seltmann, H Hiroi, N Chen, W Young, M Scherbaum, WA Orfanos, CE McCann, SM Bornstein, SR AF Zouboulis, CC Seltmann, H Hiroi, N Chen, W Young, M Scherbaum, WA Orfanos, CE McCann, SM Bornstein, SR TI CRH is an autocrine hormone for human sebocytes promoting lipogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Free Univ Berlin, Dept Dermatol, Univ Med Ctr Benjamin Franklin, Berlin, Germany. Univ Dusseldorf, Dept Endocrinol, Univ Med Ctr, D-4000 Dusseldorf, Germany. NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. Natl Cheng Kung Univ, Coll Med, Dept Dermatol, Tainan 70101, Taiwan. Pennington Biomed Res Ctr, Baton Rouge, LA USA. RI Dr. Zouboulis, Christos/I-4493-2013 OI Dr. Zouboulis, Christos/0000-0003-1646-2608 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 282 BP 254 EP 254 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100283 ER PT J AU Steinert, PM Marekov, L Raghunath, M Traupe, H Boeshans, K Ahvazi, B AF Steinert, PM Marekov, L Raghunath, M Traupe, H Boeshans, K Ahvazi, B TI Transglutaminases under pressure SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Univ Munster, Dept Dermatol, D-4400 Munster, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 288 BP 255 EP 255 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100289 ER PT J AU Kalinin, AE Idler, WW Steinert, PM AF Kalinin, AE Idler, WW Steinert, PM TI Interaction of envoplakin and periplakin with cytoskeletal proteins SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 302 BP 258 EP 258 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100305 ER PT J AU Marekov, LN Steinert, PM Jang, S Zhao, H AF Marekov, LN Steinert, PM Jang, S Zhao, H TI Biophysical properties of loricrin provide new information on its utilization in the epidermal cornified cell envelope SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 312 BP 259 EP 259 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100313 ER PT J AU Richard, G Rouan, F Willoughby, C Brown, N Amin, S Chung, P Ryynanen, M Jabs, E Bale, S DiGiovanna, J Uitto, J Russell, L AF Richard, G Rouan, F Willoughby, C Brown, N Amin, S Chung, P Ryynanen, M Jabs, E Bale, S DiGiovanna, J Uitto, J Russell, L TI Keratitis-ichthyosis-deafness syndrome is caused by dominant missense mutations in GJB2 encoding connexin-26 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Univ Liverpool, Liverpool L69 3BX, Merseyside, England. Univ Hosp, Oulu, Finland. Johns Hopkins Univ Hosp, Inst Med Genet, Baltimore, MD 21287 USA. NIAMS, Genet Studies Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 336 BP 263 EP 263 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100337 ER PT J AU Pfutzner, W Tock, CL Terunuma, A Snead, EK Kolodka, TM Vogel, JC AF Pfutzner, W Tock, CL Terunuma, A Snead, EK Kolodka, TM Vogel, JC TI Enrichment of keratinocyte progenitor cells transduced with the multidrug resistance gene by topical selection SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Munich, Klin & Poliklin Dermatol & Allergol, Munich, Germany. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 352 BP 266 EP 266 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100354 ER PT J AU Yeowell, HN Walker, LC Marini, JC Cabral, WA Willing, M Pals, G Kitamura, E Yamauchi, M AF Yeowell, HN Walker, LC Marini, JC Cabral, WA Willing, M Pals, G Kitamura, E Yamauchi, M TI Biochemical causes of Ehlers Danlos syndrome type VI in skin fibroblasts from a group of affected patients that appear unrelated to decreased collagen lysyl hydroxylation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. NICHD, Heritable Disorders Branch, Bethesda, MD USA. Univ Iowa, Iowa City, IA USA. VU Med Ctr, Amsterdam, Netherlands. Univ N Carolina, Dent Res Ctr, Chapel Hill, NC 27599 USA. RI Pals, Gerard/A-5198-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 254 BP 266 EP 266 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100355 ER PT J AU Zhou, Z Jarnick Speransky, VV Steven, AC Koch, PJ Roop, DR AF Zhou, Z Jarnick Speransky, VV Steven, AC Koch, PJ Roop, DR TI Identification of a novel family of cell envelope components that contribute to skin barrier function in the absence of loricrin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NIAMS, Bethesda, MD USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 362 BP 268 EP 268 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100365 ER PT J AU Lee, D Ahn, K Lee, C Rho, N Lee, J Lee, E Steinert, P Yang, J AF Lee, D Ahn, K Lee, C Rho, N Lee, J Lee, E Steinert, P Yang, J TI Two novel mutations in the keratin 1 gene in epidermolytic hyperkeratosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Sungkyunkwan Univ, Dept Dermatol, Sch Med, Samsung Med Ctr, Seoul, South Korea. Samsung Biomed Res Inst, Clin Res Ctr, Seoul, South Korea. NIAMSD, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 371 BP 269 EP 269 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100370 ER PT J AU Lee, J Ahn, K Lee, C Youn, S Lee, D Lee, E Steinert, P Yang, J AF Lee, J Ahn, K Lee, C Youn, S Lee, D Lee, E Steinert, P Yang, J TI Epidermolytic palmoplantar keratoderma in five Korean families caused by mutations of keratin 9 gene SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Sungkyunkwan Univ, Dept Dermatol, Sch Med, Seoul, South Korea. Samsung Biomed Res Inst, Clin Res Ctr, Seoul, South Korea. NIAMSD, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 372 BP 269 EP 269 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100373 ER PT J AU Toro, JR Anikster, Y Huizing, M White, J Shevchenko, Y Bale, S Gahl, W AF Toro, JR Anikster, Y Huizing, M White, J Shevchenko, Y Bale, S Gahl, W TI Mutation of a novel gene causes a Hermansky-Pudlak syndrome in central Puerto Rico SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 367 BP 269 EP 269 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100368 ER PT J AU Toro, JR Warren, M Turner, M Duray, P Glenn, G Linehan, M Zbar, M Schmidt, L AF Toro, JR Warren, M Turner, M Duray, P Glenn, G Linehan, M Zbar, M Schmidt, L TI Autosomal dominant spontaneous pneumothorax maps to chromosome 17p11.2, the same region of Birt-Hogg-Dube syndrome SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NCI, IRSP, SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, LIB, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 392 BP 273 EP 273 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100395 ER PT J AU Glick, AB Cooley, M Bhogte, E AF Glick, AB Cooley, M Bhogte, E TI Activation of Erk1/2 by TGF beta in the absence of a functional TGF beta type I receptor SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Lab Cellular Carcinogenesis & Tumor Promot, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 457 BP 284 EP 284 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100458 ER PT J AU Millar, SE Andl, T Reddy, ST Glick, A AF Millar, SE Andl, T Reddy, ST Glick, A TI WNT signals are required for the initiation of hair follicle development and for postnatal hair growth SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 489 BP 289 EP 289 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100489 ER PT J AU Liu, Y Morris, J Yang, Z Trempus, CS Cotsarelis, G AF Liu, Y Morris, J Yang, Z Trempus, CS Cotsarelis, G TI Isolation and characterization of epithelial stem cells from K15/eGFP transgenic mire SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Columbia Univ, New York, NY USA. NIEHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 499 BP 291 EP 291 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100500 ER PT J AU Cui, C AF Cui, C TI EDA specific gene expression profile in tabby skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 508 BP 292 EP 292 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100510 ER PT J AU Albert, MR Hematti, P Yee, CL Sloand, E Childs, RW Carvallo, CA Barrett, JA Dunbar, C Vogel, JC AF Albert, MR Hematti, P Yee, CL Sloand, E Childs, RW Carvallo, CA Barrett, JA Dunbar, C Vogel, JC TI Lack of culture expansion of donor-derived keratinocytes from skin biopsies of patients with graft-vs.-host disease SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 529 BP 296 EP 296 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100529 ER PT J AU Cardones, AR Wu, M Fang, H Hwang, ST AF Cardones, AR Wu, M Fang, H Hwang, ST TI Expression of CC chemokine receptor-4 is critical for the binding of antigen-primed, but not naive, T cells to dendritic cells in vitro SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 556 BP 300 EP 300 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100556 ER PT J AU Shibagaki, N Udey, MC AF Shibagaki, N Udey, MC TI Dendritic cells treated with TAT protein transduction domain containing recombinant murine tyrosinase-related protein-2 (Trp-2) induce B16 melanoma-reactive cytotoxic lymphocytes and antitumor immunity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 557 BP 300 EP 300 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100554 ER PT J AU Morales, RE Maki, W Fang, H Hwang, ST AF Morales, RE Maki, W Fang, H Hwang, ST TI CCR6 receptor colocalizes with beta 2 integrin during arrest of model T cells to immobilized ICAM-1 under flow conditions SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 564 BP 301 EP 301 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100563 ER PT J AU Sato, A Shibaki, A Katz, SI AF Sato, A Shibaki, A Katz, SI TI Development and maintenance of peripheral tolerance to epidermal cell-associated proteins using a transgenic approach SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 568 BP 302 EP 302 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100568 ER PT J AU Liu, Q Callendar, C Liu, Z Whitmire, J Grusby, MJ Finkelman, FD Darling, TN Cheever, AW Swearengen, J Gause, WC AF Liu, Q Callendar, C Liu, Z Whitmire, J Grusby, MJ Finkelman, FD Darling, TN Cheever, AW Swearengen, J Gause, WC TI Simultaneous deficiency in CD28 and STAT6 results in ectoparasite-induced inflammatory skin disease SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Univ Cincinnati, Coll Med, Vet Adm Med Ctr, Cincinnati, OH USA. Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. NIH, Biomed Res Inst, Rockville, MD USA. Uniformed Serv Univ Hlth Sci, Lab Anim Med, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 581 BP 304 EP 304 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100578 ER PT J AU Riedl, E Wilson, M Udey, MC AF Riedl, E Wilson, M Udey, MC TI Cloning and characterization of mouse Langerin and an alternatively spliced isoform SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 583 BP 305 EP 305 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100582 ER PT J AU Wu, M Hwang, ST AF Wu, M Hwang, ST TI Lymphatic endothelial cells directly stimulate transendothelial migration of migratory skin-derived dendritic cells in vitro SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. China Med Coll, Dept Dermatol, Taichung, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 618 BP 310 EP 310 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100617 ER PT J AU Cataisson, C Wang, A Subleski, J Joseloff, E Vinson, C Wiltrout, R Yuspa, S AF Cataisson, C Wang, A Subleski, J Joseloff, E Vinson, C Wiltrout, R Yuspa, S TI Overexpression of protein kinase C alpha in mouse epidermis causes inflammation and AP-1-mediated apoptosis in vitro SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. NCI, LE, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 654 BP 316 EP 316 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100652 ER PT J AU Talanin, NY Chung, E Orenstein, JM Trepel, J Blauvelt, A AF Talanin, NY Chung, E Orenstein, JM Trepel, J Blauvelt, A TI Histone deacetylase inhibitors reactivate Kaposi's sarcoma-associated herpesvirus SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. George Washington Univ, Dept Pathol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 651 BP 316 EP 316 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100648 ER PT J AU Kawamura, T Gulden, F McNamara, D Lederman, M Zimmerman, P Blauvelt, A AF Kawamura, T Gulden, F McNamara, D Lederman, M Zimmerman, P Blauvelt, A TI Compound CCR5 polymorphisms influence R5 HIV infection levels in Langerhans cells: Implications for sexual transmission of HIV SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 679 BP 321 EP 321 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100677 ER PT J AU von Stebut, E Belkaid, Y Kostka, SL Schmitt, E Knop, J Sacks, D Udey, MC AF von Stebut, E Belkaid, Y Kostka, SL Schmitt, E Knop, J Sacks, D Udey, MC TI Proinflammatory IL-1 alpha induces Th1 differentiation and protective immunity in Leishmania-susceptible BALB/c mice via induction of IL-12 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Mainz, Dept Dermatol, D-6500 Mainz, Germany. Univ Mainz, Inst Immunol, D-6500 Mainz, Germany. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 682 BP 321 EP 321 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100681 ER PT J AU Greiner, E Atkinson, AJ Ayala, A Chrousos, GP Contoreggi, C Eckelman, WC Gold, PW Habib, KE Jacobson, AE Whittaker, N Webster, EL Rice, KC AF Greiner, E Atkinson, AJ Ayala, A Chrousos, GP Contoreggi, C Eckelman, WC Gold, PW Habib, KE Jacobson, AE Whittaker, N Webster, EL Rice, KC TI Synthesis of doubly C-13-labelled antalarmin isotopomers for pharmacokinetic studies SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE corticotropin-releasing hormone; CRHR1 antagonist; antalarmin; carbon-13 labelling ID CORTICOTROPIN-RELEASING FACTOR; FACTOR-LIKE IMMUNOREACTIVITY; RECEPTOR ANTAGONIST; ETHANOL WITHDRAWAL; PITUITARY; STRESS; INFLAMMATION AB Antalarmin (butyl-ethyl-[2,5,6-trimethyl-7-(2,4,6-trimethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine) was doubly labelled with carbon-13. The synthesized butyl-[C-13(2)]ethyl-[2,5,6-trimethyl-7-(2,4,6-trimethyl-phenyl)- 7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine (1) and butyl-ethyl-[2-C-13] -[2,5,6-trimethyl-7-(2,4,6-trimethyl-phenyl)-7H-pyrrolo[2,3-d]-[2-C-13] pyrimidin-4-yl]amine, (2) were prepared for use as substrates for pharmacokinetic studies. These compounds were obtained in fair overall yield in a 5 and 6 step synthesis (20-24.5%, respectively) and high isotopic purity (about 99 at% C-13). Copyright (C) 2002 John Wiley Sons, Ltd. C1 NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Off Director, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat Endocrinol Sect, PREB, NIH, Bethesda, MD 20892 USA. NIDA, Brain Imaging Branch, NIH, Baltimore, MD 21224 USA. NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Rice, KC (reprint author), NIDDKD, Med Chem Lab, NIH, Bldg 8,Room B1-23,8 Ctr Dr,MSC 0815, Bethesda, MD 20892 USA. NR 19 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUL PY 2002 VL 45 IS 8 BP 637 EP 645 DI 10.1002/jlcr.576 PG 9 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 581DN UT WOS:000177276000002 ER PT J AU Zatyka, M Morrissey, C Kuzmin, I Lerman, MI Latif, F Richards, FM Maher, ER AF Zatyka, M Morrissey, C Kuzmin, I Lerman, MI Latif, F Richards, FM Maher, ER TI Genetic and functional analysis of the von Hippel-Lindau (VHL) tumour suppressor gene promoter SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID TRANSCRIPTION FACTOR E2F; RENAL-CARCINOMA; BINDING-PROTEIN; NUCLEOTIDE-SEQUENCES; MOUSE EMBRYOGENESIS; SOMATIC MUTATIONS; START SITE; EXPRESSION; HYPOXIA; DISEASE AB The VHL gatekeeper turnout suppressor gene is inactivated in the familial cancer syndrome von Hippel-Lindau disease and in most sporadic clear cell renal cell carcinomas. Recently the VHL gene product has been identified as a specific component of a SCF-like complex, which regulates proteolytic degradation of the hypoxia inducible transcription factors HIF-1 and HIF-2. pVHL is critical for normal development and mRNA expression studies suggest a role in nephrogenesis. Despite the importance of VHL in oncogenesis and development, little is known about the regulation of VHL expression. To investigate VHL promoter activity, we performed comparative sequence analysis of human, primate, and rodent 5 VHL sequences. We then proceeded to deletion analysis of regions showing significant evolutionary conservation between human and rat promoter sequences, and defined two positive and one negative regulatory regions. Analysis of specific putative transcription factor binding sites identified a functional Sp1 site, which was shown to be a regulatory element. Overlapping Sp1/AP2 sites were also identified and candidate E2F1 binding sites evaluated. Three binding sites for as yet unidentified transcription factors were mapped also. These investigations provide a basis for elucidating the regulation of VHL expression in development, the molecular pathology of epigenetic silencing of VHL in tumourigenesis, and suggest a possible link between Sp1, VHL, and nephrogenesis. C1 Univ Birmingham, Sect Med & Mol Genet, Dept Paediat & Child Hlth, Sch Med, Birmingham B15 2TT, W Midlands, England. SAIC Frederick Inc, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Immunobiol Lab, Frederick, MD 21702 USA. RP Maher, ER (reprint author), Univ Birmingham, Sect Med & Mol Genet, Dept Paediat & Child Hlth, Sch Med, Birmingham B15 2TT, W Midlands, England. RI MAHER, EAMONN/A-9507-2008; Zatyka, Malgorzata/D-9340-2017 OI MAHER, EAMONN/0000-0002-6226-6918; Zatyka, Malgorzata/0000-0003-3427-1653 FU NCI NIH HHS [N01-CO-12400] NR 50 TC 21 Z9 22 U1 1 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JUL PY 2002 VL 39 IS 7 BP 463 EP 472 DI 10.1136/jmg.39.7.463 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 577EG UT WOS:000177048100002 PM 12114475 ER PT J AU McNeil, DE Linehan, WM Glenn, GM AF McNeil, D. E. Linehan, W. M. Glenn, G. M. TI Comorbid VHL and SCA2 mutations in a large kindred: confounding diagnosis of neurological dysfunction caused by CNS VHL vascular tumours versus SCA2 atrophic neurodegeneration SO JOURNAL OF MEDICAL GENETICS LA English DT Article C1 [McNeil, D. E.; Glenn, G. M.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Linehan, W. M.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Glenn, GM (reprint author), Div Canc Epidemiol & Genet, NCI NIH EPS Room 7108,6120 Execut Blvd,MSC 7236, Bethesda, MD 20892 USA. EM glenng@nih.gov NR 23 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JUL PY 2002 VL 39 IS 7 AR e37 DI 10.1136/jmg.39.7.e37 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA V28HS UT WOS:000208672500004 PM 12114494 ER PT J AU O'Sullivan, CE Peng, RS Cole, KS Montelaro, RC Sturgeon, T Jenson, HB Ling, PD AF O'Sullivan, CE Peng, RS Cole, KS Montelaro, RC Sturgeon, T Jenson, HB Ling, PD TI Epstein-Barr virus and human immunodeficiency virus serological responses and viral burdens in HIV-infected patients treated with HAART SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE PCR; EBV; HIV; immune reconstitution; B lymphocytes ID ACTIVE ANTIRETROVIRAL THERAPY; ANTIBODY; TYPE-1; CHILDREN; ANTIGEN; LOAD AB Epstein-Barr virus (EBV) associated non-Hodgkin lymphoma is recognized as a complication of human immunodeficiency virus (HIV) infection. Little is known regarding the influence of highly active antiretroviral therapy (HAART) on the biology of EBV in this population. To characterize the EBV- and HIV-specific serological responses together with EBV DNA levels in a cohort of HIV-infected adults treated with HAART, a study was conducted to compare EBV and HIV serologies and EBV DNA copy number (DNAemia) over a 12-month period after the commencement of HAART. All patients were seropositive for EBV at baseline. Approximately 50% of patients had detectable EBV DNA at baseline, and 27/30 had detectable EBV DNAatsome point over the follow-up period of 1 year. Changes in EBV DNA copy number over time for any individual were unpredictable. Significant increases in the levels of Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr early antigen (EA) antibodies were demonstrated in the 17 patients who had a good response to HAART. Of 29 patients with paired samples tested, four-fold or greater increases in titers were detected for EA in 12/29 (41%), for EBNA in 7/29 (24%), for VCA-IgG in 4/29 (14%); four-fold decreases in titers were detected in 2/29 (7%) for EA and 12/29 (41%) for EBNA. A significant decline in the titer of anti-HIV antibodies was also demonstrated. It was concluded that patients with advanced HIV infection who respond to HAART have an increase in their EBV specific antibodies and a decrease in their HIV-specific antibodies. For the cohort overall, there was a transient increase in EBV DNA levels that had declined by 12 months. (C) 2002 Wiley-Liss, Inc. C1 Univ Alabama, Dept Med, Birmingham, AL USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA USA. Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX USA. RP O'Sullivan, CE (reprint author), NCI, Immunocompromised Host Sect, NIH, Bldg 10 Rm 13C110 9000 Rockville Pike, Bethesda, MD 20892 USA. OI Jenson, Hal/0000-0002-6549-860X FU NIAID NIH HHS [AI28243, AI36211, AI-27767] NR 20 TC 24 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUL PY 2002 VL 67 IS 3 BP 320 EP 326 DI 10.1002/jmv.10080 PG 7 WC Virology SC Virology GA 558RH UT WOS:000175980000004 PM 12116021 ER PT J AU Heymann, JB Moller, C Muller, DJ AF Heymann, JB Moller, C Muller, DJ TI Sampling effects influence heights measured with atomic force microscopy SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE AFM; Nyquist theorem; membrane; protein; resolution ID HIGH-RESOLUTION; ANGSTROM RESOLUTION; PURPLE MEMBRANE; SUBNANOMETER-RESOLUTION; CONFORMATIONAL CHANGE; SURFACE-STRUCTURES; CHOLERA-TOXIN; BACTERIORHODOPSIN; BILAYERS; ELECTRON AB The atomic force microscope (AFM) is an exquisitely delicate probe measuring the height of a specimen at discrete sampling points in a fixed two-dimensional (2D) raster. The resulting topograph is a 2D digital image, with each pixel representing a distinct height measurement. The height of an object is determined as the average of the maximum heights measured above the supporting surface. We show that such object heights derived from a variety of organic samples depend critically on the sampling or pixel size of the 2D raster. It is concluded that to obtain accurate specimen heights, the pixel size must be small enough to resolve submolecular structures and thus ensure representative sampling of the height variation on the surface. C1 Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany. NIAMS, LSBR, NIH, Bethesda, MD 20892 USA. Tech Univ Dresden, BIOTEC, Dresden, Germany. RP Muller, DJ (reprint author), Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany. RI Heymann, Bernard/F-6825-2011; Muller, Daniel/A-5967-2010; OI Muller, Daniel/0000-0003-3075-0665; Heymann, Bernard/0000-0002-8872-5326 NR 54 TC 5 Z9 5 U1 1 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD JUL PY 2002 VL 207 BP 43 EP 51 DI 10.1046/j.1365-2818.2002.01039.x PN 1 PG 9 WC Microscopy SC Microscopy GA 576VN UT WOS:000177026900005 PM 12135458 ER PT J AU Farrell, EF Gomez, AM Antaramian, A Benkusky, NA Fananapazir, L Valdivia, HH AF Farrell, EF Gomez, AM Antaramian, A Benkusky, NA Fananapazir, L Valdivia, HH TI Sorcin, a modulator of excitation contraction coupling in heart. SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract C1 Univ Wisconsin, Madison, WI 53706 USA. INSERM, Montpellier, France. NHLBI, NIH, Bethesda, MD 20892 USA. RI Gomez, Ana Maria/B-5376-2013 OI Gomez, Ana Maria/0000-0003-0009-2884 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2002 VL 34 IS 7 BP A19 EP A19 DI 10.1016/S0022-2828(02)90141-0 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 579YR UT WOS:000177207100079 ER PT J AU Gabel, SA Cross, HR Walker, VR London, RE Steenbergen, C Korach, KS Murphy, E AF Gabel, SA Cross, HR Walker, VR London, RE Steenbergen, C Korach, KS Murphy, E TI Gender effects of ischemia reperfusion injury: The role of estrogen receptor alpha and beta SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2002 VL 34 IS 7 BP A23 EP A23 DI 10.1016/S0022-2828(02)90149-5 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 579YR UT WOS:000177207100088 ER PT J AU Imahashi, K Tong, HY Steenbergen, C Murphy, E AF Imahashi, K Tong, HY Steenbergen, C Murphy, E TI Inhibition of GSK-3 beta reduces infarct size SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract C1 Duke Univ, Durham, NC USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2002 VL 34 IS 7 BP A35 EP A35 DI 10.1016/S0022-2828(02)90196-3 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 579YR UT WOS:000177207100135 ER PT J AU Hoferkamp, C Das Peddada, S AF Hoferkamp, C Das Peddada, S TI Parameter estimation in linear models with heteroscedastic variances subject to order restrictions SO JOURNAL OF MULTIVARIATE ANALYSIS LA English DT Article DE fixed effects; heteroscedastic errors; isotonic regression; maximum likelihood estimation; mixed effects; simple order restriction ID MAXIMUM-LIKELIHOOD-ESTIMATION; REPLICATED EXPERIMENTS AB Estimation of parameters in linear fixed and mixed effects models, under order restrictions on the error variances, is considered in this article. For simplicity of exposition, we shall assume that the error variances are subject to simple order restriction. Similar methodology can be developed for other forms of order restrictions as well. (C) 2001 Elsevier Science (USA). C1 Truman State Univ, Kirksville, MO USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Hoferkamp, C (reprint author), Truman State Univ, Kirksville, MO USA. RI Peddada, Shyamal/D-1278-2012 NR 17 TC 6 Z9 7 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0047-259X J9 J MULTIVARIATE ANAL JI J. Multivar. Anal. PD JUL PY 2002 VL 82 IS 1 BP 65 EP 87 DI 10.1006/jmva.2001.2010 PG 23 WC Statistics & Probability SC Mathematics GA 576NB UT WOS:000177010400004 ER PT J AU Ghribi, O Herman, MM Spaulding, NK Savory, J AF Ghribi, O Herman, MM Spaulding, NK Savory, J TI Lithium inhibits aluminum-induced apoptosis in rabbit hippocampus, by preventing cytochrome c translocation, Bcl-2 decrease, Bax elevation and caspase-3 activation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE aluminum; apoptosis; Bcl-2; caspase-3; hippocampus; lithium ID GLYCOGEN-SYNTHASE KINASE-3-BETA; CEREBELLAR GRANULE CELLS; X-L; INDUCED NEURODEGENERATION; ENDOPLASMIC-RETICULUM; CEREBRAL-ISCHEMIA; MITOCHONDRIA; PROTEIN; ALZHEIMERS; NEURONS AB A variety of studies on neuronal death models suggest that lithium has neuroprotective properties. In the present investigation, we have examined the effect of chronic lithium treatment on hippocampus, as monitored by changes at the subcellular level of apoptosis-regulatory proteins which have been induced by the neurotoxin, aluminum maltolate. Intracisternal administration of aluminum into rabbit brain induces cytochrome c release, decreases levels of the anti-apoptotic proteins Bcl-2 and Bcl-X-L , increases levels of the pro-apoptotic Bax, activates caspase-3, and causes DNA fragmentation as measured by the TUNEL assay. Pretreatment for 14 days with 7 mm of lithium carbonate in drinking water prevents aluminum-induced translocation of cytochrome c , and up-regulates Bcl-2 and Bcl-X-L,X- down-regulates Bax, abolishes caspase-3 activity and reduces DNA damage. The regulatory effect of lithium on the apoptosis-controlling proteins occurs in both the mitochondria and endoplasmic reticulum. We propose that the neuroprotective effect of lithium involves the modulation of apoptosis-regulatory proteins present in the subcellular organelles of rabbit brain. C1 Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22908 USA. NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA. RP Savory, J (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Pathol, POB 800214, Charlottesville, VA 22908 USA. NR 40 TC 74 Z9 82 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2002 VL 82 IS 1 BP 137 EP 145 DI 10.1046/j.1471-4159.2002.00957.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 566QC UT WOS:000176438900016 PM 12091474 ER PT J AU Kita, T Morrison, PF Heyes, MP Markey, SP AF Kita, T Morrison, PF Heyes, MP Markey, SP TI Effects of systemic and central nervous system localized inflammation on the contributions of metabolic precursors to the L-kynurenine and quinolinic acid pools in brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE kynurenine pathway; pharmacokinetics; protein binding; stable isotope labeling ID PERFORMANCE LIQUID-CHROMATOGRAPHY; RAT-BRAIN; IN-VIVO; NEUROLOGICAL DISEASE; PATHWAY METABOLITES; L-TRYPTOPHAN; 4-CHLORO-3-HYDROXYANTHRANILATE; BLOOD; SERUM; 6-CHLOROTRYPTOPHAN AB L-Kynurenine and quinolinic acid are neuroactive L-tryptophan-kynurenine pathway metabolites of potential importance in pathogenesis and treatment of neurologic disease. To identify precursors of these metabolites in brain, [(2) H-3 ]-L-kynurenine was infused subcutaneously by osmotic pump into three groups of gerbils: controls, CNS-localized immune-activated, and systemically immune-activated. The specific activity of L-kynurenine and quinolinate in blood, brain and systemic tissues at equilibrium was then quantified by mass spectrometry and the results applied to a model of metabolism to differentiate the relative contributions of various metabolic precursors. In control gerbils, 22% of L-kynurenine in brain was derived via local synthesis from L-tryptophan/formylkynurenine versus 78% from L-kynurenine from blood. Quinolinate in brain was derived from several sources, including: local tissue L-tryptophan/formylkynurenine (10%), blood L-kynurenine (35%), blood 3-hydroxykynurenine/3-hydroxyanthranilate (7%), and blood quinolinate (48%). After systemic immune-activation, however, L-kynurenine in brain was derived exclusively from blood, whereas quinolinate in brain was derived from three sources: blood L-kynurenine (52%), blood 3-hydroxykynurenine or 3-hydroxyanthranilate (8%), and blood quinolinate (40%). During CNS-localized immune activation, > 98% of both L-kynurenine and quinolinate were derived via local synthesis in brain. Thus, immune activation and its site determine the sources from which L-kynurenine and quinolinate are synthesized in brain. Successful therapeutic modulation of their concentrations must take into account the metabolic and compartment sources. C1 NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, ORS, Bethesda, MD USA. RP Markey, SP (reprint author), NIMH, Lab Neurotoxicol, NIH, 10 Ctr Dr,Room 3D42, Bethesda, MD 20892 USA. NR 34 TC 34 Z9 34 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2002 VL 82 IS 2 BP 258 EP 268 DI 10.1046/j.1471-4159.2002.00955.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 570HQ UT WOS:000176653200007 PM 12124427 ER PT J AU Ozsarac, N Santha, E Hoffman, BJ AF Ozsarac, N Santha, E Hoffman, BJ TI Alternative non-coding exons support serotonin transporter mRNA expression in the brain and gut SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE alternative splicing; gut; promoter; serotonin transporter; tissue-specific ID IRRITABLE-BOWEL-SYNDROME; MESSENGER-RNA; RAT-BRAIN; PROMOTER POLYMORPHISM; ASTROCYTIC PROCESSES; AFFECTIVE-DISORDERS; REGULATORY REGION; RT-PCR; GENE; ASSOCIATION AB A number of studies in recent years have linked polymorphisms within the serotonin transporter (5HTT) gene to affective disorders and anxiety traits. The human 5HTT mRNA is alternatively spliced, and the splice variants are equally expressed in the human placental cell line and dorsal raphe. In this study, using 5' rapid amplification of cDNA ends, we show that the rat 5HTT mRNA is alternatively spliced, leading to three distinct mRNAs differing in the 5' untranslated region. To determine whether the three alternatively spliced mRNA species that contain one of the following untranslated regions (i) exon 1A, 63 bp (ii) exon 1A + 1B, 125 bp or (iii) exon 1C, 101 bp, were expressed in a tissue-specific manner, we used RT-PCR and exon-specific oligonucleotide hybridization. Our results suggest two of the variants (1A + 1B and 1A) may utilize the same promoter; however, they are not equally expressed. While in the adult CNS and adrenal medulla, the shorter mRNA consisting of exon 1A was considerably more abundant, in the stomach and heart, the two variants were equally expressed. The third splice variant exon 1C is only expressed in the gut and to a lesser extent in the heart. The data from this study suggest the splice variant consisting of exon 1C may utilize a distinct promoter compared to the other two. C1 Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Ozsarac, N (reprint author), Australian Natl Univ, John Curtin Sch Med Res, GPO Box 334, Canberra, ACT 2601, Australia. NR 33 TC 17 Z9 18 U1 2 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2002 VL 82 IS 2 BP 336 EP 344 DI 10.1046/j.1471-4159.2002.00964.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 570HQ UT WOS:000176653200014 PM 12124434 ER PT J AU Jedynak, JP Ali, SF Haycock, JW Hope, BT AF Jedynak, JP Ali, SF Haycock, JW Hope, BT TI Acute administration of cocaine regulates the phosphorylation of serine-19,-31 and-40 in tyrosine hydroxylase SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE amygdala; caudate; dopamine; nucleus accumbens; ventral tegmental area ID PROTEIN KINASE-II; RAT-BRAIN; CHROMAFFIN CELLS; DOPAMINE RELEASE; NERVE-TERMINALS; ACTIVATION; BIOSYNTHESIS; SEROTONIN; SERINE-31; RECEPTORS AB Acute cocaine can inhibit catecholamine biosynthesis by regulating the enzymatic activity of tyrosine hydroxylase via alterations in the phosphorylation state of the enzyme. The mechanisms underlying acute cocaine-dependent regulation of tyrosine hydroxylase phosphorylation have not been determined. In this study, 0, 15 or 30 mg/kg cocaine was administered intraperitoneally to rats and the phosphorylation state of tyrosine hydroxylase in the brain was examined using antibodies specific for the phosphorylated forms of serine-19, -31 and -40 in tyrosine hydroxylase. In the caudate and nucleus accumbens, cocaine dose-dependently decreased the levels of phosphorylated serine-19, -31 and -40. In the ventral tegmental area, the levels of phosphorylated serine-19, but not serine-31 and -40, were decreased by 15 and 30 mg/kg cocaine. In the amygdala, the levels of phosphorylated serine-19, but not serine-31 or -40, were decreased. The functional effects of these alterations in phosphorylation state were assessed by measuring tyrosine hydroxylase activity in vivo (accumulation of DOPA after administration of the decarboxylase inhibitor NSD-1015). Acute administration of 30 mg/kg cocaine significantly decreased l-DOPA production in caudate and accumbens but not in amygdala. These data suggest that the phosphorylation of serine-31 or -40, but not serine-19, is involved in the regulation of tyrosine hydroxylase activity by acute cocaine. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, New Orleans, LA USA. RP Hope, BT (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 NR 35 TC 19 Z9 19 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2002 VL 82 IS 2 BP 382 EP 388 DI 10.1046/j.1471-4159.2002.00982.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 570HQ UT WOS:000176653200019 PM 12124439 ER PT J AU Rhen, T Crews, D AF Rhen, T Crews, D TI Variation in reproductive behaviour within a sex: Neural systems and endocrine activation SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Review DE alternative tactics; hormones; hypothalamus; intrasexual variation; reproductive behaviour ID ALTERNATIVE MALE PHENOTYPES; NAKED MOLE-RATS; PLATYFISH XIPHOPHORUS-MACULATUS; GECKO EUBLEPHARIS-MACULARIUS; HATCHLING SNAPPING TURTLES; HORMONE-RELEASING HORMONE; VOCAL CONTROL-SYSTEM; MALE CRICKET FROGS; INCUBATION-TEMPERATURE; ARGININE VASOTOCIN AB Intrasexual variation in reproductive behaviour, morphology and physiology is taxonomically widespread in vertebrates, and is as biologically and ecologically significant as the differences between the sexes. In this review, we examine the diverse patterns of intrasexual variation in reproductive behaviours within vertebrates. By illustrating the genetic, cellular, hormonal and/or neural mechanisms underlying behavioural variation in a number of species, another level of complexity is added to studies of brain organization and function. Such information increases our understanding of the unique and conserved mechanisms underlying sex and individual differences in behaviour in vertebrates as a whole. Here, we show that intrasexual variation in behaviour may be discrete or continuous in nature. Moreover, this variation may be due to polymorphism at a single genetic locus or many loci, or may even be the result of phenotypic plasticity. Phenotypic plasticity simply refers to cases where a single genotype (or individual) can produce (or display) different phenotypes. Defined in this way, plasticity subsumes many different types of behavioural variation. For example, some behavioural phenotypes are established by environmental factors during early ontogeny, others are the result of developmental transitions from one phenotype early in life to another later in life, and still other strategies are facultative with different behaviours displayed in different social contexts. C1 Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Univ Texas, Sch Biol Sci, Sect Integrat Biol, Austin, TX USA. RP Rhen, T (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 108 TC 88 Z9 91 U1 2 U2 12 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JUL PY 2002 VL 14 IS 7 BP 517 EP 531 DI 10.1046/j.1365-2826.2002.00820.x PG 15 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 570QT UT WOS:000176669600001 PM 12121488 ER PT J AU Harris, RE Coulombe, MG Feller, MB AF Harris, RE Coulombe, MG Feller, MB TI Dissociated retinal neurons form periodically active synaptic circuits SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CULTURED CORTICAL-NEURONS; STARBURST AMACRINE CELLS; CA3 NETWORK ACTIVITY; CALCIUM TRANSIENTS; GANGLION-CELLS; MAMMALIAN RETINA; IN-VITRO; OSCILLATORY ACTIVITY; HIPPOCAMPAL-NEURONS; ACTION-POTENTIALS AB Throughout the developing nervous system, immature circuits generate rhythmic activity patterns that influence the formation of adult networks. The cellular mechanisms underlying this spontaneous, correlated activity can be studied in dissociated neuronal cultures. Using calcium imaging and whole cell recording, we showed that cultured dissociated mammalian retinal neurons form networks that produce spontaneous, correlated, highly periodic activity. As the culture matures, the spatial correlations of the periodic calcium transients evolve from being highly synchronized across neighboring cells to propagating across the culture in a wavelike manner reminiscent of retinal waves recorded in vivo. Spontaneous calcium transients and synaptic currents were blocked either by cadmium, tetrodotoxin, or the glutamate receptor antagonist 6,7-dinitroquinoxaline, indicating that the periodic activity was driven primarily by synaptic transmission between retinal ganglion cells. Evoked responses between pairs of ganglion cells exhibited paired-pulse synaptic depression, and the time constant of recovery from this depression was similar to the interval between periodic events. These results suggest that synaptic depression may regulate the frequency of network activity. Together, these findings provide insight into how networks containing primarily excitatory connections generate highly correlated activity. C1 NINDS, Synapse Format & Funct Unit, NIH, Bethesda, MD 20892 USA. RP Feller, MB (reprint author), Univ Calif San Diego, Div Biol, Neurobiol Sect 0357, 9500 Gilman Dr, La Jolla, CA 92093 USA. RI Harris, Richard/F-1307-2011 NR 60 TC 21 Z9 21 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2002 VL 88 IS 1 BP 188 EP 195 DI 10.1152/jn.00722.2001 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 567PT UT WOS:000176493800018 PM 12091544 ER PT J AU Sohn, YH Wiltz, K Hallett, M AF Sohn, YH Wiltz, K Hallett, M TI Effect of volitional inhibition on cortical inhibitory mechanisms SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; HUMAN CORTICOSPINAL EXCITABILITY; SILENT PERIOD; HAND MOVEMENT; FACILITATION; SYSTEM; TASK AB To investigate the effect of volitional inhibition on cortical inhibitory mechanisms, we performed transcranial magnetic stimulation (TMS) studies with a Go/NoGo reaction task in seven healthy subjects. Subjects were asked to extend their right index finger only after Go, but to remain relaxed after NoGo. Single- and paired-pulse TMS were triggered at the average reaction time for the Go response in each subject after Go or NoGo cues. Motor evoked potentials were recorded in the extensor indicis proprius (EIP) and abductor digiti minimi (ADM) muscles of right hand. Paired-pulse TMS with subthreshold conditioning stimuli at interstimulus intervals (ISIs) of 2 ms [short intracortical inhibition (SICI)] and 15 ms [intracortical facilitation (ICF)] and that with suprathreshold conditioning stimuli at ISI of 80 ms [long intracortical inhibition (LICI)] were performed in both Go/NoGo and control conditions. Inhibition of SICI was enhanced in both EIP and ADM after NoGo and was reduced only in EIP after Go. Inhibition of LICI was reduced in both muscles during both conditions, while ICF was not altered. The present results demonstrate that volitional inhibition enhances SICI but reduces LICI nonselectively. These results suggest that these two inhibitory mechanisms act differently during execution and suppression of voluntary movements. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Yonsei Univ, Coll Med, Dept Neurol, Seoul 120752, South Korea. Yonsei Univ, Coll Med, Brain Res Inst, Seoul 120752, South Korea. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC1428, Bethesda, MD 20892 USA. NR 27 TC 74 Z9 75 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2002 VL 88 IS 1 BP 333 EP 338 DI 10.1152/jn.00863.2001 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 567PT UT WOS:000176493800032 PM 12091558 ER PT J AU Ruskin, DN Bergstrom, DA Walters, JR AF Ruskin, DN Bergstrom, DA Walters, JR TI Nigrostriatal lesion and dopamine agonists affect firing patterns of rodent entopeduncular nucleus neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID NIGRA PARS-RETICULATA; GLOBUS-PALLIDUS NEURONS; MPTP-INDUCED PARKINSONISM; BASAL GANGLIA OUTPUT; SUBSTANTIA-NIGRA; SUBTHALAMIC NUCLEUS; MULTISECOND OSCILLATIONS; RECEPTOR STIMULATION; INDUCED DYSKINESIAS; TREATED MONKEY AB Altered activity of the entopeduncular nucleus, the rodent homologue of the globus pallidus internal segment in primates, is thought to mediate behavioral consequences of midbrain dopamine depletion in rodents. Few studies, however, have examined dopaminergic modulation of spiking activity in this nucleus. This study characterizes changes in entopeduncular neuronal activity after nigrostriatal dopaminergic lesion and the effects of systemic treatment with selective D-1 (SKF 38393) and D-2 (quinpirole) agonists in lesioned rats. Extracellular single-unit recordings were performed in awake immobilized rats, either in neurologically intact animals (n = 42) or in animals that had received unilateral 6-hydroxydopamine infusion into the medial forebrain bundle several weeks previously (n = 35). Nigrostriatal lesion altered baseline activity of entopeduncular neurons in several ways. Interspike interval distributions had significantly decreased modes and significantly increased coefficient of variation, skewness and kurtosis; yet interspike interval mean (the inverse of firing rate) was not affected. Also, spectral analysis of autocorrelograms indicated that lesion significantly reduced the incidence of regular-spiking neurons and increased the incidence of neurons with 4-18 Hz oscillations. Dopamine agonist treatment reversed some lesion-induced effects: quinpirole reversed changes in interspike interval distribution mode and coefficient of variation, while combined quinpirole and SKF 38393 blocked the appearance of 4-18 Hz oscillations. However, no agonist treatment normalized all aspects of entopeduncular activity. Additionally, inhibition of firing rates by D-1 or combined D-1/D-2 receptor activation indicated that dopamine agonists affected the overall level of entopeduncular activity in a manner similar to that found in the substantia nigra pars reticulata and globus pallidus internal segment after dopamine neuron lesion. These data demonstrate that lesion of the nigrostriatal tract leads to modifications of several aspects of firing pattern in the rodent entopeduncular nucleus and so expand on similar findings in the rodent substantia nigra pars reticulata and in the globus pallidus internal segment in humans and nonhuman primates. The results support the view that dysfunction in the basal ganglia after midbrain dopamine neuron loss relates more consistently to abnormal activity patterns than to net changes in firing rate in the basal ganglia output nuclei, while overall decreases in firing rate in these structures may play a more important role in adverse motor reactions to dopamine agonist treatments. C1 NINDS, Neurophysiol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Ruskin, DN (reprint author), NINDS, Neurophysiol Pharmacol Sect, NIH, 10 Ctr Dr MSC 1406,Bldg 10,Room 5C103, Bethesda, MD 20892 USA. NR 63 TC 24 Z9 25 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2002 VL 88 IS 1 BP 487 EP 496 DI 10.1152/jn.00844.2001 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 567PT UT WOS:000176493800044 PM 12091570 ER PT J AU Muir-Robinson, G Hwang, BJ Feller, MB AF Muir-Robinson, G Hwang, BJ Feller, MB TI Retinogeniculate axons undergo eye-specific segregation in the absence of eye-specific layers SO JOURNAL OF NEUROSCIENCE LA English DT Article DE retinogeniculate segregation; retinal waves; spontaneous activity; visual-system development; eye-specific layers; nicotinic receptor subunits ID NICOTINIC ACETYLCHOLINE-RECEPTORS; DEVELOPING MAMMALIAN RETINA; POSTNATAL-DEVELOPMENT; GANGLION-CELLS; MICE LACKING; PROJECTIONS; EXPRESSION; SUBUNITS; CIRCUITS; BETA-2 AB Spontaneous retinal activity mediated by cholinergic transmission regulates the segregation of retinal ganglion cell axons in the lateral geniculate nucleus of the thalamus into eye-specific layers. The details of how the layers form are unknown. Mice lacking the beta2 subunit of the neuronal nicotinic acetylcholine receptor lack ACh-mediated waves and as a result, do not form eye-specific layers at any stage of development. However, during the second postnatal week, beta2-/- mice have glutamate-mediated waves. Here we show that after the first postnatal week, even in the absence of layers, retinothalamic axons segregate into an unlayered, patchy distribution of eye-specific regions. These results indicate that spontaneous neural activity may independently regulate eye-specific segregation and the formation of layers at the developing retinothalamic projection. C1 Univ Calif San Diego, Div Biol, Neurobiol Sect 0357, La Jolla, CA 92093 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Feller, MB (reprint author), Univ Calif San Diego, Div Biol, Neurobiol Sect 0357, 9500 Gilman Dr, La Jolla, CA 92093 USA. FU NEI NIH HHS [R01 EY013528] NR 29 TC 118 Z9 120 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 1 PY 2002 VL 22 IS 13 BP 5259 EP 5264 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 569JK UT WOS:000176599100002 PM 12097474 ER PT J AU Hamelink, C Lee, HW Chen, Y Grimaldi, M Eiden, LE AF Hamelink, C Lee, HW Chen, Y Grimaldi, M Eiden, LE TI Coincident elevation of cAMP and calcium influx by PACAP-27 synergistically regulates vasoactive intestinal polypeptide gene transcription through a novel PKA-independent signaling pathway SO JOURNAL OF NEUROSCIENCE LA English DT Article DE vasoactive intestinal polypeptide; VIP; pituitary adenylate cyclase-activating polypeptide; PACAP; calcium; cAMP; signal transduction; calcineurin; mitogen activated protein kinase; MAPK ID CYCLASE-ACTIVATING POLYPEPTIDE; RAT ADRENAL-MEDULLA; BOVINE CHROMAFFIN CELLS; PROTEIN-KINASE-C; SPLANCHNIC NERVE-STIMULATION; MESSENGER-RNA LEVELS; CATECHOLAMINE SECRETION; ENKEPHALIN BIOSYNTHESIS; TYROSINE-HYDROXYLASE; SYMPATHETIC NEURONS AB Pituitary adenylate cyclase-activating polypeptide (PACAP) causes calcium influx, intracellular calcium release, and elevation of cAMP in chromaffin cells. Calcium influx is required for PACAP-stimulated secretion of catecholamines and neuropeptides. The role of cAMP elevation in the action of PACAP at either sympathetic or adrenomedullary synapses, however, is unknown. Here, we show that PACAP-27-induced calcium influx through voltage-sensitive calcium channels (VSCCs), together with elevation of intracellular cAMP, was sufficient to stimulate vasoactive intestinal polypeptide (VIP) biosynthesis at least 40-fold. Combined treatment of chromaffin cells with 40 mM KCl, which elevates intracellular calcium, and 25 muM forskolin, which elevates intracellular cAMP, caused an increase in VIP peptide and mRNA much greater than that elicited by either agent alone, and comparable to the increase caused by 10-100 nM PACAP-27. Elevation of VIP mRNA by either KCl plus forskolin, or PACAP, (1) was independent of new protein synthesis, (2) was blocked by inhibition of calcium influx through voltage-sensitive calcium channels, (3) was calcineurin dependent, and (4) was dependent on MAP kinase activation but not activation of protein kinase A. The degree of activation of two different second-messenger pathways, calcium influx and cAMP elevation, appears to determine the magnitude of transcriptional activation of the VIP gene in chromaffin cells. Maximal stimulation of VIP biosynthesis by PACAP appears to require the coincident activation of both of these pathways. C1 NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. RP Eiden, LE (reprint author), Bldg 36,Room 2A-11,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Grimaldi, Maurizio/0000-0002-7331-7055; Eiden, Lee/0000-0001-7524-944X NR 82 TC 45 Z9 46 U1 0 U2 3 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 JUL 1 PY 2002 VL 22 IS 13 BP 5310 EP 5320 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 569JK UT WOS:000176599100010 PM 12097482 ER PT J AU Ziemann, U Wittenberg, GF Cohen, LG AF Ziemann, U Wittenberg, GF Cohen, LG TI Stimulation-induced within-representation and across-representation plasticity in human motor cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE stimulation-induced plasticity; input-specificity; across-representation plasticity; transient ischemic nerve block; transcranial magnetic stimulation; repetitive stimulation; motor evoked potential; human motor cortex ID LONG-TERM POTENTIATION; TRANSCRANIAL MAGNETIC STIMULATION; PHANTOM LIMB PAIN; INTRACORTICAL MICROSTIMULATION; MOVEMENT REPRESENTATIONS; CORTICAL REORGANIZATION; HORIZONTAL CONNECTIONS; RAPID REORGANIZATION; SOMATOSENSORY CORTEX; OUTPUT MAPS AB The human motor cortex contains a dynamic and distributed network of motor representations. Formation, maintenance, and modification of these representations is an activity-driven process. Repeated stimulation of one representation results in increased motor output from this representation, a process referred to as "within-representation plasticity." We showed previously that within-representation plasticity of the upper arm representation occurs when repetitive transcranial magnetic stimulation (rTMS) is delivered to that representation during transient ischemic nerve block (INB) of the contralateral hand. INB reduces inhibition in the motor cortex and thus lowers the threshold for stimulation-induced plasticity. Here we studied the effects of rTMS delivered to nearby body part representations on the motor output from the upper arm representation. Six healthy subjects underwent INB-alone (control), or INB plus 30 min of focal 0.1 Hz rTMS of either the face, hand, arm, leg, or overlap arm/hand representations in motor cortex. INB-alone and rTMS of the leg representation resulted in only a short-lasting (< 20 min) increase in motor output from the arm representation, as measured by motor evoked potentials in the biceps. rTMS of arm and arm/hand representations induced a prolonged (> 60 min) within-representation increase. In contrast, rTMS of face or hand representations canceled the short-lasting increase and even led to a long-lasting decrease of motor output from the arm representation. Therefore, rTMS of the experimentally disinhibited motor cortex induces within-representation increase, and across-representation decrease of motor cortical output. This bidirectional plasticity might be used for purposeful modulation of human cortical function. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Ziemann, U (reprint author), Univ Frankfurt, Neurol Clin, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. NR 55 TC 31 Z9 31 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 1 PY 2002 VL 22 IS 13 BP 5563 EP 5571 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 569JK UT WOS:000176599100035 PM 12097507 ER PT J AU Jameson, RR Carlson, BA Butz, M Esser, K Hatfield, DL Diamond, AM AF Jameson, RR Carlson, BA Butz, M Esser, K Hatfield, DL Diamond, AM TI Selenium influences the turnover of selenocysteine tRNA ([Ser]Sec) in Chinese hamster ovary cells SO JOURNAL OF NUTRITION LA English DT Article DE selenium; tRNA; selenoprotein; selenocysteine; translation ID GLUTATHIONE-PEROXIDASE ACTIVITY; TRANSFER-RNA; TRANSFER RNASEC; TRNA(SEC) GENE; MAMMALIAN-CELLS; SELENOPROTEIN; TRANSLATION; POPULATION; INHIBITION; EXPRESSION AB Selenocysteine transfer RNA (tRNA([Ser]Sec)) is a central molecule in the production of selenium-containing proteins, and may play a role in the regulation of their biosynthesis. Selenium concentration influences both the levels of tRNA([Ser]Sec) and the relative abundance of two isoforms. To study the mechanism by which selenium affects tRNA([Ser]Sec) levels, Chinese hamster ovary (CHO) cells were treated with the transcription inhibitor, actinomycin D, and tRNA([Ser]Sec) levels were determined by Northern blotting, primer extension and reverse-phase column chromatography. Turnover of tRNA([Ser]Sec) in CHO cells was faster than the total tRNA population. Supplementation of the culture media with selenium reduced turnover of tRNA([Ser]Sec), but did not influence turnover of a randomly selected serine tRNA. Inhibition of transcription with actinomycin D resulted in a relative increase in the abundance of the isoform containing methylcarboxymethyl-5'-uridine-2'-O-methylribose in the wobble position of the anticodon. Primer extension studies, which permitted the independent evaluation of the tRNA([Ser]Sec) arising from the introduced mouse gene and that derived from the host CHO gene, indicated an accelerated decline in tRNA([Ser]Sec) derived from both the transfected and the native gene. These results provide additional insight into the levels of regulation that control the translation of selenium containing proteins in mammalian cells. C1 Univ Illinois, Dept Human Nutr, Chicago, IL 60612 USA. NIH, Sect Mol Biol Selenium, Basic Res Lab, Bethesda, MD 20892 USA. Univ Illinois, Dept Kinesiol, Chicago, IL 60612 USA. RP Diamond, AM (reprint author), Univ Illinois, Dept Human Nutr, Chicago, IL 60612 USA. FU NCI NIH HHS [2R01 CA081153] NR 31 TC 9 Z9 10 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JUL PY 2002 VL 132 IS 7 BP 1830 EP 1835 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 569NP UT WOS:000176608700006 PM 12097655 ER PT J AU Zheng, TZ Cantor, KP Zhang, YW Lynch, CF AF Zheng, TZ Cantor, KP Zhang, YW Lynch, CF TI Occupation and bladder cancer: A population-based, case-control study in Iowa SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID RISK-FACTORS; DRINKING-WATER; UNITED-STATES; MORTALITY; EXPOSURE; WORKERS; COHORT; WOMEN; ASSOCIATIONS; SURVEILLANCE AB Mile considerable efforts have been made to investigate the role of occupation and industry in the risk of bladder cancer, many reported associations have not been consistent, and strong evidence of increased risk is apparent for few occupational groups. To further examine the issue, a large, population-based, case-control study was conducted in the state of Iowa among both men and women. A total of 1452 incident bladder cancer cases and 2434 controls were included in the study. Occupational history was collected from respondents for each job held for 5 years or longer since age 16. Among men excess risk was observed for, industries including plumbing, heating, and air conditioning (odds ratio [OR], = 2.2; 95 % confidence interval [CI], 1.0 to 5.0); rubber and plastic products (OR = 3.1; 95 % CI, 1.2 to 8.5), motor vehicle Parts and supplies (OR = 4.5; 95 % CI, 1.2 to 16.5), and occupations including supervisors for transportation and material moving (OR = 6.5, 95 % CI, 1.4 to 29.9), material-moving-equipment operators (OR = 1.9; 95 % CI, 1.0 to 3.6), automobile mechanics (OR = 1.6; 95 % CI, 1.0 to 2.6), painters (OR = 2.7; 95 % CI, 1.0 to 7.7), and metal- and plastic-working machine operators (OR = 2.0; 95 % CI, 1.1 to 3.4). Among women, significant excess risk was observed for secondary school teachers and record clerks. Housekeepers and butlers and workers in laundering and dry cleaning were also at increased risk. In conclusion, these results suggest that occupational exposures may play a significant role in the risk of bladder cancer. C1 Yale Univ, Sch Publ Hlth, Div Environm Hlth Sci, New Haven, CT USA. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. RP Zheng, TZ (reprint author), 129 Church St,Suite 700, New Haven, CT 06510 USA. FU NCI NIH HHS [N01-CP-51,026, N01-CP-85,614] NR 40 TC 26 Z9 27 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUL PY 2002 VL 44 IS 7 BP 685 EP 691 DI 10.1097/01.jom.0000023380.41727.e9 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 573RU UT WOS:000176845300015 PM 12134533 ER PT J AU Chebli, C Murphey, MD Wientroub, S Collins, MT AF Chebli, C Murphey, MD Wientroub, S Collins, MT TI Orthopedic concerns in children with endocrine disorders SO JOURNAL OF PEDIATRIC ORTHOPAEDICS-PART B LA English DT Review ID MCCUNE-ALBRIGHT-SYNDROME; CAPITAL FEMORAL EPIPHYSIS; GROWTH-HORMONE DEFICIENCY; STIMULATORY G-PROTEIN; FIBROUS DYSPLASIA; PERTHES-DISEASE; HYPOPHOSPHATEMIC OSTEOMALACIA; ACTIVATING MUTATIONS; BONE; PAMIDRONATE C1 NIDCR, CSDB, NIH, Bethesda, MD 20892 USA. RP Collins, MT (reprint author), NIDCR, CSDB, NIH, Bldg 30,Room 225,MSC 4320, Bethesda, MD 20892 USA. NR 63 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1060-152X J9 J PEDIATR ORTHOP B JI J. Pediatr. Orthop.-Part B PD JUL PY 2002 VL 11 IS 3 BP 183 EP 191 PG 9 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 588ZY UT WOS:000177734000001 PM 12089494 ER PT J AU Lublin, M Schwartzentruber, DJ Lukish, J Chester, C Biesecker, LG Newman, KD AF Lublin, M Schwartzentruber, DJ Lukish, J Chester, C Biesecker, LG Newman, KD TI Principles for the surgical management of patients with proteus syndrome and patients with overgrowth not meeting proteus criteria SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Section on Surgery of the American-Academy-of-Pediatrics CY OCT 19-21, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Pediat, Surg Sect DE proteus; overgrowth; mosaicism ID OF-THE-MONTH; MUSCULOSKELETAL MANIFESTATIONS; HAMARTOMATOUS SYNDROME; RADIOLOGICAL FEATURES; DIAGNOSIS; HEMIHYPERTROPHY; TRANSMISSION; LIPOMATOSIS; ANESTHESIA; PATHOLOGY AB Background: Proteus syndrome is a rare, sporadic disorder consisting of disproportionate overgrowth of multiple tissues, vascular malformations, and connective tissue or epidermal nevi. Patients with Proteus syndrome present with diverse and variable phenotypes because of the syndrome's mosaic pattern of distribution. Methods: Eighty patients with Proteus syndrome, satisfying published diagnostic criteria, and 51 patients with overgrowth not meeting Proteus criteria were identified from the literature. Three additional patients, one patient with Proteus syndrome and 2 patients with overgrowth, were treated at the author's institutions and are discussed in detail. All nonorthopedic and noncutaneous surgical interventions were reviewed. Results: Fourteen genitourinary, 9 gastrointestinal, and 5 otolaryngologic operations were performed on patients with Proteus syndrome. Six genitourinary, 5 gastrointestinal, and 2 otolaryngologic operations were performed on patients with overgrowth not meeting Proteus criteria, Eight patients with Proteus syndrome and 4 patients with overgrowth experienced thoracic manifestations, generally diffuse cystic pulmonary lesions, but only 1 of 12 underwent surgical treatment. Conclusions: Patients with visceral manifestations of either Proteus syndrome or overgrowth not meeting Proteus criteria should be treated in a similar manner. Lesions involving the ovaries and testes, because of the high incidence of neoplasm, should be managed aggressively. Gastrointestinal and renal lesions may be managed conservatively with frequent follow-up to minimize abdominal explorations. All patients undergoing surgery should have a thorough preoperative assessment of their airway and pulmonary reserve because of the relatively high frequency of tonsillar hypertrophy and pulmonary cystic involvement. C1 NCI, Surg Branch, Genet Dis Res Branch, Natl Human Genome Res Inst,NIH, Bethesda, MD 20892 USA. Childrens Hosp, Dept Surg, Washington, DC USA. Childrens Hosp, Dept Plast Surg, Washington, DC USA. George Washington Sch Med, Washington, DC USA. RP Schwartzentruber, DJ (reprint author), NCI, Surg Branch, Genet Dis Res Branch, Natl Human Genome Res Inst,NIH, Bldg 10,Rm 2B06, Bethesda, MD 20892 USA. NR 77 TC 14 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JUL PY 2002 VL 37 IS 7 BP 1013 EP 1020 DI 10.1053/jpsu.2002.33832 PG 8 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 569NX UT WOS:000176609400025 PM 12077761 ER PT J AU Guckes, AD Scurria, MS King, TS McCarthy, GR Brahim, JS AF Guckes, AD Scurria, MS King, TS McCarthy, GR Brahim, JS TI Prospective clinical trial of dental implants in persons with ectodermal dysplasia SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the American-Association-of-Dental-Research CY MAR, 1999 CL VANCOUVER, CANADA SP Amer Assoc Dental Res ID PLACEMENT AB Statement of problem. Ectodermal dysplasia is a hereditary condition in which hypodontia is the second most frequently occurring sign. Hypodontia is associated with lack of development of the alveolar ridge and results in less volume of bone for support of conventional prostheses. Minimal development of the alveolar ridge can affect the bone volume available for the placement of dental implants. Purpose. This clinical trial evaluated the survival of implants placed in individuals with a form of ectodermal dysplasia and severe hypodontia. Material and methods. Two hundred sixty-four titanium endosteal dental implants were placed in 51 subjects: 37 males and 14 females between the ages of 8 and 68 (mean age 20.5 years, median age 16.5 years). Two hundred forty-three implants were placed in the anterior mandible, and 21 were placed in the anterior maxilla with a 2-stage surgical protocol. Either fixed-detachable dentures or bar-clip overdentures were provided. Subjects were followed up for 0 to 78 months after second-stage surgery. Kaplan-Meier survival rates and curves were produced to describe the survival of the implants for the different age groups and implant locations. Repeated-measures Cox regression models were used to evaluate the hazard ratios for age and location, with alpha=.05 as the criteria for significance. Results. Of the 243 implants placed in the anterior mandible, 221 (91%) survived. Of the 21 implants placed in the anterior maxilla, 16 (76%) survived. Fourteen of the 5 1 (27%) subjects had a failed implant. All but 2 failures occurred before or at second-stage surgery. Implant- supported prostheses were provided for all patients. Conclusion. Within the limitations of this study, the results support the continued use of endosteal dental implants in this patient population with appropriate precautions in the maxilla. C1 Univ N Carolina, Sch Dent, Dept Prosthodont, Chapel Hill, NC 27599 USA. Penn State Univ, Coll Med, Dept Biostat, Hershey, PA USA. NIH, Ctr Clin, Commissioned Off Dent Clin, Bethesda, MD 20892 USA. NIDCR, NIH, Bethesda, MD 20892 USA. RP Guckes, AD (reprint author), Univ N Carolina, Sch Dent, Dept Prosthodont, Room 300A,Brauer Hall,CB 7450, Chapel Hill, NC 27599 USA. NR 19 TC 54 Z9 57 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD JUL PY 2002 VL 88 IS 1 BP 21 EP 25 DI 10.1067/mpr.2002.127099 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 600EX UT WOS:000178378600005 PM 12239475 ER PT J AU Hortin, GL Murthy, J AF Hortin, GL Murthy, J TI Substrate size selectivity of 20S proteasomes: Analysis with variable-sized synthetic substrates SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE proteasome; proteinases; protein turnover; chromogenic substrates; substrate specificity ID PROTEINASE AB Proteasomes are tubular complexes with proteolytic activities on their lumenal surfaces so that large substrates should be sterically hindered from reaching the catalytic sites. Here we examine effects of substrate size on rates of cleavage by 20S proteasomes of Methanosarcina thermophila. Synthetic chromogenic substrates of variable size were prepared by linking a constant substrate group (Ala-Ala-Phe-p-nitroanilide) to a linear polymer (methoxypolyethylene glycol) with variable chain length. The smallest macromolecular substrates were cleaved more efficiently than free tripeptide substrate, and cleavage of macromolecular substrates was saturable, whereas cleavage of free tripeptide substrate was not, indicating mechanistic differences between the cleavage of large and small substrates. Rates of macromolecular substrate cleavage decreased progressively up to 10-fold as the size of the polymeric component of substrates increased. Macromolecular synthetic substrates appear to be better models of proteasome action on natural protein substrates and demonstrate substrate size selectivity of proteasomes. C1 NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Dept Lab Med, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. NR 20 TC 6 Z9 6 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD JUL PY 2002 VL 21 IS 5 BP 333 EP 337 AR UNSP 0277-8033/02/0700-0333/0 DI 10.1023/A:1019990201364 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 587FH UT WOS:000177629500003 PM 12206507 ER PT J AU Chen, JM Friedman, FK Brandt-Rauf, PW Pincus, MR Chie, L AF Chen, JM Friedman, FK Brandt-Rauf, PW Pincus, MR Chie, L TI Comparison of the average structures, from molecular dynamics, of complexes of GTPase activating protein (GAP) with oncogenic and wild-type ras-p21: Identification of potential effector domains SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE ras-p21; GTPase activating protein; oncogenic and wild-type complexes; molecular dynamics; average structures; effector domains ID ENCODED P21 PROTEIN; NUCLEOTIDE EXCHANGE PROTEIN; OOCYTE MATURATION; 3-DIMENSIONAL STRUCTURES; CHEMOTHERAPEUTIC-AGENTS; SELECTIVE-INHIBITION; SIGNAL-TRANSDUCTION; JUN PROTEINS; RAS PROTEINS; KINASE AB GTPase activating protein (GAP) is a known regulator of ras-p21 activity and is a likely target of ras-induced mitogenic signaling. The domains of GAP that may be involved in this signaling are unknown. In order to infer which domains of GAP may be involved, we have performed molecular dynamics calculations of GAP complexed to wild-type and oncogenic (Val 12-containing) ras-p21, both bound to GTP. We have computed and superimposed the average structures for both complexes and find that there are four domains of GAP that undergo major changes in conformation: residues 821-851, 917-924, 943-953, and 1003-1020. With the exception of the 943-953 domain, none of these domains is involved in making contacts with ras-p21, and all of them occur on the surface of the protein, making them good candidates for effector domains. In addition, three ras-p21 domains undergo major structural changes in the oncogenic p21-GAP complex: 71-76 from the switch 2 domain; 100-108, which interacts with SOS, jun and jun kinase (JNK); and residues 122-138. The change in conformation of the 71-76 domain appears to be induced by changes in conformation in the switch 1 domain (residues 32-40) and in the adjacent domain involving residues 21-31. In an accompanying paper, we present results from microinjection of peptides corresponding to each of these domains into oocytes induced to undergo maturation by oncogenic ras-p21 and by insulin-activated wild-type cellular p21 to determine whether these domain peptides may be involved in ras signaling through GAP. C1 Vet Adm Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. Gilead Sci Inc, Struct Chem, Foster City, CA 94404 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Div Environm Sci, New York, NY 10032 USA. Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA. RP Pincus, MR (reprint author), Vet Adm Med Ctr, Dept Pathol & Lab Med, 800 Poly Pl, Brooklyn, NY 11209 USA. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [CA 42500] NR 37 TC 8 Z9 8 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD JUL PY 2002 VL 21 IS 5 BP 349 EP 359 AR UNSP 0277-8033/02/0700-0349/0 DI 10.1023/A:1019994302273 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 587FH UT WOS:000177629500005 PM 12206509 ER PT J AU Friedman, FK Chie, L Chung, D Robinson, R Brandt-Rauf, P Yamaizumi, Z Pincus, MR AF Friedman, FK Chie, L Chung, D Robinson, R Brandt-Rauf, P Yamaizumi, Z Pincus, MR TI Inhibition of ras-induced oocyte maturation by peptides from ras-p21 and GTPase activating protein (GAP) identified as being effector domains from molecular dynamics calculations SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE GTPase activating protein (GAP); effector domain; molecular dynamics; Val 12-p21; insulin; peptide inhibition of oocyte maturation ID NUCLEOTIDE EXCHANGE PROTEIN; N-TERMINAL KINASE; ONCOGENIC RAS-P21; SIGNAL-TRANSDUCTION; WILD-TYPE; INSULIN; SOS; TRANSFORMATION; EXPRESSION; INDUCTION AB In the accompanying article, using molecular dynamics calculations, we found that the 66-77 and 122-138 domains in ras-p21 and the 821-827, 832-845, 917-924, 943-953, and 1003-1020 domains in GAP have different conformations in complexes of GAP with wild-type and oncogenic ras-p21. We have now synthesized peptides corresponding to each of these domains and coinjected them into oocytes with oncogenic p21, which induces oocyte maturation, or injected them into oocytes incubated with insulin that induces maturation by activating wild-type cellular ras-p21. We find that all of these peptides inhibit both agents but do not inhibit progesterone-induced maturation that occurs by a ras-independent pathway. The p21 66-77 and 122-138 peptides cause greater inhibition of oncogenic p21. On the other hand, the GAP 832-845 and 1003-1021 peptides inhibit insulin-induced maturation to a significantly greater extent. Since we have found that activated wild-type and oncogenic p21 activate downstream targets like raf differently, these GAP peptides may be useful probes for identifying elements unique to the wild-type ras-p21 pathway. C1 Vet Adm Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. Long Isl Univ, Dept Biol, Brooklyn, NY 11201 USA. Long Isl Univ, Dept Chem, Brooklyn, NY 11201 USA. Columbia Univ Coll Phys & Surg, Div Environm Sci, New York, NY 10032 USA. Natl Canc Inst, Tokyo, Japan. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. RP Pincus, MR (reprint author), Vet Adm Med Ctr, Dept Pathol & Lab Med, 800 Poly Pl, Brooklyn, NY 11209 USA. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [CA 42500] NR 21 TC 7 Z9 7 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD JUL PY 2002 VL 21 IS 5 BP 361 EP 366 AR UNSP 0277-8033/02/0700-0361/0 DI 10.1023/A:1019946419111 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 587FH UT WOS:000177629500006 PM 12206510 ER PT J AU Chie, L Friedman, FK Kung, HF Lin, MCM Chung, D Pincus, MR AF Chie, L Friedman, FK Kung, HF Lin, MCM Chung, D Pincus, MR TI Identification of the site of inhibition of mitogenic signaling by oncogenic ras-p21 by a ras effector peptide SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE oncogenic ras-p21; switch 1 domain; 35-47 peptide; constitutively activated raf ID N-TERMINAL KINASE; OOCYTE MATURATION; MAP KINASE; ACTIVATION; PROTEIN; INDUCTION; TRANSFORMATION; TRANSDUCTION; P21(RAS); INSULIN AB We have previously found that a ras switch 1 domain peptide (PNC-7, residues 35-47) selectively blocks oocyte maturation induced by oncogenic (Val 12-containing) ras-p21 protein and also blocks c-raf-induced oocyte maturation. We now find that oncogenic ras-p21 does not inhibit oocyte maturation of a constitutively activated raf protein (raf BXB) that is lacking most of the first 301 amino terminal amino acids, including the major ras binding domain and accessory ras-binding regions. We also find that a dominant negative raf that completely blocks c-raf-induced maturation likewise does not block raf-BXB-induced maturation. We conclude that PNC-7 blocks ras by binding to the amino-terminal domain of raf and that raf BXB must initiate signal transduction in the cytosol. C1 Vet Adm Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. Long Isl Univ, Dept Biol, Brooklyn, NY 11201 USA. Long Isl Univ, Dept Chem, Brooklyn, NY 11201 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. Univ Hong Kong, Inst Mol Technol Drug Design & Synth, Biol Chem Lab, Inst Mol Biol, Hong Kong, Hong Kong, Peoples R China. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. RP Pincus, MR (reprint author), Vet Adm Med Ctr, Dept Pathol & Lab Med, 800 Poly Pl, Brooklyn, NY 11209 USA. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [R01-CA 42500] NR 20 TC 8 Z9 8 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD JUL PY 2002 VL 21 IS 5 BP 367 EP 370 AR UNSP 0277-8033/02/0700-0367/0 DI 10.1023/A:1019998403181 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 587FH UT WOS:000177629500007 PM 12206511 ER PT J AU Ruotolo, BT Verbeck, GF Thomson, LM Woods, AS Gillig, KJ Russell, DH AF Ruotolo, BT Verbeck, GF Thomson, LM Woods, AS Gillig, KJ Russell, DH TI Distinguishing between phosphorylated and nonphosphorylated peptides with ion mobility-mass spectrometry SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE phosphopeptides; high-throughput; MALDI; conformation ID PROTEINS; MIXTURES; IDENTIFICATION; CHROMATOGRAPHY; MALDI AB Mass spectrometry has become an indispensable tool in identifying post-translationally modified proteins, but multiple peptide mass-mapping/peptide-sequencing experiments are required to answer questions involving the site and type of modification present. Here, we apply ion mobility-mass spectrometry (IM-MS), a high-throughput analysis method having high selectivity and sensitivity, to the challenge of identifying phosphorylated peptides. Ion mobility separation is based on the collision cross-section of the ion. Phosphorylation can result in a conformational change in gas-phase peptide ions, which can be detected by IM. To demonstrate this point, a peptide mixture containing a variety of peptide sequences is examined with IM-MS and molecular dynamics calculations. During the course of these studies, two classes of phosphopeptide were identified: (i) phosphorylated peptide ions that have conformers that differ from the nonphosphorylated ion and (ii) phosphorylated peptide ions that have conformations that are very similar to the nonphosphorylated peptide. The utility of IM-MS peptide mass mapping for identifying both types of phosphorylated peptides is discussed. C1 Texas A&M Univ, Dept Chem, Lab Biol Mass Spect, College Stn, TX 77843 USA. NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Texas A&M Univ, Lab Mol Simulat, College Stn, TX 77843 USA. RP Ruotolo, BT (reprint author), Texas A&M Univ, Dept Chem, Lab Biol Mass Spect, College Stn, TX 77843 USA. RI Ruotolo, Brandon/F-2669-2013; Russell, David/C-3618-2015 OI Ruotolo, Brandon/0000-0002-6084-2328; Russell, David/0000-0003-0830-3914 NR 21 TC 57 Z9 57 U1 0 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JUL-AUG PY 2002 VL 1 IS 4 BP 303 EP 306 DI 10.1021/pr025516r PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 599QX UT WOS:000178347600002 PM 12645885 ER PT J AU Castle, PE Karp, DA Zeitlin, L Garcia-Moreno, B Moench, TR Whaley, KJ Cone, RA AF Castle, PE Karp, DA Zeitlin, L Garcia-Moreno, B Moench, TR Whaley, KJ Cone, RA TI Human monoclonal antibody stability and activity at vaginal pH SO JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE monoclonal antibodies; plantibodies; vagina; HIV; HSV; sperm ID IMMUNODEFICIENCY-VIRUS TYPE-1; 3-DIMENSIONAL STRUCTURE; FAB FRAGMENT; NEUTRALIZING ANTIBODY; COMPLEX; TRANSMISSION AB Antibodies can be delivered topically to the vagina to protect against pregnancy and sexually transmitted infections, but the acidity of vaginal secretions (pH 3.5-4.5) might inactivate them. To address this question, both experimental and computational methods were used to evaluate the effects of pH on human monoclonal antibody (MAb) stability and activity. To determine the acid-sensitivity of their antigen binding sites, human MAbs against human sperm (H6-3C4) and gp120 of HIV (1511) were tested by ELISA for binding to human sperm and recombinant gp120, respectively. at pH 3.0-7.0, after storing them for I or 20 h at the same pH. Binding was unaltered by acidic pH greater than or equal to 4 even after 20 h, and at pH 3.5 both MAbs retained greater than or equal to40% antigen binding activity. A humanized MAb against HSV-2 glycoprotein B expressed both in Chinese hamster ovary (CHO) cells and in soybean cells was incubated for I or 24 h at pH 3.5-7.6, brought to neutral pH, and tested for ability to block HSV-2 infection of foreskin fibroblast cells. Loss in blocking activity occurred only when antibodies were incubated at pH 3.5 for 24 It and was independent of the expression cell type. Using empirical structure-based methods, net charge, Z, and electrostatic contributions to free energy, DeltaG(el), were calculated as a function of pH for I human and 8 murine F(ab)s. The calculations indicate that Z changes slowly between pH 5.0 and 9.0 and that DeltaDeltaG(el) is nearly constant between pH 4.0 and 10 for all the F(ab)s and, therefore, human antibodies should remain stable in this pH range. Taken together, our data and empirical calculations suggest that vaginally applied human MAbs are likely to remain stable and active throughout the duration they are likely to reside in the vagina. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Johns Hopkins Univ, Thomas C Jenkins Dept Biophys, Baltimore, MD 21218 USA. EPleyte Inc, San Diego, CA USA. ReProtect, LLC, Baltimore, MD USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 7074, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM-43873] NR 34 TC 7 Z9 7 U1 1 U2 8 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-0378 J9 J REPROD IMMUNOL JI J. Reprod. Immunol. PD JUL-AUG PY 2002 VL 56 IS 1-2 BP 61 EP 76 AR PII S0165-0378(02)00013-X DI 10.1016/S0165-0378(02)00013-X PG 16 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 578FZ UT WOS:000177107900005 PM 12106884 ER PT J AU Woodburn, J Barker, S Helliwell, PS AF Woodburn, J Barker, S Helliwell, PS TI A randomized controlled trial of foot orthoses in rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; foot orthoses; valgus deformity ID PAIN; DISABILITY; HINDFOOT; INDEX; FEET; GAIT AB Objective. To investigate the clinical effectiveness of early foot orthosis intervention for painful correctable valgus deformity of the rearfoot in rheumatoid arthritis (RA). Methods. Patients with RA were randomized to receive custom manufactured rigid foot orthoses under podiatry supervision (n = 50) or enter a control group (n = 48). The control group received foot orthoses only when prescribed under normal medical care. Foot pain and disability, using the Foot Function Index (FFI), along with disease activity, tolerance, and adverse reactions, were serially measured over 30 mo continuous treatment. Results. The group assigned foot orthoses demonstrated an immediate clinical improvement, the effect peaking at 12 mo. At 30 mo the FFI total score was reduced by 23.1% from baseline in the intervention group. Area under the curve analysis showed a statistically significant reduction in FFI scores for total score (p = 0.026), foot pain (p = 0.014), and foot disability (p = 0.016) when intervention was compared to control scores. There were no confounding effects from differences between groups for disease activity or pharmacological or other management strategies. Most patients (96%) used their orthoses and most found them comfortable (97%), although minor adverse reactions, such as tender spots, blisters, and callus, were reported in 30% of patients in the early stages of treatment and persisted in 12% for 30 mo. Conclusion. Custom designed foot orthoses used continuously over a 30 mo treatment period resulted in a reduction in foot pain by 19.1%, foot disability by 30.8%, and functional limitation by 13.5%. Clinical effectiveness might be enhanced by their use in the early stages of rearfoot pain and deformity. C1 Univ Leeds, Rheumatol & Rehabil Res Unit, Leeds, W Yorkshire, England. St Lukes Hosp, Bradford NHS Trust, Rheumatol Unit, Bradford, W Yorkshire, England. RP Woodburn, J (reprint author), NIH, Dept Rehabil Med, Biomech Lab, Bldg 10,Room 6S235,10 Ctr Dr,MSC-1604, Bethesda, MD 20892 USA. NR 25 TC 77 Z9 80 U1 2 U2 11 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2002 VL 29 IS 7 BP 1377 EP 1383 PG 7 WC Rheumatology SC Rheumatology GA 571YD UT WOS:000176746000007 PM 12136891 ER PT J AU Kramer, PR Wray, S AF Kramer, PR Wray, S TI 17-beta-estradiol regulates expression of genes that function in macrophage activation and cholesterol homeostasis SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE macrophage; primary; peripheral blood; estrogen; estrogen receptor; ER alpha; ER beta; auto-antigens; cytokines; RT-PCR; monocytes; cDNA array ID HORMONE REPLACEMENT THERAPY; LOW-DENSITY-LIPOPROTEIN; BLOOD MONONUCLEAR-CELLS; RECEPTOR LXR-ALPHA; ESTROGEN REPLACEMENT; AUTOIMMUNE-DISEASES; POSTMENOPAUSAL WOMEN; IMMUNE-SYSTEM; SEX-HORMONES; TNF-ALPHA AB Macrophage activation and cholesterol processing can be affected by changes in estrogen concentrations. However, there is a paucity of information about the genes and mechanisms regulating this estrogen effect. In primary monocyte-derived macrophages we detected transcript and protein for estrogen receptor beta (ERbeta). Determination of genes regulated by estrogen was completed using cDNA arrays and semiquantitative RT-PCR on RNA isolated from macrophages cultured in serum free media containing (5-10) x 10(-9) M 17-beta-estradiol and subsequently deprived of estrogen for a 24 It period. The data indicate that the transcript levels of interleukin 1 receptor antagonist (IL-1ra), beta 2-microglobulin, annexin XI and the LXRalpha receptor significantly increased and that Ly-GDI transcript levels significantly decreased after estrogen withdrawal: data congruent with estrogen depletion regulating macrophage inflammatory and biochemical processes. Treatment of THP-1 cells with phorbol 12-myristate- 13-acetate in the presence or absence of estrogen indicate that differentiation to a macrophage-like cell type was a prerequisite for production of the estrogen response. In addition, experiments using cycloheximide treatment. that blocks nascent protein synthesis. indicated that estrogen withdrawal affected the transcript levels of LXRalpha and IL-1ra through dissimilar pathways. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Texas A&M Univ, Hlth Sci Ctr, Baylor Coll Dent, Dept Biomed Sci, Dallas, TX USA. NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Kramer, PR (reprint author), Texas A&M Univ, Hlth Sci Ctr, Baylor Coll Dent, Dept Biomed Sci, 3302 Gaston Ave, Dallas, TX USA. OI Kramer, Phillip/0000-0003-0117-542X NR 61 TC 48 Z9 49 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD JUL PY 2002 VL 81 IS 3 BP 203 EP 216 AR PII S0960-0760(02)00065-1 DI 10.1016/S0960-0760(02)00065-1 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 597LJ UT WOS:000178222800002 PM 12163132 ER PT J AU Bastain, TM Lewczyk, CM Sharp, WS James, RS Long, RT Eagen, PB Ebens, CL Meck, JM Chan, WY Sidransky, E Rapoport, JL Castellanos, EX AF Bastain, TM Lewczyk, CM Sharp, WS James, RS Long, RT Eagen, PB Ebens, CL Meck, JM Chan, WY Sidransky, E Rapoport, JL Castellanos, EX TI Cytogenetic abnormalities in attention-deficit/hyperactivity disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; cytogenetics; fragile X; velocardiofacial syndrome ID CARDIO-FACIAL SYNDROME; FRAGILE-X-SYNDROME; DEFICIT HYPERACTIVITY DISORDER; CGG REPEAT; CHROMOSOME-ABNORMALITIES; FMR-1 GENE; CHILDREN; IDENTIFICATION; TRANSLOCATION; ANEUPLOIDY AB Objective: To systematically assess the prevalence of fragile X syndrome, velocardiofacial syndrome, and other cytogenetic abnormalities in a group of children with attention-deficit/hyperactivity disorder (ADHD). Method: Blood samples were obtained from 100 children (64 boys) with combined type ADHD and normal intelligence and analyzed for the presence of fragile X mutation expansions, the 22q11.2 microdeletion associated with velocardiofacial syndrome, and cytogenetic abnormalities that would be detected with high resolution chromosomal banding. Results: One girl with ADHD had a sex chromosome aneuploidy (47,XXX). One boy had a premutation-sized allele for fragile X; no subjects showed the full mutation. Testing for 22q11.2 microdeletion was negative for all subjects with ADHD screened, None of these differences exceeded those expected by chance. Conclusions: In the absence of clinical signs or positive family history, these relatively expensive laboratory assessments are not clinically indicated for children with ADHD and normal intelligence, and are not recommended as a component of other genetic investigations of this disorder. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Div Genet, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Dept Pediat, Div Genet, Washington, DC 20057 USA. RP Castellanos, EX (reprint author), NYU, Ctr Child Study, 577 1St Ave, New York, NY 10016 USA. NR 40 TC 11 Z9 11 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 2002 VL 41 IS 7 AR UNSP 0890-8567/02/4107-0806 DI 10.1097/00004583-200207000-00012 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 566JQ UT WOS:000176424500012 PM 12108805 ER PT J AU Hoagwood, K Olin, SS AF Hoagwood, K Olin, SS TI The NIMH blueprint for change report: Research priorities in child and adolescent mental health SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE mental health; research priorities AB The National Institute of Mental Health established a special subgroup of its National Advisory Mental Health Council to review major research findings on child and adolescent psychiatric disorders over the past decade and to recommend research priorities for the next decade. This Workgroup on Child and Adolescent Mental Health Intervention Development and Deployment published its report, titled Blueprint for Change: Research on Child and Adolescent Mental Health, in August 2001, and several new research announcements reflecting these new directions have been issued since that time. This article summarizes the rationale for and background to the report, Its major conclusions, and the reasons why interdisciplinary and translational approaches to research questions in child and adolescent mental health will help to maximize scientific advances. C1 NIMH, Bethesda, MD 20892 USA. RP Olin, SS (reprint author), NIMH, 6001 Execut Blvd, Bethesda, MD 20892 USA. NR 14 TC 81 Z9 82 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 2002 VL 41 IS 7 AR UNSP 0890-8567/02/4107-0760 DI 10.1097/00004583-200207000-00006 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 566JQ UT WOS:000176424500006 PM 12108799 ER PT J AU Kimball, AB Turner, MLC AF Kimball, AB Turner, MLC TI Mycosis fungoides and serology for human T-cell lymphotropic virus, type 1 SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. NIH, Consult Serv, Bethesda, MD 20892 USA. RP Kimball, AB (reprint author), Stanford Univ, Sch Med, Stanford, CA 94305 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 2002 VL 47 IS 1 BP 159 EP 159 DI 10.1067/mjd.2002.120582 PG 1 WC Dermatology SC Dermatology GA 568TR UT WOS:000176560400027 PM 12077602 ER PT J AU Schecter, WP Bongard, FS Gainor, BJ Weltz, DL Horn, JK AF Schecter, WP Bongard, FS Gainor, BJ Weltz, DL Horn, JK TI Pain control in outpatient surgery SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 87th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 09-11, 2001 CL NEW ORLEANS, LOUISIANA SP Amer Coll Surg ID PREEMPTIVE ANALGESIA; POSTOPERATIVE PAIN; AMBULATORY SURGERY; NERVE BLOCK; MULTIMODAL ANALGESIA; EPIDURAL ANALGESIA; ABDOMINAL-SURGERY; THORACIC-SURGERY; CLINICAL-TRIAL; MORPHINE C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Harbor UCLA Med Ctr, Los Angeles, CA USA. Univ Missouri, Dept Orthopaed Surg, Columbia, MO USA. NIH, Dept Anesthesia, Washington, DC USA. RP Schecter, WP (reprint author), San Francisco Gen Hosp, 1001 Potrero Ave,Ward 3A33, San Francisco, CA 94110 USA. NR 80 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUL PY 2002 VL 195 IS 1 BP 95 EP 104 AR PII S1075-7515(02)01148-1 DI 10.1016/S1072-7515(02)01148-1 PG 10 WC Surgery SC Surgery GA 569JW UT WOS:000176600100012 PM 12113549 ER PT J AU Chaves, PHM Ashar, B Guralnik, JM Fried, LP AF Chaves, PHM Ashar, B Guralnik, JM Fried, LP TI Looking at the relationship between hemoglobin concentration and prevalent mobility difficulty in older women. Should the criteria currently used to define anemia in older people be reevaluated? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE anemia; hemoglobin; mobility disability; frailty; older ID LOWER-EXTREMITY FUNCTION; DISABILITY; AGE; ASSOCIATION; PREDICTION; POPULATION; COMMUNITY; HEALTH; HOME AB OBJECTIVES: The World Health Organization (WHO) and other currently used criteria for defining anemia in older women are mainly based on statistical distribution considerations. To explore their clinical appropriateness, we evaluated the relationship between hemoglobin (Hb) concentration, prevalent mobility difficulty, and the Summary Performance Score (SPS). DESIGN: Cross-sectional study. SETTING: Two population-based studies, the Women's Health and Aging Studies I and II, Baltimore, Maryland. PARTICIPANTS: Six hundred thirty-three community-dwelling women aged 70 to 80 with Hb levels obtained within 90 days from baseline assessment, MEASUREMENTS: Mobility difficulty (self-reported difficulty walking one-quarter of a mile or climbing 10 steps (primary outcome)). SPS, a performance-based summary measure of lower extremity function that combines the results of walking, chair stands, and balance tests (secondary outcome). RESULTS: Mobility difficulty prevalence was not constant within the WHO "normal" Hb range (12.0-16.0 g/dL). For example, a Hb of 13.5 g/dL was associated with a significantly lower mobility difficulty prevalence than a Hb of 12.0 g/dL (OR = 0.68, 95% Cl = 0.47-0.93), even after adjustment for chronic diseases and other relevant health indicators. A consistent trend of improvement in performance-based scores with increasing Hb categories less than 12.0 g/dL, 12.0 to 13.0 g/dL, and 13.0-14.0 g/dL was observed. CONCLUSION: Our findings raise two hypotheses: (1) Hb currently perceived as "mildly-low" and even "low-normal" might have an independent, adverse effect on mobility function, and (2) Hb of 12.0 g/dL might be a suboptimal criterion for defining anemia in older women. Formal testing of these hypotheses might prove relevant for anemia- and mobility disability-related clinical decision-making. C1 Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Med, Div Internal Med, Baltimore, MD 21205 USA. Univ Estado Rio De Janeiro, Ctr Studies Aging & Care Elderly UNATI, Rio De Janeiro, Brazil. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Chaves, PHM (reprint author), Johns Hopkins Med Inst, Ctr Aging & Hlth, 2024 E Monument St,Suite 2-700, Baltimore, MD 21205 USA. FU NCRR NIH HHS [RR00722]; NIA NIH HHS [N01 AG-12112, R01 AG11703-01] NR 44 TC 140 Z9 140 U1 2 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2002 VL 50 IS 7 BP 1257 EP 1264 DI 10.1046/j.1532-5415.2002.50313.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 571EM UT WOS:000176701900012 PM 12133021 ER PT J AU Lindberg, DAB Humphreys, BL AF Lindberg, DAB Humphreys, BL TI "You have to be there": Twenty-five years of SCAMC/AMIA symposia SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association (AMIA 2001) CY NOV 03-07, 2001 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB The AMIA Annual Symposium began life as the Symposium on Computer Applications in Medical Care (SCAMC) in 1977. Inaugurated as a multidisciplinary meeting with multiple sponsors, the Symposium quickly became a force in the development of the field of medical informatics. The authors summarize the 25-year history of the meeting and its proceedings, drawing on information in the printed programs and proceedings and on the personal recollections of some Symposium organizers and attendees. They also present the results of a study of the extent to which Symposium papers have been cited in the journal literature. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Lindberg, DAB (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2002 VL 9 IS 4 BP 332 EP 345 DI 10.1197/jamia.M1076 PG 14 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 575NU UT WOS:000176954600004 PM 12087115 ER PT J AU Yergey, AL Coorssen, JR Backlund, PS Blank, PS Humphrey, GA Zimmerberg, J Campbell, JM Vestal, ML AF Yergey, AL Coorssen, JR Backlund, PS Blank, PS Humphrey, GA Zimmerberg, J Campbell, JM Vestal, ML TI De novo sequencing of peptides using MALDI/TOF-TOF SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID TANDEM MASS-SPECTROMETRY; PROTEIN IDENTIFICATION; SPECTRAL DATA; DATABASES; COMPLEX; FUSION; INFORMATION; ALGORITHM; MS AB The recently developed MALDI TOF-TOF instrument yields relatively complex but interpretable fragmentation spectra. When coupled with a straightforward sequence extension algorithm, it is possible to develop complete peptide sequences de novo from the spectra. This approach has been applied to a set of peptides derived from typtic digestion of electrophoretically separated sea urchin egg membrane proteins. When directed to proteins that have been described previously, the results were in essential agreement with those obtained by conventional data base searching approaches, with certain important exceptions. The present method detected errors in published sequences and was able to develop sequences from peptides differing in mass by one dalton (Da). These results show both the power of the present approach and the need for using de novo methods more frequently than may be otherwise appreciated. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Appl Biosyst Inc, Framingham, MA USA. Univ Calgary, Dept Physiol & Biophys, Neurosci Res Grp, Calgary, AB T2N 1N4, Canada. RP Yergey, AL (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bldg 10,Room 9D52,MSC 1580, Bethesda, MD 20892 USA. NR 27 TC 141 Z9 152 U1 2 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD JUL PY 2002 VL 13 IS 7 BP 784 EP 791 AR PII S1044-0305(02)00393-8 DI 10.1016/S1044-0305(02)00393-8 PG 8 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 576UQ UT WOS:000177024700004 PM 12148803 ER PT J AU Kamijo, Y Hora, K Tanaka, N Usuda, N Kiyosawa, K Nakajima, T Gonzalez, FJ Aoyama, T AF Kamijo, Y Hora, K Tanaka, N Usuda, N Kiyosawa, K Nakajima, T Gonzalez, FJ Aoyama, T TI Identification of functions of peroxisome proliferator-activated receptor alpha in proximal tubules SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PPAR-ALPHA; RAT; GENE; BETA; CDNA; EXPRESSION; PATHWAYS; PROTEIN; ENZYMES; CLONING AB Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the steroid/nuclear receptor superfamily that is intensively expressed in the kidney, but its physiologic function is unknown. In this study, PPARalpha-null mice were used to help clarify the function. Starved PPARalpha-null mice were found to secrete significantly more quantities of urine albumin than starved wild-type mice. Furthermore, the appearance of giant lysosomes, marked accumulation of albumin, and an impaired ability concerning albumin digestion were found only in proximal tubules of the starved PPARalpha-null mice. These abnormalities were probably derived from ATP insufficiency as a result of the starvation-induced decline of carbohydrate metabolism and a lack of PPARalpha-dependent fatty acid metabolism. It is interesting that these abnormalities disappeared when glucose was administered. Taken together, these findings demonstrate important functions of PPARalpha in the proximal tubules, the dynamic regulation of the protein-degradation system through maintenance of ATP homeostasis, and emphasize the importance of the fatty acid metabolism in renal physiology. C1 Shinshu Univ, Sch Med, Dept Internal Med 2, Matsumoto, Nagano 3908621, Japan. Shinshu Univ, Sch Med, Dept Aging Biochem, Matsumoto, Nagano 3908621, Japan. Shinshu Univ, Sch Med, Div Artificial Kidney, Matsumoto, Nagano 3908621, Japan. Shinshu Univ, Sch Med, Dept Anat 1, Matsumoto, Nagano 3908621, Japan. Shinshu Univ, Sch Med, Dept Hyg & Med Genet, Matsumoto, Nagano 3908621, Japan. NCI, Met Lab, Bethesda, MD 20892 USA. RP Hora, K (reprint author), Shinshu Univ, Sch Med, Dept Internal Med 2, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan. NR 32 TC 41 Z9 41 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2002 VL 13 IS 7 AR UNSP 1046-6673/1307-1691 DI 10.1097/01.ASN.0000018403.61042.56 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 567GM UT WOS:000176477100001 PM 12089364 ER PT J AU Shavers, VL Shankar, S AF Shavers, VL Shankar, S TI Trend in the prevalence of overweight and obesity among urban African American hospital employees and public housing residents SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE obesity; overweight; socioeconomic status; African Americans ID NUTRITION EXAMINATION SURVEY; BODY-MASS INDEX; QUALITY-OF-LIFE; US ADULTS; UNITED-STATES; RISK-FACTORS; SOCIOECONOMIC DIFFERENCES; NATIONAL-HEALTH; WOMEN; WEIGHT AB introduction: To help understand the impact of socioeconomic status, we examined the current prevalence and age-specific trend in overweight and obesity among two socioeconomically diverse groups of African Americans in the Washington, DC, area. Materials and Methods: Data on height and weight were collected between March 1995 and December 1996 as a part of nutrition survey to develop a food frequency questionnaire. Gender-stratified multiple logistic regression analyses were used to examine factors related to the current prevalence of overweight and obesity. Results: Three hundred nine African American public housing residents and 293 African American hospital employees participated in this survey, Overall, hospital workers and public housing residents differed significantly in the distribution of BMI (p = 0.003), Among men, the prevalence of overweight and obesity were 34.9% and 29.4% for hospital workers and 27.0% and 18.2% for public housing residents, respectively, For females these rates were 31.3% and 46.3% for hospital employees and 26.1% and 42.9% for public housing residents, respectively. Conclusion: Overweight and obesity were highly prevalent among all age and socioeconomic groups. Future research should focus on a more in-depth study of the relationship between socioeconomic status and the correlates of obesity among African-Americans, particularly women. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Shavers, VL (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Execut Plaza N Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. FU NCI NIH HHS [T32CA09314-19, R03 CA77184-01, K07 CA61807-94] NR 35 TC 8 Z9 8 U1 0 U2 2 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD JUL PY 2002 VL 94 IS 7 BP 566 EP 576 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 573DW UT WOS:000176814900018 PM 12126282 ER PT J AU Keswani, SC Chauhan, N AF Keswani, SC Chauhan, N TI Antiphospholipid syndrome SO JOURNAL OF THE ROYAL SOCIETY OF MEDICINE LA English DT Review ID SYSTEMIC LUPUS-ERYTHEMATOSUS; INTRAVENOUS IMMUNOGLOBULIN THERAPY; ANTICARDIOLIPIN ANTIBODIES; RECURRENT MISCARRIAGE; CEREBRAL-ISCHEMIA; PREGNANCY LOSS; THROMBOSIS; ANTICOAGULANT; CARDIOLIPIN; PREVALENCE C1 Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Keswani, SC (reprint author), Johns Hopkins Univ Hosp, Dept Neurol, 600 N Wolfe St,Pathol 509, Baltimore, MD 21287 USA. NR 62 TC 6 Z9 8 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 0141-0768 J9 J ROY SOC MED JI J. R. Soc. Med. PD JUL PY 2002 VL 95 IS 7 BP 336 EP 342 DI 10.1258/jrsm.95.7.336 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 571WC UT WOS:000176741300005 PM 12091507 ER PT J AU Hertelendy, F Molnar, M Romero, R AF Hertelendy, F Molnar, M Romero, R TI Interferon gamma antagonizes interleukin-1 beta-induced cyclooxygenase-2 expression and prostaglandin E-2 production in human myometrial cells SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Article DE interleukin-1; interferon gamma; cyclooxygenase-2; prostaglandin E-2; myometrium ID PRETERM LABOR; HUMAN-PREGNANCY; AMNIOTIC-FLUID; IFN-GAMMA; INTERLEUKIN-4; INFECTION; BIOSYNTHESIS; FIBROBLASTS; METABOLISM; ACTIVATION AB OBJECTIVE: To evaluate the effect of interferon gamma (IFN-gamma) on the interleukin-1beta (IL-1) and tumor necrosis factor-alpha (TNFalpha)-promoted prostaglandin E-2 (PGE(2)) production and to investigate the interaction of IFNgamma and IL-1 on cyclooxygenase-2 (COX-2) expression, as well as nuclear factor-kappaB (NF-kappaB) activation in human myometrial cells. METHODS: An immortalized human myometrial cell line was cultured in Dulbecco modified Eagle medium (DMEM) fortified with 10% (v/v) fetal calf serum (FCS) in multiwell plates until near confluency. Twenty-four hours before the start of the experiments, the medium was replaced with FCS-free medium containing 0.5% bovine serum albumin. Prostaglandin E-2 was determined in the medium with a specific radioimmunoassay having a sensitivity of 10 pg. The COX-2 and NF-kappaB inhibitory protein (IkappaB) protein levels were measured in cell extracts by Western blot. RESULTS: Cell cultures primed with IFNgamma produced significantly less (P < .05-.01) PGE(2) in response to cytokines than cells exposed to IL-1, TNF-α, or the combinaton of th two. This result corresponded to a similar inhibition of IκB degradation (a prerequisite of NF-κB activation) as well as COX-2 protein steady state levels. CONCLUSION: Interferon γ acts as a partial antagonist of IL-1 signaling in this cell model at a site upstream from the activation of the NF-κB pathway, causing a partial inhibition of COX-2 expression and PGE(2) production. C1 St Marys Hlth Ctr, Dept Obstet Gynecol & Womens Hlth, St Louis, MO 63117 USA. St Louis Univ, Sch Med, Dept Obstet & Gynecol & Womens Hlth, St Louis, MO USA. Semmelweis Univ, Inst Pathophysiol, Budapest, Hungary. Hutzel Hosp, Dept Obstet & Gynecol, NICHD, Perinatal Res Branch, Detroit, MI 48201 USA. RP Hertelendy, F (reprint author), St Marys Hlth Ctr, Dept Obstet Gynecol & Womens Hlth, 6420 Clayton Rd, St Louis, MO 63117 USA. NR 28 TC 23 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD JUL-AUG PY 2002 VL 9 IS 4 BP 215 EP 219 AR PII S1071-5576(02)00157-0 DI 10.1016/S1071-5576(02)00157-0 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 574WF UT WOS:000176912000006 PM 12113880 ER PT J AU Lee, W McNie, B Chaiworapongsa, T Conoscenti, G Kalache, KD Vettraino, IM Romero, R Comstock, CH AF Lee, W McNie, B Chaiworapongsa, T Conoscenti, G Kalache, KD Vettraino, IM Romero, R Comstock, CH TI Three-dimensional ultrasonographic presentation of micrognathia SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE fetus; micrognathia; prenatal diagnosis; three-dimensional ultrasonography ID COSTO-MANDIBULAR SYNDROME; PRENATAL-DIAGNOSIS; DELANGE-SYNDROME; JAW INDEX; FETAL; MALFORMATIONS; FETUS AB Objective. To present the variable appearance of micrognathia in fetuses by three-dimensional ultrasonography and to describe practical methods for analysis of these volume data. Methods. Three-dimensional multiplanar imaging and surface-rendering techniques were used to show various syndromes and diagnostic approaches for the evaluation of fetal micrognathia. Results. Nine cases of fetal micrognathia are presented. Orthogonal multiplanar views were used to obtain a midsagittal facial profile. Examples of micrognathia include 3 cases of Pierre Robin sequence, cerebrocosto-mandibular syndrome, Cornelia de Lange syndrome, and hypochondrogenesis. Diagnostic pitfalls for micrognathia are also shown. Conclusions. Three-dimensional multiplanar imaging increases the likelihood that a true midline sagittal view of the facial profile is being analyzed. Surface rendering provides another way to qualitatively evaluate the fetal chin from different viewing perspectives. Three-dimensional ultrasonographic methods are useful adjuncts to the preliminary diagnostic impression from two-dimensional ultrasonography. C1 William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48073 USA. Wayne State Univ, NICHHD, Perinatol Res Branch, Detroit, MI 48202 USA. RP Lee, W (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. NR 17 TC 31 Z9 31 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JUL PY 2002 VL 21 IS 7 BP 775 EP 781 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 566ZD UT WOS:000176457400010 PM 12099566 ER PT J AU Carpten, J Nupponen, N Isaacs, S Sood, R Robbins, C Xu, J Faruque, M Moses, T Ewing, C Gillanders, E Hu, P Bujnovszky, P Makalowska, I Baffoe-Bonnie, A Faith, D Smith, J Stephan, D Wiley, K Brownstein, M Gildea, D Kelly, B Jenkins, R Hostetter, G Matikainen, M Schleutker, J Klinger, K Connors, T Xiang, Y Wang, Z De Marzo, A Papadopoulos, N Kallioniemi, OP Burk, R Meyers, D Gronberg, H Meltzer, P Silverman, R Bailey-Wilson, J Walsh, P Isaacs, W Trent, J AF Carpten, J Nupponen, N Isaacs, S Sood, R Robbins, C Xu, J Faruque, M Moses, T Ewing, C Gillanders, E Hu, P Bujnovszky, P Makalowska, I Baffoe-Bonnie, A Faith, D Smith, J Stephan, D Wiley, K Brownstein, M Gildea, D Kelly, B Jenkins, R Hostetter, G Matikainen, M Schleutker, J Klinger, K Connors, T Xiang, Y Wang, Z De Marzo, A Papadopoulos, N Kallioniemi, OP Burk, R Meyers, D Gronberg, H Meltzer, P Silverman, R Bailey-Wilson, J Walsh, P Isaacs, W Trent, J TI Urological oncology: Prostate cancer SO JOURNAL OF UROLOGY LA English DT Meeting Abstract C1 NHGRI, Canc Genet Branch, Genome Technol Branch, NIH, Bethesda, MD USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD USA. NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genomics, Winston Salem, NC USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Vanderbilt Univ, Div Med Genet, Nashville, TN USA. Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Tampere, Finland. Cleveland Clin Fdn, Dept Canc Biol, Lerner Res Inst, Cleveland, OH 44195 USA. Columbia Univ, Dept Pathol, Inst Canc Genet, New York, NY USA. Yeshiva Univ, Albert Einstein Sch Med, Dept Microbiol & Immunol, Bronx, NY USA. Umea Univ, Dept Oncol, Umea, Sweden. RI Brownstein, Michael/B-8609-2009; Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2002 VL 168 IS 1 BP 372 EP 372 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 562LQ UT WOS:000176198600107 ER PT J AU Smith, RA Cokkinides, V Von Eschenbach, AC Levin, B Cohen, C Runowicz, CD Sener, S Saslow, D Eyre, J AF Smith, RA Cokkinides, V Von Eschenbach, AC Levin, B Cohen, C Runowicz, CD Sener, S Saslow, D Eyre, J TI American cancer society guidelines for the early detection of cancer SO JOURNAL OF UROLOGY LA English DT Meeting Abstract C1 Amer Canc Soc, Dept Canc Control, Atlanta, GA 30329 USA. Amer Canc Soc, Dept Epidemiol & Res Surveillance, Atlanta, GA 30329 USA. NCI, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Program Ctr Genitourinary Canc, Houston, TX 77030 USA. Mt Sinai Med Ctr, Div Gynecol Oncol, New York, NY 10029 USA. Albert Einstein Coll Med, Dept Obstet & Gynecol, Bronx, NY 10467 USA. Evanston NW Healthcare, Dept Surg, Evanston, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2002 VL 168 IS 1 BP 372 EP 373 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 562LQ UT WOS:000176198600108 ER PT J AU Collins, MM Pontari, MA O'Leary, MP Calhoun, EA Santanna, J Landis, JR Kusek, JW Litwin, MS AF Collins, MM Pontari, MA O'Leary, MP Calhoun, EA Santanna, J Landis, JR Kusek, JW Litwin, MS CA Chronic Prostatis Collaborative TI Quality of life is impaired in men with chronic prostatitis. The chronic prostatitis collaborative research network SO JOURNAL OF UROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Med Serv,Gen Med Unit, Boston, MA USA. Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. Temple Univ, Sch Med, Dept Urol, Philadelphia, PA 19122 USA. Univ Penn, Med Ctr, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Northwestern Univ, Sch Med, Inst Hlth Serv & Hlth Policy Studies, Chicago, IL USA. NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA. RI Landis, J. Richard/A-9330-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2002 VL 168 IS 1 BP 395 EP 396 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 562LQ UT WOS:000176198600147 ER PT J AU Major, ME Mihalik, K Puig, M Rehermann, B Nascimbeni, M Rice, CM Feinstone, SM AF Major, ME Mihalik, K Puig, M Rehermann, B Nascimbeni, M Rice, CM Feinstone, SM TI Previously infected and recovered chimpanzees exhibit rapid responses that control hepatitis C virus replication upon rechallenge SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNE-RESPONSES; NON-A; GENOME; RNA; IDENTIFICATION; REGION; 3'-TERMINUS; PREVENTION; CLEARANCE; HUMANS AB Responses in three chimpanzees were compared following challenge with a clonal hepatitis C virus (HCV) contained in plasma from an animal that had received infectious RNA transcripts. Two of the chimpanzees (Ch1552 and ChX0186) had recovered from a previous infection with HCV, while the third (Ch1605) was a naive animal. All animals were challenged by reverse titration with decreasing dilutions of plasma and became serum RNA positive following challenge. Ch1605 displayed a typical disease profile for a chimpanzee. We observed increasing levels of serum RNA from week 1 postinoculation (p.i.), reaching a peak of 10(6) copies/ml at week 9 p.i., and alanine aminotransferase (ALT) elevations and seroconversion to HCV antibodies at week 10 p.i. In contrast, both ChI552 and ChX0186 exhibited much shorter periods of viremia (4 weeks), low serum RNA levels (peak, 10(3) copies/ml), and minimal ALT elevations. A comparison of intrahepatic cytokine levels in ChI552 and Ch1605 showed greater and earlier gamma interferon (IFN-gamma) and tumor necrosis factor alpha responses in the previously infected animal, responses that were 30-fold greater than baseline responses at week 4 p.i. for IFN-gamma in Ch1552 compared to 12-fold in Ch1605 at week 10 p.i. These data indicate (i) that clonal HCV generated from an infectious RNA transcript will lead to a typical HCV infection in naive chimpanzees, (ii) that there are memory immune responses in recovered chimpanzees that control HCV infection upon rechallenge, and (iii) that these responses seem to be T-cell mediated, as none of the animals had detectable antibody against the HCV envelope glycoproteins. These observations have encouraging implications for the development of a vaccine for HCV. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. RP Major, ME (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29A,Rm 1D10,HFM 448,8800 Rockville Pike, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA 85883, R01 CA085883] NR 31 TC 125 Z9 127 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2002 VL 76 IS 13 BP 6586 EP 6595 DI 10.1128/JVI.76.13.6586-6595.2002 PG 10 WC Virology SC Virology GA 564BF UT WOS:000176293600019 PM 12050371 ER PT J AU Lu, XB Xiong, Y Silver, J AF Lu, XB Xiong, Y Silver, J TI Asymmetric requirement for cholesterol in receptor-bearing but not envelope-bearing membranes for fusion mediated by ecotropic murine leukemia virus SO JOURNAL OF VIROLOGY LA English DT Article ID SEMLIKI-FOREST-VIRUS; LIPID RAFT MICRODOMAINS; CELL PLASMA-MEMBRANES; PROTEIN; TRANSPORT; PATHWAY; DOMAINS; ENTRY; DEPENDENCE; SIMULATION AB We show that fusion mediated by ecotropic murine leukemia virus envelope is dependent on cholesterol in receptor-bearing membranes. The effect is >10 times larger in insect cells than mammalian cells, probably because the former can be more extensively depleted of cholesterol. The fact that cholesterol is apparently not needed in envelope-bearing membranes suggests that it plays a role in an asymmetric step in membrane fusion and argues against a class of models in which cholesterol is important in symmetric fusion intermediates. The insect cell system has promise for clarifying the role of membrane rafts in other aspects of cell physiology. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Silver, J (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 336, Bethesda, MD 20892 USA. NR 52 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2002 VL 76 IS 13 BP 6701 EP 6709 DI 10.1128/JVI.76.13.6701-6709.2002 PG 9 WC Virology SC Virology GA 564BF UT WOS:000176293600031 PM 12050383 ER PT J AU Golding, H Zaitseva, M de Rosny, E King, LR Manischewitz, J Sidorov, I Gorny, MK Zolla-Pazner, S Dimitrov, DS Weiss, CD AF Golding, H Zaitseva, M de Rosny, E King, LR Manischewitz, J Sidorov, I Gorny, MK Zolla-Pazner, S Dimitrov, DS Weiss, CD TI Dissection of human immunodeficiency virus type 1 entry with neutralizing antibodies to gp41 fusion intermediates SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION; HIV-1 GP41; TRANSMEMBRANE PROTEIN; ATOMIC-STRUCTURE; COILED-COIL; CELL-LINES; EPITOPE; PEPTIDE AB Human immunodeficiency virus type 1 (HIV-1) entry requires conformational changes in the transmembrane subunit (gp41) of the envelope glycoprotein (Env) involving transient fusion intermediates that contain exposed coiled-coil (prehairpin) and six-helix bundle structures. We investigated the HIV-1 entry mechanism and the potential of antibodies targeting fusion intermediates to block Env-mediated membrane fusion. Suboptimal temperature (31.5degreesC) was used to prolong fusion intermediates as monitored by confocal microscopy. After transfer to 37degreesC, these fusion intermediates progressed to syncytium formation with enhanced kinetics compared with effector-target (E/T) cell mixtures that were incubated only at 37degreesC. gp41 peptides DP-178, DP-107, and IQN17 blocked fusion more efficiently (5- to 10-fold-lower 50% inhibitory dose values) when added to E/T cells at the suboptimal temperature prior to transfer to 37degreesC. Rabbit antibodies against peptides modeling the N-heptad repeat or the six-helix bundle of gp41 blocked fusion and viral infection at 37degreesC only if preincubated with E/T cells at the suboptimal temperature. Similar fusion inhibition was observed with human six-helix bundle-specific monoclonal antibodies. Our data demonstrate that antibodies targeting gp41 fusion intermediates are able to bind to gp41 and arrest fusion. They also indicate that six-helix bundles can form prior to fusion and that the lag time before fusion occurs may include the time needed to accumulate preformed six-helix bundles at the fusion site. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Res Ctr AIDS & HIV Infect, New York, NY 10010 USA. NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NCI, Canc Res Ctr, NIH, Frederick, MD 21702 USA. RP Golding, H (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29A,Rm 1A21,HFM-454,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Weiss, Carol/F-6438-2011; OI Weiss, Carol/0000-0002-9965-1289; Sidorov, Igor/0000-0001-6519-4983 NR 32 TC 99 Z9 101 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2002 VL 76 IS 13 BP 6780 EP 6790 DI 10.1128/JVI.76.13.6780-6790.2002 PG 11 WC Virology SC Virology GA 564BF UT WOS:000176293600039 PM 12050391 ER PT J AU Sosnovtsev, SV Garfield, M Green, KY AF Sosnovtsev, SV Garfield, M Green, KY TI Processing map and essential cleavage sites of the nonstructural polyprotein encoded by ORF1 of the feline calicivirus genome SO JOURNAL OF VIROLOGY LA English DT Article ID HEMORRHAGIC-DISEASE VIRUS; PROTEINASE-POLYMERASE PRECURSOR; DEPENDENT RNA-POLYMERASE; NUCLEOTIDE-SEQUENCE; 3C-LIKE PROTEASE; CAPSID PRECURSOR; POLIOVIRUS 2C; EXPRESSION; IDENTIFICATION; 2BC AB Feline calicivirus (FCV) nonstructural proteins are translated as part of a large polyprotein that undergoes autocatalytic processing by the virus-encoded 3C-like proteinase. In this study, we mapped three new cleavage sites (E-46/A(47), E-331/D-332, and E-685 /N-686) recognized by the virus proteinase in the N-terminal part of the open reading frame 1 (ORFI) polyprotein to complete the processing map. Taken together with two sites we identified previously (E-960/A(961) and E-1071/S-1072), the FCV ORF1 polyprotein contains five cleavage sites that define the borders of six proteins with calculated molecular masses of 5.6, 32, 38.9, 30.1, 12.7, and 75.7 kDa, which we designated p5.6, p32, p39 (NTPase), p30, p13 (VPg), and p76 (Pro-Pol), respectively. Mutagenesis of the E to A in each of these cleavage sites in an infectious FCV cDNA clone was lethal for the virus, indicating that these cleavages are essential in a productive virus infection. Mutagenesis of two cleavage sites (E-1345/T-1316 and E-1419/G(1420)) within the 75.7-kDa Pro-Pol protein previously mapped in bacterial expression studies was not lethal. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA. RP Sosnovtsev, SV (reprint author), NIAID, Infect Dis Lab, NIH, 50 South Dr,MSC8007,Bldg 50,Room 6316, Bethesda, MD 20892 USA. NR 43 TC 75 Z9 77 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2002 VL 76 IS 14 BP 7060 EP 7072 DI 10.1128/JVI.76.14.7060-7072.2002 PG 13 WC Virology SC Virology GA 567ZH UT WOS:000176517600020 PM 12072506 ER PT J AU Taraporewala, ZF Schuck, P Ramig, RF Silvestri, L Patton, JT AF Taraporewala, ZF Schuck, P Ramig, RF Silvestri, L Patton, JT TI Analysis of a temperature-sensitive mutant rotavirus indicates that NSP2 octamers are the functional form of the protein SO JOURNAL OF VIROLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; NONSTRUCTURAL PROTEIN; SEDIMENTATION ANALYSIS; GENOME REPLICATION; MESSENGER-RNA; LAMM EQUATION; OPEN CORES; IDENTIFICATION; POLYMERASE; BINDING AB Evidence that NSP2 plays a role in packaging and replication comes from studies on tsE(1400), a rotavirus mutant with a temperature-sensitive (ts) lesion in the NSP2 gene. Cells infected with tsE and maintained at nonpermissive temperature contain few replication-assembly factories (viroplasms) or replication intermediates and produce virus particles that are mostly empty. Sequence analysis has indicated that an A152V mutation in NSP2 is responsible for the ts phenotype of tsE. To gain insight into the effect of the mutation on the octameric structure and biochemical activities of tsE NSP2, the protein was expressed in bacteria and purified to homogeneity. Analytical ultracentrifugation showed that tsE NSP2 formed octamers which, like those formed by wild-type (wt) NSP2, undergo conformational change into more compact structures upon binding of nucleotides. However, exposure to Mg2+ and the nonpermissive temperature caused disruption of the tsE octamers and yielded the formation of polydisperse NSP2 aggregates, events not observed with wt octamers. Biochemical analysis showed that the RNA-binding, helix-destabilizing and NTPase activities of tsE NSP2 were significantly less at the nonpermissive temperature than at the permissive temperature. In contrast, these activities for wt NSP2 were higher at the nonpermissive temperature. Our results indicate that the octamer is the fully functional form of NSP2 and the form required for productive virus replication. The propensity of tsE NSP2 to form large aggregates provides a possible explanation for the inability of the protein to support packaging and/or replication in the infected cell at the nonpermissive temperature. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Off Director, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0720,Room 117, Bethesda, MD 20892 USA. RI Patton, John/P-1390-2014; OI Schuck, Peter/0000-0002-8859-6966 NR 41 TC 29 Z9 31 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2002 VL 76 IS 14 BP 7082 EP 7093 DI 10.1128/JVI.76.14.7082-7093.2002 PG 12 WC Virology SC Virology GA 567ZH UT WOS:000176517600022 PM 12072508 ER PT J AU Sanders, RW Venturi, M Schiffner, L Kalyanaraman, R Katinger, H Lloyd, KO Kwong, PD Moore, JP AF Sanders, RW Venturi, M Schiffner, L Kalyanaraman, R Katinger, H Lloyd, KO Kwong, PD Moore, JP TI The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120 SO JOURNAL OF VIROLOGY LA English DT Article ID EXTERIOR ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODIES; C-TYPE LECTINS; DC-SIGN; HIV GP120; CYANOVIRIN-N; SURFACE GLYCOPROTEIN; HUMORAL IMMUNITY; STRUCTURAL BASIS; CD4 RECEPTOR AB We have analyzed the unique epitope for the broadly neutralizing human monoclonal antibody (MAb) 2G12 on the gp120 surface glycoprotein of human immunodeficiency virus type 1 (HIV-1). Sequence analysis, focusing on the conservation of relevant residues across multiple HIV-1 isolates, refined the epitope that was defined previously by substitutional mutagenesis (A. Trkola, M. Purtscher, T. Muster, C. Ballaun, A. Buchacher, N. Sullivan, K. Srinivasan, J. Sodroski, J. P. Moore, and H. Katinger, J. Virol. 70:1100-1108, 1996). In a biochemical study, we digested recombinant gp120 with various glycosidase enzymes of known specificities and showed that the 2G12 epitope is lost when gp120 is treated with mannosidases. Computational analyses were used to position the epitope in the context of the virion-associated envelope glycoprotein complex, to determine the variability of the surrounding surface, and to calculate the surface accessibility of possible glycan- and polypeptide-epitope components. Together, these analyses suggest that the 2G12 epitope is centered on the high-mannose and/or hybrid glycans of residues 295, 332, and 392, with peripheral glycans from 386 and 448 on either flank. The epitope is mannose dependent and composed primarily of carbohydrate, with probably no direct involvement of the gp120 polypeptide surface. It resides on a face orthogonal to the CD4 binding face, on a surface proximal to, but distinct from, that implicated in coreceptor binding. Its conservation amidst an otherwise highly variable gp120 surface suggests a functional role for the 2G12 binding site, perhaps related to the mannose-dependent attachment of HIV-1 to DC-SIGN or related lectins that facilitate virus entry into susceptible target cells. C1 Cornell Univ, Weill Med Col, Dept Microbiol & Immunol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10021 USA. Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Agr & Forestry, Inst Appl Microbiol, A-1190 Vienna, Austria. RP Moore, JP (reprint author), Cornell Univ, Weill Med Col, Dept Microbiol & Immunol, 1300 York Av,W-805, New York, NY 10021 USA. FU NIAID NIH HHS [AI36082, AI39420, AI45463, R01 AI039420, R01 AI045463, R37 AI036082] NR 75 TC 423 Z9 429 U1 2 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2002 VL 76 IS 14 BP 7293 EP 7305 DI 10.1128/JVI.76.14.7293-7305.2002 PG 13 WC Virology SC Virology GA 567ZH UT WOS:000176517600042 PM 12072528 ER PT J AU Rooks, RN Simonsick, EM Miles, T Newman, A Kritchevsky, SB Schulz, R Harris, T AF Rooks, RN Simonsick, EM Miles, T Newman, A Kritchevsky, SB Schulz, R Harris, T TI The association of race and socioeconomic status with cardiovascular disease indicators among older adults in the health, aging, and body composition study SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; BLACK-WHITE DIFFERENCES; BLOOD-PRESSURE; JOHN-HENRYISM; RISK-FACTORS; RACIAL-DIFFERENCES; ECONOMIC-STATUS; HYPERTENSION; DISCRIMINATION; DISPARITIES AB Objectives. We hypothesized that older Black adults would have a higher prevalence of cardiovascular disease (CVD) than White adults, as indicated by elevated systolic blood pressure (SBP), low ankle-arm blood pressure index (AAI), and left ventricular hypertrophy (LVH). But, accounting for a broad interpretation of socioeconomic status (SES) (i.e., education, family income, home ownership, and other assets) would reduce these differences. Methods. Data are from the Health, Aging, and Body Composition study, a longitudinal clinical research study of 3,075 well-functioning adults aged 70-79, in which 46% of women and 33% of men are Black. Logistic regression modeled racial and SES differences in CVD indicators. Results. Being Black was significantly associated with elevated SBP (men only), low AAI, and LVH, and remained significant after accounting for each SES measure. The racial association with CVD was reduced the most by income for elevated SBP in men, other assets for low AAI in women and men, and other assets for LVH in men. Discussion. Contrary to the age-as-leveler theory, being Black was strongly associated with CVD indicators, and accounting for SES did not reduce this association. Whether other SES measures, such as access to care, could explain the racial association remains to be explored. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Clin Invest Lab, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Family Practice, San Antonio, TX USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15260 USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Social & Urban Res, Pittsburgh, PA USA. RP Rooks, RN (reprint author), Univ Michigan, Inst Social Res Social Environm & Hlth, 426 Thompson St,Room 2211, Ann Arbor, MI 48106 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2102, AG-98-002, N01-AG-2106, N01-AG-6-2103] NR 47 TC 52 Z9 52 U1 1 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JUL PY 2002 VL 57 IS 4 BP S247 EP S256 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 571JA UT WOS:000176713200015 PM 12084794 ER PT J AU Mannon, RB Griffiths, R Ruiz, P Platt, JL Coffman, TM AF Mannon, RB Griffiths, R Ruiz, P Platt, JL Coffman, TM TI Absence of donor MHC antigen expression ameliorates chronic kidney allograft rejection SO KIDNEY INTERNATIONAL LA English DT Article DE chronic rejection; kidney; transplantation; MHC; mouse; antibody; major histocompatibility complex antigens; late graft failure ID GROWTH-FACTOR-BETA; CLASS-II TRANSACTIVATOR; IMPROVED RENAL-FUNCTION; CD8+ T-CELLS; HLA CLASS-I; DEFICIENT MICE; INDIRECT RECOGNITION; CARDIAC ALLOGRAFTS; PATHOLOGICAL FEATURES; TRANSPLANT REJECTION AB Background. In previous studies, we have demonstrated that a subset of mouse kidney allografts has prolonged survival without any immunosuppressive treatment. Chronic rejection (CR) develops in these long surviving grafts. The pathologic features of CR in this model are similar to CR in human kidney grafts. Methods. To explore the role of donor major histocompatibility complex (MHC) antigens in the development of CR, we performed vascularized kidney transplants using kidneys from donor mice that lack expression of both MHC class I and II antigens (MHC-/-). Results. Survival was significantly improved in recipients of MHC-/- allografts. This enhanced survival was associated with higher glomerular filtration rate (GFR) in MHC-/- allografts (4.92 +/- 0.54 cc/min/kg) compared to controls (2.19 +/- 0.63 cc/min/kg; P = 0.004). The typical histologic features of CR were markedly reduced in MHC-/- allografts. Semiquantitative histopathological scores for MHC-/- grafts (13.3 +/- 2.1) were significantly lower than in control allografts (19.0 +/- 1.0 P = 0.04). Along with this improvement in structural abnormalities, significantly fewer CD4(+) T (38.3 cells/mm(2) vs. 75.0 cells/mm(2) P = 0.008). CD8(-) T cells (38.7 vs. 96 cells/mm(2), respectively: P = 0.008) and macrophages (60 vs. 134 cells/mm(2), respectively: P = 0.04) infiltrated MHC-/- allografts compared to controls. The levels of intragraft cytokine mRNA expression also were reduced in MHC-/- allografts compared to control allografts. Finally, serum alloantibodies were virtually undetectable in recipients of MHC-/- kidney allografts. Conclusions. Cell surface expression of donor MHC antigens promotes the development of CR. Donor antigen expression promotes the accumulation of infiltrating cells in the graft and the development of donor specific alloantibodies. Abrogation of these responses is associated with improved graft survival and reduced CR in MHC-/- grafts. C1 Duke Univ, Dept Med, Div Nephrol, Durham, NC USA. Durham VA Med Ctr, Durham, NC USA. Univ Miami, Dept Pathol, Miami, FL 33152 USA. Mayo Clin, Dept Immunol, Rochester, MN USA. Mayo Clin, Dept Surg, Rochester, MN USA. Mayo Clin, Dept Pediat, Rochester, MN USA. RP Mannon, RB (reprint author), NIDDK, Transplantat & Autoimmun Branch, NIH, 9000 Rockville Pike,Bldg 10 Room 11S224, Bethesda, MD 20892 USA. FU NIAID NIH HHS [1K08 AI 01389-01]; NIDDK NIH HHS [P01 DK 38103] NR 56 TC 13 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 2002 VL 62 IS 1 BP 290 EP 300 DI 10.1046/j.1523-1755.2002.00422.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 565YG UT WOS:000176397500034 PM 12081591 ER PT J AU Stokes, WS Hill, RN AF Stokes, WS Hill, RN TI The role of ICCVAM in evaluating new and alternative test methods SO LAB ANIMAL LA English DT Article ID IN-VITRO TESTS; SKIN CORROSIVITY; CHEMICALS C1 NIEHS, NTP Interagcy, Ctr Evaluat Alternat Toxicol Methods, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. US EPA, Off Prevent Pesticides & Tox Substances, Washington, DC 20460 USA. RP Stokes, WS (reprint author), NIEHS, NTP Interagcy, Ctr Evaluat Alternat Toxicol Methods, Environm Toxicol Program, Mail Code EC 17,POB 1233, Res Triangle Pk, NC 27709 USA. NR 31 TC 4 Z9 4 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD JUL-AUG PY 2002 VL 31 IS 7 BP 26 EP 32 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 568NT UT WOS:000176549100004 PM 12200591 ER PT J AU Kinney, JW Starosta, G Holmes, A Wrenn, CC Yang, RJ Harris, AP Long, KC Crawley, JN AF Kinney, JW Starosta, G Holmes, A Wrenn, CC Yang, RJ Harris, AP Long, KC Crawley, JN TI Deficits in trace cued fear conditioning in galanin-treated rats and galanin-overexpressing transgenic mice SO LEARNING & MEMORY LA English DT Article ID LONG-TERM POTENTIATION; SPONTANEOUS-ALTERNATION PERFORMANCE; STIMULATED ADENYLYL CYCLASES; NONMATCHING-TO-SAMPLE; RODENT MEMORY TASKS; CONTEXTUAL FEAR; VENTRAL HIPPOCAMPUS; ALZHEIMERS-DISEASE; ACETYLCHOLINE-RELEASE; BASOLATERAL AMYGDALA AB Galanin inhibits the release of several neurotransmitters and produces performance deficits in a variety of spatial and aversive learning and memory tasks. The experiments in this study investigated the role galanin has in emotional learning and memory using a standard delay cued and contextual fear conditioning task. Rats were administered galanin into the lateral ventricles before training, and scored for freezing behavior in the same context and in a novel context with and without an auditory cue (CS) that had been paired previously with an aversive stimulus (US). Galanin-overexpressing transgenic mice were tested in an identical behavioral protocol. The galanin-administered rats and the transgenic mice were not significantly different from their respective controls on this task. A more challenging trace cued and contextual fear conditioning procedure was administered to separate groups of galanin-treated rats and galanin-overexpressing transgenic mice. Subjects were trained with the same CS and US, however, a 2.5-sec delay was inserted between CS offset and US onset. Following the trace conditioning, rats administered galanin and mice overexpressing galanin both exhibited significantly less freezing to the CS in the novel context as compared with their control groups. These results indicate that the observed disruption of cued fear conditioning was specific to the more difficult trace conditioning task. These findings are the first demonstration that galanin impairs performance on an emotional memory task and support the hypothesis that galanin-induced deficits are specific to more difficult cognitive tasks. C1 NIMH, Sect Behav Genom, Bethesda, MD 20892 USA. RP Kinney, JW (reprint author), NIMH, Sect Behav Genom, Bethesda, MD 20892 USA. NR 87 TC 52 Z9 53 U1 5 U2 6 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD JUL-AUG PY 2002 VL 9 IS 4 BP 178 EP 190 DI 10.1101/m.49502 PG 13 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 586XN UT WOS:000177611600005 PM 12177231 ER PT J AU Lechner, JF Wang, YX Siddiq, F Fugaro, JM Wali, A Lonardo, F Willey, JC Harris, CC Pass, HI AF Lechner, JF Wang, YX Siddiq, F Fugaro, JM Wali, A Lonardo, F Willey, JC Harris, CC Pass, HI TI Human lung cancer cells and tissues partially recapitulate the homeobox gene expression profile of embryonic lung SO LUNG CANCER LA English DT Article DE HOX genes; defective ontogeny; lung cancer ID BRONCHIAL EPITHELIAL-CELLS; NEOPLASTIC TRANSFORMATION; NUDE-MICE; HOX; DIFFERENTIATION; TUMORIGENICITY; GROWTH; LINES; ORIGIN; VIRUS AB The fetal cell features of tumor cells suggest that neoplasia arises through a process of defective ontogeny. Homcobox (HOX) genes code for transcription factors that orchestrate organogenesis patterning and maintain tissue homeostasis. Thus. if detective ontogeny is a mechanism in cancer development, it can be hypothesized that tumor cells should express the HOX genes normally expressed by the embryonic cells of that tissue. Our data herein indicate that sonic HOX genes, whose expression is normally restricted to pulmonary embryogenesis. are re-expressed in lung cancer cells. However, lung cancer cells also frequently and inappropriately express HOX genes that are not normally expressed in lung tissue, regardless of developmental stage. Thus, whereas re-expression of some of the embryo-specific HOX genes is a common feature of lung cancer, tumors do not faithfully recapitulate the expression pattern of cells that participate in the early stages of lung development. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Karmanos Canc Inst, Detroit, MI USA. Bayer Diagnost, Emeryville, CA USA. Med Coll Ohio, Toledo, OH 43699 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Lechner, JF (reprint author), Bayer Diagnost, POB 2466, Berkeley, CA 94702 USA. NR 41 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2002 VL 37 IS 1 BP 41 EP 47 AR PII S0169-5002(02)00036-3 DI 10.1016/S0169-5002(02)00036-3 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 576JV UT WOS:000177001800008 PM 12057866 ER PT J AU Harris, RK Becker, ED de Menezes, SMC Goodfellow, R Granger, P AF Harris, RK Becker, ED de Menezes, SMC Goodfellow, R Granger, P CA Int Union Pure Applied Chemistry TI NMR nomenclature: nuclear spin properties and conventions for chemical shifts. IUPAC Recommendations 2001 SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE NMR; nomenclature; nuclear spin properties; chemical shifts; IUPAC ID SOLID-STATE NMR; MAGNETIC-RESONANCE SPECTROSCOPY; FOURIER-TRANSFORM NMR; ORGANOMETALLIC COMPOUNDS; TEMPERATURE-DEPENDENCE; QUADRUPOLE MOMENTS; C-13; PROTON; STANDARDS; ION AB A unified scale is recommended for reporting the NMR chemical shifts of all nuclei relative to the (1)H resonance of tetramethylsilane. The unified scale is designed to provide a precise ratio, Xi, of the resonance frequency of a given nuclide to that of the primary reference, the (1)H resonance of tetramethylsilane (TMS) in dilute solution (volume fraction, (p < 1%) in chloroform. Referencing procedures are discussed, including matters of practical application of the unified scale. Special attention is paid to recommended reference samples, and values of Xi for secondary references on the unified scale are listed, many of which are the results of new measurements. Some earlier recommendations relating to the reporting of chemical shifts are endorsed. The chemical shift, delta, is redefined to avoid previous ambiguities but to leave practical usage unchanged. Relations between the unified scale and recently published recommendations for referencing in aqueous solutions (for specific use in biochemical work) are discussed, as well as the special effects of working in the solid state with magic-angle spinning. In all, nine new recommendations relating to chemical shifts are made. Standardized nuclear spin data are also presented in tabular form for the stable (and some unstable) isotopes of all elements with non-zero quantum numbers. The information given includes quantum numbers, isotopic abundances, magnetic moments, magnetogyric ratios and receptivities, together with quadrupole moments and linewidth factors (where appropriate). Copyright (C) 2001 IUPAC. C1 Univ Durham, Dept Chem, Durham DH1 3LE, England. NIH, Bethesda, MD 20892 USA. PETROBRAS CENPES QUIMICA, BR-21949900 Rio De Janeiro, Brazil. Univ Bristol, Sch Chem, Bristol BS8 1TS, Avon, England. Univ Strasbourg 1, Inst Chim, F-67008 Strasbourg, France. RP Harris, RK (reprint author), Univ Durham, Dept Chem, South Rd, Durham DH1 3LE, England. EM r.k.harris@durham.ac.uk NR 75 TC 54 Z9 54 U1 2 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD JUL PY 2002 VL 40 IS 7 BP 489 EP 505 DI 10.1002/mrc.1042 PG 17 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 565MD UT WOS:000176373300014 ER PT J AU Peters, DC Ennis, DB McVeigh, ER AF Peters, DC Ennis, DB McVeigh, ER TI High-resolution MRI of cardiac function with projection reconstruction and steady-state free precession SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cardiac function; projection reconstruction; radial imaging; trabeculae; True FISP; SSFP; myocardial wall motion; papillary muscles ID LEFT-VENTRICULAR FUNCTION; RESONANCE; INFARCTION; FEASIBILITY; ANGIOGRAPHY; HEART; ECHO AB The purpose of this study was to investigate the trabecula structure of the endocardial wall of the living human heart, and the effect of that structure on the measurement of myocardial function using MRI. High-resolution MR images (0.8 x 0.8 x 3 mm voxels) of cardiac function were obtained in five volunteers using a combination of undersampled projection reconstruction (PR) and steady-state free precession (SSFP) contrast in ECG-gated breath-held scans. These images provide movies of cardiac function with new levels of endocardial detail. The trabecular-papillary muscle complex, consisting of a mixture of blood and endocardial structures, is measured to constitute as much as 50% of the myocardial wall in some sectors. Myocardial wall strain measurements derived from tagged MR images show correlation between regions of trabeculae and papillary muscles and regions of high strain, leading to an overestimation of function in the lateral wall. Published 2002 Wiley-Liss, Inc. C1 NIH, Cardiac Energet Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. RP Peters, DC (reprint author), NIH, Cardiac Energet Lab, 10 Ctr Dr,Bldg 10,B1D416, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL004608-08] NR 32 TC 30 Z9 30 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JUL PY 2002 VL 48 IS 1 BP 82 EP 88 DI 10.1002/mrm.10193 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 570FU UT WOS:000176648900010 PM 12111934 ER PT J AU Field, TS Cadoret, CA Brown, ML Ford, M Greene, SM Hill, D Hornbrook, MC Meenan, RT White, MJ Zapka, JM AF Field, TS Cadoret, CA Brown, ML Ford, M Greene, SM Hill, D Hornbrook, MC Meenan, RT White, MJ Zapka, JM TI Surveying physicians - Do components of the "Total Design Approach" to optimizing survey response rates apply to physicians? SO MEDICAL CARE LA English DT Article DE surveys; physicians; response rate ID NATIONAL MAIL SURVEY; GENERAL-PRACTITIONERS; COST-EFFECTIVENESS; RANDOMIZED TRIAL; FAMILY PHYSICIANS; TELEPHONE SURVEY; RETURN RATE; FOLLOW-UP; QUESTIONNAIRES; INCENTIVES AB BACKGROUND. Surveys serve essential roles in clinical epidemiology and health services research. However, physician surveys frequently encounter problems achieving adequate response rates. Research on enhancing response rates to surveys of the general public has led to the development of Dillman's "Total Design Approach" to the design and conduct of surveys. The impact of this approach on response rates among physicians is uncertain. OBJECTIVE. To determine the extent to which the components of the total design approach have been found to be effective in physician surveys. DESIGN. A systematic review. RESULTS. The effectiveness of prepaid financial incentives, special contacts, and personalization to enhance response rates in surveys of physicians have been confirmed by the existing research. There is suggestive evidence supporting the use of first class stamps on return envelopes and multiple contacts. The optimum amount for incentives and the number of contacts necessary have not been established. Details of questionnaire design and their impact on response rates have received almost no attention from researchers. Few studies have assessed the usefulness of combinations of components of the total design approach. CONCLUSIONS. Despite the number of surveys conducted among physicians, their cost, the level of interest in their findings, and in spite of inadequate response rates, there have been few randomized trials conducted on important aspects of enhancing response in this population. Until this gap has been filled, researchers conducting surveys of physicians should consider including all components of the total design approach whenever feasible. C1 Meyers Primary Care Inst, Fallon Healthcare Syst, Worcester, MA 01605 USA. Natl Canc Inst, Div Canc Control & Populat Sci, Rockville, MD USA. Henry Ford Hlth Syst, Detroit, MI USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. RP Field, TS (reprint author), Meyers Primary Care Inst, Fallon Healthcare Syst, 630 Plantat St, Worcester, MA 01605 USA. FU NCI NIH HHS [CA 79689] NR 63 TC 102 Z9 102 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUL PY 2002 VL 40 IS 7 BP 596 EP 605 DI 10.1097/00005650-200207000-00006 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 572XJ UT WOS:000176800000006 PM 12142775 ER PT J AU Smith, JC O'Connor, PJ Crabbe, JB Dishman, RK AF Smith, JC O'Connor, PJ Crabbe, JB Dishman, RK TI Emotional responsiveness after low- and moderate-intensity exercise and seated rest SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE anxiety; corrugator; cycling; EMG; IAPS; startle ID FEAR-POTENTIATED STARTLE; STATE ANXIETY; REFLEX; DIAZEPAM; HUMANS; TIME AB Purpose: Fe experiments have been conducted regarding the effects of exercise on emotional responsiveness. The aim of this experiment A us to determine whether anxiety-reducing conditions of low- and moderate-intensity cycling exercise lead to changes in emotional responsiveness to pictures designed to elicit pleasant. neutral. and unpleasant emotions. Methods: 24 healthy, college women completed counterbalanced conditions of 25 min of low- and moderate-intensity cycling exercise and seated rest. Indices of emotional responsiveness. including the acoustic star-tie eyeblink- and corrugator supercilii responses. as well as baseline corrugator supercilii electromyographic (EMG) activity. were measured immediately before and 20 min after each condition while participants viewed pleasant, neutral. and unpleasant pictures from the International Affective Picture System. Results: State anxiety was significantly reduced 20 min after each condition. Startle response magnitude was modulated by the affective content of the pictures and was reduced after each condition in response to each type of picture, Baseline corrugator EMG activity did not change after seated rest but decreased in an exercise intensity-dependent fashion after cycling. Corrugator EMG responses, during the pictures were not different between condition, or from pre- to post-conditions Conclusion: The findings suggest that cycling exercise results in decreased baseline activity of facial muscles involved in the expression of emotion but does not lead to changes in appetitive or defensive responses to emotional stimuli, Furthermore, anxiolytic conditions of low- and moderate-intensity cycling exercise and seated rest are related to decreased startle magnitude in healthy college women. C1 Univ Georgia, Dept Exercise Sci, Athens, GA 30602 USA. RP Smith, JC (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, Dept Clin & Hlth Psychol, POB 100165 HSC, Gainesville, FL 32610 USA. RI Smith, J. Carson/G-6404-2013 OI Smith, J. Carson/0000-0001-6142-0920 NR 35 TC 15 Z9 15 U1 5 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUL PY 2002 VL 34 IS 7 BP 1158 EP 1167 PG 10 WC Sport Sciences SC Sport Sciences GA 571GZ UT WOS:000176710800017 PM 12131257 ER PT J AU Vgontzas, AN Zoumakis, M Papanicolaou, DA Bixler, EO Prolo, P Lin, HM Vela-Bueno, A Kales, A Chrousos, GP AF Vgontzas, AN Zoumakis, M Papanicolaou, DA Bixler, EO Prolo, P Lin, HM Vela-Bueno, A Kales, A Chrousos, GP TI Chronic insomnia is associated with a shift of interleukin-6 and tumor necrosis factor secretion from nighttime to daytime SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID PITUITARY-ADRENAL AXIS; CLINICAL IMPLICATIONS; SLEEP-APNEA; TIME-SERIES; CYTOKINES; OBESITY AB Chronic insomnia, by far the most commonly encountered sleep disorder in medical practice, is characterized by difficulty failing or staying asleep at night and increased fatigue during the day. Interleukin-6 (IL-6) and tumor necrosis factor (TNF) are fatigue-inducing cytokines, and the daytime secretion of IL-6 is negatively influenced by the quantity and quality of the previous night's sleep. We hypothesize that the poor quality of insomniacs' sleep is associated with a hypersecretion of these 2 cytokines during the daytime, which, in turn, correlates with the fatigue experienced by these patients. Eleven young insomniacs (6 men and 5 women) and 11 (8 men and 3 women) age- and body mass index (BMI)-matched healthy controls participated in the study. Subjects were recorded in the sleep laboratory for 4 consecutive nights and serial 24-hour plasma measures of IL-6 and TNF were obtained during the 4th day. Insomniacs compared to controls slept poorly (sleep latency and wake were increased, whereas percentage sleep time was decreased during baseline nights, all P < .05). The mean 24-hour IL-6 and TNF secretions were not different between insomniacs and controls. However, the difference in the change (increase) of IL-6 plasma levels from midafternoon (2 Pm) to evening (9 Pm) between insomniacs and controls was significant (P < .01). Furthermore, cosinor analysis showed a significant shift of the major peak of IL-6 secretion from nighttime (4 AM) to evening (7 PM) in insomniacs compared to controls (P < .05). Also, while TNF secretion in controls showed a distinct circadian rhythm with a peak close and prior to the offset of sleep (P < .05), such a rhythm was not present in insomniacs. Finally, daytime secretion of TNF in insomniacs was characterized by a regular rhythm of 4 hours (P < .05); such a distinct periodicity was not present in controls. We conclude that chronic insomnia is associated with a shift of IL-6 and TNF secretion from nighttime to daytime, which may explain the daytime fatigue and performance decrements associated with this disorder. The daytime shift of IL-6 and TNF secretion, combined with a 24-hour hypersecretion of cortisol, an arousal hormone, may explain the insomniacs' daytime fatigue and difficulty failing asleep. Copyright 2002, Elsevier Science (USA). All rights reserved. C1 Penn State Univ, Coll Med, Dept Psychiat H073, Sleep Res & Treatment Ctr, Hershey, PA 17033 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Autonomous Univ Madrid, Dept Psychiat, E-28049 Madrid, Spain. RP Vgontzas, AN (reprint author), Penn State Univ, Coll Med, Dept Psychiat H073, Sleep Res & Treatment Ctr, 500 Univ Dr, Hershey, PA 17033 USA. NR 19 TC 147 Z9 152 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 2002 VL 51 IS 7 BP 887 EP 892 DI 10.1053/meta.2002.33357 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 569AY UT WOS:000176578200015 PM 12077736 ER PT J AU Goldfarb, LG AF Goldfarb, LG TI Kuru: the old epidemic in a new mirror SO MICROBES AND INFECTION LA English DT Review DE transmissible spongiform encephalopathy; kuru; prion; PRNP gene; Creutzfeldt-Jakob disease; genotype-phenotype correlation ID CREUTZFELDT-JAKOB-DISEASE; FATAL FAMILIAL INSOMNIA; SPONGIFORM ENCEPHALOPATHIES; VARIANT; GENOTYPE; POLYMORPHISM; STRAIN; AGENT; HOST AB The kuru epidemic lasted almost a century; it started in 1901-1902, reached epidemic proportions in the mid-1950s, and disappeared in the 1990s. Kuru is the prototype member of a group of disorders known as transmissible spongiform encephalopathies (TSEs) or prion diseases. Recent data on the genetics and pathogenesis of TSEs contribute to a better understanding of the documented kuru phenomena, and vice versa, observations made during the kuru epidemic are immensely helpful in understanding the epidemic of variant Creutzfeldt-Jakob disease that is currently developing in Europe. The major goal of this review is to identify and illustrate these points. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Goldfarb, LG (reprint author), NINDS, NIH, Room 4B37,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. NR 47 TC 14 Z9 15 U1 0 U2 5 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUL PY 2002 VL 4 IS 8 BP 875 EP 882 AR PII S1286-4579(02)01608-8 DI 10.1016/S1286-4579(02)01608-8 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 580KT UT WOS:000177234300013 PM 12270735 ER PT J AU Aliberti, J Sher, A AF Aliberti, J Sher, A TI Role of G-protein-coupled signaling in the induction and regulation of dendritic cell function by Toxoplasma gondii SO MICROBES AND INFECTION LA English DT Article DE Toxoplasma gondii; IL-12/CCR5; dendritic cell; lipoxin ID CHEMOKINE RECEPTOR EXPRESSION; IFN-GAMMA PRODUCTION; INTERFERON-GAMMA; CUTTING EDGE; INTERLEUKIN-12 PRODUCTION; INTRACELLULAR PATHOGEN; ACUTE INFECTION; P70 PRODUCTION; T-CELLS; IL-12 AB The induction of IL-12 from dendritic cells (DCs) is thought to be a critical step in the initiation of IFN-gamma-dependent cell-mediated immunity to many intracellular pathogens. We have studied this response using an in vivo model in which IL-12 production by splenic CD8alpha(+) DCs is followed after systemic injection of a soluble extract (STAg) of the protozoan parasite Toxoplasma gondii. Our findings indicate that G-protein-coupled signaling through the chemokine receptor CCR5 plays a major role in the induction of IL-12 from these cells and that downregulation of CCR5 function through endogenously produced lipoxin explains the loss of responsiveness (paralysis) seen upon STAg reinjection. Recent data on the inductive and regulatory pathways involved and their role in governing host resistance to parasite infection in vivo will be discussed. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sher, A (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 42 TC 12 Z9 14 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUL PY 2002 VL 4 IS 9 BP 991 EP 997 AR PII S1286-4579(02)01618-0 DI 10.1016/S1286-4579(02)01618-0 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 596GQ UT WOS:000178156700014 PM 12106793 ER PT J AU Garofalo, A Klager, SL Rowlinson, MC Nirmalan, N Klion, A Allen, JE Kennedy, MW Bradley, JE AF Garofalo, A Klager, SL Rowlinson, MC Nirmalan, N Klion, A Allen, JE Kennedy, MW Bradley, JE TI The FAR proteins of filarial nematodes: secretion, glycosylation and lipid binding characteristics SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE nematode; glycosylation; excretory/secretory; fatty acid binding protein; retinol binding protein; filariae ID ONCHOCERCA-VOLVULUS; RETINOIC ACID; COLLAGEN-SYNTHESIS; FIBROBLASTS; MODULATION; IVERMECTIN; BLINDNESS; INFECTION; HOMOLOGS; INVITRO AB The FAR proteins of nematodes are small (similar to 20 kDa), helix-rich. fatty acid and retinol-binding (FAR) proteins that appear to be confined to nematodes. We have carried out a comparative sequence and biochemical analysis of selected FAR proteins often species of filarial parasites (from the genera Onchocerea, Brugia, Wuchereria, Loa, Acanthocheilonema and Litomosoides). The sequences fall into two main groups corresponding broadly to the onchocercal and lymphatic filariasis parasites, and only those with unsheathed microfilariae were found to produce glycosylated FAR proteins. The proteins were released into culture medium by all the species and developmental stages investigated. Recombinant forms of two of these proteins (Ov-FAR-1 from O. volvulus and Bm-FAR-1 from B. malayi) were compared for ligand binding in fluorescence-based assays. Both were found to bind all-transretinol, (dansylamino) undecanoic acid (DAUDA), and oleic acid by competition. Both produced an identical, and dramatic, blueshift in the fluorescence emission of DAUDA (from 541 to approximately 483 nm), indicative of similarity in the binding site environments of the two proteins. These findings indicate that there is strong conservation of the biochemical activities of the FAR proteins between the different parasite species, although they appear to have different post-translational modifications which may relate to the biology of the larvae. (C) 2002 Published by Elsevier Science B.V. C1 Univ Nottingham, Sch Life & Environm Sci, Nottingham NG7 2RD, England. Univ Manchester, Inst Sci & Technol, Dept Biomol Sci, Manchester M60 1QD, Lancs, England. NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. Univ Edinburgh, ICAPB Ashworth Lab, Edinburgh EH9 3JT, Midlothian, Scotland. Univ Glasgow, Inst Biomed & Life Sci, Div Environm & Evolut Biol, Glasgow G12 8QQ, Lanark, Scotland. RP Bradley, JE (reprint author), Univ Nottingham, Sch Life & Environm Sci, Univ Pk, Nottingham NG7 2RD, England. RI Allen, Judith/C-9198-2011; OI Allen, Judith/0000-0002-3829-066X; Bradley, Janette/0000-0003-3973-7977; Klion, Amy/0000-0002-4986-5326 NR 30 TC 33 Z9 43 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUL PY 2002 VL 122 IS 2 BP 161 EP 170 AR PII S0166-6851(02)00097-X DI 10.1016/S0166-6851(02)00097-X PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 584VJ UT WOS:000177489200006 PM 12106870 ER PT J AU Duhe, RJ Clark, EA Farrar, WL AF Duhe, RJ Clark, EA Farrar, WL TI Characterization of the in vitro kinase activity of a partially purified soluble GST/JAK2 fusion protein SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE JAK2; protein-tyrosine kinase; enzyme inhibitors; tyrphostin; baculovirus; affinity chromatography ID EPIDERMAL GROWTH-FACTOR; MICE LACKING JAK3; TYROSINE KINASE; REQUIRES PHOSPHORYLATION; CONSTITUTIVE ACTIVATION; DEVELOPMENTAL DEFECTS; FACTOR RECEPTOR; STAT PATHWAY; LEUKEMIA; CELLS AB The biochemical and biophysical characteristics of Janus protein-tyrosine kinases (JAKs), which are essential early mediators of cytokine-initiated signal propagation, are virtually undefined. To facilitate the in vitro analysis of JAK-mediated catalysis, we substantially purified a soluble recombinant JAK2 and developed a novel means of quantifying JAK-catalyzed product formation. Glutathione-S-transferase fusion proteins containing active and inactive forms of rat Janus kinase 2 (GST:rJAK2 and GST: rJAK2(CDelta795)) were highly purified via affinity chromatography. A microtiterplate-based ELISA was used to measure tyrosine phosphorylation of a streptavidin-immobilized biotinylated STAT1-derived peptide. The ELISA data indicated that only about 1% of the enzyme was involved in exogenous substrate phosphorylation. Other immobilized peptides served as apparent substrates with varying efficacy. Traditional radioisotopic autokinase assays demonstrated that the activity of the purified fusion protein was inhibited by a variety of tyrphostin inhibitors. Non-radiolabeled adenine nucleotides, but not guanine nucleotides, inhibited the radioisotopic autokinase assay. These observations verify that the catalytic activity of JAK2 is highly regulated, and are consistent with the suggestion that JAK2 may require additional accessory proteins, such as a potential upstream regulatory kinase, for full catalytic activity. C1 Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, Jackson, MS 39216 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. NCI, Cytokine Mol Mech Sect, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Duhe, RJ (reprint author), Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, Jackson, MS 39216 USA. FU NCI NIH HHS [N01-CO-5600] NR 34 TC 16 Z9 16 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JUL PY 2002 VL 236 IS 1-2 BP 23 EP 35 DI 10.1023/A:1016186907376 PG 13 WC Cell Biology SC Cell Biology GA 572MV UT WOS:000176779600004 PM 12190118 ER PT J AU Lu, HX Pise-Masison, CA Fletcher, TM Schiltz, RL Nagaich, AK Radonovich, M Hager, G Cole, PA Brady, JN AF Lu, HX Pise-Masison, CA Fletcher, TM Schiltz, RL Nagaich, AK Radonovich, M Hager, G Cole, PA Brady, JN TI Acetylation of nucleosomal histones by p300 facilitates transcription from tax-responsive human T-cell leukemia virus type I chromatin template SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; CREB-BINDING-PROTEIN; COACTIVATOR CBP; ACETYLTRANSFERASE ACTIVITY; TRANSACTIVATOR TAX; 21-BASE-PAIR REPEATS; ADAPTER FUNCTION; GENE-EXPRESSION; ACTIVATION; PROMOTER AB Expression of human T-cell leukemia virus type 1 (HTLV-1) is regulated by the viral transcriptional activator Tax. Tax activates viral transcription through interaction with the cellular transcription factor CREB and the coactivators CBP/p300. One key property of the coactivators is the presence of histone acetyltransferase (HAT) activity, which enables p300/CBP to modify nucleosome structure. The data presented in this manuscript demonstrate that full-length p300 and CBP facilitate transcription of a reconstituted chromatin template in the presence of Tax and CREB. The ability of p300 and CBP to activate transcription from the chromatin template is dependent upon the HAT activity. Moreover, the coactivator HAT activity must be tethered to the template by Tax and CREB, since a p300 mutant that fails to interact with Tax did not facilitate transcription or acetylate histones. p300 acetylates histones H3 and H4 within nucleosomes located in the promoter and 5' proximal regions of the template. Nucleosome acetylation is accompanied by an increase in the level of binding of RNA polymerase 11 transcription factor TFIID and RNA polymerase H to the promoter. Interestingly, we found distinct transcriptional activities between CBP and p300. CBP, but not p300, possesses an N-terminal activation domain which directly activates Tax-mediated HTLV-1 transcription from a naked DNA template. Finally, using the chromatin immunoprecipitation assay, we provide the first direct experimental evidence that p300 and CBP are associated with the HTLV-1 long terminal repeat in vivo. C1 NCI, BRL, Virus Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NIAMSD, Muscle Gene Express Grp, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. George Washington Univ, Grad Program Genet, Inst Biomed Sci, Washington, DC 20037 USA. RP Brady, JN (reprint author), NCI, BRL, Virus Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. NR 75 TC 54 Z9 56 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2002 VL 22 IS 13 BP 4450 EP 4462 DI 10.1128/MCB.22.13.4450-4462.2002 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 562UJ UT WOS:000176217100002 PM 12052856 ER PT J AU Pile, LA Schlag, EM Wassarman, DA AF Pile, LA Schlag, EM Wassarman, DA TI The SIN3/RPD3 deacetylase complex is essential for G(2) phase cell cycle progression and regulation of SMRTER corepressor levels SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MAMMALIAN HISTONE DEACETYLASE; RAT 3Y1 FIBROBLASTS; TRANSCRIPTIONAL REPRESSION; N-COR; CHROMOSOME CONDENSATION; MEDIATED REPRESSION; SODIUM-BUTYRATE; NUCLEAR RECEPTORS; NUCLEOSOMAL DNA; TRICHOSTATIN-A AB The SIN3 corepressor and RPD3 histone deacetylase are components of the evolutionarily conserved SIN3/RPD3 transcriptional repression complex. Here we show that the SIN3/RPD3 complex and the corepressor SMRTER are required for Drosophila G(2) phase cell cycle progression. Loss of the SIN3, but not the p55, SAP18, or SAP30, component of the SIN3/RPD3 complex by RNA interference (RNAi) causes a cell cycle delay prior to initiation of mitosis. Loss of RPD3 reduces the growth rate of cells but does not cause a distinct cell cycle defect, suggesting that cells are delayed in multiple phases of the cell cycle, including G(2). Thus, the role of the SIN3/RPD3 complex in G(2) phase progression appears to be independent of p55, SAP18, and SAP30. SMRTER protein levels are reduced in SIN3 and RPD3 RNAi cells, and loss of SMRTER by RNAi is sufficient to cause a G(2) phase delay, demonstrating that regulation of SMRTER protein levels by the SIN3/RPD3 complex is a vital component of the transcriptional repression mechanism. Loss of SIN3 does not affect global acetylation of histones H3 and H4, suggesting that the G(2) phase delay is due not to global changes in genome integrity but rather to derepression of SIN3 target genes. C1 Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Wassarman, DA (reprint author), Univ Wisconsin, Sch Med, Dept Pharmacol, 1300 Univ Ave, Madison, WI 53706 USA. NR 83 TC 47 Z9 49 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2002 VL 22 IS 14 BP 4965 EP 4976 DI 10.1128/MCB.22.14.4965-4976.2002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 566VF UT WOS:000176448400001 PM 12077326 ER PT J AU Cogliati, T Good, DJ Haigney, M Delgado-Romero, P Eckhaus, MA Koch, WJ Kirsch, IR AF Cogliati, T Good, DJ Haigney, M Delgado-Romero, P Eckhaus, MA Koch, WJ Kirsch, IR TI Predisposition to arrhythmia and autonomic dysfunction in Nhlh1-deficient mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HEART-RATE-VARIABILITY; SUDDEN CARDIAC DEATH; LOOP-HELIX GENES; ACUTE MYOCARDIAL-INFARCTION; DEVELOPING NERVOUS-SYSTEM; POWER SPECTRAL-ANALYSIS; BAROREFLEX SENSITIVITY; CONSCIOUS DOGS; EXPRESSION; DIFFERENTIATION AB Nhlh1 is a basic helix-loop-helix transcription factor whose expression is restricted to the nervous system and which may play a role in neuronal differentiation. To directly study Nhlh1 function, we generated null mice. Homozygous mutant mice were predisposed to premature, adult-onset, unexpected death. Electrocardiograms revealed decreased total heart rate variability, stress-induced arrhythmia, and impaired baroreceptor sensitivity. This predisposition to arrhythmia is a likely cause of the observed death in the mutant mice. Heterozygosity for the closely related transcription factor Nhlh2 increased the severity of the Nhlh1-null phenotype. No signs of primary cardiac structural or conduction abnormalities could be detected upon necropsy of the null mice. The pattern of altered heart rhythm observed in basal and experimental conditions (stress and pharmacologically induced) suggests that a deficient parasympathetic tone may contribute to the arrhythmia in the Nhlh1-null mouse. The expression of Nhlh1 in the developing brain stem and in the vagal nuclei in the wild-type mouse further supports this hypothesis. The Nhlh1 mutant mouse may thus provide a model to investigate the contribution of the autonomic nervous system to arrhythmogenesis. C1 NCI, CCR, Genet Branch, Natl Naval Med Ctr,NIH, Bethesda, MD 20889 USA. Uniformed Serv Univ Hlth Sci, Div Cardiol, Dept Med, Bethesda, MD 20814 USA. NIH, Vet Resources Program, Off Res Serv, Off Director, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Kirsch, IR (reprint author), NCI, CCR, Genet Branch, Natl Naval Med Ctr,NIH, 8901 Wisconsin Ave,Bldg 8,Rm 5101, Bethesda, MD 20889 USA. NR 46 TC 19 Z9 19 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2002 VL 22 IS 14 BP 4977 EP 4983 DI 10.1128/MCB.22.14.4977-4983.2002 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 566VF UT WOS:000176448400002 PM 12077327 ER PT J AU Chandrasekharan, S Qiu, TH Alkharouf, N Brantley, K Mitchell, JB Liu, ET AF Chandrasekharan, S Qiu, TH Alkharouf, N Brantley, K Mitchell, JB Liu, ET TI Characterization of mice deficient in the Src family nonreceptor tyrosine kinase Frk/rak SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID THYROID-HORMONE; GASTROINTESTINAL-TRACT; IONIZING-RADIATION; CELL-PROLIFERATION; MUTANT MICE; C-SRC; EXPRESSION; GROWTH; GENE; CLONING AB Frk/rak belongs to a novel family of Src kinases with epithelial tissue-specific expression. Although developmental expression patterns and functional overexpression in vitro have associated these kinases with growth suppression and differentiation, their physiological functions remain largely unknown. We therefore generated mice carrying a null mutation in iyk, the mouse homolog of Frk/rak. We report here that frk/rak(-/-) mice are viable, show similar growth rates to wild-type animals, and are fertile. Furthermore, a 2-year study of health and survival did not identify differences in the incidence and spectrum of spontaneous tumors or provide evidence of hyperplasias in frk/rak(-/-) epithelial tissues. Histological analysis of organs failed to reveal any morphological changes in epithelial tissues that normally express high levels of Frk/rak. Ultrastructural analysis of intestinal enterocytes did not identify defects in brush border morphology or structural polarization, demonstrating that Frk/rak is dispensable for intestinal cytodifferentiation. Additionally, frk/rak-null mice do not display altered sensitivity to intestinal damage induced by ionizing radiation. cDNA microarray analysis revealed an increase in c-src expression and identified subtle changes in the expression of genes regulated by thyroid hormones. Significant decreases in the circulating levels of T3 but not T4 hormone are consistent with this observation and reminiscent of euthyroid sick syndrome, a stress-associated clinical condition. C1 Genome Inst Singapore, Singapore 117528, Singapore. Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. NCI, Div Clin Sci, Sect Cell Signaling & Oncogenesis, NIH, Gaithersburg, MD 20877 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Liu, ET (reprint author), Genome Inst Singapore, 1 Capricorn 05-01,Sci Pk 2, Singapore 117528, Singapore. RI Liu, Edison/C-4141-2008 NR 55 TC 26 Z9 27 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2002 VL 22 IS 14 BP 5235 EP 5247 DI 10.1128/MCB.22.14.5235-5247.2002 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 566VF UT WOS:000176448400025 PM 12077350 ER PT J AU Yanagisawa, LL Marchena, J Xie, ZG Li, XM Poon, PP Singer, RA Johnston, GC Randazzo, PA Bankaitis, VA AF Yanagisawa, LL Marchena, J Xie, ZG Li, XM Poon, PP Singer, RA Johnston, GC Randazzo, PA Bankaitis, VA TI Activity of specific lipid-regulated ADP ribosylation factor-GTPase-activating proteins is required for Sec14p-dependent Golgi secretory function in yeast SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PHOSPHOLIPID TRANSFER PROTEIN; PHOSPHATIDYLINOSITOL TRANSFER PROTEINS; SACCHAROMYCES-CEREVISIAE; IN-VIVO; ARF; COMPLEX; TRANSPORT; GENE; PHOSPHATIDYLCHOLINE; HYDROLYSIS AB Yeast phosphatidylinositol transfer protein (Sec14p) coordinates lipid metabolism with protein-trafficking events. This essential Sec14p requirement for Golgi function is bypassed by mutations in any one of seven genes that control phosphatidylcholine or phosphoinositide metabolism. In addition to these "bypass Sec14p" mutations, Sec14p-independent Golgi function requires phospholipase D activity. The identities of lipids that mediate Sec14p-dependent Golgi function, and the identity of the proteins that respond to Sec14p-mediated regulation of lipid metabolism, remain elusive. We now report genetic evidence to suggest that two ADP ribosylation factor-GTPase-activating proteins (ARFGAPs), Gcs1p and Age2p, may represent these lipid-responsive elements, and that Gcs1p/Age2p act downstream of Sec14p and phospholipase D in both Sec14p-dependent and Sec14p-independent pathways for yeast Golgi function. In support, biochemical data indicate that Gcs1p and Age2p ARFGAP activities are both modulated by lipids implicated in regulation of Sec14p pathway function. These results suggest ARFGAPs are stimulatory factors required for regulation of Golgi function by the Sec14p pathway, and that Sec14p-mediated regulation of lipid metabolism interfaces with the activity of proteins involved in control of the ARF cycle. C1 NCI, Div Basic Sci, Cellular Oncol Lab, Bethesda, MD 20892 USA. Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS B3H 4H7, Canada. Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS B3H 4H7, Canada. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. RP Bankaitis, VA (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. FU NIGMS NIH HHS [GM-44530, R01 GM044530] NR 46 TC 64 Z9 64 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2002 VL 13 IS 7 BP 2193 EP 2206 DI 10.1091/mbc.01-11-0563 PG 14 WC Cell Biology SC Cell Biology GA 579RX UT WOS:000177192600001 PM 12134061 ER PT J AU Bondeva, T Balla, A Varnai, P Balla, T AF Bondeva, T Balla, A Varnai, P Balla, T TI Structural determinants of Ras-Raf interaction analyzed in live cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ACTIVATED PROTEIN-KINASE; BETA-GAMMA-SUBUNITS; HETEROTRIMERIC G-PROTEINS; CYSTEINE-RICH DOMAIN; SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURE; PLASMA-MEMBRANE; PHOSPHATIDIC-ACID; TYROSINE KINASE; BINDING-SITE AB The minimum structure of the Raf-1 serine/threonine kinase that recognizes active Ras was used to create a green fluorescent fusion protein (GFP) for monitoring Ras activation in live cells. In spite of its ability to bind activated Ras in vitro, the Ras binding domain (RBD) of Raf-1 (Raf-1[51-131]GFP) failed to detect Ras in Ras-transformed NIH 3T3 fibroblasts and required the addition of the cysteine-rich domain (CRD) (Raf-1[51-220]GFP) to show clear localization to plasma membrane ruffles. In normal NIH 3T3 cells, (Raf-1[51-220]GFP) showed minimal membrane localization that was enhanced after stimulation with platelet-derived growth factor or phorbol-12-myristate-13-acetate. Mutations within either the RBD (R89L) or CRD (C168S) disrupted the membrane localization of (Raf-1 [51-220]GFP), suggesting that both domains contribute to the recruitment of the fusion protein to Ras at the plasma membrane. The abilities of the various constructs to localize to the plasma membrane closely correlated with their inhibitory effects on mitogen-activated protein kinase kinasel and mitogen-activated protein kinase activation. Membrane localization of full-length Raf-1-GFP was less prominent than that of (Raf-1[51-220]GFP) in spite of its strong binding to RasV12 and potent activation of mitogen-activated protein kinase. These finding indicate that both RBD and CRD are necessary to recruit Raf-1 to active Ras at the plasma membrane, and that these domains are not fully exposed in the Raf-1 molecule. Visualization of activated Ras in live cells will help to better understand the dynamics of Ras activation under various physiological and pathological conditions. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Balla, T (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. OI Balla, Tamas/0000-0002-9077-3335; Balla, Andras/0000-0002-6450-2793 NR 37 TC 40 Z9 41 U1 1 U2 6 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2002 VL 13 IS 7 BP 2323 EP 2333 DI 10.1091/mbc.E02-01-0019 PG 11 WC Cell Biology SC Cell Biology GA 579RX UT WOS:000177192600012 PM 12134072 ER PT J AU Sugimoto, H Sugahara, M Folsch, H Koide, Y Nakatsu, F Tanaka, N Nishimura, T Furukawa, M Mullins, C Nakamura, N Mellman, I Ohno, H AF Sugimoto, H Sugahara, M Folsch, H Koide, Y Nakatsu, F Tanaka, N Nishimura, T Furukawa, M Mullins, C Nakamura, N Mellman, I Ohno, H TI Differential recognition of tyrosine-based basolateral signals by AP-1B subunit mu 1B in polarized epithelial cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID DARBY CANINE KIDNEY; SORTING SIGNALS; MDCK CELLS; ADAPTER COMPLEXES; PROTEIN COMPLEX; STRUCTURAL REQUIREMENTS; TRANSFERRIN RECEPTOR; PLASMA-MEMBRANE; MEDIUM CHAINS; FC-RECEPTORS AB To investigate the importance of tyrosine recognition by the AP-1B clathrin adaptor subunit mu1B for basolateral sorting of integral membrane proteins in polarized epithelial cells, we have produced and characterized a mutant form of mu1B. The mutant (M-mu1B) contains alanine substitutions of each of the four conserved residues, which in the AP-2 adaptor subunit mu2 are critical for interacting with tyrosine-based endocytosis signals. We show M-mu1B is defective for tyrosine binding in vitro, but is nevertheless incorporated into AP-1 complexes in transfected cells. Using LLC-PK1 cells expressing either wild type or M-mu1B, we find that there is inefficient basolateral expression of membrane proteins whose basolateral targeting signals share critical tyrosines with signals for endocytosis. In contrast, membrane proteins whose basolateral targeting signals are distinct from their endocytosis signals (transferrin and low-density lipoprotein receptors) accumulate at the basolateral domain normally, although in a manner that is strictly dependent on mu1B or M-mu1B expression. Our results suggest that mu1B interacts with different classes of basolateral targeting signals in distinct ways. C1 Kanazawa Univ, Grad Sch Med Sci, Canc Res Inst, Div Mol Membrane Biol, Kanazawa, Ishikawa 9200934, Japan. Kanazawa Univ, Grad Sch Med Sci, Dept Otorhinolaryngol Head & Neck Surg, Kanazawa, Ishikawa 9200934, Japan. Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Ludwig Inst Canc Res, New Haven, CT 06520 USA. RIKEN, Res Ctr Allergy & Immunol, Yokohama, Kanagawa 2300045, Japan. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Ohno, H (reprint author), Kanazawa Univ, Grad Sch Med Sci, Canc Res Inst, Div Mol Membrane Biol, Kanazawa, Ishikawa 9200934, Japan. RI Ohno, Hiroshi/L-7899-2014 OI Ohno, Hiroshi/0000-0001-8776-9661 FU NIGMS NIH HHS [GM-29765, R01 GM029765] NR 36 TC 54 Z9 55 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2002 VL 13 IS 7 BP 2374 EP 2382 DI 10.1091/mbc.E01-10-0096 PG 9 WC Cell Biology SC Cell Biology GA 579RX UT WOS:000177192600016 PM 12134076 ER PT J AU Bonangelino, CJ Chavez, EM Bonifacino, JS AF Bonangelino, CJ Chavez, EM Bonifacino, JS TI Genomic screen for vacuolar protein sorting genes in Saccharomyces cerevisiae SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ADP-RIBOSYLATION FACTOR; AP-3 ADAPTER COMPLEX; TRANS-GOLGI NETWORK; ALKALINE-PHOSPHATASE; NUCLEOTIDE EXCHANGE; ACTIN CYTOSKELETON; INTRACELLULAR-TRANSPORT; INTERNALIZATION STEP; MULTIVESICULAR BODY; ENDOCYTIC PATHWAYS AB The biosynthetic sorting of hydrolases to the yeast vacuole involves transport along two distinct routes referred to as the carboxypeptidase Y and alkaline phosphatase pathways. To identify genes involved in sorting to the vacuole, we conducted a genome-wide screen of 4653 homozygous diploid gene deletion strains of Saccharomyces cerevisiae for missorting of carboxypeptidase Y. We identified 146 mutant strains that secreted strong-to-moderate levels of carboxypeptidase Y. Of these, only 53 of the corresponding genes had been previously implicated in vacuolar protein sorting, whereas the remaining 93 had either been identified in screens for other cellular processes or were only known as hypothetical open reading frames. Among these 93 were genes encoding: 1) the Ras-like GTP-binding proteins Arl1p and Arl3p, 2) actin-related proteins such as Arp5p and Arp6p, 3) the monensin and brefeldin A hypersensitivity proteins Mon1p and Mon2p, and 4) 15 novel proteins designated Vps61p-Vps75p. Most of the novel gene products were involved only in the carboxypeptidase Y pathway, whereas a few, including Mon1p, Mon2p, Vps61p, and Vps67p, appeared to be involved in both the carboxypeptidase Y and alkaline phosphatase pathways. Mutants lacking some of the novel gene products, including Arp5p, Arp6p, Vps64p, and Vps67p, were severely defective in secretion of mature a-factor. Others, such as Vps61p, Vps64p, and Vps67p, displayed defects in the actin cytoskeleton at 30degreesC. The identification and phenotypic characterization of these novel mutants provide new insights into the mechanisms of vacuolar protein sorting, most notably the probable involvement of the actin cytoskeleton in this process. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 85 TC 222 Z9 242 U1 1 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2002 VL 13 IS 7 BP 2486 EP 2501 DI 10.1091/mbc.02-01-0005 PG 16 WC Cell Biology SC Cell Biology GA 579RX UT WOS:000177192600025 PM 12134085 ER PT J AU Clark, AS West, K Streicher, S Dennis, PA AF Clark, AS West, K Streicher, S Dennis, PA TI Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE KINASE-3; SERINE-THREONINE KINASE; INTEGRIN-LINKED KINASE; GROWTH-FACTOR-I; NF-KAPPA-B; PHOSPHATIDYLINOSITOL 3-KINASE; INDUCED APOPTOSIS; CELLULAR-SURVIVAL; CD95-MEDIATED APOPTOSIS AB To evaluate the role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in breast cancer cell survival and therapeutic resistance, we analyzed a panel of six breast cancer cell lines that varied in erbB2 and estrogen receptor status. Akt activity was constitutive in four cell lines and was associated with either PTEN mutations or erbB2 overexpression. Akt promoted breast cancer cell survival because a PI3K inhibitor, LY294002, or transient transfection of a dominant-negative Akt mutant inhibited Akt activity and increased apoptosis. When combined with therapies commonly used in breast cancer treatment, LY294002 potentiated apoptosis caused by doxorubicin, trastuzumab, paclitaxel, or etoposide. Potentiation of apoptosis by LY294002 correlated with induction of Akt by doxorubicin or trastuzumab alone that occurred before the onset of apoptosis. Similar results were observed with tamoxifen. Combining LY294002 with tamoxifen in estrogen receptor-positive cells greatly potentiated apoptosis, which was correlated with tamoxifen-induced Akt phosphorylation that preceded apoptosis. To confirm that the effects of LY294002 on chemotherapy-induced apoptosis were attributable to inhibition of Akt, we transiently transfected breast cancer cells with dominant-negative Akt and observed increased doxorubicin-induced apoptosis. Conversely, stably transfecting cells with constitutively active Akt increased Akt activity and attenuated doxorubicin-induced apoptosis. These studies show that endogenous Akt activity promotes breast cancer cell survival and therapeutic resistance, and that induction of Akt by chemotherapy, trastuzumab, or tamoxifen might be an early compensatory mechanism that could be exploited to increase the efficacy of these therapies. C1 USN, Natl Canc Inst, Canc Therapeut Branch, Ctr Canc Res, Bethesda, MD 20889 USA. USN, Natl Med Ctr, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), USN, Natl Canc Inst, Canc Therapeut Branch, Ctr Canc Res, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 66 TC 437 Z9 459 U1 1 U2 16 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2002 VL 1 IS 9 BP 707 EP 717 PG 11 WC Oncology SC Oncology GA 607BM UT WOS:000178770600006 PM 12479367 ER PT J AU Pavlov, YI Newlon, CS Kunkel, TA AF Pavlov, YI Newlon, CS Kunkel, TA TI Yeast origins establish a strand bias for replicational mutagenesis SO MOLECULAR CELL LA English DT Article ID DNA-POLYMERASE-DELTA; BASE ANALOG 6-N-HYDROXYLAMINOPURINE; CEREVISIAE CHROMOSOME-III; SACCHAROMYCES-CEREVISIAE; LAGGING-STRAND; ESCHERICHIA-COLI; LEADING-STRAND; SPECIFICITY; MUTATIONS; FIDELITY AB To determine whether replicational mutagenesis in the yeast genome is influenced by the positions of active origins, a reporter gene was placed in two orientations at multiple locations within a 39,000 bp region of chromosome III possessing two strong origins. The frequency of mutations resulting from misincorporation of adenine opposite 8-hydroxyguanine in one strand and 6-hydroxylaminopurine opposite cytosine in the other strand differed by 3- to 10-fold, depending on the gene orientation and its distance from the origins. The observed patterns indicate that active origins establish a strand bias for mutations that is maintained over thousands of base pairs and results from lower nucleotide selectivity and/or less efficient proofreading or mismatch repair during leading strand DNA replication. C1 NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA. RP Kunkel, TA (reprint author), NIEHS, Genet Mol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 31 TC 73 Z9 74 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUL PY 2002 VL 10 IS 1 BP 207 EP 213 DI 10.1016/S1097-2765(02)00567-1 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 574XX UT WOS:000176916600023 PM 12150920 ER PT J AU Rodrigo, MJ Moskovitz, J Salamini, F Bartels, D AF Rodrigo, MJ Moskovitz, J Salamini, F Bartels, D TI Reverse genetic approaches in plants and yeast suggest a role for novel, evolutionarily conserved, selenoprotein-related genes in oxidative stress defense SO MOLECULAR GENETICS AND GENOMICS LA English DT Article DE oxidative stress; PilB; selenoprotein; methionine sulfoxide reductase; reverse genetics ID METHIONINE SULFOXIDE REDUCTASE; SELENOCYSTEINE-CONTAINING PROTEINS; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; ANTIOXIDANT DEFENSE; ACTIVE-SITE; IN-VIVO; EXPRESSION; RESIDUES; CLONING AB Oxidation of methionine residues during periods of oxidative stress can lead to loss of protein function. Organisms have developed defense strategies to minimize such damage. The PilB protein, which is involved in pilus formation in the pathogen Neisseria gonorrhoeae, is composed of three functional protein domains (I-III) with putative roles in oxidative stress defense. These domains are evolutionarily conserved and homologs have been discovered in diverse prokaryotes and eukaryotes. Domain III shows similarities to selenoproteins which contain selenium instead of sulfur in a conserved cysteine residue. The substitution of selenium for sulfur alters the redox properties of such proteins. Knock-out mutants were used to elucidate the function of these novel selenoprotein-like domains in yeast and in Arabidopsis thaliana. We show that organisms with non-functional genes for selenoprotein-like polypeptides accumulate higher levels of oxidized methionine residues on exposure to oxidative stress. The behavior of the mutants suggests that these novel selenoprotein-like gene products are part of a ubiquitous detoxification system that interacts with other redox-related proteins such as the thioredoxin-related protein and methionine sulfoxide reductase which are encoded by domains I and II of PilB. These proteins may be encoded by one gene as in the case of several prokaryotes, or by separate genes as in the eukaryotes examined here. C1 Max Planck Inst Zuchtungsforsch, D-50829 Cologne, Germany. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Bartels, D (reprint author), Max Planck Inst Zuchtungsforsch, Carl Von Linne Weg 10, D-50829 Cologne, Germany. RI Rodrigo, Maria/H-7720-2012 OI Rodrigo, Maria/0000-0003-2668-0684 NR 61 TC 41 Z9 44 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1617-4615 J9 MOL GENET GENOMICS JI Mol. Genet. Genomics PD JUL PY 2002 VL 267 IS 5 BP 613 EP 621 DI 10.1007/s00438-002-0692-3 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 584CL UT WOS:000177449600007 PM 12172800 ER PT J AU Kleta, R Skovby, F Christensen, E Rosenberg, T Gahl, WA Anikster, Y AF Kleta, R Skovby, F Christensen, E Rosenberg, T Gahl, WA Anikster, Y TI 3-methylglutaconic aciduria type III in a non-Iraqi-Jewish kindred: clinical and molecular findings SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE 3-methylglutaconic acid; 3-methylglutaric acid; optic atrophy; ataxia; mitochondrion ID OPTIC ATROPHY; GENE AB Type III 3-methylglutaconic aciduria (NIGA) (MIM 258501) consists of early bilateral optic atrophy, later development of spasticity, extrapyramidal dysfunction and occasionally cognitive deficits, and urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. The presence of the disorder in an Iraqi-Jewish genetic isolate led to mapping of the OPA3 gene to chromosome 19q13.2-q13.3, followed by isolation of the gene itself. OPA3 consists of two exons and codes for a peptide of 179 amino acids. Iraqi-Jewish patients with type III MGA are homozygous for a splice site founder mutation in OPA3 (IVS1-1G > C) which abolishes mRNA expression in fibroblasts. Here we report a novel mutation in OPA3 (320-337del) in a Kurdish-Turkish patient with optic atrophy and 3-methylglutaconic and 3-methylglutaric aciduria, previously carrying the diagnosis of type IV MGA. We conclude that type III MGA occurs in patients of non-Iraqi-Jewish ancestry, and should be considered in patients with type IV MGA that have optic atrophy and ataxia. (C) 2002 Elsevier Science (USA). All rights reserved. C1 NICHHD, Heritable Disorders Branch, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA. Univ Copenhagen Hosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark. Natl Eye CLin Visually Impaired, Gordon Norrie Ctr Genet Eye Dis, Hellerup, Denmark. RP Gahl, WA (reprint author), NICHHD, Heritable Disorders Branch, Sect Human Biochem Genet, NIH, 10 Ctr Dr,MSC 1830,Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. NR 14 TC 22 Z9 22 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JUL PY 2002 VL 76 IS 3 BP 201 EP 206 AR PII S1096-7192(02)00047-1 DI 10.1016/S1096-7192(02)00047-1 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 590ZM UT WOS:000177854900005 PM 12126933 ER PT J AU Gahl, WA Brantly, M Troendle, J Avila, NA Padua, A Montalvo, C Cardona, H Calis, KA Gochuico, B AF Gahl, WA Brantly, M Troendle, J Avila, NA Padua, A Montalvo, C Cardona, H Calis, KA Gochuico, B TI Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE pulmonary fibrosis; pirfenidone; albinism; platelet storage pool; vesicle formation ID VESICLE FORMATION; ANTIFIBROTIC AGENT; LUNG FIBROSIS; GENE; MUTATIONS; FORM; TRAFFICKING; DISORDERS; BETA AB Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism, a platelet storage pool deficiency and, in patients with HPS1 gene mutations, a progressive, fatal pulmonary fibrosis. We investigated the safety and efficacy of an antifibrotic agent, pirfenidone (800 mg, t.i.d.), in treating 21 adult Puerto Rican HPS patients, including 20 homozygous for the same HPS1 mutation. Patients were examined every 4 months for up to 44 months in a randomized, placebo-controlled trial, with rate of change in pulmonary function values as outcome parameters. Using the complete data set of 130 patient admissions, a repeated measures model showed that 11 pirfenidone-treated patients lost FVC at a rate 5% of predicted (similar to400 mL) per year slower than 10 placebo-treated patients (p = 0.001). A random coefficients model showed no significant difference. However, using data restricted to patients with an initial FVC > 50% of predicted, both models showed the pirfenidone group losing FVC (p < 0.022), FEV(1) (p < 0.0007), TLC (p < 0.001), and DLCO (p < 0.122) at a rate similar to8%/year slower than the placebo group. Clinical and laboratory side effects were similar in the two groups. Pirfenidone appears to slow the progression of pulmonary fibrosis in HPS patients who have significant residual lung function. (C) 2002 Elsevier Science (USA). All rights reserved. C1 NICHHD, NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NICHD, Biometry & Math Stat Branch, Bethesda, MD USA. NIH, Warren G Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. Ctr Neumol, Mayaguez, PR USA. Pulm & Crit Care Clin, Arecibo, PR USA. NIH, Warren G Magnuson Clin Ctr, Dept Nursing, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NICHHD, NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. EM bgahl@helix.nih.go NR 28 TC 91 Z9 95 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JUL PY 2002 VL 76 IS 3 BP 234 EP 242 AR PII S1096-7192(02)00044-6 DI 10.1016/S1096-7192(02)00044-6 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 590ZM UT WOS:000177854900010 PM 12126938 ER PT J AU Tian, WZ Chua, K Strober, W Chu, CC AF Tian, WZ Chua, K Strober, W Chu, CC TI ILG1: A new integrase-like gene that is a marker of bacterial contamination by the laboratory Escherichia coli strain TOP10F ' SO MOLECULAR MEDICINE LA English DT Article ID SITE-SPECIFIC RECOMBINATION; B-CELL DIFFERENTIATION; TRANSFER-RNA GENE; PATHOGENICITY ISLAND; SHIGELLA-FLEXNERI; EXPRESSED GENES; DNA-SEQUENCE; EVOLUTION; SUBTRACTION; CLONING AB Background: identification of differentially expressed genes between normal and diseased states is an area of intense current medical research that can lead to the discovery of new therapeutic targets. However, isolation of differentially expressed genes by subtraction often suffers from unreported contamination of the resulting subtraction library with clones containing DNA sequences not from the original RNA samples. Materials and Methods: Subtraction using cDNA representational difference analysis (RDA) was performed on human B cells from normal or common variable immunodeficiency patients. The material remaining after the subtraction was cloned and individual clones were sequenced. The sequence of one clone with similarity to integrases (ILG1, integrase-like gene- 1) was used to obtain the full length cDNA sequence and as a probe for the presence of this sequence in RNA or genomic DNA samples. Results: After five rounds of cDNA RDA, 23.3% of the clones from the resulting subtraction library contained Escherichia coli DNA. In addition, three clones contained the sequence of a new integrase, ILG1. The full length cDNA sequence of ILG1 exhibits prokaryotic, but not eukaryotic, features. At the DNA level, ILG1 is not similar to any known gene. At the protein level, ILG1 has 58% similarity to integrases from the cryptic P4 bacteriophage family (S clade). The catalytic domain of ILG1 contains the conserved features found in site-specific recombinases. The critical residues that form the catalytic active site pocket are conserved, including the highly conserved R-H-R-Y hallmark of these recombinases. Interestingly, ILG1 was not present in the original B cell populations. By probing genomic DNA, ILG1 could only be detected in the E. coli TOP10F' strain used in our laboratory for molecular cloning, but not in any of its precursor strains, including TOP10. Furthermore, bacteria cultured from the mouth of the laboratory worker who performed cDNA RDA were also positive for ILG1. Conclusions: In the course of our studies using cDNA RDA, we have isolated and identified ILG1 a likely active site-specific recombinase and new member of the bacteriophage P4 family of integrases. This family of integrases is implicated in the horizontal DNA transfer of pathogenic genes between bacterial species, such as those found in pathogenic strains of E. coli, Shigella, Yersinia, and Vibrio cholera. Using ILG1 as a marker of our laboratory E. coli strain TOP10F', our evidence suggests that contaminating bacterial DNA in our subtraction experiment is due to this laboratory bacterial strain, which colonized exposed surfaces of the laboratory worker. Thus, identification of differentially expressed genes between normal and diseased states could be dramatically improved by using extra precaution to prevent bacterial contamination of samples. C1 N Shore LIJ Res Inst, Manhasset, NY 11030 USA. N Shore Univ Hosp, Dept Med, Div Rheumatol Allergy & Clin Immunol, Manhasset, NY USA. NYU, Sch Med, Dept Med, Manhasset, NY USA. NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Chu, CC (reprint author), N Shore LIJ Res Inst, 350 Community Dr, Manhasset, NY 11030 USA. FU NIAID NIH HHS [AI44837-01] NR 39 TC 2 Z9 3 U1 0 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JUL PY 2002 VL 8 IS 7 BP 405 EP 416 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 597AY UT WOS:000178200900008 PM 12393938 ER PT J AU Kimchi-Sarfaty, C Gribar, JJ Gottesman, MM AF Kimchi-Sarfaty, C Gribar, JJ Gottesman, MM TI Functional characterization of coding polymorphisms in the human MDR1 gene using a vaccinia virus expression system SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE GENE; HIV-1 PROTEASE INHIBITORS; DRUG TRANSPORTERS; C3435T MUTATION; MAMMALIAN-CELLS; BRAIN; FREQUENCY; PHARMACOGENETICS; LOCALIZATION AB The human MDR1-encoded transporter is a 170-kDa plasma membrane glycoprotein [P-glycoprotein (P-gp)] capable of binding and energy-dependent extrusion of structurally diverse organic compounds and drugs. P-gp seems to play a significant role in uptake, distribution, and excretion of many different drugs. To determine whether common polymorphic forms of P-gp are likely to alter function of P-gp, we characterized five known MDR1 coding polymorphisms (N21D, F103L, S400N, A893S, and A998T) using a vaccinia virus-based transient expression system. Cell surface expression of wild-type P-gp was time-dependent over a time course of 5.5 to 34.5 h; highest expression was obtained by 22 to 26.5 h after infection/transfection, indicating that a semiquantitative assay for P-gp expression levels was possible. HeLa cells stained with the P-gp specific monoclonal antibodies MRK-16 and Western blots probed with C219 revealed similar cell surface expression for the polymorphisms and for wild-type protein. Time-dependent P-gp pump function maximal at 22 h after infection/transfection was demonstrated for the following MDR1 fluorescence substrates: 4,4-difluoro-5,7-dimethyl-4-bora-3a, 4a-diaza-s-indacene-3-pentanoic acid, succinimidyl ester (bodipy-FL)-verapamil, bodipy-FL-vinblastine, calcein-AM, bodipy-FL-prazosin, bisantrene, and bodipy-FL-forskolin, but not for daunorubicin. Transport studies of all tested substrates indicated that the substrate specificity of the pump was not substantially affected by any of the tested polymorphisms. Cell surface expression and function of double mutants including the more common polymorphisms (N21D-S400N, N21D-A893S, and S400N-A893S) showed no differences from wild-type. These results demonstrate that the common MDR1 coding polymorphisms result in P-gps with a cell surface distribution and function similar to wild-type P-gp. C1 NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bldg 37,Room 1A09,37 Convent Dr,MSC 4254, Bethesda, MD 20892 USA. NR 34 TC 108 Z9 113 U1 1 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 2002 VL 62 IS 1 BP 1 EP 6 AR UNSP 1617/989398 DI 10.1124/mol.62.1.1 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 562DR UT WOS:000176182600001 PM 12065748 ER PT J AU Gao, ZG Kim, SG Soltysiak, KA Melman, N Ijzerman, AP Jacobson, KA AF Gao, ZG Kim, SG Soltysiak, KA Melman, N Ijzerman, AP Jacobson, KA TI Selective allosteric enhancement of agonist binding and function at human A(3) adenosine receptors by a series of imidazoquinoline derivatives SO MOLECULAR PHARMACOLOGY LA English DT Article ID ACID(B) RECEPTORS; ANTAGONISTS; MODULATION; ACTIVATION; ANALOGS AB We have identified a series of 1H-imidazo-[4,5-c] quinolines as selective allosteric enhancers of human A(3) adenosine receptors. Several of these compounds potentiated both the potency and maximal efficacy of agonist-induced responses and selectively decreased the dissociation of the agonist N-6-(4-amino-3-[ I-125] iodobenzyl)-5'-N-methylcarboxamidoadenosine from human A3 adenosine receptors. There was no effect on the dissociation of the antagonist [H-3]8-ethyl-4-methyl-2-phenyl( 8R)-4,5,7,8-tetrahydro-1H-imidazo[2.1-i] purin-5-one (PSB-11) from the A(3) receptors, as well as [H-3] N-6-[(R)-phenylisopropyl] adenosine from rat brain A(1) receptors and [H-3] 2-[p-(2-carboxyethyl) phenyl-ethylamino]-5'-N-ethylcarboxamidoadenosine from rat striatal A(2A) receptors, suggesting the selective enhancement of agonist binding at A(3) receptors. The analogs were tested as antagonists of competitive binding at human A(3) receptors, and K-i values ranging from 120 nM to 101 muM were observed; as for many allosteric modulators of G protein-coupled receptors, an orthosteric effect was also present. The most promising leads from the present set of analogs seem to be the 2-cyclopentyl-1H-imidazo[4,5-c] quinoline derivatives, of which the 4-phenylamino analog DU124183 had the most favorable degree of allosteric modulation versus receptor antagonism. The inhibition of forskolin-stimulated cyclic AMP accumulation in intact cells that express human A(3) receptors was employed as a functional index of A(3) receptor activation. The enhancer DU124183 caused a marked leftward shift of the concentration-response curve of the A(3) receptor agonists in the presence of antagonist and, surprisingly, a potentiation of the maximum agonist efficacy by approximately 30%. Thus, we have identified a novel structural lead for developing allosteric enhancers of A(3) adenosine receptors; such enhancers may be useful for treating brain ischemia and other hypoxic conditions. C1 NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Med Chem, Leiden, Netherlands. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z99 DK999999, ZIA DK031117-22] NR 25 TC 42 Z9 43 U1 2 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 2002 VL 62 IS 1 BP 81 EP 89 AR UNSP 1534/989399 DI 10.1124/mol.62.1.81 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 562DR UT WOS:000176182600011 PM 12065758 ER PT J AU Gwinn-Hardy, K AF Gwinn-Hardy, K TI Genetics of parkinsonism SO MOVEMENT DISORDERS LA English DT Review DE genetics; Parkinson's disease; Lewy body; alpha-synuclein ID PROGRESSIVE SUPRANUCLEAR PALSY; MACHADO-JOSEPH-DISEASE; ALPHA-SYNUCLEIN GENE; LINKED DYSTONIA-PARKINSONISM; AUTOSOMAL-DOMINANT PARKINSONISM; LEWY BODY DISEASE; PRIMARY NEURODEGENERATIVE DISEASE; RECESSIVE JUVENILE PARKINSONISM; SPINOCEREBELLAR ATAXIA TYPE-2; POSITRON EMISSION TOMOGRAPHY AB Parkinson's disease (PD) was noted to have a familial component as early as 1880 (Leroux, 1880). More recently, the discovery of several genetic factors influencing parkinsonism has emphasized the importance of heredity in PD. The clinical spectrum of familial parkinsonism is wide; it includes not only PD, but also dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), essential tremor, and other disorders. In the general population, it is likely that PD results from combined genetic and environmental factors, most of which are not yet known. The discovery of causal mutations in the gene for alpha-synuclein, parkin, and of genetic linkages to chromosomes 2p4, 4p5, and three loci on 1q6-8 have revolutionized PD research. This review focuses on recent progress in the Mendelian genetics of PD and those diseases in which parkinsonism is a prominent feature, and considers how these discoveries modify Our beliefs regarding the etiology and pathogenesis of these disorders. C1 NINDS, Div Intramural Res, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Gwinn-Hardy, K (reprint author), NINDS, Div Intramural Res, Neurogenet Lab, NIH, NSC 2142,6001 Execut Blvd, Bethesda, MD 20892 USA. OI Gwinn, Katrina/0000-0002-8277-651X NR 145 TC 78 Z9 81 U1 1 U2 9 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL PY 2002 VL 17 IS 4 BP 645 EP 656 DI 10.1002/mds.10173 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 577UV UT WOS:000177081300003 PM 12210852 ER PT J AU Wu, RM Shan, DE Sun, CM Liu, RS Hwu, WL Tai, CH Hussey, J West, A Gwinn-Hardy, K Hardy, J Chen, J Farrer, M Lincoln, S AF Wu, RM Shan, DE Sun, CM Liu, RS Hwu, WL Tai, CH Hussey, J West, A Gwinn-Hardy, K Hardy, J Chen, J Farrer, M Lincoln, S TI Clinical, F-18-dopa PET, and genetic analysis of an ethnic chinese kindred with early-onset parkinsonism and parkin gene mutations SO MOVEMENT DISORDERS LA English DT Article DE parkin; F-18-dopa PET; Parkinson's disease; aenetics; Chinese ID RECESSIVE JUVENILE PARKINSONISM; SPINOCEREBELLAR ATAXIA TYPE-2; DOMINANT CEREBELLAR-ATAXIA; FAMILIAL PARKINSONISM; DIAGNOSTIC-CRITERIA; DISEASE; DELETIONS; SYSTEM; REPEAT; TREMOR AB We report on clinical F-18-labeled 6-fluorodopa (F-18-dopa) positron emission tomography (PET) and molecular genetic analyses of an ethnic Chinese family in which three siblings presented with early-onset Parkinson's disease. As described in some Parkin patients, neither sleep benefit nor diurnal fluctuation was noted. Interestingly, depression, anxiety, and obsessive-compulsive disorders were manifest. The F-18-dopa PET scans showed bilateral presynaptic dopaminergic dysfunction without marked lateralization. Molecular genetic analysis showed identical chromosome 6 haplotypes inherited by affected subjects, with alternate allelic deletions of parkin exons 3 and 4. Furthermore, mRNA analyses identified aberrantly spliced parkin transcripts, suggesting that unusual parkin protein isoforms may be expressed in the brain and retain some function. (C) 2002 Movement Disorder Society. C1 Natl Taiwan Univ, Coll Med, Dept Neurol, Taipei, Taiwan. Natl Taiwan Univ, Coll Med, Dept Pediat & Med Genet, Taipei, Taiwan. Natl Taiwan Univ Hosp, Taipei, Taiwan. Taipei Vet Gen Hosp, Neurol Inst, Taipei, Taiwan. Taipei Vet Gen Hosp, Natl PET Cyclotron Ctr, Taipei, Taiwan. Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan. NINDS, Div Neurogenet, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. RP Farrer, M (reprint author), Mayo Clin, Labs Neurogenet, Dept Neurosci, Birdsall Bldg, Jacksonville, FL 32224 USA. EM farrer.matthew@mayo.edu RI Hardy, John/C-2451-2009; OI Tai, Chun-Hwei/0000-0002-3493-8879; HWU, WUH-LIANG/0000-0001-6690-4879; Wu, Ruey-Meei/0000-0002-4947-5467; Gwinn, Katrina/0000-0002-8277-651X NR 23 TC 25 Z9 25 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL PY 2002 VL 17 IS 4 BP 670 EP 675 DI 10.1002/mds.10184 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 577UV UT WOS:000177081300006 PM 12210855 ER PT J AU Neuhuber, B Huang, DI Daniels, MP Torgan, CE AF Neuhuber, B Huang, DI Daniels, MP Torgan, CE TI High efficiency transfection of primary skeletal muscle cells with lipid-based reagents SO MUSCLE & NERVE LA English DT Article DE green fluorescent protein (GFP); myoblast, myotube; liposome; transfection ID MEDIATED GENE-TRANSFER; HUMAN MYOBLASTS; DELIVERY; MYOTUBES; SYSTEM AB Lipofection is a convenient method for gene transfer into muscle cells but reportedly is inefficient. We tested the efficacy of commercially available lipid-based and polyamine transfection reagents, Primary rat skeletal muscle cell cultures were transfected at three stages of development and assayed after fusion. Efficiency reached 30% during the proliferation stage and up to 23% when most myoblasts had fused into myotubes. Optimization of transfection conditions with three different vectors yielded efficiencies exceeding 50%. Thus, lipid-based transfection into primary skeletal muscle cells can be several times more efficient than previously reported. (C) 2002 Wiley Periodicals, Inc. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Torgan, CE (reprint author), NHLBI, Cell Biol Lab, NIH, 50 South Drive, Bethesda, MD 20892 USA. NR 16 TC 11 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JUL PY 2002 VL 26 IS 1 BP 136 EP 140 DI 10.1002/mus.10171 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 570FR UT WOS:000176648700017 PM 12115959 ER PT J AU Xiang, CC Kozhich, OA Chen, M Inman, JM Phan, QN Chen, YD Brownstein, MJ AF Xiang, CC Kozhich, OA Chen, M Inman, JM Phan, QN Chen, YD Brownstein, MJ TI Amine-modified random primers to label probes for DNA microarrays SO NATURE BIOTECHNOLOGY LA English DT Article ID GENE-EXPRESSION PATTERNS; CDNA MICROARRAYS; CANCER; SYSTEM AB DNA microarrays have been used to study the expression of thousands of genes at the same time in a variety of cells and tissues(1-3). The methods most commonly used to label probes for microarray studies require a minimum of 20 mug of total RNA or 2 mug of poly(A) RNA(4,5). This has made it difficult to study small and rare tissue samples. RNA amplification techniques and improved labeling methods have recently been described(6-9). These new procedures and reagents allow the use of less input RNA, but they are relatively time-consuming and expensive. Here we introduce a technique for preparing fluorescent probes that can be used to label as little as 1 mug of total RNA. The method is based on priming cDNA synthesis with random hexamer oligonucleotides, on the 5' ends of which are bases with free amino groups. These amine-modified primers are incorporated into the cDNA along with aminoallyl nucleotides, and fluorescent dyes are then chemically added to the free amines. The method is simple to execute, and amine-reactive dyes are considerably less expensive than dye-labeled bases or dendrimers. C1 NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. SAIC Frederick, Frederick, MD 21702 USA. RP Brownstein, MJ (reprint author), NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-12400] NR 17 TC 69 Z9 70 U1 1 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2002 VL 20 IS 7 BP 738 EP 742 DI 10.1038/nb0702-738 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 567QC UT WOS:000176494800031 PM 12089562 ER PT J AU Li, JM Halal, WE AF Li, JM Halal, WE TI Reinventing the biotech manager SO NATURE BIOTECHNOLOGY LA English DT Article C1 Natl Canc Inst, Washington, DC USA. George Washington Univ, Washington, DC 20052 USA. RP Li, JM (reprint author), Natl Canc Inst, Washington, DC USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2002 VL 20 SU S BP BE61 EP BE63 DI 10.1038/nbt0602supp-BE61 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 571DY UT WOS:000176700600018 PM 12089592 ER PT J AU Taylor, MD Liu, L Raffel, C Hui, CC Mainprize, TG Zhang, XY Agatep, R Chiappa, S Gao, LZ Lowrance, A Hao, AH Goldstein, AM Stavrou, T Scherer, SW Dura, WT Wainwright, B Squire, JA Rutka, JT Hogg, D AF Taylor, MD Liu, L Raffel, C Hui, CC Mainprize, TG Zhang, XY Agatep, R Chiappa, S Gao, LZ Lowrance, A Hao, AH Goldstein, AM Stavrou, T Scherer, SW Dura, WT Wainwright, B Squire, JA Rutka, JT Hogg, D TI Mutations in SUFU predispose to medulloblastoma SO NATURE GENETICS LA English DT Article ID BASAL-CELL CARCINOMAS; PRIMITIVE NEUROECTODERMAL TUMORS; CENTRAL-NERVOUS-SYSTEM; HUMAN HOMOLOG; SONIC HEDGEHOG; GORLIN SYNDROME; PATCHED PTCH; GENE; SUPPRESSOR; SKIN AB The sonic hedgehog (SHH) signaling pathway directs the embryonic development of diverse organisms and is disrupted in a variety of malignancies. Pathway activation is triggered by binding of hedgehog proteins to the multipass Patched-1 (PTCH) receptor, which in the absence of hedgehog suppresses the activity of the seven-pass membrane protein Smoothened (SMOH). De-repression of SMOH culminates in the activation of one or more of the GLI transcription factors that regulate the transcription of downstream targets. Individuals with germline mutations of the SHH receptor gene PTCH are at high risk of developmental anomalies and of basal-cell carcinomas, medulloblastomas and other cancers (a pattern consistent with nevoid basal-cell carcinoma syndrome, NBCCS). In keeping with the role of PTCH as a tumor-suppressor gene, somatic mutations of this gene occur in sporadic basal-cell carcinomas and medulloblastomas. We report here that a subset of children with medulloblastoma carry germline and somatic mutations in SUFU (encoding the human suppressor of fused) of the SHH pathway, accompanied by loss of heterozygosity of the wildtype allele. Several of these mutations encode truncated proteins that are unable to export the GLI transcription factor from nucleus to cytoplasm, resulting in the activation of SHH signaling. SUFU is a newly identified tumor-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway through a newly identified mechanism. C1 Univ Toronto, Div Clin Sci, Toronto, ON, Canada. Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Div Neurosurg, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Dept Lab Med & Pathobiol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. Mayo Clin, Dept Neurosurg, Rochester, MN USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. Univ Warsaw, Dept Pathol, Warsaw, Poland. Univ Queensland, Ritchie Res Labs, St Lucia, Qld, Australia. Univ Toronto, Ontario Canc Inst, Princess Margaret Hosp, Dept Lab Med & Pathobiol, Toronto, ON, Canada. Univ Toronto, Ontario Canc Inst, Princess Margaret Hosp, Dept Med Biophys, Toronto, ON, Canada. RP Rutka, JT (reprint author), Univ Toronto, Div Clin Sci, Toronto, ON, Canada. RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013; OI Scherer, Stephen /0000-0002-8326-1999; Squire, Jeremy/0000-0002-9863-468X NR 31 TC 436 Z9 450 U1 1 U2 22 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2002 VL 31 IS 3 BP 306 EP 310 DI 10.1038/ng916 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 567PW UT WOS:000176494100021 PM 12068298 ER PT J AU Leonard, WJ AF Leonard, WJ TI TSLP: finally in the limelight SO NATURE IMMUNOLOGY LA English DT Editorial Material ID THYMIC STROMAL LYMPHOPOIETIN; IGM(+) B-CELLS; MOLECULAR-CLONING; INTERLEUKIN-7 RECEPTOR; GROWTH-FACTOR; GAMMA-CHAIN; IN-VITRO; CYTOKINE; EXPRESSION AB TSLP is now revealed to be an important regulator of DC-mediated control of T(H)2-based human allergic responses, identifying a potentially new species-specific function for this cytokine. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7N252, Bethesda, MD 20892 USA. NR 14 TC 74 Z9 78 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUL PY 2002 VL 3 IS 7 BP 605 EP 607 DI 10.1038/ni0702-605 PG 3 WC Immunology SC Immunology GA 566RH UT WOS:000176441700008 PM 12087416 ER PT J AU Lovinger, DM AF Lovinger, DM TI NMDA receptors lose their inhibitions SO NATURE NEUROSCIENCE LA English DT Editorial Material ID VENTRAL TEGMENTAL AREA; D-ASPARTATE RECEPTORS; NUCLEUS-ACCUMBENS; ETHANOL; NEURONS; IFENPRODIL; RESPONSES; INVITRO; KINASE AB A new study suggests that interactions between dopamine and glutamate neurotransmitter pathways are important in regulating the inhibitory effects of alcohol on brain function. C1 NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, Rm 158H Pk 5 Bldg,12420 Parklawn Dr, Rockville, MD 20852 USA. NR 14 TC 11 Z9 13 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUL PY 2002 VL 5 IS 7 BP 614 EP 616 DI 10.1038/nn0702-614 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 566EP UT WOS:000176414300003 PM 12085089 ER PT J AU Baxter, MG Murray, EA AF Baxter, MG Murray, EA TI The amygdala and reward SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID PRIMATE ORBITOFRONTAL CORTEX; INFERIOR TEMPORAL CORTEX; AUDITORY SECONDARY REINFORCEMENT; VENTROMEDIAL PREFRONTAL CORTEX; LESIONS DISRUPT INCREMENTS; CROSSED UNILATERAL LESIONS; MEDIAL FOREBRAIN-BUNDLE; ANTERIOR RHINAL CORTEX; NUCLEUS-ACCUMBENS CORE; BASOLATERAL AMYGDALA AB The amygdala - an almond-shaped group of nuclei at the heart of the telencephalon has been associated with a range of cognitive functions, including emotion, learning, memory, attention and perception. Most current views of amygdala function emphasize its role in negative emotions, such as fear, and in linking negative emotions with other aspects of cognition, such as learning and memory. However, recent evidence supports a role for the amygdala in processing positive emotions as well as negative ones, including learning about the beneficial biological value of stimuli. Indeed, the amygdala's role in stimulus-reward learning might be just as important as its role in processing negative affect and fear conditioning. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Baxter, MG (reprint author), Harvard Univ, Dept Psychol, 906 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. OI Murray, Elisabeth/0000-0003-1450-1642 NR 89 TC 612 Z9 621 U1 3 U2 51 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD JUL PY 2002 VL 3 IS 7 BP 563 EP 573 DI 10.1038/nrn875 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 568UN UT WOS:000176563200016 PM 12094212 ER PT J AU Kato, Y Misra, S Puertollano, R Hurley, JH Bonifacino, JS AF Kato, Y Misra, S Puertollano, R Hurley, JH Bonifacino, JS TI Phosphoregulation of sorting signal-VHS domain interactions by a direct electrostatic mechanism SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID MANNOSE 6-PHOSPHATE RECEPTOR; CASEIN KINASE-II; TRANS-GOLGI NETWORK; CYTOPLASMIC DOMAIN; ADAPTER COMPLEX; MUTATIONAL ANALYSIS; CARBOXYL-TERMINUS; PHOSPHORYLATION; PROTEINS; RECOGNITION AB Phosphorylation of the cytosolic tails of transmembrane receptors can regulate their intracellular trafficking. The structural basis for such regulation, however, has not been explained in most cases. The cytosolic tail of the cation-independent mannose 6-phosphate receptor contains a serine residue within an acidic-cluster dileucine signal that is important for the function of the receptor in the biosynthetic sorting of lysosomal hydrolases. We show here that phosphorylation of this Ser enhances interactions of the signal with its recognition module, the VHS domain of the GGA proteins. Crystallographic analyses demonstrate that the phosphoserine residue interacts electrostatically with two basic residues on the VHS domain of GGA3, thus providing an additional point of attachment of the acidic-cluster dileucine signal to its recognition module. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI KATO, Yukio/D-8396-2015; OI Misra, Saurav/0000-0002-1385-8554; Bonifacino, Juan S./0000-0002-5673-6370 NR 29 TC 54 Z9 56 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD JUL PY 2002 VL 9 IS 7 BP 532 EP 536 DI 10.1038/nsb807 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 566RA UT WOS:000176441000013 PM 12032548 ER PT J AU Lee, JW Hampl, M Albert, P Fine, HA AF Lee, JW Hampl, M Albert, P Fine, HA TI Antitumor activity and prolonged expression from a TRAIL-expressing adenoviral vector SO NEOPLASIA LA English DT Article DE TRAIL; apoptosis; adenoviral vectors; gene therapy; cancer therapeutics ID APOPTOSIS-INDUCING LIGAND; GENE-THERAPY; MALIGNANT GLIOMA; CANCER-THERAPY; APO2 LIGAND; CELLS; FAMILY; BRAIN; INDUCTION; MEMBER AB Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of transformed cell lines, but generally spares most normal cells. Transduction by an adenoviral vector expressing human TRAIL cDNA (Ad.TRAIL-GFP) resulted in both direct tumor cell killing as well as a potent bystander effect through presentation of TRAIL by transduced normal cells. Administration of Ad.TRAIL-GFP significantly prolonged survival of mice harboring either intracerebral glioblastomas or breast carcinoma-induced peritoneal carcinomatosis. Additionally, TRAIL induced prolonged transgene expression in normal tissue, presumably as a result of diminished immune-mediated destruction of vector - transduced cells. Taken together, these data suggest that vector-mediated transduction of TRAIL may represent an effective strategy for cancer gene therapy. C1 NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA. Natl Canc Inst, Biometr Res Branch, DCTD, Bethesda, MD USA. RP Fine, HA (reprint author), NINDS, Neurooncol Branch, NCI, NIH, 10 Ctr Drive,Bldg 10-Room 12S245-MSC 1911, Bethesda, MD 20892 USA. NR 32 TC 56 Z9 62 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JUL-AUG PY 2002 VL 4 IS 4 BP 312 EP 323 DI 10.1038/sj.neo.7900245 PG 12 WC Oncology SC Oncology GA 571HJ UT WOS:000176711700005 PM 12082547 ER PT J AU Sharma, S Wilkinson, BP Gao, P Steele, VE AF Sharma, S Wilkinson, BP Gao, P Steele, VE TI Differential activity of NO synthase inhibitors as chemopreventive agents in a primary rat tracheal epithelial cell transformation system SO NEOPLASIA LA English DT Article DE chemoprevention; nitric oxide synthase inhibitors; type IINOS inhibitors; primary rat tracheal epithelial cells; in vitro transformation model ID NITRIC-OXIDE SYNTHASE; IN-VITRO; SELECTIVE INHIBITOR; S-ETHYLISOTHIOUREA; POTENT INHIBITOR; BREAST-CANCER; SCHIFF-BASES; CULTURE; ARGININE; VIVO AB A model to study the effectiveness of potential chemopreventive agents that inhibit neoplastic process by different mechanisms has been used to test the efficacy of seven nitric oxide synthase (NOS) inhibitors. Five selective inducible NOS (iNOS) inhibitors: S-methyl isothiourea (S-MITU), S-2-aminoethyl isothiourea (S-2-AEITU), S-ethyl isothiourea (S-EITU), aminoguanidine (AG), 2-amino-4-methyl pyridine (2-AMP), and two non selective general NOS inhibitors: L-N-6-(1-iminoethyl) lysine (IIEL) and N-omega-nitro-L-arginine (NNLA), were tested for efficacy against a carcinogen, benzo[a]pyrene (B[a]P)-induced primary rat tracheal epithelia[ (RTE) cell transformation assay. RTE cells were treated with B[a]P alone or with five nontoxic concentrations of an NOS inhibitor and the resulting foci at the end of 30 days were scored for inhibition of transformation. The results indicate that all three isothiourea compounds inhibited B[a]P-induced RTE foci in a dose-dependent manner. S-AEITU was the most effective inhibitor with an IC50 (the molar concentration that inhibits transformation by 50%) of 9.1 muM and 100% inhibition at the highest dose tested (30 muM). However, both S-EITU and S-MITU showed a maximum percent inhibition of 81% and 100% at 1 mM with an IC50 of 84 and 110 muM, respectively. 2-AMP did not show any dose-dependent response, but was highly effective (57% inhibition) at an intermediate dose of 30 muM and an IC50 of 25 muM. Similar to thiourea compounds, AG exhibited good dose-dependent inhibition with a maximum inhibition of 86% at 1 mM. NNLA and IEL were negative in this assay. Based on the IC50 values, NOS inhibitors were rated for efficacy from high to low as follows: S-2-AEITU<2-AMP