FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chen, ET Nichols, J Duh, S Hortin, G Gonzalez-Licea, A AF Chen, ET Nichols, J Duh, S Hortin, G Gonzalez-Licea, A TI A study of the factors that affect the performance of blood glucose monitoring devices. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Maryland, Med Syst, Baltimore, MD 21201 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S MA 622 BP A189 EP A189 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400739 ER PT J AU Eisenhofer, G Pacak, K Walther, MM Linehan, WM Keiser, HR Goldstein, DS Friberg, P Mannelli, M Lenders, JW AF Eisenhofer, G Pacak, K Walther, MM Linehan, WM Keiser, HR Goldstein, DS Friberg, P Mannelli, M Lenders, JW TI Biochemical diagnosis of pheochromocytoma: Is there a best test? SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Gothenburg, Gothenburg, Sweden. Univ Florence, Florence, Italy. St Radboud Univ, Nijmegen, Netherlands. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S MA 465 BP A140 EP A141 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400581 ER PT J AU Hu, J Bosworth, T King, C Hortin, G AF Hu, J Bosworth, T King, C Hortin, G TI Interference of ascorbic acid with quantification of urinary uric acid. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S MA 279 BP A85 EP A85 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400395 ER PT J AU Remaley, AT Chan, Y Samantha, B Hu, X Julie, P Ray, R AF Remaley, AT Chan, Y Samantha, B Hu, X Julie, P Ray, R TI Development of a home PSA test for the screening of prostate cancer. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Flexsite Diagnost Inc, Palm City, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S MA 457 BP A138 EP A138 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400573 ER PT J AU Remaley, AT Albrighi, S Sampson, M Ruddel, M AF Remaley, AT Albrighi, S Sampson, M Ruddel, M TI Development and assessment of a rapid intraoperative insulin test. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S MA 59 BP A18 EP A18 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400178 ER PT J AU Sullivan, P Csako, GA Hortin, GL AF Sullivan, P Csako, GA Hortin, GL TI Dual analysis of plasma homocysteine and cysteine. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S MA 202 BP A62 EP A62 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400319 ER PT J AU Sullivan, P Hiroi, M EisenhofeR, G Csako, G AF Sullivan, P Hiroi, M EisenhofeR, G Csako, G TI Stability of metanephrines and catecholamines in heparinized whole blood: effect of storage length and temperature SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH, Div Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S MA 52 BP A16 EP A16 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400171 ER PT J AU Aamodt, R AF Aamodt, R TI Legal, ethical and other issues for human specimen resource operations SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S BP S19 EP S19 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400026 ER PT J AU Vaught, JB AF Vaught, JB TI Overview of biorepositories SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S BP S19 EP S19 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400024 ER PT J AU Le, YY Wetzel, MA Shen, WP Gong, WH Rogers, TJ Henderson, EE Wang, JM AF Le, YY Wetzel, MA Shen, WP Gong, WH Rogers, TJ Henderson, EE Wang, JM TI Desensitization of chemokine receptor CCR5 in dendritic cells at the early stage of differentiation by activation of formyl peptide receptors SO CLINICAL IMMUNOLOGY LA English DT Article DE chemokine receptor; receptor desensitization; N-formyl peptide; N-formyl peptide receptors; HIV-1 ID HUMAN LANGERHANS CELLS; LYMPHOID-TISSUE; HUMAN MONOCYTES; T-CELLS; INFECTION; HIV; FPRL1; 7-TRANSMEMBRANE; PHOSPHORYLATION; IDENTIFICATION AB Chemokine receptors are subjected to heterologous desensitization by activation of formyl peptide receptors, We investigated the cross-talk between formyl peptide receptors and the chemokine receptor CCR5 in human monocyte-differentiated immature dendritic cells (iDC), Monocytes cultured with GM-CSF and IL-4 for 4 days exhibit markers characteristic of iDC and maintain the expression of both formyl peptide receptors FPR and FPRL1, as well as CCR5, Pretreatment of IDC with W peptide (WKYMVm), a potent agonist for FPR and FPRL1 but with preference for FPRL1, resulted in down-regulation of CCR5 from the cell surface and reduced cell response to the CCR5 ligands through a PKC-dependent pathway. Furthermore, W peptide induced a PKC-dependent phosphorylation of CCR5 and inhibited infection of iDC by R5 HIV-1. Our results indicate that the expression and functions of CCR5 in IDC can be attenuated by W peptide, which activates formyl peptide receptors, and suggest an approach to the design of novel anti-HIV-1 agents. (C) 2001 Academic Press. C1 NCI Frederick, DBS, LMI, Frederick, MD 21702 USA. NCI Frederick, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19140 USA. RP Wang, JM (reprint author), NCI Frederick, DBS, LMI, Bldg 560,Room 31-40, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000]; NIDA NIH HHS [F31DA05894, DA06650, DA11130, DA12113, T32DA07237] NR 38 TC 34 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC 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 JUN PY 2001 VL 99 IS 3 BP 365 EP 372 DI 10.1006/clim.2001.5021 PG 8 WC Immunology SC Immunology GA 441MQ UT WOS:000169234500010 PM 11358433 ER PT J AU Watts, DH AF Watts, DH TI Maternal therapy for HIV in pregnancy SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PERINATAL TRANSMISSION; ZIDOVUDINE; EXPOSURE; MICE; RISK; RESISTANCE; WOMEN; AZT C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Watts, DH (reprint author), NICHHD, NIH, 6100 Execut Blvd,Room 4B11, Bethesda, MD 20892 USA. NR 22 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD JUN PY 2001 VL 44 IS 2 BP 182 EP 197 DI 10.1097/00003081-200106000-00008 PG 16 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 426UL UT WOS:000168366700006 PM 11344987 ER PT J AU Rounsaville, BJ Carroll, KM Onken, LS AF Rounsaville, BJ Carroll, KM Onken, LS TI A Stage Model of Behavioral Therapies research: Getting started and moving on from stage I SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Article DE clinical trials; behavioral therapies; stage model; study design; methodology ID PSYCHOTHERAPY; COMPETENCE; ADHERENCE; TRIALS AB The progressively rigorous methodological requirements of conducting clinical trials of behavioral treatments has placed a large burden on individual investigators, as treatment manuals, methods of evaluating treatment quality and fidelity, and persuasive evidence of the treatment's promise are now virtual requirements of receiving support for conducting a clinical trial of a new or adapted treatment. A Stage Model of Behavioral Therapies research, by articulating the progressive stager of development and evaluation for behavioral treatments, recognizer the scientific merit and need for support for treatment development and initial evaluation designated as stage 1, This article describer the conduct of stage 1 research, including issues addressed in stage 1 research, major design decisions confronted by investigators, the close relationship of stage 1 to stage If research and proposes a time line for stage 1 research. C1 Yale Univ, New Haven, CT 06520 USA. Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Rounsaville, BJ (reprint author), VA Connecticut Healthcare, 950 Campbell Ave,Mail Route 151D, W Haven, CT 06516 USA. RI Carroll, Kathleen/A-7526-2009; OI Carroll, Kathleen/0000-0003-3263-3374 NR 29 TC 330 Z9 330 U1 1 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD SUM PY 2001 VL 8 IS 2 BP 133 EP 142 DI 10.1093/clipsy/8.2.133 PG 10 WC Psychology, Clinical SC Psychology GA 432TR UT WOS:000168712200001 ER PT J AU Rounsaville, BJ Carroll, KM Onken, LS AF Rounsaville, BJ Carroll, KM Onken, LS TI Methodological diversity and theory in the stage model: Reply to Kazdin SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Article ID BEHAVIORAL-THERAPY DEVELOPMENT; PSYCHOLOGICAL SCIENCE C1 Yale Univ, New Haven, CT 06520 USA. Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Rounsaville, BJ (reprint author), VA Connecticut Healthcare, 950 Campbell Ave,Mail Route 151D, W Haven, CT 06516 USA. RI Carroll, Kathleen/A-7526-2009 NR 2 TC 8 Z9 8 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD SUM PY 2001 VL 8 IS 2 BP 152 EP 154 DI 10.1093/clipsy/8.2.152 PG 3 WC Psychology, Clinical SC Psychology GA 432TR UT WOS:000168712200003 ER PT J AU Norquist, GS AF Norquist, GS TI Practice research networks: Promises and pitfalls SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Review DE practice research networks; mental health; services research AB Networks that incorporate community settings and populations are essential if we want to understand how well interventions work in the community and how to ensure that they are used in community practice. The challenges in setting up such networks are deciding what type of network is best, what questions are most important to address in them, and how to ensure that they are feasible in the long run. The paper by Borkovec and colleagues offers an opportunity to discuss the promises and pitfalls of practice research networks. C1 NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Norquist, GS (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd, Bethesda, MD 20892 USA. NR 5 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD SUM PY 2001 VL 8 IS 2 BP 173 EP 175 DI 10.1093/clipsy/8.2.173 PG 3 WC Psychology, Clinical SC Psychology GA 432TR UT WOS:000168712200006 ER PT J AU Shaw, JW Coons, SJ Foster, SA Leischow, SJ Hays, RD AF Shaw, JW Coons, SJ Foster, SA Leischow, SJ Hays, RD TI Responsiveness of the Smoking Cessation Quality of Life (SCQoL) questionnaire SO CLINICAL THERAPEUTICS LA English DT Article DE smoking cessation; health-related quality of life; withdrawal symptoms; responsiveness; SCQoL ID HEALTH SURVEY SF-36; OF-LIFE; TOBACCO WITHDRAWAL; EX-SMOKERS; DISEASE; RELIABILITY; ASSOCIATIONS; POPULATION; OUTCOMES; QUITTERS AB Background: The Smoking Cessation Quality of Life (SCQoL) questionnaire was developed to quantify changes in self-reported functioning and well-being associated with the smoking cessation process and to facilitate comparisons among smokers, former smokers, and nonsmokers. The SCQoL includes 5 cessation-targeted scales and the 8 multi-item scales of the Medical Outcomes Study 36-Item Short-Form Health Survey. Objective: This study was conducted to assess the responsiveness of the SCQoL by analyzing associations between SCQoL scale scores and duration of smoking abstinence. Methods: The SCQoL was administered at a screening visit and 2 to 6 weeks after screening as part of a longitudinal study. Study participants included smokers who intended to quit smoking. Subjects were required to purchase nicotine inhalers and were prompted to quit smoking before follow-up. Based on self-reported duration of abstinence at follow-up, subjects were categorized as recidivists (0 days smoke free), short-term abstainers (1-7 days smoke free), or longer-term abstainers (>7 days smoke free). Kruskal-Wallis tests were used to compare changes in scale scores from screening to follow-up among the 3 groups. Results: The internal consistency reliability of the 13 SCQoL scales ranged from 0.67 to 0.92. Subjects who maintained abstinence for longer periods experienced smaller declines in health-related quality of life between the screening and follow-up assessments. Differences among the 3 groups were driven primarily by differences between recidivists and longer-term abstainers. Conclusions: The results are consistent with research indicating that recidivists report a greater number of land more severe) cessation-related symptoms than abstainers. The: findings of this investigation provide evidence for the responsiveness of the SCQoL. C1 Univ Arizona, Coll Pharm, Ctr Hlth Outcomes & Pharmacoecon Res, Tucson, AZ 85721 USA. Eli Lilly & Co, Hlth Outcomes Evaluat Grp, Indianapolis, IN 46285 USA. NCI, Tobacco Control Res Branch, Div Canc Control & Populat Sci, Rockville, MD USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Shaw, JW (reprint author), Univ Arizona, Coll Pharm, Ctr Hlth Outcomes & Pharmacoecon Res, POB 210207, Tucson, AZ 85721 USA. RI Hays, Ronald/D-5629-2013 FU NIDA NIH HHS [DA08885] NR 48 TC 16 Z9 17 U1 1 U2 4 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 JUN PY 2001 VL 23 IS 6 BP 957 EP 969 DI 10.1016/S0149-2918(01)80083-7 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 445WU UT WOS:000169482200016 PM 11440295 ER PT J AU de la Cruz, F Koch, R AF de la Cruz, F Koch, R TI Genetic implications for newborn screening for phenylketonuria SO CLINICS IN PERINATOLOGY LA English DT Article ID PHENYLALANINE-HYDROXYLASE DEFICIENCY; MATERNAL PHENYLKETONURIA; PKU AB With the advent of newborn screening and institution in the newborn period of a diet with restricted amounts of phenylalanine, some of the phenotypic features of phenylketonuria, including impaired cognitive development, can be averted. The success of newborn screening has resulted in many intellectually capable women with phenylketonuria who are now of childbearing age and are at risk of exposing their fetus to toxic levels of phenylalanine in utero resulting in mental retardation, microcephaly, and congenital heart disease in the offspring. The earlier in pregnancy that a diet low in phenylalanine is initiated and maintained, the better the reproductive outcome. C1 NICHHD, Mental Retardat & Dev Disabil Branch, Bethesda, MD 20892 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Keck Med Sch, Dept Pediat, Los Angeles, CA USA. RP de la Cruz, F (reprint author), NICHHD, Mental Retardat & Dev Disabil Branch, 6100 Execut Blvd,4B09, Bethesda, MD 20892 USA. NR 25 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD JUN PY 2001 VL 28 IS 2 BP 419 EP + PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 458RG UT WOS:000170207900013 PM 11499062 ER PT J AU Power, RA Power, ML Layne, DG Jaquish, CE Oftedal, OT Tardif, SD AF Power, RA Power, ML Layne, DG Jaquish, CE Oftedal, OT Tardif, SD TI Relations among measures of body composition, age, and sex in the common marmoset monkey (Callithrix jacchus) SO COMPARATIVE MEDICINE LA English DT Article ID RANGING RHESUS MACAQUES; SAVANNAH BABOONS; RATS; OBESITY; SIZE; FAT; WEIGHT; ADIPOSITY; MASS; ADULTHOOD AB Few studies of body composition have been done in New World primates. In the study reported here, four methods of assessing body composition (body weight, anthropometry, labeled-water dilution, and total body electroconductivity) were compared in 20 marmosets, aged 0.96 to 7.97 years. Males and females did not differ in any measure (P > 0.05). Body weight ranged from 272 to 466 g, and body fat estimates varied from 1.6 to 19.5%. Strong positive correlations were observed between total body water and total body electroconductivity (R-2 = 0.77), body weight and fat-free mass (males R-2 = 0.95; females R-2 = 0.91), and body weight and fat mass (males R-2 = 0.86; females R-2 = 0.85; P < 0.01). Male and female slopes were equivalent (P > 0.05) for the regressions of fat and fat-free mass against body weight. Positive correlations also were observed between girth measures and fat-free mass (R-2 = 0.48 to 0.78) and fat mass (R-2 = 0.60 to 0.74; P < 0.01). A good second-order polynomial relationship was observed between age and fat-free mass for the combined sample (R-2 = 0.64). Results indicated that: subjects were lean; there was no sexual dimorphism relative to measures; body weight provided a reliable estimate of fat and fat-free mass; and within-subject body weight changes reflected a similar relationship between body weight and fat-free mass as did that across subjects. C1 Univ Florida, Coll Vet Med, Dept Physiol Sci, Gainesville, FL 32610 USA. Smithsonian Inst, Natl Zool Pk, Dept Zool Res, Washington, DC 20008 USA. Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA. Kent State Univ, Dept Biol Sci, Kent, OH 44242 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Power, RA (reprint author), Univ Florida, Coll Vet Med, Dept Physiol Sci, POB 100144, Gainesville, FL 32610 USA. FU NCRR NIH HHS [R01-RR02022] NR 48 TC 25 Z9 25 U1 2 U2 10 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 0023-6764 J9 COMPARATIVE MED JI Comparative Med. PD JUN PY 2001 VL 51 IS 3 BP 218 EP 223 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 449CG UT WOS:000169666300006 PM 11924775 ER PT J AU Bettelheim, FA Lizak, MJ Zigler, JS AF Bettelheim, FA Lizak, MJ Zigler, JS TI NMR relaxation studies of syneretic response to pressure change in bovine lenses SO CURRENT EYE RESEARCH LA English DT Article DE bovine lens; hydrostatic pressure; relaxographic imaging; syneretic response; T-1 and T-2 relaxation ID FREEZING-THAWING HYSTERESIS; NUCLEAR MAGNETIC-RESONANCE; HYPERBARIC-OXYGEN; EYE LENSES; LIGHT-SCATTERING; WATER FRACTIONS; HYDRATION; STATE; CRYSTALLINE; FISH AB Purpose. Reversible syncretic response to pressure in bovine and rhesus monkey lenses has been demonstrated previously by invasive techniques, such as differential scanning calorimetry and thermogravimetric analysis. This study is designed to investigate whether such a response could be observed by non-invasive techniques, namely by relaxographic imaging studies, in situ, in the intact, albeit excised lens. Methods. Excised bovine lenses were incubated in media at 37 degreesC in specialized pressure chambers for 24 hrs. Three pressures, 2, 1 and 0.03 atm, were employed. The pressure chambers were placed in the cavity of an NMR magnet. Seven sections of the lens, under 2 atm pressure, from anterior outer cortex to posterior outer cortex were imaged and the T-1 (spin-lattice) and T-2 (spin-spin) relaxation data on each section were collected. The pressure was then released and NMR data were collected under 1 atm. Similar arrangement was followed on lenses under initial 0.03 atm pressure. T-1 and T-2 relaxations were analyzed by fitting pixel intensity to one and two term exponential expressions. Results. Analysis of the time dependence of the T-2 relaxation time indicated that the response to a change in pressure is complete within 2 hours. Both T-1 and T-2 relaxation times showed minimal values in the nuclear region and maxima at the two outer cortexes. With increasing pressure both relaxation times decrease. The effect of pressure on both relaxation times was smaller in the nucleus and more enhanced at the outer cortexes. The pre-exponential terms of the fittings of both T-1 and T-2 relaxations indicate the amount of protons participating in the relaxation. Thus they serve as a population index. The T-2 population index had a maximum in the nucleus and minima in the two cortexes. The population index of T-1 relaxation exhibited minimal value in the nucleus and maxima at the two cortexes. The pre-exponential term of T-2 relaxation increased with increasing pressure. The preexponential term of T-1 relaxation did not show consistent pressure dependence. Conclusions. The positional dependence of T-2 relaxation times as well as that of its population index indicated that it represents the behavior of the bound water in the lens. The positional dependence of T-1 population index suggests that this relaxation represents the total water that has a minimal value in the nucleus. Both the relaxation times as well as the population indices indicated that as pressure increases the strength of hydrogen bonding as well as the amount of bound water increases. This also means that the free water/bound water ratio decreases with increasing pressure. Thus NMR imaging and relaxation Studies confirm significant syncretic response to applied hydrostatic pressure in bovine lenses. C1 Adelphi Univ, Dept Chem, Garden City, NY 11530 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20892 USA. RP Bettelheim, FA (reprint author), Adelphi Univ, Dept Chem, Garden City, NY 11530 USA. FU NEI NIH HHS [EY-12496] NR 32 TC 4 Z9 4 U1 0 U2 3 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JUN PY 2001 VL 22 IS 6 BP 438 EP 445 DI 10.1076/ceyr.22.6.438.5481 PG 8 WC Ophthalmology SC Ophthalmology GA 474WF UT WOS:000171129300006 PM 11584343 ER PT J AU Ryan, KM Phillips, AC Vousden, KH AF Ryan, KM Phillips, AC Vousden, KH TI Regulation and function of the p53 tumor suppressor protein SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID RIBONUCLEOTIDE REDUCTASE GENE; RING-FINGER DOMAIN; DNA-DAMAGE; NUCLEAR EXPORT; P53-DEPENDENT APOPTOSIS; P53-MEDIATED APOPTOSIS; PREMATURE SENESCENCE; ONCOGENIC RAS; BAX GENE; C-JUN AB Loss of the p53 tumor suppressor pathway contributes to the development of most human cancers. p53 is a nuclear protein that functions as a regulator of transcription. Significant advances have been made recently in our understanding of how p53 function is regulated and the mechanisms by which p53 mediates its effects. C1 NCI, Regulat Cell Growth Lab, Frederick, MD 21702 USA. RP Ryan, KM (reprint author), NCI, Regulat Cell Growth Lab, Bldg 560,Room 22-96, Frederick, MD 21702 USA. NR 66 TC 461 Z9 481 U1 4 U2 20 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD JUN PY 2001 VL 13 IS 3 BP 332 EP 337 DI 10.1016/S0955-0674(00)00216-7 PG 6 WC Cell Biology SC Cell Biology GA 433GY UT WOS:000168752900010 PM 11343904 ER PT J AU Sreekumar, KR Aravind, L Koonin, EV AF Sreekumar, KR Aravind, L Koonin, EV TI Computational analysis of human disease-associated genes and their protein products SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID PROGRESSIVE MYOCLONUS EPILEPSY; LINKED MENTAL-RETARDATION; DOMINANT OPTIC ATROPHY; OF-FUNCTION MUTATIONS; STRUCTURE PREDICTION; SULFATE TRANSPORTER; FUNCTIONAL MOTIFS; GENOME SEQUENCE; TYROSINE KINASE; TOOTH AGENESIS AB The complete genome sequences for human, Drosophila melanogaster and Arabidopsis thaliana have been reported recently. With the availability of complete sequences for many bacteria and archaea, and five eukaryotes, comparative genomics and sequence analysis are enabling us to identify counterparts of many human disease genes in model organisms, which in turn should accelerate the pace of research and drug development to combat human diseases. Continuous improvement of specialized protein databases, together with sensitive computational tools, have enhanced the power and reliability of computational prediction of protein function. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Sreekumar, KR (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 100 TC 11 Z9 11 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD JUN PY 2001 VL 11 IS 3 BP 247 EP 257 DI 10.1016/S0959-437X(00)00186-6 PG 11 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 437TW UT WOS:000169010500003 PM 11377959 ER PT J AU Meltzer, PS AF Meltzer, PS TI Spotting the target: microarrays for disease gene discovery SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID MESSENGER-RNA DECAY; DENSITY DNA ARRAYS; EXPRESSION PATTERNS; GENOME; CANCER; HYBRIDIZATION; ACCUMULATION; MUTATIONS; NETWORKS; PROFILES AB Microarray technologies enable genome-scale expression measurements. Already proved to be of value for the functional analysis of individual genes and biological processes, the application of expression profiling to disease gene discovery is now growing in importance and practicality. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NR 50 TC 39 Z9 44 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD JUN PY 2001 VL 11 IS 3 BP 258 EP 263 DI 10.1016/S0959-437X(00)00187-8 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 437TW UT WOS:000169010500004 PM 11377960 ER PT J AU Lewis, CM Broussard, C Czar, MJ Schwartzberg, PL AF Lewis, CM Broussard, C Czar, MJ Schwartzberg, PL TI Tec kinases: modulators of lymphocyte signaling and development SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID BRUTONS-TYROSINE-KINASE; PLECKSTRIN HOMOLOGY DOMAINS; HUMAN T-LYMPHOCYTES; B-CELL DEVELOPMENT; FAMILY KINASES; THYMOCYTE DEVELOPMENT; PLASMA-MEMBRANE; CALCIUM SIGNALS; MICE LACKING; SH2 DOMAIN AB The Tec kinases are implicated as important components of the antigen receptor signaling required for proper lymphocyte activation and development. Recent data suggest that these kinases contribute to multiprotein complexes containing LAT and SLP-76 in T cells, and BLNK/SLP-65 in B cells, which are required for activation of PLC-gamma and downstream pathways. C1 NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Schwartzberg, PL (reprint author), NIH, Natl Human Genome Res Inst, Bldg 10, Bethesda, MD 20892 USA. NR 65 TC 66 Z9 68 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2001 VL 13 IS 3 BP 317 EP 325 DI 10.1016/S0952-7915(00)00221-1 PG 9 WC Immunology SC Immunology GA 428TT UT WOS:000168477300008 PM 11406363 ER PT J AU Gadina, M Hilton, D Johnston, JA Morinobu, A Lighvani, A Zhou, YJ Visconti, R O'Shea, JJ AF Gadina, M Hilton, D Johnston, JA Morinobu, A Lighvani, A Zhou, YJ Visconti, R O'Shea, JJ TI Signaling by Type I and II cytokine receptors: ten years after SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID SERINE PHOSPHORYLATION; NEGATIVE REGULATION; INTERFERON-GAMMA; TYROSINE KINASE; T-CELLS; TRANSCRIPTIONAL ACTIVATION; PSEUDOKINASE DOMAIN; JANUS KINASES; IMMUNE-SYSTEM; SOCS PROTEINS AB Discovered during the past ten years, Janus kinases and signal transducers and activators of transcription have emerged as critical elements in cytokine signaling and immunoregulation. Recently, knockout mice for all the members of these families have been generated, with remarkably specific outcomes. Equally exciting is the discovery of a new class of inhibitors, the suppressor of cytokine signaling family. The phenotypes of mice deficient in these molecules are also striking, underscoring the importance of negative regulation in cytokine signaling. C1 NIAMSD, Lymphocyte Cell Biol Sect, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. Royal Melbourne Hosp, Cooperat Res Ctr Cellular Growlth Factors, Melbourne, Vic 3050, Australia. Queens Univ Belfast, Dept Immunol, Belfast BT9 7BL, Antrim, North Ireland. RP O'Shea, JJ (reprint author), NIAMSD, Lymphocyte Cell Biol Sect, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RI Visconti, Roberta/C-5299-2009 NR 94 TC 128 Z9 131 U1 0 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2001 VL 13 IS 3 BP 363 EP 373 DI 10.1016/S0952-7915(00)00228-4 PG 11 WC Immunology SC Immunology GA 428TT UT WOS:000168477300015 PM 11406370 ER PT J AU Buonanno, A Fischbach, GD AF Buonanno, A Fischbach, GD TI Neuregulin and ErbB receptor signaling pathways in the nervous system SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Review ID EPIDERMAL GROWTH-FACTOR; NICOTINIC ACETYLCHOLINE-RECEPTOR; CEREBELLAR GRANULE CELLS; ETS TRANSCRIPTION FACTOR; EPSILON-SUBUNIT GENE; GA-BINDING-PROTEIN; SCHWANN-CELL; NEUROMUSCULAR-JUNCTION; IN-VIVO; POSTSYNAPTIC DENSITY AB The neuregulins are a complex family of factors that perform many functions during neural development. Recent experiments have shown that neuregulins promote neuronal migration and differentiation, and regulate the selective expression of neurotransmitter receptors in neurons and at the neuromuscular junction. They also regulate glial commitment, proliferation, survival and differentiation. At interneuronal synapses, neuregulin ErbB receptors associate with PDZ- domain proteins at postsynaptic densities where they can modulate synaptic plasticity. How this combinatorial network comprising many neuregulin ligands that signal through distinct combinations of dimeric ErbB receptors - elicits its multitude of biological effects is beginning to be resolved. C1 NIH, Sect Mol Neurobiol, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Buonanno, A (reprint author), NIH, Sect Mol Neurobiol, Bldg 49,Room 5A-38, Bethesda, MD 20892 USA. NR 89 TC 332 Z9 346 U1 1 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD JUN PY 2001 VL 11 IS 3 BP 287 EP 296 DI 10.1016/S0959-4388(00)00210-5 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 442LA UT WOS:000169286200004 PM 11399426 ER PT J AU Nagai, M Jacobson, S AF Nagai, M Jacobson, S TI Immunopathogenesis of human T cell lymphotropic virus type I-associated myelopathy SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD LESIONS; HTLV TYPE-I; CEREBROSPINAL-FLUID; NEUROLOGIC DISEASE; PERIPHERAL-BLOOD; MULTIPLE-SCLEROSIS; HAM/TSP PATIENTS; VIRAL-INFECTION AB Human T cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis is a chronic progressive inflammatory neurological disease. Aspects of human T cell lymphotropic virus type I biology, host genetic susceptibility, and immune responses to this agent are important factors that are associated with disease progression. The use of novel immunological and molecular methods has improved our understanding of the pathophysiological mechanisms that are operative in human T cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. Co-existing high proviral loads and virus-specific CD8 T cells are important features of this disorder, in which a high cellular immune response continuously driven by this virus may contribute to the inflammatory process within central nervous system lesions in patients with this disease. Curr Opin Neurol 14:381-386. (C) 2001 Lippincott Williams & Wilkins. C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 47 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD JUN PY 2001 VL 14 IS 3 BP 381 EP 386 DI 10.1097/00019052-200106000-00019 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 439NM UT WOS:000169123400019 PM 11371764 ER PT J AU Ma, BY Wolfson, HJ Nussinov, R AF Ma, BY Wolfson, HJ Nussinov, R TI Protein functional epitopes: hot spots, dynamics and combinatorial libraries SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID MOLECULAR RECOGNITION; BINDING-SITES; T4 LYSOZYME; INTERFACES; DOMAIN; CONSERVATION; FLEXIBILITY; PLASTICITY; STABILITY; PROTEASES AB Recent studies increasingly point to the importance of structural flexibility and plasticity in proteins, highlighting the evolutionary advantage. There are an increasing number of cases in which given, presumably specific, binding sites have been shown to bind a range of ligands with different compositions and shapes. These studies have also revealed that evolution tends to find convergent solutions for stable intermolecular associations, largely via conservation of polar residues as hot spots of binding energy. On the other hand, the ability to bind multiple ligands at a given site is largely derived from hinge-based motions. The consideration of these two factors in functional epitopes allows more realism and robustness in the description of protein binding surfaces and, as such, in applications to mutants, modeled structures and design. Efficient multiple structure comparison and hinge-bending structure comparison tools enable the construction of combinatorial binding epitope libraries. C1 Natl Canc Inst, Intramural Res Canc Program SAIC, Frederick Canc Res & Dev Ctr, Lab Expt & Comp Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), Natl Canc Inst, Intramural Res Canc Program SAIC, Frederick Canc Res & Dev Ctr, Lab Expt & Comp Biol, Bldg 469,Rm 151, Frederick, MD 21702 USA. RI Wolfson, Haim/A-1837-2011; Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-56000] NR 38 TC 96 Z9 98 U1 2 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD JUN PY 2001 VL 11 IS 3 BP 364 EP 369 DI 10.1016/S0959-440X(00)00216-5 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 444AD UT WOS:000169375000016 PM 11406388 ER PT J AU Jeang, KT AF Jeang, KT TI Functional activities of the human T-cell leukemia virus type I Tax oncoprotein: cellular signaling through NF-kappa B SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE HTLV; adult T-cell leukemia; cellular transformation; NF-kappa B; tax; CREB; AP-1; HAM/TSP ID CREB BINDING-PROTEIN; SERUM RESPONSE FACTOR; TRANSCRIPTIONAL ACTIVATOR TAX; TRANSFORMS RAT FIBROBLASTS; PRIMARY HUMAN-LYMPHOCYTES; IMMEDIATE-EARLY GENES; HTLV-I; KINASE COMPLEX; IKK-ALPHA; TRANSACTIVATOR TAX AB Human T-cell leukemia virus type I (HTLV-I) is the etiological agent for adult T-cell leukemia (ATL), as well as for tropical spastic paraparesis (TSP) and HTLV-I associate myelopathy (HAM), A biological understanding of the involvement of HTLV-I and in ATL has focused significantly on the workings of the virally-encoded 40 kDa phospho-oncoprotein, Tax. Tax is a transcriptional activator. Its ability to modulate the expression and function of many cellular genes has been reasoned to be a major contributory mechanism explaining HTLV-I-mediated transformation of cells. In activating cellular gene expression, Tax impinges upon several cellular signal-transduction pathways, including those for CREB/ATF and NF-KB. In this paper, we review aspects of Taxs transcriptional potential with particular focus on recent evidence linking Tax to IKK (I kappaB-kinase)-complex and MAP3Ks (mitogen-activated protein kinase kinase kinases). Published by Elsevier Science Ltd. C1 NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, Room 306,Bldg 4,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 153 TC 104 Z9 108 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD JUN-SEP PY 2001 VL 12 IS 2-3 BP 207 EP 217 DI 10.1016/S1359-6101(00)00028-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 446NA UT WOS:000169518300008 PM 11325603 ER PT J AU Kaufman, J Charney, D AF Kaufman, J Charney, D TI Effects of early stress on brain structure and function: Implications for understanding the relationship between child maltreatment and depression SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; PREFRONTAL CORTICAL PROJECTIONS; RECURRENT MAJOR DEPRESSION; EARLY SOCIAL DEPRIVATION; CA3 PYRAMIDAL NEURONS; SEXUAL ABUSE; HIPPOCAMPAL VOLUME; MATERNAL SEPARATION AB Child abuse is associated with markedly elevated rates of major depression (MDD) in child. adolescent, and adult cohorts. This article reviews preclinical (e.g., animal) studies of the effects of early stress and studies of the neurobiological correlates of MDD in adults and children, and it highlights differences in the neurobiological correlates of MDD and stress at various developmental stages, The preclinical studies demonstrate that stress early in life can alter the development multiple neurotransmitter systems and promote structural and functional alterations in brain regions similar to those seen in adults with depression. Preclinical and clinical studies suggest, however, that long-term neurobiological changes associated with early stress can be modified by familial/genetic factors, the quality of the subsequent caregiving environment. and pharmacological interventions. Little is known about how developmental factors interact with experiences of early stress and these other modifying factors. Moreover. in cases of child maltreatment, the effects of early abuse are often exacerbated by failures in the child protection system and repeat out-of-home placements. Given the number of factors that impact on the long-term outcome of maltreated children. multidisciplinary research efforts are recommended to address this problem-with foci that span from neurobiology to social policy. C1 Yale Univ, Dept Psychiat, New Haven, CT 06511 USA. NIMH, Bethesda, MD USA. RP Kaufman, J (reprint author), Yale Univ, Dept Psychiat, Univ Towers,Suite 2H,100 York St, New Haven, CT 06511 USA. NR 127 TC 126 Z9 128 U1 2 U2 22 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD SUM PY 2001 VL 13 IS 3 BP 451 EP 471 DI 10.1017/S0954579401003030 PG 21 WC Psychology, Developmental SC Psychology GA 464PK UT WOS:000170540800003 PM 11523843 ER PT J AU Meyer, SE Chrousos, GP Gold, PW AF Meyer, SE Chrousos, GP Gold, PW TI Major depression and the stress system: A life span perspective SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; ISCHEMIC-HEART-DISEASE; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; RECEPTOR GENE-EXPRESSION; CORONARY-ARTERY DISEASE; RHESUS-MONKEY INFANTS; BONE-MINERAL DENSITY; PRENATAL STRESS; DEVELOPMENTAL PSYCHOPATHOLOGY AB From a transactional developmental perspective. the authors review findings from studies of animals and humans regarding a proposed relation between stress system abnormalities and major depression. The stress system has evolved to promote successful adaptation across the life span, but disruptions in its functioning may increase the risk of pathological outcomes. Emphasis is placed on the role of prenatal and early postnatal experience in contributing to individual differences in postnatal stress reactivity, which may interact with cognitive and psychosocial vulnerabilities to increase susceptibility to later onset of depression. Findings regarding cognitive, psychosocial, and medical sequelae of depression are also reviewed, with a focus on the possible mediating role of the stress system. The authors highlight the importance of multidisciplinary. longitudinal studies in attempting to gain a deeper understanding of the complex developmental processes involved in the onset and course of depression. C1 NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN 55455 USA. RP Meyer, SE (reprint author), NIMH, Clin Neuroendocrinol Branch, 10 Ctr Dr,MSC-1284,Bldg 10,Room 2D-46, Bethesda, MD 20892 USA. NR 118 TC 66 Z9 69 U1 3 U2 6 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD SUM PY 2001 VL 13 IS 3 BP 565 EP 580 DI 10.1017/S095457940100308X PG 16 WC Psychology, Developmental SC Psychology GA 464PK UT WOS:000170540800008 PM 11523848 ER PT J AU Post, RM Leverich, GS Xing, GQ Weiss, SRB AF Post, RM Leverich, GS Xing, GQ Weiss, SRB TI Developmental vulnerabilities to the onset and course of bipolar disorder SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; GLUCOCORTICOID-RECEPTOR FUNCTION; SUBGENUAL PREFRONTAL CORTEX; FAMILIAL MOOD DISORDERS; BIRTH-COHORT CHANGES; LITHIUM PROPHYLAXIS; MAJOR DEPRESSION; SUBSTANCE-ABUSE; MATERNAL-DEPRIVATION; NEUROTROPHIC FACTOR AB Different types of psychosocial stressors have long been recognized as potential precipitants of both unipolar and bipolar affective episodes and the causative agents in posttraumatic stress disorder (PTSD). New preclinical data have revealed some of the neurobiological mechanisms that could convey the long-term behavioral and biochemical consequences of early stressors, Depending on the timing, quality, quantity, and degree of repetition. maternal deprivation stress in the neonatal rodent can be associated with lifelong anxiety-like behaviors, increases in stress hormones and peptides. and proneness to drug and alcohol administration, in association with acute changes in the rate of neurogenesis and apoptosis (preprogrammed cell death) and decrements in neurotrophic factors and signal transduction enzymes necessary for learning and memory. Patients with bipolar illness who have a history of early extreme adversity (physical or sexual abuse in childhood or adolescence), compared with those without, show an earlier onset of illness, faster cycling frequencies. increased suicidality, more Axis I and Axis II comorbidities (including alcohol and substance abuse), and more time ill in more than 2 years of prospective follow-up. These findings are subject to a variety of interpretations, but to the extent that the more severe course of bipolar illness characteristics are directly and causally related to these early stressful experiences, early recognition and treatment of high-risk children could be crucial in helping to prevent or ameliorate the long-term adverse consequences of these stressors. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, 10 Ctr Dr,MSC 1272,Bldg 10,Room 3S239, Bethesda, MD 20892 USA. NR 111 TC 68 Z9 70 U1 5 U2 8 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD SUM PY 2001 VL 13 IS 3 BP 581 EP 598 DI 10.1017/S0954579401003091 PG 18 WC Psychology, Developmental SC Psychology GA 464PK UT WOS:000170540800009 PM 11523849 ER PT J AU Klimes-Dougan, B Hastings, PD Granger, DA Usher, BA Zahn-Waxler, C AF Klimes-Dougan, B Hastings, PD Granger, DA Usher, BA Zahn-Waxler, C TI Adrenocortical activity in at-risk and normally developing adolescents: Individual differences in salivary cortisol basal levels, diurnal variation, and responses to social challenges SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID INTERNALIZING BEHAVIOR PROBLEMS; DEXAMETHASONE SUPPRESSION TEST; MAJOR DEPRESSIVE DISORDER; CLINIC-REFERRED CHILDREN; NONDEPRESSED CHILDREN; DISRUPTIVE BEHAVIOR; FAMILY ENVIRONMENT; CONDUCT DISORDER; SUBSTANCE-ABUSE; SEX-DIFFERENCES AB The purpose of this study was to examine adrenocortical activity (basal, diurnal variation, and responses to social stressors) in adolescents at risk for psychopathology. Salivary cortisol levels were examined in normally developing and at-risk youth with internalizing and externalizing symptoms ranging from subclinical to clinical levels. Adolescents showed expected patterns of diurnal variation, with high early morning cortisol levels and a pattern of decline throughout the day. Females showed higher midday and late afternoon levels than mates, and these patterns interacted with risk status. Internalizing problems sometimes were associated with gradual rather than steep declines in basal cortisol production. Both immediate and delayed cortisol reactivity to a social performance stressor were associated with internalizing symptoms. There was no evidence of relations between externalizing problems and underarousal of the hypothalamic-pituitary-adrenal (HPA) system. These and other results suggest that gender is an important moderating factor linking psychopathology, development, and context with HPA axis functioning in adolescence. C1 Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA. NIMH, Bethesda, MD USA. Penn State Univ, University Pk, PA 16802 USA. RP Klimes-Dougan, B (reprint author), Catholic Univ Amer, Dept Psychol, 314 OBoyle Hall, Washington, DC 20064 USA. NR 79 TC 201 Z9 201 U1 6 U2 27 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD SUM PY 2001 VL 13 IS 3 BP 695 EP 719 DI 10.1017/S0954579401003157 PG 25 WC Psychology, Developmental SC Psychology GA 464PK UT WOS:000170540800015 PM 11523855 ER PT J AU Thomas, JM Contreras, JL Smyth, CA Lobashevsky, A Jenkins, S Hubbard, WJ Eckhoff, DE Stavrou, S Neville, DM Thomas, FT AF Thomas, JM Contreras, JL Smyth, CA Lobashevsky, A Jenkins, S Hubbard, WJ Eckhoff, DE Stavrou, S Neville, DM Thomas, FT TI Successful reversal of streptozotocin-induced diabetes with stable allogeneic islet function in a preclinical model of type 1 diabetes SO DIABETES LA English DT Article ID PERITRANSPLANT TOLERANCE INDUCTION; LONG-TERM SURVIVAL; RHESUS-MONKEYS; HUMANIZED ANTI-CD154; TRANSPLANTATION; ALLOGRAFTS; CELL; PANCREAS; IMMUNOSUPPRESSION; XENOGRAFTS AB The recent focus on islet transplantation as primary therapy for type 1 diabetes has heightened interest in the reversal of type 1 diabetes in preclinical models using minimal immunosuppression, Here, we demonstrated in a preclinical rhesus model a consistent reversal of all measured glycemic patterns of streptozotocin-induced type I diabetes. The model used single-donor islet transplantation with induction of operational tolerance. The term "operational tolerance" is used to indicate durable survival of single-donor major histocompatibility complex (MHC)-mismatched islet allografts without maintenance immunosuppressive therapy and without rejection or loss of functional islet mass or insulin secretory reserve. In this operational tolerance model, all immunosuppression was discontinued after day 14 posttransplant, and recipients recovered with excellent health, The operational tolerance induction protocol combined peritransplant anti-CD3 immunotoxin to deplete T-cells and 15-deoxyspergualin to arrest proinflammatory cytokine production and maturation of dendritic cells, T-cell deficiency was specific but temporary, in that T-cell-dependent responses in long-term survivors recovered to normal, and there was no evidence of increased susceptibility to infection. Anti-donor mixed lymphocyte reaction responses were positive in the long-term survivors, but all showed clear evidence of systemic T-helper 2 deviation, suggesting that an immunoregulatory rather than a deletional process underlies this operational tolerance model. This study provides the first evidence that operational tolerance can protect MHC nonhuman primate islets from rejection as well as loss of functional islet mass. Such an approach has potential to optimize individual recipient recovery from diabetes as well as permitting more widespread islet transplantation with the limited supply of donor islets. C1 Univ Alabama, Dept Surg, Div Transplantat, Birmingham, AL 35294 USA. NIMH, NIH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Thomas, JM (reprint author), Univ Alabama, Dept Surg, Div Transplantat, Suite 563,Boshell Diabet Res & Educ Bldg,1808 7th, Birmingham, AL 35294 USA. FU NIDDK NIH HHS [U19-DKS7958] NR 44 TC 67 Z9 71 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2001 VL 50 IS 6 BP 1227 EP 1236 DI 10.2337/diabetes.50.6.1227 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436XV UT WOS:000168961900001 PM 11375321 ER PT J AU Ebihara, K Ogawa, Y Masuzaki, H Shintani, M Miyanaga, F Aizawa-Abe, M Hayashi, T Hosoda, K Inoue, G Yoshimasa, Y Gavrilova, O Reitman, ML Nakao, K AF Ebihara, K Ogawa, Y Masuzaki, H Shintani, M Miyanaga, F Aizawa-Abe, M Hayashi, T Hosoda, K Inoue, G Yoshimasa, Y Gavrilova, O Reitman, ML Nakao, K TI Transgenic overexpression of leptin rescues insulin resistance and diabetes in a mouse model of lipoatrophic diabetes SO DIABETES LA English DT Article ID FAMILIAL PARTIAL LIPODYSTROPHY; GLUCOSE-METABOLISM; LAMIN A/C; ADIPOSE-TISSUE; MICE; OBESITY; SENSITIVITY; MUTATION; HYPOGONADISM; MELLITUS AB Lipoatrophic diabetes is caused by a deficiency of adipose tissue and is characterized by severe insulin resistance, hypoleptinemia, and hyperphagia. The A-ZIP/F-1 mouse (A-ZIPTg/+) is a model of severe Lipoatrophic diabetes and is insulin resistant, hypoleptinemic, hyperphagic, and shows severe hepatic steatosis. We have also produced transgenic "skinny" mice that have hepatic overexpression of leptin (LepTg/+) and no adipocyte triglyceride stores, and are hypophagic and show increased insulin sensitivity. To explore the pathophysiological and therapeutic roles of leptin in lipoatrophic diabetes, we crossed LepTg/+ and A-ZIPTg/+ mice, producing doubly transgenic mice (LepTg/+:A-ZIPTg/+) virtually lacking adipose tissue but having greatly elevated leptin levels. The LepTg/+:A-ZIPTg/+ mice were hypophagic and showed improved hepatic steatosis, Glucose and insulin tolerance tests revealed increased insulin sensitivity, comparable to LepTg/+ mice. These effects were stable over at least 6 months of age. Pair-feeding the A-ZIPTg/+ mice to the amount of food consumed by LepTg/+:A-ZIPTg/+ mice did not improve their insulin resistance, diabetes, or hepatic steatosis, demonstrating that the beneficial effects of leptin were not due to the decreased food intake. Continuous leptin administration that elevates plasma leptin concentrations to those of LepTg/+:A-ZIPTg/+ mice also effectively improved hepatic steatosis and the disorder of glucose and lipid metabolism in A-ZTP/F-1 mice. These data demonstrate that leptin can improve the insulin resistance and diabetes of a mouse model of severe lipoatrophic diabetes, suggesting that leptin may be therapeutically useful in the long-term treatment of lipoatrophic diabetes. C1 Kyoto Univ, Grad Sch Med, Dept Med & Clin Sci, Sakyo Ku, Kyoto 6068507, Japan. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Ogawa, Y (reprint author), Kyoto Univ, Grad Sch Med, Dept Med & Clin Sci, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 6068507, Japan. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 30 TC 147 Z9 155 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2001 VL 50 IS 6 BP 1440 EP 1448 DI 10.2337/diabetes.50.6.1440 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436XV UT WOS:000168961900026 PM 11375346 ER PT J AU Yeh, CH Sturgis, L Haidacher, J Zhang, XN Sherwood, SJ Bjercke, RJ Juhasz, O Crow, MT Tilton, RG Denner, L AF Yeh, CH Sturgis, L Haidacher, J Zhang, XN Sherwood, SJ Bjercke, RJ Juhasz, O Crow, MT Tilton, RG Denner, L TI Requirement for p38 and p44/p42 mitogen-activated protein kinases in RAGE-mediated nuclear factor-kappa B transcriptional activation and cytokine secretion SO DIABETES LA English DT Article ID GLYCATION END-PRODUCTS; DIALYSIS-RELATED AMYLOIDOSIS; CELL-SURFACE RECEPTOR; ADVANCED GLYCOSYLATION; OXIDANT STRESS; BINDING-PROTEIN; TYROSINE PHOSPHORYLATION; ENDPRODUCTS STIMULATE; DIABETIC VASCULOPATHY; SIGNALING PATHWAYS AB Advanced glycation end product (AGE) activation of the signal-transducing receptor for AGE (RAGE) has been linked to a proinflammatory phenotypic change within cells. However, the precise intracellular signaling pathways involved have not been elucidated. We demonstrate here that human serum albumin modified with N-epsilon-(carboxymethyl)lysine (CML), a major AGE adduct that progressively accumulates with aging, diabetes, and renal failure, induced nuclear factor (NF)-kappaB-driven reporter gene expression in human monocytic THP-1 cells. The NF-kappaB response was blocked with a synthetic peptide corresponding to the putative ligand-binding domain of RAGE, with anti-RAGE antiserum, and by coexpression of truncated receptors lacking the intracellular domain. Signal transduction from RAGE to NF-kappaB involved the generation of reactive oxygen species, since reporter gene expression was blocked with the antioxidant N-acetyl-L-cysteine. CML-modified albumin produced rapid transient activation of tyrosine phosphorylation, extracellular signal-regulated kinase 1 and 2, and p38 mitogen-activated protein kinase (MAPK), but not c-Jun NH2-terminal kinase. RAGE-mediated NF-kappaB activation was suppressed by the selective p38 MAPK inhibitor SB203580 and by coexpression of a kinase-dead p38 dominant-negative mutant. Activation of NF-kappaB by CML-modified albumin increased secretion of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and monocyte chemoattractant protein-1) severalfold, and inhibition of p38 MAPK blocked these increases. These results indicate that p38 MAPK activation mediates RAGE-induced NF-kappaB-dependent secretion of proinflammatory cytokines and suggest that accelerated inflammation may be a consequence of cellular activation induced by this receptor. C1 Texas Biotechnol Corp, Dept Cell Biol, Houston, TX 77030 USA. Texas Biotechnol Corp, Apoptosis Program, Houston, TX 77030 USA. Texas Biotechnol Corp, Dept Immunol, Houston, TX 77030 USA. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD USA. RP Denner, L (reprint author), Texas Biotechnol Corp, Dept Cell Biol, 7000 Fannin, Houston, TX 77030 USA. NR 60 TC 221 Z9 238 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2001 VL 50 IS 6 BP 1495 EP 1504 DI 10.2337/diabetes.50.6.1495 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436XV UT WOS:000168961900033 PM 11375353 ER PT J AU Harris, MI AF Harris, MI TI Frequency of blood glucose monitoring in relation to glycemic control in patients with type 2 diabetes SO DIABETES CARE LA English DT Article ID CARE; ADULTS; MANAGEMENT; OUTCOMES; NIDDM AB Objective-The aim of the study was to investigate the relationship between blood glucose level, measured as HbA(1c) and frequency of self-monitoring in patients with type 2 diabetes. Daily self-monitoring is believed to be important for patients treated with insulin or oral agents to detect asymptomatic hypoglycemia and to guide patient and provider behavior toward reaching blood glucose goals. Research Design and Methods-A national sample of patients with type 2 diabetes was studied in the third National Health and Nutrition Examination Survey. Data on therapy for diabetes, frequency of self-monitoring of blood glucose, and HbA(1c) values were obtained by structured questionnaires and by clinical and laboratory assessments. Results-According to the data, 29% of patients treated with insulin, 65% treated with oral agents, and 80% treated with diet alone had never monitored their blood glucose or monitored it less than once per month. Self-monitoring at least once per day was practiced by 39% of those taking insulin and 5-6% of those treated with oral agents or diet alone. For all patients combined, the proportion of patients who tested their blood glucose increased with an increasing HbA(1c) value. However, when examined by diabetes therapy category, there was little relationship between HbA(1c) value and the proportion testing at least once per day or the proportion testing at least once per week. Conclusions-In this cross-sectional study of patients with type 2 diabetes, the increase in frequency of self-monitoring of blood glucose with increasing HbA(1c) value was associated with the higher proportion of insulin-treated patients in higher HbA(1c) categories. Within diabetes therapy categories, the frequency of self-monitoring was nor related to glycemic control, as measured by HbA(1c) level. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Harris, MI (reprint author), NIDDKD, NIH, 6707 Democracy Blvd,Rm 695,MSC 5460, Bethesda, MD 20892 USA. NR 18 TC 130 Z9 136 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2001 VL 24 IS 6 BP 979 EP 982 DI 10.2337/diacare.24.6.979 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436XX UT WOS:000168962100002 PM 11375356 ER PT J AU Krakoff, J Kobes, S Hanson, RL Knowler, WC AF Krakoff, J Kobes, S Hanson, RL Knowler, WC TI Comparison of the effect of plasma glucose concentrations on microvascular disease between Pima Indian youths and adults SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; CHILDREN; PREVALENCE; ANTIBODIES; CRITERIA AB OBJECTIVE - To examine whether the current adult guidelines for diagnosis of diabetes are applicable to youth (age <20 years). RESEARCH DESIGN AND METHODS - We analyzed fasting plasma glucose (FPG) and 2-h plasma glucose (PG) in two groups of Pima Indians, youths aged 5-19 years and adults aged 20-34 years, in relation to the incidence of microvascular disease when subjects were reexamined at ages 25-39 (youths) and 40-54 (adults). Microvascular disease was defined as retinopathy or a urine protein-to-creatinine ratio 0.5 g. RESULTS - An increase in the incidence of microvascular disease occurred at nearly the same level of glycemia in both groups. For youths, this increase occurred at FPG similar to7.1 mmol/l and 2-h PG similar to 10.0 mmol/l; for adults, this increase occurred at FPG similar to7.5 mmol/l and 2-h PG similar to 10.3 mmol/l. Sensitivity of the adult diagnostic guidelines of FPG greater than or equal to7.0 mmol/l and 2-h PG greater than or equal to 11.1 mmol/l for the detection of microvascular disease was much lower (with higher specificity) in youths than in adults. Receiver operating characteristics (ROC) curve areas were lower for FPG and 2-h PG for youths, suggesting that microvascular disease was less strongly predicted by baseline glucose. CONCLUSION - The current adult guidelines for diagnosis of diabetes are applicable to youth, as they identify a population at high risk of microvascular complications. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, Diabet Arthrit & Epidemiol Sect, NIH, Phoenix, AZ 85014 USA. RP Krakoff, J (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, Diabet Arthrit & Epidemiol Sect, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 24 TC 10 Z9 10 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2001 VL 24 IS 6 BP 1023 EP 1028 DI 10.2337/diacare.24.6.1023 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436XX UT WOS:000168962100010 PM 11375364 ER PT J AU Longnecker, MP Klebanoff, MA Brock, JW Zhou, HB AF Longnecker, MP Klebanoff, MA Brock, JW Zhou, HB TI Polychlorinated biphenyl serum levels in pregnant subjects with diabetes SO DIABETES CARE LA English DT Article ID 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; CAPACITOR WORKERS; EXPOSURE; MELLITUS; PCBS; MORTALITY; CHILDREN; VETERANS; INSULIN; DIOXINS AB OBJECTIVE - Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain; detectable amounts are in the blood of nearly every one. Their effect on humans at background levels of exposure is an area of active investigation. Increased blood levels of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin), a PCB-like compound. have recently been reported among subjects with diabetes, suggesting that PCB levels could be similarly elevated. To test this hypothesis, we examined a group of pregnant women whose serum PCB levels had been measured and whose diabetes status had been previously recorded. RESEARCH DESIGN AND METHODS - Using stored serum from a large birth cohort study, we conducted a cross-sectional study of 2,245 pregnant women, of whom 44 had diabetes (primarily type 1) and 2,201 were control subjects. RESULTS - The adjusted mean serum level of PCBs among, the subjects with diabetes was 30% higher than in the control subjects (P = 0.0002), and the relationship of PCB level to adjusted odds of diabetes was linear. CONCLUSIONS - The possibility exists that PCBs and diabetes are causality related; alternatively, the pharmacokinetics of PCBs could be altered among patients with diabetes. At any event, if the association is replicated in other studies, increased serum levels of PCBs in subjects with diabetes or their offspring may put them at increased risk of PCB-induced changes in thyroid metabolism or neurodevelopment. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. NIEHS, Biostat Branch, Res Triangle Pk, NC USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, POB 12233 MD A3-05, Res Triangle Pk, NC 27709 USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 20 TC 65 Z9 71 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2001 VL 24 IS 6 BP 1099 EP 1101 DI 10.2337/diacare.24.6.1099 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436XX UT WOS:000168962100023 PM 11375377 ER PT J AU Wolford, JK Hanson, RL Bogardus, C Prochazka, M AF Wolford, JK Hanson, RL Bogardus, C Prochazka, M TI Analysis of the Lamin A/C gene as a candidate for Type II diabetes susceptibility in Pima Indians SO DIABETOLOGIA LA English DT Article DE LMNA; Type II diabetes; Pima Indians; association analysis; single nucleotide polymorphism; 1q21 ID FAMILIAL PARTIAL LIPODYSTROPHY; MELLITUS; SEARCH AB Aims/hypothesis. Lamin A/C (LMNA) is located within a region on chromosome Iq that has been linked with Type II (non-insulin-dependent) diabetes mellitus in Pima Indians. Rare mutations in exon 8 of LMNA underlie Dunnigan-Type familial partial lipodystrophy, a disease characterized by regional adipocyte degeneration and frequently accompanied by insulin resistance, glucose intolerance, and diabetes. A more common variant in exon 10 (3408C/T) has recently been associated with obesity in non-diabetic aboriginal Canadian subjects. Because obesity is a strongly predisposing factor for Type II diabetes, we hypothesized that the LMNA 3408C/T variant could be associated with diabetes and body mass index in Pima Indians. Methods. To determine whether the LMNA 3408C/T variant contributes to Type II diabetes susceptibility, we genotyped the polymorphism in 1338 Pimas using allelic discrimination technology. The locus was screened for additional variants in 20 diabetic Pima Indians and non-diabetic Pima Indians using denaturing high performance liquid chromatography and dideoxy sequencing. Results. We found no evidence for association of 3408C/T with diabetes, body mass index, total cholesterol, HDL cholesterol, triglycerides, leptin concentrations, or indices of insulin sensitivity and secretion. Subsequent screening of the remaining LMNA exons and flanking sequences revealed only rare variants in intron 4 and the 3'UTR, showing no frequency differences between diabetic and non-diabetic Pima Indians. We reassessed the linkage with diabetes following adjustment for the LMNA 3408C/T variant; adjustment for the effects of LMNA did not substantially modify the evidence for linkage. Conclusion/interpretation. We conclude that the LMNA 3408C/T variant probably does not play a role in susceptibility to diabetes or obesity in Pima Indians. C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Res Branch, NIH, Phoenix, AZ 85016 USA. RP Wolford, JK (reprint author), NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Res Branch, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 10 TC 21 Z9 22 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 2001 VL 44 IS 6 BP 779 EP 782 DI 10.1007/s001250051688 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 442CT UT WOS:000169268200015 PM 11440372 ER PT J AU Johnson, RE Jones, HE Jasinski, DR Svikis, DS Haug, NA Jansson, LM Kissin, WB Alpan, G Lantz, ME Cone, EJ Wilkins, DG Golden, AS Huggins, GR Lester, BM AF Johnson, RE Jones, HE Jasinski, DR Svikis, DS Haug, NA Jansson, LM Kissin, WB Alpan, G Lantz, ME Cone, EJ Wilkins, DG Golden, AS Huggins, GR Lester, BM TI Buprenorphine treatment of pregnant opioid-dependent women: maternal and neonatal outcomes SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE pregnancy; buprenorphine; opioid dependence; treatment; neonatal abstinence syndrome; perinatal addiction ID ADDICTION; WITHDRAWAL; METHADONE AB This open-label prospective study examined maternal and neonatal safety and efficacy outcome measures during and following prenatal buprenorphine exposure. Three opioid-dependent pregnant women received 8 or 12 mg sublingual buprenorphine tablets daily for 15-16 weeks prior to delivery. Results showed that buprenorphine in combination with comprehensive prenatal care was safe and effective in these women. Prenatal exposure to buprenorphine resulted in normal birth outcomes, a mean of 4.33 days (minimum possible = 4) hospitalization, and a 'relatively mild' neonatal abstinence syndrome comprised primarily of tremors (disturbed), hyperactive moro and shortened sleep after feeding. The infants required no pharmacological treatment. Onset of neonatal abstinence signs occurred within the first 12 h after birth, peaked by 72 h and returned to below pre-12 h levels by 120 h. It is concluded that buprenorphine has potential utility for the treatment of pregnant opioid-dependent women. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Johns Hopkins Univ, Johns Hopkins Bayview Med Ctr, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. Johns Hopkins Univ, Johns Hopkins Bayview Med Ctr, Sch Med, Ctr Addict & Pregnancy, Baltimore, MD 21224 USA. Johns Hopkins Univ, Johns Hopkins Bayview Med Ctr, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neonatol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21224 USA. NIDA, Div Intramural Res, Baltimore, MD 21224 USA. Univ Utah, Ctr Human Toxicol, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA. Brown Univ, Sch Med, Dept Pediat, Providence, RI 02905 USA. Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02905 USA. RP Jones, HE (reprint author), Johns Hopkins Univ, Johns Hopkins Bayview Med Ctr, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA09258, 2P50-DA05273-11, DA07029] NR 28 TC 74 Z9 76 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 JUN 1 PY 2001 VL 63 IS 1 BP 97 EP 103 DI 10.1016/S0376-8716(00)00194-0 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 428VE UT WOS:000168481700009 PM 11297835 ER PT J AU Lee, A Tan, S Lim, D Winslow, RM Wong, KE Allen, J Hall, W Parker, G AF Lee, A Tan, S Lim, D Winslow, RM Wong, KE Allen, J Hall, W Parker, G TI Naltrexone in the treatment of male alcoholics - an effectiveness study in Singapore SO DRUG AND ALCOHOL REVIEW LA English DT Article DE naltrexone; alcoholic; effective; Singapore; Asian; craving ID PLACEBO-CONTROLLED TRIAL; DEPENDENCE; DRINKING; THERAPY AB Naltrexone has been demonstrated in western studies to be a useful pharmacological adjunct within treatment programmes for alcoholic patients. We report the first study of its efficacy and usefulness in an Asian region. This project was designed to allow naltrexone's performance to be assessed under routine clinical conditions but with patients selected on the basis of their being likely to comply. Following in-patient detoxification, 53 male alcohol-dependent patients admitted to the Alcohol Treatment Centre at Woodbridge Hospital, Singapore, were enrolled in a 12-week, placebo-controlled trial of naltrexone hydrochloride (50 mg/day). Subjects were randomized on a 2:1 basis, with 35 receiving naltrexone and 18 receiving placebo. Analyses identified that a higher percentage of naltrexone patients completed the study (40% vs. 22%). In the study non-completers, the dropout rate due to drinking relapse was also lower in the naltrexone group (9% vs. 43%). Of the 39 patients for whom drinking status over the trial could be ascertained, fewer naltrexone-treated patients drank (33% vs. 53%). Alcohol craving scores also showed a selective and distinct reduction in the naltrexone-treated group. Results suggest that naltrexone may be an effective and safe aid to treatment of alcohol dependent patients in Asian patients, for whom the aims are to reduce alcohol craving and drinking reinstatement, but where compliance is likely to be low. C1 Woodbridge Hosp, Singapore, Singapore. NIAAA, Treatment Res Branch, Rockville, MD 20852 USA. Univ New S Wales, Natl Drug & Alcohol Ctr, Kensington, NSW 2033, Australia. Univ New S Wales, Sch Psychiat, Kensington, NSW 2033, Australia. RP Lee, A (reprint author), WH & AH, Addict Med Div, Singapore, Singapore. RI Hall, Wayne/A-3283-2008; OI Hall, Wayne/0000-0003-1984-0096; Parker, Gordon/0000-0003-3424-5519 NR 15 TC 16 Z9 16 U1 1 U2 1 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0959-5236 J9 DRUG ALCOHOL REV JI Drug Alcohol Rev. PD JUN PY 2001 VL 20 IS 2 BP 193 EP 199 DI 10.1080/09595230120058579 PG 7 WC Substance Abuse SC Substance Abuse GA 449PP UT WOS:000169695800006 ER PT J AU Gomez, G Apasov, S Sitkovsky, MV AF Gomez, G Apasov, S Sitkovsky, MV TI Immunosuppressive effects of extracellular adenosine on immune cells: Implications for the pathogenesis of ADA SCID and immunomodulation SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT 1st International Workshop on Nucleotides and their Receptors in the Immune System CY SEP 08-10, 2000 CL FERRARA, ITALY DE ADA-SCID; extracellular adenosine; adenosine receptor ID DEPENDENT PROTEIN-KINASE; DEAMINASE DEFICIENCY; PURINERGIC RECEPTOR; T-CELLS; C-ALPHA; THYMOCYTES; ACTIVATION; APOPTOSIS; PATHWAY; EXPRESSION AB Signaling through extracellular adenosine receptors is believed to account for the wide-ranging effects of adenosine. Interest of immunologists in adenosine stems from the observation that ADA deficiency leads to the inheritable SCID syndrome, and the data reviewed here indicate that at least some of the characteristics of ADA-SCID may be a consequence of extracellular adenosine signaling. Studies of adenosine receptor and ADA-deficient mice may provide the genetic evidence necessary to implicate extracellular adenosine as an important mediator in pathogenesis of ADA SCID and in demonstration of selectivity of adenosine-based immunomodulating drugs. Published 2001 Wiley-Liss, Inc. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sitkovsky, MV (reprint author), NIAID, Immunol Lab, NIH, 10-11 N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. NR 50 TC 8 Z9 8 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JUN-JUL PY 2001 VL 53 IS 2-3 BP 218 EP 224 DI 10.1002/ddr.1190 PG 7 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 484PJ UT WOS:000171698500022 ER PT J AU Blizard, D Sueyoshi, T Negishi, M Dehal, SS Kupfer, D AF Blizard, D Sueyoshi, T Negishi, M Dehal, SS Kupfer, D TI Mechanism of induction of cytochrome P450 enzymes by the proestrogenic endocrine disrupter pesticide-methoxychlor: Interactions of methoxychlor metabolites with the constitutive androstane receptor system SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID RING-HYDROXYLATION; ANDROGEN RECEPTOR; MONOOXYGENASES; ESTROGEN; CYP2B; RAT; OXYGENASE; PREGNANCY; PROTEINS; CYP3A4 AB Methoxychlor, a structural analog of the DDT pesticide, was previously shown to induce rat hepatic CYP2B and -3A mRNAs and the corresponding proteins [J Biochem Mol Toxicol 1998;12:315-323], Additionally, methoxychlor was found to activate the constitutive androstane receptor (CAR) system and induce CYP2B6 (J Biol Chem 1999;274:6043-6046), suggesting a mechanism for methoxychlor-mediated cytochrome P450 (P450) 2B induction. However, it has not been established whether CAR activation and P450 induction was due to methoxychlor per se and/or due to its metabolites. Also, a possible link between the estrogenic potency of methoxychlor metabolites and CAR activation or P450 induction was not investigated. The current study explores the ability of methoxychlor and its metabolites to activate CAR and whether their potency of CAR activation correlates with their respective estrogenicity, Methoxychlor and its metabolites (mono-OH-M [1,1,1-trichloro-2 (4-hydroxyphenyl)-2'-(4-methoxyphenyl)ethane]; bis-OH-M [1,1,1-trichloro-2,2'-bis(4-hydroxyphenyl)ethane]; ring-OH-M [1,1,1-trichloro-2(4-methoxyphenyl)-2'-(4-methoxyphenyl)-2'-(3-hydroxy-4-methoxy- phenyl)ethane]; and tris-OH-M [1,1,1-trichloro-2(4-hydroxyphenyl)-2'-(3,4-dihydroxyphenyl)ethane]; were found to be potent activators of CAR. Dose response curves indicated that tris-CH-M is a more potent CAR activator than methoxychlor, mono-CH-M, and bis-OH-M, Since tris-CH-M is a much weaker estrogen receptor-alpha agonist than mono-OH-M and bis-OH-M, it seems that estrogenicity is not a significant factor in CAR activation, These findings indicate that alteration of methoxychlor-benzene rings, i.e., generation of phenolic constituents, does not appreciably alter CAR activation and suggest that a common structural motif in the methoxychlor class of compounds controls CAR activation, Studies are needed to identify the structural motif necessary for CAR activation and CYP2B induction. C1 Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01655 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Kupfer, D (reprint author), Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, 55 Lake Ave N, Worcester, MA 01655 USA. FU NIEHS NIH HHS [ES00834] NR 31 TC 33 Z9 35 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUN PY 2001 VL 29 IS 6 BP 781 EP 785 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 437TG UT WOS:000169009200002 PM 11353743 ER PT J AU Nakayama, J Allshire, RC Klar, AJS Grewal, SIS AF Nakayama, J Allshire, RC Klar, AJS Grewal, SIS TI Role for DNA polymerase alpha in epigenetic control of transcriptional silencing in fission yeast SO EMBO JOURNAL LA English DT Article DE DNA polymerase; epigenetic; fission yeast; heterochromatin; silencing ID ORIGIN RECOGNITION COMPLEX; POSITION-EFFECT VARIEGATION; SCHIZOSACCHAROMYCES-POMBE; CHROMOSOME SEGREGATION; REPRESS TRANSCRIPTION; STRAND BREAKS; HP1 PROTEINS; REPLICATION; CHROMATIN; INHERITANCE AB In the fission yeast Schizosaccharomyces pombe, transcriptional silencing at the mating-type region, centromeres and telomeres is epigenetically controlled, and results from the assembly of higher order chromatin structures. Chromatin proteins associated with these silenced loci are believed to serve as molecular bookmarks that help promote inheritance of the silenced state during cell division. Specifically, a chromo-domain protein Swi6 is believed to be an important determinant of the epigenetic imprint. Here, we show that a mutation in DNA polymerase alpha (pol alpha) affects Swi6 localization at the mating-type region and causes a 45-fold increase in spontaneous transition from the silenced epigenetic state to the expressed state. We also demonstrate that pol alpha mutant cells are defective in Swi6 localization at centromeres and telomeres, Genetic analysis suggests that Pola and Swi6 are part of the same silencing pathway, Interestingly, we found that Swi6 directly binds to Pol alpha in vitro. Moreover, silencing-defective mutant Pol alpha displays reduced binding to Swi6 protein. This work indicates involvement of a DNA replication protein, Pol alpha, in heterochromatin assembly and inheritance of epigenetic chromatin structures. C1 Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. Natl Canc Inst, Frederick, MD USA. MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland. RP Grewal, SIS (reprint author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA. RI Nakayama, Jun-ichi/C-6003-2011 FU NIGMS NIH HHS [R01 GM059772, R01 GM59772-02] NR 46 TC 56 Z9 57 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 1 PY 2001 VL 20 IS 11 BP 2857 EP 2866 DI 10.1093/emboj/20.11.2857 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 441LL UT WOS:000169231800023 PM 11387218 ER PT J AU Frank, EG Tissier, A McDonald, JP Rapic-Otrin, V Zeng, XM Gearhart, PJ Woodgate, R AF Frank, EG Tissier, A McDonald, JP Rapic-Otrin, V Zeng, XM Gearhart, PJ Woodgate, R TI Altered nucleotide misinsertion fidelity associated with pol iota-dependent replication at the end of a DNA template SO EMBO JOURNAL LA English DT Article DE DNA polymerase eta; DNA polymerase zeta; Rad30; Rad30B; somatic mutation ID XERODERMA-PIGMENTOSUM VARIANT; ESCHERICHIA-COLI DINB; BASE EXCISION-REPAIR; DOUBLE-STRAND BREAKS; SOMATIC HYPERMUTATION; IMMUNOGLOBULIN GENES; POLYMERASE-BETA; IMMUNE-RESPONSE; MOUSE HOMOLOGS; THYMINE DIMER AB A hallmark of human DNA polymerase iota (pol iota) is the asymmetric fidelity of replication at template A and T when the enzyme extends primers annealed to a single-stranded template. Here, we report on the efficiency and accuracy of pol iota -dependent replication at a nick, a gap, the very end of a template and from a mispaired primer, Pol iota cannot initiate synthesis on a nicked DNA substrate, but fills short gaps efficiently. Surprisingly, pol iota 's ability to blunt-end a 1 bp recessed terminus is dependent upon the template nucleotide encountered and is highly erroneous. At template G, both C and T are inserted with roughly equal efficiency, whilst at template C, C and A are misinserted 8- and 3-fold more often than the correct base, G, Using substrates containing mispaired primer termini, we show that pol iota can extend all 12 mispairs, but with differing efficiencies. Pol iota can also extend a tandem mispair, especially when it is located within a short gap. The enzymatic properties of pol iota appear consistent with that of a somatic hypermutase and suggest that pol iota may be one of the low-fidelity DNA polymerases hypothesized to participate in the hypermutation of immunoglobulin variable genes in vivo. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. NR 58 TC 47 Z9 52 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 JUN 1 PY 2001 VL 20 IS 11 BP 2914 EP 2922 DI 10.1093/emboj/20.11.2914 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 441LL UT WOS:000169231800029 PM 11387224 ER PT J AU Phan, L Schoenfeld, LW Valasek, L Nielson, KH Hinnebusch, AG AF Phan, L Schoenfeld, LW Valasek, L Nielson, KH Hinnebusch, AG TI A subcomplex of three eIF3 subunits binds eIF1 and eIF5 and stimulates ribosome binding of mRNA and tRNA(i)(Met) SO EMBO JOURNAL LA English DT Article DE eIF3; initiation; ribosome; translation; yeast ID EUKARYOTIC TRANSLATION INITIATION-FACTOR-3; SACCHAROMYCES-CEREVISIAE; COMPLEX-FORMATION; IN-VITRO; YEAST; INTERACTS; VIVO AB Yeast translation initiation factor 3 contains five core subunits (known as TIF32, PRT1, NIP1, TIF34 and TIF35) and a less tightly associated component known as HCR1, We found that a stable subcomplex of His(8)-PRT1, NIP1 and TIF32 (PN2 subcomplex) could be affinity purified from a strain overexpressing these eIF3 subunits, eIF5, eIF1 and HCR1 co-purified with this subcomplex, but not with distinct His(8)-PRT1-TIF34-TIF35 (P45) or His(8)-PRT1-TIF32 (P2) subcomplexes. His(8)-PRT1 and NIP1 did not form a stable binary subcomplex, These results provide in vivo evidence that TIF32 bridges PRT1 and NIP1, and that eIFs 1 and 5 bind to NIP1, in native eIF3, Heat-treated prt1-1 extracts are defective for Met-tRNA(i)(Met) binding to 40S subunits, and we also observed defective 40S binding of mRNA, eIFs 1 and 5 and eIF3 itself in these extracts. We could rescue 40S binding of Met-tRNA(i)(Met) and mRNA, and translation of luciferase mRNA, in a prt1-1 extract almost as well with purified PN2 subcomplex as with five-subunit eIF3, whereas the P45 subcomplex was nearly inactive. Thus, several key functions of eIF3 can be carried out by the PRT1-TIF32-NIP1 subcomplex. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Silver Spring, MD 20910 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Eukaryot Gene Regulat, NIH, Silver Spring, MD 20910 USA. RI Valasek, Leos/I-5743-2014 NR 26 TC 78 Z9 82 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 1 PY 2001 VL 20 IS 11 BP 2954 EP 2965 DI 10.1093/emboj/20.11.2954 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 441LL UT WOS:000169231800033 PM 11387228 ER PT J AU Pine, DS Grun, J Zarahn, E Fyer, A Koda, V Li, W Szeszko, PR Ardekani, B Bilder, RM AF Pine, Daniel S. Grun, Joseph Zarahn, Eric Fyer, Abby Koda, Vivian Li, Wei Szeszko, Philip R. Ardekani, Babak Bilder, Robert M. TI Cortical Brain Regions Engaged by Masked Emotional Faces in Adolescents and Adults: An fMRI Study SO EMOTION LA English DT Article AB Face-emotion processing has shown signs of developmental change during adolescence. Functional magnetic resonance imaging (fMRI) was used on 10 adolescents and 10 adults to contrast brain regions engaged by a masked emotional-face task (viewing a fixation cross and a series of masked happy and masked fearful faces), while blood oxygen level dependent signal was monitored by a 1.5-T MRI scanner. Brain regions differentially engaged in the 2 age groups were mapped by using statistical parametric mapping. Summed across groups, the contrast of masked face versus fixation-cross viewing generated activations in occipital-temporal regions previously activated in passive face-viewing tasks. Adolescents showed higher maxima for activations in posterior association cortex for 3 of the 4 statistical contrasts. Adolescents and adults differed in the degree to which posterior hemisphere brain areas were engaged by viewing masked facial displays of emotion. C1 [Pine, Daniel S.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Grun, Joseph; Zarahn, Eric; Fyer, Abby; Koda, Vivian; Li, Wei] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Szeszko, Philip R.; Bilder, Robert M.] N Shore Long Isl Jewish Med Ctr, Hillside Hosp Div, Garden City, NY USA. [Ardekani, Babak; Bilder, Robert M.] Nathan S Kline Inst Psychiat Res, Ctr Adv Brain Imaging, Orangeburg, NY USA. RP Pine, DS (reprint author), NIMH, Mood & Anxiety Disorders Program, Bldg 1,Room B310,Mailstop 0135, Bethesda, MD 20892 USA. EM daniel.pine@nih.gov RI Szeszko, Philip/G-9336-2013; Bilder, Robert/A-8894-2008 OI Bilder, Robert/0000-0001-5085-7852 FU NIMH NIH HHS [MH-01391] NR 34 TC 27 Z9 28 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD JUN PY 2001 VL 1 IS 2 BP 137 EP 147 DI 10.1037//1528-3542.1.2.137 PG 11 WC Psychology, Experimental SC Psychology GA V21RG UT WOS:000208224100003 PM 12899193 ER PT J AU Wood, J Mathews, A Dalgleish, T AF Wood, Jacqueline Mathews, Andrew Dalgleish, Tim TI Anxiety and Cognitive Inhibition SO EMOTION LA English DT Article AB In 3 experiments, the authors investigated whether anxiety proneness is associated with impaired inhibitory processing. Participants made speeded decisions requiring inhibition of threatening or neutral meanings of ambiguous words, which were inappropriate in their current context. In Experiment 1 there were no differences found in inhibitory processing associated with anxiety. However, in Experiment 2, when the capacity for controlled processing was reduced by imposition of a mental load, anxious individuals showed a response pattern consistent with a general impairment of inhibitory processing. In Experiment 3, a group who had experienced a traumatic event also showed evidence of impaired inhibition, despite the absence of additional load. Thus anxiety proneness is associated with a general deficit of inhibitory processing, but this may be revealed only under conditions that limit the availability of controlled processing resources. C1 [Wood, Jacqueline; Mathews, Andrew; Dalgleish, Tim] MRC, Cognit & Brain Sci Unit, Cambridge CB2 2EF, England. RP Wood, J (reprint author), Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, Bldg 10,Room 5C205,10 Ctr Dr,Mailstop 1440, Bethesda, MD 20892 USA. EM woodj@ninds.nih.gov; andrew.mathews@mrc-cbu.cam.ac.uk RI dalgleish, tim/E-8341-2010 NR 34 TC 32 Z9 33 U1 2 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD JUN PY 2001 VL 1 IS 2 BP 166 EP 181 DI 10.1037//1528-3542.1.2.166 PG 16 WC Psychology, Experimental SC Psychology GA V21RG UT WOS:000208224100005 PM 12899195 ER PT J AU Latinkic, BV Mo, FE Greenspan, JA Copeland, NG Gilbert, DJ Jenkins, NA Ross, SR Lau, LF AF Latinkic, BV Mo, FE Greenspan, JA Copeland, NG Gilbert, DJ Jenkins, NA Ross, SR Lau, LF TI Promoter function of the angiogenic inducer Cyr61 gene in transgenic mice: Tissue specificity, inducibility during wound healing, and role of the serum response element SO ENDOCRINOLOGY LA English DT Article ID IMMEDIATE-EARLY GENE; HUMAN SKIN FIBROBLASTS; GROWTH-FACTOR; AXON GUIDANCE; EXTRACELLULAR-MATRIX; CELL-MIGRATION; CCN FAMILY; C-FOS; EXPRESSION; ADHESION AB The cysteine-rich angiogenic protein 61 (Cyr61) is an extracellular matrix-associated, heparin-binding protein that mediates cell adhesion, stimulates cell migration, and enhances growth factor-induced cell proliferation. Cyr61 also promotes chondrogenic differentiation and induces neovascularization. In this study, we show that a 2-kb fragment of the Cyr61 promoter, which confers growth factor-inducible expression in cultured fibroblasts, is able to drive accurate expression of the reporter gene lacZ in transgenic mice. Thus, transgene expression was observed in the developing placenta and embryonic cardiovascular, skeletal, and central and peripheral nervous systems. The sites of transgene expression are consistent with those observed of the endogenous Cyr61 gene as determined by in situ hybridization and immunohistochemistry. The transgene expression in the cardiovascular system does not require the serum response element, a promoter sequence essential for transcriptional activation of Cyr61 by serum growth factors in cultured fibroblasts. Because the serum response element contains the CArG box, a sequence element implicated in cardiovascular-specific gene expression, the nonessential nature of this sequence for cardiovascular expression of Cyr61 is unexpected. Furthermore, the Cyr61 promoter-driven lacZ expression is inducible in granulation tissue during wound healing, as is synthesis of the endogenous Cyr61 protein, suggesting a role for Cyr61 in wound healing. Consistent with this finding, purified Cyr61 protein promotes the healing of a wounded fibroblast monolayer in culture. In addition, we mapped the mouse Cyr61 gene to the distal region of chromosome 3. Together, these results define the functional Cyr61 promoter in vivo, and suggest a role of Cyr61 in wound healing through its demonstrated angiogenic activities upon endothelial cells and its chemotactic and growth promoting activities upon fibroblasts. C1 Univ Illinois, Coll Med, Dept Mol Genet, Chicago, IL 60607 USA. Munin Corp, Chicago, IL 60612 USA. NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. RP Lau, LF (reprint author), Univ Illinois, Coll Med, Dept Mol Genet, 900 S Ashland Ave, Chicago, IL 60607 USA. FU NCI NIH HHS [CA46565, CA52220, CA78044] NR 43 TC 45 Z9 45 U1 0 U2 0 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 JUN PY 2001 VL 142 IS 6 BP 2549 EP 2557 DI 10.1210/en.142.6.2549 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 435VP UT WOS:000168903100049 PM 11356704 ER PT J AU Samet, JM Dearry, A Eggleston, PA Ford, J Froines, J Gelobter, M Gong, H Kinney, PL Leikauf, GD Lipsett, M Lwebuga-Mukasa, JS Mannino, D McDonnell, W Morandi, MT Neas, LM Porras, C Prasad, S Redd, S Schwab, M Servin, T Shepard, P Spengler, JD Sugerman-Brozan, J Targ, N Wallace, D Wallace, R White, RH Woodruff, T AF Samet, JM Dearry, A Eggleston, PA Ford, J Froines, J Gelobter, M Gong, H Kinney, PL Leikauf, GD Lipsett, M Lwebuga-Mukasa, JS Mannino, D McDonnell, W Morandi, MT Neas, LM Porras, C Prasad, S Redd, S Schwab, M Servin, T Shepard, P Spengler, JD Sugerman-Brozan, J Targ, N Wallace, D Wallace, R White, RH Woodruff, T CA Amer Lung Assoc TI Urban air pollution and health inequities: A workshop report SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE air pollution; community intervention; environmental justice; environmental monitoring; genetic susceptibility; health status susceptibility; population surveillance; public policy; urban health ID OBSTRUCTIVE PULMONARY-DISEASE; SOUTHERN CALIFORNIA COMMUNITIES; CHRONIC RESPIRATORY SYMPTOMS; DIESEL EXHAUST PARTICLES; NORTH-AMERICAN CHILDREN; DAILY ASTHMA SEVERITY; PEAK EXPIRATORY FLOW; INNER-CITY CHILDREN; SMALL-AREA ANALYSIS; LOW-BIRTH-WEIGHT AB Over the past three decades, an array of legislation with attendant regulations has been implemented to enhance the quality of the environment and thereby improve the public's health. Despite the many beneficial changes that have followed, there remains a disproportionately higher prevalence of harmful environmental exposures, particularly air pollution, for certain populations. These populations most often reside in urban settings, have low socioeconomic status, and include a large proportion of ethnic minorities. The disparities between racial/ethnic minority and/or low-income populations in cities and the general population in terms of environmental exposures and related health risks have prompted the "environmental justice" or "environmental equity" movement, which strives to create cleaner environments for the most polluted communities. Achieving cleaner environments will require interventions based on scientific data specific to the populations at risk; however, research in this area has been relatively limited. To assess the current scientific information on urban air pollution and its health impacts and to help set the agenda for immediate intervention and future research, the American Lung Association organized an invited workshop on Urban Air Pollution and Health Inequities held 22-24 October 1999 in Washington, DC. This report builds on literature reviews and summarizes the discussions of working groups charged with addressing key areas relevant to air pollution and health effects in urban environments. An overview was provided of the state of the science for health impacts of air pollution and technologies available for air quality monitoring and exposure assessment. The working groups then prioritized research needs to address the knowledge gaps and developed recommendations for community interventions and public policy to begin to remedy the exposure and health inequities. C1 Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Johns Hopkins Hosp, Dept Pediat, Div Immunol & Allergy, Baltimore, MD 21287 USA. Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, Div Pulm Med, New York, NY 10032 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Environm Hlth Sci, Ctr Environm & Occupat Hlth, Los Angeles, CA 90024 USA. Rutgers State Univ, Grad Dept Publ Adm, Newark, NJ 07102 USA. Univ So Calif, Rancho Los Amigos Med Ctr, Environm Hlth Serv, Downey, CA 90242 USA. Columbia Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA. Univ Cincinnati, Med Ctr, Dept Environm Hlth, Cincinnati, OH 45267 USA. Univ Cincinnati, Med Ctr, Dept Physiol Biophys, Cincinnati, OH 45267 USA. Univ Cincinnati, Med Ctr, Dept Med, Cincinnati, OH 45267 USA. Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Buffalo Gen Hosp, Dept Med, Buffalo, NY 14203 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. US EPA, Chapel Hill, NC USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. US EPA, Res Triangle Pk, NC 27711 USA. Communities Better Environm, Los Angeles, CA USA. Calif Environm Protect Agcy, Sacramento, CA USA. Johns Hopkins Sch Publ Hlth, Risk Sci & Publ Policy Inst, Baltimore, MD USA. Calif Air Resources Board, Sacramento, CA USA. W Harlem Environm Act, New York, NY USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Sci & Engn Program, Boston, MA 02115 USA. Alternat Community & Environm, Roxbury, MA USA. US EPA, Off Environm Justice, Washington, DC 20460 USA. Columbia Univ, Joseph L Mailman Sch Publ Hlth, Ctr Childrens Environm Hlth, New York, NY 10027 USA. Columbia Univ, Joseph L Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY 10027 USA. New York State Psychiat Inst, Epidemiol Mental Disorders Res Dept, New York, NY 10032 USA. Amer Lung Assoc, Washington, DC 20460 USA. US EPA, Off Policy Econ & Innovat, Natl Ctr Environm Econ, Washington, DC 20460 USA. RP Samet, JM (reprint author), Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Suite 6041, Baltimore, MD 21205 USA. NR 155 TC 8 Z9 9 U1 0 U2 13 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 JUN PY 2001 VL 109 SU 3 BP 357 EP 374 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 448FU UT WOS:000169616900003 ER PT J AU Arcury, TA Quandt, SA Dearry, A AF Arcury, TA Quandt, SA Dearry, A TI Farmworker pesticide exposure and community-eased participation research: Rationale and practical applications SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE agricultural health; community participation; environmental health; environmental justice; farmworkers; health disparities; migrant health; minority health; pesticides; translational research ID CAROLINA MIGRANT FARMWORKERS; NORTH-CAROLINA; SEASONAL FARMWORKERS; OCCUPATIONAL-HEALTH; PUBLIC-HEALTH; CANCER; INTERVENTION; PARTNERSHIPS; WORKERS AB The consequences of agricultural pesticide exposure continue to be major environmental health problems in rural communities. Community-based participatory research (CBPR) is an important approach to redressing health disparities resulting from environmental causes. In this article we introduce a collection of articles that describe projects using CBPR to address the health disparities resulting from pesticide exposure in agricultural communities, particularly the communities of migrant and seasonal farmworkers. The articles in this collection are based on a workshop convened at the 1999 American Public Health Association meeting. The goals in presenting this collection are to provide those endeavoring to initiate CBPR projects needed information, guidelines, and procedures to improve the quality of the CBPR experience; to increase the scientific validity of CBPR projects; and to reduce the potential difficulties and stress of these collaborations. In this introduction we discuss the context in which these projects operate, summarizing background information about farmworkers in the United States, what is known about farmworker pesticide exposure, and the concept of community-based participatory research. Finally, the articles in this collection are summarized, and major themes common to successful CBPR projects are identified. These common features are taking the time to interact with the community, using multiple approaches to engage the different parts of the community, understanding different participants often have different goals, appreciating each group's strengths, valuing community knowledge, and being flexible and creative in conducting research. The final article in this collection describes the translational research program at the National Institute of Environmental Health Sciences (NIEHS) highlighting activities pertinent to the health of rural communities, giving an overview of NIEHS-supported projects addressing health concerns of Native Americans and rural African-American communities in addition to farmworkers, and discussing future plans for CBPR at NIEHS. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Family & Community Med, Winston Salem, NC 27157 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. NIEHS, Chem Exposures & Mol Biol Branch, Div Extramural Res & Training, NIH, Res Triangle Pk, NC 27709 USA. RP Arcury, TA (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Family & Community Med, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA. FU NIEHS NIH HHS [R21-ES08739, R13-ES10197] NR 79 TC 43 Z9 46 U1 3 U2 11 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 JUN PY 2001 VL 109 SU 3 BP 429 EP 434 DI 10.2307/3434791 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 448FU UT WOS:000169616900011 PM 11427392 ER PT J AU Kamel, F Moreno, T Rowland, AS Stallone, L Ramirez-Garnica, B Sandler, DP AF Kamel, F Moreno, T Rowland, AS Stallone, L Ramirez-Garnica, B Sandler, DP TI Recruiting a community sample in collaboration with farmworkers SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE community access; defined population; farmworkers; pesticides; response rate ID PESTICIDE; EXPOSURE; MIGRANT AB Few studies have examined health effects of pesticides in farmworkers, possibly because researchers perceive this population to be relatively inaccessible. We conducted an epidemiologic study of health effects among farmworkers in two towns in central Florida-Apopka and Pierson. Apopka is a suburb of Orlando with a diffuse farmworker community working in many crops, whereas Pierson is a small rural town with a tightly knit farmworker community working mainly in ferns. We collaborated with the Farmworker Association of Florida, a grassroots organization representing 6,700 farmworker families. We identified potential participants using membership lists of the Community Trust Federal Credit Union. Members of the Farmworker Association served as recruiters for the study, locating randomly selected Credit Union members and administering a screening interview to determine eligibility. In Apopka 90% of contacted workers were screened, and 79% of eligible workers participated in the study; corresponding proportions in Pierson were 94 and 85%. Farmworkers who had worked for 6-15 years and those who worked in a defined type of agriculture (nursery, citrus, or ferns) were more likely to enroll than others. Thus, while the response rate was good for a multistage recruiting process, study participants had a slightly different work history from those who chose not to enroll. We conclude that it is possible to conduct a study of health outcomes in farmworkers with a defined population and good response rates. Collaboration with the community is essential to the success of such a project, and community characteristics can affect response rates. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Farmworker Associat Florida, Apopka, FL USA. CODA, Durham, NC USA. RP Kamel, F (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05,Bldg 101,Rm A357,111 TW Alexan, Res Triangle Pk, NC 27709 USA. OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 NR 10 TC 9 Z9 9 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 2001 VL 109 SU 3 BP 457 EP 459 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 448FU UT WOS:000169616900015 PM 11427396 ER PT J AU O'Fallon, LR Dearry, A AF O'Fallon, LR Dearry, A TI Commitment of the national institute of environmental health sciences to community-based participatory research for rural health SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE community-based participatory research; livestock farming; migrant farmworkers; Native Americans; pesticide exposure; rural health; translational research ID NORTH-CAROLINA; AGRICULTURAL HEALTH; INSECTICIDES; METABOLISM; CHILDREN AB The National Institute of Environmental Health Sciences (NIEHS) is the leading biomedical research institution in the United States whose mission is to support research that seeks to understand how environmental exposures affect human health. NIEHS possesses a longstanding interest in the health effects of agrochemical and other environmental exposures in rural America, including pesticides, to farmers and their families and to migrant farmworkers and their families. In recent years. NIEHS has begun augmenting traditional basic science investigations with innovative programs that translate findings from the laboratory to affected populations. It is through community-based participatory research that NIEHS strives to advance the public health field by fostering the development of culturally relevant interventions that will reduce exposures to environmental contaminants and the risk of environmentally induced disease. In this article, we describe the translational research program at NIEHS as it relates to the NIEHS mission and highlight activities pertinent to the health of rural communities, especially underserved populations. We provide an overview of NIEHS-supported projects addressing health concerns of Native American and rural African-American communities in addition to farmworkers. We conclude with a discussion of future plans for community-based participatory research at NIEHS. C1 NIEHS, Chem Exposures & Mol Biol Branch, Div Extramural Res & Training, NIH, Res Triangle Pk, NC 27709 USA. RP O'Fallon, LR (reprint author), NIEHS, Chem Exposures & Mol Biol Branch, Div Extramural Res & Training, NIH, POB 12233 EC-21, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [R13-ES10197] NR 31 TC 25 Z9 25 U1 1 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 2001 VL 109 SU 3 BP 469 EP 473 DI 10.2307/3434797 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 448FU UT WOS:000169616900017 PM 11427398 ER PT J AU Tchounwou, PB Wilson, BA Ishaque, AB Schneider, J AF Tchounwou, PB Wilson, BA Ishaque, AB Schneider, J TI Transcriptional activation of stress genes and cytotoxicity in human liver carcinoma cells (HepG(2)) exposed to 2,4,6-trinitrotoluene, 2,4-dinitrotoluene, and 2,6-dinitrotoluene SO ENVIRONMENTAL TOXICOLOGY LA English DT Article DE TNT; DNTs; gene expression; cytotoxicity; HepG(2); cells; stress genes ID NF-KAPPA-B; DNA-DAMAGE; INDUCIBLE TRANSCRIPTION; PROTEIN; EXPRESSION; INDUCTION; PROMOTER; AGENTS; METALLOTHIONEIN; PROLIFERATION AB The CAT-Tox (L) assay has recently been developed and validated for detecting and quantifying the specific molecular mechanisms that underlie toxicity of various xenobotic chemicals. We performed this assay to measure the transcriptional responses associated with 2,4,6-trinitrotoluene (TNT) and 2 of its byproducts [2,4 and 2,6-dinitotoluenes (DNTs)] to 13 different recombinant cell lines generated from human liver carcinoma cells (HepG(2)) by creating stable transfectants of mammalian promoter chloramphenicol acetyltransferase (CAT) gene fusions. Cytoxicity test with the parental HepG(2) cells, using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]-based assay for cell viability, yielded LC,, values of 105 +/- 6 mg/mL for TNT in 1% dimethyl sulfoxide (DMSO), and > 300 mg/mL for DNTs, upon 48 h of exposure. TNT appeared to be more toxic than 2,4-DNT, which also showed a higher toxicity compared to 2,6-DNT. Of the 13 recombinant constructs evaluated, 8 (CYP 1A1, GST Ya, XRE, HMTIIA, c-fos, HSP70, GADD153, and GADD45), 5 (c-fos, HSP70, GADD153, GADD45, and GRP78), and none showed inductions to significant levels (p < 0.05), for TNT, 2,4-DNT, and 2,6-DNT, respectively. For most constructs, the induction of stress genes was concentration-dependent. These results show the potential for TNT and 2,4-DNT to cause protein damage and/or perturbations of protein biosynthesis (HSP70 and GRP78), alterations in DNA sequence or its helical structure (c-fos, GADD153, GADD45), and the potential involvement of INT in the biotransformation process (CYP 1A1, GST Ya, XRE), and in the toxicokinetics of metal ions (HMTIIA). Within the range of concentrations tested (0-300 mg TNT or DNT/mL in 1% DMSO), no significant inductions (p > 0.05) of NFK BRE, p53RE, CRE, and RARE were found. (C) 2001 by John Wiley & Sons, Inc. C1 Jackson State Univ, Sch Sci & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS 39217 USA. Xenometrix Inc, Client Res Lab, Boulder, CO 80301 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Sch Sci & Technol, NIH Ctr Environm Hlth, Mol Toxicol Res Lab, 1400 Lynch St,Box 18540, Jackson, MS 39217 USA. EM paul@stallion.jsums.edu NR 41 TC 26 Z9 26 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1520-4081 J9 ENVIRON TOXICOL JI Environ. Toxicol. PD JUN PY 2001 VL 16 IS 3 BP 209 EP 216 DI 10.1002/tox.1026 PG 8 WC Environmental Sciences; Toxicology; Water Resources SC Environmental Sciences & Ecology; Toxicology; Water Resources GA 438XX UT WOS:000169080500002 PM 11409192 ER PT J AU Theodore, WH AF Theodore, William H. TI Transcranial Magnetic Stimulation in Epilepsy SO EPILEPSY & BEHAVIOR LA English DT Article DE transcranial magnetic stimulation; epilepsy; TMS language lateralization; cortical excitability in epilepsy; seizure treatment; antiepileptic drugs; therapeutic TMS; repetitive TMS functional mapping AB There are several possible roles for transcranial magnetic stimulation (TMS) in epilepsy. Studies of underlying cortical excitability have shown increased motor evoked potentials and altered intracortical inhibition and facilitation, primarily in generalized epilepsy syndromes. Activation of seizure foci for preoperative mapping in patients with partial seizures has not shown clear advantages over other localizing techniques. Evaluation of the effects of antiepileptic drugs revealed differences between agents acting primarily on ion channels and those acting at the g-aminobutyric acid-benzodiazepine receptor complex. Studies comparing TMS language lateralization with the Wada test have shown interesting differences within the context of general agreement. TMS cannot be used as a clinical tool but has research potential. Preliminary studies of seizure treatment are in progress, based on preclinical data and a few encouraging anecdotal reports. (C) 2001 Academic Press C1 NIH, Bethesda, MD 20892 USA. RP Theodore, WH (reprint author), NIH, Bldg 10,Room 5N-250, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov NR 65 TC 2 Z9 2 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD JUN PY 2001 VL 2 IS 3 SU S BP S36 EP S40 DI 10.1006/ebeh.2001.0216 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA V21LF UT WOS:000208208400008 ER PT J AU Wassermann, EM AF Wassermann, Eric M. TI Transcranial Magnetic Stimulation in Disorders of Movement: The Therapeutic Outlook SO EPILEPSY & BEHAVIOR LA English DT Article DE transcranial magnetic stimulation; movement disorders; Parkinson's disease; focal dystonia; tic disorder; cortical myoclonus AB Transcranial magnetic stimulation (TMS) has been proposed as a means of improving or restoring cortical function in psychiatric and neurologic disorders. Movement disorders have attracted the attention of neurologists interested in the use of TMS as treatment. In Parkinson's disease, physiologic data and some clinical trials suggest that TMS may have a beneficial effect on movement. However, some of the laboratory data have been impossible to replicate, and the trials have lacked appropriate controls. In focal dystonia and tic disorder, TMS may suppress abnormal movements, but the data are preliminary. In the epileptic movement disorder cortical myoclonus, benefits have been elusive so far. TMS may have therapeutic potential in movement disorders, but further work is needed. (C) 2001 Academic Press C1 Natl Inst Neurol Disorders & Stroke, Brain Stimulat Unit, NIH, Bethesda, MD 20853 USA. RP Wassermann, EM (reprint author), Natl Inst Neurol Disorders & Stroke, Brain Stimulat Unit, NIH, Bldg 10,Room 5N-226, Bethesda, MD 20853 USA. EM wassermann@nih.gov NR 37 TC 2 Z9 2 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 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD JUN PY 2001 VL 2 IS 3 SU S BP S41 EP S44 DI 10.1006/ebeh.2001.0217 PG 4 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA V21LF UT WOS:000208208400009 ER PT J AU Lands, WEM AF Lands, WEM TI Biochemistry and physiology of eicosanoid precursors in cell membranes SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Article; Proceedings Paper CT Consensus Meeting on Clinical effect, Biological Background, and Research Priorities on n-3 Fatty Acids CY FEB 17-19, 2000 CL FLORENCE, ITALY SP Res Ctr Italian Natl Assoc Hosp Cardiol DE arrhythmia; eicosanoids; food choices; thrombosis ID POLYUNSATURATED FATTY-ACIDS; DIETARY FISH OIL; PROSTAGLANDINS; BIOSYNTHESIS; PHOSPHOLIPIDS; INFARCTION; MECHANISM; MYOCYTES; PLASMA AB Excessive action of omega-6 eicosanoids formed from the body's omega-6 essential fats occurs in many health disorders, and it can be diminished with dietary omega-3 fats. The current abundance of omega-6 (n-6) eicosanoid-mediated disorders (e.g. thrombotic heart attack and stroke, cardiac arrhythmia, atherogenesis, arthritis, asthma, osteoporosis, tumour metastases, etc.) accompanies n-6 acid intakes that are more than ten times than the adequate level of 0.5% of energy. The n-3 and n-6 highly unsaturated fatty acids (HUFAs) are maintained in tissue phospholipids in a competitive, hyperbolic relationship to the dietary abundance of their, 18-carbon polyunsaturated fatty acid (PUFA) precursors. In contrast, 18:2n-6 and 18:3n-3 acids are maintained in tissue triacylglycerols in a linear proportion to their dietary abundance expressed as percentage of daily caloric energy. The near absence of 20:3n-9 acid in plasma phospholipids in the U.S.A. population reflects very high intakes of polyunsaturated fats that compete with oleate for conversion to tissue HUFAs. The ethnic food combinations for Greenland, Japanese, Mediterranean, and American populations give proportions of omega-6 isomers in the body long-chain acids near 30%, 50% 60% and 80%, respectively. It is of interest that these values mimic clinical outcomes associated with cardiovascular mortalities ranging from 20 to 50 to 90 to 200 per 100 000, respectively. Therapeutic treatment to cut excessive omega-6 eicosanoid signalling has involved billions of dollars being spent to develop and market new pharmaceutical agents while a preventive nutrition approach to cut excessive omega-6 eicosanoid signalling has yet to be applied systematically in dietetics, clinical nutrition and public health. Voluntary choices of food combinations can produce proportions of omega-6 HUFAs and of omega-3 plus omega-6 HUFAs in the total body ranging from 30% to 90%, respectively. Adverse effects of excessive omega-6 eicosanoid signalling can be lowered by two interdependent dietary changes: first, reduce the daily intake of foods overly rich in the precursors of 20:4n-6 acid; and second, simultaneously increase the omega-3 PUFAs in the diet to competitively inhibit the conversion of LA into tissue omega-6 HUFAs. An inter active computer software application has been developed to combine the complex biomedical information on competitive interactions among essential fats and eicosanoids, and to interpret and display the finding in terms of multiple daily food choices understandable by the general public. (C) 2001 The European Society of Cardiology. C1 NIAAA, NIH, Bethesda, MD 20892 USA. RP Lands, WEM (reprint author), NIAAA, NIH, 6000 Execut Blvd,Suite 400, Bethesda, MD 20892 USA. NR 30 TC 2 Z9 2 U1 1 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD JUN PY 2001 VL 3 IS D BP D22 EP D25 DI 10.1016/S1520-765X(01)90114-2 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 491JR UT WOS:000172105700004 ER PT J AU You, WC Chang, YS Heinrich, J Ma, JL Liu, WD Zhang, L Brown, LM Yang, CS Gail, MH Fraumeni, JF Xu, GW AF You, WC Chang, YS Heinrich, J Ma, JL Liu, WD Zhang, L Brown, LM Yang, CS Gail, MH Fraumeni, JF Xu, GW TI An intervention trial to inhibit the progression of precancerous gastric lesions: compliance, serum micronutrients and S-allyl cysteine levels, and toxicity SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE intervention trial; precancerous gastric lesions; compliance; toxicity ID ALPHA-TOCOPHEROL; RETINOL; CHINA AB Gastric cancer is the second most frequent cause of death from cancer in the world and the leading cause of death from cancer in China, In September 1995, we launched a randomized multi-intervention trial to inhibit the progression of precancerous gastric lesions in Linqu County, Shandong Province, an area of China with one of the world's highest rates of gastric cancer. Treatment compliance was measured by pill counts and quarterly serum concentrations of vitamin C, vitamin E and S-allyl cysteine, In 1999, toxicity information was collected from each trial participant to evaluate treatment-related side-effects during the trial, Compliance rates were 93% and 92.9% for 39 months of treatment with the vitamins/mineral and garlic preparation, respectively. The means for serum concentrations of vitamins C and E were 7.2 mug/ml and 1695 mug/dl among subjects in the active treatment groups compared with 3.1 mug/ml and 752 mug/dl among subjects in the placebo treatment group, respectively. No significant differences in side-effects were observed between the placebo treatment group and the vitamins/mineral and garlic preparation treatment groups during the 39-month trial period. (C) 2001 Lippincott Williams & Wilkins. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Peking Univ, Beijing Inst Canc Res, Beijing 100034, Peoples R China. Peking Univ, Sch Oncol, Beijing 100034, Peoples R China. Westat Corp, Rockville, MD 20850 USA. Linqu Publ Hlth Bur, Linqu 262600, Shandong, Peoples R China. Rutgers State Univ, Piscataway, NJ 08855 USA. RP You, WC (reprint author), NCI, Div Canc Epidemiol & Genet, EPS Room 8030, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CP-71103] NR 16 TC 37 Z9 39 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD JUN PY 2001 VL 10 IS 3 BP 257 EP 263 DI 10.1097/00008469-200106000-00009 PG 7 WC Oncology SC Oncology GA 442TT UT WOS:000169301600009 PM 11432713 ER PT J AU Semba, RD Kumwenda, N Taha, TE Mtimavalye, L Broadhead, R Garrett, E Miotti, PG Chiphangwi, JD AF Semba, RD Kumwenda, N Taha, TE Mtimavalye, L Broadhead, R Garrett, E Miotti, PG Chiphangwi, JD TI Impact of vitamin A supplementation on anaemia and plasma erythropoietin concentrations in pregnant women: a controlled clinical trial SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE anaemia; erythropoietin; iron deficiency; Malawi; pregnancy; vitamin A ID IRON; CHILDREN; ANEMIA; RECEPTOR; CELLS; ZINC AB Introduction: Although studies suggest that vitamin A or its metabolites influence the synthesis of erythropoietin in vitro and in animal models, it is unclear whether vitamin A supplementation increases plasma erythropoietin concentrations in humans. Objective: To determine whether daily vitamin A supplementation increases plasma erythropoietin concentrations in pregnant women with a high prevalence of anaemia. Methods: A randomized, double-blind, controlled clinical trial was conducted to examine the effect of daily vitamin A (3000 tg retinol equivalent), iron (30 mg), and folate (400 mug) versus iron (30 mg) and folate (400 tg) (control) on haemoglobin and plasma erythropoietin concentrations in 203 pregnant women in Malawi, Africa. Results: Mean gestational age at enrollment was 23 wk, at which time 50% of the women were anaemic (haemoglobin < 110 g/L). Mean ( SEM) change in haemoglobin from enrollment to 38 wk was 4.7 +/- 1.6 g/L (p = 0.003) and 7.3 +/- 2.3 g/L (p = 0.003) in the vitamin A and control groups, respectively. Mean change in plasma erythropoietin concentrations from enrollment to 38 wk was 2.39 +/-5.00 (p=0.63) and -2.87 +/-3.92 IU/L (p = 0.46) in the vitamin A and controls groups, respectively. There were no significant differences between vitamin A and control groups in the slope of the regression line between log(10) erythropoietin and haemoglobin at enrollment or 38 wk, and between enrollment and follow-up within either group. Conclusions: Vitamin A supplementation does not appear to increase haemoglobin and plasma erythropoietin concentrations among pregnant women with a high prevalence of anaemia in Malawi. C1 Johns Hopkins Univ, Sch Med & Hyg & Publ Hlth, Dept Ophthalmol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med & Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med & Hyg & Publ Hlth, Ctr Human Nutr, Baltimore, MD USA. NIAID, Bethesda, MD 20892 USA. Univ Malawi, Coll Med, Dept Obstet, Blantyre, Malawi. Univ Malawi, Coll Med, Dept Gynaecol, Blantyre, Malawi. Univ Malawi, Coll Med, Dept Paediat, Blantyre, Malawi. Univ Malawi, Coll Med, Dept Child Hlth, Blantyre, Malawi. RP Semba, RD (reprint author), 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. FU NIAID NIH HHS [N01-AI-35173-117]; NICHD NIH HHS [HD32247, HD30042] NR 26 TC 31 Z9 33 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JUN PY 2001 VL 66 IS 6 BP 389 EP 395 DI 10.1034/j.1600-0609.2001.066006389.x PG 7 WC Hematology SC Hematology GA 458LW UT WOS:000170196700005 PM 11488938 ER PT J AU Anisimov, SV Lakatta, EG Boheler, KR AF Anisimov, SV Lakatta, EG Boheler, KR TI Discovering altered genomic expression patterns in heart: transcriptome determination by serial analysis of gene expression SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Review DE SAGE; heart failure; rodent; human; transcriptome ID GENETICALLY-ENGINEERED ANIMALS; MOLECULAR PHENOTYPE; SAGE; GROWTH; CANCER; PROFILES; MOUSE; HYPERTROPHY; MEDICINE; RESOURCE AB The development of cardiovascular diseases such as heart failure involve functional changes that are beneficial short-term, but may be fatal long-term. Current therapeutic approaches are tailored to limit progression of a disease and to maintain quality of life. At a molecular level, these disease processes involve quantitative and qualitative changes in gene expression. Although some changes in mRNA abundance may not have direct protein correlates, analysis of all the mRNAs present in a cell population (the cells transcriptome) has become a focal point of genomic research. The aim is to provide information about the dynamics of total genome expression in response to environmental changes and point to candidate genes responsible for the cascade of events that result in a disease state. One way of performing these analyses utilizes the technique of Serial Analysis of Gene Expression (SAGE). This method evaluates thousands of expressed transcripts both quantitatively and qualitatively in a single assay. In the first of two reviews on transcriptome analysis, we describe the current state of genomic research for determination of the transcriptome by Serial Analysis of Gene Expression, present the first limited SAGE analysis of rodent heart gene expression, and discuss how results generated with this approach can be applied to the study and treatment of cardiovascular diseases. Published by Elsevier Science Ireland Ltd on behalf of European Society of Cardiology. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Boheler, KR (reprint author), NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 46 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD JUN PY 2001 VL 3 IS 3 BP 271 EP 281 DI 10.1016/S1388-9842(01)00131-3 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 440TE UT WOS:000169189700002 PM 11377997 ER PT J AU Dina, OA Aley, KO Isenberg, W Messing, RO Levine, JD AF Dina, OA Aley, KO Isenberg, W Messing, RO Levine, JD TI Sex hormones regulate the contribution of PKC epsilon and PKA signalling in inflammatory pain in the rat SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE cutaneous hyperalgesia; epinephrine; gender; oestrogen; primary afferent nociceptors ID PROTEIN-KINASE-C; BETA-ADRENERGIC-RECEPTOR; NERVE GROWTH-FACTOR; PRIMARY SENSORY NEURONS; FEMALE RATS; GENDER DIFFERENCES; NOCICEPTOR SENSITIZATION; NEUROPATHIC PAIN; PERSISTENT PAIN; SWIM ANALGESIA AB We have evaluated the contribution of differences in second messenger signalling to sex differences in inflammatory pain and its control by sex hormones. In normal male but not female rats, epinephrine-induced mechanical hyperalgesia was antagonized by inhibitors of protein kinase C epsilon (PKC epsilon), protein kinase A (PKA) and nitric oxide synthetase (NOS). Similarly, in PKC epsilon knockout mice, a contribution of PKC epsilon to epinephrine-dependent mechanical hyperalgesia occurred in males only. In contrast, hyperalgesia induced by prostaglandin E-2, in both females and males, was dependent on PKA and NO. In both sexes, inhibitors of mitogen-activated protein kinase/extracellular-signal related kinase kinase (MEK) inhibited epinephrine hyperalgesia. In gonadectomized females, the second messenger contributions to epinephrine hyperalgesia demonstrated the pattern seen in males. Administration of oestrogen to gonadectomized females fully reconstituted the phenotype of the normal female. These data demonstrate gender differences in PKC epsilon, PKA and NO signalling in epinephrine-induced hyperalgesia which are oestrogen dependent and appear to be exerted at the level of the beta -adrenergic receptor or the G-protein to which it is coupled. C1 Univ Calif San Francisco, NIH, Pain Ctr, Program Biomed Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Ernest Gallo Clin & Res Ctr, Emeryville, CA 94608 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH, Pain Ctr, Program Biomed Sci, C522 Box 0440,521 Parnassus Ave, San Francisco, CA 94143 USA. RI Messing, Robert/D-3642-2015 OI Messing, Robert/0000-0002-5345-4431 FU NINDS NIH HHS [NS 21647]; NINR NIH HHS [NR 04880] NR 60 TC 70 Z9 70 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUN PY 2001 VL 13 IS 12 BP 2227 EP 2233 DI 10.1046/j.0953-816x.2001.01614.x PG 7 WC Neurosciences SC Neurosciences & Neurology GA 458EJ UT WOS:000170180000005 PM 11454025 ER PT J AU Zelazny, E Li, BL Anagnostopoulos, AM Coleman, A Perkins, AS AF Zelazny, E Li, BL Anagnostopoulos, AM Coleman, A Perkins, AS TI Cooperating oncogenic events in murine mammary tumorigenesis: Assessment of ErbB2, mutant p53, and mouse mammary tumor virus SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article ID HUMAN-BREAST-CANCER; WILD-TYPE P53; TRANSGENIC MICE; FUNCTION MUTATIONS; NEU PROTOONCOGENE; CELLS; GENE; EXPRESSION; PROTEIN; IMMORTALIZATION AB We are investigating cooperating genetic events in the genesis of breast cancer, using the mouse as a model system. We have shown cooperativity between a mutant allele of p53 (p53-172H) and overexpressed ErbB2 in mammary tumorigenesis in transgenic mice. We are now performing additional crosses to further examine oncogene cooperativity with ErbB2 and p53-172H. We attempted to test the dominant oncogenic potential of p53-172H in an in I ha setting by crossing the p53-172H transgene together with ErbB2 onto either a p53(-/-) or a p53(+/-) background. We show that the p53-172H allele and the heterozygous p53 genotype have an identical impact on the latency of ErB2-induced mammary tumors; there was no evidence of additivity or synergy between p53-172H and the p53(+/-) genotype. On the p53-/- background, we obtained no mammary tumors due to the early onset of lymphomas and sarcomas, thus precluding assessment of the effect of the p53-172H transgene on mammary tumorigenesis in a p53-null background. Thus, in this in vivo model for breast cancer, we failed to find evidence that p53-172H can function as a dominant oncogenic allele, but rather found support for its being essentially equivalent to a null allele in its impact on ErbB2-induced mammary tumorigenesis. By comparative genome analysis, we showed that a common feature of turners arising in ErbB2/mutant p53 mice (p53-null allele with or without p53-172H) is a loss of chromosome 4, a feature of many epithelial tumors in mice and one that is consistent with a role for loss of INK4a/ARF in such tumors. We also attempted to accelerate ErbB2-induced mammary tumorigenesis with mouse mammary tumor virus (MMTV) proviral tagging mutagenesis, but we were surprised to find that mice with MMTV alone had the same latency as mice with both MMTV and ErbB2, indicating no cooperativity between ErbB2 and MMTV. This may have been due to the mixed C3H/HeN x FVB strain background used in this cross. (C) 2001 Academic Press. C1 Yale Univ, Dept Pathol, New Haven, CT 06520 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Perkins, AS (reprint author), Yale Univ, Dept Pathol, 310 Cedar St, New Haven, CT 06520 USA. NR 43 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD JUN PY 2001 VL 70 IS 3 BP 183 EP 193 DI 10.1006/exmp.2001.2357 PG 11 WC Pathology SC Pathology GA 448GR UT WOS:000169619600003 PM 11417997 ER PT J AU Ghanayem, BI Long, PH Ward, SM Chanas, B Nyska, M Nyska, A AF Ghanayem, BI Long, PH Ward, SM Chanas, B Nyska, M Nyska, A TI Hemolytic anemia, thrombosis, and infarction in male and female F344 rats following gavage exposure to 2-butoxyethanol SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE rats; 2-butoxyethanol; hemolysis; thrombosis; tissue infarction; bone; teeth ID INHALATION EXPOSURE; TOXICITY; ALCOHOL AB 2-butoxyethanol (BE; ethylene glycol monobutyl ether) is used extensively in the manufacture of a wide range of domestic and industrial products which may result in human exposure and toxicity. BE causes severe hemolytic anemia in male and female rats and mice. In a recent report, female F344 rats exposed to 500 ppm BE by inhalation and sacrificed moribund on day 4 of treatment exhibited disseminated thrombosis associated with infarction in several organs. In contrast, no such lesions were observed in male rats similarly exposed to BE. Additional studies were therefore undertaken to compare the effects of BE in rats of both sexes. Rats received 250 mg BE/kg/day by gavage for 1, 2 or 3 days and were sacrificed 24 or 48 hr after the last dose. Control rats received 5 ml/kg water. Progressive time-dependent hemolytic anemia-macrocytic, hypochromic, and regenerative-was observed in both sexes of rats exposed to BE. Additionally, BE caused significant morphological changes in erythrocytes, first observed 24 hr after a single dose, including stomatocytosis, macrocytosis with moderate rouleaux formation, and spherocytosis. These morphological changes became progressively more severe as BE dosing continued and included the occasional occurrence of schistocytes and ghost cells. rouleaux formation in rats of both sexes, and an increased number of red blood cells with micronuclei in female rats. Overall, the progression of hemolytic anemia and morphological changes as a function of the number of days of exposure varied with gender and suggested a faster onset of hemolysis in female rats. The range of BE-related histopathological changes noted in both sexes was comparable: however, while these lesions were observed in female rats following a single dose, similar effects were first observed in males after 3 consecutive days of exposure to BE. Pathological changes involved disseminated thrombosis in the lungs, nasal submucosa. eyes, liver, heart, bones and teeth, with evidence of infarction in the heart, eyes, teeth and bones. Hemoglobinuric nephrosis and splenic extramedullary hematopoiesis were also noted. An apparent correlation between the severity of hemolytic anemia and subsequent disseminated thrombosis in BE-treated rats is proposed. Thrombosis map be related to intravascular hemolysis. which could be triggered by procoagulant release and/or alterations in erythrocyte morphology, as well as increased rigidity. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Pathol Associates Int, W Chester, PA USA. Hebrew Univ Jerusalem, Hadassah Univ Hosp, Dept Orthoped, Jerusalem, Israel. RP Ghanayem, BI (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 21 TC 17 Z9 18 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD JUN PY 2001 VL 53 IS 2-3 BP 97 EP 105 DI 10.1078/0940-2993-00177 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 455QU UT WOS:000170039000001 PM 11484844 ER PT J AU Gregersen, R Christensen, T Lehrmann, E Diemer, NH Finsen, B AF Gregersen, R Christensen, T Lehrmann, E Diemer, NH Finsen, B TI Focal cerebral ischemia induces increased myelin basic protein and growth-associated protein-43 gene transcription in peri-infarct areas in the rat brain SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE oligodendrocyte; myelin oligodendrocyte glycoprotein; axonal sprouting; regeneration; myelination; rat ID CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA LEVELS; MULTIPLE-SCLEROSIS; OLIGODENDROCYTE PROLIFERATION; SYNAPTIC PLASTICITY; ARTERY OCCLUSION; EXPRESSION; DEMYELINATION; REMYELINATION; GLYCOPROTEIN AB Although oligodendrocytes are vulnerable to focal cerebral ischemia, remyelination of denuded or regenerating axons in the peri-infarct area has been observed in the central nervous system. We studied the expression of myelin basic protein (MBP), a major component of central nervous system myelin, in peri-infarct areas in adult rat brain after transient middle cerebral artery occlusion (MCAO) and correlated it to the expression of the growth-associated protein-43 (GAP-43), a marker for axonal regeneration and sprouting, using nonradioactive in situ hybridization techniques. Within the infarct, MBP messenger RNA (mRNA) had disappeared by 24 h, whereas myelin protein, identified by MBP and myelin oligodendrocyte glycoprotein (MOG) immunohistochemistry, appeared structurally intact until day 3. Peri-infarct oligodendrocytes increased their expression of MBP mRNA from 24 h to maximal levels at day 7, corresponding to the appearance of process-bearing MBP and occasional MOG-immunoreactive oligodendrocytes in parallel sections. Quantitative analysis revealed significant increases in the density of oligodendrocytes (up to 7.6-fold) and in the level of MBP mRNA expressed by individual cells. Parallel sections showed that increased expression of GAP-43 mRNA in neurons was concomitant to MBP mRNA upregulation in oligodendrocytes. While the mechanisms regulating oligodendrocyte survival and myelination signals are not clear at this point, axonal sprouting could putatively serve as a stimulus for the upregulation of oligodendrocyte cell numbers, differentiation state, and/or active myelination in the peri-infarct areas. C1 Univ So Denmark, Odense Univ, Dept Anat & Neurobiol, Inst Med Biol, Odense 5000, Denmark. Univ Copenhagen, Inst Mol Pathol, Neuropathol Lab, Copenhagen 2100, Denmark. NIDA, IRP, Baltimore, MD 21224 USA. RP Gregersen, R (reprint author), Univ So Denmark, Odense Univ, Dept Anat & Neurobiol, Inst Med Biol, Winslowparken 21, Odense 5000, Denmark. NR 40 TC 56 Z9 65 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUN PY 2001 VL 138 IS 3 BP 384 EP 392 DI 10.1007/s002210100715 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 442UH UT WOS:000169303000012 PM 11460777 ER PT J AU Hanakawa, T Ikeda, A Sadato, N Okada, T Fukuyama, H Nagamine, T Honda, M Sawamoto, N Yazawa, S Kunieda, T Ohara, S Taki, W Hashimoto, N Yonekura, Y Konishi, J Shibasaki, H AF Hanakawa, T Ikeda, A Sadato, N Okada, T Fukuyama, H Nagamine, T Honda, M Sawamoto, N Yazawa, S Kunieda, T Ohara, S Taki, W Hashimoto, N Yonekura, Y Konishi, J Shibasaki, H TI Functional mapping of human medial frontal motor areas - The combined use of functional magnetic resonance imaging and cortical stimulation SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE epilepsy; brain mapping; supplementary motor areas; somatotopy; mental calculations; human ID ELECTRICAL-STIMULATION; SENSORY STIMULATION; NEURONAL-ACTIVITY; MACAQUE MONKEY; CORTEX; ACTIVATION; ORGANIZATION; HEMISPHERE; MOVEMENT; PET AB Two functional brain-mapping techniques, functional magnetic resonance imaging (fMRI) and cortical stimulation by chronically implanted subdural electrodes, were used in combination for presurgical evaluation of three patients with intractable, partial motor seizures. Brain mapping was focused on characterizing motor-related areas in the medial frontal cortex, where all patients had organic lesions. Behavioral tasks for fMRI involved simple finger and foot movements in all patients and mental calculations in one of them. These tasks allowed us to discriminate several medial frontal motor areas: the presupplementary motor areas (pre-SMA), the somatotopically organized SMA proper, and the foot representation of the primary motor cortex. All patients subsequently underwent cortical stimulation through subdural electrodes placed onto the medial hemispheric wall. In each patient, the cortical stimulation map was mostly consistent with that patient's brain map by fMRI, By integrating different lines of information, the combined fMRI and cortical stimulation map will contribute not only to safe and effective surgery but also to further understanding of human functional neuro-anatomy. C1 Kyoto Univ, Grad Sch Med, Dept Brain Pathophysiol, Human Brain Res Ctr, Kyoto 6068507, Japan. Kyoto Univ, Grad Sch Med, Dept Nucl Med, Kyoto 6068507, Japan. Kyoto Univ, Grad Sch Med, Dept Neurosurg, Kyoto 6068507, Japan. Fukui Med Univ, Biomed Imaging Res Ctr, Fukui 9101193, Japan. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Physiol Sci, Lab Cerebral Integrat, Okazaki, Aichi 4448585, Japan. RP Shibasaki, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Brain Pathophysiol, Human Brain Res Ctr, Kyoto 6068507, Japan. OI Ikeda, Akio/0000-0002-0790-2598 NR 35 TC 35 Z9 35 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUN PY 2001 VL 138 IS 4 BP 403 EP 409 DI 10.1007/s002210100727 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 442UK UT WOS:000169303200001 PM 11465737 ER PT J AU Poulaki, V Mitsiades, N Mastorakos, G Caspi, RR Chrousos, GP Bouzas, E AF Poulaki, V Mitsiades, N Mastorakos, G Caspi, RR Chrousos, GP Bouzas, E TI Fas/Fas Ligand-associated apoptosis in experimental autoimmune uveoretinitis in rodents: Role of proinflammatory corticotropin-releasing hormone SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE apoptosis; Fas Ligand; Fas; autoimmune uveoretinitis; corticotropin-releasing hormone ID HUMAN FETAL MEMBRANES; FAS LIGAND; RECEPTOR ANTAGONIST; MEDIATED APOPTOSIS; CD95 LIGAND; EXPRESSION; MECHANISM; CELLS; ANTALARMIN; UVEITIS AB We have previously shown that corticotropin-releasing hormone plays an important proinflammatory role in the induction of experimental autoimmune uveoretinitis. In this study, we examined the role of apoptosis in the destruction of the retina during experimental autoimmune uveoretinitis, and the role of corticotropin-releasing hormone as a local regulator of Fas and Fas Ligand expression in this condition. We evaluated apoptosis by the terminal deoxynucleotidyl transferase dUTP nick end labeling method and Fas and Fas Ligand presence by immunohistochemistry. We examined formalin-fixed, paraffin-embedded eye sections from female Lewis rats or B10.A mice immunized with the major pathogenetic epitope (R16 peptide) of the interphotoreceptor retinoid-binding protein. Female B10.A mice similarly immunized were treated with intraperitoneal injections of the rabbit anti-corticotropin-releasing hormone antibody TS-2 or nonimmune rabbit serum. The percentage of retinal cells undergoing apoptosis and the expression of Fas and Fas Ligand were increased in inflamed retinas in immunized Lewis rats and B10.A mice, compared to controls, Retinas from immunized B10.A mice treated with anti-corticotropin-releasing hormone antibody showed significantly lower apoptosis and Fas and Fas Ligand expression than placebo-treated animals. In conclusion, retinal cells in experimental autoimmune uveoretinitis undergo apoptosis associated with concurrent upregulation of Fas and Fas Ligand. The local presence of corticotropin-releasing hormone appears to be of pivotal importance in this process. C1 Evgenidion Hosp, Natl Canc Inst, Pathol Lab, Natl Inst Hlth, Athens, Greece. Evgenidion Hosp, Endocrine Unit, Athens, Greece. Red Cross Hosp, Natl Eye Inst, Immunol Lab, Natl Inst Hlth, Athens, Greece. Red Cross Hosp, Natl Inst Child Hlth & Human Dev, Pediat & Reprod Endocrinol Branch, Natl Inst Hlth, Athens, Greece. Red Cross Hosp, Dept Ophthalmol, Athens, Greece. RP Mitsiades, N (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Mayer Bldg,Room M557,44 Binney St, Boston, MA 02115 USA. OI Caspi, Rachel/0000-0002-7140-7671 NR 23 TC 17 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUN PY 2001 VL 72 IS 6 BP 623 EP 629 DI 10.1006/exer.2001.0992 PG 7 WC Ophthalmology SC Ophthalmology GA 442RK UT WOS:000169298600002 PM 11384150 ER PT J AU Byrd, JC Shinn, C Willis, CR Flinn, IW Lehman, T Suasville, E Lucas, D Gerver, MR AF Byrd, JC Shinn, C Willis, CR Flinn, IW Lehman, T Suasville, E Lucas, D Gerver, MR TI UCN-01 induces cytotoxicity toward human CLL cells through a p53-independent mechanism SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; P53 GENE MUTATION; DRUG-RESISTANCE; APOPTOSIS; BCL-2; ACTIVATION; EXPRESSION; KINASE; CHLORAMBUCIL; FLUDARABINE AB Objectives. UCN-01, a novel protein kinase C inhibitor, is currently being tested in phase I clinical trials after being noted to induce apoptosis in lymphoid cell lines, We sought to study the in vitro activity of UCN-01 against human chronic lymphocytic leukemia (CLL) cells and potential mechanisms of action for inducing this cytotoxicity. Methods. Detailed in vitro studies were performed from turner cells derived from patients with CLL cells following attainment of written informed consent. Results. The 50% loss of viability (LC50) in mononuclear cells from CLL patients (n = 10) following exposure to UCN-01 for 4 days was 0.4 muM (95 % CI +/- 0.21; range 0.09-1.16). Loss of viability in human CLL cells correlated with early induction of apoptosis, Exposure of CLL cells to 0.4 and 5.0 muM Of UCN-01 resulted in decreased expression of p53 protein, We therefore investigated the dependence of UCN-01 on intact p53 by exposing splenocytes from wildtype (p53(+/+)) and p53 null (p53(-/-)) mice, which demonstrated no preferential cytotoxicity when compared to the marked differential induced by F-Ara-A and radiation. Conclusion. UCN-01 has significant in vitro activity against human CLL cells that appears to occur independent of p53 status, While demonstration of in vitro cytotoxicity does not establish in vivo efficacy, the findings described support the early introduction of UCN-01 into clinical trials for patients with B-CLL, (C) 2001 International Society for Experimental Hematology, Published by Elsevier Science Inc. C1 Ohio State Univ, Div Hematol Oncol, Dept Internal Med, Columbus, OH 43210 USA. NCI, Biol Chem Lab, Div Basic Sci, Bethesda, MD 20892 USA. BioServ Biotechnol Ltd, Laurel, MD USA. Johns Hopkins Oncol Ctr, Div Hematol Malignancies, Baltimore, MD USA. Walter Reed Army Med Ctr, Div Hematol Oncol, Washington, DC 20307 USA. RP Byrd, JC (reprint author), Ohio State Univ, Div Hematol Oncol, Dept Internal Med, B302 Sterling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. RI Lucas, David/E-3555-2011 FU NCI NIH HHS [P01 CA81534-02] NR 29 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUN PY 2001 VL 29 IS 6 BP 703 EP 708 DI 10.1016/S0301-472X(01)00649-X PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 440KR UT WOS:000169174900006 PM 11378265 ER PT J AU Giri, N Kaushiva, A Wu, T Sellers, SE Tisdale, JF AF Giri, N Kaushiva, A Wu, T Sellers, SE Tisdale, JF TI The effects of SCF/G-CSF prestimulation on radiation sensitivity and engraftment in nonmyeloablated murine hosts SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; STEM-CELL FACTOR; CHRONIC GRANULOMATOUS-DISEASE; RHESUS PERIPHERAL-BLOOD; LONG-TERM ENGRAFTMENT; BONE-MARROW; REPOPULATING CELLS; GENE-TRANSFER; HEMATOPOIETIC PROGENITOR; NONHUMAN-PRIMATES AB Objective. Previous studies have shown improved engraftment in a murine model when granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) were administered for 5 days prior to irradiation, with significant levels of engraftment in the growth factor-preconditioned group even at very low radiation doses. We sought to explore the mechanisms behind this effect, Methods. The radiation sensitivity of mice with or without 5 days of prestimulation with G-CSF (200 mug/kg/d) and SCF (50 mug/kg/d) was compared. To further evaluate whether growth factor prestimulation enhances engraftment by mobilization of hematopoietic progenitors into peripheral blood, thus creating less endogenous competition within the marrow compartment, female mice were pretreated with 5 days of G-CSF/SCF or control diluent, Engraftment of 40 X 10(6) peripheral blood stem cells (PBSCs) harvested from G-CSF/SCF-mobilized male mice was compared in the two recipient groups. Results, There was no difference in survival between the pretreated and control mice at the radiation doses tested. Additionally, there was no significant difference in the recovery of blood counts, bone marrow cellularity, colony-forming unit (CFU) content, or stem cell numbers assessed 4 months later in a competitive repopulation model. Engraftment levels of male cells did not differ between G-CSF/SCF-pretreated and control recipients, and could be detected in 30% of recipients at 20-24 weeks (4/12 in each group) at overall levels of 0.1-1%, Conclusions. The enhanced engraftment in cytokine pretreated recipients is unlikely to be due to increased endogenous stem-cell killing or to the creation of endogenous marrow "space" by egress of endogenous stem cells after cytokine prestimulation. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, 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 28 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUN PY 2001 VL 29 IS 6 BP 779 EP 785 DI 10.1016/S0301-472X(01)00646-4 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 440KR UT WOS:000169174900015 PM 11378274 ER PT J AU Guidetti, P Charles, V Chen, EY Reddy, PH Kordower, JH Whetsell, WO Schwarcz, R Tagle, DA AF Guidetti, P Charles, V Chen, EY Reddy, PH Kordower, JH Whetsell, WO Schwarcz, R Tagle, DA TI Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production SO EXPERIMENTAL NEUROLOGY LA English DT Article DE mitochondrial; Huntington's; Golgi; neurodegeneration; transgenic; mouse; dendrites; striatum ID CEREBRAL GLUCOSE-METABOLISM; SELECTIVE NEURONAL LOSS; LENGTH HD CDNA; NEURODEGENERATIVE DISEASES; EXCITOTOXIC LESIONS; RAT-BRAIN; GLUTAMATE EXCITOTOXICITY; 3-NITROPROPIONIC ACID; WIDESPREAD EXPRESSION; H-1-NMR SPECTROSCOPY AB Mitochondrial defects, which occur in the brain of late-stage Huntington's disease (HD) patients, have been proposed to underlie the selective neuronal loss in the disease. To shed light on the possible role of mitochondrial energy impairment in the early phases of HD pathophysiology, we carried out Golgi impregnation and quantitative histochemical/biochemical studies in HD full-length cDNA transgenic mice that were symptomatic but had not developed to a stage in which neuronal loss could be documented. Golgi staining showed morphologic abnormalities that included a significant decrease in the number of dendritic spines and a thickening of proximal dendrites in striatal and cortical nenrons, In contrast, measurements of mitochondrial electron transport Complexes I-IV did not reveal changes in the striatum and cerebral cortex in these mice. Examination of the neostriatum and cerebral cortex in human presymptomatic and pathological Grade I HD cases also showed no change in the activity of mitochondrial Complexes I-IV. These data suggest that dendritic alterations precede irreversible cell loss in HD, and that mitochondrial energy impairment is a consequence, rather than a cause, of early neuropathological changes. (C) 2001 Academic Press. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA. Rush Med Sch, Res Ctr Brain Repair, Chicago, IL 60612 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA. RP Tagle, DA (reprint author), Bldg 49,Room 3A26,49 Convent Dr, Bethesda, MD 20892 USA. FU NIMH NIH HHS [MH/NS 31862]; NINDS NIH HHS [NS 28236] NR 77 TC 118 Z9 121 U1 0 U2 4 PU ACADEMIC PRESS INC 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 JUN PY 2001 VL 169 IS 2 BP 340 EP 350 DI 10.1006/exnr.2000.7626 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 440TF UT WOS:000169189800011 PM 11358447 ER PT J AU Jaffe, ES AF Jaffe, ES TI The pathology of NK-cell lymphomas and leukemias SO EXPERIMENTAL ONCOLOGY LA English DT Review DE NK-cell lymphomas; extranodal NK/T-cell lymphoma; aggressive NK-cell leukemia/lymphoma ID EPSTEIN-BARR-VIRUS; ANGIOCENTRIC IMMUNOPROLIFERATIVE LESIONS; NATURAL-KILLER; T-CELL; LYMPHOBLASTIC LYMPHOMA; LYMPHOPROLIFERATIVE DISEASE; HEMOPHAGOCYTIC SYNDROME; MALIGNANT-LYMPHOMA; NASAL LYMPHOMAS; VIRAL-DNA AB Cytotoxic T-cell and NK-cell lymphomas are a group of closely related neoplasms with many clinical, histologic, and immunophenotypic features in common. Most of them are extranodal in origin containing areas of necrosis or apoptotic cells. Several distinct entities have been delineated within this group of lymphoid neoplasms. Extranodal NK/T-cell lymphoma, nasal type is EBV-associated and characterized by aggressive clinical course, high incidence of p53 abnormalities, and high levels of MDR expression. Aggressive NK-cell leukemia/lymphoma has been regarded as a separate nosologic entity characterized by generalized lymphadenopathy, hepatosplenomegaly, the presence of atypical lymphocytes with large azurophilic cytoplasmic granules in the peripheral blood. Blastic or blastoid NK-cell leukemia/lymphoma with CD3(-), CD56(+) medium-sized cells has been also described. C1 NCI, Hematopathol Sect, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Bethesda, MD 20892 USA. NR 43 TC 0 Z9 0 U1 1 U2 1 PU INST EXP PATHOL ONCOL RADIOBIOL PI KIEV PA AKAD NAUK UKR SSR, UL VASILKOVSKAYA 45, KIEV 252022, UKRAINE SN 0204-3564 J9 EXP ONCOL JI Exp. Oncol. PD JUN PY 2001 VL 23 IS 2 BP 97 EP 100 PG 4 WC Oncology SC Oncology GA 464RB UT WOS:000170544600003 ER PT J AU Illei, GG Czirjak, L AF Illei, GG Czirjak, L TI Novel approaches in the treatment of lupus nephritis SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE biological products; clinical trials; lupus nephritis; mycophenolate mofetil; systemic lupus erythematosus; therapy ID INTRAVENOUS IMMUNOGLOBULIN TREATMENT; MYCOPHENOLATE-MOFETIL THERAPY; ALLEVIATES DISEASE SEVERITY; VARIABLE REGION GENES; CONTROLLED TRIAL; AUTOIMMUNE-DISEASE; MURINE LUPUS; PULSE CYCLOPHOSPHAMIDE; CD40 LIGAND; B-CELL AB In systemic lupus erythematosus hyperactive helper T-cells drive polyclonal B-cell activation and secretion of pathogenic auto-antibodies. The autoantibodies form immune complexes with their respective auto-antigens, which in turn deposit in sites such as the kidney and initiate a destructive inflammatory reaction. Lupus nephritis can be managed successfully in the majority of cases; however, the most widely used immunosuppressive therapies, notably corticosteroids and cyclophosphamide are non-specific and are associated with substantial toxicities. Novel treatments for lupus nephritis have to be at least as effective and less toxic than existing therapies. The ultimate aim is to develop treatments that target specific steps in the disease process. Novel therapeutic strategies in the short-term more likely will focus on refining regimens of drugs that are already in use (mycophenolate mofetil, adenosine analogues) and combinations of existing chemotherapeutic agents, as well as attempts to achieve immunological reconstitution using immunoablative chemotherapy with or without haematopoietic stem cell rescue. Several new agents targeting specific steps in the pathogenesis of lupus are in various phases of clinical development. Interrupting the interactions between T-lymphocytes and other cells by blocking co-stimulatory molecules, such as CD40 ligand or CTLA4-Ig, may interfere with the early steps of pathogenesis. Blocking IL-10 may decrease auto-antibody production and help normalise T-cell function. Treating patients with DNase or interfering with the complement cascade by blocking C5, or neutralising pathogenic antibodies by administering specific binding peptides or inducing specific anti-idiotype antibodies may prevent immune complex formation and/or deposition. C1 NIAMSD, Off Clin Director, NIH, Bethesda, MD 20892 USA. Univ Pecs, Clin Immunol Unit, Nephrol Ctr, Pecs, Hungary. Univ Pecs, Clin Immunol Unit, Dept Internal Med 2, Pecs, Hungary. RP Illei, GG (reprint author), NIAMSD, Off Clin Director, NIH, 9000 Rockville Pike,Bldg 10,Rm 9S205, Bethesda, MD 20892 USA. NR 112 TC 5 Z9 8 U1 0 U2 1 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JUN PY 2001 VL 10 IS 6 BP 1117 EP 1130 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 438XZ UT WOS:000169080700009 PM 11772239 ER PT J AU Ponce, ML Nomizu, M Kleinman, HK AF Ponce, ML Nomizu, M Kleinman, HK TI An angiogenic laminin site and its antagonist bind through the alpha v beta 3 and alpha 5 beta 1 integrins SO FASEB JOURNAL LA English DT Article DE angiogenesis; laminin-1; bFGF; endothelium; peptides ID HUMAN-ENDOTHELIAL CELLS; TUMOR-GROWTH; SYNTHETIC PEPTIDES; ADHESION MOLECULE; ALPHA-1 CHAIN; GAMMA-1 CHAIN; IDENTIFICATION; ALPHA(V)BETA(3); RECEPTORS; PROTEIN AB Angiogenesis is important for wound healing, tumor growth, and metastasis. Endothelial cells differentiate into capillary-like structures on a laminin-1-rich matrix (Matrigel). We previously identified 20 angiogenic sites on laminin-1 (alpha1 beta1 gamma1) by screening 559 overlapping synthetic peptides. C16, the most potent gamma1 chain peptide, blocked laminin-1-mediated adhesion and was the only gamma1 chain peptide to block attachment to both collagen I and fibronectin. This suggested that C16 was acting via a receptor common to these substrates. We demonstrated that C16 is angiogenic in vivo. Affinity chromatography identified the integrins alpha5 beta1 and alphav beta3 as surface receptors. Blocking antibodies confirmed the role of these receptors in C16 adhesion. C16 does not contain an RGD sequence and, as expected, an RGD-containing peptide did not block C16 adhesion nor did C16 act via MAP kinase phosphorylation. Furthermore, we identified a C16 scrambled sequence, C16S, which antagonizes the angiogenic activity of bFGF and of C16 by binding to the same receptors. Because the laminin gamma1 chain is ubiquitous in most tissues, C16 is likely an important functional site. Since the biological activity of C16 is blocked by a scrambled peptide, C16S may serve as an anti-angiogenic therapeutic agent. C1 NIDCR, CDBRB, NIH, Bethesda, MD 20892 USA. Hokkaido Univ, Grad Sch Environm Earth Sci, Sapporo, Hokkaido 060, Japan. RP Kleinman, HK (reprint author), NIDCR, CDBRB, NIH, Bldg 30,Room 433,30 Convent Dr, Bethesda, MD 20892 USA. EM hkleinman@dir.nidcr.nih.gov NR 36 TC 57 Z9 59 U1 1 U2 5 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 JUN PY 2001 VL 15 IS 8 BP 1389 EP 1397 DI 10.1096/fj.00-0736com PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 442AF UT WOS:000169261200006 PM 11387236 ER PT J AU Azuma, Y Tan, SH Cavenagh, MM Ainsztein, AM Saitoh, H Dasso, M AF Azuma, Y Tan, SH Cavenagh, MM Ainsztein, AM Saitoh, H Dasso, M TI Expression and regulation of the mammalian SUMO-1 E1 enzyme SO FASEB JOURNAL LA English DT Article DE SUMO-1; Uba2; Aos1; Ubc9 ID UBIQUITIN-CONJUGATING ENZYME; GTPASE-ACTIVATING PROTEIN; NUCLEAR-PORE COMPLEX; YEAST; HOMOLOG; RANGAP1; DEGRADATION; KINASE; RANBP2; UBC9P AB SUMO-1 is a small ubiquitin-related protein. SUMO-1 conjugation requires enzymes with sequence and biochemical similarity to ubiquitin E1 and E2 enzymes. We have examined the expression, localization, and biochemical behavior of Aos1 and Uba2, subunits of the mammalian SUMO-1 E1 enzyme. Both of these proteins are expressed in multiple tissues and localized to the nucleus. Aos1 protein levels vary through the cell cycle. These changes in Aos1 concentration may play a role in the regulation of the SUMO-1 pathway, because they correlate with changes in the abundance of some SUMO-1-conjugated species. Biochemical analysis reveals that Aos1 and Uba2 associate with each other in a simple heterodimeric complex without other subunits, unlike the budding yeast Uba2 homologue, which apparently associates with several different proteins. Although it is possible to reconstitute SUMO-1 conjugation with purified Uba2, Aos1, and Ubc9, this reaction is significantly less efficient than conjugation observed in cellular extracts, suggesting the possibility that there may be activators of SUMO-1 conjugation in vivo that have not yet been characterized. Taken together, these observations reveal that the SUMO-1 pathway is controlled on multiple levels during the cell cycle. C1 NICHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Dasso, M (reprint author), NICHD, Mol Embryol Lab, NIH, Bldg 18,Room 106, Bethesda, MD 20892 USA. EM mdasso@helix.nih.gov RI Tan, Shyh-Han/I-7037-2013; OI Tan, Shyh-Han/0000-0001-8250-7005; Dasso, Mary/0000-0002-5410-1371 NR 26 TC 39 Z9 44 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUN PY 2001 VL 15 IS 8 BP 1825 EP + DI 10.1096/fj.00-0818fje PG 15 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 442AF UT WOS:000169261200028 PM 11481243 ER PT J AU Mandal, AK Zhang, ZJ Chou, JY Mukherjee, AB AF Mandal, AK Zhang, ZJ Chou, JY Mukherjee, AB TI Pancreatic phospholipase A(2) via its receptor regulates the expression of key enzymes of phospholipid and sphingolipid metabolism SO FASEB JOURNAL LA English DT Article DE phospholipase A(2-)receptor; signal-transduction/cyclooxygenase-2; Mg++-dependent neutral sphingomyelinase; acid ceramidase ID ACTIVATED PROTEIN-KINASE; CYCLOOXYGENASE-2 GENE-EXPRESSION; SMOOTH-MUSCLE CELLS; BINDING-SITE; TRANSCRIPTIONAL REGULATION; MOLECULAR-CLONING; ARACHIDONIC-ACID; MESANGIAL CELLS; MESSENGER-RNA; CANCER-CELLS AB Although the pancreatic secretory phospholipase A(2) (sPLA(2)IB) is considered a digestive enzyme, it has several important, nonenzymatic, receptor-mediated functions. In this study, we demonstrate that via its receptor, sPLA(2)IB stimulates the expression of cytosolic PLA(2) (cPLA(2))-, cyclooxygenase-2 (COX-2)-, Mg++-dependent neutral sphingomyelinase (NSMase)- and acid ceramidase (AC)- mRNAs in NIH 3T3 cells. Moreover, through its receptor, sPLA(2)IB also mediates the activation of cPLA(2) and p38 MAPK. We also found similar effects when the NIH 3T3 cells were treated with interleukin 1 beta (IL-beta), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF) under identical conditions. These effects are not dependent on the catalytic activity of sPLA(2)IB, as both heat- and chemically inactivated enzyme induced these effects. Although protein kinase C and p38 mitogen-activated protein kinases are critical for the sPLA(2) receptor-mediated stimulation of expression of cytosolic PLA(2) and cyclooxygenase-2 mRNAs, respectively, the activation of these kinases is not required for neutral sphingomyelinase and acid ceramidase mRNA expression. Our results, for the first time, raise the possibility that, via its receptor, sPLA(2)IB plays important roles in the regulation of both phospholipid and sphingolipid metabolism. C1 NICHHD, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Mukherjee, AB (reprint author), NICHHD, Sect Dev Genet, NIH, Bldg 10,Room 9S241, Bethesda, MD 20892 USA. EM mukherja@exchange.nih.gov NR 60 TC 17 Z9 18 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUN PY 2001 VL 15 IS 8 BP 1834 EP + DI 10.1096/fj.00-0831fje PG 15 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 442AF UT WOS:000169261200009 PM 11481246 ER PT J AU Sohrab, MH Mazid, MA Rahman, E Hasan, CM Rashid, MA AF Sohrab, MH Mazid, MA Rahman, E Hasan, CM Rashid, MA TI Antibacterial activity of Clausena heptaphylla SO FITOTERAPIA LA English DT Editorial Material DE Clausena heptaphylla; antibacterial activity; coumarins AB The antibacterial activity of different crude extracts of Clausena heptaphylla leaves as well as three purified coumarins, obtained from the cold methanol extract, is reported. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Dhaka, Fac Pharm, Phytochem Res Lab, Dhaka 1000, Bangladesh. RP Rashid, MA (reprint author), NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bldg 560,Rm 32-63B,Post Box B, Frederick, MD 21702 USA. RI Kabir, Eva Rahman/C-7218-2015 OI Kabir, Eva Rahman/0000-0001-9016-0865 NR 16 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0367-326X J9 FITOTERAPIA JI Fitoterapia PD JUN PY 2001 VL 72 IS 5 BP 547 EP 549 DI 10.1016/S0367-326X(00)00320-8 PG 3 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 457VB UT WOS:000170156600014 PM 11429251 ER PT J AU Takikawa, Y Miyoshi, H Rust, C Roberts, P Siegel, R Mandal, PK Millikan, RE Gores, GJ AF Takikawa, Y Miyoshi, H Rust, C Roberts, P Siegel, R Mandal, PK Millikan, RE Gores, GJ TI The bile acid-activated phosphatidylinositol 8-kinase pathway inhibits fas apoptosis upstream of bid in rodent hepatocytes SO GASTROENTEROLOGY LA English DT Article ID CYTOCHROME-C RELEASE; RAT HEPATOCYTES; CELL-DEATH; SIGNALING COMPLEX; MECHANISM; SURVIVAL; MITOCHONDRIA; CHOLESTASIS; CLEAVAGE AB <(Background & Aims)>: Bile acids differentially modulate hepatocyte injury in cholestasis, Although glycochenode-oxycholate (GCDC) induces Fas-mediated hepatocyte apoptosis, taurochenodeoxycholate (TCDC) simultaneously activates a phosphatidylinositol 3-kinase (PI 3-K)-mediated survival pathway blocking Fas apoptosis, In this study, the mechanisms by which the TCDC/PI 3-K survival signal disrupts Fas signaling were examined. (Methods) under bar: Studies were performed in primary cultures of mouse hepatocytes and the bile-salt-transporting Mc-Ntcp.24 rat hepatoma cell line. (Results) under bar: GCDC, but not TCDC, resulted in cytochrome c release demonstrating that TCDC blocked apoptosis upstream of mitochondria. In contrast, both GCDC and TCDC treatment resulted in Fas aggregation and recruitment of a dominant-negative FADD green fluorescent protein (GFP) and C360S pro-caspase 8-GFP to the plasma membrane. Despite recruitment of procaspase 8 to the plasma membrane by both bile acids, only GCDC resulted in increases of caspase 8 activity and Bid-GFP mitochondrial translocation, However, when PI-3K was inhibited with wortmannin or dominant-negative PI 3-K, TCDC-induced Bid-GFP mitochondrial translocation and cytochrome c release. (Conclusions) under bar: The TCDC/PI 3-K survival signal blocks Fas-mediated apoptosis by preventing caspase 8 activation and Bid mitochondrial translocation, Potentiation of this survival pathway in cholestasis has the potential to attenuate liver injury. C1 Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. RP Gores, GJ (reprint author), Mayo Med Sch Clin & Fdn, 200 1st St SW, Rochester, MN 55905 USA. RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 FU NIDDK NIH HHS [DK 41876] NR 35 TC 69 Z9 70 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 JUN PY 2001 VL 120 IS 7 BP 1810 EP 1817 DI 10.1053/gast.2001.24835 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 437QA UT WOS:000169004000028 PM 11375961 ER PT J AU Lok, AS Heathcote, EJ Hoofnagle, JH AF Lok, AS Heathcote, EJ Hoofnagle, JH TI Management of hepatitis B: 2000 - Summary of a workshop SO GASTROENTEROLOGY LA English DT Review ID TERM FOLLOW-UP; E-ANTIGEN SEROCONVERSION; CHRONIC ACTIVE HEPATITIS; ORTHOTOPIC LIVER-TRANSPLANTATION; RANDOMIZED CONTROLLED TRIAL; ENHANCED ANTIVIRAL BENEFIT; INTERFERON-ALPHA THERAPY; VIRUS-INFECTED PATIENTS; HEPATOCELLULAR-CARCINOMA; LAMIVUDINE THERAPY C1 Univ Michigan, Dept Clin Hepatol, Div Gastroenterol, Ann Arbor, MI 48109 USA. Univ Toronto, Toronto Western Hosp, Div Gastroenterol, Toronto, ON M5T 2S8, Canada. NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Lok, AS (reprint author), Univ Michigan, Dept Clin Hepatol, Div Gastroenterol, 1500 E Med Ctr Dr,3912 Taubman Ctr,Box 0362, Ann Arbor, MI 48109 USA. RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 NR 204 TC 523 Z9 587 U1 1 U2 9 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 JUN PY 2001 VL 120 IS 7 BP 1828 EP 1853 DI 10.1053/gast.2001.24839 PG 26 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 437QA UT WOS:000169004000030 PM 11375963 ER PT J AU Furuya, T Joe, B Salstrom, JL Hashiramoto, A Dobbins, DE Wilder, RL Remmers, EF AF Furuya, T Joe, B Salstrom, JL Hashiramoto, A Dobbins, DE Wilder, RL Remmers, EF TI Polymorphisms of the tumor necrosis factor alpha locus among autoimmune disease susceptible and resistant inbred rat strains SO GENES AND IMMUNITY LA English DT Article DE single nucleotide polymorphisms (SNPs); autoimmunity; major histocompatibility complex ID COLLAGEN-INDUCED ARTHRITIS; MAJOR HISTOCOMPATIBILITY COMPLEX; RHEUMATOID-ARTHRITIS; TNF; MODEL; MICE; IDENTIFICATION; LOCALIZATION; AMELIORATION; EXPRESSION AB Inbred rat strains manifest remarkable differences in susceptibility/severity to autoimmune disease. MHC alleles strongly influence the pathogenesis of autoimmune disease in rats, but the precise mechanism(s) remain inadequately defined. The TNF alpha gene is located in the class III region of the MHC. Polymorphisms, influencing either the structure or expression of the TNF protein, might contribute to differences in autoimmune disease susceptibility/severity. We therefore sequenced the Tnf locus using genomic DNA from ACI, BB(DR), BN, DA, F344, and LEW rats that vary in susceptibility/severity to autoimmune diseases. We found 42 polymorphisms among these six strains. Although none of these polymorphisms are predicted to change the amino acid sequence of the TNF protein, several reside in potential non-coding regulatory regions and may influence expression levels. These polymorphisms may serve as good candidates for analysis of TNF expression to elucidate the mechanism(s) by which the MHC regulates susceptibility and/or severity of autoimmune diseases. C1 NIAMSD, Inflammatory Joint Dis Sect, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. RP Remmers, EF (reprint author), NIAMS, Inflammatory Joint Dis Sect, NIH, 900 Rockville Pike,Bldg 10,Room 9N240, Bethesda, MD 20892 USA. NR 23 TC 3 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD JUN PY 2001 VL 2 IS 4 BP 229 EP 232 DI 10.1038/sj.gene.6363761 PG 4 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 451VG UT WOS:000169822600008 PM 11477479 ER PT J AU Dunn, KJ Incao, A Watkins-Chow, D Li, Y Pavan, WJ AF Dunn, KJ Incao, A Watkins-Chow, D Li, Y Pavan, WJ TI In utero complementation of a neural crest-derived melanocyte defect using cell directed gene transfer SO GENESIS LA English DT Article DE RCAS; tyrosinase; neural crest; complementation; melanocyte ID MOUSE TYROSINASE; TRANSGENIC MICE; NERVOUS-SYSTEM; ALBINO MICE; EXPRESSION; MELANOBLASTS; PROLIFERATION; DELIVERY; VECTORS; VIRUSES AB This study describes an in utero approach for overexpressing genes in a cell-type directed manner. It uses an avian leukosis retroviral expression system coupled with a transgenic mouse line expressing the viral receptor tv-a from a tissue-specific promoter (RCAS-TVA system) (Federspiel et at, 1994, and reviewed in Fisher ef at, 1999), A transgenic mouse line was generated expressing tv-a from the Dopachrome tautomerase promoter (DCT-tv-a) in embryonic melanocyte precursors (melanoblasts). RCAS virus encoding beta -galactosidase (RCAS-LacZ) or tyrosinase (RCAS-Tyr) was injected in utero into embryonic day 12.5 albino (tyrosinase inactive) mouse embryos. Animals were analyzed for beta -galactosidase activity or tyrosinase activity (hair pigmentation). RCAS gene expression was detected in 44% and 25% of the transgenic mice, respectively. We demonstrate the RCAS-TVA system coupled with the DCT-tv-a line of mice can be used for in utero infection. (C) 2001 Wiley-Liss, Inc. C1 NHGRI, Mouse Embryol Sect, Genet Dis Res Branch, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Pavan, WJ (reprint author), NHGRI, Mouse Embryol Sect, Genet Dis Res Branch, 49 Convent Dr,MSC4472,49 Room 4A82, Bethesda, MD 20892 USA. OI Li, Yi/0000-0002-9976-518X NR 27 TC 11 Z9 12 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1526-954X J9 GENESIS JI Genesis PD JUN PY 2001 VL 30 IS 2 BP 70 EP 76 DI 10.1002/gene.1035 PG 7 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 451GU UT WOS:000169793600005 PM 11416866 ER PT J AU Lindor, NM Dechet, CB Greene, MH Jenkins, RB Zincke, MT Weaver, AL Wilson, M Zincke, H Liu, WG AF Lindor, NM Dechet, CB Greene, MH Jenkins, RB Zincke, MT Weaver, AL Wilson, M Zincke, H Liu, WG TI Papillary renal cell carcinoma: Analysis of germline mutations in the MET proto-oncogene in a clinic-based population SO GENETIC TESTING LA English DT Article ID SOMATIC MUTATIONS; PTEN/MMAC1 MUTATIONS; COLORECTAL-CANCER; RECEPTOR GENE; KINASE DOMAIN; PROTOONCOGENE; FAMILIES; TUMORS; AMPLIFICATION; TRANSLOCATION AB Approximately 10% of all renal cell carcinomas (RCCs) present a distinctive papillary histology. Familial papillary RCC (PRCC) has been described, but the majority of cases appear to be sporadic. Recently, germline mutations in the MET proto-oncogene on chromosome 7 have been identified in families with hereditary PRCC. We evaluated 59 patients with PRCC for the frequency of MET germline mutations to determine the value of genetic screening of this patient population. Between 1976 and 1997, 165 patients were identified with PRCC by retrospective chart review. Fifty-nine of 133 surviving patients agreed to provide a family history, a blood specimen, and informed consent for genetic research. DNA was isolated from peripheral blood leukocytes. Denaturing high-performance liquid chromatography (DHPLC) followed by genomic sequencing was performed on eight exons of the MET proto-oncogene, including exons 5-7 of the extracellular domain, exon 14, and exons 16-19 of the tyrosine kinase domain. The 59 patients in this study included 49 men and 10 women with a mean age at diagnosis of 61 years. Bilateral and/or multifocal disease was present in 13 cases (22%). No germline mutations were detected in the studied exons of the MET proto-oncogene (exons previously reported to contain deleterious mutations in familial PRCC). No pathological MET proto-oncogene germline mutations were identified in 59 patients with PRCC. The germline mutation rate in this clinic-based population of individuals with PRCC approaches 0% (CI = 0-6.18). MET proto-oncogene germline mutation screening does not appear to be clinically indicated in patients with PRCC without additional evidence for a genetic predisposition (positive family history, unusual age at onset, bilateral disease). C1 Mayo Clin, Dept Med Genet, Rochester, MN 55905 USA. Mayo Clin, Dept Urol, Rochester, MN 55905 USA. Mayo Clin, Dept Lab Med, Rochester, MN 55905 USA. Mayo Clin, Dept Biostat, Rochester, MN 55905 USA. Mayo Clin, Dept Expt Pathol, Rochester, MN 55905 USA. NCI, Clin Genet Branch, Rockville, MD 20850 USA. RP Lindor, NM (reprint author), Mayo Clin, Dept Med Genet, E-7B,200 1st St SW, Rochester, MN 55905 USA. NR 31 TC 28 Z9 29 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD SUM PY 2001 VL 5 IS 2 BP 101 EP 106 DI 10.1089/109065701753145547 PG 6 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 469KN UT WOS:000170813200004 PM 11551094 ER PT J AU Klar, AJS Srikantha, T Soll, DR AF Klar, AJS Srikantha, T Soll, DR TI A histone deacetylation inhibitor and mutant promote colony-type switching of the human pathogen Candida albicans SO GENETICS LA English DT Article ID WHITE-OPAQUE TRANSITION; FISSION YEAST; ASPARTYL PROTEINASES; GENE; VIRULENCE; MISEXPRESSION; INHERITANCE; EXPRESSION; PHENOTYPE; MITOSIS AB Most strains of Candida albicans undergo high frequency phenotypic snitching. Strain WO-1 undergoes the white-opaque transition, which involves changes in colony and cellular morphology, gene expression, and virulence. We have hypothesized that the switch event involves heritable changes in chromatin structure. To test this hypothesis, we transiently exposed cells to the histone deacetylase inhibitor trichostatin-A (TSA). Treatment promoted a dramatic increase in the frequency of switching from white to opaque, but not opaque to white. Targeted deletion of HDA1, which encodes a deacetylase sensitive to TSA, had the same selective effect. These results support the model that the acetylation of histones plays a selective role in regulating the switching process. C1 NCI Frederick, DHHS, DBS,Dev Genet Sect, Gene Regulat & Chromosome Biol Lab, Ft Detrick, MD 21702 USA. Univ Iowa, Dept Biol Sci, Iowa City, IA 52242 USA. RP Klar, AJS (reprint author), NCI Frederick, DHHS, DBS,Dev Genet Sect, Gene Regulat & Chromosome Biol Lab, POB B, Ft Detrick, MD 21702 USA. FU NIAID NIH HHS [AI-2392] NR 34 TC 54 Z9 59 U1 1 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUN PY 2001 VL 158 IS 2 BP 919 EP 924 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 442FY UT WOS:000169275600038 PM 11404352 ER PT J AU Jourdan-Le Saux, C Tomsche, A Ujfalusi, A Jia, LB Csiszar, K AF Jourdan-Le Saux, C Tomsche, A Ujfalusi, A Jia, LB Csiszar, K TI Central nervous system, uterus, heart, and leukocyte expression of the LOXL3 gene, encoding a novel lysyl oxidase-like protein SO GENOMICS LA English DT Article ID PURIFICATION; ADHESION; DEFENSE AB A BLASTN search using the mouse lor-2 cDNA identified three overlapping ESTs (AI752772, AA852888, and R557o6) in the GenBank database. These expressed sequence tags were assembled into a contig of 3121 nucleotides with an open reading frame of 2262 bp. The encoded putative polypeptide of 754 amino acids presented all structural characteristics of the lysyl oxidase (LOX) enzyme family, a copper-binding site with four histidyl residues, the lysyl and tyrosyl residues known to be involved in LOX enzyme in the formation of the quinone cofactor and surrounding sequences, and the cytokine receptor-like domain. In addition, four scavenger receptor cysteine-rich (SRCR) domains were found in the N-terminal region of the protein. The gene encoding this new cDNA, which we have referred to as human lysyl oxidase-like 3 (humanLOXL3), has been mapped to chromosome 2p13.3, overlapping at its 3 ' end the HtrA2 serine protease gene. The structure of the humanLOXL3 gene was deduced from the BAC clone bac91a19 sequence and contained 14 exons. The expression pattern of this new member of the LOX gene family appears to be different from that of the LOX and LOX-like genes, as the central nervous system, neurons, and also leukocytes expressed humanLOXL3. A BLASTN search of the human EST database indicated the presence of ESTs, corresponding to alternative splice variants of LOXL3, that lacked exon 5 and exon 8. The putative resulting protein retained the region encoding the structural and functional elements of the amine oxidase but the second and fourth SRCR domains were truncated and the potential BMP-1 cleavage site was not present. The presence of domains unrelated to the traditional amine oxidase activity is a strong indication that humanLOXL3 might fulfill other functions in addition to intrinsic enzyme activity. (C) 2001 Academic Press. C1 Univ Hawaii, Pacific Biomed Res Ctr, Honolulu, HI 96822 USA. NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. RP Csiszar, K (reprint author), Univ Hawaii, Pacific Biomed Res Ctr, 1993 East West Rd, Honolulu, HI 96822 USA. FU NCI NIH HHS [CA76580]; NCRR NIH HHS [RR03061] NR 24 TC 44 Z9 45 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 1 PY 2001 VL 74 IS 2 BP 211 EP 218 DI 10.1006/geno.2001.6545 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 440ML UT WOS:000169179000009 PM 11386757 ER PT J AU Wilson, SM Householder, DB Coppola, V Tessarollo, L Fritzsch, B Lee, EC Goss, D Carlson, GA Copeland, NG Jenkins, NA AF Wilson, SM Householder, DB Coppola, V Tessarollo, L Fritzsch, B Lee, EC Goss, D Carlson, GA Copeland, NG Jenkins, NA TI Mutations in Cdh23 cause nonsyndromic hearing loss in waltzer mice SO GENOMICS LA English DT Article ID MYOSIN VIIA; UNCONVENTIONAL MYOSIN; ALPHA-CATENIN; CELL-ADHESION; HAIR-CELLS; E-CADHERIN; GENE; DEAFNESS; PROTEIN; MOUSE AB Mutations at the waltzer (v) locus result in deafness and vestibular dysfunction due to degeneration of the neuroepithelium within the inner ear. Here, we use a positional cloning approach to show that waltzer encodes a novel cadherin (Cdh23), which is most closely related to the Drosophila Fat protein. A single nucleotide deletion in the v(J) allele and a single nucleotide insertion in the v allele are predicted to truncate each protein near the N-terminus and produce a functional null allele. In situ hybridization analysis showed that Cdh23 is expressed in the sensory hair cells of the inner ear, where it has been suggested to be a molecule critical for crosslinking of the stereocilia. In addition, Cdh23 is expressed in the urticulo-saccular foremen, the ductus reuniens, and Reissner's membrane, suggesting that Cdh23 may also be involved in maintaining the ionic composition of the endolymph. Finally, mutations in human CDH23 have recently been described for two loci, DFNB12 and USH1D, which cause nonsyndromic deafness, identifying waltzer as a mouse model for human hearing loss. (C) 2001 Academic Press. C1 NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. McLaughlin Res Inst, Great Falls, MT 59405 USA. Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. RP Jenkins, NA (reprint author), NCI, Mouse Canc Genet Program, Bldg 539,Room 229, Frederick, MD 21702 USA. RI Coppola, Vincenzo/E-2917-2011; OI Coppola, Vincenzo/0000-0001-6163-1779; Fritzsch, Bernd/0000-0002-4882-8398 FU NIDCD NIH HHS [P01 DC00215]; NINDS NIH HHS [NS22786] NR 35 TC 78 Z9 82 U1 2 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 1 PY 2001 VL 74 IS 2 BP 228 EP 233 DI 10.1006/geno.2001.6554 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 440ML UT WOS:000169179000011 PM 11386759 ER PT J AU Witt, LA Hilton, TF Hochwarter, WA AF Witt, LA Hilton, TF Hochwarter, WA TI Addressing politics in matrix teams SO GROUP & ORGANIZATION MANAGEMENT LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the Academy-of-Management CY AUG, 1999 CL CHICAGO, ILLINOIS SP Acad Management ID ORGANIZATIONAL CITIZENSHIP BEHAVIOR; EMPIRICAL-EVIDENCE; JOB-SATISFACTION; DECISION-MAKING; GOAL CONGRUENCE; COMMITMENT; PERCEPTIONS; MODEL; PERFORMANCE; WORK AB Analyses of data collected from 172 members of 23 matrix teams indicated that member perceptions of team-level politics were negatively related to executive and member ratings of effectiveness and to member expressions of satisfaction with and commitment to the matrix team. In addition, results of moderated multiple regression analyses indicated that member-team goal congruence moderated these relationships. Perceptions of politics were more strongly related to the outcome variables among individuals who did not share the priorities of their team members than among those whose goal priorities were consistent. These results suggest that leaders can help their team members cope with politics by making efforts to ensure that they share goal priorities of team members. C1 Univ New Orleans, Dept Management, New Orleans, LA 70148 USA. NIDA, Lexington, KY USA. Univ Alabama, Tuscaloosa, AL 35487 USA. RP Witt, LA (reprint author), Univ New Orleans, Dept Management, New Orleans, LA 70148 USA. NR 58 TC 22 Z9 22 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1059-6011 J9 GROUP ORGAN MANAGE JI Group Organ. Manage. PD JUN PY 2001 VL 26 IS 2 BP 230 EP 247 DI 10.1177/1059601101262006 PG 18 WC Psychology, Applied; Management SC Psychology; Business & Economics GA 575RR UT WOS:000176962300006 ER PT J AU Cuello, M Ettenberg, SA Nau, MM Lipkowitz, S AF Cuello, M Ettenberg, SA Nau, MM Lipkowitz, S TI Synergistic induction of apoptosis by the combination of TRAIL and chemotherapy in chemoresistant ovarian cancer cells SO GYNECOLOGIC ONCOLOGY LA English DT Article DE TRAIL; apoptosis; ovarian cell line; chemotherapy ID S-TRANSFERASE-PI; DRUG-RESISTANCE; DECOY RECEPTORS; DEATH RECEPTORS; P53-MEDIATED APOPTOSIS; ACQUIRED-RESISTANCE; MISMATCH REPAIR; LEUKEMIA CELLS; LIGAND TRAIL; IN-VIVO AB Objectives. The aim of this study was to investigate whether TNF-related apoptosis-inducing ligand (TRAIL) alone or in combination with chemotherapy could induce apoptosis in ovarian cancer cells resistant to chemotherapy, Methods. Twelve chemoresistant epithelial cancer cell lines were treated with each chemotherapeutic drug alone (cisplatin, doxorubicin, or paclitaxel), TRAIL alone, or the combination. Toxicity was assessed using the MTS assay. To assess whether growth inhibition was due to apoptosis, TUNEL assay, caspase activation (measured by caspase-3 and PARP cleavage), and the sub G0/G1 fraction of cells were measured. Synergism was confirmed by fractional inhibition and dose- effect analysis. Expression of death and decoy receptors was studied by immunoblotting and an RNase protection assay. Statistical comparison of means was performed using Student's t test. Results. The majority of the chemoresistant cells were also resistant to TRAIL alone. In contrast, the combination of TRAIL and chemotherapy resulted in a significant growth inhibition over a wide range of concentrations. This interaction was synergistic by dose-effect analysis. Flow cytometry demonstrated a significant increase in the fraction of apoptotic cells by the combination compared to each reagent alone. A significant enhancement in caspase and PARR cleavage was observed upon treatment with the combination. Finally, no correlation between induction of apoptosis and level of death receptors was found. Conclusions. The data suggest that almost all the ovarian cancer cells, which are resistant to chemotherapy, are also resistant to TRAIL, The combination of TRAIL and chemotherapy overcomes this resistance in a synergistic fashion by triggering caspase-mediated apoptosis. The combination of TRAIL and chemotherapy could be useful as a therapy for chemoresistant ovarian cancers. (C) 2001 Academic Press. C1 NCI, Dept Genet, Med Branch, NIH,Natl Naval Med Ctr, Bethesda, MD 20889 USA. Uniformed Serv Univ Hlth Sci, Moll & Cell Biol Program, Bethesda, MD 20889 USA. Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Fac Med, Santiago, Chile. RP Lipkowitz, S (reprint author), NCI, Dept Genet, Med Branch, NIH,Natl Naval Med Ctr, Bldg 8,Room 5101, Bethesda, MD 20889 USA. NR 68 TC 118 Z9 131 U1 0 U2 7 PU ACADEMIC PRESS INC 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 JUN PY 2001 VL 81 IS 3 BP 380 EP 390 DI 10.1006/gyno.2001.6194 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 441ME UT WOS:000169233500007 PM 11371126 ER PT J AU Zha, XM Bishop, JF Hansen, MR Victoria, L Abbas, PJ Mouradian, MM Green, SH AF Zha, XM Bishop, JF Hansen, MR Victoria, L Abbas, PJ Mouradian, MM Green, SH TI BDNF synthesis in spiral ganglion neurons is constitutive and CREB-dependent SO HEARING RESEARCH LA English DT Article DE promoter region; brain-derived neurotrophic factor; cell survival; spiral ganglion neuron; gene expression regulation; Ca2+/cyclic AMP response element binding protein; Ca2+/calmodulin-dependent protein kinase; autocrine mechanism ID MESSENGER-RNA EXPRESSION; NEUROTROPHIC FACTOR BDNF; INNER-EAR INNERVATION; IMMEDIATE-EARLY GENE; SENSORY NEURONS; IN-VIVO; HIPPOCAMPAL-NEURONS; TRANSGENIC MICE; HAIR-CELLS; RAT BDNF AB Brain-derived neurotrophic factor (BDNF), which supports spiral ganglion neuron (SGN) survival in vivo and in vitro, is synthesized by SGNs. The BDNF gene generates multiple different transcripts, each from its own promoter region. Using reverse transcriptase-polymerase chain reaction (RT-PCR), we find that SGNs express only the downstream transcripts III and IV in vivo and in vitro. Using RT-PCR assays of BDNF transcripts and transfection of BDNF promoter-reporter constructs, we tested the hypothesis, originally derived from studies of cortical neurons, that depolarization induces BDNF expression via a signaling pathway that includes Ca2+/calmodulin-dependent kinases (CaMKs) and the transcription factor, Ca2+/cyclic AMP response element binding protein (CREB). In contrast, we found that in SGNs in vivo BDNF expression is constitutive and is not increased by electrical activation. Similarly, BDNF expression in vitro is not increased by stimuli that activate CREB, including depolarization, cAMP, or transfection of activated CaMK mutants. However, transfection of dominant-negative CREB mutants did abrogate gene expression driven by BDNF promoters III and IV, indicating that CREB is necessary for constitutive BDNF expression. Thus, BDNF synthesis within SGNs makes possible an autocrine or paracrine mechanism that can contribute to support SGN survival but SGNs are distinctive in that this mechanism is constitutive and not activity-regulated. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Iowa, Dept Sci Biol, Iowa City, IA 52242 USA. Univ Iowa, Dept Otolaryngol, Iowa City, IA 52242 USA. NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, Bethesda, MD 20892 USA. Univ Iowa, Dept Speech, Iowa City, IA 52242 USA. Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA. Univ Iowa, Dept Otolaryngol, Iowa City, IA 52242 USA. RP Green, SH (reprint author), Univ Iowa, Dept Sci Biol, 138 Biol Bldg, Iowa City, IA 52242 USA. OI Mouradian, M. Maral/0000-0002-9937-412X FU NIDCD NIH HHS [R01 DC002961, DC00040, DC02961]; NIDDK NIH HHS [DK25295] NR 63 TC 50 Z9 51 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUN PY 2001 VL 156 IS 1-2 BP 53 EP 68 DI 10.1016/S0378-5955(01)00267-2 PG 16 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 442GB UT WOS:000169275900006 PM 11377882 ER PT J AU Ghizzoni, L Barreca, A Mastorakos, G Furlini, M Vottero, A Ferrari, B Chrousos, GP Bernasconi, S AF Ghizzoni, L Barreca, A Mastorakos, G Furlini, M Vottero, A Ferrari, B Chrousos, GP Bernasconi, S TI Leptin inhibits steroid biosynthesis by human granulosa-lutein cells SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE ovary; leptin; granulosa cells; hCG; IGFs ID GROWTH-FACTOR-I; IGF-I; HUMAN OVARY; METABOLIC SIGNAL; HORMONAL ACTION; WEIGHT-LOSS; OBESE GENE; EXPRESSION; RECEPTORS; WOMEN AB Absence of leptin secretion compromises reproductive function and fertility in the ob/ob mouse which, when given leptin, shows a rise in serum LH levels and becomes fertile. Recently, the long and active isoform of the leptin receptor was detected in the ovary. indicating that leptin may also show direct gonad-related activity. To examine this, we studied the effect of graded doses of human leptin on estradiol (E-2) and progesterone (P-4) concentrations in the culture media of human granulosa-lutein cells obtained from follicular fluid of women undergoing in vitro fertilization. We also evaluated the mRNA expression of steroidogenic acute regulatory protein (StAR), aromatase, and cytochrome P450 17 alpha (CYP17) in these cells at baseline and after exposure to leptin, Estradiol levels were significantly decreased in the media 24 hours after incubation of the cells with increasing hLeptin concentrations (10(-11) -10(-7) mol/l). The maximal 30 % decrease in E-2 production was caused by the 10(-9) mol/l hLeptin concentration; however, P-4 levels in the media were not influenced by leptin, Exposure of granulosa-lutein cells to 10-9 mol/l hLeptin did not produce any measurable changes on StAR, aromatase, or CYP17 mRNA expression, When hLeptin (10(-9) mol/l) was co-incubated with increasing concentrations of hCC (1.25-10 mIU/ml), IGF-II (15-50 ng/ml) or 1-6 desaminated ICF-II (desIGF-II; 15-60 ng/ml), it did not modify the elevation of E, concentrations caused by each of the different stimuli, We conclude that leptin suppresses E-2 secretion by human granulosa-lutein cells but does not impair the stimulatory effects of hCG and IGFs on these cells. Leptin may play a minor, but direct regulatory role on unstimulated human ovarian steroidogenesis by interfering with either the translational or post-translational steps of the baseline C/P17 and/or aromatase synthesis and/or the activation of the enzymes. C1 Univ Parma, Dept Pediat, I-43100 Parma, Italy. Univ Genoa, Dept Endocrinol & Metab, Genoa, Italy. Univ Athens, Evgenidion Hosp, Endocrine Unit, Athens, Greece. Univ Parma, Dept Obstet & Gynecol, I-43100 Parma, Italy. NICHHD, NIH, Bethesda, MD 20892 USA. RP Ghizzoni, L (reprint author), Univ Parma, Dept Pediat, 14 Via Gramsci, I-43100 Parma, Italy. NR 27 TC 46 Z9 51 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 JUN PY 2001 VL 33 IS 6 BP 323 EP 328 DI 10.1055/s-2001-15419 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 451QQ UT WOS:000169813100001 PM 11456279 ER PT J AU Main, P Attenborough, R Chelvanayagam, G Gao, X AF Main, P Attenborough, R Chelvanayagam, G Gao, X TI The peopling of New Guinea: Evidence from class I human leukocyte antigen SO HUMAN BIOLOGY LA English DT Article DE major histocompatibility complex; class I human leukocyte antigens; population affinities; genetic distance; Papua New Guinea ID PAPUA-NEW-GUINEA; SEQUENCE POLYMORPHISMS; FINGERPRINT VARIATION; MULTIVARIATE APPROACH; NUCLEOTIDE-SEQUENCE; HLA-B; POPULATIONS; FREQUENCIES; DNA; OVALOCYTOSIS AB This study utilizes newly developed direct DNA typing methods for human leukocyte antigens (HLA) to provide new information about the peopling of New Guinea. The complete polymorphism of eight Melanesian populations was examined. The groups included were highlanders, northern and southern highlands fringe populations, a Sepik population. northern and southern coastal New Guinea populations, and populations from the Bismarck Archipelago and New Caledonia. The study concluded that, based on HLA and other evidence, Melanesians are likely to have evolved largely from the same ancestral stock as Aboriginal Australians but to have since differentiated. Highlanders are likely to be descendants of earlier migrations who have been isolated for a long period of time. Northern highlands fringe and Sepik populations are likely to share a closer common ancestry but to have differentiated due to long term isolation and the relative proximity to the coast of the Sepik. Southern fringe populations are likely to have a different origin, possibly from the Gulf region, although there may be some admixture with neighboring groups. Coastal populations have a wider range of polymorphisms because of the genetic trail left by later population movement along the coast from Asia that did not reach Australia or remote Oceania, Other polymorphisms found in these populations may have been introduced by the movement of Austronesian-speaking and other more recent groups of people into the Pacific, because they share many polymorphisms with contemporary southeast Asians, Polynesians, and Micronesians that are nor found in highlanders or Aboriginal Australians. There is evidence suggestive of later migration to Melanesia from Polynesia and Micronesia. C1 Australian Natl Univ, John Curtin Sch Med Res, Dept Human Genet, Canberra, ACT 2601, Australia. Australian Natl Univ, Sch Archaeol & Anthropol, Canberra, ACT, Australia. Univ Western Australia, Dept Comp Sci, Perth, WA 6009, Australia. NCI, IRSP, SAIC Frederick, FCRD, Frederick, MD 21701 USA. RP Australian Natl Univ, John Curtin Sch Med Res, Dept Human Genet, Canberra, ACT 2601, Australia. NR 64 TC 16 Z9 16 U1 1 U2 2 PU WAYNE STATE UNIV PRESS PI DETROIT PA 4809 WOODWARD AVE, DETROIT, MI 48201-1309 USA SN 0018-7143 EI 1534-6617 J9 HUM BIOL JI Hum. Biol. PD JUN PY 2001 VL 73 IS 3 BP 365 EP 383 DI 10.1353/hub.2001.0036 PG 19 WC Anthropology; Biology; Genetics & Heredity SC Anthropology; Life Sciences & Biomedicine - Other Topics; Genetics & Heredity GA 450AP UT WOS:000169719600003 PM 11459419 ER PT J AU Cobo, MF Jobes, DV Yanagihara, R Nerurkar, VR Yamamura, Y Ryschkewitsch, CF Stoner, GL AF Cobo, MF Jobes, DV Yanagihara, R Nerurkar, VR Yamamura, Y Ryschkewitsch, CF Stoner, GL TI Reconstructing population history using JC virus: Amerinds, Spanish, and Africans in the ancestry of modern Puerto Ricans SO HUMAN BIOLOGY LA English DT Article DE polyomavirus; JC virus; genotypes; hispanic americans; migration; genetic admixture ID HUMAN POLYOMAVIRUS JC; COMPLETE GENOMES; ADMIXTURE PROPORTIONS; SEQUENCE-ANALYSIS; GENETIC-MARKERS; DNA-SEQUENCE; BK VIRUS; AMERICANS; GENOTYPES; BRAZIL AB The roots of the Hispanic populations of the Caribbean Islands and Central and South America go back to three continents of the Old World. In Puerto Rico major genetic contributions have come from (1) Asians in the form of the aboriginal Taino population, an Arawak tribe, present when Columbus arrived on the Island, (2) Europeans, largely Spanish explorers, settlers, government administrators, and soldiers, and (3) Africans who came as part of the slave trade. Since JC virus (JCV) genotypes characteristic of Asia, Europe, and Africa have been identified, and excretion of JCV in urine has been proposed as a marker for human migrations, we sought to characterize the JCV strains present in a Caribbean Hispanic population. We found that the strains of JCV present today in Puerto Rico are those derived from the Old World populations represented there: Types 1B and 4 from Spain, Types 3A, 3B, and 6 from Africa, and Type 2A from Asia. The Type 2A genotype represents the indigenous Taino people. This JCV genotype was represented much more frequently (61%) than would be predicted by the trihybrid model of genetic admixture. This might be attributable to characteristics of JCV Type 2A itself, as well as to the nature of the early relationships between Spanish men and native women. These findings indicate that the JCV strains carried by the Taino Indians can be found in today's Puerto Rican population despite the apparent demise of these people more than two centuries ago. Therefore, molecular characterization of JCV provides a tool to supplement genetic techniques for reconstructing population histories including admired populations. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. Univ Hawaii Manoa, Retrovirol Res Lab, Pacific Biomed Res Ctr, Honolulu, HI 96822 USA. Ponce Sch Med, AIDS Res Program, Ponce, PR 00732 USA. INEI, ANLIS, Dept Virus, Serv Biol Mol, RA-1281 Buenos Aires, DF, Argentina. RP Cobo, MF (reprint author), NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. FU NCRR NIH HHS [G12RR/AI-03061, G12RR/AI03050] NR 50 TC 5 Z9 5 U1 0 U2 0 PU WAYNE STATE UNIV PRESS PI DETROIT PA 4809 WOODWARD AVE, DETROIT, MI 48201-1309 USA SN 0018-7143 EI 1534-6617 J9 HUM BIOL JI Hum. Biol. PD JUN PY 2001 VL 73 IS 3 BP 385 EP 402 PG 18 WC Anthropology; Biology; Genetics & Heredity SC Anthropology; Life Sciences & Biomedicine - Other Topics; Genetics & Heredity GA 450AP UT WOS:000169719600004 PM 11459420 ER PT J AU Clark, VJ Metheny, N Dean, M Peterson, RJ AF Clark, VJ Metheny, N Dean, M Peterson, RJ TI Statistical estimation and pedigree analysis of CCR2-CCR5 haplotypes SO HUMAN GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; HIV-1 DISEASE PROGRESSION; HUMAN LIPOPROTEIN-LIPASE; LINKAGE DISEQUILIBRIUM; CHEMOKINE-RECEPTOR; GENETIC RESTRICTION; SEQUENCE VARIATION; AIDS PROGRESSION; CXC CHEMOKINES; LUNG-CANCER AB As more SNP marker data becomes available, researchers have used haplotypes of markers, rather than individual polymorphisms, for association analysis of candidate genes. In order to perform haplotype analysis in a population-based case-control study, haplotypes must be determined by estimation in the absence of family information or laboratory methods for establishing phase. Here, we test the accuracy of the Expectation-Maximization (EM) algorithm for estimating haplotype state and frequency in the CCR2-CCR5 gene region by comparison with haplotype state and frequency determined by pedigree analysis. To do this, we have characterized haplotypes comprising alleles at seven biallelic loci in the CCR2-CCR5 chemokine receptor gene region, a span of 20 kb on chromosome 3p21. Three-generation CEPH families (n=40), totaling 489 individuals, were genotyped by the 5 ' nuclease assay (TaqMan). Haplotype states and frequencies were compared in 103 grandparents who were assumed to have mated at random. Both pedigree analysis and the EM algorithm yielded the same small number of haplotypes for which linkage disequilibrium was nearly maximal. The haplotype frequencies generated by the two methods were nearly identical. These results suggest that the EM algorithm estimation of haplotype states, frequency, and linkage disequilibrium analysis will be an effective strategy in the CCR2-CCR5 gene region. For genetic epidemiology studies, CCR2-CCR5 allele and haplotype frequencies were determined in African-American (n=30), Hispanic (n=24) and European-American (n=34) populations. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. Celadon Labs Inc, College Pk, MD 20742 USA. RP Clark, VJ (reprint author), NCI, Lab Genom Divers, Bldg 560,Room 11-70, Frederick, MD 21702 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 50 TC 26 Z9 27 U1 0 U2 0 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 JUN PY 2001 VL 108 IS 6 BP 484 EP 493 DI 10.1007/s004390100512 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 461WA UT WOS:000170385400006 PM 11499673 ER PT J AU Iwata, T Li, CL Deng, CX Francomano, CA AF Iwata, T Li, CL Deng, CX Francomano, CA TI Highly activated Fgfr3 with the K644M mutation causes prolonged survival in severe dwarf mice SO HUMAN MOLECULAR GENETICS LA English DT Article ID GROWTH-FACTOR RECEPTOR-3; THANATOPHORIC DYSPLASIA; SKELETAL DYSPLASIA; CHONDROCYTE PROLIFERATION; ACANTHOSIS NIGRICANS; DEVELOPMENTAL DELAY; LYS650MET MUTATION; KINASE ACTIVATION; POINT MUTATION; PC12 CELLS AB Several gain-of-function mutations in a receptor tyrosine kinase, fibroblast growth factor receptor 3 (FGFR3), cause dwarfism in humans. Two particularly severe dwarfisms, thanatophoric dysplasia type II (TDII) and severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), are associated with glutamic acid (E) and methionine (M) substitutions at the K650 residue in the kinase domain, TDII is lethal at birth, whereas most of the SADDAN patients survive the perinatal period. However, FGFR3 with the SADDAN mutation is more activated than FGFR3 with the TDII mutation in vitro. To find out whether the K650M mutation also causes the SADDAN phenotype, we introduced the corresponding point mutation (K644M) into the mouse Fgfr3 gene. Heterozygous mutant mice show a phenotype similar to human SADDAN, e,g, the majority of the SADDAN mice survive the perinatal period. This suggests that the survival of SADDAN patients is indeed attributed to the K650M mutation in FGFR3, The long bone abnormalities in SADDAN mice are milder than the TDII model, In addition, overgrowth of the cartilaginous tissues is observed in the rib cartilage, trachea and nasal septum, The FGF ligand at the low concentration differentially activates Map kinase in primary chondrocyte cultures from wildtype and SADDAN mice, Comparisons of the molecular bases of the phenotypic differences in SADDAN and TDII mice may increase our understanding of the factors that influence the severity in these two related skeletal dysplasias. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Iwata, T (reprint author), European Mol Biol Lab, Dev Biol Programme, Meyerhofstr 1, D-69117 Heidelberg, Germany. RI deng, chuxia/N-6713-2016 NR 27 TC 77 Z9 81 U1 2 U2 2 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 JUN 1 PY 2001 VL 10 IS 12 BP 1255 EP 1264 DI 10.1093/hmg/10.12.1255 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 444LG UT WOS:000169400500003 PM 11406607 ER PT J AU Berman, J O'Leary, TJ AF Berman, J O'Leary, TJ TI Gastrointestinal stromal tumor workshop SO HUMAN PATHOLOGY LA English DT Article DE KIT; CD117; STI-571; sarcoma; workshop AB Gastrointestinal stromal tumor (GIST) has emerged in the past year as a prototypical neoplasm that responds to therapy directed against a single target molecule - the KIT receptor tyrosine kinase protein. Although GIST seldom responds to conventional chemotherapeutic agents, early experience with the tyrosine kinase inhibitor, STI-571 (Gleevec; Novartis, Basel, Switzerland), has been extremely encouraging. Early results have appeared in a recent case report in the Neu England Journal of Medicine (April 5, 2001),(1) and in early clinical trials from the United States and Europe that were reported at the plenary session of the American Society of Clinical Oncology in San Francisco on May 14, 2001. STI-571 is one of the earliest examples of a nontoxic chemotherapeutic agent tan agent whose anticancer activity is not predicated on a cytotoxic mechanism). STI-571 has already shown clinical value in BCR-ABL-positive leukemias. Early clinical results in GIST are so encouraging that oncologists may soon be wrestling with the opportunity of referring every patient with malignant GIST into clinical trials with STI-571. To ensure appropriate treatment, pathologists need to understand the biology and treatment of this tumor and to have standard methods and criteria for providing diagnosis (GIST or not GIST) and consistent prognostic classification thigh risk of metastasis or low risk of metastasis). C1 NCI, Resources Dev Branch, Canc Diagnost Program, DCTD,NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Cellular Pathol & Genet, Washington, DC 20306 USA. RP Berman, J (reprint author), NCI, Resources Dev Branch, Canc Diagnost Program, DCTD,NIH, EPN Room 6082,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 2 TC 169 Z9 201 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUN PY 2001 VL 32 IS 6 BP 578 EP 582 DI 10.1053/hupa.2001.25484 PG 5 WC Pathology SC Pathology GA 448MN UT WOS:000169630800003 PM 11431711 ER PT J AU Weiss, JM Stojilkovic, SS Diedrich, K Ortmann, O AF Weiss, J. M. Stojilkovic, S. S. Diedrich, K. Ortmann, O. TI Effects of testosterone on the LH secretory capacity of gonadotrophs SO HUMAN REPRODUCTION LA English DT Meeting Abstract C1 [Weiss, J. M.; Diedrich, K.; Ortmann, O.] Med Univ Lubeck, Dept Gynecol & Obstet, Lubeck, Germany. [Stojilkovic, S. S.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 2001 VL 16 SU 1 BP 208 EP 208 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA V23AN UT WOS:000208315800516 ER PT J AU Kaur, H Richardson, E Murty, L AF Kaur, H Richardson, E Murty, L TI Preparation of monoclonal antibodies against human telomerase SO HYBRIDOMA LA English DT Article ID CANCER-THERAPY; CELLS; GENE; AMPLIFICATION; EXPRESSION AB Telomerase, a ribonucleoprotein enzyme that extends telomeres of eukaryotic chromosomes, consists of the catalytic protein submit telomerase reverse transcriptase (TERT) and a telomerase RNA subunit. Nearly 85% of human tumors have tested positive for high telomerase activity. Telomerase activity is very low or not present in normal cells, whereas it is up-regulated in immortalized cells. Telomerase, partially purified from the breast tumor cell line MCF-7, was used to immunize Balb/C mice. Monoclonal antibodies (MAbs) were prepared by conventional hybridoma technology and screened by enzyme-linked immunoadsorbent assay (ELISA), followed by a polymerase chain reaction (PCR) based telomeric amplification repeat protocol (TRAP) assay to detect binding to or inhibition of telomerase activity. Reactive MAbs were found to be of IgM type by mu -specific ELISA. Two MAbs were characterized, one that neutralizes telomerase activity in TRAP assay and the other non-neutralizing. In Western blotting, crude telomerase extract and HIV-1 virus lysate (control) were blotted on nitrocellulose membranes and the strips were treated with both MAbs and a nonrelated HIV polymerase-specific MAb, also IgM type. A band of approx. 65-kDa was detected in extracts of 293 cells with both the MAbs, but no reaction occurred with the HIV polymerase-specific MAb used as control. Similarly, when HIV-1 virus lysate strips were treated with HIV polymerase-specific MAb, a 65-kDa band was detected and no band was observed with either of the hybridoma supernatants. These antibodies may be useful for studying regulatory mechanism of telomerase and inhibition of its activity in vitro and in vivo. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor & Gene Express, NIH, Bethesda, MD 20892 USA. RP Kaur, H (reprint author), 34133 Finnigan Terrace, Fremont, CA 94555 USA. NR 23 TC 4 Z9 5 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 2001 VL 20 IS 3 BP 183 EP 188 DI 10.1089/027245701750293510 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA 451GR UT WOS:000169793400006 PM 11461667 ER PT J AU Cruz, DN Simon, DB Nelson-Williams, C Farhi, A Finberg, K Burleson, L Gill, JR Lifton, RP AF Cruz, DN Simon, DB Nelson-Williams, C Farhi, A Finberg, K Burleson, L Gill, JR Lifton, RP TI Mutations in the Na-Cl cotransporter reduce blood pressure in humans SO HYPERTENSION LA English DT Article DE blood pressure; sodium, dietary; hypokalemia; human; diuretics; genetics ID BARTTERS-SYNDROME; ALKALOSIS; GITELMANS AB The relationship between salt homeostasis and blood pressure has remained difficult to establish from epidemiological studies of the general population. Recently, mendelian forms of hypertension have demonstrated that mutations that increase renal salt balance lead to higher blood pressure, suggesting that mutations that decrease the net salt balance might have the converse effect. Gitelman's syndrome, caused by loss of function mutations in the Na-Cl cotransporter of the distal convoluted tubule (NCCT), features inherited hypokalemic alkalosis with so-called "normal" blood pressure. We hypothesized that the mild salt wasting of Gitelman's syndrome results in reduced blood pressure and protection from hypertension. We have formally addressed this question through the study of 199 members of a large Amish kindred with Gitelman's syndrome. Through genetic testing, family members were identified as inheriting 0 (n=60), 1 (n=113), or 2 (n=26) mutations in NCCT, permitting an unbiased assessment of the clinical consequences of inheriting these mutations by comparison of the phenotypes of relatives with contrasting genotypes. The results demonstrate high penetrance of hypokalemic alkalosis, hypomagnesemia, and hypocalciuria in patients inheriting 2 mutant NCCT alleles. In addition, the NCCT genotype was a significant predictor of blood pressure, with homozygous mutant family members having significantly lower age- and gender-adjusted systolic and diastolic blood pressures than those of their wild-type relatives. Moreover, both homozygote and heterozygote subjects had significantly higher 24-hour urinary Na+ than did wild-type subjects, reflecting a self-selected higher salt intake. Finally, heterozygous children, but not adults, had significantly lower blood pressures than those of the wild-type relatives. These findings provide formal demonstration that inherited mutations that impair renal salt handling lower blood pressure in humans. C1 Yale Univ, Boyer Ctr Mol Med, Sch Med, Dept Med, New Haven, CT 06510 USA. Yale Univ, Boyer Ctr Mol Med, Sch Med, Dept Genet, New Haven, CT 06510 USA. NIH, Bethesda, MD 20892 USA. RP Lifton, RP (reprint author), Yale Univ, Boyer Ctr Mol Med, Sch Med, Dept Med, 295 Congress Ave, New Haven, CT 06510 USA. NR 12 TC 106 Z9 115 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 2001 VL 37 IS 6 BP 1458 EP 1464 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 444YK UT WOS:000169428000020 PM 11408395 ER PT J AU Barker, WC Szajek, LP Green, SL Carson, RE AF Barker, WC Szajek, LP Green, SL Carson, RE TI Improved quantification for Tc-94m PET imaging SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT Medical Imaging Conference (MIC) CY OCT 15-20, 2000 CL LYON, FRANCE DE biomedical nuclear imaging; Compton scattering; poistron emission tomography (PET) ID POSITRON; PURITY AB The positron emitter Tc-94m (52.5-min half-life) has the potential to improve quantification of tracers currently labeled with Tc-99m. The successful production of Tc-94m and the development of an accurate multiisotope decay correction have improved quantification for Tc-94m positron emission tomography (PET) imaging. However, the presence of gamma rays emitted in coincidence with the positrons produces an apparent increase in scatter of 40% to 90%. Furthermore, the contaminant positron emitter Tc-94 (293-min half-life) produced with Tc-94m also has positron-coincident gammas, so the effect is time-dependent. In this study, modification of the kernel parameters of the Bergstrom two-dimensional (2-D) scatter correction is proposed as a simple way to improve technetium PET quantification. Parameter optimization was performed using line source scatter phantom data for F-18 and technetium for a variety of positions in cylindrical and elliptical phantoms over a 3-h period. The accuracy of the correction was evaluated with remnant scatter fraction measurements using uniformly filled phantoms with 5-cm cold cylindrical inserts. On average, remnant 2-D scatter fractions of 10 +/- 3% were observed when parameters optimized for F-18 were used. The use of parameters optimized for technetium reduced the remnant scatter fractions to 1 +/- 3%, showing that accurate quantification with Tc-94m can be achieved. C1 NIH, Warren Grant Magnuson Clin Ctr, PET Dept, Bethesda, MD 20892 USA. RP Barker, WC (reprint author), NIH, Warren Grant Magnuson Clin Ctr, PET Dept, Bldg 10, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 12 TC 11 Z9 11 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 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD JUN PY 2001 VL 48 IS 3 BP 739 EP 742 DI 10.1109/23.940156 PN 2 PG 4 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 465EH UT WOS:000170576300022 ER PT J AU Cherukuri, A Dykstra, M Pierce, SK AF Cherukuri, A Dykstra, M Pierce, SK TI Floating the raft hypothesis: Lipid rafts play a role in immune cell activation SO IMMUNITY LA English DT Article ID RECEPTOR; TCR; MEMBRANES C1 NIAID, NIH, Immunogenet Lab, Rockville, MD 20852 USA. RP Pierce, SK (reprint author), NIAID, NIH, Immunogenet Lab, Rockville, MD 20852 USA. NR 15 TC 182 Z9 188 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2001 VL 14 IS 6 BP 657 EP 660 DI 10.1016/S1074-7613(01)00156-X PG 4 WC Immunology SC Immunology GA 446CJ UT WOS:000169495100001 PM 11420035 ER PT J AU Chen, WJ Frank, ME Jin, WW Wahl, SM AF Chen, WJ Frank, ME Jin, WW Wahl, SM TI TGF-beta released by apoptotic T cells contributes to an immunosuppressive milieu SO IMMUNITY LA English DT Article ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; MEDIATED ACTIVATION; TARGETED DISRUPTION; AUTOIMMUNE-DISEASE; IMMUNE-RESPONSES; DEATH FACTOR; FAS; TOLERANCE; MICE AB T cell apoptosis is critical to development and homeostasis of the immune system. The most salient feature of apoptosis is the lack of an attendant inflammatory response or tissue damage. Here, we present evidence that apoptotic T cells release TGF-beta, thereby contributing to an immunosuppressive milieu. Apoptotic T cells released not only latent but also bio-active TGF-beta. Nonetheless, TGF-beta transcription was not upregulated, suggesting release of existing rather than synthesis of new TGF-beta. Localized within the intracellular membrane-bound compartment, which includes mitochondria, TGF-beta was redistributed into the cytosol following loss of mitochondrial membrane potential. TGF-beta secreted from apoptotic T cells inhibited proinflammatory cytokine production by activated macrophages to foster immune suppression. These findings broaden the potential mechanisms whereby induction of immune tolerance or deficiency occurs through T cell deletion. C1 Natl Inst Dent & Craniofacial Res, Cellular Immunol Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Cellular Immunol Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NR 51 TC 253 Z9 268 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2001 VL 14 IS 6 BP 715 EP 725 DI 10.1016/S1074-7613(01)00147-9 PG 11 WC Immunology SC Immunology GA 446CJ UT WOS:000169495100008 PM 11420042 ER PT J AU Kalesnikoff, J Huber, M Lam, V Damen, JE Zhang, J Siraganian, RP Krystal, G AF Kalesnikoff, J Huber, M Lam, V Damen, JE Zhang, J Siraganian, RP Krystal, G TI Monomeric IgE stimulates signaling pathways in mast cells that lead to cytokine production and cell survival SO IMMUNITY LA English DT Article ID FC-EPSILON-RI; PROTEIN-KINASE; IN-VIVO; STEEL FACTOR; LIPID RAFTS; GAMMA-RIII; RECEPTOR; ACTIVATION; EXPRESSION; BINDING AB Although IgE binding to mast cells is thought to be a passive presensitization step, we demonstrate herein that monomeric IgE (mIgE) in the absence of antigen (Ag) stimulates multiple phosphorylation events in normal murine bone marrow-derived mast cells (BMMCs). While mIgE does not induce degranulation or leukotriene synthesis, it leads to a more potent production of cytokines than IgE + Ag. Moreover, mIgE prevents the apoptosis of cytokine-deprived BMMCs, likely by maintaining Bcl-X-L levels and producing autocrine-acting cytokines. The addition of Ag does not increase this IgE-induced survival. Since IgE concentrations as low as 0.1 mug/ml enhance BMMC survival, elevated plasma IgE levels in humans with atopic disorders may contribute to the elevated mast cell numbers seen in these individuals. C1 British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. NIDCR, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Univ Freiburg, Dept Mol Immunol Biol 3, D-79108 Freiburg, Germany. Max Planck Inst Immunbiol, D-79108 Freiburg, Germany. RP Krystal, G (reprint author), British Columbia Canc Agcy, Terry Fox Lab, 601 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. NR 48 TC 275 Z9 282 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2001 VL 14 IS 6 BP 801 EP 811 DI 10.1016/S1074-7613(01)00159-5 PG 11 WC Immunology SC Immunology GA 446CJ UT WOS:000169495100015 PM 11420049 ER PT J AU Sawicki, MW Dimasi, N Natarajan, K Wang, J Margulies, DH Mariuzza, RA AF Sawicki, MW Dimasi, N Natarajan, K Wang, J Margulies, DH Mariuzza, RA TI Structural basis of MHC class I recognition by natural killer cell receptors SO IMMUNOLOGICAL REVIEWS LA English DT Review ID C-TYPE LECTIN; MANNOSE-BINDING PROTEIN; LEUKOCYTE ANTIGEN (HLA)-CW4; CRYSTAL-STRUCTURE; INHIBITORY RECEPTOR; T-CELL; 3-DIMENSIONAL STRUCTURE; PEPTIDE DEPENDENCY; ANTIFREEZE PROTEIN; LY-49A RECOGNIZES AB Natural killer (NK)-cell function is regulated by NK receptors that recognize MHC class I (MHC-I) molecules on target cells. Two structurally distinct families of NK receptors have been identified, the immunoglobulin-like family (killer cell immunoglobulin-like receptors (KIRs), leukocyte immunoglobulin-ne receptors (LIRs)) and the C-type lectin-like family (Ly49, CD94/NKG2A, NKG2D, CD69). Recently, the three-dimensional structures of several NK receptors were determined, in free form or bound to MHC-I. These include those of unbound KIRs, NKG2D, CD69, LIR-1 and the CD94 subunit of the CD94/NKG2A heterodimer. Together, these structures define the basic molecular architecture of both the immunoglobulin-like and C-type lectin-like families of NK receptors. In addition, crystal structures hive been reported for the complex between Ly49A and H-2D(d), and for KIRDL2 bound to HLA-Cw3. The complex structures provide a framework for understanding MHC-I recognition by NK receptors from both families and reveal striking differences in the nature of this recognition, despite the receptors' functional similarity. C1 Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Mariuzza, RA (reprint author), Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 FU NIAID NIH HHS [R01 AI47900]; PHS HHS [R37 36900] NR 64 TC 41 Z9 41 U1 1 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2001 VL 181 BP 52 EP 65 DI 10.1034/j.1600-065X.2001.1810104.x PG 14 WC Immunology SC Immunology GA 460ZW UT WOS:000170341300004 PM 11513152 ER PT J AU Boyington, JC Brooks, AG Sun, PD AF Boyington, JC Brooks, AG Sun, PD TI Structure of killer cell immunoglobulin-like receptors and their recognition of the class I MHC molecules SO IMMUNOLOGICAL REVIEWS LA English DT Review ID LEUKOCYTE ANTIGEN (HLA)-CW4; HLA-B ALLOTYPES; COMPLEX CLASS-I; INHIBITORY RECEPTOR; CRYSTAL-STRUCTURE; DIRECT BINDING; NK CELLS; MEDIATED LYSIS; T-CELLS; FUNCTIONAL TRANSFER AB The recognition of class I MHC molecules by killer cell immunoglobulin-like receptors (KIR) constitutes an integral part of immune surveillance by the innate immune system. To understand the molecular basis of this recognition, the structures of several members of this superfamily have been determined. Despite their functional diversity, members of this superfamily share many conserved structural features. A central question is how these receptors recognize their ligands. The recent determination of the crystal structure of KIR2DL2 in complex with HLA-Cw3 has revealed the molecular mechanisms underpinning this interaction, which ultimately modulates the cytolytic activity of natural killer cells. While the recognition of I IHC molecules by KIR is characterized by a number of unique features, some unexpected similarities with T-cell receptor recognition of MHC molecules are also observed. The detailed interactions between KIR2DL2 and HLA-Cw3 and their functional implications will be reviewed here. C1 NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia. RP Sun, PD (reprint author), NIAID, LIG, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 86 TC 63 Z9 66 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2001 VL 181 BP 66 EP 78 DI 10.1034/j.1600-065X.2001.1810105.x PG 13 WC Immunology SC Immunology GA 460ZW UT WOS:000170341300005 PM 11513153 ER PT J AU Anderson, SK Ortaldo, JR McVicar, DW AF Anderson, SK Ortaldo, JR McVicar, DW TI The ever-expanding Ly49 gene family: repertoire and signaling SO IMMUNOLOGICAL REVIEWS LA English DT Review ID NATURAL-KILLER-CELLS; PROTEIN-TYROSINE KINASE; SRC HOMOLOGY-2 DOMAINS; CLASS-I MOLECULES; NK CELLS; INHIBITORY RECEPTORS; PHOSPHATASE SH-PTP1; CYTOPLASMIC DOMAIN; CYTOKINE SECRETION; GAMMA-INTERFERON AB The mouse lectin-related Ly49 family and the human killer cell Ig-like receptor (EM) family represent structurally distinct, yet functionally analogous, class I MHC receptors that are expressed on natural killer cells and some T cells. The functional similarity of these two families has been borne out by the demonstration of identical signal transduction pathways associated with each receptor family. The Ly49 family therefore provides a useful model system to study the role of this class of receptors in the regulation of the immune system. Recent data relating to the Ly49 repertoire in several mouse strains has revealed an additional evolutionary parallel between KIR and Ly49 receptor families. There is now an appreciation of the variation in the number and type of Ly49s expressed in different mouse strains, similar to the previously demonstrated differences in the number of ICR genes found in humans. This review summarizes the current members of the Ly49 gene family, their MHC class I recognition and associated signal transduction pathways. C1 NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. SAIC, Intramural Res Support Program, Frederick, MD USA. RP McVicar, DW (reprint author), NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Bldg 560-Rm 31-93, Frederick, MD 21702 USA. RI Anderson, Stephen/B-1727-2012; McVicar, Daniel/G-1970-2015 OI Anderson, Stephen/0000-0002-7856-4266; FU NCI NIH HHS [N01-CO-56000] NR 70 TC 97 Z9 97 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2001 VL 181 BP 79 EP 89 DI 10.1034/j.1600-065X.2001.1810106.x PG 11 WC Immunology SC Immunology GA 460ZW UT WOS:000170341300006 PM 11513154 ER PT J AU Long, EO Barber, DF Burshtyn, DN Faure, M Peterson, M Rajagopalan, S Renard, V Sandusky, M Stebbins, CC Wagtmann, N Watzl, C AF Long, EO Barber, DF Burshtyn, DN Faure, M Peterson, M Rajagopalan, S Renard, V Sandusky, M Stebbins, CC Wagtmann, N Watzl, C TI Inhibition of natural killer cell activation signals by killer cell immunoglobulin-like receptors (CD158) SO IMMUNOLOGICAL REVIEWS LA English DT Review ID CLASS-I MOLECULES; LINKED LYMPHOPROLIFERATIVE DISEASE; TYROSINE-PHOSPHATASE SHP-1; COMPLEX CLASS-I; DOMAIN-CONTAINING PHOSPHATASE-1; HUMAN NK CELLS; HLA-C; KINASE ACTIVATION; CRYSTAL-STRUCTURE; CUTTING EDGE AB The killer cell immunoglobulin-like receptor (KIR) family includes receptors that bind to HLA class I molecules on target cells and inhibit natural killer (NK)-cell cytotoxicity, and receptors such as KIR3DL7 with no known ligand and function. Inhibitory KIR recruit the tyrosine phosphatase SHP-1 to block signals transduced by any one of a number of activation receptors. Inhibition of overall protein tyrosine phosphorylation by SHP-1 during binding of KIR to MHC class I on target cells is selective, suggesting that a limited number of substrates a-re dephosphorylated by SHP-1. We have chosen to study KIR inhibition as it occurs during binding of KIR to MHC class I on target cells, despite the technical limitations inherent to studies of processes regulated by cell contact. KIR binding to MHC class I on target cells inhibits tyrosine phosphorylation of the activation receptor 2B4 (CD244) and disrupts adhesion of NK cells to target cells. Inhibition of proximal events in NK activation may increase the availability of NK cells by liberating them from non-productive interactions with resistant target cells. As the receptors and the signaling pathways that induce NK cytotoxicity a-re not fully characterized, elucidation of the inhibitory mechanism employed by KIR may provide insight into NK activation. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Univ Alberta, Dept Med Microbiol & Immunol, Heritage Med Res Ctr, Edmonton, AB T6G 2M7, Canada. M&E Biotech, Copenhagen, Denmark. Novo Nordisk AS, DK-2880 Bagsvaerd, Denmark. RP Long, EO (reprint author), NIAID, LIG, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. RI Barber, Domingo/G-1257-2010; Long, Eric/G-5475-2011; Watzl, Carsten/B-4911-2013 OI Barber, Domingo/0000-0001-8824-5405; Long, Eric/0000-0002-7793-3728; Watzl, Carsten/0000-0001-5195-0995 NR 77 TC 103 Z9 105 U1 1 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2001 VL 181 BP 223 EP 233 DI 10.1034/j.1600-065X.2001.1810119.x PG 11 WC Immunology SC Immunology GA 460ZW UT WOS:000170341300019 PM 11513144 ER PT J AU Murphy, WJ Koh, CY Raziuddin, A Bennett, M Longo, DL AF Murphy, WJ Koh, CY Raziuddin, A Bennett, M Longo, DL TI Immunobiology of natural killer cells and bone marrow transplantation: merging of basic and preclinical studies SO IMMUNOLOGICAL REVIEWS LA English DT Review ID VERSUS-HOST DISEASE; HEMATOPOIETIC STEM-CELLS; MURINE NK CELLS; T-CELLS; HLA-E; RECEPTOR EXPRESSION; GRAFT-REJECTION; LY-49 FAMILY; ALLOGRAFTS; MICE AB Natural killer (NK) cells mediate acute rejection of bone marrow, but not solid tissue, allografts in lethally irradiated mice. Precisely how and why this rejection occurs is still unclear. In allogeneic bone marrow transplantation (BMT), a spectrum of results is possible; one result can be marrow graft failure due to host rejection of the graft by NK and T cells and, at the opposite spectrum, the occurrence of graft-versus-host disease (GVHD). Donor NK cells, however, appear capable of improving donor engraftment without giving rise to GVHD and thus may be of use as an immunotherapy following BMT. As NK-cell inhibitory receptors play a role in bone marrow cell rejection, these same inhibitory receptors may also affect NK responses towards tumor cells. It has been demonstrated that blocking the interaction of inhibitory receptors with MHC determinants on tumor cells can result in greater antitumor effects. Thus, NK cells are capable of mediating both positive and negative effects during BMT depending on whether they are of host versus donor origin and their state of activation. Understanding their role in BMT provides insights as to their physiological roles and points the way to potential clinical uses. C1 NCI, Intramural Res Support Program, SAIC, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21701 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Murphy, WJ (reprint author), NCI, Intramural Res Support Program, SAIC, Bldg 567,Room 210, Frederick, MD 21702 USA. RI Koh, Crystal/D-9986-2013 FU NCI NIH HHS [CA36922, CA70134, N01-CO-56000]; NIAID NIH HHS [AI38938] NR 71 TC 57 Z9 66 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2001 VL 181 BP 279 EP 289 DI 10.1034/j.1600-065X.2001.1810124.x PG 11 WC Immunology SC Immunology GA 460ZW UT WOS:000170341300024 PM 11513149 ER PT J AU Rosner, K Winter, DB Tarone, RE Skovgaard, GL Bohr, VA Gearhart, PJ AF Rosner, K Winter, DB Tarone, RE Skovgaard, GL Bohr, VA Gearhart, PJ TI Third complementarity-determining region of mutated V-H immunoglobulin genes contains shorter V, D, J, P, and N components than non-mutated genes SO IMMUNOLOGY LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; ANTIBODY-ANTIGEN COMPLEX; 3-DIMENSIONAL STRUCTURE; B-CELLS; PREFERENTIAL UTILIZATION; JUNCTIONAL DIVERSITY; HEAVY; REPERTOIRE; SEGMENTS; FETAL AB The third complementarity-determining region (CDR3) of immunoglobulin variable genes for the heavy chain (V-H) has been shown to be shorter in length in hypermutated antibodies than in non-hypermutated antibodies. To determine which components of CDR3 contribute to the shorter length, and if there is an effect of age on the length, we analysed 235 cDNA clones from human peripheral blood of V(H)6 genes rearranged to immunoglobulin M (IgM) constant genes. There was similar use of diversity (D) and joining (J(H)) gene segments between clones from young and old donors, and there was similar use of D segments among the mutated and non-mutated heavy chains. However, in the mutated heavy chains, there was increased use of shorter J(H)4 segments and decreased use of longer J(H)6 segments compared to the non-mutated proteins. The overall length of CDR3 did not change with age within the mutated and non-mutated categories, but was significantly shorter by three amino acids in the mutated clones compared to the non-mutated clones. Analyses of the individual components that comprise CDR3 indicated that they were all shorter in the mutated clones. Thus, there were more nucleotides deleted from the ends of V-H, D, and JH gene segments, and fewer P and N nucleotides added. The results suggest that B cells bearing immunoglobulin receptors with shorter CDR3s have been selected for binding to antigen. A smaller CDR3 may allow room in the antibody binding pocket for antigen to interact with CDRs 1 and 2 as well, so that as the VDJ gene undergoes hypermutation, substitutions in all three CDRs can further contribute to the binding energy. C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. Rigshosp, Lab Mol Gerontol & Dermatol, DK-2100 Copenhagen, Denmark. NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA. Bispebjerg Hosp, Dept Dermatol, DK-2400 Copenhagen, Denmark. RP Gearhart, PJ (reprint author), NIA, Mol Genet Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 39 TC 45 Z9 45 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JUN PY 2001 VL 103 IS 2 BP 179 EP 187 DI 10.1046/j.1365-2567.2001.01220.x PG 9 WC Immunology SC Immunology GA 443ZL UT WOS:000169373400007 PM 11412305 ER PT J AU Tsai, YL Hayward, RE Langer, RC Fidock, DA Vinetz, JM AF Tsai, YL Hayward, RE Langer, RC Fidock, DA Vinetz, JM TI Disruption of Plasmodium falciparum chitinase markedly impairs parasite invasion of mosquito midgut SO INFECTION AND IMMUNITY LA English DT Article ID HUMAN MALARIA PARASITE; TRANSMISSION-BLOCKING ANTIBODIES; HUMAN DIHYDROFOLATE-REDUCTASE; PERITROPHIC MEMBRANE; GALLINACEUM; PROTEIN; PENETRATION; PROGUANIL; DOMAINS; PFS28 AB To initiate invasion of the mosquito midgut, Plasmodium ookinetes secrete chitinolytic activity to penetrate the peritrophic matrix surrounding the blood meal. While ookinetes of the avian malaria parasite Plasmodium gallinaceum appear to secrete products of two chitinase genes, to date only one chitinase gene, PfCHT1, has been identified in the nearly completed Plasmodium falciparum strain 3D7 genome database. To test the hypothesis that the single identified chitinase of P. falciparum is necessary for ookinete invasion, the PfCHT1 gene was disrupted 39 bp upstream of the stop codon, PfCHT1-disrupted parasites had normal gametocytogenesis, exflagellation, and ookinete formation but were markedly impaired in their ability to form oocysts in Anopheles freeborni midguts, Confocal microscopy demonstrated that the truncated PfCHT1 protein aas present in mutant ookinetes but, that the concentration of mutant PfCHT1 within the apical end of the ookinetes was substantially reduced. These data suggest that full-length PfCHT1 is essential for intracellular trafficking and secretion and that the PfCHT1 gene product is necessary for ookinetes to invade the mosquito midgut. C1 Univ Texas, Med Branch, Dept Pathol, WHO,Colloborating Ctr Trop Dis, Galveston, TX 77555 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Vinetz, JM (reprint author), Univ Texas, Med Branch, Dept Pathol, WHO,Colloborating Ctr Trop Dis, Keiller 2-138,301 Univ Blvd, Galveston, TX 77555 USA. OI Fidock, David/0000-0001-6753-8938; Vinetz, Joseph/0000-0001-8344-2004 FU NIAID NIH HHS [T32 AI007536, T32-AI07536, R01 AI045999, R01-AI 45999] NR 25 TC 64 Z9 65 U1 1 U2 8 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 JUN PY 2001 VL 69 IS 6 BP 4048 EP 4054 DI 10.1128/IAI.69.6.4048-4054.2001 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 433WU UT WOS:000168784300067 PM 11349075 ER PT J AU Babb, K El-Hage, N Miller, JC Carroll, JA Stevenson, B AF Babb, K El-Hage, N Miller, JC Carroll, JA Stevenson, B TI Distinct regulatory pathways control expression of Borrelia burgdorferi infection-associated OspC and Erp surface proteins SO INFECTION AND IMMUNITY LA English DT Article ID 32-KILOBASE CIRCULAR PLASMIDS; LYME-DISEASE SPIROCHETE; IN-VITRO; DIFFERENTIAL EXPRESSION; MOLECULAR-CLONING; GENE-EXPRESSION; MAMMALIAN HOST; IXODES-RICINUS; MICE; B31 AB Deciphering the mechanisms by which Borrelia. burgdorferi controls the synthesis of proteins associated with mammalian infection will be an important step toward understanding the pathogenic properties of Lyme disease-causing bacteria. We present results of studies indicating that B. burgdorferi senses a wide variety of environmental stimuli, including soluble chemicals, which enables it to independently control synthesis of the Erp and OspC proteins. Regulation of OspC and Erp expression appears to occur at the level of transcription. In this regard, we observed that one or more DNA-binding proteins interact specifically with erp promoter DNA but not with the ospC promoter. C1 Univ Kentucky, Coll Med, Dept Microbiol & Immunol, Lexington, KY 40536 USA. NIAID, Microscopy Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Stevenson, B (reprint author), Univ Kentucky, Coll Med, Dept Microbiol & Immunol, MS 415 Chandler Med Ctr, Lexington, KY 40536 USA. FU NIAID NIH HHS [R01-AI44254, R01 AI044254] NR 54 TC 46 Z9 47 U1 0 U2 0 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 JUN PY 2001 VL 69 IS 6 BP 4146 EP 4153 DI 10.1128/IAI.69.6.4146-4153.2001 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 433WU UT WOS:000168784300082 PM 11349090 ER PT J AU Feng, CG Palendira, U Demangel, C Spratt, JM Malin, AS Britton, WJ AF Feng, CG Palendira, U Demangel, C Spratt, JM Malin, AS Britton, WJ TI Priming by DNA immunization augments protective efficacy of Mycobacterium bovis bacille Calmette-Guerin against tuberculosis SO INFECTION AND IMMUNITY LA English DT Article ID CD8(+) T-CELLS; PLASMID DNA; VACCINATION; INFECTION; MICE; IMMUNOGENICITY; VIRUS; RESISTANCE; STRATEGIES; DEFICIENT AB Sequential immunization with mycobacterial antigen Ag85B-expressing DNA and Mycobacterium bovis bacille Calmette-Guerin (BCG) was more effective than BCG immunization in protecting against Mycobacterium tuberculosis infection. Depletion of the CD8(+) T cells in the immunized mice impaired protection in their spleens, indicating that this improved efficacy was partially mediated by CD8(+) T cells. C1 Centenary Inst Canc Med & Cell Biol, Newtown, NSW 2042, Australia. Univ Sydney, Dept Med, Sydney, NSW 2006, Australia. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Inst Pasteur, Lab Ingn Anticorps, F-75724 Paris 15, France. Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England. RP Britton, WJ (reprint author), Centenary Inst Canc Med & Cell Biol, Locked Bag 6, Newtown, NSW 2042, Australia. RI Demangel, Caroline/H-9570-2014 NR 20 TC 105 Z9 121 U1 0 U2 2 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 JUN PY 2001 VL 69 IS 6 BP 4174 EP 4176 DI 10.1128/IAI.69.6.4174-4176.2001 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 433WU UT WOS:000168784300087 PM 11349095 ER PT J AU Wang, L Yan, L McGuire, C Kozak, CA Wang, M Kim, UJ Siciliano, M Weinshilboum, RM AF Wang, L Yan, L McGuire, C Kozak, CA Wang, M Kim, UJ Siciliano, M Weinshilboum, RM TI Mouse histamine N-methyltransferase: cDNA cloning, expression, gene cloning and chromosomal localization SO INFLAMMATION RESEARCH LA English DT Article DE histamine N-methyltransferase; histamine; methylation; mouse cDNA; mouse gene ID NUCLEOTIDE-SEQUENCE; PHARMACOGENETICS; RAT; PROTEIN; RNA; POLYMORPHISM; METABOLISM; CATABOLISM; BINDING; KIDNEY AB Objective: Histamine N-methyltransferase (HNMT) catalyzes the N-tau-methylation of histamine. We set out to clone a mouse liver HNMT cDNA and the mouse HNMT gene as steps toward characterizing molecular genetic mechanisms involved in the regulation of this important histamine-metabolizing enzyme. Design: A PCR-based strategy was used to clone both the mouse HNMT cDNA and the gene encoding that cDNA, Hnmt. The cDNA was used both to express recombinant mouse HNMT and to determine the chromosomal localization of Hnmt. Results: The mouse liver HNMT cDNA was 1657 bp in length with an 888 bp open reading frame (ORF) that encoded a 296 amino acid protein with a predicted Mr value of approximately 32.5 kDa. The amino acid sequence of the encoded protein was 84% identical to that of human kidney HNMT. Mouse HNMT was expressed in COS-1 cells, and its apparent K-m values for histamine and S-adenosyl-L-methionine (Ado-Met), the two cosubstrates for the reaction, were 5.3 and 5.8 muM, respectively. The mouse HNMT gene, Hnmt, spanned approximately 25 kb and had 7 exons. Its structure differed from that of the human gene primarily by the presence of an additional exon at the 5'-terminus. Hnmt mapped to mouse chromosome 2 in an area of conserved synteny to human chromosome 2q, the location of the human gene (2q22) on the basis of fluorescence in situ hybridization. Conclusions: Cloning and functional characterization of the mouse HNMT cDNA and gene will now make it possible to study in the mouse molecular genetic mechanisms involved the regulation of this important histamine-metabolizing enzyme. C1 Mayo Clin & Mayo Fdn, Mayo Grad Sch, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA. NIAID, Mol Med Lab, NIH, Bethesda, MD 20892 USA. CALTECH, Div Biol, Genome Res Lab, Pasadena, CA 91125 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. RP Weinshilboum, RM (reprint author), Mayo Clin & Mayo Fdn, Mayo Grad Sch, Dept Mol Pharmacol & Expt Therapeut, 200 1st St SW, Rochester, MN 55905 USA. FU NCI NIH HHS [R01 CA34936]; NIGMS NIH HHS [UO1 GM61388, R01 GM35720, R01 GM28157] NR 39 TC 5 Z9 6 U1 0 U2 1 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD JUN PY 2001 VL 50 IS 6 BP 300 EP 308 DI 10.1007/PL00000248 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 450JC UT WOS:000169738000003 PM 11475331 ER PT J AU Dastych, J Wyczolkowska, J Metcalfe, DD AF Dastych, J Wyczolkowska, J Metcalfe, DD TI Characterization of alpha 5-integrin-dependent mast cell adhesion following Fc epsilon RI aggregation SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE adhesion to fibronectin; integrins; mouse mast cells; IgE cross-linking ID EXTRACELLULAR-MATRIX PROTEINS; AFFINITY MODULATION; KINASE-C; FIBRONECTIN; RECEPTORS; STAUROSPORINE; VITRONECTIN; MONOCYTES; LAMININ AB Background: Integrin receptors are engaged in the upregulation of mast cell adhesion to extracellular matrix components upon stimulation with cytokines and antigen. Fibronectin receptor containing the alpha5-integrin subunit is critical for mast cell interaction with the extracellular matrix protein fibronectin (FN). Methods: The murine MCP5/L mast cell line was employed to investigate the process of Fc epsilon RI-mediated mast cell adhesion to FN. RT-PCR and cytofluorimetric analysis were used to assess the expression of alpha5 integrin in MCP5/L mast cells. Radiolabelled mast cells were sensitized with monoclonal IgE and used in adhesion assays. Anti-alpha5-integrin antibody (Ab), mo nova rent hapten and metabolic inhibitors were used to characterize antigen-mediated mast cell adhesion to FN. Results: Addition of antigen to IgE-sensitized cells resulted in transient upregulation of mast cell adhesion to FN with a maximum adhesion following 30 min of incubation. Mast cell adhesion was inhibited with anti-alpha5-integrin monoclonal antibodies blocking FN receptor or with excess monovalent hapten preventing antigen-mediated IgE cross-linking. The presence of the protein kinase C (PKC) inhibitor staurosporine also inhibited mast cell adhesion in a dose-dependent fashion. The process of Fc epsilon RI-mediated upregulation of mast cell adhesion to FN was not associated with an increase in surface expression of mast cell FN receptors. Conclusion: The major FN receptor on MCP5/L mast cell surface, an integrin containing the a5 subunit mediates a transient change in mast cell adhesiveness following IgE cross-linking. Fc epsilon RI-derived signals engage PKC and upregulate mast cell adhesion in a process which might involve changes in integrin avidity rather than integrin expression. Copyright (C) 2001 S. Karger AG, Basel. C1 Polish Acad Sci, Dept Biogenic Amines, PL-90950 Lodz, Poland. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Dastych, J (reprint author), Polish Acad Sci, Dept Biogenic Amines, POB 225, PL-90950 Lodz, Poland. NR 20 TC 7 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD JUN PY 2001 VL 125 IS 2 BP 152 EP 159 DI 10.1159/000053809 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 450JE UT WOS:000169738300008 PM 11435732 ER PT J AU Portugal, K Dozmorov, I Sidorov, I Marrero, I Fonseca, JA Spadafora-Ferreira, M Kalil, J Coelho, V AF Portugal, K Dozmorov, I Sidorov, I Marrero, I Fonseca, JA Spadafora-Ferreira, M Kalil, J Coelho, V TI Renal transplant patients show variations in their self-reactive repertoires: a serial study SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE autologous limiting dilution assay; autoreactivity; multi-hit limiting dilution assay; regulatory cells; renal transplantation ID LIMITING DILUTION ANALYSIS; MIXED LYMPHOCYTE-REACTION; T-CELL RESPONSES; VERSUS-HOST DISEASE; AUTOIMMUNE-DISEASES; MULTIPLE-SCLEROSIS; IMMUNOLOGICAL SELF; PROTEIN; CLONES; MICE AB We addressed the question of whether allo-transplantation (Tx) induces breakdown of tolerance to self-antigens or alteration of the autoreactive T cell repertoire in humans. The serial variation of T cell autoreactivity was studied in the peripheral blood of 12 renal transplant patients, by autologous limiting dilution assay and autologous mixed lymphocyte reaction. Ten of 12 patients presented a positive response in autologous peripheral blood mononuclear cells in the post-Tx period, in contrast to four of 12 patients before Tx (P = 0.038), Multi-hit kinetics was found in 57% of the assays analyzed, indicating frequent regulatory control of the autologous response. Quantitative analysis performed in eight patients showed an increase in precursor frequency at >1 year post-Tx in five patients. These data indicate that autoreactivity increases or develops following Tx, in humans. Post-Tx events such as alloreactivity, infections or immunosuppression could interfere with the balance of autoreactive and regulatory cells, leading to changes in the T cell repertoires to self-antigens and eventually breakdown of self-tolerance, Further investigation is needed to elucidate whether post-Tx autoreactivity contributes to rejection, plays a regulatory role over alloreactivity or both, at separate times. C1 Univ Sao Paulo, Sch Med, Hosp Clin, Heart Inst InCor, BR-05403000 Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Hosp Clin, Div Renal Transplantat, BR-05403000 Sao Paulo, Brazil. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. NCI, NIH, Frederick, MD 21702 USA. RP Coelho, V (reprint author), Univ Sao Paulo, Sch Med, Hosp Clin, Heart Inst InCor, Av Dr Eneas de Carvalho Aguiar 500,3A, BR-05403000 Sao Paulo, Brazil. RI Spadafora-Ferreira, Monica/G-2635-2012; COELHO, VERONICA/D-1433-2013 OI Spadafora-Ferreira, Monica/0000-0001-8823-9929; NR 60 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 2001 VL 13 IS 6 BP 747 EP 755 DI 10.1093/intimm/13.6.747 PG 9 WC Immunology SC Immunology GA 440PU UT WOS:000169184100004 PM 11369701 ER PT J AU Lechner, O Dietrich, H Wiegers, GJ Vacchio, M Wick, G AF Lechner, O Dietrich, H Wiegers, GJ Vacchio, M Wick, G TI Glucocorticoid production in the chicken bursa and thymus SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE B cell development; ectopic steroidogenesis; T cell development ID T-CELL DEVELOPMENT; THYMIC EPITHELIAL-CELLS; THYMOCYTE APOPTOSIS; POSITIVE SELECTION; 3-BETA-HYDROXYSTEROID DEHYDROGENASE; FEEDBACK LOOP; IN-VITRO; ACTIVATION; CORTISOL; RAT AB Glucocorticoid (GC) hormones play an important role in thymic T cell selection and in the development of autoimmune diseases. Previous studies have shown that the mammalian thymus itself is able to produce GC, In order to assess the importance of these findings in terms of the evolutionary development of the immune system, we investigated the functional presence of steroidogenic enzymes in primary lymphoid organs of chickens, which represent one of the best studied non-mammalian species. To this end, we attempted to demonstrate enzyme activities of the whole set of steroidogenic enzymes for the synthesis of GC in the bursa of Fabricius and the thymus, We isolated steroidogenic organelles from primary lymphoid tissues, incubated these with radioactive (precursor) steroids in vitro and visualized the resulting products by thin-layer chromatography. Our results show that the chicken bursa as well as the chicken thymus possesses all enzymes end cofactors required for GC production, The observation of GC production in an organ responsible for a cell selection and maturation is a further step in uncovering the yet ill-defined mechanism of a cell selection. These results provide the biochemical basis for the in situ hormonal effects, and underline the general importance of GC hormones on T and a lymphocyte development and selection. C1 Univ Innsbruck, Sch Med, Inst Gen & Expt Pathol, A-6020 Innsbruck, Austria. Univ Innsbruck, Sch Med, Cent Lab Anim Facil, A-6020 Innsbruck, Austria. German Res Ctr Biotechnol, Mucosal Immun Grp, D-38124 Braunschweig, Germany. NCI, Lab Immune Cell Biol, Bethesda, MD 20892 USA. RP Wick, G (reprint author), Univ Innsbruck, Sch Med, Inst Gen & Expt Pathol, Fritz Pregl Str 3-4, A-6020 Innsbruck, Austria. NR 46 TC 43 Z9 43 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 2001 VL 13 IS 6 BP 769 EP 776 DI 10.1093/intimm/13.6.769 PG 8 WC Immunology SC Immunology GA 440PU UT WOS:000169184100007 PM 11369704 ER PT J AU Zhu, JH Shearer, GM Marincola, FM Norman, JE Rott, D Zou, JP Epstein, SE AF Zhu, JH Shearer, GM Marincola, FM Norman, JE Rott, D Zou, JP Epstein, SE TI Discordant cellular and humoral immune responses to cytomegalovirus infection in healthy blood donors: existence of a T(h)1-type dominant response SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE antibody; cellular proliferation; cytokines; infectious immunity; virus ID MONONUCLEAR-CELLS; VIRUS-INFECTION; RISK FACTOR; T-CELLS; ATHEROSCLEROSIS; TYPE-1; TRANSPLANTATION; SUSCEPTIBILITY; RESPONSIVENESS; ASSOCIATION AB Previous studies have documented discordant cellular and humoral immune responses to subjects exposed to HIV-1, and that the nature of such responses may determine susceptibility and resistance to disease. We determined whether there is a spectrum of cellular versus humoral immunodominant responses to cytomegalovirus (CMV) infection. Blood samples from 50 healthy blood donors were tested for anti-CMV IgG antibodies and for proliferative responses of peripheral blood mononuclear cells (PBMC) to CMV antigens, Four patterns of immune responses to CMV were found: no detectable response (30%, Ab(-)/Tc-), anti-CMV IgG only (28%, Ab(+)/Tc-), both anti-CMV IgG and T lymphocyte proliferation to CMV antigens (18%, Ab(+)/Tc+), and, interestingly, T lymphocyte proliferation to CMV only (24%, Ab(-)/Tc+). To determine whether these immunodominant phenotypes correlate with the ability of PBMC to secrete IL-2 and IFN-gamma in response to CMV antigens, we found that a greater percentage of individuals with a T cell proliferative response to CMV antigens (Ab(-/)Tc(+) and Ab(+/)Tc(+)) responded with increased IL-2 (P = 0.001) and IFN-gamma levels (P = 0.002), compared to those without a proliferative response (Ab(-)/Tc- and Ab(+)/Tc-). Our data therefore demonstrate that different individuals exhibit different immunodominant patterns of response to CMV. In particular, some individuals who are exposed to CMV fail to develop an antibody response but do develop cellular immunity. Whether these different patterns predict susceptibility or resistance to CMV-induced disease remains to be determined. C1 Washington Hosp Ctr, Cardiovasc Res Inst, Washington, DC 20010 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Epstein, SE (reprint author), Washington Hosp Ctr, Cardiovasc Res Inst, 110 Irving St NW,Suite 4B-1, Washington, DC 20010 USA. NR 32 TC 28 Z9 29 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 2001 VL 13 IS 6 BP 785 EP 790 DI 10.1093/intimm/13.6.785 PG 6 WC Immunology SC Immunology GA 440PU UT WOS:000169184100009 PM 11369706 ER PT J AU Derby, MA Wang, J Margulies, DT Berzofsky, JA AF Derby, MA Wang, J Margulies, DT Berzofsky, JA TI Two intermediate-avidity cytotoxic T lymphocyte clones with a disparity between functional avidity and MHC tetramer staining SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE antigen binding; FACS; TCR; vaccinia; mouse ID CLASS-I; CELL ACTIVATION; HIV-1 GP160; PEPTIDE; COMPLEXES; VIRUS; MOLECULE; CTL; STIMULATION; SPECIFICITY AB The efficacy of cytotoxic T lymphocytes (CTL) has been shown to be highly dependent upon their functional avidity (the sensitivity of their cellular response to MHC-peptide complexes), To examine this relationship, we employed target cell lysis as a quantitative measure and established a set of four CTL clones that exhibited a range of functional avidities spanning more than three orders of magnitude. Within this set, clones displayed a linear correlation between functional avidity and the TCR down-regulation that occurred in response to increasing antigen density. Staining intensity of MHC-peptide tetramer, however, correlated only with the very highest and very lowest avidity clones; the two intermediate-avidity clones showed an inverse relationship between tetramer staining and functional avidity. Compensation for differences in surface levels of TCR improved the correlation, but failed to fully account for this discrepancy. Comparison of TCR signals generated by stimulation of CTL with substrate-bound soluble MHC-peptide or antigen-presenting cells suggested that internal TCR signaling efficiency accounts for at least a portion of the observed functional avidity and suggests the need for caution in directly relating tetramer staining to avidity. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 27 TC 49 Z9 49 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 2001 VL 13 IS 6 BP 817 EP 824 DI 10.1093/intimm/13.6.817 PG 8 WC Immunology SC Immunology GA 440PU UT WOS:000169184100013 PM 11369710 ER PT J AU Panza, JA AF Panza, JA TI Real-time three-dimensional echocardiography: An overview SO INTERNATIONAL JOURNAL OF CARDIAC IMAGING LA English DT Article DE cardiac ultrasound; three-dimensional echocardiography; ventricular function ID VOLUMETRIC IMAGING-SYSTEM; 3-DIMENSIONAL ECHOCARDIOGRAPHY; DISPLAY AB Conventional echocardiography and its representation of the heart in a two-dimensional format only provide partial information about cardiac function. Real-time three-dimensional echocardiography is a recently developed technique based on the design of an ultrasound transducer with a matrix array that instantaneously acquires the image contained in a pyramidal volume. The simultaneous display of multiple tomographic images allows the anatomically correct examination of any structure contained within the volumetric image. Software and technologies based on high performance computers designed for graphic handling of three-dimensional images permit the rapid mapping of the volumetric image and provide possibilities beyond those of the echograph. Using this methodology, it is possible to simultaneously visualize multiple superimposed planes in an interactive manner. Real-time three-dimensional echocardiography also allows a quantitative assessment of cardiac volumes, ventricular mass, and myocardium with contraction and/or perfusion abnormalities. This technique thus expands the abilities of non-invasive cardiology and may open new doors for the evaluation of cardiac disease. C1 NHLBI, Sect Echocardiog, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Panza, JA (reprint author), Washington Hosp Ctr, 110 Irving St NW,Suite 2A-74, Washington, DC 20010 USA. NR 11 TC 25 Z9 37 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-9899 J9 INT J CARDIAC IMAG JI Int. J. Card. Imaging PD JUN PY 2001 VL 17 IS 3 BP 227 EP 235 DI 10.1023/A:1010669009889 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 460BV UT WOS:000170286700009 PM 11587457 ER PT J AU Luo, T Matsuo-Takasaki, M Lim, JH Sargent, TD AF Luo, T Matsuo-Takasaki, M Lim, JH Sargent, TD TI Differential regulation of Dlx gene expression by a BMP morphogenetic gradient SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE Xenopus; ectoderm; Dlx3; Dlx5; Dlx6 ID DISTAL-LESS; HOMEOBOX GENES; NEURAL PLATE; BRANCHIAL ARCHES; MICE LACKING; XENOPUS; MUTATIONS; FOREBRAIN; TISSUE AB Three members of the vertebrate Distal-less gene family, DIx3, 5 and 6, are transcribed in early gastrula embryos of Xenopus laevis. This expression is confined to ectoderm and is excluded from the presumptive neural plate region. Expression of all three genes is dependent upon BMP signaling, with significant differences in how the three genes respond to the BMP antagonist chordin. This correlates with the different expression domain boundaries in vivo for DIx3 compared to DIx5 and 6, suggesting that BMP signal attenuation could be the primary factor in determining these different patterns in the gastrula ectoderm. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Sargent, TD (reprint author), NICHHD, Mol Genet Lab, NIH, Bldg 6B,Rm 412,NIH MSC 2790,6 Ctr Dr, Bethesda, MD 20892 USA. NR 27 TC 63 Z9 64 U1 0 U2 2 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD JUN PY 2001 VL 45 IS 4 BP 681 EP 684 PG 4 WC Developmental Biology SC Developmental Biology GA 452RP UT WOS:000169872800008 PM 11461005 ER PT J AU Weed, DL AF Weed, DL TI Commentary: A radical future for public health SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE causation; epidemiology; ethics; prevention; public health; screening ID EPIDEMIOLOGY; PREVENTION; SCIENCE; CANCER; POLICY; IDENTIFICATION; RESPONSIBILITY; INTERVENTION; POPULATIONS; PROMOTION C1 NCI, Off Prevent Oncol, Bethesda, MD 20892 USA. RP Weed, DL (reprint author), NCI, Off Prevent Oncol, EPS T-41,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 39 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 2001 VL 30 IS 3 BP 440 EP 441 DI 10.1093/ije/30.3.440 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 449TM UT WOS:000169703300007 PM 11416060 ER PT J AU Johnson, JM Harrod, R Franchini, G AF Johnson, JM Harrod, R Franchini, G TI Molecular biology and pathogenesis of the human T-cell leukaemia/lymphotropic virus type-1 (HTLV-1) SO INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY LA English DT Review ID I-ASSOCIATED MYELOPATHY; CREB-BINDING-PROTEIN; TROPICAL SPASTIC PARAPARESIS; NF-KAPPA-B; READING-FRAME-I; CHRONIC PROGRESSIVE MYELOPATHY; LEUKEMIA-VIRUS; TAX PROTEIN; CONSTITUTIVE ACTIVATION; TRANSCRIPTION FACTORS AB Retroviruses are associated with a variety of diseases, including immunological and neurological disorders, and various forms of cancer. In humans, the Human T-cell Leukaemia/Lymphotropic virus type 1 (HTLV-1), which belongs to the Oncovirus family, is the aetiological agent of two diverse diseases: Adult T-cell leukaemia/lymphoma (ATLL) (Poiesz et al. 1980; Hinuma et al. 1981; Yoshida et al. 1982), as well as the neurological disorder tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) (Gessain et al. 1985; Rodgers-Johnson et al. 1985; Osame et al. 1986). HTLV-1 is the only human retrovirus known to be the aetiological agent of cancer. A genetically related virus, HTLV-2, has been identified and isolated (Kalyanaraman et al. 1982). However, there has been no demonstration of a definitive aetiological role for HTLV-2 in human disease to date. Simian T-cell lymphotropic viruses types 1 and 2 (STLV-1 and -2) and bovine leukaemia virus (BLV) have also been classified in same group, Oncoviridae, based upon their similarities in genetic sequence and structure to HTLV-1 and -2 (Burny et al. 1988; Dekaban et al. 1995; Slattery et al. 1999). This article will focus on HTLV-1, reviewing its discovery, molecular biology, and its role in disease pathogenesis. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41 Lib Dr,Bldg 41,Room D804,MSC 5055, Bethesda, MD 20892 USA. NR 154 TC 62 Z9 62 U1 2 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0959-9673 J9 INT J EXP PATHOL JI Int. J. Exp. Pathol. PD JUN PY 2001 VL 82 IS 3 BP 135 EP 147 DI 10.1046/j.1365-2613.2001.00191.x PG 13 WC Pathology SC Pathology GA 462BL UT WOS:000170400000001 PM 11488989 ER PT J AU Brown, GK Bruce, ML Pearson, JL AF Brown, GK Bruce, ML Pearson, JL CA PROSPECT Study Grp TI High-risk management guidelines for elderly suicidal patients in primary care settings SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE suicide prevention; older adults; suicide risk management; primary care ID DEPRESSION AB Older adults, especially older white men, are more likely to commit suicide than other age-groups. The assessment and management of suicide ideation and behavior for the elderly is especially relevant for primary care physicians because many patients visit their physician shortly before committing suicide. In 1993, the Agency for Health Care Policy and Research (AHCPR) released clinical practice guidelines for the treatment of depression in primary care settings. The AHCPR guidelines offered some assistance with respect to detecting and treating patients who are suicidal. However, these guidelines lacked detailed and specific instructions for managing high-risk patients within the context of intervention research. The current set of guidelines builds upon this previous work by describing (1) a general approach for interacting with suicidal patients; (2) structured assessments for determining the degree of risk for suicide; (3) crisis intervention strategies; and (4) ongoing management procedures for working with suicidal patients in primary care settings. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 Univ Penn, Philadelphia, PA 19104 USA. Cornell Univ, Weill Med Coll, White Plains, NY USA. NIMH, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Brown, GK (reprint author), Ctr Sci, Room 754,3600 Market St, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [P30 MH52247, R01 MH59380, P30 MH25129, R01 MH59381, P30 MH49762, R01 MH59366] NR 26 TC 29 Z9 29 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JUN PY 2001 VL 16 IS 6 BP 593 EP 601 DI 10.1002/gps.468 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 448TW UT WOS:000169646900006 PM 11424168 ER PT J AU March, JS Vitiello, B AF March, JS Vitiello, B TI Advances in paediatric neuropsychopharmacology: an overview SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE neuropsychopharmacology; child; adolescent; NIMH; treatment; diagnosis; PANDAS ID OBSESSIVE-COMPULSIVE-DISORDER; PEDIATRIC NEUROPSYCHIATRIC DISORDERS; DEFICIT HYPERACTIVITY DISORDER; TOURETTES-SYNDROME; RHEUMATIC-FEVER; MENTAL-ILLNESS; CHILDREN; ADOLESCENTS; PSYCHOPHARMACOLOGY; METHYLPHENIDATE AB This Special Section of the International Journal of Neuropsychopharmacology highlights current progress in paediatric neuropsychopharmacology. Combining critical reviews and, in some cases, new data, specific topics include: biological findings in major depression, sleep dysregulation in depressed youth, cardiovascular and ventilatory dysregulation in panic disorder, paediatric autoimmune neuropsychiatric disorder associated with strep (PANDAS), age of onset as a subtype marker in tic and obsessive-compulsive disorders (OCD), functional and pharmaconeuroanatomy of OCD and the behavioural pharmacokinetics of methylphenidate. In this introductory section, these articles are placed in the context of the state-of-the field and, more specifically, within the framework of recent NIMH initiatives in paediatric neuropsychopharmacology. C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Psychol Social & Hlth Sci, Durham, NC 27710 USA. NIMH, Child & Adolescent Treatment Intervent Res Branch, Bethesda, MD 20892 USA. RP March, JS (reprint author), Duke Univ, Med Ctr, Dept Psychiat, Box 3527, Durham, NC 27710 USA. NR 54 TC 5 Z9 5 U1 3 U2 4 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2001 VL 4 IS 2 BP 141 EP 147 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 452HU UT WOS:000169852900007 PM 11466164 ER PT J AU Leonard, HL Swedo, SE AF Leonard, HL Swedo, SE TI Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE obsessive-compulsive disorder; tic disorders; Tourette syndrome; streptococcal infection; basal ganglia disease ID OBSESSIVE-COMPULSIVE DISORDER; ACUTE RHEUMATIC-FEVER; CHRONIC TIC DISORDER; 7-YEAR FOLLOW-UP; TOURETTES-SYNDROME; SYDENHAMS CHOREA; ANTINEURONAL ANTIBODIES; LYME-DISEASE; PLASMA-EXCHANGE; BASAL GANGLIA AB The evidence to date. both published and unpublished, which addresses the validity of the proposed unique subgroup of children with early and abrupt onset of obsessive-compulsive disorder (OCD) and/or tic disorders subsequent to streptococcal infections was reviewed. The aetiology of OCD and tic disorders is unknown, although it appears that both disorders may arise from a variety of genetic and environmental factors. Post-streptococcal autoimmunity has been postulated as one possible mechanism for some. The acronym PANDAS (for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been given to a subgroup of paediatric patients who meet five inclusionary criteria: presence of OCD and/or tic disorder, pre-pubertal symptom onset, sudden onset or episodic course of symptoms, temporal association between streptococcal infections and neuropsychiatric symptom exacerbations, and associated neurological abnormalities. The proposed model of pathophysiology provides for several unique treatment strategies, including the use of antibiotic prophylaxis to prevent streptococcal-triggered exacerbations, and the use of immunomodulatory interventions (such as intravenous immunoglobulin or therapeutic plasma exchange) in the treatment severe neuropsychiatric symptoms. For the latter study group, long-term (2-5 yr) follow-up revealed continued symptom improvement for the majority of patients, particularly when antibiotic prophylaxis had been effective in preventing recurrent streptococcal infections. In addition, the episodic nature of the subgroup's illness provides for opportunities to study brain structure and function during health and disease, as well as allowing for investigations of the aetiologic role of anti-neuronal antibodies and neuroimmune dysfunction in both OCD and tic disorders. Although much research remains to be done, an increasing body of evidence provides support for the postulate that OCD and tic disorders may arise from post-streptococcal autoimmunity. The unique clinical characteristics of the PANDAS subgroup, the presence of volumetric changes in the basal ganglia, and the dramatic response to immunomodulatory treatments, suggest that symptoms arise from a combination of local, regional and systemic dysfunction. Ongoing research is directed at understanding the nature of the abnormal immune response, as well as identifying at-risk children, in order to provide for novel strategies of prevention and treatment. C1 Brown Univ, Dept Psychiat, Providence, RI 02903 USA. NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. RP Leonard, HL (reprint author), Rhode Isl Hosp, 593 Eddy St, Providence, RI 02903 USA. NR 53 TC 63 Z9 66 U1 5 U2 8 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2001 VL 4 IS 2 BP 191 EP 198 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 452HU UT WOS:000169852900012 PM 11466169 ER PT J AU Tomovska, S Richter, J Suess, K Wagner, U Rozenblum, E Gasser, TC Moch, H Mihatsch, MJ Sauter, G Schraml, P AF Tomovska, S Richter, J Suess, K Wagner, U Rozenblum, E Gasser, TC Moch, H Mihatsch, MJ Sauter, G Schraml, P TI Molecular cytogenetic alterations associated with rapid tumor cell proliferation in advanced urinary bladder cancer SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE bladder neoplasm; comparative genomic hybridization; Ki67 LI; tumor cell proliferation; chromosome 6p ID COMPARATIVE GENOMIC HYBRIDIZATION; CYCLIN D1 OVEREXPRESSION; GROWTH-FACTOR RECEPTORS; CHROMOSOMAL IMBALANCES; OVER-EXPRESSION; AMPLIFICATION; CARCINOMA; PATTERNS; GENE AB Invasive urinary bladder carcinomas are characterized by a high number of cytogenetic alterations which are thought to pinpoint the location of critical genes, some of which may be involved in cell cycle control. To identify genomic alterations that may affect such genes the proliferative activity (Ki67 labeling index) was assessed in 93 invasively growing bladder carcinomas analyzed by comparative genomic hybridization. Only a few changes were significantly associated with rapid tumor cell proliferation, including 3p+ (p=0.0357), 6p+ (p=0.003), 8q+ (p=0.0273), and 11q- (p=0.0329). Among these alterations 6p+ is of particular interest because high level 6p22 amplifications occur frequently in bladder cancel. The particular strong association between 6p+ and a high tumor cell proliferation being independent of grade and stage suggests that a putative oncogene on 6p22 involved in cell cycle regulation. C1 Univ Basel, Inst Pathol, CH-4031 Basel, Switzerland. Univ Basel, Urol Clin, CH-4031 Basel, Switzerland. NHGRI, Canc Genet Lab, NIH, Bethesda, MD 20892 USA. RP Schraml, P (reprint author), Univ Basel, Inst Pathol, CH-4031 Basel, Switzerland. NR 22 TC 19 Z9 21 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUN PY 2001 VL 18 IS 6 BP 1239 EP 1244 PG 6 WC Oncology SC Oncology GA 434UM UT WOS:000168834300016 PM 11351257 ER PT J AU Weber, AM Abrams, P Brubaker, L Cundiff, G Davis, G Dmochowski, RR Fischer, J Hull, T Nygaard, I Weidner, AC AF Weber, AM Abrams, P Brubaker, L Cundiff, G Davis, G Dmochowski, RR Fischer, J Hull, T Nygaard, I Weidner, AC TI The standardization of terminology for researchers in female pelvic floor disorders SO INTERNATIONAL UROGYNECOLOGY JOURNAL AND PELVIC FLOOR DYSFUNCTION LA English DT Article DE clinical research; fecal incontinence; pelvic organ prolapse; standardization of terminology; urinary incontinence ID URINARY-TRACT DYSFUNCTION; QUALITY-OF-LIFE; FECAL INCONTINENCE; WOMEN; CONSTIPATION; PROLAPSE; SYMPTOMS AB The lack of standardized terminology in pelvic floor disorders (pelvic organ prolapse, urinary incontinence, and fecal incontinence) is a major obstacle to performing and interpreting research. The National Institutes of Health convened the Terminology Workshop for Researchers in Female Pelvic Floor Disorders to: (1) agree on standard terms for defining conditions and outcomes; (2) make recommendations for minimum data collection for research; and (3) identify high priority issues for future research. Pelvic organ prolapse was defined by physical examination staging using the International Continence Society system. Stress urinary incontinence was defined by symptoms and testing; 'cure' was defined as no stress incontinence symptoms, negative testing, and no new problems due to intervention. Overactive bladder was defined as urinary frequency and urgency, with and without urge incontinence. Detrusor instability was defined by cystometry. For all urinary symptoms, defining 'improvement' after intervention was identified as a high priority. For fecal incontinence, more research is needed before recommendations can be made. A standard terminology for research on pelvic floor disorders is presented and areas of high priority for future research are identified. C1 NICHHD, Populat Res Ctr, Bethesda, MD 20892 USA. Southmead Hosp, Bristol Urol Inst, Bristol, Avon, England. Rush Med Coll, Chicago, IL 60612 USA. Johns Hopkins Univ, Baltimore, MD USA. Madigan Army Med Ctr, Tacoma, WA 98431 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Wright Patterson AFB 74th Med Grp, Wright Patterson AFB, OH USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Iowa, Iowa City, IA USA. Duke Univ, Durham, NC USA. RP Weber, AM (reprint author), NICHHD, Populat Res Ctr, 6100 Execut Blvd,8B-13C, Bethesda, MD 20892 USA. NR 21 TC 209 Z9 234 U1 0 U2 10 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J PEL JI Int. Urogynecol. J. Pelvic Floor Dysfunct. PD JUN PY 2001 VL 12 IS 3 BP 178 EP 186 DI 10.1007/PL00004033 PG 9 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 449UM UT WOS:000169705600007 PM 11451006 ER PT J AU Ma, JX Zhang, JZ Othersen, KL Moiseyev, G Ablonczy, Z Redmond, TM Chen, YM Crouch, RK AF Ma, JX Zhang, JZ Othersen, KL Moiseyev, G Ablonczy, Z Redmond, TM Chen, YM Crouch, RK TI Expression, purification, and MALDI analysis of RPE65 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; MEMBRANE-RECEPTOR; BINDING PROTEIN; CONGENITAL AMAUROSIS; MICROSOMAL PROTEIN; MOUSE MODEL; MUTATIONS; CLONING; GENE; CELLS AB PURPOSE. RPE65 is preferentially expressed in the retinal pigment epithelium (RPE) and is essential for retinal function. The purpose of the Study was to develop methods for the expression of the protein, determine the accurate molecular weight of this expressed protein, and quantitate the amount of RPE65 in the bovine RPE. METHODS. Human RPE65 was expressed in Sf9 cells using the baculovirus system. The subcellular localization was determined by Western blot analysis and immunocytochemistry. An ELISA was developed for RPE65 and used to measure levels in bovine RPE. Recombinant and native RPE65 were purified by affinity chromatography. Molecular mass was determined by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. RESULTS. Recombinant human (rH)RPE65 was expressed as a major protein associated with cell membrane in Sf9 cells. The recombinant protein was purified to apparent homogeneity from both the membrane and nonmembrane fractions. The identity of the purified protein was confirmed by Western blot analysis and by partial peptide sequencing. rHRPE65 from the nonmembrane fraction has a mass of 64,867 +/- 80 which is close to the calculated molecular weight from the amino acid sequence including the His-tag (64,663), whereas the membrane-associated rHRPE65 has a molecular mass of 65,380 +/- 150, which is significantly higher than that of the non-membrane-associated form and the calculated molecular weight, suggesting posttranslational modifications. Similarly, native RPE65 was detected in the cytosolic and microsomal fractions of the bovine RPE, with an average level of 3.8 +/- 1.3 and 7.2 +/-: 0.4 mug RPE65 per eye, respectively. The cytosolic form had a molecular mass of 61,161 +/- 60, which is close to the calculated value (60,944), whereas that of the microsomal form was 61,961 +/- 170. CONCLUSIONS. RPE65 is expressed in two forms, one of which is membrane associated and contains significant posttranslational modifications, similar to the native membrane-associated form. C1 Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Ma, JX (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA. OI Redmond, T. Michael/0000-0002-1813-5291 FU NEI NIH HHS [EY04939, EY12231] NR 20 TC 52 Z9 52 U1 0 U2 1 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 JUN PY 2001 VL 42 IS 7 BP 1429 EP 1435 PG 7 WC Ophthalmology SC Ophthalmology GA 437XE UT WOS:000169024000004 PM 11381042 ER PT J AU Becker, S Fisher, A Flexner, C Gerber, JG Haubrich, R Kashuba, ADM Luber, AD Piscitelli, SC AF Becker, S Fisher, A Flexner, C Gerber, JG Haubrich, R Kashuba, ADM Luber, AD Piscitelli, SC TI Pharmacokinetic parameters of protease inhibitors and the Cmin/IC50 ratio: Call for consensus SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID HUMAN-IMMUNODEFICIENCY-VIRUS; INDINAVIR C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Johns Hopkins Univ, Sch Med, Div Clin Pharmacol, Baltimore, MD 21218 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Univ Calif San Diego, Div Infect Dis, San Diego, CA 92103 USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. Pacific Oaks Med Grp, Pacific Oaks Res, Beverly Hills, CA USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. RP Becker, S (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 11 TC 13 Z9 13 U1 0 U2 2 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 JUN 1 PY 2001 VL 27 IS 2 BP 210 EP 211 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 442YK UT WOS:000169312400016 PM 11404545 ER PT J AU Sparber, A Wootton, JC AF Sparber, A Wootton, JC TI Surveys of complementary and alternative medicine: Part II. Use of alternative and complementary cancer therapies SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID BREAST-CANCER; UNITED-STATES; PREVALENCE; OUTPATIENTS; CHILDREN; WOMEN AB The second part of this series on surveys of complementary and alternative medicine (CAM) in the United States provides a "point-of-information" summary of the studies on patients with cancer and their use of CAM therapies. Surveys of patients with cancer were the precursors of the recent wave of studies on CAM prevalence and use. Three tables summarize the findings from a total of 18 surveys categorized by Childhood Cancer, Adult Cancer, and Breast Cancer studies. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. Alternat Med Fdn, Bethesda, MD USA. RP Sparber, A (reprint author), NIH, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 23 TC 47 Z9 47 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD JUN PY 2001 VL 7 IS 3 BP 281 EP 287 DI 10.1089/107555301300328179 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 445ZN UT WOS:000169488600021 PM 11439851 ER PT J AU Goodpaster, BH Carlson, CL Visser, M Kelley, DE Scherzinger, A Harris, TB Stamm, E Newman, AB AF Goodpaster, BH Carlson, CL Visser, M Kelley, DE Scherzinger, A Harris, TB Stamm, E Newman, AB TI Attenuation of skeletal muscle and strength in the elderly: The Health ABC Study SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE aging; computed tomography; adipose tissue; muscle strength ID SUBCUTANEOUS ABDOMINAL FAT; CROSS-SECTIONAL AREA; COMPUTED-TOMOGRAPHY; INSULIN SENSITIVITY; DIABETES-MELLITUS; WOMEN; AGE; OBESITY; THIGH; MASS AB Although loss of muscle mass is considered a cause of diminished muscle strength with aging, little is known regarding whether composition of aging muscle affects strength. The skeletal muscle attenuation coefficient, as determined by computed tomography, is a noninvasive measure of muscle density, and lower values reflect increased muscle lipid content. This investigation examined the hypothesis that lower values for muscle attenuation are associated with lower voluntary isokinetic knee extensor strength at 60 degrees /s in 2,627 men and women aged 70-79 yr participating in baseline studies of the Health ABC Study, a longitudinal study of health, aging, and body composition. Strength was higher in men than in women (132.3 +/- 34.5 vs. 81.4 +/- 22.0 N.m, P < 0.01). Men had greater muscle attenuation values (37.3 6.5 vs. 34.7 +/- 7.0 Hounsfield units) and muscle cross-sectional area (CSA) at the midthigh than women (132.7 +/- 22.4 vs. 93.3 +/- 17.5 cm(2), P < 0.01 for both). The strength per muscle CSA (specific force) was also higher in men (1.00 0.21 vs. 0.88 +/- 0.21 N.m.cm(-2)). The attenuation coefficient was significantly lower for hamstrings than for quadriceps (28.7 +/- 8.7 vs. 41.1 +/- 6.9 Hounsfield units, P < 0.01). Midthigh muscle attenuation values were lowest (P < 0.01) in the eldest men and women and were negatively associated with total body fat (r = -0.53, P < 0.01). Higher muscle attenuation values were also associated with greater specific force production (r = 0.26, P < 0.01). Multivariate regression analysis revealed that the attenuation coefficient of muscle was independently associated with muscle strength after adjustment for muscle CSA and midthigh adipose tissue in men and women. These results demonstrate that the attenuation values of muscle on computed tomography in older persons can account for differences in muscle strength not attributed to muscle quantity. C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. NIA, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80261 USA. Vrije Univ Amsterdam, Inst Res Extramural Med, Amsterdam, Netherlands. RP Goodpaster, BH (reprint author), Univ Pittsburgh, Dept Med, E 1140 Biomed Sci Tower, Pittsburgh, PA 15261 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [K01-AG-00851, N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106] NR 31 TC 398 Z9 405 U1 3 U2 21 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUN PY 2001 VL 90 IS 6 BP 2157 EP 2165 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 436WC UT WOS:000168958000019 PM 11356778 ER PT J AU Spouge, JL AF Spouge, JL TI Finite-size corrections to Poisson approximations of rare events in renewal processes SO JOURNAL OF APPLIED PROBABILITY LA English DT Article DE renewals; Chen-Stein method; generating functions ID STRONG LIMIT-THEOREMS; PARTIAL-SUMS; SEQUENCE DATABASES; LOCAL SEQUENCE; PROTEIN; STATISTICS; ALIGNMENT; VALUES; DISTRIBUTIONS; EXCEEDANCES AB Consider a renewal process. The renewal events partition the process into i.i.d. renewal cycles. Assume that on each cycle, a rare event called 'success' can occur. Such successes lend themselves naturally to approximation by Poisson point processes. If each success occurs after a random delay, however. Poisson convergence may be relatively slow. because each success corresponds to a time interval, not a point. In 1996. Altschul and Gish proposed a finite-size correction to a particular approximation by a Poisson point process. Their correction is now used routinely (about once a second) when computers compare biological sequences, although it lacks a mathematical foundation. This paper generalizes their correction. For a single renewal process or several renewal processes operating in parallel, this paper gives an asymptotic expansion that contains in successive terms a Poisson point approximation, a generalization of the Aitschul-Gish correction. and a correction term beyond that. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Spouge, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 49 TC 8 Z9 8 U1 0 U2 1 PU APPLIED PROBABILITY TRUST PI SHEFFIELD PA THE UNIVERSITY, SCHOOL MATHEMATICS STATISTICS, SHEFFIELD S3 7RH, ENGLAND SN 0021-9002 J9 J APPL PROBAB JI J. Appl. Probab. PD JUN PY 2001 VL 38 IS 2 BP 554 EP 569 PG 16 WC Statistics & Probability SC Mathematics GA 450QF UT WOS:000169754100018 ER PT J AU Higaki, K Ninomiya, H Sugimoto, Y Suzuki, T Taniguchi, M Niwa, H Pentchev, PG Vanier, MT Ohno, K AF Higaki, K Ninomiya, H Sugimoto, Y Suzuki, T Taniguchi, M Niwa, H Pentchev, PG Vanier, MT Ohno, K TI Isolation of NPC1-deficient Chinese hamster ovary cell mutants by gene trap mutagenesis SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE CHO; cholesterol; LDL; Niemann-Pick C; SREBP ID LOW-DENSITY-LIPOPROTEIN; PICK TYPE-C; COENZYME-A REDUCTASE; CHOLESTEROL-METABOLISM; INTRACELLULAR TRAFFICKING; PROTEIN; FIBROBLASTS; RECEPTOR; DISEASE; INHIBITION AB Chinese hamster ovary cell mutants defective in the NPC1 gene (NPC1-trap) were generated by retrovirus-mediated gene trap mutagenesis from a parental cell line JP17 expressing an ecotropic retrovirus receptor. Insertion of the gene trap vector in the NPC1 gene and the absence of the gene product were verified by 5'RACE and immunological analyses, respectively, NPC1-trap cells showed intracellular accumulation of low-density lipoprotein (LDL)-derived cholesterol and had an increased level of unesterified cellular cholesterol. Cholesterol biosynthesis through the mevalonate pathway was upregulated in the mutant cells as assessed by [C-14]acetate incorporation into cellular sterols, When JP17 cells were depleted of lipoproteins and then loaded with LDL, cell surface LDL receptors were promptly downregulated and the mature form of the sterol regulatory element-binding protein-1 disappeared from the nucleus, These responses to LDL were obviously retarded in NPC1-trap cells, suggesting an impaired response of the cholesterol-regulatory system to LDL, NPC1-trap cells will be a useful tool to study the regulation of cellular cholesterol homeostasis and the pathogenesis of Niemann-Pick disease type C. C1 Tottori Univ, Fac Med, Sch Life Sci, Dept Neurobiol, Yonago, Tottori 6838503, Japan. Osaka Univ, Fac Med, Dept Nutr, Suita, Osaka 565, Japan. NINDS, Dev & Metab Neurol Branch, Cellular & Mol Pathophysiol Sect, NIH, Bethesda, MD 20892 USA. Lyon Sud Med Sch, INSERM, U189, F-69921 Oullins, France. RP Ohno, K (reprint author), Tottori Univ, Fac Med, Sch Life Sci, Dept Neurobiol, Yonago, Tottori 6838503, Japan. NR 30 TC 18 Z9 20 U1 0 U2 2 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F, 25-16 HONGO-5-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD JUN PY 2001 VL 129 IS 6 BP 875 EP 880 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 440LM UT WOS:000169176800004 PM 11388901 ER PT J AU Ho, MWY Kaetzel, MA Armstrong, DL Shears, SB AF Ho, MWY Kaetzel, MA Armstrong, DL Shears, SB TI Regulation of a human chloride channel - A paradigm for integrating input from calcium, type II calmodulin-dependent protein kinase, and inositol 3,4,5,6-tetrakisphosphate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CA-2+-DEPENDENT CL CHANNELS; COLONIC CELLS HT-29; CYSTIC-FIBROSIS; CAM KINASE; INS(3,4,5,6)P-4; CONDUCTANCE; ACTIVATION; CLONING; LINE; CA2+ AB We have studied the regulation of Ca2+-dependent chloride (Cl-Ca) channels in a human pancreatoma epithelial cell line (CFPAC-1), which does not express functional cAMP-dependent cystic fibrosis transmembrane conductance regulator chloride channels. In cell-free patches from these cells, physiological Ca2+ concentrations activated a single class of 1-picosiemens Cl--selective channels. The same channels were also stimulated by a purified type II calmodulin-dependent protein kinase (CaMKII), and in cell-attached patches by purinergic agonists. In whole-cell recordings, both Ca2+- and CaMKII-dependent mechanisms contributed to chloride channel stimulation by Ca2+, but the CaMKII-dependent pathway was selectively inhibited by inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P-4). This inhibitory effect of Ins(3,4,5,6)P, on Cl-Ca channel stimulation by CaMKII was reduced by raising [Ca2+] and prevented by inhibition of protein phosphatase activity with 100 nM okadaic acid. These data provide a new context for understanding the physiological relevance of Ins(3,4,5,6)P, in the longer term regulation of Ca2+-dependent Cl- fluxes in epithelial cells. C1 NIEHS, Inositide Signaling Grp, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Membrane Signaling Grp, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Univ Cincinnati, Coll Med, Dept Cellular & Mol Physiol, Cincinnati, OH 45267 USA. RP Ho, MWY (reprint author), NIEHS, Inositide Signaling Grp, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. FU NIDDK NIH HHS [DK 46433] NR 37 TC 49 Z9 49 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2001 VL 276 IS 22 BP 18673 EP 18680 DI 10.1074/jbc.M101128200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439BM UT WOS:000169091000005 PM 11279175 ER PT J AU Ling, P Meyer, CF Redmond, LP Shui, JW Davis, B Rich, RR Hu, MCT Wange, RL Tan, TH AF Ling, P Meyer, CF Redmond, LP Shui, JW Davis, B Rich, RR Hu, MCT Wange, RL Tan, TH TI Involvement of hematopoietic progenitor kinase 1 in T cell receptor signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-TERMINAL KINASE; GERMINAL CENTER KINASE; STE20-RELATED PROTEIN-KINASE; ADAPTER PROTEINS; ANTIGEN-RECEPTOR; GENETIC-EVIDENCE; TYROSINE KINASE; ACTIVATION; PATHWAY; HPK1 AB Hematopoietic progenitor kinase 1 (HPK1), a mammalian Ste20-related serine/threonine protein kinase, is a hematopoietic-specific upstream activator of the c-Jun N-terminal kinase. Here, we provide evidence to demonstrate the involvement of HPK1 in T cell receptor (TCR) signaling. HPK1 was activated and tyrosine-phosphorylated with similar kinetics following TCR/CD3 or pervanadate stimulation. Co-expression of protein-tyrosine kinases, Lck and Zap70, with HPK1 led to HPK1 activation and tyrosine phosphorylation in transfected mammalian cells. Upon TCR/CD3 stimulation, HPK1 formed inducible complexes with the adapters Nck and Grk with different kinetics, whereas it constitutively interacted with the adapters Grb2 and CrkL in Jurkat T cells. Interestingly, HPK1 also inducibly associated with linker for activation of T cells (LAT) through its proline-rich motif and translocated into glycolipid-enriched microdomains (also called lipid rafts) following TCR/CD3 stimulation, suggesting a critical role for LAT in the regulation of HPK1, Together, these results identify HPK1 as a new component of TCR signaling. T cell-specific signaling molecules Lck, Zap70, and LAT play roles in the regulation of HPK1 during TCR signaling. Differential complex formation between HPK1 and adapters highlights the possible involvement of HPK1 in multiple signaling pathways in T cells. C1 Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. Baylor Coll Med, Interdept Program Cell & Mol Biol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA. NIA, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. RP Tan, TH (reprint author), Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. RI Tan, Tse-Hua/E-3983-2010 OI Tan, Tse-Hua/0000-0003-4969-3170 FU NIAID NIH HHS [R01-AI38649, R01-AI42532] NR 41 TC 34 Z9 35 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2001 VL 276 IS 22 BP 18908 EP 18914 DI 10.1074/jbc.M101485200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439BM UT WOS:000169091000036 PM 11279207 ER PT J AU Chung, HK Derse, D AF Chung, HK Derse, D TI Binding sites for Rev and ASF/SF2 map to a 55-nucleotide purine-rich exonic element in equine infectious anemia virus RNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEAR EXPORT SIGNALS; PRE-MESSENGER-RNA; SPLICING ENHANCER; RESPONSE ELEMENT; SR PROTEINS; NUCLEOCYTOPLASMIC TRANSPORT; ACTIVATION DOMAIN; CELL; TYPE-1 AB The equine infectious anemia virus (EIAV) Rev protein (ERev) negatively regulates its own synthesis by inducing alternative splicing of its mRNA. This bicistronic mRNA contains four exons; exons 1 and 2 encode Tat, and exons 3 and 4 encode Rev. When Rev is expressed, exon 3 is skipped to produce an mRNA that contains only exons 1, 2, and 4, The interaction of ERev with its cis-acting RNA response element, the RRE, is also essential for nuclear export of intron-containing viral mRNAs that encode structural and enzymatic gene products. The primary ERev binding site and the manner in which ERev interacts with RNA or cellular proteins to exert its regulatory function have not been defined. We have performed in vitro RNA binding experiments to show that recombinant ERev binds to a 55-nucleotide, purine-rich tract proximal to the 5 ' splice site of exon 3, Because of its proximity to the 5 ' splice site and since it contains elements related to consensus exonic splicing enhancer sequences, we asked whether cellular proteins recognize the EIAV RRE, The cellular protein, ASF/SF2, a member of the serine- and arginine-rich family of splicing factors (SR proteins) bound to repeated sequences within the 55-nucleotide RRE region, Electrophoretic mobility shift and UV cross-linking experiments indicated that ERev and SR proteins bind simultaneously to the RRE, Furthermore, in vitro protein-protein interaction studies revealed an association between ERev and SR proteins. These data suggest that EIAV Rev-induced exon skipping observed in vivo may be initiated by simultaneous binding of Rev and SR proteins to the RRE that alter the subsequent assembly or catalytic activity of the spliceosomal complex. C1 NCI, Basic Res Lab, NIH, Frederick, MD 21702 USA. RP Derse, D (reprint author), NCI, Basic Res Lab, NIH, Frederick, MD 21702 USA. NR 49 TC 13 Z9 13 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2001 VL 276 IS 22 BP 18960 EP 18967 DI 10.1074/jbc.M008996200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439BM UT WOS:000169091000043 PM 11278454 ER PT J AU Shankavaram, UT Lai, WC Netzel-Arnett, S Mangan, PR Ardans, JA Caterina, N Stetler-Stevenson, WG Birkedal-Hansen, H Wahl, LM AF Shankavaram, UT Lai, WC Netzel-Arnett, S Mangan, PR Ardans, JA Caterina, N Stetler-Stevenson, WG Birkedal-Hansen, H Wahl, LM TI Monocyte membrane type 1-matrix metalloproteinase - Prostaglandin-dependent regulation and role in metalloproteinase-2 activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MACROPHAGE COLLAGENASE PRODUCTION; HUMAN MONONUCLEAR PHAGOCYTES; IV COLLAGENASE; MATRIX METALLOPROTEINASE; TISSUE INHIBITOR; EXTRACELLULAR-MATRIX; GELATINASE-A; H SYNTHASE-2; TUMOR-CELLS; IN-VITRO AB Membrane type 1-matrix metalloproteinase (MT1-MMP)-mediated activation of MMP-2 is thought to be important in the proteolysis of extracellular matrix in pathological events in which monocytes/macrophages are found. Here we report on the induction and regulation of human monocyte MT1-MMP and its role in MMP-2 activation. Activation of monocytes by lipopolysaccharide resulted in the induction of MT1-MMP mRNA and protein that was suppressed by inhibitors of prostaglandin synthesis (indomethacin), adenylyl cyclase (SQ 22536), and protein kinase A (Rp-cAMPs). Suppression of MT1-MMP by indomethacin and SQ 22536 was reversed by prostaglandin E, and dibutyryl cyclic AMP, respectively, demonstrating that induction of monocyte MT1-MMP is regulated through a prostaglandin-cAMP pathway. Functional analysis revealed that pro-MMP-2 in the supernatants from human bone marrow stromal fibroblasts, normal male-derived fibroblasts and melanoma cells (A2058) was converted to active MMP-2 when cultured with activated but not control monocytes, Antibodies against MT1-MMP blocked the activation of MMP-2. Tissue inhibitor of metalloproteinase-2 regulation of MMP-2 activation was shown through the addition of varying amounts of recombinant tissue inhibitor of metalloproteinase-2 with pro-MMP-2 to MT1-MMP-expressing monocytes, These findings demonstrate that activated monocytes express functionally active MT1-MMP that may play a significant role in the activation of MMP-2 produced by other cells and as such influence developmental and pathological conditions. C1 NIDCR, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. NIDCR, Matrix Metalloprot Unit, NIH, Bethesda, MD 20892 USA. NCI, Extracellular Matrix Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Wahl, LM (reprint author), NIDCR, Immunopathol Sect, NIH, 30 Convent Dr,Bldg 30,Rm 325, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 50 TC 62 Z9 66 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2001 VL 276 IS 22 BP 19027 EP 19032 DI 10.1074/jbc.M009562200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439BM UT WOS:000169091000052 PM 11259424 ER PT J AU Yamada, H Vijayachandra, K Penner, C Glick, A AF Yamada, H Vijayachandra, K Penner, C Glick, A TI Increased sensitivity of transforming growth factor (TGF) beta 1 null cells to alkylating agents reveals a novel link between TGF beta signaling and O-6-methylguanine methyltransferase promoter hypermethylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SKIN TUMORS; MICROSATELLITE INSTABILITY; MALIGNANT CONVERSION; CARCINOMA-CELLS; HUMAN-CANCERS; II RECEPTOR; CPG ISLAND; HIGH-RISK; GENE; DNA AB Inactivation of the transforming growth factor P (TGF beta)-signaling pathway and gene silencing through hypermethylation of promoter CpG islands are two frequent alterations in human and experimental cancers. Here we report that nonneoplastic TGF beta1-/- keratinocyte cell lines exhibit increased sensitivity to cell killing by alkylating agents, and this is due to lack of expression of the DNA repair enzyme O-6-methylguanine DNA methyltransferase (MGMT), In TGF beta1-/- but not TGF beta1+/- cell lines, the CpG dinucleotides in the MGMT promoter are hypermethylated, as measured by restriction enzyme analysis and methylation specific polymerase chain reaction. In one unstable TGF beta1+/- cell line, loss of the wild type TGF beta1 allele correlates with the appearance of methylation in the MGMT promoter. Bisulfite sequencing shows that in the KO3 TGF beta1-/-cell line nearly all of the 28 CpG: sites in the MGMT promoter 475 base pairs upstream of the start site of transcription are methylated, whereas most are unmethylated in the H1 TGF beta1+/- line. Treatment of the TGF beta1-/- cell lines with 5-azacytidine causes reexpression of MGMT mRNA and demethylation of CpG islands in the promoter. Analysis of the time course of methylation using methylation-specific polymerase chain reaction shows a lack of methylation in primary TGF beta1-/-keratinocytes and increasing methylation with passage number of immortalized clones. Subcloning of early passage clones reveals a remarkable heterogeneity and instability of the methylation state in the TGF beta1-/- keratinocytes, Thus, the TGF beta1-/- genotype does not directly regulate MGMT methylation but predisposes cells to immortalization-associated MGMT hypermethylation. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Taisho Pharmaceut Co Ltd, Toxicol Lab, Pharmaceut Res Labs, Tokyo 1708633, Japan. RP Glick, A (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37 3B19, Bethesda, MD 20892 USA. NR 45 TC 15 Z9 18 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2001 VL 276 IS 22 BP 19052 EP 19058 DI 10.1074/jbc.M100615200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439BM UT WOS:000169091000056 PM 11262404 ER PT J AU Parks, WT Frank, DB Huff, C Haft, CR Martino, J Meng, XW de Caestecker, MP McNally, JG Reddi, A Taylor, SI Roberts, AB Wang, TW Lechleider, RJ AF Parks, WT Frank, DB Huff, C Haft, CR Martino, J Meng, XW de Caestecker, MP McNally, JG Reddi, A Taylor, SI Roberts, AB Wang, TW Lechleider, RJ TI Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I RECEPTORS; SMAD PROTEINS; ACTIVIN; COMPLEX; ACTIVATION; MEMBRANE; CLONING; IDENTIFICATION; BIOSYNTHESIS; RESPONSES AB Sorting nexins (SNX) comprise a family of proteins with homology to several yeast proteins, including Vps5p and Mvp1p, that are required for the sorting of proteins to the yeast vacuole. Human SNX1, -2, and -4 have been proposed to play a role in receptor trafficking and have been shown to bind to several receptor tyrosine kinases, including receptors for epidermal growth factor, platelet-derived growth factor, and insulin as well as the long form of the leptin receptor, a glycoprotein 130-associated receptor. We now describe a novel member of this family, SNX6, which interacts with mem bers of the transforming growth factor-p family of receptor serine-threonine kinases. These receptors belong to two classes: type II receptors that bind ligand, and type I receptors that are subsequently recruited to transduce the signal. Of the type II receptors, SNX6 was found to interact strongly with ActRIIB and more moderately with wild type and kinase-defective mutants of T beta RII. Of the type I receptors, SNX6 was found to interact only with inactivated T beta RI. SNXs 1-4 also interacted with the transforming growth factor-p receptor family, showing different receptor preferences. Conversely, SNX6 behaved similarly to the other SNX proteins in its interactions with receptor tyrosine kinases. Strong heteromeric interactions were also seen among SNX1, -2, -4, and -6, suggesting the formation in vivo of oligomeric complexes. These findings are the first evidence for the association of the SNX family of molecules with receptor serine-threonine kinases. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Surg, Boston, MA 02114 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. OI Parks, W. Tony/0000-0001-7341-3277 NR 36 TC 93 Z9 99 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2001 VL 276 IS 22 BP 19332 EP 19339 DI 10.1074/jbc.M100606200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439BM UT WOS:000169091000093 PM 11279102 ER PT J AU Wurthner, JU Frank, DB Felici, A Green, HM Cao, ZH Schneider, MD McNally, JG Lechleider, RJ Roberts, AB AF Wurthner, JU Frank, DB Felici, A Green, HM Cao, ZH Schneider, MD McNally, JG Lechleider, RJ Roberts, AB TI Transforming growth factor-beta receptor-associated protein 1 is a Smad4 chaperone SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WD-DOMAIN PROTEIN; SIGNALING PATHWAYS; I RECEPTOR; PHOSPHORYLATION; INHIBITION; COMPLEX; FKBP12; FORM; IDENTIFICATION; TRANSCRIPTION AB Members of the transforming growth factor-beta (TGF-beta) superfamily signal through unique cell membrane receptor serine-threonine kinases to activate downstream targets. TRAP1 is a previously described 96-kDa cytoplasmic protein shown to bind to TGF-beta receptors and suggested to play a role in TGF-beta signaling. We now fully characterize the binding properties of TRAP1, and show that it associates strongly with inactive heteromeric TGF-beta and activin receptor complexes and is released upon activation of signaling. Moreover, we demonstrate that TRAP1 plays a role in the Smad-mediated signal transduction pathway, interacting with the common mediator, Smad4, in a ligand-dependent fashion. While TRAP1 has only a small stimulatory effect on TGF-beta signaling in functional assays, deletion constructs of TRAP1 inhibit TGF-beta signaling and diminish the interaction of Smad4 with Smad2. These are the first data to identify a specific molecular chaperone for Smad4, suggesting a model in which TRAP1 brings Smad4 into the vicinity of the receptor complex and facilitates its transfer to the receptor-activated Smad proteins. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bldg 41,Rm C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. EM Robertsa@dce41.nci.nih.gov NR 40 TC 48 Z9 55 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2001 VL 276 IS 22 BP 19495 EP 19502 DI 10.1074/jbc.M006473200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439BM UT WOS:000169091000112 PM 11278302 ER PT J AU Wang, QMJ Fang, TW Nacro, K Marquez, VE Wang, SM Blumberg, PM AF Wang, QMJ Fang, TW Nacro, K Marquez, VE Wang, SM Blumberg, PM TI Role of hydrophobic residues in the C1b domain of protein kinase C delta on ligand and phospholipid interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; PHORBOL ESTER-BINDING; CYSTEINE-RICH REGION; INDUCED TRANSLOCATION; MEMBRANE-BINDING; TUMOR PROMOTERS; DIACYLGLYCEROL; AFFINITY; ALPHA; LOCALIZATION AB The C1 domains of conventional and novel protein kinase C (PKC) isoforms bind diacylglycerol and phorbol esters with high affinity. Highly conserved hydrophobic residues at or near the rim of the binding cleft in the second cysteine-rich domain of PKC-delta (PKC-delta C1b) were mutated to probe their roles in ligand recognition and lipid interaction. [H-3]Phorbol 12,13-dibutyrate (PDBu) binding was carried out both in the presence and absence of phospholipids to determine the contribution of lipid association to the ligand affinity. Lipid dependence was determined as a function of lipid concentration and composition. The binding properties of a high affinity branched diacylglycerol with lipophilicity similar to PDBu were compared with those of PDBu to identify residues important for ligand selectivity. As expected, Leu-20 and Leu-24 strongly influenced binding. Substitution of either by aspartic acid abolished binding in either the presence or absence of phosphatidylserine, Mutation of Leu-20 to Arg or of Leu-24 to Lys caused a dramatic (340- and 250-fold, respectively) reduction in PDBu binding in the presence of lipid but only a modest reduction in the weaker binding of PDBu observed in the absence of lipid, suggesting that the main effect was on C1 domain -phospholipid interactions. Mutation of Leu-20 to Lys or of Trp-22 to Lys had modest (S-fold) effects and mutation of Phe-13 to Tyr or Lys was without effect. Binding of the branched diacylglycerol was less dependent on phospholipid and was more sensitive to mutation of Trp-22 to Tyr or Lys, especially in the presence of phospholipid, than was PDBu, In terms of specific PKC isoforms, our results suggest that the presence of Arg-20 in PKC-zeta may contribute to its lack of phorbol ester binding activity. More generally, the results emphasize the interplay between the C1 domain, ligand, and phospholipid in the ternary binding complex. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Mol Mechanisms Tumor Promot Sect, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Georgetown Inst Cognit & Computat Sci, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA. RP Blumberg, PM (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Mol Mechanisms Tumor Promot Sect, NIH, Bldg 37,Rm 3A01,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. RI Wang, Qiming/B-6064-2012 NR 37 TC 40 Z9 40 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2001 VL 276 IS 22 BP 19580 EP 19587 DI 10.1074/jbc.M010089200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439BM UT WOS:000169091000122 PM 11278612 ER PT J AU Cebral, JR Lohner, R Choyke, PL Yim, PJ AF Cebral, JR Lohner, R Choyke, PL Yim, PJ TI Merging of intersecting triangulations for finite element modeling SO JOURNAL OF BIOMECHANICS LA English DT Article DE surface intersection; grid generation; finite element analysis; hemodynamics; magnetic resonance images; carotid artery ID BLOOD-FLOW; UNSTRUCTURED GRIDS; BIFURCATION; GEOMETRIES AB Surface mesh generation over intersecting triangulations is a problem common to many branches of biomechanics. A new strategy for merging intersecting triangulations is described. The basis of the method is that object surfaces are represented as the zero-level iso-surface of the distance-to-surface function defined on a background grid. Thus, the triangulation of intersecting objects reduces to the extraction of an iso-surface from an unstructured grid. In a first step, a regular background mesh is constructed. For each point of the background grid, the closest distance to the surface of each object is computed. Background points are then classified as external or internal by checking the direction of the surface normal at the closest location and assigned a positive or negative distance, respectively. Finally, the zero-level iso-surface is constructed. This is the final triangulation of the intersecting objects. The overall accuracy is enhanced by adaptive refinement of the background grid elements. The resulting surface models are used as support surfaces to generate three-dimensional grids for finite element analysis. The algorithms are demonstrated by merging arterial branches independently reconstructed from contrast-enhanced magnetic resonance images and by adding extra features such as vascular stents, Although the methodology is presented in the context of finite element analysis of blood flow, the algorithms are general and can be applied in other areas as well. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 George Mason Univ, Sch Computat Sci, Fairfax, VA 22030 USA. NIH, Imaging Sci Program, Bethesda, MD 20892 USA. RP Cebral, JR (reprint author), George Mason Univ, Sch Computat Sci, 4400 Univ Dr,MS 4C7, Fairfax, VA 22030 USA. NR 16 TC 48 Z9 47 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD JUN PY 2001 VL 34 IS 6 BP 815 EP 819 DI 10.1016/S0021-9290(01)00018-5 PG 5 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 435XD UT WOS:000168906700014 PM 11470121 ER PT J AU Potter, K Landis, WJ Spencer, RGS AF Potter, K Landis, WJ Spencer, RGS TI Histomorphometry of the embryonic avian growth plate by proton nuclear magnetic resonance microscopy SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE nuclear magnetic resonance microscopy; cartilage; growth plate; mineral deposits ID MR-IMAGING CHARACTERISTICS; ARTICULAR-CARTILAGE; HYALINE CARTILAGE; BONE-FORMATION; CHICK; RELAXATION; DIFFUSION; MORPHOLOGY; APPEARANCE; SEQUENCES AB Quantitative nuclear magnetic resonance (NMR) microscopy was used to characterize the biochemical and morphological properties of the different zones within the growth plate of an embryonic chick femur. For precalcified tissue, water proton transverse relaxation times (T-2) and magnetization transfer values (MT) were directly and inversely dependent, respectively, on tissue cellularity, defined as the intracellular area per unit area on histological sections. T-2 values extrapolated for intra- and extracellular water were 96 ms and 46 ms, respectively. The extracellular T-2 was comparable with that measured for mature cartilage. The MT values extrapolated for intra- and extracellular compartments were 0.32 and 0.85, respectively, These values were comparable with those values reported in the literature for cell pellets and for mature cartilage tissue. Thus, cellularity dominated the NMR properties of this immature cartilage tissue. Mineral deposits within calcified cartilage and periosteal bone invoked NMR relaxation processes that were dependent on the inorganic mineral phase; Additionally, collagen molecules present in mineralized zones gave rise to a significant MT effect. These results show the utility of water proton NMR microscopy for assessing both the organic and inorganic ph ases within mineralized tissues. C1 NIA, Nucl Magnet Resonance Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NICHHD, Sect Tissue Biophys & Biomimet, Bethesda, MD 20892 USA. Northeastern Ohio Univ, Coll Med, Dept Biochem & Mol Pathol, Rootstown, OH USA. RP Spencer, RGS (reprint author), NIA, Nucl Magnet Resonance Unit, Intramural Res Program, NIH, GRC 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIAMS NIH HHS [AR 41452] NR 39 TC 10 Z9 11 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 JUN PY 2001 VL 16 IS 6 BP 1092 EP 1100 DI 10.1359/jbmr.2001.16.6.1092 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 433XX UT WOS:000168786900013 PM 11393786 ER PT J AU Stewart, K Gronthos, S Bord, S Zannettino, A Simmons, P Beresford, JN AF Stewart, K Gronthos, S Bord, S Zannettino, A Simmons, P Beresford, JN TI Further characterisation and molecular cloning of the antibody H8G SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Bath, Dept Pharm & Pharmacol, Bone Res Grp, Bath BA2 7AY, Avon, England. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Cambridge CB2 2QQ, England. JMVS, Adelaide, SA, Australia. Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia. 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 JUN PY 2001 VL 16 IS 6 MA P14 BP 1183 EP 1183 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 433XX UT WOS:000168786900070 ER PT J AU Abel, K Anderson, RA Shears, SB AF Abel, K Anderson, RA Shears, SB TI Phosphatidyl inositol and inositol phosphate metabolism SO JOURNAL OF CELL SCIENCE LA English DT Editorial Material C1 NIEHS, Inositide Signaling Sect, Res Triangle Pk, NC 27709 USA. Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. RP Shears, SB (reprint author), NIEHS, Inositide Signaling Sect, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 5 TC 22 Z9 22 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN PY 2001 VL 114 IS 12 BP 2207 EP 2208 PG 2 WC Cell Biology SC Cell Biology GA 451FL UT WOS:000169790400001 PM 11493657 ER PT J AU Putney, JW Broad, LM Braun, FJ Lievremont, JP Bird, GSJ AF Putney, JW Broad, LM Braun, FJ Lievremont, JP Bird, GSJ TI Mechanisms of capacitative calcium entry SO JOURNAL OF CELL SCIENCE LA English DT Article DE calcium channels; capacitative calcium entry; calcium signaling; signal transduction ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; INTRACELLULAR CA2+ STORES; OPERATED HTRP3 CHANNELS; INFLUX FACTOR; SIGNAL-TRANSDUCTION; XENOPUS OOCYTES; FUNCTIONAL EXPRESSION; CATION CHANNELS; T-LYMPHOCYTES; CELLS AB Capacitative Ca2+ entry involves the regulation of plasma membrane Ca2+ channels by the filling state of intracellular Ca2+ stores in the endoplasmic reticulum (ER). Several theories have been advanced regarding the mechanism by which the stores communicate with the plasma membrane. One such mechanism, supported by recent findings, is conformational coupling: inositol 1,4,5-trisphosphate (Ins(1 4,5)P-3) receptors in the ER may sense the fall in Ca2+ levels through Ca2+-binding sites on their lumenal domains, and convey this conformational information directly by physically interacting with Ca2+ channels in the plasma membrane. In support of this idea, in some cell types, store-operated channels in excised membrane patches appear to depend on the presence of both Ins(1,4,5)P3 and Ins(1,4,5)P-3 receptors for activity; in addition, inhibitors of Ins(1,4,5)P-3 production that either block phospholipase C or inhibit phosphatidylinositol 4-kinase can block capacitative Ca2+ entry. However, the electrophysiological current underlying capacitative Ca2+ entry is not blocked by an Ins(1,4,5)P-3 receptor antagonist, and the blocking effects of a phospholipase C inhibitor are not reversed by the intracellular application of Ins(1,4,5)P-3. Furthermore, cells whose Ins(1,4,5)P-3 receptor genes have been disrupted can nevertheless maintain their capability to activate capacitative Ca2+ entry channels in response to store depletion. A tentative conclusion is that multiple mechanisms for signaling capacitative Ca2+ entry may exist, and involve conformational coupling in some cell types and perhaps a diffusible signal in others. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NR 64 TC 416 Z9 432 U1 1 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN PY 2001 VL 114 IS 12 BP 2223 EP 2229 PG 7 WC Cell Biology SC Cell Biology GA 451FL UT WOS:000169790400003 PM 11493662 ER PT J AU Rambourg, A Jackson, CL Clermont, Y AF Rambourg, A Jackson, CL Clermont, Y TI Three dimensional configuration of the secretory pathway and segregation of secretion granules in the yeast Saccharomyces cerevisiae SO JOURNAL OF CELL SCIENCE LA English DT Article DE secretory pathway; Golgi apparatus; secretion granules; yeast; brefeldin A; BFA; trafficking ID 3-DIMENSIONAL ELECTRON-MICROSCOPY; GOLGI-APPARATUS; PROTEIN-TRANSPORT; BREFELDIN-A; ELEMENTS; COMPLEX; MUTANTS; CELLS; RAT; ORGANIZATION AB The structural elements of the secretory pathway in the budding yeast Saccharomyces cerevisiae were analyzed by 3D stereo-electron microscopy using relatively thick sections in which membranes were selectively impregnated. In a wild-type strain, tubular networks of various sizes and staining properties were distributed throughout the cytoplasm, As a rule, wide-meshed, lightly stained polygonal networks were connected to more or less fenestrated sheets of endoplasmic reticulum (ER), Some of these networks were continuous with more intensely stained networks and narrower meshes that displayed at their intersections nodular dilations that progressively increased in size and staining properties to reach those of secretion granules. Such networks presumably corresponded to Golgi elements. Indeed, stacked cisternae typical of the mammalian Golgi apparatus are rarely found in wild-type cells. However, if it is assumed that the Golgi apparatus plays a Key role in the segregation and maturation of secretion granules, then tubular networks with nodular dilations should be equivalent to parts of this organelle, In correlation with the increase in size and density of the nodules there was a decrease in diameter and staining intensity of the interconnecting tubules, These results parallel observations on the formation of secretory granules in mammalian cells and suggest that the segregation of secretory material is concomitant with the progressive perforation and tubulization of previously unperforated sheets. When the sec21-3 thermosensitive mutant was examined at the nonpermissive temperature (37 degreesC), the secretory pathway was blocked at exit from the ER, which started to accumulate as clusters of narrow, anastomosed, unperforated ribbon-like elements. When the block was released by shifting down to permissive temperature (24 degreesC), tubular networks of various sizes and caliber, presumably Golgi in nature, formed as soon as 5 minutes after release of the block. At later time intervals, granules of various sizes and densities appeared to be released by rupture of these tubular networks or even to form at the edges of ER fenestrae, These observations support a dynamic maturation process in which the formation of secretion granules occurs by means of an oriented series of membrane transformations starting at the ER and culminating with the liberation of secretion granules from Golgi networks. C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. CEA Saclay, Dept Biol Cellulaire & Mol, F-91191 Gif Sur Yvette, France. McGill Univ, Dept Anat & Cell Biol, Montreal, PQ H3A 2B2, Canada. RP Jackson, CL (reprint author), NICHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101,18 Library Dr, Bethesda, MD 20892 USA. RI Jackson, Catherine/A-3421-2013 OI Jackson, Catherine/0000-0002-0843-145X NR 28 TC 28 Z9 35 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN PY 2001 VL 114 IS 12 BP 2231 EP 2239 PG 9 WC Cell Biology SC Cell Biology GA 451FL UT WOS:000169790400004 PM 11493663 ER PT J AU Peyroche, A Courbeyrette, R Rambourg, A Jackson, CL AF Peyroche, A Courbeyrette, R Rambourg, A Jackson, CL TI The ARF exchange factors Gea1p and Gea2p regulate Golgi structure and function in yeast SO JOURNAL OF CELL SCIENCE LA English DT Article DE ADP-ribosylation factor (ARF); guanine nucleotide exchange factor (GEF); Sec7 domain; GTP-binding protein; brefeldin A (BFA); trafficking; secretory pathway; Golgi apparatus; yeast ID ADP-RIBOSYLATION FACTOR; BREFELDIN-A; GUANINE-NUCLEOTIDE; SACCHAROMYCES-CEREVISIAE; VESICLE FORMATION; PROTEIN-TRANSPORT; SEC7 DOMAIN; HEAT-SHOCK; LOCALIZATION; APPARATUS AB The Sec7 domain guanine nucleotide exchange factors (GEFs) for the GTPase ARF are highly conserved regulators of membrane dynamics. Their precise molecular roles in different trafficking steps within the cell have not been elucidated. We present a functional analysis of two members of this family, Gea1p and Gea2p, in the yeast Saccharomyces cerevisiae, Gea1p and Gea2p can functionally replace each other, but at least one is necessary for viability. Temperature sensitive gea mutants were generated and found to have defects in ER-Golgi and intra-Golgi transport. Similar to mutants in COPI subunits in yeast, gen mutants had a cargo-selective secretion defect, in that some proteins continued to be secreted whereas others were blocked in the ER or early Golgi, Like yeast arf mutants, the rate of transport of those proteins that continued to be secreted was slowed. In addition, the structure of Golgi elements was severly perturbed in gea mutants. We conclude that Gea1p and Gea2p play an important role in the structure and functioning of the Golgi apparatus in yeast. C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. CEA Saclay, Dept Biol Cellulaire & Mol, Serv Biochim & Genet Mol, F-91191 Gif Sur Yvette, France. RP Jackson, CL (reprint author), NICHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101,18 Library Dr, Bethesda, MD 20892 USA. RI Jackson, Catherine/A-3421-2013; PEYROCHE, Anne /C-5548-2014 OI Jackson, Catherine/0000-0002-0843-145X; PEYROCHE, Anne /0000-0002-8808-8785 NR 53 TC 49 Z9 51 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN PY 2001 VL 114 IS 12 BP 2241 EP 2253 PG 13 WC Cell Biology SC Cell Biology GA 451FL UT WOS:000169790400005 PM 11493664 ER PT J AU Miyafuji, Y Zhong, XL Uchida, I Koi, M Hemmi, H AF Miyafuji, Y Zhong, XL Uchida, I Koi, M Hemmi, H TI Growth inhibition due to complementation of transforming growth factor-beta receptor type II-defect by human chromosome 3 transfer in human colorectal carcinoma cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID DNA MISMATCH REPAIR; NONPOLYPOSIS COLON-CANCER; MICROSATELLITE MUTATOR PHENOTYPE; TUMOR-CELLS; REPEATED SEQUENCES; PROXIMAL COLON; GENE; INSTABILITY; MUTATIONS; HMLH1 AB The transforming growth-beta receptor type II (TGF-beta R11) gene is one of the target genes of the DNA mismatch repair (MMR) defect. The human colorectal carcinoma cell line HCT116 has mutations in the hMLH1 gene and in the microsatellite region of the TGF-beta RII gene, both located on the short arm of chromosome 3. Introduction of the wild-type hMLH1 gene on transferred human chromosome 3 restores many characteristics of MMR-deficiency in HCT116. In this study, we determined whether transfer of chromosome 3 into HCT116 also complements the TGF-beta RII gene defect. We compared in vitro growth characteristics between HCT116 and HCT116 with a transferred chromosome 3 (HCT116 + ch3). The growth was suppressed in HCT116 + ch3 compared with parental HCTI16. This suppression was abolished by frequent replacement with fresh medium, suggesting that the autocrine TCF-beta -TCF-beta RII system may be responsible for growth suppression. To explore this possibility, we determined several characteristics essential for the autocrine system. We found that HCT116 + ch3 expresses wild-type as well as mutated TCF-beta RII mRNA. In addition, phosphorylation of TCF-beta RI and growth inhibition were observed in HCT116 + ch3 but not in HCT116 by exposure to exogenous TGF-P. The amount of TGF-beta1 in HCT116 + ch3 cultures was remarkably less than that in the HCT116, suggesting that TGF-P produced by HCT116 + ch3 cells may be consumed by the cells. The conditioned medium from HCT116 cultures inhibits HCT116 + ch3 growth. This inhibition was neutralized by the anti-TCF-beta antibody. Taken together, these results strongly suggest that the TGF-beta RII gene defect in HCT116 is complemented by a wild-type gene on the transferred chromosome 3 and that HCT116 + ch3 gained the ability to respond to TCF-beta. Simultaneous complementation of defects of a responsible gene and a major target gene by the chromosome transfer is useful to prove the inactivated phenotypes acquired during colorectal tumorigenesis. J. Cell. Physiol. 187: 356-364, 2001. (C) 2001 Wiley-Liss, Inc. C1 Toho Univ, Sch Med, Dept Biol Mol, Ohta Ku, Tokyo 1438540, Japan. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Hemmi, H (reprint author), Toho Univ, Sch Med, Dept Biol Mol, Ohta Ku, Ohmori Nishi 5-21-16, Tokyo 1438540, Japan. RI Koi, Minoru/C-3489-2012; Koi, Minoru/G-9197-2014 NR 49 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUN PY 2001 VL 187 IS 3 BP 356 EP 364 DI 10.1002/jcp.1084 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 428AC UT WOS:000168438100010 PM 11319759 ER PT J AU Ross, GN Fales, HM Lloyd, HA Jones, T Sokoloski, EA Marshall-Batty, K Blum, MS AF Ross, GN Fales, HM Lloyd, HA Jones, T Sokoloski, EA Marshall-Batty, K Blum, MS TI Novel chemistry of abdominal defensive glands of nymphalid butterfly Agraulis vanillae SO JOURNAL OF CHEMICAL ECOLOGY LA English DT Article DE Agraulis vanillae; defensive glands; 6-methyl-5-hepten-2-one; 6-methyl-5-hepten-2-ol esters; 1,15-hexadecanediol diacetate; 1,16-hexadecanediol diacetate AB Abdominal defensive glands of both sexes of the Gulf fritillary butterfly, Agraulis vanillae (Linnaeus) (Nymphalidae:Heliconiinae) emit a pronounced odor when disturbed. We have identified 6-methyl-5-hepten-2-one; oleic, palmitic, and stearic esters of the corresponding alcohol 6-methyl-5-hepten-2-ol; hexadecyl acetate; 1,16-hexadecanediol diacetate; and 1,15-hexadecanediol diacetate in the glandular exudate. Since we have determined that free-flying birds or birds in a butterfly conservatory discriminate against A. vanillae as prey, we suggest that the constituents in the glands may play a defensive role against potential avian predators. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA. Univ Georgia, Dept Entomol, Athens, GA 30602 USA. RP Fales, HM (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 13 TC 7 Z9 7 U1 1 U2 6 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0098-0331 J9 J CHEM ECOL JI J. Chem. Ecol. PD JUN PY 2001 VL 27 IS 6 BP 1219 EP 1228 DI 10.1023/A:1010372114144 PG 10 WC Biochemistry & Molecular Biology; Ecology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology GA 457JF UT WOS:000170133100011 PM 11504024 ER PT J AU Pearl, PL Krasnewich, D AF Pearl, PL Krasnewich, D TI Neurologic course of congenital disorders of glycosylation SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID DEFICIENT GLYCOPROTEIN SYNDROME AB Congenital disorders of glycosylation, formerly called carbohydrate-deficient glycoprotein syndrome, may present in infancy with slowly progressive neurologic deficits including cognitive impairment, ataxia, pigmentary retinal degeneration, and neuropathy. The metabolic defect is in N-linked oligosaccharide synthesis, and diagnosis is made by a serum transferrin isoelectric focusing. We reviewed the neurologic course of 10 children with congenital disorders of glycosylation (ages 13 months to 7 years). All had severe developmental delay and ataxia; none walked Unassisted, and the highest level of communication was simple sign language in one patient. Five of 10 children had seizures (absence, complex partial, tonic clonic). Only one patient has had strokelike episodes, despite reports that they are common in this population. The underlying basis of these episodes has been hypothesized to be coagulopathy due to dysfunctional, incorrectly glycosylated coagulation factors. This 5-year-old patient with congenital disorders of glycosylation type Ia had two strokelike episodes, with evolving hemiparesis over 5 to 6 days' duration, followed by focal tonic-clonic seizures. Coagulation studies were normal. Electroencephalography showed transient hemispheric polymorphous delta-range slowing and suppression. Magnetic resonance imaging revealed corresponding cortical swelling. Magnetic resonance angiography was normal. Magnetic resonance spectroscopy revealed a decrease in the N-acetylaspartate peak, suggesting neuronal loss, with normal lactate peak. The neuroradiologic data do not support a thrombotic, embolic, or hemorrhagic basis for strokelike episodes in carbohydrate-deficient glycoprotein syndrome; other mechanisms must be considered. C1 George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. NIH, Med Genet Branch, Bethesda, MD 20892 USA. RP Pearl, PL (reprint author), George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 7 TC 16 Z9 16 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD JUN PY 2001 VL 16 IS 6 BP 409 EP 413 DI 10.1177/088307380101600604 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 473DY UT WOS:000171025800004 PM 11417605 ER PT J AU Tallent, KA Weinberger, DR Goldberg, TE AF Tallent, KA Weinberger, DR Goldberg, TE TI Associating semantic space abnormalities with formal thought disorder in schizophrenia: Use of triadic comparisons SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID LISTENERS TASK; LANGUAGE; ATTENTION; NETWORK AB Recent studies of schizophrenia have suggested that thought disorder results from abnormalities in semantic processing. In the following pilot study, the cognitive system used for organizing and associating concepts was examined using a triadic comparison task. The semantic maps of schizophrenia patients with high thought disorder (N = 5) were compared to that of schizophrenia patients with low levels of thought disorder (N = 5) and normal controls (N = 10) with multidimensional scaling analysis. At initial testing and at retest, patients with high levels of thought disorder exhibited consistently lower semantic goodness of fit scores and failed to map results of triadic comparisons along well-defined dimensions. Results suggest that thought disorder in schizophrenia is related to a disturbance in the organization of semantic networks. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA. RP Goldberg, TE (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, 10 Ctr Dr,Room 4S235 MSC 1379, Bethesda, MD 20892 USA. NR 31 TC 11 Z9 11 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD JUN PY 2001 VL 23 IS 3 BP 285 EP 296 DI 10.1076/jcen.23.3.285.1185 PG 12 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 439JG UT WOS:000169112900004 PM 11404807 ER PT J AU Altemus, M Roca, C Galliven, E Romanos, C Deuster, P AF Altemus, M Roca, C Galliven, E Romanos, C Deuster, P TI Increased vasopressin and adrenocorticotropin responses to stress in the midluteal phase of the menstrual cycle SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-ADRENAL AXIS; RAT ANTERIOR-PITUITARY; ESTROGEN-INDUCED ALTERATIONS; MESSENGER-RIBONUCLEIC-ACID; GLUCOCORTICOID RECEPTOR; METABOLIC RESPONSES; LUTEAL-PHASE; NEUROENDOCRINE RESPONSES; CORTICOSTERONE SECRETION; PREMENSTRUAL SYMPTOMS AB Accumulating evidence indicates that gonadal steroids modulate functioning of the hypothalamic-pituitary-adrenal (HPA) axis, which has been closely linked to the pathophysiology of anxiety and depression. However, the effect of the natural menstrual cycle on HPA axis responsivity to stress has not been clearly described. In nine healthy women, metabolic and hormonal responses to treadmill exercise stress during the early follicular phase of the menstrual cycle, when gonadal steroid levels are low, were compared with responses in the midluteal phase of the cycle, when both progesterone and estrogen levels are relatively high. Exercise intensity was gradually increased over 20 min to reach 90% of each subject's maximal oxygen consumption during the final 5 min of exercise. Basal plasma lactate, glucose, ACTH, vasopressin, oxytocin, and cortisol levels were similar in the two cycle phases. However, in response to exercise stress, women in the midluteal phase had enhanced ACTH (P < 0.0001), vasopressin (P < 0.01), and glucose (P < 0.001) secretion. These findings suggest that relatively low levels of gonadal steroids during the early follicular phase of the menstrual cycle provide protection from the impact of stress on the HPA axis. C1 Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY 10021 USA. NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. RP Altemus, M (reprint author), Cornell Univ, Weill Med Coll, Dept Psychiat, Box 244,1300 York Ave, New York, NY 10021 USA. EM maltemus@mail.med.cornell.edu RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 66 TC 58 Z9 58 U1 1 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 JUN PY 2001 VL 86 IS 6 BP 2525 EP 2530 DI 10.1210/jc.86.6.2525 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444QX UT WOS:000169412000031 PM 11397850 ER PT J AU Erickson, K Thorsen, P Chrousos, G Grigoriadis, DE Khongsaly, O McGregor, J Schulkin, J AF Erickson, K Thorsen, P Chrousos, G Grigoriadis, DE Khongsaly, O McGregor, J Schulkin, J TI Preterm birth: Associated neuroendocrine, medical, and behavioral risk factors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; CRF-BINDING-PROTEIN; MATERNAL PLASMA; HUMAN-PLACENTA; MESSENGER-RNA; FETAL MEMBRANES; PRENATAL STRESS; DELIVERY; PREGNANCY; LABOR AB Increased CRH secretion by the placenta of pregnant women has been associated with preterm birth. Certain indices of risk, both medical and psychosocial in nature, have been linked to preterm delivery. Levels of total, bound, and free CRH, CRH-binding protein (CRH-BP), and cortisol were measured prospectively in a large sample of pregnant Danish women who delivered preterm and term infants. Measures of maternal serum hormones were taken at 7-23 and 27-37 weeks gestation and, for those who delivered at term, at 37-43 weeks gestation. At 7-23 weeks gestation, maternal levels of total CRH (P = 0.01), bound CRH (P = 0.03), and CRH-BP (P = 0.01) were higher in the preterm than in the term group. At 27-37 weeks gestation, levels of total CRH (P < 0.0001), bound CRH (P < 0.0001), free CRH (P < 0.0001), and cortisol (P < 0.0001) were all higher in the preterm than the term group, whereas levels of CRH-BP (P < 0.0001) were lower in the preterm than in the term group. The best medical and behavioral factors associated with preterm delivery were, respectively, previous preterm delivery (P < 0.0001) and engagement in certain risk-taking behaviors (P = 0.008). The positive relations between preterm delivery and various adverse medical and socioeconomic variables with increases in placental secretion of CRH suggest that the latter may participate in the pathophysiology of preterm delivery. C1 Georgetown Univ, Dept Physiol & Biophys, Washington, DC 20007 USA. Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80217 USA. Neurocrine Biosci Inc, San Diego, CA 92121 USA. NICHHD, Pediat & Reprod Emdocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Aarhus, Danish Epidemiol Sci Ctr, Aarhus, Denmark. Ctr Dis Control & Prevent, Div Child Dev Disabil & Hlth, Atlanta, GA 30333 USA. American Univ, Dept Psychol, Washington, DC 20016 USA. RP Schulkin, J (reprint author), Georgetown Univ, Dept Physiol & Biophys, Basic Sci Bldg, Washington, DC 20007 USA. EM jschulkin@acog.org NR 48 TC 91 Z9 94 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2001 VL 86 IS 6 BP 2544 EP 2552 DI 10.1210/jc.86.6.2544 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444QX UT WOS:000169412000034 PM 11397853 ER PT J AU Hiroi, N Chrousos, GP Kohn, B Lafferty, A Abu-Asab, M Bonat, S White, A Bornstein, SR AF Hiroi, N Chrousos, GP Kohn, B Lafferty, A Abu-Asab, M Bonat, S White, A Bornstein, SR TI Adrenocortical-pituitary hybrid tumor causing Cushing's syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LEUKEMIA INHIBITORY FACTOR; NEUROENDOCRINE PROPERTIES; ADRENAL-CORTEX; CHROMOGRANIN-A; RECEPTORS; CELLS; ORGANOGENESIS; PATHOGENESIS; SF-1; PTX1 AB We describe the first case of an adrenocortical-pituitary hybrid tumor causing Cushing's syndrome in a 17-yr-old boy. Adrenal vein sampling confirmed elevated secretion of both cortisol and ACTH precursors from a right adrenal mass, whereas pituitary ACTH levels, as determined by bilateral inferior petrosal sinus samples (IPSS), were unresponsive to CRH and equal to peripheral levels. There was no biochemical or histological evidence for a pheochromocytoma, but, rather, the tumor demonstrated lipid-rich clear cells characteristic of an adrenocortical adenoma. Immunohistochemical analysis revealed ACTH immunoreactivity and synaptophysin proteins in the tumor. Isolation of tumor cells by the novel technique of laser capture microdissection and subsequent RT-PGR showed expression of POMC messenger ribonucleic acid and cytochrome p450 enzyme messenger ribonucleic acid within the same cells. Finally, ultrastructural analysis provided ultimate proof for adrenocortical-pituitary hybrid cells exhibiting the characteristic vesicular mitochondria and abundant smooth endoplasmic reticulum of steroid cells and the typical secretory granules of corticotrophs within the cytoplasm of the same cells. The adrenocortical tumor expressed the pituitary transcription factor pituitary homeobox factor 1 and the steroidogenic factor 1. The intermingling of the centrally located ectodermally derived pituitary tissue with the mesodermally derived adrenocortical tissue in this adenoma suggests a hitherto unrecognized genetic and phenotypic plasticity within the hypothalamic-pituitary-adrenal axis. C1 Univ Dusseldorf, Dept Endocrinol, D-40225 Dusseldorf, Germany. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Monash Univ, Dept Pediat, Clayton, Vic 3168, Australia. NYU, Med Ctr, Div Pediat Endocrinol, New York, NY 10016 USA. Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England. Univ Manchester, Dept Med, Manchester M13 9PT, Lancs, England. RP Bornstein, SR (reprint author), Univ Dusseldorf, Dept Endocrinol, Mooren Str 5, D-40225 Dusseldorf, Germany. EM STEFAN.BORNSTEIN@UNI-DUSSELDORF.DE RI White, Anne/C-3753-2011 NR 29 TC 12 Z9 12 U1 0 U2 1 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 JUN PY 2001 VL 86 IS 6 BP 2631 EP 2637 DI 10.1210/jc.86.6.2631 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444QX UT WOS:000169412000045 PM 11397864 ER PT J AU Charmandari, E Hindmarsh, PC Johnston, A Brook, CGD AF Charmandari, E Hindmarsh, PC Johnston, A Brook, CGD TI Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: Alterations in cortisol pharmacokinetics at puberty SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN ADRENOCORTICAL-CELLS; 11-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY; GROWTH-HORMONE REPLACEMENT; INSULIN SENSITIVITY; IGF-I; STEROIDOGENIC ENZYME; SEXUAL-DIMORPHISM; RAT; MODULATION; METABOLISM AB In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, treatment with glucocorticoid and mineralocorticoid substitution is not always satisfactory. Suboptimal control is often observed in pubertal patients, despite adequate replacement doses and adherence to treatment. We investigated whether the pubertal process is associated with alterations in cortisol pharmacokinetics resulting in a loss of control of the hypothalamic-pituitary-adrenal axis. We determined the pharmacokinetics of hydrocortisone administered iv as a bolus. A dose of 15 mg/m(2) body surface area was given to 14 prepubertal (median age, 9.4 yr; range, 6.1-10.8 yr), 20 pubertal (median, 13.5 yr; range, 10.6-16.8 yr), and 6 postpubertal (median, 18.2 yr; range, 17.2-20.3 yr) patients with salt-wasting CAH. All patients were on standard replacement therapy with hydrocortisone and 9 alpha -fludrocortisone. Serum total cortisol concentrations were measured at 10-min intervals for 6 h following iv hydrocortisone bolus and analyzed using a solid-phase RIA. The serum total cortisol clearance curve was monoexponential. Mean clearance was significantly higher in the pubertal group (mean, 427.0 mL/min; SD, 133.4) compared with the prepubertal (mean, 248.7 mL/min; SD, 100.6) and postpubertal (mean, 292.4 mL/min; SD, 106.3) tone-way ANOVA, F = 9.8, P < 0.001) groups. This effect persisted after adjustment for body mass index. The mean volume of distribution was also significantly higher in the pubertal (mean, 49.5 L; so, 12.2) than the prepubertal (mean, 27.1 L; SD, 8.4) patients but not in the postpubertal(mean, 40.8 L; sn, 16) (ANOVA, F = 15.2, P < 0.001) patients. The significance remained after correction for body mass index. There was no significant difference in mean half-life of total cortisol in prepubertal (mean, 80.2 min; SD, 19.4), pubertal (mean, 84.4 min; SD, 24.9), and postpubertal (mean, 96.7 min; SD, 9.9) patients. Similar differences between groups were observed when the pharmacokinetic parameters of free cortisol were examined. In addition, the half-life of free cortisol was significantly shorter in females compared with males (P = 0.04). These data suggest that puberty is associated with alterations in cortisol pharmacokinetics resulting in increased clearance and volume of distribution with no change in half-life. These alterations probably reflect changes in the endocrine milieu at puberty and may have implications for therapy of CAH and other conditions requiring cortisol substitution in the adolescent years. C1 UCL, London Ctr Paediat Endocrinol, London, England. St Bartholomews & Royal London Sch Med & Dent, Dept Clin Pharmacol, London, England. RP Charmandari, E (reprint author), NICHHD, NIH, Pediat & Reprod Endocrinol Branch, 10 Ctr Dr,Bldg 10,Suite 9D42, Bethesda, MD 20892 USA. EM charmane@mail.nih.gov RI Hindmarsh, Peter/C-4964-2008; Charmandari, Evangelia/B-6701-2011 NR 38 TC 50 Z9 54 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2001 VL 86 IS 6 BP 2701 EP 2708 DI 10.1210/jc.86.6.2701 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444QX UT WOS:000169412000055 PM 11397874 ER PT J AU Hirschfeld, S AF Hirschfeld, S TI Comment - Disclosing a diagnosis of HIV in pediatrics: Providing the best possible care SO JOURNAL OF CLINICAL ETHICS LA English DT Editorial Material ID ANTIRETROVIRAL THERAPY; CHILDREN; CANCER C1 Natl Canc Inst, US Publ Hlth Serv, NIH, Bethesda, MD 20892 USA. RP Hirschfeld, S (reprint author), Natl Canc Inst, US Publ Hlth Serv, NIH, Bethesda, MD 20892 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 7 TC 0 Z9 0 U1 1 U2 1 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 17100 COLE RD #312, HAGERSTOWN, MD 21740-6901 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD SUM PY 2001 VL 12 IS 2 BP 158 EP 160 PG 3 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 480YC UT WOS:000171489900011 PM 11642068 ER PT J AU Smith, WL Langenbach, R AF Smith, WL Langenbach, R TI Why there are two cyclooxygenase isozymes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROSTAGLANDIN E-2 BIOSYNTHESIS; ARACHIDONIC-ACID; H SYNTHASE-1; GENE DISRUPTION; MICE; MOUSE; INHIBITION; RATS; IDENTIFICATION; INFLAMMATION C1 Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. Natl Inst Environm Hlth Sci, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC USA. RP Smith, WL (reprint author), Michigan State Univ, Dept Biochem & Mol Biol, 513 Biochem Bldg, E Lansing, MI 48824 USA. FU NIDDK NIH HHS [DK22042]; NIGMS NIH HHS [P01 GM57323] NR 38 TC 417 Z9 439 U1 3 U2 10 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2001 VL 107 IS 12 BP 1491 EP 1495 DI 10.1172/JCI13271 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 445TN UT WOS:000169474800002 PM 11413152 ER PT J AU Sweetenham, JW Santini, G Qian, W Guelfi, M Schmitz, N Simnett, S Nagler, A Holte, H Kvaloy, S Bruzzi, P Goldstone, AH AF Sweetenham, JW Santini, G Qian, W Guelfi, M Schmitz, N Simnett, S Nagler, A Holte, H Kvaloy, S Bruzzi, P Goldstone, AH TI High-dose therapy and autologous stem-cell transplantation versus conventional-dose consolidation/maintenance therapy as postremission therapy for adult patients with lymphoblastic lymphoma: Results of a randomized trial of the European group for blood and marrow transplantation and the United Kingdom lymphoma group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; 1ST COMPLETE REMISSION; WEEKLY CHEMOTHERAPY; CLASSIFICATION AB Purpose: To determine whether a combination of high-dose therapy and autologous stem-cell transplantation (ASCT) is superior to conventional-dose consolidation and maintenance chemotherapy as postremission therapy in adults with lymphoblastic lymphoma. Patients and Methods: One hundred nineteen patients were entered onto this prospective randomized trial from 37 centers. Patients received standard remission induction therapy, and responding patients were randomized either to continue with a conventional consolidation/maintenance protocol (CC) or to receive high-dose therapy and ASCT. In some centers, patients with HLA-identical sibling donors were registered on the trial but proceeded to allogeneic bone marrow transplantation (BMT) without randomization. Results: Of the 119 patients entered, 111 were assessable for response to induction therapy. The overall response rate was 82% (56% complete response, 26% partial response). Of the 98 patients eligible for randomization, 65 were randomized, 31 to ASCT and 34 to CC. Reasons for failure to randomize included patient refusal (12 patients), early progression or death on induction therapy (eight patients), excessive toxicity of induction regimen (six patients), and elective allogeneic PMT (12 patients). With a median follow-up of 37 months, the actuarial 8-year relapse-free survival rate is 24% for the CC arm and 55% for the ASCT arm (hazards ratio = 0.55 in favor of the ASCT arm; 95% confidence interval [CI], 0.29 to 1.04; P =.065). The corresponding figures for overall survival are 45% and 56%, respectively (hazards ratio = 0.87 in favor of the ASCT arm; 95% CI, 0.42 to 1.81; P =.71). Conclusion: The use of ASCT in adults with lymphoblastic lymphoma in first remission produced a trend for improved relapse-free survival but did not improve overall survival compared with conventional-dose therapy in this small randomized trial. (C) 2001 by American Society of Clinical Oncology. C1 Univ Kiel, Dept Internal Med 2, D-2300 Kiel, Germany. Norwegian Radium Hosp, Dept Oncol, Oslo, Norway. Hadassah Univ Hosp, Dept Bone Marrow Transplant, IL-91120 Jerusalem, Israel. Natl Canc Inst, Unit Epidemiol & Clin Trials, Genoa, Italy. San Martino Hosp, Dept Haematol, Genoa, Italy. UCL Hosp, Dept Haematol, London, England. MRC, Canc Trials Off, Cambridge, England. Univ Southampton, Wessex Med Oncol Unit, Canc Res Campaign, Southampton, Hants, England. RP Sweetenham, JW (reprint author), Univ Colorado, Hlth Sci Ctr, Div Med Oncol B171, 4200 E 9th Ave, Denver, CO 80262 USA. EM john.sweetenham@uchsc.edu NR 21 TC 56 Z9 69 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2001 VL 19 IS 11 BP 2927 EP 2936 PG 10 WC Oncology SC Oncology GA 438BN UT WOS:000169034000021 PM 11387366 ER PT J AU Dupont, J Le Roith, D AF Dupont, J Le Roith, D TI Insulin-like growth factor 1 and oestradiol promote cell proliferation of MCF-7 breast cancer cells: new insights into their synergistic effects SO JOURNAL OF CLINICAL PATHOLOGY-MOLECULAR PATHOLOGY LA English DT Review DE breast cancer; oestrogen receptor; insulinlike growth factor 1 receptor; cell cycle ID I SOMATOMEDIN RECEPTOR; ESTROGEN-RECEPTOR; CYCLIN D1; IGF-I; CDK INHIBITORS; KINASE; MICE; EXPRESSION; PROTEIN; SYSTEM AB In MCF-7 breast cancer cells, the insulinlike growth factor 1 receptor (IGF-1R) and the oestrogen receptor (ER) are coexpressed and the two signalling systems are engaged in a crosstalk that results in synergistic growth. However, coupling between the signalling cascades is poorly understood. Oestradiol enhances IGF-1R signalling by inducing the expression of insulin receptor substrate 1 (IRS-1), a substrate of the IGF-1R. Oestradiol induced expression of IRS-1 results in enhanced tyrosine phosphorylation of IRS-1 after IGF-1 stimulation, followed by enhanced mitogen activated protein kinase, phosphoinositide 3 ' kinase, and Akt activation. Oestradiol can also potentiate the effect of IGF-1 on the expression of cyclin D1 and cyclin E, and on the phosphorylation of the retinoblastoma protein (RB). These effects are greatly diminished in SX13 cells, which exhibit a 50% reduction in IGF-1R expression but few functional IGF-1Rs at the surface. Oestradiol and IGF-1 regulate the expression of two cyclin dependent kinase inhibitors, p21 and p27, differently. Whereas IGF-1 increases p21 expression and reduces p27 expression, oestradiol has no effect on p21. In summary, in MCF-7 cells, oestrogen potentiates the effect of IGF-1 on IGF-1R signalling and its effects on certain cell cycle components. C1 NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Le Roith, D (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Room 8D12,Bldg 10, Bethesda, MD 20892 USA. NR 43 TC 33 Z9 33 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1366-8714 J9 J CLIN PATHOL-MOL PA JI J. Clin. Pathol.-Mol. Pathol. PD JUN PY 2001 VL 54 IS 3 BP 149 EP 154 PG 6 WC Pathology SC Pathology GA 440WX UT WOS:000169200600006 ER PT J AU Goldszal, AF Brown, GK McDonald, HJ Vucich, JJ Staab, EV AF Goldszal, AF Brown, GK McDonald, HJ Vucich, JJ Staab, EV TI The National Institutes of Health clinical center digital imaging network, picture archival and communication system, and radiology information system SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Computer-Applications-in-Radiology CY MAY 03-06, 2001 CL SALT LAKE CITY, UTAH SP Soc Comp Applicat Radiol AB In this work, we describe the digital imaging network (DIN), picture archival and communication system (PACS), and radiology information system (RIS) currently being implemented at the Clinical Center, National Institutes of Health (NIH). These systems are presently in clinical operation. The DIN is a redundant meshed network designed to address gigabit density and expected high bandwidth requirements for image transfer and server aggregation. The PACS projected workload is 5.0 TB of new imaging data per year. Its architecture consists of a central, high-throughput Digital Imaging and Communications in Medicine (DICOM) data repository and distributed redundant array of inexpensive disks (RAID) servers employing fiber-channel technology for immediate delivery of imaging data. On demand distribution of images and reports to clinicians and researchers is accomplished via a clustered web server. The RIS follows a client-server model and provides tools to order exams, schedule resources, retrieve and review results, and generate management reports. The RIS-hospital information system (HIS) interfaces include admissions, discharges, and transfers (ATDs)/demographics, orders. appointment notifications, doctors update, and results. Copyright (C) 2001 by W.B. Saunders Company. C1 NIH, Ctr Clin, Imaging Sci Program, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Goldszal, AF (reprint author), Univ Penn Hlth Syst, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD JUN PY 2001 VL 14 IS 2 SU 1 BP 177 EP 181 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 444MX UT WOS:000169404200048 PM 11442088 ER PT J AU Colliver, JD Hughes, A AF Colliver, JD Hughes, A TI Substance use survey data collection methodologies and selected papers - Commentary SO JOURNAL OF DRUG ISSUES LA English DT Editorial Material C1 NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. RP Colliver, JD (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 1 U2 1 PU J DRUG ISSUES INC PI TALLAHASSEE PA FLORIDA STATE UNIV, SCHOOL CRIMINOLOGY CRIMINAL JUSTICE, PO BOX 66696, TALLAHASSEE, FL 32313-6696 USA SN 0022-0426 J9 J DRUG ISSUES JI J. Drug Issues PD SUM PY 2001 VL 31 IS 3 BP 717 EP 720 PG 4 WC Substance Abuse SC Substance Abuse GA 474FZ UT WOS:000171096800007 ER PT J AU Pandiani, JA Schacht, LM Banks, SM AF Pandiani, JA Schacht, LM Banks, SM TI After children's services: A longitudinal study of significant life events SO JOURNAL OF EMOTIONAL AND BEHAVIORAL DISORDERS LA English DT Article ID OUTCOMES; DISTURBANCE; TRANSITION; ADULTHOOD; YOUTH AB In this article we examined the long-term (3 year) treatment outcomes of all adolescents who received services in a statewide system of care. The outcomes included rates of hospitalization, incarceration, and maternity. Because the outcome measures were derived from existing administrative and public health data, outcome data were available for all participants. Results indicate that recipients of services had substantially elevated rates of incarceration and hospitalization (compared to the general population) but that maternity rates in the treatment groups were not different from other young women in the same age group, interestingly the amount of elevation of incarceration and hospitalization rates decreased over time. C1 Vermont Dept Dev & Mental Hlth Serv, Waterbury, VT 05671 USA. Univ Massachusetts, Sch Med, Dept Psychiat, Amherst, MA 01003 USA. NIH, Bethesda, MD USA. RP Pandiani, JA (reprint author), Vermont Dept Dev & Mental Hlth Serv, 103 S Main St, Waterbury, VT 05671 USA. NR 16 TC 3 Z9 3 U1 0 U2 1 PU PRO-ED INC PI AUSTIN PA 8700 SHOAL CREEK BLVD, AUSTIN, TX 78757-6897 USA SN 1063-4266 J9 J EMOT BEHAV DISORD JI J. Emot. Behav. Disord. PD SUM PY 2001 VL 9 IS 2 BP 131 EP 138 DI 10.1177/106342660100900208 PG 8 WC Education, Special; Psychology, Educational; Psychology, Multidisciplinary SC Education & Educational Research; Psychology GA 434WX UT WOS:000168839800008 ER PT J AU Sternberg, EM AF Sternberg, EM TI Neuroendocrine regulation of autoimmune/inflammatory disease SO JOURNAL OF ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT EUROSTERONE Meeting on Nuclear Receptors and their Role in Regulation of Inflammation CY SEP 27, 2000 CL HUDDINGE, SWEDEN ID PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING HORMONE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; STRESS-INDUCED ENHANCEMENT; INFLUENZA VIRAL-INFECTION; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; LEWIS RATS; IMMUNOENDOCRINE COMMUNICATION; DIFFERENTIALLY AFFECTS AB Interactions between the immune and nervous systems play an important role in modulating host susceptibility and resistance to inflammatory disease. Neuroendocrine regulation of inflammatory and immune responses and disease occurs at multiple levels: systematically, through the anti-inflammatory action of glucocorticoids released via hypothalamic-pituitary-adrenal axis stimulation; regionally, through production of glucocorticoids within and sympathetic innervation of immune organs such as the thymus; locally, at sites of inflammation. Estrogens also play an important role ill immune modulation, and contribute to the approximately 2- to 10-fold higher lncidence of autoimmune/inflammatory diseases seen in females of all mammalian species. During inflammation, cytokines from the periphery activate the central nervous system through multiple routes. This results in stimulation of the hypothalamic-pituitary-adrenal axis which. in turn through the immunosuppressive effects of the glucocorticoids, generally inhibits inflammation. Recent studies indicate that physiological levels of glucocorticoids are immunomodulatory rather than solely immunosuppressive, causing a shift in patterns of cytokine production from a TH1- to a TH2-type pattern. Interruption of this loop at any level and through multiple mechanisms, whether genetic, or through surgical or pharmacological interventions, can render an inflammatory resistant host susceptible to inflammation disease. Over-activation of this axis, as occurs during stress, can also affect severity of infectious disease through the immunosuppressive effects of the glucocorticoids. These interactions have been clearly demonstrated in many animal models, across species, strains and diseases, and are also relevant to human inflammatory. autoimmune and allergic illnesses, including rheumatoid arthritis, systemic lupus erythematosus. Sjorgen's syndrome, allergic asthma and atopic skin disease, While many genes and environmental factors contribute to susceptibility and resistance to autoimmune inflammatory diseases, a full understanding of the molecular effects on immune responses of combinations of neuropeptides, neurohormones and neurotransmitters at all levels has opened up new therapeutic approaches and are essential for the design of future therapies based on such principles. C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, NIH, Bldg 10,Room 2D-46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. NR 68 TC 193 Z9 204 U1 3 U2 10 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 JUN PY 2001 VL 169 IS 3 BP 429 EP 435 DI 10.1677/joe.0.1690429 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 440TT UT WOS:000169190900002 PM 11375112 ER PT J AU Kino, T Chrousos, GP AF Kino, T Chrousos, GP TI Glucocorticoid and mineralocorticoid resistance/hypersensitivity syndromes SO JOURNAL OF ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT EUROSTERONE Meeting on Nuclear Receptors and their Role in Regulation of Inflammation CY SEP 27, 2000 CL HUDDINGE, SWEDEN ID IMMUNODEFICIENCY-VIRUS TYPE-1; PRIMARY CORTISOL RESISTANCE; CELL-CYCLE; PSEUDOHYPOALDOSTERONISM TYPE-1; RECEPTOR-BETA; HIV-1 VPR; CHANNEL; MUTATION; INFECTION; SUBUNITS AB Glucocorticoids and mineralocorticoids regulate diverse functions important to maintain central nervous system, cardiovascular, metabolic, and immune homeostasis. The actions of these hormones are mediated by their specific intracellular receptors: the glucocorticoid (GR) and mineralocorticoid (MR) receptors, Pathologic conditions associated with changes of tissue sensitivity to these hormones have been described. The syndrome of familial glucocorticoid resistance is characterized by hypercortisolism without Cushing's syndrome stigmata. The molecular defects of four kindreds and one sporadic case have been elucidated as inactivating mutations in the ligand-binding: domain of GR. Two cases developed glucocorticoid resistance at the heterozygous state. In these patients, mutant receptors possessed transdominant negative activity upon the wild type receptor. Insensitivity to mineralocorticoids (which may also be caused by loss of function mutations of the MR gene) was found in one sporadic case and four autosomal dominant cases of Pseudohypoaldosteronism type 1. These included two frameshift mutations and a premature termination codon in exon 2, leading to gene products lacking the entire DNA- and ligand-binding domains, and a single base-pair deletion in the intron-5 splice donor site. Tissue hypersensitivity to glucocorticoids was recently hypothesized in patients with Human Immunodeficiency Virus (HIV) type-1 infection via the accessory proteins Vpr and Tat which enhance GR transactivation. Since HIV-1 long terminal repeat (LTR) and glucocorticoid-responsive promoters use the satire set of coactivators, these proteins may stimulate HIV-1-LTR and glucocorticoid-inducible genes concurrently. The former may directly stimulate viral proliferation, while the latter may indirectly enhance viral propagation by suppressing the host immune system through glucocorticoid-mediated mechanisms. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Chrousos, GP (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Rm 9D42,10 Ctr Dr MSC 1583, Bethesda, MD 20892 USA. NR 69 TC 79 Z9 82 U1 0 U2 2 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 JUN PY 2001 VL 169 IS 3 BP 437 EP 445 DI 10.1677/joe.0.1690437 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 440TT UT WOS:000169190900003 PM 11375113 ER PT J AU Sekiya, I Koopman, P Tsuji, K Mertin, S Harley, V Yamada, Y Shinomiya, K Nifuji, A Noda, M AF Sekiya, I Koopman, P Tsuji, K Mertin, S Harley, V Yamada, Y Shinomiya, K Nifuji, A Noda, M TI Dexamethasone enhances SOX9 expression in chondrocytes SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID SRY-RELATED GENE; TRANSPLANTABLE RAT CHONDROSARCOMA; RABBIT COSTAL CHONDROCYTES; AUTOSOMAL SEX REVERSAL; II COLLAGEN; GLUCOCORTICOID INHIBITION; HORMONE RESPONSIVENESS; CAMPOMELIC DYSPLASIA; CELL-POPULATION; CARTILAGE AB SOX9 is a transcription factor that activates type II procollagen (Col2a1) gene expression during chondrocyte differentiation. Glucocorticoids are also known to promote chondrocyte differentiation via unknown molecular mechanisms. We therefore investigated the effects of a synthetic glucocorticoid, dexamethasone (DEX), on Sox9 gene expression in chondrocytes prepared From rib cartilage of newborn mice. Sox9 mRNA was expressed at high levels in these chondrocytes. Treatment with DEX enhanced Sox9 mRNA expression within 24 h and this effect was observed at least up to 48 h. The effect of DEX was dose dependent, starting at 0.1 nM and maximal at 10 nM. The half life of Sox9 mRNA was approximately 45 min in the presence or absence of DEX. Western blot analysis revealed that DEX also enhanced the levels of SOX9 protein expression. Treatment with DEX enhanced Col2a1 mRNA expression in these chondrocytes and furthermore, DEX enhanced the activity of Col2-CAT (chloramphenicol acetyltransferase) construct containing a 1.6 kb intron fragment where chondrocyte-specific Sry/Sox-consensus sequence is located. The enhancing effect of DEX was specific to SOX9, as DEX did not alter the levels of Sox6 mRNA expression. These data suggest that DEX promotes ch differentiation through enhancement of SOX9. C1 Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Chiyoda Ku, Tokyo 101, Japan. Univ Queensland, Ctr Mol & Cellular Biol, Brisbane, Qld, Australia. Univ Melbourne, Howard Florey Inst Expt Physiol & Med, Parkville, Vic 3052, Australia. NIDR, Dev Biol Lab, Bethesda, MD 20892 USA. Natl Inst Craniofacial Res, Dev Biol Lab, Bethesda, MD USA. Tokyo Med & Dent Univ, Dept Orthopaed Surg, Tokyo, Japan. RP Noda, M (reprint author), Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Chiyoda Ku, 2-3-10 Kanda Surugadai, Tokyo 101, Japan. RI Koopman, Peter /C-9416-2009; OI Koopman, Peter /0000-0001-6939-0914; Harley, Vincent/0000-0002-2405-1262 NR 36 TC 46 Z9 48 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 JUN PY 2001 VL 169 IS 3 BP 573 EP 579 DI 10.1677/joe.0.1690573 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 440TT UT WOS:000169190900017 PM 11375127 ER PT J AU McCarron, P Hart, CL Hole, D Smith, GD AF McCarron, P Hart, CL Hole, D Smith, GD TI The relation between adult height and haemorrhagic and ischaemic stroke in the Renfrew/Paisley study SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID RISK; POPULATION; WOMEN; MEN C1 Univ Bristol, Dept Social Med, Bristol, Avon, England. Univ Glasgow, Dept Publ Hlth, Glasgow, Lanark, Scotland. RP McCarron, P (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,Execut Plaza N,Suite 4097, Bethesda, MD 20892 USA. OI Davey Smith, George/0000-0002-1407-8314 NR 8 TC 30 Z9 30 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD JUN PY 2001 VL 55 IS 6 BP 404 EP 405 DI 10.1136/jech.55.6.404 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 433FY UT WOS:000168750600013 PM 11350997 ER PT J AU Ribeiro, JMC Charlab, R Valenzuela, JG AF Ribeiro, JMC Charlab, R Valenzuela, JG TI The salivary adenosine deaminase activity of the mosquitoes Culex quinquefasciatus and Aedes aegypti SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE saliva; blood-feeding insect; haematophagy; adenosine deaminase; mosquito; Culex quinquefasciatus; Aedes aegypti; Anopheles gambiae ID FLY LUTZOMYIA-LONGIPALPIS; HISTAMINE-BINDING; PROBING TIME; MAST-CELLS; PROTEIN; GLANDS; PURIFICATION; NOCICEPTION; RECEPTORS; DATABASE AB A cDNA coding for a protein with significant similarity to adenosine deaminase (ADA) was found while randomly sequencing a cDNA library constructed from salivary gland extracts of adult female Culex quinquefasciatus. Prompted by this result, we found high ADA activities in two culicine mosquitoes, Culex quinquefasciatus and Aedes aegypti, but not in the anopheline Anopheles gambiae. Homogenates from Culex quinquefasciatus also have an AMP deaminase activity that is three times greater than the ADA activity, whereas in Aedes aegypti the AMP deaminase activity is less than 10 % of the ADA activity. Evidence for secretion of ADA during blood feeding by Aedes aegypti includes the presence of ADA activity in warm solutions probed through a membrane by mosquitoes and in serotonin-induced saliva and a statistically significant reduction in the levels of the enzyme in Aedes aegypti following a blood meal. We could not demonstrate, however, that C, quinquefasciatus secrete ADA in their saliva. Male Aedes aegypti and C, quinquefasciatus, which do not feed on blood, have less than 3 % of the levels of ADA found in females. We propose that ADA activity in A. aegypti may help blood feeding by removing adenosine, a molecule associated with both the initiation of pain perception and the induction of mast cell degranulation in vertebrates, and by producing inosine, a molecule that potently inhibits the production of inflammatory cytokines, The role of salivary ADA in Culex quinquefasciatus remains unclear. C1 NIAID, Parasit Dis Lab, Med Entomol Sect, NIH, Bethesda, MD 20892 USA. RP Ribeiro, JMC (reprint author), NIAID, Parasit Dis Lab, Med Entomol Sect, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. OI Ribeiro, Jose/0000-0002-9107-0818 NR 34 TC 53 Z9 56 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD JUN PY 2001 VL 204 IS 11 BP 2001 EP 2010 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 443YJ UT WOS:000169370900016 PM 11441041 ER PT J AU Pennington, JAT AF Pennington, JAT TI Use of the core food model to estimate mineral intakes part 1. Selection of US core foods SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article; Proceedings Paper CT 24th National Nutrient Databank Conference CY JUL 27-29, 2000 CL ST PAUL, MINNESOTA SP Univ Minnesota, Nutrit Coordinating Ctr DE core foods; dietary assessment; dietary exposure model; food intake ID TOTAL DIET; REVISION; HISTORY AB The core food dietary intake model may be used to assess the average daily consumption of nutrients and other food components by a population and by population subgroups. The core food model identifies the most commonly consumed foods for a population and uses these foods to represent the entire food supply. For this project, 306 core foods of the U.S. diet were selected using food consumption data from the 1994-1996 U.S. Department of Agriculture (USDA) Continuing Survey of Food Intakes by Individuals (CSFII). The USDA CSFII included about 15 000 participants, who provided a 24-h diet recall and a I-day food record. The core foods were identified by aggregating the 5703 foods consumed by survey participants into groups based on food type, food use, and similarity of composition. The foods within each grouping were ranked in terms of frequency of use and gram intake, and one food item within each group was selected to become a core food and represent its group. Each core food assumed the full dietary intake (gram weight) for all the foods in its group. The 306 core foods are listed within 42 subgroups organized by food type and common use, The list of 306 core foods may be shortened by further aggregation to match the needs of different investigators. For example, limited data on food composition may warrant the use of a shorter core food list. (C) 2001 Academic Press. C1 NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. RP Pennington, JAT (reprint author), NIH, Div Nutr Res Coordinat, 6707 Democracy Blvd,Room 629, Bethesda, MD 20892 USA. NR 8 TC 2 Z9 4 U1 2 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD JUN PY 2001 VL 14 IS 3 BP 295 EP 300 DI 10.1006/jfca.2001.1000 PG 6 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 473XP UT WOS:000171074700010 ER PT J AU Strestik, BD Olbrich, ARM Hasenkrug, KJ Dittmer, U AF Strestik, BD Olbrich, ARM Hasenkrug, KJ Dittmer, U TI The role of IL-5, IL-6 and IL-10 in primary and vaccine-primed immune responses to infection with Friend retrovirus (Murine leukaemia virus) SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID T-CELL RESPONSES; INDUCED LEUKEMIA; INDUCED ERYTHROLEUKEMIA; MICE; PROTECTION; RECOVERY; INTERLEUKIN-6; ANTIBODY; CD4(+); GENE AB The defence of a host against viral infections is strongly influenced by cytokines, We investigated the role of the B-cell stimulating cytokines IL-5 and IL-6, and the immune-suppressive cytokine IL-10, during primary and secondary immune responses in mice against infection with Friend retrovirus (FV) (Murine leukaemia virus). IL-5(-/-) mice were comparable to C57BL/6 wild-type mice in their ability to control acute FV infection. In contrast, IL-6(-/-) and IL-10(-/-) mice showed significantly enhanced virus loads in spleen cells. However, this impaired control of acute FV replication did not alter the long-term control over persistent FV in IL-6(-/-) and IL-10(-/-) mice. Immunization with a live attenuated vaccine virus prior to challenge protected all three types of cytokine-deficient mice from high levels of spleen virus, despite the finding that the vaccinated IL-5- and IL-6-deficient mice had significantly reduced titres of virus-neutralizing IgG class antibodies. The results indicate that IL-6 and IL-10 contribute to primary immune responses against FV, but are dispensable during persistent infection and vaccine-primed secondary responses. C1 Univ Wurzburg, Inst Virol, D-97078 Wurzburg, Germany. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Dittmer, U (reprint author), Univ Wurzburg, Inst Virol, Versbacher Str 7, D-97078 Wurzburg, Germany. NR 36 TC 10 Z9 10 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JUN PY 2001 VL 82 BP 1349 EP 1354 PN 6 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 435TE UT WOS:000168896600011 PM 11369878 ER PT J AU Brown, MJ Hallam, JA Colucci-Guyon, E Shaw, S AF Brown, MJ Hallam, JA Colucci-Guyon, E Shaw, S TI Rigidity of circulating lymphocytes is primarily conferred by vimentin intermediate filaments SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTEGRIN-MEDIATED ADHESION; PROTEIN-KINASE-C; T-LYMPHOMA CELLS; VISCOELASTIC PROPERTIES; HUMAN NEUTROPHILS; DEFORMABILITY; POLARIZATION; COLCHICINE; ACTIVATION; MIGRATION AB Lymphocytes need rigidity while in circulation, but must abruptly become deformable to undergo transmigration into tissue. Previously, the control of leukocyte deformability has been attributed to microfilaments or microtubules, but the present studies demonstrate the greater importance of vimentin intermediate filaments (IFs). In circulating T lymphocytes, IFs form a distinctive spherical cage that undergoes a rapid condensation into a juxtanuclear aggregate during chemokine-induced polarization. Measurements of the resistance of peripheral blood T lymphocytes to global deformation demonstrate that their rigidity is primarily dependent on intact vimentin filaments. Microtubules, in contrast, are not sufficient to maintain rigidity. Thus, vimentin IFs are a primary source of structural support in circulating human lymphocytes, and their regulated collapse is likely to be an essential element in chemokine-induced transendothelial migration. C1 NCI, Expt Immunol Branch, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. Inst Pasteur, Unite Biol Dev, Unite Rech Associee, CNRS, Paris, France. RP Shaw, S (reprint author), NCI, Expt Immunol Branch, Human Immunol Sect, NIH, Bldg 10,Room 4B36,10 Ctr Dr MSC 1360, Bethesda, MD 20892 USA. NR 37 TC 93 Z9 96 U1 0 U2 13 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2001 VL 166 IS 11 BP 6640 EP 6646 PG 7 WC Immunology SC Immunology GA 471VG UT WOS:000170948900023 PM 11359818 ER PT J AU Chaves-Dias, C Hundley, TR Gilfillan, AM Kirshenbaum, AS Cunha-Melo, JR Metcalfe, DD Beaven, MA AF Chaves-Dias, C Hundley, TR Gilfillan, AM Kirshenbaum, AS Cunha-Melo, JR Metcalfe, DD Beaven, MA TI Induction of telomerase activity during development of human mast cells from peripheral blood CD34(+) cells: Comparisons with tumor mast-cell lines SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE ACTIVATION; RECEPTOR TYROSINE KINASE; HYBRID POLAR INDUCERS; C-KIT; HEMATOPOIETIC-CELLS; ANTIGEN RECEPTOR; RBL-2H3 CELLS; B-CELL; PHOSPHATIDYLINOSITOL 3-KINASE; MOLECULAR MECHANISMS AB To further characterize the development of mast cells from human hemopoietic pluripotent cells we have investigated the expression of telomerase activity in cultured human peripheral blood CD34(+) cells, and CD34(+)/CD117(+)/CD13(+) progenitor mast cells selected therefrom, with the idea that induction of telomerase is associated with clonal expansion of CD34(+)/CD117(+)/CD13(+) cells. A rapid increase in telomerase activity preceded proliferation of both populations of cells in the presence of stern Cell factor and either IL-3 or IL-6. The induction was transient, and telomerase activity declined to basal levels well before the appearance of mature mast cells. Studies with pharmacologic inhibitors suggested that this induction was initially dependent on the p38 mitogen-activated protein kinase and phosphatidylinositol 3 ' -kinase, but once cell replication was underway telomerase activity, but not cell replication, became resistant to the effects of inhibitors. Tumor mast cell lines, in contrast, expressed persistently high telomerase activity throughout the cell cycle, and this expression was unaffected by inhibitors of all known signaling pathways in mast cells even when cell proliferation was blocked for extended periods. These results suggest that the transient induction of telomerase activity in human progenitor mast cells was initially dependent on growth factor-mediated signals, whereas maintenance of high activity in tumor mast cell lines was not dependent on intracellular signals or cell replication. C1 NHLBI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Beaven, MA (reprint author), NHLBI, Immunol Lab, NIH, Bldg 10,Room 8N109, Bethesda, MD 20892 USA. RI Cunha-Melo, Jose Renan/C-6262-2013 NR 74 TC 21 Z9 24 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 JUN 1 PY 2001 VL 166 IS 11 BP 6647 EP 6656 PG 10 WC Immunology SC Immunology GA 471VG UT WOS:000170948900024 PM 11359819 ER PT J AU Nishikomori, R Gurunathan, S Nishikomori, K Strober, W AF Nishikomori, R Gurunathan, S Nishikomori, K Strober, W TI BALB/c mice bearing a transgenic IL-12 receptor beta 2 gene exhibit a nonhealing phenotype to Leishmania major infection despite intact IL-12 signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; TH2 CELLS; INTERLEUKIN-4 PRODUCTION; INTERFERON-GAMMA; SUSCEPTIBLE MICE; IMMUNE-RESPONSE; IFN-GAMMA; EXPRESSION; UNRESPONSIVENESS; RESOLUTION AB In BALB/c mice infected with Leishmania major, early secretion of IL-4 leads to a Th2-type response and nonhealing. We explored the role of IL-4-induced down -regulation of the IL-12R beta2 chain in the establishment of this Th2 response. First, we showed that the draining lymph nodes of resistant C57BL/6 mice infected with L. major were enriched in CD4(+)/IL-12R beta2 chain' cells producing IFN-gamma. Next, we demonstrated that BALB/c background mice bearing an IL-12R beta2-chain transgene manifested a nonhealing phenotype similar to wild-type littermates despite the persistence of their ability to undergo STAT4 activation. Finally, we found that such transgenic mice display more severe infection than wild-type littermates when treated with IL-12 7 days after infection, and under this condition, the mice display increased Leishmania Ag-Induced IL-4 secretion. These studies indicate that although CD4(+)/IL-12R beta2 chain' T cells are important components of the Th1 response, maintenance of 1L-12R beta2 chain expression is not sufficient to change a Th2 response to a Th1 response in vivo and thus to allow BALB/c mice to heal L major infection. The Journal of Immunology, 2001, 166: 6776-6783. C1 NIAID, Mucosal Immun Sect, Lab Clin Invest, NIH, Bethesda, MD 20892 USA. NIAID, Clin Immunol Sect, Lab Clin Invest, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Lab Clin Invest, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 33 TC 30 Z9 32 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2001 VL 166 IS 11 BP 6776 EP 6783 PG 8 WC Immunology SC Immunology GA 471VG UT WOS:000170948900041 PM 11359836 ER PT J AU Schito, ML Kennedy, PE Kowal, RP Berger, EA Sher, A AF Schito, ML Kennedy, PE Kowal, RP Berger, EA Sher, A TI A human immunodeficiency virus-transgenic mouse model for assessing interventions that block microbial-induced proviral expression SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on HIV Pathogenesis CY APR, 2000 CL KEYSTONE, COLORADO ID NECROSIS-FACTOR-ALPHA; AIDS-LIKE DISEASE; IN-VITRO; MYCOBACTERIUM-TUBERCULOSIS; CD4-PSEUDOMONAS EXOTOXIN; ANTIRETROVIRAL THERAPY; REVERSE TRANSCRIPTION; TYPE-1 REPLICATION; HUMAN MACROPHAGES; GENE-EXPRESSION AB A human immunodeficiency virus (HIV) type 1-transgenic mouse line (166) that previously showed up-regulated expression of viral proteins and infectious particles after infection with pathogenic agents was tested as a model for screening the in vitro and in vivo efficacy of inhibitors of HIV-1 immune activation. Two types of interventions were assessed: use of either the immunosuppressive drug prednisolone or an HIV-1 envelope-targeted toxin (sCD4-PE40). Both agents inhibited lipopolysaccharide-induced p24 expression by splenocytes in vitro and, when administered to transgenic mice, suppressed the induction of plasma p24, as well as the ex vivo production of p24 and infectious virus stimulated by in vivo infection with Mycobacterium avium. Moreover, HIV-1 mRNA levels in the spleen were greatly reduced in mice treated with either agent. Because HIV-1 expression cannot be induced in T lymphocytes from line 166 mice, this model may be of particular advantage for testing interventions that target virus production by non-T cell virus reservoirs. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Struct Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Schito, ML (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 4 Ctr Dr,Rm 4-132, Bethesda, MD 20892 USA. NR 48 TC 14 Z9 15 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2001 VL 183 IS 11 BP 1592 EP 1600 DI 10.1086/320716 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 430XZ UT WOS:000168601900006 PM 11343207 ER PT J AU Nomura, T Carlton, JMR Baird, JK del Portillo, HA Fryauff, DJ Rathore, D Fidock, DA Su, XZ Collins, WE McCutchan, TF Wootton, JC Wellems, TE AF Nomura, T Carlton, JMR Baird, JK del Portillo, HA Fryauff, DJ Rathore, D Fidock, DA Su, XZ Collins, WE McCutchan, TF Wootton, JC Wellems, TE TI Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium species that cause human malaria SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID VIVAX MALARIA; AOTUS MONKEYS; ANOPHELINE MOSQUITOS; IRIAN-JAYA; IN-VITRO; STRAIN; FALCIPARUM; GENE; INDONESIA; PYRIMETHAMINE AB Chloroquine (CQ)-resistant Plasmodium vivax malaria was first reported 12 years ago, nearly 30 years after the recognition of CQ-resistant P. falciparum. Loss of CQ efficacy now poses a severe problem for the prevention and treatment of both diseases. Mutations in a digestive vacuole protein encoded by a 13-exon gene, pfcrt, were shown recently to have a central role in the CQ resistance (CQR) of P. falciparum. Whether mutations in pfcrt orthologues of other Plasmodium species are involved in CQR remains an open question. This report describes pfcrt homologues from P. vivax, P. knowlesi, P. berghei, and Dictyostelium discoideum. Synteny between the P. falciparum and P. vivax genes is demonstrated. However, a survey of patient isolates and monkey-adapted lines has shown no association between in vivo CQR and codon mutations in the P. vivax gene. This is evidence that the molecular events underlying P. vivax CQR differ from those in P. falciparum. C1 NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD USA. USN, Med Res Ctr, Malaria Program, Silver Spring, MD USA. Ctr Dis Control & Prevent, Chamblee, GA USA. USN, Med Res Unit 2, Jakarta, Indonesia. Univ Sao Paulo, Dept Parasitol, Sao Paulo, Brazil. RP Wellems, TE (reprint author), Bldg 4,Rm 126,Natl Inst Hlth Campus, Bethesda, MD 20892 USA. RI del Portillo, Hernando /L-2131-2014; OI del Portillo, Hernando /0000-0002-5278-3452; Fidock, David/0000-0001-6753-8938; Su, Xinzhuan/0000-0003-3246-3248 FU NIAID NIH HHS [R01 AI050234] NR 54 TC 112 Z9 118 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2001 VL 183 IS 11 BP 1653 EP 1661 DI 10.1086/320707 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 430XZ UT WOS:000168601900014 PM 11343215 ER PT J AU Cooper, PJ Mancero, T Espinel, M Sandoval, C Lovato, R Guderian, RH Nutman, TB AF Cooper, PJ Mancero, T Espinel, M Sandoval, C Lovato, R Guderian, RH Nutman, TB TI Early human infection with onchocerca volvulus is associated with an enhanced parasite-specific cellular immune response SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IVERMECTIN TREATMENT; PROTECTIVE IMMUNITY; SIMULIUM-EXIGUUM; CYTOKINES IL-10; IFN-GAMMA; RESPONSIVENESS; INDIVIDUALS; ANTIGEN; MICROFILARIAE; FILARIASIS AB The immune response after early exposure to or infection with Onchocerca volvulus was investigated in an autochthonous focus caused by the migration of infected persons to a previously unaffected area in Ecuador. Peripheral blood mononuclear cell (PBMC) proliferative and cytokine responses (interferon [IFN]-gamma and interleukin [IL]-5) to filarial antigens were measured in 14 subjects with serologic evidence of exposure and in 7 subjects with evidence of dermal microfilarial DNA and were compared with responses in 43 subjects with chronic O. volvulus infections. PBMC proliferative and cytokine responses (IFN-gamma and IL-5) to parasite antigens were elevated in the early exposure/infection group, compared with those in the chronic infection group. Addition of an IL-10-neutralizing antibody to filaria antigen-stimulated cultures resulted in significantly elevated proliferative responses in the chronic infection group. The findings suggest that early exposure and early parasite patency are associated with a vigorous cellular response, but, as infections become chronic, the cellular response becomes down-regulated, partly through an IL-10-dependent mechanism. C1 NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. Hosp Vozandes, Dept Clin Invest, Quito, Ecuador. RP Cooper, PJ (reprint author), St George Hosp, Sch Med, Div Infect Dis, Cranmer Terrace, London SW17 0RE, England. NR 32 TC 43 Z9 44 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2001 VL 183 IS 11 BP 1662 EP 1668 DI 10.1086/320709 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 430XZ UT WOS:000168601900015 PM 11343216 ER PT J AU Huang, JQ Muegge, K AF Huang, JQ Muegge, K TI Control of chromatin accessibility for V(D)J recombination by interleukin-7 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review ID RECEPTOR-DEFICIENT MICE; SEVERE COMBINED IMMUNODEFICIENCY; DEFECTIVE LYMPHOID DEVELOPMENT; GAMMA GENE REARRANGEMENT; T-CELL DEVELOPMENT; TCR-BETA LOCUS; IL-7 RECEPTOR; IN-VITRO; HISTONE ACETYLATION; VDJ RECOMBINATION AB IL-7 is a key factor for lymphoid development, and it contributes to V(D)J recombination at multiple loci in immune-receptor genes, IL-7 signal transduction, involving gamma (c) and Jak3, is required for successful recombination at the TCR-gamma locus, IL-7 signaling controls the initiation phase of V(D)J recombination by controlling access of the V(D)J recombinase to the locus. in the absence of IL-7, the TCR-gamma locus is methylated and packaged in a repressed form of chromatin consisting of hypoacetylated histones, IL-7 signaling likely increases the acetylation state of the nucleosomal core histones resulting in an "open" form of chromatin. This opening leads to a higher accessibility for the transcription machinery and increased accessibility of the Rag heterodimer that performs the cleavage of DNA. C1 NCI, SAIC, FCRDC, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Muegge, K (reprint author), NCI, SAIC, FCRDC, Mol Immunoregulat Lab, Bldg 560,Rm 31-45, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 49 TC 23 Z9 23 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUN PY 2001 VL 69 IS 6 BP 907 EP 911 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 442RW UT WOS:000169299600009 PM 11404375 ER PT J AU Bodor, J Feigenbaum, L Bodorova, J Bare, C Reitz, MS Gress, RE AF Bodor, J Feigenbaum, L Bodorova, J Bare, C Reitz, MS Gress, RE TI Suppression of T-cell responsiveness by inducible cAMP early repressor (ICER) SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE transcription factors; cytokines; chemokines ID CYTOKINE GENE-EXPRESSION; BINDING PROTEIN; TRANSCRIPTIONAL COACTIVATORS; RHYTHMIC TRANSCRIPTION; AUTOREGULATORY LOOPS; MOLECULAR REGULATION; INTERFERON-GAMMA; CYCLIC-AMP; CREM; INTERLEUKIN-2 AB Depending on the: nature of the costimulation of T lymphocytes, expression of regulatory cytokines slid chemokines is either susceptible or resistant to cyclic AMP (cAMP)-mediated inhibition. Our data show that cAMP-mediated inhibition of endogenously expressed cytokines, which is characteristic for T helper (Th) 1- and Th 2-like phenotypes, correlates with the induction of a potent transcriptional repressor, inducible cAMP early repressor (ICER), in both subsets of T cells activated under conditions of suboptimal interleukin-2 (IL-2) expression. Importantly, Th-specific expression of certain chemokines is also susceptible to cAMP-mediated transcriptional attenuation. To determine whether ICER per se, rather than forskolin-mediated elevation of intracellular cAMP, is responsible for the observed inhibitory effect, we generated transgenic mice expressing ICER under the control of a lymphocyte-specific lck promoter. On stimulation, transgenic thymocytes overexpressing ICER exhibited reduced levels of IL-2 and interferon (IFN)-gamma and failed to express the macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta genes. Splenic T cells from ICER-transgenic mice showed a defect in proliferation and lacked a mixed lymphocyte reaction response., implying that ICER-mediated inhibition of cytokine and chemokine expression might play an important role in T-cell inactivation. C1 NCI, Expt Immunol Branch, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Transgen Mouse Model, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. RP Gress, RE (reprint author), NCI, Expt Immunol Branch, Div Basic Sci, NIH, Bldg 10,Rm 4B14,10 Ctr Dr, Bethesda, MD 20892 USA. NR 34 TC 37 Z9 40 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUN PY 2001 VL 69 IS 6 BP 1053 EP 1059 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 442RW UT WOS:000169299600028 PM 11404394 ER PT J AU Julian, TB AF Julian, TB TI MRI: A role in clinical trials SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Review DE MRI; breast cancer; clinical trials; mammography; breast conserving therapy ID SURGICAL-ADJUVANT-BREAST; RADIATION-THERAPY; PATHOLOGICAL CORRELATION; CONSERVING SURGERY; CANCER; MAMMOGRAPHY; PROJECT; CHEMOTHERAPY; WOMEN; MASTECTOMY AB The diagnosis and treatment of breast cancer has evolved significantly over the last 20 years. Breast-conserving therapy Is replacing the Halstedian concept of "en bloc" resection. Difficulties In detection, pre- and postoperative planning and follow up continue to challenge the clinician. Women at high risk present a significant clinical dilemma. MRI technology in many of these areas is providing more Information about detection, tumor size, extent, and response to treatment. The careful and thoughtful inclusion of MRI in clinical trials may help continue the advancement of breast cancer care. (C) 2001 Wiley-Liss, Inc. C1 Western Penn Allegheny Hlth Syst, Div Surg Oncol, Pittsburgh, PA USA. RP Julian, TB (reprint author), NSABP, 320 E North Ave, Pittsburgh, PA 15212 USA. NR 60 TC 3 Z9 3 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUN PY 2001 VL 13 IS 6 BP 837 EP 841 DI 10.1002/jmri.1119 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 477QV UT WOS:000171296500004 PM 11382941 ER PT J AU Ben-Yosef, T Wattenhofer, M Riazuddin, S Ahmed, ZM Scot, HS Kudoh, J Shibuya, K Antonarakis, SE Bonne-Tamir, B Radhakrishna, U Naz, S Ahmed, Z Riazuddin, S Pandya, A Nance, WE Wilcox, ER Friedman, TB Morell, RJ AF Ben-Yosef, T Wattenhofer, M Riazuddin, S Ahmed, ZM Scot, HS Kudoh, J Shibuya, K Antonarakis, SE Bonne-Tamir, B Radhakrishna, U Naz, S Ahmed, Z Riazuddin, S Pandya, A Nance, WE Wilcox, ER Friedman, TB Morell, RJ TI Novel mutations of TMPRSS3 in four DFNB8/B10 families segregating congenital autosomal recessive deafness SO JOURNAL OF MEDICAL GENETICS LA English DT Letter ID SERINE-PROTEASE; HEARING-LOSS; TRANSMEMBRANE; PAKISTAN; LINKAGE; 21Q22.3; DFNB10; GENES; MAPS C1 NIDCD, Genet Mol Lab, NIH, Rockville, MD 20850 USA. Univ Geneva, Sch Med, Grad Program Mol & Cellular Biol, CH-1211 Geneva, Switzerland. Punjab Univ, Ctr Excellence Mol Biol, Lahore, Pakistan. Univ Geneva, Sch Med, Div Med Genet, CH-1211 Geneva, Switzerland. Keio Univ, Sch Med, Dept Mol Biol, Shinjuku Ku, Tokyo 1608582, Japan. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23298 USA. RP Friedman, TB (reprint author), NIDCD, Genet Mol Lab, NIH, 5 Res Court,Room 2A-19, Rockville, MD 20850 USA. RI Scott, Hamish/B-2122-2009; Antonarakis, Stylianos/N-8866-2014 OI Scott, Hamish/0000-0002-5813-631X; Antonarakis, Stylianos/0000-0001-8907-5823 FU NIDCD NIH HHS [1 Z01 DC 00035-04, 1 Z01 DC 00039-04] NR 18 TC 35 Z9 36 U1 0 U2 1 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 JUN PY 2001 VL 38 IS 6 BP 396 EP 400 DI 10.1136/jmg.38.6.396 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 442XN UT WOS:000169310400010 PM 11424922 ER PT J AU Smucny, DA Allison, DB Ingram, DK Roth, GS Kemnitz, JW Kohama, SG Lane, MA AF Smucny, DA Allison, DB Ingram, DK Roth, GS Kemnitz, JW Kohama, SG Lane, MA CA Primate Aging Database Working Grp TI Changes in blood chemistry and hematology variables during aging in captive rhesus macaques (Macaca mulatta) SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE age effects; monkeys; veterinary care of older primates ID CALORIE RESTRICTION; LABORATORY-ANIMALS; REFERENCE VALUES; MONKEYS; AGE; SEX; BIOMARKERS; ALBUMIN AB Identifying changes with age in physiological variables of captive nonhuman primates will aid in the proper treatment and clinical diagnosis of these animals, as well as enhance our understanding of nonhuman primate models for human aging. Information for 33 physiological variables was obtained from the Primate Aging Database, a multi-centered database being developed for clinical and research use. Using multiple regression analyses, we investigated the relationship of age to hematological variables, blood chemistry and body weight in 345 captive rhesus monkeys (age range 7-30 years) from three different primate research facilities. The analyses revealed that 15 of these variables show a significant relationship with chronological ages and altered in older as compared with adult animals. Here we present the first phase of a project that will: a) identify changes with age in physiological variables among adult captive rhesus macaques; and b) characterize normative values for the aging rhesus population. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI USA. St Lukes Roosevelt Hosp, Obes Res Ctr, New York, NY 10025 USA. Columbia Univ, Coll Phys & Surg, Inst Human Nutr, New York, NY USA. Univ Wisconsin, Sch Med, Dept Physiol, Madison, WI 53706 USA. Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. RP Lane, MA (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Allison, David/0000-0003-3566-9399 FU NCRR NIH HHS [RR00167] NR 34 TC 27 Z9 27 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD JUN PY 2001 VL 30 IS 3 BP 161 EP 173 DI 10.1111/j.1600-0684.2001.tb00005.x PG 13 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 460ZY UT WOS:000170341500005 PM 11515672 ER PT J AU Hallett, M AF Hallett, M TI Brain plasticity and recovery from hemiplegia SO JOURNAL OF MEDICAL SPEECH-LANGUAGE PATHOLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; INDUCED MOVEMENT THERAPY; CENTRAL MOTOR REORGANIZATION; CROSS-MODAL PLASTICITY; ADULT SQUIRREL-MONKEYS; HUMAN CEREBRAL-CORTEX; FUNCTIONAL REORGANIZATION; ISCHEMIC STROKE; HORIZONTAL CONNECTIONS; PROGNOSTIC VALUE AB The brain is capable of considerable reorganization even in adult life. This has been extensively studied in the motor system and can be demonstrated in a number of situations including deafferentation of a body part (such as in an amputation) and motor learning. Techniques including neuroimaging and transcranial magnetic stimulation (TMS) can be used to demonstrate this plasticity by mapping representations in the brain; TMS can also be useful in assessing excitability and briefly deactivating brain regions. With brain lesions such as stroke there can be considerable spontaneous recovery, and this appears to be due to plastic changes. Some recovery may be mediated by enhanced activity in ipsilateral pathways, and this is most clear in the recovery of swallowing. The best recovery of the upper extremity after stroke, however, is due to reorganization of the lesioned hemisphere. Rehabilitative strategies might well be able to enhance rehabilitative efforts. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov NR 61 TC 1 Z9 1 U1 0 U2 1 PU DELMAR CENGAGE LEARNING PI FLORENCE PA PO BOX 6904, FLORENCE, KY 41022-6904 USA SN 1065-1438 J9 J MED SPEECH-LANG PA JI J. Med. Speech-Lang. Pathol. PD JUN PY 2001 VL 9 IS 2 BP 107 EP 115 PG 9 WC Audiology & Speech-Language Pathology; Clinical Neurology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology GA 439VJ UT WOS:000169138000003 ER PT J AU Hjalmarsson, S Blomberg, J Grillner, L Pipkorn, R Allander, T AF Hjalmarsson, S Blomberg, J Grillner, L Pipkorn, R Allander, T TI Sequence evolution and cross-reactive antibody responses to hypervariable region 1 in acute hepatitis C virus infection SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE synthetic peptides; envelope protein; nosocomial infection; humoral immunity; cross-reactivity; chronic infection ID ENVELOPE GLYCOPROTEIN GP70; HYPERIMMUNE SERUM; IMMUNE-RESPONSE; E2/NS1 REGION; PATIENT; GENOME; TRANSMISSION; VARIANTS; PROTEIN AB Hepatitis C virus (HCV) infection may result in acute resolving or chronic infection. Patients that clear the infection have a more vigorous cellular immune response and an early humoral response to the hypervariable region 1 (HVR1) of the E2 envelope protein. To analyse further the properties of the early anti-HVR1 response, crossreactivity of anti-HVR1 responses was assessed in five patients with acute HCV infection, who were infected by the same virus strain during a nosocomial outbreak. The sequence evolution of HVR1 was examined in sequential serum samples up to 37 months post infection. Peptides were synthesised corresponding to the obtained HVR1 sequences and unrelated HVR1 sequences, and antibody reactivity to the peptides in sequential sera was investigated by ELISA, The results suggest an association between specific gaps in humoral immunity and the HVR1 sequence evolution during early infection. Possible interpretations of this phenomenon include immune escape mechanisms or suppression of specific anti-HVR1 antibodies. (C) 2001 Wiley-Liss. Inc. C1 Univ Uppsala Hosp, Sect Virol, Dept Med Sci, Uppsala, Sweden. Karolinska Hosp, Dept Clin Microbiol, S-10401 Stockholm, Sweden. Replico Med AB, Uppsala, Sweden. RP Allander, T (reprint author), NIAID, Hepatitis Viruses Sect, LID, NIH, Bldg 7,Room 201,7 Ctr Dr,MSC 0740, Bethesda, MD 20892 USA. NR 32 TC 7 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 2001 VL 64 IS 2 BP 117 EP 124 DI 10.1002/jmv.1026 PG 8 WC Virology SC Virology GA 425AU UT WOS:000168266800005 PM 11360243 ER PT J AU Liu, X Liao, D Ambudkar, IS AF Liu, X Liao, D Ambudkar, IS TI Distinct mechanisms of [Ca2+](i) oscillations in HSY and HSG cells: Role of Ca2+ influx and internal Ca2+ store recycling SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE Ca2+-activated K+ channel; [Ca2+](i) oscillations; salivary gland cell lines; Ca2+store; SERCA; IP3R ID INOSITOL 1,4,5-TRISPHOSPHATE; LUMINAL CA2+; LINE; K+; STIMULATION; TRANSPORT; CHANNELS; RELEASE; PROTEIN; SIGNALS AB This study examined [Ca2+](i) oscillations in the human salivary gland cell lines, HSY and HSG. Relatively low concentrations of carbachol (CCh) induced oscillatory, and higher [CCh] induced sustained, steady state increases in [Ca2+](i) and K-Ca currents in both cell types. Low IP3 but not thapsigargin (Tg), induced [Ca2+](i) oscillations, whereas Tg blocked CCh-stimulated [Ca2+](i) oscillations in both cell types. Unlike in HSG cells, removal of extracellular Ca2+ from HSY cells (i) did not affect CCh-stimulated [Ca2+](i) oscillations or intemal Ca2+ store refill, and (ii) converted high [CCh]-induced steady-state increase in [Ca2+](i) into oscillations. CCh- or thapsigargin-induced Ca2+ influx was higher in HSY, than in HSG, cells. Importantly, HSY cells displayed relatively higher levels of sarcoendoplasmic reticulum Ca2+ pump (SERCA) and inositoltrisphosphate receptors (IP(3)Rs) than HSG cells. These data demonstrate that [Ca2+](i) oscillations in both HSY and HSG cells are priInarily determined by the uptake of Ca2+ from, and release of Ca2+ into, the cytosol by the SERCA and IP3R activities, respectively. In HSY cells, Ca2+ influx does not acutely contribute to this process, although it determines the steady-state increase in [Ca2+](i). In HSG cells, [Ca2+](i) oscillations directly depend on Ca2+ influx; Ca2+ coming into the cell is rapidly taken up into the store and then released into the cytosol. We suggest that the differences in the mechanism of [Ca2+](i) oscillations HSY and HSG cells is related to their respective abilities to recycle internal Ca2+ stores. C1 NIDR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), NIDR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. NR 26 TC 14 Z9 15 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JUN 1 PY 2001 VL 181 IS 3 BP 185 EP 193 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 441WX UT WOS:000169253500004 PM 11420605 ER PT J AU Shneyvays, V Mamedova, L Zinman, T Jacobson, K Shainberg, A AF Shneyvays, V Mamedova, L Zinman, T Jacobson, K Shainberg, A TI Activation of A(3) adenosine receptor protects against doxorubicin-induced cardiotoxicity SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE doxorubicin; adenosine receptors; adriamycine; cardioprotection; image analysis; lipid peroxidation; ATP; calcium overloading ID CYTOCHROME-C-OXIDASE; GLUTATHIONE-PEROXIDASE; INDUCED CARDIOMYOPATHY; CARDIAC MYOCYTES; ADRIAMYCIN; HEART; APOPTOSIS; SUPPRESSION; INDUCTION; CALCIUM AB Adenosine exerts a marked protective effect on the heart during cardiac ischemia. This protection is mediated by binding to the A(1) and A(3) subtypes of adenosine receptor (A(1)R and A(3)R, respectively). The objective of the present study was to investigate whether activation of A(1) and A(3) adenosine receptors may reduce doxorubicin-induced damage to cardiomyocytes in culture, Cultured cardiomyocytes from newborn rats were treated with 0.5-5 muM doxorubicin (DOX) for 18 h and then incubated in drug-free medium for an additional 24 h. This treatment resulted in cell damage and lactate dehydrogenase release, even after low (0.5 muM) doses of the drug, and increased in a concentration-dependent manner, Activation of A(3)-subtype but not A(1)-subtype receptors attenuated doxorubicin-cardiotoxicity after drug treatment for 18 h followed by 24 h incubation in drug-free medium. Modulation of intracellular calcium mediated by activation of A(3)R. but not by A(2)R, in cultured myocytes suggested an important pathophysiological significance of this subtype of adenosine receptors. Protection by A(3)R agonist Cl-IB-MECA (2-chloro-N-6-(3-iodobenzyl)adenosine-5'-N-methyluronamide) following DOX treatment is evident in: (1) decreases in intracellular calcium overloading and abnormalities in Ca2+ transients; (2) reduction of free-radical generation and lipid peroxidation: (3) attenuation of mitochondrial damage by protection of the terminal link (COX-complex) of respiratory chain: (4) attenuation of the decrease in ATP production and irreversible cardiomyocyte damage. Cardioprotection caused by Cl-IB-MECA was antagonized considerably by the selective A(3) adenosine receptor antagonist MRS1523. (C) 2001 Academic Press. C1 Bar Ilan Univ, Fac Life Sci, Gonda Goldschmied Med Diagnost Res Ctr, IL-52900 Ramat Gan, Israel. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shainberg, A (reprint author), Bar Ilan Univ, Fac Life Sci, Gonda Goldschmied Med Diagnost Res Ctr, IL-52900 Ramat Gan, Israel. EM shaina@ma1l.biu.ac.il RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 47 TC 55 Z9 56 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 JUN PY 2001 VL 33 IS 6 BP 1249 EP 1261 DI 10.1006/jmcc.2001.1387 PG 13 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 478BH UT WOS:000171322700016 PM 11444927 ER PT J AU Guia, A Stern, MD Lakatta, EG Josephson, IR AF Guia, A Stern, MD Lakatta, EG Josephson, IR TI Ion concentration-dependence of rat cardiac unitary L-type calcium channel conductance SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract C1 NIA, NIH, Cardiovasc Sci Lab, Baltimore, MD 21224 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 JUN PY 2001 VL 33 IS 6 BP A41 EP A41 DI 10.1016/S0022-2828(01)90162-2 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 478BH UT WOS:000171322700183 ER PT J AU Patrick, CB Rapoport, SI Goldstein, D Murphy, EJ AF Patrick, CB Rapoport, SI Goldstein, D Murphy, EJ TI Sympathetic denervation decreases arachidonic acid flux in rat heart SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ N Dakota, Grand Forks, ND 58201 USA. 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 JUN PY 2001 VL 33 IS 6 BP A91 EP A91 DI 10.1016/S0022-2828(01)90362-1 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 478BH UT WOS:000171322700383 ER PT J AU Pepe, S Altschuld, R Lakatta, EG AF Pepe, S Altschuld, R Lakatta, EG TI delta-opioid peptide receptors activate pertussis toxin-sensitive and pertussis toxin-insensitive pathways during myocardial contraction SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract C1 Monash Univ, Alfred Hosp, Melbourne, Vic 3181, Australia. Ohio State Univ, Columbus, OH 43210 USA. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 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 JUN PY 2001 VL 33 IS 6 BP A92 EP A92 DI 10.1016/S0022-2828(01)90366-9 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 478BH UT WOS:000171322700387 ER PT J AU Song, LS Wang, SQ Iakatta, EG Cheng, HP AF Song, LS Wang, SQ Iakatta, EG Cheng, HP TI beta-adrenergic stimulation synchronizes intracellular Ca2+ release during E-C coupling in heart cells SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract C1 NIA, NIH, GRC, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. 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 JUN PY 2001 VL 33 IS 6 BP A113 EP A113 DI 10.1016/S0022-2828(01)90451-1 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 478BH UT WOS:000171322700472 ER PT J AU Wang, MY Lakatta, EG AF Wang, MY Lakatta, EG TI Imbalance of protease activators and inhibitors in age associated aortic remodeling SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 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 JUN PY 2001 VL 33 IS 6 BP A128 EP A128 DI 10.1016/S0022-2828(01)90509-7 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 478BH UT WOS:000171322700530 ER PT J AU Wang, SQ Lakatta, EG Cheng, HP AF Wang, SQ Lakatta, EG Cheng, HP TI Post-spark refractoriness of a single Ca2+-release unit in cardiac myocytes SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract C1 NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 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 JUN PY 2001 VL 33 IS 6 BP A128 EP A128 DI 10.1016/S0022-2828(01)90511-5 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 478BH UT WOS:000171322700532 ER PT J AU Younes, A Pepe, S Caffrey, J Lakatta, EG AF Younes, A Pepe, S Caffrey, J Lakatta, EG TI Enkephalins metabolism and coronary release of during cardiac ischemia-reperfusion SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 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 JUN PY 2001 VL 33 IS 6 BP A134 EP A134 DI 10.1016/S0022-2828(01)90535-8 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 478BH UT WOS:000171322700556 ER PT J AU Hsiou, Y Ding, JP Das, K Clark, AD Boyer, PL Lewi, P Janssen, PAJ Kleim, JP Rosner, M Hughes, SH Arnold, E AF Hsiou, Y Ding, JP Das, K Clark, AD Boyer, PL Lewi, P Janssen, PAJ Kleim, JP Rosner, M Hughes, SH Arnold, E TI The Lys103Asn mutation of HIV-1 RT: A novel mechanism of drug resistance SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE AIDS; drug resistance; HIV-1 reverse transcriptase; non-nucleoside inhibitor; X-ray crystallography ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 REVERSE-TRANSCRIPTASE; ANTIBODY FAB FRAGMENT; DOUBLE-STRANDED DNA; ANGSTROM RESOLUTION; NONNUCLEOSIDE INHIBITORS; CONFORMATIONAL-CHANGES; CRYSTAL-STRUCTURE; HBY-097; COMPLEX AB Inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT) are widely used in the treatment of HIV infection. Loviride (an alpha -APA derivative) and HEY 097 (a quinoxaline derivative) are two potent non-nucleoside RT inhibitors (NNRTIs) that have been used in human clinical trials. A major problem for existing anti-retroviral therapy is the emergence of drug-resistant mutants with reduced susceptibility to the inhibitors. Amino acid residue 103 in the p66 subunit of HIV-1 RT is located near a putative entrance to a hydrophobic pocket that binds NNRTIs. Substitution of asparagine for lysine at position 103 of HIV-1 RT is associated with the development of resistance to NNRTIs; this mutation contributes to clinical failure of treatments employing NNRTIs. We have determined the structures of the unliganded form of the Lys103Asn mutant HIV-1 RT and in complexes with loviride and HEY 097. The structures of wild-type and Lys103Asn mutant HIV-1 RT in complexes with NNRTIs are quite similar overall as well as in the vicinity of the bound NNRTIs. Comparison of unliganded wild-type and Lys103Asn mutant HIV-1 RT structures reveals a network of hydrogen bonds in the Lys103Asn mutant that is not present in the wild-type enzyme. Hydrogen bonds in the unliganded Lys103Asn mutant but not in wild-type HIV-1 RT are observed between (1) the side-chains of Asn103 and Tyr188 and (2) well-ordered water molecules in the pocket and nearby pocket residues. The structural differences between unliganded wild-type and Lys103Asn mutant HIV-1 RT may correspond to stabilization of the closed-pocket form of the enzyme, which could interfere with the ability of inhibitors to bind to the enzyme. These results are consistent with kinetic data indicating that NNRTIs bind more slowly to Lys103Asn mutant than to wild-type HIV-1 RT. This novel drug-resistance mechanism explains the broad cross-resistance of Lys103Asn mutant HIV-1 RT to different classes of NNRTIs. Design of NNRTIs that make favorable interactions with the Asn103 side-chain should be relatively effective against the Lys103Asn drug-resistant mutant. (C) 2001 Academic Press. C1 Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA. Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Janssen Res Fdn, Ctr Mol Design, B-2350 Vosselaar, Belgium. Hoechst AG, Gen Pharma Res, D-65926 Frankfurt, Germany. RP Arnold, E (reprint author), Rutgers State Univ, Ctr Adv Biotechnol & Med, 679 Hoes Lane, Piscataway, NJ 08854 USA. FU NIAID NIH HHS [AI 27690, AI 36144] NR 38 TC 125 Z9 132 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 1 PY 2001 VL 309 IS 2 BP 437 EP 445 DI 10.1006/jmbi.2001.4648 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442CB UT WOS:000169266700008 PM 11371163 ER PT J AU McKay, R AF McKay, R TI Building animals from stem cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2001 VL 77 SU 1 MA S0301 BP 3 EP 3 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 441RL UT WOS:000169243300010 ER PT J AU Pettit, DL Shao, Z Yakel, JL AF Pettit, DL Shao, Z Yakel, JL TI beta-amyloid peptide directly modulates nicotinic receptors in rat hippocampal slices SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIEHS, NIH, RTP, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2001 VL 77 SU 1 MA W0403 BP 9 EP 10 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 441RL UT WOS:000169243300032 ER PT J AU Paolini, S Bosetti, F Aleardi, AM Solaini, G AF Paolini, S Bosetti, F Aleardi, AM Solaini, G TI ATP synthesis in cells of Alzheimer's disease patients SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Scuola Super Univ & Perfezionamento S Anna, I-56127 Pisa, Italy. NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2001 VL 77 SU 1 MA P0136 BP 28 EP 28 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 441RL UT WOS:000169243300096 ER PT J AU Erlenbach, I Kostenis, E Schmidt, C Hamdan, FF Pausch, MH Wess, J AF Erlenbach, I Kostenis, E Schmidt, C Hamdan, FF Pausch, MH Wess, J TI Functional expression of M-1, M-3 and M-5 muscarinic acetylcholine receptors in yeast SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE G protein-coupled receptors; G proteins; receptor/G protein coupling; muscarinic receptors; Saccharomyces cerevisiae ID PHEROMONE RESPONSE PATHWAY; PROTEIN-COUPLED RECEPTOR; ALPHA-FACTOR RECEPTOR; 3RD CYTOPLASMIC LOOP; PHARMACOLOGICAL CHARACTERIZATION; SACCHAROMYCES-CEREVISIAE; DIFFERENTIAL REGULATION; TRANSMEMBRANE SEGMENTS; SIGNAL-TRANSDUCTION; C5A RECEPTOR AB The goal of this study was to functionally express the three G(q)-coupled muscarinic receptor subtypes, M-1, M-3 and M-5, in yeast (Saccharomyces cerevisiae). Transformation of yeast with expression constructs coding for the full-length receptors resulted in very low numbers of detectable muscarinic binding sites (B-max <5 fmol/mg). Strikingly, deletion of the central portion of the third intracellular loops of the M-1, M-3 and M-5 muscarinic receptors resulted in dramatic increases in B-max values (53-214 fmol/mg). To monitor productive receptor/G-protein coupling, we used specifically engineered yeast strains that required agonist-stimulated receptor/G-protein coupling for cell growth, These studies showed that the shortened versions of the M-1, M-3 and M-5 receptors were unable to productively interact with the endogenous yeast G protein a-subunit, Gpa1p, or a Gpa1 mutant subunit that contained C-terminal mammalian Ga, sequence. In contrast, all three receptors gained the ability to efficiently couple to a Gpa1/G alpha (q), hybrid subunit containing C-terminal mammalian G alpha (q), sequence, indicating that the M,, M, and Mg muscarinic receptors retained proper G-protein coupling selectivity in yeast. This is the first study to report the expression of muscarinic receptors in a coupling-competent form in yeast. The strategy described here, which involves structural modification of both receptors and cc-expressed G proteins, should facilitate the functional expression of other classes of G protein-coupled receptors in yeast. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Wyeth Ayerst Res, Dept Neurosci, Princeton, NJ 08543 USA. RP NIDDK, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-05, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov NR 58 TC 39 Z9 40 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2001 VL 77 IS 5 BP 1327 EP 1337 DI 10.1046/j.1471-4159.2001.00344.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 440CR UT WOS:000169158800016 PM 11389184 ER PT J AU Pare, M Wurtz, RH AF Pare, M Wurtz, RH TI Progression in neuronal processing for saccadic eye movements from parietal cortex area LIP to superior colliculus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LATERAL INTRAPARIETAL AREA; FUNCTIONAL-PROPERTIES; OCULOMOTOR BEHAVIOR; MOTOR CONVERGENCE; FIXATION CELLS; ANTI-SACCADES; PRO-SACCADES; MONKEY; FIELD; MACAQUE AB Neurons in both the lateral intraparietal area (LIP) of the monkey parietal cortex and the intermediate layers of the superior colliculus (SC) are activated well in advance of the initiation of saccadic eye movements. To determine whether there is a progression in the covert processing for saccades from area LIP to SC, we systematically compared the discharge properties of LTP output neurons identified by antidromic activation with those of SC neurons collected from the same monkeys. First, we compared activity patterns during a delayed saccade task and found that LIP and SC neurons showed an extensive overlap in their responses to visual stimuli and in their sustained activity during the delay period. The saccade activity of LIP neurons was, however, remarkably weaker than that of SC neurons and never occurred without any preceding delay activity. Second, we assessed the dependence of LIP and SC activity on the presence of a visual stimulus by contrasting their activity in delayed saccade trials in which the presentation of the visual stimulus was either sustained (visual trials) or brief (memory trials). Both the delay and the presaccadic activity levels of the LIP neuronal sample significantly depended on the sustained presence of the visual stimulus, whereas those of the SC neuronal sample did not. Third, we examined how the LTP and SC delay activity relates to the future production of a saccade using a delayed GO/NOGO saccade task, in which a change in color of the fixation stimulus instructed the monkey either to make a saccade to a peripheral visual stimulus or to withhold its response and maintain fixation. The average delay activity of both Ln! and SC neuronal samples significantly increased by the advance instruction to make a saccade, but LIP neurons were significantly less dependent on the response instruction than SC neurons, and only a minority of LIP neurons was significantly modulated. Thus despite some overlap in their discharge properties, the neurons in the SC intermediate layers showed a greater independence from sustained visual stimulation and a tighter relationship to the production of an impending saccade than the LIP neurons supplying inputs to the SC. Rather than representing the transmission of one processing stage in parietal cortex area LIP to a subsequent processing stage in SC, the differences in neuronal activity that we observed suggest instead a progressive evolution in the neuronal processing for saccades. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Pare, M (reprint author), Queens Univ, Dept Physiol, Botterell Hall,Rm 438, Kingston, ON K7L 3N6, Canada. NR 74 TC 96 Z9 97 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 JUN PY 2001 VL 85 IS 6 BP 2545 EP 2562 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 442HY UT WOS:000169280200023 PM 11387400 ER PT J AU Coghill, RC Gilron, I Iadarola, MJ AF Coghill, RC Gilron, I Iadarola, MJ TI Hemispheric lateralization of somatosensory processing SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; PAIN PERCEPTION; MEDIAL THALAMUS; HUMAN BRAIN; CEREBRAL ACTIVATION; AUTOMATED ALGORITHM; DIRECTED ATTENTION; PARIETAL CORTICES; SINGLE-SUBJECT; SPLIT-BRAIN AB Processing of both painful and nonpainful somatosensory information is generally thought to be subserved by brain regions predominantly contralateral to the stimulated body region. However, lesions to right, but not left, posterior parietal cortex have been reported to produce a unilateral tactile neglect syndrome, suggesting that components of somatosensory information are preferentially processed in the right half of the brain. To better characterize right hemispheric lateralization of somatosensory processing, (H2O)-O-15 positron emission tomography (PET) of cerebral blood flow was used to map brain activation produced by contact thermal stimulation of both the left and right arms of right-handed subjects. To allow direct assessment of the lateralization of activation, left- and right-sided stimuli were delivered during separate PET scans. Both innocuous (35 degreesC) and painful (49 degreesC) stimuli were employed to determine whether lateralized processing occurred in a manner related to perceived pain intensity. Subjects were also scanned during a nonstimulated rest condition to characterize activation that was not related to perceived pain intensity. Pain intensity-dependent and -independent changes in activation were identified in separate multiple regression analyses. Regardless of the side of stimulation, pain intensity-dependent activation was localized to contralateral regions of the primary somatosensory cortex, secondary somatosensory cortex, insular cortex, and bilateral regions of the cerebellum, putamen, thalamus, anterior cingulate cortex, and frontal operculum. No hemispheric lateralization of pain intensity-dependent processing was detected. In sharp contrast, portions of the thalamus, inferior parietal cortex (BA 40), dorsolateral prefrontal cortex (BA 9/46), and dorsal frontal cortex (BA 6) exhibited right lateralized activation during both innocuous and painful stimulation, regardless of the side of stimulation. Thus components of information arising from the body surface are processed, in part, by right lateralized systems analogous to those that process auditory and visual spatial information arising from extrapersonal space. Such right lateralized processing can account for the left somatosensory neglect arising from injury to brain regions within the right cerebral hemisphere. C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. RP Coghill, RC (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Neurobiol & Anat, Winston Salem, NC 27157 USA. NR 52 TC 147 Z9 152 U1 4 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 2001 VL 85 IS 6 BP 2602 EP 2612 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 442HY UT WOS:000169280200027 PM 11387404 ER PT J AU Taber, KH Murphy, DD Blurton-Jones, MM Hurley, RA AF Taber, KH Murphy, DD Blurton-Jones, MM Hurley, RA TI An update on estrogen: Higher cognitive function, receptor mapping, neurotrophic effects SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID MESSENGER-RNA EXPRESSION; DENDRITIC SPINE DENSITY; CEREBRAL BLOOD-FLOW; REPLACEMENT THERAPY; ALZHEIMERS-DISEASE; CHOLINE-ACETYLTRANSFERASE; ESTRADIOL INCREASES; GENDER DIFFERENCES; BRAIN INJURY; WOMEN C1 Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Baylor Coll Med, Dept Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Herbert J Frensley Ctr Imaging Res, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Psychiat Serv, Houston, TX USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Taber, KH (reprint author), Baylor Coll Med, Dept Radiol, 1 Baylor Plaza, Houston, TX 77030 USA. OI Blurton-Jones, Mathew/0000-0002-7770-7157 NR 41 TC 17 Z9 18 U1 4 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 2001 VL 13 IS 3 BP 313 EP 317 DI 10.1176/appi.neuropsych.13.3.313 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 462RP UT WOS:000170433800001 PM 11514636 ER PT J AU Haak, LL Song, LS Molinski, TF Pessah, IN Cheng, HP Russell, JT AF Haak, LL Song, LS Molinski, TF Pessah, IN Cheng, HP Russell, JT TI Sparks and puffs in oligodendrocyte progenitors: Cross talk between ryanodine receptors and inositol trisphosphate receptors SO JOURNAL OF NEUROSCIENCE LA English DT Article DE calcium; confocal microscopy; cross talk; development; IP3 receptor; muscarinic receptor; ryanodine receptor; oligodendrocyte progenitor; puffs; SERCA; sparks; Xestospongin C; wave ID SIGNAL-TRANSDUCTION SYSTEMS; CA2+ RELEASE SITES; 1,4,5-TRISPHOSPHATE RECEPTOR; XENOPUS OOCYTES; CALCIUM SPARKS; SARCOPLASMIC-RETICULUM; SKELETAL-MUSCLE; IN-VIVO; ELEMENTARY EVENTS; CHANNEL KINETICS AB Investigating how calcium release from the endoplasmic reticulum (ER) is triggered and coordinated is crucial to our understanding of how oligodendrocyte progenitor cells (OPs) develop into myelinating cells. Sparks and puffs represent highly localized Ca2+ release from the ER through ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP(3)Rs), respectively. To study whether sparks or puffs trigger Ca2+ waves in OPs, we performed rapid high-resolution line scan recordings in fluo-4-loaded OP processes. We found spontaneous and evoked sparks and puffs, and we have identified functional cross talk between IP(3)Rs and RyRs. Local events evoked using the IP3-linked agonist methacholine (MeCh) showed significantly different morphology compared with events evoked using the caffeine analog 3,7-dimethyl-1-propargylxanthine (DMPX). Pretreatment with MeCh potentiated DMPX-evoked events, whereas inhibition of RyRs potentiated events evoked by low concentrations of MeCh. Furthermore, activation of IP(3)Rs but not RyRs was critical for Ca2+ wave initiation. Using immunocytochemistry, we show OPs express the specific Ca2+ release channel subtypes RyR3 and IP(3)R2 in patches along OP processes. RyRs are coexpressed with IP(3)Rs in some patches, but IP(3)Rs are also found alone. This differential distribution pattern may underlie the differences in local and global Ca2+ signals mediated by these two receptors. Thus, in OPs, interactions between IP(3)Rs and RyRs determine the spatial and temporal characteristics of calcium signaling, from microdomains to intracellular waves. C1 NICHHD, Cellular & Mol Neurophysiol Lab, NIH, Bethesda, MD 20814 USA. NIA, NIH, Baltimore, MD 21224 USA. Univ Calif Davis, Sch Vet Med, Dept Chem, Davis, CA 95616 USA. Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA. Peking Univ, Coll Life Sci, Natl Lab Biomembranes & Membrane Technol, Beijing 100871, Peoples R China. RP Cheng, HP (reprint author), NICHHD, Cellular & Mol Neurophysiol Lab, NIH, Bldg 49,Room 5A78,49 Convent Dr, Bethesda, MD 20814 USA. EM chengp@grc.nia.nih.gov RI Haak, Laurel/C-4986-2008; Song, Long-Sheng/D-5899-2012 OI Haak, Laurel/0000-0001-5109-3700; FU PHS HHS [1PO 05707, 1RO3 10173] NR 75 TC 61 Z9 63 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 JUN 1 PY 2001 VL 21 IS 11 BP 3860 EP 3870 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 436VY UT WOS:000168957600021 PM 11356874 ER PT J AU Mima, T Oluwatimilehin, T Hiraoka, T Hallett, M AF Mima, T Oluwatimilehin, T Hiraoka, T Hallett, M TI Transient interhemispheric neuronal synchrony correlates with object recognition SO JOURNAL OF NEUROSCIENCE LA English DT Article DE object recognition; neuronal synchronization; EEG; interhemispheric coherence; perceptual binding; visual recognition task ID CAT VISUAL-CORTEX; PARTIAL COHERENCE ANALYSIS; HUMAN BRAIN; CORTICAL SYNCHRONIZATION; OSCILLATORY RESPONSES; EXTRASTRIATE CORTEX; VOLUME CONDUCTION; STRUCTURAL BASIS; EEG COHERENCE; AREAS AB Object recognition might be achieved by the recreation of a meaningful internal image from visual fragments. This recreation might be achieved by neuronal synchronization that has been proposed as a solution for the perceptual binding problem. In this study, we evaluated synchronization between the occipitotemporal regions bilaterally using electroencephalograms during several visual recognition tasks. Conscious recognition of familiar objects spanning the visual midline induced transient interhemispheric electroencephalographic coherence in the alpha band, which did not occur with meaningless objects or with passive viewing. Moreover, there was no interhemispheric coherence when midline objects were not recognized as meaningful or when familiar objects were presented in one visual hemifield. These data suggest a close link between site-specific interregional synchronization and object recognition. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1428, Bethesda, MD 20892 USA. OI Mima, Tatsuya/0000-0001-7787-4855 NR 56 TC 93 Z9 94 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 JUN 1 PY 2001 VL 21 IS 11 BP 3942 EP 3948 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 436VY UT WOS:000168957600029 PM 11356882 ER PT J AU Gioio, AE Eyman, M Zhang, HS Lavina, ZS Giuditta, A Kaplan, BB AF Gioio, AE Eyman, M Zhang, HS Lavina, ZS Giuditta, A Kaplan, BB TI Local synthesis of nuclear-encoded mitochondrial proteins in the presynaptic nerve terminal SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE presynaptic nerve ending; local protein synthesis; nuclear-encoded mitochondrial mRNAs; polyribosomes ID SQUID GIANT-AXON; MESSENGER-RNA; SYNAPTOSOMAL FRACTION; ACTIVE POLYSOMES; BETA-TUBULIN; IMPORT; BRAIN; COMPLEXITY; TRANSPORT; RIBOSOMES AB One of the central tenets in neuroscience has been that the protein constituents of distal compartments of the neuron (e,g,, the axon and nerve terminal) are synthesized in the nerve cell body and are subsequently transported to their ultimate sites of function. In contrast to this postulate, we have established previously that a heterogeneous population of mRNAs and biologically active polyribosomes exist in the giant axon and presynaptic nerve terminals of the photoreceptor neurons in squid. We report that these mRNA populations contain mRNAs for nuclear-encoded mitochondrial proteins to include: cytochrome oxidase subunit 17, propionyl-CoA carboxylase (EC 6.4.1.3), dihydrolipoamide dehydrogenase (EC 1.8.1.4), and coenzyme Q subunit 7. The mRNA for heat shock protein 70, a chaperone protein known to be involved in the import of proteins into mitochondria, has also been identified. Electrophoretic gel analysis of newly synthesized proteins in the synaptosomal fraction isolated from the squid optic lobe revealed that the large presynaptic terminals of the photoreceptor neuron contain a cytoplasmic protein synthetic system. Importantly, a significant amount of the cycloheximide resistant proteins locally synthesized in the terminal becomes associated with mitochondria, PCR analysis of RNA from synaptosomal polysomes establishes that COX17 and CoQ7 mRNAs are being actively translated. Taken together, these findings indicate that proteins required for the maintenance of mitochondrial function are synthesized locally in the presynaptic nerve terminal, and call attention to the intimacy of the relationship between the terminal and its energy generating system. Published 2001 Wiley-Liss, Inc.(dagger) C1 NIMH, Mol Biol Lab, Ctr Clin, NIH, Bethesda, MD 20892 USA. Univ Naples, Dept Gen & Environm Physiol, Naples, Italy. RP Kaplan, BB (reprint author), NIMH, Mol Biol Lab, Ctr Clin, NIH, Room 4N-222,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 28 TC 52 Z9 52 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN 1 PY 2001 VL 64 IS 5 BP 447 EP 453 DI 10.1002/jnr.1096 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 438AZ UT WOS:000169032700002 PM 11391699 ER PT J AU Christiani, DC Sharp, RR Collman, GW Suk, WA AF Christiani, DC Sharp, RR Collman, GW Suk, WA TI Applying genomic technologies in environmental health research: Challenges and opportunities SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID LUNG-CANCER; SOCIAL IMPLICATIONS; P53 MUTATIONS; SMOKING; GENES; PROJECT; SUSCEPTIBILITY; EXPOSURE; LEGAL; ADENOCARCINOMA AB Recent discoveries in molecular biology and genetics have made it possible for environmental health researchers to examine how genetic characteristics affect response to environmental exposures. Understanding such gene-environment interactions offers exciting possibilities for the prevention and control of environmentally induced diseases. Despite these potential benefits, the collection and analysis of genetic information in environmental health research presents many of the same ethical, legal, and social (ELSI) challenges found in other types of genetic research. In this article, we describe a number of ELSI challenges in environmental genomic research and the opportunities and responsibilities that accompany this research. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NIEHS, Off Sci Director, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Div Extramural Res, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Ctr Study Med Eth & Humanities, Durham, NC 27706 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES00002, ES05947] NR 45 TC 17 Z9 18 U1 0 U2 0 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 JUN PY 2001 VL 43 IS 6 BP 526 EP 533 DI 10.1097/00043764-200106000-00003 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 440CT UT WOS:000169158900002 PM 11411324 ER PT J AU Aley, KO Levine, JD AF Aley, KO Levine, JD TI Rapid onset pain induced by intravenous streptozotocin in the rat SO JOURNAL OF PAIN LA English DT Article DE diabetes; hyperalgesia; insulin; neuropathic pain; streptozotocin ID INDUCED DIABETES-MELLITUS; PERIPHERAL NEUROPATHY; BLADDER FUNCTION; NERVE INJURY; SHORT-TERM; HYPERALGESIA; MODEL; INGESTION; BEHAVIOR; INSULIN AB Pain in diabetes is a common debilitating condition for which pathophysiology remains poorly understood. To evaluate the underlying mechanisms, we used intravenous injection of streptozotocin to produce rapid (24-hour) onset of diabetes (blood glucose > 300 mg/dL and urine glucose > 2,000 mg/dL with polyuria). In this model, mechanical and thermal hyperalgesia and tactile allodynia are detectable by 48 hours after streptozotocin administration in the absence of ketonuria or physical debility. Treatment with insulin attenuated hyperglycemia and prevented the development of mechanical and thermal hyperalgesia. Direct application of streptozotocin to peripheral nerve did not produce hyperalgesia. We conclude that streptozotocin can induce pain independent of a general debility or direct toxic effect of streptozotocin on peripheral nerve and that elevated blood glucose may contribute to the enhanced nociception. (C) 2001 by the American Pain Society. C1 Univ Calif San Francisco, NIH, Pain Ctr, San Francisco, CA 94143 USA. RP Aley, KO (reprint author), Univ Calif San Francisco, NIH, Pain Ctr, San Francisco, CA 94143 USA. NR 32 TC 34 Z9 35 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD JUN PY 2001 VL 2 IS 3 BP 146 EP 150 DI 10.1054/jpai.2001.21592 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 444HV UT WOS:000169394800002 PM 14622824 ER PT J AU Mackall, CL Helman, LJ AF Mackall, CL Helman, LJ TI High-dose chemotherapy for rhabdomyosarcoma: Where do we go from here SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Editorial Material ID BONE-MARROW TRANSPLANTATION; CHILDREN; MELPHALAN; THERAPY C1 NCI, Canc Res Ctr, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Mackall, CL (reprint author), NCI, Canc Res Ctr, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 11 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JUN-JUL PY 2001 VL 23 IS 5 BP 266 EP 267 DI 10.1097/00043426-200106000-00005 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 451LU UT WOS:000169804200003 PM 11464979 ER PT J AU Goldman, SC Bracho, F Davenport, V Slack, R Areman, E Shen, V Lenarsky, C Weinthal, J Hughes, R Cairo, MS AF Goldman, SC Bracho, F Davenport, V Slack, R Areman, E Shen, V Lenarsky, C Weinthal, J Hughes, R Cairo, MS TI Feasibility study of IL-11 and granulocyte colony-stimulating factor after myelosuppressive chemotherapy to mobilize peripheral blood stem cells from heavily pretreated patients SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article; Proceedings Paper CT Meeting of the International-Society-for-Experimental-Hematology CY AUG 01-05, 1998 CL VANCOUVER, CANADA SP Int Soc Experimental Hematol DE IL-11; G-CSF; ifosfamide; carboplatin; etoposide; peripheral blood stem cells; mobilization ID RECOMBINANT HUMAN INTERLEUKIN-11; HIGH-DOSE CHEMOTHERAPY; RAPID HEMATOPOIETIC RECOVERY; PROGENITOR CELLS; CANCER-PATIENTS; G-CSF; FILGRASTIM; CYCLOPHOSPHAMIDE; THROMBOCYTOPENIA; TRANSPLANTATION AB Purpose: Pediatric patients with solid tumors treated with prolonged dose-intensive chemoradiotherapy are poor mobilizers of peripheral blood stem cells (PBSC). We have conducted a pilot study to mobilize PBSC in eight pediatric patients with relapsed solid tumors using ifosfamide, carboplatin, and etoposide (ICE) followed-up by IL-11 plus granulocyte colony-stimulating factor (G-CSF). Patients and Methods: Patients received ifosfamide 1.8 g/m(2) per day for 5 days, carboplatin 400 mg/m(2) per day for 2 days, and etoposide 100 mg/m(2) per day for 5 days. After completion of ICE chemotherapy, patients received daily subcutaneous injections of G-CSF (5 mug/kg per day) and IL-11 (50-100 mug/kg per day) until peripheral stem cell apheresis. Results: The median age was 11 years. Diagnosis included three relapsed Hodgkin disease, three relapsed central nervous system tumors, one relapsed Wilms tumor, and one relapsed rhabdomyosarcoma. The median number of apheresis procedures required to obtain 5 x 10(6) CD34(+) cells/kg was one. The mean +/- standard error of mean (SEM) total CD34(+) cells collected was 14.0 +/- 2.7 x 10(6)/kg. The mean +/- SEM total CD34(+)/CD41(+) cells collected was 4.6 +/- 1.9 x 10(6)/kg. Seven of the eight patients have subsequently undergone myeloablative chemotherapy with autologous PBSC transplantation and have reconstituted hematopoiesis with a median time to neutrophil recovery of 10 days and platelet recovery of 15.5 days. Conclusions: We conclude that the regimen of ICE/IL-11 plus G-CSF is successful in mobilizing large numbers of CD34(+) PBSC cells with a limited number (one) of apheresis collections in patients that have previously been heavily pretreated with chemotherapy/radiotherapy. C1 N Texas Hosp Children, Dallas, TX USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr,Dept Pediat, Div Pediat Hematol Oncol & Blood & Marrow Transpl, Washington, DC 20007 USA. Columbia Univ, Rainbow Babies & Childrens Hosp, Div Pediat Oncol & Blood & Marrow Transplantat, New York, NY USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Biostat Unit, Washington, DC 20007 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Childrens Hosp Orange Cty, Orange, CA 92668 USA. RP Cairo, MS (reprint author), Columbia Univ, 161 Ft Washington Ave,Irving 7, New York, NY 10032 USA. NR 19 TC 9 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JUN-JUL PY 2001 VL 23 IS 5 BP 300 EP 305 DI 10.1097/00043426-200106000-00013 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 451LU UT WOS:000169804200011 PM 11464987 ER PT J AU Croen, LA Grether, JK Curry, CJ Nelson, KB AF Croen, LA Grether, JK Curry, CJ Nelson, KB TI Congenital abnormalities among children with cerebral palsy: More evidence for prenatal antecedents SO JOURNAL OF PEDIATRICS LA English DT Article ID POPULATION; INFANTS; PREVALENCE; RISK AB Objectives: To investigate the association between cerebral palsy (CP) and congenital abnormalities among children with very low, low, and normal birth weight. Study design: A population-based, case-control study among the cohort of 155,636 live births delivered between 1983 and 1985 in 4 California counties. Children with moderate or severe congenital CP (n = 192) diagnosed by age 3 were identified from 2 California State service agencies, and 551 control children were randomly sampled from birth certificate files. Information on congenital abnormalities diagnosed by the age of 1 year was obtained from the California Birth Defects Monitoring Program registry. Odds ratios (OR) and 95% CIs were calculated to estimate risk 1;1 CP associated with congenital abnormalities. Results: Among singletons, congenital abnormalities were present in 33 (19.2%) children with CP and 21 (4.3%) control children (OR = 5.2, 95%, CI 2.8-9.7). For each birth weight group, the percent of children with congenital abnormalities among children with CP exceeded that among control children. Structural abnormalities of the central nervous system were more common among children with CP (OR = 16.2, 95% CI 5.8-49.3) than control children. In contrast, the percent of children with non-central nervous system abnormalities only was similar between case patients and control subjects. Conclusion: These findings provide further evidence that factors operating in the prenatal period contribute significantly to the etiology of CP. C1 Calif Dept Hlth Serv, Calif Birth Defects Monitoring Program, March Dimes Birth Defects Fdn, Oakland, CA USA. Valley Childrens Hosp, Madera, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NINDS, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Croen, LA (reprint author), Kaiser Permanente, Div Res, 3505 Broadway, Oakland, CA 94611 USA. NR 15 TC 43 Z9 45 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 2001 VL 138 IS 6 BP 804 EP 810 DI 10.1067/mpd.2001.114473 PG 7 WC Pediatrics SC Pediatrics GA 440LH UT WOS:000169176400006 PM 11391320 ER PT J AU Tangsinmankong, N Wayne, AS Howenstine, MS Washington, KR Langston, C Gatti, RA Good, RA Nelson, RP AF Tangsinmankong, N Wayne, AS Howenstine, MS Washington, KR Langston, C Gatti, RA Good, RA Nelson, RP TI Lymphocytic interstitial pneumonitis, elevated IgM concentration, and hepatosplenomegaly in ataxia-telangiectasia SO JOURNAL OF PEDIATRICS LA English DT Article ID ATM GENE; MUTATIONS; FAMILIES; CANCER AB An 8-year-old girl developed ataxia-telangiectasia. Western blotting of lysate revealed absence of the ATM protein, and 2 mutations in the ATM gene were found. Subsequently, the patient developed increased respiratory symptoms. Open lung biopsy revealed lymphocytic interstitial pneumonitis, which is nut characteristic of ataxia-telangiectasia. There was a therapeutic response to glucocorticosteroid treatment. C1 Univ S Florida, All Childrens Hosp, Dept Pediat, Div Allergy & Immunol, St Petersburg, FL 33701 USA. Univ S Florida, All Childrens Hosp, Dept Pathol & Lab Med, St Petersburg, FL 33701 USA. NIH, NCI, Pediat Oncol Branch, Bethesda, MD USA. James Whitcomb Riley Hosp Children, Sect Pulmonol, Indianapolis, IN 46202 USA. Texas Childrens Hosp, Dept Pediat & Pathol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA. Indiana Univ Sch Med, Dept Med, Hematol Malignancy Program Immunol, Div Hematol Oncol, Indianapolis, IN USA. RP Tangsinmankong, N (reprint author), Univ S Florida, All Childrens Hosp, Dept Pediat, Div Allergy & Immunol, 801 6th St S, St Petersburg, FL 33701 USA. NR 12 TC 11 Z9 11 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 2001 VL 138 IS 6 BP 939 EP 941 DI 10.1067/mpd.2001.113356 PG 3 WC Pediatrics SC Pediatrics GA 440LH UT WOS:000169176400036 PM 11391347 ER PT J AU Leschek, EW Chan, WY Diamond, DA Kaefer, M Jones, J Barnes, KM Cutler, GB AF Leschek, EW Chan, WY Diamond, DA Kaefer, M Jones, J Barnes, KM Cutler, GB TI Nodular Leydig cell hyperplasia in a boy with familial male-limited precocious puberty SO JOURNAL OF PEDIATRICS LA English DT Article ID LUTEINIZING-HORMONE RECEPTOR; ACTIVATING MUTATION; TUMORS; GENE AB In boys with familial male-limited precocious puberty, an activating mutation of the luteinizing hormone receptor causes Leydig cell hyperplasia, resulting in excess testosterone production. There are no reports of Leydig cell masses in boys with familial male-limited precocious puberty. We describe a 10-year-old boy with familial male-limited precocious puberty who developed Leydig cell nodules. C1 NIH, NICHHD, Bethesda, MD 20892 USA. NIH, Dept Nursing, Bethesda, MD USA. Georgetown Univ, Ctr Med, Washington, DC USA. Boston Childrens Hosp, Boston, MA USA. James Whitcomb Riley Hosp Children, Indianapolis, IN USA. Eli Lilly & Co, Indianapolis, IN USA. RP Leschek, EW (reprint author), NIH, NICHHD, Bldg 10,Rm 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. NR 12 TC 18 Z9 22 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 2001 VL 138 IS 6 BP 949 EP 951 DI 10.1067/mpd.2001.114477 PG 3 WC Pediatrics SC Pediatrics GA 440LH UT WOS:000169176400039 PM 11391350 ER PT J AU Lung, FDT Long, YQ King, CR Varady, J Wu, XW Wang, S Roller, PP AF Lung, FDT Long, YQ King, CR Varady, J Wu, XW Wang, S Roller, PP TI Functional preference of the constituent amino acid residues in a phage-library-based nonphosphorylated inhibitor of the Grb2-SH2 domain SO JOURNAL OF PEPTIDE RESEARCH LA English DT Article DE alanine scan; BIAcore surface plasmon resonance; cyclic peptide; molecular modeling; nonphosphorylated inhibitor of Grb2-SH2 ID MOLECULAR-DYNAMICS SIMULATION; HIGHLY POTENT INHIBITORS; SH2 DOMAIN; HIGH-AFFINITY; STRUCTURAL BASIS; PEPTIDE LIGANDS; DRUG DESIGN; BINDING; REQUIREMENTS; TARGETS AB A nonphosphorylated disulfide-bridged peptide, cyclo(Cys-Glu(1)- Leu-Tyr-Glu-Asn-Val-Gly-Met-Tyr(9)-Cys)-amide (termed G1) has been identified, by phage library, that binds to the Grb2-SH2 domain but not the src SH2 domain. Synthetic G1 blocks the Grb2-SH2 domain association (IC50 of 15.5 muM) With natural phosphopeptide ligands. As a new structural motif that binds to the Grb2-SH2 domain in a pTyr-independent manner, the binding affinity of G1 is contributed by the highly favored interactions of its structural elements interacting with the binding pocket of the protein. These interactions involve sidechains of amino acids Glu(1), Tyr(3), Glu(4) Asn(5), and Met(8). Also a specific conformation is required for the cyclic peptide when bound to the protein. Ala scanning within G1 and molecular modeling analysis suggest a promising model in which G1 peptide binds in the phosphotyrosine binding site of the Grb2-SH2 domain in a P-turn-like conformation. Replacement of Tyr(3) or Asn5 with Ala abrogates the inhibitory activity of the peptide, indicating that G1 requires a Y-X-N consensus sequence similar to that found in natural pTyr-containing ligands, but without Tyr phosphorylation. Significantly, the Ala mutant of Glu(1), i.e. the amino acid N-terminal to Y-3, remarkably reduces the binding affinity. The position of the Glu(1) side-chain is confirmed to provide a complementary role for pTyr(3), as demonstrated by the low micromolar inhibitory activity (IC50 = 1.02 muM) of the nonphosphorylated peptide 11, G1(Gla(1)), in which Glu(1) was replaced by gamma -carboxy-glutamic acid (Gla). C1 NCI, Frederick Canc Res & Dev Ctr, Med Chem Lab, NIH,Div Basic Sci, Frederick, MD 21702 USA. Georgetown Univ, Lombardi Canc Ctr, Washington, DC 20007 USA. RP Roller, PP (reprint author), NCI, Frederick Canc Res & Dev Ctr, Med Chem Lab, NIH,Div Basic Sci, Boyles St,Bldg 376,POB B, Frederick, MD 21702 USA. NR 33 TC 23 Z9 23 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-002X J9 J PEPT RES JI J. Pept. Res. PD JUN PY 2001 VL 57 IS 6 BP 447 EP 454 DI 10.1034/j.1399-3011.2001.00833.x PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 445NZ UT WOS:000169465300002 PM 11437948 ER PT J AU Sun, MK Alkon, DL AF Sun, MK Alkon, DL TI Pharmacological enhancement of synaptic efficacy, spatial learning, and memory through carbonic anhydrase activation in rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HIPPOCAMPAL PYRAMIDAL CELLS; CHOLINERGIC NEURONS; RYANODINE RECEPTOR; GABAERGIC SYNAPSES; GABA(A) RECEPTORS; THETA-RHYTHM; TRANSFORMATION; EXCITATION; ACETYLCHOLINE; DEPOLARIZATION AB CA1 pyramidal cells were recorded in rat hippocampal slices. In the presence of carbonic anhydrase activators, comicrostimulation of cholinergic inputs from stratum oriens and gamma -aminobutyric acid (GABA)ergic inputs from stratum pyramidale at low intensities switched the hyperpolarizing GABA-mediated inhibitory postsynaptic potentials to depolarizing responses. In the absence of the activators, however, the same stimuli were insufficient to trigger the synaptic switch. This synaptic switch changed the function of the GABAergic synapses from excitation filter to amplifier and was prevented by carbonic anhydrase inhibitors, indicating a dependence on HCO3-. Intralateral ventricular administration of these same carbonic anhydrase activators caused the rats to exhibit superior learning of the Morris water maze task, suggesting that the GABAergic synaptic switch is critical for gating the synaptic plasticity that underlies spatial memory formation. Increased carbonic anhydrase activity might, therefore, also enhance perception, processing, and storing of temporally associated relevant signals and represents an important therapeutic target in learning and memory pharmacology. C1 Blanchette Rockefeller Neurosci Inst, Rockville, MD 20850 USA. NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. RP Sun, MK (reprint author), Blanchette Rockefeller Neurosci Inst, Johns Hopkins Acad & Res Bldg,Room 319,9601 Med C, Rockville, MD 20850 USA. NR 39 TC 47 Z9 49 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 2001 VL 297 IS 3 BP 961 EP 967 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 437QN UT WOS:000169005200016 PM 11356917 ER PT J AU Sun, HY Bungay, PM Elmquist, WF AF Sun, HY Bungay, PM Elmquist, WF TI Effect of capillary efflux transport inhibition on the determination of probe recovery during in vivo microdialysis in the brain SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID POTENT CYCLOPROPYLDIBENZOSUBERANE MODULATOR; P-GLYCOPROTEIN INHIBITOR; FREELY-MOVING RATS; QUANTITATIVE MICRODIALYSIS; MULTIDRUG-RESISTANCE; EXTRACTION FRACTION; CEREBROSPINAL-FLUID; CONCENTRATION PROFILES; QUINOLINIC ACID; BLOOD AB Intracerebral microdialysis probe recovery (extraction fraction) may be influenced by several mass transport processes in the brain, including efflux and uptake exchange between brain and blood. Therefore, changes in probe recovery under various experimental conditions can be useful to characterize fundamental drug transport processes. Accordingly, the effect of inhibiting transport on probe recovery was investigated for two capillary efflux transporters with potentially different membrane localization and transport mechanisms, P-glycoprotein and an organic anion transporter. Fluorescein/probenecid and quinidine/LY-335979 were chosen as the substrate/inhibitor combinations for organic anion transport and P-glycoprotein-medicated transport, respectively. Probenecid decreased the probe recovery of fluorescein in frontal cortex, from 0.21 +/- 0.017 to 0.17 +/- 0.020 (p < 0.01). Quantitative microdialysis calculations indicated that probenecid treatment reduced the total brain elimination rate constant by 3-fold from 0.37 to 0.12 (ml/min.ml of extracellular fluid). In contrast, the microdialysis recovery of quinidine, delivered locally to the brain via the probe perfusate, was not sensitive to P-glycoprotein inhibition by systemically administered LY-335979, a potent and specific inhibitor of P-glycoprotein. Recovery of difluorofluorescein, an analog of fluorescein, was also decreased by probenecid in the frontal cortex but not in the ventricle cerebrospinal fluid. These experimental observations are in qualitative agreement with microdialysis theory incorporating mathematical models of transporter kinetics. These studies suggest that only in certain circumstances will efflux inhibition at the blood-brain barrier and blood-cerebrospinal fluid barrier influence the microdialysis probe recovery, and this may depend upon the substrate and inhibitor examined and their routes of administration, the localization and mechanism of the membrane transporter, as well as the microenvironment surrounding the probe. C1 Univ Nebraska, Med Ctr, Coll Pharm, Dept Pharmaceut Sci, Omaha, NE USA. NIH, Drug Delivery & Kinet Resource, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. RP Elmquist, WF (reprint author), Nebraska Med Ctr, Dept Pharmaceut Sci, 986025, Omaha, NE 68198 USA. FU NCI NIH HHS [CA-75466] NR 32 TC 24 Z9 25 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 2001 VL 297 IS 3 BP 991 EP 1000 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 437QN UT WOS:000169005200020 PM 11356921 ER PT J AU Schlitzer, M Rodriguez, L Kador, PF AF Schlitzer, M Rodriguez, L Kador, PF TI Synthesis of potential aldose reductase inhibitors based on minimal pharmacophore requirements SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article ID DIABETIC COMPLICATIONS AB A series of 17 compounds were synthesized based on the premise that the minimal pharmacophore for aldose reductase inhibition requires the presence of both an aryl group and polar group connected by a linking structure. Three groups of compounds were synthesized, the first possessing an aniline-4-(2'-6'-methylbenzothiazole) or 2-aminobenzothiazole group as the aryl group, the second possessing a 2-naphthyl as the aryl group and the third possessing either a 4-(2-phenylthianole) or 2-(5-2'-nitrophenylfuran) as the aryl group. In all three of these groups the carboxylate or its methyl ester are linked to the aryl group through various lengths of methylene carbons and amide or cinnamide groups. Optimal activity was observed when the carboxylic group was separated from the aryl group by a linking structure of five atoms in length. Both a double bond and an amide moiety are well tolerated in the linking structure. C1 Univ Marburg, Inst Pharmazeut Chem, D-35032 Marburg, Germany. NEI, NIH, Bethesda, MD 20892 USA. RP Schlitzer, M (reprint author), Univ Marburg, Inst Pharmazeut Chem, Marbacher Weg 6, D-35032 Marburg, Germany. NR 11 TC 7 Z9 7 U1 0 U2 0 PU ROYAL PHARMACEUTICAL SOC GREAT BRITAIN PI LONDON PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD JUN PY 2001 VL 53 IS 6 BP 831 EP 839 DI 10.1211/0022357011776180 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 442RM UT WOS:000169298800008 PM 11428659 ER PT J AU Ader, DN South-Paul, J Adera, T Deuster, PA AF Ader, DN South-Paul, J Adera, T Deuster, PA TI Cyclical mastalgia: prevalence and associated health and behavioral factors SO JOURNAL OF PSYCHOSOMATIC OBSTETRICS AND GYNECOLOGY LA English DT Article DE cyclical mastalgia; pain; premenstrual syndrome ID PREMENSTRUAL SYMPTOMS; WOMEN; MASTOPATHY; EXERCISE; IMPACT; DIET AB Perimenstrual breast pain (cyclical mastalgia) is a common problem that can be sufficiently severe to interfere with usual activities and has been associated with elevated mammography usage in young women. This study was undertaken to replicate clinic-based research on cyclical mastalgia, and to examine the association between this disorder and health-related behaviors and perceived stress. Using random digit dialing throughout Virginia, 874 women aged 18-44 were interviewed Sixty-eight per cent of women experienced cyclical breast symptoms; 22% experienced moderate to extreme discomfort (classified as cyclical mastalgia). Hormonal contraceptive usage war associated with significantly less mastalgia and premenstrual syndrome (PMS). Smoking, caffeine consumption and perceived stress were associated with mastalgia (odds ratios = 1.52, 1.53 and 1.7, respectively). Young women (under 35 years) with mastalgia were more likely to have had a mammogram (20.2%) than those without mastalgia (9.9%). Most women with this disorder (77.5%) did not have PMS. The prevalence of cyclical mastalgia and its association with mammography replicate clinic-based findings. Associations with smoking and stress had not previously been reported. Prospective research is needed to determine the biopsychosocial factors contributing to this disorder. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Family Med, Bethesda, MD 20814 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Prevent Med & Community Hlth, Richmond, VA 23298 USA. Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. RP Ader, DN (reprint author), NIAMSD, NIH, 45 Ctr Dr,MSC 6500,Bldg 45,Room 5AS-19H, Bethesda, MD 20892 USA. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 28 TC 33 Z9 38 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 0167-482X J9 J PSYCHOSOM OBST GYN JI J. Psychosomat. Obstet. Gynecol. PD JUN PY 2001 VL 22 IS 2 BP 71 EP 76 DI 10.3109/01674820109049956 PG 6 WC Psychology, Clinical; Obstetrics & Gynecology; Psychiatry SC Psychology; Obstetrics & Gynecology; Psychiatry GA 448JH UT WOS:000169623400003 PM 11446156 ER PT J AU Siriphant, P Drury, TF Horowitz, AM Harris, RM AF Siriphant, P Drury, TF Horowitz, AM Harris, RM TI Oral cancer knowledge and opinions among Maryland nurse practitioners SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE oral cancer; nurse practitioners; knowledge; risk factors; diagnostic procedures ID PREVENTION; DENTISTS AB Objectives: As part of a Maryland statewide oral cancer needs assessment, a census of adult and family practice nurse practitioners was conducted to determine their knowledge of oral cancer risk factors, diagnostic procedures and related opinions. Methods: Information was obtained through a pretested, 40-item, self-administered mail questionnaire of 389 nurse practitioners. A second complete mailing was sent three weeks after the initial mailing, two postal card reminders were mailed at 10 and 17 days after the second mailing, which yielded a response rate of 56 percent. Results: Most nurse practitioners identified the use of tobacco, alcohol, and prior oral cancer lesions as real risk factors. But only 35 percent identified exposure to the sun as a risk for lip cancer. Respondents were not overly knowledgeable about the early signs of oral cancer, most common forms, or sites for oral cancer. Only 19 percent believed their knowledge of oral cancer was current Nurse practitioners who reported having a continuing education course on oral cancer within the past two to five years were 3.1 times more likely to have a high score on knowledge of risk factors and 2.9 times more likely to have a high score on knowledge of both risk factors and of diagnostic procedures than were those who had never had a continuing education course. Conclusions: The reported knowledge of oral cancer, in conjunction with opinions about level of knowledge and training, point to a need for systematic educational updates in oral cancer prevention and early detection. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Thammasat Univ, Fac Dent, Bangkok, Thailand. Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA. Univ Maryland, Sch Nursing, Dept Adult Hlth Nursing, Baltimore, MD 21201 USA. RP Horowitz, AM (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bldg 45,Room 3AN-44B,45 Ctr Dr,MSC 6401, Bethesda, MD 20892 USA. NR 19 TC 14 Z9 14 U1 0 U2 1 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD SUM PY 2001 VL 61 IS 3 BP 138 EP 144 DI 10.1111/j.1752-7325.2001.tb03380.x PG 7 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 472FU UT WOS:000170973500002 PM 11603316 ER PT J AU Siriphant, P Horowitz, AM Child, WL AF Siriphant, P Horowitz, AM Child, WL TI Perspectives of Maryland adult and family practice nurse practitioners on oral cancer SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE oral cancer; focus groups; qualitative descriptive study; nurse practitioners ID QUALITATIVE RESEARCH; FOCUS AB Objectives: Because oral and pharyngeal cancer mortality in Maryland ranks seventh among states and sixth for black males, a statewide oral cancer needs assessment was conducted. The purposes of this qualitative descriptive study were to obtain indepth information on nurse practitioners' awareness and opinions of oral cancer, oral cancer examinations, and related factors. These findings were intended to supplement a previous survey conducted among Maryland nurse practitioners. Methods: A professional focus group moderator conducted one face-to-lace focus group with 11 nurse practitioners and one telephone focus group with eight nurse practitioners. Criterion-purposeful sampling and qualitative content analysis were employed. Results: Findings showed that oral cancer is a neglected public health problem and, based on their formal training, not one considered by nurse practitioners to be their responsibility. Although aware of other cancers, none of the nurse practitioners recognized that oral cancer was a public health problem in the state. Numerous barriers were cited for this neglect, including their lack of training and, in one case, unpleasant feelings about examining the mouth. Participants concluded that oral cancer is part of their responsibilities and that they are interested in related continuing education courses. Conclusions: The focus groups of nurse practitioners provided rich and insightful suggestions for future strategies to help solve the oral cancer problem in Maryland, which supplemented the quantitative mail survey conducted earlier. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Thammasat Univ, Fac Dent, Bangkok, Thailand. Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA. RP Horowitz, AM (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bldg 45,Room 3AN-44B,45 Ctr Dr MSC 6401, Bethesda, MD 20892 USA. NR 24 TC 8 Z9 8 U1 1 U2 2 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD SUM PY 2001 VL 61 IS 3 BP 145 EP 149 DI 10.1111/j.1752-7325.2001.tb03381.x PG 5 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 472FU UT WOS:000170973500003 PM 11603317 ER PT J AU Rainford, M Adair, R Scialli, AR Ghidini, A Spong, CY AF Rainford, M Adair, R Scialli, AR Ghidini, A Spong, CY TI Amniotic fluid index in the uncomplicated term pregnancy - Prediction of outcome SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE amniotic fluid index; pregnancy outcome; oligohydramnios ID VOLUME; OLIGOHYDRAMNIOS AB OBJECTIVE: To establish whether an association between oligohydramnios and pregnancy outcome is present in the uncomplicated term pregnancy. STUDY DESIGN: Pregnancies with a singleton fetus in cephalic presentation at term (greater than or equal to 37 weeks), a reactive nonstress test and an antepartum amniotic fluid index performed within four days of delivery between January 1994 and September 1998 were identified. Excluded were those with any maternal or fetal complication or unavailable outcome information. The primary outcome measure was rate of operative vaginal or abdominal delivery for a nonreassuring fetal heart rate tracing. Statistical analysis included Fisher's exact test and one-way analysis of variance, with a two-tailed P<.05 considered significant. RESULTS: Two hundred thirty-two women met the inclusion criteria; of them, 44 (19%) had an amniotic fluid index 5 cm. There was no difference in the operative delivery rate for a nonreassuring fetal heart tracing between those with a normal amniotic fluid index >5 cm vs. less than or equal to5 cm (39 [21%] vs. 5 [11%], P>.05). In addition, there were no differences between the two groups in rates of neonatal intensive care unit admissions or five-minute Apgar scores <7. Patients with a normal amniotic fluid index had a significantly lower labor induction rate (96 [51%] vs. 42 [98%], P<.001) and higher rate of meconium-stained amniotic fluid (65 [35%] vs. 7 [16%], P=.01) than those with a low amniotic fluid index. CONCLUSION: In the uncomplicated pregnancy at term, an amniotic fluid index less than or equal to5 cm increases the incidence of labor induction but does not appear to affect the rate of operative delivery for abnormal fetal heart rate tracings. C1 Georgetown Univ Hosp, Dept Obstet & Gynecol, Washington, DC 20007 USA. NICHD, Ctr Res Mothers & Children, NIH, Bethesda, MD USA. RP Ghidini, A (reprint author), Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, 3PHC,3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 11 TC 25 Z9 29 U1 0 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD JUN PY 2001 VL 46 IS 6 BP 589 EP 592 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 447QV UT WOS:000169584700008 PM 11441685 ER PT J AU Taaffe, DR Suominen, H Ollikainen, S Cheng, S AF Taaffe, DR Suominen, H Ollikainen, S Cheng, S TI Calcaneal bone mineral and ultrasound attenuation in male athletes exposed to weight-bearing and nonweight-bearing activity - A cross-sectional report SO JOURNAL OF SPORTS MEDICINE AND PHYSICAL FITNESS LA English DT Article DE bone mineral content; bone mineral density; ultrasound attenuation ID X-RAY ABSORPTIOMETRY; HIGH-IMPACT EXERCISE; QUANTITATIVE ULTRASOUND; PHYSICAL-ACTIVITY; YOUNG-WOMEN; MECHANICAL-PROPERTIES; POSTMENOPAUSAL WOMEN; MASS ACCUMULATION; HIP FRACTURE; DENSITY AB Background. To determine if the expected differences in bone mineral content/density of the calcaneus among male athletic groups that undertake weight-bearing and nonweight-bearing activity are also apparent for bone "quality" as assessed by quantitative ultrasound (QUS) attenuation. Methods. Experimental design: cross-sectional. Setting: a University research laboratory. Participants: we studied 30 young men: 10 Finnish national level jumpers whose training incorporates repeated impacts to the heel, 10 aquatics athletes whose skeletons are exposed to nonweight-bearing activity, and 10 sedentary men matched for age and body weight. Measures: bone mineral content (BMC, g(.)cm(-1)), areal bone mineral density (BMDa; g(.)cm(-2)) and presumed volumetric BMD (BMDv, g(.)cm(-3)) was measured by single energy photon absorption (SPA). Broadband ultrasound attenuation (BUA using Fourier spectral estimation and UBI-4 using Burg spectral estimation, both in db/MHz) was assessed by a new QUS device (QUS-1TM, Metra Biosystems). Results. There was no difference in years of sport specific training or total training time per week between athlete groups. BMC, BMDa and BMDv were significantly different among groups (p=0.0001) With jumpers being higher than aquatics athletes and controls. BMC of jumpers was 52% and 39% higher than controls and aquatics athletes, respectively, while the corresponding values for BMDv were 34% and 28%. However, BUA values were not significantly different (p=0.10) among groups nor was UBI-4 (p=0.03; jumpers values were 7% and 6% higher than aquatics athletes and controls, respectively). Conclusions. These cross-sectional results indicate that bone mineral content and density of the calcaneus are substantially higher in jumpers than individuals engaged in nonweight-bearing or regular weight-bearing activity. However, parameters assessed by QUS attenuation are not markedly different, which suggests that bone "quality" properties may not be as responsive as that of bone mineral content/density to habitual skeletal loading. C1 Univ Jyvaskyla, Dept Hlth Sci, SF-40351 Jyvaskyla, Finland. RP Taaffe, DR (reprint author), NIA, Epidemiol Demog & Biometry Program, NIH, 7201 Wisconsin Ave 3C-309, Bethesda, MD 20892 USA. NR 41 TC 14 Z9 14 U1 0 U2 2 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0022-4707 J9 J SPORT MED PHYS FIT JI J. Sports Med. Phys. Fit. PD JUN PY 2001 VL 41 IS 2 BP 243 EP 249 PG 7 WC Sport Sciences SC Sport Sciences GA 460UD UT WOS:000170326200017 PM 11447369 ER PT J AU Korn, EL Teeter, DM Baumrind, S AF Korn, EL Teeter, DM Baumrind, S TI Using explicit clinician preferences in nonrandomized study designs SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE causal effects; causation; observational studies; randomized clinical trial; selection bias ID DECISION; EXTRACT AB Nonrandomized study designs are proposed that utilize statements by individual clinicians specifying how they would prefer to treat each patient based on the patient's pre-treatment records. Using these stated preferences allows us to eliminate selection biases in an analysis to estimate treatment effects. The analysis of a pilot study using one of the new designs to examine two orthodontic treatments is presented. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NCI, Clin Trials Sect, Biometr Res Branch, Bethesda, MD 20892 USA. Univ Pacific, Dept Orthodont, San Francisco, CA 94115 USA. Univ Med & Dent New Jersey, Newark, NJ USA. NR 6 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUN 1 PY 2001 VL 96 IS 1 SI SI BP 67 EP 82 DI 10.1016/S0378-3758(00)00324-4 PG 16 WC Statistics & Probability SC Mathematics GA 430RL UT WOS:000168589300005 ER PT J AU Proschan, MA McMahon, RP Shih, JH Hunsberger, SA Geller, NL Knatterud, G Wittes, J AF Proschan, MA McMahon, RP Shih, JH Hunsberger, SA Geller, NL Knatterud, G Wittes, J TI Sensitivity analysis using an imputation method for missing binary data in clinical trials SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE missing data; multiple imputation; hypothesis testing; p-values ID ISCHEMIA PILOT ACIP AB Missing data in clinical trials can result in biased treatment effect estimates and tests if the analysis includes only the observed data. Two simple methods of compensating for this potential bias in trials with a binary endpoint were suggested by Wittes et al. (Statist. Med. 8 (1989) 415-425). We study the statistical properties of these procedures and show that they are robust against certain model departures. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NHLBI, Off Biostat Res, Rockledge Ctr 2, Bethesda, MD 20892 USA. RI McMahon, Robert/C-5462-2009 NR 10 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUN 1 PY 2001 VL 96 IS 1 SI SI BP 155 EP 165 DI 10.1016/S0378-3758(00)00332-3 PG 11 WC Statistics & Probability SC Mathematics GA 430RL UT WOS:000168589300010 ER PT J AU Gail, MH Pee, D Carroll, R AF Gail, MH Pee, D Carroll, R TI Effects of violations of assumptions on likelihood methods for estimating the penetrance of an autosomal dominant mutation from kin-cohort studies SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE kin-cohort design; genotyped-proband design; penetrance; cancer risk; robustness; segregation analysis ID GENETIC-ANALYSIS; CANCER AB Struewing et al, (1997) used the kin-cohort design to estimate the risk of breast cancer in women with autosomal dominant mutations in the genes BRCA1 and BRCA2. In this design, a proband volunteers to be genotyped and then reports the disease history (phenotype) of his or her first-degree relatives. call et al. (1999) developed maximum likelihood estimation of parameters for autosomal dominant genes with the kin-cohort design. In this paper we examine the effects of violations of key assumptions on likelihood-based inference. Serious overestimates of disease risk (penetrance) and allele frequency result if people with affected relatives tend to volunteer to be probands more readily than people without affected relatives. Penetrance will be underestimated if probands fail to report all the disease present among their relatives, and serious overestimates of penetrance and allele frequency can result if probands give false positive reports of disease. Sources of familial disease aggregation other than the gene under study result in overestimates of the penetrance in mutation carriers, underestimates of penetrance in noncarriers, and overestimates of allele frequency. Unless sample sizes are quite large, confidence intervals based on the Wald procedure can have subnominal coverage; limited numerical studies indicate that likelihood ratio-based confidence intervals perform better. Published by Elsevier Science B.V. C1 NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. Informat Management Serv, Rockville, MD USA. Texas A&M Univ, College Stn, TX USA. NR 9 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUN 1 PY 2001 VL 96 IS 1 SI SI BP 167 EP 177 DI 10.1016/S0378-3758(00)00333-5 PG 11 WC Statistics & Probability SC Mathematics GA 430RL UT WOS:000168589300011 ER PT J AU Lee, YJ AF Lee, YJ TI Post-stratification based direct adjustment approach to a missing data problem in clinical trials SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article AB In clinical trials we always expect some missing data. If data are missing completely at random, then missing data can be ignored for the purpose of statistical inference. In most situation, however, ignoring missing data will introduce bias. Adjustment is possible for missing data if the missing mechanism is known, which is rare in real problems. Our approach is to estimate directly the mean outcome of each treatment group in the presence of missing data. To this end, we post-stratify all the subjects by the expected value of outcome (or by a variable predictive of the outcome) so that subjects within a stratum may be considered homogeneous with respect to the expected outcome, and assume that subjects within a stratum are missing at random. We apply this post-stratification approach to a recently concluded clinical trial where a high proportion of data are missing and the missingness depends on the same factors affecting the outcome variable. A simulation study shows that the post-stratification approach reduces the bias substantially compared to the naive approach where only non-missing subjects are analyzed. Published by Elsevier Science B.V. C1 NIH, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUN 1 PY 2001 VL 96 IS 1 SI SI BP 247 EP 262 DI 10.1016/S0378-3758(00)00338-4 PG 16 WC Statistics & Probability SC Mathematics GA 430RL UT WOS:000168589300016 ER PT J AU Ernst, M Moolchan, ET Robinson, ML AF Ernst, M Moolchan, ET Robinson, ML TI Behavioral and neural consequences of prenatal exposure to nicotine SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Review DE in utero; smoking; nicotinic acetylcholine receptors; disruptive behavior disorders ID RAT-BRAIN REGIONS; DEFICIT HYPERACTIVITY DISORDER; INFANT-DEATH-SYNDROME; MONOAMINE-OXIDASE-B; LOW-BIRTH-WEIGHT; MATERNAL CIGARETTE-SMOKING; NERVOUS-SYSTEM DEVELOPMENT; FETAL BREATHING MOVEMENTS; HIGH-RISK SAMPLE; ACETYLCHOLINE-RECEPTORS AB Objective: To review evidence for the neurodevelopmental effects of in utero exposure to nicotine. Concerns about long-term cognitive and behavioral effects of prenatal exposure to nicotine arise from reports of increased rates of disruptive behavioral disorders in children whose mothers smoked during pregnancy. The relatively high rate of tobacco smoking among pregnant women (25% of all pregnancies in the U.S.) underlines the seriousness of these concerns. Method: This review examines the largest and most recent epidemiological and clinical studies that investigated the association of prenatal nicotine exposure with health, behavioral, and cognitive problems. Because of the numerous potential confounding variables in human research, findings from animal studies, in which environmental factors are strictly controlled, are also discussed. Finally, neural and molecular mechanisms that are likely to underlie neurodevelopmental disruptions produced by prenatal nicotine exposure are outlined. Results: A dose-response relationship between maternal smoking rates and low birth weight (potentially associated with lower cognitive ability) and spontaneous abortion is consistently found, whereas long-term developmental and behavioral effects in the offspring are still controversial, perhaps because of the difficulty of separating them from other genetic and environmental factors. Despite the wide variability of experimental paradigms used in animal studies, common physical and behavioral effects of prenatal exposure to nicotine have been observed, including low birth weight, enhanced locomotor activity, and cognitive impairment. Finally, disturbances in neuronal pathfinding, abnormalities in cell proliferation and differentiation, and disruptions in the development of the cholinergic and catecholaminergic systems all have been reported in molecular animal studies of in utero exposure to nicotine. Conclusions: Prenatal exposure to nicotine may lead to dysregulation in neurodevelopment and can indicate higher risk for psychiatric problems, including substance abuse. Knowledge of prenatal exposure to nicotine should prompt child psychiatrists to closely monitor at-risk patients. C1 NIDA, Brain Imaging Ctr, Neuroimaging Branch, Intramural Res Program, Lexington, KY 40583 USA. NIDA, Clin Pharmacol & Therapeut Branch, IRP, Baltimore, MD USA. RP Ernst, M (reprint author), NIMH, MADP, 1-B3-10,1 Ctr Dr,MSC 0135, Bethesda, MD 20892 USA. NR 120 TC 331 Z9 338 U1 3 U2 42 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 JUN PY 2001 VL 40 IS 6 BP 630 EP 641 DI 10.1097/00004583-200106000-00007 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 433XR UT WOS:000168786400007 PM 11392340 ER PT J AU Peterson, BS Pine, DS Cohen, P Brook, JS AF Peterson, BS Pine, DS Cohen, P Brook, JS TI Prospective, longitudinal study of tic, obsessive-compulsive, and attention-deficit/hyperactivity disorders in an epidemiological sample SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE tics; obsessive-compulsive disorder; attention-deficit/hyperactivity disorder; epidemiology; risk factors ID DIAGNOSTIC INTERVIEW SCHEDULE; DEFICIT HYPERACTIVITY DISORDER; LA-TOURETTES SYNDROME; AUTOSOMAL-DOMINANT TRANSMISSION; COMMUNITY SAMPLE; GENETIC-RELATIONSHIP; PSYCHIATRIC STATUS; YOUNG ADOLESCENTS; CONDUCT DISORDER; LATE CHILDHOOD AB Objective: Understanding the interrelatedness of ties, obsessive-compulsive disorder (OCD), and attention-deficit, hyperactivity disorder (ADHD) has been complicated by studying only cross-sectional samples of clinically referred subjects. The authors report the cross-sectional and longitudinal associations of these disorders in an epidemiological sample of children followed prospectively into early adulthood. Method: Structured diagnostic interview information was acquired on 976 children, aged 1 to 10 years, who were randomly selected from families living in upstate New York in 1975. Reassessments were acquired in 776 of these subjects 8, 10, and 15 years later. Diagnostic prevalences were estimated at each time point. The associations among ties, OCD, and ADHD were assessed within and across time points, as were their associations with comorbid illnesses and demographic risk factors. Results: In temporal cross-section, ties and ADHD symptoms were associated with OCD symptoms in late adolescence and early adulthood after demographic features and comorbid psychiatric symptoms were controlled. In prospective analyses, ties in childhood and early adolescence predicted an increase in OCD symptoms in late adolescence and early adulthood. ADHD symptoms in adolescence predicted more OCD symptoms in early adulthood, and OCD in adolescence predicted more ADHD symptoms in adulthood. The associations of ties with ADHD were unimpressive in temporal cross-section and were not significant in prospective analyses. Ties, OCD, and ADHD shared numerous complex associations with demographic and psychopathological risk factors. ADHD was associated with lower IQ and lower social status, whereas OCD was associated with higher IQ. Conclusions: Ties and OCD were significantly associated in this sample, as were OCD and ADHD. These findings are in general consistent with those from family studies, and they help to define the natural history, comorbid illnesses, and interrelatedness of these conditions. C1 Yale Univ, Ctr Child Study, Sch Med, New Haven, CT 06520 USA. NIMH, Program Mood & Anxiety Disorders, Intramural Res Program, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Columbia Univ, Joseph Mailman Sch Publ Hlth, New York, NY USA. Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA. RP Peterson, BS (reprint author), Yale Univ, Ctr Child Study, Sch Med, 230 S Frontage Rd, New Haven, CT 06520 USA. FU NIDA NIH HHS [K05-DA-00244, DA-03188]; NIMH NIH HHS [MH-16432, MH01232, MH01391, MH36971, MH43878] NR 75 TC 152 Z9 158 U1 6 U2 17 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 JUN PY 2001 VL 40 IS 6 BP 685 EP 695 DI 10.1097/00004583-200106000-00014 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 433XR UT WOS:000168786400014 PM 11392347 ER PT J AU Weissenberger, AA Dell, ML Liow, K Theodore, W Frattali, CM Hernandez, D Zametkin, AJ AF Weissenberger, AA Dell, ML Liow, K Theodore, W Frattali, CM Hernandez, D Zametkin, AJ TI Aggression and psychiatric comorbidity in children with hypothalamic hamartomas and their unaffected siblings SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE hypothalamic hamartomas; seizures; aggression; sibling pathology ID GELASTIC SEIZURES; EPILEPSY; BEHAVIOR; EEG; GABAPENTIN; LAUGHTER; GABA; CAT AB Objective: To assess aggression and psychiatric comorbidity in a sample of children with hypothalamic hamartomas and gelastic seizures and to assess psychiatric diagnoses in siblings of study subjects. Method: Children with a clinical history of gelastic seizures and hypothalamic hamartomas (n = 12; age range 3-14 years) had diagnoses confirmed by video-PEG and head magnetic resonance imaging. Structured interviews were administered, including the Diagnostic Interview for Children and Adolescents-Revised Parent Form (DICA-R-P), the Test of Broad Cognitive Abilities, and the Vitiello Aggression Scale. Parents were interviewed with the DICA-R-P about each subject and a sibling closest in age without seizures and hypothalamic hamartomas. Patients were seen from 1998 to 2000. Results: Children with gelastic seizures and hypothalamic hamartomas displayed a statistically significant increase in comorbid psychiatric conditions, including oppositional defiant disorder (83.3%) and attention-deficit/hyperactivity disorder (75%). They also exhibited high rates of conduct disorder (33.3%), speech retardation/learning impairment (33.3%), and anxiety and mood disorders (16.7%). Significant rates of aggression were noted. with 58% of the seizure patients meeting criteria for the affective subtype of aggression and 30.5% having the predatory aggression subtype. Affective aggression was significantly more common (p <.05). Unaffected siblings demonstrated low rates of psychiatric pathology on semistructured parental interview and no aggression as measured by the Vitiello Aggression Scale. Conclusions: Children with hypothalamic hamartomas and gelastic seizures had high rates of psychiatric comorbidity and aggression. Parents reported that healthy siblings had very low rates of psychiatric pathology and aggression. C1 NIMH, Bethesda, MD 20814 USA. Catholic Univ, Washington, DC USA. Univ Kansas, Sch Med, Dept Med, Wichita, KS 67214 USA. NINDS, Clin Epilepsy Sect, Bethesda, MD 20892 USA. NIH, WG Magnuson Clin Ctr, Speech Language Pathol Sect, Bethesda, MD 20892 USA. RP Zametkin, AJ (reprint author), NIMH, Bldg 10,Room 3N 238,MSC 1276, Bethesda, MD 20814 USA. NR 42 TC 63 Z9 66 U1 0 U2 6 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 JUN PY 2001 VL 40 IS 6 BP 696 EP 703 DI 10.1097/00004583-200106000-00015 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 433XR UT WOS:000168786400015 PM 11392348 ER PT J AU Liu, JE Palmieri, V Roman, NJ Bella, JN Fabsitz, R Howard, BV Welty, TK Lee, ET Devereux, RB AF Liu, JE Palmieri, V Roman, NJ Bella, JN Fabsitz, R Howard, BV Welty, TK Lee, ET Devereux, RB TI The impact of diabetes on left ventricular filling pattern in normotensive and hypertensive adults: The strong heart study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PRESSURE-OVERLOAD HYPERTROPHY; AMERICAN-INDIANS; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ECHOCARDIOGRAPHIC ASSESSMENT; ARTERIAL-HYPERTENSION; SHORTENING RELATIONS; DIASTOLIC FUNCTION; MELLITUS; FRAMINGHAM AB OBJECTIVES We sought to determine the effect of diabetes mellitus (DM) on left ventricular (LV) filling pattern in normotensive (NT) and hypertensive (HTN) individuals. BACKGROUND Diastolic abnormalities have been extensively described in HTN but are less well characterized in DM, which frequently coexists with HTN. METHODS We analyzed the transmitral inflow velocity profile at the mitral annulus in four groups from the Strong Heart Study: NT-non-DM (n = 730), HTN-non-DM (n = 394), NT-DM (n = 616) and HTN-DM (n = 671). The DM subjects were further divided into those with normal filling pattern (n = 107) and those with abnormal relaxation (AbnREL) (n = 447). RESULTS The peak E velocity was lowest in HTN-DM, intermediate in NT-DM and HT-non-DM and highest in the NT-non-DM group (p < 0.001), with a reverse trend seen for peak A velocity (p < 0.001). In multivariate analysis, E/A ratio was lowest in HTN-DM and highest in NT-non-DM, with no difference between NT-DM and HTN-non DM (p < 0.001). Likewise, mean atrial filling fraction and deceleration time were highest in HTN-DM, followed by HTN-non-DM or NT-DM and lowest in NT-non-DM (both p < 0.05). Among DM subjects, those with AbnREL had higher fasting glucose (p = 0.03) and hemoglobin A1C (p = 0.04). CONCLUSIONS Diabetes mellitus, especially with worse glycemic control, is independently associated with abnormal LV relaxation. The severity of abnormal LV relaxation is similar to the well-known impaired relaxation associated with HTN. The combination of DM and HTN has more severe abnormal LV relaxation than groups with either condition alone. In addition, AbnREL in DM is associated with worse glycemic control. (J Am Coll Cardiol 2001;37: 1943-9) (C) 2001 by the American College of Cardiology. C1 Cornell Univ, Med Ctr, New York Hosp, Dept Med, New York, NY 10021 USA. NHLBI, Bethesda, MD 20892 USA. Medstar Res Inst, Washington, DC USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. Univ Oklahoma, Hlth Sci Ctr, Sch Publ Hlth, Oklahoma City, OK USA. RP Liu, JE (reprint author), New York Presbyterian Hosp, Weill Cornell Med Ctr, Div Cardiol, Box 222,525 E 68th St, New York, NY 10021 USA. FU NHLBI NIH HHS [U01-HL41652, U01-HL41642, U01-HL41654] NR 40 TC 184 Z9 191 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 1 PY 2001 VL 37 IS 7 BP 1943 EP 1949 DI 10.1016/S0735-1097(01)01230-X PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 439EE UT WOS:000169097200029 PM 11401136 ER PT J AU Dionne, RA Yagiela, JA Moore, PA Gonty, A Zuniga, J Beirne, OR AF Dionne, RA Yagiela, JA Moore, PA Gonty, A Zuniga, J Beirne, OR CA Collaborative Sedation Study Grp TI Comparing efficacy and safety of four intravenous sedation regimens in dental outpatients SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID GASTROINTESTINAL ENDOSCOPY; ANESTHESIA; AVOIDANCE; SCALE; FEAR AB Background. Management of patients' fear and anxiety during dental treatment is a primary concern of dental practitioners. Pharmacological strategies used in outpatient dental settings must be both safe and effective. Regimens of intravenously administered sedative drugs were evaluated in a collaborative, multicenter study of outpatients undergoing removal of impacted third molars. Methods. A total of 997 patients randomly received one of five treatments: placebo; midazolam administered to a clinical endpoint of conscious sedation (mean dose, 8.6 milligrams); midazolam plus additional midazolam as needed during the procedure (man total dose 12.2 mg); fentanyl (1.4 micrograms/kilogram) plus midazolam to achieve the same endpoint of conscious sedation (mean dose, 5.7 mg); or fentanyl (1.4 (mug/kg), midazolam (mean dose, 5.8 mg) and methohexital as needed during the procedure (mean dose, 61.0 mg). Results. Each drug regimen reduced anxiety during surgery in comparison with placebo, with the combination of midazolam, fentanyl and methohexital resulting in significantly less anxiety in comparison with the other treatment groups. Pain reports by patients during surgery also were reduced significantly by the combination of fentanyl, midazolam and methohexital. Patients' global evaluations of the efficacy of sedation ranked midazolam with supplemental midazolam and the combination of fentanyl, midazolam and methohexital as significantly mor efficacious than the other two drug regimens. The authors noted transient respiratory depression in patients in the two opioid-treated groups, but no other physiological changes were detected. Conclusions. These data provide evidence that the drugs and doses evaluated resulted in therapeutic benefit to dental outpatients, with minimal incidence of potentially serious adverse effects. Clinical Implications. The results of this large-scale study provide assurance to both the public and the dental profession of the safety of parenteral sedation wit these drugs and combinations of these drugs when titrated slowly in the recommended doses by appropriately trained dentists. C1 NIDCR, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Dent, Div Diagnost U Surg Sci, Ctr Hlth Sci, Los Angeles, CA 90024 USA. Univ Pittsburgh, Sch Dent Med, Dept Publ Hlth Dent, Pittsburgh, PA 15260 USA. Univ Kentucky, Sch Dent, Div Oral & Maxillofacial Surg, Lexington, KY 40506 USA. Univ N Carolina, Sch Dent, Chapel Hill, NC USA. Univ Washington, Dept Oral & Maxillofacial Surg, Seattle, WA 98195 USA. RP Dionne, RA (reprint author), NIDCR, Pain & Neurosensory Mech Branch, NIH, Bldg 10,Room 1N-117,10 Ctr Dr, Bethesda, MD 20892 USA. FU NIDCR NIH HHS [DE-72565-69] NR 29 TC 29 Z9 32 U1 0 U2 2 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUN PY 2001 VL 132 IS 6 BP 740 EP 751 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 445ZL UT WOS:000169488400018 PM 11433853 ER PT J AU Smith, KW Hoelscher, DM Lytle, LA Dwyer, JT Nicklas, TA Zive, MM Clesi, AL Garceau, AO Stone, EJ AF Smith, KW Hoelscher, DM Lytle, LA Dwyer, JT Nicklas, TA Zive, MM Clesi, AL Garceau, AO Stone, EJ TI Reliability and validity of the Child and Adolescent Trial for Cardiovascular Health (CATCH) Food Checklist: A self-report instrument to measure fat and sodium intake by middle school students SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID NHANES-II SURVEY; FREQUENCY QUESTIONNAIRE; QUANTITATIVE DATA; PHYSICAL-ACTIVITY; NUTRIENT SOURCES; DIETARY-INTAKE; AMERICAN DIET; CHOLESTEROL; VALIDATION; EDUCATION AB Objective To develop a scoring algorithm and evaluate the reliability and validity of scores from the Child and Adolescent Trial for Cardiovascular Health (CATCH) Food Checklist (CFC) as measures of total fat, saturated fat, and sodium intake in middle school students. Design Randomized, controlled trial in which participants were assigned to 1 of 3 study protocols that varied the order of CFC and 24-hour dietary recall administration. Criterion outcomes were percent energy from total fat, percent energy from saturated fat, and sodium intake in milligrams. Subjects/setting A multiethnic sample (33% ethnic and racial minorities) of 365 seventh-grade students from 8 schools in 4 states. Statistical analyses Multivariable regression models were used to calibrate the effects of individual food checklist items; bootstrap estimates were used for cross-validation; and kappa statistics, Pearson correlations, t tests, and effect sizes were employed to assess reliability and validity. Results The median same-day test-retest reliability kappa for the 40 individual CFC food items was 0.85. With respect to item validity, the median kappa statistic comparing student choices to those identified by staff dietitions was 0.54. Test-retest reliability coefficients pranged from 0.84 to 0.89 for CFC total nutrient scores. Correlations between CFC scores and 24-hour recall values were 0.36 for total fat, 0.36 for saturated fat, and 0.34 for sodium; CFC scores were consistent with hypothesized gender differences in nutrient intake. Applications/conclusions The CFC is a reliable and valid tool for measuring fat, saturated fat, and sodium intake in middle school students. Its brevity and ease of administration make the CFC a cost-effective way to measure middle school students' previous day's intake of selected nutrients in school surveys and intervention studies. C1 New England Res Inst, Watertown, MA 02472 USA. Univ Texas, Sch Publ Hlth, Ctr Hlth Promot Res & Dev, Houston, TX USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Tufts Univ, Sch Nutr, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr Hosp, Boston, MA 02111 USA. N Dakota State Univ, Dept Food & Nutr, Coll Human Dev & Educ, Fargo, ND 58105 USA. Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. WESTAT Corp, Rockville, MD 20850 USA. NHLBI, CATCH Prevent Sci Res Grp, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Smith, KW (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. OI Dwyer, Johanna/0000-0002-0783-1769 FU NHLBI NIH HHS [UO1-HL-39852, UO1-HL-39870, UO1-HL-39880, UO1-HL-39906, UO1-HL-39927] NR 42 TC 28 Z9 29 U1 2 U2 5 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUN PY 2001 VL 101 IS 6 BP 635 EP + DI 10.1016/S0002-8223(01)00161-4 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 460MX UT WOS:000170312300009 PM 11424542 ER PT J AU Robbins, J Hirsch, C Whitmer, R Cauley, J Harris, T AF Robbins, J Hirsch, C Whitmer, R Cauley, J Harris, T CA Cardiovascular Hlth Study TI The association of bone mineral density and depression in an older population SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE human; older; depression; bone mineral density; osteoporosis ID CES-D; RISK-FACTORS; OSTEOPOROSIS; ADULTS; WOMEN; FRACTURE AB OBJECTIVE: To evaluate the association between bone mineral density (BMD) and measurements of depression in an older population. DESIGN: Population-based, cross-sectional study. SETTING: Study subjects were participants in the Cardiovascular Health Study (CHS), a longitudinal, longterm, follow-up study, at the University of California Davis (Sacramento, California) and the University of Pittsburgh (Pittsburgh, Pennsylvania) clinical centers. PARTICIPANTS: A random sample of 1,566 Medicare enrollees age 65 and older enrolled in the CHS. MEASUREMENTS: Total hip BMD, measured using dual energy x-ray absorptiometry (DEXA), after adjustment for multiple covariates, was compared with depression evaluated with the Center for Epidemiological Studies 10-item Depression Scale (CES-Dm). Risk factors for os reoporosis were compared in depressed and nondepressed participants. Potential correlates were entered into a regression model. Depression scores were compared in normal, osteopenic, and osteoporotic individuals. RESULTS: Sixteen percent of participants were clinically depressed; 9% had BMDs in the osteoporotic range. Mean BMD was 40 mg/cm(2) lower in those with clinical depression. High CES-Dm scores were associated with lower BMD (P < .001) when adjusted for body mass index (BMI), age, kilocalories of activity, estrogen use, gender, race, smoking and drinking. When stratified by race, this remained true for all Caucasians (P < .01), all African Americans (P < .05), and when stratified by race and gender the association remained only for all Caucasian women (P < .001). In women and Caucasian men there was an increase in depression scores among individuals with osteoporotic-range BMDs. CONCLUSIONS: A significant association was found between BMD and depressive symptoms after adjustment tor osteoporosis risk factors, in Caucasians, depressive symptoms were associated with both osteoporotic and osteopenic levels of BMD. Causality cannot be ascribed, with only one measurement of BMD. We postulate that there may be an unmeasured third factor, such as an endogenous steroid, that is responsible for both low BMD and depression. C1 NIA, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA. RP Robbins, J (reprint author), Div Gen Med, Patient Support Serv Bldg,4150 V St,Suite 2400, Sacramento, CA 95817 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NHLBI NIH HHS [N01-HC-85086, HL 15103, HL-35129, N01-HC-85079] NR 19 TC 99 Z9 102 U1 0 U2 2 PU BLACKWELL SCIENCE 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 JUN PY 2001 VL 49 IS 6 BP 732 EP 736 DI 10.1046/j.1532-5415.2001.49149.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 453EG UT WOS:000169903100006 PM 11454111 ER PT J AU McDermott, MM Ohlmiller, SM Liu, K Guralnik, JM Martin, GJ Pearce, WH Greenland, P AF McDermott, MM Ohlmiller, SM Liu, K Guralnik, JM Martin, GJ Pearce, WH Greenland, P TI Gait alterations associated with walking impairment in people with peripheral arterial disease with and without intermittent claudication SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE peripheral arterial disease; physical activity; intermittent claudication; physical functioning ID PHYSICAL-ACTIVITY; CALTRAC ACCELEROMETER; 6-MINUTE WALK; INDEX; QUESTIONNAIRES AB OBJECTIVES: To describe gait alterations associated with impaired walking endurance in patients with and without lower-extremity peripheral arterial disease (PAD) and determine whether the Caltrac accelerometer provides a valid measure of physical activity in PAD. DESIGN: Cross-sectional. SETTING: Academic medical center. PARTICIPANTS: PAD (n = 40) and non-PAD patients (n = 22) from two Chicago hospitals. MEASUREMENTS: Participants underwent measurement of the ankle brachial index (ABI), leg length, and 6-minure walk. Steps per minute and step length were measured during the first and last 100 feet of the 6-minute walk. Participants wore a Caltrac accelerometer, sensitive to vertical acceleration, during the 6-minute walk and for 7 continuous days. RESULTS: Five PAD participants (13%) and one non-PAD participant (5%) ceased walking before the end of 6 minutes. Among the remaining participants, distance walked in 6 minutes was more highly related to walking velocity during the last 100 feet of the walk than walking velocity during the first 100 feet. ABI was associated significantly with cadence (20.77 steps/minute per unit ASI, P < .001) but not step length (10.12 centimeters/unit ABI, P < .08). ABI was associated significantly with 6-minute walk distance (493 feet/unit ABI, P = .018), but this association disappeared completely after adjustment for step length and cadence. We found no difference in accelerometer scores between PAD and non-PAD participants over a fixed distance of 800 feet (7.34 vs 7.17 activity units, P = .789). However, scores were significantly different after 7 days (730.8 vs 1,485.0 activity units, P = .003). CONCLUSION: Walking performance in PAD patients who completed 6 minutes of walking was largely determined by a decline in walking velocity rather than slower initial walking velocity. ABI was more closely associated with cadence than step length. Future studies should assess the effect of exercise programs and revascularization on cadence and step length in PAD. C1 Northwestern Univ, Sch Med, Dept Surg, Div Vasc Surg, Chicago, IL 60611 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. RP McDermott, MM (reprint author), 675 N St Clair,Suite 18-200, Chicago, IL 60611 USA. FU NCRR NIH HHS [RR-00048]; PHS HHS [R01-58099] NR 20 TC 53 Z9 54 U1 0 U2 0 PU BLACKWELL SCIENCE 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 JUN PY 2001 VL 49 IS 6 BP 747 EP 754 DI 10.1046/j.1532-5415.2001.49151.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 453EG UT WOS:000169903100008 PM 11454113 ER PT J AU Ilercil, A O'Grady, MJ Roman, MJ Paranicas, M Lee, ET Welty, TK Fabsitz, RR Howard, BV Devereux, RB AF Ilercil, A O'Grady, MJ Roman, MJ Paranicas, M Lee, ET Welty, TK Fabsitz, RR Howard, BV Devereux, RB TI Reference values for echocardiographic measurements in urban and rural populations of differing ethnicity: The Strong Heart Study SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID LEFT-VENTRICULAR MASS; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; CORONARY-ARTERY DISEASE; AMERICAN-INDIANS; SYSTEMIC HYPERTENSION; NORMAL-CHILDREN; NORMAL ADULTS; BODY-MASS; HYPERTROPHY; VOLUME AB Discrepancies in reported reference values for left ventricular (LV) dimensions and mass may be due to imaging errors with early echocardiographic methods or effects of subject characteristics and inclusion criteria. To determine whether contemporary echocardiographic methods provide stable normal limits for left ventricular measurements in different populations, M-mode/2-dimensional echocardiography was applied in 176 American Indian participants in the Strong Heart Study and 237 New York City residents who were clinically normal. No consistent difference in any measure of LV size or function existed between populations. Upper normal limits (98th percentile) for LV mass were 96 g/m(2) in women and 116 g/m(2) in men and 3.27 cm/m for LV chamber diameter normalized for height. Thus contemporary M-mode/2D echocardiography provides reference ranges for LV measurements that approximate necropsy measurements and have acceptable stability in apparently normal white, African-American/Caribbean, and American Indian populations. C1 Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Dept Med, New York, NY USA. Univ Oklahoma, Sch Publ Hlth Sci, Oklahoma City, OK USA. Aberdeen Area Indian Hlth Serv, Rapid City, SD USA. NHLBI, Div Epidemiol & Dis Control, Bethesda, MD 20892 USA. MedStar Res Inst, Washington, DC USA. RP Devereux, RB (reprint author), New York Presbyterian Hosp, Weill Cornell Med Ctr, Div Cardiol, Box 222,525 E 68th St, New York, NY 10021 USA. FU NCRR NIH HHS [M10-RR0047]; NHLBI NIH HHS [HL-18323, HL-47450, UO1-HL-41642]; PHS HHS [UO1-41652, UO1-41654] NR 41 TC 56 Z9 58 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JUN PY 2001 VL 14 IS 6 BP 601 EP 611 DI 10.1067/mje.2001.113258 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 440MB UT WOS:000169178100008 PM 11391289 ER PT J AU Hostetter, TH Brenner, GM AF Hostetter, TH Brenner, GM TI Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation - Commentary SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID GLOMERULAR ULTRAFILTRATION; RAT; PATHOGENESIS; DYNAMICS; DISEASE C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hostetter, TH (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL-07066, HL-22602]; NIADDK NIH HHS [AM-16749, 1 F32 AM-05660, AM-19467] NR 7 TC 100 Z9 103 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2001 VL 12 IS 6 BP 1315 EP 1318 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 435WY UT WOS:000168906200027 PM 11373357 ER PT J AU Baker, SG Pinsky, PF AF Baker, SG Pinsky, PF TI A proposed design and analysis for comparing digital and analog mammography: Special receiver operating characteristic methods for cancer screening SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE cancer screening; diagnostic testing; double sampling; permutation test; sample size; verification bias; sensitivity; specificity ID DIAGNOSTIC-TESTS; ROC CURVES; SENSITIVITY; ACCURACY; BREAST; VERIFICATION; PROGRAMS AB Because randomized trials have shown a reduction in breast cancer mortality, analog mammography for the early detection of breast cancer has gained widespread use. Recently, several manufacturers have developed digital mammography, which promises great advantages in the storage and transmission of images. We were asked to design a study to compare the two types of mammography in terms of their performance for the early detection of breast cancer. A standard measure of mammography performance is the receiver operating characteristic (ROC) curve, which is a plot of false- and true-positive rates for each ordered classification of the mammography images. Methods for study design and data analysis based on ROC curves have been well developed for diagnostic tests, particularly in radiology. But for comparing the performance of mammography for the early detection of breast cancer among asymptomatic women, special considerations motivate new designs and methodology. First, digital mammography may cost substantially more than analog mammography. If this is the case, then the standard paired design, in which each subject undergoes both types of mammography, may be more expensive than necessary. To reduce costs, we propose a partial testing design, in which all subjects undergo analog mammography and those recommended for biopsy and a random sample not recommended for biopsy also undergo digital mammography. Second, the false-positive rate for analog mammography, defined as the rate of unnecessary biopsy, is near 1%. A standard ROC analysis that compares areas under the entire ROC curve would summarize performance over false-positive rates that are not relevant for evaluating the performance of cancer screening. As a more appropriate alternative, we propose basing inference on the-areas under the small parr of the ROC curves near the false-positive rates corresponding to a biopsy recommendation. Third, the vast majority of screened subjects are not biopsied, and so have an unknown cancer state at the time of screening. To make inference about the performance of a cancer screening test, the standard approach is to follow subjects not biopsied for some period, usually 1 year, and assume that those who developed cancer were missed on screening and those who did not develop cancer were cancer-free at screening. Unfortunately, this follow-up period can greatly lengthen the duration of the study. To compare the performance of digital and analog mammography without the need for a follow-up period, we propose estimating the ratio of areas under the ROC curves near the small false-positive rates associated with a biopsy recommendation. To compute sample sizes, our null hypothesis is that the ratio of partial ROC areas is 1, and our two possible alternative hypotheses are ratios of 1.6 and 2, both indicating superior performance for digital mammography. We assume a breast cancer prevalence of .003 and specify various parameters for the shapes of the ROC curves and their dependence. For a two-sided type I error of .05 and a power of .9, a standard paired design would require that 22,000 subjects undergo both analog and digital mammography. For the same type I error and power, the proposed partial testing design would require that 35,000 subjects undergo analog mammography and 10,000 subjects undergo both analog and digital mammography. Compared to the paired design, the reduction in the cost per subject is 23% if digital mammography costs four times as much as analog mammography and 41% if digital mammography costs 10 times as much as analog mammography. C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. NCI, Early Detect Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Biometry Res Grp, Bethesda, MD 20892 USA. NR 34 TC 27 Z9 27 U1 0 U2 4 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 2001 VL 96 IS 454 BP 421 EP 428 DI 10.1198/016214501753168136 PG 8 WC Statistics & Probability SC Mathematics GA 437HN UT WOS:000168986400006 ER PT J AU DeVore, GR Romero, R AF DeVore, GR Romero, R TI Combined use of genetic sonography and maternal serum triple-marker screening - An effective method for increasing the detection of trisomy 21 in women younger than 35 years SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE triple-marker screening; genetic sonography; trisomy 21 ID TRIMESTER NUCHAL TRANSLUCENCY; FETAL DOWNS-SYNDROME; ALPHA-FETOPROTEIN; RISK ASSESSMENT; AGE; 2ND-TRIMESTER; ULTRASOUND; FETUSES; ABNORMALITIES; PREGNANCIES AB Objective. The current standard of practice is to screen women younger than 35 years for trisomy 21 with maternal triple-marker screening, followed by amniocentesis in high-risk (1:10-1:190) patients. Non-high-risk patients are not offered further diagnostic testing. This study was conducted to determine whether genetic sonography of fetuses considered to be at moderate risk (1:190-1:1000) after maternal triple-marker screening increases the detection for trisomy 21, is cost-effective, and reduces the number of amniocenteses required to detect a single fetus with trisomy 21. Methods. After triple-marker screening, mathematical modeling was used to classify 500,000 theoretical fetuses as high, moderate, or low risk (>1:1001-1:10,000) for trisomy 21. The sensitivity for genetic sonography varied between 60% and 90%, and false-positive rates varied between 5% and 25%. Two programs (I and II) were compared with the control program. The control program included patients with highrisk fetuses (1:10-1:190) who had amniocentesis. Program I consisted of patients in the moderate-risk group (1:191-1:1000)who had genetic sonography followed by amniocentesis only when an abnormal sonographic finding was present. Program II used an approach in which genetic sonography was done for both high- and moderate-risk fetuses, and amniocentesis was performed only when an abnormal sonographic finding was present. Results. When added to the control program, genetic sonography significantly increased the detection rate of Down syndrome (range, 68.1%-77.8% versus 49%), reduced the cost of detection, and resulted in a ratio of fetuses with Down syndrome detected to normal fetuses lost because of amniocentesis of greater than 1 (range, 2.1-4.2). Compared with the control program, program II significantly increased the detection of fetuses with trisomy 21 (range, 56%-72%) when the sensitivity of genetic sonography was > 70%, reduced the cost of detection, and had ratios of trisomy 21 detection to normal fetuses lost because of amniocentesis of between 2.38 and 17.88. Conclusion. Women younger than 35 years and classified as having moderate risk after triple-marker screening could undergo genetic sonography under 1 of 2 approaches, either of which would result in an increased detection rate of trisomy 21 and be cost-effective without increasing the loss rate of normal fetuses after genetic amniocentesis. C1 NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA. RP DeVore, GR (reprint author), Suite 206,301 S Fair Oaks Ave, Pasadena, CA 91105 USA. NR 26 TC 18 Z9 20 U1 0 U2 1 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 JUN PY 2001 VL 20 IS 6 BP 645 EP 654 PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 437RP UT WOS:000169007600012 PM 11400939 ER PT J AU Walther, MM Choyke, PL AF Walther, MM Choyke, PL TI Re: Pheochromocytoma coexisting with renal artery lesions SO JOURNAL OF UROLOGY LA English DT Letter ID STENOSIS; CALCIFICATION; HYPERTENSION; DISEASE C1 NCI, Urol Oncol Branch, Dept Radiol, Clin Ctr,NIH, Bethesda, MD 20892 USA. RP Walther, MM (reprint author), NCI, Urol Oncol Branch, Dept Radiol, Clin Ctr,NIH, 10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. NR 13 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 JUN PY 2001 VL 165 IS 6 BP 2005 EP 2006 DI 10.1016/S0022-5347(05)66273-8 PN 1 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 431GL UT WOS:000168623400058 PM 11371912 ER PT J AU Buffington, CAT Pacak, K AF Buffington, CAT Pacak, K TI Increased plasma norepinephrine concentration in cats with interstitial cystitis SO JOURNAL OF UROLOGY LA English DT Article DE bladder; cystitis, interstitial; norepinephrine; cats; sympathetic nervous system ID LOCUS-COERULEUS; ELECTROCHEMICAL DETECTION; PARAVENTRICULAR NUCLEUS; LIQUID-CHROMATOGRAPHY; NERVOUS-SYSTEM; STRESS; AMITRIPTYLINE; NEURONS; CATECHOLAMINES; MICRODIALYSIS AB Purpose: Interstitial cystitis is a chronic urological syndrome affecting humans and domestic animals, including cats (feline interstitial cystitis). The symptoms of interstitial cystitis seem to be exacerbated by stress, suggesting involvement of the sympathetic nervous system and/or hypothalamic-pituitary-adrenal axis. Others have described sympathetic nervous system abnormalities in patients with interstitial cystitis but to our knowledge no data on plasma catecholamine concentrations or hyp othalamic-pituitary-adrenal axis function in such patients have been reported. To evaluate the role of these systems in cats with feline interstitial cystitis we simultaneously measured baseline plasma concentrations of catecholamines and their metabolites to assess sympathetic activity, and the response of plasma adenocorticotropic hormone and cortisol concentrations to the infusion of corticotropin-releasing factor. Materials and Methods: Eight healthy cats and 8 with feline interstitial cystitis were anesthetized and a catheter was placed in the external jugular vein. Four hours after recovery samples were obtained for high performance liquid chromatography analysis of plasma norepinephrine, dihydroxyphenylglycol, epinephrine, dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid. In 4 cats per group 1 mug. ovine corticotropin-releasing factor per kg. body weight was infused and blood samples were collected at intervals for 120 minutes for determining adenocorticotropic hormone and cortisol. Results: Significant increases in plasma norepinephrine and dihydroxyphenylglycol as well as a trend toward increased epinephrine were found, whereas no effect on dihydroxyphenylalanine, dopamine, dihydroxyphenylacetic acid, adenocorticotropic hormone or cortisol was identified in cats with feline interstitial cystitis. Conclusions: These results support and extend previous studies identifying an increase in sympathetic activity in cats with feline interstitial cystitis. C1 Ohio State Univ, Coll Vet Med, Dept Vet Clin Sci, Columbus, OH 43210 USA. NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. RP Buffington, CAT (reprint author), Ohio State Univ, Coll Vet Med, Dept Vet Clin Sci, Columbus, OH 43210 USA. RI Buffington, Tony/B-7135-2009 FU NIDDK NIH HHS [DK 47538] NR 33 TC 29 Z9 30 U1 1 U2 6 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 JUN PY 2001 VL 165 IS 6 BP 2051 EP 2054 DI 10.1016/S0022-5347(05)66292-1 PN 1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 431GL UT WOS:000168623400080 PM 11371926 ER PT J AU Crow, MT AF Crow, MT TI Cytoplasmic signaling and the cytoskeleton SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract C1 NIA, Cardiovasc Sci Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2001 VL 33 IS 6 BP 1286 EP 1287 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 444TR UT WOS:000169416600034 ER PT J AU Barsov, EV Payne, WS Hughes, SH AF Barsov, EV Payne, WS Hughes, SH TI Adaptation of chimeric retroviruses in vitro and in vivo: Isolation of avian retroviral vectors with extended host range SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; VESICULAR-STOMATITIS-VIRUS; CELLS EXPRESSING GP160; MEDIATED GENE-TRANSFER; ROUS-SARCOMA VIRUS; ENVELOPE GLYCOPROTEIN; G-PROTEIN; SYNCYTIUM FORMATION; HIV ENVELOPE AB We have designed and characterized two new replication-competent avian sarcoma/leukosis virus-based retroviral vectors with amphotropic and ecotropic host ranges. The amphotropic vector RCASBP-M2C(797-8), was obtained by passaging the chimeric retroviral vector RCASBP-M2C(4070A) (6) in chicken embryos. The ecotropic vector, RCASBP(Eco), was created by replacing the env-coding region in the retroviral vector RCASBP(A) with the env region from an ecotropic murine leukemia virus. It replicates efficiently in avian DFJ8 cells that express murine ecotropic receptor. For both vectors, permanent cell lines that produce viral stocks with titers of about 5 x 10(6) CFU/ml on mammalian cells can be easily established by passaging transfected avian cells. Some chimeric viruses, for example, RCASBP(Eco), replicate efficiently without modifications, For those chimeric viruses that do require modification, adaptation by passage in vitro or in vivo is a general strategy. This strategy has been used to prepare vectors with altered host range and could potentially be used to develop vectors that would be useful for targeted gene delivery. C1 NCI, HIV Drug Resistance Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Michigan State Univ, Dept Microbiol & Publ Hlth, E Lansing, MI 48824 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, Frederick Canc Res & Dev Ctr, POB B,Bldg 539,Room 130A, Frederick, MD 21702 USA. NR 84 TC 24 Z9 25 U1 0 U2 1 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 JUN PY 2001 VL 75 IS 11 BP 4973 EP 4983 DI 10.1128/JVI.75.11.4973-4983.2001 PG 11 WC Virology SC Virology GA 430UJ UT WOS:000168593600003 PM 11333876 ER PT J AU Katen, LJ Januszeski, MM Anderson, WF Hasenkrug, KM Evans, LH AF Katen, LJ Januszeski, MM Anderson, WF Hasenkrug, KM Evans, LH TI Infectious entry by amphotropic as well as ecotropic murine leukemia viruses occurs through an endocytic pathway SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEMLIKI FOREST VIRUS; RETROVIRAL VECTORS; BAFILOMYCIN A(1); MEMBRANE-FUSION; CELL-FUSION; ENVELOPE GLYCOPROTEIN; ATPASE ACTIVITY; CULTURED-CELLS; ANIMAL-CELLS AB Infectious entry of enveloped viruses is thought to proceed by one of two mechanisms. pH-dependent viruses enter the cells by receptor-mediated endocytosis and are inhibited by transient treatment with agents that prevent acidification of vesicles in the endocytic pathway, while pa-independent viruses are not inhibited by such agents and are thought to enter the cell by direct fusion with the plasma membrane. Nearly all retroviruses, including amphotropic murine leukemia virus (MuLV) and human immunodeficiency virus type 1, are classified as pH independent. However, ecotropic MuLV is considered to be a pH-dependent virus. We have examined the infectious entry of ecotropic and amphotropic MuLVs and found that they were equally inhibited by NH,CI and bafilomycin A. These agents inhibited both viruses only partially over the course of the experiments, Agents that block the acidification of endocytic vesicles also arrest vesicular trafficking. Thus, partial inhibition of the MuLVs could be the result of virus inactivation during arrest in this pathway. In support of this contention, we found that that the loss of infectivity of the MuLVs during treatment of target cells with the drugs closely corresponded to the loss of activity due to spontaneous inactivation at 37 degreesC in the same period of time. Furthermore, the drugs had no effect on the efficiency of infection under conditions in which the duration of infection was held to a very short period to minimize the effects of spontaneous inactivation. These results indicate that the infectious processes of both ecotropic and amphotropic MuLVs were arrested rather than aborted by transient treatment of the cells with the drugs. We also found that infectious viruses were efficiently internalized during treatment. This indicated that the arrest occurred in an intracellular compartment and that the infectious process of both the amphotropic and ecotropic MuLVs very likely involved endocytosis. An important aspect of this study pertains to the interpretation of experiments in which agents that block endocytic acidification inhibit infectivity. As we have found with the MuLVs, inhibition of infectivity may be secondary to the block of endocytic acidification, While this strongly suggests the involvement of an endocytic pathway, it does not necessarily indicate a requirement for an acidic compartment during the infectious process. Likewise, a lack of inhibition during transient treatment with the drugs would not preclude an endocytic pathway for viruses that are stable during the course of the treatment. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. Univ So Calif, Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Gene Therapy Labs, Los Angeles, CA 90033 USA. RP Evans, LH (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. NR 52 TC 47 Z9 47 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 JUN PY 2001 VL 75 IS 11 BP 5018 EP 5026 DI 10.1128/JVI.75.11.5018-5026.2001 PG 9 WC Virology SC Virology GA 430UJ UT WOS:000168593600008 PM 11333881 ER PT J AU Barouch, DH Santra, S Kuroda, MJ Schmitz, JE Plishka, R Buckler-White, A Gaitan, AE Zin, R Nam, JH Wyatt, LS Lifton, MA Nickerson, CE Moss, B Montefiori, DC Hirsch, VM Letvin, NL AF Barouch, DH Santra, S Kuroda, MJ Schmitz, JE Plishka, R Buckler-White, A Gaitan, AE Zin, R Nam, JH Wyatt, LS Lifton, MA Nickerson, CE Moss, B Montefiori, DC Hirsch, VM Letvin, NL TI Reduction of simian-human immunodeficiency virus 89.6P viremia in rhesus monkeys by recombinant modified vaccinia virus Ankara vaccination SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; POLYMERASE CHAIN-REACTION; VIRAL LOAD; DISEASE PROGRESSION; PRIMARY ISOLATE; ATTENUATED SIV; MACAQUES; INFECTION; TYPE-1; DNA AB Since cytotoxic T lymphocytes (CTLs) are critical for controlling human immunodeficiency virus type 1 (HIV-1) replication in infected individuals, candidate HIV-1 vaccines should elicit virus-specific CTL responses. In this report, we study the immune responses elicited in rhesus monkeys by a recombinant poxvirus vaccine and the degree of protection afforded against a pathogenic simian-human immunodeficiency virus SHIV-89.6P challenge. Immunization with recombinant modified vaccinia virus Ankara (MVA) vectors expressing SIVmac239 gag-pol and HIV-1 89.6 env elicited potent Gag-specific CTL responses but no detectable SHIV-specific neutralizing antibody (NAb) responses. Following intravenous SHIV-89.6P challenge, sham-vaccinated monkeys developed low-frequency CTL responses, low-titer NAb responses, rapid loss of CD4(+) T lymphocytes, high-setpoint viral RNA levels, and significant clinical disease progression and death in half of the animals by day 168 postchallenge. In contrast, the recombinant MVA-vaccinated monkeys demonstrated high-frequency secondary CTL responses, high-titer secondary SHIV-89.6-specific NAb responses, rapid emergence of SHIV-89.6P-specific NAb responses, partial preservation of CD4(+) T lymphocytes, reduced setpoint viral RNA levels, and no evidence of clinical disease or mortality by day 168 postchallenge. There was a statistically significant correlation between levels of vaccine-elicited CTL responses prior to challenge and the control of viremia following challenge. These results demonstrate that immune responses elicited by live recombinant vectors, although unable to provide sterilizing immunity, can control viremia and prevent disease progression following a highly pathogenic AIDS virus challenge. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. NIAID, Mol Microbiol Lab, Rockville, MD 20852 USA. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. RP Barouch, DH (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Res E Room 113,330 Brookline Ave, Boston, MA 02215 USA. FU NIAID NIH HHS [AI-26507, AI-85343, P01 AI026507, U01 AI026507] NR 43 TC 159 Z9 160 U1 0 U2 1 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 JUN PY 2001 VL 75 IS 11 BP 5151 EP 5158 DI 10.1128/JVI.75.11.5151-5158.2001 PG 8 WC Virology SC Virology GA 430UJ UT WOS:000168593600023 PM 11333896 ER PT J AU Israel, BF Pickles, RJ Segal, DM Gerard, RD Kenney, SC AF Israel, BF Pickles, RJ Segal, DM Gerard, RD Kenney, SC TI Enhancement of adenovirus vector entry into CD70-positive B-cell lines by using a bispecific CD70-adenovirus fiber antibody SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; NERVOUS-SYSTEM LYMPHOMA; LATENT GENE-EXPRESSION; LYTIC CYCLE GENES; SUBGROUP-C; LYMPHOPROLIFERATIVE DISORDERS; NASOPHARYNGEAL CARCINOMAS; HEMATOPOIETIC-CELLS; ALPHA(V) INTEGRINS; VIRAL LATENCY AB Although many recombinant adenovirus vectors (rAd) have been developed, especially by using group C adenoviruses, to transfer and express genes, such rAd do not readily infect B-cell lines due to the lack of the coxsackievirus-adenovirus receptor. Bispecific antibodies have been used in different cell systems to facilitate entry of rAd into otherwise nonpermissive cells. Bispecific antibody is synthesized by covalently linking two monoclonal antibodies with distinct specificities. It has been shown that lymphoproliferative tumors commonly express the cell surface protein CD70, while this receptor is normally expressed on only a small subset of highly activated B cells and T cells. We therefore investigated whether a bispecific antibody with specificities for the adenovirus fiber protein and CD70 can facilitate rAd entry and subsequent expression of rAd-encoded genes in CD70-positive B cells, We found high CD70 expression on Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs), as well as some, but not all, Burkitt lymphoma (BL) lines. We show here that rAd encoding green fluorescent protein (Ad-GFP) infects EBV-transformed LCLs and a CD70-positive BL line 10- to 20-fold more efficiently in the presence of the CD70-fiber bispecific antibody. In contrast, the bispecific antibody does not enhance Ad-GFP infection in CD70-deficient BL cells. Using the CD70-fiber bispecific antibody, we increased the ability of rAd vectors encoding the EBV immediate-early proteins BZLF1 and BRLF1 to induce the lytic form of EBV infection in LCLs. These results indicate that the CD70-fiber bispecific antibody can enhance rAd infection of CD70-positive B cells and suggest the use of this vector to explore EBV-positive LCLs. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Div Infect Dis, Chapel Hill, NC 27599 USA. Univ N Carolina, Cyst Fibrosis Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Div Cardiol, Dallas, TX 75390 USA. RP Kenney, SC (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Div Infect Dis, CB 7295, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [R01 CA 66519, R01 CA066519]; NIAID NIH HHS [5-T32-AI07151-21, T32 AI007151] NR 50 TC 19 Z9 24 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 JUN PY 2001 VL 75 IS 11 BP 5215 EP 5221 DI 10.1128/JVI.75.11.5215-5221.2001 PG 7 WC Virology SC Virology GA 430UJ UT WOS:000168593600030 PM 11333903 ER PT J AU Zolotukhin, AS Michalowski, D Smulevitch, S Felber, BK AF Zolotukhin, AS Michalowski, D Smulevitch, S Felber, BK TI Retroviral constitutive transport element evolved from cellular TAP(NXF1)-binding sequences SO JOURNAL OF VIROLOGY LA English DT Article ID MESSENGER-RNA EXPORT; HUMAN-IMMUNODEFICIENCY-VIRUS; PFIZER MONKEY VIRUS; HUMAN TAP PROTEIN; NUCLEAR EXPORT; SECONDARY STRUCTURE; POSTTRANSCRIPTIONAL REGULATION; GENOMIC SELEX; MEX67P; BINDING AB The constitutive transport element (CTE) of type D retroviruses serves as a signal of nuclear export of unspliced viral RNAs, The human TAP(NXF1) protein, a cellular mRNA export factor, directly binds to CTE and mediates nuclear export of CTE-containing RNAs, Here, we use genomic SELEX (systematic evolution of ligands by exponential enrichment) to show that the human genome encodes a family of high-affinity TAP ligands. These TAP-binding elements (TEE) are 15-bp minisatellite repeats that are homologous to the core TAP-binding sites in CTE, The repeats are positioned similarly in the RNA secondary structures of CTE and TEE. Like CTE, TEE is an active nuclear export signal. CTE elements of different species share sequence similarities to TEE in the regions that are neutral for CTE function. This conservation points to a possible common ancestry of the two elements, and in fact, TEE has properties expected from a primordial CTE, Additionally, a molecular fossil of a TEE-like minisatellite is found in the genome of a modern retroelement, These findings constitute direct evidence of an evolutionary link between TEE-related minisatellites and CTE. C1 NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Human Retrovirus Pathogenesis Sect,Ctr Canc Res, Frederick, MD 21702 USA. RP Felber, BK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Human Retrovirus Pathogenesis Sect,Ctr Canc Res, Bldg 535,Rm 110, Frederick, MD 21702 USA. NR 46 TC 18 Z9 20 U1 0 U2 1 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 JUN PY 2001 VL 75 IS 12 BP 5567 EP 5575 DI 10.1128/JVI.75.12.5567-5575.2001 PG 9 WC Virology SC Virology GA 435JF UT WOS:000168877800015 PM 11356964 ER PT J AU Roth, SM Martel, GF Ivey, FM Lemmer, JT Tracy, BL Metter, EJ Hurley, BF Rogers, MA AF Roth, SM Martel, GF Ivey, FM Lemmer, JT Tracy, BL Metter, EJ Hurley, BF Rogers, MA TI Skeletal muscle satellite cell characteristics in young and older men and women after heavy resistance strength training SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID RAT SOLEUS MUSCLE; SLOW-TONIC MUSCLE; TRAPEZIUS MUSCLE; HIGH-VOLUME; ADULT-RATS; HYPERTROPHY; ACTIVATION; FIBERS; DAMAGE; AGE AB Skeletal muscle satellite cell proportions and morphology were assessed in healthy, sedentary young and older men and women in response to heavy resistance strength training (HRST). Fourteen young (20-30 years) men (n = 7) and women (n = 7) and 15 older (65-75 years) men (n = 8) and women (n = 7) completed 9 weeks of unilateral knee extension exercise training 3 days per week. Muscle biopsies were obtained from each vastus lateralis before and after training, with the nondominant leg serving as an untrained control. All four groups demonstrated a significant increase in satellite cell proportion in response to HRST (2.3 +/- 0.4% vs 3.1 +/- 0.4% for ail subjects combined, before and after training, respectively; p < .05), with older women demonstrating the greatest increase (p < .05). Morphology data indicated a significant increase in the proportion of active satellite cells in after-training muscle samples compared with before-training samples and with control leg samples (31% vs 6% and 7%, respectively; p < .05). The present results indicate that the proportion of satellite cells is increased after HRST in young and older men and women, with an exaggerated response in older women. Furthermore, the proportion of satellite cells that appear morphologically active is increased as a result of HRST. C1 Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. Univ Maryland Eastern Shore, Dept Phys Therapy, Princess Anne, MD USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Roth, SM (reprint author), Univ Pittsburgh, Dept Human Genet, A300 Crabtree Hall, Pittsburgh, PA 15261 USA. FU NIA NIH HHS [AG-42148, AG-05893, AG-00268] NR 43 TC 54 Z9 54 U1 0 U2 7 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2001 VL 56 IS 6 BP B240 EP B247 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 439NV UT WOS:000169124200004 PM 11382785 ER PT J AU Bruggeman, LA Adler, SH Klotman, PE AF Bruggeman, LA Adler, SH Klotman, PE TI Nuclear factor-kappa B binding to the HIV-1 LTR in kidney: Implications for HIV-associated nephropathy SO KIDNEY INTERNATIONAL LA English DT Article DE viral gene expression; chronic renal disease; LTR; end-stage renal disease; epithelial cells; 5 ' long terminal repeat ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; TRANSGENIC MICE; EPITHELIAL-CELLS; FUNCTIONAL INTERACTIONS; RENAL EPITHELIUM; GENE-EXPRESSION; INFECTION; PROMOTER; ACTIVATION AB Background We have recently shown that renal epithelium is infected by HIV-1 and supports HIV-1 transcription in seropositive patients with renal disease. To investigate the regulation of HIV-1 gene expression in kidney, an HIV-1 transgenic mouse model was used to analyze the host transcriptional proteins that bind the 5' long-terminal repeat (LTR). Methods. Viral gene expression was assessed in transgenic mouse tissue using Northern blotting and mRNA in situ hybridization. The transcription factors involved in LTR binding were determined using electrophoretic mobility shift assays. Cytoplasmic and nuclear extracts were prepared from tissues with varied levels of transgene expression. The binding of transcription factors to specific LTR fragments was determined using DNA competition experiments and supershifts with transcription factor-specific antibodies. Results. Tissue-specific expression of the transgene was variable, with viral gene expression in the kidney at an intermediate level as compared with other tissues. Overall, the level of transgene expression directly correlated with abundance of nuclear factor-kappaB (NF-kappaB) in the nuclear extracts. High expressing tissue, however, had a constitutively active form of NF-kappaB. In contrast, the kidney contained an inducible NF-kappaB, which bound the LTR in combination with Spl, suggesting a requirement for an activating event in renal HIV-1 expression of the LTR. Conclusions. These studies indicate that the regulation of the HIV-1 LTR in the kidney is similar to lymphoid tissues, and may explain, in part, why the HIV-1 life cycle is supported in kidney. C1 Mt Sinai Sch Med, Div Nephrol, New York, NY 10029 USA. Natl Inst Hlth Res Scholars Program, Howard Hughes Med Inst, NIH, Bethesda, MD USA. RP Bruggeman, LA (reprint author), Mt Sinai Sch Med, Div Nephrol, Box 1243,1 Gustave L Levy Pl, New York, NY 10029 USA. NR 41 TC 19 Z9 19 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2001 VL 59 IS 6 BP 2174 EP 2181 DI 10.1046/j.1523-1755.2001.0590062174.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 431ER UT WOS:000168619300017 PM 11380819 ER PT J AU Lewis, W Copeland, WC Day, BJ AF Lewis, W Copeland, WC Day, BJ TI Mitochondrial DNA depletion, oxidative stress, and mutation: Mechanisms of dysfunction from nucleoside reverse transcriptase inhibitors SO LABORATORY INVESTIGATION LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; PHASE-I TRIAL; HUMAN MUSCLE-CELLS; POLYMERASE-GAMMA; PERIPHERAL NEUROPATHY; ZIDOVUDINE THERAPY; ULTRASTRUCTURAL-CHANGES; DEGENERATIVE DISEASES; ACCESSORY SUBUNIT C1 Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Natl Jewish Med Res Ctr, Dept Med, Denver, CO USA. RP Lewis, W (reprint author), Emory Univ, Dept Pathol, 1639 Pierce Dr,Room 7117, Atlanta, GA 30322 USA. FU NHLBI NIH HHS [R01 HL59798, HL65167, R01 HL59602] NR 164 TC 103 Z9 105 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUN PY 2001 VL 81 IS 6 BP 777 EP 790 PG 14 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 443JM UT WOS:000169338100001 PM 11406640 ER PT J AU Blagosklonny, MV AF Blagosklonny, MV TI Unwinding the loop of Bcl-2 phosphorylation SO LEUKEMIA LA English DT Review DE Bcl-2; mitosis; apoptosis; paclitaxel; microtubule-active drugs ID ACTIVATED PROTEIN-KINASE; TAXOL-INDUCED APOPTOSIS; PACLITAXEL-INDUCED APOPTOSIS; SIGNAL-REGULATED KINASE; CELL-CYCLE PROGRESSION; LEUKEMIA-CELLS; RAF-1/BCL-2 PHOSPHORYLATION; MITOCHONDRIAL DYSFUNCTION; MICROTUBULE DYNAMICS; CYTOKINE DEPENDENCY AB Recent evidence indicates that anti-apoptotic functions of Bcl-2 can be regulated by its phosphorylation. According to the 'mitotic arrest-induced' model, multi-site phosphorylation of the Bcl-2 loop domain is followed by cell death. In contrast, in cytokine-dependent cell lines, cytokines mediate phosphorylation of Bcl-2 on S70, preventing apoptosis. As discussed in this review, these models are not mutually exclusive but reflect different cellular contexts. During mitotic arrest, signal transduction is unique and is fundamentally different from classical mitogenic signaling, since the nucleus membrane is dissolved, gene expression is reduced, and numerous kinases and regulatory proteins are hyperphosphorylated. Hyperphosphorylation of Bcl-2 mediated by paclitaxel and other microtubule-active drugs is strictly dependent on targeting microtubules that in turn cause mitotic arrest. In addition to serine-70 (S70), microtubule-active agents promote phosphorylation of S87 and threonine-69 (T69), inactivating Bcl-2. A major obstacle for identification of the mitotic Bcl-2 kinase(s) is that inhibition of putative kinase(s) by any means (dominant-negative mutants, antisense oligonucleotides, pharmacological agents) may arrest cycle, preventing mitosis and Bcl-2 phosphorylation. The role of Bcl-2 phosphorylation in cell death is discussed. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Blagosklonny, MV (reprint author), NCI, Med Branch, NIH, Bldg 10,R 12N226, Bethesda, MD 20892 USA. NR 87 TC 108 Z9 113 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 2001 VL 15 IS 6 BP 869 EP 874 DI 10.1038/sj.leu.2402134 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 441DA UT WOS:000169214700001 PM 11417471 ER PT J AU Blagosklonny, MV AF Blagosklonny, MV TI Treatment with inhibitors of caspases, that are substrates of drug transporters, selectively permits chemotherapy-induced apoptosis in multidrug-resistant cells but protects normal cells SO LEUKEMIA LA English DT Article DE leukemia; cancer; resistance; caspases; flavopiridol ID DEPENDENT KINASE INHIBITOR; P-GLYCOPROTEIN; EFFLUX PUMP; FLAVOPIRIDOL; CANCER; LEUKEMIA; PACLITAXEL; INDUCTION; THERAPY; DEATH AB Many chemotherapeutic agents induce apoptosis in tumor cells, but killing of normal cells remains a major obstacle. Development of multidrug resistance further limits chemotherapy in cancer. Here, I show that multidrug resistance can be exploited for selective killing of multidrug-resistant cells by a combination of an apoptosis-inducing agent that is not a substrate of either Pgp or MRP (eg flavopiridol) with a caspase inhibitor that is a substrate (eg Z-DEVD-fmk). In normal cells, treatment with caspase inhibitors prevented PARP cleavage, nuclear fragmentation, and cell death caused by flavopiridol or epothilone B. In contrast, Pgp- and MRP-expressing cells were not rescued by caspase inhibitors. Furthermore, reversal of drug resistance renders Pgp cells sensitive to caspase inhibitors abolishing therapeutic advantage. Thus, caspase inhibitors, that are inactive in multidrug-resistant cells, protect normal but not multidrug-resistant cells against chemotherapy, permitting selective eradication of multidrug-resistant cells. Clinical application of this approach may diminish the toxic side-effects of chemotherapy in patients with multidrug-resistant tumors. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Blagosklonny, MV (reprint author), NCI, Med Branch, NIH, Bldg 10,R 12N226, Bethesda, MD 20892 USA. NR 37 TC 63 Z9 63 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 2001 VL 15 IS 6 BP 936 EP 941 DI 10.1038/sj.leu.2402127 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 441DA UT WOS:000169214700010 PM 11417480 ER PT J AU Ishibe, N Sgambati, MT Fontaine, L Goldin, LR Jain, N Weissman, N Marti, GE Caporso, NE AF Ishibe, N Sgambati, MT Fontaine, L Goldin, LR Jain, N Weissman, N Marti, GE Caporso, NE TI Clinical characteristics of familial B-CLL in the National Cancer Institute Familial Registry SO LEUKEMIA & LYMPHOMA LA English DT Article DE pedigrees; familial; B-CLL; sporadic; descriptive; clinical ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMAS; ANIMAL BREEDING WORKERS; POPULATION CASE-CONTROL; HISTOLOGICAL TYPE; ANTICIPATION; MALIGNANCIES; REMISSION; EXPOSURE AB In an ongoing study, families with two or more living cases of B-CLL in first-degree relatives have been recruited through physician and self-referral. Since 1967, 28 kindreds with 73 cases of B-CLL have been enrolled within the National Cancer Institute (NCI) Familial B-CLL Registry. Medical, clinical, and demographic information have been obtained from private physicians, patient interview, hospital records, and death certificates. We used SEER Registry data to compare characteristics of sporadic B-CLL to familial B-CLL. The mean age at diagnosis was approximately 10 years younger among familial cases (57.9 +/- 12.1) than that observed in sporadic cases (70.1 +/- 11.9). A higher percentage of second primary rumors among familial CLL cases compared to reports in sporadic was also observed (16% vs. 8.8%). However, the transformation rate to non-Hodgkin's lymphoma does not appear to be different from that reported for sporadic cases. In conclusion, we observed some differences between familial and sporadic cases; whether any of these characteristics affect survival time or severity of disease is unknown. The study of families with multiple B-CLL cases will aid in delineating the genes and environmental factors that may play a role in the development of both forms of B-CLL. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. RP Ishibe, N (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC 7236, Rockville, MD 20852 USA. NR 34 TC 49 Z9 50 U1 1 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUN PY 2001 VL 42 IS 1-2 BP 99 EP 108 DI 10.3109/10428190109097681 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 458HD UT WOS:000170188200012 PM 11699227 ER PT J AU Dyer, KD Rosenberg, HF AF Dyer, KD Rosenberg, HF TI Transcriptional regulation of galectin-10 (eosinophil Charcot-Leyden crystal protein) - A GC box (-44 to -50) controls butyric acid induction of gene expression SO LIFE SCIENCES LA English DT Article DE eosinophils; clone-15; promoter; transcription; Charcot-Leyden crystal protein ID MURINE MYELOPEROXIDASE; EMBRYONAL CARCINOMA; BINDING PROTEINS; CELL-ADHESION; C/EBP-ALPHA; MAST-CELLS; PROMOTER; LYSOPHOSPHOLIPASE; HEMATOPOIESIS; LEUKEMIA AB Galectin-10 (gal-10, also known as Charcot-Leetden crystal protein) is a member of the galectin family of beta -galactoside binding proteins that is expressed uniquely in eosinophilic and basophilic leukocytes. To gain a better understanding of galectin gene expression, we present an analysis of the transcriptional regulation of the gene encoding gal-10. Analysis of the minimal promoter revealed nine consensus-binding sites for transcription factors, including several that are also found in the minimal promoters of galectins -1, -2, and -3. The decrease in gal-10 promoter activity after disruption of either the GC box (-44 to -50) or the Oct site (-255 to -261) suggests that these sites, along with the previously characterized GATA and EoTF sites, are necessary for full promoter activity. By supershift analysis, we demonstrate binding of the transcription factors Sp1 and Oct1 to the consensus GC box and the Oct site, respectively. Similar to gal-1,gal-10 expression is induced by butyric acid, an effect that is lost upon ablation of the GC box. Additionally, we demonstrate AML3 binding to the consensus AML site and YY1 binding to the Inr sequence, both elements functioning as silencers in the gal-10 promoter. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Physiol & Biophys, Washington, DC 20052 USA. RP Rosenberg, HF (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N104,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 44 TC 15 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUN 1 PY 2001 VL 69 IS 2 BP 201 EP 212 DI 10.1016/S0024-3205(01)01104-3 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 441CR UT WOS:000169213900009 PM 11441910 ER PT J AU Geissler, E Hecht, AM Horkay, F AF Geissler, E Hecht, AM Horkay, F TI Structure of polymer solutions and gels containing fillers SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 15th Polymer-Networks-Group Meeting Polymer Network 2000 Formation Structure Properties CY JUL 17-21, 2000 CL CRACKOW, POLAND ID SCATTERING; DYNAMICS AB Small angle neutron scattering (SANS) gives information on the structure of binary systems such as polymer solutions or swollen networks. By using mixtures of protonated and deuterated solvent the neutron scattering contrast can be varied, thus allowing ternary systems to be investigated. Here we describe SANS measurements in poly(dimethyl siloxane) (PDMS) solutions and gels containing fumed silica fillers with different surface treatments. Three different partial structure factors of the filled polymer samples can be distinguished, S-pp(q), S-pf(q) and S-ff(q), where the subscripts p and f refer to polymer and filler. The structure factor of the polymer S-pp(q) resembles that of star polymers. The distribution of the polymer in the network depends on the surface treatment. C1 Univ Grenoble 1, CNRS UMR5588, Spectrometrie Phys Lab, F-38402 St Martin Dheres, France. NIH, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Univ Grenoble 1, CNRS UMR5588, Spectrometrie Phys Lab, BP87, F-38402 St Martin Dheres, France. NR 14 TC 0 Z9 0 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1022-1360 EI 1521-3900 J9 MACROMOL SYMP JI Macromol. Symp. PD JUN PY 2001 VL 171 BP 171 EP 180 DI 10.1002/1521-3900(200106)171:1<171::AID-MASY171>3.0.CO;2-1 PG 10 WC Polymer Science SC Polymer Science GA 460FM UT WOS:000170297600021 ER PT J AU Horkay, F Basser, PJ Hecht, AM Geissler, E AF Horkay, F Basser, PJ Hecht, AM Geissler, E TI Ion-exchange induced change in the structure and osmotic properties of sodium polyacrylate hydrogels SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 15th Polymer-Networks-Group Meeting Polymer Network 2000 Formation Structure Properties CY JUL 17-21, 2000 CL CRACKOW, POLAND ID GELS AB The swelling and volume transition of fully neutralized sodium polyacrylate gels were investigated in salt solutions using osmotic and small angle neutron scattering measurements. The volume transition was induced by monovalent/divalent cation exchange. The overall salt concentration and the ratio of monovalent to divalent cations were varied in the biologically significant range. The neutron scattering response of fully neutralized polyacrylate gels in the presence of excess salt is described by the sum of a dynamic and a static component. The thermal correlation length determined from the intensity of the dynamic component displays a maximum at the transition. C1 Nichhd, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Univ Grenoble 1, Spectrometrie Phys Lab, F-38402 St Martin Dheres, France. RP Horkay, F (reprint author), Nichhd, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, 13 South Dr, Bethesda, MD 20892 USA. RI Basser, Peter/H-5477-2011 NR 18 TC 0 Z9 0 U1 1 U2 4 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD JUN PY 2001 VL 171 BP 201 EP 207 DI 10.1002/1521-3900(200106)171:1<201::AID-MASY201>3.0.CO;2-P PG 7 WC Polymer Science SC Polymer Science GA 460FM UT WOS:000170297600024 ER PT J AU Brooks, RA Moiny, F Gillis, P AF Brooks, RA Moiny, F Gillis, P TI On T-2-shortening by weakly magnetized particles: The chemical exchange model SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE chemical exchange; susceptibility; T-2-shortening; gradients ID TRANSVERSE RELAXATION; WATER PROTONS; SUSCEPTIBILITY; BLOOD; NMR; DIFFUSION; CONTRAST; TISSUES; FIELDS; ENHANCEMENT AB Chemical exchange (CE) theory is compared with two theories of T-2-shortening caused by microscopic magnetic centers: inner- and outer-sphere relaxation theory (long-echo limit) and mean gradient diffusion theory (short-echo limit). The CE equation is shown to be identical to these theories in the respective limits and appropriate parameter relationships are derived for spherical particles. The theories are then compared with computer simulations of spherical particles and with a recent general theory, with good agreement in the asymptotic regions. The CE model also reproduces the essential relaxation characteristics in the intermediate range. Finally good agreement of a CE model with simulations for magnetized cylinders is also demonstrated. the discussion is limited to weakly magnetized particles such that the maximum phase shift during an echo interval is less than one radian, permitting the use of the Luz-Meiboom CE equation, published 2001 Wiley-Liss, Inc.(dagger). C1 NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. Univ Mons, Biol Phys Dept, B-7000 Mons, Belgium. RP Brooks, RA (reprint author), 15501 Sweetbirch Court, Rockville, MD 20853 USA. EM RodneyABrooks@cs.com NR 24 TC 128 Z9 129 U1 2 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUN PY 2001 VL 45 IS 6 BP 1014 EP 1020 DI 10.1002/mrm.1135 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 435JT UT WOS:000168878900011 PM 11378879 ER PT J AU Barbier, EL Silva, AC Kim, SG Koretsky, AP AF Barbier, EL Silva, AC Kim, SG Koretsky, AP TI Perfusion imaging using dynamic arterial spin labeling (DASL) SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cerebral blood flow; cerebral blood volume; MR; frequency filtering; transit time ID CEREBRAL BLOOD-FLOW; CONTROLLED CORTICAL IMPACT; MAGNETIZATION-TRANSFER; ISOFLURANE ANESTHESIA; RAT-BRAIN; WATER; TIME; VOLUME; HALOTHANE; INVERSION AB Recently, a technique based on arterial spin labeling, called dynamic arterial spin labeling (DASL (Magn Reson Med 1999;41:299-308)), has been introduced to measure simultaneously the transit time of the labeled blood from the labeling plane to the exchange site, the longitudinal relaxation time of the tissue, and the perfusion of the tissue. This technique relies on the measurement of the tissue magnetization response to a time varying labeling function. The analysis of the characteristics of the tissue magnetization response (transit time, filling time constant, and perfusion) allows for quantification of the tissue perfusion and for transit time map computations. In the present work, the DASL scheme is used in conjuction with echo planar imaging at 4.7 T to produce brain maps of perfusion and transit time in the anesthetized rat, under graded hypercapnia. The data obtained show the variation of perfusion and transit time as a function of arterial pCO(2), Based on the data, CO2 reactivity maps are computed. Published 2001 Wiley-Liss, Inc.(dagger). C1 NINDS, LFMI, NIH, Bethesda, MD 20892 USA. NINDS, MRI Res Facil, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Med, Dept Radiol, Ctr Magnet Resonance Res, Minneapolis, MN 55455 USA. RP Koretsky, AP (reprint author), NINDS, LFMI, NIH, Room 10-B1D118,MSC 1065, Bethesda, MD 20892 USA. RI Silva, Afonso/A-7129-2009; Barbier, Emmanuel/E-6302-2011; Koretsky, Alan/C-7940-2015; Kim, Seong-Gi/O-8480-2014 OI Barbier, Emmanuel/0000-0002-4952-1240; Koretsky, Alan/0000-0002-8085-4756; Kim, Seong-Gi/0000-0003-1960-4464 FU NCRR NIH HHS [RR03631, RR08079]; NINDS NIH HHS [NS38295] NR 37 TC 44 Z9 45 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JUN PY 2001 VL 45 IS 6 BP 1021 EP 1029 DI 10.1002/mrm.1136 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 435JT UT WOS:000168878900012 PM 11378880 ER PT J AU Sun, S Murphy, WJ Menotti-Raymond, M O'Brien, SJ AF Sun, S Murphy, WJ Menotti-Raymond, M O'Brien, SJ TI Integration of the feline radiation hybrid and linkage maps SO MAMMALIAN GENOME LA English DT Article ID COMPARATIVE GENOMICS; ZEBRAFISH GENOME; GENETIC-LINKAGE; MOUSE GENOME; CAT; CONSERVATION; ORGANIZATION; PANEL; RAT AB The recent development of genome mapping resources for the domestic cat provides a unique opportunity to study comparative medicine in this companion animal which can inform and benefit both veterinary and human biomedical concerns. We describe here the integration and order comparison of the feline radiation hybrid (RH) map with the feline interspecies backcross (ISB) genetic linkage map, constructed by a backcross of F-1 hybrids between domestic cat (Felis catus) and the Asian leopard cat (Prionailurus bengalensis). Of 253 microsatellite loci mapped in the ISB, 176 equivalently spaced markers were ordered among a framework of 424 Type I coding markers in the RH map. The integration of the RH and ISB maps resolves the orientation of multiple linkage groups and singleton loci from the ISB genetic map. This integrated map provides the foundation for gene mapping assessments in the domestic cat and in related species of the Felidae family. C1 NCI, Lab Genome Divers, Frederick, MD 21702 USA. George Mason Univ, Grad Program Biol, Fairfax, VA 22030 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genome Divers, Frederick, MD 21702 USA. NR 30 TC 19 Z9 19 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUN PY 2001 VL 12 IS 6 BP 436 EP 441 DI 10.1007/s003350010289 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 437JG UT WOS:000168988100005 PM 11353390 ER PT J AU Fronicke, L Wienberg, J AF Fronicke, L Wienberg, J TI Comparative chromosome painting defines the high rate of karyotype changes between pigs and bovids SO MAMMALIAN GENOME LA English DT Article ID GENETIC-LINKAGE MAP; SHEEP OVIS-ARIES; ZOO-FISH; GENOME ORGANIZATION; SEGMENTS; CATTLE; CONSERVATION; REVEALS; SYNTENY; PORCINE AB Human and sheep chromosome-specific probes were used to construct comparative painting maps between the pig (Suiformes), cattle and sheep (Bovidae), and humans. Various yet unknown translocations were observed that would assist in a more complete reconstruction of homology maps of these species. The number of homologous segments that can be identified with sheep probes in the pig karyotype exceeds that described previously by chromosome painting between two non-primate mammals belonging to the same order. Sheep probes painted 62 segments on pig autosomes and delineated not only translocations, but also 9 inversions. AII inversions were paracentric and indicate that these rearrangements may be characteristic for chromosomal changes in suiforms. Hybridizations of all sheep painting probes to cattle chromosomes confirmed the chromosome conservation in bovids. In addition, we observed a small translocation that was previously postulated from linkage mapping data, but was not yet described by physical mapping. The chromosome painting data are complemented with a map of available comparative gene mapping data between pig and sheep genomes. A detailed table listing the comparative gene mapping data between pig and cattle genomes is provided. The reanalysis of the pig karyotype with a new generation of human paint probes provides an update of the human/pig comparative genome map and demonstrates two new chromosome homologies. Seven conserved segments not yet identified by chromosome painting are also reported. C1 NCI, Basic Res Lab, Frederick, MD 21702 USA. Univ Munich, Inst Anthropol & Human Genet, D-8000 Munich, Germany. RP Wienberg, J (reprint author), NCI, Basic Res Lab, Bldg 560,Room 11-75, Frederick, MD 21702 USA. NR 30 TC 26 Z9 29 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUN PY 2001 VL 12 IS 6 BP 442 EP 449 DI 10.1007/s003350010288 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 437JG UT WOS:000168988100006 PM 11353391 ER PT J AU Ruangpanit, N Chan, D Holmbeck, K Birkedal-Hansen, H Polarek, J Yang, CL Bateman, JF Thompson, EW AF Ruangpanit, N Chan, D Holmbeck, K Birkedal-Hansen, H Polarek, J Yang, CL Bateman, JF Thompson, EW TI Gelatinase A (MMP-2) activation by skin fibroblasts: dependence on MT1-MMP expression and fibrillar collagen form SO MATRIX BIOLOGY LA English DT Article DE collagen; fibril; MMP-2 activation; MT1-MMP ID MATRIX METALLOPROTEINASE-2 ACTIVATION; HUMAN BREAST-CARCINOMA; CANCER CELL-LINES; I COLLAGEN; METASTATIC PROGRESSION; OVARIAN-CARCINOMA; PLATELET-ADHESION; TUMOR-CELLS; INTEGRIN; MATRIX-METALLOPROTEINASE-2 AB The respective requirements of collagen and MT1-MMP in the activation of MMP-2 by primary fibroblast cultures were explored further. Three-dimensional gels enriched in human collagen types I and III or composed of recombinant human type II or III collagen, caused increased MT1-MMP production (mRNA and protein) and induced MMP-2 activation, Only marginal induction was seen with dried monomeric collagen confirming the need for collagen fibrillar organisation for activation. To our surprise, relatively low amounts (as low as 25 mug/ml) of acid soluble type I collagen added to fibroblast cultures also induced potent MMP-2 activation. However, the requirement for collagen fibril formation by the added collagen was indicated by the inhibition seen when the collagen was pre-incubated with a fibril-blocking peptide, and the reduced activation seen with alkali-treated collagen preparations known to have impaired fibrilisation, Pre-treatment of the collagen with sodium periodate also abrogated MMP-2 activation induction. Further evidence of the requirement for collagen fibril formation was provided by the lack of activation when type IV collagen, which does not form collagen fibrils, was added in the cultures. Fibroblasts derived from MT1-MMP-deficient mice were unable to activate MMP-2 in response to either three-dimensional collagen gel or added collagen solutions, compared to their littermate controls. Collectively, these data indicate that the fibrillar structure of collagen and MT1-MMP are essential for the MMP-2 activational response in fibroblasts. (C) 2001 Elsevier Science B.V./International Society of Matrix Biology. All rights reserved. C1 St Vincents Inst Med Res, VNCRC Breast Canc Invas & Metastasis Unit, Fitzroy, Vic 3065, Australia. Univ Melbourne, Dept Pediat, Melbourne, Vic, Australia. Natl Inst Dent & Craniofacial Res, MMP Unit, NIH, Bethesda, MD USA. FibroGen Inc, San Francisco, CA USA. Univ Melbourne, Dept Surg, Melbourne, Vic, Australia. Chulalongkorn Univ, Fac Dent, Dept Anat, Bangkok, Thailand. RP Thompson, EW (reprint author), St Vincents Inst Med Res, VNCRC Breast Canc Invas & Metastasis Unit, 9 Princes St, Fitzroy, Vic 3065, Australia. RI Chan, Danny/C-4203-2009; Thompson, Erik/A-1425-2009; OI Thompson, Erik/0000-0002-9723-4924; Bateman, John/0000-0001-8542-0730 FU NIAMS NIH HHS [R01 AR45879] NR 51 TC 46 Z9 47 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD JUN PY 2001 VL 20 IS 3 BP 193 EP 203 DI 10.1016/S0945-053X(01)00135-4 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 451CB UT WOS:000169782600004 PM 11420151 ER PT J AU Pillemer, SR Matteson, EL Jacobsson, LTH Martens, PB Melton, LJ O'Fallon, WM Fox, PC AF Pillemer, SR Matteson, EL Jacobsson, LTH Martens, PB Melton, LJ O'Fallon, WM Fox, PC TI Incidence of physician-diagnosed primary Sjogren syndrome in residents of Olmsted County, Minnesota SO MAYO CLINIC PROCEEDINGS LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ELDERLY POPULATION; ADULT-POPULATION; DRY MOUTH; PREVALENCE; CRITERIA; CLASSIFICATION; EPIDEMIOLOGY; COMMUNITY; ROCHESTER AB Objectives: To estimate the incidence of physician-diagnosed primary Sjogren syndrome (SS) among residents of Olmsted County, Minnesota, in the setting of usual medical care and to determine how often objective criteria are available in the medical records of such patients. Patients and Methods: We reviewed all medical records of residents in Olmsted County with physician-diagnosed SS from 1976 to 1992 to determine whether they had undergone objective tests for keratoconjunctivitis sicca, salivary dysfunction, or serologic abnormality. Confounding illnesses were excluded. To identify misclassified eases, all records from patients with xerostomia or keratoconjunctivitis sicca were also reviewed. The average annual SS incidence rates were calculated by considering the entire population to be at risk. Results: Of 75 patients with onset of SS during the study period, 53 had primary SS, All patients were white, 51 (96.2%) were women, and the mean +/- SD age was 59 +/- 15.8 years. The age- and sex-adjusted annual incidence was 3.9 per 100,000 population (95% confidence interval, 2.8-4.9) for patients with primary SS, Eleven patients (20.8%) with physician-diagnosed SS had no documentation of objective eye, mouth, or laboratory abnormalities. Objective evaluations performed most frequently were laboratory and ocular tests and least often were investigations of xerostomia, Conclusions: The average annual incidence rate for physician-diagnosed primary SS in Olmsted County is about 4 cases per 100,000 population, These data probably underestimate the true incidence because they are based on usual medical care of patients with SS in a community setting, rather than on a case-detection survey, In the future, a true incidence may be possible with a higher index of suspicion, greater attention to objective tests, and increased awareness of new classification criteria for SS, For epidemiological studies based on existing data, application of current criteria may not be feasible, and consensus on criteria for such studies would be useful. C1 NIDCR, NIH, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. Mayo Clin, Div Rheumatol & Internal Med, Rochester, MN USA. Mayo Clin, Clin Epidemiol Sect, Rochester, MN USA. Mayo Clin, Biostat Sect, Rochester, MN USA. Univ Lund, Malmo, Sweden. RP Pillemer, SR (reprint author), NIDCR, NIH, Gene Therapy & Therapeut Branch, Bldg 10,Room 1N113,10 Ctr Dr,MSC 1190, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR30582] NR 43 TC 98 Z9 103 U1 1 U2 3 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUN PY 2001 VL 76 IS 6 BP 593 EP 599 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 437QG UT WOS:000169004600006 PM 11393497 ER PT J AU Andreazzoli, M Broccoli, V Dawid, IB AF Andreazzoli, M Broccoli, V Dawid, IB TI Cloning and expression of noz1, a zebrafish zinc finger gene related to Drosophila nocA SO MECHANISMS OF DEVELOPMENT LA English DT Article DE noz1; nocA; zinc finger; zebrafish; hindbrain patterning; rhombomeres; retinoic acid; Hox genes ID FATE AB We report the isolation of noz1, a novel zebrafish zinc finger gene which displays sequence similarity to Drosophila nocA. noz1 transcripts are detected at the shield stage within the germ ring and excluded from the most dorsal region. By the end of gastrulation, noz1 is expressed in the presumptive hindbrain and spinal cord as well as in the forming tailbud. During somitogenesis noz1 shows a dynamic expression in the midbrain-hindbrain boundary, hindbrain and spinal cord. This results, at 23 hpf, in a graded expression with the highest level in rhombomeres 2 and 3, and the lowest in the spinal cord. Expression analysis in swirl and chordino mutants as well as in retinoic acid treated embryos indicate that noz1 is activated by BMP antagonists and neural posteriorizing signals. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Pisa, Lab Biol Cellulare & Sviluppo, I-56010 Pisa, Italy. Hosp San Raffaele, DIBIT, SCRI Stem Cell Res Inst, I-20132 Milan, Italy. NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Andreazzoli, M (reprint author), Univ Pisa, Lab Biol Cellulare & Sviluppo, Via Carducci 13, I-56010 Pisa, Italy. OI Andreazzoli, Massimiliano/0000-0001-9633-204X NR 8 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JUN PY 2001 VL 104 IS 1-2 BP 117 EP 120 DI 10.1016/S0925-4773(01)00359-8 PG 4 WC Developmental Biology SC Developmental Biology GA 444YB UT WOS:000169426700012 PM 11404087 ER PT J AU Tchounwou, PB Ishaque, AB Schneider, J AF Tchounwou, PB Ishaque, AB Schneider, J TI Cytotoxicity and transcriptional activation of stress genes in human liver carcinoma cells (HepG(2)) exposed to cadmium chloride SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Molecular Mechanisms of Metal Toxicity and Carcinogenesis CY SEP 10-12, 2000 CL MORGANTOWN, VIRGINIA DE cadmium; cytotoxicity; stress genes; transcriptional activation; human liver carcinoma cells ID PROTEIN-KINASE-C; ESTROGEN-RECEPTOR; AH-RECEPTOR; INDUCED HEPATOTOXICITY; OCCUPATIONAL STANDARD; SIGNALING PATHWAYS; BINDING ACTIVITY; METALLOTHIONEIN; TOXICITY; TOXICOLOGY AB Epidemiological studies have shown that there exists some correlation between cadmium exposure and human cancers. The evidence that cadmium and cadmium compounds are probable human carcinogens is also supported by experimental studies reporting induction of malignant tumors formation in multiple species of laboratory animals exposed to these compounds. In vitro studies with mammalian cells have also shown that cadmium is clastogenic, but its mutagenic potential is rather weak. In this research, we performed the MTT assay for cell viability to assess the cytotoxicity of cadmium chloride (CdCl2), and the CAT-Tox (L) assay to measure the induction of stress genes in thirteen different recombinant cell lines generated from human liver carcinoma cells (HepG(2)), by creating stable transfectants of different mammalian promoter - chloramphenicol acetyltransferase (CAT) gene fusions. Cytotoxicity experiments with the parental cell line yielded a LC50 of 6.1 +/- 0.8 mug/mL, upon 48 h of exposure. Four (metallothionein - HMTIIA, 70-kDa heat shock protein - HSP70, xenobitic response element - XRE, and cyclic adenosine monophosphate response element - CRE) out of the 13 constructs evaluated showed statistically significant inductions (p < 0.05). The induction of these genes was concentration-dependent. Marginal inductions were also recorded for the c-fos, and 153-kDa growth arrest DNA damage (GADD153) promoters, indicating a potential for CdC1(2) to damage DNA. However, no significant inductions (p > 0.05) of gene expression were recorded for cytochrome P450 1A1 - CYP1A1, glutathion-S-transferase Ya subunit - GST Ya, nuclear factor kappa (B site) response element - NFkBRE, tumor suppressor protein response element - p53RE, 45-kDa growth arrest DNA damage - GADD45, 78-kDa glucose regulated protein - GRP78, and retinoic acid response element - RARE. As expected, these results indicate that metallothioneins and heat shock proteins appear to be excellent candidates for biomarkers for detecting cadmium-induced proteotoxic effects at the molecular and cellular levels. Induction of XRE indicates the potential involvement of CdC1(2) in the biotransformation process in the liver, while activation of CRE indicates stimulation of cellular signaling through the protein kinases pathway. C1 Jackson State Univ, Sch Sci & Technol, NIH, Ctr Environm Hlth,Mol Toxicol Res Lab, Jackson, MS 39217 USA. Xenometrix Inc, Client Res Lab, Boulder, CO USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Sch Sci & Technol, NIH, Ctr Environm Hlth,Mol Toxicol Res Lab, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. NR 65 TC 31 Z9 31 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JUN PY 2001 VL 222 IS 1-2 BP 21 EP 28 DI 10.1023/A:1017922114201 PG 8 WC Cell Biology SC Cell Biology GA 471UR UT WOS:000170947500004 PM 11678604 ER PT J AU Tchounwou, PB Wilson, BA Ishaque, AB Schneider, J AF Tchounwou, PB Wilson, BA Ishaque, AB Schneider, J TI Atrazine potentiation of arsenic trioxide-induced cytotoxicity and gene expression in human liver carcinoma cells (HepG(2)) SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Molecular Mechanisms of Metal Toxicity and Carcinogenesis CY SEP 10-12, 2000 CL MORGANTOWN, VIRGINIA DE atrazine; potentiation; arsenic; cytotoxicity; gene expression; HepG(2) cells ID NF-KAPPA-B; INDUCIBLE TRANSCRIPTION; SPONTANEOUS-ABORTION; ENVIRONMENTAL RISKS; NORTHERN SWEDEN; DRINKING-WATER; SURFACE WATERS; DNA DAMAGE; PROTEIN; PROMOTER AB Recent studies in our laboratory indicated that arsenic trioxide has the ability to cause significant cytotoxicity, and induction of a significant number of stress genes in human liver carcinoma cells, HepG2 [1]. However, similar investigations with atrazine did not show any significant effects of this chemical on HepG2 cells, even at its maximum solubility of 100 mug/mL in 1% dimethyl sulfoxide (DMSO). Further cytogenetic studies were therefore carried out to investigate the combined effects of arsenic trioxide and atrazine on cell viability and gene expression in immortalized human hepatocytes. Cytotoxicity was evaluated using the MTT-assay for cell viability, while the CAT-Tox (L) assay was performed to measure the induction of stress genes in thirteen different recombinant cell lines generated from human liver carcinoma cells (HepG(2)), by creating stable transfectants of different mammalian promoter - chloramphenicol acetyltransferase (CAT) gene fusions. Cytotoxicity experiments yielded LC50 values of 11.9 +/- 2.6 mug/mL for arsenic trioxide in de-ionized water, and 3.6 +/- 0.4 mug/mL for arsenic trioxide in 100 mug/mL atrazine; indicating a 3 fold increase in arsenic toxicity associated with the atrazine exposure. Co-exposure of HepG(2) cells to atrazine also resulted in a significant increase in the potency of arsenic trioxide to upregulate a number of stress genes including those of the glutathione-S-transferase Ya subunit-GST Ya, metallothionein(IIa)-HMTIIA, 70-kDa heat shock protein-HSP70, c-fos, 153-kDa growth arrest and DNA damage (GADD153), 45-kDa growth arrest and DNA damage (GADD45), and 78-kDa glucose regulated protein-GRP78 promoters, as well as the xenobiotic response element-XRE, tumor suppressor protein response element-p53RE, cyclic adenosine monophosphate response element-CRE, and retinoic acid response element-RARE. No significant changes were observed with respect to the influence of atrazine on the modulation of cytochrome P450 1A1-CYP 1A1, and nuclear factor kappa (B site) response element-NF kappa BRE by arsenic trioxide. These results indicate that co-exposure to atrazine strongly potentiates arsenic trioxide-induced cytotoxicity and transcriptional activation of stress genes in transformed human hepatocytes. C1 Jackson State Univ, Sch Sci & Technol, NIH, Ctr Environm Hlth,Mol Toxicol Res Lab, Jackson, MS 39217 USA. Xenometrix Inc, Client Res Lab, Boulder, CO USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Sch Sci & Technol, NIH, Ctr Environm Hlth,Mol Toxicol Res Lab, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. FU NCRR NIH HHS [1G12RR13459] NR 62 TC 37 Z9 47 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JUN PY 2001 VL 222 IS 1-2 BP 49 EP 59 DI 10.1023/A:1017903005541 PG 11 WC Cell Biology SC Cell Biology GA 471UR UT WOS:000170947500008 PM 11678611 ER PT J AU Bal, W Dyba, M Szewczuk, Z Jezowska-Bojczuk, M Lukszo, J Ramakrishna, G Kasprzak, KS AF Bal, W Dyba, M Szewczuk, Z Jezowska-Bojczuk, M Lukszo, J Ramakrishna, G Kasprzak, KS TI Differential zinc and DNA binding by partial peptides of human protamine HP2 SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Molecular Mechanisms of Metal Toxicity and Carcinogenesis CY SEP 10-12, 2000 CL MORGANTOWN, VIRGINIA DE protamine P2; protamine peptides; DNA; zinc; protamine-zinc binding ID N-TERMINAL SEQUENCE; HUMAN-SPERM PROTAMINES; SECONDARY STRUCTURE; METAL-BINDING; MAMMALIAN SPERM; P2 PROTAMINES; 2 FORMS; CHROMATIN; COMPLEXES; COORDINATION AB The Zn(II) binding by partial peptides of human protamine HP2: HP2(1-15); HP2(1-25), HP2(26-40), HP2(37-47), and HP2(43)-57 was studied by circular dichroism (CD). Precipitation of a 20-mer DNA by these partial peptides and the effects of Zn(II) thereon were investigated using polyacrylamide gel electrophoresis (GE). The results of this study suggest that reduced HP2 (thiol groups intact) can bind Zn(II) at various parts of the molecule. In the absence of DNA, the primary Zn(II) binding site in reduced HP2 is located in the 37-47 sequence (involving Cys-37, His-39, His-43, and Cys-47), while in the presence of DNA, the strongest Zn(II) binding is provided by sequences 12-22 (by His-12, Cys-13, His-19, and His-22) and 43-57 (His-43, Cys-47, Cys-53, and His-57). In its oxidized form, HP2 can bind zinc through His residues of the 7-22 sequence. Zn(II) markedly enhances DNA binding by all partial peptides. These findings suggest that Zn(II) ions may be a regulatory factor for sperm chromatin condensation processes. C1 Univ Wroclaw, Fac Chem, PL-50383 Wroclaw, Poland. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NIAID, Peptide Anal & Synth Unit, Res Technol Branch, Rockville, MD USA. RP Bal, W (reprint author), Univ Wroclaw, Fac Chem, F Joliot Curie 14, PL-50383 Wroclaw, Poland. OI Szewczuk, Zbigniew/0000-0001-5884-9363; Dyba, Marcin/0000-0001-6311-6877 NR 43 TC 9 Z9 9 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JUN PY 2001 VL 222 IS 1-2 BP 97 EP 106 DI 10.1023/A:1017971525105 PG 10 WC Cell Biology SC Cell Biology GA 471UR UT WOS:000170947500013 PM 11686187 ER PT J AU Smith, M Burke, Z Humphries, A Wells, T Klein, D Carter, D Baler, R AF Smith, M Burke, Z Humphries, A Wells, T Klein, D Carter, D Baler, R TI Tissue-specific transgenic knockdown of Fos-related antigen 2 (Fra-2) expression mediated by dominant negative Fra-2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; SEROTONIN N-ACETYLTRANSFERASE; TRANSCRIPTION FACTOR FRA-2; DNA-BINDING ACTIVITY; RAT PINEAL-GLAND; C-FOS; CIRCADIAN EXPRESSION; MOUSE DEVELOPMENT; JUN PROTEINS; FACTOR AP-1 AB Fos-related antigen 2 (Fra-2) is a member of the Fos family of immediate-early genes, most of which are rapidly induced by second messengers, All members of this family act by binding to AP-1 sites as heterodimeric complexes with other proteins. However, each appears to have a distinct role, The role and biology of Fra-2 are less well understood than those of its relatives c-Fos, Fra-1, and FosB; moreover, Fra-2 target genes remain largely unknown, as does the basis of its selective effects on transcriptional activity, To pursue these issues, we created a transgenic rat line (NATDNF2) in which a dominant negative fra-2 (DNF2) gene is strongly expressed in the pineal gland; tissue selectivity was achieved by putting the DNF2 gene under the control of the rat arylalkylamine N-acetyltransferase (AANAT) regulatory region, which targets gene expression to a very restricted set of tissues (pineal gland much greater than retina), Expression of AANAT is normally turned on after the onset of darkness in the rat; as a result, pineal DNF2 expression occurs only at night. This was associated with marked suppression of the nocturnal increase in fra-2 mRNA and protein Levels, indicating that DNF2 expression inhibits downstream effects of Fra-2, including the maintenance of high levels of fra-2 gene expression. Analysis of 1,190 genes in the NATDNF2 pineal gland, including the AANAT gene, identified two whose expression is strongly linked to fra-2 expression: the genes encoding type II iodothyronine deiodinase and nectadrin (CD24). C1 NICHHD, NIH, Sect Neuroendocrinol, Lab Dev Neurobiol, Bethesda, MD 20892 USA. Cardiff Univ, Sch Biosci, Cardiff, S Glam, Wales. NIMH, NIH, Unit Temporal Gene Express, Lab Cell & Mol Regulat, Bethesda, MD 20892 USA. RP Baler, R (reprint author), NICHHD, NIH, Sect Neuroendocrinol, Lab Dev Neurobiol, Bldg 36,Room 2A-09, Bethesda, MD 20892 USA. RI Wells, Timothy/A-6484-2010; Carter, David/A-4479-2010; OI Carter, David/0000-0002-8419-3975; Wells, Timothy/0000-0003-3618-0595 NR 50 TC 42 Z9 43 U1 0 U2 0 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 JUN PY 2001 VL 21 IS 11 BP 3704 EP 3713 DI 10.1128/MCB.21.11.3704-3713.2001 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 432QF UT WOS:000168706600010 PM 11340164 ER PT J AU Manetz, TS Gonzalez-Espinosa, C Arudchandran, R Xirasagar, S Tybulewicz, V Rivera, J AF Manetz, TS Gonzalez-Espinosa, C Arudchandran, R Xirasagar, S Tybulewicz, V Rivera, J TI Vav1 regulates phospholipase C gamma activation and calcium responses in mast cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AFFINITY IGE RECEPTOR; FC-EPSILON-RI; JUN NH2-TERMINAL KINASE; EXCHANGE FACTOR VAV; T-CELL; ANTIGEN RECEPTOR; PROTOONCOGENE PRODUCT; TYROSINE PHOSPHORYLATION; SIGNALING PATHWAY; B-CELL AB The hematopoietic cell-specific protein Vav1 is a substrate of tyrosine kinases activated following engagement of many receptors, including Fc epsilon RI. Vav1-deficient mice contain normal numbers of mast cells but respond more weakly than their normal counterparts to a passive systemic anaphylaxis challenge. Vav1-deficient bone marrow-derived mast cells also exhibited reduced degranulation and cytokine production, although tyrosine phosphorylation of FceRI, Syk, and LAT (linker for activation of T cells) was normal. In contrast, tyrosine phosphorylation of phospholipase C gamma1 (PLC gamma1) and PLC gamma2 and calcium mobilization were markedly inhibited. Reconstitution of deficient mast cells with Vav1 restored normal tyrosine phosphorylation of PLC gamma1 and PLC gamma2 and calcium responses, Thus, Vav1 is essential to Fc epsilon RI-mediated activation of PLC gamma and calcium mobilization in mast cells, In addition to its known role as an activator of Rac1 GTPases, these findings demonstrate a novel function for Vav1 as a regulator of PLC gamma -activated calcium signals. C1 NIAMSD, Sect Chem Immunol, NIH, Bethesda, MD 20892 USA. Natl Inst Med Res, London NW7 1AA, England. RP Rivera, J (reprint author), NIAMSD, Sect Chem Immunol, NIH, Bldg 10,Room 9N228,10 Ctr Dr,MSC 1820, Bethesda, MD 20892 USA. NR 66 TC 113 Z9 114 U1 0 U2 0 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 JUN PY 2001 VL 21 IS 11 BP 3763 EP 3774 DI 10.1128/MCB.21.11.3763-3774.2001 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 432QF UT WOS:000168706600015 PM 11340169 ER PT J AU Moustafa, ME Carlson, BA El-Saadani, MA Kryukov, GV Sun, QA Harney, JW Hill, KE Combs, GF Feigenbaum, L Mansur, DB Burk, RF Berry, MJ Diamond, AM Lee, BJ Gladyshev, VN Hatfield, DL AF Moustafa, ME Carlson, BA El-Saadani, MA Kryukov, GV Sun, QA Harney, JW Hill, KE Combs, GF Feigenbaum, L Mansur, DB Burk, RF Berry, MJ Diamond, AM Lee, BJ Gladyshev, VN Hatfield, DL TI Selective inhibition of selenocysteine tRNA maturation and selenoprotein synthesis in transgenic mice expressing isopentenyladenosine-deficient selenocysteine tRNA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSFER-RNA GENE; GLUTATHIONE-PEROXIDASE; RAT-LIVER; TRANSFER RNASEC; DIETARY SELENIUM; MAMMALIAN THIOREDOXIN; TRNA(SEC) GENE; MESSENGER-RNAS; CELLS; TRANSLATION AB Selenocysteine (Sec) tRNA (tRNA([Ser]Sec)) serves as both the site of Sec biosynthesis and the adapter molecule for donation of this amino acid to protein. The consequences on selenoprotein biosynthesis of overexpressing either the wild type or a mutant tRNA([Ser]Sec) lacking the modified base, isopentenyladenosine, in its anticodon loop were examined by introducing multiple copies of the corresponding tRNA([Ser]Sec) genes into the mouse genome. Overexpression of wild-type tRNA([Ser]Sec) did not affect selenoprotein synthesis. In contrast, the levels of numerous selenoproteins decreased in mice expressing isopentenyladenosine-deficient (i(6)A(-)) tRNA([Ser]Sec) in a protein- and tissue-specific manner. Cytosolic glutathione peroxidase and mitochondrial thioredoxin reductase 3 were the most and least affected selenoproteins, while selenoprotein expression was most and least affected in the liver and testes, respectively. The defect in selenoprotein expression occurred at translation, since selenoprotein mRNA levels were largely unaffected. Analysis of the tRNA([Ser]Sec) population showed that expression of i(6)A(-) tRNA([Ser]Sec) altered the distribution of the two major isoforms, whereby the maturation of tRNA([Ser]Sec) by methylation of the nucleoside in the wobble position was repressed. The data suggest that the levels of i(6)A(-) tRNA([Ser]Sec) and wild-type tRNA([Ser]Sec) are regulated independently and that the amount of wild-type tRNA([Ser]Sec) is determined, at least in part, by a feedback mechanism governed by the level of the tRNA([Ser]Sec) population. This study marks the first example of transgenic mice engineered to contain functional tRNA transgenes and suggests that i(6)A(-) tRNA([Ser]Sec) transgenic mice will be useful in assessing the biological roles of selenoproteins. C1 NCI, Sect MolBiol Selenium, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Univ Alexandria, Fac Sci, Dept Biochem, Alexandria, Egypt. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Thyroid, Boston, MA 02115 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. Cornell Univ, Div Nutr Sci, Dept Nutr, Ithaca, NY 14853 USA. Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. Washington Univ, Radiat Oncol Ctr, St Louis, MO 63110 USA. Univ Illinois, Dept Human Nutr, Chicago, IL 60612 USA. Seoul Natl Univ, Sch Biol Sci, Genet Mol Lab, Seoul 151742, South Korea. RP Hatfield, DL (reprint author), NCI, Sect MolBiol Selenium, Basic Res Lab, NIH, Bldg 37,Room 2D09, Bethesda, MD 20892 USA. RI Kryukov, Gregory/A-9592-2008; Gladyshev, Vadim/A-9894-2013 FU NCI NIH HHS [CAA81153]; NIDDK NIH HHS [R56 DK047320, DK47320, R01 DK047320]; NIEHS NIH HHS [R37 ES002497, ES02497, R01 ES002497]; NIGMS NIH HHS [GM616603] NR 46 TC 89 Z9 90 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 JUN PY 2001 VL 21 IS 11 BP 3840 EP 3852 DI 10.1128/MCB.21.11.3840-3852.2001 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 432QF UT WOS:000168706600021 PM 11340175 ER PT J AU Devin, A Lin, Y Yamaoka, S Li, ZW Karin, M Liu, ZG AF Devin, A Lin, Y Yamaoka, S Li, ZW Karin, M Liu, ZG TI The alpha and beta subunits of I kappa B kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GAMMA-DEFICIENT MICE; CELL-DEATH; INCONTINENTIA PIGMENTI; TRANSCRIPTION FACTOR; LIVER DEGENERATION; ACTIVATION; COMPLEX; RIP; DOMAIN; APOPTOSIS AB The activation of I kappaB kinase (IKK) is a key step in the nuclear translocation of the transcription factor NF-kappaB. IKK is a complex composed of three subunits: IKK alpha, IKK beta, and IKK gamma (also called NEMO). In response to the proinflammatory cytokine tumor necrosis factor (TNF), IKK is activated after being recruited to the TNF receptor 1 (TNF-R1) complex via TNF receptor-associated factor 2 (TRAF2). We found that the IKK alpha and IKK beta catalytic subunits are required for IKK-TRAF2 interaction. This interaction occurs through the leucine zipper motif common to IKK alpha, IKK beta, and the RING finger domain of TRAF2, and either IKKa or IKK beta alone is sufficient for the recruitment of IKK to TNF-R1. Importantly, IKK gamma is not essential for TNF-induced IKK recruitment to TNF-R1, as this occurs efficiently in IKK gamma -deficient cells. Using TRAF2(-/-) cells, we demonstrated that the TNF-induced interaction between IKK gamma and the death domain kinase RIP is TRAF2 dependent and that one possible function of this interaction is to stabilize the IKK complex when it interacts with TRAF2. C1 NCI, Div Clin Sci, Med Branch, Dept Cell & Canc Biol, Bethesda, MD 20892 USA. Tokyo Med & Dent Univ, Sch Med, Dept Microbiol, Tokyo 113, Japan. Univ Calif San Diego, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. RP Liu, ZG (reprint author), NCI, Div Clin Sci, Med Branch, Dept Cell & Canc Biol, Bldg 10,Rm 6N105,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 42 TC 99 Z9 105 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 JUN PY 2001 VL 21 IS 12 BP 3986 EP 3994 DI 10.1128/MCB.21.12.3986-3994.2001 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 436XY UT WOS:000168962200013 PM 11359906 ER PT J AU Huber, LJ Yang, TW Sarkisian, CJ Master, SR Deng, CX Chodosh, LA AF Huber, LJ Yang, TW Sarkisian, CJ Master, SR Deng, CX Chodosh, LA TI Impaired DNA damage response in cells expressing an exon 11-deleted murine Brca1 variant that localizes to nuclear foci SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID POLYMERASE-II HOLOENZYME; MAMMARY EPITHELIAL-CELLS; INTERACT IN-VIVO; BREAST-CANCER; SUBCELLULAR-LOCALIZATION; CYCLE REGULATION; GENE BRCA1; RAD51 GENE; PROTEIN; PHOSPHORYLATION AB Both human and mouse cells express an alternatively spliced variant of BRCA1, BRCA1-Delta 11, which lacks exon 11 in its entirety, including putative nuclear localization signals. Consistent with this, BRCA1-Delta 11 has been reported to reside in the cytoplasm, a localization that would ostensibly preclude it from playing a role in the nuclear processes in which its full-length counterpart has been implicated. Nevertheless, the finding that murine embryos bearing homozygous deletions of exon 11 survive longer than embryos that are homozygous for Brca1 null alleles suggests that exon 11-deleted isoforms may perform at least some of the functions of Brca1. We have analyzed both the full-length and the exon 11-deleted isoforms of the murine Brca1 protein. Our results demonstrate that full-length murine Brca1 is identical to human BRCA1 with respect to its cell cycle regulation, DNA damage-induced phosphorylation, nuclear localization, and association with Rad51. Surprisingly, we show that endogenous Brca1-Delta 11 localizes to discrete nuclear foci indistinguishable from those found in wild-type cells, despite the fact that Brca1-Delta 11 lacks previously defined nuclear localization signals. However, we further show that DNA damage-induced phosphorylation of Brca1-Delta 11 is significantly reduced compared to full-length Brca1, and that gamma irradiation-induced Rad51 focus formation is impaired in cells in which only Brca1-Delta 11 is expressed. Our results suggest that the increased viability of embryos bearing homozygous deletions of exon 11 may be due to expression of Brca1-Delta 11 and suggest an explanation for the genomic instability that accompanies the loss of full-length Brca1. C1 Univ Penn, Sch Med, Dept Mol & Cellular Engn, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. NIDDKD, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. RP Chodosh, LA (reprint author), Univ Penn, Sch Med, Dept Mol & Cellular Engn, 612 Biomed Res Bldg 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. RI deng, chuxia/N-6713-2016 FU NCI NIH HHS [CA71513, CA78410] NR 65 TC 76 Z9 77 U1 0 U2 0 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 JUN PY 2001 VL 21 IS 12 BP 4005 EP 4015 DI 10.1128/MCB.21.12.4005-4015.2001 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 436XY UT WOS:000168962200015 PM 11359908 ER PT J AU Boissinot, S Entezam, A Furano, AV AF Boissinot, S Entezam, A Furano, AV TI Selection against deleterious LINE-1-containing loci in the human lineage SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE LI/LINE-1; human; sex chromosome; evolution; retrotransposon ID TRANSPOSABLE ELEMENT; Y-CHROMOSOME; DROSOPHILA-MELANOGASTER; LINE-1 ELEMENTS; L1 RETROTRANSPOSITION; MOUSE GENOME; EVOLUTION; RECOMBINATION; GENE; SEQUENCES AB We compared sex chromosomal and autosomal regions of similar GC contents and found that the human Y chromosome contains nine times as many full-length (FL) ancestral LINE-1 (L1) elements per megabase as do autosomes and that the X chromosome contains three times as many. In addition, both sex chromosomes contain a ca. twofold excess of elements that are > 500 bp but not long enough to be capable of autonomous replication. In contrast, the autosomes are not deficient in short (< 500 bp) L1 elements or SINE elements relative to the sex chromosomes. Since neither the Y nor the X chromosome, when present in males, can be cleared of deleterious genetic loci by recombination, we conclude that most FL L1s were deleterious and thus subject to purifying selection. Comparison between nonrecombining and recombining regions of autosome 21 supported this conclusion. We were able to identify a subset of loci in the human DNA database that once contained active L1 elements, and we found by using the polymerase chain reaction that 72% of them no longer contain L1 elements in a representative of each of eight different ethnic groups. Genetic damage produced by both L1 retrotransposition and ectopic (nonallelic) recombination between L1 elements could provide the basis for their negative selection. C1 NIDDKD, Mol & Cellular Biol Lab, Sect Genom Struct & Funct, NIH, Bethesda, MD 20892 USA. RP Furano, AV (reprint author), NIDDKD, Mol & Cellular Biol Lab, Sect Genom Struct & Funct, NIH, Bldg 8,Room 203,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. NR 48 TC 110 Z9 110 U1 0 U2 3 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 USA SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JUN PY 2001 VL 18 IS 6 BP 926 EP 935 PG 10 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 440MZ UT WOS:000169180200004 PM 11371580 ER PT J AU Culver, M Menotti-Raymond, MA O'Brien, SJ AF Culver, M Menotti-Raymond, MA O'Brien, SJ TI Patterns of size homoplasy at 10 microsatellite loci in pumas (Puma concolor) SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Letter DE size homoplasy; puma microsatellites; microsatellite sequences ID ALLELE FREQUENCIES; MUTATION MODEL; EVOLUTION; POPULATIONS; SEQUENCES; POLYMORPHISMS; CONSERVATION; DYNAMICS; FELIDAE C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Bldg 560,Room 21-105, Frederick, MD 21702 USA. NR 31 TC 26 Z9 29 U1 0 U2 6 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 USA SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JUN PY 2001 VL 18 IS 6 BP 1151 EP 1156 PG 6 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 440MZ UT WOS:000169180200030 PM 11371606 ER PT J AU Parker, CE Graham, LB Nguyen, MN Gladen, BC Kadiiska, MB Barrett, JC Tomer, KB AF Parker, CE Graham, LB Nguyen, MN Gladen, BC Kadiiska, MB Barrett, JC Tomer, KB TI An improved GC/MS-based procedure for the quantitation of the isoprostane 15-F-2t-IsoP in rat plasma SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE isoprostanes; GC/MS; oxidative stress; negative ion chemical ionization mass spectrometry ID RADICAL-CATALYZED MECHANISM; DEPENDENT FORMATION; MASS-SPECTROMETRY; OXIDATIVE STRESS; F-2-ISOPROSTANES; PROSTANOIDS; NONCYCLOOXYGENASE; MARKERS; HUMANS AB This article describes a procedure for the quantitation of the isoprostane 15-F-2t-IsoP (9a, 11a, 15S-trihydroxy-(8b)-prosta-5Z, 13E-dien-1-oic acid [CAS#27415-26-5] formerly known as 8-epi-PGF2, or 8-iso-PGF(2a), and also as iPF(2a)-III). We have combined features from several earlier methods for 15-F-2t-IsoP and prostaglandins, and identified and modified those steps that may lead to poor recoveries. The resulting protocol is precise and reliable, and was validated by a blind time-course study of plasma levels in rats treated with 120 and 1200 mg CCl4/ kg body weight. Plasma levels of 15-F-2t-IsoP, as measured according to the procedure described above, are good indicators of acute oxidative stress as induced by CCl4. The precision of the measurements allows detection of elevated plasma 15-F-2t-IsoP levels as long as 16 h after an acute exposure of 120 mg CCl4/kg body weight, and 2 h after an exposure of 1 mg CCl4/kg body weight. The results of this low-dose, pilot study suggest that this method has sufficient analytical precision to allow the detection of the small changes in plasma isoprostane levels, which result from chronic and/or lower-level exposures to agents causing oxidative stress. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 30 TC 9 Z9 9 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD JUN PY 2001 VL 18 IS 2 BP 105 EP 118 DI 10.1385/MB:18:2:105 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 450YN UT WOS:000169772600002 PM 11471453 ER PT J AU Wang, XW AF Wang, XW TI Microinjection technique used to study functional interaction between p53 and hepatitis B virus X gene in apoptosis SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE microinjection; p53; hepatitis B virus; apoptosis; HBx; liver cancer ID TUMOR-SUPPRESSOR GENE; WILD-TYPE P53; TATA-BINDING PROTEIN; LONG TERMINAL REPEAT; HEPATOCELLULAR-CARCINOMA; HBX PROTEIN; TRANSGENIC MICE; IN-VIVO; TRANSACTIVATOR PROTEIN; SIGNALING PATHWAY AB Microinjection of expression vectors into cultured cells has been utilized to study functional interaction of p53 and the hepatitis B virus HBx gene in apoptosis. This approach allows us to determine protein-protein interactions in primary cultured human cells at a single cell level, including fibroblasts, mammary epithelial cells, renal epithelial cells, and hepatocytes. In principle, this approach can be used to study functional interaction of p53 and any gene that is either pro- or anti-apoptotic. The use of primary cultured human cells minimizes ambiguous results associated with immortalized or tumorigenic cell lines. Moreover, it is an easy and effective way to introduce genes of interests into primary human cells with defined genetic defects, thereby facilitating the delineation of genetic pathways. C1 NCI, Human Carcinogenesis Lab, Liver Carcinogenesis Sect, NIH, Bethesda, MD 20892 USA. RI Wang, Xin/B-6162-2009 NR 79 TC 6 Z9 6 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD JUN PY 2001 VL 18 IS 2 BP 169 EP 177 DI 10.1385/MB:18:2:169 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 450YN UT WOS:000169772600007 PM 11471458 ER PT J AU Devereux, TR Stern, MC Flake, GP Yu, MC Zhang, ZQ London, SJ Taylor, JA AF Devereux, TR Stern, MC Flake, GP Yu, MC Zhang, ZQ London, SJ Taylor, JA TI CTNNB1 mutations and beta-catenin protein accumulation in human hepatocellular carcinomas associated with high exposure to aflatoxin B1 SO MOLECULAR CARCINOGENESIS LA English DT Article DE hepatocellular carcinoma; aflatoxin B1; CTNNB1 mutations; beta-catenin protein ID TUMOR-SUPPRESSOR GENE; HEPATITIS-B; EXON 3; CANCER; ACTIVATION; APC; GUANGXI; VIRUS; MOUSE; CHINA AB beta -Catenin plays a key role in the Wnt signaling pathway, and mutations of CTNNB1, the gene that encodes beta -catenin, have been identified in about one-fourth of human hepatocellular carcinomas from regions of low aflatoxin B1 exposure. In this study 62 hepatocellular carcinomas (HCCs) from people highly exposed to aflatoxin B1 in Guangxi, People's Republic of China, were laser-capture microdissected and examined for CTNNB1 mutations. In addition, 41 of the HCCs were evaluated for the presence of the beta -catenin protein by immunohistochemical methods. Twenty of the HCCs showed positive results for beta -catenin, with strong membrane staining, while adjacent non-neoplastic liver tissue lacked or showed only weak membrane staining. One HCC, in which a CTNNB1 mutation was not detected, showed nuclear staining for the beta -catenin protein. Mutations of CTNNB1 were identified in five HCCs. These consisted of four point mutations in the glycogen serine kinase-3 beta phosphorylation region of codons 32-45 and one deletion of codons 32-38. These mutations were similar to those previously reported for human HCC, although at a lower frequency. A signature mutation profile associated with aflatoxin B1 exposure could not be identified. The immunohistochemical findings indicate a role for accumulation of beta -catenin and possibly increased Wnt signaling in aflatoxin B1-associated HCC. The low frequency of CTNNB1 mutations, however, suggests that mutation of another Wnt signaling component, such as the Wnt scaffolding protein axin or the adenomatous polyposis coli protein, both of which modulate beta -catenin stability, also may be involved in aflatoxin-associated HCC. Published (C) zool Wiley-Liss. Inc.(dagger) C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Canc Inst Guangxi, Nanning, Guangxi, Peoples R China. NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP NIEHS, Mol Carcinogenesis Lab, NIH, MD D4-04,POB 12233, Res Triangle Pk, NC 27709 USA. OI taylor, jack/0000-0001-5303-6398; London, Stephanie/0000-0003-4911-5290 FU NCI NIH HHS [R35 CA 53890] NR 20 TC 64 Z9 69 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 EI 1098-2744 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUN PY 2001 VL 31 IS 2 BP 68 EP 73 DI 10.1002/mc.1041 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 449KN UT WOS:000169683900002 PM 11429783 ER PT J AU Gold, B Hanson, M Dean, M AF Gold, B Hanson, M Dean, M TI Two rare confounding polymorphisms proximal to the factor V Leiden mutation SO MOLECULAR DIAGNOSIS LA English DT Article; Proceedings Paper CT 6th Annual Meeting of the Association-for-Molecular-Pathology CY NOV 09-12, 2000 CL DENVER, COLORADO SP Assoc Molec Pathol DE PCR-RFLP; PCR; variant ID COAGULATION-FACTOR-V; VENOUS THROMBOSIS; RISK; PCR AB Background: Comprehensive assessment of thrombophilia risk includes characterization of the R506Q (Leiden) mutation in factor V in many patients. Although activated protein C resistance is often assessed by means of a coagulation test, molecular interrogation of the G1691A mutation provides confirmation and interpretive utility in patients undergoing anticoagulation. Many molecular methods are available to provide genotyping at this locus. Among these, PCR-restriction fragment length polymorphism (RFLP) is widely used. Unfortunately, because this common mutation is 11 bp from the 3 ' end of exon 10, one PCR primer often anneals within intron 10. As a consequence, polymorphism can confound test results. Methods and Results: In the course of a clinical diagnostic test of 15,301 patients, two samples repeatedly showed two different unusual electrophoretic mobilities after PCR and restriction enzyme digestion. After stripping patient identifiers and entering a research protocol, the amplicons from these DNAs were sequenced in parallel with normal and heterozygous G1691A control genomic DNA samples. This sequencing showed two novel polymorphisms, each mapping to intron 10. Conclusion: PCR-RFLP-based methods rely on sequence conservation in the interrogated region. Amplification of mutated loci adjacent to introns present a special risk for confounding restriction patterns. Sequencing amplicons with reproducibly unusual restriction patterns resolved the paradoxical restriction pattern in this case. C1 NCI, Human Genet Sect, Lab Genom Divers, Frederick, MD 21702 USA. Quest Diagnost, Van Nuys, CA USA. RP Gold, B (reprint author), NCI, Human Genet Sect, Lab Genom Divers, Frederick, MD 21702 USA. OI Dean, Michael/0000-0003-2234-0631 NR 9 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1084-8592 J9 MOL DIAGN JI Mol. Diagn. PD JUN PY 2001 VL 6 IS 2 BP 137 EP 140 PG 4 WC Biotechnology & Applied Microbiology; Medical Laboratory Technology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Medical Laboratory Technology; Research & Experimental Medicine GA 451FM UT WOS:000169790500009 PM 11468699 ER PT J AU Kostic, TS Andric, SA Stojilkovic, SS AF Kostic, TS Andric, SA Stojilkovic, SS TI Spontaneous and receptor-controlled soluble guanylyl cyclase activity in anterior pituitary cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; HORMONE-RELEASING HORMONE; DEPENDENT PROTEIN-KINASE; GROWTH-HORMONE; SIGNALING PATHWAY; CA2+ OSCILLATIONS; RAT SOMATOTROPHS; INTERFERON-GAMMA; MESSENGER-RNA; SECRETION AB Nitric oxide (NO)-dependent soluble guanylyl cyclase (sGC) is operative in mammalian cells, but its presence and the role in cGMP production in pituitary cells have been incompletely characterized. Here we show that sGC is expressed in pituitary tissue and dispersed cells, enriched lactotrophs and somatotrophs, and GH(3) immortalized cells, and that this enzyme is exclusively responsible for cGMP production in unstimulated cells. Basal sGC activity was partially dependent on voltage-gated calcium influx, and both calcium-sensitive NO synthases (NOS), neuronal and endothelial, were expressed in pituitary tissue and mixed cells, enriched lactotrophs and somatotrophs, and GH(3) cells. Calcium-independent inducible NOS was transiently expressed in cultured lactotrophs and somatotrophs after the dispersion of cells, but not in GH(3) cells and pituitary tissue. This enzyme participated in the control of basal sGC activity in cultured pituitary cells. The overexpression of inducible NOS by lipopolysaccharide + interferon-gamma further increased NO and cGMP levels, and the majority of de novo produced cGMP was rapidly released. Addition of an NO donor to perifused pituitary cells also led to a rapid cGMP release. Calcium-mobilizing agonists TRH and GnRH slightly increased basal cGMP production, but only when added in high concentrations. In contrast, adenylyl cyclase agonists GHRH and CRF induced a robust increase in cGMP production, with EC(50)s in the physiological concentration range. As in cells overexpressing inducible NOS, the stimulatory action of GHRH and CRF was preserved in cells bathed in calcium-deficient medium, but was not associated with a measurable increase in NO production. These results indicate that sGC is present in secretory anterior pituitary cells and is regulated in an NO-dependent manner through constitutively expressed neuronal and endothelial NOS and transiently expressed inducible NOS, as well as independently of NO by adenylyl cyclase coupled-receptors. C1 NICHHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. NR 47 TC 47 Z9 47 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 2001 VL 15 IS 6 BP 1010 EP 1022 DI 10.1210/me.15.6.1010 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436GR UT WOS:000168928600014 PM 11376118 ER PT J AU Leandro, P Lechner, MC de Almeida, IT Konecki, D AF Leandro, P Lechner, MC de Almeida, IT Konecki, D TI Glycerol increases the yield and activity of human phenylalanine hydroxylase mutant enzymes produced in a prokaryotic expression system SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE phenylalanine hydroxylase enzyme; chemical chaperones; protein folding; protein stabilizers ID PROTEIN STABILIZATION; CHEMICAL CHAPERONES; CYSTIC-FIBROSIS; MUTATION AB Chemical chaperones are low molecular weight compounds known to stabilize proteins in vitro. Recently it was shown that, in transfected cells, these molecules can also correct the defective folding of some mutant proteins. Hyperphenylalaninemia (HPA) has been proposed to be classified as a "conformational disease," since it has been shown that the majority of the PAH mutations affect protein folding, thereby causing an increasing tendency toward aggregation and proteolytic degradation. Based on these observations, the effect of glycerol as a stabilizer agent of recombinant mutant forms of human phenylalanine hydroxylase enzymes (hPAH) produced in a prokaryotic expression system was investigated. The wild-type and two mutant forms of the hPAH protein (R270K and V388M) were expressed in the presence of glycerol in the culture medium. The yield, specific enzymatic activities, and kinetic properties of the recombinant proteins were determined and compared with the data obtained under normal growth conditions. The results obtained demonstrate that glycerol not only improved the yield of the soluble hPAH proteins (2- to 3-fold depending on the mutant enzyme) produced but also increased the specific activity of the purified recombinant enzymes. We speculate that correction of protein folding abnormalities by chemical chaperones may be a possible therapeutic approach to correct conformational diseases. (C) 2001 Academic Press. C1 Univ Lisbon, Fac Farm, Ctr Patogenese Mol, P-1649003 Lisbon, Portugal. NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. RP Univ Lisbon, Fac Farm, Ctr Patogenese Mol, R Prof Gama Pinto, P-1649003 Lisbon, Portugal. EM italmeida@ff.ul.pt RI iMed.ULisboa, iMed.ULisboa/C-6292-2014; Tavares de Almeida, Isabel/F-8319-2014; Leandro, Paula/A-8323-2014; iMed.ULisboa, MetGen /B-5293-2014; OI Leandro, Paula/0000-0002-2946-9342; Tavares de Almeida, Isabel/0000-0002-4024-8305 NR 18 TC 29 Z9 31 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 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JUN PY 2001 VL 73 IS 2 BP 173 EP 178 DI 10.1006/mgme.2001.3172 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 443DA UT WOS:000169323700007 PM 11386853 ER PT J AU Terlouw, SA Masereeuw, R Russel, FGM Miller, DS AF Terlouw, SA Masereeuw, R Russel, FGM Miller, DS TI Nephrotoxicants induce endothelin release and signaling in renal proximal tubules: Effect on drug efflux SO MOLECULAR PHARMACOLOGY LA English DT Article; Proceedings Paper CT Experimental Biology 2000 Meeting CY APR 14-18, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nutr Sci ID EPITHELIAL-CELLS; ORGANIC-ANIONS; SECRETION; CALCIUM; PATHOPHYSIOLOGY; MECHANISMS; TRANSPORT; FAILURE AB We previously used killifish proximal tubules, fluorescent substrates, and confocal microscopy to demonstrate that transport mediated by the multidrug resistance protein (Mrp2) and by P-glycoprotein was reduced by nanomolar concentrations of endothelin-1 (ET), acting through a basolateral B-type ET receptor and protein kinase C (PKC). Here we show that representatives of two classes of nephrotoxicants decrease transport by activating the endothelin-PKC signaling pathway. Exposing tubules to radiocontrast agents (iohexol, diatrizoate) or aminoglycoside antibiotics (gentamicin, amikacin) reduced Mrp2-mediated fluorescein methotrexate (FL-M-DC) transport from cell to tubular lumen. Pretreating the tubules with an ETB-receptor antagonist or with PKC-selective inhibitors abolished these effects. The nephrotoxicants activated signaling by inducing release of ET from the tubules, because adding of an antibody against ET to the medium abolished the effects. Elevating medium Ca2+ also reduced FL-MTX transport; this reduction was abolished when tubules were pretreated with an ET antibody, an FTB-receptor antagonist, PKC-selective inhibitors, or the Ca2+ channel blocker, nifedipine. None of these drugs by themselves affected FL-MTX transport. Importantly, nifedipine also blocked the ETB-receptor/PKC-dependent reduction in FL-MTX transport caused by gentamicin and diatrizoate. These results for two classes of structurally unrelated nephrotoxicants suggest that Ca2+-dependent ET release and subsequent action through an autocrine mechanism may be an early response to tubular injury. C1 Univ Nijmegen, Med Ctr, Dept Pharmacol & Toxicol, NL-6500 HB Nijmegen, Netherlands. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Mt Desert Isl Biol Lab, Salisbury Cove, ME USA. RP Masereeuw, R (reprint author), Univ Nijmegen, Med Ctr, Dept Pharmacol Toxicol 233, POB 9101, NL-6500 HB Nijmegen, Netherlands. RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014; OI Russel, Frans/0000-0002-7959-2314; Masereeuw, Rosalinde/0000-0002-1560-1074 NR 37 TC 34 Z9 36 U1 0 U2 0 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 JUN PY 2001 VL 59 IS 6 BP 1433 EP 1440 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 437RX UT WOS:000169008300011 PM 11353803 ER PT J AU Kang, EM Hanazano, Y Frare, P Vanin, EF De Witte, M Metzger, M Liu, JM Tisdale, JF AF Kang, EM Hanazano, Y Frare, P Vanin, EF De Witte, M Metzger, M Liu, JM Tisdale, JF TI Persistent low-level engraftment of rhesus peripheral blood progenitor cells transduced with the Fanconi anemia C gene after conditioning with low-dose irradiation SO MOLECULAR THERAPY LA English DT Article DE hematopoietic stem cell; gene transduction; nonmyeloablative conditioning; autologous transplantation ID HEMATOPOIETIC STEM-CELLS; HUMAN GLUCOCEREBROSIDASE GENE; GREEN FLUORESCENT PROTEIN; LONG-TERM EXPRESSION; IN-VIVO EXPRESSION; BONE-MARROW CELLS; NONHUMAN-PRIMATES; ADENOSINE-DEAMINASE; RETROVIRAL VECTORS; REPOPULATING CELLS AB The hematopoietic stem cell has long been considered an ideal target for the introduction of therapeutic genes to treat human disorders such as Fanconi anemia (FA). Although recent progress in large animal models is encouraging, application to nonmalignant conditions is limited by the perceived necessity of myeloablative conditioning. We and others have shown that very low irradiation doses are sufficient to allow significant hematopoietic engraftment in murine hosts even after the introduction of xenogeneic genes. To determine the degree of engraftment of genetically modified cells attainable with very low irradiation doses in larger animals, we employed the rhesus macaque competitive repopulation model. Four animals underwent mobilization with stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) followed by apheresis. The apheresis product was enriched for the CD34-positive fraction by immunomagnetic selection and split equally for transduction with either G1FC26, a retroviral vector carrying the Fanconi anemia complementation group C gene, or PLII, a nonexpression control retroviral vector carrying both neomycin and beta -galactosidase gene sequences modified to prevent translation. Transductions were performed daily in the presence of fresh IL-3, IL-6, SCF, and Flt-3 ligand on fibronectin-coated plates over 96 h. Animals were conditioned with a single dose of either 100 (n = 2) or 200 (n = 2) cGy and received the combined products of transduction on the following day. None of the animals experienced clinically significant neutropenia nor required the use of central line placement, transfusional support with blood products, or intravenous antibiotics. Using real-time PCR, circulating levels of genetically modified cells as high as 1% were initially detected. Stable, albeit, significantly lower levels from both vector-transduced aliquots (<0.1%) persisted beyond 12 months posttransplant in all four animals. Although not sufficient to correct the phenotype in many human disorders, stable low-level engraftment by genetically modified cells following low-intensity conditioning may prove adequate in disorders such as FA due to the selective advantage conferred upon corrected cells. C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Div Expt Hematol, Memphis, TN 38101 USA. RP Tisdale, JF (reprint author), NIDDK, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N116, Bethesda, MD 20892 USA. EM JohnTis@intra.niddk.nih.gov NR 44 TC 25 Z9 26 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2001 VL 3 IS 6 BP 911 EP 919 DI 10.1006/mthe.2001.0337 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 444TZ UT WOS:000169417300013 PM 11407905 ER PT J AU Morgen, K Jeffries, NO Stone, R Martin, R Richert, ND Frank, JA McFarland, HF AF Morgen, K Jeffries, NO Stone, R Martin, R Richert, ND Frank, JA McFarland, HF TI Ring-enhancement in multiple sclerosis: marker of disease severity SO MULTIPLE SCLEROSIS LA English DT Article DE multiple sclerosis; magnetic resonance; ring-enhancing lesions; enhancement pattern ID RESONANCE-IMAGING FINDINGS; MAGNETIC-RESONANCE; LESION DEVELOPMENT; SPIN-ECHO; MR; DISABILITY; IMPAIRMENT; IMAGES; BRAIN AB Correlations between conventional MRI measures of disease activity and clinical disability in multiple sclerosis (MS) have been disappointing. Because ring-enhancing lesions may reflect a more destructive pathology, we tested their potential association with disease severity. We evaluated active lesions with regard to their enhancement pattern on serial magnetic resonance images in a cohort of 28 patients with relapsing-remitting MS. The percentage of ring-enhancing lesions correlated with EDSS T2 lesion load and duration of disease and predicted the occurrence of relapses during the baseline period of observation as well as after 3 years of follow-up in multiple logistic regression analysis. The findings suggest that the Pathological process reflected by ring-enhancing lesions may contribute to more severe clinical disease. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Biostat Branch, NIH, Bethesda, MD 20892 USA. NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. RP Morgen, K (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B16,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 19 TC 30 Z9 31 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD JUN PY 2001 VL 7 IS 3 BP 167 EP 171 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 451YM UT WOS:000169830400006 PM 11475440 ER PT J AU Chiariello, M Marinissen, MJ Gutkind, JS AF Chiariello, M Marinissen, MJ Gutkind, JS TI Regulation of c-myc expression by PDGF through Rho GTPases SO NATURE CELL BIOLOGY LA English DT Article ID SRC FAMILY KINASES; PROTEIN-COUPLED RECEPTORS; FACTOR-KAPPA-B; SIGNAL-TRANSDUCTION; TYROSINE KINASES; CELL-CYCLE; CDC42; ACTIVATION; RAC; BINDING AB Src family protein-tyrosine kinases have a central role in several biological functions, including cell adhesion and spreading, chemotaxis, cell cycle progression, differentiation and apoptosis. surprisingly, these kinases also participate in mitogenic signalling by receptors that themselves exhibit an intrinsic protein-tyrosine kinase activity, including those for platelet-derived growth factor (PDGF), epidermal growth factor and colony-stimulating factor-1. Indeed, Src kinases are strictly required for the nuclear expression of the c-myc proto-oncogene and thus for DNA synthesis in response to PDGF. However, the nature of the signalling pathways by which Src kinases participate in the induction of c-myc expression by tyrosine kinase receptors is still unknown. Here we show that PDGF enhances c-myc expression and stimulates the c-myc promoter in a Src-dependent manner, and that neither Ras nor the mitogen-activated protein kinase pathway mediate these effects. In contrast, we present evidence that PDGF stimulates Vav2 through Src, thereby initiating the activation of a Rac-dependent pathway that controls the expression of the c-myc proto-oncogene. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; Chiariello, Mario/O-3642-2014 OI Chiariello, Mario/0000-0001-8434-5177 NR 50 TC 98 Z9 98 U1 0 U2 2 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JUN PY 2001 VL 3 IS 6 BP 580 EP 586 DI 10.1038/35078555 PG 7 WC Cell Biology SC Cell Biology GA 440VC UT WOS:000169194400014 PM 11389443 ER PT J AU Rogozin, IB Pavlov, YI Bebenek, K Matsuda, T Kunkel, TA AF Rogozin, IB Pavlov, YI Bebenek, K Matsuda, T Kunkel, TA TI Somatic mutation hotspots correlate with DNA polymerase eta error spectrum SO NATURE IMMUNOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; IMMUNOGLOBULIN GENES; XERODERMA-PIGMENTOSUM; CLONAL SELECTION; V-KAPPA; HYPERMUTATION; SEQUENCES; HYPERMUTAGENESIS; SPECIFICITY; MUTAGENESIS AB Mutational spectra analysis of 15 immunoglobulin genes suggested that consensus motifs R (G) under bar YW and W (A) under bar were universal descriptors of somatic hypermutation. Highly mutable sites, "hotspots", that matched W (A) under bar were preferentially found in one DNA strand and R (G) under bar YW hotspots were found in both strands, Analysis of base-substitution hotspots in DNA polymerase error spectra showed that 33 of 36 hotspots in the human polymerase eta spectrum conformed to the W (A) under bar consensus. This and four other characteristics of polymerase eta substitution specificity suggest that errors introduced by this enzyme during synthesis of the nontranscribed DNA strand in variable regions may contribute to strand-specific somatic hypermutagenesis of immunoglobulin genes at A-T base pairs. C1 NIEHS, Labs Mol Genet, Res Triangle Pk, NC 27709 USA. Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, Novosibirsk 630090, Russia. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Labs Mol Genet, POB 12233, Res Triangle Pk, NC 27709 USA. NR 55 TC 222 Z9 226 U1 0 U2 4 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 JUN PY 2001 VL 2 IS 6 BP 530 EP 536 DI 10.1038/88732 PG 7 WC Immunology SC Immunology GA 438WV UT WOS:000169078000016 PM 11376340 ER PT J AU Zeng, XM Winter, DB Kasmer, C Kraemer, KH Lehmann, AR Gearhart, PJ AF Zeng, XM Winter, DB Kasmer, C Kraemer, KH Lehmann, AR Gearhart, PJ TI DNA polymerase eta is an A-T mutator in somatic hypermutation of immunoglobulin variable genes SO NATURE IMMUNOLOGY LA English DT Article ID XERODERMA-PIGMENTOSUM VARIANT; DOUBLE-STRAND BREAKS; MISMATCH REPAIR PROTEIN; THYMINE-THYMINE DIMER; B-CELL LINE; TRANSLESION SYNTHESIS; MICE DEFICIENT; BYPASS; IOTA; RECOMBINATION AB To determine whether DNA polymerase eta plays a role in the hypermutation of immunoglobulin variable genes, we examined the frequency and pattern of substitutions in variable V(H)6 genes from the peripheral blood lymphocytes of three patients with xeroderma pigmentosum variant disease, whose polymerase eta had genetic defects. The frequency of mutation was normal but the types of base changes were different: there was a decrease in mutations at A and T and a concomitant rise in mutations at G and C. We propose that more than one polymerase contributes to hypermutation and that if one is absent, others compensate. The data indicate that polymerase eta is involved in generating errors that occur predominantly at A and T and that another polymerase(s) may generating errors that occur predominantly at A preferentially generate errors opposite G and C. C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. Walter Reed Army Inst Res, Dept Cellular Injury, Silver Spring, MD 20910 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Univ Sussex, MRC, Cell Mutat Unit, Brighton, E Sussex, England. RP Gearhart, PJ (reprint author), NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 49 TC 304 Z9 308 U1 0 U2 5 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 JUN PY 2001 VL 2 IS 6 BP 537 EP 541 DI 10.1038/88740 PG 5 WC Immunology SC Immunology GA 438WV UT WOS:000169078000017 PM 11376341 ER PT J AU Doody, GM Bell, SE Vigorito, E Clayton, E McAdam, S Tooze, R Fernandes, C Lee, IJ Turner, M AF Doody, GM Bell, SE Vigorito, E Clayton, E McAdam, S Tooze, R Fernandes, C Lee, IJ Turner, M TI Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation SO NATURE IMMUNOLOGY LA English DT Article ID EXCHANGE FACTOR VAV; HEAT-STABLE ANTIGEN(HI); T-CELL; DEFICIENT MICE; RHO-GTPASES; RECEPTOR; FAMILY; LYMPHOCYTE; REGULATOR; LACKING AB B and T lymphocytes develop normally in mice lacking the guanine nucleotide exchange factor Vav-2, However, the immune responses to type II thymus-independent antigen as well as the primary response to thymus-dependent (TD) antigen are defective. Vav-2-deficient mice are also defective in their ability to switch immunoglobulin class, form germinal centers and generate secondary immune responses to TD antigens, Mice lacking both Vav-1 and Vav-2 contain reduced numbers of B lymphocytes and display a maturational block in the development of mature B cells. B cells from Vav-1(-/-)Vav-2(-/-) mice respond poorly to antigen receptor triggering, both in terms of proliferation and calcium release. These studies show the importance of Vav-2 in humoral immune responses and B cell maturation. C1 Babraham Inst, Mol Immunol Programme, Lab Lymphocyte Signaling & Dev, Cambridge CB2 4AT, England. Addenbrookes Hosp, Dept Histopathol, Cambridge CB2 2QQ, England. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20906 USA. RP Turner, M (reprint author), Babraham Inst, Mol Immunol Programme, Lab Lymphocyte Signaling & Dev, Cambridge CB2 4AT, England. RI Turner, Martin/N-9976-2014 OI Turner, Martin/0000-0002-3801-9896 NR 39 TC 128 Z9 129 U1 1 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 JUN PY 2001 VL 2 IS 6 BP 542 EP 547 DI 10.1038/88748 PG 6 WC Immunology SC Immunology GA 438WV UT WOS:000169078000018 PM 11376342 ER PT J AU Leppla, SH AF Leppla, SH TI A dominant-negative therapy for anthrax - The oligomeric structure of anthrax toxin might be exploited as a preventative or therapeutic vaccine. SO NATURE MEDICINE LA English DT Editorial Material ID PROTECTIVE ANTIGEN AB The oligomeric structure of anthrax toxin might be exploited as a preventative or therapeutic vaccine. C1 NIH, Oral Infect & Immun Branch, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIH, Oral Infect & Immun Branch, Natl Inst Dent & Craniofacial Res, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 7 Z9 7 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 2001 VL 7 IS 6 BP 659 EP 660 DI 10.1038/89025 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 438YH UT WOS:000169081500024 PM 11385497 ER PT J AU Khan, J Wei, JS Ringner, M Saal, LH Ladanyi, M Westermann, F Berthold, F Schwab, M Antonescu, CR Peterson, C Meltzer, PS AF Khan, J Wei, JS Ringner, M Saal, LH Ladanyi, M Westermann, F Berthold, F Schwab, M Antonescu, CR Peterson, C Meltzer, PS TI Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks SO NATURE MEDICINE LA English DT Article ID MOLECULAR CLASSIFICATION; DIFFERENTIAL-DIAGNOSIS; NEUROECTODERMAL TUMOR; CDNA MICROARRAYS; EWINGS-SARCOMA; HUMAN BREAST; CELL TUMORS; ROUND-CELL; GROWTH; PATTERNS AB The purpose of this study was to develop a method of classifying cancers to specific diagnostic categories based on their gene expression signatures using artificial neural networks (ANNs). We trained the ANNs using the small, round blue-cell tumors (SRBCTs) as a model. These cancers belong to four distinct diagnostic categories and often present diagnostic dilemmas in clinical practice. The ANNs correctly classified all samples and identified the genes most relevant to the classification. Expression of several of these genes has been reported in SRBCTs, but most have not been associated with these cancers. To test the ability of the trained ANN models to recognize SRSCTs, we analyzed additional blinded samples that were not previously used for the training procedure, and correctly classified them in all cases. This study demonstrates the potential applications of these methods for tumor diagnosis and the Identification of candidate targets for therapy. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Ctr Adv Technol, Gaithersburg, MD USA. Univ Lund, Dept Theoret Phys, Complex Syst Div, S-22362 Lund, Sweden. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. German Canc Res Ctr, Dept Cytogenet, D-6900 Heidelberg, Germany. Univ Cologne, Klin Kinderheilkunde, Dept Pediat, Cologne, Germany. RP Khan, J (reprint author), NHGRI, Canc Genet Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Saal, Lao/A-2919-2011; Ringner, Markus/G-3641-2011; Khan, Javed/P-9157-2014 OI Saal, Lao/0000-0002-0815-1896; Ringner, Markus/0000-0001-5469-8940; Khan, Javed/0000-0002-5858-0488 FU NCI NIH HHS [Z01 SC010366-05] NR 40 TC 1316 Z9 1410 U1 8 U2 116 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 2001 VL 7 IS 6 BP 673 EP 679 DI 10.1038/89044 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 438YH UT WOS:000169081500034 PM 11385503 ER PT J AU Duckers, HJ Boehm, M True, AL Yet, SF San, H Park, JL Webb, RC Lee, ME Nabel, GJ Nabel, EG AF Duckers, HJ Boehm, M True, AL Yet, SF San, H Park, JL Webb, RC Lee, ME Nabel, GJ Nabel, EG TI Heme oxygenase-1 protects against vascular constriction and proliferation SO NATURE MEDICINE LA English DT Article ID SMOOTH-MUSCLE CELLS; CARBON-MONOXIDE; NITRIC-OXIDE; ENDOTHELIAL-CELLS; ARTERIAL INJURY; EXPRESSION; GENE; P21; INHIBITORS; REGULATOR AB Heme oxygenase (HO-1, encoded by Hmox1) is an inducible protein activated in systemic inflammatory conditions by oxidant stress. Vascular injury is characterized by a local reparative process with inflammatory components, indicating a potential protective role for HO-1 in arterial wound repair. Here we report that HO-1 directly reduces vasoconstriction and inhibits cell proliferation during vascular injury. Expression of HO-1 in arteries stimulated vascular relaxation, mediated by guanylate cyclase and cGMP, independent of nitric oxide. The unexpected effects of HO-1 on vascular smooth muscle cell growth were mediated by cell-cycle arrest involving p21(Cip1). HO-1 reduced the proliferative response to vascular injury in vivo; expression of HO-1 in pig arteries inhibited lesion formation and Hmox1(-/-) mice produced hyperplastic arteries compared with controls. Induction of the HO-1 pathway moderates the severity of vascular injury by at least two adaptive mechanisms independent of nitric oxide, and is a potential therapeutic target for diseases of the vasculature. C1 NHLBI, Vasc Biol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. RP Nabel, EG (reprint author), NHLBI, Vasc Biol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Yet, Shaw-Fang/B-1067-2010; OI Yet, Shaw-Fang/0000-0001-9097-3962 NR 36 TC 386 Z9 407 U1 0 U2 18 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 2001 VL 7 IS 6 BP 693 EP 698 DI 10.1038/89068 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 438YH UT WOS:000169081500037 PM 11385506 ER PT J AU Li, H Chen, AQ Xing, GQ Wei, ML Rogawski, MA AF Li, H Chen, AQ Xing, GQ Wei, ML Rogawski, MA TI Kainate receptor-mediated heterosynaptic facilitation in the amygdala SO NATURE NEUROSCIENCE LA English DT Article ID METABOTROPIC GLUTAMATE-RECEPTOR; PHASEOLUS-VULGARIS-LEUKOAGGLUTININ; EXCITATORY SYNAPTIC TRANSMISSION; RAT BASOLATERAL AMYGDALA; LONG-TERM POTENTIATION; IN-VITRO; PLASTICITY; HIPPOCAMPUS; GLUR5; NMDA AB Prolonged low-frequency stimulation of excitatory afferents to basolateral amygdala neurons results in enduring enhancement of excitatory synaptic responses. The induction of this form of synaptic plasticity is eliminated by selective antagonists of GluR5 kainate receptors and can be mimicked by the GluR5 agonist ATPA. Kainate receptor-mediated synaptic facilitation generalizes to include inactive afferent synapses on the target neurons, and therefore contrasts with other types of activity-dependent enduring synaptic facilitation that are input-pathway specific. Such heterosynaptic spread of synaptic facilitation could account for adaptive and pathological expansion in the set of critical internal and external stimuli that trigger amygdala-dependent behavioral responses. C1 NINDS, Neuronal Excitabil Sect, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. RP Rogawski, MA (reprint author), NINDS, Neuronal Excitabil Sect, NIH, 10 Ctr Dr,Room 5N-250 MSC 1408, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 50 TC 78 Z9 81 U1 0 U2 3 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 JUN PY 2001 VL 4 IS 6 BP 612 EP 620 DI 10.1038/88432 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 438PG UT WOS:000169061800014 PM 11369942 ER PT J AU Lippincott-Schwartz, J Snapp, E Kenworthy, A AF Lippincott-Schwartz, J Snapp, E Kenworthy, A TI Studying protein dynamics in living cells SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID GREEN FLUORESCENT PROTEIN; RESONANCE ENERGY-TRANSFER; GPI-ANCHORED PROTEINS; CORRELATION SPECTROSCOPY; ENDOPLASMIC-RETICULUM; ANOMALOUS DIFFUSION; LIVE CELLS; PHOTOBLEACHING RECOVERY; CORRELATION MICROSCOPY; FUSION PROTEINS AB Since the advent of the green fluorescent protein, the subcellular localization, mobility, transport routes and binding interactions of proteins can be studied in living cells. Live cell imaging, in combination with photobleaching, energy transfer or fluorescence correlation spectroscopy are providing unprecedented insights into the movement of proteins and their interactions with cellular components. Remarkably, these powerful techniques are accessible to non-specialists using commercially available microscope systems. C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHD, Cell Biol & Metab Branch, NIH, 18 Lib Dr, Bethesda, MD 20892 USA. NR 132 TC 752 Z9 771 U1 18 U2 135 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD JUN PY 2001 VL 2 IS 6 BP 444 EP 456 DI 10.1038/35073068 PG 13 WC Cell Biology SC Cell Biology GA 440FP UT WOS:000169165500016 PM 11389468 ER PT J AU Becker, KG AF Becker, KG TI The sharing of cDNA microarray data SO NATURE REVIEWS NEUROSCIENCE LA English DT Editorial Material ID GENE-EXPRESSION; TRANSCRIPTIONAL PROGRAM AB During the initial development of microarrays, much discussion revolved around the technology itself. The discussion has now shifted to data analysis and data sharing. There is great interest in the sharing of cDNA microarray data, but several issues related to format, quality and validation will need to be resolved before microarray data can be meaningfully integrated into other molecular databases. C1 NIA, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. RP Becker, KG (reprint author), NIA, Ctr Gerontol Res, NIH, Room 4-D16,Nathan Shock Dr, Baltimore, MD 21224 USA. OI Becker, Kevin/0000-0002-6794-6656 NR 14 TC 24 Z9 25 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD JUN PY 2001 VL 2 IS 6 BP 438 EP 440 DI 10.1038/35077580 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 440FN UT WOS:000169165400021 PM 11389478 ER PT J AU Schilling, G Jinnah, HA Gonzales, V Coonfield, ML Kim, Y Wood, JD Price, DL Li, XJ Jenkins, N Copeland, N Moran, T Ross, CA Borchelt, DR AF Schilling, G Jinnah, HA Gonzales, V Coonfield, ML Kim, Y Wood, JD Price, DL Li, XJ Jenkins, N Copeland, N Moran, T Ross, CA Borchelt, DR TI Distinct behavioral and neuropathological abnormalities in transgenic mouse models of HD and DRPLA SO NEUROBIOLOGY OF DISEASE LA English DT Article ID DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY; NEURONAL INTRANUCLEAR INCLUSIONS; SPINOCEREBELLAR ATAXIA TYPE-6; EXPANDED CAG REPEAT; HUNTINGTONS-DISEASE; NUCLEAR-LOCALIZATION; NEUROLOGICAL PHENOTYPE; MUTANT HUNTINGTIN; STRIATAL NEURONS; GENE-PRODUCT AB Huntington's disease (HD) and Dentatorubral and pallidoluysian atrophy (DRPLA) are autosomal dominant, neurodegenerative disorders caused by the expansion of polyglutamine tracts in their respective proteins, huntingtin and atrophin-1. We have previously generated mouse models of these disorders, using transgenes expressed via the prion protein promoter. Here, we report the first direct comparison of abnormalities in these models. The Ho mice show abbreviated lifespans (4-6 months), hypoactivity, and mild impairment of motor skills. The DRPLA mice show severe tremors, are hyperactive, and are profoundly uncoordinated. Neuropathological analyses reveal that the distribution of diffuse nuclear immunolabeling and neuronal intranuclear inclusions (NII's), in the CNS of both models, was remarkably similar. Cytoplasmic aggregates of huntingtin were the major distinguishing neuropathological feature of the Ho mice; mutant atrophin-1 accumulated/aggregated only in the nucleus. We suggest that the distinct behavioral and neuropathological phenotypes in these mice reflect differences in the way these mutant proteins perturb neuronal function. (C) 2001 Academic Press. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Emory Univ, Sch Med, Dept Genet, Atlanta, GA 30322 USA. NCI, Frederick Canc Res & Dev Ctr, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Schilling, G (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RI Wood, Jonathan/A-5060-2009; Ross, Christopher/H-8395-2013; Kim, Yujin/P-4270-2014 OI Kim, Yujin/0000-0003-4290-0974 FU NINDS NIH HHS [NS38144, NS16375, NS34172] NR 53 TC 34 Z9 35 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUN PY 2001 VL 8 IS 3 BP 405 EP 418 DI 10.1006/nbdi.2001.0385 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 445LM UT WOS:000169459000004 PM 11442350 ER PT J AU Pedersen, WA McCullers, D Culmsee, C Haughey, NJ Herman, JP Mattson, MP AF Pedersen, WA McCullers, D Culmsee, C Haughey, NJ Herman, JP Mattson, MP TI Corticotropin-releasing hormone protects neurons against insults relevant to the pathogenesis of Alzheimer's disease SO NEUROBIOLOGY OF DISEASE LA English DT Article DE apoptosis; calcium; cyclic AMP; glucocorticoid; glutamate; lipid peroxidation; stress ID AMYLOID BETA-PEPTIDE; IMPAIRED STRESS-RESPONSE; FOCAL CEREBRAL-ISCHEMIA; PITUITARY-ADRENAL AXIS; TRANSGENIC MICE; PARAVENTRICULAR NUCLEUS; RECEPTOR ANTAGONIST; LIPID-PEROXIDATION; PRECURSOR PROTEIN; OXIDATIVE STRESS AB We previously reported that mice over-expressing the human amyloid precursor protein gene with the double Swedish mutation of familial Alzheimer's disease (mtAPP), which exhibit progressive deposition of amyloid beta -peptide in hippocampal and cortical brain regions, have an impaired ability to maintain a sustained glucocorticoid response to stress. Corticotropin releasing hormone (CRH), which initiates neuroendocrine responses to stress by activating the hypothalamic-pituitary-adrenal (HPA) axis, is expressed in brain regions prone to degeneration in Alzheimer's disease. We therefore tested the hypothesis that CRH can modify neuronal vulnerability to amyloid beta -peptide toxicity. In primary neuronal culture, CRH was protective against cell death caused by an amyloid-beta peptide, an effect that was blocked by a CRH receptor antagonist and by an inhibitor of cyclic AMP-dependent protein kinase. The increased resistance of CRH-treated neurons to amyloid toxicity was associated with stabilization of cellular calcium homeostasis. Moreover, CRH protected neurons against death caused by lipid peroxidation and the excitotoxic neurotransmitter glutamate. The level of mRNA encoding CRH was unchanged in mtAPP mouse brain, whereas the levels of mRNAs encoding glucocorticoid and mineralocorticoid receptors were subtly altered. Our results suggest that disturbances in HPA axis function can occur independently of alterations in CRH mRNA levels in Alzheimer's disease brain and further suggest an additional role for CRH in protecting neurons against cell death. (C) 2001 Academic Press. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY 40536 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Pedersen, WA (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012; Herman, James/D-4960-2015 OI Herman, James/0000-0003-3571-2406 NR 64 TC 69 Z9 71 U1 1 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUN PY 2001 VL 8 IS 3 BP 492 EP 503 DI 10.1006/nbdi.2001.0395 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 445LM UT WOS:000169459000011 PM 11442356 ER PT J AU Pierpaoli, C Barnett, A Pajevic, S Chen, R Penix, L Virta, A Basser, P AF Pierpaoli, C Barnett, A Pajevic, S Chen, R Penix, L Virta, A Basser, P TI Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture SO NEUROIMAGE LA English DT Article DE diffusion; tensor; MRI; anisotropy; white matter; Wallerian; degeneration; brain; human ID HUMAN BRAIN; TENSOR MRI; IN-VIVO; ANISOTROPY; ARTIFACTS; TISSUES; IMAGES AB This study investigates water diffusion changes in Wallerian degeneration. We measured indices derived from the diffusion tensor (DT) and TB-weighted signal intensities in the descending motor pathways of patients with small chronic lacunar infarcts of the posterior limb of the internal capsule on one side. We compared these measurements in the healthy and lesioned sides at different levels in the brainstem caudal to the primary lesion. We found that secondary white matter degeneration is revealed by a large reduction in diffusion anisotropy only in regions where fibers are arranged in isolated bundles of parallel fibers, such as in the cerebral peduncle. In regions where the degenerated pathway crosses other tracts, such as in the rostral pens, paradoxically there is almost no change in diffusion anisotropy, but a significant change in the measured orientation of fibers. The trace of the diffusion tensor is moderately increased in all affected regions. This allows one to differentiate secondary and primary fiber loss where the increase in trace is considerably higher. We show that DT-MRI is more sensitive than TS-weighted MRI in detecting Wallerian degeneration. Significant diffusion abnormalities are observed over the entire trajectory of the affected pathway in each patient. This finding suggests that mapping degenerated pathways noninvasively with DT-MRI is feasible. However, the interpretation of water diffusion data is complex and requires a priori information about anatomy and architecture of the pathway under investigation. In particular, our study shows that in regions where fibers cross, existing DT-MRI-based fiber tractography algorithms may lead to erroneous conclusion about brain connectivity. C1 NICHHD, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Pierpaoli, C (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. RI Pierpaoli, Carlo/E-1672-2011; Chen, Robert/B-3899-2009; Basser, Peter/H-5477-2011 OI Chen, Robert/0000-0002-8371-8629; NR 38 TC 572 Z9 590 U1 1 U2 11 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 BP 1174 EP 1185 DI 10.1006/nimg.2001.0765 PN 1 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 438MA UT WOS:000169056500023 PM 11352623 ER PT J AU Beauchamp, MS Lee, KE Haxby, JV Martin, A AF Beauchamp, MS Lee, KE Haxby, JV Martin, A TI Cortical responses to visual motion: complex human and tool motion compared with simple radial gratings SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S860 EP S860 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300859 ER PT J AU Bellgowan, PSF Saad, Z Bandettini, P AF Bellgowan, PSF Saad, Z Bandettini, P TI Voxel-wise estimation of hemodynamic onset delays during a lexical decision task SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RI Bandettini, Peter/F-5871-2012 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S503 EP S503 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300504 ER PT J AU Berman, K Schmidt, P Meyer-Lindenberg, A Dixit, N Kohn, PD Danaceau, R Weinberger, D Rubinow, D AF Berman, K Schmidt, P Meyer-Lindenberg, A Dixit, N Kohn, PD Danaceau, R Weinberger, D Rubinow, D TI The gonadal steroid hormones, estrogen and progesterone, affect functional connectivity and hippocampal function during working memory SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Integrat Neuroimaging Unit, Clin Brain Disorders Branch, NIH,IRP, Bethesda, MD 20892 USA. NIMH, Behav Endocrinol Branch, NIH, IRP, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1026 EP S1026 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301025 ER PT J AU Birn, RM Bandettini, PA AF Birn, RM Bandettini, PA TI Estimated BOLD impulse response depends on stimulus ON/OFF ratio SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S971 EP S971 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300970 ER PT J AU Blumenthal, J Molloy, E Liu, T Jeffries, NO Zijdenbos, A Rapoport, J Giedd, JN AF Blumenthal, J Molloy, E Liu, T Jeffries, NO Zijdenbos, A Rapoport, J Giedd, JN TI Gender differences in the relationship between cognition and corpus callosum in healthy children and adolescents SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. NINDS, Biostat Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S384 EP S384 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300385 ER PT J AU Bodurka, J Bandettini, PA AF Bodurka, J Bandettini, PA TI Toward direct mapping of neuronal activity: MRI detection of ultra weak transient magnetic field changes. SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S964 EP S964 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300963 ER PT J AU Chung, MK Worsley, KJ Robbins, S Paus, T Taylor, J Giedd, JN Rapoport, JL Evans, AC AF Chung, MK Worsley, KJ Robbins, S Paus, T Taylor, J Giedd, JN Rapoport, JL Evans, AC TI Statistical analysis of cortical surface area change, with are application to brain growth SO NEUROIMAGE LA English DT Meeting Abstract C1 McGill Univ, Dept Math & Stat, Montreal, PQ, Canada. Montreal Neurol Inst, Montreal, PQ, Canada. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 4 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S96 EP S96 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300097 ER PT J AU Cox, R Saad, ZS AF Cox, R Saad, ZS TI Direct estimation of DOF in FMRI regression analyses SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S101 EP S101 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300102 ER PT J AU de Zwart, JA Kellman, P van Gelderen, P Duyn, JH AF de Zwart, JA Kellman, P van Gelderen, P Duyn, JH TI On the potential of sensitivity encoded EPI for BOLD functional brain imaging SO NEUROIMAGE LA English DT Meeting Abstract C1 NINDS, LFMI, Bethesda, MD 20892 USA. NHLBI, LCE, NIH, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010 NR 5 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S7 EP S7 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300008 ER PT J AU Dong, Y Simon, S Berman, S Miotto, K Woods, R Mazziotta, JC Mandelken, M Rawson, R Ling, W London, ED AF Dong, Y Simon, S Berman, S Miotto, K Woods, R Mazziotta, JC Mandelken, M Rawson, R Ling, W London, ED TI Regional cerebral metabolic deficits in methamphetamine abusers SO NEUROIMAGE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Integrated Subst Abuse Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Radiol, Los Angeles, CA 90024 USA. NIDA, Brain Imaging Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1043 EP S1043 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301042 ER PT J AU Dreher, JC Kohn, PD Berman, K AF Dreher, JC Kohn, PD Berman, K TI Neural basis of backward inhibition during task switching SO NEUROIMAGE LA English DT Meeting Abstract ID PREFRONTAL CORTEX C1 NIMH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S311 EP S311 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300312 ER PT J AU Ebmeier, K Doris, A Glabus, M Belton, E Marshall, I Wardlaw, J AF Ebmeier, K Doris, A Glabus, M Belton, E Marshall, I Wardlaw, J TI Structural magnetic resonance imaging in poor prognosis bipolar illness - a voxel based study SO NEUROIMAGE LA English DT Meeting Abstract C1 Univ Edinburgh, Dept Psychiat, Edinburgh EH8 9YL, Midlothian, Scotland. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1045 EP S1045 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301044 ER PT J AU Ebmeier, K Prohovnik, I Pupi, A Rodriguez, G Nobili, F Migneco, O Koulibali, M Herholz, K Scheidhauer, K Glabus, M AF Ebmeier, K Prohovnik, I Pupi, A Rodriguez, G Nobili, F Migneco, O Koulibali, M Herholz, K Scheidhauer, K Glabus, M TI Using SPM as a diagnostic help with HMPAO-SPECT in Alzheimer's disease SO NEUROIMAGE LA English DT Meeting Abstract C1 Univ Edinburgh, Edinburgh, Midlothian, Scotland. Yale Univ, New Haven, CT 06520 USA. Univ Florence, I-50121 Florence, Italy. Univ Genoa, I-16126 Genoa, Italy. Univ Nice, Nice, France. Max Planck Inst Neurol, Cologne, Germany. Tech Univ Munich, D-8000 Munich, Germany. NIMH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1044 EP S1044 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301043 ER PT J AU Fera, F Mattay, V Tessitore, A Callicott, J Hariri, A Das, S Weinberger, D AF Fera, F Mattay, V Tessitore, A Callicott, J Hariri, A Das, S Weinberger, D TI Age-related changes in human motor function: A BOLD fMRI study SO NEUROIMAGE LA English DT Meeting Abstract ID BRAIN C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1164 EP S1164 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301163 ER PT J AU Fong, G Knutson, B Adams, C Hommer, D AF Fong, G Knutson, B Adams, C Hommer, D TI Event-related FMRI reveals distinct neural correlates of reward anticipation versus feedback SO NEUROIMAGE LA English DT Meeting Abstract ID VISUALIZATION C1 NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S399 EP S399 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300400 ER PT J AU Furey, ML Tanskanen, T Beauchamp, MB Avikainen, S Haxby, JV Hari, R AF Furey, ML Tanskanen, T Beauchamp, MB Avikainen, S Haxby, JV Hari, R TI Temporal characteristics of selective attention to faces and houses: A MEG study SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Lab Brain & Cognit 1, NIH, Bethesda, MD 20892 USA. Helsinki Univ Technol, Low Temp Lab 2, Brain Res Unit, FIN-02015 HUT, Finland. RI Tanskanen, Topi/A-6123-2011; Hari, Riitta/J-1880-2012 OI Hari, Riitta/0000-0002-3142-2703 NR 0 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S316 EP S316 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300317 ER PT J AU Garrido, GEJ Furuie, SS Buchpiguel, CA Bottino, CMC Glabus, MF Cid, CG Camargo, CHP Castro, CC Busatto, GF AF Garrido, GEJ Furuie, SS Buchpiguel, CA Bottino, CMC Glabus, MF Cid, CG Camargo, CHP Castro, CC Busatto, GF TI Frontal-hippocampal connectivity during cognitive activation in Alzheimer's disease evaluated with SPECT SO NEUROIMAGE LA English DT Meeting Abstract C1 Univ Sao Paulo, Sch Med, Inst Heart InCor, Div Informat, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Fac Med, Dept Radiol, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Fac Med, Dept Psychiat, BR-05508 Sao Paulo, Brazil. NIMH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RI Buchpiguel, Carlos/C-3774-2012; Castro, Claudio/J-3139-2012; Busatto, Geraldo/D-4431-2009; Furuie, Sergio/A-7219-2008 OI Buchpiguel, Carlos/0000-0003-0956-2790; Castro, Claudio/0000-0002-3531-4232; Furuie, Sergio/0000-0002-1557-3018 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S673 EP S673 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300673 ER PT J AU Giedd, J Castellanos, X Blumenthal, O Molloy, E Clasen, L Jeffries, N Zijdenbos, A Rapoport, J AF Giedd, J Castellanos, X Blumenthal, O Molloy, E Clasen, L Jeffries, N Zijdenbos, A Rapoport, J TI Cerebellum: Unique developmental morphometric characteristics during childhood and adolescence SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NINDS, Biostat Branch, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1304 EP S1304 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301303 ER PT J AU Glabus, MF Horwitz, B Kohn, PD Meyer-Lindenberg, A Weinberger, D Berman, KF AF Glabus, MF Horwitz, B Kohn, PD Meyer-Lindenberg, A Weinberger, D Berman, KF TI Single-subject analysis of 2-back working memory using SEM SO NEUROIMAGE LA English DT Meeting Abstract ID FMRI; PET C1 NIMH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Natl Inst Deafness & Commun Disorders, Language Sect, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S676 EP S676 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300676 ER PT J AU Gobbini, MI Martin, A Haxby, JV AF Gobbini, MI Martin, A Haxby, JV TI Altered responses to faces due to experimentally-induced familiarity SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S408 EP S408 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300409 ER PT J AU Gollub, R Aquino, P Kong, J Gracely, R Kramer, T Dershwitz, M AF Gollub, R Aquino, P Kong, J Gracely, R Kramer, T Dershwitz, M TI Reliable intensity and laterality encoding of noxious pressure and heat pain in cortex within single subjects using 1.5T fMRI SO NEUROIMAGE LA English DT Meeting Abstract ID SURFACE-BASED ANALYSIS; RATIO SCALES; DESCRIPTORS C1 MGH Dept Psychiat, Boston, MA USA. MGH NMR Ctr, Boston, MA USA. NIDR, Bethesda, MD 20892 USA. UMass Mem Med Ctr, Dept Anesthesiol, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1173 EP S1173 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301172 ER PT J AU Hanakawa, T Immisch, I Toma, K Dimyan, M Hallett, M AF Hanakawa, T Immisch, I Toma, K Dimyan, M Hallett, M TI Shared and segregated brain areas for motor execution and imagery SO NEUROIMAGE LA English DT Meeting Abstract C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD USA. RI Dimyan, Michael/B-1715-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1180 EP S1180 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301179 ER PT J AU Hariri, AR Mattay, VS Tessitore, A Fera, F Smith, WG Das, S Weinberger, DR AF Hariri, AR Mattay, VS Tessitore, A Fera, F Smith, WG Das, S Weinberger, DR TI Effects of dextroamphetamine on neural circuits subserving emotion processing SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011 NR 3 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S416 EP S416 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300417 ER PT J AU Haxby, JV Gobbini, MI Furey, ML Ishai, A Pietrini, P AF Haxby, JV Gobbini, MI Furey, ML Ishai, A Pietrini, P TI Distinct, overlapping representations of faces and multiple categories of objects in ventral temporal cortex SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Univ Pisa, Pisa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S891 EP S891 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300890 ER PT J AU Hoffman, EA Phillips, ML Haxby, JV AF Hoffman, EA Phillips, ML Haxby, JV TI Dynamic changes in facial configuration evoke differential strengths of activity in face-responsive neural regions SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Inst Psychiat, London, England. GKT Sch Med, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1316 EP S1316 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301315 ER PT J AU Husain, FT Tagamets, MA Braun, AR Horwitz, B AF Husain, FT Tagamets, MA Braun, AR Horwitz, B TI Large-scale computational model for simulating PET/fMRI studies of auditory pattern recognition SO NEUROIMAGE LA English DT Meeting Abstract C1 NIDCD, Language Sect, NIH, Bethesda, MD USA. Univ Maryland, MPRC, Baltimore, MD 21201 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1307 EP S1307 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301306 ER PT J AU Immisch, I Waldvogel, D van Gelderen, P Hallett, M AF Immisch, I Waldvogel, D van Gelderen, P Hallett, M TI The role of the medial wall and its anatomical variations for bimanual anti-phase and in-phase movements SO NEUROIMAGE LA English DT Meeting Abstract ID COORDINATION C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Tech Univ Munich, Neurol Klin, D-8000 Munich, Germany. NINDS, In Vivo NMR Res Ctr, NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1194 EP S1194 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301193 ER PT J AU Japee, S Meyer-Lindenberg, A Dixit, N Verchinski, B Kohn, P Egan, M Bigelow, L Callicott, J Bertolino, A Mattay, V Berman, K Weinberger, D AF Japee, S Meyer-Lindenberg, A Dixit, N Verchinski, B Kohn, P Egan, M Bigelow, L Callicott, J Bertolino, A Mattay, V Berman, K Weinberger, D TI A method for template-based volumetry: Investigation of gender and age-related structural differences in schizophrenic patients, their siblings and normal controls SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, IRP, Unit Integrat Neuroimaging, Clin Brain Disorders Branch,NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S162 EP S162 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300163 ER PT J AU Job, D Whalley, H Glabus, M Johnstone, E Lawrie, S AF Job, D Whalley, H Glabus, M Johnstone, E Lawrie, S TI Voxel Based Morphometry of Grey matter reductions in schizophrenia and the impact of generic versus specific normalisation templates. SO NEUROIMAGE LA English DT Meeting Abstract C1 Univ Edinburgh, Dept Psychiat, Edinburgh EH8 9YL, Midlothian, Scotland. NIMH, NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1061 EP S1061 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301060 ER PT J AU Keller, A Vaituzis, AC Tran, L Jeffries, NO Blumenthal, J Giedd, JN Rapoport, JL Castellanos, FX AF Keller, A Vaituzis, AC Tran, L Jeffries, NO Blumenthal, J Giedd, JN Rapoport, JL Castellanos, FX TI A longitudinal MRI study of posterior inferior vermis volume in Childhood Onset Schizophrenia (COS) SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 1 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1065 EP S1065 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301064 ER PT J AU Kelley, D Birn, R Saad, Z Bandettini, P AF Kelley, D Birn, R Saad, Z Bandettini, P TI Voxel - Wise balloon model parameter estimation from BOLD time series SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. RI Bandettini, Peter/F-5871-2012 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S990 EP S990 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300989 ER PT J AU Knutson, B Adams, C Fong, G Walker, J Hommer, D AF Knutson, B Adams, C Fong, G Walker, J Hommer, D TI Parametric FMRI confirms selective recruitment of nucleus accumbens during anticipation of monetary reward SO NEUROIMAGE LA English DT Meeting Abstract ID VISUALIZATION C1 NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S430 EP S430 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300431 ER PT J AU Kumari, V Gray, J ffytche, D Mitterschiffthaler, M Das, M Zachariah, E Vythelingum, G Williams, S Coppola, R Goldberg, T Sharma, T AF Kumari, V Gray, J ffytche, D Mitterschiffthaler, M Das, M Zachariah, E Vythelingum, G Williams, S Coppola, R Goldberg, T Sharma, T TI Cognitive effects of nicotine in man: A functional MRI investigation SO NEUROIMAGE LA English DT Meeting Abstract C1 Inst Psychiat, Dept Psychol, London, England. Inst Psychiat, Neuroimaging Res Grp, London, England. NIMH, Clin Brain Disorders Unit, Bethesda, MD 20892 USA. RI Williams, Steve/D-6979-2011 OI Williams, Steve/0000-0003-4299-1941 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S696 EP S696 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300696 ER PT J AU Liu, H Blumenthal, J Jeffries, N Vaituzis, C Zijdenbos, A Rapoport, J Giedd, J AF Liu, H Blumenthal, J Jeffries, N Vaituzis, C Zijdenbos, A Rapoport, J Giedd, J TI A fully automatic method for human corpus callosum MRI analysis SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NINDS, Biostat Branch, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2T5, Canada. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S188 EP S188 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300189 ER PT J AU Lotze, M Braun, C Birbaumer, N Cohen, LG AF Lotze, M Braun, C Birbaumer, N Cohen, LG TI Differential enhancement of motor excitability with active and passive motor training SO NEUROIMAGE LA English DT Meeting Abstract C1 Univ Tubingen, Inst Med Psychol & Behav Biol, Tubingen, Germany. Dept Gen Psychol, Padua, Italy. NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RI Braun, Christoph/E-4561-2010; Braun, Christoph/J-4160-2014 OI Braun, Christoph/0000-0002-7836-4010; Braun, Christoph/0000-0002-7836-4010 NR 1 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1217 EP S1217 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301216 ER PT J AU Luo, YJ Jiang, Y Caggiano, H Parasuraman, R AF Luo, YJ Jiang, Y Caggiano, H Parasuraman, R TI Event-related brain potentials are correlated with perception of visual motion sweeps SO NEUROIMAGE LA English DT Meeting Abstract C1 Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China. Catholic Univ Amer, Cognit Sci Lab, Washington, DC 20064 USA. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S908 EP S908 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300907 ER PT J AU McKenna, M Gutierrez, E Ungerleider, L Pessoa, L AF McKenna, M Gutierrez, E Ungerleider, L Pessoa, L TI Attention increases selectivity to emotional stimuli SO NEUROIMAGE LA English DT Meeting Abstract ID FACIAL EXPRESSIONS; HUMAN AMYGDALA C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S443 EP S443 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300444 ER PT J AU Meyer-Lindenberg, A Miletich, R Kohn, PD Esposito, G Carson, R Quarantelli, M Weinberger, D Berman, K AF Meyer-Lindenberg, A Miletich, R Kohn, PD Esposito, G Carson, R Quarantelli, M Weinberger, D Berman, K TI Presynaptic dopamine function and cognitive activation in schizophrenia SO NEUROIMAGE LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. RI Quarantelli, Mario/A-6154-2009; Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1072 EP S1072 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301071 ER PT J AU Molloy, E Blumenthal, J Giedd, JN Lin, H Jeffries, NO Zijdenbos, A Rapoport, JL AF Molloy, E Blumenthal, J Giedd, JN Lin, H Jeffries, NO Zijdenbos, A Rapoport, JL TI The relationship between brain morphometry and cognitive abilities in healthy pediatric monozygotic twins SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NINDS, Biostat Branch, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S447 EP S447 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300448 ER PT J AU Momenan, R Kerich, M Hommer, D AF Momenan, R Kerich, M Hommer, D TI Detection and computation of mesial and orbital cortical volumes in frontal lobe SO NEUROIMAGE LA English DT Meeting Abstract C1 NIAAA, Sect Brain Electrophysiol & Imaging, NIH, Bethesda, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S205 EP S205 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300206 ER PT J AU Mulert, C Gallinat, J Dorn, H Herrmann, W Winterer, G AF Mulert, C Gallinat, J Dorn, H Herrmann, W Winterer, G TI The relationship between the auditory evoked N1 potential, reaction time and anterior cingulate cortex (ACC) activity SO NEUROIMAGE LA English DT Meeting Abstract C1 Free Univ Berlin, Dept Psychiat, Lab Clin Psychophysiol, D-1000 Berlin, Germany. Univ Munich, Dept Psychiat, Neurophysiol Lab, D-8000 Munich, Germany. NIMH, Clin Brain Disorder Branch, NIH, Bethesda, MD 20892 USA. RI Mulert, Christoph/F-2576-2012 NR 4 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S336 EP S336 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300337 ER PT J AU Pessoa, L Gutierrez, E Bandettini, PA Ungerleider, L AF Pessoa, L Gutierrez, E Bandettini, PA Ungerleider, L TI Neural correlates of visual working memory: BOLD predicts task performance SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S720 EP S720 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300720 ER PT J AU Petridou, N Bodurka, J Bandettini, PA AF Petridou, N Bodurka, J Bandettini, PA TI Modeling of MRI fractional signal changes and phase shifts induced by cortical neuronal activity SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, LBC, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1311 EP S1311 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301310 ER PT J AU Rio, D Rawlings, R Knutson, B Hommer, D AF Rio, D Rawlings, R Knutson, B Hommer, D TI Statistical estimation of the hemodynamic response function by application of a linear time invariant model in the fourier domain to functional magnetic resonance data SO NEUROIMAGE LA English DT Meeting Abstract C1 NIAAA, Sect Brain Electrophysiol & Imaging, Clin Studies Lab, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S234 EP S234 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300235 ER PT J AU Saad, ZS Ropella, KM DeYoe, EA Bandettini, PA AF Saad, ZS Ropella, KM DeYoe, EA Bandettini, PA TI Extensive expansion of FMRI activation volume with scan averaging SO NEUROIMAGE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Marquette Univ, Milwaukee, WI 53233 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1002 EP S1002 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301001 ER PT J AU Senior, C David, A AF Senior, C David, A TI Pictures moving in the mind: Higher level cognition in V5? SO NEUROIMAGE LA English DT Meeting Abstract C1 Inst Psychiat, London, England. NIMH, Lab Brain & Cognit, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S936 EP S936 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300935 ER PT J AU Shen, J Rio, D Momenan, R Knutson, B Rawlings, B Moon, K Woltz, L Hommer, D AF Shen, J Rio, D Momenan, R Knutson, B Rawlings, B Moon, K Woltz, L Hommer, D TI Differential brain activation response to different frequency of electroacupuncture SO NEUROIMAGE LA English DT Meeting Abstract C1 NIAAA, LCS, NIH, Bethesda, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S937 EP S937 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300936 ER PT J AU Tessitore, A Mattay, VS Hariri, AR Fera, F Callicott, JH Hyde, T Chase, T Weinberger, DR AF Tessitore, A Mattay, VS Hariri, AR Fera, F Callicott, JH Hyde, T Chase, T Weinberger, DR TI Dopaminergic modulation of the neocortical network that subserves facial affect recognition: A study in patients with Parkinson's disease SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011 NR 5 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S847 EP S847 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300846 ER PT J AU Thompson, PM Vidal, C Giedd, JN Blumenthal, J Gochman, P Nicolson, R Toga, AW Rapoport, JL AF Thompson, PM Vidal, C Giedd, JN Blumenthal, J Gochman, P Nicolson, R Toga, AW Rapoport, JL TI Mapping adolescent brain change reveals dynamic profile of accelerated gray matter loss in childhood-onset schizophrenia SO NEUROIMAGE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab Neuro Imaging,Brain Mapping Div, Los Angeles, CA 90024 USA. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Nicolson, Robert/E-4797-2011; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-2002-8978 NR 3 TC 2 Z9 2 U1 2 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1105 EP S1105 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301104 ER PT J AU Verchinski, BA Elvevaag, B Goldberg, TE Mattay, VS Weissbrod, P Coppola, R Gallicott, JH Winberger, D AF Verchinski, BA Elvevaag, B Goldberg, TE Mattay, VS Weissbrod, P Coppola, R Gallicott, JH Winberger, D TI Memory processing during encoding and retrieval of words revealed by fMRI. SO NEUROIMAGE LA English DT Meeting Abstract C1 NCI, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S756 EP S756 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300755 ER PT J AU Vidal, C Rapoport, JL Giedd, JN Gochman, P Blumenthal, J Nicolson, R Toga, AW Thompson, PM AF Vidal, C Rapoport, JL Giedd, JN Gochman, P Blumenthal, J Nicolson, R Toga, AW Thompson, PM TI Dynamic patterns of accelerated gray matter loss are linked with clinical and cognitive change in childhood-onset schizophrenia SO NEUROIMAGE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Brain Mapping Div,Lab Neuro Imaging, Los Angeles, CA USA. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Nicolson, Robert/E-4797-2011; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 3 TC 0 Z9 0 U1 2 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1113 EP S1113 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301112 ER PT J AU Wang, A Dapretto, M Hariri, A Sigman, M Bookheimer, SY AF Wang, A Dapretto, M Hariri, A Sigman, M Bookheimer, SY TI Processing affective and linguistic prosody in autism: An fMRI study SO NEUROIMAGE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Brain Mapping Ctr, Los Angeles, CA 90024 USA. NIMH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. NR 0 TC 4 Z9 4 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S621 EP S621 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300622 ER PT J AU Weisberg, J Martin, A AF Weisberg, J Martin, A TI Different patterns of neural activity associated with social and mechanical knowledge SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S485 EP S485 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300486 ER PT J AU Xu, B Gaillard, W Grafman, J Spanaki, M Ishii, K Balsamo, L Pugliese, M Theodore, W AF Xu, B Gaillard, W Grafman, J Spanaki, M Ishii, K Balsamo, L Pugliese, M Theodore, W TI Asymmetrical coupling of neural activities in the frontal and temporal regions during phonological and semantic processing of written words SO NEUROIMAGE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S630 EP S630 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300631 ER PT J AU Ye, FQ St Lawrence, K Mattay, VS Frank, JA Weinberger, DR McLaughlin, AC AF Ye, FQ St Lawrence, K Mattay, VS Frank, JA Weinberger, DR McLaughlin, AC TI Inter-session variation in arterial spin tagging studies of cognitive activation SO NEUROIMAGE LA English DT Meeting Abstract C1 NIMH, CBDB, NIH, Bethesda, MD 20892 USA. NIH, LDRR, CC, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S288 EP S288 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300289 ER PT J AU Dickerman, RD Jaikumar, S AF Dickerman, RD Jaikumar, S TI Secondary partial empty sella syndrome in an elite bodybuilder SO NEUROLOGICAL RESEARCH LA English DT Article DE anabolic steroids; axis; negative feedback; hormones; intracranial pressure; weightlifting ID SLIDING HIATAL-HERNIA; STEROID PULSE THERAPY; PRESSURE; HEMORRHAGE AB The pituitary gland is a hormone-responsive gland and is known to vary in size depending on the hormonal status of the patient a nd the multifaceted positive and negative feedback hypothalamic-pituitary-gonadal axis. Partial empty sella syndrome with an atrophied pituitary gland is seen in primary neuroendocrinopathies such as growth hormone deficiency, primary hypothyroidism, central diabetes insipidus and hypogonadism. Partial empty sella has also been shown to occur in patients with elevations in intracranial pressure. Secondary partial empty sella syndrome with significant pituitary gland atrophy from negative feedback inhibition of long-term exogenous hormonal use has not been previously reported. We are reporting on a case of partial empty sella syndrome occurring in an elite bodybuilder with a long history of exogenous abuse of growth hormone, testosterone and thyroid hormone. The pathophysiological mechanisms of secondary partial empty sells syndrome from exogenous hormone use and the possibility for elevations in intracranial pressure contributing to this syndrome will be discussed. C1 NINDS, NIH, Surg Neurol Branch, Bethesda, MD 20892 USA. RP Dickerman, RD (reprint author), Long Isl Jewish Med Ctr, Dept Surg, Div Neurosurg, 270-05 76th Ave, New Hyde Park, NY 11042 USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU FOREFRONT PUBL GROUP PI WILTON PA C/O MARY J RAWLINS, 5 RIVER RD, STE 113, WILTON, CT 06897 USA SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD JUN PY 2001 VL 23 IS 4 BP 336 EP 338 DI 10.1179/016164101101198712 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 443RX UT WOS:000169355100008 PM 11428511 ER PT J AU Yoshida, K Watanabe, D Ishikane, H Tachibana, M Pastan, I Nakanishi, S AF Yoshida, K Watanabe, D Ishikane, H Tachibana, M Pastan, I Nakanishi, S TI A key role of starburst amacrine cells in originating retinal directional selectivity and optokinetic eye movement SO NEURON LA English DT Article ID GANGLION-CELLS; RABBIT RETINA; MAMMALIAN RETINA; RAT RETINA; GABA; IMMUNOREACTIVITY; ACETYLCHOLINE; ORGANIZATION; EXPRESSION; DETECTORS AB The directional selectivity of retinal ganglion cell responses represents a primitive pattern recognition that operates within a retinal neural circuit. The cellular origin and mechanism of directional selectivity were investigated by selectively eliminating retinal starburst amacrine cells, using immunotoxin-mediated cell targeting techniques. Starburst cell ablation in the adult retina abolished not only directional selectivity of ganglion cell responses but also an optokinetic eye reflex derived by stimulus movement. Starburst cells therefore serve as the key element that discriminates the direction of stimulus movement through integrative synaptic transmission and play a pivotal role in information processing that stabilizes image motion. C1 Kyoto Univ, Fac Med, Dept Biol Sci, Kyoto 6068501, Japan. Kyoto Univ, Grad Sch Biostudies, Dept Mol & Syst Biol, Kyoto 6068501, Japan. Univ Tokyo, Grad Sch Humanities & Sociol, Dept Psychol, Tokyo 1130033, Japan. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Nakanishi, S (reprint author), Kyoto Univ, Fac Med, Dept Biol Sci, Kyoto 6068501, Japan. NR 35 TC 203 Z9 209 U1 4 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN PY 2001 VL 30 IS 3 BP 771 EP 780 DI 10.1016/S0896-6273(01)00316-6 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 446HY UT WOS:000169508900017 PM 11430810 ER PT J AU Hirasawa, M Cho, A Sreenath, T Sauer, B Julien, JP Kulkarni, AB AF Hirasawa, M Cho, A Sreenath, T Sauer, B Julien, JP Kulkarni, AB TI Neuron-specific expression of Cre recombinase during the late phase of brain development SO NEUROSCIENCE RESEARCH LA English DT Article DE Cre recombinase; neurofilament heavy subunit; transgenic mouse ID SITE-SPECIFIC RECOMBINATION; TRANSGENIC MICE; DNA RECOMBINATION; NERVOUS-SYSTEM; MOUSE-BRAIN; GENE; CELLS; BACTERIOPHAGE-P1; DISRUPTION; SUBUNIT AB Gene targeting to disrupt gene expression in a temporal and spatial manner in a specific tissue using Cre recombinase-mediated gene inactivation has been proven to be useful to study in vivo gene function. To delete genes specifically in neurons during the late phase of brain development, we have generated transgenic mouse lines that express Cre recombinase under the control of the murine neurofilament-H (mNF-H) gene promoter. In this study, we report that one of these mouse lines expresses Cre recombinase specifically in the neurons of the brain and spinal cord during the late stage of their development. The transgenic line displays specific excision of the loxP-flanked gene in the neurons just after embryonic day 18.5 (E.18.5). which coincides with the later phase of brain maturation including spinal cord and olfactory bulb area. This mNF-H-cre transgenic mouse line will be valuable for studying in vivo functions of neuron-specific genes, particularly: defining their precise roles in the mature nervous system using conditional gene targeting strategies. (C) 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. C1 Natl Inst Dental & Craniofacial Res, Funct Genom Unit, NIH, Bethesda, MD 20892 USA. Natl Inst Dental & Craniofacial Res, Gene Targeting Facil, NIH, Bethesda, MD 20892 USA. Oklahoma Med Res Fdn, Dev Biol Programme, Oklahoma City, OK 73104 USA. McGill Univ, Montreal Gen Hosp, Inst Res, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada. RP Kulkarni, AB (reprint author), Natl Inst Dental & Craniofacial Res, Funct Genom Unit, NIH, Room 529,Bldg 30,30 Convent Dr, Bethesda, MD 20892 USA. NR 33 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PD JUN PY 2001 VL 40 IS 2 BP 125 EP 132 DI 10.1016/S0168-0102(01)00216-4 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 443LX UT WOS:000169343600003 PM 11377750 ER PT J AU Story, M Stevens, J Evans, M Cornell, CE Juhaeri Gittelsohn, J Going, SB Clay, TE Murray, DM AF Story, M Stevens, J Evans, M Cornell, CE Juhaeri Gittelsohn, J Going, SB Clay, TE Murray, DM TI Weight loss attempts and attitudes toward body size, eating, and physical activity in American Indian children: Relationship to weight status and gender SO OBESITY RESEARCH LA English DT Article DE American Indian; children; weight loss; body image; obesity ID PSYCHOSOCIAL CONCERNS; SCHOOL-CHILDREN; ADOLESCENTS; OBESITY; HEALTH; GIRLS; OVERWEIGHT; DISTURBANCES; DISORDERS; BEHAVIORS AB Objective: This study examined dieting, weight perceptions, and self-efficacy to eat healthy foods and engage in physical activity and their relationships to weight status and gender among American Indian elementary schoolchildren. Research Methods and Procedures: Data for this study were collected as part of the baseline examination for the Pathways study. Participants were 1441 second- through third-grade American Indian children in 41 schools representing seven tribes in Arizona, New Mexico, and South Dakota who filled out a questionnaire and had heights and weights taken. Results: Forty-two percent of the children were overweight or obese. No differences were found between overweight/obese and normal weight children for healthy food intentions or self-efficacy. Heavier children (especially those with body mass index > 95th percentile) were more likely to have tried to lose weight or were currently trying to lose weight. No gender differences were found. Normal weight children chose a slightly heavier body size as most healthy compared with overweight/obese children. Discussion: The results indicate that children are concerned about their weight and that weight modification efforts are common among overweight American Indian children. School, community, and family-based programs cue needed to help young people adopt lifelong healthful eating and physical activity practices. C1 Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. Univ N Carolina, Sch Publ Hlth, Dept Nutr & Epidemiol, Chapel Hill, NC USA. NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Behav Med, Birmingham, AL USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Baltimore, MD USA. Univ Arizona, Tucson, AZ USA. Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA. Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. RP Story, M (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. FU NHLBI NIH HHS [U02-HL-50867, U01-HL-50885, U01-HL-50905, UO1-HL-50869, U01-HL-50907] NR 46 TC 28 Z9 28 U1 1 U2 7 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD JUN PY 2001 VL 9 IS 6 BP 356 EP 363 DI 10.1038/oby.2001.46 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 442VV UT WOS:000169306400004 PM 11399782 ER PT J AU Tamm, SA Whitcup, SM Gery, I Wiggert, B Nussenblatt, RB Kaiser-Kupfer, MI AF Tamm, SA Whitcup, SM Gery, I Wiggert, B Nussenblatt, RB Kaiser-Kupfer, MI TI Immune response to retinal antigens in patients with gyrate atrophy and other hereditary retinal dystrophies SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 10-15, 1998 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol DE Gyrate atrophy; retinitis pigmentosa; cell-mediated immune response; S-Ag; IRBP; adhesion molecules ID RETINITIS-PIGMENTOSA; S-ANTIGEN; UVEITIS PATIENTS; BINDING PROTEIN; DISEASE; UVEORETINITIS; ICAM-1; RESPONSIVENESS; AUTOIMMUNITY; MUTATIONS AB Purpose: Gyrate atrophy (GA) is a rare hereditary disease that causes retinal destruction. Retinal damage in GA and other heredodegenerative diseases such as retinitis pigmentosa (RP) releases sequestered antigens and may trigger immune response to these molecules. Here, we studied the immune response to retinal antigens in patients with GA and RP and compared it with that of patients with inactive posterior uveitis and normal volunteers. Patients and methods: Peripheral blood was collected from 24 patients with RP, 10 patients with GA, 10 patients with inactive posterior uveitis, and 16 normal volunteers. Cell-mediated immune responses to human S-antigen (HS-Ag), bovine S-antigen (BS-Ag), and interphotoreceptor retinoid-binding protein (IRBP) were investigated by lymphocyte proliferation assay. In addition, serum levels of soluble intercellular adhesion molecule-r (sICAM-I) and soluble vascular cell adhesion molecule-I (sVCAM-I) were studied by ELISA. Immunologic data were correlated with clinical and electrophysiological findings. Results: Patients with GA or RP responded to HS-Ag and BS-Ag more vigorously than patients with uveitis or healthy controls, as shown by higher mean stimulation indices and larger proportions of responders. Unlike S-Ag, IRBP stimulated low lymphocyte responses in only a small proportion of RP patients. The mean sVCAM-I levels were significantly higher in the sera from patients with GA than in that from normal controls. Conclusion: An elevated cellular immune response to S-Ag is common in patients with GA and RP. This elevated cellular immune response to S-Ag may exacerbate retinal destruction in patients with GA and RP. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Tamm, SA (reprint author), Univ Erlangen Nurnberg, Dept Anat 2, Univ Str 19, D-91054 Erlangen, Germany. NR 33 TC 7 Z9 7 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD JUN PY 2001 VL 9 IS 2 BP 75 EP 84 DI 10.1076/ocii.9.2.75.3972 PG 10 WC Ophthalmology SC Ophthalmology GA 455NF UT WOS:000170032400002 PM 11449323 ER PT J AU de Smet, MD Ramadan, A AF de Smet, MD Ramadan, A TI Circulating antibodies to inducible heat shock protein 70 in patients with uveitis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Behcet's disease; Vogt-Koyanagi-Harada (VKH); pars planitis; sarcoidosis; heat shock protein ID SYSTEMIC LUPUS-ERYTHEMATOSUS; STRESS PROTEINS; MULTIPLE-SCLEROSIS; MOLECULAR CHAPERONES; AUTOIMMUNE-DISEASE; IMMUNE-RESPONSE; BEHCETS-DISEASE; EXPRESSION; PEPTIDES; AUTOANTIBODIES AB Heat shock proteins with molecular weight 70 kDa (hsp70) are highly conserved immunogenic intracellular molecules. There are two main subtypes: one is expressed constitutively (hsc70), while the other is induced under stressful conditions (ihsp70). Using an ELISA directed against recombinant human ihsp70, antibody titers were determined in patients with defined ocular inflammatory conditions (Behcet's disease, Vogt-Koyanagi-Harada (VKH), pars planitis, and sarcoidosis) as well as in a group of age-matched normal volunteers. In comparison to healthy controls (n = 14, absorbance 0.269), levels were significantly elevated in Behcet's disease (n = 18; 0.412), sarcoidosis (n = 15; 0.432), and pars planitis (n = 13; 0.346), but not in VKH (n = 10; 0.263). A correlation was also noted for treatment versus no treatment in pars planitis (p = 0.028), but not in other inflammatory conditions. There was no correlation with the level of intraocular disease activity as defined by vitreous haze and vision drop. Since pars planitis is a purely ocular condition, circulating levels of ihsp antibodies likely reflect the extent of disease involvement within the eye. C1 Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands. NEI, Clin Immunol Sect, Immunol Lab, Bethesda, MD 20892 USA. RP de Smet, MD (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, Kamer G2-217,Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. OI de Smet, Marc/0000-0002-9217-5603 NR 32 TC 21 Z9 21 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD JUN PY 2001 VL 9 IS 2 BP 85 EP 92 PG 8 WC Ophthalmology SC Ophthalmology GA 455NF UT WOS:000170032400003 PM 11449324 ER PT J AU Dancey, JE Schoenfeldt, M AF Dancey, JE Schoenfeldt, M TI Epidermal growth factor receptor inhibitors in clinical trials SO ONCOLOGY-NEW YORK LA English DT Article ID CELL LUNG-CANCER; POOR-PROGNOSIS; C225; OVEREXPRESSION; APOPTOSIS; CARCINOMA; ANTIBODY; THERAPY; P53 C1 NCI, Bethesda, MD 20892 USA. RP Dancey, JE (reprint author), NCI, Bethesda, MD 20892 USA. NR 20 TC 4 Z9 5 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUN PY 2001 VL 15 IS 6 BP 748 EP + PG 5 WC Oncology SC Oncology GA 442MH UT WOS:000169289200013 PM 11430207 ER PT J AU Leske, MC Nemesure, B He, Q Wu, SY Hejtmancik, JF Hennis, A AF Leske, MC Nemesure, B He, Q Wu, SY Hejtmancik, JF Hennis, A CA Barbados Family Study Grp TI Patterns of open-angle glaucoma in the Barbados Family Study SO OPHTHALMOLOGY LA English DT Article ID BALTIMORE EYE SURVEY; INTRAOCULAR-PRESSURE; RISK-FACTORS; PREVALENCE; POPULATION; LOCUS; GENE; REGION; LOCALIZATION; 2CEN-Q13 AB Objective: To describe the Barbados Family Study of open-angle glaucoma (OAG) and present risk factors for OAG in siblings of study probands. Design: Observational study of families of probands with OAG. Participants: Two hundred thirty probands and 1056 relatives (from 207 families). Methods: Probands and their family members underwent standardized examinations, including automated perimetry, applanation tonometry, ophthalmologic evaluation, fundus photography, blood pressure, interview, and genotyping. Generalized estimation equation methods were used to evaluate risk factors. Main Outcome Measures: Presence of OAG in the relatives, as defined by both visual field and optic disc findings, after ophthalmologic exclusion of other causes. Results: The median ages of probands and relatives were 68 and 47 years, respectively. In the 207 families, 29% of the probands had one relative with OAG and 10% had two or more relatives affected, Of the 1056 family members, 10% had OAG, 13% had suspect OAG, and 6% had ocular hypertension. One fifth of the 338 siblings had OAG (n = 67); they tended to be older and more often were male. Multivariate comparisons between siblings with and without OAG found that age, higher intraocular pressure (IOP), myopia, and lower diastolic blood pressure-IOP differences were related to OAG, whereas hypertension and diabetes were not. Conclusions: Based on standardized protocols and examinations, approximately one quarter of the relatives had OAG or suspected OAG, despite their relatively young age. Risk factors for OAG in siblings were similar to risk factors in unrelated individuals, Analyses are ongoing to determine OAG inheritance and to localize potential gene(s) involved. Ophthalmology 2001;108:1015-1022 (C) 2001 by the American Academy of Ophthalmology. C1 SUNY Stony Brook, Med Ctr, Sch Med, Dept Prevent Med, Stony Brook, NY 11794 USA. NEI, Bethesda, MD 20892 USA. Minist Hlth, Barbados, W Ind Assoc St. Univ W Indies, Sch Clin Med & Res, Dept Cardiol, Barbados, W Ind Assoc St. Johns Hopkins Univ, Baltimore, MD USA. Univ W Indies, Sch Clin Med & Res, Chron Dis Res Ctr, Barbados, W Ind Assoc St. Queen Elizabeth Hosp, Dept Ophthalmol, Barbados, W Ind Assoc St. RP Leske, MC (reprint author), SUNY Stony Brook, Med Ctr, Sch Med, Dept Prevent Med, HSC L3 086, Stony Brook, NY 11794 USA. FU NEI NIH HHS [EY01100] NR 45 TC 52 Z9 54 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUN PY 2001 VL 108 IS 6 BP 1015 EP 1022 DI 10.1016/S0161-6420(01)00566-8 PG 8 WC Ophthalmology SC Ophthalmology GA 437YN UT WOS:000169027100025 PM 11382622 ER PT J AU Rimer, BK Halabi, S Skinner, CS Kaplan, EB Crawford, Y Samsa, GP Strigo, TS Lipkus, IM AF Rimer, BK Halabi, S Skinner, CS Kaplan, EB Crawford, Y Samsa, GP Strigo, TS Lipkus, IM TI The short-term impact of tailored mammography decision-making interventions SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE tailored; mammography; decision-making; telephone counseling ID BREAST-CANCER RISK; INCREASE MAMMOGRAPHY; FAMILY HISTORY; WOMEN; ADOPTION; STAGE; PARTICIPATION; MEDICINE; BEHAVIOR; FUTURE AB Background: We assessed the short-term impact of decision-making interventions on knowledge about mammography, accuracy of women's breast cancer risk perceptions, attitudes toward mammography, satisfaction with decisions, and mammography use since the intervention. Methods: The study was conducted among women who were members of Blue Cross Blue Shield of North Carolina and were in their 40s or 50s at the time the study began in 1997. Women were randomly assigned to usual care (UC), tailored print booklets (TP) alone, or TP plus telephone counseling (TP + TC). Results: 12-month interviews were completed by 1127 women to assess short-term intervention effects. Generally, women who received TP + TC were significantly more knowledgeable about mammography and breast cancer risk and were more accurate in their breast cancer risk perceptions than women in the TP and UC groups. They also were more likely to have had a mammogram since the baseline interview, In multivariable analyses, we found significant benefits of the combination of TP + TC compared to TP and to UC for knowledge, accuracy of risk perceptions, and mammography use. Discussion: For complex decision-making tasks, such as women's decisions about mammography in the face of controversy, the combination of TP and TC may be more effective than TP alone, and certainly more effective; than UC. It is critical that investigators determine the topics for which TP is appropriate and the situations that require additional supportive interventions. Published by Elsevier Science Ireland Ltd. C1 NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. Duke Univ, Med Ctr, Dept Community & Family Med, Div Biometry, Durham, NC 27710 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Detect & Control Res Program, Durham, NC 27710 USA. Duke Univ, Med Ctr, Ctr Canc, Durham, NC 27710 USA. RP Rimer, BK (reprint author), NCI, Div Canc Control & Populat Sci, Room 242,6130 Execut Blvd, Rockville, MD 20852 USA. FU NCI NIH HHS [5P01-CA-72099-03] NR 64 TC 56 Z9 56 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JUN PY 2001 VL 43 IS 3 BP 269 EP 285 PG 17 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 444BP UT WOS:000169378300006 PM 11384825 ER PT J AU Eid, J Johnsen, BH Thayer, JF AF Eid, J Johnsen, BH Thayer, JF TI Post-traumatic stress symptoms following shipwreck of a Norwegian Navy frigate - an early follow-up SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE post-traumatic stress; acute stress reactions; coping style; navy; shipwreck ID FREE-ENTERPRISE DISASTER; ATTRIBUTIONAL STYLE; CRISIS SUPPORT; SURVIVORS; RESPONSES; DISORDER; HERALD; COLLISION; RESCUERS; PATTERNS AB The purpose of this study was to conduct an early follow-up of survivors from the shipwreck of a Norwegian Naval frigate, In the accident one person died and nine were injured of a total crew of 114 persons. Two weeks after the shipwreck, the crew were assigned to a new identical frigate for a period of 4 months in order to complete their scheduled operational duties. Post-traumatic stress reactions were measured by the Impact of Event Scale (IES) and the Post-Traumatic Symptom Scale (PTSS-10) at 3 weeks, 4 and 12 months after the shipwreck. The results showed that even a trained military crew displayed a high number of acute stress reactions. Contextual factors like social role (e.g. being a conscript) and personality factors like an avoidance focused coping style, measured by the Coping Style Questionnaire (CSQ-30), were strongly associated with more acute stress reactions. Over time, the overall level of post-traumatic stress reactions were reduced and the scores of the conscripts did not differ from those of the officers. One implication of these findings could be the need to develop more sophisticated screening procedures in order to target early preventive interventions and acute treatment after maritime accidents. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Royal Norwegian Naval Acad, N-5034 Ytre Laksevag, Norway. NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Eid, J (reprint author), Royal Norwegian Naval Acad, Postboks 25, N-5034 Ytre Laksevag, Norway. RI Eid, Jarle/G-1346-2014 NR 46 TC 18 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD JUN PY 2001 VL 30 IS 8 BP 1283 EP 1295 DI 10.1016/S0191-8869(00)00111-2 PG 13 WC Psychology, Social SC Psychology GA 433TZ UT WOS:000168777000002 ER PT J AU Gong, QH Cho, JW Huang, T Potter, C Gholami, N Basu, NK Kubota, S Carvalho, S Pennington, MW Owens, IS Popescu, NC AF Gong, QH Cho, JW Huang, T Potter, C Gholami, N Basu, NK Kubota, S Carvalho, S Pennington, MW Owens, IS Popescu, NC TI Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus SO PHARMACOGENETICS LA English DT Article DE human UGT1 locus; exons 1; UDP-glucuronosyltransferases ID BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE; I PATIENT; CLONING; PHENOL; EXPRESSION; CELLS AB The original novel UCT1 complex locus previously shown to encode six different UDP-glucuronosyltransferase (transferase) genes has been extended and demonstrated to specify a total of IS isoforms, The genes are designated UGT1A1 through UGT1A13p with four pseudo ones. UGT1A2p and UGT1A11p through UGT1A13p have either nucleotide deletions or flawed TATA boxes and are therefore pseudo. In the 5' region of the locus, the 13 unique exons 1 are arranged in a tandem array with each having its own proximal TATA box element and, in turn, are linked to four common exons to allow for the independent transcriptional initiation to generate overlapping primary transcripts. Only the lead exon in the nine viable primary transcripts is predicted to undergo splicing to the four common exons generating mRNAs with identical 3' ends and transferase isozymes with an identical carboxyl terminus. The unique amino terminus specifies acceptor-substrate selection, and the common carboxyl terminus apparently specifies the interaction with the common donor substrate, UDP-glucuronic acid. in the extended region, the viable TATA boxes are either A(A)T(9)A(AA)T or AT(14)AT; in the original locus the element for UGT1A1 is A(TA)(7)A and TAATT/CAA(A) for all of the other genes. UGT1A1 specifies the critically important bilirubin transferase isoform, The relationships of the exons 1 to each other are as follows: UGT1A2p through UGT1A5 comprises a cluster A that is 87-92% identical, and UGT1A7 through UGT1A13p comprises a cluster B that is 67-91% identical. For the two not included in a cluster, UGT1A1 is more identical to cluster A at 60-63%, whereas UGT1A6 is identical by between 48% and 56% to all other unique exons, The locus was expanded from 95 kb to 218 kb, Extensive probing of clones beyond 218 lib with coding nucleotides for a highly conserved amino acid sequence present in all transferases was unable to detect other exons 1. The mRNAs are differentially expressed in hepatic and extrahepatic tissues. This locus is indeed novel, indicating the least usage of exon sequences in specifying different transferase isozymes that have an expansive substrate range. Pharmacogenetics 11:357-368 (C) 2001 Lippincott Williams & Wilkins. C1 NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Owens, IS (reprint author), NICHHD, Heritable Disorders Branch, NIH, Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. NR 11 TC 211 Z9 228 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD JUN PY 2001 VL 11 IS 4 BP 357 EP 368 DI 10.1097/00008571-200106000-00011 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 441YG UT WOS:000169256700011 PM 11434514 ER PT J AU Sarnyai, Z Shaham, Y Heinrichs, SC AF Sarnyai, Z Shaham, Y Heinrichs, SC TI The role of corticotropin-releasing factor in drug addiction SO PHARMACOLOGICAL REVIEWS LA English DT Review ID PITUITARY-ADRENAL AXIS; PLASMA-CORTICOSTERONE LEVELS; COCAINE-SEEKING BEHAVIOR; STRESS-INDUCED RELAPSE; FACTOR-BINDING PROTEIN; FACTOR-LIKE IMMUNOREACTIVITY; MALE RHESUS-MONKEYS; PROOPIOMELANOCORTIN GENE-EXPRESSION; HYPOTHALAMIC NORADRENERGIC ACTIVITY; OBSESSIVE-COMPULSIVE DISORDER AB The goal of this article is to summarize available data examining the physiological significance of brain corticotropin-releasing factor (CRF) systems in mediating the behavioral and physiological effects of several classes of abused drugs, including opioid and psychostimulant drugs, alcohol and sedative hypnotics, nicotine, and cannabinoids. An initial discussion of CRF neurobiology is followed by consideration of the role of CRF in drug-induced activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, the behavioral effects of drugs (e.g., locomotor activity, anxiogenic-like responses), drug self-administration, drug withdrawal, and relapse to drug-seeking. Subsequently, neurochemical changes in brain CRF in response to acute and chronic drug exposure are examined. A major conclusion derived hom the data reviewed is that extrahypothalamic brain CRF systems are critically involved in behavioral and physiological manifestations of drug withdrawal and in relapse to drug-taking behavior induced by environmental stressors. On the other hand, it appears that hypothalamic CRF, via its action on the HPA axis, is involved in the reinforcing effects of cocaine and alcohol, and the locomotor activating effects of psychostimulant drugs. These preclinical data may provide a rationale for the development of CRF-based pharmacotherapies for the treatment of compulsive drug use in humans. C1 PsychoGenics Inc, Hawthorne, NY 10532 USA. Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA. Rockefeller Univ, Lab Biol Addict Dis, New York, NY 10021 USA. NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD USA. Boston Coll, Dept Psychol, Chestnut Hill, MA 02167 USA. RP Sarnyai, Z (reprint author), PsychoGenics Inc, 4 Skyline Dr, Hawthorne, NY 10532 USA. EM zoltan.sarnyai@psychogenics.com RI shaham, yavin/G-1306-2014; Sarnyai, Zoltan/A-3283-2009 NR 378 TC 287 Z9 305 U1 0 U2 19 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 EI 1521-0081 J9 PHARMACOL REV JI Pharmacol. Rev. PD JUN PY 2001 VL 53 IS 2 BP 209 EP 243 PG 35 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 434ZV UT WOS:000168846500003 PM 11356984 ER PT J AU Ito, S Wakamatsu, K Matsunaga, N Hearing, VJ Carey, KD Anderson, S Dooley, TP AF Ito, S Wakamatsu, K Matsunaga, N Hearing, VJ Carey, KD Anderson, S Dooley, TP TI Cyclic oscillations in melanin composition within hairs of baboons SO PIGMENT CELL RESEARCH LA English DT Article DE baboon; hair; eumelanin; pheomelanin ID MELANOCORTIN-1 RECEPTOR; RED HAIR; CHEMICAL CHARACTERIZATION; PIGMENTATION; EUMELANIN; PHEOMELANIN; VARIANTS; HUMANS; SKIN AB The wild-type agouti-banding pattern for hair is well characterized in lower mammals such as mice. The switch between eumelanin and pheomelanin in bands in the hair results from the interaction of alpha-melanocyte stimulating hormone and agouti signal protein through the melanocortin 1 receptor on melanocytes, However, such banding patterns have not been described to date in higher mammals. We now report such 'agouti'-banding patterns that occur in several subspecies of baboons, and characterize those hairs using chemical and immunohistochemical methods. Hair and skin samples were obtained from the dorsa of adult male baboons of different subspecies (Papio cynocephalus hamadryas (PCH) and Papio cynocephalus anubis (PCA)), The hairs were excised with scissors into the gray and the white bands of the PCH subspecies and into the black and the yellow bands of the PCA subspecies, and were analyzed for total melanin, eumelanin, and pheomelanin by spectrophotometric and chemical methods. Hairs in the PCA subspecies oscillate between a eumelanic band (with high melanin content) and a pheomelanic band, while hairs in the PCH subspecies oscillate between a eumelanic band (with low melanin content) and a non-pigmented band, Those chemical data are consistent with the histological appearance of the hair bulbs stained by the Fontana-Masson technique. The difference in the melanin content between PCH and PCA subspecies is most likely related to tyrosinase levels, as suggested by the presence of unpigmented muzzle in the PCH subspecies compared with the black muzzle in the PCA subspecies. C1 Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, Aichi 4701192, Japan. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. SW Fdn Biomed Res, San Antonio, TX 78245 USA. Amer Museum Nat Hist, Dept Mammal, New York, NY 10024 USA. IntergriDerm Inc, Huntsville, AL 35801 USA. RP Ito, S (reprint author), Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, 1-98 Dengakugakubo,Kutsukake Cho, Aichi 4701192, Japan. NR 17 TC 6 Z9 6 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD JUN PY 2001 VL 14 IS 3 BP 180 EP 184 DI 10.1034/j.1600-0749.2001.140307.x PG 5 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 445GU UT WOS:000169450400006 PM 11434565 ER PT J AU Bass, LE Casper, LM AF Bass, LE Casper, LM TI Impacting the political landscape: Who registers and votes among naturalized Americans? SO POLITICAL BEHAVIOR LA English DT Article DE voting register; elect; immigrant; naturalize ID SEGMENTED ASSIMILATION; PARTICIPATION; IMMIGRANTS; 2ND-GENERATION; TURNOUT; GENDER AB Little is known about the voting behavior of naturalized Americans, primarily due to a lack of good quality data on the national level. Using data from the Voting and Registration Supplement to the November 1996 Current Population Survey (CPS), we examine whether region of origin and length of time spent in the United States affect the likelihood of registering and voting among naturalized citizens, net of other socioeconomic and demographic factors already known to influence electoral behavior. We find that naturalized citizens who have a longer length of time at current residence and in the United States, and those who are older, with more education and higher income are more likely to register and vote. Region of origin is not a major explanatory variable, but there are differences in registering and voting by country of origin among naturalized citizens from Asia and Latin America. Finally, being registered is a necessary but not sufficient condition that predicts voting among naturalized citizens from Asia and from Latin America. C1 Univ Oklahoma, Dept Sociol, Norman, OK 73019 USA. Natl Inst Child Hlth & Human Dev, Demograph & Behav Sci Branch, Bethesda, MD USA. RP Bass, LE (reprint author), Univ Oklahoma, Dept Sociol, Kaufman Hall,Room 331,780 Van Fleet Oval, Norman, OK 73019 USA. NR 58 TC 16 Z9 16 U1 1 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0190-9320 J9 POLIT BEHAV JI Polit. Behav. PD JUN PY 2001 VL 23 IS 2 BP 103 EP 130 DI 10.1023/A:1013013530506 PG 28 WC Political Science SC Government & Law GA 523VB UT WOS:000173977000001 ER PT J AU Brown, LM Lopez, GE AF Brown, LM Lopez, GE TI Political contacts: Analyzing the role of similarity in theories of prejudice SO POLITICAL PSYCHOLOGY LA English DT Article DE group contact; contact hypothesis; prejudice; similarity-attraction ID INTERGROUP SIMILARITY; SUBGROUP RELATIONS; ATTRIBUTIONS; RESOLUTION; EDUCATION AB Over the last 50 years, many theories of prejudice reduction in social psychology have embraced the premise that intergroup contact allows people to recognize similarities between themselves, and that this perceived similarity overwhelms the social distance associated With intergroup antipathy. Given the mired empirical evidence, however, we suggest that the positive effects of perceived similarity have been overemphasized. Although similarity may be sufficient for improved intergroup relations, the relationship between similarity and intergroup relations is far more complex than the literature usually suggests. Moreover, studying difference in intergroup contexts may yield new ways to resolve intergroup conflict and address group inequalities. C1 Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA. Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. RP Brown, LM (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, POB 100165, Gainesville, FL 32610 USA. NR 54 TC 15 Z9 15 U1 0 U2 3 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0162-895X J9 POLIT PSYCHOL JI Polit. Psychol. PD JUN PY 2001 VL 22 IS 2 BP 279 EP 292 DI 10.1111/0162-895X.00239 PG 14 WC Political Science; Psychology, Social SC Government & Law; Psychology GA 438MB UT WOS:000169056600005 ER PT J AU Kumar, S Nussinov, R AF Kumar, S Nussinov, R TI Fluctuations in ion pairs and their stabilities in proteins SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE salt bridge; ion pair; electrostatics; conformer; NMR ensemble; protein stability ID MOLECULAR-DYNAMICS SIMULATION; IMMUNOGLOBULIN-BINDING DOMAIN; HIV-INACTIVATING PROTEIN; SIDE-CHAIN DYNAMICS; SALT BRIDGES; FOLDING FUNNELS; ELECTROSTATIC CONTRIBUTIONS; CRYSTAL-STRUCTURE; LEUCINE-ZIPPER; NMR STRUCTURE AB This report investigates the effect of systemic protein conformational flexibility on the contribution of ion pairs to protein stability. Toward this goal, we use all NMR conformer ensembles in the Protein Data Bank (1) that contain at least 40 conformers, (2) whose functional form is monomeric, (3) that are nonredundant, and (4) that are large enough. We find 11 proteins adhering to these criteria. Within these proteins, we identify 22 ion pairs that are close enough to be classified as salt bridges. These are identified in the high-resolution crystal structures of the respective proteins or in the minimized average structures (if the crystal structures are unavailable) or, if both are unavailable, in the "most representative" conformer of each of the ensembles. We next calculate the electrostatic contribution of each such ion pair in each of the conformers in the ensembles. This results in a comprehensive study of 1,201 ion pairs, which allows us to look for consistent trends in their electrostatic contributions to protein stability in large sets of conformers. We find that the contributions of ion pairs vary considerably among the conformers of each protein. The vast majority of the ion pairs interconvert between being stabilizing and destabilizing to the structure at least once in the ensembles. These fluctuations reflect the variabilities in the location of the ion pairing residues and in the geometric orientation of these residues, both with respect to each other, and with respect to other charged groups in the remainder of the protein. The higher crystallographic B-factors for the respective side-chains are consistent with these fluctuations. The major conclusion from this study is that salt bridges observed in crystal structure may break, and new salt bridges may be formed. Hence, the overall stabilizing (or, destabilizing) contribution of an ion pair is conformer population dependent. Proteins 2001;43:433-454. (C) 2001 Wiley-Liss, Inc. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr,Lab Expt & Computat, Frederick, MD 21702 USA. NCI, Lab Expt & Computat Biol, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr,Lab Expt & Computat, Bldg 469,Room 151, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 63 TC 41 Z9 41 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD JUN 1 PY 2001 VL 43 IS 4 BP 433 EP 454 DI 10.1002/prot.1056 PG 22 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 436DJ UT WOS:000168921000010 PM 11340660 ER PT J AU Mahalingam, B Louis, JM Hung, J Harrison, RW Weber, IT AF Mahalingam, B Louis, JM Hung, J Harrison, RW Weber, IT TI Structural implications of drug-resistant mutants of HIV-1 protease: High-resolution crystal structures of the mutant protease/substrate analogue complexes SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE aspartic protease; crystallography; inhibitors; conserved water; structural changes ID IMMUNODEFICIENCY-VIRUS TYPE-1; RETROVIRAL PROTEASES; DIMER STABILITY; INHIBITOR; SUBSTRATE; SPECIFICITY; INFECTIVITY; PROTEINASES; MUTATIONS AB Emergence of drug-resistant mutants of HIV-1 protease is an ongoing problem in the fight against AIDS. The mechanisms governing resistance are both complex and varied. We have determined crystal structures of HIV-1 protease mutants, D30N, K45I, N88D, and L90M complexed with peptide inhibitor analogues of CA-p2 and p2-NC cleavage sites in the Gag-pol precursor in order to study the structural mechanisms underlying resistance. The structures were determined at 1.55-1.9-Angstrom resolution and compared with the wild-type structure. The conformational disorder seen for most of the hydrophobic side-chains around the inhibitor binding site indicates flexibility of binding. Eight water molecules are conserved in all 9 structures; their location suggests that they are important for catalysis as well as structural stability. Structural differences among the mutants were analyzed in relation to the observed changes in protease activity and stability. Mutant L90M shows steric contacts with the catalytic Asp25 that could destabilize the catalytic loop at the dimer interface, leading to its observed decreased dimer stability and activity. Mutant K45I reduces the mobility of the flap and the inhibitor and contributes to an enhancement in structural stability and activity. The side-chain variations at residue 30 relative to wild-type are the largest in D30N and the changes are consistent with the altered activity observed with peptide substrates, Polar interactions in D30N are maintained, in agreement with the observed urea sensitivity. The side-chains of D30N and N88D are linked through a water molecule suggesting correlated changes at the two sites, as seen with clinical inhibitors. Structural changes seen in N88D are small; however, water molecules that mediate interactions between Asn88 and Thr74/Thr31/Asp30 in other complexes are missing in N88D, Proteins 2001;43:455-464. (C) 2001 Wiley-Liss, Inc. C1 Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA. Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Weber, IT (reprint author), Georgia State Univ, Dept Biol, POB 4010, Atlanta, GA 30303 USA. FU NIAID NIH HHS [AI41380]; NIGMS NIH HHS [GM62920, R01 GM062920] NR 31 TC 93 Z9 94 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD JUN 1 PY 2001 VL 43 IS 4 BP 455 EP 464 DI 10.1002/prot.1057 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 436DJ UT WOS:000168921000011 PM 11340661 ER PT J AU Wyatt, RJ Henter, ID Jamison, JC AF Wyatt, RJ Henter, ID Jamison, JC TI Lithium revisited: Savings brought about by the use of lithium, 1970-1991 SO PSYCHIATRIC QUARTERLY LA English DT Article DE lithium; manic-depressive illness; bipolar disorder; pharmacoeconomics; cost-effectiveness ID MANIC-DEPRESSIVE PATIENTS; BIPOLAR DISORDER; MENTAL-ILLNESS; MORTALITY; BURDEN AB Background: Recent estimates of the cost of manic-depressive illness totaled roughly $45 billion in 1991. Using data from the Epidemiological Catchment Area (ECA) study, this study estimates the savings brought about by the use of lithium between 1970 and 1991. Methods: Total savings are the difference between estimated actual costs and projected costs had lithium never been introduced. Actual yearly costs were interpolated from data for 1970 and 1991, and projected costs were obtained by adjusting 1970 costs with Consumer Price Index (CPD and population inflaters. All costs for 1970 were obtained using methods almost identical to those used to calculate the 1991 costs of manic-depressive illness, presented in a previous publication. All savings are presented in 1991 dollars. Results: Between 1970 and 1991, lithium saved over $170 billion, or roughly over $8 billion per year. Approximately $15 billion in direct casts, which included inpatient and outpatient care as well as research, was saved between 1970 and 1991. The savings are more dramatic for indirect costs, which include the last productivity of wage-earners, homemakers, family caregivers, and individuals who are in institutions or who committed suicide; these totaled roughly $155 billion. Conclusions: Our results suggest that, although manic-depressive illness is still costly, lithium has been tremendously successful in treating the illness, and has provided enormous financial savings in the process. C1 NIMH, Neurospychiat Brnach, NIH, Bethesda, MD 20892 USA. RP Wyatt, RJ (reprint author), NIMH, Neurospychiat Brnach, NIH, 5415 W Cedar Lane,Suite 106B,MSC 2610, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 MH999999] NR 34 TC 7 Z9 7 U1 0 U2 1 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0033-2720 J9 PSYCHIAT QUART JI Psychiatr. Q. PD SUM PY 2001 VL 72 IS 2 BP 149 EP 166 DI 10.1023/A:1010319610021 PG 18 WC Psychiatry SC Psychiatry GA 445VL UT WOS:000169479200005 PM 11433880 ER PT J AU Heinssen, RK Cuthbert, BN AF Heinssen, RK Cuthbert, BN TI Commentary on "The development at interpersonal relationships in individuals with schizophrenia" - Barriers to relationship formation in schizophrenia: Implications for treatment, social recovery, and translational research SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Editorial Material ID QUALITY-OF-LIFE; COMMUNITY C1 NIMH, Div Mental Disorders Behav Res & AIDS, Adult Psychopathol & Prevent Res Branch, Psychot Disorders Res Program, Bethesda, MD 20892 USA. RP Heinssen, RK (reprint author), NIMH, Div Mental Disorders Behav Res & AIDS, Adult Psychopathol & Prevent Res Branch, Psychot Disorders Res Program, Rm 6181,Mail Stop 9615,6001 Execut Bld, Bethesda, MD 20892 USA. NR 19 TC 3 Z9 3 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD SUM PY 2001 VL 64 IS 2 BP 126 EP 131 DI 10.1521/psyc.64.2.126.18617 PG 6 WC Psychiatry SC Psychiatry GA 457CJ UT WOS:000170119300003 PM 11495359 ER PT J AU Shalev, U Morales, M Hope, B Yap, J Shaham, Y AF Shalev, U Morales, M Hope, B Yap, J Shaham, Y TI Time-dependent changes in extinction behavior and stress-induced reinstatement of drug seeking following withdrawal from heroin in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE corticotropin-releasing factor; in situ hybridization; heroin; relapse; stress ID CORTICOTROPIN-RELEASING-FACTOR; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; HORMONE MESSENGER-RNA; COCAINE-SEEKING; INDUCED RELAPSE; PHYSICAL-DEPENDENCE; STRIA TERMINALIS; BED NUCLEUS; ADDICTION; AMYGDALA AB Rationale and objectives: Footshock stress reliably reinstates heroin seeking in rats. but the time course of the development of this effect following drug withdrawal is not known. Here we studied the effect of intermittent footshock stress on reinstatement of heroin seeking following different withdrawal periods (1-66 days). We also studied whether changes in corticotropin-releasing factor (CRF) mRNA in the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST) are correlated with this reinstatement after 1 day and 6 days of heroin withdrawal. Methods: Rats were trained to self-administer heroin (9 h/day; 0.1 mg/kg per infusion) for 10 days. Tests for extinction behavior and footshock-induced reinstatement of heroin seeking were then conducted after 1, 6, 12, 25, or 66 days of heroin withdrawal. On the test day, rats were given five to ten 60-min extinction sessions until they reached the extinction criterion of less than 15 responses per 60 min on the lever previously associated with heroin. Rats were then exposed to intermittent footshock (0.8 mA; 10 min), and lever-pressing behavior was recorded for 120 min. Results: Reinstatement of lever-pressing behavior by footshock followed an inverted U-shaped curve with maximal responding after 6 days and 12 days of heroin withdrawal. Surprisingly, footshock did not reinstate lever-pressing behavior on day 1 of withdrawal. Lever pressing during extinction, prior to exposure to footshock, also followed an inverted U-shaped curve, with higher responding after 6, 12, and 25 days of heroin withdrawal. Finally, compared with control groups not exposed to shock, CRF mRNA levels in response to footshock were increased in the CeA (day I of withdrawal) and the dorsal BNST (day 1 and day 6), but not in the ventral BNST. Conclusions: The duration of the heroin withdrawal period is an important factor in the manifestation of (1) footshock stress-induced reinstatement of heroin seeking and (2) extinction of the heroin-reinforced behavior. Finally, the time-dependent changes in footshock stress induced reinstatement following withdrawal from heroin were not correlated with alterations in CRF mRNA in the CeA and BNST. C1 NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014 OI Hope, Bruce/0000-0001-5804-7061; NR 58 TC 133 Z9 138 U1 5 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUN PY 2001 VL 156 IS 1 BP 98 EP 107 DI 10.1007/s002130100748 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 447XT UT WOS:000169598300013 PM 11465640 ER PT J AU Foo, TKF Ho, VB Hood, MN Marcos, HB Hess, SL Choyke, PL AF Foo, TKF Ho, VB Hood, MN Marcos, HB Hess, SL Choyke, PL TI High-spatial-resolution multistation MR imaging of lower-extremity peripheral vasculature with segmented volume acquisition: Feasibility study SO RADIOLOGY LA English DT Article DE angiography, comparative studies; angiography, technology; magnetic resonance (MR), pulse sequences; magnetic resonance (MR), vascular studies ID MAGNETIC-RESONANCE ANGIOGRAPHY; DIGITAL SUBTRACTION ANGIOGRAPHY; AORTA; OPTIMIZATION; ALGORITHM; ARTERIES; ARRIVAL; ORDER; TIME AB A method of three-station three-dimensional magnetic resonance (MR) angiography of the lower extremities with segmented volume acquisition is presented. Three-dimensional MR angiographic data were acquired in two passes, with the central re-space views acquired during the arterial phase for the more proximal stations. This allowed a faster bolus injection rate and potentially improved visualization of the tibioperoneal arteries. C1 GE Med Syst, Appl Sci Lab, Baltimore, MD 21287 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD USA. NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Foo, TKF (reprint author), GE Med Syst, Appl Sci Lab, 600 N Wolfe St,Rm 110-MRI, Baltimore, MD 21287 USA. NR 20 TC 40 Z9 43 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2001 VL 219 IS 3 BP 835 EP 841 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 435EQ UT WOS:000168864800037 PM 11376279 ER PT J AU Gastel, JA AF Gastel, JA TI Early indicators of response in biologically based risk assessment for nongenotoxic carcinogens SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; LOW-DOSE EXTRAPOLATION; GENE-EXPRESSION; CHRONIC EXPOSURE; INDUCTION; RECEPTOR; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; MECHANISMS; TOXICITY; MODELS AB The proposed existence of dose-response thresholds for nongenotoxic carcinogens has led to a major controversy in the risk extrapolation process. To resolve this debate, there has been a significant investment in mechanism-based risk assessment research. The ability to utilize this mechanistic research for risk assessment procedures is still limited and may not warrant the expense. Alternatively, an approach can be used to identify dose-response thresholds through the utilization of sensitive indicators of biological response. This approach does not rely upon a mechanistic framework for the development of pathology, is solely dependent on already existing technology, and takes into account the possibility of background levels of pathway activation. For this approach, sensitive biochemical responses need to be identified and linked to the introduction of the toxicant through dose response, by time of response, and, when possible, through a proposed biochemical mechanism. The weakness of this approach is that more sensitive unidentified responses may exist requiring that a safety factor of 10 be used to define a NOEL. For dioxin-like compounds, using a surrogate marker of response CYP1A1 induction, this approach yields an estimate of the acceptable daily intake of 550 fg/kg/day. This limit is remarkably similar to the results of the original EPA linear extrapolation (6 fg/kg/day). A similar approach can be used for other nongenotoxic carcinogens and the analysis can be completed within 1 year. C1 NIH, Bethesda, MD 20892 USA. RP Gastel, JA (reprint author), NIH, Bldg 49,Room 5A-32, Bethesda, MD 20892 USA. NR 62 TC 8 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUN PY 2001 VL 33 IS 3 BP 393 EP 398 DI 10.1006/rtph.2001.1358 PG 6 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 445PX UT WOS:000169467400011 PM 11407940 ER PT J AU Li, YZ Chen, ZY Wang, WR Baker, CC Krug, RM AF Li, YZ Chen, ZY Wang, WR Baker, CC Krug, RM TI The 3 '-end-processing factor CPSF is required for the splicing of single-intron pre-mRNAs in vivo SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE 3 '-end processing; CPSF; influenza virus NS1A protein; PABII; pre-mRNA splicing ID RNA-POLYMERASE-II; VIRUS NS1 PROTEIN; POLYADENYLATION SPECIFICITY FACTOR; VERTEBRATE POLY(A) POLYMERASE; MESSENGER-RNA; INFLUENZA-VIRUS; 3'-END FORMATION; NUCLEOCYTOPLASMIC TRANSPORT; CARBOXYL-TERMINUS; NUCLEAR EXPORT AB We describe a new approach to elucidate the role of 3'-end processing in pre-mRNA splicing in vivo using the influenza virus NS1A protein. The effector domain of the NS1A protein, which inhibits the function of the CPSF and PABII factors of the cellular 3'-end-processing machinery, is sufficient for the inhibition of not only 3'-end formation but also the splicing of single-intron pre-mRNAs in vivo. We demonstrate that inhibition of the splicing of single-intron pre-mRNAs results from inhibition of 3'-end processing, thereby establishing that 3'-end processing is required for the splicing of a 3' terminal intron in vivo. Because the NS1A protein causes a global suppression of 3'-end processing in trans, we avoid the ambiguities caused by the activation of cryptic poly(A) sites that occurs when mutations are introduced into the AAUAAA sequence in the pre-mRNA. In addition, this strategy enabled us to establish that the function of a particular 3'-end-processing factor, namely CPSF, is required for the splicing of single-intron pre-mRNAs in vivo: splicing is inhibited only when the effector domain of the NS1A protein binds and inhibits the function of the 30-kDa CPSF protein in 3'-end formation. In contrast, the 3'-end processing factor PABII is not required for splicing. We discuss the implications of these results for cellular and influenza viral mRNA splicing. C1 Univ Texas, Inst Mol & Cellular Biol, Sect Mol Genet & Microbiol, Austin, TX 78712 USA. NCI, Basic Res Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Krug, RM (reprint author), Univ Texas, Inst Mol & Cellular Biol, Sect Mol Genet & Microbiol, Austin, TX 78712 USA. FU NIAID NIH HHS [AI11772] NR 40 TC 88 Z9 93 U1 0 U2 5 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD JUN PY 2001 VL 7 IS 6 BP 920 EP 931 DI 10.1017/S1355838201010226 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442UY UT WOS:000169304400012 PM 11421366 ER PT J AU Puertollano, R Aguilar, RC Gorshkova, I Crouch, RJ Bonifacino, JS AF Puertollano, R Aguilar, RC Gorshkova, I Crouch, RJ Bonifacino, JS TI Sorting of mannose 6-phosphate receptors mediated by the GGAs SO SCIENCE LA English DT Article ID FACTOR-II RECEPTOR; CYTOPLASMIC DOMAIN; GAMMA-ADAPTIN; TRANS-GOLGI; SIGNALS; PROTEINS; BINDING; FAMILY; RECOGNITION; TRAFFICKING AB The delivery of soluble hydrolases to lysosomes is mediated by the cation-independent and cation-dependent mannose 6-phosphate receptors. The cytosolic tails of both receptors contain acidic-cluster-dileucine signals that direct sorting from the trans-Golgi network to the endosomal-lysosomal system. We found that these signals bind to the VHS domain of the Golgi-localized, gamma -ear-containing, ARF-binding proteins (GGAs). The receptors and the GGAs left the trans-Golgi network on the same tubulo-vesicular carriers. A dominant-negative GGA mutant blocked exit of the receptors from the trans-Golgi, network. Thus, the GGAs appear to mediate sorting of the mannose 6-phosphate receptors at the trans-Golgi network. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Genet Mol Lab, 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 17 TC 274 Z9 285 U1 0 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 1 PY 2001 VL 292 IS 5522 BP 1712 EP 1716 DI 10.1126/science.1060750 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 438AP UT WOS:000169031800044 PM 11387475 ER PT J AU Condit, CM Ferguson, A Kassel, R Thadhani, C Gooding, HC Parrott, R AF Condit, CM Ferguson, A Kassel, R Thadhani, C Gooding, HC Parrott, R TI An exploratory study of the impact of news headlines on genetic determinism SO SCIENCE COMMUNICATION LA English DT Article AB Critics have suggested that news headlines about generics with inappropriately deterministic content will produce increased levels of determinism in the public er en when news article contents are not highly deterministic. This might result from a replacement effect (headlines stand in for the content of the article because few people read it fully) or from framing effect (headlines frame the interpretation of the article content). A quantitative e impact study and an interview method were used to rest the impact of the framing effect in a news article on genes and diabetes. This exploratory study found no support for a framing effect. Directions for future research are discussed. C1 Univ Georgia, Dept Speech Commun, Athens, GA 30602 USA. NHGRI, Bethesda, MD 20892 USA. Penn State Univ, University Pk, PA 16802 USA. RP Condit, CM (reprint author), Univ Georgia, Dept Speech Commun, Terrell Hall, Athens, GA 30602 USA. NR 16 TC 32 Z9 32 U1 0 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1075-5470 J9 SCI COMMUN JI Sci. Commun. PD JUN PY 2001 VL 22 IS 4 BP 379 EP 395 DI 10.1177/1075547001022004002 PG 17 WC Communication SC Communication GA 439NP UT WOS:000169123700002 ER PT J AU Bardeesy, N Sharpless, NE DePinho, RA Merlino, G AF Bardeesy, N Sharpless, NE DePinho, RA Merlino, G TI The genetics of pancreatic adenocarcinoma: a roadmap for a mouse model SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE pancreatic cancer; transgenic mouse; genetics ID TRANSFORMING-GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; PEUTZ-JEGHERS-SYNDROME; TRANSGENIC MICE; EXOCRINE PANCREAS; FACTOR-BETA; CANCER-CELLS; TGF-BETA; TELOMERASE ACTIVITY; JUVENILE POLYPOSIS AB Pancreatic cancer is among the leading causes of cancer death. Although a genetic profile for pancreatic cancer is emerging, many biological aspects of this disease are poorly understood. Indeed fundamental questions regarding progenitor cell lineages, host stromal milieu, and the role of specific genetic alterations in tumor progression remain unresolved. A mouse model engineered with signature mutations would provide a powerful ally in the study of pancreatic cancer biology and may guide improved prognostic assessment and treatment for the human disease. In this review, we discuss the molecular basis for normal pancreatic development and the genetics of human pancreatic adenocarcinoma in the hope of charting a course for the development of a faithful mouse model for this lethal cancer. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Bardeesy, N (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 151 TC 24 Z9 25 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD JUN PY 2001 VL 11 IS 3 BP 201 EP 218 DI 10.1006/scbi.2000.0371 PG 18 WC Oncology SC Oncology GA 447YW UT WOS:000169600900004 PM 11407945 ER PT J AU Hennighausen, L AF Hennighausen, L TI The genetics and pathology of mouse mammary cancer SO SEMINARS IN CANCER BIOLOGY LA English DT Editorial Material ID TRANSGENIC MICE; T-ANTIGEN; EXPRESSION; MUTATION; CELLS; DELETION; GLAND; GENES; RAS C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Room 101, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD JUN PY 2001 VL 11 IS 3 BP 239 EP 244 DI 10.1006/scbi.2000.0370 PG 6 WC Oncology SC Oncology GA 447YW UT WOS:000169600900007 PM 11407948 ER PT J AU Yang, FC Merlino, G Chin, L AF Yang, FC Merlino, G Chin, L TI Genetic dissection of melanoma pathways in the mouse SO SEMINARS IN CANCER BIOLOGY LA English DT Article DE melanoma; mouse model; 16(INK4a); p19(ARF); INK4; p53; RB; H-RAS(V12G) ID HUMAN-MALIGNANT MELANOMA; TUMOR-SUPPRESSOR GENE; HUMAN MELANOCYTIC LESIONS; CLINIC-BASED POPULATION; CUTANEOUS MELANOMA; CELL-CYCLE; FAMILIAL MELANOMA; P53 GENE; ULTRAVIOLET-RADIATION; GERMLINE MUTATIONS AB The frequent loss of the INK4a/ARF locus, encoding for both p16(INK4a) and p19(ARF) in, human melanoma, raises the question as to which INK4a/ARF gene product functions to suppress melanoma-genesis in vivo. Studies in the mouse have shown that activated RAS mutation can cooperate with INK4a(Delta2/3) deficiency (null for both p16(INK4a) and P19(ARF)) to promote development of melanoma, and these melanomas retain wild-type p53. Given the functional link between p19(ARF) and p53, we have shown shown that activated RAS can also cooperate with p53 deficiency to produce melanoma in the mouse Moreover, genome-wide analysis of RAS-induced p53 mutant melanomas reveals alterations of key components governing RB-regulated G1/S transition, such as c-Myc. These experimental findings suggest that both RE and p53 pathways function to suppress melanocyte transformation in vivo in the mouse. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Chin, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,Mayer448, Boston, MA 02115 USA. NR 73 TC 15 Z9 16 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD JUN PY 2001 VL 11 IS 3 BP 261 EP 268 DI 10.1006/scbi.2000.0376 PG 8 WC Oncology SC Oncology GA 447YW UT WOS:000169600900009 PM 11407950 ER PT J AU Mamounas, T Swain, S AF Mamounas, T Swain, S TI Breast cancer at the millennium: The new frontier SO SEMINARS IN ONCOLOGY LA English DT Editorial Material C1 Aultman Hlth Fdn, Canton, OH USA. NCI, Bethesda, MD 20892 USA. RP Mamounas, T (reprint author), Aultman Hlth Fdn, Canton, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 2001 VL 28 IS 3 BP 219 EP 220 DI 10.1016/S0093-7754(01)90113-7 PG 2 WC Oncology SC Oncology GA 444WM UT WOS:000169423100001 ER PT J AU Wickerham, DL Tan-Chiu, E AF Wickerham, DL Tan-Chiu, E TI Breast cancer chemoprevention: Current status and future directions SO SEMINARS IN ONCOLOGY LA English DT Review ID RECEPTOR-POSITIVE TUMORS; BONE-MINERAL DENSITY; OVARIECTOMIZED RATS; ADJUVANT TAMOXIFEN; WOMEN; RALOXIFENE; ESTROGEN; GROWTH; TRIAL; PREVENTION C1 Natl Surg Adjuvant Breast & Bowel Project, Allegheny Ctr 4, Pittsburgh, PA 15212 USA. RP Wickerham, DL (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Allegheny Ctr 4, E Commons Profess Bldg,5th Floor, Pittsburgh, PA 15212 USA. FU NCI NIH HHS [U10-CA-37377, U10-CA-69974] NR 38 TC 8 Z9 8 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 2001 VL 28 IS 3 BP 253 EP 259 DI 10.1053/sonc.2001.23491 PG 7 WC Oncology SC Oncology GA 444WM UT WOS:000169423100006 PM 11402435 ER PT J AU Paik, S AF Paik, S TI Incorporating genomics into the cancer clinical trial process SO SEMINARS IN ONCOLOGY LA English DT Review ID BREAST-CANCER; EXPRESSION C1 Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, Pittsburgh, PA 15212 USA. RP Paik, S (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, 4 Allegheny Ctr ,5th Floor,E Commons Profess Bldg, Pittsburgh, PA 15212 USA. FU NCI NIH HHS [U10-CA-12027, U10-CA-69974, U10-CA-69651, U10-CA-373777] NR 8 TC 7 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 2001 VL 28 IS 3 BP 305 EP 309 DI 10.1016/S0093-7754(01)90123-X PG 5 WC Oncology SC Oncology GA 444WM UT WOS:000169423100011 PM 11402440 ER PT J AU Kacena, KA Dohnal, K Benesova, V Grivna, M Deliopolu, J Tryzna, R Horak, J Gaydos, CA Quinn, TC AF Kacena, KA Dohnal, K Benesova, V Grivna, M Deliopolu, J Tryzna, R Horak, J Gaydos, CA Quinn, TC TI Chlamydia, gonorrhea, and HIV-1 prevalence among five populations of women in the Czech and Slovak Republics SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID LIGASE CHAIN-REACTION; URINE SAMPLES; INFECTIONS; ACCURACY AB Background: Five populations at risk for sexually transmitted diseases (STDs) in the Czech and Slovak Republics mere sampled, Goal: To estimate prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, and HIV-1 infections. Study Design: Urine specimens were collected serially from women at a Prague prenatal clinic (n = 134), a Prague dermatovenerealogy clinic (n = 91), sex workers from northern and central Bohemia (n = 35), students from a northern Bohemian school (n = 217), and Gypsies from Jarovnice, Slovakia (n = 128). These specimens were tested for chlamydia and gonorrhea using a ligase chain reaction pooling algorithm, and for HIV using an enzyme immunoassay confirmed by Western blot. Results: The prevalence of chlamydia was 2.2% (95% CI, 0.4-6.4) in the prenatal clinic, 5.5% (95% CI, 1.8-12.4) in the STD clinic, 22.9% (95% CI, 10.4-40.1) among street sex workers, 8.2% (95% CI, 3.6-15.6) among sexually active female high school students, and 3.9% (95% CI, 1.3-8.9) among Gypsy women. Gonorrhea was found in only two populations: 2.2% (95% CI, 0.3-7.7) in the STD clinic, and 2.9% (95% CI, 0.1-14.9) among sex workers. No HIV-1 infection was detected. Conclusions: Urine screening was an efficient and accurate method for identifying groups at risk for STDs in the Czech Republic and Slovakia because sample collection was fast and noninvasive, and potential participation bias was reduced by high acceptability. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. Charles Univ, Fac Med 1, Prague, Czech Republic. Charles Univ, Fac Med 2, Prague, Czech Republic. NIAID, NIH, Bethesda, MD 20892 USA. RP Quinn, TC (reprint author), Johns Hopkins Univ, Div Infect Dis, Ross Res Bldg,Room 1159,720 Rutland Ave, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 14 TC 10 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JUN PY 2001 VL 28 IS 6 BP 356 EP 362 DI 10.1097/00007435-200106000-00010 PG 7 WC Infectious Diseases SC Infectious Diseases GA 438QD UT WOS:000169063800010 PM 11403195 ER PT J AU Ahn, NU Nallamshetty, L Ahn, UM Buchowski, JM Rose, PS Garrett, ES Kebaish, KM Sponseller, PD AF Ahn, NU Nallamshetty, L Ahn, UM Buchowski, JM Rose, PS Garrett, ES Kebaish, KM Sponseller, PD TI Dural ectasia and conventional radiography in the Marfan lumbosacral spine SO SKELETAL RADIOLOGY LA English DT Article DE Marfan syndrome; dural ectasia; lumbosacral spine; radiographic findings ID BACK PAIN; MENINGOCELE; MUTATIONS; PATIENT AB Objective. To determine how well conventional radiographic findings can predict the presence of dural ectasia in Marfan patients. Design and patients. Twelve Marfan patients without dural ectasia and 21 Marfan patients with dural ectasia were included in the study. Five radiographic measurements were made of the lumbosacral spine: interpediculate distance, scalloping value, sagittal canal diameter, vertebral body width, and transverse process width. Results. The following measurements were significantly larger in patients with dural ectasia: interpediculate distances at L3-L4 levels (P <0.03); scalloping values at the L1 and L5 levels (P <0.05); sagittal diameters of the vertebral canal at L5-S1 (P <0.03); transverse process to width ratios at L2 (P <0.03). Criteria were developed for diagnosis of dural ectasia in Marfan patients. These included presence of one of the following: interpediculate distance at L4 greater than or equal to 38.0 mm, sagittal diameter at S1 greater than or equal to 18.0 mm, or scalloping value at L5 greater than or equal to5.5 mm. Conclusion. Dural ectasia in Marfan syndrome is commonly associated with several osseous changes that are observable on conventional radiographs of the lumbosacral spine. Conventional radiography can detect dural ectasia in patients with Marfan syndrome with a very high specificity (91.7%) but a low sensitivity (57.1%). C1 Johns Hopkins Univ, Sch Med, Dept Orthopaed Surg, Baltimore, MD USA. Johns Hopkins Outpatient Ctr, Dept Orthopaed Surg, Baltimore, MD 21287 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Div Biostat, Baltimore, MD 21218 USA. RP Ahn, NU (reprint author), Johns Hopkins Outpatient Ctr, Dept Orthopaed Surg, 601 N Caroline St,5th Floor, Baltimore, MD 21287 USA. OI Buchowski, Jacob/0000-0001-8880-8490 NR 30 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JUN PY 2001 VL 30 IS 6 BP 338 EP 345 PG 8 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 442VE UT WOS:000169305000008 PM 11465775 ER PT J AU Moutsopoulos, NM Moutsopoulos, HM AF Moutsopoulos, NM Moutsopoulos, HM TI Therapy of Sjogren's syndrome SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID PREVENTING DENTAL-CARIES; KERATOCONJUNCTIVITIS SICCA; INVOLVEMENT; LYMPHOMA; DISEASE; TRIAL; AUTOANTIGENS C1 Natl Inst Dental Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Natl Tech Univ Athens, Sch Med, Dept Pathophysiol, GR-15773 Athens, Greece. RP Moutsopoulos, NM (reprint author), Natl Inst Dental Craniofacial Res, Oral Infect & Immun Branch, NIH, BL 30,Room 327,30 Convent Dr, Bethesda, MD 20892 USA. NR 37 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD JUN PY 2001 VL 23 IS 1-2 BP 131 EP 145 DI 10.1007/s002810100070 PG 15 WC Immunology; Pathology SC Immunology; Pathology GA 442TZ UT WOS:000169302200010 PM 11455852 ER PT J AU Worrall, BB Chen, DT Meschia, JF AF Worrall, BB Chen, DT Meschia, JF TI Ethical and methodological issues in pedigree stroke research SO STROKE LA English DT Article DE ethics, medical; family; patient selection; pedigree; stroke ID AUTOSOMAL-DOMINANT ARTERIOPATHY; HUMAN GENETIC-VARIATION; HEALTH-CARE DATABASE; SICKLE-CELL DISEASE; PROTECTING COMMUNITIES; SUBCORTICAL INFARCTS; INFORMED CONSENT; NATURAL-HISTORY; PRIVACY; ICELAND AB Background - Stroke is a complex genetic disorder with a variable phenotype, Investigations of heritable factors in complex genetic disorders use pedigree and genetic techniques, which pose different ethical and methodological challenges than those routinely encountered in therapeutic research. Building consensus on acceptable research practices in this field is vital to the success of multicentered collaborations. Summary of Review - We review important ethical and methodological concerns related to the collection, storage, and release of pedigree research information. The human studies aspects of pedigree research are complicated methodologically because individuals can be active or passive participants and pedigrees can be proband derived, partially validated, or fully validated. Current research ethics frameworks do not work well outside of a dyadic researcher-subject relationship. Privacy and confidentiality for family members must be considered in pedigree research, Investigators should anticipate potential conflicts of interest among family members when designing a pedigree research protocol. Conclusions - We propose a "proband-initiated contact" methodology in which the proband or the proband's designate allows identification of potential families without breaching the privacy of individuals in the family. In situations in which family history data are collected without direct contact between researchers and individuals in the proband's family, an Institutional Review Board may waive consent by family members after appropriate review of the protocol and application of rules for granting waivers of consent. Certificates of Confidentiality should be considered. C1 Univ Virginia, Dept Neurol, Charlottesville, VA 22903 USA. Univ Virginia, Dept Hlth Evaluat Sci, Charlottesville, VA 22903 USA. Univ Virginia, SE Rural Mental Hlth Res Ctr, Charlottesville, VA 22903 USA. Univ Virginia, Inst Law Psychiat & Publ Policy, Charlottesville, VA 22903 USA. Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA. RP Chen, DT (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bldg 10,10 Ctr Dr,Room 1C-118, Bethesda, MD 20892 USA. FU NIMH NIH HHS [P50 MH49173]; NINDS NIH HHS [R01 NS039987, NS39987, R01 NS039987-02] NR 69 TC 16 Z9 16 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2001 VL 32 IS 6 BP 1242 EP 1249 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 440PZ UT WOS:000169184600002 PM 11387482 ER PT J AU Chalela, JA Katzan, I Liebeskind, DS Rasmussen, P Zaidat, O Suarez, JI Chiu, D Klucznick, RP Jauch, E Cucchiara, BL Saver, J Kasner, SE AF Chalela, JA Katzan, I Liebeskind, DS Rasmussen, P Zaidat, O Suarez, JI Chiu, D Klucznick, RP Jauch, E Cucchiara, BL Saver, J Kasner, SE TI Safety of intra-arterial thrombolysis in the postoperative period SO STROKE LA English DT Article DE complications; retrospective studies; stroke management; thrombolysis ID ACUTE ISCHEMIC STROKE; LOCAL INTRAARTERIAL THROMBOLYSIS; PULMONARY-EMBOLISM; OCCLUSION; THERAPY; ANGIOPLASTY AB Background and Purpose-Limited systemic fibrinolysis and reduced dosage are features of intra-arterial thrombolyis (IAT) that may be advantageous in the treatment of postoperative strokes. However, IAT may increase the risk of surgical bleeding. We sought to determine the safety of postoperative IAT. Methods-This was a retrospective case series from 6 university hospitals. All cases of IAT within 2 weeks of surgery were identified. Demographics, stroke mechanism, stroke severity, imaging and angiographic findings, time between surgery and lysis, thrombolytic agent used, surgical site bleeding, intracranial bleeding, and mortality rates were determined. Death or complications directly related to IAT were determined. Results-Thirty-six patients (median age, 71.5 years; range, 45 to 85) were identified. Median time from surgery to stroke was 21.5 hours (range, 1 to 120). Open heart surgery was done in 18 (50%), carotid endarterectomy in 6 (17%), craniotomy in 3 (8%), ophthalmologic-ear, nose and throat surgery in 2 (6%), urologic-gynecologic surgery in 4 (11%), orthopedic surgery in 2 (6%), and plastic surgery in 1 (3%). The stroke causes were cardioembolism in 24 (67%), large-vessel atherosclerosis in 4 (11%), dissection in 3 (8%), postendarterectomy occlusion in 4 (11%), and radiation arteriopathy in 1 (3%). Median time to angiogram was 2.5 hours (0.1 to 5,5). Occlusion sites were M1 in 19 (53%), M2 in 9 (25%), internal carotid artery in 5 (14%), basilar artery in 2 (6%), and posterior communicating artery in 1 (3%). Thrombolysis was completed at a median of 4.5 hours (range, 1 to 8.0). Tissue plasminogen activator was used in 19 (53%) and urokinase in 17 (47%). Nine (26%) patients died. Surgical site bleeding occurred in 9 (25%) cases (minor in 6, major in 3). The major surgical bleeds were 2 post-craniotomy intracranial hemorrhages and 1 hemopericardium after coronary artery bypass grafting; all were fatal. Six deaths were non-IAT related: 3 caused by cerebral edema and 3 by systemic causes. Major bleeding complications were significantly more common among patients with craniotomy (P <0.02). Conclusions-Postoperative IAT carries a risk of bleeding in up to 25% of patients but is usually minor surgical site bleeding. Avoiding IAT in intracranial surgery patients may reduce complications. Mortality rate in this series was similar to that reported in prior IAT trials. IAT remains a viable therapeutic option for postoperative strokes. C1 Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Radiol, Cleveland, OH 44195 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. Univ Cincinnati, Coll Med, Dept Emergency Med, Greater Cincinnati No Kentucky Stroke Team, Cincinnati, OH USA. RP Chalela, JA (reprint author), NINDS, NIH, 36 Convent Dr,Room 4A03,MSC 4129, Bethesda, MD 20892 USA. RI Kasner, Scott/C-6109-2011; OI Saver, Jeffrey/0000-0001-9141-2251 NR 16 TC 49 Z9 52 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2001 VL 32 IS 6 BP 1365 EP 1368 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 440PZ UT WOS:000169184600025 PM 11387500 ER PT J AU Foster, MW Sharp, RR Mulvihill, JJ AF Foster, MW Sharp, RR Mulvihill, JJ TI Pharmacogenetics, race, and ethnicity: Social identities and individualized medical care SO THERAPEUTIC DRUG MONITORING LA English DT Article DE pharmacogenetics; race; ethnicity; ethics; research methods ID HUMAN-GENOME-PROJECT; POPULATION; HEALTH; DISEASE; CANCER; ASSOCIATION; DIAGNOSTICS; GENEALOGY; PEDIGREES; GENETICS AB Social categories such as race and ethnicity have long been used in interpreting patient symptoms, diagnosing disease, and predicting therapeutic response. DNA-based diagnostic tests and pharmacogenetic screens could make these uses of social categories largely irrelevant by allowing clinicians to base diagnosis and treatment decisions on the unique genetic features of individual patients. Despite this attractive vision of individualized care. however, social categories are likely to continue playing a significant role in the coming era of genetic medicine. Current uses of social categories in pharmacogenetic research, for example, illustrate how drug development and marketing will perpetuate the use of social categories such as race and ethnicity. Those uses may unintentionally blunt the precision of genetic technologies and pose new threats to socially identifiable populations. These implications suggest the need for greater caution in using social categories as indicators for specific tests or therapies and for federal legislation to protect against discriminatory uses of individuals' genetic information. In addition, more precise social classifications than those presently in use may allow us to realize the full potential of DNA-based technologies, thus minimizing social disparities in health care. Those more precise social classifications should reflect extended patient pedigrees and not the self-reported claims of racial and/or ethnic affiliation. C1 Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Ctr Study Med Eth & Humanities, Durham, NC USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK 73190 USA. RP Foster, MW (reprint author), Univ Oklahoma, Dept Anthropol, 455 W Lindsey Ave,Rm 520, Norman, OK 73019 USA. FU NCI NIH HHS [CA75311]; NHGRI NIH HHS [HG010302] NR 51 TC 16 Z9 16 U1 4 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD JUN PY 2001 VL 23 IS 3 BP 232 EP 238 DI 10.1097/00007691-200106000-00009 PG 7 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 436PX UT WOS:000168945200009 PM 11360031 ER PT J AU Elhassan, YM Wu, G Leanez, AC Tasca, RJ Watson, AJ Westhusin, ME AF Elhassan, YM Wu, G Leanez, AC Tasca, RJ Watson, AJ Westhusin, ME TI Amino acid concentrations in fluids from the bovine oviduct and uterus and in KSOM-based culture media SO THERIOGENOLOGY LA English DT Article DE amino acids; oviductal fluid; uterine fluid; culture medium; bovine embryo ID PREIMPLANTATION MOUSE EMBRYOS; IN-VITRO; REPRODUCTIVE-TRACT; RABBIT EMBRYOS; UTERINE FLUIDS; ARGININE; GLYCINE; METABOLISM; OSMOLARITY; SECRETION AB Amino acids in bovine oviductal and uterine fluids were measured and compared with those in modified simplex optimized medium (KSOM) supplemented with either fetal calf serum or Minimum Essential Medium amino acids in addition to bovine serum albumin, fetal calf serum or polyvinyl alcohol. Concentrations of cysteine, threonine, tryptophan, alanine, aspartate, glycine, glutamate, proline, a-alanine, and citrulline were higher in oviductal fluids than in KSOM-based culture media. Nonessential and essential amino acids were present in ratios of 5:1 and 2:1 in oviductal and uterine fluids, respectively. Concentrations of alanine (3.7 mM), glycine (14.1 mM) and glutamate (5.5 mM) were high in oviductal fluids, comprising 73% of the free amino acid pool. Of the amino acids measured in uterine fluids, alanine (3.1 mM), glycine (12.0 mM), glutamate (4.2 mM), and serine (2.7 mM) were highest in concentration, and the first three comprised 43% of the free amino acid pool. In conclusion, amino acid concentrations in the bovine reproductive tract were substantially higher than those in embryo culture media. Certain amino acids, particularly alanine, glutamate, glycine and taurine, are present in strikingly high concentrations in both oviductal and uterine fluids, suggesting that they might play important roles in early embryo development. The particular pattern of amino acid concentrations may be an important factor to be considered for the improvement of embryo culture media. (C) 2001 by Elsevier Science Inc. C1 Care Of Dr G Wu, Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA. Texas A&M Univ, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Univ Western Ontario, Dept Obstet & Gynaecol & Physiol, London, ON, Canada. RP Elhassan, YM (reprint author), Care Of Dr G Wu, Texas A&M Univ, Dept Anim Sci, 2471 TAMU, College Stn, TX 77843 USA. EM g-wu@tamu.edu RI Watson, Andrew/A-5636-2015 OI Watson, Andrew/0000-0002-2344-3061 FU NICHD NIH HHS [HD 34580] NR 32 TC 31 Z9 35 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0093-691X J9 THERIOGENOLOGY JI Theriogenology PD JUN 1 PY 2001 VL 55 IS 9 BP 1907 EP 1918 DI 10.1016/S0093-691X(01)00532-5 PG 12 WC Reproductive Biology; Veterinary Sciences SC Reproductive Biology; Veterinary Sciences GA 441EW UT WOS:000169218900014 PM 11414495 ER PT J AU Stillman, FA Cronin, KA Evans, WD Ulasevich, A AF Stillman, FA Cronin, KA Evans, WD Ulasevich, A TI Can media advocacy influence newspaper coverage of tobacco: measuring the effectiveness of the American stop smoking intervention study's (ASSIST) media advocacy strategies SO TOBACCO CONTROL LA English DT Article DE ASSIST; intervention study; media advocacy strategy ID NATIONAL-CANCER-INSTITUTE; PROGRAM; HEALTH; MODEL; NEWS AB Objective-To compare the rate and slant of local tobacco control print media coverage in ASSIST (American stop smoking intervention study) states as compared with non-ASSIST states. Methods-Local tobacco control policy articles, editorials, and letters to the editors published from 1994 to 1998 clipped from all daily local newspapers in the USA were analysed (n = 95 911). The main hypothesis tested for the existence of an interaction between ASSIST intervention and time. This interaction would represent a change in the difference between ASSIST and non-ASSIST states over the course of the intervention. Results-No evidence of an ASSIST-year interaction was found. However, a main effect for ASSIST was significant for the percentage of articles with the model predicting higher rates of articles for ASSIST states. Similarly the rate of letters to the editor expressing protobacco control views was higher in ASSIST states than non-ASSIST states. No main effects or interactions were found for analyses of percentage of protobacco control editorials. Models controlled for a measure of preintervention tobacco control conditions at baseline. Conclusions-The presence of an ASSIST main effect should be interpreted with caution because of the quasi-experimental design and the lack of information on article rates before the ASSIST intervention. Nonetheless, these preliminary findings suggest some possible effects of the media advocacy activities of ASSIST when controlling for differences in states' initial tobacco control conditions. C1 NCI, Bethesda, MD 20892 USA. Amer Inst Res, Prospect Ctr, Silver Spring, MD USA. RP Stillman, FA (reprint author), NCI, Execut Plaza N,Room 4040,6130 Execut Blvd,MSC 733, Bethesda, MD 20892 USA. NR 24 TC 36 Z9 36 U1 0 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD JUN PY 2001 VL 10 IS 2 BP 137 EP 144 DI 10.1136/tc.10.2.137 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 442YF UT WOS:000169312000017 PM 11387534 ER PT J AU Malson, JL Sims, K Murty, R Pickworth, WB AF Malson, JL Sims, K Murty, R Pickworth, WB TI Comparison of the nicotine content of tobacco used in bidis and conventional cigarettes SO TOBACCO CONTROL LA English DT Article DE bidis; beedies; youth ID INDIAN BIDI; ADDICTION; SMOKERS AB Objective-To compare the nicotine content of 12 unfiltered brands of bidi cigarettes (hand rolled cigarettes imported from India) with 8 popular brands of filtered and unfiltered US and conventional cigarettes from India. Main outcome measures-Identical laboratory procedures were used to determine nicotine content tin duplicate) and physical characteristics. Results-The nicotine concentration in the tobacco of bidi cigarettes (21.2 mg/g) was significantly greater than the tobacco from the commercial filtered (16.3 mg/g) and unfiltered cigarettes (13.5 mg/g). Conclusions-Bidi cigarettes contain higher concentrations of nicotine than conventional cigarettes. Therefore, it is logical to presume that bidi smokers are at risk of becoming nicotine dependent. These findings belie a popular belief among US teens that bidis are a safe alternative to commercial cigarettes. C1 NIDA, Addict Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA. Murty Pharmaceut Inc, Lexington, KY USA. RP Pickworth, WB (reprint author), NIDA, Addict Res Ctr, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 25 TC 44 Z9 44 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD JUN PY 2001 VL 10 IS 2 BP 181 EP 183 DI 10.1136/tc.10.2.181 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 442YF UT WOS:000169312000024 PM 11387541 ER PT J AU Haseman, JK Bailer, AJ Kodell, RL Morris, R Portier, K AF Haseman, JK Bailer, AJ Kodell, RL Morris, R Portier, K TI Statistical issues in the analysis of low-dose endocrine disruptor data SO TOXICOLOGICAL SCIENCES LA English DT Article AB The National Institute of Environmental Health Sciences (NIEHS) and the U,S, Environmental Protection Agency (U.S. EPA) recently cosponsored the Endocrine Disrupters Low-Dose Peer Review. The purpose of this meeting was to examine data supporting the presence or absence of low-dose effects of endocrine disrupters in specific studies and then to evaluate the likelihood and significance of these and/or other potential low-dose effects for humans. All invited speakers agreed to provide their raw data in advance of the meeting to a Statistics Subpanel, which was asked to reevaluate the authors' experimental design, data analysis, and interpretation of experimental results, The purpose of this statistical reevaluation was to provide an independent assessment of the experimental design and data analysis used in each of the studies and to identify key statistical issues relevant to the evaluation and interpretation of the data. This paper presents a summary of the Statistics Subpanel's evaluation. Specific examples are presented to illustrate problems that arose in the experimental design and data analysis of certain studies, The statistical principles and issues that are discussed in this paper are not unique to endocrine disrupter studies and should provide important guidelines regarding appropriate experimental design and statistical analysis for other types of laboratory investigations. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Miami Univ, Dept Math & Stat, Oxford, OH 45056 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Univ Florida, Dept Stat, Gainesville, FL 32611 USA. Analyt Sci Inc, Durham, NC 27713 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Miami Univ, Dept Math & Stat, Oxford, OH 45056 USA. RP Haseman, JK (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 9 TC 31 Z9 31 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2001 VL 61 IS 2 BP 201 EP 210 DI 10.1093/toxsci/61.2.201 PG 10 WC Toxicology SC Toxicology GA 438XJ UT WOS:000169079300003 PM 11353128 ER PT J AU Liu, J Kadiiska, MB Liu, Y Lu, T Qu, W Waalkes, MP AF Liu, J Kadiiska, MB Liu, Y Lu, T Qu, W Waalkes, MP TI Stress-related gene expression in mice treated with inorganic arsenicals SO TOXICOLOGICAL SCIENCES LA English DT Article DE arsenite; arsenate; acute toxicity; cDNA microarray; heme oxygenase-1 ID AORTIC ENDOTHELIAL-CELLS; NF-KAPPA-B; REACTIVE OXYGEN; DNA-DAMAGE; SODIUM ARSENITE; DIMETHYLARSINIC ACID; OXIDATIVE STRESS; MAMMALIAN-CELLS; HEME OXYGENASE; OXIDANT STRESS AB Arsenic (As) is an environmental chemical of high concern for human health. Acute toxicity of arsenic is dependent on its chemical forms and proximity to high local arsenic concentrations is one of the mechanisms for cell death. This study was designed to define acute arsenic-induced stress-related gene expression in vivo. Mice were injected sc with either sodium arsenite [As(III), 100 mu mol/kg], sodium arsenate [As(V), 300 mu mol/kg], or saline. To examine stress-related gene expression, livers were removed 3 h after arsenic injection for RNA and protein extraction. The Atlas Mouse Stress/Toxicology array revealed that the expression of genes related to stress, DNA damage, and metabolism was altered by acute arsenic treatments. Expression of heme oxygenase 1 (HO-1), a hallmark for arsenic-induced stress, was increased 10-fold, along with increases in heat shock protein-60 (HSP60), DNA damage inducible protein GADD45, and the DNA excision repair protein ERCC1. Downregulation of certain cytochrome P450 enzymes occurred with arsenic treatment. Multiprobe RNase protection assay revealed the activation of the c-Jun/AP-1 transcription complex after arsenic treatments. Western blot analysis further confirmed the enhanced production of arsenic-induced stress proteins such as HO-1, HSP70, HSP90, metallothionein, the metal-responsive transcription factor MTF-1, nuclear factor kappa B and c-Jun/AP-1. Increases in caspase-1 and cytokines such as tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 were also evident. In summary, this study profiled the gene expression pattern in mice treated with inorganic arsenicals, which adds to our understanding of acute arsenic poisoning and toxicity. C1 NIEHS, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. Univ Kansas, Med Ctr, Kansas City, KS 66160 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Liu, J (reprint author), NIEHS, Comparat Carcinogenesis Lab, NCI, Mail Drop F0-09, Res Triangle Pk, NC 27709 USA. NR 39 TC 147 Z9 152 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2001 VL 61 IS 2 BP 314 EP 320 DI 10.1093/toxsci/61.2.314 PG 7 WC Toxicology SC Toxicology GA 438XJ UT WOS:000169079300015 PM 11353140 ER PT J AU Khan, QA Anderson, LM AF Khan, QA Anderson, LM TI Hydrocarbon carcinogens evade cellular defense mechanism of G1 arrest in nontransformed and malignant lung cell lines SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE lung type II cells; lung carcinomas; polycyclic aromatic hydrocarbon diolepoxides; DNA damage; G1 arrest ID WILD-TYPE P53; CANCER CELLS; DNA-DAMAGE; G(1) CHECKPOINT; DIHYDRODIOL EPOXIDE; MCF-7 CELLS; GENE; INDUCTION; MUTATIONS; ADDUCTS AB In previous studies using human breast carcinoma cells (MCF-7) and human colon carcinoma cells (RKO) we have shown that, in response to treatment with hydrocarbon carcinogens, these cell lines failed to undergo a p53-mediated cell cycle arrest in G1 phase; rather, the cells were accumulated in the S phase with damaged DNA, a situation that may lead to replication of DNA on a damaged template, resulting in the enhanced frequency of mutations in the daughter cells. This has been termed a stealth effect. In the present work we have demonstrated that the stealth effect also pertains for lung cells. In E10 nontransformed mouse lung type II cells, two potent hydrocarbon carcinogens, benzo[a]pyrene dihydrodiol epoxide and benzo[g]chrysene dihydrodiol epoxide, damaged DNA as suggested by retardation in S phase, but did not cause G1 arrest, in contrast to the positive control, actinomycin D. Human lung adenocarcinoma A549 cells, with normal p53, likewise exhibited G1 arrest after actinomycin D, but not after treatment with the diol epoxides. Several human lung cancer cell lines with absent or mutant p53, such as H358, H1734, and H82, exhibited no G1 arrest after any of the compounds. However, lung H441 adenocarcinoma cells, with a mutation in exon 5, codon 158 of p53, exhibited partial G1 arrest after the diol epoxides as well as actinomycin D, and H2030 adenocarcinoma cells did not show G1 arrest after any of the chemicals despite a normal p53. The stealth effect of evasion of G1 arrest may contribute to initiation of lung adenocarcinomas and to progression of tumors. A role in resistance to chemotherapy by certain drugs is also likely. C1 NCI, Comparat Carcinogenesis Lab, Cellular Pathogenesis Sect, Frederick, MD 21702 USA. RP Khan, QA (reprint author), NCI, Comparat Carcinogenesis Lab, Cellular Pathogenesis Sect, Frederick, MD 21702 USA. NR 52 TC 21 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUN 1 PY 2001 VL 173 IS 2 BP 105 EP 113 DI 10.1006/taap.2001.9172 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 441QQ UT WOS:000169241400004 PM 11384212 ER PT J AU Lazarus, EF Browning, J Norman, J Oblitas, J Leitman, SF AF Lazarus, EF Browning, J Norman, J Oblitas, J Leitman, SF TI Sustained decreases in platelet count associated with multiple, regular plateletpheresis donations SO TRANSFUSION LA English DT Article ID COLLECTION AB BACKGROUND: Transient but significant decreases in platelet counts have been documented to occur in donors undergoing single and serial short-term plateletpheresis collections. The effect of long-term regular plateletpheresis on donor platelet counts has not been characterized. STUDY DESIGN AND METHODS: A retrospective study was performed to evaluate the effects of long-term regular plateletpheresis donation on donor platelet counts. A computerized database containing records of 11,464 apheresis collections from 939 donors over a Lt-year period was queried for serial preapheresis platelet counts. Donors were categorized by sex, age, and cumulative number of donations. The average difference in platelet counts (m Delta PC) between each donor's first and last platelet count during this period was calculated for each category. A subgroup of frequent donors was selected for analysis of m Delta PC, using the baseline platelet count obtained before the first plateletpheresis procedure. RESULTS: A significant and sustained decrease in platelet count was identified for all donation frequency categories. The frequency of donation correlated directly with decrease in platelet count for ail but the highest-frequency donation group, in which deferrals for low platelet count blunted the extent of the m Delta PC. A mean decrease of 40,000 per muL from baseline occurred in the frequent-donor subgroup. A total of 84 donors (9%) were deferred for tow platelet count. The majority returned to donate successfully after temporary deferral. CONCLUSIONS: Regular plateletpheresis donors develop sustained decreases in platelet count. However, clinically significant thrombocytopenia is unusual when rigorous ongoing review and prudent deferral policies are established and followed. C1 NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Leitman, SF (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 12 TC 32 Z9 34 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2001 VL 41 IS 6 BP 756 EP 761 DI 10.1046/j.1537-2995.2001.41060756.x PG 6 WC Hematology SC Hematology GA 440AK UT WOS:000169150600007 PM 11399815 ER PT J AU Matsuo, K Procter, JL Chanock, S Stroncek, DF AF Matsuo, K Procter, JL Chanock, S Stroncek, DF TI The expression of NA antigens in people with unusual Fc gamma receptor III genotypes SO TRANSFUSION LA English DT Article ID HUMAN-NEUTROPHILS; FORMS; GENES; POLYMORPHISMS; NEUTROPENIA; DISEASE; CD16 AB BACKGROUND: The Fc gamma receptor IIIb (Fc gamma RIIIB) genes that encode neutrophil-specific antigens NAI and NA2 differ at 5 nucleotides (nts); in 4, the result is an amino acid (AA) difference between the two alleles. The role of each of these differences in antigen expression is not known. Persons with Fc gamma RIIIB genes that differ from NA1-Fc gamma RIIIB and NA2-Fc gamma RIIIB by 1 nt have been described. This study compared NAI and NA2 expression on granulocytes in persons with variant Fc gamma RIIIB genes and in healthy blood donors. STUDY DESIGN AND METHODS: Reactions of NA1- and NA2-specific MoAbs and alloantibodies with granulocytes were assessed by flow cytometry in 74 healthy blood donors and 6 persons with known variant Fc gamma RIIIB genes. The granulocytes were tested with 1 NAI-specific MoAb, 1 NAP-specific MoAb, 4 NA1-specific alloantibodies, and 4 NAP-specific alloantibodies. RESULTS: Analysis of granulocytes from persons with variant NA genotypes found that single-base substitutions in Fc gamma RIIIB at 141 and at 349 are important in NAI expression and those at 227 and 277 are important in NA2 expression. Among blood donors, neither age, sex, nor race affected the expression of NA1 or NA2. The NAP-specific MoAb reacted more intensely with granulocytes from NAP-double-dose cells than with those from NA-single-dose cells, but this was not true for the NAP-specific alloantibodies. There was no difference in the reactions of the NA1-specific MoAbs and alloantibodies with donor samples of known NA1-double-dose or NA-single-dose cells. The intensity of reactions of both the NA1- and NAP-specific MoAbs and alloantibodies were strongly correlated on double-dose cells but not on single-dose cells. In fact, granulocytes from 74 healthy blood donors, phenotyped as NA-single-dose with the MoAbs, were phenotyped as NAP-double-dose with the alloantibodies. Variations in Fc gamma RIIIB are common in blacks, but 5 of the 6 donors were white. These results suggest that Fc gamma RIIIB variations may be common in both whites and blacks. CONCLUSIONS: NA2 expression is affected by polymorphisms in Fc gamma RIIIB227 and Fc gamma RIIIB 277, both of which are involved in an Fc gamma RIIIb N-glycosylation site. Polymorphisms in Fc gamma RIIIB at 141 and 349 appear more important to NAI expression. C1 Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Kurume Univ, Dept Internal Med 1, Fukuoka, Japan. RP Stroncek, DF (reprint author), Warren G Magnuson Clin Ctr, Dept Transfus Med, 10 Ctr Dr,MSC 1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 18 TC 7 Z9 8 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2001 VL 41 IS 6 BP 775 EP 782 DI 10.1046/j.1537-2995.2001.41060775.x PG 8 WC Hematology SC Hematology GA 440AK UT WOS:000169150600011 PM 11399819 ER PT J AU Bolan, CD Conry-Cantilena, C Mason, G Rouault, TA Leitman, SF AF Bolan, CD Conry-Cantilena, C Mason, G Rouault, TA Leitman, SF TI MCV as a guide to phlebotomy therapy for hemochromatosis SO TRANSFUSION LA English DT Article ID HEREDITARY HEMOCHROMATOSIS; IDIOPATHIC HEMOCHROMATOSIS; VENESECTION THERAPY; IRON-METABOLISM; TRANSFERRIN; MANAGEMENT; FERRITIN; GENE; ATHEROSCLEROSIS; DEFICIENCY AB BACKGROUND: A multitude of recommendations exist for laboratory assays to monitor the pace and endpoints of phlebotomy therapy for hemochromatosis. All of these recommendations rely on an assessment of storage iron to guide treatment, and none have been prospectively evaluated. STUDY DESIGN AND METHODS: Nine consecutive patients underwent serial monitoring of Hb, MCV, transferrin saturation, and ferritin during weekly phlebotomy to deplete iron stores (induction therapy) and less frequent sessions to prevent iron reaccumulation (maintenance therapy). Changes in MCV and Hb were used to guide the pace of phlebotomy over a median of 7 years of follow-up. RESULTS: During induction therapy, the MCV increased transiently because of reticulocytosis and then stabilized for a prolonged period before decreasing more sharply which reflected iron-limited erythropoiesis. Iron depletion was achieved after a median of 38 phlebotomies and removal of 9.0 g of iron. Maintenance phlebotomy was targeted to maintain the MCV at 5 to 10 percent below prephlebotomy values and the Hb at > 13 g per dL. Transferrin saturation fluctuated considerably during treatment, but remained below 35 percent during MCV-guided maintenance therapy. Ferritin values were not useful guides to the pace of phlebotomy. The median maintenance therapy phlebotomy interval was 7.5 weeks (range, 6-16), which corresponded to an average daily iron removal of 35 to 67 mug per kg. Most patients showed evidence of iron reaccumulation at phlebotomy intervals of 8 weeks or more. CONCLUSION: The MCV is an inexpensive, precise, physiologic indicator of erythropoietic iron availability. When used in conjunction with the Hb, it is a clinically useful guide to the pace of phlebotomy therapy for hemochromatosis. C1 NICHHD, Dept Transfus Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Leitman, SF (reprint author), NICHHD, Dept Transfus Med, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 65 TC 22 Z9 23 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2001 VL 41 IS 6 BP 819 EP 827 DI 10.1046/j.1537-2995.2001.41060819.x PG 9 WC Hematology SC Hematology GA 440AK UT WOS:000169150600019 PM 11399827 ER PT J AU Eisenhaber, F Wechselberger, C Kreil, G AF Eisenhaber, F Wechselberger, C Kreil, G TI The Brix domain protein family - a key to the ribosomal biogenesis pathway? SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CLONING AB Six (one archaean and five eukaryotic) protein families have similar domain architecture that includes a central globular Brix domain, and optional N- and obligatory C-terminal segments, both with charged low-complexity regions. Biological data for some proteins in this superfamily suggest a role in ribosome biogenesis and rRNA binding. C1 Res Inst Mol Pathol, A-1030 Vienna, Austria. NCI, Tumor Growth Factor Sect, NIH, Bethesda, MD 20892 USA. Austrian Acad Sci, Inst Mol Biol, A-5020 Salzburg, Austria. RP Eisenhaber, F (reprint author), Res Inst Mol Pathol, Dr Bohr-Gasse 7, A-1030 Vienna, Austria. NR 13 TC 31 Z9 31 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUN PY 2001 VL 26 IS 6 BP 345 EP 347 DI 10.1016/S0968-0004(01)01851-5 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 444VH UT WOS:000169420400003 PM 11406393 ER PT J AU Zimmerberg, J AF Zimmerberg, J TI How can proteolipids be central players in membrane fusion? SO TRENDS IN CELL BIOLOGY LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; EXOCYTOSIS; PORES; CA2+; BILAYERS; PROTEIN; COMPLEX; BINDING; STAGE; SITES AB Proton transport ATPases have been celebrated as rotating motors that energize membranes. Now studies of membrane fusion in yeast suggest that the hydrophobic subunits of the vacuolar ATPase participate in formation of fusion pores. This work confirms previous studies showing that membrane approximation by alpha -helical protein bundles is inadequate for complete intracellular fusion and reopens a debate over whether the core of the central intermediate of membrane fusion is lipidic or proteinaceous. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NR 30 TC 32 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JUN PY 2001 VL 11 IS 6 BP 233 EP 235 DI 10.1016/S0962-8924(01)02003-7 PG 3 WC Cell Biology SC Cell Biology GA 432WB UT WOS:000168717800001 PM 11356343 ER PT J AU Ingram, DK AF Ingram, DK TI Vaccine development for Alzheimer's disease: a shot of good news SO TRENDS IN NEUROSCIENCES LA English DT Article AB Studies in transgenic mouse models of Alzheimer's disease suggest the potential for vaccine development for this disease. Specifically, inoculation with A beta peptide reduces A beta plaque formation. However, this vaccination strategy has raised safety concerns. Recent studies have reduced these concerns by demonstrating that long-term A beta vaccination in transgenic mice does not produce detrimental behavioral effects and in fact appears to protect against age-related functional decline in spatial memory tasks. C1 NIA, Gerontol Res Ctr, Behav Neursci Sect, Lab Neurosci,NIH, Baltimore, MD 21224 USA. RP Ingram, DK (reprint author), NIA, Gerontol Res Ctr, Behav Neursci Sect, Lab Neurosci,NIH, 5600 Nathan Shock Lane Dr, Baltimore, MD 21224 USA. NR 2 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUN PY 2001 VL 24 IS 6 BP 305 EP 307 DI 10.1016/S0166-2236(00)01796-3 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 433NK UT WOS:000168766300001 PM 11356488 ER PT J AU Dammann, O Durum, S Leviton, A AF Dammann, O Durum, S Leviton, A TI Do white cells matter in white matter damage? SO TRENDS IN NEUROSCIENCES LA English DT Editorial Material ID BIRTH-WEIGHT INFANTS; SPINAL-CORD INJURY; FOCAL CEREBRAL-ISCHEMIA; NECROSIS-FACTOR-ALPHA; CRANIAL ULTRASOUND ABNORMALITIES; FETAL INFLAMMATORY RESPONSE; CENTRAL-NERVOUS-SYSTEM; PERIVENTRICULAR LEUKOMALACIA; BRAIN-DAMAGE; PRETERM PARTURITION AB Support is provided for the hypothesis that activated leukocytes, especially monocytes/macrophages, contribute to cerebral white matter damage in extremely low gestational age newborns. Much of the evidence is indirect and comes from analogies to brain diseases in adults, and from models of brain damage in adult and newborn animals. If the recruitment of circulating cells to the brain contributes to white matter damage in extremely low gestational age newborns, then minimizing the transendothelial migration of circulating cells by pharmacological manipulation might prevent or reduce the occurrence of neonatal white matter damage and the disabilities that follow. C1 Childrens Hosp, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. NCI, Bethesda, MD 20892 USA. RP Dammann, O (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. NR 69 TC 53 Z9 53 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUN PY 2001 VL 24 IS 6 BP 320 EP 324 DI 10.1016/S0166-2236(00)01811-7 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 433NK UT WOS:000168766300021 PM 11356502 ER PT J AU Kayar, SR Fahlman, A AF Kayar, SR Fahlman, A TI Decompression sickness risk reduced by native intestinal flora in pigs after H-2 dives SO UNDERSEA & HYPERBARIC MEDICINE LA English DT Article DE biochemical decompression; decompression illness; hydrogen diving; Methanobrevibacter smithii; methanogens ID HYDROGEN; RATS; SATURATION; HELIUM; MODEL AB Decompression sickness (DCS) risk following a simulated dive in H-2 was lower in pigs with a native intestinal flora that metabolized H-2. Pigs (n = 27; 19.4 +/- 0.2 kg body mass) were placed in a chamber that was pressurized to 22.2-25.5 atm (absolute; 2.2-2.5 MPa) with 84-93% H-2 for 3 h. Chamber concentrations of O-2, H-2, He, N-2, and CH4 were monitored by gas chromatography. Release of CH4 from the pigs indicated that intestinal microbes had metabolized H-2 After decompressing to 11 atm, the pigs were observed for DCS. Animals with DCS released significantly less (P < 0.05) methane (0.53 +/- 0.37 ppm CH4; n = 5) than those without DCS (1.40 +/- 0.17 ppm CH4; n = 22). The DCS risk reduction was attributed to the loss of roughly 12% of the total volume of H-2 that could be stored in the tissues of the pigs. Thus, H-2 metabolism by the native intestinal flora of pigs may protect against DCS following a simulated H-2 dive. C1 USN, Med Res Ctr, Silver Spring, MD 20903 USA. Carleton Univ, Dept Biol, Ottawa, ON K1S 5B6, Canada. RP Kayar, SR (reprint author), NIH, Natl Ctr Res Resources, Rockledge Ctr 1, Suite 6030,6705 Rockledge Dr,MSC 7965, Bethesda, MD 20892 USA. RI Fahlman, Andreas/A-2901-2011 OI Fahlman, Andreas/0000-0002-8675-6479 NR 23 TC 4 Z9 4 U1 0 U2 0 PU UNDERSEA & HYPERBARIC MEDICAL SOC INC PI KENSINGTON PA 10531 METROPOLITAN AVE, KENSINGTON, MD 20895 USA SN 1066-2936 J9 UNDERSEA HYPERBAR M JI Undersea Hyperb. Med. PD SUM PY 2001 VL 28 IS 2 BP 89 EP 97 PG 9 WC Marine & Freshwater Biology; Medicine, Research & Experimental SC Marine & Freshwater Biology; Research & Experimental Medicine GA 526HA UT WOS:000174123300006 PM 11908700 ER PT J AU Bartlett, JE Washburn, T Eddy, EM Korach, KS Temelcos, C Hutson, JM AF Bartlett, JE Washburn, T Eddy, EM Korach, KS Temelcos, C Hutson, JM TI Early development of the gubernaculum and cremaster sac in estrogen receptor knockout mice SO UROLOGICAL RESEARCH LA English DT Article DE ERKO; estrogen receptor alpha; gubernacular development; cremaster muscle; cremaster sac ID TESTICULAR DESCENT; REPRODUCTIVE TRACTS; GENE DISRUPTION; FETAL MICE; ER-ALPHA; MOUSE; BETA; CLONING AB AIM exogenous estrogen causes gubernacular atrophy and cryptorchidism in fetal rodents. Mice with an estrogen receptor-alpha (ER alpha) disrupted gene mutation (alpha ERKO) were studied to determine whether ablation of endogenous estrogen action, through ER alpha, had an effect on gubernacular development. Serial sagittal sections were made of the pelvis in fetal and day 7 postnatal wild-type and alpha ERKO mice with the estrogen receptor-alpha "knockout" gene mutation. Wild-type (n = 24), heterozygote (n = 13) and alpha ERKO mice (n = 12) were sacrificed at 16, 17 and 18 days fetal life and at 7 days postnatally. The size of the gubernaculum, cremaster muscle, cremaster sac, and the width of the sac at both ends in day 7 mice were quantitated by computer analysis. Visually and statistically the ERKO mice could not be separated from the wild-type mice during fetal life. At day 7 postnatally, a thicker cremaster sac was noted morphologically, and also a statistically significant difference was seen in the width of the cremaster sac at the sac's tip. Sac area, cremaster muscle area and the width of the sac at the sac's end did not differ significantly. Overall there is minimal phenotypic change observed in the alpha ERKO mouse compared to wild-type at the early developmental stages investigated. However, at postnatal day 7, there is a difference in the width of the cremasteric sac tip. This suggests that the effect of ER alpha, and thus signaling on the developing gubernaculum, occurs late in development. Alternatively, an action from the recently discovered ER beta may be involved. Exploration of a beta ERKO and the double knock-out alpha ERKO/beta ERKO mouse should be informative in evaluating the effect of endogenous estrogens in gubernacular development. C1 Royal Childrens Hosp, Dept Gen Surg, Parkville, Vic 3052, Australia. Royal Childrens Hosp, Res Inst, F Douglas Stephens Surg Res Lab, Melbourne, Vic, Australia. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Hutson, JM (reprint author), Royal Childrens Hosp, Dept Gen Surg, Parkville, Vic 3052, Australia. OI Korach, Kenneth/0000-0002-7765-418X NR 25 TC 10 Z9 17 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0300-5623 J9 UROL RES JI Urol. Res. PD JUN PY 2001 VL 29 IS 3 BP 163 EP 167 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 448NL UT WOS:000169632900004 PM 11482439 ER PT J AU Liebert, M AF Liebert, M TI Basic science research on the urinary bladder and interstitial cystitis: New genetic approaches SO UROLOGY LA English DT Article; Proceedings Paper CT Joint Meeting of the National-Institute-of-Diabetes-and Digestive-and-Kidney-Diseases/Interstitial-Cystitis-Association CY OCT, 2000 CL MINNEAPOLIS, MINNESOTA SP Natl Inst Diabetes & Digest & Kidney Dis, Interstitial Cystitis Assoc ID TRANSGENIC MICE; EXPRESSION; INCONTINENCE; MICROARRAYS; EPITHELIUM; RECEPTOR AB This article summarizes recent genetic research that promises to advance understanding of the functioning of the urinary bladder and further our knowledge about interstitial cystitis. Results reported at the Tenth International Research Symposium on Interstitial Cystitis and Bladder Research and in the current literature are presented. Three specific areas of genetic research are summarized: gene expression via DNA arrays, development of new animal models through transgenic or gene knockout approaches, and gene therapy. Advances in genetic research (specifically in gene therapy; development of new, genetically engineered mouse models; and study of gene expression using DNA array assays) will contribute to further understanding the functioning of the urinary bladder in health and disease. (C) 2001, Elsevier Science Inc. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Liebert, M (reprint author), 1120 N Charles St, Baltimore, MD 21201 USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD JUN PY 2001 VL 57 IS 6A SU S BP 7 EP 8 DI 10.1016/S0090-4295(01)01160-8 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 437AR UT WOS:000168968500003 PM 11378042 ER PT J AU Tomaszewski, JE Landis, JR Russack, V Williams, TM Wang, LP Hardy, C Brensinger, C Matthews, YL Abele, ST Kusek, JW Nyberg, LM AF Tomaszewski, JE Landis, JR Russack, V Williams, TM Wang, LP Hardy, C Brensinger, C Matthews, YL Abele, ST Kusek, JW Nyberg, LM CA Interstitial Cystitis Database Stu TI Biopsy features are associated with primary symptoms in interstitial cystitis: Results from the Interstitial Cystitis Database Study SO UROLOGY LA English DT Article; Proceedings Paper CT Joint Meeting of the National-Institute-of-Diabetes-and Digestive-and-Kidney-Diseases/Interstitial-Cystitis-Association CY OCT, 2000 CL MINNEAPOLIS, MINNESOTA SP Natl Inst Diabetes & Digest & Kidney Dis, Interstitial Cystitis Assoc ID DATA-BASE; MAST-CELLS; DIAGNOSIS; LIGHT AB The purpose of this study was to investigate associations between bladder biopsy features and urinary symptoms for patients enrolled in the Interstitial Cystitis Database (ICDB) Study. Bladder biopsies were obtained during baseline screening in the ICDB Study and were evaluated for histopathologic features. Multivariable models for nighttime voiding frequency, urinary urgency, and pain were developed, incorporating biopsy features from the most diseased area of the bladder as predictors, adjusting for significant clinical factors, and clinical center variation. Among 204 interstitial cystitis (TC) patients providing biopsy specimens, cystoscopic pathology findings were not statistically associated (P >0.1 ) with primary IC symptoms, although the presence of Hunner's ulcer (n = 12) was suggestive of increased urinary frequency. Within a multivariable predictive model for nighttime voiding frequency, adjusting for age and minimum volume per void. 4 pathology features were noted: (1) mast cell count in lamina propria on tryptase stain; (2) complete loss of urothelium; (3) granulation tissue in lamina propria; and (4) vascular density in lamina propria on factor VIII (F8) stain were statistically significant (P <0.01). Similarly, in a multivariable model for urinary urgency, minimum volume, and percentage of submucosal granulation tissue remained statistically significant (P <0.01). Finally, the percentage of mucosa denuded of urothelium and the percentage of submucosal hemorrhage remained highly associated (P <0.01) with pain in a multivariable predictive model. The fact that: the presence or severity of glomerulations was not selected for any of these predictive models suggests that cystoscopic findings of glomerulations are not predictive of IC symptoms. Furthermore, these results suggest an important role for certain pathologic features in the predictive modeling of IC symptoms. (C) 2001, Elsevier Science Inc. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Scripps Clin & Res Fdn, La Jolla, CA 92037 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Hershey, PA 17033 USA. NIDDK, Bethesda, MD USA. RP Tomaszewski, JE (reprint author), Hosp Univ Penn, Surg Pathol F6-042,3400 Spruce St, Philadelphia, PA 19104 USA. RI Landis, J. Richard/A-9330-2010 FU NIDDK NIH HHS [U01-DK-45021, U01-DK-45013, U01-DK-45022, U01-DK-45026, U01-DK-45859, U01-DK-54127, U01-DK44998] NR 23 TC 101 Z9 104 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD JUN PY 2001 VL 57 IS 6A SU S BP 67 EP 81 DI 10.1016/S0090-4295(01)01166-9 PG 15 WC Urology & Nephrology SC Urology & Nephrology GA 437AR UT WOS:000168968500014 PM 11378053 ER PT J AU Kusek, JW Nyberg, LM AF Kusek, JW Nyberg, LM TI The epidemiology of interstitial cystitis: Is it time to expand our definition? SO UROLOGY LA English DT Article; Proceedings Paper CT Joint Meeting of the National-Institute-of-Diabetes-and Digestive-and-Kidney-Diseases/Interstitial-Cystitis-Association CY OCT, 2000 CL MINNEAPOLIS, MINNESOTA SP Natl Inst Diabetes & Digest & Kidney Dis, Interstitial Cystitis Assoc ID CHRONIC PELVIC PAIN; QUALITY-OF-LIFE; CYSTOSCOPIC FINDINGS; CHRONIC PROSTATITIS; SYMPTOM INDEX; PRIMARY-CARE; WOMEN; PREVALENCE; DIAGNOSIS; DATABASE AB Very few epidemiologic studies of interstitial cystitis ([C) have been published over the past 5 years. One population-based study focused only on women and suggested that the prevalence of the IC symptom complex in the United States is much higher than previously reported. Future epidemiologic studies of TC must overcome major obstacles to obtain more accurate population-based estimates. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) criteria used to assist in identifying patients with IC have proven to be cumbersome and too restrictive. Other obstacles include (l)the relative infrequency of the condition; [2] the long duration between development of symptoms and diagnosis; and (3) the perception that the disorder occurs predominantly in white women. Evidence suggests men with the IC symptom complex are often misdiagnosed by physicians and identified as having chronic prostatitis (also called the chronic pelvic pain syndrome) or benign prostatic hyperplasia. Children who present with the IC symptom complex are often thought to have voiding dysfunction. We propose that the more inclusive, less restrictive term chronic pelvic pain of the bladder (CPPB) be used in future epidemiologic studies of persons with the characteristic IC symptoms of urinary frequency, urgency, and pain. Early studies of chronic pelvic pain in general suggest that it is most common in women, of unknown etiology, and, in many patients, is associated with urinary bladder symptoms. It is necessary to develop case definitions for CPPB to accurately identify those patients with symptoms currently identified as IC. (C) 2001, Elsevier Science Inc. C1 NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Kusek, JW (reprint author), NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Room 617,2 Democracy Plaza, Bethesda, MD 20892 USA. NR 32 TC 37 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD JUN PY 2001 VL 57 IS 6A SU S BP 95 EP 99 DI 10.1016/S0090-4295(01)01141-4 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 437AR UT WOS:000168968500017 PM 11378056 ER PT J AU Biesecker, B AF Biesecker, B TI Prenatal diagnoses of sex chromosome conditions SO WESTERN JOURNAL OF MEDICINE LA English DT Editorial Material ID CHILDREN C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Biesecker, B (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU B M J PUBLISHING INC PI SAN FRANCISCO PA 221 MAIN ST, PO BOX 7690, SAN FRANCISCO, CA 94120-7690 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD JUN PY 2001 VL 174 IS 6 BP 377 EP 379 DI 10.1136/ewjm.174.6.377 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 438PM UT WOS:000169062300005 ER PT J AU Mattson, MP Fu, WM Zhang, PS AF Mattson, MP Fu, WM Zhang, PS TI Emerging roles for telomerase in regulating cell differentiation and survival: a neuroscientist's perspective SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE Alzheimer's disease; cancer; differentiation; mitochondria; neurons ID REVERSE-TRANSCRIPTASE; CATALYTIC SUBUNIT; INDUCED APOPTOSIS; HTERT GENE; IN-VITRO; KAPPA-B; EXPRESSION; PROLIFERATION; INHIBITION; CANCER AB Telomerase is a reverse transcriptase that adds repeats of a DNA sequence (TTAGGG) to the ends of chromosomes (telomeres) in mitotic cells, thus maintaining their length and preventing cell cycle arrest and cell death (cellular senescence). During development of the nervous system, telomerase activity levels are high in neural progenitor cells, but then they decrease as cells differentiate or die. The catalytic subunit of telomerase (TERT) remains at relatively high levels during the process of neuronal differentiation and then decreases sharply during the period when synapses form and programmed cell death occurs. TERT promotes survival of developing brain neurons. Suppression of telomerase activity and TERT expression promotes apoptosis of neurons, whereas overexpression of TERT prevents apoptosis by suppressing cell death at a premitochondrial step in the death cascade TERT may suppress DNA damage and/or apoptotic signals activated by damaged DNA. Recent studies of the transcriptional regulation of the TERT gene suggest that this enzyme may mediate the cell survival-promoting actions of diverse signals including estrogen, cytokines and neurotrophic factors. The elucidation of the functions of telomerase activity and TERT in neuronal differentiation and survival may lead to novel approaches for preventing neuronal death and promoting recovery of function in various neurodegenerative conditions. (C) 2001 Published by Elsevier Science Ireland Ltd. C1 NIA, Lab Neurosci 4F02, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Lab Neurosci 4F02, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 54 TC 42 Z9 50 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD MAY 31 PY 2001 VL 122 IS 7 BP 659 EP 671 DI 10.1016/S0047-6374(01)00221-4 PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 432FB UT WOS:000168680600005 PM 11322991 ER PT J AU Rao, MS Mattson, MP AF Rao, MS Mattson, MP TI Stem cells and aging: expanding the possibilities SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Review DE Alzheimer's disease; apoptosis; brain; differentiation; endothelial; hematopoietic; neurons; Notch; telomerase ID HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW TRANSPLANTATION; NEURONAL PRECURSOR CELLS; CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR-I; DENTATE GYRUS; HIPPOCAMPAL-NEURONS; ADULT-RAT; DOPAMINERGIC-NEURONS; DIETARY RESTRICTION AB In the very early stages of embryonic development, cells have the capability of dividing indefinately and then differentiating into any type of cell in the body. Recent studies have revealed that much of this remarkable developmental potential of embryonic stem cells is retained by small populations of cells within most tissues in the adult. Intercellular signals that control the proliferation, differentiation and survival of stem cells are being identified and include a diverse array of growth factors, cytokines and cell adhesion molecules. Intracellular mechanisms that regulate stem cell fate are also emerging and include established second messenger pathways, novel transcription factors and telomerase. The possibility that a decline in the numbers or plasticity of stem cell populations contributes to aging and age-related disease is suggested by recent findings. The remarkable plasticity of stem cells suggests that endogenous or transplanted stem cells can be 'tweaked' in ways that will allow them to replace lost or dysfunctional cell populations in diseases ranging from neurodegenerative and hematopoietic disorders to diabetes and cardiovascular disease. (C) 2001 Published by Elsevier Science Ireland Ltd. C1 NIA, Neurosci Lab, Gerontol Res Ctr 4F01, Baltimore, MD 21224 USA. Univ Utah, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr 4F01, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 100 TC 211 Z9 283 U1 1 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD MAY 31 PY 2001 VL 122 IS 7 BP 713 EP 734 DI 10.1016/S0047-6374(01)00224-X PG 22 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 432FB UT WOS:000168680600008 PM 11322994 ER PT J AU Mattson, MP Duan, WZ Lee, J Guo, ZH AF Mattson, MP Duan, WZ Lee, J Guo, ZH TI Suppression of brain aging and neurodegenerative disorders by dietary restriction and environmental enrichment: molecular mechanisms SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Review DE Alzheimer's disease; calories; heat shock protein; oxidative stress; mitochondria; neurotrophic factor; Parkinson's disease; stroke ID PROTECTS HIPPOCAMPAL-NEURONS; CORTICAL SYNAPTIC TERMINALS; AMYLOID PRECURSOR PROTEIN; ADULT-RAT HIPPOCAMPUS; PARKINSONS-DISEASE; LIFE-SPAN; ALZHEIMERS-DISEASE; FOOD RESTRICTION; DENTATE GYRUS; SACCHAROMYCES-CEREVISIAE AB Dietary restriction (reduced calorie intake with nutritional maintenance) can extend lifespan and may increase the resistance of the nervous system to age-related diseases including neurodegenerative disorders. An environment enriched in intellectual and physical activities can also allay many of the adverse effects of aging on the brain. The mechanisms underlying the beneficial effects of dietary restriction and environmental enrichment on the brain involve stimulation of the expression of neurotrophic factors and 'stress proteins'. The neurotrophic factors and stress proteins induced by dietary restriction may protect neurons by suppressing oxyradical production, stabilizing cellular calcium homeostasis and inhibiting a form of programmed cell death called apoptosis. Interestingly, dietary restriction and environmental enrichment also increase numbers of newly-generated neural cells in the adult brain suggesting that these behavioral modifications can increase the brain's capacity for plasticity and self-repair. A better understanding of the cellular and molecular mechanisms underlying these effects of diet and behavior on the brain is leading to novel therapeutic agents that mimick their beneficial effects. (C) 2001 Published by Elsevier Science ireland Ltd. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012; Lee, Jaewon/N-9064-2013 NR 84 TC 103 Z9 108 U1 0 U2 10 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD MAY 31 PY 2001 VL 122 IS 7 BP 757 EP 778 DI 10.1016/S0047-6374(01)00226-3 PG 22 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 432FB UT WOS:000168680600010 PM 11322996 ER PT J AU Zeiger, E AF Zeiger, E TI Mutagens that are not carcinogens: faulty theory or faulty tests? SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Salmonella; Ames test; mutagenicity; carcinogenicity; non-carcinogen; false-positive ID GENETIC TOXICITY TESTS; NATIONAL-TOXICOLOGY-PROGRAM; SALMONELLA-TYPHIMURIUM; CHEMICALS; INVITRO; RODENT; 2,6-DIAMINOTOLUENE; NONCARCINOGEN; ASSAY; 2,4-DIAMINOTOLUENE AB In the National Toxicology Program database of 172 chemicals that were judged non-carcinogenic or equivocal in 2 year rodent studies in both sexes of rats and mice, there are 38 chemicals that were mutagenic in Salmonella. All but two of the chemicals had structural alerts for mutagenicity. The largest proportion of the mutagenic non-carcinogens were benzeneamines and substituted benzeneamines. In all, 12 of the mutagenic non-carcinogens had mutagenic carcinogen analogues, and for two chemicals, the carcinogenic analogues were not mutagenic. Non-carcinogens that were mutagenic in Salmonella also tended to be mutagenic and clastogenic in mammalian in vitro tests. The mutagenic responses are discussed and explanations offered for the mutagenicity and lack of carcinogenic activity of these chemicals. Published by Elsevier Science B.V. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Zeiger, E (reprint author), 1504 Lamont Court, Chapel Hill, NC 27514 USA. NR 43 TC 42 Z9 48 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD MAY 31 PY 2001 VL 492 IS 1-2 BP 29 EP 38 DI 10.1016/S1383-5718(01)00153-X PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 439FK UT WOS:000169100000004 PM 11377241 ER PT J AU Gao, XJ Nelson, GW Karacki, P Martin, MP Phair, J Kaslow, R Goedert, JJ Buchbinder, S Hoots, K Vlahov, D O'Brien, SJ Carrington, M AF Gao, XJ Nelson, GW Karacki, P Martin, MP Phair, J Kaslow, R Goedert, JJ Buchbinder, S Hoots, K Vlahov, D O'Brien, SJ Carrington, M TI Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTES; HIV-1 INFECTION; HLA-B; HLA-B35; EPITOPES; ALLELE; IDENTIFICATION; RESTRICTION; ASSOCIATION AB Background: From studies of genetic polymorphisms and the rate of progression from human immunodeficiency virus type 1 (HIV-1) infection to the acquired immunodeficiency syndrome (AIDS), it appears that the strongest susceptibility is conferred by the major-histocompatibility-complex (MHC) class I type HLA-B*35,Cw*04 allele. However, cytotoxic T-lymphocyte responses have been observed against HIV-1 epitopes presented by HLA-B*3501, the most common HLA-B*35 subtype. We examined subtypes of HLA-B*35 in five cohorts and analyzed the relation of structural differences between HLA-B*35 subtypes to the risk of progression to AIDS. Methods: Genotyping of HLA class I loci was performed for 850 patients who seroconverted and had known dates of HIV-1 infection. Survival analyses with respect to the rate of progression to AIDS were performed to identify the effects of closely related HLA-B*35 subtypes with different peptide-binding specificities. Results: HLA-B*35 subtypes were divided into two groups according to peptide-binding specificity: the HLA-B*35-PY group, which consists primarily of HLA-B*3501 and binds epitopes with proline in position 2 and tyrosine in position 9; and the more broadly reactive HLA-B*35-Px group, which also binds epitopes with proline in position 2 but can bind several different amino acids (not including tyrosine) in position 9. The influence of HLA-B*35 in accelerating progression to AIDS was completely attributable to HLA-B*35-Px alleles, some of which differ from HLA-B*35-PY alleles by only one amino acid residue. Conclusions: This analysis shows that, in patients with HIV-1 infection, a single amino acid change in HLA molecules has a substantial effect on the rate of progression to AIDS. The different consequences of HLA-B*35-PY and HLA-B*35-Px in terms of disease progression highlight the importance of the epitope specificities of closely related class I molecules in the immune defense against HIV-1. (N Engl J Med 2001;344:1668-75.) Copyright (C) 2001 Massachusetts Medical Society. C1 NCI, FCRDC, Frederick, MD 21702 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD USA. Johns Hopkins Sch Med, Baltimore, MD USA. Northwestern Univ, Sch Med, Comprehens AIDS Ctr, Chicago, IL USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. Univ Texas, Hlth Sci Ctr, Gulf State Hemophilia Ctr, Houston, TX USA. Johns Hopkins Sch Hyg & Publ Hlth, Baltimore, MD USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP Carrington, M (reprint author), NCI, FCRDC, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N0-1-CO-56000]; NIAID NIH HHS [R01-AI-41951] NR 42 TC 326 Z9 341 U1 0 U2 10 PU MASSACHUSETTS MEDICAL SOC 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 MAY 31 PY 2001 VL 344 IS 22 BP 1668 EP 1675 DI 10.1056/NEJM200105313442203 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 436YG UT WOS:000168963000003 PM 11386265 ER PT J AU Sacks, FM Porschan, MA Svetkey, LP AF Sacks, FM Porschan, MA Svetkey, LP CA DASH-Sodium Collaborative Res Grp TI Dietary sodium and blood pressure. Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Duke Univ, Sch Med, Durham, NC 27710 USA. RP Sacks, FM (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC 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 MAY 31 PY 2001 VL 344 IS 22 BP 1718 EP 1719 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 436YG UT WOS:000168963000016 ER PT J AU Leone, A Mitsiades, N Ward, Y Spinelli, B Poulaki, V Tsokos, M Kelly, K AF Leone, A Mitsiades, N Ward, Y Spinelli, B Poulaki, V Tsokos, M Kelly, K TI The Gem GTP-binding protein promotes morphological differentiation in neuroblastoma SO ONCOGENE LA English DT Article DE Gem; neuroblastoma; ganglia; morphology; RGK proteins; cytoskeleton ID RAS-FAMILY; MEMBER; CELLS; PHOSPHORYLATION; ACTIVATION; KIR; REM AB Gem is a small GTP-binding protein within the Ras superfamily whose function has not been determined. We report here that ectopic Gem expression is sufficient to stimulate cell flattening and neurite extension in N1E-115 and SH-SY5Y neuroblastoma cells, suggesting a role for Gem in cytoskeletal rearrangement and/or morphological differentiation of neurons. Consistent with this potential function, in clinical samples of neuroblastoma, Gem protein was most highly expressed within cells which had differentiated to express ganglionic morphology. Gem was also observed in developing trigeminal nerve ganglia in 12.5 day mouse embryos, demonstrating that Gem expression is a property of normal ganglionic development. Although Gem expression is rare in epithelial and hematopoietic cancer cell lines, constitutive Gem levels were detected in several neuroblastoma cell lines and could be further induced as much as 10-fold following treatment with PMA or the acetylcholine muscarinic agonist, carbachol. C1 NCI, Div Clin Sci, Med Branch, Cell & Canc Biol Dept, Bethesda, MD 20892 USA. NCI, Pathol Lab, Div Clin Sci, Pediat Tumor Biol Sect, Bethesda, MD 20892 USA. RP Kelly, K (reprint author), NCI, Div Clin Sci, Med Branch, Cell & Canc Biol Dept, Bldg 10,Room 3B43,9000, Bethesda, MD 20892 USA. RI Leone, Alvaro/K-6410-2016 OI Leone, Alvaro/0000-0003-3815-9052 NR 21 TC 34 Z9 34 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 31 PY 2001 VL 20 IS 25 BP 3217 EP 3225 DI 10.1038/sj.onc.1204420 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 440ET UT WOS:000169163500005 PM 11423971 ER PT J AU Gao, Y Wei, CQ Burke, TR AF Gao, Y Wei, CQ Burke, TR TI Olefin metathesis in the design and synthesis of a globally constrained Grb2 SH2 domain inhibitor SO ORGANIC LETTERS LA English DT Article ID RING-CLOSING METATHESIS; CONJUGATE ADDITION; ORGANIC-SYNTHESIS; PEPTIDOMIMETICS; MIMETICS; ALPHA AB [GRAPHICS] One drawback frequently associated with olefin metathesis-mediated peptide macrocyclization, the loss of side chain functionality at sites of ring closure, may be circumvented by incorporation of side chain functionality within the ring-closing olefin segments, This approach is demonstrated in the preparation of a macrocyclic Grb2 SH2 domain antagonist designed as a conformationally constrained beta -bend mimic. C1 NCI, Med Chem Lab, DBS, FCRDC,NIH, Frederick, MD 20892 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, DBS, FCRDC,NIH, Frederick, MD 20892 USA. RI Burke, Terrence/N-2601-2014 NR 24 TC 40 Z9 41 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD MAY 31 PY 2001 VL 3 IS 11 BP 1617 EP 1620 DI 10.1021/ol0157609 PG 4 WC Chemistry, Organic SC Chemistry GA 437JD UT WOS:000168987800007 PM 11405669 ER PT J AU Nyska, A Lomnitski, L Spalding, J Dunson, DB Goldsworthy, TL Grossman, S Bergman, M Boorman, G AF Nyska, A Lomnitski, L Spalding, J Dunson, DB Goldsworthy, TL Grossman, S Bergman, M Boorman, G TI Topical and oral administration of the natural water-soluble antioxidant from spinach reduces the multiplicity of papillomas in the Tg.AC mouse model SO TOXICOLOGY LETTERS LA English DT Article DE natural antioxidant; papilloma; skin; Tg.AC mouse; transgenic ID NITRIC-OXIDE; SKIN TUMORIGENESIS; OXIDATIVE STRESS; CARCINOGENESIS; CANCER; CYCLOOXYGENASE-2; EXPRESSION; BIOASSAYS; MICE; SUSCEPTIBILITY AB The Tg.AC mouse carrying the v-Ha-ras structural gene is a useful model for the study of chemical carcinogens, especially those acting via non-genotoxic mechanisms. This study evaluated the efficacy of the non-toxic, water-soluble antioxidant from spinach. natural antioxidant (NAO), in reducing skin papilloma induction in female hemizygous Tg.AC mice treated dermally five times over 2.5 weeks with 2.5 mug 13-O-tetradecanoylphorbol-13-acetate (TPA). The TPA-only group was considered as a control; the other two groups received, additionally: NAO topically (2 mg) or orally (100 mg/kg). 5 days/week For 5 weeks. Papilloma counts made macroscopically during the clinical observations showed a significant decrease in multiplicity (P<0.01) in the NAO topically treated group. According to histological criteria, papilloma multiplicity were lower in both topical-NAG and oral-NAG groups. but significantly so only in the oral-NAG mice (P < 0.01). The beneficial effect of NAG in the Tg.AC mouse is reported. (C) 2001 Elsevier Science ireland Ltd. All rights reserved. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Environm Carcinogenesis Mutagenesis, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Bar Ilan Univ, IL-52900 Ramat Gan, Israel. ILS Inc, Res Triangle Pk, NC 27709 USA. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, POB 12233, Res Triangle Pk, NC 27709 USA. NR 33 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD MAY 31 PY 2001 VL 122 IS 1 BP 33 EP 44 DI 10.1016/S0378-4274(01)00345-9 PG 12 WC Toxicology SC Toxicology GA 446YF UT WOS:000169541200004 PM 11397555 ER PT J AU Gowdak, LHW Poliakova, L Wang, XT Lakatta, EG Talan, M Fishbein, KW Spencer, RGS Kovesdi, I Zacheo, A Palumbo, R Straino, S Emanueli, C Marrocco-Trischitta, M Capogrossi, MC Anversa, P AF Gowdak, LHW Poliakova, L Wang, XT Lakatta, EG Talan, M Fishbein, KW Spencer, RGS Kovesdi, I Zacheo, A Palumbo, R Straino, S Emanueli, C Marrocco-Trischitta, M Capogrossi, MC Anversa, P TI Estrogen stimulates angiogenesis in normoperfused skeletal muscle in rabbits - Response SO CIRCULATION LA English DT Letter C1 NIA, Gene Therapy Unit, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. NIA, Nucl Magnet Resonance Unit, Lab Cellular & Mol Biol, Ctr Gerontol Res, Baltimore, MD 21224 USA. GenVec Inc, Rockville, MD USA. RP Gowdak, LHW (reprint author), NIA, Gene Therapy Unit, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RI Marrocco-Trischitta, Massimiliano M./A-9081-2016; Wolff Gowdak, Luis Henrique/C-4844-2012 OI Marrocco-Trischitta, Massimiliano M./0000-0003-1707-9627; Wolff Gowdak, Luis Henrique/0000-0002-6785-7506 NR 5 TC 0 Z9 0 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2001 VL 103 IS 21 BP E107 EP + PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 437UW UT WOS:000169012800004 ER PT J AU Hong, F Nguyen, VA Gao, B AF Hong, F Nguyen, VA Gao, B TI Tumor necrosis factor alpha attenuates interferon-alpha signaling in the liver: involvement of SOCS3 and SHP2 and implication in resistance to interferon therapy SO FASEB JOURNAL LA English DT Article DE interleukin 6; suppressor of cytokine signaling 3; SH2-containing protein-tyrosine phosphatase liver ID CHRONIC HEPATITIS-C; PROTEIN-TYROSINE PHOSPHATASES; STIMULATED JAK/STAT PATHWAY; MESSENGER-RNA EXPRESSION; CHRONIC VIRAL-HEPATITIS; GENE-EXPRESSION; DIFFERENTIAL REGULATION; TARGETED DISRUPTION; SUSTAINED RESPONSE; CYTOKINE RELEASE AB Although interferon alpha (IFN-alpha) has been used for a decade to treat viral hepatitis, a disease that affects millions of people worldwide, more than 60% of viral hepatitis patients respond poorly. It has been reported that high levels of tumor necrosis factor alpha (TNF-alpha) correlated highly with resistance to IFN-alpha therapy. Here we demonstrate that injection of TNF-alpha suppresses IFN-alpha signaling and markedly induces expression of suppressor of cytokine signaling 3 (SOCS3) and SH2 containing protein-tyrosine phosphatase 2 (SHP2) in the liver. TNF-alpha induction of SOCS3 and SHP2 remains unchanged while induction of STAT1 protein expression is completely abolished in IL-6-deficient mice. Immunoprecipitation experiments show that injection of TNF-alpha increases SHP2 association with JAKs. Overexpression of SOCS3 and SHP2 inhibits IFN-alpha signaling in hepatic cells. Injection of carbon tetrachloride, which is known to induce TNF-alpha in the liver, attenuates IFN-alpha signaling in the liver. This attenuation is also observed in TNF-alpha receptor II- (TNF-R2-) deficient mice but is markedly diminished in TNF-R1-deficient mice. Taken together, these findings suggest that TNF-alpha may be involved in resistance to IFN-alpha therapy by induction of SOCS3 and SHP2, and they could be therapeutic targets for improving the efficacy of IFN-alpha therapy. C1 NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Pk Bldg,Rm 120,12420 Parklawn Dr,MSC 8115, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov NR 68 TC 51 Z9 54 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 29 PY 2001 VL 15 IS 7 BP 1595 EP + DI 10.1096/fj.00-0908fje PG 22 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 519CQ UT WOS:000173707700026 PM 11427497 ER PT J AU Singh, BB Zheng, CY Liu, XB Lockwich, T Liao, D Zhu, MX Birnbaumer, L Ambudkar, IS AF Singh, BB Zheng, CY Liu, XB Lockwich, T Liao, D Zhu, MX Birnbaumer, L Ambudkar, IS TI Trp1-dependent enhancement of salivary gland fluid secretion: role of store-operated calcium entry SO FASEB JOURNAL LA English DT Article DE store-operated calcium influx; calcium channel; fluid secretion; salivary glands; basolateral plasma membrane ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; CHANNELS; CELLS; EXPRESSION; TRP1; PROTEIN AB This study examined the involvement of store-operated Ca2+ entry in agonist-stimulation of salivary gland fluid secretion. A recombinant adenovirus (AdCMV-hTrp1) encoding the store-operated Ca2+ channel protein, human transient receptor potential 1 (hTrp1), was used to direct expression of HA (hemaglutinin)-tagged hTrp1 in vivo in rat submandibular glands (SMG) and in vitro in the human submandibular gland cell line (HSG). Studies with HSG cells demonstrated that AdCMV-hTrp1 was successful in directing the expression of functional hTrp1 and that it did not affect early Ca2+ signaling events. AdCMV-hTrp1-infected SMG displayed an increase in the level of Trp1 and a fivefold increase in pilocarpine-stimulated fluid secretion, compared with glands infected with a control adenovirus encoding luciferase (AdCMV-Luc). The expressed hTrp1 demonstrated polarized localization in the basolateral plasma membrane region of SMG acinar cells and was co-immunoprecipitated with IP(3)Rs. Further, acinar cells isolated from AdCMV-hTrp1-infected glands demonstrated a significant increase in carbachol- and Tg-stimulated Ca2+ entry compared with cells isolated from AdCMV-Luc-infected glands. We conclude that in vivo expression of Trp1 in SMG induces an enhancement of agonist-stimulated fluid secretion via increasing store-operated Ca2+ entry into acinar cells. These data suggest that store-operated Ca2+ entry has a role in agonist-stimulated fluid secretion from salivary glands. C1 Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Gene Transfer Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Neurobiotechnol Ctr, Columbus, OH 43210 USA. Univ Calif Los Angeles, Dept Anesthesiol, Los Angeles, CA 90095 USA. RP Ambudkar, IS (reprint author), Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, NIH, Bldg 10,Room 1N-113, Bethesda, MD 20892 USA. EM ambudkar@yoda.nidcr.nih.gov OI Singh, Brij/0000-0003-0535-5997 NR 29 TC 52 Z9 53 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 29 PY 2001 VL 15 IS 7 BP 1652 EP + DI 10.1096/fj.00-0749/fje PG 17 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 519CQ UT WOS:000173707700006 PM 11427516 ER PT J AU Kirk, AD Blair, PJ Tadaki, DK Xu, H Harlan, DM AF Kirk, AD Blair, PJ Tadaki, DK Xu, H Harlan, DM TI The role of CD154 in organ transplant rejection and acceptance SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Review DE CD154; T cell; B cell; immunosuppression; tolerance ID RENAL-ALLOGRAFT REJECTION; LONG-TERM SURVIVAL; T-CELL ACTIVATION; INTRAHEPATIC ISLET ALLOGRAFTS; VASCULAR ENDOTHELIAL-CELLS; DONOR-SPECIFIC TRANSFUSION; HUMAN DENDRITIC CELLS; HUMAN B-CELLS; CD40 LIGAND; ANTI-CD154 ANTIBODY AB CD154 plays a critical role in determining the outcome of a transplanted organ. This simple statement is amply supported by experimental evidence demonstrating that anti-CD154 antibodies are potent inhibitors of allograft rejection in many rigorous transplant models. Unfortunately; despite intensive investigation over the past ten years, the precise mechanisms by which antibodies against CD154 exert their anti-rejection effects have remained less obvious. Though originally classified with reference to B-cell function, CD154-CD40 interactions have also been shown to be important in T cell-antigen-presenting cell interactions. Accordingly; CD154 has I,een classified as a T-cell co-stimulator) molecule. However, mounting data suggest that treatment with anti-CD154 antibodies does not simply block co-stimulatory signals, but rather that the antibodies appear to induce signalling in receptor-bearing T cells. Other data suggest that anti-CD154 effects may be mediated hy endothelial cells and possibly even platelets. In fact, the current literature suggests that CD154 can either stimulate or attenuate an immune response, depending upon the model system under study. CD154 has secured a fundamental place in transplant biology and general immunology that will no doubt be the source of considerable investigation and therapeutic manipulation in the coming decade. C1 NIDDKD, NIH, USN, Transplantat & Autoimmun Branch,Med Res Ctr, Bethesda, MD 20892 USA. RP Kirk, AD (reprint author), NIDDKD, NIH, USN, Transplantat & Autoimmun Branch,Med Res Ctr, Bldg 10,Room 11S-219,Ctr Dr, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 NR 101 TC 49 Z9 49 U1 0 U2 0 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD MAY 29 PY 2001 VL 356 IS 1409 BP 691 EP 702 DI 10.1098/rstb.2001.0855 PG 12 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 443TT UT WOS:000169357600010 PM 11375072 ER PT J AU Chen, WV Hejtmancik, JF Piatigorsky, J Duncan, MK AF Chen, WV Hejtmancik, JF Piatigorsky, J Duncan, MK TI The mouse beta B1-crystallin promoter: strict regulation of lens fiber cell specificity SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE lens; transgenic mouse; promoter; transcription; fiber cell; immunohistochemistry; confocal microscopy ID A-CRYSTALLIN PROMOTER; BETA-CRYSTALLIN; EYE LENS; ALPHA-CRYSTALLIN; GENE FAMILY; EXTRALENTICULAR EXPRESSION; TRANSGENIC MICE; XENOPUS-LAEVIS; MESSENGER-RNAS; DIFFERENTIATION AB Previous studies have shown that the chicken beta B1-crystallin promoter (-434/+30) contains all of the signals necessary to specifically direct high level expression of heterologous genes to the lens fiber cells of mice. In the present study, the mouse beta B1-crystallin gene was cloned, and its regulation was investigated to further elucidate the mechanisms controlling lens fiber cell-specific gene expression. Phylogenetic footprinting analysis of the 5' flanking sequence from the mouse, rat, human and chicken beta B1-crystallin genes identified several known and putative functional cis elements including the PL2 element which is required for lens-specific expression of the chicken PBI promoter. Surprisingly, however, all six mouse beta B1-crystallin/CAT constructs tested (-1493/+43, - 1493/+30, -870/+30, -250/+30, -1351+30 and -98/+30) were inactive in three different mammalian lens-derived cell lines while only the -870/+30 and -98/+30 constructs were active in chicken primary patched lens epithelial cells. In contrast, the chicken beta B1-crystallin promoter (-434/+30) was transcriptionally active in all lens-derived cells tested. Transgenic mice harboring a mouse beta B1-crystallin -1493/+44 CAT construct did express the transgene specifically in lens fiber cells, however, at lower levels than that previously reported for a chicken -434/+30 CAT construct. These data suggest that, as in other crystallin genes, the regulatory signals controlling lens fiber cell-specific expression are conserved between chicken and mouse. However, the inability of the mouse beta B1-crystallin promoter to function in mammalian lens-derived cultured cells implies that this gene has acquired additional cis-regulatory elements to ensure lens fiber cell specificity. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. NEI, Ophthalm Genet & Clin Serv Branch, Sect Ophthalm Mol Genet, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. RP Duncan, MK (reprint author), Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. FU NCRR NIH HHS [5P20RR11820-02]; NEI NIH HHS [1RO1EY12221-01, 1Z01EY00126-17] NR 39 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD MAY 28 PY 2001 VL 1519 IS 1-2 BP 30 EP 38 DI 10.1016/S0167-4781(01)00201-9 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 444TE UT WOS:000169415500003 PM 11406268 ER PT J AU Palmer, S Groves, N Schindeler, A Yeoh, T Biben, C Wang, CC Sparrow, DB Barnett, L Jenkins, NA Copeland, NG Koentgen, F Mohun, T Harvey, RP AF Palmer, S Groves, N Schindeler, A Yeoh, T Biben, C Wang, CC Sparrow, DB Barnett, L Jenkins, NA Copeland, NG Koentgen, F Mohun, T Harvey, RP TI The small muscle-specific protein Csl modifies cell shape and promotes myocyte fusion in an insulin-like growth factor 1-dependent manner SO JOURNAL OF CELL BIOLOGY LA English DT Article DE costameres; heart; lamellipodia; Nkx2-5; skeletal muscle ID TINMAN-RELATED GENES; DEPENDENT TRANSCRIPTIONAL PATHWAY; SERUM RESPONSE FACTOR; SKELETAL-MUSCLE; HEART DEVELOPMENT; MYOBLAST FUSION; HOMEOBOX GENES; SIGNALING PATHWAYS; VERTEBRATE HEART; FACTOR NKX2-5 AB We have isolated a murine cDNA encoding a 9-kD protein, Chisel (Csl), in a screen for transcriptional targets of the cardiac homeodomain factor Nkx2-5. Csl transcripts were detected in atria and ventricles of the heart and in all skeletal muscles and smooth muscles of the stomach and pulmonary veins. Csl protein was distributed throughout the cytoplasm in fetal muscles, although costameric and M-line localization to the muscle cytoskeleton became obvious after further maturation. Targeted disruption of Csl showed no overt muscle phenotype, However, ectopic expression in C2C12 myoblasts induced formation of lamellipodia in which Csl protein became tethered to membrane ruffles. Migration of these cells was retarded in a monolayer wound repair assay. Csl-expressing myoblasts differentiated and fused normally, although in the presence of insulin-like growth factor (IGF)-1 they showed dramatically enhanced fusion, leading to formation of large dysmorphogenic "myosacs." The activities of transcription factors nuclear factor of activated T cells (NFAT) and myocyte enhancer-binding factor (MEF)2, were also enhanced in an IGF-1 signaling-dependent manner. The dynamic cytoskeletal localization of Csl and its dominant effects on cell shape and behavior and transcription factor activity suggest that Csl plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair. C1 Victor Chang Cardiac Res Inst, Darlinghurst, NSW 2010, Australia. Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. Res Council Inst Med Res, London NW7 1AA, England. Univ New S Wales, Fac Med & Life Sci, Kensington, NSW 2051, Australia. RP Harvey, RP (reprint author), Victor Chang Cardiac Res Inst, 384 Victoria St, Darlinghurst, NSW 2010, Australia. RI Sparrow, Duncan/B-3994-2008; Palmer, Stephen/F-2822-2013 OI Sparrow, Duncan/0000-0002-1141-6613; Palmer, Stephen/0000-0002-4907-4719 FU NIA NIH HHS [R03 AG14811] NR 58 TC 56 Z9 58 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 28 PY 2001 VL 153 IS 5 BP 985 EP 997 DI 10.1083/jcb.153.5.985 PG 13 WC Cell Biology SC Cell Biology GA 438HA UT WOS:000169046500009 PM 11381084 ER PT J AU Martina, JA Bonangelino, CJ Aguilar, RC Bonifacino, JS AF Martina, JA Bonangelino, CJ Aguilar, RC Bonifacino, JS TI Stonin 2: An adaptor-like protein that interacts with components of the endocytic machinery SO JOURNAL OF CELL BIOLOGY LA English DT Article DE receptor-mediated endocytosis; clathrin; AP-2; Eps15; intersection ID CLATHRIN-MEDIATED ENDOCYTOSIS; ALPHA-ADAPTIN; DROSOPHILA-MELANOGASTER; SORTING SIGNALS; PLASMA-MEMBRANE; COATED PITS; EH DOMAINS; EPS15; RECOGNITION; VESICLE AB Endocytosis of cell surface proteins is mediated by a complex molecular machinery that assembles on the inner surface of the plasma membrane. Here, we report the identification of two ubiquitously expressed human proteins, stonin 1 and stonin 2, related to components of the endocytic machinery. The human stonins are homologous to the Drosophila melanogaster stoned B protein and exhibit a modular structure consisting of an NH2-terminal proline-rich domain, a central region of homology specific to the stonins, and a COOH-terminal region homologous to the mu subunits of adaptor protein (AP) complexes. Stonin 2, but not stonin 1, interacts with the endocytic machinery proteins Eps15, Eps15R, and intersectin 1. These interactions occur via two NPF motifs in the proline-rich domain of stonin 2 and Eps15 homology domains of Eps15, Eps15R, and intersectin 1. Stonin 2 also interacts indirectly with the adaptor protein complex. AP-2, In addition, stonin 2 binds to the C2B domains of synaptotagmins I and II. Overexpression of GFP-stonin 2 interferes with recruitment of AP-2 to the plasma membrane and impairs internalization of the transferrin, epidermal growth factor, and low density lipoprotein receptors. These observations suggest that stonin 2 is a novel component of the general endocytic machinery. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101, Bethesda, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 50 TC 101 Z9 107 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 28 PY 2001 VL 153 IS 5 BP 1111 EP 1120 DI 10.1083/jcb.153.5.1111 PG 10 WC Cell Biology SC Cell Biology GA 438HA UT WOS:000169046500019 PM 11381094 ER PT J AU Kuznetsov, SA Mankani, MH Gronthos, S Satomura, K Bianco, P Robey, PG AF Kuznetsov, SA Mankani, MH Gronthos, S Satomura, K Bianco, P Robey, PG TI Circulating skeletal stem cells SO JOURNAL OF CELL BIOLOGY LA English DT Article DE blood cells; tissue culture; adherent colonies; transplantation; osteogenesis ID MARROW STROMAL FIBROBLASTS; HUMAN-BONE-MARROW; IN-VIVO; DIFFERENTIATION; TRANSPLANTATION; PROGENITORS; PRECURSORS; EXPRESSION; VITRO AB We report the isolation of adherent, clonogenic, fibroblast-like cells with osteogenic and adipogenic potential from the blood of four mammalian species. These cells phenotypically resemble but are distinguishable from skeletal stem cells found in bone marrow (stromal stem cells,''mesenchymal stem cells"), The osteogenic potential of the blood-borne cells was proven by an in vivo transplantation assay in which either polyclonal or single colony-derived strains were trans-planted into the subcutis of immunocompromised mice, and the donor origin of the fully differentiated bone cells was proven using species-specific probes. This is the first definitive proof of the existence of circulating skeletal stem cells in mammals. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Tokushima, Sch Dent, Dept Oral & Maxillofacial Surg 1, Tokushima 7708504, Japan. Univ La Sapienza, Dipartimento Med Sperimental & Patol, I-00161 Rome, Italy. RP Kuznetsov, SA (reprint author), Bldg 30,Room 228,30 Convent Dr,MSC 4320, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [E.1029] NR 20 TC 450 Z9 489 U1 1 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 28 PY 2001 VL 153 IS 5 BP 1133 EP 1139 DI 10.1083/jcb.153.5.1133 PG 7 WC Cell Biology SC Cell Biology GA 438HA UT WOS:000169046500022 PM 11381097 ER PT J AU Deroo, BJ Archer, TK AF Deroo, BJ Archer, TK TI Glucocorticoid receptor-mediated chromatin remodeling in vivo SO ONCOGENE LA English DT Review DE glucocorticoid receptor; chromatin; mouse mammary tumor virus; BRG1; Swi/Snf; histone ID HUMAN BREAST-CANCER; TUMOR VIRUS PROMOTER; LINKER HISTONE H1; TRANSCRIPTION IN-VIVO; YEAST SWI/SNF COMPLEX; SWI-SNF COMPLEX; GENE-EXPRESSION; MMTV PROMOTER; RAPID EXCHANGE; LIVING CELLS AB The compaction of DNA into chromatin provides an additional level of gene regulation in eukaryotes that may not be available to prokaryotes. When packaged as chromatin, most promoters are transcriptionally repressed, and transcription factors have reduced access to their binding sites. The glucocorticoid receptor (GR) is a ligand-activated transcription factor that regulates the activity of genes involved in many physiological processes. To regulate eukaryotic genes, the GR binds to target sites within promoter regions of genes assembled as chromatin, This interaction alters the nucleosomal architecture to allow binding of other transcription factors, and formation of the preinitiation complex. The mouse mammary tumor virus (MMTV) promoter has been used extensively as a model to explore the processes by which the GR remodels chromatin and activates transcription. Significant progress has been made in our understanding of the mechanisms used by the GR to modify chromatin structure, and the limits placed on the GR by post-translational modifications of histones, We will describe recent developments in the processes used by the GR to activate transcription in vivo via chromatin remodeling complexes, histone H1 phosphorylation, and recruitment of diverse coactivators. C1 NIEHS, Chromatin & Gene Express Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), NIEHS, Chromatin & Gene Express Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 60 TC 63 Z9 63 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 28 PY 2001 VL 20 IS 24 BP 3039 EP 3046 DI 10.1038/sj.onc.1204328 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 442WT UT WOS:000169308500007 PM 11420719 ER PT J AU Robertson, KD AF Robertson, KD TI DNA methylation, methyltransferases, and cancer SO ONCOGENE LA English DT Review DE DNA methylation; cancer; DNA methyltransferase; ICF syndrome ID EMBRYONIC STEM-CELLS; TUMOR-SUPPRESSOR GENE; DE-NOVO METHYLATION; HISTONE DEACETYLASE COMPLEX; MESSENGER-RNA EXPRESSION; ICF SYNDROME; CPG ISLAND; ANNEXIN-V; CYTOSINE-5 METHYLTRANSFERASES; CHROMOSOME INSTABILITY AB The field of epigenetics has recently moved to the forefront of studies relating to diverse processes such as transcriptional regulation, chromatin structure, genome integrity, and tumorigenesis. Recent work has revealed how DNA methylation and chromatin structure are linked at the molecular level and how methylation anomalies play a direct causal role in tumorigenesis and genetic disease. Much new information has also come to light regarding the cellular methylation machinery, known as the DNA methyltransferases, in terms of their roles in mammalian development and the types of proteins they are known to interact with, This information has forced a new view for the role of DNA methyltransferases. Rather than enzymes that act in isolation to copy methylation patterns after replication, the types of interactions discovered thus far indicate that DNA methyltransferases may be components of larger complexes actively involved in transcriptional control and chromatin structure modulation. These new findings will likely enhance our understanding of the myriad roles of DNA methylation in disease as well as point the may to novel therapies to prevent or repair these defects. C1 NCI, Epigenet Gene Regulat & Canc Sect, NIH, Bethesda, MD 20892 USA. RP Robertson, KD (reprint author), NCI, Epigenet Gene Regulat & Canc Sect, NIH, Bldg 41,41 Lib Dr, Bethesda, MD 20892 USA. NR 162 TC 399 Z9 423 U1 4 U2 51 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 28 PY 2001 VL 20 IS 24 BP 3139 EP 3155 DI 10.1038/sj.onc.1204341 PG 17 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 442WT UT WOS:000169308500019 PM 11420731 ER PT J AU He, M Sibille, E Benjamin, D Toth, M Shippenberg, T AF He, M Sibille, E Benjamin, D Toth, M Shippenberg, T TI Differential effects of 5-HT1A receptor deletion upon basal and fluoxetine-evoked 5-HT concentrations as revealed by in vivo microdialysis SO BRAIN RESEARCH LA English DT Article DE 5-hydroxytryptamine; 5-hydroxytryptamine(1A) receptor; dialysis; fluoxetine; knockout ID DORSAL RAPHE NUCLEUS; IN-VIVO; DOPAMINE RELEASE; RAT-BRAIN; SEROTONIN(1A) RECEPTOR; EXTRACELLULAR 5-HT; REUPTAKE INHIBITOR; ANXIETY; ANTAGONISTS; MICE AB An involvement of serotonin (5-HT) 1A receptors in the etiology of psychiatric disorders has been suggested. Hypo-responsiveness of the 5-HT1A receptor is linked to anxiety and constitutive deletion of the 5-HT1A receptor produces anxiety-like behaviors in the mouse. Evidence that 5-HT1A receptor inactivation increases the therapeutic effects of antidepressants has also been presented. The present studies used in vivo microdialysis and homologous recombination techniques to examine the contribution of 5-HT1A autoreceptors to these effects. Basal and fluoxetine-evoked extracellular concentrations of 5-HT were quantified in the striatum, a projection area of dorsal raphe neurons (DRN), of wild-type (WT) and 5-HT1A receptor knock out (KO) mice. The density of 5-HT transporters was also determined. Basal 5-HT concentrations did not differ in WT and KO mice. Fluoxetine (10 mg/kg) increased 5-HT concentrations in both genotypes. This increase was, however, 2-fold greater in KO mice, In contrast, no differences in Kt-evoked 5-HT concentrations were seen. Similarly, neither basal nor stimulation-evoked DA differed across genotype, Autoradiography revealed no differences between genotype in the density of 5-HT transporters or post-synaptic 5-HT2A receptors. an index of 5-HT neuronal activity. These experiments demonstrate that, under basal and KCI stimulated conditions, adaptive mechanisms in the 5-HT system compensate for the lack of 5-HT1A autoreceptor regulation of DRN. Furthermore, they suggest that the absence of release-regulating 5-HT1A autoreceptors in the DRN can not account for the anxiety phenotype of KO mice. The enhanced response to fluoxetine in KO mice is consistent with pharmacological studies and suggests that adaptive mechanisms that occur in response to 5-HT1A receptor deletion are insufficient to oppose increases in 5-HT concentrations produced by acute inhibition of the 5-HT transporter. Published by Elsevier Science B.V. C1 NIDA, Intramural Res Program, Behav Neurosci Branch, Integrat Neurosci Unit, Baltimore, MD 21224 USA. Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA. Rutgers State Univ, Ctr Alcohol Studies, Div Neuropharmacol, Piscataway, NJ 08855 USA. RP Shippenberg, T (reprint author), NIDA, Intramural Res Program, Behav Neurosci Branch, Integrat Neurosci Unit, Baltimore, MD 21224 USA. NR 42 TC 41 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 25 PY 2001 VL 902 IS 1 BP 11 EP 17 DI 10.1016/S0006-8993(01)02271-5 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 437YG UT WOS:000169026500002 PM 11376590 ER PT J AU Lovekamp, T Cooper, PS Hardison, J Bryant, SD Guerrini, R Balboni, G Salvadori, S Lazarus, LH AF Lovekamp, T Cooper, PS Hardison, J Bryant, SD Guerrini, R Balboni, G Salvadori, S Lazarus, LH TI Inhibition of human multidrug resistance P-glycoprotein 1 by analogues of a potent delta-opioid antagonist SO BRAIN RESEARCH LA English DT Article DE Dmt-Tic; delta-opioid receptor antagonists; hMDR1; P-glycoprotein; hydrophobicity ID BLOOD-BRAIN-BARRIER; DMT-TIC PHARMACOPHORE; D-PENICILLAMINE(2,5) ENKEPHALIN; DIKETOPIPERAZINES; ANTINOCICEPTION; PERMEABILITY; DERIVATIVES; PEPTIDES; CELLS; MICE AB Analogues Dmt-Tic (2 ' ,6 ' -dimlthyl-L-tyrosine-1,2,3,3-tetrahydroisquinoline-3-carboxylic acid) pharmacophore. a potent delta -opioid receptor antagonist, inhibited hMDRI P-GP expressed in a G-185 fibroblast cell line in a manner similar to verapamil. N,N(Me)(2)-Dmt-Tic-NH-1 -adamantane. H-Dmt-Tic-NH-1-adamantane, H-Dmt-Tic-Ala-NH-1-adamantane and N,N(Me)(2)-Dmt-Tic-NH-tBut were highly effective inhibitors. Weaker inhibition was observed with N,N(Er)(2)-Dmt-Tic-OH, H-Dmt-Tic-Ala-NH-tert-butyl amide and cyclo(Dmt- Tie). Results demonstrate that N- and C-terminal hydrophobic /lipophilic analogues of the Dmt-Tic pharmacophore inhibit hMDR1 and point to a potential role as chemosensitizing agents in chemotherapy for cancers containing hMDR1. (C) 2001 Published by Elsevier Science B.V. C1 NIEHS, LCBRA, Peptide Neurochem Grp, Res Triangle Pk, NC 27709 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. RP Lazarus, LH (reprint author), NIEHS, LCBRA, Peptide Neurochem Grp, POB 12233, Res Triangle Pk, NC 27709 USA. OI Guerrini, Remo/0000-0002-7619-0918 NR 19 TC 10 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 25 PY 2001 VL 902 IS 1 BP 131 EP 134 DI 10.1016/S0006-8993(01)02363-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 437YG UT WOS:000169026500015 PM 11376603 ER PT J AU Lakatta, EG AF Lakatta, EG TI Heart aging - A fly in the ointment? SO CIRCULATION RESEARCH LA English DT Editorial Material DE heart rate; aging heart; Drosophila ID INTRACELLULAR CA2+ RELEASE; TOAD PACEMAKER CELLS; PIG SINOATRIAL NODE; DROSOPHILA-MELANOGASTER; SARCOPLASMIC-RETICULUM; MOLECULAR MECHANISMS; AGE; STIMULATION; CALCIUM; GENOME C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 35 TC 23 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAY 25 PY 2001 VL 88 IS 10 BP 984 EP 986 DI 10.1161/hh1001.091963 PG 3 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 438ZY UT WOS:000169085200004 PM 11375266 ER PT J AU Adhikari, BB Wang, K AF Adhikari, BB Wang, K TI S100A1 modulates skeletal muscle contraction by desensitizing calcium activation of isometric tension, stiffness and ATPase SO FEBS LETTERS LA English DT Article DE thin filament regulation; actin; myosin; nebulin; calcium sensor ID ACTIN CAPPING PROTEIN; ALPHA-ALPHA PROTEIN; BINDING-PROTEIN; PASSIVE TENSION; CROSS-BRIDGES; CALDESMON; MYOSIN; SLOW; LOCALIZATION; INHIBITION AB S100, a subfamily of the EF-hand type calcium sensing proteins, is implicated in many cellular functions including muscle contractility. Two isoforms, S100A1 and S100B, at 2-10 muM significantly inhibit active tension, stiffness and ATPase of skinned single rabbit psoas muscle fibers at submaximal (pCa similar to 6.1-5.6), but not at maximal levels of activation (pCa 4.0). S100A1 is a more potent inhibitor than S100B. Hill analysis of the ATPase-pCa and tension-pCa curves indicates that these proteins reduce calcium sensitivity and enhance the cooperativity toward calcium. We propose S100A1, and perhaps S100B, are viable candidates as physiological modulators of muscle contraction. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 NIAMSD, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wang, K (reprint author), NIAMSD, Phys Biol Lab, NIH, Bldg 6,Room 408, Bethesda, MD 20892 USA. NR 28 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 25 PY 2001 VL 497 IS 2-3 BP 95 EP 98 DI 10.1016/S0014-5793(01)02444-9 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 439MP UT WOS:000169120900007 PM 11377420 ER PT J AU Liu, SH Bugge, TH Leppla, SH AF Liu, SH Bugge, TH Leppla, SH TI Targeting of tumor cells by cell surface urokinase plasminogen activator-dependent anthrax toxin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-BOUND UROKINASE; LEWIS LUNG-CARCINOMA; SPONTANEOUS METASTASIS MODEL; HUMAN BREAST-CANCER; PROTECTIVE ANTIGEN; LETHAL FACTOR; MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; MESSENGER-RNA; CATALYTIC DOMAIN AB Urokinase plasminogen activator receptor (uPAR) binds pro-urokinase plasminogen activator (pro-uPA) and thereby localizes it near plasminogen, causing the generation of active uPA and plasmin on the cell surface. uPAR and uPA are overexpressed in a variety of human tumors and tumor cell lines, and expression of uPAR and uPA is highly correlated to tumor invasion and metastasis. To exploit these characteristics in the design of tumor cell-selective cytotoxins, we constructed mutated anthrax toxin-protective antigen (PrAg) proteins in which the furin cleavage site is replaced by sequences cleaved specifically by uPA. These uPA-targeted PrAg proteins were activated selectively on the surface of uPAR-expressing tumor cells in the presence of pro-uPA and plasminogen. The activated PrAg proteins caused internalization of a recombinant cytotoxin, FP59, consisting of anthrax toxin lethal factor residues 1-254 fused to the ADP-ribosylation domain of Pseudomonas exotoxin A, thereby killing the uPAR-expressing tumor cells. The activation and cytotoxicity of these uPA-targeted PrAg proteins were strictly dependent on the integrity of the tumor cell surface-associated plasminogen activation system. We also constructed a mutated PrAg protein that selectively killed tissue plasminogen activator-expressing cells. These mutated PrAg proteins may be useful as new therapeutic agents for cancer treatment. C1 NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, 30 Convent Dr,MSC 4350,Bldg 30,Rm 303, Bethesda, MD 20892 USA. NR 81 TC 124 Z9 132 U1 3 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 2001 VL 276 IS 21 BP 17976 EP 17984 DI 10.1074/jbc.M011085200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 435FJ UT WOS:000168866500049 PM 11278833 ER PT J AU Mullick, J Anandatheerthavarada, HK Amuthan, G Bhagwat, SV Biswas, G Camasamudram, V Bhat, NK Reddy, SEP Rao, V Avadhani, NG AF Mullick, J Anandatheerthavarada, HK Amuthan, G Bhagwat, SV Biswas, G Camasamudram, V Bhat, NK Reddy, SEP Rao, V Avadhani, NG TI Physical interaction and functional synergy between glucocorticoid receptor and Ets2 proteins for transcription activation of the rat cytochrome P-450c27 promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE AMINOTRANSFERASE GENE; HEPATIC STEROL 27-HYDROXYLASE; BILE-ACID BIOSYNTHESIS; DNA-BINDING DOMAIN; RNA-POLYMERASE-II; NF-KAPPA-B; NUCLEAR FACTOR; MESSENGER-RNA; RESPONSIVE UNITS; C-JUN AB We demonstrate that dexamethasone-mediated transcription activation of the cytochrome P-450c27 promoter involves a physical interaction and functional synergy between glucocorticoid receptor (GR) and Ets2 factor. Ets2 protein binding to a "weak" Ets-like site of the promoter is dependent on Oh bound to the adjacent cryptic glucocorticoid response element. Coimmunoprecipitation and chemical cross-linking experiments show physical interaction between GR and Ets2 proteins. Mutational analyses show synergistic effects of Ets2 and GR in dexamethasone-mediated activation of the cytochrome P-450c27 promoter. The DNA-binding domain of GR, lacking the transcription activation and ligand-binding domains, was fully active in synergistic activation of the promoter with intact Ets2. The DNA-binding domain of Ets2 lacking the transcription activation domain showed a dominant negative effect on the transcription activity. Finally, a fusion protein consisting of the GR DNA-binding domain and the transcription activation domain of Ets2 fully supported the transcription activity, suggesting a novel synergy between the two proteins, which does not require the transactivation domain of GR. Our results also provide new insights on the role of putative weak consensus Ets sites in transcription activation, possibly through synergistic interaction with other gene-specific transcription activators. C1 Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Mari Lowe Ctr Comparat Oncol, Philadelphia, PA 19104 USA. Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Med Coll Penn & Hahnemann Univ, Ctr Canc, Program Canc Genet, Philadelphia, PA 19102 USA. RP Avadhani, NG (reprint author), Univ Penn, Sch Vet Med, Dept Anim Biol, 3800 Spruce St, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA22762]; NIGMS NIH HHS [GM34883] NR 65 TC 30 Z9 32 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 2001 VL 276 IS 21 BP 18007 EP 18017 DI 10.1074/jbc.M100671200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 435FJ UT WOS:000168866500053 PM 11279115 ER PT J AU Kao, SC Jaiswal, RK Kolch, W Landreth, GE AF Kao, SC Jaiswal, RK Kolch, W Landreth, GE TI Identification of the mechanisms regulating the differential activation of the MAPK cascade by epidermal growth factor and nerve growth factor in PC12 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTRACELLULAR SIGNALING PATHWAYS; INSULIN-RECEPTOR SUBSTRATE-1; CRK PROTEIN BINDS; B-RAF; TYROSINE PHOSPHORYLATION; PHEOCHROMOCYTOMA CELLS; KINASE ACTIVATION; NEURONAL DIFFERENTIATION; ADAPTER PROTEINS; EGF STIMULATION AB In PC12 cells, epidermal growth factor (EGF) transiently stimulates the mitogen-activated protein (MAP) kinases, ERK1 and ERK2, and provokes cellular proliferation. In contrast, nerve growth factor (NGF) stimulation leads to the sustained activation of the MAPKs and subsequently to neuronal differentiation. It has been shown that both the magnitude and longevity of MAPK activation governs the nature of the cellular response. The activations of MAPKs are dependent upon two distinct small G-proteins, Has and Rap1, that link the growth factor receptors to the MAPK cascade by activating c-Raf and B-Raf, respectively. We found that Res was transiently stimulated upon both EGF and NGF treatment of PC12 cells. However, EGF transiently activated Rap1, whereas NGF stimulated prolonged Rap1 activation. The activation of the ERKs was due almost exclusively (>90%) to the action of B-Raf, The transient activation of the MAPKs by EGF was a consequence of the formation of a short lived complex assembling on the EGF receptor itself, composed of Crk, C3G, Rap1, and B-Raf, In contrast, NGF stimulation of the cells resulted in the phosphorylation of FRS2. FRS2 scaffolded the assembly of a stable complex of Crk, C3G, Rap1, and B-Raf resulting in the prolonged activation of the MAPKs. Together, these data provide a signaling link between growth factor receptors and MAPK activation and a mechanistic explanation of the differential MAPK kinetics exhibited by these growth factors. C1 Case Western Reserve Univ, Sch Med, Alzheimer Res Lab, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. NINDS, NIH, Bethesda, MD 20892 USA. Beatson Inst Canc Res, CRC, Beatson Labs, Glasgow G61 1BD, Lanark, Scotland. RP Landreth, GE (reprint author), Case Western Reserve Univ, Sch Med, Alzheimer Res Lab, E504,10900 Euclid Ave, Cleveland, OH 44106 USA. OI Kolch, Walter/0000-0001-5777-5016 NR 62 TC 274 Z9 280 U1 1 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 2001 VL 276 IS 21 BP 18169 EP 18177 DI 10.1074/jbc.M008870200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 435FJ UT WOS:000168866500075 PM 11278445 ER PT J AU Heron-Milhavet, L Karas, M Goldsmith, CM Baum, BJ LeRoith, D AF Heron-Milhavet, L Karas, M Goldsmith, CM Baum, BJ LeRoith, D TI Insulin-like growth factor-I (IGF-I) receptor activation rescues UV-damaged cells through a p38 signaling pathway - Potential role of the IGF-I receptor in DNA repair SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE PATHWAYS; 4-NITROQUINOLINE 1-OXIDE; INHIBITS APOPTOSIS; PROLIFERATION; TYROSINE; SURVIVAL; STRESS; GENE; PHOSPHORYLATION; TRANSDUCTION AB The activated insulin-like growth factor-I receptor (IGF-IR) is implicated in mitogenesis, transformation, and anti-apoptosis. To investigate the role of the IGF-IR in protection from UV-mimetic-induced DNA damage, 4-nitroquinoline N-oxide (4-NQO) was used. In this study we show that the activation of the IGF-IR is capable of rescuing NWTb3 cells overexpressing normal IGF-IRs from 4-NQO-induced DNA damage as demonstrated by cellular proliferation assays, This action was specific for the IGF-IR since cells expressing dominant negative IGF-IRs were not rescued from 4-NQO UV-mimetic treatment. DNA damage induced by 4-NQO in NWTb3 cells was significantly decreased after IGF-IR activation as measured by comet assay, IGF-I was also able to overcome the cell cycle arrest, observed after 4-NQO treatment, thereby enhancing the ability of NWTb3 cells to enter S phase. Interestingly, the p38 mitogen-activated protein kinase pathway was shown to represent the main signaling pathway involved in the TGF-IR-mediated rescue of UV-like damaged cells. The ability of the IGF-IR to induce DNA repair was also demonstrated by infecting NWTb3 cells with W-irradiated adenovirus, Activation of the IGF-IR resulted in enhanced P-galactosidase reporter gene activity demonstrating repair of the damaged DNA, This study indicates a direct role of the IGF system in the rescue of damaged cells via DNA repair. C1 NIDDK, Sect Cellular & Mol Physiol, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Sect Cellular & Mol Physiol, Clin Endocrinol Branch, NIH, Rm 8D12,Bldg 10, Bethesda, MD 20892 USA. NR 37 TC 60 Z9 60 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 2001 VL 276 IS 21 BP 18185 EP 18192 DI 10.1074/jbc.M011490200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 435FJ UT WOS:000168866500077 PM 11278917 ER PT J AU Isaacs, JS Saito, S Neckers, LM AF Isaacs, JS Saito, S Neckers, LM TI Requirement for HDM2 activity in the rapid degradation of p53 in neuroblastoma SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WILD-TYPE P53; NUCLEAR EXPORT SIGNAL; RING-FINGER DOMAIN; DNA-DAMAGE; CELL-LINES; MDM2-MEDIATED DEGRADATION; APOPTOTIC FUNCTION; DOUBLE MINUTE-2; ACTIVATES P53; UV-RADIATION AB The wild type p53 tumor suppressor protein is rapidly degraded in normal cells by MDM2, the ubiquitin ligase that serves as the key regulator of p53 function by modulating protein stability. Cellular exposure to genotoxic stress triggers the stabilization of p53 by multiple pathways that converge upon interference with MDM2 function. In this study, we first investigated the ability of HDM2 (MDM2 human homologue) to degrade endogenous p53 in neuroblastoma (NB), Although the p53 protein in NE has been reported to be constitutively stabilized, we find that HDM2 in NE is functional and facilitates the rapid turnover of p53 in nonstressed cells via the proteasome pathway. Second, we examined the relationship between p53 and HDM2 in the adriamycin-mediated stabilization of p53 in NE. We demonstrate that while p53 stabilization depends neither upon the phosphorylation of specific N-terminal sites nor upon dissociation from HDM2, it requires inactivation of functional HDM2, In support of this notion, p53 stabilization following adriamycin resulted in an inhibition of both p53 ubiquitination and HDM2 ligase activity. Taken together, these data implicate a requirement for enzymatic inactivation of HDM2 as a novel mechanism for p53 stabilization in the DNA damage response pathway. C1 NCI, Tumor Cell Biol Sect, Med Branch, NIH, Rockville, MD 20850 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Neckers, LM (reprint author), NCI, Tumor Cell Biol Med Branch, NIH, KWC Ste 300,9610 Med Ctr Dr, Rockville, MD 20850 USA. NR 60 TC 20 Z9 21 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 2001 VL 276 IS 21 BP 18497 EP 18506 DI 10.1074/jbc.M100638200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 435FJ UT WOS:000168866500118 PM 11279110 ER PT J AU Moreira, EF Jaworski, C Li, A Rodriguez, IR AF Moreira, EF Jaworski, C Li, A Rodriguez, IR TI Molecular and biochemical characterization of a novel oxysterol-binding protein (OSBP2) highly expressed in retina SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHOLESTEROL OXIDES; GOLGI LOCALIZATION; CDNA CLONING; GENE; PHOSPHORYLATION; METABOLISM; DOMAIN AB We are interested in understanding the possible function(s) of the oxysterol-binding proteins in mediating oxysterol cytotoxicity in the retina. In this study we describe the cloning, localization, and biological activity of a novel oxysterol-binding protein (OSBP2), and complete the molecular characterization of the previously known OSBP1. Both OSBP genes contain 14 exons and have similar exon sizes and splice sites suggesting they may have arisen from a gene duplication event. OSBP1 is located in chromosome 11q12.1, and OSBP2 is located in 22q12. At the protein level they share 63% overall similarity and although they have unique N termini, both have similar pleckstrin homology domains within the N terminus region. Northern blot analyses indicate that OSBP1 is broadly expressed in human and monkey tissues. OSBP2 is detected mainly in retina, testis, and fetal liver. Western blot analysis using peptide antibodies specific to OSBP1 and OSBP2 detected the proteins in different subcellular fractions in the retinal monkey tissue. OSBP1 is detected mainly in the soluble or cytosolic fraction and nuclei whereas OSBP2 is detected exclusively in the detergent soluble fraction suggesting association with membranes. Immunohistochemical localization of OSBP1 and OSBP2 in the monkey retina placed these two proteins in similar but distinct areas of the inner retina. OSBP2 was found to bind 7-ketocholesterol but to have very little affinity for cholesterol or 25-hydroxycholesterol. C1 NEI, NIH, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. RP Rodriguez, IR (reprint author), NEI, NIH, Retinal Cell & Mol Biol Lab, 6 Ctr Dr,MSC 2740,Bldg 6,Rom 304, Bethesda, MD 20892 USA. NR 27 TC 36 Z9 38 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 2001 VL 276 IS 21 BP 18570 EP 18578 DI 10.1074/jbc.M011259200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 435FJ UT WOS:000168866500127 PM 11278871 ER PT J AU Nedvidkova, J Pacak, K Haluzik, M Nedvidek, J Schreiber, V AF Nedvidkova, J Pacak, K Haluzik, M Nedvidek, J Schreiber, V TI The role of dopamine in methylene blue-mediated inhibition of estradiol benzoate-induced anterior pituitary hyperplasia in rats SO NEUROSCIENCE LETTERS LA English DT Article DE methylene blue; estradiol; anterior pituitary; dopamine ID DIHYDROXYPHENYLACETIC ACID; NEURONS AB Recently, we demonstrated that methylene blue partially inhibited estradiol-benzoate-induced anterior pituitary hyperplasia in rats. Since central dopaminergic systems participate in the regulation of estrogen-induced anterior pituitary growth and tumor transformation, this study examined whether a 3-week treatment with methylene blue could affect anterior pituitary levels of dopamine (DA), dihydroxyphenylalanine (DOPA), and dihydroxyphenylacetic acid and dopamine (D-2) receptors in male rats. Compared to controls, methylene blue significantly decreased anterior pituitary weight, increased basal anterior pituitary DA levels, and inhibited estradiol benzoate-induced decreases in anterior pituitary DA concentrations. Furthermore, we found that methylene blue alone decreased anterior pituitary D-2 receptor number. Methylene blue given in combination with estradiol benzoate partially inhibited estradiol benzoate-induced anterior pituitary growth and estradiol benzoate-induced increases in D-2 receptor number. Estradiol benzoate-treated rats had significantly lower anterior pituitary DOPA accumulation after intraperitoneal administration of 3,4-hydroxybenzyl-hydrazine dihydrochloride (NSD-1015), an irreversible inhibitor of L-aromatic amino acid decarboxylase whereas methylene blue did not affect anterior pituitary DOPA accumulation when compared to controls. Methylene blue decreased anterior pituitary prolactin levels and inhibited increases in anterior pituitary prolactin after estradiol benzoate administration. The present results suggest that anterior pituitary DA may play an important role in estrogen-induced anterior pituitary hyperplasia and tumor formation and that antioxidant drugs such as methylene blue may attenuate estrogen-induced pituitary growth. This may occur via increases in anterior pituitary DA levels associated with down-regulation of anterior pituitary D-2 receptors. (C) 2001 Published by Elsevier Science Ireland Ltd. C1 NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. Charles Univ, Fac Med 1, Dept Internal Med 3, Prague, Czech Republic. Czech Acad Sci, Inst Physiol, Prague, Czech Republic. RP Nedvidkova, J (reprint author), Inst Endocrinol, Narodni Trida 8, Prague 1, Czech Republic. NR 14 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 25 PY 2001 VL 304 IS 3 BP 194 EP 198 DI 10.1016/S0304-3940(01)01752-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 434FG UT WOS:000168804000017 PM 11343835 ER PT J AU Smirnov, DA Hou, SH Liu, XH Claudio, E Siebenlist, UK Ricciardi, RP AF Smirnov, DA Hou, SH Liu, XH Claudio, E Siebenlist, UK Ricciardi, RP TI COUP-TFII is up-regulated in adenovirus type 12 tumorigenic cells and is a repressor of MHC class I transcription SO VIROLOGY LA English DT Article ID NF-KAPPA-B; 12-TRANSFORMED CELLS; RESPONSE ELEMENT; EXPRESSION; PROMOTER; ENHANCER; BINDING; MEMBERS; LEVEL; GAMMA AB Down-regulation of the MHC class I enhancer in tumorigenic Ad12 cells is associated with strong binding of COUP-TF and negligible binding of activator NF-KB. By comparison, in nontumorigenic Ad5 cells, class I expression is high due to negligible binding of COUP-TF and strong binding of NF-KB. Here, we show that COUP-TFII, but not COUP-TFI, is expressed in Ad72-transformed cells. The dramatically stronger DNA binding of COUP-TFII to the class I enhancer in Ad12- compared to Ad5-transformed cells correlates with higher COUP-TFII promoter activity and higher levels of COUP-TFII mRNA and protein. significantly NF-kappaB p50/p52 double-knockout cells enabled us to demonstrate directly that COUP-TFII can completely repress both nonactivated and NF-kappaB-activated MHC class 1 transcription. (C) 2001 Academic Press. C1 Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Arts & Sci, Dept Biol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. NIH, Rockville, MD 20852 USA. RP Ricciardi, RP (reprint author), Univ Penn, Sch Dent Med, Dept Microbiol, Levy Res Bldg,Room 221,4010 Locust St, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA29797] NR 24 TC 20 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 25 PY 2001 VL 284 IS 1 BP 13 EP 19 DI 10.1006/viro.2001.0913 PG 7 WC Virology SC Virology GA 438PA UT WOS:000169061200002 PM 11352663 ER PT J AU Pak, Y Enyedy, IJ Varady, J Kung, JW Lorenzo, PS Blumberg, PM Wang, SM AF Pak, Y Enyedy, IJ Varady, J Kung, JW Lorenzo, PS Blumberg, PM Wang, SM TI Structural basis of binding of high-affinity ligands to protein kinase C: Prediction of the binding modes through a new molecular dynamics method and evaluation by site-directed mutagenesis SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CONFORMATIONALLY CONSTRAINED ANALOGS; PHORBOL ESTER BINDING; 5-DISUBSTITUTED TETRAHYDRO-2-FURANONE TEMPLATE; TUMOR PROMOTERS; TSALLIS STATISTICS; INDOLACTAM-V; PHARMACOPHORE; DIACYLGLYCEROL; ACTIVATION; DOMAIN AB The structural basis of protein kinase C (PKC) binding to several classes of high-affinity ligands has been investigated through complementary computational and experimental methods. Employing a recently developed q-jumping molecular dynamics (MD) simulation method, which allows us to consider the flexibility of both the ligands and the receptor in docking studies, we predicted the binding models of phorbol-13-acetate, phorbol-12,13-dibutyrate (PDBu), indolactam V (ILV), ingenol-3-benzoate, and thymeleatoxin to PKC. The "predicted" binding model for phorbol-13-acetate is virtually identical to the experimentally determined binding model for this ligand. The predicted binding model for PDBU is the same as that for phorbol-13-acetate in terms of the hydrogen-bonding network and hydrophobic contacts. The predicted binding model for ILV is the same as that obtained in a previous docking study using a Monte Carlo method and is consistent with the structure-activity relationships for this class of ligands. Together with the X-ray structure of phorbol-13-acetate in complex with PKCG Gib, the predicted binding models of PDBu, ILV, ingenol-3-benzoate, and thymeleatoxin in complex with PKC showed that the binding of these ligands to PKC is governed by a combination of several highly specific and optimal hydrogen bonds and hydrophobic contacts. However, the hydrogen-bonding network for each class of ligand is somewhat different and the number of hydrogen bonds formed between PKC and these ligands has no correlation with their binding affinities. To provide a direct and quantitative assessment of the contributions of several conserved residues around the binding site to PKC-ligand binding, we have made 11 mutations and measured the binding affinities of the high-affinity PKC ligands to these mutants. The results obtained through site-directed mutagenic analysis support our predicted binding models for these ligands and provide new insights into PKC-ligand binding. Although all the ligands have high affinity for the wild-type PKCG Gib, our site-directed mutagenic results showed that ILV is the ligand most sensitive to structural perturbations of the binding site while ingenol-3-benzoate is the least sensitive among the four classes of ligands examined here. Finally, we have employed conventional MD simulations to investigate the structural perturbations caused by each mutation to further examine the role played by each individual residue in PKC-ligand binding. MD simulations revealed that several mutations, including Proll --> Gly, Leu21 --> Gly, Leu24 --> Gly, and Gln27 --> Gly, cause a rather large conformational alteration to the PKC binding site and, in some cases, to the overall structure of the protein. The complete abolishment or the significant reduction in PKC-ligand binding observed for these mutants thus reflects the loss of certain direct contacts between the side chain of the mutated residue in PKC and ligands as well as the large conformational alteration to the binding site caused by the mutation. C1 Georgetown Univ, Lombardi Canc Ctr, Med Ctr, Washington, DC 20007 USA. Georgetown Univ, Dept Oncol, Med Ctr, Washington, DC 20007 USA. Georgetown Univ, Dept Neurosci, Med Ctr, Washington, DC 20007 USA. NCI, Cellular Carcinogenesis & Tumor Promot, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Wang, SM (reprint author), Georgetown Univ, Lombardi Canc Ctr, Med Ctr, Res Bldg,Room WP05, Washington, DC 20007 USA. RI Wang, Shaomeng/E-9686-2010 NR 39 TC 31 Z9 31 U1 0 U2 3 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 MAY 24 PY 2001 VL 44 IS 11 BP 1690 EP 1701 DI 10.1021/jm000488e PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 434XQ UT WOS:000168841500006 PM 11356104 ER PT J AU Boguna, M Berezhkovskii, AM Weiss, GH AF Boguna, M Berezhkovskii, AM Weiss, GH TI Rate constants for slow conformational transitions and their sampling errors using single-molecule fluorescence spectroscopy SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID FLUCTUATIONS; SYSTEMS AB Single-molecule fluorescence spectroscopy can be used to estimate the rate constants for slow transitions between two states characterized by different lifetimes of a fluorescent probe.:The fluorescence decay for this system is a biexponential, the coefficients of each exponential being the fraction of time spent. by the system in each of the states.:This paper explains how to estimate the rate constants for the transitions and derives the sampling error for the estimates on the assumption that the data are gathered on M molecules, each monitored for a time T. Results of the analysis indicate that the dominant factor in determining the precision of the rate constant is M and that the role of T is less significant. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Karpov Inst Phys Chem, Moscow 103064, Russia. RP Weiss, GH (reprint author), NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RI Boguna, Marian/B-7795-2011 OI Boguna, Marian/0000-0001-7833-3487 NR 16 TC 3 Z9 4 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD MAY 24 PY 2001 VL 105 IS 20 BP 4898 EP 4901 DI 10.1021/jp004023b PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 436AT UT WOS:000168914900012 ER PT J AU Pradhan, P Tirumala, S Liu, XH Sayer, JM Jerina, DM Yeh, HJC AF Pradhan, P Tirumala, S Liu, XH Sayer, JM Jerina, DM Yeh, HJC TI Solution structure of a trans-opened (10S)-dA adduct of (+)-(7S,8R,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]p yrene in a fully complementary DNA duplex: Evidence for a major syn conformation SO BIOCHEMISTRY LA English DT Article ID RAS CODON-61 SEQUENCE; DEOXYADENOSINE N-6-AMINO GROUP; DG MISMATCH OPPOSITE; RELAXATION MATRIX APPROACH; DOSE-DEPENDENT DIFFERENCES; NMR SOLUTION STRUCTURE; DIOL EPOXIDE; NUCLEIC-ACIDS; MODIFIED DEOXYGUANOSINE; NONANUCLEOTIDE DUPLEX AB Two-dimensional NMR was used to determine the solution structure of an undecanucleotide duplex, d(CGGTCACGAGG).d(CCTCGTGACCG), in which (+)-(7S,8R,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10- 10-tetrahydrobenzo[a]pyrene is covalently bonded to the exocyclic N-6 amino group of the central deoxyadenosine, dA(6), through trans addition at C10 of the epoxide (to give a 10S adduct). The present study represents the first NMR structure of a benzo[a]pyrene (10S)-dA adduct in DNA with a complementary T opposite the modified dA. Exchangeable and nonexchangeable protons of the modified duplex were assigned by the use of TOCSY (in D2O) and NOESY spectra (in H2O and D2O). Sequential NOEs expected for a B-type DNA conformation with typical Watson-Crick base pairing are observed along the duplex, except at the lesion site. We observed a strong intraresidue NOE cross-peak between H1' and H8 of the modified dA(6). The sugar H2' and H2" of dC(5) lacked NOE cross-peaks with H8 of dA(6) but showed weak interactions with H2 of dA(6) instead. In addition, the chemical shift of the H8 proton (7.51 ppm) of dA(6) appears at a higher field than that of H2 (8.48 ppm). These NOE and chemical shift data for the dA(6) base protons are typical of a syn glycosidic bond at the modified base. Restrained molecular dynamics/energy minimization calculations show that the hydrocarbon is intercalated from the major groove on the 3'-side of the modified base between base pairs A(6)-T-17 and C-7-G(16) and confirm the syn glycosidic angle (58 degrees) of the modified dA(6). In the syn structure, a weak A-T hydrogen bond is possible between the N3-H proton of T-17 and N7 of dA(6) (at a distance of 3.11 Angstrom), whereas N1, the usual hydrogen bending partner for N3-H of T when dA is in the anti conformation, is 6.31 Angstrom away from this proton. The 10(S)-dA modified DNA duplex remains in a right-handed helix, which bends in the direction of the aliphatic ring of BaP at about 42 degrees from the helical axis. ROESY experiments provided evidence for interconversion between the major, syn conformer and a minor, possibly anti, conformer. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Yeh, HJC (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 59 TC 36 Z9 37 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 22 PY 2001 VL 40 IS 20 BP 5870 EP 5881 DI 10.1021/bi002896q PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 436JN UT WOS:000168932900004 PM 11352722 ER PT J AU Spooner, PM Albert, C Benjamin, EJ Boineau, R Elston, RC George, AL Jouven, X Kuller, LH MacCluer, JW Marban, E Muller, JE Schwartz, PJ Siscovick, DS Tracy, RP Zareba, W Zipes, DP AF Spooner, PM Albert, C Benjamin, EJ Boineau, R Elston, RC George, AL Jouven, X Kuller, LH MacCluer, JW Marban, E Muller, JE Schwartz, PJ Siscovick, DS Tracy, RP Zareba, W Zipes, DP TI Sudden cardiac death, genes, and arrhythmogenesis - Consideration of new population and mechanistic approaches from a National Heart, Lung, and Blood Institute Workshop, part II SO CIRCULATION LA English DT Article DE genetics; death, sudden; arrhythmia; tachyarrhythmias; epidemiology; mortality; ion channels ID CORONARY-ARTERY DISEASE; APPARENTLY HEALTHY-MEN; OXIDE SYNTHASE GENE; MYOCARDIAL-INFARCTION; VENOUS THROMBOSIS; RATE-VARIABILITY; RISK FACTOR; POLYMORPHISM; RECEPTOR; MUTATION AB This is Part II of a 2-part article dealing with malignant ventricular arrhythmias, which are the leading mechanism of death in common cardiac diseases. Genetic population studies directed at discovering common proximal sources of inherited molecular risk most directly linked to arrhythmia initiation and propagation would appear to have considerable potential in helping reduce cardiovascular mortality. C1 NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Boston, MA 02215 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Vanderbilt Univ, Nashville, TN USA. Hosp Boucicaut, Paris, France. Univ Pittsburgh, Pittsburgh, PA USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Pavia, I-27100 Pavia, Italy. Univ Washington, Seattle, WA 98195 USA. Univ Vermont, Colchester, VT USA. Univ Rochester, Rochester, NY USA. Indiana Univ, Indianapolis, IN 46204 USA. RP Spooner, PM (reprint author), NHLBI, Div Heart & Vasc Dis, 2 Rockledge Ctr,Suite 9192,6701 Rockledge Dr,MSC, Bethesda, MD 20892 USA. RI Schwartz, Peter/J-4267-2016; OI Schwartz, Peter/0000-0003-0367-1048; Zipes, Douglas/0000-0001-7141-6829 NR 27 TC 48 Z9 50 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 22 PY 2001 VL 103 IS 20 BP 2447 EP 2452 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 436KC UT WOS:000168934200006 PM 11369684 ER PT J AU Belova, GI Prasad, R Kozyavkin, SA Lake, JA Wilson, SH Slesarev, AI AF Belova, GI Prasad, R Kozyavkin, SA Lake, JA Wilson, SH Slesarev, AI TI A type IB topoisomerase with DNA repair activities SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLYMERASE-BETA; REVERSE GYRASE; METHANOPYRUS-KANDLERI; ACTIVE-SITE; DESULFUROCOCCUS-AMYLOLYTICUS; EUKARYOTIC TOPOISOMERASE; PHOSPHATE LYASE; CIRCULAR DNA; BINDING; PROTEIN AB Previously we have characterized type IB DNA topoisomerase V (topo V) in the hyperthermophile Methanopyrus kandleri. The enzyme has a powerful topoisomerase activity and is abundant in M, kandleri. Here we report two characterizations of topo V, First, we found that its N-terminal domain has sequence homology with both eukaryotic type IB topoisomerases and the integrase family of tyrosine recombinases, The C-terminal part of the sequence includes 12 repeats, each repeat consisting of two similar but distinct helix-hairpin-helix motifs; the same arrangement is seen in recombination protein RuvA and mammalian DNA polymerase P, Second, on the basis of sequence homology between topo V and polymerase p, we predict and demonstrate that topo V possesses apurinic/ apyrimidinic (AP) site-processing activities that are important in base excision DNA repair: (i) it incises the phosphodiester backbone at the AP site, and Iib at the AP endonuclease cleaved AP site, it removes the 5 ' 2-deoxyribose 5-phosphate moiety so that a single-nucleotide gap with a 3 ' -hydroxyl and 5 ' -phosphate can be filled by a DNA polymerase. Topo V is thus the prototype for a new subfamily of type IB topoisomerases and is the first example of a topoisomerase with associated DNA repair activities. C1 Fidel Syst Inc, Gaithersburg, MD 20879 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117871, Russia. RP Slesarev, AI (reprint author), Fidel Syst Inc, 7961 Cessna Ave, Gaithersburg, MD 20879 USA. NR 40 TC 29 Z9 31 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 22 PY 2001 VL 98 IS 11 BP 6015 EP 6020 DI 10.1073/pnas.111040498 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 435LV UT WOS:000168883700017 PM 11353838 ER PT J AU Paull, TT Cortez, D Bowers, B Elledge, SJ Gellert, M AF Paull, TT Cortez, D Bowers, B Elledge, SJ Gellert, M TI Direct DNA binding by Brca1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DOUBLE-STRAND BREAKS; ATM-DEPENDENT PHOSPHORYLATION; SUPPRESSOR GENE BRCA1; DAMAGE RESPONSE; CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; NUCLEAR PHOSPHOPROTEIN; ATAXIA-TELANGIECTASIA; EMBRYONIC LETHALITY; FUNCTIONAL-LINK AB The tumor suppressor Brca1 plays an important role in protecting mammalian cells against genomic instability, but little is known about its modes of action. In this work we demonstrate that recombinant human Brca1 protein binds strongly to DNA, an activity conferred by a domain in the center of the Brca1 polypeptide. As a result of this binding, Brca1 inhibits the nucleolytic activities of the Mre11/Rad50/Nbs1 complex, an enzyme implicated in numerous aspects of double-strand break repair. Brca1 displays a preference for branched DNA structures and forms protein-DNA complexes cooperatively between multiple DNA strands, but without DNA sequence specificity. This fundamental property of Brca1 may be an important part of its role in DNA repair and transcription. C1 Univ Texas, Dept Mol Genet & Microbiol, Austin, TX 78712 USA. Baylor Coll Med, Howard Hughes Med Inst, Dept Biochem, Houston, TX 77030 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Paull, TT (reprint author), Univ Texas, Dept Mol Genet & Microbiol, Austin, TX 78712 USA. NR 47 TC 186 Z9 190 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 22 PY 2001 VL 98 IS 11 BP 6086 EP 6091 DI 10.1073/pnas.111125998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 435LV UT WOS:000168883700029 PM 11353843 ER PT J AU Williams, MC Rouzina, I Wenner, JR Gorelick, RJ Musier-Forsyth, K Bloomfield, VA AF Williams, MC Rouzina, I Wenner, JR Gorelick, RJ Musier-Forsyth, K Bloomfield, VA TI Mechanism for nucleic acid chaperone activity of HIV-1 nucleocapsid protein revealed by single molecule stretching SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PLUS-STRAND TRANSFER; PRIMER BINDING-SITE; STRONG-STOP DNA; REVERSE TRANSCRIPTION; MINUS-STRAND; ZINC-FINGER; ORDERED AGGREGATION; MODEL RNA; IN-VITRO AB The nucleocapsid protein (NC) of HIV type 1 is a nucleic acid chaperone that facilitates the rearrangement of nucleic acids into conformations containing the maximum number of complementary base pairs. We use an optical tweezers instrument to stretch single DNA molecules from the helix to coil state at room temperature in the presence of NC and a mutant form (SSHS NC) that lacks the two zinc finger structures present in NC. Although both NC and SSHS NC facilitate annealing of complementary strands through electrostatic attraction, only NC destabilizes the helical form of DNA and reduces the cooperativity of the helix-coil transition. In particular, we find that the helix-coil transition free energy at room temperature is significantly reduced in the presence of NC. Thus, upon NC binding, it is likely that thermodynamic fluctuations cause continuous melting and reannealing of base pairs so that DNA strands are able to rapidly sample configurations to find the lowest energy state. The reduced cooperativity allows these fluctuations to occur in the middle of complex double-stranded structures. The reduced stability and cooperativity, coupled with the electrostatic attraction generated by the high charge density of NC, is responsible for the nucleic acid chaperone activity of this protein. C1 Univ Minnesota, Dept Biochem Mol Biol & Biophys, St Paul, MN 55108 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, AIDS Vaccine Program, Frederick, MD 21702 USA. Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. RP Musier-Forsyth, K (reprint author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, 1479 Gortner Ave, St Paul, MN 55108 USA. OI Williams, Mark C./0000-0003-3219-376X FU NCI NIH HHS [N01-CO-56000]; NIGMS NIH HHS [GM28093, GM49928, R01 GM028093, R01 GM049928] NR 43 TC 138 Z9 141 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 22 PY 2001 VL 98 IS 11 BP 6121 EP 6126 DI 10.1073/pnas.101033198 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 435LV UT WOS:000168883700035 PM 11344257 ER PT J AU Tansey, JT Sztalryd, C Gruia-Gray, J Roush, DL Zee, JV Gavrilova, O Reitman, ML Deng, CX Li, C Kimmel, AR Londos, C AF Tansey, JT Sztalryd, C Gruia-Gray, J Roush, DL Zee, JV Gavrilova, O Reitman, ML Deng, CX Li, C Kimmel, AR Londos, C TI Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HORMONE-SENSITIVE LIPASE; DEPENDENT PROTEIN-KINASE; LIPID STORAGE DROPLET; INSULIN-RESISTANCE; DIABETES-MELLITUS; RAT ADIPOCYTES; MICE; LIPODYSTROPHY; MECHANISMS; CELLS AB Perilipin coats the lipid droplets of adipocytes and is thought to have a role in regulating triacylglycerol hydrolysis. To study the role of perilipin in vivo, we have created a perilipin knockout mouse. Perilipin null (peri(-/-)) and wild-type (peri(+/+)) mice consume equal amounts of food, but the adipose tissue mass in the null animals is reduced to approximate to 30% of that in wild-type animals. Isolated adipocytes of perilipin null mice exhibit elevated basal lipolysis because of the loss of the protective function of perilipin. They also exhibit dramatically attenuated stimulated lipolytic activity, indicating that perilipin is required for maximal lipolytic activity. Plasma leptin concentrations in null animals were greater than expected for the reduced adipose mass. The peri(-/-) animals have a greater lean body mass and increased metabolic rate but they also show an increased tendency to develop glucose intolerance and peripheral insulin resistance. When fed a high-fat diet, the perilipin null animals are resistant to diet-induced obesity but not to glucose intolerance. The data reveal a major role for perilipin in adipose lipid metabolism and suggest perilipin as a potential target for attacking problems associated with obesity. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Londos, C (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bldg 6,Room B1-32, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016; Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 FU NIDDK NIH HHS [P30 DK056336, P30-DK56336] NR 24 TC 464 Z9 485 U1 3 U2 21 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 22 PY 2001 VL 98 IS 11 BP 6494 EP 6499 DI 10.1073/pnas.101042998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 435LV UT WOS:000168883700099 PM 11371650 ER PT J AU Burke, TR Yao, ZJ Ye, B Miyoshi, K Otaka, A Wu, L Zhang, ZY AF Burke, TR Yao, ZJ Ye, B Miyoshi, K Otaka, A Wu, L Zhang, ZY TI Phospho-azatyrosine, a less effective protein-tyrosine phosphatase substrate than phosphotyrosine SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID TRANSDUCTION INHIBITORY PEPTIDES; POTENT INHIBITION; DEPHOSPHORYLATION; CONVERSION; MECHANISM; DESIGN; STATE; CELLS; 1B AB Azatyrosine (AzaTyr, 4) is a natural product isolated from Streptomyces chihanesis, whose structure is characterized by a nitrogen atom in the aryl ring of a tyrosyl residue. This seemingly minor modification to the tyrosyl residue results in profound physiological effects, as AzaTyr has been shown to promote permanent reversion of ras-dependent transformed cells to the normal phenotype in culture and to inhibit chemical induction of carcinogenesis in transgenic mice bearing oncogenic human ras. The mechanisms underlying these effects are not known, however ras-pathways involve an intricate balance between both protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs). The present study was undertaken to examine the general utility of AzaTyr as a structural motif for PTP inhibitor design by examining the phospho-azatyrosine (pAzaTyr)-containing peptide Ac-Asp-Ala-Asp-Glu-pAzaTyr-Leu-amide (8) in a PTP1 enzyme system. Kinetic analysis indicated that 8 binds with a K-m value of 210 muM and a catalytic turnover rate, k(cat) of 52 s(-1). This represents a greater than 50-fold reduction in binding affinity relative to the parent phosphotyrosine-containing peptide, indicating that the aryl nitrogen adversely affects binding affinity. The much lower PTP affinity of the pAzaTyr-containing peptide reduces the potential utility of the AzaTyr pharmacophore for PTP inhibitor design. These results are discussed from the point of view that incorporation of AzaTyr residues into proteins could result in perturbation of protein-tyrosine phosphorylation/dephosphorylation cascades that control signal transduction processes, including,as-dependent pathways. Published by Elsevier Science Ltd. C1 NCI, Med Chem Lab, Div Basic Sci, NIH,FCRDC, Frederick, MD 21702 USA. Kyoto Univ, Fac Pharmaceut Sci, Sakyo Ku, Kyoto 606, Japan. Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH,FCRDC, Bldg 376,Boyles St,POB B, Frederick, MD 21702 USA. RI Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 21 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 21 PY 2001 VL 11 IS 10 BP 1265 EP 1268 DI 10.1016/S0960-894X(01)00197-4 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 432RZ UT WOS:000168710600004 PM 11392533 ER PT J AU Lee, K Ravi, G Ji, XD Marquez, VE Jacobson, KA AF Lee, K Ravi, G Ji, XD Marquez, VE Jacobson, KA TI Ring-constrained (N)-methanocarba nucleosides as adenosine receptor agonists: Independent 5 '-uronamide and 2 '-deoxy modifications SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID RAT-BRAIN; BIOLOGICAL-ACTIVITY; ANALOGS; LIGANDS; ISCHEMIA; AFFINITY AB Novel methanocarba adenosine analogues, having the pseudo-ribose northern (N) conformation preferred at adenosine receptors (ARs), were synthesized and tested in binding assays. The 5'-uronamide modification preserved [N-6-(3-iodobenzyl)] or enhanced (N-6-methyl) affinity at A(3)ARs, while the 2'-deoxy modification reduced affinity and efficacy in a functional assay. Published by Elsevier Science Ltd. C1 NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Frederick, MD 21702 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 16 TC 44 Z9 46 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 21 PY 2001 VL 11 IS 10 BP 1333 EP 1337 DI 10.1016/S0960-894X(01)00213-X PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 432RZ UT WOS:000168710600020 PM 11392549 ER PT J AU Yan, B Miura, RM Chen, Y AF Yan, B Miura, RM Chen, Y TI Direction reversal of fluctuation-induced biased Brownian motion on distorted ratchets SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article ID MOLECULAR MOTORS; DRIVEN RATCHETS; PARTICLES; TRANSPORT; NOISE AB The biased movement of Brownian particles on a fluctuating two-state periodic potential made of identical distorted ratchets is studied. The purpose is to investigate how the direction of the particle movement is related to the asymmetry of the potential. In general, distorting one of the two linear arms of a regular symmetric ratchet (with equal arm lengths) can create a driving force for the Brownian particle to execute biased movement. The direction of the induced biased movement depends on the type of the distortion. It has been found that if one linear arm is kinked into two linear sub-arms, the direction of the movement can be either positive or negative depending on the frequency of the fluctuation and the location and the degree of the kink. In contrast, if one arm of the symmetric ratchet is replaced by a continuous nonlinear sinusoidal function, the movement is always unidirectional. Thus, for the fatter case to generate the direction reversal phenomenon, the ratchets have to have an additional asymmetry. We also have found that two potentials with different distorted ratchets can generate identical fluxes if the distortions are polar symmetric about the mid-point of the arm(s) of the basic linear two-arm ratchet. The results are useful for designing experimental apparatuses for the separation of protein particles based on their sizes and charges and the viscosity of the medium. (C) 2001 Academic Press. C1 NIDDKD, Math Res Branch, NIH, Bethesda, MD 20892 USA. Univ British Columbia, Dept Math, Vancouver, BC V6T 1Z2, Canada. RP Yan, B (reprint author), NIDDKD, Math Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 15 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD MAY 21 PY 2001 VL 210 IS 2 BP 141 EP 150 DI 10.1006/jtbi.2000.2288 PG 10 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 445VX UT WOS:000169480200002 PM 11371171 ER PT J AU Kohn, MC Walker, NJ Kim, AH Portier, CJ AF Kohn, MC Walker, NJ Kim, AH Portier, CJ TI Physiological modeling of a proposed mechanism of enzyme induction by TCDD SO TOXICOLOGY LA English DT Article DE PBPK modeling; pharmacodynamics; TCDD; enzyme induction; gene expression kinetics ID ARYL-HYDROCARBON RECEPTOR; SPRAGUE-DAWLEY RATS; MULTICOMPARTMENT GEOMETRIC MODEL; DOSE-RESPONSE RELATIONSHIPS; MESSENGER-RNA STABILITY; AH-RECEPTOR; TISSUE DISTRIBUTION; CELL-PROLIFERATION; CHRONIC EXPOSURE; DNA-BINDING AB A physiological model was previously constructed to facilitate extrapolation of surrogates for the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rat liver to doses comparable to human environmental exposures. The model included induction of P450 isozymes and suggested the presence of multiple binding sites with different affinities for the TCDD-liganded Ah receptor at CYP1A1 dioxin responsive elements. The model also indicated that protein synthesis on the mRNA template exhibited saturation kinetics with respect to message levels. In the present work the earlier model was revised to include the increased proteolysis of the Ah receptor on binding TCDD, more realistic representations of gene transcription and mRNA translation, and different stability for each mRNA. The revised model includes multiple TCDD-liganded Ah receptor binding sites for CYP1A1 and CYP1B1 genes, a lag of 0.2 day for production of mRNA and induced proteins, and stabilization of mRNA by a poly(A) tail. The model reproduced the transient depletion of the Ah receptor subsequent to binding ligand and the dose-response of the receptor in rats treated with biweekly oral doses of TCDD in corn oil. The model reproduced tissue TCDD concentrations observed for several dosing scenarios. Such robustness indicates the utility of the model in estimating internal dose. The model also reproduced the observed dose-response patterns for mRNA and protein for CYP1A1, CYP1A2, and CYP1B1 after repeated dosing. Neither of the two dissociation constants for the Ah receptor bound to the CYP1B1 gene is negligible, supporting the assumption of multiple response elements for this gene. The poorer induction of CYP1B1 was predicted to be due to lower affinity of the dioxin responsive elements for binding the liganded Ah receptor, suggesting the involvement of other regulatory factors, and a shorter poly(A) tail on CYP1B1 mRNA, leading to a shorter lifetime. Saturation in the kinetics of protein synthesis was linked to the limited number of ribosomes that could bind to each message molecule, resulting in fewer ribosomes bound per message at higher doses. Predicted induction at low doses was found to vary widely with the assumptions used in the construction of a model. More detailed descriptions of biological processes might provide more reliable predictions of enzyme induction. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Kohn, MC (reprint author), NIEHS, Lab Computat Biol & Risk Anal, POB 12233, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010; Walker, Nigel/D-6583-2012 OI Portier, Christopher/0000-0002-0954-0279; Walker, Nigel/0000-0002-9111-6855 NR 45 TC 20 Z9 22 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD MAY 21 PY 2001 VL 162 IS 3 BP 193 EP 208 DI 10.1016/S0300-483X(01)00363-8 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 439EK UT WOS:000169097700005 PM 11369115 ER PT J AU Allen, M Israel, H Rybczyk, K Pugliese, MA Loughran, K Wagner, L Erb, S AF Allen, M Israel, H Rybczyk, K Pugliese, MA Loughran, K Wagner, L Erb, S TI Trial-related discrimination in HIV vaccine clinical trials SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID EFFICACY TRIALS; PREVENTING DISCRIMINATION; SOCIAL-ISSUES; VOLUNTEERS; RISK; MEN; PARTICIPATE; WILLINGNESS; INFECTION; GAY AB Participants in preventive HIV vaccine trials may experience negative social consequences of trial participation, including problems related to a vaccine-induced positive HIV antibody test, yet few vaccine studies have reported on this issue. From October 1995 through November 1998, 1516 AIDS Vaccine Evaluation Group (AVEG) volunteers were assessed for reports of trial-related discrimination (TRD), Ninety TRD events were reported by 76 (5%) of 1516 volunteers, The most commonly reported incidents (n = 52, 57.8%) were negative reactions of friends, family, and co-workers to the volunteer. Few incidents (approximately 10%) were reported as linked to HIV testing. The majority of events (n = 47, 52%) were described by volunteers as "resolved" at the time of reporting, 36 (40%) as "not resolved," and for 7 (8%) events: volunteers did not report resolution status. Reported incidents were analyzed by logistic regression to determine their association with the volunteer's age, sex, race, sexual orientation, and HIV risk category. There was no association between volunteer characteristics and TRD, Logistic regression and analysis of variance (ANOVA) were used to analyze association of trial sites with the number of TRD events reported. After controlling for site variation in data collection and reporting, no significant differences were found between the sites in terms of the number or type of TRD reported. Fears that TRD would be widespread and severe have not been borne out by this analysis. While the results of this study are reassuring, they should be interpreted with caution, as it is unclear whether these results may be extended to phase III trials enrolling large numbers of individuals at higher risk of HIV acquisition. C1 NIAID, Bethesda, MD 20892 USA. St Louis Univ, Sch Med, St Louis, MO 63104 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA. Univ Rochester, Sch Med, Rochester, NY 14642 USA. EMMES Corp, Potomac, MD 20854 USA. RP Allen, M (reprint author), NIAID, 6700-B Rockledge Dr,Room 4218, Bethesda, MD 20892 USA. OI Allen, Mary/0000-0001-8163-0714 FU NIAID NIH HHS [N01-AI-45211, N01-AI-45207, N01-AI-45209, N01-AI-45205, N01-AI-45208, N01-AI-45206]; PHS HHS [N01-45210] NR 23 TC 40 Z9 43 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 MAY 20 PY 2001 VL 17 IS 8 BP 667 EP 674 DI 10.1089/088922201750236942 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 441HX UT WOS:000169225900002 PM 11429107 ER PT J AU Lee, CGL Vieira, WD Pastan, I Gottesman, MM AF Lee, CGL Vieira, WD Pastan, I Gottesman, MM TI An episomally maintained MDR1 gene for gene therapy SO HUMAN GENE THERAPY LA English DT Article ID EPSTEIN-BARR-VIRUS; MULTIDRUG-RESISTANCE GENE; RETROVIRAL-MEDIATED TRANSFER; BONE-MARROW CELLS; P-GLYCOPROTEIN; SHUTTLE VECTORS; MAMMALIAN-CELLS; BICISTRONIC VECTOR; NUCLEAR ANTIGEN-1; PROGENITOR CELLS AB Potential applications of the MDR1 multidrug transporter in gene therapy include protecting sensitive bone marrow cells against cytotoxic drugs during cancer chemotherapy and serving as a dominant selectable marker when coexpressed with a corrective passenger gene. To address safety concerns associated with integrating viral systems, such as retroviruses, we tested the feasibility of maintaining a nonvirally delivered MDR1 gene (pEpiHaMA) episomally. An MDR1 vector containing the Epstein-Barr virus (EBV) origin of replication (OriP) and its nuclear retention protein (EBNA-1) was transfected into human (KB-3-1) cells. MDR1 was expressed at a higher level in cells carrying the episomal vector, pEpiHaMA, compared with the vector lacking sequences needed for episomal maintenance (pHaMA). Furthermore, more drug-resistant KB-3-1 colonies were obtained on selection after transfection with pEpiHaMA. These observations correlated with longer maintenance of episomes in cells transfected with pEpiHaMA, In addition, episomes could still be recovered for more than 1 month from tumor explants in nude mice that were injected with pEpiHaMA-liposome complexes after drug selection, suggesting that these constructs can be maintained extrachromosomally in vivo. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1A09,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 54 TC 7 Z9 10 U1 0 U2 0 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 MAY 20 PY 2001 VL 12 IS 8 BP 945 EP 953 DI 10.1089/104303401750195908 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 437EW UT WOS:000168978900008 PM 11387059 ER PT J AU Finegold, AA Perez, FM Iadarola, MJ AF Finegold, AA Perez, FM Iadarola, MJ TI In vivo control of NMDA receptor transcript level in motoneurons by viral transduction of a short antisense gene SO MOLECULAR BRAIN RESEARCH LA English DT Article DE NR1 subunit; gene therapy; adenovirus; motor neuron; excitotoxicity; excitatory amino acid; spinal muscular atrophy; neurodegenerative disorder ID CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD NEURONS; IN-VIVO; RECOMBINANT ADENOVIRUS; CELLS; SUBUNIT; VECTORS; BINDING; THERAPY; BRAIN AB Glutamate receptors play critical roles in normal and pathological processes. We developed an antisense gene delivery strategy to modulate the NMDA type of glutamate receptor, Using transient transfection in vitro and viral mediated gene transfer in vitro and in vivo, the effect of expression of an antisense gene fragment (60 bp) of the NR1 subunit was tested. Immunoblot analysis showed an antisense-concentration-dependent reduction in the NR1 subunit upon transient co-transfection of a plasmid expressing a sense NR1 gene and a plasmid expressing the antisense fragment into COS-7 cells. After recombination into an adenoviral vector, this antisense fragment reduced the amount of endogenous NR1 protein in PC12 cells. Finally, direct intraparenchymal injection of the viral vector into rat spinal cord resulted in diminished NR1 in motor neurons. Our results demonstrate the efficacy of this approach, which combines antisense with viral gene delivery to control the expression of specific genes in vivo. This approach may also be useful in reducing excitatory neurotransmission in vivo, with implications for the treatment of spinal disorders such as amyotrophic lateral sclerosis or chronic pain. (C) 2001 Published by Elsevier Science B.V. C1 NIDCR, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. RP Iadarola, MJ (reprint author), NIDCR, Pain & Neurosensory Mechanisms Branch, NIH, Bldg 49,Rm 1A11,49 Convent Dr,MSC 4410, Bethesda, MD 20892 USA. NR 32 TC 8 Z9 9 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY 20 PY 2001 VL 90 IS 1 BP 17 EP 25 DI 10.1016/S0169-328X(01)00062-6 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 435KW UT WOS:000168881500002 ER PT J AU Villar, J Ba'aqeel, H Piaggio, G Lumbiganon, P Belizan, JM Farnot, U Al-Mazrou, Y Carroli, G Pinol, A Donner, A Langer, A Nigenda, G Mugford, M Fox-Rushby, J Hutton, G Bergsjo, P Bakketeig, L Berendes, H AF Villar, J Ba'aqeel, H Piaggio, G Lumbiganon, P Belizan, JM Farnot, U Al-Mazrou, Y Carroli, G Pinol, A Donner, A Langer, A Nigenda, G Mugford, M Fox-Rushby, J Hutton, G Bergsjo, P Bakketeig, L Berendes, H CA WHO Antenatal Care Trial Res Grp TI WHO antenatal care randomised trial for the evaluation of a new model of routine antenatal care SO LANCET LA English DT Article ID LOW-RISK WOMEN; ECONOMIC-EVALUATION; COLORECTAL-CANCER; SCIENTIFIC BASIS; CLINICAL-TRIALS; PRENATAL-CARE; VISITS; DESIGN; POWER; ELIMINATE AB Background We undertook a multicentre randomised controlled trial that compared the standard model of antenatal care with a new model that emphasises actions known to be effective in improving maternal or neonatal outcomes and has fewer clinic visits. Methods Clinics in Argentina, Cuba, Saudi Arabia, and Thailand were randomly allocated to provide either the new model (27 clinics) or the standard model currently in use (26 clinics). All women presenting for antenatal care at these clinics over an average of 18 months were enrolled. Women enrolled in clinics offering the new model were classified on the basis of history of obstetric and clinical conditions. Those who did not require further specific assessment or treatment were offered the basic component of the new model, and those deemed at higher risk received the usual care for their conditions; however, all were included in the new-model group for the analyses, which were by intention to treat. The primary outcomes were low birthweight (<2500 g), pre-eclampsia/eclampsia, severe postpartum anaemia (<90 g/L haemoglobin), and treated urinary-tract infection. There was an assessment of quality of care and an economic evaluation. Findings Women attending clinics assigned the new model (n = 12 568) had a median of five visits compared with eight within the standard model (n = 11 958). More women in the new model than in the standard model were referred to higher levels of care (13.4% vs 7.3%), but rates of hospital admission, diagnosis, and length of stay were similar. The groups had similar rates of low birthweight (new model 7.68% vs standard model 7.14%; stratified rate difference 0.96 [95% CI -0.01 to 1.92]), postpartum anaemia (7.59% vs 8.67%; 0.32), and urinary-tract infection (5.95% vs 7.41%; -0.42 [-1.65 to 0.80]). For pre-eclampsia/eclampsia the rate was slightly higher in the new model (1.69% vs 1.38%; 0.21 [-0.25 to 0.67]). Adjustment by several confounding variables did not modify this pattern. There were negligible differences between groups for several secondary outcomes. Women and providers in both groups were, in general, satisfied with the care received, although some women assigned the new model expressed concern about the timing of visits. There was no cost increase, and in some settings the new model decreased cost. Interpretations Provision of routine antenatal care by the new model seems not to affect maternal and perinatal outcomes. It could be implemented without major resistance from women and providers and may reduce cost. C1 WHO, Dept Reprod Hlth & Res, UNDP,UNFPA, World Bank Special Programme Res Dev & Res Traini, CH-1211 Geneva 27, Switzerland. Natl Guard King Khalid Hosp, Jeddah, Saudi Arabia. Khon Kaen Univ, Khon Kaen, Thailand. Ctr Rosarino Estudios Perinatales, Rosario, Santa Fe, Argentina. Hosp Ginecoobstet Amer Arias, Havana, Cuba. Minist Hlth, Riyadh, Saudi Arabia. Univ Western Ontario, London, ON, Canada. Populat Council, Off Latin Amer & Caribbean, Mexico City, DF, Mexico. Inst Nacl Salud Publ, Ctr Invest Sistemas Salud, Mexico City, DF, Mexico. Univ E Anglia, Sch Hlth Policy & Practice, Norwich NR4 7TJ, Norfolk, England. London Sch Hyg & Trop Med, Hlth Policy Unit, London WC1, England. Univ Bergen, Dept Obstet & Gynaecol, Bergen, Norway. Natl Publ Hlth Inst, Oslo, Norway. NICHHD, NIH, Bethesda, MD 20892 USA. RP Villar, J (reprint author), WHO, Dept Reprod Hlth & Res, UNDP,UNFPA, World Bank Special Programme Res Dev & Res Traini, CH-1211 Geneva 27, Switzerland. RI Sandall, Jane/D-4146-2009; OI Sandall, Jane/0000-0003-2000-743X; Baaqeel, Hassan/0000-0002-0774-2790; Belizan, Jose/0000-0002-8412-3010 NR 42 TC 230 Z9 252 U1 4 U2 25 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 19 PY 2001 VL 357 IS 9268 BP 1551 EP 1564 DI 10.1016/S0140-6736(00)04722-X PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 434RR UT WOS:000168830100008 PM 11377642 ER PT J AU Chen, XL Lee, K Hartzell, DL Dean, RG Hausman, GJ McGraw, RA Della-Fera, MA Baile, CA AF Chen, XL Lee, K Hartzell, DL Dean, RG Hausman, GJ McGraw, RA Della-Fera, MA Baile, CA TI Adipocyte insensitivity to insulin in growth hormone-transgenic mice SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE growth hormone; adipogenesis; insulin; peroxisome proliferator-activated receptor-gamma; GLUT4; C/EBP alpha; C/EBP beta; preadipocyte factor-1; tumor necrosis factor-alpha; leptin ID GENE-EXPRESSION; DIFFERENTIATION; LEPTIN; PREADIPOCYTES; RECEPTOR; BINDING; PROTEIN; CELLS; GAMMA AB Growth hormone (GH) has an inhibitory effect on adipogenesis, and its effect is associated with insulin action in obesity. In this study, the relationship between GH effect on insulin sensitivity and adipocyte differentiation in vivo was investigated. Transgenic (TG) female mice expressing porcine GH had reduced body weights and weights of retroperitoneal and parametrial fat depots. Insulin treatment increased PPAR gamma and GLUT4 expression in adipose tissue of WT mice but had no effect in TG mice. Content of transcription factors, PPAR gamma and C/EBP alpha and beta, was higher in adipose tissue of WT mice, and for C/EBP alpha and PPAR gamma, the difference occurred primarily in 24-, compared to 12-week-old, mice. Expression of preadipocyte factor-1 was higher in adipose tissue of TG mice, and expression of TNF-alpha and leptin was reduced in adipose tissue of 24-week-old TG mice. Our results suggest that increased expression of GH reduces adipogenesis by inducing adipocyte resistance to the adipogenic effect of insulin. (C) 2001 Academic Press. C1 Univ Georgia, Dept Dairy & Anim Sci, Athens, GA 30605 USA. Univ Georgia, Dept Physiol & Pharmacol, Athens, GA 30605 USA. Univ Georgia, USDA ARS, Athens, GA 30602 USA. NIDDK, Diabet Branch, NIH, Bethesda, MD USA. Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA. RP Baile, CA (reprint author), Univ Georgia, Dept Dairy & Anim Sci, 444 Anim Sci Complex, Athens, GA 30605 USA. RI Lee, Kichoon/G-2234-2012; OI Della-Fera, Mary Anne/0000-0002-6660-8727 NR 19 TC 15 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 18 PY 2001 VL 283 IS 4 BP 933 EP 937 DI 10.1006/bbrc.2001.4882 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 436GP UT WOS:000168928400034 PM 11350075 ER PT J AU Perabo, FGE Kamp, S Schmidt, D Lindner, H Steiner, G Mattes, RH Wirger, A Pegelow, K Albers, P Kohn, EC von Ruecker, A Mueller, SC AF Perabo, FGE Kamp, S Schmidt, D Lindner, H Steiner, G Mattes, RH Wirger, A Pegelow, K Albers, P Kohn, EC von Ruecker, A Mueller, SC TI Bladder cancer cells acquire competent mechanisms to escape Fas-mediated apoptosis and immune surveillance in the course of malignant transformation SO BRITISH JOURNAL OF CANCER LA English DT Article DE bladder cancer; Fas; Fas-ligand; apoptosis; immune escape ID NECROSIS-FACTOR FAMILY; SOLUBLE FAS; ANTI-FAS; LIGAND EXPRESSION; ANTICANCER DRUGS; T-LYMPHOCYTES; DEATH; CARCINOMA; METALLOPROTEINASE; ACTIVATION AB Mechanisms of resistance against Fas-mediated cell killing have been reported in different malignancies. However, the biological response of immune escape mechanisms might depend on malignant transformation of cancer cells. In this study we investigated different mechanisms of immune escape in 2 well-differentiated low-grade (RT4 and RT112) and 2 poorly differentiated high-grade (T24 and TCCSUP) bladder cancer cell lines. Fas, the receptor of Fas-ligand, is expressed and shedded by human transitional bladder carcinoma cell lines RT4, RT112, T24 and TCCSUP. Cytotoxicity and apoptosis assays demonstrate that in spite of the Fas expression, poorly differentiated T24 and TCCSUP cells are insensitive towards either recombinant Fas-ligand or agonistic apoptosis-inducing monoclonal antibody against Fas. In poorly differentiated T24 and TCCSUP cell lines we were able to detect marked Fas-ligand protein by flow cytometry and Western blot analysis. In grade 1 RT4 and RT112 cells only minor expression of Fas-ligand possibly because of proteinase action. Fas-ligand mRNA translation or post-translational processing seems to be regulated differentially in the cancer cell lines depending on malignant transformation. In co-culture experiments we show that poorly differentiated cells can induce apoptosis and cell death in Jurkat cells and activated peripheral blood mononuclear cells. This in vitro study suggests that bladder cancer cells can take advantage of different mechanisms of immune evasion and become more competent in avoiding immune surveillance during transformation to higher-grade malignant disease. (C) 2001 Cancer Research Campaign. C1 Univ Bonn, Dept Urol, D-53105 Bonn, Germany. Univ Hosp Ulm, Dept Urol, D-89075 Ulm, Germany. Med Univ Lubeck, Dept Urol, D-23938 Lubeck, Germany. Univ Bonn, Inst Clin Biochem, D-53105 Bonn, Germany. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Perabo, FGE (reprint author), Univ Bonn, Dept Urol, D-53105 Bonn, Germany. NR 52 TC 28 Z9 31 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY 18 PY 2001 VL 84 IS 10 BP 1330 EP 1338 DI 10.1054/bjoc.2001.1808 PG 9 WC Oncology SC Oncology GA 438FK UT WOS:000169042800009 PM 11355943 ER PT J AU Johnson, JI Decker, S Zaharevitz, D Rubinstein, LV Venditti, J Schepartz, S Kalyandrug, S Christian, M Arbuck, S Hollingshead, M Sausville, EA AF Johnson, JI Decker, S Zaharevitz, D Rubinstein, LV Venditti, J Schepartz, S Kalyandrug, S Christian, M Arbuck, S Hollingshead, M Sausville, EA TI Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials SO BRITISH JOURNAL OF CANCER LA English DT Article DE anticancer drug discovery; in vitro-to-in vivo correlations; clinical trials ID TUMOR-CELL-LINES; DISCOVERY; FEASIBILITY; ASSAY; PANEL AB An analysis of the activity of compounds tested in pre-clinical in vivo and in vitro assays by the National Cancer Institute's Developmental Therapeutics Program was performed. For 39 agents with both xenograft data and Phase II clinical trials results available, in vivo activity in a particular histology in a tumour model did not closely correlate with activity in the same human cancer histology, casting doubt on the correspondence of the pre-clinical models to clinical results. However, for compounds with in vivo activity in at least one-third of tested xenograft models, there was correlation with ultimate activity in at least some Phase II trials. Thus. an efficient means of predicting activity in vivo models remains desirable for compounds with anti-proliferative activity in vitro. For 564 compounds tested in the hollow fibre assay which were also tested against in vivo tumour models. the likelihood of finding xenograft activity in at least one-third of the in vivo models tested rose with increasing intraperitoneal hollow fibre activity, from 8% for all compounds tested to 20% in agents with evidence of response in more than 6 intraperitoneal fibres (P < 0.0001). Intraperitoneal hollow fibre activity was also found to be a better predictor of xenograft activity than either subcutaneous hollow fibre activity or intraperitoneal plus subcutaneous activity combined. Since hollow fibre activity was a useful indicator of potential in vivo response, correlates with hollow fibre activity were examined for 2304 compounds tested in both the NCI 60 cell line in vitro cancer drug screen and hollow fibre assay. A positive correlation was found for histologic selectivity between in vitro and hollow fibre responses. The most striking correlation was between potency in the 60 cell line screen and hollow fibre activity; 56% of compounds with mean 50% growth inhibition below 10(-75) M were active in more than 6 intraperitoneal fibres whereas only 4% of compounds with a potency of 10(-4) M achieved the same level of hollow fibre activity (P < 0.0001). Structural parameters of the drugs analysed included compound molecular weight and hydrogen-bonding factors, both of which were found to be predictive of hollow fibre activity. (C) 2001 Cancer Research Campaign. C1 NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. SAIC Frederick, Frederick, MD 21701 USA. RP Sausville, EA (reprint author), NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-5600, N01-CM-47000] NR 22 TC 406 Z9 415 U1 0 U2 20 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY 18 PY 2001 VL 84 IS 10 BP 1424 EP 1431 DI 10.1054/bjoc.2001.1796 PG 8 WC Oncology SC Oncology GA 438FK UT WOS:000169042800024 PM 11355958 ER PT J AU Kuhelj, R Rizzo, CJ Chang, CH Jadhav, PK Towler, EM Korant, BD AF Kuhelj, R Rizzo, CJ Chang, CH Jadhav, PK Towler, EM Korant, BD TI Inhibition of human endogenous retrovirus-K10 protease in cell-free and cell-based assays SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS PROTEASE; TIGHT-BINDING INHIBITORS; CYCLIC UREA AMIDES; HIV PROTEASE; HERV-K; MOLECULAR RECOGNITION; TROPHOBLASTIC TUMORS; STRUCTURAL-ANALYSIS; DRUG-RESISTANCE; GERM-CELL AB A full-length and C-terminally truncated version of human endogenous retrovirus (HERV)-K10 protease were expressed in Escherichia coli and purified to homogeneity. Both versions of the protease efficiently processed HERV-K10 Gag polyprotein substrate. HERV-K10 Gag was also cleaved by human immunodeficiency virus, type 1 (HIV-1) protease, although at different sites. To identify compounds that could inhibit protein processing dependent on the HERV-K10 protease, a series of cyclic ureas that had previously been shown to inhibit HIV-1 protease was tested. Several symmetric bisamides acted as very potent inhibitors of both the truncated and full-length form of HERV-K10 protease, in subnanomolar or nanomolar range, respectively. One. of the cyclic ureas, SD146, can inhibit the processing of in vitro translated HERV-K10 Gag polyprotein substrate by HERV-K10 protease. In addition, in virus-like particles isolated from the teratocarcinoma cell line NCCIT, there is significant accumulation of Gag and Gag-Pol precursors upon treatment with SD146, suggesting the compound efficiently blocks HERV-K Gag processing in cells. This is the first report of an inhibitor able to block cell-associated processing of Gag polypeptides of an endogenous retrovirus. C1 Dupont Merck Pharmaceut Co, Dept Virol, Expt Stn E336 22, Wilmington, DE 19880 USA. Dupont Merck Pharmaceut Co, Dept Chem & Phys Sci, Expt Stn E336 22, Wilmington, DE 19880 USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Prot Chem Lab,NIH, Frederick, MD USA. RP Korant, BD (reprint author), Dupont Merck Pharmaceut Co, Dept Virol, Expt Stn E336 22, POB 80336, Wilmington, DE 19880 USA. EM bruce.d.korant@dupontpharma.com NR 48 TC 6 Z9 7 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 18 PY 2001 VL 276 IS 20 BP 16674 EP 16682 DI 10.1074/jbc.M008763200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 432ZG UT WOS:000168730400013 PM 11278433 ER PT J AU Kotamraju, S Hogg, N Joseph, J Keefer, LK Kalyanaraman, B AF Kotamraju, S Hogg, N Joseph, J Keefer, LK Kalyanaraman, B TI Inhibition of oxidized low-density lipoprotein-induced apoptosis in endothelial cells by nitric oxide - Peroxyl radical scavenging as an antiapoptotic mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN ATHEROSCLEROTIC INTIMA; SMOOTH-MUSCLE CELLS; SUPEROXIDE-DISMUTASE; LIPID-PEROXIDATION; IN-VITRO; REACTIVE OXYGEN; OXIDATIVE MODIFICATION; ALPHA-TOCOPHEROL; UP-REGULATION; LDL AB Proatherogenic oxidized low-density lipoprotein (oxLDL) induces endothelial apoptosis, We investigated the anti-apoptotic effects of intracellular and extracellular nitric oxide ((NO)-N-.) donors, iron chelators, cell-permeable superoxide dismutase (SOD), glutathione peroxidase mimetics, and nitrone spin traps. Peroxynitrite (ONOO-)-modified oxLDL induced endothelial apoptosis was measured by DNA fragmentation, TUNEL assay, and caspase-3 activation. Results indicated the following: (i) the lipid fraction of oxLDL was primarily responsible for endothelial apoptosis, (ii) Endothelial apoptosis was potently inhibited by (NO)-N-. donors and lipophilic phenolic antioxidants, OxLDL severely depleted Bcl-2 levels in endothelial cells and (NO)-N-. donors restored Bcl-2 protein in oxLDL-treated cells. (iii) The pretreatment of a lipid fraction derived from oxLDL with sodium borohydride or potassium iodide completely abrogated apoptosis in endothelial cells, suggesting that lipid hydroperoxides induce apoptosis, (iv) Metalloporphyrins dramatically inhibited oxLDL-induced apoptosis in endothelial cells. Neither S-nitrosation of caspase-3 nor induction of Hsp70 appeared to play a significant role in the antiapoptotic mechanism of (NO)-N-. in oxLDL-induced endothelial apoptosis, We propose that cellular lipid peroxyl radicals or lipid hydroperoxides induce an apoptotic signaling cascade in endothelial cells exposed to oxLDL, and that (NO)-N-. inhibits apoptosis by scavenging cellular lipid peroxyl radicals. C1 Med Coll Wisconsin, Biophys Res Inst, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Free Rad Res Ctr, Milwaukee, WI 53226 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Kalyanaraman, B (reprint author), Med Coll Wisconsin, Biophys Res Inst, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCRR NIH HHS [RR01008]; NHLBI NIH HHS [HL47250-09, HL63119] NR 73 TC 55 Z9 57 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 18 PY 2001 VL 276 IS 20 BP 17316 EP 17323 DI 10.1074/jbc.M011731200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 432ZG UT WOS:000168730400096 PM 11278975 ER PT J AU Xiang, Y Moss, B AF Xiang, Y Moss, B TI Determination of the functional epitopes of human interleukin-18-binding protein by site-directed mutagenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA-INDUCING FACTOR; BINDING-PROTEIN; IMMUNOGLOBULIN SUPERFAMILY; IL-18 BINDING; RECEPTOR; POXVIRUS; CLONING; INTERLEUKIN-1-BETA; EXPRESSION; CYTOKINE AB The human interleukin (IL)-18-binding protein (hIL-18BP) is a naturally occurring antagonist of IL-18, a proinflammatory cytokine that is related to IL-1 beta and has an important role in defense against microbial invaders. As its name implies, the hIL-18BP binds to IL-18 with high affinity and prevents the interaction of IL-18 with its receptor. We genetically modified the C terminus of hIL-18BP by appending a 15-amino acid biotinylation recognition site and a six-histidine tag and then performed site-directed mutagenesis to determine the functional epitopes that mediate efficient binding to IL-18. The mutated IL-18BPs were secreted from mammalian cells, captured by metal affinity chromatography, biotinylated in situ, eluted, and immobilized on streptavidin-coated chips. Using surface plasmon resonance, we identified seven amino acids of hIL-18BP which, when changed individually to alanine, caused an 8-750-fold decrease in binding affinity, largely because of increased off-rates. These seven amino acids localized to the predicted P-strand c and d of hIL-18BP immunoglobulin-like domain, and most had hydrophobic side chains. Just two amino acids, tyrosine 97 and phenylalanine 104, contributed similar to 50% of the binding free energy. Information obtained from these studies could contribute to the design of molecular antagonists of IL-18 for treatment of inflammatory diseases. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Drt Dr,MSC 0445, Bethesda, MD 20892 USA. NR 29 TC 30 Z9 31 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 18 PY 2001 VL 276 IS 20 BP 17380 EP 17386 DI 10.1074/jbc.M009581200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 432ZG UT WOS:000168730400105 PM 11278524 ER PT J AU Ten Hagen, KG Bedi, GS Tetaert, D Kingsley, PD Hagen, FK Balys, MM Beres, TM Degand, P Tabak, LA AF Ten Hagen, KG Bedi, GS Tetaert, D Kingsley, PD Hagen, FK Balys, MM Beres, TM Degand, P Tabak, LA TI Cloning and characterization of a ninth member of the UDP-GalNAc : polypeptide N-acetylgalactosaminyltransferase family, ppGaNTase-T9 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACETYL-D-GALACTOSAMINE; ALPHA-D-GALACTOSAMINE; O-LINKED GLYCOSYLATION; CDNA CLONING; TANDEM REPEAT; CHROMOSOMAL LOCALIZATION; MOLECULAR-CLONING; EXPRESSION; MUCIN; SITE AB We have cloned, expressed and characterized the gene encoding a ninth member of the mammalian UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (ppGaNTase) family, termed ppGaNTase-T9. This type II membrane protein consists of a 9-amino acid N-terminal cytoplasmic region, a 20-amino acid hydrophobic/transmembrane region, a 94-amino acid stem region, and a 480-amino acid conserved region. Northern blot analysis revealed that the gene encoding this enzyme is expressed in a broadly distributed manner across many adult tissues. Significant levels of 5- and 4.2-kilobase transcripts were found in rat sublingual gland, testis, small intestine, colon, and ovary, with lesser amounts in heart, brain, spleen, lung, stomach, cervix, and uterus. In situ hybridization to mouse embryos (embryonic day 14.5) revealed significant hybridization in the developing mandible, maxilla, intestine, and mesencephalic ventricle. Constructs expressing this gene transiently in COS7 cells resulted in no detectable transferase activity in vitro against a panel of unmodified peptides, including MUC5AC (GTTPSPVPTTSTTSAP) and E6A2 (PTTDSTTPAPTTK). However, when incubated with MUC5AC and EA2 glycopeptides (obtained by the prior action of ppGaNTase-T1), additional incorporation of GalNAc was achieved, resulting in new hydroxyamino acid modification. The activity of this glycopeptide transferase is distinguished from that of ppGaNTase-T7 in that it forms a tetra-glycopeptide species from the MUC5AC tri-glycopeptide substrate, whereas ppGaNTase-T7 forms a hexa-glycopeptide species. This isoform thus represents the second example of a glycopeptide transferase and is distinct from the previously identified form in enzymatic activity as well as expression in embryonic and adult tissues. These findings lend further support to the existence of a hierarchical network of differential enzymatic activity within the diversely regulated ppGaNTase family, which may play a role in the various processes governing development. C1 Univ Rochester, Aab Inst Biomed Sci, Ctr Oral Biol, Rochester, NY 14627 USA. INSERM, Unite 377, F-59045 Lille, France. RP Tabak, LA (reprint author), NIDCR, NIH, 31 Ctr Dr,MSC 2290,Bldg 31,Rm 2C39, Bethesda, MD 20892 USA. FU NIDCR NIH HHS [DE-08108] NR 39 TC 77 Z9 80 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 18 PY 2001 VL 276 IS 20 BP 17395 EP 17404 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 432ZG UT WOS:000168730400107 PM 11278534 ER PT J AU Fukumoto, S Hsieh, CM Maemura, K Layne, RD Yet, SF Lee, KH Matsui, T Rosenzweig, A Taylor, WG Rubin, JS Perrella, MA Lee, ME AF Fukumoto, S Hsieh, CM Maemura, K Layne, RD Yet, SF Lee, KH Matsui, T Rosenzweig, A Taylor, WG Rubin, JS Perrella, MA Lee, ME TI Akt participation in the Wnt signaling pathway through dishevelled SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3-BETA; BETA-CATENIN STABILITY; PROTEIN-KINASE-B; PC12 CELLS; CYCLIN D1; GENE; ACTIVATION; EXPRESSION; WINGLESS; AXIN AB Inactivation of glycogen synthase kinase 3 beta (GSKS beta) and the resulting stabilization of free beta -catenin are critical steps in the activation of Wnt target genes. While Akt regulates GSK3 alpha/beta in the phosphatidylinositide 3-OH kinase signaling pathway, its role in Wnt signaling is unknown. Here we report that expression of Wnt or Dishevelled (Dvl) increased Akt activity. Activated Akt bound to the Axrin-GSK3 beta complex in the presence of Dvl, phosphorylated GSK3 beta and increased free beta -catenin levels. Furthermore, in Wnt-overexpressing PC12 cells, dominant-negative Akt decreased free beta -catenin and derepressed nerve growth factor-induced differentiation. Therefore, Akt acts in association with Dvl as an important regulator of the Wnt signaling pathway. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. NCI, Cellular & Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Perrella, MA (reprint author), Brigham & Womens Hosp, Dept Med, Div Pulm, 75 Francis St,Thorn Bldg,Rm TH1133, Boston, MA 02115 USA. RI Yet, Shaw-Fang/B-1067-2010; OI Yet, Shaw-Fang/0000-0001-9097-3962 FU NHLBI NIH HHS [HL57977, HL60788]; NIGMS NIH HHS [GM53249] NR 35 TC 213 Z9 220 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 18 PY 2001 VL 276 IS 20 BP 17479 EP 17483 DI 10.1074/jbc.C000880200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 432ZG UT WOS:000168730400119 PM 11278246 ER PT J AU Lumelsky, N Blondel, O Laeng, P Velasco, I Ravin, R McKay, R AF Lumelsky, N Blondel, O Laeng, P Velasco, I Ravin, R McKay, R TI Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets SO SCIENCE LA English DT Article ID IN-VITRO; HUMAN BLASTOCYSTS; MICE; NEURONS; EXPRESSION; LINES; TRANSCRIPTION; CULTURE; PDX-1; GENE AB Although the source of embryonic stem (ES) cells presents ethical concerns, their use may lead to many clinical benefits if differentiated cell types can be derived from them and used to assemble functional organs. in pancreas, insulin is produced and secreted by specialized structures, islets of Langerhans. Diabetes, which affects 16 million people in the United States, results from abnormal function of pancreatic islets. We have generated cells expressing insulin and other pancreatic endocrine hormones from mouse ES cells. The cells self-assemble to form three-dimensional clusters similar in topology to normal pancreatic islets where pancreatic cell types are in close association with neurons. Glucose triggers insulin release from these cell clusters by mechanisms similar to those employed in vivo. When injected into diabetic mice, the insulin-producing cells undergo rapid vascularization and maintain a clustered, islet-like organization. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA. Human Genome Sci, Rockville, MD 20850 USA. Psychiat Genom, Rockville, MD 20852 USA. RP NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM mckay@codon.nih.gov RI Velasco, Ivan/D-3593-2014 OI Velasco, Ivan/0000-0002-8953-6578 NR 39 TC 955 Z9 1100 U1 15 U2 119 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAY 18 PY 2001 VL 292 IS 5520 BP 1389 EP 1394 DI 10.1126/science.1058866 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 435DV UT WOS:000168862900050 PM 11326082 ER PT J AU Evan, GI Vousden, KH AF Evan, GI Vousden, KH TI Proliferation, cell cycle and apoptosis in cancer SO NATURE LA English DT Article ID S-PHASE ENTRY; HUMAN NEUROBLASTOMA-CELLS; MYC-INDUCED APOPTOSIS; GROWTH-FACTOR-ALPHA; C-MYC; TRANSCRIPTION FACTOR; ONCOGENIC RAS; STEM-CELLS; TUMOR-SUPPRESSOR; TRANSGENIC MICE AB Beneath the complexity and idiopathy of every cancer lies a limited number of 'mission critical' events that have propelled the tumour cell and its progeny into uncontrolled expansion and invasion. One of these is deregulated cell proliferation, which, together with the obligate compensatory suppression of apoptosis needed to support it, provides a minimal 'platform' necessary to support further neoplastic progression. Adroit targeting of these critical events should have potent and specific therapeutic consequences. C1 Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. NCI, Frederick, MD 20842 USA. RP Evan, GI (reprint author), Univ Calif San Francisco, Ctr Canc, 2340 Sutter St, San Francisco, CA 94143 USA. NR 89 TC 1630 Z9 1760 U1 29 U2 239 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 17 PY 2001 VL 411 IS 6835 BP 342 EP 348 DI 10.1038/35077213 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432RT UT WOS:000168710000056 PM 11357141 ER PT J AU Liotta, LA Kohn, EC AF Liotta, LA Kohn, EC TI The microenvironment of the tumour-host interface SO NATURE LA English DT Article ID CARCINOMA IN-SITU; APOPTOTIC SIGNALING PATHWAY; GROWTH-FACTOR RECEPTOR; FOCAL ADHESION KINASE; EXTRACELLULAR-MATRIX; CANCER METASTASIS; OVARIAN-CANCER; METALLOPROTEINASE INHIBITION; MALIGNANT KERATINOCYTES; CELL-SURVIVAL AB Throughout the entire process of cancer aetiology, progression and metastasis, the microenvironment of the local host tissue can be an active participant. Invasion occurs within a tumour-host microecology, where stroma and tumour cells exchange enzymes and cytokines that modify the local extracellular matrix, stimulate migration, and promote proliferation and survival. A new class of cancer therapies that targets this pathological communication interface between tumour cells and host cells is currently under development. C1 NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. NR 65 TC 1520 Z9 1610 U1 26 U2 250 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 17 PY 2001 VL 411 IS 6835 BP 375 EP 379 DI 10.1038/35077241 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432RT UT WOS:000168710000060 PM 11357145 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI Progress in human tumour immunology and immunotherapy SO NATURE LA English DT Article ID CYTOLYTIC T-LYMPHOCYTES; RENAL-CELL CARCINOMA; RECOMBINANT INTERLEUKIN-2 THERAPY; HUMAN CARCINOEMBRYONIC ANTIGEN; HIGH-DOSE INTERLEUKIN-2; ACTIVATED KILLER CELLS; HLA-DR MOLECULES; HUMAN-MELANOMA; METASTATIC MELANOMA; INFILTRATING LYMPHOCYTES AB Studies of the administration of interleukin-2 to patients with metastatic melanoma or kidney cancer have shown that immunological manipulations can mediate the durable regression of metastatic cancer. The molecular identification of cancer antigens has opened new possibilities for the development of effective immunotherapies for patients with cancer. Clinical studies using immunization with peptides derived from cancer antigens have shown that high levels of lymphocytes with anti-tumour activity can be raised in cancer-bearing patients. Highly avid anti-tumour lymphocytes can be isolated from immunized patients and grown in vitro for use in cell-transfer therapies. Current studies are aimed at understanding the mechanisms that enable the cancer to escape from immune attack. C1 NCI, Div Clin Sci, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Div Clin Sci, Bldg 10,Room 2B42,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. NR 74 TC 925 Z9 977 U1 16 U2 138 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 17 PY 2001 VL 411 IS 6835 BP 380 EP 384 DI 10.1038/35077246 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432RT UT WOS:000168710000061 PM 11357146 ER PT J AU Nicholas, GM Newton, GL Fahey, RC Bewley, CA AF Nicholas, GM Newton, GL Fahey, RC Bewley, CA TI Novel bromotyrosine alkaloids: Inhibitors of mycothiol S-conjugate amidase SO ORGANIC LETTERS LA English DT Article ID THIOL AB [GRAPHICS] The novel alkaloids 1 and 4 were isolated from an Australian non-verongid sponge, Oceanapia sp, Compound 1 contains an unprecedented imidazolyl-quinolinone substructure attached to a bromotyrosine-derived spiro isoxazoline. Three other known alkaloids were isolated in addition to 1 and 4 and together represent the first examples of inhibitors of a new mycobacterial enzyme mycothiol S-conjugate amidase (MCA). C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. RP Bewley, CA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 13 TC 61 Z9 65 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD MAY 17 PY 2001 VL 3 IS 10 BP 1543 EP 1545 DI 10.1021/ol015845+ PG 3 WC Chemistry, Organic SC Chemistry GA 433AU UT WOS:000168733800033 PM 11388862 ER PT J AU Caffrey, JJ Shears, SB AF Caffrey, JJ Shears, SB TI Genetic rationale for microheterogeneity of human diphosphoinositol polyphosphate phosphohydrolase type 2 SO GENE LA English DT Article DE diphosphoinositol polyphosphate phosphohydrolases; intron/exon; signal transduction; inositol phosphates ID INOSITOL HEXAKISPHOSPHATE; TURNOVER; TETRAKISPHOSPHATE; METABOLISM; PHOSPHATE; KINASE; CELLS AB S elective expression of enzymes that adjust the intensity of turnover of diphosphoinositolpolyphosphates may regulate vesicle trafficking and DNA repair. For example, the type 2 human diphosphoinositolpolyphosphate phosphohydrolases (hDIPP2 alpha and 2 beta) are distinguished by a solitary amino-acid residue; the type 2 beta isoform contains Gln86 whereas the type 2 alpha isoform does not, yet the latter has 2-5 fold more catalytic activity than its beta counterpart (J. Biol.Chem. (2000) 12730). We discovered that both alpha and beta -type mRNAs were co-expressed in clonal cell-lines. We sought a genetic explanation for this microheterogeneity. Two BACs containing distinct, but intronless, hDIPP2 beta genes were cloned. Only one of these genes could potentially give rise to our previously characterized hDIPP2 beta mRNA; the other gene has several sequence differences and, in any case, is likely a processed pseudogene. These BAGS were mapped to 1q12-q21 and 1p12-p13 by FISH. No analogous intronless hDIPP2 alpha gene was detected by analysis of 21 individual genomic DNAs. However, sequence analysis of a third hDIPP2 gene (at 12q21) places the Gln86 CAG codon within an AGCAG pentamer, offering adjacent, alternate intronic 3'-boundaries. Thus, 'intron boundary skidding' by spliceosomes provides a mechanism for yielding both hDIPP2 alpha and hDIPP2 beta mRNAs. Our studies expand the repertoire of molecular mechanisms regulating diphosphoinositolpolyphosphate metabolism and function. Published by Elsevier Science B.V. C1 NIEHS, Inositide Signaling Grp, NIH, Res Triangle Pk, NC 27709 USA. InforMax Inc, Bethesda, MD 20814 USA. RP Shears, SB (reprint author), NIEHS, Inositide Signaling Grp, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 18 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 16 PY 2001 VL 269 IS 1-2 BP 53 EP 60 DI 10.1016/S0378-1119(01)00446-2 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 440AP UT WOS:000169151100006 PM 11376937 ER PT J AU Collins, FS McKusick, VA AF Collins, FS McKusick, VA TI Translation of genomic research into health care - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NHGRI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Hosp, Inst Med Genet, Baltimore, MD 21287 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 16 PY 2001 VL 285 IS 19 BP 2447 EP 2448 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 429ZC UT WOS:000168547600017 ER PT J AU Hediger, ML Overpeck, MD Kuczmarski, RJ Ruan, WJ AF Hediger, ML Overpeck, MD Kuczmarski, RJ Ruan, WJ TI Association between infant breastfeeding and overweight in young children SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; GESTATIONAL-AGE; FEEDING PRACTICES; UNITED-STATES; BIRTH-WEIGHT; OBESITY; GROWTH; BORN; ADIPOSITY AB Context it has been suggested that breastfeeding is protective against children becoming overweight, and that there is a dose-dependent effect of its duration. Objective To determine whether breastfeeding and its duration are associated with a reduced risk of being overweight among young children in the United States. Design and Setting Data on infant feeding and child overweight status were taken from the third National Health and Nutrition Examination Survey (NHANES iii), a cross-sectional health examination survey conducted from 1988-1994. Subjects Sample of 2685 US-born children between the ages of 3 and 5 years, with birth certificates, height and weight measures, and information on infant feeding. Main Outcome Measures A body mass index (BMI) between the 85th and 94th percentile was considered at risk of overweight and a BMI in the 95th percentile or higher was considered being overweight. Results After adjusting for potential confounders, there was a reduced risk of being at risk of overweight for ever breastfed children (adjusted odds ratio [AOR], 0.63; 95% confidence interval [CI], 0.41-0.96) compared with those never breastfed. There was no reduced risk of being overweight (AOR, 0.84; 95% CI, 0.62-1.13), There was no clear dose-dependent effect of the duration of full breastfeeding on being at risk of overweight or overweight and no threshold effect. The strongest predictor of child overweight status was the mother's concurrent weight. The rate of children being overweight nearly tripled with maternal overweight status (BMI, 25.0-29.9 kg/m(2); AOR, 2.95; 95% CI, 1.35-6.42) and more than quadrupled with maternal obesity status (BMI greater than or equal to 30.0 kg/m(2); AOR, 4.34; 95% CI, 2.50-7.54). Conclusions There are inconsistent associations among breastfeeding, its duration, and the risk of being overweight in young children, Breastfeeding continues to be strongly recommended, but may not be as effective as moderating familial factors, such as dietary habits and physical activity, in preventing children from becoming overweight. C1 NICHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. US Hlth Resources & Serv Adm, Maternal & Child Hlth Bur, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Div Hlth Examinat Stat, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Hediger, ML (reprint author), NICHD, Div Epidemiol Stat & Prevent Res, NIH, Bldg 6100,Room 7B03,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 38 TC 213 Z9 225 U1 1 U2 5 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 MAY 16 PY 2001 VL 285 IS 19 BP 2453 EP 2460 DI 10.1001/jama.285.19.2453 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 429ZC UT WOS:000168547600026 PM 11368697 ER PT J AU Cleeman, JI Grundy, SM Becker, D Clark, LT Cooper, RS Denke, MA Howard, WJ Hunninghake, DB Illingworth, DR Luepker, RV McBride, P McKenney, JM Pasternak, RC Stone, NJ Van Horn, L Brewer, HB Ernst, ND Gordon, D Levy, D Rifkind, B Rossouw, JE Savage, P Haffner, SM Orloff, DG Proschan, MA Schwartz, JS Sempos, CT Shero, ST Murray, EZ AF Cleeman, JI Grundy, SM Becker, D Clark, LT Cooper, RS Denke, MA Howard, WJ Hunninghake, DB Illingworth, DR Luepker, RV McBride, P McKenney, JM Pasternak, RC Stone, NJ Van Horn, L Brewer, HB Ernst, ND Gordon, D Levy, D Rifkind, B Rossouw, JE Savage, P Haffner, SM Orloff, DG Proschan, MA Schwartz, JS Sempos, CT Shero, ST Murray, EZ CA Natl Cholesterol Educ Program Expe TI Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 NHLBI, Natl Cholesterol Educ Program, Bethesda, MD 20892 USA. RP Cleeman, JI (reprint author), NHLBI, Natl Cholesterol Educ Program, 31 Ctr Dr,Room 4A16,MSC 2480, Bethesda, MD 20892 USA. NR 0 TC 12928 Z9 13557 U1 59 U2 707 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 MAY 16 PY 2001 VL 285 IS 19 BP 2486 EP 2497 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 429ZC UT WOS:000168547600031 ER PT J AU Laden, F Collman, G Iwamoto, K Alberg, AJ Berkowitz, GS Freudenheim, JL Hankinson, SE Helzlsouer, KJ Holford, TR Huang, HY Moysich, KB Tessari, JD Wolff, MS Zheng, TZ Hunter, DJ AF Laden, F Collman, G Iwamoto, K Alberg, AJ Berkowitz, GS Freudenheim, JL Hankinson, SE Helzlsouer, KJ Holford, TR Huang, HY Moysich, KB Tessari, JD Wolff, MS Zheng, TZ Hunter, DJ TI 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and polychlorinated biphenyls and breast cancer: Combined analysis of five US studies SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ADIPOSE-TISSUE CONCENTRATIONS; ORGANOCHLORINE EXPOSURE; BLOOD-LEVELS; SERUM ORGANOCHLORINES; RISK; WOMEN; DDE; PESTICIDES; LACTATION; RESIDUES AB Background: Environmental exposure to organochlorines has been examined as a potential risk factor for breast cancer, in 1993, five large U.S. studies of women located mainly in the northeastern United States were funded to evaluate the association of levels of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and polychlorinated biphenyls (PCBs) in blood plasma or serum with breast cancer risk. We present a combined analysis of these results to increase precision and to maximize statistical power to detect effect modification by other breast cancer risk factors, Methods: We reanalyzed the data from these five studies, consisting of 1400 case patients with breast cancer and 1642 control subjects, by use of a standardized approach to control for confounding and assess effect modification. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) by use of the random-effects model. All statistical tests were two-sided, Results: When we compared women in the fifth quintile of lipid-adjusted values with those in the first quintile, the multivariate pooled OR for breast cancer associated with PCBs was 0.94 (95% CI = 0.73 to 1.21), and that associated with DDE was 0.99 (95% CI = 0.77 to 1.27). Although in the original studies there were suggestions of elevated breast cancer risk associated with PCBs in certain groups of women stratified by parity and lactation, these observations were not evident in the pooled analysis. No statistically significant associations were observed in any other stratified analyses, except for an increased risk with higher levels of PCBs among women in the middle tertile of body mass index (25-29.9 kg/m(2)); however, the risk was statistically nonsignificantly decreased among heavier women. Conclusions: Combined evidence does not support an association of breast cancer risk with plasma/serum concentrations of PCBs or DDE. Exposure to these compounds, as measured in adult women, is unlikely to explain the high rates of breast cancer experienced in the northeastern United States. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Mt Sinai Med Ctr, Div Environm & Occupat Med, New York, NY 10029 USA. SUNY Buffalo, Sch Med & Biomed Sci, Dept Social & Prevent Med, Buffalo, NY 14260 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Yale Univ, Sch Med, New Haven, CT USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Colorado State Univ, Dept Environm Hlth, Ft Collins, CO 80523 USA. Harvard Univ, Sch Publ Hlth, Ctr Canc Prevent, Cambridge, MA 02138 USA. RP Laden, F (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CAES62951, CA/ES62988, CA/ES62995, CA40356, CA49449, CAES62984, CAES62986, U10CA11535]; NHLBI NIH HHS [T32HL07427] NR 49 TC 102 Z9 104 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 16 PY 2001 VL 93 IS 10 BP 768 EP 776 DI 10.1093/jnci/93.10.768 PG 9 WC Oncology SC Oncology GA 432TF UT WOS:000168711200011 PM 11353787 ER PT J AU Hsing, AW Chua, S Gao, YT Gentzschein, E Chang, L Deng, J Stanczyk, FZ AF Hsing, AW Chua, S Gao, YT Gentzschein, E Chang, L Deng, J Stanczyk, FZ TI Prostate cancer risk and serum levels of insulin and leptin: a population-based study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BODY-FAT DISTRIBUTION; GROWTH-FACTOR-I; IMPAIRED GLUCOSE-TOLERANCE; HORMONE-BINDING GLOBULIN; DIABETES-MELLITUS; PLASMA LEPTIN; UNITED-STATES; SENSITIVITY; MEN; PREVALENCE AB Background: In a previous study of Chinese men, we found that men with a higher waist-to-hip ratio (WHR) have a higher prostate cancer risk. Because leptin and insulin are related to body fat distribution, we examined whether leptin and insulin were associated with prostate cancer risk. Methods: Blood samples were collected from 128 case patients with incident prostate cancer and from 306 healthy control subjects randomly selected from residents of Shanghai, China. Epidemiologic information and anthropometric measurements were collected in personal interviews. Serum leptin, insulin, and sex hormone levels were measured by radioimmunoassay, and insulin-like growth factor-I (IGF-I) was measured by enzyme-linked immunosorbent assay. Multiple logistic regression analyses were used to estimate odds ratios for prostate cancer in relation to serum insulin and leptin levels. All statistical tests were two-sided, Results: After adjustment for body mass index, WHR, IGF-I, and sex hormone levels, higher serum insulin levels were associated with a statistically significantly elevated risk of prostate cancer (P < .001). Men in the highest tertile of insulin levels had a 2.56-fold (95% confidence interval [CI] = 1.38 to 4.75) risk of prostate cancer compared with men in the lowest tertile. Regardless of the tertile level of WHR, higher serum insulin levels were associated with an increased risk of prostate cancer: Men in the highest tertiles of WHR (>0.900) and insulin (>8.83 rhoU/mL) had 8.55 times (95% CI = 2.80 to 26.10) the prostate cancer risk of men in the lowest tertiles of both, and those in the lowest tertile of WHR (<0.873) and highest tertile of insulin had 4.30 times (95% CI = 1.17 to 15.70) the risk. By contrast, the association between leptin levels and prostate cancer risk was not statistically significant. Conclusion: Our results suggest that serum insulin levels may influence the risk of prostate cancer in Chinese men. Further research, especially prospective studies, is needed to confirm these findings in high-risk populations and to clarify the underlying mechanisms involved. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. Columbia Univ, Dept Pediat, Div Mol Genet, New York, NY 10027 USA. Shanghai Canc Inst, Shanghai, Peoples R China. Univ So Calif, Sch Med, Dept Obstet & Gynecol & Prevent Med, Los Angeles, CA USA. RP Hsing, AW (reprint author), NIH, EPS-MSC 7234,6120 Execut Blvd, Bethesda, MD 20892 USA. NR 58 TC 200 Z9 204 U1 1 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 16 PY 2001 VL 93 IS 10 BP 783 EP 789 DI 10.1093/jnci/93.10.783 PG 7 WC Oncology SC Oncology GA 432TF UT WOS:000168711200013 PM 11353789 ER PT J AU Schatzkin, A Flood, A AF Schatzkin, A Flood, A TI Diet and cancer prevention - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID COLORECTAL-CANCER; COLON C1 NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. RP Schatzkin, A (reprint author), NIH, Execut Plaza N,6130 Execut Blvd,Rm 211, Rockville, MD 20852 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 16 PY 2001 VL 93 IS 10 BP 791 EP 792 PG 2 WC Oncology SC Oncology GA 432TF UT WOS:000168711200016 ER PT J AU Djousse, L Levy, D Cupples, LA Evans, JC D'Agostino, RB Ellison, RC AF Djousse, L Levy, D Cupples, LA Evans, JC D'Agostino, RB Ellison, RC TI Total serum bilirubin and risk of cardiovascular disease in the Framingham Offspring Study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY HEART-DISEASE; LOW-DENSITY-LIPOPROTEIN; ARTERY DISEASE; BILE-PIGMENTS; ANTIOXIDANT; ALBUMIN; BILIVERDIN; DAMAGE AB The association between bilirubin and cardiovascular disease is controversial. In a prospective study of 4.276 subjects, we demonstrated that a higher concentration of serum bilirubin was associated with lower risk of myocardial infarction and cardiovascular disease in men, but the pattern was not clear in women. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat & Epidemiol, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02118 USA. RP Djousse, L (reprint author), Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Dept Med, Room B-612,715 Albany St, Boston, MA 02118 USA. RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU NHLBI NIH HHS [N01-HC-38038] NR 19 TC 156 Z9 166 U1 4 U2 13 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 MAY 15 PY 2001 VL 87 IS 10 BP 1196 EP + DI 10.1016/S0002-9149(01)01494-1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 431BB UT WOS:000168611100013 PM 11356398 ER PT J AU England, LJ Kendrick, JS Gargiullo, PM Zahniser, SC Hannon, WH AF England, LJ Kendrick, JS Gargiullo, PM Zahniser, SC Hannon, WH TI Measures of maternal tobacco exposure and infant birth weight at term SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE birth weight; cotinine; pregnancy; smoking; tobacco ID SERUM COTININE LEVELS; CIGARETTE-SMOKING; PREGNANCY; NICOTINE; FETAL; SMOKERS; GROWTH; HUMANS; URINE; AGE AB This study was undertaken to determine the relation between self-reported number of cigarettes smoked per day and urine cotinine concentration during pregnancy and to examine the relations between these two measures of tobacco exposure and birth weight. Data were obtained from the Smoking Cessation in Pregnancy project, conducted between 1987 and 1991. Cigarette smoking information and urine cotinine concentration were collected for 3,395 self-reported smokers who were receiving prenatal care at public clinics in three US states (Colorado, Maryland, and Missouri) and who delivered term infants. General linear models were used to quantify urine cotinine variability explained by the number of cigarettes smoked per day and to generate mean adjusted birth weights for women with different levels of tobacco exposure. Self-reported number of cigarettes smoked per day explained only 13.9% of the variability in urine cotinine concentration. Birth weight declined as tobacco exposure increased; however, the relation was not linear. The sharpest declines in birth weight occurred at low levels of exposure. Furthermore, urine cotinine concentration did not explain more variability in birth weight than did number of cigarettes smoked. These findings should be considered by researchers studying the effects of smoking reduction on birth outcomes. C1 CDCP, Epidemiol Program Off, Div Appl Publ Hlth Training, Epidem Intelligence Serv, Atlanta, GA USA. CDCP, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, Pregnancy & Infant Hlth Branch, Atlanta, GA USA. CDCP, Natl Immunizat Program, Childhood Vaccine Preventable Dis Branch, Epidemiol & Surveillance Div, Atlanta, GA USA. CDCP, Natl Ctr Environm Hlth, Div Sci Lab, Clin Biochem Branch, Atlanta, GA USA. RP England, LJ (reprint author), NICHHD, 6100 Execut Blvd,Room 7B03,MSC 7510, Bethesda, MD 20892 USA. NR 28 TC 77 Z9 79 U1 2 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 MAY 15 PY 2001 VL 153 IS 10 BP 954 EP 960 DI 10.1093/aje/153.10.954 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 431AR UT WOS:000168610200006 PM 11384951 ER PT J AU Wu, JW Davis, MD Owens, RA AF Wu, JW Davis, MD Owens, RA TI A rep recognition sequence is necessary but not sufficient for nicking of DNA by adeno-associated virus type-2 rep proteins SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE adeno-associated virus; Rep78; endonuclease; nicking; site-specific integration ID SITE-SPECIFIC INTEGRATION; ADENOASSOCIATED VIRUS; MUTATIONAL ANALYSIS; TERMINAL REPEATS; GROWTH-FACTOR; HUMAN-CELLS; IN-VITRO; BIOCHEMICAL-CHARACTERIZATION; TARGETED INTEGRATION; MOLECULAR-CLONING AB The strand-specific, site-specific endonuclease (nicking) activity of the Rep68 and Rep78 (Rep68/78) proteins of adeno-associated virus type 2 (AAV) is involved in AAV replication, and appears to be involved in AAV site-specific integration. Rep68/78 cuts within the inverted terminal repeats (ITRs) of the AAV genome and in the AAV preferred integration locus on human chromosome 19 (AAVS1). The known endonuclease cut sites are 11-16 bases away from the primary binding sites, known as Rep recognition sequences (RRSs). A linear, double-stranded segment of DNA, containing an RRS and a cut site, has previously been shown to function as a substrate for the Rep68/78 endonuclease activity. We show here that mutation of the Rep recognition sequence, within such a DNA segment derived from the AAV ITRs, eliminates the ability of this substrate to be cleaved detectably by Rep78. Rep78 nicks the RRS-containing site from AAVS1 about half as well as the linear ITR sequence. Eighteen other RRS-containing sequences found in the human genome, but outside AAVS1, are not cleaved by Rep78. These results may help to explain the specificity of AAV integration. (C) 2001 Academic Press. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Davis, MD (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, Bldg 8,Room 310,8 Ctr Dr,MSC 0840, Bethesda, MD 20892 USA. NR 72 TC 10 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 15 PY 2001 VL 389 IS 2 BP 271 EP 277 DI 10.1006/abbi.2001.2348 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 436AH UT WOS:000168914000015 PM 11339817 ER PT J AU Sakata, K Yamashita, T Maeda, M Moriyama, Y Shimada, S Tohyama, M AF Sakata, K Yamashita, T Maeda, M Moriyama, Y Shimada, S Tohyama, M TI Cloning of a lymphatic peptide/histidine transporter SO BIOCHEMICAL JOURNAL LA English DT Article DE cellular localization; lysosome; macrophage; molecular cloning; subcellular localization ID CARBOXYL CYTOPLASMIC TAIL; PROTEIN LIMP-II; OLIGOPEPTIDE TRANSPORTER; H+/PEPTIDE COTRANSPORTER; CHROMOSOME 11Q12-Q13.1; PEPTIDE TRANSPORTER; EXPRESSION; LYSOSOMES; ARABIDOPSIS; REGION AB Although peptide transport across the plasma membrane has been characterized well in the kidney and the intestine, the functional relevance of this transport in other organs has not been addressed. Here we report the cloning of a cDNA for a novel peptide/histidine transporter found in the rat (rPHT2), whose mRNA is expressed mainly in the lymphatic system. rPHT2 encodes a protein of 582 amino acids and showed 49% identity with the brain PHT (PHT1) [Yamashita, Shimada, Guo, Sate, Kohmura, Hayakawa, Takagi and Tohyama (1997) J. Biol, Chem. 272, 10205-10211]. rPHT2 mRNA was abundant in lung, spleen and thymus, and detected faintly in brain, liver, adrenal gland and heart by Northern-blot analysis and reverse transcriptase PCR (RT-PCR). Intense signals for the gene were found in immunocytes using in situ hybridization. Ectopic expression of rPHT2 protein in HEK-293T cells and BHK cells was nor found on the cell surface, but was found on the lysosomal membrane using light- and electron-microscopic analysis, Recombinant rPHT2 protein reconstituted into liposomes showed proton-dependent transport activity with histidine and histidyl-leucine, These findings suggest that rPHT2 is involved in the protein catabolic pathway in the lymphatic system. C1 Osaka Univ, Grad Sch Med, Dept Anat & Neurosci, Osaka 5650871, Japan. Core Res Evolut Sci & Technol, Kawagutchi 3320012, Japan. Max Planck Inst Neurobiol, Dept Neurobiochem, D-82152 Martinsried, Germany. Osaka City Univ, Sch Med, Dept Anat 1, Abeno Ku, Osaka 5458585, Japan. Okayama Univ, Fac Pharmaceut Sci, Dept Biochem, Okayama 7008530, Japan. Nagoya City Univ, Sch Med, Dept Anat 2, Mizuho Ku, Nagoya, Aichi 4670001, Japan. RP Sakata, K (reprint author), NICHD, Unit Synapse Dev & Plast, LCSN, Bldg 49,Rm 6A67,49 Convent Dr,MSC 4480, Bethesda, MD 20892 USA. NR 38 TC 71 Z9 74 U1 0 U2 6 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 15 PY 2001 VL 356 BP 53 EP 60 DI 10.1042/0264-6021:3560053 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 438LX UT WOS:000169056200006 PM 11336635 ER PT J AU Aghaiypour, K Wlodawer, A Lubkowski, J AF Aghaiypour, K Wlodawer, A Lubkowski, J TI Structural basis for the activity and substrate specificity of Erwinia chrysanthemi L-asparaginase SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI ASPARAGINASE; 7A GLUTAMINASE-ASPARAGINASE; CRYSTAL-STRUCTURE; SUCCINOGENES; CATALYSIS; LEUKEMIA; SITE AB Bacterial L-asparaginases, enzymes that catalyze the hydrolysis of L-asparagine to aspartic acid, have been used for over 30 years as therapeutic agents in the treatment of acute childhood lymphoblastic leukemia. Other substrates of asparaginases include L-glutamine, D-asparagine. and succinic acid monoamide. In this report, we present high-resolution crystal structures of the complexes of Erwinia chrysanthemi L-asparaginase (ErA) with the products of such reactions that also can serve as substrates, namely L-glutamic acid (L-Glu), D-aspartic acid (D-Asp), and succinic acid (Suc). Comparison of the four independent active sites within each complex indicates unique and specific binding of the ligand molecules; the mode of binding is also similar between complexes. The lack of the alpha -NH3+ group in Sue, compared to L-Asp, does not affect the binding mode. The side chain of L-Glu, larger than chat of L-Asp, causes several structural distortions in the ErA active side. The active site flexible loop (residues 15-33) does not exhibit stable conformation, resulting in suboptimal orientation of the nucleophile, Thr15. Additionally, the delta -COO- plane of L-Glu is approximately perpendicular to the plane of gamma -COO- in L-Asp bound to the asparaginase active site. Binding of D-Asp to the ErA active site is very distinctive compared to the other ligands, suggesting that the low activity of ErA against D-Asp could be mainly attributed to the low k(cat) value. A comparison of the amino acid sequence and the crystal structure of ErA with those of other bacterial L-asparaginases shows that the presence of two active-site residues, Glu63(ErA) and Ser254(ErA), may correlate with significant glutaminase activity, while their substitution by Gin and Asn, respectively, may lead to minimal L-glutaminase activity. C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Lubkowski, J (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. NR 46 TC 79 Z9 86 U1 0 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 15 PY 2001 VL 40 IS 19 BP 5655 EP 5664 DI 10.1021/bi0029595 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 431MV UT WOS:000168635900009 PM 11341830 ER PT J AU Sen, A Chen, YD Yan, B Chalovich, JM AF Sen, A Chen, YD Yan, B Chalovich, JM TI Caldesmon reduces the apparent rate of binding of myosin S1 to actin-tropomyosin SO BIOCHEMISTRY LA English DT Article ID SMOOTH-MUSCLE CALDESMON; ACTOMYOSIN SUBFRAGMENT-1 ATPASE; HEAVY-MEROMYOSIN; SKELETAL-MUSCLE; F-ACTIN; TROPONIN-TROPOMYOSIN; COOPERATIVE BINDING; THIN FILAMENT; STEADY-STATE; INHIBITION AB Equilibrium measurements of the rate of binding of caldesmon and myosin S1 to actin-tropomyosin from different laboratories have yielded different results and have led to different models of caldesmon function. An alternate approach to answering these questions is to study the kinetics of binding of both caldesmon and S1 to actin. We observed that caldesmon decreased the rate of binding of S1 to actin in a concentration-dependent manner. The inhibition of the rate of S1 binding was enhanced by tropomyosin, but the effect of tropomyosin on the binding was small. Premixing actin with S1 reduced the amplitude (extent) of caldesmon binding in proportion to the fraction of actin that contained bound S1, but the rate of binding of caldesmon to free sites was not greatly altered. No evidence for a stable caldesmon-actin-tropomyosin-S1 complex was observed, although S1 did apparently bind to gaps between caldesmon molecules. These results indicate that experiments involving caldesmon, actin, tropomyosin, and myosin are inherently complex. When the concentration of either S1 or caldesmon is varied, the amount of the other component bound to actin-tropomyosin cannot be assumed to remain fixed. The results are not readily explained by a mechanism in which caldesmon acts only by stabilizing an inactive state of actin-tropomyosin. The results support regulatory mechanisms that involve changes in the actin-S1 interaction. C1 E Carolina Univ, Brody Sch Med, Dept Biochem, Greenville, NC 27858 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Chalovich, JM (reprint author), E Carolina Univ, Brody Sch Med, Dept Biochem, Greenville, NC 27858 USA. OI Chalovich, Joseph/0000-0002-1243-4055 FU NIAMS NIH HHS [AR35216] NR 46 TC 16 Z9 17 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 15 PY 2001 VL 40 IS 19 BP 5757 EP 5764 DI 10.1021/bi002724t PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 431MV UT WOS:000168635900020 PM 11341841 ER PT J AU Li, BQ Wetzel, MA Mikovits, JA Henderson, EE Rogers, TJ Gong, WH Li, YY Ruscetti, FW Wang, JM AF Li, BQ Wetzel, MA Mikovits, JA Henderson, EE Rogers, TJ Gong, WH Li, YY Ruscetti, FW Wang, JM TI The synthetic peptide WKYMVm attenuates the function of the chemokine receptors CCR5 and CXCR4 through activation of formyl peptide receptor-like 1 SO BLOOD LA English DT Article ID LIPOXIN A(4) RECEPTOR; SERUM AMYLOID-A; HUMAN MONOCYTES; STABLE ANALOGS; DESENSITIZATION; CELLS; 7-TRANSMEMBRANE; IDENTIFICATION; MOBILIZATION; BLOCKS AB The G protein-coupled 7 transmembrane (STM) chemoattractant receptors can be inactivated by heterologous desensitization. Earlier work showed that formly peptide receptor-like 1 (FPRL1), an STM receptor with low affinity for the bacterial chemotactic, peptide formyl-methionyl-leucyl-phenylalamine (fMLF), is activated by peptide domains derived from the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp120 and its activation results in desensitization and downregulation of the chemokine receptors CCR5 and CXCR4 from monocyte surfaces. This study Investigated the possibility of interfering with the function of CCR5 or CXCR4 as HIV-1 coreceptors by activating FPRL1. Cell lines were established expressing FPRL1 in combination with CD4/CXCR4 or CD4/CCR5 and the effect of a synthetic peptide, WKYMVm, a potent activator of formyl peptide receptors with preference for FPRL1 was determined. Both CXCR4 and CCR5 were desensitized by activation of the cells with WKYMVm via a staurosporine-sensitive pathway. This desensitization of CXCR4 and CCR5 also attenuated their capacity as the fusion cofactors for HIV-1 envelope glycoprotein and resulted in a significant inhibition of p24 production by cell lines infected with HIV-1 that use CCR5 or CXCR4 as coreceptors. Furthermore, WKYMVm inhibited the infection of human peripheral monocyte-derived macrophages and CD4(+) T lymphocytes by R5 or X4 strains of HIV-1, respectively. These results indicate that heterologous desensitization of CCR5 and CXCR4 by an FPRL1 agonist attenuates their major biologic functions and suggest an approach to the development of additional anti-HIV-1 agents. (Blood. 2001;97:2941-2947) (C) 2001 by The American Society of Hematology. C1 NCI, LMI, DBS, FCRDC, Frederick, MD 21702 USA. SAIC Frederick, Immunogenet Mol Lab, Intramural Res Support Program, Frederick, MD USA. SAIC Frederick, Immunogenet Mol Lab, Lab Antiviral Drug Mechanism, NCI Screening Technol Branch, Frederick, MD USA. Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19122 USA. RP Wang, JM (reprint author), NCI, LMI, DBS, FCRDC, Bldg 560,Rm 31-40, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000]; NIDA NIH HHS [DA05894, DA06650, DA11130, DA12113, T32DA07237] NR 26 TC 43 Z9 43 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 MAY 15 PY 2001 VL 97 IS 10 BP 2941 EP 2947 DI 10.1182/blood.V97.10.2941 PG 7 WC Hematology SC Hematology GA 460HC UT WOS:000170301300003 PM 11342415 ER PT J AU Fry, TJ Connick, E Falloon, J Lederman, MM Liewehr, DJ Spritzler, J Steinberg, SM Wood, LV Yarchoan, R Zuckerman, J Landay, A Mackall, CL AF Fry, TJ Connick, E Falloon, J Lederman, MM Liewehr, DJ Spritzler, J Steinberg, SM Wood, LV Yarchoan, R Zuckerman, J Landay, A Mackall, CL TI A potential role for interleukin-7 in T-cell homeostasis SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; INTENSIVE CHEMOTHERAPY; DENDRITIC CELLS; TRANSGENIC MICE; HIV-INFECTION; ANTIRETROVIRAL THERAPY; LYMPHOCYTE SUBSETS; IN-VIVO; C-MPL; IL-7 AB Interleukin (IL)-7 is known to up-regulate thymopoietic pathways of T-cell regeneration. Recent work also has shown it to potently enhance thymic-independent peripheral expansion and to restore immunocompetence in athymic T-cell-depleted hosts, We hypothesized that endogenous IL-7 could contribute to the restoration of T-cell homeostasis following T-cell depletion. To analyze this, we evaluated circulating IL-7 levels and lymphocyte subsets in multiple clinical cohorts with T-cell depletion of varying etiologies. In pediatric (n = 41) and adult (n = 51) human immunodeficiency virus-infected CD4- depleted patients, there were strong inverse correlations between IL-7 levels and CD4 counts (r = -0.77, P<.0001, and r = -0.68, P<.0001). Declines in IL-7 were temporally correlated with recovery of CD4 counts. Similar patterns were observed in CD4-depleted patients receiving cancer chemotherapy (r = -0.65, P =.009). Therefore, in 2 disparate clinical scenarios involving CD4 depletion, IL-7 levels dynamically respond to changes in CD4 T-cell number, making this cytokine uniquely suited as a candidate regulator of T-cell homeostasis. Furthermore, in patients with idiopathic CD4 lymphopenia, a much weaker relationship between IL-7 levels and peripheral blood CD4 counts was observed, suggesting that an impaired IL-7 response to CD4 depletion may contribute to the impaired lymphocyte homeostasis observed in this population. In light of the known effects of IL-7 on T-cell regeneration, we postulate that increased availability of IL-7 could play a critical role in restoring T-cell homeostasis following T-cell depletion. (Blood. 2001;97:2983-2990) (C) by The American Society of Hematology. C1 NCI, Pediat Oncol Branch, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Rush Med Coll, Chicago, IL 60612 USA. RP Fry, TJ (reprint author), Bldg 10,Rm 13N240,MSC 1982,10 Center Dr, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA-46934]; NCRR NIH HHS [RR-00051]; NIAID NIH HHS [AI-25879, AI-25915, AI-32770, AI-38855, AI-44748]; PHS HHS [R-0080] NR 66 TC 290 Z9 294 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 MAY 15 PY 2001 VL 97 IS 10 BP 2983 EP 2990 DI 10.1182/blood.V97.10.2983 PG 8 WC Hematology SC Hematology GA 460HC UT WOS:000170301300009 PM 11342421 ER PT J AU Koh, CY Blazar, BR George, T Welniak, LA Capitini, CM Raziuddin, A Murphy, WJ Bennett, M AF Koh, CY Blazar, BR George, T Welniak, LA Capitini, CM Raziuddin, A Murphy, WJ Bennett, M TI Augmentation of antitumor effects by NK cell inhibitory receptor blockade in vitro and in vivo SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I EXPRESSION; IMMUNE-RESPONSE; DOWN-REGULATION; RECOGNITION; CYTOTOXICITY; RESISTANCE; CARCINOMA; MOLECULES AB Subsets of natural killer (NK) cells are characterized by the expression of inhibitory and/or stimulatory receptors specific for major histocompatibility complex (MHC) class I determinants. In mice, these include the Ly49 family of molecules. One mechanism by which tumor cells may evade NK cell killing is by expressing the appropriate MHC class I and binding inhibitory Ly49 receptors. Therefore, the question of whether blocking the interaction between the Ly49 inhibitory receptors on NK and MHC class I cells on tumor cells augments antitumor activity was investigated. Blockade of Ly49C and I inhibitory receptors using F(ab')(2) fragments of the 5E6 monoclonal antibody (mAb) resulted in increased cytotoxicity against syngeneic tumors and decreased tumor cell growth in vitro. The effect of 5E6 F(ab)(2) was specific for the MHC of the tumor, as the use of F(ab')(2) of the mAb against Ly49G2 failed to increase NK activity. Treatment of leukemia-bearing mice with 5E6 F(ab')(2) fragments or adoptive transfer of NK cells treated ex vivo with the F(ab')(2) resulted in significant increases in survival. These results demonstrate that blockade of NK inhibitory receptors enhances antitumor activity both in vitro and in vivo, suggesting that NK inhibitory receptors can be responsible for diminishing antitumor responses. Therefore, strategies to block inhibitory receptors may be of potential use in increasing the efficacy of immunotherapy. (Blood. 2001;97:3132-3137) (C) 2001 by The American Society of Hematology. C1 NCI, Lab Leukocyte Biol, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Univ Minnesota, Ctr Canc, Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX USA. RP Murphy, WJ (reprint author), SAIC Frederick, Intramural Res Support Program, Bldg 567,Rm 210, Ft Detrick, MD 21702 USA. RI Koh, Crystal/D-9986-2013; OI Capitini, Christian/0000-0002-2276-6731 FU NCI NIH HHS [CA 70134, N01-CO-56000, R01 CA 72669] NR 29 TC 112 Z9 116 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 MAY 15 PY 2001 VL 97 IS 10 BP 3132 EP 3137 DI 10.1182/blood.V97.10.3132 PG 6 WC Hematology SC Hematology GA 460HC UT WOS:000170301300028 PM 11342440 ER PT J AU Lopatin, U Yao, X Williams, RK Bleesing, JJH Dale, JK Wong, D Teruya-Feldstein, J Fritz, S Morrow, MR Fuss, I Sneller, MC Raffeld, M Fleisher, TA Puck, JM Strober, W Jaffe, ES Straus, SE AF Lopatin, U Yao, X Williams, RK Bleesing, JJH Dale, JK Wong, D Teruya-Feldstein, J Fritz, S Morrow, MR Fuss, I Sneller, MC Raffeld, M Fleisher, TA Puck, JM Strober, W Jaffe, ES Straus, SE TI Increases in circulating and lymphoid tissue interleukin-10 in autoimmune lymphoproliferative syndrome are associated with disease expression SO BLOOD LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; FAS GENE-MUTATIONS; CANALE-SMITH SYNDROME; APOPTOTIC CELL-DEATH; T-CELLS; RHEUMATOID-ARTHRITIS; PEDIATRIC-PATIENTS; BCL-2 PROTEIN; B-CELLS; IL-10 AB Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which genetic defects in proteins that mediate lymphocyte apoptosis, most often Fas, are associated with enlargement of lymph nodes and the spleen and a variety of autoimmune manifestations. Some patients with ALPS have relatives with these same apoptotic defects, however, who are clinically well. This study showed that the circulating levels of interleukin 10 (IL-10) were significantly higher (P < .001) in 21 patients with ALPS than in healthy controls. Moreover, the peripheral blood mononuclear cells (PBMCs) and lymphoid tissues of these patients with ALPS contained significantly higher levels of IL-10 messenger RNA (mRNA; P < .001 and P < .01, respectively). By fractionating PBMC populations, disproportionately high concentrations of IL-10 mRNA were found in the CD4(-)CD8(-) T-cell population, expansion of which is virtually pathognomonic for ALPS. Immunohistochemical staining showed intense IL-10 protein signals in lymph node regions known to contain CD4(-)CD8(-) T cells. Nonetheless, in vitro studies showed no influence of IL-10 on the survival of CD4(-)CD8(-) T cells. Overexpression of IL-10 in patients with inherited apoptotic defects is strongly associated with the overt manifestations of ALPS. (Blood. 2001;97:3161-3170) (C) 2001 by The American Society of Hematology. C1 NIAID, Clin Invest Lab, Clin Res Training Program, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Warren G Magnuson Clin Ctr, Bethesda, MD USA. SAIC Inc, Frederick, MD USA. RP Straus, SE (reprint author), NIAID, Clin Invest Lab, Clin Res Training Program, NIH, 10 Ctr Dr,Rm 10-11N228, Bethesda, MD 20892 USA. NR 42 TC 68 Z9 70 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 MAY 15 PY 2001 VL 97 IS 10 BP 3161 EP 3170 DI 10.1182/blood.V97.10.3161 PG 10 WC Hematology SC Hematology GA 460HC UT WOS:000170301300032 PM 11342444 ER PT J AU Davis, DA Rinderknecht, AS Zoeteweij, JP Aoki, Y Read-Connole, EL Tosato, G Blauvelt, A Yarchoan, R AF Davis, DA Rinderknecht, AS Zoeteweij, JP Aoki, Y Read-Connole, EL Tosato, G Blauvelt, A Yarchoan, R TI Hypoxia induces lytic replication of Kaposi sarcoma-associated herpesvirus SO BLOOD LA English DT Article ID DNA-SEQUENCES; PERMEABILITY FACTOR; INDUCIBLE FACTOR-1; ENDEMIC AFRICAN; GENE-EXPRESSION; GROWTH-FACTOR; CELLS; IDENTIFICATION; INTERLEUKIN-6; ANGIOGENESIS AB There is substantial evidence that Kaposi sarcoma-associated herpesvirus (KSHV) plays an important role in the pathogenesis of all forms of Kaposi sarcoma (KS). It has been noted that KS commonly occurs in locations, such as the feet, where tissue may be poorly oxygenated. On the basis of this observation, the potential role of hypoxia in the reactivation of KSHV replication was explored by studying 2 KSHV-infected primary effusion lymphoma B-cell lines (BC-3 and BCBL-1) latently infected with KSHV. Acute and chronic exposure of these cells to hypoxia (11% O-2) induced KSHV lytic replication, as indicated by an increase in intracellular lytic protein expression and detection of virus in cell supernatants by Western immunoblotting. In addition, hypoxia increased the levels of secreted viral interleukin-6. Moreover, hypoxia enhanced the lytic replication initiated by the viral inducer 12-O-tetradecanoylphorbol-13-acetate. Desferoxamine and cobalt chloride, 2 compounds that increase the intracellular levels of hypoxia-inducible factor 1, were also able to induce KSHV lytic replication. These studies suggest that hypoxia is an inducer of KSHV replication. This process may play an important role in the pathogenesis of KS. (Blood. 2001;97:3244-3250) (C) 2001 by The American Society of Hematology. C1 NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Davis, DA (reprint author), NCI, HIV & AIDS Malignancy Branch, NIH, Bldg 10,Rm 10S255,MSC 1868,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 51 TC 112 Z9 116 U1 0 U2 4 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 MAY 15 PY 2001 VL 97 IS 10 BP 3244 EP 3250 DI 10.1182/blood.V97.10.3244 PG 7 WC Hematology SC Hematology GA 460HC UT WOS:000170301300043 PM 11342455 ER PT J AU Gamain, B Smith, JD Miller, LH Baruch, DI AF Gamain, B Smith, JD Miller, LH Baruch, DI TI Modifications in the CD36 binding domain of the Plasmodium falciparum variant antigen are responsible for the inability of chondroitin sulfate A adherent parasites to bind CD36 SO BLOOD LA English DT Article ID ERYTHROCYTE-MEMBRANE PROTEIN-1; INTERCELLULAR-ADHESION MOLECULE-1; INFECTED ERYTHROCYTES; CEREBRAL MALARIA; CYTOADHERENCE; RECEPTOR; SEQUESTRATION; IDENTIFICATION; CHILDREN; PFEMP1 AB Adhesion of mature Plasmodium falciparum parasitized erythrocytes to microvascular endothelial cells or to placenta contributes directly to the virulence and severe pathology of P falciparum malaria. Whereas CD36 is the major endothelial receptor for microvasculature sequestration, infected erythrocytes adhering in the placenta bind chondroitin sulfate A (CSA) but not CD36. Binding to both receptors is mediated by different members of the large and diverse protein family P falciparum erythrocyte membrane protein-1 (PfEMP-1) and involves different regions of the molecule. The PfEMP-1-binding domain for CD36 resides in the cysteine-rich interdomain region 1 (CIDR-1). To explore why CSA-binding parasites do not bind CD36, CIDR-1 domains from CD36- or CSA-binding parasites were expressed in mammalian cells and tested for adhesion. Although CIDR-1 domains from CD36-adherent strains strongly bound CD36, those from CSA-adherent parasites did not. The CIDR-1 domain has also been reported to bind CSA. However, none of the CIDR-1 domains tested bound CSA. Chimeric proteins between CIDR-1 domains that bind or do not bind CD36 and mutagenesis experiments revealed that modifications in the minimal CD36-binding region (M2 region) are responsible for the inability of CSA-selected parasites to bind CD36. One of these modifications, mapped to a 3-amino acid substitution in the M2 region, ablated binding in one variant and largely reduced binding of another. These findings provide a molecular explanation for the inability of placental sequestered parasites to bind CD36 and provide additional insight into critical residues for the CIDR-1/CD36 interaction. (Blood. 2001;97:3268-3274) (C) 2001 by The American Society of Hematology. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Colorado State Univ, Dept Pathol, Ft Collins, CO 80523 USA. RP Baruch, DI (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Rm B1-37,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. NR 45 TC 28 Z9 30 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 MAY 15 PY 2001 VL 97 IS 10 BP 3268 EP 3274 DI 10.1182/blood.V97.10.3268 PG 7 WC Hematology SC Hematology GA 460HC UT WOS:000170301300046 PM 11342458 ER PT J AU Persons, DA Allay, ER Sabatino, DE Kelly, P Bodine, DM Nienhuis, AW AF Persons, DA Allay, ER Sabatino, DE Kelly, P Bodine, DM Nienhuis, AW TI Functional requirements for phenotypic correction of murine beta-thalassemia: implications for human gene therapy SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; HEMATOPOIETIC STEM-CELLS; GAMMA-GLOBIN GENE; IN-VIVO SELECTION; LOCUS-CONTROL REGION; MIXED CHIMERISM; TRANSGENIC MICE; MOUSE MODEL; RETROVIRUS VECTORS; ERYTHROID-CELLS AB As initial human gene therapy trials for beta -thalassemia are contemplated, 2 critical questions important to trial design and planning have emerged. First, what proportion of genetically corrected hematopoietic stem cells (HSCs) will be needed to achieve a therapeutic benefit? Second, what level of expression of a transferred globin gene will be required to improve beta -thalassemic erythropoiesis? These questions were directly addressed by means of a murine model of severe beta -thalassemia. Generation of beta -thalassemic mice chimeric for a minority proportion of genetically normal HSCs demonstrated that normal HSC chimerism levels as low as 10% to 20% resulted in significant increases in hemoglobin (Hb) level and diminished extramedullary erythropoiesis. A large majority of the peripheral red cells in these mice were derived from the small minority of normal HSCs. In a separate set of independent experiments, beta -thalassemic mice were bred with transgenic mice that expressed different levels of human globins. Human gamma -globin messenger RNA (mRNA) expression at 7% of the level of total endogenous alpha -globin mRNA in thalassemic erythroid cells resulted in improved red cell morphology, a greater than 2-g/dL increase in Hb, and diminished reticulocytosis and extramedullary erythropoiesis. Furthermore, gamma -globin mRNA expression at 13% resulted in a 3-g/dL increase in Hb and nearly complete correction of red cell morphology and other indices of inefficient erythropoiesis. These data indicate that a significant therapeutic benefit could be achieved with expression of a transferred globin gene at about 15% of the level of total alpha -globin mRNA in patients with severe beta -thalassemia in whom 20% of erythroid precursors express the vector genome. (Blood. 2001;97:3275-3282) (C) 2001 by The American Society of Hematology. C1 St Jude Childrens Res Hosp, Div Expt Hematol, Dept Hematol & Oncol, Memphis, TN 38105 USA. NIH, Hematopoiesis Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Persons, DA (reprint author), St Jude Childrens Res Hosp, Div Expt Hematol, Dept Hematol & Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM derek.persons@stjude.org FU NHLBI NIH HHS [K08 HL04205-01, P01 HL53749] NR 57 TC 65 Z9 66 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 MAY 15 PY 2001 VL 97 IS 10 BP 3275 EP 3282 DI 10.1182/blood.V97.10.3275 PG 8 WC Hematology SC Hematology GA 460HC UT WOS:000170301300047 PM 11342459 ER PT J AU Cheson, BD Bennett, JM Greenberg, PL AF Cheson, BD Bennett, JM Greenberg, PL TI Clarifications of response criteria in myelodysplastic syndrome - Response SO BLOOD LA English DT Letter C1 NCI, Rockville, MD 20852 USA. RP Cheson, BD (reprint author), NCI, Execut Plaza N,Rm 741, Rockville, MD 20852 USA. NR 1 TC 0 Z9 0 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 MAY 15 PY 2001 VL 97 IS 10 BP 3322 EP 3322 PG 1 WC Hematology SC Hematology GA 460HC UT WOS:000170301300065 ER PT J AU Hough, CD Cho, KR Zonderman, AB Schwartz, DR Morin, PJ AF Hough, CD Cho, KR Zonderman, AB Schwartz, DR Morin, PJ TI Coordinately up-regulated genes in ovarian cancer SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; BREAST CARCINOMAS; MOLECULAR-CLONING; MUTATION ANALYSIS; EPITHELIAL-CELLS; TISSUE INHIBITOR; EXPRESSION; ONCOGENE; PROTEIN; AMPLIFICATION AB A better understanding of the molecular circuitry in normal ovarian tissues and in ovarian cancer will likely provide new targets for diagnosis and therapy. Recently, much has been learned about the genes expressed in ovarian cancer through studies with cDNA arrays and serial analysis of gene expression, However, these methods do not allow highly quantitative analysis of gene expression on a large number of specimens. Here, we have used quantitative real-time RT-FCR in a panel of 39 microdissected ovarian carcinomas of various subtypes to systematically analyze the expression of 13 genes, many of which were previously identified as up-regulated in a subset of ovarian cancers by serial analyses of gene expression. The genes analyzed are glutathione peroxidase 3 (GPX3), apolipoprotein J/clusterin, insulin-like growth factor-binding protein 2, epithelial cell adhesion molecule/GA733-2, Kop protease inhibitor, matrix gla protein, tissue inhibitor of metalloproteinase 3, folate receptor 1, S100A2, signal transducer and activator of transcription 1, secretory leukocyte protease inhibitor, apolipoprotein E, and ceruloplasmin. All of the genes were found overexpressed, some at extremely high levels, in the vast majority of ovarian carcinomas irrespective of the subtype. Interestingly, GPX3 was found at much higher levels in tumors with clear cell histology and may represent a biomarker for this subtype. Some of the genes studied here may thus represent targets for early detection ovarian cancer. The gene expression patterns were not associated with age at diagnosis, stage, or K-ras mutation status in ovarian cancer. We find that several genes are coordinately regulated in ovarian cancer, likely representing the fact that many genes are activated as part of common signaling pathways or that extensive cross-talk exists between several pathways in ovarian cancer, A statistical analysis shows that genes commonly upregulated in ovarian cancer may result from the aberrant activation of a limited number of pathways, providing promising targets for novel therapeutic strategies. C1 NIA, Ctr Gerontol Res, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. NIA, Res Resources Branch, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA. RP Morin, PJ (reprint author), NIA, Ctr Gerontol Res, Cellular & Mol Biol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Zonderman, Alan B/0000-0002-6523-4778 NR 42 TC 206 Z9 210 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2001 VL 61 IS 10 BP 3869 EP 3876 PG 8 WC Oncology SC Oncology GA 436HC UT WOS:000168929600005 PM 11358798 ER PT J AU MacDonald, CJ Ciolino, HP Yeh, GC AF MacDonald, CJ Ciolino, HP Yeh, GC TI Dibenzoylmethane modulates aryl hydrocarbon receptor function and expression of cytochromes P450 1A1, 1A2, and 1B1 SO CANCER RESEARCH LA English DT Article ID AH RECEPTOR; SIGNAL-TRANSDUCTION; MAMMARY-TUMORS; HEPG2 CELLS; CYP1A1; TRANSCRIPTION; INDUCTION; ACTIVATION; BINDING; PROTEIN AB The phytochemical dibenzoylmethane (DBM) has been shown to prevent polycyclic aromatic hydrocarbon (PAH)-induced tumorigenesis in rodents. However, the biochemical basis of this activity is unclear. We have therefore investigated the effects of DBM on the activity and expression of carcinogen-activating enzymes, the cytochromes P450 (CYP) 1A1, 1A2, and 1B1. Oral administration of DBM to female Sprague Dawley rats inhibited the increase in hepatic enzyme activity and mRNA levels of CYP1A1, 1A2, and 1B1 caused by the PAH 7,12-dimethylbenz[a]anthracene (DMBA). However, DBM administration alone caused an increase in both activity and expression in the liver, albeit to levels much lower than that induced by DMBA. To characterize the molecular mechanisms involved in this dual action of DBM, we examined the effects of DBM in vitro. In HepG2 human hepatoma cells, DBM inhibited DMBA-and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced enzyme activity and CYP1A1, 1A2, and 1B1 mRNA levels, whereas DBM itself induced activity and mRNA expression. Modulation of CYP1A1 expression by DBM occurred at the transcriptional level, as transient transfection assays demonstrated. Because the transcription of CYP1A1 is regulated by the aryl hydrocarbon receptor (AhR), we investigated the effect of DBM on AhR activation. DBM inhibited TCCD-induced DNA-binding of the AhR to the xenobiotic-responsive element (XRE) of CYP1A1 as measured by electrophoretic mobility shift assay. Those data suggest that the chemopreventive activity of DBM results from its ability to affect Phase 1 enzyme expression by modulation of AhR function. C1 NCI, Cellular Def & Carcinogenesis Sect, Basic Res Lab, NIH, Frederick, MD 21702 USA. RP Yeh, GC (reprint author), NCI, Cellular Def & Carcinogenesis Sect, Basic Res Lab, NIH, Bldg 560,Room 12-05A, Frederick, MD 21702 USA. NR 31 TC 50 Z9 51 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 MAY 15 PY 2001 VL 61 IS 10 BP 3919 EP 3924 PG 6 WC Oncology SC Oncology GA 436HC UT WOS:000168929600013 PM 11358806 ER PT J AU Brognard, J Clark, AS Ni, YC Dennis, PA AF Brognard, J Clark, AS Ni, YC Dennis, PA TI Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; AKT PROTEIN-KINASE; CYCLE CHECKPOINT PATHWAY; SERINE-THREONINE KINASE; INTEGRIN-LINKED KINASE; HUMAN TUMOR-CELLS; NF-KAPPA-B; PHOSPHATIDYLINOSITOL 3-KINASE; INDUCED APOPTOSIS; PHOSPHOINOSITIDE 3-KINASE AB To evaluate the role of Akt/PKB in non-small cell lung cancer (NSCLC) survival, we analyzed NSCLC cell lines that differed in tumor histology as well as p53, Rb, and K-ras status. Constitutive Akt/protein kinase B (PI(B) activity was demonstrated in 16 of 17 cell lines by maintenance of S473 phosphorylation with serum deprivation, Additional analysis of five of these NSCLC lines revealed that phosphorylation of S473 and T308 correlated with in vitro kinase activity. Akt/PKB activation was phosphatidylinositol 3-kinase-dependent and promoted survival because the phosphatidylinositol 3 inhibitors LY294002 and wortmannin inhibited Akt/PKB phosphorylation, Akt/PKB activity, and increased apoptosis only in cells with active Akt/PKB. To test whether Akt/PKB activity promoted therapeutic resistance, LY294002 was added with individual chemotherapeutic agents or irradiation. LY294002 greatly potentiated chemotherapy-induced apoptosis in cells with high Akt/PKB levels, but did not significantly increase chemotherapy-induced apoptosis in cells with low Akt/PKB levels. Combined with radiation in cells with active Akt/PKB, LY294002 additively increased apoptosis and inhibited clonogenic growth. These results mere extended with transiently transfected Akt/PKB mutants. Transfecting dominant negative Akt/PKB decreased Akt/PKB activity and increased basal apoptosis as well as chemotherapy- and irradiation-induced apoptosis only in cells with high Akt/PKB activity. Conversely, transfecting constitutively active Akt/PKB into cells with low Akt/PKB activity increased Akt/PKB activity and attenuated chemotherapy- and radiation-induced apoptosis. We therefore identify Akt/PKB as a constitutively active kinase that promotes survival of NSCLC cells and demonstrate that modulation of Akt/PKB activity by pharmacological or genetic approaches alters the cellular responsiveness to therapeutic modalities typically used to treat patients with NSCLC. C1 USN Med Oncol, NCI, Dev Therapeut Dept, Med Branch,Div Clin Sci, Bethesda, MD 20889 USA. USN Med Oncol, Natl Naval Med Ctr, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), USN Med Oncol, NCI, Dev Therapeut Dept, Med Branch,Div Clin Sci, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 90 TC 702 Z9 740 U1 2 U2 30 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 MAY 15 PY 2001 VL 61 IS 10 BP 3986 EP 3997 PG 12 WC Oncology SC Oncology GA 436HC UT WOS:000168929600023 PM 11358816 ER PT J AU Mi, QW Cui, BL Silva, GL Lantvit, D Lim, E Chai, H You, M Hollingshead, MG Mayo, JG Kinghorn, AD Pezzuto, JM AF Mi, QW Cui, BL Silva, GL Lantvit, D Lim, E Chai, H You, M Hollingshead, MG Mayo, JG Kinghorn, AD Pezzuto, JM TI Pervilleine A, a novel tropane alkaloid that reverses the multidrug-resistance phenotype SO CANCER RESEARCH LA English DT Article ID TRANSPORTER P-GLYCOPROTEIN; MULTIPLE-DRUG RESISTANCE; HUMAN-LEUKEMIC CELLS; IN-VIVO REVERSAL; P388 LEUKEMIA; TUMOR-MODEL; VERAPAMIL; EXPRESSION; AGENTS; VINCRISTINE AB P-Glycoprotein-mediated drug efflux can yield a multidrug-resistance (MDR) phenotype that is associated with a poor response to cancer chemotherapy, Pervilleine A, a novel tropane alkaloid obtained from a chloroform extract of Erythroxylum pervillei as the result of bioactivity-guided fractionation, was found to restore the vinblastine sensitivity of cultured multidrug-resistant I(B-VI and CEM/VLB100 cells, with IC50 values of 0.36 and 0.02 muM, respectively. Similarly, the chemosensitivity of KB-8-5 cells to colchicine was restored with an IC50 value of 0.61 muM The mechanism of this response was evaluated with a number of model systems. First, incubation of multidrug-resistant KB-VI and CEM/VLB100 cells with up to 45 muM pervilleine A for 72 h did not significantly affect either the transcription of MDR1, as revealed by reverse transcriptional-PCR-based analysis of MDR1 mRNA, or levels of P-glycoprotein, as shown by Western blots. ATP-dependent binding of [H-3]vinblastine observed with isolated multidrug-resistant KB-V1 cell membrane vesicles was inhibited by pervilleine A in a dose-dependent manner, and kinetic analysis indicted competitive inhibition with respect to vinblastine binding with a Ki of 7.3 muM. Consistent with this effect, intracellular accumulation of [H-3]vinblastine was increased from 0.18 pmol [H-3]vinblastine/50 x 10(4) cells to approximately 5 pmol [H-3]vinblastine/50 x 10(4) cells in the presence of 40 muM pervilleine A. To explore the potential relevance of these responses, KB-VI or KB-8-5 cells were placed in hollow fibers and implanted into NCr nu/nu mice. Cell growth was not significantly inhibited when vinblastine or pervilleine A were administered as single agents, but when used in combination, inhibition of up to 75% was observed. Equimolar doses of verapamil were less effective. These data suggest that pervilleine A is an effective inhibitor of P-glycoprotein and should be further evaluated for clinical utility. C1 Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Program Collaborat Res Pharmaceut Sci, Chicago, IL 60612 USA. NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Biol Testing Branch, Frederick, MD 21702 USA. RP Pezzuto, JM (reprint author), Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, M-C 781,833 S Wood St, Chicago, IL 60612 USA. RI You, Min/I-4973-2012; OI Silva, Gloria/0000-0002-0763-8096; Kinghorn, A. Douglas/0000-0002-6647-8707 FU NCI NIH HHS [U19 CA52956] NR 50 TC 44 Z9 46 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 MAY 15 PY 2001 VL 61 IS 10 BP 4030 EP 4037 PG 8 WC Oncology SC Oncology GA 436HC UT WOS:000168929600029 PM 11358822 ER PT J AU Roth, MJ Hu, N Emmert-Buck, MR Wang, QH Dawsey, SM Li, G Guo, WJ Zhang, YZ Taylor, PR AF Roth, MJ Hu, N Emmert-Buck, MR Wang, QH Dawsey, SM Li, G Guo, WJ Zhang, YZ Taylor, PR TI Genetic progression and heterogeneity associated with the development of esophageal squamous cell carcinoma SO CANCER RESEARCH LA English DT Article ID UPPER AERODIGESTIVE TRACT; ALLELIC LOSS; FIELD CANCERIZATION; FHIT GENE; PREMALIGNANT LESIONS; BARRETT-ESOPHAGUS; DIGESTIVE-TRACT; LUNG-CANCER; EVOLUTION; BREAST AB Esophageal squamous cell carcinoma is a common fatal cancer, and Shanxi province, a region in north-central China, has some of the highest esophageal cancer rates in the world. Chromosomal regions with frequent allelic loss may point to major susceptibility genes that will assist us in understanding the molecular events involved in esophageal carcinogenesis and may serve as the basis for the development of markers for genetic susceptibility and screening for early detection of this cancer, This study was designed to identify events in the molecular progression of precursor and invasive lesions of squamous esophageal cancer, Twelve marker loci identified during our previous studies as having some of the highest rates of loss of heterozygosity (LOH) in invasive esophageal cancer were evaluated in laser-microdissected DNA obtained from low- and high-grade dysplastic lesions and invasive tumor foci from 10 fully embedded esophageal resection specimens, Each resection specimen contained a spectrum of disease, from epithelium that appeared histologically normal to invasive cancer, including a single dominant tumor surrounded by a region of precursor lesions (low- and high-grade dysplasia) and occasional "remote," nonadjacent precancerous foci, Using the 12 polymorphic markers, LOH was found in all of the three stages of disease. The frequency of LOW for all of the markers together increased with increasing disease severity. Among the informative low-grade dysplasia samples, LOH was detected with markers D3S1766 (3p), D4S2632 (4p), D9S910 (9q), and D13S1493 (13q), suggesting that LOH at these loci may be associated with early stages of tumor initiation and/or progression. LOH was detected among the informative high-grade (but not low-grade) dysplasia samples for the other eight markers tested, suggesting that LOH at these loci may occur later in the neoplastic process. In addition to the association between disease progression and these genetic changes, considerable genetic heterogeneity was found in each fully embedded resection specimen both between and within geographically separate neoplastic lesions. C1 NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Shanxi Canc Hosp & Inst, Taiyuan 030013, Shanxi, Peoples R China. RP Roth, MJ (reprint author), NCI, Canc Prevent Studies Branch, 6006 Execut Plaza,Room 321, Bethesda, MD 20892 USA. NR 52 TC 34 Z9 36 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 MAY 15 PY 2001 VL 61 IS 10 BP 4098 EP 4104 PG 7 WC Oncology SC Oncology GA 436HC UT WOS:000168929600039 PM 11358832 ER PT J AU Hsu, TC Nair, R Tulsian, P Camalier, CE Hegamyer, GA Young, MR Colburn, NH AF Hsu, TC Nair, R Tulsian, P Camalier, CE Hegamyer, GA Young, MR Colburn, NH TI Transformation nonresponsive cells owe their resistance to lack of p65/nuclear factor-kappa B activation SO CANCER RESEARCH LA English DT Article ID NEOPLASTIC TRANSFORMATION; JB6 CELLS; MALIGNANT TRANSFORMATION; TRANSCRIPTIONAL ACTIVITY; AP-1 TRANSACTIVATION; SKIN CARCINOGENESIS; HUMAN KERATINOCYTES; P65 SUBUNIT; EXPRESSION; PROTEINS AB Clonal variants of mouse epidermal JB6 cells that are genetically susceptible (P+) or resistant (P-) to tumor promoter-induced neoplastic transformation exhibit differential activator protein-1 (AP-1) response. Transactivation of AP-1 appears to be necessary but not sufficient to promote transformation in JB6 cells. Inhibition of AP-1 is invariably accompanied by inhibition of nuclear factor-kappaB (NF-kappaB) when transformation is suppressed, suggesting that NF-kappaB may also play a role in neoplastic transformation. We report here that transactivation of NF-kappaB is inducible by tumor promoters in P+ but not in P- JB6 cells. Inhibition of NF-kappaB using a nondegradable mutant of I kappaB alpha suppressed inducible anchorage-independent transformation of P+ JB6 cells, suggesting that NF-kappaB activation is required for tumor promotion, Induced degradation of I kappaB alpha occurred in both P+ and P- JB6 cells, indicating that failure to activate NF-kappaB in P- JB6 cells cannot be attributed to failure to degrade I kappaB alpha. Slightly higher levels of nuclear p65 were seen in P+ than in P-JB6 cells, The p65-specific DNA binding activity was also higher in P+ cells upon induction by tumor necrosis factor-alpha, suggesting that differential NF-kappaB activation may be attributable to changes in p65 activity. Transactivation of p65 protein was substantially higher in P+ than in P-JB6 cells, as determined by assay of Ga14-p65 fusion constructs, Thus activated, p65 may be a limiting factor for NF-kappaB activation and transformation responses. Stable expression of p65 in P- JB6 cells conferred not only inducible NF-kappaB and AP-1 activation but also transformation response to tumor promoters. Therefore, p65/NF-kappaB appears to be not only necessary for but also sufficient to confer tumor promotion response, Although stable expression of p65 in P- cells produced p65 increases in whole cell extracts, only the transfectants exhibiting increased nuclear p65 showed transformation response. Thus, elevation of nuclear p65 appears to be a necessary step for a transformation response, The P-/p65 transfectants showing acquired transformation response also shelved elevated p65-specific transactivation response, thus recapitulating the NF-kappaB phenotypes seen in P+ cells. Expression of a transactivation-deficient mutant of Jun or dominant-negative extracellular signal-regulated kinase suppressed both AP-1 activation and p65-specific transactivation in JB6 cells, suggesting that AP-1 activity is needed for p65 transactivation and consequently for NF-kappaB activation. Thus, the transformation nonresponsive P- JB6 cells owe their resistance to lack of NF-kappaB activation and p65 transactivation that appears in turn to be attributable to insufficient AP-1 activation. C1 NCI, Frederick Canc Res & Dev Ctr, Gene Regulat Sect, Frederick, MD 21702 USA. Sci Applicat Int Corp, IRSP, Frederick, MD 21702 USA. RP Colburn, NH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Gene Regulat Sect, Bldg 560,Room 21-31, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 47 TC 39 Z9 41 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 MAY 15 PY 2001 VL 61 IS 10 BP 4160 EP 4168 PG 9 WC Oncology SC Oncology GA 436HC UT WOS:000168929600047 PM 11358840 ER PT J AU Mariani, L McDonough, WS Hoelzinger, DB Beaudry, C Kaczmarek, E Coons, SW Giese, A Moghaddam, M Seiler, RW Berens, ME AF Mariani, L McDonough, WS Hoelzinger, DB Beaudry, C Kaczmarek, E Coons, SW Giese, A Moghaddam, M Seiler, RW Berens, ME TI Identification and validation of P311 as a glioblastoma invasion gene using laser capture microdissection SO CANCER RESEARCH LA English DT Article ID HUMAN ASTROCYTOMA MIGRATION; POLYMERASE-CHAIN-REACTION; EXTRACELLULAR-MATRIX; MALIGNANT GLIOMA; BRAIN; CELLS; DIFFERENTIATION; EXPRESSION; AMPLIFICATION; MOTILITY AB The mRNA expression profiles from glioblastoma cells residing at the tumor core and invasive rim of a human tumor resection mere compared. From a single tumor specimen, 20,000 single cells from each region were collected by laser capture microdissection, Differential expression of 50-60 cDNA bands was detected. One of the sequences overexpressed by the invasive cells showed 99% homology to the P311 gene, the protein product of which is reported to localize at focal adhesions. Relative overexpression of P311 by invading glioblastoma cells compared with tumor core was confirmed by quantitative reverse transcription-PCR of six glioblastoma specimens after laser capture microdissection collection of rim and core cells. In vitro studies using antisense oligodeoxynucleotides and integrin activation confirmed the role of P311 in supporting migration of malignant glioma cells. Immunochemistry studies confirmed the presence of the P311 protein in tumor cells, particularly at the invasive edge of human glioblastoma specimens. C1 Barrow Neurol Inst, Dept Neurol, Neurooncol Lab, Phoenix, AZ 85013 USA. Barrow Neurol Inst, Dept Neuropathol, Phoenix, AZ 85013 USA. Univ Hamburg, Krankenhaus Eppendorf, Neurochirurg Klin, D-20246 Hamburg, Germany. Univ Hosp Bern, Inselspital, CH-3010 Bern, Switzerland. NHGRI, NIH, Bethesda, MD 20892 USA. RP Berens, ME (reprint author), Barrow Neurol Inst, Dept Neurol, Neurooncol Lab, 350 W Thomas Rd, Phoenix, AZ 85013 USA. OI Hoelzinger, Dominique/0000-0003-0861-9310 NR 32 TC 87 Z9 96 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 MAY 15 PY 2001 VL 61 IS 10 BP 4190 EP 4196 PG 7 WC Oncology SC Oncology GA 436HC UT WOS:000168929600051 PM 11358844 ER PT J AU Gho, YS Kim, PN Li, HC Elkin, M Kleinman, HK AF Gho, YS Kim, PN Li, HC Elkin, M Kleinman, HK TI Stimulation of tumor growth by human soluble intercellular adhesion molecule-1 SO CANCER RESEARCH LA English DT Article ID MELANOMA CELL-LINES; ENDOTHELIAL-CELLS; ANGIOGENESIS; ICAM-1; CANCER; FORMS; EXPRESSION; RELEASE; MICE AB Because serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) are elevated in cancer and sICAM-1 is angiogenic, we tested the ability of sICAM-1 to promote tumor growth. Our preliminary experiments showed that exogenous sICAM-1 significantly stimulated the growth of human tumors in vivo. Human fibrosarcoma transfectants, which express ICAM-1, produce ICAM-1 on the cell surface and release sICAM-1 into the medium without any apparent effect on cell growth in vitro. We found that conditioned medium from sense ICAM-1 transfectants compared with mock or antisense ICAM-1 transfectants stimulates endothelial cell migration in vitro and neovascularization in the chick chorioallantoic membrane assay. Tumor cells transfected,vith sense constructs form faster growing tumors than mock- and antisense-transfected cells in both chick embryos and nude mice models. Serum levels of human sICAM-1 from nude mice bearing sense ICAM-1 transfectants correlate positively with tumor weight. Sense ICAM-1 transfectants are more proliferative and induce more blood vessel formation than mock and antisense transfectants in nude mice, Because expression of ICAM-1 does not affect tumor cell growth in vitro the angiogenic activity of sICAM-1 produced by sense ICAM-1 transfectants may be involved in the stimulation of tumor growth, Therefore, sICAM-1 map perform dual functions that are essential for tumor growth: angiogenesis and escape from immune surveillance. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Kleinman, HK (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Room 433,30 Convent Dr MSC-4370, Bethesda, MD 20892 USA. NR 25 TC 58 Z9 70 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 MAY 15 PY 2001 VL 61 IS 10 BP 4253 EP 4257 PG 5 WC Oncology SC Oncology GA 436HC UT WOS:000168929600059 PM 11358852 ER PT J AU Ishii, Y Balbach, JJ Tycko, R AF Ishii, Y Balbach, JJ Tycko, R TI Measurement of dipole-coupled lineshapes in a many-spin system by constant-time two-dimensional solid state NMR with high-speed magic-angle spinning SO CHEMICAL PHYSICS LA English DT Article DE magnetic resonance; solid state NMR; two-dimensional spectroscopy; structure ID ROTATING SOLIDS; ANTIPARALLEL; SPECTROSCOPY; PARALLEL; EXCHANGE; PEPTIDE; SHEET AB A two-dimensional solid state NMR technique for measurements of dipole-dipole couplings in many-spin systems under high-speed magic-angle spinning (MAS) is described. The technique, called constant-time finite-pulse radiofrequency-driven recoupling (fpRFDR-CT), uses the fpRFDR pulse sequence to generate non-zero effective homonuclear dipole-dipole couplings under high-speed MAS that have the same operator symmetry as static dipole-dipole couplings. By incorporating fpRFDR into a multiple-pulse cycle based on the Waugh-Huber-Haeberlen (WAHUHA) homonuclear decoupling cycle, a constant-time ti evolution period is created. The constant-time tl period minimizes distortions of the experimental data due to various pulse sequence imperfections. The fpRFDR-CT technique is demonstrated experimentally in C-13 NMR spectroscopy of carboxylate-labeled, polycrystalline L-alanine. 2D fpRFDRCT spectra correlate the dipole-coupled lineshape of the C-13 carboxylate groups with their isotropic chemical shift. Good agreement is obtained between the experimental second and fourth moments of the dipole-coupled lineshapes and calculated moments based on the L-alanine crystal structure and an average Hamiltonian analysis of the fpRFDR sequence. Applications in structural investigations of biologically relevant systems are anticipated. This technique illustrates many of the important concepts in modern multi-dimensional solid state NMR. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. RI Ishii, Yoshitaka/F-4558-2014 OI Ishii, Yoshitaka/0000-0002-7724-6469 NR 24 TC 55 Z9 57 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0104 J9 CHEM PHYS JI Chem. Phys. PD MAY 15 PY 2001 VL 266 IS 2-3 BP 231 EP 236 DI 10.1016/S0301-0104(01)00250-6 PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 432GZ UT WOS:000168685000008 ER PT J AU Spooner, PM Albert, C Benjamin, EJ Boineau, R Elston, RC George, AL Jouven, X Kuller, LH MacCluer, JW Marban, E Muller, JE Schwartz, PJ Siscovick, DS Tracy, RP Zareba, W Zipes, DP AF Spooner, PM Albert, C Benjamin, EJ Boineau, R Elston, RC George, AL Jouven, X Kuller, LH MacCluer, JW Marban, E Muller, JE Schwartz, PJ Siscovick, DS Tracy, RP Zareba, W Zipes, DP TI Sudden cardiac death, genes, and arrhythmogenesis - Consideration of new population and mechanistic approaches from a national heart, lung, and blood institute workshop, part I SO CIRCULATION LA English DT Article DE genetics; death, sudden; arrhythmia; tachyarrhythmias; epidemiology; mortality; ion channels ID FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; LONG-QT; MISSENSE MUTATIONS; RISK FACTOR; DISEASE; ARRHYTHMIAS; DEFECTS; IMPACT AB Malignant ventricular arrhythmias are the leading mechanism of death in patients with acute and chronic cardiac pathologies. The extent to which inherited mutations and polymorphic variation in genes determining arrhythmogenic mechanisms affect these patients remains unknown, but based on recent population studies, this risk appears significant, deserving much greater investigation. This report summarizes a National Heart, Lung, and Blood Institute workshop that considered sources of genetic variation that may contribute to sudden cardiac death in common cardiac diseases. Evidence on arrhythmogenic mechanisms in recent population studies suggests a significant portion of the risk of sudden cardiac death in such broad populations may be unrelated to traditional risk factors for predisposing conditions such as atherosclerosis, hypertension, and diabetes and instead may involve unrecognized genetic and environmental interactions that influence arrhythmic susceptibility more directly. Additional population and genetic studies directed at discovering the sources of inherited molecular risk that are most directly linked to arrhythmia initiation and propagation. in addition to studies on previously well-described risk factors, would appear to have considerable potential for reducing premature cardiovascular mortality. C1 NHLBI, Div Heart & Vasc Dis, Rockledge Ctr 2, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Boston, MA 02215 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Vanderbilt Univ, Nashville, TN USA. Hosp Boucicaut, Paris, France. Univ Pittsburgh, Pittsburgh, PA USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. Johns Hopkins Med Sch, Baltimore, MD USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Pavia, I-27100 Pavia, Italy. Univ Washington, Seattle, WA 98195 USA. Univ Vermont, Colchester, VT USA. Univ Rochester, Rochester, NY USA. Indiana Univ, Indianapolis, IN 46204 USA. RP Spooner, PM (reprint author), NHLBI, Div Heart & Vasc Dis, Rockledge Ctr 2, Suite 9192,6701 Rockledge Dr,MSC 7940, Bethesda, MD 20892 USA. RI Schwartz, Peter/J-4267-2016; OI Schwartz, Peter/0000-0003-0367-1048; Zipes, Douglas/0000-0001-7141-6829 NR 28 TC 71 Z9 76 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 15 PY 2001 VL 103 IS 19 BP 2361 EP 2364 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 434FH UT WOS:000168804100011 PM 11352884 ER PT J AU Mattera, R Stone, GP Bahhur, N Kuryshev, YA AF Mattera, R Stone, GP Bahhur, N Kuryshev, YA TI Increased release of arachidonic acid and eicosanoids in iron-overloaded cardiomyocytes SO CIRCULATION LA English DT Article DE cardiomyopathy; prostaglandins; signal transduction; myocytes; iron ID RAT VENTRICULAR MYOCYTES; CARDIAC MYOCYTES; PHOSPHOLIPASE A(2); GENE-EXPRESSION; ANGIOTENSIN-II; MUSCLE-CELLS; FATTY-ACIDS; HEART-CELLS; INHIBITION; INDUCTION AB Background-Patients with transfusional iron overload may develop a life-limiting cardiomyopathy. The sensitivity of lipid-metabolizing enzymes to peroxidative injury, as well as the reported effects of arachidonic acid (AA) and metabolites on cardiac rhythm, led us to hypothesize that iron-overloaded cardiomyocytes display alterations in the release of AA and prostaglandins. Methods and Results-Neonatal rat ventricular myocytes (NRVMs) cultured for 72 hours in the presence of 80 mug/mL ferric ammonium citrate displayed an increased rate of AA release, both under resting conditions and after stimulation with agonists such as [Sar(1)]Ang II. Although iron treatment did not affect overall incorporation of [H-3]AA into NRVM phospholipids, it caused a 2-fold increase in the distribution of precursor in phosphatidylcholine species, with a proportional decrease in phosphatidylinositol, phosphatidylserine, and phosphatidylethanolamine. Increased release of AA in iron-overloaded NRVMs was reduced by the diacylglycerol lipase inhibitor RHC80267 but was largely insensitive to inhibitors of phospholipases A(2) and C, Iron-overloaded cardiomyocytes also displayed increased production of eicosanoids and induction of cyclooxygenase-a after stimulation with interleukin-1 alpha. Conclusions-Iron overload enhances AA release and incorporation of AA into phosphatidylcholine, as well as cyclooxygenase-2 induction and eicosanoid production, in NRVMs, The effects of AA and metabolites on cardiomyocyte rhythmicity suggest a causal connection between these signals and electromechanical alterations in iron-overload-induced cardiomyopathy. C1 Metrohlth Med Ctr, Rammelkamp Ctr Educ & Res, Cleveland, OH USA. Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44106 USA. RP Mattera, R (reprint author), NICHD, Cell Biol & Metab Branch, Bldg 18T,Room 101, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL07147-22, HL61642] NR 35 TC 11 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 15 PY 2001 VL 103 IS 19 BP 2395 EP 2401 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 434FH UT WOS:000168804100017 PM 11352890 ER PT J AU Semba, RD Taha, TE Kumwenda, N Mtimavalye, L Broadhead, R Miotti, PG Chiphangwi, JD AF Semba, RD Taha, TE Kumwenda, N Mtimavalye, L Broadhead, R Miotti, PG Chiphangwi, JD TI Iron status and indicators of human immunodeficiency virus disease severity among pregnant women in Malawi SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HIV-INFECTION; TRANSFERRIN RECEPTOR; METABOLISM; SURVIVAL; CONSEQUENCES; FERRITIN AB The relationships among hemoglobin, ferritin, and transferrin receptor levels and 2 markers of human immunodeficiency virus (HIV) disease severity-HIV load and CD4(+) lymphocyte count-were characterized among 483 pregnant women in Malawi, Africa. The only significant correlation was an inverse correlation between hemoglobin level and plasma HIV load (r = -.104; P < .03). The prevalence of iron deficiency anemia was not significantly different across quartiles of HIV load or CD4(+) lymphocyte count. In contrast to previous studies, these data suggest that iron status is not related to markers of HIV disease severity in pregnant women in Africa. C1 Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Malawi, Coll Med, Dept Obstet & Gynaecol, Blantyre, Malawi. Univ Malawi, Coll Med, Dept Paediat & Child Hlth, Blantyre, Malawi. RP Semba, RD (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, 550 N Broadway,Ste 700, Baltimore, MD 21205 USA. FU NIAID NIH HHS [N01-AI-35173-117]; NICHD NIH HHS [HD-30042, HD-32247] NR 20 TC 21 Z9 22 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2001 VL 32 IS 10 BP 1496 EP 1499 DI 10.1086/320167 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 430FB UT WOS:000168562900018 PM 11317253 ER PT J AU Hewitt, RG Yiannoutsos, CT Higgs, ES AF Hewitt, RG Yiannoutsos, CT Higgs, ES TI Paromomycin in cryptosporidiosis - Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 SUNY Buffalo, Buffalo, NY 14260 USA. Harvard Univ, Cambridge, MA 02138 USA. NIAID, Bethesda, MD 20892 USA. RP Hewitt, RG (reprint author), Erie Cty Med Ctr & Labs, 462 Grider St, Buffalo, NY 14215 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2001 VL 32 IS 10 BP 1517 EP 1517 DI 10.1086/320175 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 430FB UT WOS:000168562900023 ER PT J AU Krettli, AU Miller, LH AF Krettli, AU Miller, LH TI Malaria: A sporozoite runs through it SO CURRENT BIOLOGY LA English DT Article ID PLASMODIUM-BERGHEI SPOROZOITES; CIRCUMSPOROZOITE PROTEIN; TOXOPLASMA INVASION; PLASMA-MEMBRANE; MOSQUITO BITE; FALCIPARUM; CELLS; HEPATOCYTES; PARASITES; INFECTIVITY AB A recent study reveals new insights into the development of Plasmodium sporozoites, the infectious agents of malaria. These findings may lead to changes in the approach to malaria vaccines and novel interpretations of the mechanisms of immunity to malaria. C1 FIOCRUZ, Ctr Pesquisas Rene Rachou, BR-30190002 Belo Horizonte, MG, Brazil. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Krettli, AU (reprint author), FIOCRUZ, Ctr Pesquisas Rene Rachou, BR-30190002 Belo Horizonte, MG, Brazil. NR 28 TC 4 Z9 4 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 15 PY 2001 VL 11 IS 10 BP R409 EP R412 DI 10.1016/S0960-9822(01)00221-4 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 433NA UT WOS:000168765100013 PM 11378408 ER PT J AU Mozer, BA AF Mozer, BA TI Dominant Drop mutants are gain-of-function alleles of the muscle segment homeobox gene (msh) whose overexpression leads to the arrest of eye development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Drosophila; msh; Drop; eye development; gain-of-function mutation; morphogenetic furrow ID DROSOPHILA EYE; MORPHOGENETIC FURROW; ECTOPIC EXPRESSION; SIGNALING PATHWAYS; CELL-PROLIFERATION; TOOTH DEVELOPMENT; NERVOUS-SYSTEM; MSX2 GENE; DIFFERENTIATION; MUTATIONS AB Dominant Drop (Dr) mutations are nearly eyeless and have additional recessive phenotypes including lethality and patterning defects in eye and sensory bristles due to cis-regulatory lesions in the cell cycle regulator string (stg). Genetic analysis demonstrates that the dominant small eye phenotype is the result of separate gain-of-function mutations in the closely linked muscle segment homeobox (msh) gene, encoding a homeodomain transcription factor required for patterning of muscle and nervous system, Reversion of the Dr(Mio) allele was coincident with the generation of lethal loss-of-function mutations in msh in cis, suggesting that the dominant eye phenotype is the result of ectopic expression. Molecular genetic analysis revealed that two dominant Dr alleles contain lesions upstream of the msh transcription start site. In the Dr(Mio) mutant, a 3S18 retrotransposon insertion is the target of second-site mutations (P-element insertions or deletions) which suppress the dominant eye phenotype following reversion. The pattern of 3S18 expression and the absence of msh in eye imaginal discs suggest that transcriptional activation of the msh promoter accounts for ectopic expression. Dr dominant mutations arrest eye development by blocking the progression of the morphogenetic furrow leading to photoreceptor cell loss via apoptosis. Gal4-mediated ubiquitous expression of msh in third-instar larvae tvas sufficient to arrest the morphogenetic furrow in the eye imaginal disc and resulted in lethality prior to eclosion. Dominant mutations in the human msx2 gene, one of the vertebrate homologs of msh, are associated with craniosynostosis, a disease affecting cranial development. The Dr mutations are the first example of gain-of-function mutations in the msh/msx gene family identified in a genetically tractible model organism and may serve as a useful tool to identify additional genes that regulate this class of homeodomain proteins. (C) 2001 Academic Press. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mozer, BA (reprint author), NHLBI, Biochim Genet Lab, NIH, Bldg 36,Room 1C23, Bethesda, MD 20892 USA. NR 64 TC 12 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 15 PY 2001 VL 233 IS 2 BP 380 EP 393 DI 10.1006/dbio.2001.0229 PG 14 WC Developmental Biology SC Developmental Biology GA 436JB UT WOS:000168931800010 PM 11336502 ER PT J AU Gajewski, K Zhang, Q Choi, CY Fossett, N Dang, A Kim, YH Kim, Y Schulz, RA AF Gajewski, K Zhang, Q Choi, CY Fossett, N Dang, A Kim, YH Kim, Y Schulz, RA TI Pannier is a transcriptional target and partner of tinman during Drosophila cardiogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE cardiogenic factors; D-MEF2; heart; Pannier; protein interactions; Tinman; transcriptional enhancer ID ZINC-FINGER PROTEIN; HEART DEVELOPMENT; GENE-EXPRESSION; DORSAL MESODERM; HOMEOBOX GENES; CELL FATES; FOG-2; COFACTOR; SPECIFICATION; ACTIVATION AB During Drosophila embryogenesis, the homeobox gene tinman is expressed in the dorsal mesoderm where it functions in the specification of precursor cells of the heart, visceral, and dorsal body wall muscles. The GATA factor gene pannier is similarly expressed in the dorsal-most part of the mesoderm where it is required for the formation of the cardial cell lineage. Despite these overlapping expression and functional properties, potential genetic and molecular interactions between the two genes remain largely unexplored. Here, we show that pannier is a direct transcriptional target of Tinman in the heart-forming region. The resulting coexpression of the two factors allows them to function combinatorially in the regulation of cardiac gene expression, and a physical interaction of the proteins has been demonstrated in cultured cells. We also define functional domains of Tinman and Pannier that are required for their synergistic activation of the D-mef2 differentiation gene in vivo. Together, these results provide important insights into the genetic mechanisms controlling heart formation in the Drosophila model system. (C) 2001 Academic Press. C1 Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, GRad Program Genes & Dev, Houston, TX 77030 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Schulz, RA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, GRad Program Genes & Dev, 1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [CA16672]; NHLBI NIH HHS [HL59151] NR 46 TC 51 Z9 51 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 15 PY 2001 VL 233 IS 2 BP 425 EP 436 DI 10.1006/dbio.2001.0220 PG 12 WC Developmental Biology SC Developmental Biology GA 436JB UT WOS:000168931800013 PM 11336505 ER PT J AU Wornat, MJ Ledesma, EB Sandrowitz, AK Roth, MJ Dawsey, SM Qiao, YL Chen, W AF Wornat, MJ Ledesma, EB Sandrowitz, AK Roth, MJ Dawsey, SM Qiao, YL Chen, W TI Polycyclic aromatic hydrocarbons identified in soot extracts from domestic goal burning stoves of Henan Province, China SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID FIRED RESIDENTIAL STOVES; MASS-SPECTROMETRY; COAL; PYROLYSIS; MUTAGENICITY; ANTHRACENE; COMBUSTION; FLAMES; DICYCLOPENTAPYRENES; CHROMATOGRAPHY AB Using high-pressure liquid chromatography with ultra-violet-visible diode-array detection; we have analyzed polycyclic aromatic hydrocarbons (PAH) in the dichloromethane extracts of soot deposits fiom coal-burning staves in several homes of Henan Province, China-including Linxian County, where esophageal cancer rates-are some of the highest in the world, Thirthy-two individual polycyclic aromatic compounds, ranging in size from three to eight fused aromatic rings, have been unequivocally identified among the soot extract components-including 20 benzenoid PAH, 6 fluoranthene benzologues, 1 cyclopenta-fused PAH, 1 indene benzalogue, 3 oxygenated PAH, and 1 ring-sulfur-containing aromatic. Most of the identified compounds have been observed before among the products of laboratory coal pyrolysis experiments,but two of the components, the six-ring C24H14 naphtho[ 1,2-b]fluoranthene and the eight-ring C30H16 tribenzo[e,ghi,k]perylene, have never before been documented as products of coal in any system. All of the Henan coal soot extracts are remarkably similar qualitatively in that they contain the same set of identified PAH, but absolute levels of individual species vary by up to 5 orders of magnitude, from sample to sample. The bulk of the identified component mass in all of these soot extracts lies in the five- and six-ring PAH-the largest single class being the family of five-ring C20H12 isomers, to which the samples' most abundant components, benzo[b]fluoranthene and benzo[e]pyrene, belong. The five- and six-ring PAH also account for the majority of the samples' known mutagens. The three strong mutagens identified in these soot samples are the C20H12 benzo[a]pyrene and two C24H14 PAH dibenzo[a,e]pyrene and naphtho[21-a]pyrene. Seven moderate mutagens are found among the C20H12, C22H12, C22H14, and C-24H14 PAH. A major class of mutagens, the cyclopenta-fused PAH, appears to be absent from these samples, but our detection of an oxidation product of the major mutagen cyclopenta[cd]-pyrene-itself mutagenic-suggests that these soot deposits may contain additional mutagenic cyclopenta-fused PAH oxidation products as well. C1 Princeton Univ, Dept Mech & Aerosp Engn, Princeton, NJ 08544 USA. NCI, Canc Prevent Studies Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Dept Epidemiol, Beijing 10021, Peoples R China. RP Wornat, MJ (reprint author), Princeton Univ, Dept Mech & Aerosp Engn, Engn Quadrangle,Room D328, Princeton, NJ 08544 USA. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 93 TC 62 Z9 64 U1 2 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD MAY 15 PY 2001 VL 35 IS 10 BP 1943 EP 1952 DI 10.1021/es001664b PG 10 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 433LA UT WOS:000168759800007 PM 11393972 ER PT J AU Wechselberger, C Ebert, AD Bianco, C Khan, NI Sun, YP Wallace-Jones, B Montesano, R Salomon, DS AF Wechselberger, C Ebert, AD Bianco, C Khan, NI Sun, YP Wallace-Jones, B Montesano, R Salomon, DS TI Cripto-1 enhances migration and branching morphogenesis of mouse mammary epithelial cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE cripto-1; mouse mammary epithelial cells; migration; branching; epithelial-mesenchymal transition ID EPIDERMAL GROWTH-FACTOR; DIFFERENTIAL IMMUNOHISTOCHEMICAL DETECTION; TRANSCRIPTION FACTOR LEF-1; FACTOR-RELATED PROTEINS; ONE-EYED PINHEAD; BETA-CATENIN; TYROSINE PHOSPHORYLATION; E-CADHERIN; FACTOR-ALPHA; EPITHELIOMESENCHYMAL TRANSFORMATION AB Cripto-1 is an EGF-CFC protein that performs an important role during early vertebrate development and is overexpressed in several types of human cancer. In the present study mouse EpH4, NMuMG, and TAC-2 mammary epithelial cells that are negative for endogenous cripto-1 expression were transfected with the murine cripto-1 cDNA. Cripto-1-transfected cell lines exhibited functional and physiological differences from the original cell lines including enhanced anchorage-independent growth in soft agar (EpH4 cells), growth in serum-free medium, increased proliferation, and formation of branching, duct-like structures when grown in a three-dimensional collagen type I matrix. Furthermore, cripto-1-expressing cell lines showed elevated migration in vitro in Boyden chamber and wound-healing assays. These results indicate that cripto-1 can function through an autocrine pathway that enables mammary epithelial cells to undergo an epithelial to mesenchymal transition. C1 NCI, Tumor Immunol & Biol Lab, Tumor Growth Factor Sect, NIH, Bethesda, MD 20892 USA. Free Univ Berlin, Med Ctr Benjamin Franklin, Dept Obstet & Gynecol, D-12200 Berlin, Germany. Univ Geneva, Med Ctr, Dept Morphol, CH-1211 Geneva, Switzerland. RP Salomon, DS (reprint author), NCI, Tumor Immunol & Biol Lab, Tumor Growth Factor Sect, NIH, Bldg 10,Room 5B39,10 Ctr Dr,MSC-1750, Bethesda, MD 20892 USA. NR 75 TC 66 Z9 68 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 15 PY 2001 VL 266 IS 1 BP 95 EP 105 DI 10.1006/excr.2001.5195 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 431WG UT WOS:000168654300010 PM 11339828 ER PT J AU Vassilev, A Kaneko, KJ Shu, HJ Zhao, YM DePamphilis, ML AF Vassilev, A Kaneko, KJ Shu, HJ Zhao, YM DePamphilis, ML TI TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm SO GENES & DEVELOPMENT LA English DT Article DE TEAD; TEF; YAP; 14-3-3; transcription; Src ID ENHANCER FACTOR-I; DNA-BINDING DOMAIN; GENE-EXPRESSION; MOUSE DEVELOPMENT; MASS-SPECTROMETRY; WW DOMAIN; TEF-1; FAMILY; YES; IDENTIFICATION AB Mammals express four highly conserved TEAD/TEF transcription factors that bind the same DNA sequence, but serve different functions during development. TEAD-2/TEF-4 protein purified from mouse cells was associated predominantly with a novel TEAD-binding domain at the amino terminus of YAP65, a powerful transcriptional coactivator. YAP65 interacted specifically with the carboxyl terminus of all four TEAD proteins. Both this interaction and sequence-specific DNA binding by TEAD were required for transcriptional activation in mouse cells. Expression of YAP in lymphocytic cells that normally do not support TEAD-dependent transcription (e.g., MPC11) resulted in up to 300-fold induction of TEAD activity. Conversely, TEAD overexpression squelched YAP activity. Therefore, the carboxy-terminal acidic activation domain in YAP is the transcriptional activation domain for TEAD transcription factors. However, whereas TEAD was concentrated in the nucleus, excess YAP65 accumulated in the cytoplasm as a complex with the cytoplasmic localization protein, 14-3-3. Because TEAD-dependent transcription was limited by YAP65, and YAP65 also binds Src/Yes protein tyrosine kinases, we propose that YAP65 regulates TEAD-dependent transcription in response to mitogenic signals. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. RP DePamphilis, ML (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 37 TC 294 Z9 301 U1 3 U2 20 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 2001 VL 15 IS 10 BP 1229 EP 1241 DI 10.1101/gad.888601 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 436HN UT WOS:000168930600007 PM 11358867 ER PT J AU Mohiddin, S Fananapazir, L AF Mohiddin, S Fananapazir, L TI Advances in understanding hypertrophic cardiomyopathy SO HOSPITAL PRACTICE LA English DT Article ID MUTATIONS AB The single most common cause of sudden death in otherwise healthy young people, the disease is inherited by at least one in 1,000 to one in 500 of the general population. Nine genes are implicated; continued research can be expected to uncover others, along with modifying factors that offer hope of inducing regression. New interventions are being tested for value in addressing symptoms and risk of death. C1 NHLBI, Inherited Heart Dis Sect, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Mohiddin, S (reprint author), NHLBI, Inherited Heart Dis Sect, Cardiol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD MAY 15 PY 2001 VL 36 IS 5 BP 23 EP + PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 431NV UT WOS:000168638200003 PM 11361156 ER PT J AU Miller, AN Raghavan, N FitzGerald, PC Lewis, FA Knight, M AF Miller, AN Raghavan, N FitzGerald, PC Lewis, FA Knight, M TI Differential gene expression in haemocytes of the snail Biomphalaria glabrata: effects of Schistosoma mansoni infection SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Article DE Biomphalaria glabrata; differential display reverse transcriptase polymerase chain reaction; gene regulation; haemocytes; Schistosoma mansoni ID INTERMEDIATE HOST; INTERNAL DEFENSES; RICH GLYCOPROTEIN; IDENTIFICATION; RESISTANCE; CLONING; MOLLUSK; MARKERS; DISPLAY; SEQUENCE AB Parasite encapsulation and destruction in Biomphalaria glabrata has been shown to involve the cellular component of the snail's internal defence system, the haemocytes. To identify genes involved in the immunobiology of these cells, we used the method of differential display reverse transcriptase polymerase chain reaction (DDRT-PCR) to investigate differential gene regulation in haemocytes isolated from Schistosoma mansoni exposed and unexposed snails. RNA isolated from circulating haemocytes from resistant snails (BS-90 stock), previously exposed to S. mansoni, was analysed using 12 different arbitrary primers in conjunction with an anchored Oligo d(T(11)CG) primer. Transcription profiles between haemocytes of parasite exposed and unexposed snails were compared and a total of 87 differentially regulated bands were identified and isolated. Of these, 65 bands were cloned and used as probes in Southern blots to show the presence of corresponding sequences in the snail genome. RT-PCR was performed to verify the regulation of these transcripts. DNA sequence analysis showed that the majority of the cloned sequences were novel, although a few showed a high degree of sequence similarity to other sequences in the DNA and protein databases. One of these included a differentially expressed transcript that showed a significant degree of sequence identity to E. coli transposase Tn5, an enzyme whose activity is normally associated with generating mobility and instability in the genome. (C) 2001 Australian Society for parasitology Inc. Published by Elsevier Science Ltd. All rights reserved. C1 Biomed Res Inst, Rockville, MD 20852 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Knight, M (reprint author), Biomed Res Inst, 12111 Parklawn Rd, Rockville, MD 20852 USA. FU NIAID NIH HHS [AI-27777] NR 35 TC 41 Z9 45 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD MAY 15 PY 2001 VL 31 IS 7 BP 687 EP 696 DI 10.1016/S0020-7519(01)00133-3 PG 10 WC Parasitology SC Parasitology GA 435RC UT WOS:000168894100006 PM 11336750 ER PT J AU Buggiano, V Schere-Levy, C Abe, K Vanzulli, S Piazzon, I Smith, GH Kordon, EC AF Buggiano, V Schere-Levy, C Abe, K Vanzulli, S Piazzon, I Smith, GH Kordon, EC TI Impairment of mammary lobular development induced by expression of TGF beta 1 under the control of WAP promoter does not suppress tumorigenesis in MMTV-infected transgenic mice SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE mammary tumor; MMTV; TGF beta 1; stem cells ID TRANSFORMING GROWTH-FACTOR-BETA-1 TRANSGENE; GROWTH-FACTOR-ALPHA; FACTOR TYPE-BETA; TUMOR VIRUS; EPITHELIAL-CELLS; GLAND; DNA; DIFFERENTIATION; INTEGRATION; PREGNANCY AB It has previously been shown that transgenic female mice expressing TGF beta1 under control of regulatory elements of the whey-acidic protein (WAP) gene were unable to lactate. This was due to the increased apoptosis of the cells committed to the lobular-lactogenic phenotype, Our goal was to determine whether the expression of WAP-TGF beta1 transgene could inhibit MMTV (mouse mammary tumor virus) tumorigenic activity in the mammary gland. It is well known that the infection with this virus produces focal hyperplastic secretory nodules (HANs) and. some variants can also induce ductal pregnancy-dependent lesions (plaques). In either case, MMTV infection leads ultimately to the appearance of malignant mammary tumors. The results shown herein demonstrate that TGF beta1 expression in the secretory mammary epithelium does not suppress mammary tumorigenesis in MMTV infected mice. Although MMTV infected WAP-TGF beta1 transgenic females displayed a strong impairment of lobule-alveolar development, carcinogenesis induced by any of the four MMTV variants used herein proceeded unabated, WAP-TGF beta1 tumors that showed a strong expression at the WAP promoter, appeared later and grew more slowly than their wild-type counterparts. Transgenic females also had a lower incidence of HANs and plaques. Our study suggests that the epithelial target cells for tumorigenic mutations are probably progenitor cells that are not susceptible to the apoptotic effect of TGF beta1. Alternatively, their daughters cells that display the secretory phenotype and could be more involved in the formation of premalignant lesions continue to die due to the expression of the transgene. (C) 2001 Wiley-Liss. Inc. C1 Acad Nacl Med, Div Med Expt, Inst Invest Hematol, CONICET,ILEX, RA-1425 Buenos Aires, DF, Argentina. Acad Nacl Med, Inst Estudios Oncol, RA-1425 Buenos Aires, DF, Argentina. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kordon, EC (reprint author), Acad Nacl Med, Div Med Expt, Inst Invest Hematol, CONICET,ILEX, JA Pacheco de Melo 3081, RA-1425 Buenos Aires, DF, Argentina. NR 29 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 15 PY 2001 VL 92 IS 4 BP 568 EP 576 DI 10.1002/ijc.1232 PG 9 WC Oncology SC Oncology GA 424LJ UT WOS:000168233500016 PM 11304693 ER EF