FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Fedorova, OV Talan, MI Lakatta, EG Bagrov, AY AF Fedorova, OV Talan, MI Lakatta, EG Bagrov, AY TI Na/K-ATPase (NKA) isoforms and sodium pump ligands (SPL) during development of left ventricular hypertrophy (LVH) and transition to chronic heart failure (CHF) in Dahl hypertension SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE Na,K ATPase; digitalis-like factors; left ventricular remodeling C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2003 VL 16 IS 5 MA P132 BP 87A EP 87A DI 10.1016/S0895-7061(03)00297-8 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 677LK UT WOS:000182809000214 ER PT J AU Phillips, RA Appel, LJ Gabriel, A Gassman, J AF Phillips, RA Appel, LJ Gabriel, A Gassman, J CA AASK Study Grp TI Diurnal patterns of BP in African Americans with hypertensive kidney disease: Results from the AASK cohort study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE ambulatory blood pressure; nocturnal blood pressure; African Americans C1 Lenox Hill Hosp, Dept Med, New York, NY 10021 USA. NYU, Sch Med, New York, NY USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2003 VL 16 IS 5 MA P166 BP 99A EP 99A DI 10.1016/S0895-7061(03)00331-5 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 677LK UT WOS:000182809000248 ER PT J AU Najjar, SS Scuteri, A Harik-Khan, RI Yin, FC Chen, CH Lakatta, EG AF Najjar, SS Scuteri, A Harik-Khan, RI Yin, FC Chen, CH Lakatta, EG TI A risky partnership: Cardiovascular alterations in isolated systolic hypertension SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE isolated systolic hypertension; vascular stiffness; vascular structure C1 NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. INRCA, UO Geriatria, Rome, Italy. Washington Univ, Dept Biomed Engn, St Louis, MO 63130 USA. Natl Yang Ming Univ, Dept Social Med, Taipei 112, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2003 VL 16 IS 5 MA P295 BP 143A EP 143A DI 10.1016/S0895-7061(03)00460-6 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 677LK UT WOS:000182809000377 ER PT J AU Scuter, A Najjar, S Muller, D Andres, R Lakatta, EG AF Scuter, A Najjar, S Muller, D Andres, R Lakatta, EG TI Metabolic syndrome amplifies the age-associated increases in vascular thickness and stiffness SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE metabolic syndrome; carotid artery; aging C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. INRCA, UO Geriatria, Rome, Italy. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2003 VL 16 IS 5 MA P302 BP 145A EP 146A DI 10.1016/S0895-7061(03)00467-9 PN 2 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 677LK UT WOS:000182809000384 ER PT J AU St-Louis, J Brochu, M Beausejour, A Agalakova, NI Fedorova, OV Lakatta, EG Bagrov, AY AF St-Louis, J Brochu, M Beausejour, A Agalakova, NI Fedorova, OV Lakatta, EG Bagrov, AY TI High sodium intake stimulates endogenous sodium pump inhibitor, marinobufagenin, and increases blood pressure in pregnant rats SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE NaCl; pregnancy induced hypertension; Na,K-ATPase inhibitors C1 Univ Montreal, Hop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2003 VL 16 IS 5 MA P318 BP 151A EP 152A DI 10.1016/S0895-7061(03)00483-7 PN 2 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 677LK UT WOS:000182809000400 ER PT J AU Fedorova, OV Zhuravin, IA Agalakova, NI Talan, MI Lakatta, EG Bagrov, AY AF Fedorova, OV Zhuravin, IA Agalakova, NI Talan, MI Lakatta, EG Bagrov, AY TI Cross talk between central and peripheral digitalis-like sodium pump ligands (SPL) in Dahl-S rats (DS) following NaCl loading SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE Na/K-ATPase; marinobufagenin; AT signalling C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2003 VL 16 IS 5 MA P319 BP 152A EP 152A DI 10.1016/S0895-7061(03)00484-9 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 677LK UT WOS:000182809000401 ER PT J AU Lloyd-Jones, DM Leip, EP Larson, MG Vasan, RS Levy, D AF Lloyd-Jones, DM Leip, EP Larson, MG Vasan, RS Levy, D TI Competing risks for first cardiovascular events after hypertension onset: The Framingham Heart Study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE hypertension; epidemiology; outcomes C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2003 VL 16 IS 5 MA P484 BP 213A EP 214A DI 10.1016/S0895-7061(03)00656-3 PN 2 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 677LK UT WOS:000182809000566 ER PT J AU Goldstein, DS Brentzel, S Holmes, C Eldadah, B Sharabi, Y AF Goldstein, DS Brentzel, S Holmes, C Eldadah, B Sharabi, Y TI Association between supine hypertension and orthostatic hypotension in chronic autonomic failure SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE sympathetic nervous system; baroreflex; orthostatic hypotension C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2003 VL 16 IS 5 MA P508 BP 222A EP 222A DI 10.1016/S0895-7061(03)00681-2 PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 677LK UT WOS:000182809000590 ER PT J AU Babiarz, LS Yousem, DM Wasserman, BA Wu, C Bilker, W Beauchamp, NJ AF Babiarz, LS Yousem, DM Wasserman, BA Wu, C Bilker, W Beauchamp, NJ TI Cavernous carotid artery calcirication and white matter ischemia SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ULTRAFAST COMPUTED-TOMOGRAPHY; CARDIOVASCULAR HEALTH; ANATOMIC CHARACTERISTICS; ATHEROSCLEROSIS RISK; DISEASE; RACE; MR; CALCIFICATION; LESIONS; BRAIN AB BACKGROUND AND PURPOSE: The relevance of cavernous carotid artery calcification on unenhanced CT scans of the brain has recently been investigated against the backdrop of the widespread implementation of coronary artery calcification scoring. We sought to determine whether the degree of cavernous carotid artery calcification correlated with scores of white matter hyperintensity seen on MR images. In so doing, we sought to establish a relative risk for future stroke on the grade of carotid calcification. METHODS: Neuroradiologic findings in 187 patients who underwent CT and MR imaging examinations within 1 month of each other were retrospectively reviewed. The degree of circumferential calcification and thickness of calcification were graded for the cavernous carotid arteries on the basis of CT findings. Using the scale developed by the Cardiovascular Health Study, the white matter was graded for degree of disease on the basis of MR findings. Correlation tests and regression analyses were performed to determine the impact of age, race, and sex on results. RESULTS: Although the cavernous carotid calcification scores and the MR imaging white matter scores showed good correlation (P < .001), the effect was mediated by age. With age factored in as a covariant, no correlation was shown between CT calcification scores and MR imaging white matter scores. Sex had no effect, but African American study participants had worse MR imaging white matter scores than did white participants. CONCLUSION. After adjusting for age, cavernous carotid calcification grades and MR imaging white matter scores do not show a significant correlation. The relative risk for future stroke cannot be predicted from cavernous carotid calcifications. C1 Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. NHLBI, Div Epidemiol & Clin Applicat, Off Biostat Res, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Ctr Clin Epidemiol & Biostat, Philadelphia, PA USA. RP Yousem, DM (reprint author), Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol & Radiol Sci, 600 N Wolfe St,Phipps B-112, Baltimore, MD 21287 USA. NR 27 TC 20 Z9 22 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 2003 VL 24 IS 5 BP 872 EP 877 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 681DF UT WOS:000183021100019 PM 12748087 ER PT J AU Guedez, L Rivera, AM Salloum, R Miller, ML Diegmueller, JJ Bungay, PM Stetler-Stevenson, WG AF Guedez, L Rivera, AM Salloum, R Miller, ML Diegmueller, JJ Bungay, PM Stetler-Stevenson, WG TI Quantitative assessment of angiogenic responses by the directed in vivo angiogenesis assay SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID THROMBOSPONDIN-1; INHIBITION; CANCER; PROGRESSION; MECHANISMS; TNP-470; GROWTH; SWITCH AB One of the major problems in angiogenesis research remains the lack of suitable methods for quantifying the angiogenic response in vivo. We describe the development and application of the directed in vivo angiogenesis assay (DIVAA) and demonstrated that it is reproducible and quantitative. This assay consists of subcutaneous implantation of semiclosed silicone cylinders (angioreactors) into nude mice. Angioreactors are filled with only 18 mul of extracellular matrix premixed with or without angiogenic factors. Vascularization within angioreactors is quantified by the intravenous injection of fluorescein isothiocyanate (FITC)-dextran before their recovery, followed by spectrofluorimetry. Angioreactors examined by immunofluorescence show cells and invading angiogenic vessels at different developmental stages. The minimally detectable angiogenic response requires 9 days after implantation and greater than or equal to50 ng/ml (P < 0.01) of either fibroblast growth factor-2 or vascular endothelial growth factor. Characterization of this assay system demonstrates that the FITC-labeled dextran quantitation is highly reproducible and that levels of FITC-dextran are not significantly influenced by vascular permeability. DIVAN allows accurate dose-response analysis and identification of effective doses of angiogenesis-modulating factors in vivo. TNP-470 potently inhibits angiogenesis (EC50 = 88 pmol/L) induced by 500 ng/ml of fibroblast growth factor-2. This inhibition correlates with decreased endothelial cell invasion. DIVAN efficiently detects differences in anti-angiogenic potencies of thrombospondin-1 peptides (25 mumol/L) and demonstrates a partial inhibition of angiogenesis (similar to40%) in a matrix metalloprotease (MMP)-2-deficient mouse compared with that in wild-type animals. Zymography of angioreactors from MMP-deficient and control animals reveals quantitative changes in MMP expression. These results support DIVAN as an assay to compare potencies of angiogenic factors or inhibitors, and for profiling molecular markers of angiogenesis in vivo. C1 NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Extracellular Matrix Sect, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Vasc Biol Fac, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Guedez, L (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Rm 2A33 MSc 1500, Bethesda, MD 20892 USA. RI Guedez, Liliana/H-4951-2012; Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 28 TC 86 Z9 88 U1 2 U2 9 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2003 VL 162 IS 5 BP 1431 EP 1439 DI 10.1016/S0002-9440(10)64276-9 PG 9 WC Pathology SC Pathology GA 670XE UT WOS:000182434700006 PM 12707026 ER PT J AU Ingram, JL Rice, AB Santos, J Van Houten, B Bonner, JC AF Ingram, JL Rice, AB Santos, J Van Houten, B Bonner, JC TI Vanadium-induced HB-EGF expression in human lung fibroblasts is oxidant dependent and requires MAP kinases SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE pulmonary fibrosis; fibroblast; growth factors; reactive oxygen species; heparin-binding epidermal growth factor-like growth factor ID EPIDERMAL-GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; GASTRIC EPITHELIAL-CELLS; HYDROGEN-PEROXIDE; GENE-EXPRESSION; FACTOR-ALPHA; INDUCTION; VANADATE; MITOGEN AB Vanadium pentoxide (V2O5) is a transition metal derived from the burning of petrochemicals that causes airway fibrosis and remodeling. Vanadium compounds activate many intracellular signaling pathways via the generation of hydrogen peroxide (H2O2) or other reactive oxygen species. In this study, we investigated the regulation of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in human lung fibroblasts after V2O5 treatment. V2O5-induced HB-EGF mRNA expression was abolished by N-acetyl-L-cysteine, suggesting an oxidant-mediated effect. Exogenous H2O2 (> 10 muM) mimicked the effect of V2O5 in upregulating HB-EGF expression. Fibroblasts spontaneously released low levels of H2O2 (1-2 muM), and the addition of V2O5 depleted the endogenous H2O2 pool within minutes. V2O5 caused a subsequent increase of H2O2 into the culture medium at 12 h. However, the burst of V2O5-induced H2O2 occurred after V2O5-induced HB-EGF mRNA expression at 3 h, indicating that the V2O5-stimulated H2O2 burst did not mediate HB-EGF expression. Either V2O5 or H2O2 activated ERK-1/2 and p38 MAP kinase. Inhibitors of the ERK-1/2 pathway (PD-98059) or p38 MAP kinase (SB-203580) significantly reduced either V2O5- or H2O2-induced HB-EGF expression. These data indicate that vanadium upregulates HB-EGF via ERK and p38 MAP kinases. The induction of HB-EGF is not related to a burst of H2O2 in V2O5 treated cells, yet the action of V2O5 in upregulating HB-EGF is oxidant dependent and could be due to the reaction of V2O5 with endogenous H2O2. C1 NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Bonner, JC (reprint author), NIEHS, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 45 TC 30 Z9 31 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD MAY PY 2003 VL 284 IS 5 BP L774 EP L782 DI 10.1152/ajplung.00189.2002 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 662VB UT WOS:000181968600011 PM 12676768 ER PT J AU Li, CL Wang, WD Knepper, MA Nielsen, S Forkiaer, J AF Li, CL Wang, WD Knepper, MA Nielsen, S Forkiaer, J TI Downregulation of renal aquaporins in response to unilateral ureteral obstruction SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE collecting duct; proximal tubule; water channel; obstructive nephropathy; vasopressin; Brattleboro rats ID WATER CHANNEL EXPRESSION; VASOPRESSIN-INDUCED ANTIDIURESIS; INDUCED DOWN-REGULATION; RAT-KIDNEY MEDULLA; COLLECTING DUCT; TRANSGENIC MICE; NULL MICE; PATHOPHYSIOLOGY; FAILURE; ESCAPE AB The expression of aquaporin- 2 ( AQP2) is decreased in rats with bilateral ureteral obstruction ( BUO) and unilateral ureteral obstruction ( UUO). Therefore, the expression of additional renal aquaporins ( AQP1 - 4) and phosphorylated AQP2 ( p- AQP2), known to play a role in urinary concentration, was examined in a Wistar rat model with 24 h of UUO. In obstructed kidneys, immunoblotting revealed a significant decrease in the expression of inner medullary AQP2 to 42 +/- 4, p- AQP2 to 23 +/- 5, AQP3 to 19 +/- 6, AQP4 to 11 +/- 5, and AQP1 to 64 +/- 8% of sham levels. AQP1 expression located in the proximal tubule decreased to 74 +/- 4% of sham levels ( P < 0.05). Immunocytochemistry confirmed the downregulation of AQP3, AQP4, and p- AQP2. In contralateral nonobstructed kidneys, immunoblotting also revealed significant reductions of AQP1 in the inner medulla, outer medulla, and cortex, whereas expression of AQP2, AQP3, AQP4, and p- AQP2 was unchanged. Furthermore, we collected the urine from both obstructed and nonobstructed kidneys for 2 h, respectively, after 24 h of UUO. Urine collection from obstructed kidneys during 2 h after release of UUO revealed a significant reduction in urine osmolality and solute- free water reabsorption ( T(c)H(2)O). Moreover, an increase in urine production and T(c)H(2)O was observed in contralateral kidneys. To examine whether vasopressin- independent mechanisms are involved in AQP2 regulation, vasopressin- deficient Brattleboro ( BB) rats with 24 h of UUO were examined. Immunoblotting revealed downregulation of AQP2, p- AQP2, AQP3, and AQP1 in obstructed kidneys and downregulation of p- AQP2 and AQP1 in nonobstructed kidneys. In conclusion, 1) UUO is associated with severe downregulation of AQP2, AQP3, AQP4, and AQP1; thus all of these AQPs may play important roles in the impaired urinary concentrating capacity in the obstructed kidney; 2) the reduced levels of AQP1 in the nonobstructed kidney may contribute to the compensatory increase in urine production; and 3) downregulation of AQPs in BB rats supports the view that vasopressin- independent pathways may be involved in AQP2 and AQP3 regulation in the obstructed kidney. C1 Aarhus Univ Hosp Skejby, Inst Expt Clin Res, Water & Salt Res Ctr, DK-8200 Aarhus N, Denmark. Aarhus Univ, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark. Aarhus Univ, Inst Anat, DK-8000 Aarhus C, Denmark. Aarhus Univ Hosp Skejby, Dept Clin Physiol, DK-8200 Aarhus N, Denmark. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Forkiaer, J (reprint author), Aarhus Univ Hosp Skejby, Inst Expt Clin Res, Water & Salt Res Ctr, DK-8200 Aarhus N, Denmark. EM JF@IEKF.AU.DK FU Intramural NIH HHS [Z01 HL001285-21] NR 39 TC 44 Z9 48 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 2003 VL 284 IS 5 BP F1066 EP F1079 DI 10.1152/ajprenal.00090.2002 PG 14 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 663RF UT WOS:000182018200022 PM 12517734 ER PT J AU Nelson, DE Bolen, J Marcus, S Wells, HE Meissner, H AF Nelson, DE Bolen, J Marcus, S Wells, HE Meissner, H TI Cancer screening estimates for US metropolitan areas SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID CLINICAL BREAST EXAMINATIONS; FECAL-OCCULT-BLOOD; CERVICAL-CANCER; INNER-CITY; COLORECTAL-CANCER; IMPROVING ACCESS; HEALTH PROMOTION; WHITE WOMEN; MAMMOGRAPHY; MORTALITY AB Objectives: To provide estimates of breast, cervical, and colorectal cancer screening for metropolitan areas in the United States. Methods: Behavioral Risk Factor Surveillance System (BRFSS) data from 1997 to 1999 were reweighted and analyzed for 69 U.S. metropolitan areas for the receipt of a Papanicolaou (Pap) test (ages greater than or equal to18 years); mammography (ages greater than or equal to40 years); fecal occult blood testing and sigmoidoscopy (ages greater than or equal to50 years). Stratified analyses by demographics were performed for 25 metropolitan areas with populations of greater than or equal to1.5 million. Results: Metropolitan estimates ranged from 64.6% to 82.0% for mammography and from 77.2% to 91.7% for Pap tests. There was much greater variability in estimates for colorectal cancer screening, with a 3.6-fold difference in the range of estimates for fecal occult blood testing (9.9% to 35.2%) and a 2.5-fold difference for sigmoidoscopy (17.3% to 43.3%). In the 25 largest areas, prevalence of cancer screening was generally lower for persons with a high school education or less and for those without health insurance. Compared with women aged 50 to 64 years, mammography estimates were lower for women aged 40 to 49 years in 13 of the 25 metropolitan areas. Pap testing was less common among women aged greater than or equal to65 years, and colorectal cancer screening was less common for persons aged 50 to 64 years. Conclusions: Estimates of cancer screening varied substantially across metropolitan areas. Increased efforts to improve cancer screening are needed in many urban areas, especially for colorectal cancer screening. The BRFSS is a useful, inexpensive, and timely resource for providing metropolitan-area cancer screening estimates and may be used in the future to guide local or county-level screening efforts. C1 Ctr Dis Control & Prevent, Div Adult & Community Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Nelson, DE (reprint author), Ctr Dis Control & Prevent, Div Adult & Community Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Hwy NE,Mailstop K-50, Atlanta, GA 30341 USA. NR 59 TC 32 Z9 32 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2003 VL 24 IS 4 BP 301 EP 309 DI 10.1016/S0749-3797(03)00024-2 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 679MV UT WOS:000182927100002 PM 12726867 ER PT J AU Zubenko, GS Zubenko, WN McPherson, S Spoor, E Marin, DB Farlow, MR Smith, GE Geda, YE Cummings, JL Petersen, RC Sunderland, T AF Zubenko, GS Zubenko, WN McPherson, S Spoor, E Marin, DB Farlow, MR Smith, GE Geda, YE Cummings, JL Petersen, RC Sunderland, T TI A collaborative study of the emergence and clinical features of the major depressive syndrome of Alzheimer's disease SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NUCLEUS RAPHE DORSALIS; SENILE DEMENTIA; LOCUS COERULEUS; PREVALENCE; DIAGNOSIS; NEUROBIOLOGY; GENOTYPE; HISTORY; SCALE AB Objective: This report provides a description of the prevalence and clinical features of the major depressive syndrome of Alzheimer's disease using data derived from structured diagnostic assessments of 243 patients with probable Alzheimer's disease and 151 nondemented elderly comparison subjects. Method: Subjects were characterized by a consortium of four Alzheimer's disease research centers and the Geriatric Psychiatry Branch of the National Institute of Mental Health. All sites administered the Clinical Assessment of Depression in Dementia, a structured, anchored diagnostic interview that was developed to reliably diagnose and characterize major depressive episodes in this population. Results: Despite the use of a common, reliable methodology for the assessment and diagnosis of major depressive episodes, the prevalence of major depression in Alzheimer's disease ranged widely from 22.5% to 54.4% across the recruitment sites. The prevalence of major depressive episodes among Alzheimer's disease patients in the aggregate sample exceeded that for elderly comparison subjects and reached nearly 50% among the most severely demented patients. Alzheimer's disease patients with a current major depressive episode had earlier mean ages at onset, a higher mean Hamilton Depression Rating Scale score, and were more likely to be experiencing psychotic symptoms than those who had not developed a major depressive episode. Although the major depressive episodes of Alzheimer's disease patients and nondemented elderly comparison subjects included similar numbers of depressive symptoms, patients with Alzheimer's disease were more likely to report a diminished ability to concentrate or indecisiveness and less likely to experience sleep disturbances and feelings of worthlessness or excessive guilt during their major depressive episodes. None of the clinical features of major depression differed significantly in frequency among depressed Alzheimer's disease patients with mild, moderate, or severe dementia. Concurrent psychotic symptoms progressively increased with dementia severity. Conclusions: The high rate of major depressive episodes that occur after the onset of cognitive impairment among patients with Alzheimer's disease (the majority of whom had no premorbid history of major depression), common emergence in the early stages of dementia when symptoms of cognitive impairment are least likely to contribute to the syndromal diagnosis of major depression, and differences in the. clinical presentations of the major depressive episodes of Alzheimer's disease patients and nondemented elderly comparison subjects, all support the validity of the major depressive syndrome of Alzheimer's disease. our findings suggest that the major depressive syndrome of Alzheimer's disease may be among the most common mood disorders of older adults. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Carnegie Mellon Univ, Dept Biol Sci, Mellon Coll Sci, Pittsburgh, PA 15213 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA USA. NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mayo Clin, Dept Neurol, Rochester, MN USA. Indiana Univ, Sch Med, Dept Neurol, Indianapolis, IN USA. RP Zubenko, GS (reprint author), Western Psychiat Inst & Clin, Room E1230,3811 OHara St, Pittsburgh, PA 15213 USA. RI Geda, Yonas/D-9570-2012; OI Smith, Glenn/0000-0003-1506-9484 FU NIA NIH HHS [AG 05138, AG 16574, AG 10133, AG 16570]; NIMH NIH HHS [MH 00540, MH/AG 47346] NR 43 TC 141 Z9 151 U1 5 U2 8 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2003 VL 160 IS 5 BP 857 EP 866 DI 10.1176/appi.ajp.160.5.857 PG 10 WC Psychiatry SC Psychiatry GA 673ZC UT WOS:000182610400009 PM 12727688 ER PT J AU Frye, MA Altshuler, LL McElroy, SL Suppes, T Keck, PE Denicoff, K Nolen, WA Kupka, R Leverich, GS Pollio, C Grunze, H Walden, J Post, RM AF Frye, MA Altshuler, LL McElroy, SL Suppes, T Keck, PE Denicoff, K Nolen, WA Kupka, R Leverich, GS Pollio, C Grunze, H Walden, J Post, RM TI Gender differences in prevalence, risk, and clinical correlates of alcoholism comorbidity in bipolar disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 2nd European-Stanley-Foundation Conference on Bipolar Disorder CY AUG, 2000 CL AMSTERDAM, NETHERLANDS SP European Stanley Fdn ID SUBSTANCE-ABUSE; PSYCHIATRIC-DISORDERS; DRUG-ABUSE; ILLNESS; IMPACT; DEPRESSION; DEPENDENCE; POPULATION; WOMEN AB Objective: The prevalence of lifetime alcohol abuse and/or dependence (alcoholism) in patients with bipolar disorder has been reported to be higher than in all other axis I psychiatric diagnoses. This study examined gender-specific relationships between alcoholism and bipolar illness, which have previously received little systematic study. Method: The prevalence of lifetime alcoholism in 267 outpatients enrolled in the Stanley Foundation Bipolar Network was evaluated by using the Structured Clinical Interview for DSM-IV. Alcoholism and its relationship to retrospectively assessed measures of the course of bipolar illness were evaluated by patient-rated and clinician-administered questionnaires. Results: As in the general population, more men (49%, 57 of 116) than women with bipolar disorder (29%, 44 of 151) met the criteria for lifetime alcoholism. However, the risk of having alcoholism was greater for women with bipolar disorder (odds ratio=7.35) than for men with bipolar disorder (odds ratio=2.77), compared with the general population. Alcoholism was associated with a history of polysubstance use in women with bipolar disorder and with a family history of alcoholism in men with bipolar disorder. Conclusions: This study suggests that there are gender differences in the prevalence, risk, and clinical correlates of alcoholism in bipolar illness. Although this study is limited by the retrospective assessment of illness variables, the magnitude of these gender-specific differences is substantial and warrants further prospective study. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Biopolar Res Program, Los Angeles, CA 90095 USA. Univ Cincinnati, Sch Med, Dept Biol Psyhiat, Cincinnati, OH USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Med Ctr, Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Univ Munich, Psychiat Klin, Munich, Germany. Univ Freiburg, Psychiat Klin, Freiburg, Germany. RP Frye, MA (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Biopolar Res Program, 300 Ucla Med Plaza,Suite 1544, Los Angeles, CA 90095 USA. RI Nolen, Willem/E-9006-2014 FU NIMH NIH HHS [R01 MH079261] NR 40 TC 128 Z9 130 U1 1 U2 10 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2003 VL 160 IS 5 BP 883 EP 889 DI 10.1176/appi.ajp.160.5.883 PG 7 WC Psychiatry SC Psychiatry GA 673ZC UT WOS:000182610400012 PM 12727691 ER PT J AU Compton, WM Cottler, LB Jacobs, JL Ben-Abdallah, A Spitznagel, EL AF Compton, WM Cottler, LB Jacobs, JL Ben-Abdallah, A Spitznagel, EL TI The role of psychiatric disorders in predicting drug dependence treatment outcomes SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; SUBSTANCE-ABUSERS; RELIABILITY; VALIDITY; COCAINE; ALCOHOL AB Objective: Previous research has demonstrated that psychiatric disorders are common among people who abuse alcohol and drugs, but few studies have examined the relationship of psychiatric disorders to drug treatment outcome. The authors conducted such an examination. Method: They successfully reinterviewed 401 drug-dependent subjects (94% of the baseline in-treatment sample) and determined their drug abuse status at follow-up 12 months later. Results: Analyses indicated that several baseline psychiatric disorders predicted worse outcomes at follow-up. Major depression predicted using a larger number of substances and having more drug dependence diagnoses and symptoms. Alcohol dependence predicted more dependence diagnoses, antisocial personality disorder predicted using a larger number of substances, and generalized anxiety disorder predicted having more dependence diagnoses. Outcomes among men were more closely associated with psychiatric status than outcomes among women, except for phobias, which predicted a better outcome among women. Conclusions: These results are unique in their assessment of individuals dependent on illicit substances. Overall, the authors found that women with phobias had better outcomes and that men with psychiatric disorders in general, men with major depression, and men with antisocial personality disorder had worse outcomes. C1 NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. Washington Univ, Dept Math, Sch Med, Dept Psychiat, St Louis, MO USA. RP Compton, WM (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, 6001 Execut Blvd,MSC 9589, Bethesda, MD 20892 USA. FU NIDA NIH HHS [DA 00488, DA 05619] NR 22 TC 159 Z9 160 U1 1 U2 5 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2003 VL 160 IS 5 BP 890 EP 895 DI 10.1176/appi.ajp.160.5.890 PG 6 WC Psychiatry SC Psychiatry GA 673ZC UT WOS:000182610400013 PM 12727692 ER PT J AU Bremner, JD Vythilingam, M Vermetten, E Southwick, SM McGlashan, T Nazeer, A Khan, S Vaccarino, LV Soufer, R Garg, PK Ng, CK Staib, LH Duncan, JS Charney, DS AF Bremner, JD Vythilingam, M Vermetten, E Southwick, SM McGlashan, T Nazeer, A Khan, S Vaccarino, LV Soufer, R Garg, PK Ng, CK Staib, LH Duncan, JS Charney, DS TI MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; SCRIPT-DRIVEN IMAGERY; SHORT-TERM-MEMORY; VERBAL MEMORY; COMBAT VETERANS; MAJOR DEPRESSION; EPISODIC MEMORY; NEURON LOSS; BRAIN; RETRIEVAL AB Objective: Animal studies have suggested that early stress is associated with alterations in the hippocampus, a brain area that plays a critical role in learning and memory. The purpose of this study was to measure both hippocampal structure and function in women with and without early childhood sexual abuse and the diagnosis of posttraumatic stress disorder (PTSD). Method: Thirty-three women participated in this study, including women with early childhood sexual abuse and PTSD (N=10), women with abuse without PTSD (N=12), and women without abuse or PTSD (N=11). Hippocampal volume was measured with magnetic resonance imaging in all subjects, and hippocampal function during the performance of hippocampal-based verbal declarative memory tasks was measured by using positron emission tomography in abused women with and without PTSD. Results: A failure of hippocampal activation and 16% smaller volume of the hippocampus were seen in women with abuse and PTSD compared to women with abuse without PTSD. Women with abuse and PTSD had a 19% smaller hippocampal volume relative to women without abuse or PTSD. Conclusions: These results are consistent with deficits in hippocampal function and structure in abuse-related PTSD. C1 Emory Univ, Sch Med, Emory Ctr Positron Emiss Tomog, Atlanta, GA USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. Emory Univ, Sch Med, Dept Radiol, Atlanta, GA USA. Emory Univ, Sch Med, Dept Med Cardiol, Atlanta, GA USA. Atlanta Vet Affairs Med Ctr, Decatur, GA USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Yale Univ, Sch Med, Dept Med Cardiol, New Haven, CT USA. Yale Univ, Sch Med, Dept Radiol, New Haven, CT USA. RP Bremner, JD (reprint author), Emory Clin Neurosci Res Unit, 1256 Briarcliff Rd, Atlanta, GA 30306 USA. RI Bremner, James/B-1632-2013; OI Vermetten, Eric/0000-0003-0579-4404; Staib, Lawrence/0000-0002-9516-5136 FU NHLBI NIH HHS [HL 059619-02]; NIMH NIH HHS [1R01 MH 56120-01A1] NR 70 TC 343 Z9 352 U1 5 U2 40 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2003 VL 160 IS 5 BP 924 EP 932 DI 10.1176/appi.ajp.160.5.924 PG 9 WC Psychiatry SC Psychiatry GA 673ZC UT WOS:000182610400018 PM 12727697 ER PT J AU Siahpush, M Singh, GK AF Siahpush, M Singh, GK TI Rurality and suicide - Response SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. VicHlth Ctr Tobacco Control, Carlton, Vic, Australia. RP Siahpush, M (reprint author), NCI, Div Canc Control & Populat Sci, 6116 Execut Blvd,suite 504,MSC 8316, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2003 VL 93 IS 5 BP 698 EP 699 DI 10.2105/AJPH.93.5.698-a PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 675GG UT WOS:000182685100002 ER PT J AU Brown, TM Fee, E AF Brown, TM Fee, E TI Nathan Allen SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 Univ Rochester, Dept Hist, Rochester, NY 14627 USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. NIH, Natl Lib Med, Hist Med Div, Bethesda, MD 20892 USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, Rochester, NY 14627 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2003 VL 93 IS 5 BP 722 EP 722 DI 10.2105/AJPH.93.5.722 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 675GG UT WOS:000182685100018 PM 12721131 ER PT J AU Fee, E Brown, TM AF Fee, E Brown, TM TI The Indian Club exercise SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2003 VL 93 IS 5 BP 723 EP 723 DI 10.2105/AJPH.93.5.723 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 675GG UT WOS:000182685100019 PM 12721132 ER PT J AU Weidner, G Cain, VS AF Weidner, G Cain, VS TI The gender gap in heart disease: Lessons from Eastern Europe SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID RUSSIAN HEALTH-CARE; LIFE EXPECTANCY; MORTALITY; DEPRESSION; SYSTEM; MEN C1 Res Inst Prevent Med, Sausalito, CA 94965 USA. NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Weidner, G (reprint author), Res Inst Prevent Med, 900 Bridgeway, Sausalito, CA 94965 USA. NR 24 TC 24 Z9 25 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2003 VL 93 IS 5 BP 768 EP 770 DI 10.2105/AJPH.93.5.768 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 675GG UT WOS:000182685100027 PM 12721140 ER PT J AU Montoya, ID Herbeck, DM Svikis, DS Fitek, DJ Marcus, SC Pincus, HA AF Montoya, ID Herbeck, DM Svikis, DS Fitek, DJ Marcus, SC Pincus, HA TI Demographic and practice characteristics of psychiatrists who primarily treat patients with substance use disorders SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID POSITION STATEMENT; ADDICTION; ABUSE AB This study examined the sociodemographic and practice characteristics of psychiatrists whose caseloads consist primarily of patients with Substance Use Disorders (SUD). A survey instrument was completed by a random sample of 865 psychiatrists. Study groups were defined as high-SUD providers if psychiatrists reported having 51% or more patients with SUD (n = 92) and non-SUD providers as those who reported not having any patients with SUD (n = 128). High-SUD providers tended to be younger, more likely to graduate from international medical schools, have larger caseloads, work more hours per week, and have a higher proportion of inpatients and publicly funded patients than non-SUD providers. Results suggest that psychiatrists who primarily treat patients with SUD are in their early careers and treat patients with more clinical, psychosocial, and economic disadvantages. The implications of these findings for psychiatry training programs and policy makers will be discussed. C1 NIDA, Div Treatment Res & Dev, Bethesda, MD 20892 USA. Amer Psychiat Inst Res & Educ, Practice Res Network, Washington, DC USA. Virginia Commonwealth Univ, Richmond, VA USA. Univ Penn, Sch Social Work, Philadelphia, PA 19104 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. RAND Univ Pittsburgh, Hlth Inst, Pittsburgh, PA USA. RP Montoya, ID (reprint author), NIDA, Div Treatment Res & Dev, 6001 Execut Blvd, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 DA999999]; PHS HHS [99M003132701D] NR 18 TC 3 Z9 3 U1 0 U2 0 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2003 VL 12 IS 3 BP 181 EP 191 DI 10.1080/10550490390201759 PG 11 WC Substance Abuse SC Substance Abuse GA 694PD UT WOS:000183782200001 PM 12851014 ER PT J AU Parks, CG Cooper, GS Nylander-French, LA Storm, JF Archer, JD AF Parks, CG Cooper, GS Nylander-French, LA Storm, JF Archer, JD TI Assessing exposure to crystalline silica from farm work: A population-based study in the southeastern United States SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE silica; quartz; occupational exposure; dust; agricultural workers ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; OCCUPATIONAL-EXPOSURE; RISK-FACTORS; DUST AB PURPOSE: Farm workers are exposed to crystalline silica, but there are no established questionnaires to assess silica dust exposure from farm work in epidemiologic studies. This study examines aspects of farm work that were used to estimate potential silica dust exposure in a population-based study conducted in the southeastern United States. METHODS: We collected work and farming histories through in-person interviews with 620 participants in a population-based case-control study of systemic lupus erythematosus. A dust-exposure matrix was used to develop a telephone interview for 69 participants with potential medium- or high-level exposure, including questions on tasks, frequency, and farm location. Soil systems maps were used to infer soil type (sandy/other). Exposure indices were constructed based on tasks, frequency, and soil type. RESULTS: Thirty-six percent of study participants worked on a farm, but only 52 (8%) were classified in the high (n = 16) or medium (n = 36) exposure groups based on responses to follow-up interview questions. Exposure indices based on open-ended job descriptions in initial interviews correctly categorized 52% of participants who answered prompted questions on relevant dusty tasks in follow-up interviews. CONCLUSIONS: Specific questions on dusty tasks and frequency are needed to accurately assess silica exposure from farm work. Published by Elsevier Inc. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. RP Parks, CG (reprint author), NIEHS, Epidemiol Branch, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. OI Parks, Christine/0000-0002-5734-3456 NR 26 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 2003 VL 13 IS 5 BP 385 EP 392 DI 10.1016/S1047-2797(03)00007-3 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 695CL UT WOS:000183813500011 PM 12821278 ER PT J AU Taaffe, DR Lang, TF Fuerst, T Cauley, JA Nevitt, MC Harris, TB AF Taaffe, DR Lang, TF Fuerst, T Cauley, JA Nevitt, MC Harris, TB TI Sex- and race-related differences in cross-sectional geometry and bone density of the femoral mid-shaft in older adults SO ANNALS OF HUMAN BIOLOGY LA English DT Article ID NORMAL POSTMENOPAUSAL WOMEN; BLACK-WHITE DIFFERENCES; AGE-RELATED-CHANGES; MINERAL DENSITY; BODY-COMPOSITION; SHAFT FRACTURES; CORTICAL BONE; HIP FRACTURE; ELDERLY MEN; PHYSICAL ACTIVITIES AB Background : Femoral shaft fracture incidence increases in older adults and is associated with low-energy trauma. Apart from bone density, the distribution and size of bone contributes to its strength. Aim : To examine if bone geometry and density of the femoral mid-shaft in older adults differs by sex and race, we studied 197 White women, 225 Black women, 242 White men, and 148 Black men aged 70-79 years participating in the Health, Aging, and Body Composition study; a prospective cohort study in the USA. A secondary purpose of the study was to examine the association of site-specific muscle and fat to bone geometry and density. Subjects and methods : Subjects were community-dwelling and reported no difficulty walking one-quarter of a mile or climbing stairs. Mid-femoral volumetric bone mineral density (vBMD, mg cm -3 ), total area (TA), cortical area (CA), medullary area (MA), cross-sectional moments of inertia (CSMI: I x , I y , J ), and muscle and fat areas (cm 2 ) were determined by computed tomography (CT; GE CT-9800, 10 mm slice thickness). Results : vBMD was greater in men than women with no difference by race ( p < 0.001). Bone areas and area moments of inertia were also greater in men than women ( p < 0.001), with Black women having higher values than White women for TA and CA. Standardizing geometric parameters for body size differences by dividing by powers of femur length did not negate the sex difference for TA and MA. Significant differences ( p < 0.05) among the four groups also remained for I x and J . Mid-thigh muscle area was an independent contributor to TA in all groups (Std beta = 0.181-0.351, p < 0.05) as well as CA in women (Std beta = 0.246-0.254, p < 0.01) and CSMI in White women (Std beta = 0.175-0.185, p < 0.05). Further, muscle area was a significant contributor to vBMD in Black women. Conclusion : These results indicate that bone geometry and density of the femoral diaphysis differs primarily by sex, rather than race, in older well-functioning adults. In addition, site-specific muscle area appears to have a potential contributory role to bone geometry parameters, especially in women. C1 Univ Queensland, Fac Hlth Sci, Sch Human Movement Studies, St Lucia, Qld 4072, Australia. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Synarc Inc, San Francisco, CA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Taaffe, DR (reprint author), Univ Queensland, Fac Hlth Sci, Sch Human Movement Studies, Connell Bldg, St Lucia, Qld 4072, Australia. RI Lang, Thomas/B-2685-2012; Cauley, Jane/N-4836-2015 OI Lang, Thomas/0000-0002-3720-8038; Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106] NR 68 TC 24 Z9 24 U1 2 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0301-4460 J9 ANN HUM BIOL JI Ann. Hum. Biol. PD MAY-JUN PY 2003 VL 30 IS 3 BP 329 EP 346 DI 10.1080/0301446031000089588 PG 18 WC Anthropology; Biology; Public, Environmental & Occupational Health SC Anthropology; Life Sciences & Biomedicine - Other Topics; Public, Environmental & Occupational Health GA 690ZY UT WOS:000183581400008 PM 12850965 ER PT J AU Geerlings, MI Launer, LJ de Jong, FH Ruitenberg, A Stijnen, T van Swieten, JC Hofman, A Witteman, JCM Pols, HAP Breteler, MMB AF Geerlings, MI Launer, LJ de Jong, FH Ruitenberg, A Stijnen, T van Swieten, JC Hofman, A Witteman, JCM Pols, HAP Breteler, MMB TI Endogenous estradiol and risk of dementia in women and men: The Rotterdam Study SO ANNALS OF NEUROLOGY LA English DT Article ID ESTROGEN-REPLACEMENT THERAPY; ALZHEIMERS-DISEASE; COGNITIVE DECLINE; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; VASCULAR DEMENTIA; CONTROLLED TRIAL; DIAGNOSIS; MENOPAUSE; TESTOSTERONE AB We determined whether higher endogenous estradiol levels were associated with lower risk of dementia in older men and women not using hormonal replacement therapy, using a case-cohort design within the Rotterdam Study, a population-based follow-up study on chronic diseases, including dementia, in 7,983 subjects aged 55 years or older, and ongoing since 1990. The analyses were based on a random subcohort of 508 women and 438 men, and on 76 women and 53 men with incident dementia. Cox proportional hazards models with robustly estimated standard errors showed that in women higher levels of total estradiol were associated with higher risk of dementia (age-adjusted hazard ratio per standard deviation increase 1.38; 95% CI 1.04-1.84). Age-adjusted HR's of Alzheimer's disease and vascular dementia associated with higher levels of total estradiol (per SD increase) were 1.24 (95% CI 0.87-1.76) and 2.19 (95% CI 1.22-3.92), respectively. Similar results were observed for bioavailable estradiol. Additional adjustments for potential confounders did not change the results substantially. In men, no clear association was observed between estradiol levels and risk of dementia or its subtypes. The findings do not support the hypothesis that higher levels of endogenous estradiol reduce risk of dementia, neither in women nor in men. C1 Erasmus Med Ctr Rotterdam, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands. Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. NIA, NIH, Bethesda, MD 20892 USA. Erasmus Med Ctr, Dept Internal Med, Rotterdam, Netherlands. Erasmus Med Ctr, Dept Neurol, Rotterdam, Netherlands. RP Geerlings, MI (reprint author), Erasmus Med Ctr Rotterdam, Dept Epidemiol & Biostat, POB 1738, NL-3000 DR Rotterdam, Netherlands. RI de Jong, Frank/A-9876-2011; Breteler, Monique /J-5058-2014 OI de Jong, Frank/0000-0003-3578-1065; NR 37 TC 45 Z9 46 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2003 VL 53 IS 5 BP 607 EP 615 DI 10.1002/ana.10521 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 673EC UT WOS:000182566400007 PM 12730994 ER PT J AU Messam, CA Hou, J Gronostajski, RM Major, EO AF Messam, CA Hou, J Gronostajski, RM Major, EO TI Lineage pathway of human brain progenitor cells identified by JC virus susceptability SO ANNALS OF NEUROLOGY LA English DT Article ID NUCLEAR FACTOR-I; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HUMAN POLYOMAVIRUS; TRANSCRIPTION FACTOR; REGULATORY REGION; MOLECULAR-BIOLOGY; DNA-REPLICATION; GLIAL-CELLS; STEM-CELL; HUMAN CNS AB Multipotential human central nervous system progenitor cells, isolated from human fetal brain tissue by selective growth conditions, were cultured as undifferentiated, attached cell layers. Selective differentiation yielded highly purified populations of neurons or astrocytes. This report describes the novel use of this cell culture model to study cell type-specific recognition of a human neurotropic virus, JC virus. Infection by either JC virions or a plasmid encoding the JC genome demonstrated susceptibility in astrocytes and, to a lesser degree, progenitor cells, whereas neurons remained nonpermissive. JC virus susceptibility correlated with significantly higher expression of the NFI-X transcription factor in astrocytes than in neurons. Furthermore, transfection of an NFI-X expression vector into progenitor-derived neuronal cells before infection resulted in viral protein production. These results indicate that susceptibility to JC virus infection occurs at the molecular level and also suggest that differential recognition of the viral promoter sequences can predict lineage pathways of multipotential progenitor cells in the human central nervous system. C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Dept Biochem, Buffalo, NY 14214 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, 36 Convent Dr,Bldg 36,Room 5W21, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD34908]; NIDDK NIH HHS [DK58401] NR 44 TC 49 Z9 49 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2003 VL 53 IS 5 BP 636 EP 646 DI 10.1002/ana.10523 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 673EC UT WOS:000182566400011 PM 12730998 ER PT J AU Norton, JA Alexander, HR Fraker, DL Venzon, DJ Gibril, F Jensen, RT AF Norton, JA Alexander, HR Fraker, DL Venzon, DJ Gibril, F Jensen, RT TI Possible primary lymph node gastrinoma: Occurrence, natural history, and predictive factors a prospective study SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 114th Annual Meeting of the Southern-Surgical-Association CY DEC 01-04, 2002 CL PALM BEACH, FLORIDA SP SO Surg Assoc ID ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; ENDOCRINE NEOPLASIA TYPE-1; DUODENAL GASTRINOMAS; SECRETIN INJECTION; LONG-TERM; MANAGEMENT; RESECTION; CURE; DIAGNOSIS AB Objective To analyze the results of a prospective study of 176 patients with Zollinger-Ellison syndrome (ZES) (138 sporadic, 38 MEN1) undergoing 207 operations over a 17-year period. Summary Background Data The existence of lymph node (LN) primary gastrinoma causing ZES is controversial. Methods Three groups of patients were compared: LN only resected cured, and no relapse (likely LN primary); same criteria but relapse (unlikely LN primary); and duodenal primary and LN metastases (Duo-LN). Results Forty-five (26%) had only LN(s) as the initial tumor found Twenty-six of the 45 (58%) fit the definition of a likely LN primary because they were apparently cured postresection. At 10.4 +/- 1.2 years, 69% of the 26 patients with likely LN primary tumors have remained cured and have LN primaries. In the 8 of 26 with recurrent ZES, it occurred at 5 1 years, and 3 had duodenal gastrinoma that had been missed. Ten percent (13/138) of all patients with sporadic ZES and 0% (0/38) with ZES and MEN1 remained cured with only a LN tumor removed. In patients with sporadic gastrinomas no clinical, laboratory, or radiographic localization feature differed among patients with likely LN primary (n = 16) and those with unlikely LN primary (n = 6) or those with Duo-LN (n 37). In the likely LN primary group, the largest LN was 2.2 +/- 0.2 cm, the number of LNs removed was 1.3 +/- 0.1 (25% greater than or equal to 1 LN), and 78% were in the gastrinoma triangle, which also did not differ from the other 2 groups. Disease-free survival was similar in the likely LN primary group, patients with Duo-LN, and those with pancreatic primaries. Conclusions These results support the conclusion that primary LN gastrinomas occur and are not rare (approximately 10% of sporadic cases). These results suggest that a proportion (25%) of these tumors are either multiple or malignant. Because no clinical, laboratory, or tumoral characteristic distinguishes patients with LN primary tumors, all patients with ZES undergoing surgery should have an extensive exploration to exclude duodenal or pancreatic tumors and routine removal of lymph nodes in the gastrinoma triangle. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. NCI, Surg Branch, Surg Metab Sect, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. NIDDK, Digest Dis Branch, Bethesda, MD 20892 USA. RP Norton, JA (reprint author), Univ Calif San Francisco, Dept Surg, 533 Parnassus Ave,U-371,Box 0790, San Francisco, CA 94143 USA. RI Venzon, David/B-3078-2008 FU NCI NIH HHS [R01 CA094143] NR 45 TC 70 Z9 71 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2003 VL 237 IS 5 BP 650 EP 657 DI 10.1097/00000658-200305000-00007 PG 8 WC Surgery SC Surgery GA 730MN UT WOS:000185834700012 PM 12724631 ER PT J AU Valentin, A Pavlakis, GN AF Valentin, A Pavlakis, GN TI Natural killer cells are persistently infected and resistant to direct killing by HIV-1 SO ANTICANCER RESEARCH LA English DT Article; Proceedings Paper CT 4th International Confrence on Gene Regulation, Oncogenesis and AIDS CY SEP 22-26, 2002 CL ATHENS, GREECE DE AIDS; green fluorescent protein; HIV-1 pathogenesis; Natural Killer cells; NKT cells monocyte/macrophage ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECEPTORS; INVITRO; TYPE-1 AB We have reported the presence of a CD4+ subpopulation of Natural Killer cells (NK) in humans. These cells also express HIV coreceptors CCR5 or CXCR4 and are infectable by HTV- 1. Infection is productive and persistent in vitro and in vivo. Infected people under therapy have evidence of viral DNA in their NK pool. fit vitro experiments show that the NK compartment is important for virus propagation, since HIV-1 growth is significantly reduced in PBMC depleted of NK cells. This reduction was observed for both R5 and X4 molecular clones of HTV- 1. In addition, evidence is presented demonstrating that infected NK cells are killed less efficiently by the virus as compared to T cells. This is reminiscent of macrophage infection, where the virus-infected cells survive for long periods of time. Therefore few infected NK cells may contribute significantly to the infectious virus produced in vitro. These results further underscore the importance of NK injection for understanding pathogenic mechanisms leading to AIDS, as well as the various reservoirs and sanctuaries for HIV upon antiretroviral treatment. C1 NCI, BRL, Human Retrovirus Sect, Frederick, MD 21702 USA. RP Pavlakis, GN (reprint author), NCI, BRL, Human Retrovirus Sect, Bldg 535,Rm 210, Frederick, MD 21702 USA. NR 14 TC 8 Z9 8 U1 0 U2 4 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 2003 VL 23 IS 3A BP 2071 EP 2075 PG 5 WC Oncology SC Oncology GA 704UN UT WOS:000184359100011 PM 12894580 ER PT J AU Athanasiou, M Blair, DG Mavrothalassitis, G AF Athanasiou, M Blair, DG Mavrothalassitis, G TI ERF, an ETS-related transcriptional repressor, can induce erythroid differentiation SO ANTICANCER RESEARCH LA English DT Article; Proceedings Paper CT 4th International Confrence on Gene Regulation, Oncogenesis and AIDS CY SEP 22-26, 2002 CL ATHENS, GREECE DE ERF; ETS; ERK; erythroid differentiation; erythroleukemia ID ERYTHROLEUKEMIC CELL-LINES; TUMOR-SUPPRESSOR GENE; K562 CELLS; MEGAKARYOCYTIC DIFFERENTIATION; V-ETS; INCREASED EXPRESSION; TARGETED DISRUPTION; LEUKEMIA-CELLS; T-CELLS; H-RAS AB Ets-family genes have been implicated in leukemia, as well as in normal hematopoiesis. ERF is an ets-related gene that represses transcription and is regulated by MAPK phosphorylation through its effect on ERF sub-cellular localization. Using pluripotent human cell lines, we studied the effect of ERF on erythroid differentiation. K562 and HEL cells expressing ERF expressed elevated levels of the etythroid-specific markers CD71 and Glycophorin A, as well as hemoglobin and GATA1. Treatment with the Erk kinase inhibitor PD98058 further enhanced the erythroid phenotype in ERF-expressing cells and cells expressing a non-phosphorylatable ERF mutant exhibited an even more enhanced phenontype. These results are consistent with the fact that ERF function is regulated by MAPK, and suggest that the effect of the MAPK pathway in erythroid differentiation is partially mediated by ERF. The effect of ERF is similar to the one shown for ETS1 and opposite to the FLI1 function in these cells, suggesting that several ets genes may play key roles in hematopoietic differentiation. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Basic Res Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, OMS, BRL,DBS,NCI,NIH, Frederick, MD 21702 USA. FORTH, IMBB, GR-71110 Iraklion, Crete, Greece. Med Univ Crete, GR-71110 Iraklion, Crete, Greece. RP Athanasiou, M (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC, Basic Res Program, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 54 TC 3 Z9 3 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 2003 VL 23 IS 3A BP 2143 EP 2153 PG 11 WC Oncology SC Oncology GA 704UN UT WOS:000184359100020 PM 12894589 ER PT J AU Lelong-Rebel, IH Rebel, G Cardarelli, CO Pastan, I Gottesman, MM AF Lelong-Rebel, IH Rebel, G Cardarelli, CO Pastan, I Gottesman, MM TI Modulation by the ATP/GTP ratio of the phosphorylation level of P-glycoprotein and of various plasma membrane proteins of KB-V1 multidrug resistant cells SO ANTICANCER RESEARCH LA English DT Article DE KB-V1; plasma membrane; vesicles; protein phosphorylation; GTP; ATP; kinases ID NUCLEOSIDE DIPHOSPHATE KINASE; KB CARCINOMA-CELLS; MYOSIN LIGHT-CHAIN; ATP-GAMMA-S; ALKALINE-PHOSPHATASE; DRUG ACCUMULATION; HUMAN-NEUTROPHILS; POTENT INHIBITOR; STATE KINETICS; GTP AB The level of protein phosphorylation is known to affect the properties of various membrane proteins. We have previously shown that GTP is capable of greatly enhancing the phosphorylation by [gamma-P-32]ATP of P-glycoprotein (Pgp) from KB-V1 cells (3). Investigating the possibility of a general modulation of [gamma-P-32]ATP plasma membrane protein phosphorylation, we found that phosphorylation of other membrane proteins are also modulated by various combinations of [ATP+GTP]. The ATP/GTP ratio giving the highest phosphorylation level depended on the protein studied. Modulation of the [gamma-P-32]ATP-mediated phosphorylation of numerous membrane proteins requires hydrolysis of both ATP and GTP. ADP and GDP also increased [gamma-P-32]ATP-driven phosphorylation but to a lesser extent than GTP. This plasma membrane endogenous phosphorylation activity was neither inhibited by specific inhibitors of protein kinase C, nor by inhibitors of cAMP- or cGMP-dependent protein kinases or of casein kinase II, respectively. Mastoparan, a G-protein regulator, increased the phosphorylation of some proteins that were already enhanced by the presence of [ATP+GTP] mixtures, especially proteins migrating in gels at the same position as P-glycoprotein. C1 Hop Univ Strasbourg, UPR 9003 CNRS, IRCAD, F-67091 Strasbourg, France. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lelong-Rebel, IH (reprint author), Hop Univ Strasbourg, UPR 9003 CNRS, IRCAD, BP 426, F-67091 Strasbourg, France. NR 82 TC 5 Z9 5 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 2003 VL 23 IS 3B BP 2363 EP 2375 PG 13 WC Oncology SC Oncology GA 704UP UT WOS:000184359200023 PM 12894516 ER PT J AU Pitcher, WH Kirby, TW DeRose, EF London, RE AF Pitcher, WH Kirby, TW DeRose, EF London, RE TI Metabolic transformation of AZTp(4)A by Ap(4)A hydrolase regenerates AZT triphosphate SO ANTIVIRAL RESEARCH LA English DT Article DE Ap(4)A hydrolase; HIV; reverse transcriptase; AZT(p4)A; AZT; P-31 NMR ID VIRUS REVERSE-TRANSCRIPTASE; BLOOD MONONUCLEAR-CELLS; DIADENOSINE 5',5'''-P1,P4-TETRAPHOSPHATE; DINUCLEOSIDE TETRAPHOSPHATASE; INTRACELLULAR METABOLISM; PURIFICATION; MECHANISM; 3'-AZIDO-3'-DEOXYTHYMIDINE; POLYPHOSPHATES; HOMOGENEITY AB The reverse transcriptase (RT) of HIV which has been inhibited by the incorporation of AZT into the primer strand is subject to a deblocking reaction by cellular ATP. This reaction yields unblocked primer plus the dinucleoside tetraphosphate, AZT(P4)A. In the present study, we report that AZT(P4)A is an excellent substrate for the enzyme A(P4)A hydrolase (asymmetrical dinucleoside tetraphosphatase, EC 3.6.1.17), an enzyme that is widely distributed in many cell types. Progress of the reaction has been monitored by P-31 NMR, and it was found that hydrolysis results in the production of AZTTP:ATP in a 7:1 ratio. The AZT(P4)A was also hydrolyzed at a rate 1.8-fold more rapidly than A(P4)A. Spectrophotometric assays yielded Michaelis constants of 2.35 and 0.71 muM for A(P4)A and AZT(P4)A, respectively. It, therefore. appears that A(P4)A hydrolase can play a useful role in the regeneration of the AZTTP, the active form of AZT, for the inhibition of HIV RT. Published by Elsevier Science B.V. C1 NIEHS, Dept Hlth & Human Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Dept Hlth & Human Sci, Struct Biol Lab, POB 12233,MR-01, Res Triangle Pk, NC 27709 USA. NR 27 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2003 VL 58 IS 3 BP 227 EP 233 DI 10.1016/S0166-3542(03)00003-2 PG 7 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 688GC UT WOS:000183425000005 PM 12767470 ER PT J AU Gadomski, A Bennett, S Young, M Wissow, LS AF Gadomski, A Bennett, S Young, M Wissow, LS TI Guidelines for adolescent preventive services - The GAPS in practice SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04-07, 2002 CL BALTIMORE, MARYLAND SP Pediatr Acad Soc ID PRIMARY-CARE; HEALTH; WELL AB Design: Pre- and post-Guidelines for Adolescent Preventive Services (GAPS) comparison of outcomes gathered via chart audit. Setting: A rural hospital-based general pediatric clinic. Participants: Adolescents who underwent annual examinations between April 1, 1998, and March 31, 2001. A random sample of 441 medical records was reviewed. Intervention: Training in the GAPS model and use of the questionnaire began in April 1998. Main Outcome Measures: Detection of, discussion of, and referrals for GAPS-related risk behavior. Results: The medical records of 162 younger adolescents (aged 11-15 years) and 279 older adolescents (aged 16-19 years) were audited. Detection of risk behaviors increased from 19% at baseline to 95% with the initial GAPS and 87% with the periodic GAPS. The most prevalent risk factor was having a rifle or gun in the home (younger adolescents, 47% and older adolescents, 39%). The mean number of risk behaviors and health concerns documented was higher in the initial GAPS (4.8 and 1.3, respectively) than in the periodic GAPS (3.8 and 0.7) (P = .01 and .006). The GAPS questionnaires detected lower levels of risk behavior compared with a local Youth Risk Behavior Survey. Controlling for sex, age, and clinician, discussion of psychosocial topics increased during the study period; however, there was considerable variation among clinicians regarding the topics addressed. The GAPS-related referral rate did hot change significantly. Conclusion: The GAPS model increases clinicians' detection and discussion of risk behaviors. C1 Bassett Healthcare, Res Inst, Cooperstown, NY 13326 USA. Bassett Healthcare, Dept Adult & Pediat Med, Cooperstown, NY 13326 USA. NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. RP Gadomski, A (reprint author), Bassett Healthcare, Res Inst, 1 Atwell Rd, Cooperstown, NY 13326 USA. FU NIMH NIH HHS [MH01790] NR 20 TC 18 Z9 18 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAY PY 2003 VL 157 IS 5 BP 426 EP 432 DI 10.1001/archpedi.157.5.426 PG 7 WC Pediatrics SC Pediatrics GA 675FX UT WOS:000182684000003 PM 12742877 ER PT J AU Hunt, CE Lesko, SM Vezina, RM McCoy, R Corwin, MJ Mandell, F Willinger, M Hoffman, HJ Mitchell, AA AF Hunt, CE Lesko, SM Vezina, RM McCoy, R Corwin, MJ Mandell, F Willinger, M Hoffman, HJ Mitchell, AA TI Infant sleep position and associated health outcomes SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID DEATH-SYNDROME AB Background: The incidence of sudden infant death syndrome has decreased in the United States as the percentage of infants sleeping prone has decreased, but persisting concerns about the safety of supine sleeping likely contribute to prone sleeping prevalence rates that remain higher than 10%. Objective: To document health outcomes in infants aged 1 to 6 months in relation to sleep position. Design: Prospective cohort study. Setting: Massachusetts and Ohio, from February 21, 1995, to December 31, 1998. Study Participants: A total of 3733 infants with consistent sleep positions at ages 1, 3, and 6 months. Main Outcome Measures: Descriptive statistics and multiple logistic regression analysis relating sleep position at each follow-up age to symptoms in the prior week (fever, cough, wheezing, stuffy nose, trouble breathing or sleeping, diarrhea, vomiting, or spitting up) and outpatient visits in the prior month (ear infection, breathing problem, vomiting, spitting up, colic, seizure, accident, or injury). Results: No symptoms or outpatient visits were significantly more common among infants sleeping on the side or supine than in infants sleeping prone, and 3 symptoms were less common: (1) fever at 1 month in infants sleeping in the supine (adjusted odds ratio [OR], 0.56; 95% confidence interval [CI], 0.34-0.93) and side positions (OR, 0.48; 95% CI, 0.28-0.82); (2) stuffy nose at 6 months in the supine (OR, 0.74; 95% CI, 0.61-0.89) and side positions (OR, 0.82; 95% CI, 0.68-0.99); and (3) trouble sleeping at 6 months in the supine (OR, 0.57; 95% CI] 0.44-0.73) and side positions (OR, 0.69; 95% CI, 0.53-0.89) Also, outpatient visits for ear infections were less common at 3 and 6 months in infants sleeping in the supine position (OR, 0.64; 95% CI, 0.46-0.88; and OR, 0.73; 95% CI, 0.58-0.92, respectively) and at 3 months in the side position (OR, 0.68; 95% CI, 0.49-0.96). Concluslons: No identified symptom or illness was significantly increased among nonprone sleepers during the first 6 months of life. These reassuring results may contribute to increased use of the supine position for infant sleeping. C1 Med Coll Ohio, Dept Pediat, Toledo, OH 43699 USA. Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA USA. NICHHD, Bethesda, MD 20892 USA. NIDCD, Dept Hlth & Human Services, NIH, Bethesda, MD USA. RP Hunt, CE (reprint author), NHLBI, Natl Ctr Sleep Disorders Res, Rockledge Ctr 2, Room 1003,6701 Rockledge Dr,MSC 7920, Bethesda, MD 20892 USA. FU NICHD NIH HHS [N01-HD-4-3221] NR 13 TC 16 Z9 17 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAY PY 2003 VL 157 IS 5 BP 469 EP 474 DI 10.1001/archpedi.157.5.469 PG 6 WC Pediatrics SC Pediatrics GA 675FX UT WOS:000182684000009 PM 12742883 ER PT J AU Blaney, JE Manipon, GG Murphy, BR Whitehead, SS AF Blaney, JE Manipon, GG Murphy, BR Whitehead, SS TI Temperature sensitive mutations in the genes encoding the NS1, NS2A, NS3, and NS5 nonstructural proteins of dengue virus type 4 restrict replication in the brains of mice SO ARCHIVES OF VIROLOGY LA English DT Article ID LIVE ATTENUATED VACCINE; TICK-BORNE ENCEPHALITIS; HOST-RANGE; CANDIDATE; IMMUNOGENICITY; MUTAGENESIS; CELLS; NEUROVIRULENCE; PHENOTYPES; FLAVIVIRUS AB Using reverse genetics, it is possible to readily add well-defined attenuating mutations to the genome of wild type or incompletely attenuated dengue (DEN) viruses to generate vaccine candidates that exhibit the desired balance between attenuation and immunogenicity. Here, we describe the identification of eight temperature sensitive missense mutations distributed in four non-structural protein genes that specify a 60- to 10,000-fold range of restricted replication in the suckling mouse brain compared to wild type recombinant DEN4 virus. The usefulness of such mutations in flavivirus vaccine design and development is discussed. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Blaney, JE (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NR 27 TC 15 Z9 15 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD MAY PY 2003 VL 148 IS 5 BP 999 EP 1006 DI 10.1007/s00705-003-0007-y PG 8 WC Virology SC Virology GA 675NQ UT WOS:000182701800013 PM 12721805 ER PT J AU Begg, M Lovinger, D Kunos, G AF Begg, M Lovinger, D Kunos, G TI Identification of a Ca2+-dependent K+ current and its modulation by atypical cannabinoid ligands in cultured human umbilical vein endothelial cells SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P202 BP A36 EP A36 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500226 ER PT J AU Freeman, LA Remaley, AT Bark, S Brewer, B Santamarina-Fojo, S AF Freeman, LA Remaley, AT Bark, S Brewer, B Santamarina-Fojo, S TI Transcriptional regulation of the ABCG5/ABCG8 promoters SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P438 BP A76 EP A76 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500445 ER PT J AU Joyce, CW Amar, M Knapper, C Syed, J Vaisman, B Basso, F Hoyt, R Brewer, HB Santamarina-Fojo, S AF Joyce, CW Amar, M Knapper, C Syed, J Vaisman, B Basso, F Hoyt, R Brewer, HB Santamarina-Fojo, S TI Overexpression of ABCA1 in an LDLr-/- background results in cholesterol enrichment of plasma ApoB-containing lipoproteins and enhanced aortic atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA 29 BP A6 EP A6 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500066 ER PT J AU Kamei, M Weinstein, B AF Kamei, M Weinstein, B TI Characterization of a zebrafish homologue of vascular endothelial cadherin SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P233 BP A41 EP A41 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500253 ER PT J AU Kruth, HS Huang, W Zhao, B Ishii, I Zhang, WY AF Kruth, HS Huang, W Zhao, B Ishii, I Zhang, WY TI PMA activation of macrophages stimulates fluid-phase endocytic uptake of native LDL generating foam cells SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P55 BP A11 EP A11 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500092 ER PT J AU Mugford, JW Lawson, ND Pham, VP Weinstein, BM AF Mugford, JW Lawson, ND Pham, VP Weinstein, BM TI y11, a zebrafish mutant affecting blood vessel morphogenesis and arterial-venous identity SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P174 BP A31 EP A31 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500199 ER PT J AU Torres-Vazquez, J Kamei, M Pine, H Berk, JD Weinstein, BM AF Torres-Vazquez, J Kamei, M Pine, H Berk, JD Weinstein, BM TI An F3 genetic screen using Transgenic zebrafish to uncover mutations affecting vascular development SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P178 BP A32 EP A32 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500203 ER PT J AU Wang, MY Lakatta, EG AF Wang, MY Lakatta, EG TI Matrix metalloproteinase type II activity and internal elastic lamina remodeling of coronary arteries with ageing in rodents SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P463 BP A80 EP A80 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500470 ER PT J AU Wu, JE Basso, F Shamburek, RD Amar, MJ Vaisman, B Tansey, T Lita, F Paigen, B Fruchart-Najib, J Brewer, HB Santamarina-Fojo, S AF Wu, JE Basso, F Shamburek, RD Amar, MJ Vaisman, B Tansey, T Lita, F Paigen, B Fruchart-Najib, J Brewer, HB Santamarina-Fojo, S TI Overexpression of human ABCG5 and ABCG8 in transgenic mice: Effects on intestinal cholesterol absorption, biliary sterol excretion and atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 4th Annual Conference on Arteriosclerosis Thrombosisand Vascular Biology CY MAY 08-10, 2003 CL WASHINGTON, D.C. C1 NHLBI, Bethesda, MD 20892 USA. Jackson Labs, Bar Harbor, ME USA. Inst Pasteur, F-59019 Lille, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2003 VL 23 IS 5 MA P241 BP A42 EP A43 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 676GG UT WOS:000182742500261 ER PT J AU Jacobi, AM Odendahl, M Reiter, K Bruns, A Burmester, GR Radbruch, A Valet, G Lipsky, PE Dorner, T AF Jacobi, AM Odendahl, M Reiter, K Bruns, A Burmester, GR Radbruch, A Valet, G Lipsky, PE Dorner, T TI Correlation between circulating CD27(high) plasma cells and disease activity in patients with systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Article ID BLOOD MONONUCLEAR-CELLS; CONSENSUS-STUDY-GROUP; B-CELLS; PERIPHERAL-BLOOD; AUTOANTIBODY PRODUCTION; CD40 LIGAND; RHEUMATOLOGY RESEARCH; EUROPEAN WORKSHOP; SJOGRENS-SYNDROME; 9G4 IDIOTOPE AB Objective. Disease activity in systemic lupus erythematosus (SLE) is usually assessed with complex disease activity scores comprising a variety of different parameters. In order to determine whether SLE disease activity correlates with abnormal B lymphocyte activity, B cell subsets were analyzed, and their relationship to clinical and humoral measures of disease activity was assessed. Methods. The distribution of B cell subsets was determined by fluorescence-activated cell sorting analysis and assessed in relation to the autoantibody profile, disease activity measured by the SLE Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measure scores, disease duration, and therapy. Results. The number and frequency of CD27(high) plasma cells were significantly correlated with the SLE disease activity indices and with the titer of anti-double-stranded DNA (anti-dsDNA) autoantibodies. Circulating B cell subsets were not influenced by age or sex, but appeared to relate to the duration of disease and the therapeutic regimen, with the number and frequency of CD27(high) plasma cells increasing and those of CD27- naive B cells decreasing over time. Patients were divided into those with a SLEDAI score of 0-8 (low disease activity) and those with SLEDAI score >8 (high disease activity). Patients with high disease activity had an increased frequency of both CD19+ B cells and CD27(high) plasma cells. By using a nonparametric data sieving algorithm, we observed that these B cell abnormalities provided predictive values for nonactive and active disease of 78.0% and 78.9%, respectively. The predictive value of the B cell abnormalities (78.9%) was greater than that of the humoral/clinical data pattern (71.4%), including anti-dsDNA antibody levels, circulating immune complexes, increased erythrocyte sedimentation rate, mucocutaneous involvement, and acute renal involvement. Conclusion. Flow cytometric monitoring of B cell subsets in the peripheral blood provides new insights into abnormalities of B cell function in SLE and may also be a diagnostically valuable option for monitoring the activity of this autoimmune disease. C1 Univ Hosp Charite, Dept Med Rheumatol & Clin Immunol, D-10098 Berlin, Germany. Deutsch Rheumaforschungszentrum, Berlin, Germany. Max Planck Inst Biochem, D-8000 Munich, Germany. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Dorner, T (reprint author), Univ Hosp Charite, Dept Med Rheumatol & Clin Immunol, Schumannstr 20-21, D-10098 Berlin, Germany. NR 53 TC 189 Z9 200 U1 0 U2 9 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 2003 VL 48 IS 5 BP 1332 EP 1342 DI 10.1002/art.10949 PG 11 WC Rheumatology SC Rheumatology GA 676DL UT WOS:000182736600018 PM 12746906 ER PT J AU van Laar, JM Pavletic, SZ AF van Laar, JM Pavletic, SZ TI CD34-selected versus unmanipulated grafts for severe rheumatoid arthritis: comment on the article by Moore et al SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID STEM-CELL TRANSPLANTATION C1 Leiden Univ, Med Ctr, Leiden, Netherlands. NCI, NIH, Bethesda, MD 20892 USA. RP van Laar, JM (reprint author), Leiden Univ, Med Ctr, Leiden, Netherlands. NR 9 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 2003 VL 48 IS 5 BP 1463 EP 1464 DI 10.1002/art.11071 PG 2 WC Rheumatology SC Rheumatology GA 676DL UT WOS:000182736600038 PM 12746925 ER PT J AU Peterson, C Ringner, M AF Peterson, C Ringner, M TI Analyzing tumor gene expression profiles SO ARTIFICIAL INTELLIGENCE IN MEDICINE LA English DT Article DE artificial neural networks; biomformatics; diagnostic prediction; drug target identification; genes; microarray ID MOLECULAR CLASSIFICATION; CLUSTER-ANALYSIS; MICROARRAY DATA; BREAST-CANCER; PATTERNS; HYBRIDIZATION; PREDICTION; SIGNATURES AB A brief introduction to high throughput technologies for measuring and analyzing gene expression is given. Various supervised and unsupervised data mining methods for analyzing the produced high-dimensional data are discussed. The main emphasis is on supervised machine learning methods for classification and prediction of tumor gene expression profiles. Furthermore, methods to rank the genes according to their importance for the classification are explored. The approaches are illustrated by exploratory studies using two examples of retrospective clinical data from routine tests; diagnostic prediction of small round blue cell tumors (SRBCT) of childhood and determining the estrogen receptor (ER) status of sporadic breast cancer. The classification performance is gauged using blind tests. These studies demonstrate the feasibility of machine learning-based molecular cancer classification. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Lund Univ, Dept Theoret Phys, Complex Syst Div, SE-22362 Lund, Sweden. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Peterson, C (reprint author), Lund Univ, Dept Theoret Phys, Complex Syst Div, Solvegatan 14A, SE-22362 Lund, Sweden. EM carsten@thep.lu.se; markus@thep.lu.se RI Ringner, Markus/G-3641-2011 OI Ringner, Markus/0000-0001-5469-8940 NR 28 TC 24 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0933-3657 J9 ARTIF INTELL MED JI Artif. Intell. Med. PD MAY PY 2003 VL 28 IS 1 BP 59 EP 74 DI 10.1016/S0933-3657(03)00035-6 PG 16 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 701JQ UT WOS:000184164800003 PM 12850313 ER PT J AU Subramaniam, S Zhang, PJ Lefman, J Juliani, J Kessel, M AF Subramaniam, S Zhang, PJ Lefman, J Juliani, J Kessel, M TI Electron tomography: a powerful tool for 3D cellular microscopy SO ASM NEWS LA English DT Article ID ARCHITECTURE C1 NCI, Biochem Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Subramaniam, S (reprint author), NCI, Biochem Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 7 TC 2 Z9 2 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0044-7897 J9 ASM NEWS JI ASM News PD MAY PY 2003 VL 69 IS 5 BP 240 EP + PG 5 WC Microbiology SC Microbiology GA 757HT UT WOS:000187557500014 ER PT J AU Desai, RI Terry, P Katz, JL AF Desai, RI Terry, P Katz, JL TI Comparison of the discriminative-stimulus effects of SKF 38393 with those of other dopamine receptor agonists SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE dopamine D1 receptors; drug discrimination; cocaine; quinpirole; SKIF 38393; adenylyl cyclase; rat ID ADENYLATE-CYCLASE ACTIVITY; GTP-GAMMA-S; VARYING EFFICACIES; PHARMACOLOGICAL CHARACTERIZATION; D1-RECEPTOR AGONISTS; D-1-LIKE RECEPTOR; SQUIRREL-MONKEYS; RHESUS-MONKEYS; SKF 38393; RATS AB The dopamine D-1-like receptor agonists have traditionally been defined molecularly by their efficacy in stimulating adenylyl cyclase. However, evidence correlating the effectiveness of these drugs in behavioral assays and their effectiveness biochemically has not been forthcoming. The present study compared the discriminative-stimulus effects of the D-1-like partial agonist SKF 38393 with several other D-1-like agonists, an indirect agonist, cocaine, and a D-2-like agonist, quinpirole. Rats were trained under a fixed-ratio 30-response schedule to discriminate SKF 38393 (5.6 mg/kg) from vehicle. Under this schedule, 30 consecutive responses on one of two keys were reinforced with food presentation after a pre-session injection of 5.6 mg/kg SKF 38393, and 30 consecutive responses on the alternative key were reinforced after saline injection. When daily performances were stable, substitution patterns for several compounds were assessed during test sessions in which 30 consecutive responses on either key were reinforced. Quinpirole and cocaine each produced saline-appropriate responding. In contrast, the D-1-like agonists, SKF 75670 and SKF 77434, fully substituted for SKF 38393. Curiously, SKF 82958, which is considered a full agonist based on adenylyl cyclase assays, was less effective in substituting for SKF 38393 (maximum drug-appropriate responding 66%) than was the partial agonist SKF 75670. The present results suggest that second messenger effects other than stimulation of adenylyl cyclase may play an important role in the behavioral effects of dopamine D-1-like agonists. C1 NIDA, Psychobiol Sect, Intramural Res Program, NIH,US Dept HHS, Baltimore, MD 21224 USA. Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England. RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, NIH,US Dept HHS, POB 5180, Baltimore, MD 21224 USA. OI Katz, Jonathan/0000-0002-1068-1159 NR 46 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD MAY PY 2003 VL 14 IS 3 BP 223 EP 228 DI 10.1097/01.fbp.0000073701.15098.fa PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 693TZ UT WOS:000183735600006 PM 12799524 ER PT J AU Cho, H Harrison, K Schwartz, O Kehrl, JH AF Cho, H Harrison, K Schwartz, O Kehrl, JH TI The aorta and heart differentially express RGS (regulators of G-protein signalling) proteins that selectively regulate sphingosine 1-phosphate, angiotensin II and endothelin-1 signalling SO BIOCHEMICAL JOURNAL LA English DT Article DE heterotrimeric G-protein signalling; regulators of G-protein signalling (RGS) protein; sphingosine 1-phosphate (S1P) receptors ID SMOOTH-MUSCLE CELLS; SPHINGOSINE-1-PHOSPHATE RECEPTOR EDG-1; COUPLED RECEPTOR; MESSENGER-RNA; CARDIAC-HYPERTROPHY; OLFACTORY NEURONS; MICE LACKING; MORPHOGENESIS; STIMULATION; INHIBITION AB Normal cardiovascular development and physiology depend in part upon signalling through G-protein-coupled receptors (GPCRs), such as the angiotensin 11 type I (AT(1)) receptor, sphingosine I-phosphate (SIP) receptors and endothelin-1 (ET-1) receptor. Since regulator of G-protein signalling (RGS) proteins function as GTPase-activating proteins for the Galpha subunit of heterotrimeric G-proteins, these proteins undoubtedly have functional roles in the cardiovascular system. In the present paper, we show that human aorta and heart differentially express RGS1, RGS2, RGS3S (short-form), RGS3L (long-form), PDZ-RGS3 (PDZ domain-containing) and RGS4. The aorta prominently expresses mRNAs for all these RGS proteins except PDZ-RGS3. Various stimuli that are critical for both cardiovascular development and function regulate dynamically the mRNA smooth muscle cells. Both RGS1 and RGS3 inhibit signalling through the SIP, (formerly known as EDG-1), S1P(2) (formerly known as EDG-5) and S1P(3) (formerly known as EDG-3) receptors, whereas RGS2 and RGS4 selectively attenuate S1P(2)- and S1P(3)-receptor signalling respectively. All of the tested RGS proteins inhibit AT(1)-receptor signalling, whereas only RGS3 and, to a lesser extent, RGS4 inhibit ETA-receptor signalling. The conspicuous expression of RGS proteins in the cardiovascular system and their selective effects on relevant GPCR-signalling pathways provide additional evidence that they have functional roles in cardiovascular development and physiology. C1 NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Biol Imaging Facil, Res Technol Branch, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Room 11B-08,Bldg 10,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. OI Kehrl, John/0000-0002-6526-159X NR 48 TC 56 Z9 57 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 2003 VL 371 BP 973 EP 980 DI 10.1042/BJ20021769 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 676CB UT WOS:000182733400034 PM 12564955 ER PT J AU Rigourd, M Bec, G Benas, P Le Grice, SFJ Ehresmann, B Ehresmann, C Marquet, R AF Rigourd, M Bec, G Benas, P Le Grice, SFJ Ehresmann, B Ehresmann, C Marquet, R TI Effects of tRNA(3)(Lys) aminoacylation on the initiation of HIV-1 reverse transcription SO BIOCHIMIE LA English DT Article DE tRNA; primer; polymerase; retrovirus; AIDS ID TRANSFER-RNA-SYNTHETASE; IMMUNODEFICIENCY-VIRUS TYPE-1; DEPENDENT DNA POLYMERASE; ROUS-SARCOMA VIRUS; MACROMOLECULAR COMPLEXES; POLYPEPTIDE COMPONENTS; WILD-TYPE; PRIMER; TRNA(LYS3); MUTANT AB HIV-1 utilizes cellular tRNA(3)(Lys) to prime the initiation of reverse transcription. The selective incorporation of cytoplasmic tRNA(3)(Lys) into HIV-1 particles was recently shown to involve the lysyl-tRNA synthetase, and hence, the encapsidated tRNA(3)(Lys) is likely to be aminoacylated. Here, we tested the effect of aminoacylation on the initiation of reverse transcription. We show that HIV-1 reverse transcriptase is unable to extend lysyl-tRNA(3)(Lys). In addition, the viral polymerase does not significantly enhance the rate of tRNA deacylation, in contrast with previous studies on avian retroviruses. Thus, aminoacylation of the primer tRNA might prevent the initiation of HIV-1 reverse transcription from taking place before viral budding and maturation. (C) 2003 Editions scientifiques et medicales Elsevier SAS and Societe francaise de biochimie et biologic moleculaire. All rights reserved. C1 Univ Strasbourg 1, CNRS, Unite Propre Rech 9002, IBMC, F-67084 Strasbourg, France. NCI, HIV Drug Resistance Program, Resistance Mech Lab, Frederick, MD 21702 USA. RP Marquet, R (reprint author), Univ Strasbourg 1, CNRS, Unite Propre Rech 9002, IBMC, 15 Rue Rene Descartes, F-67084 Strasbourg, France. OI Marquet, Roland/0000-0002-4209-3976 NR 33 TC 5 Z9 5 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD MAY PY 2003 VL 85 IS 5 BP 521 EP 525 DI 10.1016/S0300-9084(03)00045-2 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 687BL UT WOS:000183355900005 PM 12763311 ER PT J AU Pei, S AF Pei, S TI Review of French bioethics laws SO BIOFUTUR LA French DT Article ID STEM-CELLS; CANCER C1 NIH, Bethesda, MD 20892 USA. European Patent Off, Bur Reglementat Brevets Niveau Europeen, Munich, Germany. RP Pei, S (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0294-3506 J9 BIOFUTUR JI Biofutur PD MAY PY 2003 IS 233 BP 33 EP 34 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 705LV UT WOS:000184397300006 ER PT J AU Dobbin, K Shih, JH Simon, R AF Dobbin, K Shih, JH Simon, R TI Statistical design of reverse dye microarrays SO BIOINFORMATICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; DIFFERENTIALLY-EXPRESSED GENES; CDNA MICROARRAY; MODELS; IDENTIFICATION; REPLICATION; CARCINOMAS; PATTERNS; PROFILES AB Motivation: In cDNA microarray experiments all samples are labelled with either Cy3 dye or Cy5 dye. Certain genes exhibit dye bias-a tendency to bind more efficiently to one of the dyes. The common reference design avoids the problem of dye bias by running all arrays 'forward', so that the samples being compared are always labelled with the same dye. But comparison of samples labelled with different dyes is sometimes of interest. In these situations, it is necessary to run some arrays 'reverse'-with the dye labelling reversed-in order to correct for the dye bias. The design of these experiments will impact one's ability to identify genes that are differentially expressed in different tissues or conditions. We address the design issue of how many specimens are needed, how many forward and reverse labelled arrays to perform, and how to optimally assign Cy3 and Cy5 labels to the specimens. Results: We consider three types of experiments for which some reverse labelling is needed: paired samples, samples from two predefined groups, and reference design data when comparison with the reference is of interest. We present simple probability models for the data, derive optimal estimators for relative gene expression, and compare the efficiency of the estimators for a range of designs. In each case, we present the optimal design and sample size formulas. We show that reverse labelling of individual arrays is generally not required. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Dobbin, K (reprint author), NCI, Biometr Res Branch, 6130 Execut Blvd,MSC 7434, Bethesda, MD 20892 USA. NR 33 TC 70 Z9 73 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 1 PY 2003 VL 19 IS 7 BP 803 EP 810 DI 10.1093/bioinformatics/btg076 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 674JZ UT WOS:000182634800003 PM 12724289 ER PT J AU Peddada, SD Lobenhofer, EK Li, LP Afshari, CA Weinberg, CR Umbach, DM AF Peddada, SD Lobenhofer, EK Li, LP Afshari, CA Weinberg, CR Umbach, DM TI Gene selection and clustering for time-course and dose-response microarray experiments using order-restricted inference SO BIOINFORMATICS LA English DT Article ID SAMPLE CLASSIFICATION; EXPRESSION DATA; DISCOVERY AB We propose an algorithm for selecting and clustering genes according to their time-course or dose-response profiles using gene expression data. The proposed algorithm is based on the order-restricted inference methodology developed in statistics. We describe the methodology for time-course experiments although it is applicable to any ordered set of treatments. Candidate temporal profiles are defined in terms of inequalities among mean expression levels at the time points. The proposed algorithm selects genes when they meet a bootstrap-based criterion for statistical significance and assigns each selected gene to the best fitting candidate profile. We illustrate the methodology using data from a cDNA microarray experiment in which a breast cancer cell line was stimulated with estrogen for different time intervals. In this example, our method was able to identify several biologically interesting genes that previous analyses failed to reveal. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Gene Regulat Grp, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, NIEHS Microarray Ctr, Res Triangle Pk, NC 27709 USA. RP Peddada, SD (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. RI Peddada, Shyamal/D-1278-2012 NR 17 TC 97 Z9 100 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 1 PY 2003 VL 19 IS 7 BP 834 EP 841 DI 10.1093/bioinformatics/btg093 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 674JZ UT WOS:000182634800007 PM 12724293 ER PT J AU Friedman, MJ Foa, EB Charney, DS AF Friedman, MJ Foa, EB Charney, DS TI Toward evidence-based early interventions for acutely traumatized adults and children SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 VA Med & Reg Off Ctr, White River Jct, VT 05009 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Friedman, MJ (reprint author), VA Med & Reg Off Ctr, 215 N Main St, White River Jct, VT 05009 USA. NR 8 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2003 VL 53 IS 9 BP 765 EP 768 DI 10.1016/S0006-3223(03)00255-5 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 672VV UT WOS:000182544400001 PM 12725968 ER PT J AU Pine, DS AF Pine, DS TI Developmental psychobiology and response to threats: Relevance to trauma in children and adolescents SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the Anxiety-Disorders-Association-of-America CY MAR, 2002 CL NEW YORK, NEW YORK SP Anixiety Disorders Assoc Amer DE trauma; childhood; adolescence; developmental psychobiology; threat response; posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL ABUSE; CORTICOTROPIN-RELEASING HORMONE; POSITRON-EMISSION-TOMOGRAPHY; INFERIOR TEMPORAL CORTEX; MONKEY SAIMIRI-SCIUREUS; EVENT-RELATED FMRI; COLOR-NAMING TASK; PREFRONTAL CORTEX; ANXIETY DISORDERS AB Interest in developmental and psychobiological aspects of trauma has grown with recent research in adults with mood and anxiety disorders reporting histories of trauma during childhood. Studies conducted directly in children and adolescents could add much to ongoing research in this area. This review summarizes data in three areas of developmental science that might inform future studies. First, the review briefly summarizes current data on clinical aspects of trauma in juveniles, focusing on associations with psychopathology and moderators of outcome. Second, the review summarizes data from the basic sciences delineating experiential and developmental changes in brain systems involved in threat perception and response. This review incorporates knowledge gained from research examining the effects of rearing manipulations on regulation of the stress response in rodents and primates. Third, the review summarizes data from cognitive neuroscience studies among both adults and children, again focusing on studies examining aspects of the threat response. This summary includes a review from studies in patients with posttraumatic stress disorder. Biol Psychiatry 2003;53:796-808 (C) 2003 Society of Biological Psychiatry. C1 NIMH, Sect Dev & Affect Neurosci, NIH, MAP, Bethesda, MD 20892 USA. RP Pine, DS (reprint author), NIMH, Sect Dev & Affect Neurosci, NIH, MAP, 15K North Dr,Room 110,MSC 2670, Bethesda, MD 20892 USA. NR 94 TC 37 Z9 39 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2003 VL 53 IS 9 BP 796 EP 808 DI 10.1016/S0006-3223(03)00112-4 PG 13 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 672VV UT WOS:000182544400005 PM 12725972 ER PT J AU Lissek, S Powers, AS AF Lissek, S Powers, AS TI Sensation seeking and startle modulation by physically threatening images SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE sensation seeking; anxious reactivity; resilience; affective modulation of startle; psychophysiology ID FEAR-POTENTIATED STARTLE; CONDITIONED FEAR; PSYCHOPHYSIOLOGICAL RESPONSES; ELECTRODERMAL RESPONSE; PERSONALITY-DISORDER; TRAIT ANXIETY; REFLEX; EMOTION; PARADIGM; DIAZEPAM AB The potential moderating effect of sensation seeking on anxious reactivity to threatening experiences was assessed using the affective modulation of startle-blink paradigm. Startle blinks, as measured by electromyographic (EMG) activity in response to loud (100 dB) white-noise stimuli, were elicited during the presentation of positive, neutral, and threatening visual images. Unlike participants low in sensation seeking who showed blink potentiation during threatening versus neutral images, participants high in sensation seeking showed equal magnitudes of startle to neutral and threatening images. The results suggest that individuals high compared with low on sensation seeking are less anxiously reactive to physically threatening visual stimuli. No attenuation in startle magnitude was elicited by positive images among low or high sensation seekers suggesting that the positive images employed in the current study were not arousing enough to activate the appetitive arousal system. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Natl Inst Mental Hlth, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. St Johns Univ, Dept Psychol, Jamaica, NY 11439 USA. RP Lissek, S (reprint author), Natl Inst Mental Hlth, Mood & Anxiety Disorders Program, 15K North Dr,Bldg 15K,MSC 2670, Bethesda, MD 20892 USA. RI Lissek, Shmuel/B-6577-2008 NR 64 TC 20 Z9 20 U1 8 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD MAY PY 2003 VL 63 IS 2 BP 179 EP 197 DI 10.1016/S0301-0511(03)00053-X PG 19 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 693TL UT WOS:000183734400006 PM 12738407 ER PT J AU Yang, GY Zhang, YL Buchold, GM Jetten, AM O'Brien, DA AF Yang, GY Zhang, YL Buchold, GM Jetten, AM O'Brien, DA TI Analysis of germ cell nuclear factor transcripts and protein expression during spermatogenesis SO BIOLOGY OF REPRODUCTION LA English DT Article DE GCNF; gene regulation; nuclear orphan receptor; spermatogenesis; testis ID TESTIS-ASSOCIATED RECEPTOR; ORPHAN RECEPTOR; MESSENGER-RNA; DNA-BINDING; TRANSLATIONAL REGULATION; DIFFERENTIAL EXPRESSION; MOUSE SPERMIOGENESIS; RESPONSE ELEMENT; MAMMALIAN TESTIS; XENOPUS-LAEVIS AB Germ cell nuclear factor (GCNF), an orphan receptor in the nuclear receptor superfamily, is expressed predominantly in developing germ cells in the adult mouse. Two Gcnf transcripts (7.4 and 2.1 kilobase [kb]) encoded by a single copy gene are expressed in the testis of several mammalian species. To identify features that regulate Gcnf expression, we characterized the structure and sequence of the mouse gene and its two transcripts and determined the expression profile of the GCNF protein during spermatogenesis. Genomic fragments spanning part of the 5'-untranslated region (UTR), the coding sequence, and the complete 3'-UTR (similar to80 kb) were isolated and sequenced. The 3'-UTRs of the two transcripts are quite distinct. The 7.4 kb transcript, which appears earlier in spermatogenesis, has a very long 3'-UTR of 4451 nucleotides. In contrast, the 2.1 kb transcript, which is expressed predominantly during the haploid phase of spermatogenesis, has a 3'-UTR that is only 202 nucleotides in length. Additional analyses indicate that both transcripts share the same coding region and are associated with polysomes. A single GCNF protein band was detected in testis extracts by Western blotting with a specific antiserum. Immunohistochemical analysis showed that GCNF is localized in the nuclei of pachytene spermatocytes and round spermatids. GCNF is first detectable in early pachytene spermatocytes (stage II) and is continuously expressed until spermatids begin to elongate in stage IX. Although GCNF is generally distributed throughout the nucleus, it is particularly prominent in heterochromatic regions at some stages and in condensed chromosomes undergoing the meiotic divisions. This expression profile suggests that GCNF plays a role in transcriptional regulation during meiosis and the early haploid phase of spermatogenesis. C1 Univ N Carolina, Dept Cell & Dev Biol, Sch Med, Labs Reprod Biol, Chapel Hill, NC 27599 USA. NIEHS, Pulm Pathobiol Lab, Cell Biol Sect, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Med, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China. Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA. RP O'Brien, DA (reprint author), Univ N Carolina, Dept Cell & Dev Biol, Sch Med, Labs Reprod Biol, CB 7090,214A Taylor Hall, Chapel Hill, NC 27599 USA. OI Jetten, Anton/0000-0003-0954-4445 FU FIC NIH HHS [TW/HD00627]; NCI NIH HHS [CA16086]; NICHD NIH HHS [U54 HD035041, U54 HD35041] NR 54 TC 23 Z9 26 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAY PY 2003 VL 68 IS 5 BP 1620 EP 1630 DI 10.1095/bioleprod.102.012013 PG 11 WC Reproductive Biology SC Reproductive Biology GA 673PQ UT WOS:000182589700019 PM 12606326 ER PT J AU Stubbe, BG Horkay, F Amsden, B Hennink, WE De Smedt, SC Demeester, J AF Stubbe, BG Horkay, F Amsden, B Hennink, WE De Smedt, SC Demeester, J TI Tailoring the swelling pressure of degrading dextran hydroxyethyl methacrylate hydrogels SO BIOMACROMOLECULES LA English DT Article ID DEGRADABLE NETWORKS; RELEASE BEHAVIOR; GELS; DELIVERY; SWOLLEN; DESIGN AB Swelling pressure measurements were performed on degrading dextran hydroxyethyl methacrylate (dexHEMA) hydrogels. In these networks, the cross-links are hydrolyzable carbonate ester bonds formed between methacrylate groups and dextran molecules. It is demonstrated that dex-HEMA gels made in the presence of a known amount of free dextran chains exhibit osmotic properties similar to those of partially degraded dex-HEMA gels. The swelling pressure, Pi(sw), of degrading dex-HEMA gels is controlled primarily by the cross-linked dex-HEMA polymer and the free dextran molecules, while the contribution of short poly-HEMA fragments (produced in the degradation process) is negligible. It is found that Pi(sw) only slightly changes during the first 15 days of degradation. Close to the end of the degradation process, however, a much faster increase in Pi(sw) is observed. The swelling pressure profile of these gels strongly depends on the concentration of the cross-linked dex-HEMA and its chemical composition (amount of HEMA groups per 100 glucose units). C1 State Univ Ghent, Dept Pharmaceut, Gen Biochem & Phys Pharm Labs, B-9000 Ghent, Belgium. NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. Queens Univ, Dept Chem Engn, Kingston, ON K7L 3N6, Canada. Univ Utrecht, Utrech Inst Pharmaceut Sci, Dept Pharmaceut, NL-3508 TB Utrecht, Netherlands. RP De Smedt, SC (reprint author), State Univ Ghent, Dept Pharmaceut, Gen Biochem & Phys Pharm Labs, Harelbekestr 72, B-9000 Ghent, Belgium. OI De Smedt, Stefaan/0000-0002-8653-2598 NR 23 TC 31 Z9 34 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD MAY-JUN PY 2003 VL 4 IS 3 BP 691 EP 695 DI 10.1021/bm020129w PG 5 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 679QQ UT WOS:000182933800030 PM 12741786 ER PT J AU Dundr, M Misteli, T AF Dundr, M Misteli, T TI Gene expression dynamics SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Editorial Material C1 NCI, NIH, Bethesda, MD 20892 USA. RP Dundr, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD MAY-JUN PY 2003 VL 57 IS 3-4 BP 180 EP 180 DI 10.1016/S0753-3322(02)00347-5 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 702FF UT WOS:000184213500013 ER PT J AU Okada, Y Fujita, Y Motoyama, T Tsuda, Y Yokoi, T Li, TY Sasaki, Y Ambo, A Jinsmaa, Y Bryant, SD Lazarus, LH AF Okada, Y Fujita, Y Motoyama, T Tsuda, Y Yokoi, T Li, TY Sasaki, Y Ambo, A Jinsmaa, Y Bryant, SD Lazarus, LH TI Structural studies of [2 ',6 '-dimethyl-L-tyrosine(1)]endomorphin-2 analogues: Enhanced activity and cis orientation of the Dmt-Pro amide bond SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID DIPEPTIDYL-PEPTIDASE-IV; OPIOID-PEPTIDES; ENZYMATIC DEGRADATION; RECEPTOR SELECTIVITY; AGONIST; ENDOMORPHIN-1; ANTAGONISTS; POTENT; IDENTIFICATION; SPECTROSCOPY AB Analogues of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) (1) were designed to examine the importance of each residue on mu-opioid receptor interaction. Replacement of Tyr(1) by 2',6'-dimethyl-L-tyrosine (Dmt) (9-12) exerted profound effects: [Dmt(1)]EM-2 (9) elevated mu-opioid affinity 4.6-fold (K(i)mu = 0.15 nM) yet selectivity fell 330-fold as delta-affinity rose (K(i)delta = 28.2 nM). This simultaneous increased mu- and delta-receptor bioactivities resulted in dual agonism (IC50 = 0.07 and 1.87 nM, respectively). While substitution of Phe(4) by a phenethyl group (4) decreased mu affinity (K(i)mu 13.3 nM), the same derivative containing Dmt (12) was comparable to EM-2 but also acquired weak delta antagonism (pA(2) = 7.05). H-1 NMR spectroscopy revealed a trans configuration (1:2 to 1:3, cis/trans) in the Tyr-Pro amide bond, but a cis configuration (5:3 to 13:7, cis/trans) with Dmt-Pro analogues. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Kobe Gakuin Univ, Fac Pharmaceut Sci, Dept Med Chem, Nishi Ku, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, High Technol Res Ct, Nishi Ku, Kobe, Hyogo 6512180, Japan. Tohoku Pharmaceut Univ, Dept Biochem, Aoba Ku, Sendai, Miyagi 9818558, Japan. NIEHS, LCBRA, Res Triangle Pk, NC 27709 USA. RP Okada, Y (reprint author), Kobe Gakuin Univ, Fac Pharmaceut Sci, Dept Med Chem, Nishi Ku, Kobe, Hyogo 6512180, Japan. NR 36 TC 51 Z9 53 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAY 1 PY 2003 VL 11 IS 9 BP 1983 EP 1994 DI 10.1016/S0968-1896(03)00068-3 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 665CA UT WOS:000182101000005 PM 12670649 ER PT J AU Munch, U Chen, L Bayly, SF Torrence, PF AF Munch, U Chen, L Bayly, SF Torrence, PF TI Probing the activation site of ribonuclease L with new N-6-substituted 2 ',5 '-adenylate trimers SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID CONVERTIBLE NUCLEOSIDE APPROACH; SYNCYTIAL VIRUS-REPLICATION; RNASE-L; 2-5A ANTISENSE; NUCLEIC-ACIDS; TELOMERASE RNA; TARGETING RNA; MESSENGER-RNA; OLIGONUCLEOTIDES; DEGRADATION AB 2-5A trimer [5'-monophosphoryladenylyl(2'-5')adenylyl(2'-5')adenosine] activates RNase L. While the 5'-terminal and 2'-terminal adenosine N-6-amino groups. play a key role in binding to and activation of RNase L, the exocyclic amino function of the second adenylate (from the 5-terminus) plays a relatively minor role in 2-5A's biological activity. To probe the available space proximal to the amino function of the central adenylate of 2-5A trimer during binding to RNase L, a variety of substituents were placed at that position. To accomplish this, the convertible building block 5'-O-dimethoxytrityl-3'-O-(tert-butyldimethylsilyi)-6-(2,4-dinitrophenyl)thioinosine 2-(2-cyanoethylN,N-diisopropylphosphoramidite) was prepared as a synthon to introduce 6-(2,4-dinitrophenyl)thioinosine into the middle position of the 2-5A trimer during automated synthesis. Post-synthetic treatment with aqueous amines transformed the (2,4-dinitrophenyl)thioinosine into N-6-substituted adenosines. Assays of these modified trimers for their ability to bind and activate RNase L showed that activation activity could be retained, albeit with some sacrifice compared to unmodified p5'A2'p5'A2'p5A. Thus, the spatial domain about this N-6-amino function could be available for modifications to enhance the biological potency of 2-5A analogues and to ligate 2-5A to targeting vehicles such as antisense molecules. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20892 USA. No Arizona Univ, Dept Chem, Flagstaff, AZ 86011 USA. RP Torrence, PF (reprint author), NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 38 TC 2 Z9 2 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAY 1 PY 2003 VL 11 IS 9 BP 2041 EP 2049 DI 10.1016/S0968-1896(03)00060-9 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 665CA UT WOS:000182101000011 PM 12670655 ER PT J AU Zhang, M Goforth, P Bertram, R Sherman, A Satin, L AF Zhang, M Goforth, P Bertram, R Sherman, A Satin, L TI The Ca2+ dynamics of isolated mouse beta-cells and islets: Implications for mathematical models SO BIOPHYSICAL JOURNAL LA English DT Article ID PANCREATIC B-CELLS; INDUCED (I) OSCILLATIONS; BURSTING ELECTRICAL-ACTIVITY; INSULIN-SECRETING CELLS; SENSITIVE K+ CHANNELS; ENDOPLASMIC-RETICULUM; CYTOPLASMIC CA2+; SINGLE-MOUSE; ACTION-POTENTIALS; SYNCHRONOUS OSCILLATIONS AB [Ca2+](i) and electrical activity were compared in isolated beta-cells and islets using standard techniques. In islets, raising glucose caused a decrease in [Ca2+](i) followed by a plateau and then fast (2-3 min(-1)), slow (0.2-0.8 min(-1)), or a mixture of fast and slow [Ca2+](i) oscillations. In beta-cells, glucose transiently decreased and then increased [Ca2+](i), but no islet-like oscillations occurred. Simultaneous recordings of [Ca2+](i) and electrical activity suggested that differences in [Ca2+](i) signaling are due to differences in islet versus beta-cell electrical activity. Whereas islets exhibited bursts of spikes on medium/slow plateaus, isolated P-cells were depolarized and exhibited spiking, fast-bursting, or spikeless plateaus. These electrical patterns in turn produced distinct [Ca2+](i) patterns. Thus, although isolated beta-cel Is display several key features of islets, their oscillations were faster and more irregular. beta-cells could display islet-like [Ca2+](i) oscillations if their electrical activity was converted to a slower islet-like pattern using dynamic clamp. Islet and beta-cell [Ca2+](i) changes followed membrane potential, suggesting that electrical activity is mainly responsible for the [Ca2+](i) dynamics of beta-cells and islets. A recent model consisting of two slow feedback processes and passive endoplasmic reticulum. Ca2+ release was able to account for islet [Ca2+](i) responses to glucose, islet oscillations, and conversion of single cell to islet-like [Ca2+](i) oscillations. With minimal parameter variation, the model could also account for the diverse behaviors of isolated beta-cells, suggesting that these behaviors reflect natural cell heterogeneity. These results support our recent model and point to the important role of beta-cell electrical events in controlling [Ca2+](i) over diverse time scales in islets. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Florida State Univ, Kash Lab Biophys, Tallahassee, FL 32306 USA. NIDDKD, Math Res Branch, NIH, Bethesda, MD 20892 USA. RP Satin, L (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, POB 980524, Richmond, VA 23298 USA. FU NIDDK NIH HHS [R01 DK-46409, R01 DK046409] NR 88 TC 84 Z9 84 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 2003 VL 84 IS 5 BP 2852 EP 2870 PG 19 WC Biophysics SC Biophysics GA 683AA UT WOS:000183123200007 PM 12719219 ER PT J AU Antzutkin, ON Balbach, JJ Tycko, R AF Antzutkin, ON Balbach, JJ Tycko, R TI Site-specific identification of non-beta-strand conformations in Alzheimer's beta-amyloid fibrils by solid-state NMR SO BIOPHYSICAL JOURNAL LA English DT Article ID CHEMICAL-SHIFT TENSORS; ANGLE-SPINNING NMR; NUCLEAR-MAGNETIC-RESONANCE; X-RAY-DIFFRACTION; MAGIC-ANGLE; SECONDARY-STRUCTURE; EXCHANGE SPECTROSCOPY; VIRULENCE FACTOR; POWDER PATTERNS; SHEET STRUCTURE AB The most well-established structural feature of amyloid fibrils is the cross-beta motif, an extended beta-sheet structure formed by beta-strands oriented perpendicular to the long fibril axis. Direct experimental identification of non-beta-strand conformations in amyloid fibrils has not been reported previously. Here we report the results of solid-state NMR measurements on amyloid fibrils formed by the 40-residue beta-amyloid peptide associated with Alzheimer's disease (Abeta(1-40)), prepared synthetically with pairs of C-13 labels at consecutive backbone carbonyl sites. The measurements probe the peptide backbone conformation in residues 24-30, a segment where a non-beta-strand conformation has been suggested by earlier sequence analysis, cross-linking experiments, and molecular modeling. Data obtained with the fpRFDR-CT, DQCSA, and 2D MAS exchange solid-state NMR techniques, which provide independent constraints on the phi and psi backbone torsion angles between the labeled carbonyl sites, indicate non-beta-strand conformations at G25, S26, and G29. These results represent the first site-specific identification and characterization of non-beta-strand peptide conformations in an amyloid fibril. C1 Lulea Univ Technol, Dept Inorgan Chem, Lulea, Sweden. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. NR 62 TC 69 Z9 72 U1 1 U2 8 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 2003 VL 84 IS 5 BP 3326 EP 3335 PG 10 WC Biophysics SC Biophysics GA 683AA UT WOS:000183123200050 PM 12719262 ER PT J AU Sayers, T AF Sayers, T TI Granzyme M, a profiler of innate immune lymphocytes? SO BLOOD LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Sayers, T (reprint author), NCI, Bethesda, MD 20892 USA. RI Sayers, Thomas/G-4859-2015 NR 0 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 1 PY 2003 VL 101 IS 9 BP 3342 EP 3343 PG 2 WC Hematology SC Hematology GA 674EZ UT WOS:000182625600005 ER PT J AU Toro, JR Liewehr, DJ Pabby, N Sorbara, L Raffeld, M Steinberg, SM Jaffe, ES AF Toro, JR Liewehr, DJ Pabby, N Sorbara, L Raffeld, M Steinberg, SM Jaffe, ES TI Gamma-delta T-cell phenotype is associated with significantly decreased survival in cutaneous T-cell lymphoma SO BLOOD LA English DT Article ID DISTINCT CLINICOPATHOLOGICAL ENTITY; MYCOSIS-FUNGOIDES; CLASSIFICATION; PANNICULITIS; RECEPTORS; PROPOSAL; LYMPHOCYTES; EXPRESSION; LEUKEMIA; MUCOSAL AB The importance of alphabeta versus gammadelta T-cell subset antigen expression in the classification of peripheral T-cell lymphomas is still unclear. The objective of this study was to investigate the prognostic value of T-cell receptor-delta1 (TCRdelta1) expression in primary cutaneous T-cell lymphomas. TCRdelta1 cellular expression was assessed in skin biopsy specimens of 104 individuals with cutaneous T-cell lymphoma by immunohistochemistry. Both univariate (Kaplan-Meier) and multivariate (Cox regression) analyses were conducted to determine which variables (T-cell subtype, hemophagocytosis, histologic profile, age, sex, and adenopathy) were significantly associated with survival. Univariate analysis indicated that there was a statistically significant difference in survival between the patients with alphabeta cutaneous T-cell lymphoma and patients with gammadelta cutaneous T-cell lymphoma (P < .0001). There was also a statistically significant decrease in survival among patients who had subcutaneous involvement compared with patients who had epidermotropic and/or dermal involvement (P < .0001). Cox model analysis indicated that TCR61 expression was the factor that was most closely associated with decreased survival (P < .0001). Among those patients with cutaneous gammadelta T-cell lymphoma (n = 33), there was a trend for decreased survival for patients who had histologic evidence of subcutaneous fat involvement in comparison with patients who had epidermotropic or dermal patterns of infiltration (P = .067). No other prognostic factors were identified as having a notable association with outcome in this subgroup. TCRdelta1 expression in primary cutaneous lymphomas is an independent prognostic factor associated with decreased survival. (C) 2003 by The American Society of Hematology. C1 NCI, Pathol Lab, NIH, Bethesda, MD USA. Hematopathol Sect, Bethesda, MD USA. RP Toro, JR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd Execut Pl S,Rm 7012, Bethesda, MD 20892 USA. NR 41 TC 124 Z9 137 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 1 PY 2003 VL 101 IS 9 BP 3407 EP 3412 DI 10.1182/blood-2002-05-1597 PG 6 WC Hematology SC Hematology GA 674EZ UT WOS:000182625600022 PM 12522013 ER PT J AU Krenacs, L Smyth, MJ Bagdi, E Krenacs, T Kopper, L Rudiger, T Zettl, A Muller-Hermelink, HK Jaffe, ES Raffeld, M AF Krenacs, L Smyth, MJ Bagdi, E Krenacs, T Kopper, L Rudiger, T Zettl, A Muller-Hermelink, HK Jaffe, ES Raffeld, M TI The serine protease granzyme M is preferentially expressed in NK-cell, gamma delta T-cell, and intestinal T-cell lymphomas: evidence of origin from lymphocytes involved in innate immunity SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; INTRAEPITHELIAL LYMPHOCYTES; INHIBITORY RECEPTORS; DISEASE; SUBSET; DIFFERENTIATION; MATURATION; MET-ASE-1; REPRESENT; PROTEINS AB Granzyme M (GM) is a novel serine protease whose expression is highly restricted to natural killer (NK) cells, CD3(+)CD56(+) T cells, and gammadelta T cells. Using a GM-specific monoclonal antibody, We analyzed the expression of GM in 214 mature T-cell and NK-cell lymphomas. GM was preferentially expressed in nasal NK/T-cell lymphomas (100%), gammadelta T-cell lymphomas (100%), and intestinal T-cell lymphomas (85%). In contrast, GM expression was present at low prevalence in mycosis fungoides/Sezary syndrome (3%) anaplastic large-cell lymphoma (6%), panniculitis-like T-cell lymphoma (11%), and angioimmunoblastic T-cell lymphoma (0%) cases. Peripheral T-cell lymphomas of unspecified subtype showed an intermediate frequency (37%) of GM expression, consistent with their heterogeneous origin. We conclude that GM expression is a distinctive feature of the nasal NK/T-cell, gammadelta T-cell, and intestinal T-cell lymphomas, and suggest that these tumors develop from lymphocytes involved in innate: immunity.(C) 2003 by The American Society of Hematology. C1 NCI, Specialized Diagnost Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. Bay Zoltan Fdn Appl Res, Lab Tumor Pathol & Mol Diagnost, Inst Biotechnol, Szeged, Hungary. Peter MacCallum Canc Inst, Div Canc Immunol, E Melboune, Vic, Australia. Semmelweis Univ, Inst Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary. Univ Wurzburg, Dept Pathol, D-97070 Wurzburg, Germany. NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Raffeld, M (reprint author), NCI, Specialized Diagnost Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. EM mraff@box-m.nih.gov RI Krenacs, Laszlo/L-8063-2014; Smyth, Mark/H-8709-2014 OI Krenacs, Laszlo/0000-0001-6541-3031; Smyth, Mark/0000-0001-7098-7240 NR 26 TC 51 Z9 52 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2003 VL 101 IS 9 BP 3590 EP 3593 DI 10.1182/blood-2002-09-2908 PG 4 WC Hematology SC Hematology GA 674EZ UT WOS:000182625600048 PM 12506019 ER PT J AU Yamaguchi, H Aridgides, LJ Zeng, WH Osgood, C Young, NS Liu, JM AF Yamaguchi, H Aridgides, LJ Zeng, WH Osgood, C Young, NS Liu, JM TI Genetic and transcriptional analysis of spindle checkpoint genes in bone marrow failure patients SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE aplastic anemia; myelodysplastic syndrome; aneuploidy; hBUB1; hMAD2 ID ACQUIRED APLASTIC-ANEMIA; MYELODYSPLASTIC SYNDROME; MUTATION ANALYSIS; LUNG-CANCER; HBUB1; INACTIVATION; INSTABILITY; EXPRESSION; DISEASES; LEUKEMIA AB The evolution of bone marrow failure syndromes such as aplastic anemia (AA) to clonal hematologic diseases such as myelodysplastic syndrome is well recognized. Cytogenetic abnormalities are commonly seen late events, particularly aneuploidy of chromosomes 7 and 8. A proportion of bone marrow failure patients may also develop aneuploidy that is detectable by fluorescence in situ hybridization but not by standard cytogenetic analysis. The molecular basis for aneuploidy in this setting is currently unknown but may include abnormalities in the mitotic spindle checkpoint. For this reason, we searched for mutations in the mitotic spindle checkpoint genes hBUB1 and hMAD2, and also examined the expression of hBUB1 in cells of bone marrow failure patients. No pathogenic mutations were found in 59 patients. Of 170 bone marrow failure patients, less than one-third expressed hBUB I transcript. Gene expression profiling confirmed a significant down-regulation of hBUB1 message in patients. We conclude that mutations in mitotic spindle checkpoint genes do not account for aneuploidy in marrow failure states. However, we cannot exclude epigenetic inactivation of hBUB I as a potential mechanism in some patients. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Ctr Pediat Res, Norfolk, VA 23510 USA. Old Dominion Univ, Norfolk, VA 23529 USA. RP Liu, JM (reprint author), Mt Sinai Sch Med, Div Hematol Oncol, 1 Gustave L Levy Pl,Box 1079, New York, NY 10029 USA. NR 25 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2003 VL 30 IS 3 BP 307 EP 311 DI 10.1016/S1079-9796(03)00042-1 PG 5 WC Hematology SC Hematology GA 683GF UT WOS:000183139500014 PM 12737950 ER PT J AU Hausler, KD Quinn, JMW Horwood, NJ Ellis, J Lengel, C Martin, TJ Rubin, JS Gillespie, MT AF Hausler, KD Quinn, JMW Horwood, NJ Ellis, J Lengel, C Martin, TJ Rubin, JS Gillespie, MT TI Secreted frizzled-related protein inhibits TNFalpha- or RANKL-dependent osteoclast formation SO BONE LA English DT Meeting Abstract CT 1ST Joint meeting of the International-Bone-and-Mineral-Society/Japanese-Society-for-Bone-and-Min eral-Research CY JUN 03-07, 2003 CL OSAKA, JAPAN SP Int Bone & Mineral Soc, Japanese Soc bone & Mineral Res C1 NCI, NIH, Bethesda, MD 20892 USA. RI Horwood, Nicole/B-4351-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 2003 VL 32 IS 5 SU S BP S74 EP S74 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683AB UT WOS:000183123300023 ER PT J AU Riminucci, M Holmbeck, K Cherman, N Bianco, P Robey, PG AF Riminucci, M Holmbeck, K Cherman, N Bianco, P Robey, PG TI GS-alpha expression is biallelic in normal and fibrous dysplastic bone SO BONE LA English DT Meeting Abstract CT 1ST Joint meeting of the International-Bone-and-Mineral-Society/Japanese-Society-for-Bone-and-Min eral-Research CY JUN 03-07, 2003 CL OSAKA, JAPAN SP Int Bone & Mineral Soc, Japanese Soc bone & Mineral Res C1 Univ Aquila, Dipartimento Med Sperimentale, I-67100 Laquila, Italy. NIDCR, NIH, Bethesda, MD USA. Univ Roma La Sapienza, Dip Med Sperimentale & Patol, Rome, Italy. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 2003 VL 32 IS 5 SU S BP S92 EP S92 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683AB UT WOS:000183123300097 ER PT J AU Solomon, SR Nakamura, R Read, EJ Leltman, SF Carter, C Childs, R Dunbar, CE Young, NS Barrett, AJ AF Solomon, SR Nakamura, R Read, EJ Leltman, SF Carter, C Childs, R Dunbar, CE Young, NS Barrett, AJ TI Cyclosporine is required to prevent severe acute GVHD following T-cell-depleted peripheral blood stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE cyclosporine; graft-versus-host disease; T-cell depletion; peripheral blood stem cell transplantation ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; TOTAL-BODY IRRADIATION; LOW-DOSE CYCLOSPORINE; SELECTIVE DEPLETION; LYMPHOCYTES-T; HEMATOLOGICAL MALIGNANCIES; MYELOID-LEUKEMIA; GRAFT; RELAPSE AB Reduced immunosuppression may improve immune recovery and increase the graft-versus-leukemia effect after allogeneic stem cell transplantation. Furthermore, the requirement for post-transplant immunosuppression following extensive T-cell depletion remains unclear. We therefore evaluated the role of cyclosporine (CSA) in recipients of HLA-identical T-cell-depleted peripheral blood stem cell transplants (PBSCT), followed by donor lymphocyte infusions (DLIs) scheduled on days + 45 and + 100. Before day + 45, successive cohorts of patients received decreasing amounts of CSA: standard-dose (SD) CSA, low-dose (LD) CSA, or no CSA until day + 45. LD CSA was as effective as SD CSA in preventing acute graft-versus-host disease (GVHD). However, moderate-to-severe acute GVHD was significantly more frequent before the day + 45 DLI in patients receiving no CSA (33.3 vs 12.7%, P = 0.036, including the only four grade III-IV cases). As a result of higher rates of early acute GVHD, more patients in the 'no CSA' group failed to receive any DLI (30.7 vs 7.1%, P = 0.01). Overall, there was no difference in the incidence of acute GVHD, as patients receiving CSA developed more GVHD after DLI. Similarly, no significant differences were found in chronic GVHD, transplant-related mortality, or survival. These results define a role for CSA in preventing GVHD at low T-cell doses following PBSCT. C1 NHLBI, NIH, Hematol Branch, Stem Cell Allotransplantat Sect, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Cell Proc Sect, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, NIH, Hematol Branch, Stem Cell Allotransplantat Sect, Bldg 10,Room 7C103,9000 Rockville Pike,MSC 1652, Bethesda, MD 20892 USA. NR 18 TC 23 Z9 23 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 2003 VL 31 IS 9 BP 783 EP 788 DI 10.1038/sj.bmt.1703928 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 681FB UT WOS:000183025300008 PM 12732885 ER PT J AU Brasted, PJ Bussey, TJ Murray, EA Wise, SP AF Brasted, PJ Bussey, TJ Murray, EA Wise, SP TI Role of the hippocampal system in associative learning beyond the spatial domain SO BRAIN LA English DT Review DE fornix; conditional motor learning; conditional discrimination; declarative memory ID MEDIAL TEMPORAL-LOBE; TRANSVERSE PATTERNING TASK; FORNIX-TRANSECTED MONKEYS; RHESUS-MONKEYS; EPISODIC MEMORY; CONNECTIONIST MODELS; EXCITOTOXIC LESIONS; VISUAL RECOGNITION; NEUROTOXIC LESIONS; PREFRONTAL CORTEX AB Expert opinion remains divided on the issue of whether the hippocampal system functions exclusively in spatial information processing, e.g. in navigation or in understanding spatial relations, or whether it plays a more general role in higher brain function. Previous work on monkeys and rats has tended to support the former view, whereas observations in the clinic point to the latter, including functions as diverse as declarative knowledge, episodic memory, word learning, and understanding relations among objects. One influential theory posits a general role for the hippocampal system in associative learning, with emphasis on associations learned rapidly and recently. The results presented here are consistent with this theory, along with previous clinical and theoretical studies indicating that the hippocampal system is necessary for associative learning even if no component of the association relies on spatial information. In the study reported here, rhesus monkeys learned a series of conditional stimulus-response associations involving complex visual stimuli presented on a video monitor. Each stimulus instructed one of three responses: tapping the stimulus with the hand, steady hand contact with the stimulus for a brief period of time, or steady contact for a longer time. Fornix transection impaired the learning of these associations, even though both the stimuli and the responses were nonspatially differentiated, and this deficit persisted for at least 2 years. This finding indicates that the hippocampal system plays an important role in associative learning regardless of the relevance of spatial information to any aspect of the association. Fornix-transected monkeys were impaired in learning new stimulus-response associations even when the stimuli were highly familiar. Thus, the deficit was one of associating each stimulus with a response, as opposed to problems in distinguishing the stimuli from each other. In contrast to these effects, fornix transection did not impair performance when familiar stimuli instructed a response according to an already-learned association, which shows that the deficit was one of learning new associations rather than one of retention or retrieval of previously learned ones. Taken together, these results show that fornix transection causes a long-lasting impairment in associative learning outside of the spatial domain, in a manner consistent with theories of hippocampal-system function that stress a general role in the rapid acquisition of associative knowledge. C1 NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Brasted, PJ (reprint author), NIMH, Lab Syst Neurosci, Bldg 49,Room B1EE17,49 Convent Dr,MSC 4401, Bethesda, MD 20892 USA. RI Bussey, Timothy/M-2758-2016; OI Bussey, Timothy/0000-0001-7518-4041; Murray, Elisabeth/0000-0003-1450-1642 NR 105 TC 91 Z9 91 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 2003 VL 126 BP 1202 EP 1223 DI 10.1093/brain/awg103 PN 5 PG 22 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 668ZR UT WOS:000182327900019 PM 12690059 ER PT J AU Lyles, J Cadet, JL AF Lyles, J Cadet, JL TI Methylenedioxymethamphetamine (MDMA, Ecstasy) neurotoxicity: cellular and molecular mechanisms SO BRAIN RESEARCH REVIEWS LA English DT Review DE methylenedioxymethamphetamine; MDMA; ecstasy; neurotoxicity ID BRAIN-SEROTONIN NEURONS; POSITRON-EMISSION-TOMOGRAPHY; 3,4-METHYLENEDIOXYMETHAMPHETAMINE-INDUCED DOPAMINE RELEASE; ORALLY-ADMINISTERED MDMA; CENTRAL-NERVOUS-SYSTEM; DARK AGOUTI RATS; LONG-TERM; (+/-)3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; COGNITIVE PERFORMANCE; IN-VIVO AB Methylenedioxymethamphetamine (MDMA, Ecstasy) is a very popular drug of abuse. This has led to new intense concerns relevant to its nefarious neuropsychiatric effects. These adverse events might be related to the neurotoxic effects of the drug. Although the mechanisms of MDMA-induced neurotoxicity remain to be fully characterized, exposure to the drug can cause acute and long-term neurotoxic effects in animals and nonhuman primates. Recent studies have also documented possible toxic effects in the developing fetus. Nevertheless, there is still much debate concerning the effects of the drug in humans and how to best extrapolate animal and nonhuman primate data to the human condition. Herein, we review the evidence documenting the adverse effects of the drug in some animal models. We also discuss possible mechanisms for the development of MDMA neurotoxicity. Data supporting deleterious effects of this drug on the developing fetus are also described. Much remains to be done in order to clarify the molecular and biochemical pathways involved in the long-term neuroplastic changes associated with MDMA abuse. Published by Elsevier Science B.V. C1 NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Univ Maryland, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 195 TC 116 Z9 123 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD MAY PY 2003 VL 42 IS 2 BP 155 EP 168 DI 10.1016/S0165-0173(03)00173-5 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 687BC UT WOS:000183355100004 PM 12738056 ER PT J AU Kenney, NJ Bowman, A Korach, KS Barrett, JC Salomon, DS AF Kenney, NJ Bowman, A Korach, KS Barrett, JC Salomon, DS TI Effect of exogenous epidermal-like growth factors on mammary gland development and differentiation in the estrogen receptor-alpha knockout (ERKO) mouse SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE EGF-like peptides; estrogen receptor; mammary gland; transplantation ID BREAST-CANCER CELLS; DUCTAL MORPHOGENESIS; MESSENGER-RNA; EXPRESSION; PROGESTERONE; MICE; PROLIFERATION; BETA AB The development of the mouse mammary gland requires the interaction between several different ovarian and pituitary hormones such as estrogen, progesterone and prolactin as well as several locally-derived growth factors in the mammary gland such as epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha), amphiregulin (AR) and heregulin (HRG). The focus of this study was to investigate the degree of mammary growth and differentiation in the adult, virgin mammary gland of wild type (wt) and estrogen receptor knockout (ERKO) females that lack estrogen receptor alpha (ERalpha) after reciprocal transplantation into the cleared mammary fat pad of virgin wt or ERKO mice. In addition, we assessed the local response of ERKO mammary tissue to TGFalpha or HRGbeta1 delivered from slow release-Elvax pellets. Our initial results indicated that when we transplanted virgin wt mammary tissue into ERKO mammary fat pads, mammary morphogenesis failed to occur. However, when transplanted virgin ERKO mammary tissue was transplanted into fat pads of virgin or pregnant wt mice, the development and differentiation of lobuloalveoli was readily observed. In addition, treatment of the virgin ERKO mammary gland with TGFalpha or HRGbeta1 stimulated ducts to undergo localized branching and growth and both growth factors induced secretory differentiation as evidenced by the production of milk proteins, caseins and/or whey acidic protein (WAP). The results from this study imply that in ERKO mammary tissue, ERKO ductal epithelium has the capacity to proliferate and differentiate in response to non-estrogenic, morphogenic stimuli. C1 Hampton Univ, Dept Biol Sci, Hampton, VA 23668 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kenney, NJ (reprint author), Hampton Univ, Dept Biol, Hampton, VA 23668 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 27 TC 19 Z9 19 U1 2 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAY PY 2003 VL 79 IS 2 BP 161 EP 173 DI 10.1023/A:1023938510508 PG 13 WC Oncology SC Oncology GA 682VG UT WOS:000183112600003 PM 12825851 ER PT J AU Shcherbina, A Candotti, F Rosen, FS Remold-O'Donnell, E AF Shcherbina, A Candotti, F Rosen, FS Remold-O'Donnell, E TI High incidence of lymphomas in a subgroup of Wiskott-Aldrich syndrome patients SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE Wiskott-Aldrich syndrome; lymphoma; splice site mutations; WASP; primary immune deficiency ID THROMBOCYTOPENIA; GENE C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Res Inst Paediat Hematol, Moscow, Russia. NHGRI, NIH, Bethesda, MD 20892 USA. RP Shcherbina, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 7 TC 21 Z9 23 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2003 VL 121 IS 3 BP 529 EP 530 DI 10.1046/j.1365-2141.2003.04310.x PG 4 WC Hematology SC Hematology GA 671QN UT WOS:000182475700023 PM 12716381 ER PT J AU Cabay, L Willermain, F Bruyns, C Verdebout, JM Witta, Y Baffi, J Velu, T Libert, J Caspers-Velu, L Maho, A Lespagnard, L AF Cabay, L Willermain, F Bruyns, C Verdebout, JM Witta, Y Baffi, J Velu, T Libert, J Caspers-Velu, L Maho, A Lespagnard, L TI CXCR4 expression in vitreoretinal membranes SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PROLIFERATIVE VITREORETINOPATHY; CHEMOKINES; CELLS AB Background/aim: Proliferative vitreoretinopathy (PVR) and macular pucker (MP) vitreoretinal membranes are caused by abnormal cell migration. By their role in chemotactism, chemokine receptors represent good candidates to sustain this process. The authors thus investigated the expression of one of them, CXCR4, in these pathologies. Methods: Three PVR and four MP membranes were surgically removed and processed for immunochemical studies with antibodies for CXCR4, cytokeratins or smooth muscle actin. Results: CXCR4 expression was found in all membranes. There was no relation between severity of PVR or MP and presence of CXCR4. In addition, there was no difference in CXCR4 expression between MP and PVR. Conclusion: CXCR4 is expressed in PVR and MP. Further experiments are needed to test if CXCR4 and other chemokine receptors are implicated in vitreoretinal membrane formation. C1 ULB Erasme, IRIBHM, B-1070 Brussels, Belgium. CHU St Pierre, Dept Ophthalmol, Brussels, Belgium. Free Univ Brussels, Inst Bordet, Dept Anatomopathol, Brussels, Belgium. Univ Hlth Sci & LI, Dept Pharmacol, NEI, NIH, Bethesda, MD USA. RP Willermain, F (reprint author), ULB Erasme, IRIBHM, Bat C,808 Route Lennik, B-1070 Brussels, Belgium. NR 11 TC 3 Z9 4 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAY PY 2003 VL 87 IS 5 BP 567 EP 569 DI 10.1136/bjo.87.5.567 PG 3 WC Ophthalmology SC Ophthalmology GA 671MT UT WOS:000182469100014 PM 12714394 ER PT J AU Ergun, A Camphausen, K Wein, LM AF Ergun, A Camphausen, K Wein, LM TI Optimal scheduling of radiotherapy and angiogenic inhibitors SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article ID IONIZING-RADIATION; TUMOR ANGIOGENESIS; DOSE-RATE; THERAPY; GROWTH; ANGIOSTATIN; ENDOSTATIN; CANCER; MODEL; CELLS AB We incorporate a previously validated mathematical model of a vascularized tumor into an optimal control problem to determine the temporal scheduling of radiotherapy and angiogenic inhibitors that maximizes the control of a primary tumor. Our results reveal that optimal antiangiogenic monotherapy gives a large initial injection to attain a 20: 1 ratio of tumor cell volume to supporting vasculature volume. It thereafter maintains this 20: 1 ratio via a continuous dose rate that is intensified over time. The optimal radiation monotherapy schedule is characterized by a modest dose intensification over time. The best performance is achieved by our optimal combination regimen, where the antiangiogenic treatment again maintains a constant tumor-to-vasculature ratio, but is administered in a dose-intensified manner only during the latter portion of the radiation fractionation schedule. (C) 2003 Society for Mathematical Biology. Published by Elsevier Science Ltd. All rights reserved. C1 Stanford Univ, Grad Sch Business, Stanford, CA 94305 USA. MIT, Ctr Operat Res, Cambridge, MA 02139 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Wein, LM (reprint author), Stanford Univ, Grad Sch Business, Stanford, CA 94305 USA. NR 41 TC 77 Z9 78 U1 0 U2 7 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD MAY PY 2003 VL 65 IS 3 BP 407 EP 424 DI 10.1016/S0092-8240(03)00006-5 PG 18 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 675PJ UT WOS:000182703500004 PM 12749532 ER PT J AU Chen, XD Allen, MR Bloomfield, S Xu, T Young, M AF Chen, XD Allen, MR Bloomfield, S Xu, T Young, M TI Biglycan-deficient mice have delayed osteogenesis after marrow ablation SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE biglycan; marrow ablation; bone formation; bone repair ID RAT TIBIAL BONE; GROWTH-FACTOR-BETA; PROTEOGLYCANS BIGLYCAN; EXTRACELLULAR-MATRIX; EXPRESSION; DECORIN; COLCHICINE; GENE; LOCALIZATION; COLLAGEN AB Biglycan (bgn) is a small proteoglycan in skeletal tissue that binds and regulates collagen and TGF-beta activities. Mice deficient in bgn (bgn-KO) develop age-dependent osteopenia and have multiple metabolic defects in their bone marrow stromal cells including increased apoptosis, reduced numbers of colony-forming units-fibroblastic (CFU-F) and decreased collagen production. In the present study we tested the hypothesis that bone formation capability in response to a physiological stress is compromised in bgn deficiency. We tested this theory using an in vivo bone marrow ablation assay. Ablation was performed on 6-week-old wild type (wt) and bgn-KO mice and bones were analyzed at days 7, 10, and 17 postsurgery. X-ray analysis showed that bone marrow ablation in femora induced vigorous new bone formation within 10 days in both genotypes but appeared greater in the ivt compared to the bgn-KO. In order to quantitate the changes in bone formation in the ablated animals, bone densities of the proximal, midshaft, and distal femora were assessed using peripheral quantitative computed tomography (pQCT). The ratio of cancellous bone density at the midshaft (ablated limb/control limb) was significantly higher in wt compared to bgn-KO at day 10 postsurgery. Wt and bgn-KO femora had similar total and cancellous bone densities at days 7 and 17 postsurgery at all three locations indicating that the ablation effects were temporal and limited to the cancellous bone of the mid-shaft region. These data indicate that the absence of bgn directly impeded bone formation. Our results support the concept that bgn is important in controlling osteogenesis following marrow ablation. C1 NIDCR, Craniofacial & Skeletal Dis Branch, Bethesda, MD USA. Texas A&M Univ, Dept Hlth & Kinesiol, College Stn, TX 77843 USA. RP Young, M (reprint author), NIDCR, Craniofacial & Skeletal Dis Branch, Bethesda, MD USA. RI Allen, Matthew/A-8799-2015 OI Allen, Matthew/0000-0002-1174-9004 NR 29 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD MAY PY 2003 VL 72 IS 5 BP 577 EP 582 DI 10.1007/s00223-002-1101-y PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 685ZG UT WOS:000183294500006 PM 12724831 ER PT J AU Thomas, RR Quinn, MG Schuler, B Grem, JL AF Thomas, RR Quinn, MG Schuler, B Grem, JL TI Hypersensitivity and idiosyncratic reactions to oxaliplatin SO CANCER LA English DT Article DE oxaliplatin; platinum compounds; hypersensitivity; allergic reactions; idiosyncratic reactions ID METASTATIC COLORECTAL-CANCER; HIGH-DOSE LEUCOVORIN; SIMPLIFIED BIMONTHLY LEUCOVORIN; MULTICENTER PHASE-II; FIRST-LINE TREATMENT; FOLINIC ACID; 5-FLUOROURACIL REGIMEN; ANAPHYLACTIC REACTION; CONTINUOUS-INFUSION; 1ST-LINE TREATMENT AB BACKGROUND. Oxaliplatin is a third-generation platinum analog that is used to treat a variety of solid tumors, particularly colorectal. carcinoma. Patients may develop hypersensitivity reactions, although this complication occurs infrequently. METHODS. Three patients developed hypersensitivity reactions to oxaliplatin while undergoing treatment on a Phase I trial of oxaliplatin and capecitabine. An Entrez PUBMED search was performed to identify other cases. RESULTS. Two patients experienced the abrupt onset of erythema alone or with pruritis during the 9th and 11th infusions of oxaliplatin, whereas the other patient developed fever and mild dyspnea a few hours after the 9th oxaliplatin infusion. All 3 patients were rechallenged successfully for at least I additional oxaliplatin infusion by using oral dexamethasone, 20 mg orally, 6 and 12 hours before the administration of oxaliplatin and by administering intravenously 125 mg of solumedrol, 50 mg of diphenhydramine, and 50 mg of cimetidine 30 minutes before oxaliplatin. The literature review suggests two distinct patterns of reactions: classic hypersensitivity (as experienced by the first two patients) and idiosyncratic reactions (as experienced by the third patient). CONCLUSIONS. Patients who develop Mild to moderate hypersensitivity to oxaliplatin may be pretreated with steroids and antagonists of Type I and 2 histamine receptors, whereas patients who develop severe reactions are unlikely to tolerate further therapy. Published 2003 by the American Cancer Society.*. C1 Natl Naval Med Res Inst, NCI, Ctr Canc Res, Canc Therapeut Branch, Bethesda, MD 20889 USA. RP Grem, JL (reprint author), Natl Naval Med Res Inst, NCI, Ctr Canc Res, Canc Therapeut Branch, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. EM gremj@mail.nih.gov NR 39 TC 69 Z9 77 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 2003 VL 97 IS 9 BP 2301 EP 2307 DI 10.1002/cncr.11379 PG 7 WC Oncology SC Oncology GA 671BT UT WOS:000182445700027 PM 12712487 ER PT J AU Sedelnikova, OA Pilch, DR Redon, C Bonner, WM AF Sedelnikova, OA Pilch, DR Redon, C Bonner, WM TI Histone H2AX in DNA damage and repair SO CANCER BIOLOGY & THERAPY LA English DT Review DE gamma-H2AX; DNA double strand breaks; ionizing radiation ID DOUBLE-STRAND BREAKS; CHROMATIN; STRESS; ATM C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bonner, WM (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 5050A,MSC 4255,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 180 Z9 186 U1 0 U2 16 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAY-JUN PY 2003 VL 2 IS 3 BP 233 EP 235 PG 3 WC Oncology SC Oncology GA 702VC UT WOS:000184244400002 PM 12878854 ER PT J AU Dracheva, T Jen, J AF Dracheva, T Jen, J TI Profiling lung adenocarcinoma - Insights from genes and more genes SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE cell cycle; NSCLC; expression profiling; lung cancer; G(1) phase; S phase; G(2) phase ID CANCER; AMPLIFICATION; EXPRESSION; MYC C1 NCI, Lab Populat Genet, Ctr Canc Res, Bethesda, MD 20892 USA. RP Jen, J (reprint author), NCI, Lab Populat Genet, Ctr Canc Res, Bldg 41,Rm D702,41 Lib Dr, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAY-JUN PY 2003 VL 2 IS 3 BP 299 EP 300 PG 2 WC Oncology SC Oncology GA 702VC UT WOS:000184244400018 PM 12878870 ER PT J AU Troisi, R Potischman, N Roberts, J Siiteri, P Daftary, A Sims, C Hoover, RN AF Troisi, R Potischman, N Roberts, J Siiteri, P Daftary, A Sims, C Hoover, RN TI Associations of maternal and umbilical cord hormone concentrations with maternal, gestational and neonatal factors (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE androgens; birth weight; cancer; estrogens; fetal origins; pregnancy; race ID BREAST-CANCER RISK; DEHYDROEPIANDROSTERONE-SULFATE; SEX-DIFFERENCES; ESTRIOL LEVELS; BIRTH-WEIGHT; PREGNANCY; ESTRADIOL; BLOOD; TERM; TESTOSTERONE AB Objective: Risks of some cancers in adults have been associated with several pregnancy factors, including greater maternal age and birth weight. For hormone-related cancers, these effects are hypothesized to be mediated through higher in utero estrogen concentrations. In addition, racial differences in pregnancy hormone levels have been suggested as being responsible for differences in testicular and prostate cancer risk by race. How ever, data on hormonal levels related to these characteristics of pregnancy are sparse, particularly those from studies of the fetal circulation. Methods: Estrogen and androgen concentrations were measured in maternal and umbilical cord sera from 86 normal, singleton pregnancies. Results: Birth size measures (weight, length and head circumference) were positively correlated with maternal estriol (r = 0.25-0.36) and with cord DHEAS concentrations (r = 0.24-0.41), but not with estrogens in cord sera. Maternal age was inversely correlated with maternal DHEAS, androstenedione and testosterone concentrations (r = -0.30, -0.25 and -0.30, respectively), but uncorrelated with estrogens in either the maternal or cord circulation. Black mothers had higher androstenedione and testosterone concentrations than white mothers, however, there were no racial differences in any of the androgens in cord sera. Cord testosterone concentrations were higher in mothers of male fetuses, while both maternal and cord concentrations of estriol were lower in these pregnancies. Conclusions: These data demonstrate associations between hormone concentrations and pregnancy factors associated with offspring's cancer risk, however, the hormones involved and their patterns of association differ by whether the maternal or fetal circulation was sampled. Horm one concentrations in the fetal circulation in this study are not consistent with the hypothesis that greater estrogen concentrations in high birth weight babies mediate the positive association with breast cancer risk observed in epidemiologic studies, or with the hypothesis that higher testosterone exposure in the in utero environment of black males explains their higher subsequent prostate cancer risk. C1 Dartmouth Coll Sch Med, Dept Community & Family Med, Lebanon, NH 03756 USA. NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Troisi, R (reprint author), Dartmouth Coll Sch Med, Dept Community & Family Med, 7927 Rubin Bldg,DHMC,1 Med Ctr Dr, Lebanon, NH 03756 USA. NR 25 TC 87 Z9 87 U1 0 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2003 VL 14 IS 4 BP 347 EP 355 DI 10.1023/A:1023934518975 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 684JC UT WOS:000183201000007 PM 12846366 ER PT J AU Edelman, MJ Bauer, K Khanwani, S Tait, N Trepel, J Karp, J Nemieboka, N Chung, EJ Van Echo, D AF Edelman, MJ Bauer, K Khanwani, S Tait, N Trepel, J Karp, J Nemieboka, N Chung, EJ Van Echo, D TI Clinical and pharmacologic study of tributyrin: an oral butyrate prodrug SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE butyrate; histone deacetylase inhibitor; differentiating agent ID COLON-CANCER CELLS; HISTONE DEACETYLASE; GENE-EXPRESSION; DIFFERENTIATION; ACID; LINES; AGENT AB Purpose: Butyrate is a small polar compound able to produce terminal differentiation and apoptosis in a variety of in vitro models at levels above 50-100 muM. Previously our group demonstrated that daily oral administration of the prodrug, tributyrin, is able to briefly achieve levels >100 muM. Given in vitro data that differentiating activity requires continuous butyrate exposure, the short t1/2 of the drug and a desire to mimic the effects of an intravenous infusion, we evaluated a three times daily schedule. Patients and methods: Enrolled in this study were 20 patients with advanced solid tumors for whom no other therapy was available, had life expectancy greater than 12 weeks, and normal organ function. They were treated with tributyrin at doses from 150 to 200 mg/kg three times daily. Blood was sampled for pharmacokinetic analysis prior to dosing and at 15 and 30 min and 1, 1.5, 2, 2.5, 3, 3.5 and 4 h thereafter. Results: The patients entered comprised 15 men and 5 women with a median age of 61 years (range 30-74 years). Prior therapy regimens included: chemotherapy (median two prior regimens, range none to five), radiation therapy (one), no prior therapy (one). There was no dose-limiting toxicity. Escalation was halted at the 200 mg/kg three times daily level due to the number of capsules required. A median butyrate concentration of 52 muM was obtained but there was considerable interpatient variability. No objective responses were seen. There were four patients with prolonged disease stabilization ranging from 3 to 23 months; median progression-free survival was 55 days. Two patients with chemotherapy-refractory non-small-cell lung cancer had survived for >1 year at the time of this report without evidence of progression. Conclusion: Tributyrin is well tolerated and levels associated with in vitro activity are achieved with three times daily dosing. C1 Univ Maryland, Greenebaum Canc Ctr, Div Hematol Oncol, Baltimore, MD 21201 USA. VA Maryland Hlth Care Syst, Baltimore, MD 21201 USA. Univ Maryland, Sch Pharm, Dept Pharm Practice & Sci, Baltimore, MD 21201 USA. NCI, Med Oncol Clin Res Unit, Ctr Canc Res, Bethesda, MD 20892 USA. RP Edelman, MJ (reprint author), Univ Maryland, Greenebaum Canc Ctr, Div Hematol Oncol, 22 S Greene St, Baltimore, MD 21201 USA. FU NCI NIH HHS [U01 CA 69854] NR 18 TC 39 Z9 39 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 2003 VL 51 IS 5 BP 439 EP 444 DI 10.1007/s00280-003-0580-5 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 687VU UT WOS:000183398300011 PM 12736763 ER PT J AU Skinner, HG Michaud, DS Colditz, GA Giovannucci, EL Stampfer, MJ Willett, WC Fuchs, CS AF Skinner, HG Michaud, DS Colditz, GA Giovannucci, EL Stampfer, MJ Willett, WC Fuchs, CS TI Parity, reproductive factors, and the risk of pancreatic cancer in women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-3; HUMAN-PREGNANCY SERUM; NATIONAL DEATH INDEX; REPLACEMENT THERAPY; CIRCULATING LEVELS; DIABETES-MELLITUS; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; BREAST-CANCER AB Incidence rates for pancreatic cancer are consistently lower in women than in men. Previous studies suggest that reproductive factors, particularly parity, may reduce pancreatic cancer risk in women. We examined parity, breast feeding history, age at first birth, menstrual factors, and exogenous hormone use in relation to pancreatic cancer risk in a prospective cohort study of women. Information on parity and other reproductive factors was assessed by questionnaires in 1976 and updated biennially. Multivariate relative risks were adjusted for cigarette smoking, body mass index, diabetes, and height. During 22 years of. follow-up (1976 1998), 115,474 women contributed 2.4 million years of person time, and 243 cases of pancreatic cancer were identified. Compared with nulliparous women, the relative risk of pancreatic cancer was 0.86 [95% confidence interval (CI), 0.55-1.36] for women with 1-2 births, 0.75 (95% CI, 0.48-1.17) for 3-4 births, and 0.58 (95% CI, 0.34-0.98) for those with greater than or equal to5 births after adjusting for other factors. An analysis for linear trend indicates a 10% reduction in risk for each birth (P-trend = 0.008). Other reproductive factors and exogenous hormone use were not significantly related to pancreatic cancer risk. In this large prospective cohort of women, parity was associated significantly with a reduced risk of pancreatic cancer. Additional studies should examine the physiological or hormonal changes underlying pregnancy or childbirth that may explain this finding. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Skinner, HG (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. RI Skinner, Halcyon/A-1049-2009; Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA55075, CA86102, CA87969, CA9001] NR 45 TC 49 Z9 50 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2003 VL 12 IS 5 BP 433 EP 438 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 680CU UT WOS:000182959400007 PM 12750238 ER PT J AU Troisi, R Potischman, N Roberts, JM Harger, G Markovic, N Cole, B Lykins, D Siiteri, P Hoover, RN AF Troisi, R Potischman, N Roberts, JM Harger, G Markovic, N Cole, B Lykins, D Siiteri, P Hoover, RN TI Correlation of serum hormone concentrations in maternal and umbilical cord samples SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; BIRTH-WEIGHT; DEHYDROEPIANDROSTERONE-SULFATE; PREGNANCY ESTROGENS; SEX-DIFFERENCES; ESTRIOL LEVELS; YOUNG-WOMEN; TERM; BLOOD; TESTOSTERONE AB Evidence suggests that adult cancer risk of hormonally related tumors may be influenced by the in utero environment, and most speculation on the biological mechanism has focused on the hormonal component. Epidemiological studies investigating the biological nature of pregnancy and maternal factors associated with offspring's cancer risk have relied on maternal hormone measurements. The degree to which maternal hormone levels represent the fetal environment, however, is not widely known. Pregnancy estrogen, androstenedione, testosterone, dehydroepiandrosterone (DHEA), and DHEA-sulfate concentrations were measured in maternal and mixed umbilical cord sera from 86 singleton pregnancies. Spearman correlations between maternal and cord hormone levels generally ranged between 0.2 and 0.3. The correlation was 0.26 for estriol, the estrogen of highest concentration in pregnancy, and 0.27 for estradiol, the most biologically active estrogen. The correlations between mother and offspring for the estrogens and DHEA appeared similar for males and females, whereas there was a suggestion that the maternal-umbilical cord correlations for other androgens varied in magnitude by fetal sex, and all correlations appeared higher in pregnancies lasting <38 weeks compared with longer gestational lengths, although these stratified findings may have been attributable to chance. These data show a moderate degree of correlation in hormone concentrations between the maternal and fetal circulation. Studies using maternal hormone concentrations as a proxy for the fetal environment should consider the misclassification. resulting with the use of this marker. C1 NCI, Div Canc Epidemiol & Genet, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Hanover, NH 03755 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15238 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94122 USA. RP Troisi, R (reprint author), NCI, Div Canc Epidemiol & Genet, Epidemiol & Biostat Program, 6120 Execut Blvd, Bethesda, MD 20892 USA. FU NICHD NIH HHS [2 P01 HD30367] NR 34 TC 57 Z9 57 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2003 VL 12 IS 5 BP 452 EP 456 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 680CU UT WOS:000182959400010 PM 12750241 ER PT J AU Rollison, DEM Helzlsouer, KJ Alberg, AJ Hoffman, S Hou, J Daniel, R Shah, KV Major, EO AF Rollison, DEM Helzlsouer, KJ Alberg, AJ Hoffman, S Hou, J Daniel, R Shah, KV Major, EO TI Serum antibodies to JC virus, BK virus, simian virus 40, and the risk of incident adult astrocytic brain tumors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SV40 INFECTIONS; DNA-SEQUENCES; T-ANTIGEN; SIMIAN-VIRUS-40; EXPRESSION; MEDULLOBLASTOMAS; EPENDYMOMAS; ASSOCIATION; EXPOSURE; PROTEIN AB Genomic sequences of the human polyomaviruses, JC virus (JCV) and BK virus (BKV), and simian virus 40 (SV40) have been reported from several types of human brain tumors, but there have been no population-based seroepidemiologic studies to evaluate the association between polyomavirus infection and brain tumors. We conducted a case-control study, nested within a prospective cohort, to investigate the association between antibodies to JCV, BKV, and SV40, as measured in serum collected 1-22 years before diagnosis and incident primary malignant brain tumors. Brain tumor cases (n = 44) and age-, gender-, and race-matched controls (n = 88) were identified from participants of two specimen banks in Washington County, Maryland. IgG antibodies to the capsid proteins of JCV and BKV were assessed using ELISAs. SV40-neutralizing antibodies were measured using plaque neutralization assays. Similar to the general population, the prevalence of JCV and BKV infection was high in our study population (77 and 85%, respectively). Antibodies to SV40 were less prevalent (11%). The odds ratio for subsequent brain tumor development was 1.46 [95% confidence interval (CI), 0.61-3.5] for JCV, 0.66 for BKV (95% CI, 0.22-1.95), and 1.00 for SV40 (95% CI, 0.30-3.32). Given the high prevalence of JCV and BKV infections and the millions who were potentially exposed to SV40 through contaminated polio vaccines, future studies should attempt to replicate these findings. C1 Johns Hopkins Univ, Bloomberg Sch Publ HLth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ HLth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. NINDS, Rockville, MD 20852 USA. RP Helzlsouer, KJ (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ HLth, Dept Epidemiol, 615 N Wolfe St,Suite 6030, Baltimore, MD 21205 USA. FU NCI NIH HHS [2 T32 CA093-14-19, K07 CA73790, 5U01 CA86308-04] NR 28 TC 52 Z9 53 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2003 VL 12 IS 5 BP 460 EP 463 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 680CU UT WOS:000182959400012 PM 12750243 ER PT J AU Pastan, I AF Pastan, I TI Immunotoxins containing Pseudomonas exotoxin A: a short history SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; RECOMBINANT IMMUNOTOXIN; GROWTH-FACTOR; POLYETHYLENE-GLYCOL; ANTITUMOR-ACTIVITY; SOLID TUMORS; CELLS; MICE; XENOGRAFTS; MESOTHELIN C1 NCI, Mol Biol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. NR 22 TC 67 Z9 73 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD MAY PY 2003 VL 52 IS 5 BP 338 EP 341 DI 10.1007/s00262-002-0353-8 PG 4 WC Oncology; Immunology SC Oncology; Immunology GA 682QT UT WOS:000183103800008 PM 12700949 ER PT J AU Koh, E Clair, T Woodhouse, EC Schiffmann, E Liotta, L Stracke, M AF Koh, E Clair, T Woodhouse, EC Schiffmann, E Liotta, L Stracke, M TI Site-directed mutations in the tumor-associated cytokine, autotaxin, eliminate nucleotide phosphodiesterase, lysophospholipase D, and motogenic activities SO CANCER RESEARCH LA English DT Article ID HUMAN-MELANOMA CELLS; PHOSPHOLIPASE-D; MOTILITY; SUPERFAMILY; PROTEIN AB The exo-enzyme autotaxin/NPP2 (ATX/NPP2) is a potent stimulator of cell migration, invasion, metastasis, and angiogenesis. Recently, ATX/NPP2 was found to possess lysophospholipase D (lyso-LPD) activity, generating the bioactive mediator lysophosphatidic acid from precursors. In the present study, we used site-directed mutagenesis to delineate the active domain of lysophospholipid catalytic activity and to examine potential overlap with the nucleotide phosphodiesterase domain. We found four amino acid residues obligatory for the phosphodiesterase, lyso-PLD, and migration-stimulating activities of ATX/NPP2, suggesting that 5'-nucleotide phosphodiesterase (PDE) and lyso-PLD share a common reaction mechanism and inviting design of enzymatic inhibitors as therapeutic agents for neoplastic disease. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Koh, E (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 46 Z9 46 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2003 VL 63 IS 9 BP 2042 EP 2045 PG 4 WC Oncology SC Oncology GA 674MK UT WOS:000182640400010 PM 12727817 ER PT J AU Wang, LH Yang, XY Zhang, XH Mihalic, K Xiao, WH Farrar, WL AF Wang, LH Yang, XY Zhang, XH Mihalic, K Xiao, WH Farrar, WL TI The cis decoy against the estrogen response element suppresses breast cancer cells via target disrupting c-fos not mitogen-activated protein kinase activity SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR DECOY; RETINOID-X-RECEPTOR; CROSS-TALK; GENE-EXPRESSION; IN-VIVO; MOLECULAR TARGETS; MCF-7 CELLS; E2F DECOY; OLIGONUCLEOTIDE; BINDING AB Breast cancer, the most common malignancy in women, has been demonstrated to be associated with the steroid hormone estrogen and its receptor (ER), a ligand-activated transcription factor. Therefore, we developed a phosphorothiolate cis-element decoy against the estrogen response element (ERE decoy) to target disruption of ER DNA binding and transcriptional activity. Here, we showed that the ERE decoy potently ablated the 17beta-estrogen-inducible cell proliferation and induced apoptosis of human breast carcinoma cells by functionally affecting expression of c-fos gene and AP-1 luciferase gene reporter activity. Specificity of the decoy was demonstrated by its ability to directly block ER binding to a cis-element probe and transactivation. Moreover, the decoy failed to inhibit ER-mediated mitogen-activated protein kinase signaling pathways and cell growth of ER-negative breast cancer cells. Taken together, these data suggest that estrogen-mediated cell growth of breast cancer cells can be preferentially restricted via targeted disruption of ER at the level of DNA binding by a novel and specific decoy strategy applied to steroid nuclear receptors. C1 NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. NCI, Cytokine Mol Mech Sect, Lab Mol Immunoregulat, NIH, Frederick, MD 21702 USA. RP Wang, LH (reprint author), NCI, Intramural Res Support Program, Sci Applicat Int Corp, POB B,Bldg 560,Room 31-76, Frederick, MD 21702 USA. RI Xiao, Weihua/N-2775-2013 OI Xiao, Weihua/0000-0001-9102-6326 FU NCI NIH HHS [N01-CO-12400] NR 62 TC 24 Z9 24 U1 2 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 1 PY 2003 VL 63 IS 9 BP 2046 EP 2051 PG 6 WC Oncology SC Oncology GA 674MK UT WOS:000182640400011 PM 12727818 ER PT J AU Montagna, C Lyu, MS Hunter, K Lukes, L Lowther, W Reppert, T Hissong, B Weaver, Z Ried, T AF Montagna, C Lyu, MS Hunter, K Lukes, L Lowther, W Reppert, T Hissong, B Weaver, Z Ried, T TI The septin 9 (MSF) gene is amplified and overexpressed in mouse mammary gland adenocarcinomas and human breast cancer cell lines SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; ACUTE MYELOID-LEUKEMIA; TRANSGENIC MICE; METASTATIC DISEASE; OVARIAN-TUMORS; FUSION GENE; EXPRESSION; AMPLIFICATION; REGION; MUTANT AB The expression of polyomavirus middle T antigen under the control of the mouse mammary tumor virus promoter in transgenic mice results in the induction of aggressive mammary gland adenocarcinomas at an early age. We screened 26 tumors for chromosomal aneuploidies using SKY and CGH. In 70% of the tumor samples we could detect high-level copy number gains, which mapped to chromosome band 11E2, a region orthologous to human 17q25.3. We then identified a bacterial artificial chromosome clone that labeled double-minute chromosomes found in the tumor metaphases. This bacterial artificial chromosome clone showed sequence homology to a member of the septin gene family. Real-time PCR analysis revealed a consistently increased expression of septin 9 (Sept9), not only in polyomavirus middle T antigen-induced, but in a wide variety of mouse models of breast cancer. Six of 9 human tumor cell lines also revealed elevated expression levels of Sept9. The family of septin genes is involved in a plethora of cellular processes, including cytokinesis in yeast and vesicle transport, and possesses GTPase activity. We identified down-regulation of Thsp1- and Bax-regulated apoptotic response in those tumors with Sept9 overexpression, an effect that could be reversed by inhibiting Sept9 expression using transfection with small interference RNA. Our results now suggest that signaling via members of the septin family plays a novel and common role in breast tumorigenesis. C1 NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Lab Populat Genet, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Ried, T (reprint author), NCI, Genet Branch, Canc Res Ctr, NIH, 50 South Dr,Bldg 50,Room 1306, Bethesda, MD 20892 USA. NR 35 TC 90 Z9 96 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 1 PY 2003 VL 63 IS 9 BP 2179 EP 2187 PG 9 WC Oncology SC Oncology GA 674MK UT WOS:000182640400030 PM 12727837 ER PT J AU Takino, T Nakada, M Miyamori, H Yamashita, J Yamada, KM Sato, H AF Takino, T Nakada, M Miyamori, H Yamashita, J Yamada, KM Sato, H TI CrkI adapter protein modulates cell migration and invasion in glioblastoma SO CANCER RESEARCH LA English DT Article ID FOCAL ADHESION KINASE; EXTRACELLULAR-MATRIX; ACTIVATION; RAP1; PTEN; INHIBITION; COMPLEXES; JUNCTIONS; SURVIVAL; PATHWAY AB The human crk gene is translated into crkI and crkII by alternative splicing. crkII mRNA was detected both in normal brain and glioblastoma tissues, whereas crkI mRNA levels were quite low in normal brain and up-regulated in glioblastoma tissues. Expression of CrkI but not CrkII in glioblastoma U87MG cells induced transformation that stimulated cell migration and invasion concomitant with tyrosine phosphorylation of p130 Crk-associated substrate. N-cadherin-mediated signal transduction, which was essential for invasion by U87MG cells, was no longer required for CrkI-transformed cells. These results suggest that CrkI contributes to malignancy of glioblastoma by inducing phosphorylation of p130 Crk-associated substrate. C1 Kanazawa Univ, Canc Res Inst, Dept Mol Virol & Oncol, Grad Sch Med Sci, Kanazawa, Ishikawa 9200934, Japan. Kanazawa Univ, Div Neurosci, Dept Neurosurg, Grad Sch Med Sci, Kanazawa, Ishikawa 9200934, Japan. Natl Inst Dental & Cranofacial Res, Cranoifacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. RP Takino, T (reprint author), Kanazawa Univ, Canc Res Inst, Dept Mol Virol & Oncol, Grad Sch Med Sci, 13-1 Takaramachi, Kanazawa, Ishikawa 9200934, Japan. RI TAKINO, Takahisa/D-8460-2015; SATO, Hiroshi/D-8454-2015; OI Yamada, Kenneth/0000-0003-1512-6805 NR 20 TC 59 Z9 66 U1 1 U2 6 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 1 PY 2003 VL 63 IS 9 BP 2335 EP 2337 PG 3 WC Oncology SC Oncology GA 674MK UT WOS:000182640400052 PM 12727859 ER PT J AU Opresko, PL Cheng, WH von Kobbe, C Harrigan, JA Bohr, VA AF Opresko, PL Cheng, WH von Kobbe, C Harrigan, JA Bohr, VA TI Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process SO CARCINOGENESIS LA English DT Review ID SYNDROME GENE-PRODUCT; DNA-POLYMERASE-DELTA; BLOOM-SYNDROME HELICASES; BASE-EXCISION-REPAIR; SYNDROME CELLS; TELOMERE LENGTH; IN-VITRO; SYNDROME FIBROBLASTS; BIOCHEMICAL-CHARACTERIZATION; HOMOLOGOUS RECOMBINATION AB Werner syndrome (WS) is a hallmark premature aging disease, in which the patients appear much older than their chronological age, and exhibit many of the clinical signs and symptoms of normal aging at an early stage in life. They develop many age-associated diseases early in life including atherosclerosis, osteoporosis, cataracts and display a high incidence of cancer. WS is also marked by increased genomic instability, manifested as chromosomal alterations. Characterization and study of the Werner protein (WRN) suggests that it participates in several important DNA metabolic pathways, and that its primary function may be in DNA repair processes. Thus, the WRN protein represents an important link between defective DNA repair and the processes related to aging and cancer. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Schock Dr, Baltimore, MD 21224 USA. OI Opresko, Patricia/0000-0002-6470-2189 NR 131 TC 123 Z9 129 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2003 VL 24 IS 5 BP 791 EP 802 DI 10.1093/carcin/bgg034 PG 12 WC Oncology SC Oncology GA 684YX UT WOS:000183235000001 PM 12771022 ER PT J AU Hung, RJ Boffetta, P Brockmoller, J Butkiewicz, D Cascorbi, I Clapper, ML Garte, S Haugen, A Hirvonen, A Anttila, S Kalina, I Le Marchand, L London, SJ Rannug, A Romkes, M Salagovic, J Schoket, B Gaspari, L Taioli, E AF Hung, RJ Boffetta, P Brockmoller, J Butkiewicz, D Cascorbi, I Clapper, ML Garte, S Haugen, A Hirvonen, A Anttila, S Kalina, I Le Marchand, L London, SJ Rannug, A Romkes, M Salagovic, J Schoket, B Gaspari, L Taioli, E TI CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers: a pooled analysis SO CARCINOGENESIS LA English DT Article ID GLUTATHIONE S-TRANSFERASES; DNA ADDUCT LEVELS; AFRICAN-AMERICANS; N-ACETYLTRANSFERASE; LOS-ANGELES; CLASS-MU; SUSCEPTIBILITY; POPULATION; GENOTYPE; CARCINOGENS AB Polymorphisms for genes encoding the metabolic enzymes cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) might contribute to the variability in individual susceptibility to lung cancer. The role of CYP1A1 and GSTM1 in lung carcinogenesis might be more important at low levels of exposure to carcinogens. Non-smokers represent a population at low exposure, however, they are often overlooked because of the small number of cases. We therefore conducted a pooled analysis of 14 case-control studies on lung cancer in Caucasian non-smokers with comparable information on genetic polymorphisms included in the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. We pooled the raw data from a total of 302 cases and 1631 controls with random effects models. We also evaluated the possibility of inclusion bias and conducted influence analyses. The odds ratio (OR) of lung cancer for the variant CYP1A1 Ile(462)Val polymorphism (Ile/Val, Val/Val) was 2.99 [95% confidence interval (95%CI) 1.51-5.91]; this effect was stronger on lung adenocarcinoma (OR 4.85, 95%CI 2.03-11.6). After excluding outlying or imprecise studies, we did not observe a significant effect of the CYP1A1 MspI ((TC)-C-3801) polymorphism or GSTM1 null genotype (OR 1.20, 95%CI 0.89-1.63). Furthermore, our analyses suggested a combined effect of the CYP1A1 Ile(462)Val polymorphism and GSTM1 null genotype. The OR for the combination of the CYP1A1 Ile(462)Val variant and GSTM1 null genotype was 4.67 (95%CI 2.00-10.9) compared with the concurrent presence of the CYP1A1 wild-type and GSTM1 non-null genotype. We did not observe a modification of the effect of the GSTM1 null genotype according to exposure to environmental tobacco smoke and urban/rural residence. Our study therefore suggests that the CYP1A1 Ile(462)Val variant allele might play a role in lung carcinogenesis among non-smokers, possibly in combination with the GSTM1 null genotype. C1 Int Agcy Res Canc, Unit Environm Canc Epidemiol, F-69372 Lyon 08, France. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. Univ Gottingen, Inst Clin Pharmacol, D-3400 Gottingen, Germany. Ctr Oncol, Dept Tumor Biol, Gliwice, Poland. Univ Greifswald, Inst Pharmacol, D-17487 Greifswald, Germany. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. Genet Res Inst ONLUS, Milan, Italy. Natl Inst Occupat Hlth, Dept Toxicol, Oslo, Norway. Finnish Inst Occupat Hlth, Helsinki, Finland. Safarik Univ, Sch Med, Dept Med Biol, Kosice, Slovakia. Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. Univ Pittsburgh, Ctr Clin Pharmacol, Pittsburgh, PA USA. Natl Inst Environm Hlth, Dept Biochem, Budapest, Hungary. Univ Milan, IRCCS, Dept Environm Med, Milan, Italy. RP Boffetta, P (reprint author), Int Agcy Res Canc, Unit Environm Canc Epidemiol, 150 Cours Albert Thomas, F-69372 Lyon 08, France. RI Cascorbi, Ingolf/A-4519-2009; Hung, Rayjean/A-7439-2013; OI London, Stephanie/0000-0003-4911-5290 NR 60 TC 132 Z9 150 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2003 VL 24 IS 5 BP 875 EP 882 DI 10.1093/carcin/bgg026 PG 8 WC Oncology SC Oncology GA 684YX UT WOS:000183235000010 PM 12771031 ER PT J AU Fischer, SM Conti, CJ Viner, J Aldaz, CM Lubet, RA AF Fischer, SM Conti, CJ Viner, J Aldaz, CM Lubet, RA TI Celecoxib and difluoromethylornithine in combination have strong therapeutic activity against UV-induced skin tumors in mice SO CARCINOGENESIS LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; ALPHA-DIFLUOROMETHYLORNITHINE; ORNITHINE-DECARBOXYLASE; MOUSE SKIN; CYCLOOXYGENASE-2 INHIBITOR; COLON CARCINOGENESIS; ANTIINFLAMMATORY DRUGS; POLYAMINE BIOSYNTHESIS; IRREVERSIBLE INHIBITOR; BREAST-CANCER AB The cyclooxygenase-2 (COX-2) inhibitor celecoxib and the ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO) were each previously shown to prevent skin tumor development when administered throughout the course of UV irradiation. This raised the question of whether maintenance or continued growth of existing tumors required prostaglandins, the product of COX, or polyamines, the product of ODC. To address this question, SKH hairless mice were irradiated 3 times/week with 90 mJ/cm(2); this dose was increased 10% weekly to a maximum of 175 mJ/cm(2). UV was stopped at 27 weeks, at which time there were an average of 5 papillomas/mouse. The mice were then placed in one of four treatment groups: group 1, no treatment; group 2, 0.4% DFMO in the drinking water; group 3, 500 p.p.m. celecoxib in the diet (AIN76); group 4, both DFMO and celecoxib. The control group continued to produce new tumors in a nearly linear manner such that by week 31 the tumor number had nearly doubled, i.e. similar to10 tumors/mouse. The group receiving DFMO showed significant tumor regression, losing an average of 1 tumor/mouse/week, such that 50% of the tumors remained at week 31. The celecoxib group showed a 25% reduction in tumor number. The group receiving the combination of celecoxib and DFMO showed the greatest regression, with an 89% reduction in tumor number compared with the control group. There was also a corresponding reduction in the size of the tumors. To determine whether tumor regression was permanent or required continued treatment, all treatments were stopped at 31 weeks. Over the next 4 weeks, tumors reappeared at the same rate in all treatment groups. It is concluded that the combination of celecoxib and DFMO are potent therapeutic agents for skin cancer, although the benefits are lost with the cessation of treatment. C1 Univ Texas, MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX 78957 USA. NIH, Div Canc Prevent & Control, Rockville, MD 20852 USA. RP Fischer, SM (reprint author), Univ Texas, MD Anderson Canc Ctr, Div Sci Pk Res, POB 389,Pk Rd 1C, Smithville, TX 78957 USA. FU NCI NIH HHS [CA-16672, CA-34443, CN-65110-72]; NIEHS NIH HHS [P30 ES07784] NR 43 TC 59 Z9 60 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2003 VL 24 IS 5 BP 945 EP 952 DI 10.1093/carcin/bgg046 PG 8 WC Oncology SC Oncology GA 684YX UT WOS:000183235000019 PM 12771040 ER PT J AU Tsutsui, T Kumakura, S Tamura, Y Tsutsui, TW Sekiguchi, M Higuchi, T Barrett, JC AF Tsutsui, T Kumakura, S Tamura, Y Tsutsui, TW Sekiguchi, M Higuchi, T Barrett, JC TI Immortal, telomerase-negative cell lines derived from a Li-Fraumeni syndrome patient exhibit telomere length variability and chromosomal and minisatellite instabilities SO CARCINOGENESIS LA English DT Article ID WILD-TYPE P53; GENE AMPLIFICATION; HUMAN FIBROBLASTS; HOMOLOGOUS RECOMBINATION; SKIN FIBROBLASTS; DNA; EXPRESSION; CANCER; ASSOCIATION; IRRADIATION AB Five immortal cell lines derived from a Li-Fraumeni syndrome patient (MDAH 087) with a germline mutant p53 allele were characterized with respect to telomere length and genomic instability. The remaining wild-type p53 allele is lost in the cell lines. Telomerase activity was undetectable in all immortal cell lines. Five subclones of each cell line and five re-subclones of each of the subclones also showed undetectable telomerase activity. All five immortal cell lines exhibited variability in the mean length of terminal restriction fragments (TRFs). Subclones of each cell line, and re-subclones of the subclones also showed TRF variability, indicating that the variability is owing to clonal heterogeneity. Chromosome aberrations were observed at high frequencies in these cell lines including the subclones and re-subclones, and the principal types of aberrations were breaks, double minute chromosomes and dicentric chromosomes. In addition, minisatellite instability detected by DNA fingerprints was observed in the immortal cell lines. However, all of the cell lines were negative for microsatellite instability. As minisatellite sequences are considered recombinogenic in mammalian cells, these results suggest that recombination rates can be increased in these cell lines. Tumor-derived human cell lines, HT1080 cells and HeLa cells that also lack p53 function, exhibited little genomic instability involving chromosomal and minisatellite instabilities, indicating that chromosomal and minisatellite instabilities observed in the immortal cell lines lacking telomerase activity could not result from loss of p53 function. C1 NCI, NIH, Bethesda, MD 20892 USA. Nippon Dent Univ Tokyo, Sch Dent, Dept Pharmacol, Tokyo, Japan. TSL Inc, Mol Pathol Grp, Tokyo, Japan. RP Barrett, JC (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 49 TC 14 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2003 VL 24 IS 5 BP 953 EP 965 DI 10.1093/carcin/bgg024 PG 13 WC Oncology SC Oncology GA 684YX UT WOS:000183235000020 PM 12771041 ER PT J AU Meyer, K Lee, JS Dyck, PA Cao, WQ Rao, MS Thorgeirsson, SS Reddy, JK AF Meyer, K Lee, JS Dyck, PA Cao, WQ Rao, MS Thorgeirsson, SS Reddy, JK TI Molecular profiling of hepatocellular carcinomas developing spontaneously in acyl-CoA oxidase deficient mice: comparison with liver tumors induced in wild-type mice by a peroxisome proliferator and a genotoxic carcinogen SO CARCINOGENESIS LA English DT Article ID ACTIVATED RECEPTOR-ALPHA; GLUTAMYL-TRANSFERASE TRANSPEPTIDASE; GENE-EXPRESSION; MOUSE-LIVER; PPAR-ALPHA; INDUCED HEPATOCARCINOGENESIS; PROSTATE-CANCER; CDNA MICROARRAY; TERM EXPOSURE; RAT-LIVER AB By using cDNA microarrays, we studied the expression profiles of 26 hepatocellular carcinomas (HCC) developing spontaneously in peroxisomal fatty acyl-CoA oxidase null (AOX-/-) mice. The development of liver tumors in AOX-/- mice is due to sustained activation of peroxisome proliferator-activated receptor alpha (PPARalpha) by the unmetabolized substrates of AOX, which serve as natural PPARalpha ligands. We then compared the AOX-/- liver tumor expression profiles with those induced by ciprofibrate, a non-genotoxic peroxisome proliferator, or by the genotoxic carcinogen diethylnitrosamine (DENA) to discern differences in gene expression patterns that may predict or distinguish PPARalpha-mediated liver tumors from genotoxically derived tumors. Our results show that HCCs developing in AOX-/- mice share a number of deregulated (up- or down-regulated) genes with ciprofibrate-induced liver tumors. The overall commonality of expression between AOX-/- and ciprofibrate-induced liver tumors but not with DENA-induced tumors strongly implicates the activation of PPARalpha and PPARalpha-regulated genes in liver, including those participating in lipid catabolism, as key factors in the development of HCC in AOX-/- and in ciprofibrate-treated mice. Northern blot analysis confirmed the differential expression of some of the genes identified in the present study, and also some genes identified previously as PPARalpha regulated, such as CD36, lymphocyte antigen 6 complex locus (Ly-6D), and C3f. We found a panel of 12 genes upregulated in all three classes of liver tumors, namely AOX-/-, ciprofibrate-induced and DENA-induced. These include an uncharacterized RIKEN cDNA, lipocalin 2, insulin-like growth factor-binding protein 1, Ly-6D and CD63 among others. In conclusion, these results identify distinguishing features between non-genotoxic and genotoxic carcinogen derived liver tumors as well as genes that are upregulated in both types and suggest that RIKEN cDNA, Ly-6D and lipocalin 2 in particular appear to be desirable molecular markers for further study in liver carcinogenesis and progression. C1 Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Ctr Genet Med, Feinberg Sch Med, Chicago, IL 60611 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Reddy, JK (reprint author), Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. FU NCI NIH HHS [CA 84472]; NIGMS NIH HHS [GM 23750] NR 56 TC 40 Z9 40 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2003 VL 24 IS 5 BP 975 EP 984 DI 10.1093/carcin/bgg040 PG 10 WC Oncology SC Oncology GA 684YX UT WOS:000183235000022 PM 12771043 ER PT J AU Kearney, DL Perez-Atayde, AR Easley, KA Bowles, NE Bricker, JT Colan, SD Kaplan, S Lai, WW Lipshultz, SE Moodie, DS Sopko, G Starc, TJ Towbin, JA AF Kearney, DL Perez-Atayde, AR Easley, KA Bowles, NE Bricker, JT Colan, SD Kaplan, S Lai, WW Lipshultz, SE Moodie, DS Sopko, G Starc, TJ Towbin, JA CA Natl Heart Lung Blood Inst TI Postmortem cardiomegaly and echocardiographic measurements of left ventricular size and function in children infected with the human immunodeficiency virus - The Prospective P2C2HIV Multicenter Study SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE postmortem; cardiomegaly; HIV; children; echocardiography ID PROSPECTIVE (PCHIV)-C-2-H-2 MULTICENTER; DILATED CARDIOMYOPATHY; SELENIUM DEFICIENCY; CARDIAC DYSFUNCTION; HIV; DISEASE; MORTALITY; MALNUTRITION; HYPERTROPHY; INFANTS AB Background: Cardiomegaly, seen postmortem in over 50% of HIV-infected children, may occur in the absence of clinical or histopathologic cardiac disease. Premortem echocardiography has also demonstrated clinical and subclinical cardiac disease, including increased left ventricular mass (LVM) and functional abnormalities. No studies have compared these echocardiographic measures of heart size and function with postmortem findings in this population. We sought to determine the postmortem prevalence, clinicopathologic relationships and importance of cardiomegaly in HIV-infected children. Methods: We reviewed clinical and postmortem cardiac findings in 30 HIV-infected children who were part of the Prospective (PC2)-C-2 HIV Study. Postmortem heart weight was compared with clinical measures of heart size and function, with cardiac pathology and with clinical measures reflecting chronic effects of HIV disease. Results: Postmortem cardiomegaly (heart weight z score greater than or equal to 2) was identified in 53% of the children. Children with cardiomegaly had increased LVM, increased heart rate, more frequent clinical chronic heart disease and a higher prevalence of postmortem pericardial effusions compared to children without cardiomegaly (P less than or equal to .05). The association with LV end-diastolic dimension (LVEDD) did not reach statistical significance (P= .08). No association was found with LV posterior wall thickness (LVPWT), CD4(+) T-cell counts, HIV-1 viral load, hemoglobin, encephalopathy, myocardial histology or myocardial organisms. Conclusions: Postmortem cardiomegaly was associated with echocardiographic measures of increased LVM. The pathogenesis appears not to be related to chronic anemia, HIV viral load, the degree of immune suppression or encephalopathy. Autonomic dysregulation, reflected by chronically increased heart rate, may be of pathoetiologic significance. (C) 2003 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Cardiol & Pediat, Boston, MA 02115 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Baylor Coll Med, Dept Pediat, Div Pediat Cardiol, Houston, TX 77030 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Div Pediat Cardiol, Los Angeles, CA 90024 USA. Mt Sinai Sch Med, Dept Pediat, Div Pediat Cardiol, New York, NY USA. Cleveland Clin Fdn, Dept Pediat Cardiol, Cleveland, OH 44195 USA. NHLBI, Cardiac Dis Branch, Bethesda, MD 20892 USA. Presbyterian Univ Hosp, Dept Pediat, Div Pediat Cardiol, New York, NY USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Kearney, DL (reprint author), Texas Childrens Hosp, Dept Pathol, 6621 Fannin St, Houston, TX 77030 USA. RI Easley, Kirk/K-6910-2015 OI Easley, Kirk/0000-0003-4419-2617 FU NCRR NIH HHS [RR-00645, RR-02172, RR-00043, RR-00865, RR-00188]; NHLBI NIH HHS [N01-HR-96040, N01-HR-96043, N01-HR-96038, N01-HR-96041, N01 HR096037, N01-HR-96042, N01-HR-96039] NR 35 TC 7 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD MAY-JUN PY 2003 VL 12 IS 3 BP 140 EP 148 DI 10.1016/S1054-8807(03)00035-8 PG 9 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 681BL UT WOS:000183016800002 PM 12763553 ER PT J AU Birnbaumer, L Yidirim, E Abramowitz, J AF Birnbaumer, L Yidirim, E Abramowitz, J TI A comparison of the genes coding for canonical TRP channels and their M, V and P relatives SO CELL CALCIUM LA English DT Article DE TRP channel; Drosophila; polycystic kidney diseases 1 and 2; chromosome; human; mouse ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; CA2+-PERMEABLE CATION CHANNEL; HUMAN HOMOLOG; CALMODULIN-BINDING; MOLECULAR-CLONING; IDENTIFICATION; PROTEIN; FAMILY AB The mammalian transient receptor potential (TRP) protein gene family consists of a diverse group of cation channels that currently contain at least 26 members. The physiologic functions of many remain unknown. They are structurally similar to Drosophila TRP and have a wide tissue distribution. In the present report, we compare the chromosomal locations, the gene, and primary structures of each of these 26 human TRP family members. Based on primary amino acid analyses, these channels comprise four different subfamilies: C- (canonical or classical), V- (or vaniloid receptor related), M- (melastatin related), and P (PKD)-type. The highest homology within each subfamily and between subfamilies exists in the predicted ion channel domains. Belonging to a given subfamily, however, does not determine the activating stimuli. This is exemplified by the V- and M-subfamilies, both of which have members that respond to temperature and osmolarity. TRP genes vary in their intron-exon organization, with the greatest diversity in the P subfamily. Chromosomal organization analyses revealed that two TRP members are found as direct repeats; TRPV3 follows TRPV1 and TRPV6 follows TRPV5. Both of these duplications appear to be recent as TRPV1 and V3 are more similar to each other than to other members of the TRPV subfamily. The same holds true for TRPV5 and V6. The article presents complication of comparisons including exon-intron boundaries, the amino acid sequence alignments, and the chromosomal organization of each of the presently known TRP channels. Published by Elsevier Science Ltd. C1 Natl Inst Environm Hlth Res, Lab Signal Transduct, Dept Human Hlth Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Birnbaumer, L (reprint author), Natl Inst Environm Hlth Res, Lab Signal Transduct, Dept Human Hlth Serv, NIH, Res Triangle Pk, NC 27709 USA. RI Abramowitz, Joel/A-2620-2015; OI Yildirim, Eda/0000-0002-4796-3854 NR 23 TC 50 Z9 53 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 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD MAY-JUN PY 2003 VL 33 IS 5-6 BP 419 EP 432 DI 10.1016/S0143-4160(03)00068-X PG 14 WC Cell Biology SC Cell Biology GA 692RH UT WOS:000183673700013 PM 12765687 ER PT J AU Trebak, M Vazquez, G Bird, GSJ Putney, JW AF Trebak, M Vazquez, G Bird, GSJ Putney, JW TI The TRPC3/6/7 subfamily of cation channels SO CELL CALCIUM LA English DT Article DE Ca2+ entry; PLC signaling; TRPC; store-operated Ca2+ entry ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; CAPACITATIVE CALCIUM-ENTRY; SMOOTH-MUSCLE CELLS; OPERATED HTRP3 CHANNELS; ACTIVATED CA2+ CHANNELS; TRP CHANNELS; TRISPHOSPHATE RECEPTOR; STORE DEPLETION; FUNCTIONAL-CHARACTERIZATION; SIGNAL-TRANSDUCTION AB The mammalian transient receptor potential (TRP) proteins consist of a superfamily of Ca2+-permeant non-selective cation channels with structural similarities to Drosophila TRP. The TRP superfamily can be divided into three major families, among them the "canonical TRP" family (TRPC). The seven protein products of the mammalian TRPC family of genes (designated TRPC1-7) share in common the activation through PLC-coupled receptors and have been proposed to encode components of native store-operated channels in different cell types. In addition, the three members of the TRPC3/6/7 subfamily of TRPC channels can be activated by diacylglycerol analogs, providing a possible mechanism of activation of these channels by PLC-coupled receptors. This review summarizes the current knowledge about the mechanism of activation of the TRPC3/6/7 subfamily, as well as the potential role of these proteins as components of native Ca2+-permeant channels. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Trebak, Mohamed/E-7405-2014 NR 84 TC 137 Z9 144 U1 0 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD MAY-JUN PY 2003 VL 33 IS 5-6 BP 451 EP 461 DI 10.1016/S0143-4160(03)00056-3 PG 11 WC Cell Biology SC Cell Biology GA 692RH UT WOS:000183673700016 PM 12765690 ER PT J AU Hebbar, PB Archer, TK AF Hebbar, PB Archer, TK TI Chromatin remodeling by nuclear receptors SO CHROMOSOMA LA English DT Article; Proceedings Paper CT 9th International Symposium on Spermatology CY OCT 06-11, 2002 CL CAPE TOWN, SOUTH AFRICA ID TUMOR VIRUS PROMOTER; HUMAN BREAST-CANCER; LONG TERMINAL REPEAT; RNA-POLYMERASE-II; GLUCOCORTICOID-RECEPTOR; HISTONE H1; IN-VIVO; MMTV PROMOTER; TRANSCRIPTION FACTORS; TRANS-DISPLACEMENT AB The eukaryotic genome is structurally organized into nucleosomes to form chromatin, which regulates gene expression, in part, by controlling the accessibility of regulatory factors. When packaged as chromatin, many promoters are transcriptionally repressed, thus reducing the access of transcription factors to their binding sites. However, nuclear receptors (NRs) are a group of transcription factors that have the ability to access their binding sites in this repressive chromatin structure. Nuclear receptors are able to bind to their sites and recruit chromatin-remodeling proteins such as ATP-dependent chromatin-remodeling complexes and histone-modifying enzymes, resulting in transcriptional activation. In this review, we present the role of NRs in recruiting these chromatin-modifying enzymes by means of an extensively studied model system, the glucocorticoid receptor-mediated transactivation of the mouse mammary tumor virus (MMTV) promoter. We use these findings as a template to begin to understand the effect of chromatin changes on gene expression during spermatogenesis. C1 NIEHS, Reprod & Dev Toxicol Lab, Chromatin & Gene Express Sect, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Chromatin & Gene Express Sect, 111 Alexander Dr,MD-E4-06,POB 12233, Res Triangle Pk, NC 27709 USA. NR 102 TC 70 Z9 70 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD MAY PY 2003 VL 111 IS 8 BP 495 EP 504 DI 10.1007/s00412-003-0232-x PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 690LM UT WOS:000183550700005 PM 12743713 ER PT J AU Plaeger, SF AF Plaeger, SF TI Clinical immunology and traditional herbal medicines SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Editorial Material ID SHOSAIKO-TO; RESPONSES; MODEL C1 NIAID, DAIDS, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Plaeger, SF (reprint author), NIAID, DAIDS, US Dept HHS, NIH, 6700-B Rockledge Dr,Room 4134, Bethesda, MD 20892 USA. NR 13 TC 20 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAY PY 2003 VL 10 IS 3 BP 337 EP 338 DI 10.1128/CDLI.10.3.337-338.2003 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 681EA UT WOS:000183022900001 PM 12738627 ER PT J AU Palena, C Schlom, J Tsang, KY AF Palena, C Schlom, J Tsang, KY TI Differential gene expression profiles in a human T-cell line stimulated with a tumor-associated self-peptide versus an enhancer agonist peptide SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN CARCINOEMBRYONIC ANTIGEN; DENDRITIC CELLS; CHEMOKINE EXPRESSION; IN-VIVO; PHASE-I; COSTIMULATORY MOLECULE; ANTITUMOR IMMUNITY; PERIPHERAL-BLOOD; GAMMA-INTERFERON; DNA MICROARRAY AB Purpose: Previous studies have shown that a specific 9-mer amino acid epitope (designated CAP-1) of the human "self" tumor-associated carcinoembryonic antigen can be used to stimulate CD8+ T cells from peripheral blood mononuclear cells of carcinoma patients vaccinated with pox vector-based carcinoembryonic antigen vaccines. A T-cell receptor agonist epitope of CAP-1 (designated CAP1-6D) has been shown to enhance the stimulation of T cells over levels obtained using CAP-1. The purpose of this study was to analyze gene expression profiles in T cells stimulated with the native CAP-1 versus the agonist CAP1-6D peptide. Experimental Design: Microarray analyses were conducted to analyze differential gene expression profiles of a T-cell line stimulated with native versus agonist peptides. Results: Numerous genes and gene clusters are identified as differentially expressed as a consequence of stimulation with the agonist peptide versus the native peptide; two genes, however, stand out in magnitude: the chemokine lymphotactin and granzyme B. In particular, lymphotactin expression is >12 times more pronounced in agonist-stimulated T cells. An ELISA assay was developed that confirmed marked lymphotactin secretion in T cells when stimulated with the agonist versus the native peptide. A chemotaxis assay also demonstrated the biological activity of the lymphotactin produced. Conclusions: To our knowledge, these are the first studies of gene expression profiles of a defined T-cell line in response to stimulation with a defined antigen. They are also the first to compare, via cDNA microarray, responses of a T-cell line to (a) a tumor-associated self-antigen and (b) a native epitope versus an agonist epitope. C1 NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. NR 57 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2003 VL 9 IS 5 BP 1616 EP 1627 PG 12 WC Oncology SC Oncology GA 677MY UT WOS:000182813200007 PM 12738714 ER PT J AU Kawakami, K Kawakami, M Husain, SR Puri, RK AF Kawakami, K Kawakami, M Husain, SR Puri, RK TI Effect of interleukin (IL)-4 cytotoxin on breast tumor growth after in vivo gene transfer of IL-4 receptor alpha chain SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; CANCER-CELLS; KAPOSIS-SARCOMA; IN-VIVO; ANTITUMOR-ACTIVITY; SYSTEMIC DELIVERY; GAMMA-CHAIN; EXPRESSION AB Although human breast cancer cells express interleukin-4 receptors (IL-4Rs), a recombinant fusion protein, IL-4 cytotoxin, did not mediate desirable antitumor activity in tumor models of breast cancer. Recent studies have identified that a primary IL-4 binding protein, IL-4Ralpha chain, is internalized after binding to IL-4 in cancer cells. The consequent expression of high-level IL-4Ralpha in tumor cells sensitizes them to the cytotoxic effect of IL-4 cytotoxin in vitro. To assess whether overexpression of IL-4Ralpha chain in vivo by plasmid-mediated gene transfer can enhance antitumor activity of IL-4 cytotoxin in mouse models of breast tumor, we injected MDA-MB-231 human breast cancer cells in both flanks of athymic nude mice. Animals then received three intratumoral (i.t.) injections of either IL-4Ralpha encoding vector (left flank) or vector only (right flank) mixed with liposome followed by IL-4 cytotoxin administration. Both i.p. and i.t. administration of IL-4 cytotoxin profoundly reduced the growth of IL-4Ralpha plasmid-injected MDA-MB-231 tumors, compared with control. Innate immune cells, including macrophages and neutrophils, were found to infiltrate at the regressing tumor site. This study provides proof of principle that i.t. IL-4Ralpha plasmid injection followed by systemic or i.t. IL-4 cytotoxin administration may be a useful strategy for the treatment of breast cancer. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 67 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2003 VL 9 IS 5 BP 1826 EP 1836 PG 11 WC Oncology SC Oncology GA 677MY UT WOS:000182813200034 PM 12738741 ER PT J AU Hodge, JW Grosenbach, DW Aarts, WM Poole, DJ Schlom, J AF Hodge, JW Grosenbach, DW Aarts, WM Poole, DJ Schlom, J TI Vaccine therapy of established tumors in the absence of autoimmunity SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN CARCINOEMBRYONIC ANTIGEN; RECOMBINANT ANTICANCER VACCINES; TYROSINASE-RELATED PROTEIN-2; COSTIMULATORY MOLECULE B7; PROSTATE-SPECIFIC ANTIGEN; CD4(+) T-LYMPHOCYTES; ANTITUMOR IMMUNITY; PHASE-I; COMBINATION IMMUNOTHERAPY; DIFFERENTIATION ANTIGEN AB Purpose: Many current clinical trials involve vaccination of patients with vaccines directed against tumor-associated antigens, which are, in actuality, "self-antigens" over-expressed in tumors as compared with normal tissues. As tumor vaccines become more potent through the addition of costimulatory molecules and cytokines and the use of diversified prime and boost regimes, the level of concern rises regarding the balance between antitumor immunity and pathological autoimmunity. Studies were conducted using mice bearing a transgenic self-antigen [human carcinoembryonic antigen (CEA)], which is expressed in some normal adult tissues, and tumor expressing the same self-antigen. These mice were vaccinated with recombinant poxviral vectors [recombinant vaccinia, recombinant fowlpox (rF)] encoding the CEA transgene as well as a triad of costimulatory molecules [B7-1, ICAM-1, and LFA-3 (TRICOM)]. Here we investigate the mechanism of tumor therapy and evaluate the safety of such a regimen in a self-antigen system. To our knowledge, the study reported here is the first description of a vaccine to a defined antigen where the regimen is potent enough to induce tumor therapy in the absence of autoimmunity. Experimental Design: CEA transgenic mice were transplanted with CEA-expressing tumors. Fourteen days later, mice were vaccinated with recombinant vaccinia-CEA/TRICOM admixed with recombinant murine granulocyte macrophage colony-stimulating factor and then given low-dose interleukin 2. Mice were boosted on days 21, 28, and 35 with rF-CEA/TRICOM admixed with rF-granulocyte macrophage colony-stimulating factor and then given low-dose interleukin 2. Mice were monitored for survival and compared with groups of mice vaccinated in a similar manner with poxviral vectors containing CEA/B7-1 or CEA transgenes. To determine the mechanism of antitumor therapy, mice were depleted of T-cell subpopulations before vaccination with the CEA/TRICOM regimen. Mice successfully cured of tumor and age-matched control, mice were monitored for 1 year. At 1 year, several clinical assays were carried out involving analysis of 9 serological parameters, 11 urinalysis parameters, and 14 immunological parameters. In addition, histopathology was performed on 42 tissues/mouse. Results: The CEA/TRICOM vaccination regimen induced a therapeutic antitumor response as measured by increased survival; which was due largely to induced T-cell responses (both CD4(+) and CD8(+)) as determined by selective T-cell subset depletion. The CEA/TRICOM vaccination regimen induced a significant increase in proliferation of CD4(+) T cells to CEA protein and a significant increase in secretion of IFN-gamma from CD8(+) T cells in response to a defined CEA epitope. Despite CEA expression in normal adult gastrointestinal tissues, no toxicity was observed in the CEA/TRICOM-vaccinated group when an array of clinical serum and urine chemistry assays was conducted 1 year after vaccination. Moreover, a comprehensive histopathological evaluation of all tissues from these groups also showed no evidence of toxicity. Conclusions: Activation of T cells directed against a tumor-associated self-antigen, sufficient to mediate therapeutic antitumor immunity, was observed in vivo without the development of autoimmunity as analyzed by a comprehensive evaluation of biochemical, immunological, and histopathological criteria. These studies demonstrate that the use of vectors containing as many as three costimulatory molecules does not induce autoimmunity or other pathology. These studies thus demonstrate that a balance can indeed be achieved between the induction of an immune response to a self-antigen, which is capable of antitumor therapy, and the absence of autoimmunity. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 66 TC 82 Z9 85 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2003 VL 9 IS 5 BP 1837 EP 1849 PG 13 WC Oncology SC Oncology GA 677MY UT WOS:000182813200035 PM 12738742 ER PT J AU Gunning, WT Kramer, PM Lubet, RA Steele, VE End, DW Wouters, W Pereira, MA AF Gunning, WT Kramer, PM Lubet, RA Steele, VE End, DW Wouters, W Pereira, MA TI Chemoprevention of benzo(a)pyrene-induced lung tumors in mice by the farnesyltransferase inhibitor R115777 SO CLINICAL CANCER RESEARCH LA English DT Article ID MOUSE LUNG; RAS; PROGRESSION AB Purpose: Inhibitors of farnesyltransferase (e.g., 8115777) are being developed for therapy and prevention of various cancers. The efficacy of 8115777 [Zarnestra; (B)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)-methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone] to prevent the development of lung tumors in mice was determined. Experimental Design: Female strain A mice (7-8 weeks of age) were given 100 mg/kg benzo(a)pyrene [B(a)P] by i.p. injection, and 4 or 14 weeks later, they were given 50 or 100 mg/kg 8115777 by oral gavage 5 days/week. The mice were sacrificed 22 weeks after they received the B(a)P. Results: Tumor multiplicity was 5.0 +/- 0.85, 4.5 +/- 0.52, 2.1 +/- 0.31, and 1.5 +/- 0.31 tumors/mouse in mice that received 0, 50, 100 (weeks 4-22), or 100 (weeks 14-22) mg/kg R115777. Thus; 100 mg/kg 8115777 was similarly effective in preventing lung tumors when administered during the promotional phase of carcinogenesis [that is, either 4 or 14 weeks after B(a)P], whereas the lower dose of 50 mg/kg 8115777 was ineffective. The proliferating cell nuclear antigen labeling index was also significantly reduced in lung tumors from mice treated with 100 mg/kg 8115777 starting at 4 or 14 weeks. Conclusions: These results demonstrated that 8115777 can prevent the development of lung tumors in the A/J mouse model, where tumors routinely have mutations in the Ki-Ras oncogene. C1 Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Janssen Res Fdn, Spring House, PA 19477 USA. Janssen Res Fdn, B-2340 Beerse, Belgium. RP Gunning, WT (reprint author), Med Coll Ohio, Dept Pathol, Block Hlth Sci Bldg,3035 Arlington Ave, Toledo, OH 43614 USA. RI Gunning, William/E-4681-2010 FU NCI NIH HHS [N01-CN-95107] NR 15 TC 23 Z9 24 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2003 VL 9 IS 5 BP 1927 EP 1930 PG 4 WC Oncology SC Oncology GA 677MY UT WOS:000182813200044 PM 12738751 ER PT J AU Rotman-Pikielny, P Patronas, N Papanicolaou, DA AF Rotman-Pikielny, P Patronas, N Papanicolaou, DA TI Pituitary apoplexy induced by corticotrophin-releasing hormone in a patient with Cushing's disease SO CLINICAL ENDOCRINOLOGY LA English DT Article ID ADENOMA AB Pituitary apoplexy can occur spontaneously or following anterior pituitary stimulation tests. Apoplexy is a rare complication of Cushing's disease. We report a 19-year-old woman who was admitted to the National Institutes of Health for evaluation of possible Cushing's syndrome. Her symptoms and initial laboratory work were suggestive of Cushing's disease. Magnetic resonance imaging (MRI) revealed a macroadenoma of the pituitary gland. As part of her evaluation she received corticotrophin-releasing hormone (CRH). Two days later she developed severe headache, accompanied by nausea and vomiting, followed by meningismus, ptosis and diplopia. A diagnosis of pituitary apoplexy was made and she was treated conservatively with dexamethasone. Her neurological symptoms resolved shortly afterwards. By the time of discharge her anterior pituitary function was suppressed. All symptoms and signs of Cushing's syndrome resolved thereafter. This is the first case to demonstrate that CRH administration can induce pituitary apoplexy in a patient with Cushing's disease. Therapy with glucocorticoids was effective in our case, suggesting that conservative treatment can be successfully and safely applied in certain cases with pituitary apoplexy. C1 Emory Univ, Sch Med, Dept Med, Div Endocrinol, Atlanta, GA 30322 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Papanicolaou, DA (reprint author), Emory Univ, Sch Med, Dept Med, Div Endocrinol, Room 1307 W Wing WMRB,1639 Pierce Dr, Atlanta, GA 30322 USA. NR 15 TC 22 Z9 23 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD MAY PY 2003 VL 58 IS 5 BP 545 EP 549 DI 10.1046/j.1365-2265.2003.01720.x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 668RA UT WOS:000182305900003 PM 12699434 ER PT J AU Neeman, Z Wood, BJ AF Neeman, Z Wood, BJ TI Angiographic findings in tumoral calcinosis SO CLINICAL IMAGING LA English DT Article DE tumoral calcinosis; angiography AB Tumor calcinosis is uncommon, typically manifesting as paraarticular, extracapsular soft tissue deposits containing amorphous calcium phosphate and calcium carbonate, with associated hydroxyapatite crystal. CT and MRI are the primary diagnostic radiological tools evaluating these lesions. Primary treatment is early surgical excision with wide margins, as there is a high recurrence rate. We describe the angiographic findings in tumoral calcinosis, demonstrating hypervascularity beyond the calcified mass periphery. Exact margin definition with angiography may influence management and surgical approach. (C) 2003 Elsevier Science Inc. All rights reserved. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), NIH, Dept Diagnost Radiol, Bldg 10,Room 1C-660,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. NR 14 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD MAY-JUN PY 2003 VL 27 IS 3 BP 184 EP 186 DI 10.1016/S0899-7071(02)00523-5 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 674YP UT WOS:000182665500008 PM 12727056 ER PT J AU Perfect, JR Marr, KA Walsh, TJ Greenberg, RN DuPont, B de la Torre-Cisneros, J Just-Nubling, G Schlamm, HT Lutsar, I Espinel-Ingroff, A Johnson, E AF Perfect, JR Marr, KA Walsh, TJ Greenberg, RN DuPont, B de la Torre-Cisneros, J Just-Nubling, G Schlamm, HT Lutsar, I Espinel-Ingroff, A Johnson, E TI Voriconazole treatment for less-common, emerging, or refractory fungal infections SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; B LIPID COMPLEX; AMPHOTERICIN-B; INVASIVE ASPERGILLOSIS; TRIAZOLE VORICONAZOLE; TRANSPLANT RECIPIENTS; ANTIFUNGAL THERAPY; PATIENT; SAFETY; FLUCONAZOLE AB Treatments for invasive fungal infections remain unsatisfactory. We evaluated the efficacy, tolerability, and safety of voriconazole as salvage treatment for 273 patients with refractory and intolerant-to-treatment fungal infections and as primary treatment for 28 patients with infections for which there is no approved therapy. Voriconazole was associated with satisfactory global responses in 50% of the overall cohort; specifically, successful outcomes were observed in 47% of patients whose infections failed to respond to previous antifungal therapy and in 68% of patients whose infections have no approved antifungal therapy. In this population at high risk for treatment failure, the efficacy rates for voriconazole were 43.7% for aspergillosis, 57.5% for candidiasis, 38.9% for cryptococcosis, 45.5% for fusariosis, and 30% for scedosporiosis. Voriconazole was well tolerated, and treatment-related discontinuations of therapy or dose reductions occurred for <10% of patients. Voriconazole is an effective and well-tolerated treatment for refractory or less-common invasive fungal infections. C1 Duke Univ, Med Ctr, Dept Med & Microbiol, Durham, NC 27710 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Bethesda, MD 20892 USA. Univ Kentucky, Lexington, KY USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Pfizer, New York, NY USA. Hop Necker Enfants Malad, Paris, France. Univ Hosp Reina Sofia, Sofia, Bulgaria. Univ Frankfurt, D-6000 Frankfurt, Germany. Pfizer Ltd, Sandwich CT13 9NJ, Kent, England. Bristol Publ Hlth Lab, Bristol, Avon, England. RP Perfect, JR (reprint author), Duke Univ, Med Ctr, Dept Med & Microbiol, 0554 Hosp S, Durham, NC 27710 USA. RI lutsar, irja/H-3177-2015 NR 42 TC 419 Z9 446 U1 2 U2 12 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 1 PY 2003 VL 36 IS 9 BP 1122 EP 1131 DI 10.1086/374557 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 671QA UT WOS:000182474500006 PM 12715306 ER PT J AU Winterer, G Weinberger, DR AF Winterer, G Weinberger, DR TI Cortical signal-to-noise ratio: insight into the pathophysiology and genetics of schizophrenia SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Review DE schizophrenia; signal-to-noise ratio; dopamine; genetics; catechol-o-methyltransferase ID CATECHOL-O-METHYLTRANSFERASE; DORSOLATERAL PREFRONTAL CORTEX; SPATIAL WORKING-MEMORY; CEREBRAL BLOOD-FLOW; DELAYED-RESPONSE TASK; NEUROLEPTIC-NAIVE PATIENTS; POSITRON-EMISSION-TOMOGRAPHY; MONOZYGOTIC TWINS DISCORDANT; NEONATAL HIPPOCAMPAL DAMAGE; ANTERIOR CINGULATE CORTEX AB During the past two decades, it has been convincingly demonstrated that schizophrenic patients and subjects genetically at risk for schizophrenia show abnormalities of cortical and particularly prefrontal function. Depending on clinical state and task conditions, hypo- and hyperfrontality have been frequently described with functional neuroimaging and electrophysiological techniques; however, the underlying neurophysiological deficits remained largely obscure. There is now growing empirical evidence that cortical signal-to-noise ratio (SNR) during information processing is fundamentally disturbed and may be key to a further understanding of schizophrenic pathophysiology. The evidence comes from animal and human electrophysiological and neuroimaging investigations as well as neuropsychological and computational simulation studies. This research has also shown that dopamine signaling in prefrontal cortex is a critical factor in modulation of cortical SNR and in neurocognitive performance. Moreover, it was recently demonstrated that genetically determined variations in dopamine signaling, mediated by a functional polymorphism in the gene for the enzyme catechol-o-methyltransferase, has a significant impact on the cortical SNR, prefrontal information processing, and as a result, is a susceptibility gene for schizophrenia. This review summarizes the current state of research on the pathophysiology of schizophrenia with emphasis on cortical-SNR and the involvement of potentially relevant, molecular and genetic determinants of the cortical dopaminergic signaling. (C) 2003 Elsevier Science B.V. All rights reserved. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Winterer, G (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bldg 10,Room 4s235, Bethesda, MD 20892 USA. NR 222 TC 11 Z9 11 U1 5 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD MAY PY 2003 VL 3 IS 1-2 BP 55 EP 66 DI 10.1016/S1566-2772(03)00019-7 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 722GR UT WOS:000185367500007 ER PT J AU Roth, BL Sheffler, D Potkin, SG AF Roth, BL Sheffler, D Potkin, SG TI Atypical antipsychotic drug actions: unitary or multiple mechanisms for 'atypicality"? SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article ID SEROTONIN 5-HT2A RECEPTORS; 5-HYDROXYTRYPTAMINE(2A) RECEPTOR; PREFRONTAL CORTEX; ARIPIPRAZOLE OPC-14597; CLOZAPINE TREATMENT; APICAL DENDRITES; CLINICAL POTENCY; DOPAMINE NEURONS; PYRAMIDAL CELLS; PARTIAL AGONIST AB Over the past decade or so, atypical antipsychotic drugs have revolutionized the pharmacologic treatment of schizophrenia and related disorders. All currently approved atypical antipsychotic drugs, which are available in the US, are characterized by relatively weak affinities for D2-family dopamine receptors and relatively high affinities for 5-HT2A-serotonin receptors, when compared with typical antipsychotic drugs. The potent interaction with 5-HT2A receptors, with a relative sparing of D2-family dopamine receptors, is likely responsible for the salutary effects of atypical antipsychotic drugs on mood and cognition in comparison with typical antipsychotic drugs. Another class of atypical antipsychotic drugs, available in Europe, is characterized by potent and relatively selective interactions with D2- and D3-dopamine receptors. These drugs, as a class, have weak affinity for 5-HT2A-serotonin receptors and exert their 'atypical actions' presumably via combined D2/D3-dopamine receptor blockade. A new class of atypical antipsychotic drugs, exemplified by aripiprazole, is characterized by partial agonist actions at a variety of dopaminergic and serotonergic receptors. We also highlight the various neuronal circuits involved in atypical antipsychotic drug actions. In addition to these actions, several atypical antipsychotic drugs are characterized by a 'fast dissociation' rate from D2-dopamine receptors and/or relatively high affinities for alpha2-adrenergic receptors. It is clear that multiple molecular targets can be targeted to yield drugs with appreciable 'atypical' actions in humans. It is also evident that no unitary pharmacologic mechanism can account for the multiplicity of actions of atypical antipsychotic drugs. Instead, we suggest that elucidating the actions of atypical antipsychotic drugs requires a combined understanding of the circuitry of neocortical and subcortical regions which will provide a framework on which to posit the actions of atypical antipsychotic drugs. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, NIMH, Psychoact Drug Screening Program, Sch Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Psychiat, Sch Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Neurosci, Sch Med, Cleveland, OH 44106 USA. Univ Calif Irvine, Dept Psychiat, Irvine, CA 92717 USA. RP Roth, BL (reprint author), Case Western Reserve Univ, Sch Med, Dept Biochem, Rm W438,10900 Euclid Ave, Cleveland, OH 44106 USA. RI Roth, Bryan/F-3928-2010; Potkin, Steven/A-2021-2013 NR 92 TC 47 Z9 53 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD MAY PY 2003 VL 3 IS 1-2 BP 108 EP 117 DI 10.1016/S1566-2772(03)00021-5 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 722GR UT WOS:000185367500010 ER PT J AU Frank, SM Satitpunwaycha, P Bruce, SR Herscovitch, P Goldstein, DS AF Frank, SM Satitpunwaycha, P Bruce, SR Herscovitch, P Goldstein, DS TI Increased myocardial perfusion and sympathoadrenal activation during mild core hypothermia in awake humans SO CLINICAL SCIENCE LA English DT Article DE body temperature; catecholamines; coronary blood flow; sympathetic nervous system ID RANDOMIZED CLINICAL-TRIAL; ISCHEMIC HEART-DISEASE; CORONARY-ARTERY SPASM; COLD PRESSOR TEST; BLOOD-FLOW; MORTALITY; ASSOCIATIONS; TEMPERATURE; RESPONSES; ATENOLOL AB Potential mechanisms of cold-induced myocardial ischaemia are sympathetically mediated coronary vasoconstriction and/or catecholamine-induced increases in cardiac work. To examine these parameters, 11 human volunteers were each studied on one day with, and on another day without, beta-adrenoceptor blockade. On each day, warm (37degreesC) saline (control) and cold (4degreesC) saline (hypothermia) were given intravenously. Myocardial perfusion was assessed by positron emission tomography using (H2O)-O-15, and coronary vascular resistance was calculated. Plasma catecholamines were measured to assess sympathoadrenal activation. The core temperature decreased by 1.0+/-0.2degreesC with the cold saline, and was unchanged with warm saline. Myocardial perfusion increased by 20 % (P=0.01) and the rate-pressure product by 33 % (P=0.0004) with cold saline compared with warm saline. beta-Blockade eliminated these increases. Coronary vascular resistance was similar with warm and cold saline, and was unaffected by beta-blockade. Plasma adrenaline increased by 120 % and noradrenaline by 25 1 % during cold saline, but were unchanged during warm saline. In conclusion, core hypothermia triggers beta-adrenoceptor-mediated increased cardiac work, sympathoadrenal activation and increased myocardial perfusion. There is no evidence for hypothermia-induced coronary vasoconstriction. C1 Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NIH, PET Imaging Sect, Bethesda, MD 20892 USA. RP Frank, SM (reprint author), Greater Baltimore Med Ctr, Dept Anesthesiol, 6701 N Charles St,Room 4226, Baltimore, MD 21204 USA. NR 25 TC 27 Z9 32 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD MAY PY 2003 VL 104 IS 5 BP 503 EP 508 DI 10.1042/CS20020256 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 676EF UT WOS:000182738000006 PM 12540290 ER PT J AU Martin, A Caramazza, A AF Martin, A Caramazza, A TI Neuropsychological and neuroimaging perspectives on conceptual knowledge: An introduction SO COGNITIVE NEUROPSYCHOLOGY LA English DT Editorial Material ID CATEGORY-SPECIFIC DEFICITS; SENSORY-QUALITY CATEGORIES; SEMANTIC MEMORY; NEURAL BASIS; MODALITY SPECIFICITY; LIVING THINGS; OBJECT RECOGNITION; TEMPORAL CORTEX; FACE PERCEPTION; FUNCTIONAL MRI C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Martin, A (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C-104,10 Ctr Dr MSC 1366, Bethesda, MD 20892 USA. EM alex@codon.nih.gov RI martin, alex/B-6176-2009 NR 80 TC 40 Z9 41 U1 0 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0264-3294 J9 COGN NEUROPSYCHOL JI Cogn. Neuropsychol. PD MAY-SEP PY 2003 VL 20 IS 3-6 BP 195 EP 212 DI 10.1080/02643290342000050 PG 18 WC Psychology; Psychology, Experimental SC Psychology GA 700UF UT WOS:000184129000001 PM 20957570 ER PT J AU Martin, A Weisberg, J AF Martin, A Weisberg, J TI Neural foundations for understanding social and mechanical concepts SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article ID HUMAN AMYGDALA; IMPAIRED RECOGNITION; MIND IMPAIRMENTS; BIOLOGICAL BASIS; TEMPORAL CORTEX; SEMANTIC MEMORY; ACQUIRED THEORY; BRAIN; PERCEPTION; OBJECTS AB Motivated by neuropsychological investigations of category-specific impairments, many functional brain imaging studies have found distinct patterns of neural activity associated with different object categories. However, the extent to which these category-related activation patterns reflect differences in conceptual representation remains controversial. To investigate this issue, functional magnetic resonance imaging (fMRI) was used to record changes in neural activity while subjects interpreted animated vignettes composed of simple geometric shapes in motion. Vignettes interpreted as conveying social interactions elicited a distinct and distributed pattern of neural activity, relative to vignettes interpreted as mechanical actions. This neural system included regions in posterior temporal cortex associated with identifying human faces and other biological objects. In contrast, vignettes interpreted as conveying mechanical actions resulted in activity in posterior temporal lobe sites associated with identifying manipulable objects such as tools. Moreover, social, but not mechanical, interpretations elicited activity in regions implicated in the perception and modulation of emotion (right amygdala and ventromedial prefrontal cortex). Perceiving and understanding social and mechanical concepts depends, in part, on activity in distinct neural networks. Within the social domain, the network includes regions involved in processing and storing information about the form and motion of biological objects, and in perceiving, expressing, and regulating affective responses. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Martin, A (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C-104,10 Ctr Dr MSC 1366, Bethesda, MD 20892 USA. EM alex@codon.nih.gov RI martin, alex/B-6176-2009 FU Intramural NIH HHS [Z01 MH002588-15]; NIMH NIH HHS [Z01 MH002588-15] NR 48 TC 138 Z9 142 U1 0 U2 17 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0264-3294 J9 COGN NEUROPSYCHOL JI Cogn. Neuropsychol. PD MAY-SEP PY 2003 VL 20 IS 3-6 BP 575 EP 587 DI 10.1080/02643290342000005 PG 13 WC Psychology; Psychology, Experimental SC Psychology GA 700UF UT WOS:000184129000017 PM 16648880 ER PT J AU Bloch, M Daly, RC Rubinow, DR AF Bloch, M Daly, RC Rubinow, DR TI Endocrine factors in the etiology of postpartum depression SO COMPREHENSIVE PSYCHIATRY LA English DT Review ID OVARIAN-STEROID REGULATION; MESSENGER-RNA EXPRESSION; PITUITARY-ADRENAL AXIS; POST-NATAL DEPRESSION; POSTNATAL DEPRESSION; PUERPERAL PSYCHOSIS; THYROID-DYSFUNCTION; MOOD DISORDERS; FOLLOW-UP; PSYCHIATRIC-ILLNESS AB This article reviews the literature regarding endocrine factors postulated or presumed to be relevant in postpartum depression (PPD), a condition affecting at least 10% of childbearing women. The phenomenology and epidemiology of PPD are also described. Data suggest that parturition-related endocrine changes are causally implicated in PPD in a vulnerable sub-group of women. More specifically, studies by our group and others suggest a role for changes in estradiol and progesterone in precipitating mood symptoms among women with PPD. The mechanisms underlying such differential sensitivities remain undetermined. Future directions for research are explored. (C) 2003 Elsevier Inc. All rights reserved. C1 Rambam Med Ctr, Div Psychiat, Haifa, Israel. NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. RP Rubinow, DR (reprint author), 10-3N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 124 TC 161 Z9 172 U1 7 U2 22 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAY-JUN PY 2003 VL 44 IS 3 BP 234 EP 246 DI 10.1053/comp.2003.50014 PG 13 WC Psychiatry SC Psychiatry GA 681BN UT WOS:000183017000010 PM 12764712 ER PT J AU Shorr, AF Abbott, KC Agadoa, LY AF Shorr, AF Abbott, KC Agadoa, LY TI Acute respiratory distress syndrome after kidney transplantation: Epidemiology, risk factors, and outcomes SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; epidemiology; kidney; mortality; outcome; risk transplant ID INTENSIVE-CARE UNIT; ANTITHYMOCYTE GLOBULIN; RENAL-TRANSPLANTATION; READMISSION; RECIPIENTS; SURVIVAL; CELLS; LIVER; ICU AB Objective: To determine the rate of the acute respiratory distress syndrome (ARDS) after kidney transplantation and to identify risk factors associated with the development of ARDS after kidney transplantation and outcomes for patients diagnosed with ARDS in this setting. Design: Retrospective analysis of the national registry for end-stage renal disease in the United States. Patients: We studied all patients who underwent kidney transplantation between July 1, 1994 and June 30, 1998 and identified patients diagnosed with ARDS. The diagnosis of ARDS was based on coding of patients records. We also compared the rate of ARDS after kidney transplantation with the rate of ARDS in the remainder of the U.S. population based on the results of the National Hospital Discharge Survey for 1997. Measurements and Main Results; During the study period, 42,190 kidney transplantations were performed in the United States and ARDS was diagnosed in 86 of these subjects (0.2%) resulting in an annualized rate of ARDS of 51.0 cases per 100,000 patients per year. The rate of ARDS after kidney transplantation was significantly higher than the reported rate of ARDS in the U.S. population (p <.050). Demographic factors, indications for transplantation, comorbid illness, antigen mismatch, cytomegalovirus status, and development of rejection did not correlate with the development of ARDS. Of the immunosuppressive agents (e.g., cyclosporine, FK-506, mycophenolate mofetil, azathioprine, OKT-3, antilymphocyte globulin), only the use of antilymphocyte globulin when used to treat rejection was linked with an increased risk for ARDS (odds ratio: 3.85; 95% confidence interval: 1.36 to 10.87). Subjects with graft failure were 2.70 (95% confidence interval: 1.33 to 5.52) times more likely to develop ARDS. The 28-day mortality in subjects with ARDS was 52.1%. The 3-yr survival after kidney transplantation was 88.9% in those without ARDS compared with 57.8% in persons with ARDS (p < .001). Conclusions: Although ARDS is a rare event after kidney transplantation, undergoing renal transplantation increases the risk for ARDS. Among patients receiving kidney transplants, graft failure and the use of antilymphocyte globulin for rejection are associated with the development of ARDS. Patients who develop ARDS after kidney transplantation face significant mortality. (Crit Care Med 2003; 31:1325-1330). C1 Walter Reed Army Med Ctr, Pulm & Crit Care Med Serv, Dept Med, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Serv Nephrol, Dept Med, Washington, DC 20307 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Shorr, AF (reprint author), Walter Reed Army Med Ctr, Pulm & Crit Care Med Serv, Dept Med, Washington, DC 20307 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 25 TC 37 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2003 VL 31 IS 5 BP 1325 EP 1330 DI 10.1097/01.CCM.0000053645.38356.A6 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 680ME UT WOS:000182981300005 PM 12771598 ER PT J AU Haas, CE Kaufman, DC Jones, CE Burstein, AH Reiss, W AF Haas, CE Kaufman, DC Jones, CE Burstein, AH Reiss, W TI Cytochrome P450 3A4 activity after surgical stress SO CRITICAL CARE MEDICINE LA English DT Article DE cytochrome P450; surgical procedures; operative; cytokines; interleukin-6; drug metabolism; erythromycin ID ERYTHROMYCIN BREATH TEST; P450-MEDIATED DRUG-METABOLISM; COLON-CARCINOMA CELLS; ACTIVITY IN-VITRO; ELECTIVE SURGERY; PHARMACOKINETIC INTERACTION; TRANSPLANT RECIPIENTS; MULTIDRUG-RESISTANCE; SERUM INTERLEUKIN-6; INTERFERON-ALPHA AB Objective: To evaluate the relationship between the acute inflammatory response after surgical trauma and changes in hepatic cytochrome P450 3A4 activity, compare changes in cytochrome P450 3A4 activity after procedures with varying degrees of surgical stress, and to explore the time course of any potential drug-cytokine interaction after surgery. Design: Prospective, open-label study with each patient serving as his or her own control. Setting: University-affiliated, acute care, general hospital. Patients: A total of 16 patients scheduled for elective repair of an abdominal aortic aneurysm (n = 5), complete or partial colectomy (n = 6), or peripheral vascular surgery with graft (n = 5). Interventions: Cytochrome P450 3A4 activity was estimated using the carbon-14 [C-14]erythromycin breath test (ERMBT) before surgery and 24, 48, and 72 hrs after surgery. Abdominal aortic aneurysm and colectomy patients also had an ERMBT performed at discharge. Blood samples were obtained before surgery, immediately after surgery, and 6, 24, 32, 48, and 72 hrs after surgery for determination of plasma concentrations of interleukin-6, interieukin-1beta, and tumor necrosis factor-alpha. Clinical markers of surgical stress that were collected included duration of surgery, estimated blood loss, and volume of fluids administered in the operating room. Measurements and Main Results: ERMBT results significantly declined in all three surgical groups, with the lowest value at the time of the 72-hr study in all three groups. There was a trend toward differences in ERMBT results among groups that did not reach statistical significance (p =.06). The nadir ERMBT result was significantly and negatively correlated with both peak interleukin-6 concentration (r(s) = -.541, p =.03) and log interleukin-6 area under the curve from 0 to 72 hrs (r(s) = -.597, p =.014). Subjects with a peak interleukin-6 of >100 pg/mL had a significantly lower nadir ERMBT compared with subjects with a peak interieukin-6 of <100 pg/mL (35.5% +/- 5.2% vs. 74.7% +/- 5.1%, p <.001). Conclusions: Acute inflammation after elective surgery was associated with a significant decline in cytochrome P450 3A4 activity, which is predictive of clinically important changes in the metabolism of commonly used drugs that are substrates for this enzyme. (Crit Care Med 2003; 31:1338-1346). C1 SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Buffalo, NY 14260 USA. Univ Rochester, Med Ctr, Dept Surg, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA. NIH, Clin Pharmacokinet Res Lab, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. Immunex Res & Dev Corp, Clin Dev Dept, Seattle, WA 98101 USA. RP Haas, CE (reprint author), SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Buffalo, NY 14260 USA. NR 63 TC 45 Z9 48 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2003 VL 31 IS 5 BP 1338 EP 1346 DI 10.1097/01.CCM.0000063040.24541.49 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 680ME UT WOS:000182981300007 PM 12771600 ER PT J AU Patroniti, N Verweij, M Kolobow, T AF Patroniti, N Verweij, M Kolobow, T TI Glottic-modulated lung ventilation during continuous transtracheal gas insufflation: An experimental study SO CRITICAL CARE MEDICINE LA English DT Article DE tracheal intubation; mechanical ventilation; positive end-expiratory pressure; acute respiratory failure; transtracheal gas insufflation ID PRESSURE-CONTROL VENTILATION; MECHANICAL VENTILATION; MINITRACHEOTOMY; CATHETER; FLOW; HYPERVENTILATION; INJURY AB We investigated a new method of pulmonary ventilation that included a minitracheostomy, a reverse thrust catheter to deliver continuous flow of gas to the carina, and a threshold valve to avoid lung overinflation. In six lightly sedated healthy sheep, at a continuous flow of 5, 10, or 15 L/min and a threshold valve of 5, 10, 15, or 20 cm H2O, we observed a novel respiratory pattern that was characterized either by active lung inflation followed by passive and prolonged inspiratory hold (mixed pattern) or by an absence of all active inspiratory effort and only passive inflation of the lungs (passive pattern). We correlated airway pressure changes with direct visualization of the glottic opening through a fiberoptic bronchoscope. We measured airway pressures at the level of the carina, the subglottic level, and in the pleural space, and respiratory events were monitored through inductive plethysmography. An increase in continuous flow, threshold valve, or both resulted in 1) an increase in glottic breathing; 2) a decrease in respiratory rate, with a decrease in inspiratory pleural pressure excursion; or 3) an increased inspiratory/expiratory ratio and mean airway pressure. During transtracheal gas insufflation, as in this study, a novel respiratory pattern evolved that was modulated by the glottis, accompanied by a decreased effort of breathing; coughing and swallowing remained, and vocalization remained unimpaired. C1 Univ Milano Bicocca, San Gerardo Hosp, Dept Surg Sci & Intens Care, I-20052 Monza, MI, Italy. NHLBI, Pulm Crit Care Med Branch, Sect Pulm & Cadiac Assist Devices, NIH, Bethesda, MD 20892 USA. RP Patroniti, N (reprint author), Univ Milano Bicocca, San Gerardo Hosp, Dept Surg Sci & Intens Care, Via Donizetti 106, I-20052 Monza, MI, Italy. RI Patroniti, Nicolo/K-6347-2016 OI Patroniti, Nicolo/0000-0003-3600-193X NR 26 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2003 VL 31 IS 5 BP 1461 EP 1467 DI 10.1097/01.CCM.0000065780.29668.72 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 680ME UT WOS:000182981300026 PM 12771619 ER PT J AU Ferrucci, L Guralnik, JM Cavazzini, C Bandinelli, S Lauretani, F Bartali, B Repetto, L Longo, DL AF Ferrucci, L Guralnik, JM Cavazzini, C Bandinelli, S Lauretani, F Bartali, B Repetto, L Longo, DL TI The frailty syndrome: a critical issue in geriatric oncology SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE elderly; cancer; frailty; comprehensive geriatric assessment ID RANDOMIZED CONTROLLED TRIAL; DWELLING OLDER-PEOPLE; CONGESTIVE-HEART-FAILURE; ELDERLY PATIENTS; CLINICAL-TRIAL; PHYSICAL PERFORMANCE; FUNCTIONAL DISABILITY; SCREENING INSTRUMENT; CASE-MANAGEMENT; RISK-FACTORS AB Evidence exists that the geriatric intervention guided by Comprehensive Geriatric Assessment (CGA) has positive effects on a number of important health outcomes in frail older patients. Although a number of observational studies, editorials, special articles and clinical reports, suggest that CGA should be used to guide the assessment and clinical decision-making in older cancer patients, there is limited support to this view in the literature. Older patients that are diagnosed with cancer are usually healthier and less problematic than persons of the same age who are randomly sampled from the general population. In these persons, the cancer dominates the clinical picture and, therefore, instruments especially tuned for the frail elderly may provide little information. The concept of the frailty syndrome, characterized by high susceptibility, low functional reserve and unstable homeostasis, has recently received a lot of attention by the geriatric community. A CGA approach, which also evaluates elements of the frailty syndrome, may be of great interest for those oncologists who want to identify older patients likely to develop severe toxicity and severe side effects in response to aggressive treatment. Improvements in the definition of the frailty syndrome may profit from the clinical experience of oncologists. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NIA, Clin Res Branch, Baltimore, MD 21224 USA. Italian Natl Inst Res & Care Aging, Lab Clin Epidemiol, Florence, Italy. NIA, Epidemiol Demog & Biometry Lab, Bethesda, MD 20892 USA. Natl Inst Res & Care Aging, Clin Unit Geriatr Oncol, Rome, Italy. RP Ferrucci, L (reprint author), NIA, Clin Res Branch, Baltimore, MD 21224 USA. RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 NR 87 TC 87 Z9 89 U1 4 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD MAY PY 2003 VL 46 IS 2 BP 127 EP 137 DI 10.1016/S1040-8428(02)00177-4 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 678RE UT WOS:000182879600004 PM 12711358 ER PT J AU Thyagarajan, T Totey, S Danton, MJS Kulkarni, AB AF Thyagarajan, T Totey, S Danton, MJS Kulkarni, AB TI Genetically alteredmouse models: The good, the bad, and the ugly SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE craniofacial development; growth factors; hereditary disease; knockout mice; teeth; transgenic mice ID GROWTH-FACTOR RECEPTOR-3; LINKED AMELOGENESIS IMPERFECTA; SAETHRE-CHOTZEN-SYNDROME; EPITHELIAL-MESENCHYMAL INTERACTIONS; HYPOHIDROTIC ECTODERMAL DYSPLASIA; TUMOR ALVEOLAR RHABDOMYOSARCOMA; EARLY TOOTH DEVELOPMENT; MOUSE HOMEOBOX GENE; PAIRED BOX GENE; SYNDROME TYPE-I AB Targeted gene disruption in mice is a powerful tool for generating murine models for human development and disease. While the human genome program has helped to generate numerous candidate genes, few genes have been characterized for their precise in vivo functions. Gene targeting has had an enormous impact on our ability to delineate the functional roles of these genes. Many gene knockout mouse models faithfully mimic the phenotypes of the human diseases. Because some models display an unexpected or no phenotype, controversy has arisen about the value of gene-targeting strategies. We argue in favor of gene-targeting strategies, provided they are used with caution, particularly in interpreting phenotypes in craniofacial and oral biology, where many genes have pleiotropic roles. The potential pitfalls are outweighed by the unique opportunities for developing and testing different therapeutic strategies before they are introduced into the clinic. In the future, we believe that genetically engineered animal models will be indispensable for gaining important insights into the molecular mechanisms underlying development, as well as disease pathogenesis, diagnosis, prevention, and treatment. C1 Natl Inst Dent & Craniofacial Res, Funct Genom Unit, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Gene Targeting Facil, NIH, Bethesda, MD 20892 USA. RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Unit, NIH, Bldg 30,Room 527,30 Convent Dr, Bethesda, MD 20892 USA. EM akulkarni@dir.nidcr.nih.gov NR 263 TC 62 Z9 67 U1 0 U2 5 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PD MAY PY 2003 VL 14 IS 3 BP 154 EP 174 PG 21 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 891QG UT WOS:000226595000001 PM 12799320 ER PT J AU Neckers, L AF Neckers, L TI Development of small molecule Hsp90 inhibitors: Utilizing both forward and reverse chemical genomics for drug identification SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE molecular chaperones; heat shock protein 90; kinase inhibitors; benzoquinone ansamycins; radicicol; novobiocin; geldanamycin; molecularly targeted therapeutics ID HEAT-SHOCK-PROTEIN; C-TERMINAL DOMAIN; STEROID-HORMONE RECEPTORS; BREAST-CANCER CELLS; GENE-PRODUCT P185; TYROSINE KINASE; ATP-BINDING; IN-VIVO; HEAT-SHOCK-PROTEIN-90 HSP90; BENZOQUINOID ANSAMYCINS AB Heat shock protein 90 (Hsp90) is a molecular chaperone whose association is required for stability and function of multiple mutated, chimeric, and over-expressed signaling proteins that promote cancer cell growth and/or survival. Hsp90 client proteins include mutated p53, Bcr-Abl, Raf-1, Akt, HER2/Neu (ErbB2), and HIF-1alpha. Hsp90 inhibitors, by interacting specifically with a single molecular target, cause the destabilization and eventual degradation of Hsp90 client proteins, and they have also shown promising anti-tumor activity in preclinical model systems. One Hsp90 inhibitor, 17-AAG, is currently in Phase I clinical trial. Hsp90 inhibitors are unique in that, although they are directed towards a specific molecular target, they simultaneously inhibit multiple signaling pathways on which cancer cells depend for growth and survival. Benzoquinone ansamycin binding to Hsp90 led to the identification of radicicol as an additional Hsp90 inhibitor. Additional target-based screening uncovered novobiocin as a third structurally distinct small molecule with Hsp90 inhibitory properties. Use of novobiocin, in turn, led to identification of a previously uncharacterized C-terminal ATP binding site in the chaperone. Small molecule inhibitors of Hsp90 have been very useful in understanding Hsp90 biology and in validating this protein as a molecular target for anti-cancer drug development. C1 NCI, Cell & Canc Biol Branch, NIH, Rockville, MD 20850 USA. RP Neckers, L (reprint author), NCI, Cell & Canc Biol Branch, NIH, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 73 TC 69 Z9 73 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD MAY PY 2003 VL 10 IS 9 BP 733 EP 739 DI 10.2174/0929867033457818 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 667VQ UT WOS:000182255300004 PM 12678776 ER PT J AU Beutler, JA McKee, TC AF Beutler, JA McKee, TC TI Novel marine and microbial natural product inhibitors of vacuolar ATPase SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE V-ATPase; salicylihalamides; lobatamides; inhibitors; cancer; osteoporosis; isolation; synthesis ID CHONDROMYCES SPECIES MYXOBACTERIA; H+-ATPASE; APICULAREN-A; V-ATPASE; CYTOTOXIC MACROLIDES; SELECTIVE INHIBITOR; SALICYLIHALAMIDE-A; BAFILOMYCIN A(1); STRUCTURAL ELUCIDATION; CONCANAMYCIN-A AB Vacuolar-ATPase (V-ATPase) has been proposed as a drug target in osteoporosis due to its involvement in bone resorption, and as a target in cancer due to potential involvement in tumor invasion and metastasis. The classical selective inhibitors of V-ATPase are microbial macrolides of the bafilomycin and concanamycin class. These inhibitors have proven to be too toxic for therapeutic use, however recent structure-activity studies on bafilomycins, and the isolation of novel macrolide structures from marine sources, have provided new avenues for development of potentially less toxic V-ATPase inhibitors. The novel salicylihalamide and lobatamide series of compounds were predicted to share a common mechanism of action based on the patterns of cytotoxicity produced in the NCI 60-cell cancer screen. They have subsequently been shown to selectively interact with mammalian V-ATPases, but not with fungal V-ATPases. With the recent achievement of total syntheses of salicylihalamide, lobatamide, and related compounds, the elaboration of congeners with specificity for particular enzyme isoforms may provide drug candidates which are less toxic. This review summarizes recent advances in V-ATPase inhibition and the prospects for further progress. C1 NCI, Mol Targets Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Beutler, JA (reprint author), NCI, Mol Targets Discovery Program, Ctr Canc Res, Bldg 1052,Room 121, Frederick, MD 21702 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 78 TC 63 Z9 66 U1 3 U2 17 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD MAY PY 2003 VL 10 IS 9 BP 787 EP 796 DI 10.2174/0929867033457827 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 667VQ UT WOS:000182255300010 PM 12678782 ER PT J AU Eells, JB AF Eells, JB TI The control of dopamine neuron development, function and survival: Insights from transgenic mice and the relevance to human disease SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE dopamine neurotransmission; transgenic mice; knockout mice ID RECEPTOR-DEFICIENT MICE; TYROSINE-HYDROXYLASE GENE; SPORADIC PARKINSONS-DISEASE; ORPHAN NUCLEAR RECEPTOR; ENTERIC NERVOUS-SYSTEM; CYCLOHYDROLASE-I GENE; ALPHA-SYNUCLEIN; NEUROTROPHIC FACTOR; D2 RECEPTORS; SUPEROXIDE-DISMUTASE AB Transgenic technology, especially the use of homologous recombination to disrupt specific genes to produce knockout mice, has added considerably to the understanding of dopamine (DA) neuron develop survival and function. The current review summarizes results from knockout mice with the target disruption of genes involved in the development of DA neurons (engrailed I and 2, 1mx1b, and Nurr1), in 4 maintaining DA neurotransmission (tyrosine hydroxylase, vesicular monoamine transporter, DA transporter, DA D2 and D3 receptors) and important for DA neuron survival (alpha-synuclein, glia cell line-derived neurotrophic factor and superoxide dismutase). As alterations in DA neurotransmission have been implicated in a number of human neuropathologies including Parkinson's disease, schizophrenia and attention deficit/hyperactivity disorder, understanding how specific genes are involved in the function of DA neurons and the compensatory changes that result from loss or reduction in gene expression could provide important insight for the treatment of these diseases. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Eells, JB (reprint author), NIDDKD, NIH, Bldg 10,Rm 9D-06,MSC 1810, Bethesda, MD 20892 USA. NR 161 TC 30 Z9 32 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD MAY PY 2003 VL 10 IS 10 BP 857 EP 870 DI 10.2174/0929867033457700 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 667VR UT WOS:000182255500005 PM 12678688 ER PT J AU Mascola, JR AF Mascola, JR TI Defining the protective antibody response for HIV-1 SO CURRENT MOLECULAR MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; INFECTIOUS-ANEMIA VIRUS; NEUTRALIZING ANTIBODIES; PASSIVE-IMMUNIZATION; RHESUS MACAQUES; PERSISTENT INFECTION; ENVELOPE GLYCOPROTEINS; 1-INFECTED INDIVIDUALS; VAGINAL TRANSMISSION AB The development of an effective HIV-1 vaccine would be greatly facilitated by. knowledge regarding the type and quantity of antibodies that are protective. Since definitive immune correlates are established only after a vaccine has been shown to be effective in humans, animal models are often used to guide vaccine development. Experimental lentivirus infection of non-human primates has shown that neutralizing antibodies can protect against infection. Most specifically, studies of passive antibody transfer in the chimeric SIV/HIV-1 immunodeficiency virus (SHIV) model have provided quantitative data on the level of protective antibody required. While direct extrapolation to humans is difficult, these data likely provide important insights into the protection afforded by antibodies against HIV-1. When used alone, high levels of neutralizing antibodies are required to completely block infection. However, even modest levels of antibody can provide partial protection and affect disease course. Understanding the exact level of protective antibody becomes even more complex in the setting of active immunization and coexisting cellular immunity. Despite this uncertainty, recent findings from lentiviral animal models strongly suggest that neutralizing antibodies will contribute to protection against HIV-1. Based on these data, a major goal of HIV-1 vaccine strategies is the. induction of neutralizing antibodies against circulating primary HIV-1 strains. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. NR 90 TC 101 Z9 105 U1 1 U2 1 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD MAY PY 2003 VL 3 IS 3 BP 209 EP 216 DI 10.2174/1566524033479799 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 677GL UT WOS:000182798500004 PM 12699358 ER PT J AU Chertova, E Crise, BJ Morcock, DR Bess, JW Henderson, LE Lifson, JD AF Chertova, E Crise, BJ Morcock, DR Bess, JW Henderson, LE Lifson, JD TI Sites, mechanism of action and lack of reversibility of primate lentivirus inactivation by preferential covalent modification of virion internal proteins SO CURRENT MOLECULAR MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 NUCLEOCAPSID PROTEIN; MURINE LEUKEMIA-VIRUS; ACID CHAPERONE ACTIVITY; ZINC-FINGER STRUCTURES; VIRAL-DNA SYNTHESIS; IN-VITRO; DENDRITIC CELLS; ENVELOPE GLYCOPROTEIN; STRAND TRANSFER AB By exploiting the intrinsic chemistry of retroviruses, we have developed a novel method for generating whole inactivated virion vaccine immunogens with functional envelope glycoproteins. The method takes advantage of the fact that the internal proteins of retroviruses are adapted to the intracellular (reducing) environment, and have cysteine residues present in thiol-form (S-H), while the surface proteins of retroviruses (the envelope glycoproteins SU and TM) are adapted to the (oxidizing) environment of the extracellular milieu, and have their cysteines present as disulfides (S-S). Treatment of retroviral virions with appropriate mild oxidizing agents thus results in preferential covalent modification and functional inactivation of key S-H-containing internal viral proteins, such as the nucleocapsid (NC) protein, that are required for infectivity, while the envelope glycoproteins with their disulfide bonded cysteines remain unaffected. This treatment thus results in virions that do not retain detectable infectivity, but preserves the conformational and functional integrity of the envelope glycoproteins. We have extensively used the disulfide reagent 2,2'-dithiodipyridine (aldrithiol-2, AT-2) to inactivate HIV and SIV via this mechanism and such inactivated virions, appear to be a promising vaccine immunogen based on macaque studies. We have biochemically characterized the targets and mechanisms of inactivation involved in AT-2 treatment of virions, and investigated the kinetics of inactivation. Although extremely unlikely under physiological conditions, reversibility of this type of inactivation is a theoretical concern. We have therefore conducted a series of in vitro experiments, in cell free systems and in cell culture, to evaluate this possibility. The results indicate that as judged by, both biochemical and biological (infectivity) criteria, inactivation by AT-2 does not appear to be reversible under conditions likely to obtain in vivo. C1 NCI, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21702 USA. RP Lifson, JD (reprint author), NCI, AIDS Vaccine Program, SAIC Frederick, Bldg 535,5th Floor, Frederick, MD 21702 USA. RI Bess, Jr., Julian/B-5343-2012 FU NCI NIH HHS [N01-CO-124000] NR 44 TC 35 Z9 35 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD MAY PY 2003 VL 3 IS 3 BP 265 EP 272 DI 10.2174/1566524033479889 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 677GL UT WOS:000182798500008 PM 12699362 ER PT J AU Voltan, R Robert-Guroff, M AF Voltan, R Robert-Guroff, M TI Live recombinant vectors for AIDS vaccine development SO CURRENT MOLECULAR MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HERPES-SIMPLEX-VIRUS; CYTOTOXIC T-LYMPHOCYTES; VESICULAR STOMATITIS-VIRUS; EQUINE ENCEPHALITIS-VIRUS; HIV-1/SIV CHIMERIC VIRUS; HUMORAL IMMUNE-RESPONSES; EXPRESSING HIV ENVELOPE; SIMIAN IMMUNODEFICIENCY; RHESUS MACAQUES AB Live recombinant vectors entered the AIDS vaccine field with the realization that live attenuated HIV vaccines posed too great a safety risk, and that subunit vaccines elicited antibodies which lacked the breadth or potency needed to induce sterilizing immunity. Vectored vaccines provided a means to bring the cellular arm of the immune system into play by mimicking natural viral infection. By delivering antigens within host cells, processing and presentation could occur for induction of cellular immune responses. This recombinant vector approach, either alone or combined with other strategies, has produced impressive results. Recombinants have been generated from DNA and RNA viruses and bacteria. With few exceptions, each vector poses some risk, yet each possesses unique features that make it attractive. In addition to safety, key considerations in vector selection have included previous success as a vaccine against the wild-type agent or other pathogens; ability to induce potent, persistent immune responses; ability to target mucosal inductive sites and antigen presenting cells; lack of integration into the host genome; presence of pre-existing immunity in people; ease of mucosal administration; cloning capacity; ease of engineering and production; and stability of the final product. Here we up-date the status of several live recombinant vectors that have shown good potential in pre-clinical studies. Some have progressed to human clinical trials, and others will shortly. The abundance of vectors, coupled with the complexity arising from use of combination regimens with other vaccine types and heterologous vectors, will necessitate selection of the most promising candidates for large-scale efficacy trials in people. The sooner comparative studies can be designed and implemented in which live recombinant vectors containing the same inserted genes are evaluated head-to-head, the closer we will be to an eventual vaccine. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP Robert-Guroff, M (reprint author), NCI, Basic Res Lab, NIH, 41 Lib Dr,MSC5055,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM guroffm@exchange.nih.gov NR 142 TC 19 Z9 20 U1 2 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD MAY PY 2003 VL 3 IS 3 BP 273 EP 284 DI 10.2174/1566524033479816 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 677GL UT WOS:000182798500009 PM 12699363 ER PT J AU Ahlers, JD Belyakov, IM Berzofsky, JA AF Ahlers, JD Belyakov, IM Berzofsky, JA TI Cytokine, chemokine, and costimulatory molecule modulation to enhance efficacy of HIV vaccines SO CURRENT MOLECULAR MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; COLONY-STIMULATING-FACTOR; CYTOTOXIC T-LYMPHOCYTES; PLASMACYTOID DENDRITIC CELLS; CELLULAR IMMUNE-RESPONSES; ANTIGEN-PRESENTING CELLS; HEAT-LABILE ENTEROTOXIN; RECEPTOR GAMMA-CHAIN; DNA VACCINE; IN-VIVO AB Understanding key intervention points in developing immune responses may allow the rational inclusion of biological adjuvants into vaccines that could potentiate the immune response both quantitatively and qualitatively and enhance effective memory responses. Cytokine and chemokine combinations can potentially help target antigen to the appropriate antigen presenting cell and initiate maturation of these presenting cells, attract cells expressing different chemokine receptors, steer cellular immune responses toward Th1 and CD8 CTL, and enhance systemic and mucosal IgG and secretory IgA antibodies and determine their isotype balance. Animal protection studies suggest that synergistic combinations of cytokines and immunomodulating molecules may be required to protect from a viral challenge. For example, GM-CSF has been shown to be synergistic with IL-12 or CD40 ligand for induction of CTL and for antiviral protection, and the triple combination of GM-CSF, IL-12, and TNF alpha appears to induce the most effective protection in some mouse models. Chemokine-antigen fusions have also been shown to enhance immunogenicity of the antigen. Combinations of costimulatory molecules have been found to be synergistic when incorporated in a vaccine. Combined use of newer more potent vaccine constructs, containing codon optimized epitopes, relevant CpG motifs, cytokines, costimulatory molecules and chemokines, used in heterologous prime-boost strategies with viral vector vaccines or recombinant proteins, might afford the most potent vaccine approaches yet developed. In this review we will discuss the application and delivery of cytokines, costimulatory molecules, and chemokines toward improving current vaccine strategies. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bldg 10,Room 6B-12,MSC 1578, Bethesda, MD 20892 USA. NR 206 TC 62 Z9 66 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD MAY PY 2003 VL 3 IS 3 BP 285 EP 301 DI 10.2174/1566524033479843 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 677GL UT WOS:000182798500010 PM 12699364 ER PT J AU Barisoni, L Kopp, JB AF Barisoni, L Kopp, JB TI Update in podocyte biology: putting one's best foot forward SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE proteinuria; slit-diaphragm; nephrin; podocin; CD2-associated protein ID RESISTANT NEPHROTIC SYNDROME; GLOMERULAR SLIT DIAPHRAGM; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; NAIL-PATELLA SYNDROME; EPITHELIAL-CELLS; RENAL-DISEASE; COLLAPSING GLOMERULOPATHIES; TRANSCRIPTIONAL REGULATION; CD2-ASSOCIATED PROTEIN; DIABETIC NEPHROPATHY AB Purpose of review The rapidly developing field of podocyte cell biology is reviewed, focusing on papers published in the last 12 months. Recent findings Four areas of particular progress can be discerned. First, podocytes proliferate during early metanephric development, are quiescent after the capillary loop stage, and re-enter the cell cycle only in the disease group termed collapsing glomerulopathy. We have learned that control of the podocyte cell cycle involves both expression of cell-cycle regulating proteins and the process of cytokinesis. Second, the podocyte slit diaphragm is the final component of the filtration barrier. The structure and maintenance of the slit diaphragm has been a major focus of research activity, and a multiplicity of relevant molecular interactions have been defined. Significant advances have been made in understanding the complex and interacting role of nephrin and podocin mutations in the genesis of clinical glomerular disease. Third, several proteins essential to controlling discrete podocyte transcriptional programs have been defined. Finally, conditionally-immortalized podocyte cell lines, derived from mouse and human tissue, have proven their worth as models to advance investigations of podocyte biology. Summary Podocyte injury occurs as a consequence of genetic mutation, immunological injury, viral infection, or abnormal hemodynamic forces within the glomerulus. As we understand more about the podocyte proteome and cell biology, we gain an increasingly detailed molecular understanding of podocyte structure and function. In this drama we have many molecular players and increasing stretches of molecular dialogue, but the script remains largely to be deciphered. Nevertheless, we do understand the consequences that arise when the podocyte cannot put its best foot (processes) forward. C1 NIDDKD, Kidney Dis Sect, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Kopp, JB (reprint author), NIDDKD, Kidney Dis Sect, NIH, Dept Hlth & Human Serv, 10 Ctr Dr, Bethesda, MD 20892 USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 78 TC 21 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAY PY 2003 VL 12 IS 3 BP 251 EP 258 DI 10.1097/01.mnh.0000069861.94246.8c PG 8 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 680AU UT WOS:000182954800005 PM 12698062 ER PT J AU Langford, CA Balow, JE AF Langford, CA Balow, JE TI New insights into the immunopathogenesis and treatment of small vessel vasculitis of the kidney SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE vasculitis; glomerulonephritis; antineutrophil cytoplasmic autoantibodies (ANCA); Wegener granulomatosis; microscopic polyangiitis ID ANCA-ASSOCIATED VASCULITIS; LOW-DOSE METHOTREXATE; TNF-ALPHA BLOCKADE; WEGENERS-GRANULOMATOSIS; MYCOPHENOLATE-MOFETIL; MICROSCOPIC POLYANGIITIS; SYSTEMIC VASCULITIDES; GLOMERULONEPHRITIS; THERAPY; AUTOANTIBODIES AB Purpose of review Glomerulonephritis is an important manifestation of small vessel vasculitides such as Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Renal involvement in these diseases is characterized by a pauci-immune segmental necrotizing and crescentic glomerulonephritis that is strongly associated with circulating antineutrophil cytoplasmic autoantibodies. We will review recent advances in understanding the pathogenesis of antineutrophil cytoplasmic autoantibody-related renal vasculitides and innovative approaches to their treatment. Recent findings An experimental milestone in antineutrophil cytoplasmic autoantibody research has been reached in the past year. Using an innovative mouse model, investigators from the University of North Carolina in Chapel Hill have recently acquired robust data supporting the pathogenic role of antineutrophil cytoplasmic autoantibodies in the glomerulonephritis and small vessel vasculitis, analogous to those seen in microscopic polyangiitis and Wegener granulomatosis. Novel immunosuppressive approaches have been examined including preliminary studies using biologic agents, such as antagonists of tumor necrosis factor and monoclonal antibodies to B lymphocytes. Summary Recent insights into the pathogenesis of antineutrophil cytoplasmic autoantibody-related vascular injury and the availability of new biologic, immune response modifiers to complement standard chemical immunosuppressive agents offer exciting new prospects for investigation in the management of patients with small vessel renal vasculitides. C1 NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Balow, JE (reprint author), NIDDK, Kidney Dis Sect, NIH, Bldg 10,Room 9N-222, Bethesda, MD 20892 USA. NR 40 TC 8 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAY PY 2003 VL 12 IS 3 BP 267 EP 272 DI 10.1097/01.mnh.0000069857.94246.e5 PG 6 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 680AU UT WOS:000182954800007 PM 12698064 ER PT J AU Freitag, MH Vasan, RS AF Freitag, MH Vasan, RS TI What is normal blood pressure? SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE blood pressure; hypertension; prevention; epidemiology; risk ID NUTRITION EXAMINATION SURVEY; CORONARY HEART-DISEASE; CHRONIC RENAL-DISEASE; 3RD NATIONAL-HEALTH; CARDIOVASCULAR-DISEASE; UNCONTROLLED HYPERTENSION; UNITED-STATES; ANTIHYPERTENSIVE TREATMENT; MYOCARDIAL-INFARCTION; RANDOMIZED TRIAL AB Purpose of review Given the continuous relations of blood pressure to cardiovascular risk, any definition of high blood pressure is arbitrary, and based on thresholds at which there is clear evidence that treatment benefits outweigh potential risks. This review examines what constitutes optimal blood pressure. Recent findings A recent report raised the possibility of an age- and sex-dependent threshold for risk associated with systolic blood pressure, questioning the use of a single threshold (such as 140/90 mmHg) for defining hypertension. Several subsequent studies have questioned this notion and reemphasized that lower blood pressure levels are associated with less morbidity and mortality even within the nonhypertensive range. A recent meta-analysis confirmed that a blood pressure of 115/75 mmHg is associated with minimal vascular mortality and likely constitutes optimal blood pressure. Such blood pressure levels are infrequent in westernized societies. The target blood pressure goal for treated hypertensives is higher at 140/90 mmHg but is infrequently achieved. Select individuals at high absolute risk of cardiovascular disease events and/or with specific conditions (notably diabetes, renal insufficiency and prior vascular disease) may benefit from blood pressure lowering below this threshold. Summary At a population level, a blood pressure of 115/75 mmHg seems optimal because it is associated with minimal vascular risk. Over half of all hypertensives do not have their blood pressure controlled underscoring the challenges facing health care providers. Efforts should be strengthened for the primary prevention of hypertension and the promotion of optimal blood pressure through lifestyle measures. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. MetroW Med Ctr, Framingham, MA USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. RI Freitag, Michael/G-4887-2011; OI Freitag, Michael/0000-0002-7572-2011; Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [K24-HL-04334-01, N01-HC-25195] NR 66 TC 11 Z9 11 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAY PY 2003 VL 12 IS 3 BP 285 EP 292 DI 10.1097/01.mnh.0000069866.94246.42 PG 8 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 680AU UT WOS:000182954800010 PM 12698067 ER PT J AU He, LS Bradrick, TD Karpova, TS Wu, XL Fox, MH Fischer, R McNally, JG Knutson, JR Grammer, AC Lipsky, PE AF He, LS Bradrick, TD Karpova, TS Wu, XL Fox, MH Fischer, R McNally, JG Knutson, JR Grammer, AC Lipsky, PE TI Flow cytometric measurement of fluorescence (Forster) resonance energy transfer from cyan fluorescent protein to yellow fluorescent protein using single-laser excitation at 458 nm SO CYTOMETRY PART A LA English DT Article DE fluorescence (Forster) resonance energy transfer (FRET); flow cytometry; green fluorescent protein; cyan fluorescent protein; yellow fluorescent protein; confocal microscopy; spectrofluorometry ID TRANSFER FRET; LIVING CELLS; NUCLEIC-ACIDS; GREEN; DNA; RECEPTOR; MICROSCOPY; COMPLEX; ASSAYS; GFP AB Background: Use of distinct green fluorescent protein (GFP) variants permits the study of protein-protein interactions and colocalization in viable transfected cells by fluorescence (Forster) resonance energy transfer (FRET). Flow cytometry is a sensitive method to detect FRET. However, the typical dual-laser methods used in flow cytometric FRET assays are not generally applicable because they require a specialized krypton ultraviolet (UV) laser. The purpose of this work was to develop a flow cytometric method to detect FRET between cyan fluorescent protein (CFP; donor) and yellow fluorescent protein (YFP; acceptor) by using the 458-nm excitation from a single tunable argon-ion laser. Methods: FUSE-binding protein (FBP) interacting repressor (FIR) and FBP are c-myc transcription factors and are known to interact physically. To examine their interaction within viable cells, FIR and the binding motif of FBP, the FBP central domain (FBPcd), were fused with CFP and YFP, respectively, and this pair of fluorescently-tagged proteins was used to detect FRET in vivo. Cells transfected with expression plasmids encoding a CFP-FIR fusion protein and YFP as a negative control, a CFP-YFP fusion protein as a positive control, or CFP-FIR and YFP-FBPcd fusion proteins were examined for FRET after excitation with a 458-nm line from a tunable argon-ion laser. FRET was measured as the ratio of YFP:CFP emission or as YFP emission at 564606 nm. Conventional FRET using the 413-nm UV line from a krypton laser was examined for comparison. Fluorescence signals were separated with a customized optical filter configuration using 530-nm shortpass, 500-nm longpass, and 560-nm shortpass dichroics in addition to 488/30 nm (CFP), 530/30 nm (YFP), and 585/42 nm (FRET) bandpass filters. Further, a laser-scanning confocal microscopic photobleach technique was used to document that FRET occurred by showing that the intensity of donor CFP fluorescence increased after its acceptor YFP was photobleached. Steady-state spectrofluorometry was used to confirm and validate the results detected by flow cytometry. Results: Upon excitation with the 458-nm line of the argon-ion laser, the enhancement of the acceptor YFP signal and the decrease of the CFP signal were easily detected in cells transfected with the CFP-YFP construct or CFP-FIR and YFP-FBPcd. Similarly, FRET was detected under these conditions when the YFP emission was assessed at 564 - 606 nm. A strong correlation was observed between the increase in the YFP:CFP ratio and the YFP emission detected at 564 - 606 nm, consistent with the conclusion that FRET was detected comparably by both methods. A conventional flow cytometric krypton UV-laser technique was also used to confirm that FRET occurred with the CFP-YFP fusion protein and from CFP-FIR YFP-FBPcd. FRET also was confirmed by a confocal photobleaching technique, in which donor CFP intensity was enhanced after its acceptor YFP was photobleached. The flow cytometric and confocal microscopic results were confirmed by spectrofluorometry. Conclusion: These results demonstrated the feasibility of flow cytometric detection of FRET signals from CFP to YFP by excitation with the 458-nm line from the tunable argon-ion laser. The method was as efficient as excitation with the krypton UV laser and therefore should make FRET a more generally available flow cytometric technique. Cytometry Part A 53A:39-54, 2003. Published 2003 Wiley-Liss, Inc.(dagger) C1 NIAMSD, Flow Cytometry Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. Colorado State Univ, Dept Radiol Hlth Sci, Ft Collins, CO 80523 USA. RP Lipsky, PE (reprint author), NIAMS, NIH, 9000 Rockville Pike,Bldg 10,Room 9N228, Bethesda, MD 20892 USA. NR 57 TC 34 Z9 34 U1 2 U2 14 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOM PART A JI Cytom. Part A PD MAY PY 2003 VL 53A IS 1 BP 39 EP 54 DI 10.1002/cyto.a.10037 PG 16 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 675VW UT WOS:000182718000005 PM 12701131 ER PT J AU Benfield, TL AF Benfield, TL TI Clinical and experimental studies on inflammatory mediators during AIDS-associated Pneumocystis carinii pneumonia SO DANISH MEDICAL BULLETIN LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; TUMOR-NECROSIS-FACTOR; BRONCHOALVEOLAR LAVAGE FLUID; MAJOR SURFACE GLYCOPROTEIN; SERUM LACTATE-DEHYDROGENASE; IMMUNE-DEFICIENCY-SYNDROME; EPITHELIAL-CELL LINE; HIV-INFECTED PATIENTS; CULTURED LUNG-CELLS; INTERLEUKIN-8 GENE-EXPRESSION C1 Univ Copenhagen, Rigshosp, Dept Infect Dis, DK-2100 Copenhagen O, Denmark. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Benfield, TL (reprint author), Univ Copenhagen, Rigshosp, Dept Infect Dis, M5132,Blegdamsvej 9, DK-2100 Copenhagen O, Denmark. NR 229 TC 4 Z9 4 U1 0 U2 1 PU DANISH MEDICAL ASSN PI COPENHAGEN PA TRONDHJEMSGADE 9, DK-2100 COPENHAGEN, DENMARK SN 0907-8916 J9 DAN MED BULL JI Dan. Med. Bull. PD MAY PY 2003 VL 50 IS 2 BP 161 EP 176 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 689KG UT WOS:000183491100004 PM 12812139 ER PT J AU Dorsky, RI Itoh, M Moon, RT Chitnis, A AF Dorsky, RI Itoh, M Moon, RT Chitnis, A TI Two tcf3 genes cooperate to pattern the zebrafish brain SO DEVELOPMENT LA English DT Article DE tcf3b; headless; zebrafish; Wnt; neural patterning; morphogen gradient ID WNT SIGNALING PATHWAY; EMBRYONIC EXPRESSION; HMG-DOMAIN; SPECIFICATION; XENOPUS; DIFFERENTIATION; HINDBRAIN; DORSAL; CELLS; BETA AB Caudalizing factors operate in the context of Wnt/beta-catenin signaling to induce gene expression in discrete compartments along the rostral-caudal axis of the developing vertebrate nervous system. In zebrafish, basal repression of caudal genes is achieved through the function of Headless (Hdl), a Tcf3 homolog. In this study, we show that a second Tcf3 homolog, Tcf3b, limits caudalization caused by loss of Hdl function and although this Lef/Tcf family member can rescue hdl mutants, Lefl cannot. Wnts can antagonize repression mediated by Tcf3 and this derepression is dependent on a Tcf3 beta-catenin binding domain. Systematic changes in gene expression caused by reduced Tcf3 function help predict the shape of a caudalizing activity gradient that defines compartments along the rostral-caudal axis. In addition, Tcf3b has a second and unique role in the morphogenesis of rhombomere boundaries, indicating that it controls multiple aspects of brain development. C1 Univ Utah, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA. NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Howard Hughes Med Inst, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Ctr Dev Biol, Seattle, WA 98195 USA. RP Dorsky, RI (reprint author), Univ Utah, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA. RI Moon, Randall/B-1743-2014 OI Moon, Randall/0000-0002-9352-1408 NR 52 TC 95 Z9 100 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 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 2003 VL 130 IS 9 BP 1937 EP 1947 DI 10.1242/dev.00402 PG 11 WC Developmental Biology SC Developmental Biology GA 677MF UT WOS:000182811600019 PM 12642497 ER PT J AU Xu, XL Aprelikova, O Moens, P Deng, CX Furth, PA AF Xu, XL Aprelikova, O Moens, P Deng, CX Furth, PA TI Impaired meiotic DNA-damage repair and lack of crossing-over during spermatogenesis in BRCA1 full-length isoform deficient mice SO DEVELOPMENT LA English DT Article DE BRCA1; MLH1; gamma H2AX; crossing-over; apoptosis ID EMBRYONIC STEM-CELLS; DOUBLE-STRAND BREAKS; GENETIC INSTABILITY; CHROMOSOME SYNAPSIS; HISTONE H2AX; NUCLEAR FOCI; FEMALE MICE; PROPHASE-I; MOUSE; EXPRESSION AB Breast tumor suppressor gene I (BRCA1) plays an essential role in maintaining genomic integrity. Here we show that mouse Brca1 is required for DNA-damage repair and crossing-over during spermatogenesis. Male Brca1(Delta11/Delta11)p53(+/-) mice that carried a homozygous deletion of Brca1 exon 11 and a p53 heterozygous mutation had significantly reduced testicular size and no spermatozoa in their seminiferous tubules. During spermatogenesis, homologous chromosomes from the mutant mice synapsed and advanced to the pachytene stage but failed to progress to the diplotene stage. Our analyses revealed that the Brca1 mutation affected cellular localization of several DNA damage-repair proteins. This included prolonged association of gammaH2AX with sites of DNA damage, reduced sex body formation, diminished Rad51 foci and absence of Mlh1 foci in the pachytene stage. Consequently, chromosomes from mutant mice did not form chiasmata, a point that connects exchanging homologous chromosomes. Brca1 -mutant spermatocytes also exhibited decreased RNA expression levels of several genes that are involved in DNA-damage repair, including RuvB-like DNA helicase, XPB, p62 and TFIID. Of note, the premature termination of spermatogenesis at the pachytene stage was accompanied by increased apoptosis by both p53-dependent and p53-independent mechanisms. Thus, our study revealed an essential role of Brca1 in DNA-damage repair and crossingover of homologous chromosomes during spermatogenesis. C1 Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Biosyst & Canc, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. York Univ, Dept Biol, N York, ON M3J 1P3, Canada. Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Canc Ctr, Washington, DC 20007 USA. RP Xu, XL (reprint author), Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. RI deng, chuxia/N-6713-2016 NR 62 TC 96 Z9 101 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 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 2003 VL 130 IS 9 BP 2001 EP 2012 DI 10.1242/dev.00410 PG 12 WC Developmental Biology SC Developmental Biology GA 677MF UT WOS:000182811600024 PM 12642502 ER PT J AU Allhusen, V Belsky, J Booth, C Bradley, R Brownell, CA Burchinal, M Caldwell, B Campbell, SB Clarke-Stewart, KA Friedman, SL Hirsh-Pasek, K Jaeger, E Johnson, DJ Kelly, JF Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Payne, C Phillips, D Pianta, R Randolph, SM Robeson, WW Spieker, S Vandell, DL Weinraub, M AF Allhusen, V Belsky, J Booth, C Bradley, R Brownell, CA Burchinal, M Caldwell, B Campbell, SB Clarke-Stewart, KA Friedman, SL Hirsh-Pasek, K Jaeger, E Johnson, DJ Kelly, JF Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Payne, C Phillips, D Pianta, R Randolph, SM Robeson, WW Spieker, S Vandell, DL Weinraub, M CA NICHD Early Child Care Res Network TI Does quality of child care affect child outcomes at age 4(1)/(2)? SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID BEHAVIOR; DELINQUENCY; EDUCATION; PROGRAMS AB Research reveals associations between child-care quality and child outcomes. But are these associations causal? Data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care, a longitudinal study of children from birth to age 4(1)/(2), were used to explore 5 propositions that would support a causal argument. Three propositions received support, principally in the cognitive domain: (a) Associations between quality and outcomes remained even with child and family factors controlled; (b) associations between care and outcomes were domain specific; and (c) outcomes were predicted by quality of earlier care with concurrent care controlled. The 4th proposition, that associations between quality and outcomes would be significant with earlier abilities controlled, received limited support. There was no support for the 5th proposition, that quality and outcomes would exhibit dose-response relations. C1 Univ Calif Irvine, Irvine, CA USA. Univ London, Birkbeck Coll, London, England. Univ Washington, Seattle, WA 98195 USA. Univ Arkansas, Little Rock, AR 72204 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NICHD, Bethesda, MD USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Texas, Austin, TX 78712 USA. St Josephs Univ, Philadelphia, PA 19131 USA. Michigan State Univ, E Lansing, MI 48824 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Wellesley Coll, Wellesley, MA 02181 USA. Harvard Univ, Cambridge, MA 02138 USA. Univ N Carolina, Greensboro, NC 27412 USA. Univ Texas, Dallas, TX 75230 USA. Univ Calif Riverside, Riverside, CA 92521 USA. Georgetown Univ, Washington, DC 20057 USA. Univ Virginia, Charlottesville, VA 22903 USA. Univ Maryland, College Pk, MD 20742 USA. Wellesley Coll, Wellesley, MA 02181 USA. Univ Wisconsin, Madison, WI USA. Temple Univ, Philadelphia, PA 19122 USA. RP Allhusen, V (reprint author), NICHD, Early Child Care Res Network, Off Extramural Policy, Off Director, 6100 Execut Blvd,4A01, Rockville, MD 20852 USA. RI Marshall, Nancy/C-3428-2012 NR 62 TC 92 Z9 92 U1 9 U2 18 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD MAY PY 2003 VL 39 IS 3 BP 451 EP 469 DI 10.1037/0012-1649.39.3.451 PG 19 WC Psychology, Developmental SC Psychology GA 674CQ UT WOS:000182619600009 ER PT J AU Allhusen, V Belsky, J Kersey, HB Booth, C Bradley, R Brownell, CA Burchinal, M Caldwell, B Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasek, K Houts, R Huston, A Jaeger, E Kelly, JF Knoke, B Kochanoff, A Marshall, N McCartney, K McLeod, L Morrison, FJ O'Brien, M Owen, MT Payne, C Phillips, D Pianta, R Robeson, WW Spieker, S Vandell, DL Wallner-Allen, KE AF Allhusen, V Belsky, J Kersey, HB Booth, C Bradley, R Brownell, CA Burchinal, M Caldwell, B Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasek, K Houts, R Huston, A Jaeger, E Kelly, JF Knoke, B Kochanoff, A Marshall, N McCartney, K McLeod, L Morrison, FJ O'Brien, M Owen, MT Payne, C Phillips, D Pianta, R Robeson, WW Spieker, S Vandell, DL Wallner-Allen, KE CA NICHD Early Child Care Res Network TI Do children's attention processes mediate the link between family predictors and school readiness? SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID TO-MANAGE PRESCHOOLERS; LOW-INCOME FAMILIES; EXTERNALIZING BEHAVIOR; FOLLOW-UP; INFANT INTERACTION; HOME ENVIRONMENTS; MOTHER-INFANT; LANGUAGE; ACHIEVEMENT; COMPETENCE AB The role of attention processes as possible mediators between family environment and school readiness was analyzed with data from 1,002 children and their families. Data on children's sustained attention, impulsivity, and school readiness (i.e., cognitive, achievement, language, and social development) were obtained at 54 months of age, and quality of the family environment was assessed throughout the first 54 months. Mediation tests showed that children's sustained attention partially accounted for the link between family environment and achievement and language outcomes. Impulsivity partially accounted for the link between family environment and achievement, social competence, and externalizing behaviors. The roles of sustained attention and of inhibition of impulsive responding in the relation between family characteristics and school readiness are discussed. C1 NICHD, Early Child Care Res Network, Off Extramural Policy, Off Director, Rockville, MD 20852 USA. Univ Calif Irvine, Irvine, CA USA. Univ London, Birkbeck Coll, London, England. Soc Res Child Dev Policy Fellowship Program, Ann Arbor, MI USA. Univ Washington, Seattle, WA 98195 USA. Univ Arkansas, Little Rock, AR 72204 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ Calif Irvine, Irvine, CA USA. Temple Univ, Philadelphia, PA 19122 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Univ Texas, Austin, TX 78712 USA. St Josephs Univ, Philadelphia, PA 19131 USA. Univ Washington, Seattle, WA 98195 USA. Wellesley Coll, Wellesley, MA 02181 USA. Harvard Univ, Cambridge, MA 02138 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Georgetown Univ, Washington, DC 20057 USA. Univ Virginia, Charlottesville, VA 22903 USA. Univ Wisconsin, Madison, WI USA. Temple Univ, Philadelphia, PA 19122 USA. RP Allhusen, V (reprint author), NICHD, Early Child Care Res Network, Off Extramural Policy, Off Director, 6100 Execut Blvd,4A01, Rockville, MD 20852 USA. RI Marshall, Nancy/C-3428-2012 NR 90 TC 143 Z9 144 U1 6 U2 26 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD MAY PY 2003 VL 39 IS 3 BP 581 EP 593 DI 10.1037/0012-1649.39.3.581 PG 13 WC Psychology, Developmental SC Psychology GA 674CQ UT WOS:000182619600019 ER PT J AU Kovacs, P Lehn-Stefan, A Stumvoll, M Bogardus, C Baier, LJ AF Kovacs, P Lehn-Stefan, A Stumvoll, M Bogardus, C Baier, LJ TI Genetic variation in the human winged helix/forkhead transcription factor gene FOXC2 in Pima Indians SO DIABETES LA English DT Article ID INSULIN-RESISTANCE; OBESITY AB FOXC2 is a winged helix gene that has been shown to counteract obesity, hypertriglyceridemia, and diet-induced insulin resistance in rodents. Therefore, FOXC2 was analyzed as a candidate gene for susceptibility to type 2 diabetes in Pima Indians. Four variants were identified by sequencing the coding region, as well as 638 bp of the 5' region and 300 bp of the 3' region of the gene. Two single nucleotide polymorphisms (SNPs) were found in the putative promoter region, a C-512T transition and a G-350T. In addition, two SNPs were found in the 3' region, a C154ST and a C1702T. The G-350T and the C1702T variants were in complete linkage disequilibrium, and the C154ST variant was relatively rare; therefore, only the C-512T and G-350T variants were additionally genotyped in 937 full-blooded Pima Indians. Neither of these polymorphisms were associated with type 2 diabetes; however, the C-512T variant was associated with BMI (P = 0.03) and percentage of body fat (P = 0.02) in male and female Pima subjects, as well as with basal glucose turnover and fasting plasma triglycerides in women. Our data indicate that variation in FOXC2 may have a minor role in body weight control and seems to be involved in the regulation of basal glucose turnover and plasma triglyceride levels in women, but this gene does not significantly contribute to the etiology of type 2 diabetes in Pima Indians. C1 NIDDKD, Dept Hlth & Human Serv, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. RP Baier, LJ (reprint author), NIDDK, Clin Diabet & Nutr Sect, 4212 N 16th St, Phoenix, AZ 85016 USA. NR 9 TC 23 Z9 27 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2003 VL 52 IS 5 BP 1292 EP 1295 DI 10.2337/diabetes.52.5.1292 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 674ED UT WOS:000182623500036 PM 12716768 ER PT J AU Haque, WA Oral, EA Dietz, K Bowcock, AM Agarwal, AK Garg, A AF Haque, WA Oral, EA Dietz, K Bowcock, AM Agarwal, AK Garg, A TI Risk factors for diabetes in familial partial lipodystrophy, Dunnigan variety SO DIABETES CARE LA English DT Article ID PREDICTING BODY DENSITY; LAMIN A/C GENE; MISSENSE MUTATIONS; GENERALIZED EQUATIONS; INSULIN-RESISTANCE; GLUCOSE-TOLERANCE; OBESITY; MEN; COMPLICATIONS; ADIPONECTIN AB OBJECTIVES - Familial partial lipodystrophy, Dunnigan variety (FPLD), is an autosomal dominant disorder due to missense mutations in the lamin A/C (LMNA) gene encoding nuclear lamina proteins. It is characterized by loss of subcutaneous fat from the extremities and trunk and accumulation of fat in the head and neck region beginning at puberty. Patients with FPLD are predisposed to metabolic complications of insulin resistance such as diabetes. We sought to identify risk factors for diabetes in patients with FPLD. RESEARCH DESIGN AND METHODS - A cross-sectional study comparing clinical, biochemical, and anthropometric variables and LMNA genotypes in FPLD patients with and without diabetes. RESULTS - We studied 52 women and 24 men with FPLD from 18 different families. Twenty-eight women (54%) but only four men (17%) had diabetes (P < 0.001); therefore further comparisons were mostly limited to women. Compared with women without diabetes, those with diabetes had higher BMI (median values 23 vs. 24 kg/m(2), respectively; P = 0.03), increased chin skinfold thickness (10 vs. 20 mm; P = 0.001), lower rates of nulliparity (60% vs. 28%; P = 0.04), and higher levels of fasting serum triglycerides (2.4 vs. 3.5 mmol/l; P < 0.001) but similar serum leptin levels (3.4 vs. 3.6 ng/ml; P = 0:9). The prevalence of diabetes was not related to age, menopausal status, family history of type 2 diabetes in unaffected relatives, or LMNA genotype. CONCLUSIONS - We conclude that increased adiposity as reflected by excess subcutaneous fat accumulation in the chin region and parity may predispose women with FPLD to develop diabetes. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Div Nutr & Metab Dis,Ctr Human Nutr, Dallas, TX 75390 USA. Univ Michigan, Dept Internal Med, Div Endocrinol & Metab, Ann Arbor, MI 48109 USA. NIDDK, NIH, Bethesda, MD USA. Washington Univ, Sch Med, Dept Genet & Pediat, Div Human Genet, St Louis, MO USA. RP Garg, A (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, Div Nutr & Metab Dis,Ctr Human Nutr, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. OI Oral, Elif/0000-0002-9171-1144; Dietz, Kelly/0000-0003-3670-2912 FU NCRR NIH HHS [M01-RR00633]; NIDDK NIH HHS [R01-DK54387] NR 27 TC 26 Z9 30 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2003 VL 26 IS 5 BP 1350 EP 1355 DI 10.2337/diacare.26.5.1350 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UQ UT WOS:000185505400004 PM 12716787 ER PT J AU Hirshberg, B Rother, KI Harlan, DM AF Hirshberg, B Rother, KI Harlan, DM TI Islet transplantation: where do we stand now? SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Editorial Material DE type 1 diabetes; islet transplantation ID DIABETES-MELLITUS; PREVENTION AB After many years of limited success in islet transplantation, researchers developing this procedure have made great strides, and several centers have now reported that islet transplantation can result in long-term insulin independence for patients with type 1 diabetes mellitus. The improved quality of life achieved in some islet allograft recipients suggests that this important line of investigation should proceed. Yet, several factors limit the technique and these hurdles must be overcome before it can be considered a practical treatment for the millions of individuals with diabetes, be it type 1 or type 2. Most obvious is the gross disparity between the number of islets available for clinical transplantation and the number of patients with diabetes who might benefit. Other important limitations, too often lost in the discussion, include complications associated with the technique itself, the toxicity of currently available immurrosuppressive drugs, and the imperfect glycemia control achieved in most patients. In fact, our ongoing analysis as to whether transplantation-based therapy improves survival for patients with type 1 diabetes suggests that, for many at least, the opposite may be true. Two variables, as yet undefined, also need to be considered: (1) can the procedure, when done well, prevent or reverse diabetes-associated complications and (2) what are the long-term consequences of intrahepatic islets? Published in 2003 by John Wiley Sons, Ltd. C1 NIDDK, Transplantat & Autoimmun Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Harlan, DM (reprint author), NIDDK, Transplantat & Autoimmun Branch, NIH, Dept Hlth & Human Serv, Bldg 10,Room 11-S-219, Bethesda, MD 20892 USA. NR 17 TC 18 Z9 18 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD MAY-JUN PY 2003 VL 19 IS 3 BP 175 EP 178 DI 10.1002/dmrr.378 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 686XT UT WOS:000183346800001 PM 12789649 ER PT J AU Saydah, SH Brancati, FL Golden, SH Fradkin, J Harris, MI AF Saydah, SH Brancati, FL Golden, SH Fradkin, J Harris, MI TI Depressive symptoms and the risk of type 2 diabetes mellitus in a US sample SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE depression; diabetes; NHANES; US; cohort study ID PITUITARY-ADRENAL AXIS; WEIGHT-GAIN; LIFE-STYLE; CES-D; POPULATION; ADULTS; NOREPINEPHRINE; PREVALENCE; DISEASE; PLASMA AB Objective There is some evidence to suggest that individuals with depression are at an almost twofold increased risk of developing type 2 diabetes mellitus, but results are far from conclusive. Therefore, to determine if depressive symptoms increased the risk of type 2 diabetes, we conducted longitudinal analyses using data from the NHANES I Epidemiologic Follow-up Survey (NHEFS). Research design and methods Participants included individuals who were white or African-American, did not report previous diagnosis of diabetes, and who completed the Centers for Epidemiologic Studies Depression (CES-D) questionnaire in the 1982-1984 study (n = 8870). Participants were followed up for incident-diagnosed diabetes through 1992 (mean follow-up 9.0 years). Results There were 1444 (15.9%) participants with high depressive symptoms in the 1982-1984 study (CES-D score greater than or equal to 16). During follow-up, there were 465 incident cases of diabetes. Incidence of diabetes was 6.9/1000 person years among those with high depressive symptoms, 6.0/1000 person years among those with moderate symptoms, and 5.0/1000 person years among those with no symptoms. After adjusting for age, sex, and race, the relative hazard (RH) of diabetes among those with high depressive symptoms was 1.27 (95% Cl: 0.93 to 1.73) compared to those without symptoms. Further adjustment for education and known diabetes risk factors (body mass index and physical activity) further attenuated the relationship (RH 1.11, 95% Cl: 0.79 to 1.56). Conclusions There was no increased incidence of diabetes for those with high or moderate depressive symptoms compared to those with no depressive symptoms. These results do not support the etiologic relationship of depression predisposing individuals to diabetes. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Social & Sci Syst Inc, Silver Spring, MD USA. Johns Hopkins Univ, Baltimore, MD USA. NIDDKD, Bethesda, MD 20892 USA. RP Saydah, SH (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD USA. NR 49 TC 41 Z9 45 U1 2 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD MAY-JUN PY 2003 VL 19 IS 3 BP 202 EP 208 DI 10.1002/dmrr.353 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 686XT UT WOS:000183346800005 PM 12789653 ER PT J AU Layfield, LJ Elsheikh, TM Filie, A Nayar, R Shidham, V AF Layfield, LJ Elsheikh, TM Filie, A Nayar, R Shidham, V CA Papanicolaou Soc Cytopathology Pra TI Papanicolaou Society of Cytopathology guidelines for educational notes, disclaimers, and similar comments on reports of cervical cytology specimens SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE Papanicolaou test; cervical cytology; guidelines ID BETHESDA SYSTEM; ADENOCARCINOMA; CARCINOMA; WOMEN AB Controversy exists regarding the need for and appropriate form of notes addended to cervical cytology reports. The Guidelines Task Force of the Papanicolaou Society of Cytopathology reviewed the pertinent literature and formulated a list of suggested guidelines to aid practicing cytopathologists in conforming to the National Cancer Institute Bethesda Workshop's consensus recommendations and to fill the requirements of the College of American Pathologists inspections. (C) 2003 Wiley-Liss, Inc. C1 Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84132 USA. Ball Mem Hosp, Pathologists Associates, Dept Pathol, Muncie, IN USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. Med Coll Wisconsin, Dept Pathol, Milwaukee, WI USA. RP Layfield, LJ (reprint author), Univ Utah, Sch Med, Dept Pathol, 50 N Med Dr, Salt Lake City, UT 84132 USA. EM layfiel@aruplab.com NR 10 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-1039 EI 1097-0339 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD MAY PY 2003 VL 28 IS 5 BP 282 EP 285 DI 10.1002/dc.10284 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 674ZM UT WOS:000182668200011 ER PT J AU Eckelman, WC AF Eckelman, WC TI The use of PET and knockout mice in the drug discovery process SO DRUG DISCOVERY TODAY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; RECEPTOR-BINDING RADIOTRACERS; IN-VIVO; SCHIZOPHRENIC-PATIENTS; MUSCARINIC BINDING; RAT HEPATOCYTES; OCCUPANCY; M2; IDENTIFICATION; METABOLITES AB Although [O-15]H2O, 2-[F-18]fluoro-2-deoxyglucose (FDG) and other radioligands for low-density receptors and enzymes have been used in drug discovery and drug development, the impact on the pharmaceutical industry, to date, has been anecdotal. As new chemical entities are developed, radiotracers that aid in characterizing these drugs need to be developed rapidly to have an impact on the development process. The combined use of positron emission tomography (PET) and gene-manipulated animal models to validate radioligands quickly holds great promise for accelerating the discovery process. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Eckelman, WC (reprint author), NIH, Ctr Clin, 10 Ctr Dr,1C495, Bethesda, MD 20892 USA. NR 46 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD MAY 1 PY 2003 VL 8 IS 9 BP 404 EP 410 AR PII S1359-6446(03)02678-3 DI 10.1016/S1359-6446(03)02678-3 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 671BQ UT WOS:000182445500009 PM 12706658 ER PT J AU Granvil, CP Yu, AM Elizondo, G Akiyama, TE Cheung, C Feigenbaum, L Krausz, KW Gonzalez, FJ AF Granvil, CP Yu, AM Elizondo, G Akiyama, TE Cheung, C Feigenbaum, L Krausz, KW Gonzalez, FJ TI Expression of the human CYP3A4 gene in the small intestine of transgenic mice: In vitro metabolism and pharmacokinetics of midazolam SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID FETUS-SPECIFIC CYP3A7; CYTOCHROME-P450 3A; DRUG-METABOLISM; MONOCLONAL-ANTIBODIES; CHEMICAL CARCINOGENS; GRAPEFRUIT JUICE; SMALL-BOWEL; LIVER; ENZYMES; MOUSE AB Human cytochrome P450 3A4 (CYP3A4) is the most abundant hepatic and intestinal phase I drug-metabolizing enzyme, and participates in the oxidative metabolism of approximately 50% of drugs on the market. In the present study, a transgenic-CYP3A4 ( Tg-CYP3A4) mouse model that expresses CYP3A4 in the intestine and is phenotypically normal was generated, which was genotyped by both polymerase chain reaction and Southern blotting. Intestinal microsomes prepared from Tg-CYP3A4 mice metabolized midazolam (MDZ) to 1'-hydroxymidazolam about 2 times, and to 4-hydroxymidazolam around 3 times faster than that from wild-type (WT) mice. These increased MDZ hydroxylation activities were completely inhibited by an anti-CYP3A4 monoclonal antibody. The time course of plasma MDZ and its metabolite concentrations was measured after intravenous (0.25 mg/kg) and oral (2.5 mg/kg) administration of MDZ, and pharmacokinetic parameters were estimated by fitting to a noncompartmental model. Pretreatment with ketoconazole increased orally dosed MDZ maximum plasma concentration (C-max), time of the maximum concentration, area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)), and elimination half-life (t(1/2)) to 3.2-, 1.7-, 7.7-, 2-fold, and decreased MDZ apparent oral clearance about 8-fold in Tg-CYP3A4 mice. The ratios of MDZ C-max, AUC(0-infinity), t(1/2) and bioavailability between Tg-CYP3A4 and WT mice after the oral dose of MDZ were 0.3, 0.6, 0.5, and 0.5, respectively. These results suggest that this Tg-CYP3A4 mouse would be an appropriate in vivo animal model for the evaluation of human intestine CYP3A4 metabolism of drug candidates and potential food-drug and drug-drug interactions in preclinical drug development. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NCI, Lab Anim Resources, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Rm 2A19A, Bethesda, MD 20892 USA. NR 48 TC 70 Z9 74 U1 0 U2 1 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 MAY PY 2003 VL 31 IS 5 BP 548 EP 558 DI 10.1124/dmd.31.5.548 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 667NN UT WOS:000182238700007 PM 12695342 ER PT J AU Wang, HB Faucette, SR Gilbert, D Jolley, SL Sueyoshi, T Negishi, M LeCluyse, EL AF Wang, HB Faucette, SR Gilbert, D Jolley, SL Sueyoshi, T Negishi, M LeCluyse, EL TI Glucocorticoid receptor enhancement of pregnane X receptor-mediated CYP2B6 regulation in primary human hepatocytes SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN CYTOCHROME P4502B6; CONSTITUTIVE ANDROSTANE RECEPTOR; ORPHAN NUCLEAR RECEPTORS; HUMAN LIVER-MICROSOMES; CATALYTIC ACTIVITY; SIGNALING PATHWAY; RESPONSE ELEMENT; INDUCTION; GENE; CAR AB Although the glucocorticoid receptor (GR) facilitates the xenobiotic-induced expression of CYP2B in rodents, its role in the regulation of human CYP2B6 is unclear. In this report, the role of human GR in the regulation of CYP2B6 was evaluated using primary human hepatocytes and transfection assays with Huh7 cells. CYP2B6 expression was not induced in primary hepatocytes treated with dexamethasone (DEX) concentrations (0.01-1 muM) known to activate GR. In contrast, treatment with 0.1 muM DEX enhanced CYP2B6 induction by different pregnane X receptor (PXR) activators, including rifampin, phenytoin, clotrimazole, and phenobarbital. In Huh7 cells, cotransfection of human ( h) GR and hPXR with CYP2B6-phenobarbital-responsive enhancer module (PBREM) reporter constructs revealed that all hPXR ligands induce CYP2B6 reporter gene activity, and this ligand-dependent activation is greatly enhanced by activated hGR. CYP2B6 reporter gene expression was not induced in the presence of hPXR ligands when hGR alone was cotransfected with CYP2B6 reporter construct. In hGR and human constitutive androstane receptor ( hCAR) cotransfection assays, activated hGR increased the constitutive activation of PBREM reporter constructs by hCAR in the absence of inducers. In the presence of activated hGR and known inducers of CYP2B6, only PB treatment caused a further 2-fold activation of hCAR compared with control. These studies show that hGR is involved synergistically in the xenobiotic-responsive regulation of human CYP2B6 by hPXR and hCAR. Moreover, the results suggest that the GR-enhanced expression of CYP2B6 is mediated through an indirect mechanism that does not require increased expression of nuclear receptor. C1 Univ N Carolina, Sch Pharm, Div Drug Delivery & Disposit, Chapel Hill, NC 27599 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP LeCluyse, EL (reprint author), Univ N Carolina, Sch Pharm, Div Drug Delivery & Disposit, CB 7360, Chapel Hill, NC 27599 USA. OI LeCluyse, Edward/0000-0002-2149-8990 NR 39 TC 63 Z9 67 U1 0 U2 3 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 MAY PY 2003 VL 31 IS 5 BP 620 EP 630 DI 10.1124/dmd.31.5.620 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 667NN UT WOS:000182238700016 PM 12695351 ER PT J AU Parashar, UD Hummelman, EG Bresee, JS Miller, MA Glass, RI AF Parashar, UD Hummelman, EG Bresee, JS Miller, MA Glass, RI TI Global illness and deaths caused by rotavirus disease in children SO EMERGING INFECTIOUS DISEASES LA English DT Article ID HOSPITAL ADMISSIONS; CHILDHOOD MORTALITY; DIARRHEAL DISEASE; ORAL REHYDRATION; GASTROENTERITIS; SURVEILLANCE; INFECTION; VALIDATION; VACCINES; FEATURES AB To estimate the global illness and deaths caused by rotavirus disease, we reviewed studies published from 1986 to 2000 on deaths caused by diarrhea and on rotavirus infections in children. We assessed rotavirus-associated illness in three clinical settings (mild cases requiring home care alone, moderate cases requiring a clinic visit, and severe cases requiring hospitalization) and death rates in countries in different World Bank income groups. Each year, rotavirus causes approximately 111 million episodes of gastroenteritis requiring only home care, 25 million clinic visits, 2 million hospitalizations, and 352,000-592,000 deaths (median, 440,000 deaths) in children <5 years of age. By age 5, nearly every child will have an episode of rotavirus gastroenteritis, 1 in 5 will visit a clinic, 1 in 65 will be hospitalized, and approximately 1 in 293 will die. Children in the poorest countries account for 82% of rotavirus deaths. The tremendous incidence of rotavirus disease underscores the urgent need for interventions, such as vaccines, particularly to prevent childhood deaths in developing nations. C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Viral Gastroenteritis Unit, Atlanta, GA 30333 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Parashar, UD (reprint author), Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Viral Gastroenteritis Unit, 1600 Clifton Rd NE,Mailstop G04, Atlanta, GA 30333 USA. EM uap2@cdc.gov NR 35 TC 1086 Z9 1210 U1 8 U2 60 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAY PY 2003 VL 9 IS 5 BP 565 EP 572 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 673FN UT WOS:000182569700009 PM 12737740 ER PT J AU Lu, XP Bidaud, I Ladram, A Gershengorn, MC AF Lu, XP Bidaud, I Ladram, A Gershengorn, MC TI Pharmacological studies of thyrotropin-releasing hormone (TRH) receptors from xenopus laevis: Is xTRHR3 a TRH receptor? SO ENDOCRINOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; BINDING POCKET; REFINED MODEL; MESSENGER-RNA; RAT-BRAIN; CDNA; PEPTIDES; GENE AB Previously, three receptors, xTRHR1, xTRHR2, and xTRHR3, were cloned from brain tissue of Xenopus laevis with primers designed using sequences from the mammalian TRH receptor (TRHR) subtype 1. We expressed the Xenopus receptors in HEK 293EM cells and studied their binding and signaling properties using a series of TRH analogs substituted at the first, second, and third positions. We observed that the three Xenopus receptors exhibited binding and signaling properties that were distinct. Although xTRHR1 was most similar to mouse TRHR1 ( mTRHR1), it exhibited binding affinities that were different from mTRHR1. In contrast to mTRHR2, xTRHR2 exhibited lower affinities and potencies for all TRH analogs than mTRHR1. The xTRHR3 displayed very low affinities and potencies for TRH and TRH analogs and showed little discrimination for TRH analogs; it is likely, therefore, that another peptide is the cognate ligand for xTRHR3. Our findings show differences between TRHR1 and TRHR2 from Xenopus and mammals and suggest that xTRHR3 is a receptor for a ligand other than TRH. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Paris 06, Lab Bioactivat Peptides, Inst Jacques Monod, UMR 7592,CNRS, F-75251 Paris 05, France. Univ Paris 07, Inst Jacques Monod, Lab Bioactivat Peptides, UMR 7592,CNRS, F-75251 Paris 05, France. RP Gershengorn, MC (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. NR 45 TC 12 Z9 12 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2003 VL 144 IS 5 BP 1842 EP 1846 DI 10.1210/en.2002-221074 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 668BE UT WOS:000182269800024 PM 12697690 ER PT J AU McDougall, KE Perry, MJ Gibson, RL Colley, SM Korach, KS Tobias, JH AF McDougall, KE Perry, MJ Gibson, RL Colley, SM Korach, KS Tobias, JH TI Estrogen receptor-alpha dependency of estrogen's stimulatory action on cancellous bone formation in male mice SO ENDOCRINOLOGY LA English DT Article ID HIGH-DOSE ESTROGEN; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVITY; POSTMENOPAUSAL WOMEN; INDUCED OSTEOGENESIS; MESSENGER-RNA; FEMALE MICE; RAT BONE; ER-BETA; PREVENTS AB We examined whether estrogen receptor (ER) alpha is required for estrogen to stimulate cancellous bone formation in long bones of male mice. 17beta-Estradiol (E-2) was administered to ERalpha(-/-) male mice or wild-type (WT) littermate controls at 40, 400, or 4000 mug/kg by daily sc injection for 28 d and histomorphometric analysis performed at the distal femoral metaphysis. In WT mice, treatment with E-2 (40 mug/kg.d) increased the proportion of cancellous bone surfaces undergoing mineralization and stimulated mineral apposition rate. In addition, higher doses of E-2 induced the formation of new cancellous bone formation surfaces in WT mice. In contrast, E-2 had little effect on any of these parameters in ERalpha(-/-) mice. Immunohistochemistry was subsequently performed using an ERalpha-specific C-terminal polyclonal antibody. In WT mice, ERalpha was expressed both by cancellous osteoblasts and a significant proportion of mononuclear bone marrow cells. Immunoreactivity was also observed in cancellous osteoblasts of ERalpha(-/-) mice, resulting from expression of the activation function-1-deficient 46-kDa ERalpha isoform previously reported to be expressed in normal osteoblasts and bones of ERalpha(-/-) mice. Taken together, our results suggest that estrogen stimulates bone formation in mouse long bones via a mechanism that requires the presence of full-length ERalpha possessing activation function-1. C1 Univ Bristol, Bristol Royal Infirm, Rheumatol Unit, Bristol BS2 8HW, Avon, England. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Tobias, JH (reprint author), Univ Bristol, Bristol Royal Infirm, Rheumatol Unit, Bristol BS2 8HW, Avon, England. RI Tobias, Jon/E-2832-2014; OI Tobias, Jon/0000-0002-7475-3932; Korach, Kenneth/0000-0002-7765-418X NR 38 TC 30 Z9 32 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2003 VL 144 IS 5 BP 1994 EP 1999 DI 10.1210/en.2002-0074 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 668BE UT WOS:000182269800041 PM 12697707 ER PT J AU Jezova, M Armando, I Bregonzio, C Yu, ZX Qian, SJ Ferrans, VJ Imboden, H Saavedra, JM AF Jezova, M Armando, I Bregonzio, C Yu, ZX Qian, SJ Ferrans, VJ Imboden, H Saavedra, JM TI Angiotensin II AT(1) and AT(2) receptors contribute to maintain basal adrenomedullary norepinephrine synthesis and tyrosine hydroxylase transcription SO ENDOCRINOLOGY LA English DT Article ID RAT ADRENAL-MEDULLA; CATECHOLAMINE BIOSYNTHETIC-ENZYMES; GENE-DISRUPTED MICE; PARAVENTRICULAR NUCLEUS; IMMOBILIZATION STRESS; RESPONSIVE ELEMENT; CHROMAFFIN CELLS; EXPRESSION; PITUITARY; GLAND AB Angiotensin II (Ang II) AT(1) receptors have been proposed to mediate the Ang II-dependent and the stress-stimulated adrenomedullary catecholamine synthesis and release. However, in this tissue, most of the Ang II receptors are of the AT(2) type. We asked the question whether AT(1) and AT(2) receptors regulate basal catecholamine synthesis. Long-term AT(1) receptor blockade decreased adrenomedullary AT(1) receptor binding, AT(2) receptor binding and AT(2) receptor protein, rat tyrosine hydroxylase (TH) mRNA, norepinephrine (NE) content, Fos-related antigen 2 (Fra-2) protein, phosphorylated cAMP response element binding protein (pCREB), and ERK2. Longterm AT(2) receptor blockade decreased AT(2) receptor binding, TH mRNA, NE content and Fra-2 protein, although not affecting AT(1) receptor binding or receptor protein, pCREB or ERK2. Angiotensin II colocalized with AT(1) and AT(2) receptors in ganglion cell bodies. AT(2) receptors were clearly localized to many, but not all, chromaffin cells. Our data support the hypothesis of an AT(1)/AT(2) receptor cross-talk in the adrenomedullary ganglion cells, and a role for both receptor types on the selective regulation of basal NE, but not epinephrine formation, and in the regulation of basal TH transcription. Whereas AT(1) and AT(2) receptors involve the Fos-related antigen Fra-2, AT(1) receptor transcriptional effects include pCREB and ERK2, indicating common as well as different regulatory mechanisms for each receptor type. C1 NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. Univ Bern, Inst Cell Biol, CH-3012 Bern, Switzerland. RP Jezova, M (reprint author), NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH, 10 Ctr Dr,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA. NR 50 TC 41 Z9 41 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 MAY PY 2003 VL 144 IS 5 BP 2092 EP 2101 DI 10.1210/en.2002-0019 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 668BE UT WOS:000182269800052 PM 12697718 ER PT J AU Wu, TJ Buck, GM Mendow, P AF Wu, TJ Buck, GM Mendow, P TI Blood lead levels and sexual maturation in US girls: The Third National Health and Nutrition Examination Survey, 1988-1994 SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE fecundity; lead; menarche; puberty; sexual maturation ID GROWTH; MENARCHE; EXPOSURE; RAT; TOXICITY; AGE; ABSORPTION AB Using data from the Third National Health and Nutrition Examination Survey, we assessed measures of puberty in U.S. girls in relation to blood lead levels to determine whether sexual maturation may be affected by current environmental lead exposure. The study sample included 1,706 girls 8-16 years old with pubic hair and breast development information; 1,235 girls 10-16 years old supplied information on menarche. Blood lead concentrations (range = 0.7-21.7 mug/dL) were categorized into three levels: 0.7-2.0, 2.1-4.9, and 5.0-21.7 mug/dL. Sexual maturation markers included self-reported attainment of menarche and physician determined Tanner stage 2 pubic hair and breast development. Girls who had not reached menarche or stage 2 pubic hair had higher blood lead levels than did girls who had. For example, among girls in the three levels of blood lead described above, the unweighted percentages of 10-year-olds who had attained Tanner stage 2 pubic hair were 60.0, 51.2, and 44.4%, respectively, and for girls 12 years old who reported reaching menarche, the values were 68.0, 44.3, and 38.5%, respectively. The negative relation of blood lead levels with attainment of menarche or stage 2 pubic hair remained significant in logistic regression even after adjustment for race/ethnicity, age, family size, residence in metropolitan area, poverty income ratio, and body mass index. In conclusion, higher blood lead levels were significantly associated with delayed attainment of menarche and pubic hair among U.S. girls, but not with breast development. C1 E Tennessee State Univ, Dept Publ Hlth Family Med, Johnson City, TN 37614 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, NIH, Rockville, MD USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. RP Wu, TJ (reprint author), E Tennessee State Univ, Dept Publ Hlth Family Med, POB 70672,149 Lamb Hall, Johnson City, TN 37614 USA. OI Buck Louis, Germaine/0000-0002-1774-4490 NR 41 TC 73 Z9 76 U1 0 U2 6 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 MAY PY 2003 VL 111 IS 5 BP 737 EP 741 DI 10.1289/ehp.6008 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 677CB UT WOS:000182788400032 PM 12727603 ER PT J AU Merrick, BA AF Merrick, BA TI The Human Proteome Organization (HUPO) and environmental health SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE environmental health; bioinformatics; human; proteome; proteomics; toxicogenomics; toxicology ID CANCER; EXPRESSION; SERUM; IDENTIFICATION; BIOMARKERS; ABUNDANCE; PROTEINS; ARRAYS AB The Human Proteome Organization, or HUPO, was formed to promote research and large-scale analysis of the human proteome. By consolidating national proteome organizations into an international body, HUPO will coordinate international initiatives, biological resources, protocols, standards and data for studying the human proteome. HUPO has identified five key areas to advance study of the human proteome, specifically in bioinformatics, new technologies, the plasma proteome, cell models, and a public antibody initiative. Consideration of three major issue areas may help develop HUPO's strategy for human proteome study. First is the need to distinguish the value of high throughput platforms from discovery platforms in proteomics. Second is the importance for international planning on integrating both transcriptome and proteome data and databases. Last is that effects of the environment from chemical, physical, and biological exposures alter the expression and structure of the proteome, which become manifest in long-term adverse health effects and disease. Environmental health research stands to greatly benefit from the shared resources, data, and vision of the HUPO organization as a valuable resource in exploiting knowledge of the human proteome toward improving public health. C1 NIEHS, Proteom Grp, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. RP Merrick, BA (reprint author), NIEHS, Proteom Grp, Natl Ctr Toxicogenom, POB 12233,D2-04, Res Triangle Pk, NC 27709 USA. NR 30 TC 3 Z9 3 U1 2 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 MAY PY 2003 VL 111 IS 6 BP 797 EP 801 DI 10.1289/txg.5918 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 685CA UT WOS:000183242200015 ER PT J AU Waters, M Boorman, G Bushel, P Cunningham, M Irwin, R Merrick, A Olden, K Paules, R Selkirk, J Stasiewicz, S Weis, B Van Houten, B Walker, N Tennant, R AF Waters, M Boorman, G Bushel, P Cunningham, M Irwin, R Merrick, A Olden, K Paules, R Selkirk, J Stasiewicz, S Weis, B Van Houten, B Walker, N Tennant, R TI Systems toxicology and the Chemical Effects in Biological Systems (CEBS) knowledge base SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE bioinformatics; compendia; database; global query; gene expression; heuristic algorithms; knowledge base; linkage-disequilibrium; metabonomics; microarray; molecular expression; ontologies; phenotype; phenotypic anchoring; proteomics; sequence; single nucleotide polymorphisms; systems biology; systems toxicology; toxicogenomics; transcription factors ID GENE-EXPRESSION REGULATION; RISK ASSESSMENT; MOLECULAR CLASSIFICATION; MICROARRAY TECHNOLOGY; TRANSCRIPTION FACTORS; METABOLIC RESPONSES; DRUG DISCOVERY; MOUSE-LIVER; TOXICOGENOMICS; TOXICITY AB The National Center for Toxicogenomics is developing the first public toxicogenomics knowledge base that combines molecular expression data sets from transcriptomics, proteomics, metabonomics, and conventional toxicology with metabolic, toxicological pathway, and gene regulatory network information relevant to environmental toxicology and human disease. It is called the Chemical Effects in Biological Systems (CEBS) knowledge base and is designed to meet the information needs of "systems toxicology," involving the study of perturbation by chemicals and stressors, monitoring changes in molecular expression and conventional toxicological parameters, and iteratively integrating biological response data to describe the functioning organism. Based upon functional genomics approaches used successfully in analyzing yeast gene expression data sets, relational and descriptive compendia will be assembled for toxicologically important genes, groups of genes, single nucleotide polymorphisms (SNPs), and mutant and knockout phenotypes. CEBS data sets will be fully documented in the experimental protocol and therefore searchable by compound, structure, toxicity end point, pathology end point, gene, gene group, SNP, pathway, and network as a function of dose, time, and the phenotype of the target tissue. A knowledge base is being developed by assimilating toxicological, biological, and chemical information from multiple public domain databases and by progressively refining that information about gene, protein, and metabolite expression for classes of chemicals and their biological effects in various species. By analogy to the GenBank database for genome sequences, researchers will globally query (or BLAST) CEBS using a transcriptome of a tissue of interest (or a list of outliers) to have the knowledge base return information on genes, groups of genes, metabolic and toxicological pathways, and contextually associated phenotypic information for compounds that display similar response profiles. With high-quality data content, CEBS will ultimately become a resource to support hypothesis-driven and discovery research that contributes effectively to drug safety and the improvement of risk assessments for chemicals in the environment. The CEBS development effort will span a decade or more. C1 NIEHS, Natl Ctr Toxicogenom, NIH, Res Triangle Pk, NC 27709 USA. RP Waters, M (reprint author), NIEHS, Natl Ctr Toxicogenom, NIH, POB 12233,MD F1-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 70 TC 40 Z9 43 U1 4 U2 19 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 MAY PY 2003 VL 111 IS 6 BP 811 EP 824 DI 10.1289/txg.5971 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 685CA UT WOS:000183242200017 ER PT J AU Hoppin, JA AF Hoppin, JA TI Male reproductive effects of phthalates: An emerging picture SO EPIDEMIOLOGY LA English DT Editorial Material ID METABOLITES; RATS C1 NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. NR 11 TC 17 Z9 17 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2003 VL 14 IS 3 BP 259 EP 260 DI 10.1097/00001648-200305000-00002 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 687TM UT WOS:000183393100002 PM 12859023 ER PT J AU Olshan, AF Li, RL Pankow, JS Bray, M Tyroler, HA Chambless, LE Boerwinkle, E Pittman, GS Bell, DA AF Olshan, AF Li, RL Pankow, JS Bray, M Tyroler, HA Chambless, LE Boerwinkle, E Pittman, GS Bell, DA TI Risk of atherosclerosis: Interaction of smoking and glutathione S-transferase genes SO EPIDEMIOLOGY LA English DT Article DE GSTM1; GSTT1; smoking; gene-environment interaction; atherosclerosis; coronary heart disease ID CORONARY HEART-DISEASE; CIGARETTE-SMOKING; WALL THICKNESS; MOLECULAR EPIDEMIOLOGY; ARTERIAL-WALL; COMMUNITIES; GENOTYPE; CANCER; SUSCEPTIBILITY; PROGRESSION AB Background. Cigarette smoking is a well-known risk factor for not only incident events of coronary heart disease, but also preclinical atherosclerosis. Enzymes including glutathione S-transferase mu (GSTM1) and theta (GSTT1) are involved in the metabolism of tobacco smoke chemicals and are expressed in human vessels and smooth muscle cells. Methods. We estimated the effect of interaction of smoking with the deletion polymorphisms of GSTM1 and GSTT1 on the risk of carotid artery atherosclerosis. We analyzed a stratified random sample of 1394 individuals from the Atherosclerosis Risk in Communities (ARIC) study, which is a prospective cohort study of 15,792 white and black men and women randomly selected from four U.S. communities between 1987 and 1989. As an index of generalized atherosclerosis, we used carotid artery intimal-medial thickness, as determined by B-mode ultrasound at the baseline or first follow-up examination in asymptomatic individuals. Results. We found a suggestion of an interaction between the functional GSTTI-1 genotype (GSTT-1) and heavy smoking. For 20 or more pack-years and GSTTI-1, the odds ratio for increased intimal-medial thickness was 4.7 (95% confidence interval = 1.9-11.8); for 20 or more pack-years and GS771-0, 1.7 (0.5-5-5); and for nonsmokers and GSTT1-1, 0.7 (0.3-1.5). We found no interaction between smoking and GSTM1. Conclusions. The results of this analysis of preclinical atherosclerosis extend reports from the ARIC study of an interaction between smoking and GSTT1-1 in relation to the risk of incident coronary heart disease and lower extremity arterial disease. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ Tennessee, Ctr Hlth Sci, Coll Med, Dept Prevent Med, Memphis, TN 38163 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Olshan, AF (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, CB 7435, Chapel Hill, NC 27599 USA. FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55021, N01-HC-50016, N01-HC-55015, N01-HC-55019, N01-HC-55020, N01-HC-55022]; NIEHS NIH HHS [P30ES10126] NR 34 TC 36 Z9 37 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2003 VL 14 IS 3 BP 321 EP 327 DI 10.1097/00001648-200305000-00012 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 687TM UT WOS:000183393100012 PM 12859033 ER PT J AU Hendler, RW Barnett, SM Dracheva, S Bose, S Levin, IW AF Hendler, RW Barnett, SM Dracheva, S Bose, S Levin, IW TI Purple membrane lipid control of bacteriorhodopsin conformational flexibility and photocycle activity - An infrared spectroscopic study SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE enzyme control; kinetics; lipid-protein interactions; membrane protein structure ID NEUTRON-SCATTERING; NATIVE LIPIDS; TEMPERATURE; DEPENDENCE; BEHAVIOR; PROTEIN; MOTIONS; MODEL AB Specific lipids of the purple membrane of Halobacteria are required for normal bacteriorhodopsin structure, function, and photocycle kinetics [Hendler, R.W. & Dracheva, S. (2001) Biochemistry (Moscow) 66 , 1623-1627]. The decay of the M-fast intermediate through a path including the O intermediate requires the presence of a hydrophobic environment near four charged aspartic acid residues within the cytoplasmic loop region of the protein (R. W. Hendler & S. Bose, unpublished results). On the basis of the unique ability of squalene, the most hydrophobic purple membrane lipid, to induce recovery of M-fast activity in Triton-treated purple membrane, we proposed that this uncharged lipid modulates an electrostatic repulsion between the membrane surface of the inner trimer space and the nearby charged aspartic acids of the cytoplasmic loop region to promote transmembrane alpha-helical mobility with a concomitant increase in the speed of the photocycle. We examined Triton-treated purple membranes in various stages of reconstitution with native lipid suspensions using infrared spectroscopic techniques. We demonstrate a correlation between the vibrational half-width parameter of the protein alpha-helical amide I mode at 1660 cm(-1) , reflecting the motional characteristics of the transmembrane helices, and the lipid-induced recovery of native bacteriorhodopsin properties in terms of the visible absorbance maxima of ground state bacteriorhodopsin and the mean decay times of the photocycle M-state intermediates. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Levin, IW (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 26 TC 19 Z9 19 U1 0 U2 6 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD MAY PY 2003 VL 270 IS 9 BP 1920 EP 1925 DI 10.1046/j.1432-1033.2003.03547.x PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 671DH UT WOS:000182449700004 PM 12709050 ER PT J AU Dong, VM McDermott, DH Abdi, R AF Dong, VM McDermott, DH Abdi, R TI Chemokines and diseases SO EUROPEAN JOURNAL OF DERMATOLOGY LA English DT Review DE atherosclerosis; autoimmune; cancer; chemokines; dermatology; HIV; transplantation ID MONOCYTE-CHEMOATTRACTANT PROTEIN-1; HUMAN ENDOTHELIAL-CELLS; HUMAN-MELANOMA CELLS; FACTOR-KAPPA-B; HUMAN INTERLEUKIN-8 RECEPTOR; GROWTH-FACTOR RECEPTOR; C-C CHEMOKINE; EPITHELIAL-CELLS; HIV-1 INFECTION; RHEUMATOID-ARTHRITIS AB Chemokines are a group of small, pro-inflammatory molecules first described for their pivotal role in the mobilization of specific leukocyte subsets towards sites of inflammation and their activation once they arrive. They have now emerged as key regulators in the development, differentiation and anatomic distribution of inflammatory cells. Chemokines also orchestrate both the innate immune response and antigen specific immunity through their coordination of dendritic cells and lymphocytes. Due to their vast functional responsibilities, they are linked to the pathogenesis of many seemingly unrelated diseases that include HIV infection, cancer, atherosclerosis, autoimmune diseases, graft rejection and dermatological disorders. This review focuses on the physiology of chemokines and their significant roles in the pathogenesis and progression of major diseases. C1 Solvay Pharmaceut Inc, Clin Operat & Med Affairs, Marietta, GA 30062 USA. NIAID, Mol Signaling Sect, Lab Host Def, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. RP Dong, VM (reprint author), Solvay Pharmaceut Inc, Clin Operat & Med Affairs, 901 Sawyer Rd, Marietta, GA 30062 USA. OI McDermott, David/0000-0001-6978-0867 NR 98 TC 9 Z9 16 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1167-1122 J9 EUR J DERMATOL JI Eur. J. Dermatol. PD MAY-JUN PY 2003 VL 13 IS 3 BP 224 EP 230 PG 7 WC Dermatology SC Dermatology GA 688VE UT WOS:000183457000002 PM 12804978 ER PT J AU Gonsky, R Deem, RL Young, HA Targan, SR AF Gonsky, R Deem, RL Young, HA Targan, SR TI CD2 mediates activation of the IFN-gamma intronic STAT binding region in mucosal T cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE human; mucosa; T lymphocyte; cellular activation; transcription factor ID INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; INTERFERON-GAMMA; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCER; INTESTINAL INFLAMMATION; ANTIGEN RECEPTOR; FLOW-CYTOMETRY; IL-2 SECRETION; TRANSCRIPTION AB The pathways leading to activation of mucosal lamina propria (LIP) T cells differ from those of peripheral T cells. LP T cells exhibit enhanced IFN-gamma secretion when activated through the CD2 pathway. This study demonstrates CD2 signaling is followed by activation of STAT proteins in both peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC), although, distinct differences exist in regulation of IFN-gamma promoter gene expression. Both PBMC and LPMC exhibit enhanced secretion and transactivation of the -2.7 kb IFN-gamma promoter region following CD2 signaling, but the IFN-gamma STAT-binding region (within the first intron) serves as an orientation-independent enhancer of promoter activity only in LPMC. Mutation of the STAT site impairs enhancer activity. In LPMC, but not PBMC, CD2 mediates binding of STAT1 and STAT4 to the IFN-gamma intronic element. Unstimulated LMPC exhibit low levels of phosphotyrosine-STAT4 and STAT1 and phosphoserine-STAT1, which increase substantially following CD2 activation. In PBMC, CD2-mediated phosphorylation is primarily restricted to enhanced levels of phosphotyrosine-STAT1. Thus, these results indicate that both common as well as unique molecular mechanisms are involved in CD2 signaling and activation of the STAT pathway in LP T cells which are critical for regulation of IFN-gamma expression in the gut. C1 Cedars Sinai Med Ctr, Inflammatory Bowel Dis Res Ctr, Los Angeles, CA 90048 USA. NCI, Expt Immunol Lab, FCRDC, Frederick, MD 21701 USA. RP Targan, SR (reprint author), Cedars Sinai Med Ctr, Inflammatory Bowel Dis Res Ctr, 8700 Beverly Blvd, Los Angeles, CA 90048 USA. RI Young, Howard/A-6350-2008 OI Young, Howard/0000-0002-3118-5111 NR 39 TC 11 Z9 11 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAY PY 2003 VL 33 IS 5 BP 1152 EP 1162 DI 10.1002/eji.200322857 PG 11 WC Immunology SC Immunology GA 680DM UT WOS:000182961100003 PM 12731040 ER PT J AU Okayama, Y Tkaczyk, C Metcalfe, DD Gilfillan, AM AF Okayama, Y Tkaczyk, C Metcalfe, DD Gilfillan, AM TI Comparison of Fc epsilon RI- and Fc gamma RI-mediated degranulation and TNF-alpha synthesis in human mast cells: selective utilization of phosphatidylinositol-3-kinase for Fc gamma Ri-induced degranulation SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE human mast cell; Fc receptor; signal transduction; src kinase; p72(syk); MAP kinase; phosphatidylinositol-3-kinase ID ACTIVATED PROTEIN-KINASE; AFFINITY IGG RECEPTOR; TYROSINE-KINASE; SIGNAL-TRANSDUCTION; CROSS-LINKING; IFN-GAMMA; DEPENDENT ACTIVATION; PHOSPHOLIPASE-D; UP-REGULATION; SYK AB We have demonstrated that CD34(+) IFN-gamma-treated human mast cells (HuMC) express functional FcgammaRI and that aggregation of these receptors leads to mediator release. As the signaling pathways linking FcgammaRI aggregation to mediator release are unknown, we examined FcgammaRI-dependent activation of specific signal transduction molecules and determined the relative involvement of these events in HuMC degranulation and TNF-alpha production following both FcgammaRI and FcepsilonRI aggregation. FcgammaRI aggregation resulted in the phosphorylation/activation of src kinases and P72(syk) and subsequent tyrosine phosphorylation of multiple substrates. Inhibitor studies revealed that these responses were required for degranulation and TNF-a synthesis. Both FcgammaRI and FcepsilonRI aggregation also activated the MAP kinases ERK 1/2, JNK and p38 and this was necessary for TNF-alpha synthesis, but not degranulation for both receptors. Thus, signaling events in HuMC following aggregation of FcgammaRI were generally similar to those observed following FcepsilonRI aggregation. The one exception was that, although phosphatidylinositol-3-kinase was activated after both FcepsilonRI and FcgammaRI aggregation, only the FcgammaRI appeared to require this molecule for degranulation. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Gilfillan, AM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C206,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. NR 47 TC 38 Z9 41 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAY PY 2003 VL 33 IS 5 BP 1450 EP 1459 DI 10.1002/eji.200323563 PG 10 WC Immunology SC Immunology GA 680DM UT WOS:000182961100035 PM 12731072 ER PT J AU Grass, S Crawley, JN Xu, XJ Wiesenfeld-Hallin, Z AF Grass, S Crawley, JN Xu, XJ Wiesenfeld-Hallin, Z TI Reduced spinal cord sensitization to C-fibre stimulation in mice over-expressing galanin SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE central sensitization; flexor reflex; nociception; pain; transgenic mice; wind-up ID PERIPHERAL-NERVE INJURY; ROOT GANGLION-CELLS; INTRATHECAL GALANIN; FLEXOR REFLEX; DORSAL HORN; ALZHEIMERS-DISEASE; SENSORY NEURONS; RAT; NEUROPEPTIDES; EXCITABILITY AB The neuropeptide galanin may have a role in spinal nociception. In this study, we examined the excitability of the flexor reflex and its sensitization by repetitive stimulation of nociceptive C-fibres in anaesthetized mice that over-express galanin. No difference was seen between over-expressing galanin and wild-type mice in the magnitude of the baseline flexor reflex. Repetitive conditioning stimulation of C-fibres (10 stimuli at 1 Hz) produced a gradual increase in reflex magnitude during the conditioning stimulation (wind-up), as well as an increase in spinal reflex excitability after the termination of the stimulus train (central sensitization) in wild-type mice. Although the wind-up did not differ between over-expressing galanin and wild-type mice, the magnitude of central sensitization was significantly reduced in the over-expressing galanin mice (24 +/- 13% peak increase compared with 164 +/- 65% in the wild-type). Intrathecal administration of M35, a galanin receptor antagonist, markedly enhanced central sensitization in over-expressing galanin mice in association with C-fibre conditioning stimulation, while having no effect in wild-type mice. These results provide further electrophysiological evidence for an inhibitory function of galanin in modulation of central sensitization in response to C-fibre stimulation. C1 Huddinge Univ Hosp, Karolinska Inst, Dept Lab Med, Div Clin Neurophysiol, SE-14186 Stockholm, Sweden. NIMH, Sect Behav Genom, Bethesda, MD 20815 USA. RP Grass, S (reprint author), Huddinge Univ Hosp, Karolinska Inst, Dept Lab Med, Div Clin Neurophysiol, SE-14186 Stockholm, Sweden. NR 32 TC 24 Z9 25 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2003 VL 17 IS 9 BP 1829 EP 1832 DI 10.1046/j.1460-9568.2003.02623.x PG 4 WC Neurosciences SC Neurosciences & Neurology GA 679VK UT WOS:000182942500012 PM 12752782 ER PT J AU Parada, CA Yeh, JJ Joseph, EK Levine, JD AF Parada, CA Yeh, JJ Joseph, EK Levine, JD TI Tumor necrosis factor receptor type-1 in sensory neurons contributes to induction of chronic enhancement of inflammatory hyperalgesia in rat SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE chronic pain; inflammatory hyperalgesia; protein kinase c-epsilon; sensory neuron; tumor necrosis factor-alpha ID PROTEIN-KINASE-C; RESISTANT SODIUM CURRENT; FACTOR-ALPHA; PROSTAGLANDIN E-2; STRAIN INJURY; TNF-ALPHA; IN-VITRO; PAIN; SENSITIZATION; AGONISTS AB Carrageenan-induced inflammatory pain lasting hours to days produces a protein kinase C epsilon (PKCepsilon)-dependent 'primed' state lasting several weeks, during which time injection of prostaglandin E-2 induces hyperalgesia which is markedly enhanced and prolonged compared to PGE(2) -induced hyperalgesia in normal 'unprimed' rats. In the present study, we demonstrate that while inhibition of prostaglandin synthesis and antagonism of beta(2) -adrenergic receptors markedly attenuated the hyperalgesia induced by carrageenan, these interventions did not affect hyperalgesic priming. Tumor necrosis factor-alpha (rat recombinant; rrTNFalpha), another mediator of carrageenan-induced inflammation, alone produced hyperalgesia and priming, which were attenuated and prevented, respectively, by intrathecal administration of antisense to PKCepsilon. Inhibition of TNFalpha with thalidomide or a rat polyclonal anti-TNFalpha antibody attenuated carrageenan-induced hyperalgesia and prevented priming. Intrathecal administration of antisense to tumour necrosis factor receptor type-1 (TNFR1) reduced the level of TNFR1 transported toward the peripheral terminals of sensory neurons, and attenuated both carrageenan- and rrTNFalpha-induced priming. Acute hyperalgesia induced by carrageenan or rrTNFalpha remained intact in animals treated with TNFR1 antisense. Our results demonstrate that the generation of the primed state does not require production of hyperalgesia and that TNFalpha, which is generated during acute inflammation, can act on sensory neurons to induce hyperalgesic priming by activating neuronal PKCepsilon. C1 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, NIH Pain Ctr, Sci Program, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, Dept Med, C522,Box 0440,521 Parnassus Ave, San Francisco, CA 94143 USA. RI Parada, Carlos Amilcar/C-3974-2012 NR 37 TC 105 Z9 107 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2003 VL 17 IS 9 BP 1847 EP 1852 DI 10.1046/j.1460-9568.2003.02626.x PG 6 WC Neurosciences SC Neurosciences & Neurology GA 679VK UT WOS:000182942500014 PM 12752784 ER PT J AU Kleeberger, SR AF Kleeberger, SR TI Genetic aspects of susceptibility to air pollution SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article; Proceedings Paper CT Workshop on Air Pollution Effects in the Elderly CY MAR 12-14, 2001 CL PISA, ITALY DE innate immunity; ozone; particles; polymorphism; toll-like receptor 4; tumour; necrosis factor-alpha ID OZONE-INDUCED INFLAMMATION; TOLL-LIKE RECEPTOR-4; LINKAGE ANALYSIS; TRANSGENIC MICE; MOUSE; EXPOSURE; DISEASE; CHROMOSOME; NEUTROPHILIA; PARTICLES AB Inter-individual variation in human responses to air pollutants suggests that some subpopulations are at increased risk, and it is increasingly clear that genetic background is an important susceptibility factor. Genetically standardised animal models provide useful investigative tools. Linkage analyses using inbred mice identified chromosomal segments (quantitative trait loci (QTL)), with genes controlling susceptibility to the lung inflammatory (chromosome 17), injury (chromosome 11), and hyperpermeability (chromosome 4) responses to ozone (O-3) exposure. An immune dysfunction response induced by exposure to sulphate-associated particles is linked to the identical chromosome 17 and 11 QTLs described for O-3 susceptibility, thus similar genetic mechanisms may be controlling pulmonary responses to these pollutants. Candidate genes within the QTLs on chromosomes 4 and 17 include the toll-like receptor 4 and the pro-inflammatory cytokine, tumour necrosis factor-alpha, respectively. Functional analyses strongly support a role for these candidate genes in determining susceptibility to O-3 and particulates. Because striking linkage homology exists between the human and mouse genomes, candidate susceptibility genes identified in the mouse are likely to aid research aimed at understanding human genetic factors that contribute to differential susceptibility. To date, no studies have examined the interaction between age and genetic background in the development of air pollution-induced lung disease. However, investigations have suggested an influence of age on genetic susceptibility to lung cancer and other diseases, which indicate that an interaction between age and genetic background may be important in air pollution disease pathogenesis. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. RP Kleeberger, SR (reprint author), NIEHS, Pulm Pathobiol Lab, NIH, 111 TW Alexander Dr,Bldg 101,Rm D240, Res Triangle Pk, NC 27709 USA. NR 49 TC 0 Z9 0 U1 0 U2 2 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD MAY PY 2003 VL 21 SU 40 BP 52S EP 56S DI 10.1183/09031936.03.00403003 PG 5 WC Respiratory System SC Respiratory System GA 680TN UT WOS:000182994800010 ER PT J AU Ouspenski, II Van Hooser, AA Brinkley, BR AF Ouspenski, II Van Hooser, AA Brinkley, BR TI Relevance of histone acetylation and replication timing for deposition of centromeric histone CENP-A SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE centromere; kinetochore; CENP-A; histone acetylation; replication timing; dicentric; heterochromatin ID ALPHA-SATELLITE DNA; INACTIVE X-CHROMOSOME; HUMAN ARTIFICIAL CHROMOSOMES; CHINESE-HAMSTER CHROMOSOMES; RAT 3Y1 FIBROBLASTS; HUMAN NEOCENTROMERE; MAMMALIAN-CELLS; METAPHASE CHROMOSOMES; KINETOCHORE FORMATION; DYNAMIC ORGANIZATION AB A centromere-specific variant of histone H3, centromere protein A (CENP-A), is a critical determinant of centromeric chromatin, and its location on the chromosome may determine centromere identity. To search for factors that direct CENP-A deposition at a specific chromosomal locus, we took advantage of the observation that CENP-A, when expressed at elevated levels, can get incorporated at ectopic sites on the chromosome, in addition to the centromere. As core histone hypoacetylation and DNA replication timing have been implicated as epigenetic factors that may be important for centromere identity, we hypothesized that the sites of preferential CENP-A deposition will be distinguished by these parameters. We found that, on human dicentric chromosomes, ectopically expressed CENP-A preferentially incorporates at the active centromere only, despite the fact that the levels of histone acetylation and replication timing were indistinguishable at the two centromeres. In CHO cells, ectopically expressed CENP-A is preferentially targeted to some, but not all telomeric regions. Again, these regions could not be distinguished from other telomeres by their acetylation levels or replication timing. Thus histone acetylation and replication timing are not sufficient for specifying the sites of CENP-A deposition and likely for centromere identity. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Ouspenski, II (reprint author), NICHD, Lab Gene Regulat & Dev, NIH, 18T Lib Dr,Room 106, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA64255, CA41424] NR 83 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 1 PY 2003 VL 285 IS 2 BP 175 EP 188 DI 10.1016/S0014-4827(03)00011-9 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 672EE UT WOS:000182507500002 PM 12706113 ER PT J AU Ponce, ML Kleinman, HK AF Ponce, ML Kleinman, HK TI Identification of redundant angiogenic sites in laminin alpha 1 and gamma 1 chains SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE angiogenesis; laminin; ECM; integrin ID HUMAN-ENDOTHELIAL CELLS; TUMOR-GROWTH; G-DOMAIN; A CHAIN; ADHESION; PEPTIDE; INTEGRIN; THROMBOSPONDIN-1; ALPHA(V)BETA(3); RECEPTORS AB The degradation of the extracellular matrix is one of the first steps involved in angiogenesis, the formation of new vessels from preexisting ones. Laminin, a large extracellular matrix protein, has many biological activities, including the promotion of angiogenesis. Screening of the laminin-1 chains identified 20 angiogenic peptides, of which, A13 and C16, from the alpha1 and gamma1 chains, respectively, were the most active. We recently identified the receptors for C16 as the integrins alpha5beta1 and alphavbeta3. Here, we show unexpectedly that A13 is a redundant active site to C16 present in the N-terminal globular domain of the alpha1 chain. The peptides are located in homologous sites present in the last globular domains of their respective chains, and their amino acids are 66% conserved, as compared to the inactive homologous site in the beta1 chain, B19 to B20, which is only 18%-23% conserved. Cell attachment studies demonstrated that both A13 and C16 reciprocally inhibited their adhesion activity, whereas the corresponding laminin beta1 chain peptides were inactive. Chorioallantoic membrane assays showed that the in vivo angiogenic activity of A13 is blocked by a C16 antagonist, C16S, which also binds to the same integrin receptors. A13 affinity chromatography and immumoprecipitation analysis showed that the alphavbeta3 and alpha5beta1 integrin receptors bind to this sequence. We have therefore identified redundant activity on two laminin chains. These highly conserved functional sites are likely important mediators of the biological responses of laminins because either one or both of these chains (active sites) are present in almost all laminin isoforms identified to date. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIDCR, CDBRB, NIH, Bethesda, MD 20892 USA. RP Kleinman, HK (reprint author), NIDCR, CDBRB, NIH, Bldg 30,Rm 433, Bethesda, MD 20892 USA. NR 36 TC 25 Z9 25 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE 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 1 PY 2003 VL 285 IS 2 BP 189 EP 195 DI 10.1016/S0014-4827(03)00056-9 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 672EE UT WOS:000182507500003 PM 12706114 ER PT J AU Nguyen, DH Taub, DD AF Nguyen, DH Taub, DD TI Membrane incorporation of 22-hydroxycholesterol inhibits chemokine receptor activity SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE cholesterol; oxysterol; chemokine; chemokine receptors; T cells; lipid rafts; signaling ID PROTEIN-COUPLED RECEPTOR; FOAM CELL-FORMATION; MACROPHAGE DIFFERENTIATION; PHARMACOLOGICAL EVIDENCE; OXIDIZED CHOLESTEROL; CALORIC RESTRICTION; OXYSTEROLS; CCR5; ACTIVATION; ATHEROSCLEROSIS AB Cell membrane exposure to oxysterols, such as 22-hydroxycholesterol (22-OHC), has previously been shown to induce a suppressive effect on lymphocyte activation. Based on our previous findings that chemokine binding was significantly inhibited by the extraction of membrane cholesterol, we sought to assess the effects of 22-OHC treatment on chemokine ligand-binding and receptor activity. Our results revealed that 22-OHC, but not nonoxidized cholesterol, significantly reduced the binding of both SDF-1alpha and MIP-1beta to human T-cell lines and PBMCs within 1 h of treatment. Incubating the treated cells at 37degreesC for 1 h reversed a majority of the inhibitory effects on chemokine binding. 22-OHC also inhibited intracellular calcium mobilization and cell migration in response to SDF-1alpha treatment. Interestingly, while the presence of oxysterols in cell membranes significantly inhibits chemokine receptor function, this inhibitory effect does not involve alterations in receptor conformation, expression, or a direct antagonism of chemokine binding. We propose here a novel mechanism for oxysterol-mediated inhibition of chemokine receptor function and the implications for the presence of oxysterols on immune cells. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIA, Immunol Lab, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Taub, DD (reprint author), NIA, Immunol Lab, NIH, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 49 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 1 PY 2003 VL 285 IS 2 BP 268 EP 277 DI 10.1016/S0014-4827(03)00063-6 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 672EE UT WOS:000182507500010 PM 12706121 ER PT J AU Thayer, RE Wittock, R Parr, R Zullo, S Birch-Machin, MA AF Thayer, RE Wittock, R Parr, R Zullo, S Birch-Machin, MA TI A maternal line study investigating the 4977-bp mitochondrial DNA deletion SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE mitochondrial DNA; reactive oxygen species; PCR methodology; maternal transmission ID DAMAGE; MTDNA; MOUSE; CELLS; MUTATION; SEQUENCE; DISEASE; OOCYTES; REPAIR AB The most frequently reported species of mitochondrial DNA (mtDNA) damage associated with ageing is the 4977-bp 'Common Deletion'. However, recent observations have raised several issues within the deletion debate namely: the significance of the 4977-bp deletion (CD) as a universal DNA marker of ageing and mitochondrial dysfunction; and the possibility for maternal transmission of deletions in humans. Previous attempts at answering these questions have been limited because many investigations have been cross-sectional studies of unrelated individuals. With the unique feature of the maternal inheritance of mtDNA, our study overcomes some of these limitations by investigating the CD in human maternal lines, which represent 21 families spanning four generations. Using a highly sensitive PCR methodology, we identified the presence of the CD in leukocytes from all 71 individuals (age range-8 months-99 years) including all infants and children (n = 15) which in addition were free of any known mitochondrial diseases. This is important because the few reports of the CD in infants have been linked to mitochondrial disease. These results question the significance of the CD as a universal DNA marker of ageing and subsequent mitochondrial dysfunction and provide support for the possibility for maternal transmission of deletions. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Lakehead Univ, App Biomol Sci Program, Thunder Bay, ON P7B 5Z5, Canada. NIMH, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. Univ Newcastle Upon Tyne, Sch Med, Dept Dermatol, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. RP Thayer, RE (reprint author), Lakehead Univ, App Biomol Sci Program, 310 1294 Balmoral St, Thunder Bay, ON P7B 5Z5, Canada. NR 31 TC 13 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAY PY 2003 VL 38 IS 5 BP 567 EP 571 DI 10.1016/S0531-5565(03)00033-0 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 692CJ UT WOS:000183642500012 PM 12742534 ER PT J AU Backman, C Zhang, YJ Hoffer, BJ Tomac, AC AF Backman, C Zhang, YJ Hoffer, BJ Tomac, AC TI Short interfering RNAs (siRNAs) for inhibition of gene expression in dopaminergic neurons SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 10th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY MAY 01-04, 2003 CL CLEARWATER, FLORIDA SP Amer Soc Neural Transplantat & Repair C1 NIDA, NIH, IRP, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2003 VL 181 IS 1 BP 85 EP 85 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 672NQ UT WOS:000182527400014 ER PT J AU Boger, HA Granholm, AC Middaugh, LD Hoffer, BJ Tomac, A Zaman, V AF Boger, HA Granholm, AC Middaugh, LD Hoffer, BJ Tomac, A Zaman, V TI Differential effects of the dopamine neurotoxin MPTP upon animals with a partial deletion of the GDNF receptor, GFR alpha 1, gene SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 10th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY MAY 01-04, 2003 CL CLEARWATER, FLORIDA SP Amer Soc Neural Transplantat & Repair C1 Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. NIDA, Intramural Res Program, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2003 VL 181 IS 1 BP 86 EP 86 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 672NQ UT WOS:000182527400019 ER PT J AU Chang, CF Harvey, BK Hoffer, BJ Wang, Y AF Chang, CF Harvey, BK Hoffer, BJ Wang, Y TI Pretreatment with 9-cis-retinoic acid attenuates cortical infarction induced by middle cerebral arterial ligation through BMPS. SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 10th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY MAY 01-04, 2003 CL CLEARWATER, FLORIDA SP Amer Soc Neural Transplantat & Repair C1 NIDA, NIH, Baltimore, MD USA. Natl Def Med Ctr, Tri Serv Gen Hosp, Taipei, Taiwan. RI Harvey, Brandon/A-5559-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2003 VL 181 IS 1 BP 88 EP 89 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 672NQ UT WOS:000182527400029 ER PT J AU Harvey, BK Chiang, YH Chang, CF Su, T Wang, Y AF Harvey, BK Chiang, YH Chang, CF Su, T Wang, Y TI Protective effects of diadenosine tetraphosphate against cerebral ischemia in rats. SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 10th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY MAY 01-04, 2003 CL CLEARWATER, FLORIDA SP Amer Soc Neural Transplantat & Repair C1 NIDA, NIH, Baltimore, MD USA. Natl Def Med Ctr, Tri Serv Gen Hosp, Taipei, Taiwan. RI Harvey, Brandon/A-5559-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2003 VL 181 IS 1 BP 94 EP 94 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 672NQ UT WOS:000182527400047 ER PT J AU Quintero, EM Willis, LM Lee, J Boger, HA Tomac, A Stromberg, I Granholm, AC AF Quintero, EM Willis, LM Lee, J Boger, HA Tomac, A Stromberg, I Granholm, AC TI GDNF is essential to neuronal survival in the locus coeruleus-hippocampal noradrenergic pathway. SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 10th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY MAY 01-04, 2003 CL CLEARWATER, FLORIDA SP Amer Soc Neural Transplantat & Repair C1 Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. NIDA, Baltimore, MD USA. Karolinska Inst, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2003 VL 181 IS 1 BP 103 EP 103 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 672NQ UT WOS:000182527400082 ER PT J AU Zaman, V Granholm, AC Boger, H Gerhardt, G Hoffer, B Tomac, A Middaugh, L AF Zaman, V Granholm, AC Boger, H Gerhardt, G Hoffer, B Tomac, A Middaugh, L TI Behavioral, neurochemical and histochemical studies of aged mice with a partial deletion of the GDNF receptor gene (GFR alpha-1+/-). SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 10th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY MAY 01-04, 2003 CL CLEARWATER, FLORIDA SP Amer Soc Neural Transplantat & Repair C1 Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Univ Kentucky, Albert B Chandler Med Ctr, Dept Anat & Neurobiol, Lexington, KY 40536 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2003 VL 181 IS 1 BP 111 EP 111 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 672NQ UT WOS:000182527400109 ER PT J AU Zeng, X Chen, J Sanchez, JF Coggiano, M Dillon-Carter, O Petersen, J Freed, WJ AF Zeng, X Chen, J Sanchez, JF Coggiano, M Dillon-Carter, O Petersen, J Freed, WJ TI Stable expression of HRGFP by mouse embryonic stem cells: Promoter activity in the undifferentiated state and during dopaminergic neural differentiation. SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 10th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY MAY 01-04, 2003 CL CLEARWATER, FLORIDA SP Amer Soc Neural Transplantat & Repair C1 NIDA, Sect Dev & Plast, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2003 VL 181 IS 1 BP 111 EP 111 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 672NQ UT WOS:000182527400110 ER PT J AU Johnson, MD Oberst, MD Lin, CY Dickson, RB AF Johnson, MD Oberst, MD Lin, CY Dickson, RB TI Possible role of matriptase in the diagnosis of ovarian cancer SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE diagnosis; HAI-1; matniptase; ovarian cancer; screening ID HEPATOCYTE GROWTH-FACTOR; UROKINASE PLASMINOGEN-ACTIVATOR; TRANSMEMBRANE SERINE-PROTEASE; BOWMAN-BIRK INHIBITOR; MATRIX-DEGRADING PROTEASE; FACTOR SCATTER FACTOR; BREAST-CANCER; C-MET; INCREASED EXPRESSION; SURFACE EPITHELIUM AB There are increasing data that suggest a role for the serine protease matriptase and its inhibitor, hepatocyte growth factor activator inhibitor-1, in the pathogenesis and progression of ovarian cancer. This review will discuss the matriptase/inhibitor system in the context of ovarian cancer and examine the possibility that this system might be a useful therapeutic and/or diagnostic target in this disease. C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Dept Oncol, Washington, DC 20057 USA. NCI, Canc Res Ctr, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20057 USA. RP Johnson, MD (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Dept Oncol, Washington, DC 20057 USA. EM johnsom@georgetown.edu NR 66 TC 17 Z9 17 U1 0 U2 1 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2003 VL 3 IS 3 BP 331 EP 338 DI 10.1586/14737159.3.3.331 PG 8 WC Pathology SC Pathology GA 767KB UT WOS:000188437800005 PM 12779007 ER PT J AU Choi, EH Nutman, TB Chanock, SJ AF Choi, EH Nutman, TB Chanock, SJ TI Genetic variation in immune function and susceptibility to human filariasis SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE genetic association studies; genetic suscceptibility; HLA comples; host response; linkage analysis; lymphatic filariasis ID SINGLE NUCLEOTIDE POLYMORPHISMS; MANNAN-BINDING PROTEIN; SEVERE MALARIA; BANCROFTIAN FILARIASIS; LYMPHATIC FILARIASIS; BRUGIA-MALAYI; HUMAN-DISEASE; IMMUNOGLOBULIN ALLOTYPES; WUCHERERIA-BANCROFTI; HUMAN ONCHOCERCIASIS AB The generation of a draft sequence of a the human genome has provided the opportunity to characterize human diversity, even as it pertains to differences in host response to parasitic infection with organisms that cause lymphatic filarlasis, malaria and schistosomiasis. Worldwide, human infection with filarial pathogens represents a significant cause of morbidity throughout the tropics. In particular, epidemiologic evidence suggests that a genetic component contributes to susceptibility and possibly the outcomes of filarial infection. Different approaches can be applied in population-based studies in areas where filarial infection is endemic, such as genome linkage scans and candidate gene analysis for the purpose of identifying genetic risk factors. This review summarizes recent advances in our understanding of genetic contributions to human lymphatic filariasis; and addresses the immediate questions facing the field. It is anticipated that the identification of susceptibility genes in filarial infection could provide new insights into therapeutic strategies, including pharmacological intervention and vaccine development, and influence public health measures to control or overt infection. C1 NCI, Ctr Adv Technol, Pediat Oncol Branch, Sect Genom Variat,NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, Helminth Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Ctr Adv Technol, Pediat Oncol Branch, Sect Genom Variat,NIH, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM sc83a@nih.gov NR 79 TC 14 Z9 14 U1 0 U2 1 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2003 VL 3 IS 3 BP 367 EP 374 DI 10.1586/14737159.3.3.367 PG 8 WC Pathology SC Pathology GA 767KB UT WOS:000188437800008 PM 12779010 ER PT J AU Yang, YL Yu, XD AF Yang, YL Yu, XD TI Regulation of apoptosis: the ubiquitous way SO FASEB JOURNAL LA English DT Review DE ubiquitination; caspase; IAP; ring finger protein; ubiquitin protein ligase (E3) ID PROGRAMMED CELL-DEATH; PROTEASOME-MEDIATED DEGRADATION; TUMOR-SUPPRESSOR PROTEIN; TRAIL-INDUCED APOPTOSIS; BCL-2 FAMILY MEMBERS; X-LINKED INHIBITOR; SOCS-BOX MOTIF; SERINE-PROTEASE; LIGASE ACTIVITY; DEPENDENT DEGRADATION AB Ubiquitin is a ubiquitously expressed 76 amino acid protein that can be covalently attached to target proteins, leading to their ubiquitination. Many ubiquitinated proteins are degraded by the proteasome, a 2000 kDa ATP-dependent proteolytic complex. Numerous studies have demonstrated that the ubiquitination and proteasome system plays an important role in controlling the levels of various cellular proteins and therefore regulates basic cellular processes such as cell cycle progression, signal transduction, and cell transformation. Ubiquitination also directly affects the function and location of target proteins. Recent studies found that ubiquitination-mediated degradation and change in activity regulate many molecules of the cell death machinery, such as p53, caspases, and Bcl-2 family members. Ring finger-containing members of the IAP (inhibitor of apoptosis) family proteins themselves can function as ubiquitin protein ligases to ubiquitinate their target proteins or promote autoubiquitination. It has been demonstrated that degradation of the IAP proteins is required for apoptosis to occur in some systems, indicating apoptosis proceeds by activating death pathways as well as eliminating "roadblocks" through ubiquitination. These new findings also suggest that ubiquitination is one of the major mechanisms that regulate apoptotic cell death and could be a unique target for therapeutic intervention. C1 NCI, Regulat Cell Growth Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. Inst Basic Med Sci, Dept Cell Biol, Beijing 100850, Peoples R China. RP Yang, YL (reprint author), NCI, Regulat Cell Growth Lab, Ctr Canc Res, NIH, 1050 Boyles St,Bldg 560,Room 22-45, Frederick, MD 21702 USA. EM yangyili@ncifcrf.gov NR 117 TC 146 Z9 157 U1 1 U2 12 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 PY 2003 VL 17 IS 8 BP 790 EP 799 DI 10.1096/fj.02-0654rev PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 683TE UT WOS:000183165000003 PM 12724336 ER PT J AU Boulanger, A McLemore, P Copeland, NG Gilbert, DJ Jenkins, NA Yu, SS Gentleman, S Redmond, TM AF Boulanger, A McLemore, P Copeland, NG Gilbert, DJ Jenkins, NA Yu, SS Gentleman, S Redmond, TM TI Identification of beta-carotene 15,15 '-monooxygenase as a peroxisome proliferator-activated receptor target gene SO FASEB JOURNAL LA English DT Article DE carotenoids; retinoids; transcriptional regulation; promoter; RXR ID RETINOL-BINDING PROTEIN; RAT SMALL-INTESTINE; RNA POLYMERASE-II; BETA,BETA-CAROTENE 15,15'-DIOXYGENASE; DIFFERENTIAL REGULATION; X-RECEPTOR; EXPRESSION; ENZYME; ALPHA; CLEAVAGE AB beta-Carotene 15,15'-monooxygenase (BCM) catalyzes the first step of vitamin A biosynthesis from provitamin A carotenoids. We wished to determine the factors underlying the transcriptional regulation of this gene. After cloning of the 40 kilobase pair (kbp) mouse Bcm gene and determination of its genomic organization, analysis of the 2 kb 5'-flanking region showed several putative transcription factor binding sites including TATA box, a peroxisome proliferator response element (PPRE), AP2, and bHLH. The 2 kb fragment drove specific luciferase gene expression in vitro only in cell lines that express BCM (TC7, PF11, and monkey retinal pigment epithelium). Nucleotides -41 to +163, and -60 to +163 drove basal and specific Bcm transcriptional activity, respectively. Site-directed mutagenesis and gel shift experiments demonstrate that PPRE was essential for Bcm promoter specificity and that the peroxisome proliferator activated receptor (PPAR) gamma (PPARgamma) specifically binds to this element. Furthermore, cotransfection experiments and pharmacological treatments in vitro, using the specific PPARgamma agonists LY17883 and ciglitazone, demonstrate that the PPRE element confers peroxisome proliferator responsiveness via the PPARgamma and retinoid X receptor-alpha heterodimer. Treatment of mice with the PPARalpha/gamma agonist WY14643 increases BCM protein expression in liver. Thus PPAR is a key transcription factor for the transcriptional regulation of the Bcm gene, suggesting a broader function for PPARs in the regulation of carotenoid metabolism metabolism that is consistent with their established role in neutral lipid metabolism and transport. C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mouse Canc Genet Program, Ft Detrick, MD 21702 USA. RP Redmond, TM (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bldg 6,Rm 339,6 Ctr Dr,MSC 2740, Bethesda, MD 20892 USA. EM redmond@helix.nih.gov OI Redmond, T. Michael/0000-0002-1813-5291 NR 49 TC 68 Z9 73 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2003 VL 17 IS 8 BP 1304 EP + DI 10.1096/fj.02-0690fje PG 29 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 683TE UT WOS:000183165000024 PM 12759335 ER PT J AU Kimes, AS Horti, AG London, ED Chefer, SI Contoreggi, C Ernst, M Friello, P Koren, AO Kurian, V Matochik, JA Pavlova, O Vaupel, DB Mukhin, AG AF Kimes, AS Horti, AG London, ED Chefer, SI Contoreggi, C Ernst, M Friello, P Koren, AO Kurian, V Matochik, JA Pavlova, O Vaupel, DB Mukhin, AG TI 2-[F-18]F-A85380: PET imaging of brain nicotinic acetylcholine receptors and whole body distribution in humans SO FASEB JOURNAL LA English DT Article DE dosimetry; smoking; Alzheimer's disease; Parkinson's disease; non-invasive imaging ID POSITRON-EMISSION-TOMOGRAPHY; ALZHEIMERS-DISEASE; BINDING-SITES; C-11 NICOTINE; MICE; PARKINSONS; TRACER; RADIOLIGAND; POSTMORTEM; AFFINITY AB Noninvasive imaging of nicotinic acetylcholine receptors (nAChRs) in the human brain in vivo is critical for elucidating the role of these receptors in normal brain function and in the pathogenesis of brain disorders. Here we report the first in vivo visualization of human brain areas containing nAChRs by using PET and 2-[F-18]fluoro-3-(2(S)azetidinylmethoxy)pyridine (2-[F-18]FA). We acquired scans from six healthy non-smoking volunteers after i.v. bolus administration of 2-[F-18]FA (1.6 MBq/kg or 0.043 +/- 0.002 mCi/kg). This dose was sufficient for visualizing nAChRs in the thalamus up to 5 h after injection. There were no adverse effects associated with administration of no-carrier-added 2-[F-18]FA (1.3-10 pmol/kg). Consistent with the distribution of nAChRs in human brain, accumulated radioactivity was greatest in thalamus, intermediate in the midbrain, pons, cerebellum, and cortex; and least in white matter. As similar to90% of the injected radioactivity was eliminated via the urine (biological half-life ca. 4 h), the urinary bladder wall received the highest radiation dose. The estimate of radiation dose equivalent to the urinary bladder wall (ca. 180 +/- 30 mSv/MBq or 0.7 rem/mCi with a 2.4 h void interval) suggests that multiple studies could be performed in a single subject. The results predict that quantitative PET imaging of nAChRs in human brain with 2-[F-18]FA is feasible. C1 NIDA, Intramural Res Program, Neuroimaging Res Branch, Baltimore, MD 21224 USA. Univ Calif Los Angeles, David Geffen Sch Med, Inst Neuropsychiat, Los Angeles, CA USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. RP Kimes, AS (reprint author), NIDA, Intramural Res Program, Neuroimaging Res Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM akimes@intra.nida.nih.gov NR 47 TC 82 Z9 82 U1 0 U2 6 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 PY 2003 VL 17 IS 8 BP 1331 EP + DI 10.1096/fj.02-0492fje PG 17 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 683TE UT WOS:000183165000015 PM 12759330 ER PT J AU Stratton, P Winkel, C Premkumar, A Chow, C Wilson, J Hearns-Stokes, R Heo, S Merino, M Nieman, LK AF Stratton, P Winkel, C Premkumar, A Chow, C Wilson, J Hearns-Stokes, R Heo, S Merino, M Nieman, LK TI Diagnostic accuracy of laparoscopy, magnetic resonance imaging, and histopathologic examination for the detection of endometriosis SO FERTILITY AND STERILITY LA English DT Article DE endometriosis; laparoscopy; MRI; histopathology ID PELVIC PERITONEAL DEFECTS; FAT-SATURATION TECHNIQUE AB Objective: To evaluate the utility of fat-suppressed magnetic resonance imaging (MRI) in the diagnosis of endometriosis. Design: A prospetive clinical trial. Setting: A government research hospital. Patient(s): Forty-eight women with pelvic pain. Intervention(s): Magnetic resonance imaging followed by surgical excision and pathologic diagnosis of endometriosis. Main Outcome Measure(s): Presence and extent of endometriosis suggested by preoperative MRIs compared with surgical inspection and biopsy. Result(s): A preoperative MRI in 46 women detected fewer endometriosis lesions than histopathology or laparoscopy (78 vs. 101 vs. 150). Few MRI lesions correlated with those identified by laparoscopy (50 of 150) or pathology (38 of 101). Of 42 women with surgically diagnosed endometriosis, 28 had at least one corresponding abnormality on MRI, 5 had abnormalities that didn't correlate with surgical findings, and 9 had normal MRIs. The sensitivity of MRI in detecting biopsy-proven endometriosis for any woman was 69% (25 of 36), and the specificity was 75%. Conclusion(s): Although MRI identifies fewer areas of endometriosis than seen at surgery, it suggested endometriosis in 75% of those with at least mild disease. Only 67% of lesions identified at surgery contained histologic evidence of endometriosis. (C) 2003 by American Society for Reproductive Medicine. C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Stratton, P (reprint author), NICHD, PREB, NIH, Bldg 10,Room 9D42, Bethesda, MD 20892 USA. NR 18 TC 62 Z9 62 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2003 VL 79 IS 5 BP 1078 EP 1085 DI 10.1016/S0015-0282(03)00155-9 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 677FD UT WOS:000182795500006 PM 12738499 ER PT J AU Mills, JL England, L Granath, F Cnattingius, S AF Mills, JL England, L Granath, F Cnattingius, S TI Cigarette smoking and the male-female sex ratio SO FERTILITY AND STERILITY LA English DT Editorial Material ID NEWBORN-INFANTS; MALE/FEMALE RATIO; BIRTH; COUNTRIES C1 NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. RP Mills, JL (reprint author), NICHD, Pediat Epidemiol Sect, DESPR, NIH, 6100 Bldg,Room 7B03, Bethesda, MD 20892 USA. NR 12 TC 18 Z9 18 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2003 VL 79 IS 5 BP 1243 EP 1245 DI 10.1016/S0015-0282(03)00156-0 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 677FD UT WOS:000182795500036 PM 12738529 ER PT J AU Bonvicino, CR Penna-Firme, V do Nascimento, FF Lemos, B Stanyon, R Seuanez, HN AF Bonvicino, CR Penna-Firme, V do Nascimento, FF Lemos, B Stanyon, R Seuanez, HN TI The lowest diploid number (2n=16) yet found in any primate: Callicebus lugens (Humboldt, 1811) SO FOLIA PRIMATOLOGICA LA English DT Article DE Callicebus lugens; molecular evolution; cytogenetics ID CHROMOSOMAL HOMOLOGIES; TITI MONKEYS; PLATYRRHINI; CEBIDAE; MOLOCH; KARYOTYPE; TORQUATUS; FISH; DNA AB Morphologic, molecular and karyologic analyses of Callicebus lugens (Humboldt, 1811) of known geographic origin supported the proposition that this is a valid species. Morphologic and morphometric analyses showed evident differences between C lugens and two other related taxa of the same group (Callicebus purinus and Callicebus torquatus). Cytochrome b DNA analyses (maximum parsimony, neighbour joining and maximum likelihood) were congruent in showing a strong association between C lugens and Callicebus sp. of the torquatus group in one branch and a sister branch further divided into two clades: one with species of the personatus group and another, with species of the moloch group. Karyotypic analysis showed that C lugens has the lowest diploid chromosome number of the primate order (2n = 16). Comparisons with other congeneric species clearly supported the proposition that C. lugens is karyotypically similar to others of the torquatus group. Copyright (C) 2003 S. Karger AG, Basel. C1 Univ Fed Rio de Janeiro, Div Genet, Inst Nacl Canc, BR-20230130 Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Dept Trop Med, Inst Oswaldo Cruz Fiocruz, BR-20230130 Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Dept Genet, BR-20230130 Rio De Janeiro, Brazil. NCI, Comparat Mol Cytogenet Core Genet Branch, Frederick, MD 21701 USA. RP Seuanez, HN (reprint author), Univ Fed Rio de Janeiro, Div Genet, Inst Nacl Canc, Prace Cruz Vermelha 23,6 Andar, BR-20230130 Rio De Janeiro, Brazil. RI Bonvicino, Cibele /O-3390-2014; OI Stanyon, Roscoe/0000-0002-7229-1092 NR 26 TC 13 Z9 16 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0015-5713 J9 FOLIA PRIMATOL JI Folia Primatol. PD MAY-JUN PY 2003 VL 74 IS 3 BP 141 EP 149 DI 10.1159/000070647 PG 9 WC Zoology SC Zoology GA 698DV UT WOS:000183983100003 PM 12826733 ER PT J AU Mishina, Y AF Mishina, Y TI Function of bone morphogenetic protein signaling during mouse development SO FRONTIERS IN BIOSCIENCE LA English DT Review DE BMP; embryogenesis; patterning; gastrulation; receptor; kinase; skeletalgenesis; review ID TGF-BETA-SUPERFAMILY; MULLERIAN-INHIBITING SUBSTANCE; SERINE-THREONINE KINASE; PRIMORDIAL GERM-CELLS; LEFT-RIGHT AXIS; GROWTH-FACTOR-BETA; ACTIVIN RECEPTOR; II RECEPTOR; IN-VIVO; SEXUAL DEVELOPMENT AB Bone morphogenetic proteins (BMPs) play pleiotropic roles during development and after birth in many different organisms. BMPs are members of TGF-beta superfamily. There are more than 20 members with three type II receptors and three type I receptors. Genetic approaches using the mouse as a model system revealed many of the functions of BMPs. Particularly, results obtained through loss-of-function analyses of BMP ligands and their receptors are reviewed in this article. C1 NIEHS, Mol Dev Biol Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Mishina, Y (reprint author), NIEHS, Mol Dev Biol Sect, Reprod & Dev Toxicol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 162 TC 50 Z9 53 U1 0 U2 3 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY PY 2003 VL 8 BP D855 EP D869 DI 10.2741/1097 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 669LG UT WOS:000182352300037 PM 12700086 ER PT J AU Wilson, DM Sofinowski, TM McNeill, DR AF Wilson, DM Sofinowski, TM McNeill, DR TI Repair mechanisms for oxidative DNA damage SO FRONTIERS IN BIOSCIENCE LA English DT Review DE reactive oxygen species; oxidative DNA damage; base excision repair; review ID BASE-EXCISION-REPAIR; CELL NUCLEAR ANTIGEN; HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE; STRAND BREAK REPAIR; HUMAN MUTY HOMOLOG; COLI EXONUCLEASE-III; LACKING POLY(ADP-RIBOSE) POLYMERASE-1; HUMAN APURINIC ENDONUCLEASE; HUMAN POLYNUCLEOTIDE KINASE; PHOSPHATE LYASE ACTIVITY AB Reactive oxygen species are formed as by-products of mitochondrial aerobic respiration, as induced products upon exposure to certain environmental/exogenous agents (e.g. ionizing radiation), or as intended products during the immune response against invading foreign microbes. Although serving as essential signaling molecules in certain biological processes (e.g. during gene activation responses), these chemicals, particularly during oxidative stress when at excessive concentrations, can react with cellular components, most notably DNA, and in this capacity, promote mutagenesis or cell death, and in turn, human disease. We review here several of the common oxidative DNA damages as well as the DNA repair mechanisms related to maintaining genome integrity, and thus, preventing cancer formation and age-related disease. We focus mainly on participants of the base excision repair ( BER) pathway. In brief, the steps of BER include: ( a) excision of the damaged base, (b) incision of the DNA backbone at the apurinic/ apyrimidinic (AP) site product, ( c) removal of the AP terminal fragment, (d) gap-filling synthesis, and ( e) ligation of the final nick. C1 NIA, Lab Mol Gerontol, GRC, IRP,NIH, Baltimore, MD 21224 USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, GRC, IRP,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 204 TC 47 Z9 50 U1 1 U2 11 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY PY 2003 VL 8 BP D963 EP D981 DI 10.2741/1109 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 669LG UT WOS:000182352300044 PM 12700077 ER PT J AU El-Omar, EM Rabkin, CS Gammon, MD Vaughan, TL Risch, HA Schoenberg, JB Stanford, JL Mayne, ST Goedert, J Blot, WJ Fraumeni, JF Chow, WH AF El-Omar, EM Rabkin, CS Gammon, MD Vaughan, TL Risch, HA Schoenberg, JB Stanford, JL Mayne, ST Goedert, J Blot, WJ Fraumeni, JF Chow, WH TI Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms SO GASTROENTEROLOGY LA English DT Article ID HELICOBACTER-PYLORI INFECTION; GASTROESOPHAGEAL REFLUX DISEASE; BARRETTS-ESOPHAGUS; ATROPHIC GASTRITIS; INTERLEUKIN-1 POLYMORPHISMS; CAGA(+) STRAINS; CARDIA; ACID; CARCINOMA; ADENOCARCINOMA AB Background & Aims: Genetic variations in proinflammatory and anti-inflammatory cytokine genes influence individual response to carcinogenic exposures. Polymorphisms in interleukin (IL)-1beta and its endogenous receptor antagonist are associated with risk of Helicobacter pylori-related gastric cancer. The aim of this study was to evaluate the role of proinflammatory cytokine gene polymorphisms in gastric and esophageal cancers defined by anatomic subsite. Methods: We assessed polymorphisms of the IL-1 gene cluster and 4 other cytokine genes in a population-based case-control study of upper gastrointestinal cancers, including gastric cardia (n = 126) and noncardia adenocarcinoma (n = 188), esophageal squamous cell carcinoma (n = 53), and adenocarcinoma (n = 108), and frequency-matched controls (n = 212). ORs for the different cancers were computed from logistic regression models adjusted for potential confounding factors. Results: Proinflammatory genotypes of tumor necrosis factor alpha and IL-10 were each associated with more than doubling of the risk of noncardia gastric cancer. Carriage of multiple proinflammatory polymorphisms of IL-1B(o), IL-1 receptor antagonist, tumor necrosis factor A, and IL-10 conferred greater risk, with ORs (and 95% confidence intervals) of 2.8 (1.6-5.1) for one, 5.4 (2.7-10.6) for 2, and 27.3 (7.4-99.8) for 3 or 4 high-risk genotypes. In contrast, these polymorphisms were not consistently related to the risks of esophageal or gastric cardia cancers. Polymorphisms in IL-4 and IL-6 were riot associated with any of the cancers studied. Conclusions: A proinflammatory cytokine genetic profile increases the risk of noncardia gastric adenocarcinoma but not other upper gastrointestinal cancers, possibly by inducing a hypochlorhydric and atrophic response to gastric H. pylori infection. C1 Univ Aberdeen, Inst Med Sci, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. New Jersey Dept Hlth & Senior Serv, Appl Canc Epidemiol Program, Trenton, NJ USA. Int Epidemiol Inst, Rockville, MD USA. RP El-Omar, EM (reprint author), Univ Aberdeen, Inst Med Sci, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland. NR 43 TC 554 Z9 602 U1 5 U2 35 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 MAY PY 2003 VL 124 IS 5 BP 1193 EP 1201 DI 10.1016/S0016-5085(03)00157-4 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 673GF UT WOS:000182571800007 PM 12730860 ER PT J AU Jensen, RT Delle Fave, G Bordi, C AF Jensen, RT Delle Fave, G Bordi, C TI Discussion on the effect of chronic hypergastrinemia on human enterochromaffin-like cells: Insights from patients with sporadic gastrinomas - Reply SO GASTROENTEROLOGY LA English DT Letter ID ZOLLINGER-ELLISON-SYNDROME; CARCINOID-TUMOR; OMEPRAZOLE C1 NIDDK, NIH, Digest Dis Branch, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, NIH, Digest Dis Branch, Bethesda, MD 20892 USA. NR 9 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2003 VL 124 IS 5 BP 1565 EP 1565 DI 10.1016/S0016-5085(03)00357-3 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 673GF UT WOS:000182571800051 ER PT J AU Pera, C Inglese, E Ferrara, GB AF Pera, C Inglese, E Ferrara, GB TI DNA microarray technology for HLA-class I typing SO GENES AND IMMUNITY LA English DT Meeting Abstract CT 17th European Histocompatability Conference/11th Annual Meeting of the German-Society-of-Immunogenetics CY MAY 06-09, 2003 CL BADEN BADEN, GERMANY SP German Soc Immunogenet C1 Natl Canc Inst, Genoa, Italy. Univ Genoa, I-16126 Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD MAY PY 2003 VL 4 SU 1 MA 8 BP S2 EP S2 PG 1 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 684LL UT WOS:000183208800009 ER PT J AU Levens, DL AF Levens, DL TI Reconstructing MYC SO GENES & DEVELOPMENT LA English DT Editorial Material ID REVERSE-TRANSCRIPTASE GENE; C-MYC; MYC/MAX/MAD NETWORK; RAT FIBROBLASTS; EXPRESSION; TELOMERASE; PROMOTER; PROTEIN; TARGET; REGION C1 NCI, Gene Regulat Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Levens, DL (reprint author), NCI, Gene Regulat Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 47 TC 116 Z9 117 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 2003 VL 17 IS 9 BP 1071 EP 1077 DI 10.1101/gad.1095203 PG 7 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 675AU UT WOS:000182671500001 PM 12730130 ER PT J AU Strichman-Almashanu, LZ Bustin, M Landsman, D AF Strichman-Almashanu, LZ Bustin, M Landsman, D TI Retroposed copies of the HMG genes: A window to genome dynamics SO GENOME RESEARCH LA English DT Article ID CHROMOSOMAL PROTEIN HMG-17; HUMAN CDNA SEQUENCE; PROCESSED PSEUDOGENES; BINDING PROTEINS; MULTIGENE FAMILY; DNA-SEQUENCES; RETROPSEUDOGENES; EXPRESSION; RETROTRANSPOSITION; IDENTIFICATION AB Retroposed copies (RPCs) of genes are functional (intronless paralogs) or nonfunctional (processed pseudogenes) copies derived from mRNA through a process of retrotransposition. Previous studies found that gene families involved in mRNA translation or nuclear function were more likely to have large numbers of RPCs. Here we characterize RPCs of the few families coding for the abundant high-mobility-group (HMG) proteins in humans. Using an algorithm we developed, we identified and studied 219 HMG RPCs. For slightly more than 10% of these RPCs, we found evidence indicating expression. Furthermore, eight of these are potentially new members of the HMG families of proteins. For three RPCs, the evidence indicated expression as part of other transcripts; in all of these, we found the presence of alternative splicing or multiple polyadenylation signals. RPC distribution among the HMGs was not even, with 33-65 each for HMGB1, HMGB3, HMGN1, and HMGN2, and 0-6 each for HMGA1, HMGA2, HMGB2, and HMGN3. Analysis of the sequences flanking the RPCs revealed that the junction between the target site duplications and the 5'-flanking sequences exhibited the same TT/AAAA consensus found for the L1 endonuclease, supporting an U-mediated retrotransposition mechanism. Finally, because our algorithm included aligning RPC flanking sequences with the corresponding HMG genomic sequence, we were able to identify transcribed regions of HMG genes that were not part of the published mRNA sequences. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20894 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20894 USA. EM landsman@ncbi.nim.nih.gov RI Landsman, David/C-5923-2009; Bustin, Michael/G-6155-2015; OI Landsman, David/0000-0002-9819-6675 NR 48 TC 25 Z9 27 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD MAY PY 2003 VL 13 IS 5 BP 800 EP 812 DI 10.1011/gr.893803 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 674PQ UT WOS:000182645500006 PM 12727900 ER PT J AU Cooper, GM Brudno, M Green, ED Batzoglou, S Sidow, A AF Cooper, GM Brudno, M Green, ED Batzoglou, S Sidow, A CA NISC Comparative Sequencing Prog TI Quantitative estimates of sequence divergence for comparative analyses of mammalian genomes SO GENOME RESEARCH LA English DT Article ID REGULATORY SEQUENCES; PLACENTAL MAMMALS; PHYLOGENETICS AB Comparative sequence analyses on a collection of carefully chosen mammalian genomes could facilitate identification of functional elements within the human genome and allow quantification of evolutionary constraint at the single nucleotide level. High-resolution quantification would be informative for determining the distribution of important positions within functional elements and for evaluating the relative importance of nucleotide sites that carry single nucleotide polymorphisms (SNPs). Because the level of resolution in comparative sequence analyses is a direct function of sequence diversity, we propose that the information content of a candidate mammalian genome be defined as the sequence divergence it would add relative to already-sequenced genomes. We show that reliable estimates of genomic sequence divergence can be obtained from small genomic regions. On the basis of a multiple sequence alignment of -1.4 megabases each from eight mammals, we generate such estimates for five unsequenced mammals. Estimates of the neutral divergence in these data suggest that a small number of diverse mammalian genomes in addition to human, mouse, and rat would allow single nucleotide resolution in comparative sequence analyses. C1 Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Natl Inst Hlth Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. RP Sidow, A (reprint author), Stanford Univ, Dept Genet, Stanford, CA 94305 USA. RI Cooper, Gregory/D-6914-2011 OI Cooper, Gregory/0000-0001-5509-9923 NR 20 TC 90 Z9 91 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAY PY 2003 VL 13 IS 5 BP 813 EP 820 DI 10.1101/gr.1064503 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 674PQ UT WOS:000182645500007 PM 12727901 ER PT J AU Carter, MG Hamatani, T Sharov, AA Carmack, CE Qian, Y Aiba, K Ko, NT Dudekula, DB Brzoska, PM Hwang, SS Ko, MSH AF Carter, MG Hamatani, T Sharov, AA Carmack, CE Qian, Y Aiba, K Ko, NT Dudekula, DB Brzoska, PM Hwang, SS Ko, MSH TI In situ-synthesized novel microarray optimized for mouse stem cell and early developmental expression profiling SO GENOME RESEARCH LA English DT Article ID CDNA CLONE SET; GENE-EXPRESSION; SUBTRACTIVE HYBRIDIZATION; OLIGONUCLEOTIDE ARRAYS; INITIAL ANNOTATION; DIFFERENTIATION; TROPHOBLAST; PLACENTA; IMPLANTATION; PATTERNS AB Applications of microarray technologies to mouse embryology/genetics have been limited, due to the nonavailability of microarrays containing large numbers of embryonic genes and the gap between microgram quantities of RNA required by typical microarray methods and the miniscule amounts of tissue available to researchers. To overcome these problems, we have developed a microarray platform containing in situ-synthesized 60-mer oligonucleotide probes representing approximately 22,000 unique mouse transcripts, assembled primarily from sequences of stem cell and embryo cDNA libraries. We have optimized RNA labeling protocols and experimental designs to use as little as 2 ng total RNA reliably and reproducibly. At least 98% of the probes contained in the microarray correspond to clones in our publicly available collections, making cDNAs readily available for further experimentation on genes of interest. These characteristics, combined with the ability to profile very small samples, make this system a resource for stem cell and embryogenomics research. C1 NIA, Genet Lab, Dev Genom & Aging Sect, NIH, Bethesda, MD 20892 USA. Agilent Technol, Palo Alto, CA 94304 USA. RP Ko, MSH (reprint author), NIA, Genet Lab, Dev Genom & Aging Sect, NIH, Bethesda, MD 20892 USA. RI Carter, Mark/B-5089-2010; Ko, Minoru/B-7969-2009; OI Ko, Minoru/0000-0002-3530-3015; Dudekula, Dawood/0000-0002-4054-1827 NR 39 TC 83 Z9 83 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAY PY 2003 VL 13 IS 5 BP 1011 EP 1021 DI 10.1101/gr.878903 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 674PQ UT WOS:000182645500027 PM 12727912 ER PT J AU Cohen-Mansfield, J Werner, P Hammerschmidt, K Newman, JD AF Cohen-Mansfield, J Werner, P Hammerschmidt, K Newman, JD TI Acoustic properties of vocally disruptive behaviors in the nursing home SO GERONTOLOGY LA English DT Article DE elderly; vocalizations; verbally disruptive behaviors; nursing home; acoustic analysis ID DEMENTIA; VOCALIZATIONS; RESIDENTS; NOISE AB Background: Disruptive vocalizations are among the most common behavior problems in the nursing home. However, their acoustic properties have not been previously investigated. Objective: This paper examines the acoustic properties of disruptive vocalizations and attempts to link them to resident and verbalization characteristics. Methods: This study characterizes the sounds emitted by 26 nursing home residents who manifested disruptive vocalizations. Verbalizations were audiotaped and then used in a sonographic evaluation and an acoustic analysis. Results: Vocalizations of verbally agitated nursing home residents were characterized by their relatively short duration. Consistent positive correlations were found between seemingly disturbing types of vocalizations, such as yelling. and howling, and higher levels of several parameters of the fundamental frequency. A similar positive correlation was also found between acoustic parameters and medical disease indicators. With the exception of the length of stream of utterances, the indicators did not differentiate between types of dementia. Conclusions: Because of the large number of comparisons undertaken, it is difficult to conclude which associations between acoustic properties and resident or vocalization characteristics are attributable to real underlying trends and which are due to chance and error. Consistencies that deserve further research pertain to the perceptions of the types of vocalizations the person tends to emit and to the physical health of the person. Copyright (C) 2003 S. Karger AG, Basel. C1 Hebrew Home Greater Washington, Res Inst Aging, Rockville, MD 20852 USA. Sch Publ Hlth, Washington, DC USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. Univ Haifa, Fac Social Welf & Hlth Studies, IL-31999 Haifa, Israel. NICHHD, Comparat Ethol Lab, Poolesville, MD USA. German Primate Ctr, Gottingen, Germany. George Washington Univ, Sch Publ Hlth, Washington, DC USA. RP Cohen-Mansfield, J (reprint author), Hebrew Home Greater Washington, Res Inst Aging, 6121 Montrose Rd, Rockville, MD 20852 USA. FU NIA NIH HHS [R01AG10642] NR 26 TC 10 Z9 10 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PD MAY-JUN PY 2003 VL 49 IS 3 BP 161 EP 167 DI 10.1159/000069173 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 671QD UT WOS:000182474800004 PM 12679606 ER PT J AU Pringle, B Dahlquist, LM Eskenazi, A AF Pringle, B Dahlquist, LM Eskenazi, A TI Memory in pediatric patients undergoing conscious sedation for aversive medical procedures SO HEALTH PSYCHOLOGY LA English DT Article; Proceedings Paper CT 108th Annual Convention of the American-Psychological-Association CY AUG, 2000 CL WASHINGTON, D.C. SP Amer Psychol Assoc DE conscious sedation; memory; midazolam; pediatric patients; procedural distress ID APPLE MACINTOSH COMPUTER; IMPLICIT MEMORY; MIDAZOLAM PREMEDICATION; CHILDREN; AMNESIA; ANESTHESIA; DISTRESS; PICTURES; CANCER AB This study investigated preserved memory in 26 pediatric cancer patients (65% boys, 77% Caucasian, mean age = 12.5 years) undergoing midazolam-induced conscious sedation during painful medical procedures to treat hematological or oncological diseases. The sedative midazolam had a significant anterograde amnesic effect on participants' performance on a visual recognition (explicit) memory task but not on a visual perceptual facilitation (implicit) memory task. That implicit memory scores were relatively unaffected while explicit memory scores deteriorated significantly indicates that learning occurred while participants were sedated, even when participants did not recollect the learning event. These findings, which replicate those of M. R. Polster, R. A. McCarthy, G. O'Sullivan, P. A. Gray, and G. R. Park (1993) in a study of adults, have implications for the development and treatment of conditioned anxiety reactions associated with aversive medical procedures. C1 Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. RP Pringle, B (reprint author), Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, 6001 Execut Blvd,Room 4222 MSC 9565, Bethesda, MD 20892 USA. NR 34 TC 14 Z9 16 U1 1 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAY PY 2003 VL 22 IS 3 BP 263 EP 269 DI 10.1037/0278-6133.22.3.263 PG 7 WC Psychology, Clinical; Psychology SC Psychology GA 678RV UT WOS:000182881000004 PM 12790253 ER PT J AU Hiroi, N Kino, T Bassett, M Rainey, WE Phung, M Abu-Asab, M Fojo, T Briata, P Chrousos, GP Bornstein, SR AF Hiroi, N Kino, T Bassett, M Rainey, WE Phung, M Abu-Asab, M Fojo, T Briata, P Chrousos, GP Bornstein, SR TI Pituitary homeobox, factor 1, a novel transcription factor in the adrenal regulating steroid 11 beta-hydroxylase SO HORMONE AND METABOLIC RESEARCH LA English DT Article; Proceedings Paper CT 84th Annual Meeting of the Endocrine-Society CY JUN 19-22, 2002 CL SAN FRANCISCO, CALIFORNIA SP Endocrine Soc DE pituitary homeobox factor 1 Ptx1/Pitx1; 11 beta-hydroxylase; steroidogenic factor 1 (SF-1) ID CELL-SPECIFIC TRANSCRIPTION; FACTOR-I; PROOPIOMELANOCORTIN GENE; CUSHINGS-SYNDROME; PTX1; EXPRESSION; DOMAIN; SF-1; ACTIVATION; PHENOTYPES AB Pituitary homeobox 1 (Ptx1 / Pitx1) is a homeodomain-containing transcription factor present throughout pituitary development. Ptx1 /Pitx1 interacts with steroidogenic factor 1 (SF-1) in the regulation of pituitary gene expression. SF-1 also plays a critical role in the transcription of enzymes involved in adrenal steroidogenesis. Therefore, we analyzed the presence and role of Ptx1 / Pitx1 in human adrenal cortex. Both Ptx1/Pitx1 and SF-1 mRNA were expressed in the human adrenal gland, and immuno-electron microscopy demonstrated the presence of Ptx1/Pitx1 protein in the nucleus of adrenocortical cells. Computer analysis revealed the presence of Ptx1/Pitx1 signal sequences within the promoter region of human 11beta hydroxylase (hCYP11B1). To examine the role of Ptx1 /Pitx1 in the regulation of the genes, we prepared reporter constructs using the 5'-flanking DNA of the hCYP11B1 gene and transfected them into Y-1 mouse adrenocortical cells, HeLa and CV-1 cells. Ptx1/Pitx1 stimulation of hCYP11B1 reporter activity (3-fold over basal) in Y-1 cells was equal to that observed with SF-1. The hCYP11B1 promoter activity in Y-1 cells was not synergistically increased by co-transfection with both Ptx1/ Pitx1 and SF-1. Both basal and ACTH-stimulated hCYP11B1 reporter activities in Y-1 cells were increased by co-transfection with either Ptx1/Pitx1 or SF-1 expression vectors. In contrast, cotransfection with both Ptx1/Pitx1 and SF-1 synergistically increased hCYP11B1 promoter activity in HeLa and CV-1 cells (5fold and 20-fold over basal, respectively). In conclusion, this study represents the first demonstration for a role of Ptx1/Pitx1 in the regulation of transcription of enzymes involved in adrenal steroidogenesis. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Dusseldorf, Dept Endocrinol, D-4000 Dusseldorf, Germany. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75235 USA. Univ Calif San Diego, Howard Hughes Med Inst, Sch Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Howard Hughes Med Inst, Dept Med, La Jolla, CA 92093 USA. Ist Nazl Ric Canc, I-16132 Genoa, Italy. RP Hiroi, N (reprint author), Toho Univ, Sch Med, Dept Internal Med 1, Ota Ku, 6-11-1 Omorinishi, Tokyo 1430015, Japan. OI Abu-Asab, Mones/0000-0002-4047-1232 NR 28 TC 6 Z9 6 U1 0 U2 0 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 MAY PY 2003 VL 35 IS 5 BP 273 EP 278 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 713XT UT WOS:000184883800001 PM 12915995 ER PT J AU Rosenberg, SA Yang, JC Sherry, RM Hwu, P Topalian, SL Schwartzentruber, DJ Restifo, NP Haworth, LR Seipp, CA Freezer, LJ Morton, KE Mavroukakis, SA White, DE AF Rosenberg, SA Yang, JC Sherry, RM Hwu, P Topalian, SL Schwartzentruber, DJ Restifo, NP Haworth, LR Seipp, CA Freezer, LJ Morton, KE Mavroukakis, SA White, DE TI Inability to immunize patients with metastatic melanoma using plasmid DNA encoding the gp100 melanoma-melanocyte antigen SO HUMAN GENE THERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DIRECT GENE-TRANSFER; MUSCLE INVIVO; T-LYMPHOCYTES; MOUSE MUSCLE; VACCINE; EXPRESSION; PROTECTION; ENHANCEMENT; INJECTION AB Immunization with plasmid DNA represents a theoretically attractive method for increasing T cell responses against cancer antigens. We administered plasmid DNA encoding the gp100 melanoma-melanocyte differentiation antigen to 22 patients with metastatic melanoma and evaluated immunologic and clinical responses. Patients were randomized to receive plasmid DNA either intradermally (n = 10) or intramuscularly (n = 12). One patient (4.5%) exhibited a partial response of several subcentimeter cutaneous nodules. All other patients had progressive disease. Of 13 patients with cells available before and after immunization, no patient exhibited evidence of the development of anti-gp100 cell responses using in vitro boost assays. The same assays were capable of demonstrating immunologic precursors after immunization with fowl poxvirus encoding gp100 or with gp100 peptides. We were thus unable to demonstrate significant clinical or immunologic responses to plasmid DNA encoding the "self" nonmutated gp100 tumor antigen. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10,Room 2B42,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 39 TC 81 Z9 87 U1 0 U2 2 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 PY 2003 VL 14 IS 8 BP 709 EP 714 DI 10.1089/104303403765255110 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 681NV UT WOS:000183043000001 PM 12804135 ER PT J AU Drayna, D Coon, H Kim, UK Eisner, T Cromer, K Otterud, B Baird, L Peiffer, AP Leppert, M AF Drayna, D Coon, H Kim, UK Eisner, T Cromer, K Otterud, B Baird, L Peiffer, AP Leppert, M TI Genetic analysis of a complex trait in the Utah Genetic Reference Project: a major locus for PTC taste ability on chromosome 7q and a secondary locus on chromosome 16p SO HUMAN GENETICS LA English DT Article ID LINKAGE ANALYSIS; HUMAN GENOME; SENSITIVITY; INHERITANCE; PERCEPTION; RECEPTORS; FAMILY AB The ability to taste phenylthiocarbamide (PTC) shows complex inheritance in humans. We obtained a quantitative measure of PTC tasting ability in 267 members of 26 large three-generation families that were part of a set of CEPH families that had been used for genetic mapping. Significant bimodality was found for the distribution of age and gender adjusted scores (P<0.001), with estimated means of 3.16 (SD=1.80) and 9.26 (SD=1.54). Using the extensive genotyping available in these families from the genetic mapping efforts, we performed a genome scan by using 1324 markers with an average spacing of 4cM. Analyses were first carried out with a recessive genetic model that has traditionally been assumed for the trait, and a threshold score of 8.0 delineating tasters from nontasters. In this qualitative analysis, the maximum genomewide lod score was 4.74 at 246 cM on chromosome 7; 17 families showed segregation of the dichotomous PTC phenotype. No other lod scores were significant; the next highest score was on chromosome 10 (lod= 1.64 at 85 cM), followed by chromosome 3 (lod= 1.29 at 267 cM). Because PTC taste ability exhibited substantial quantitative variation. the quantitative trait was also analyzed by using a variance components approach in SOLAR. The maximum quantitative genome-wide lod score was 8.85 at 246 cM on chromosome 7. Evidence for other possible quantitative loci was found on chromosomes I (lod=2.31 at 344 cM) and 16 (lod=2.01 at 14 cM). A subsequent two-locus whole-genome scan conditional on the chromosome 7 quantitative trait locus identified the chromosome 16 locus (two-locus lod=3.33 at 14 cM). C1 Univ Utah, Med Ctr, Dept Psychiat, Utah Neurodev Genet Project, Salt Lake City, UT 84108 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. Univ Utah, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA. Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA. Univ Utah, Ctr Med, Dept Pediat, Salt Lake City, UT 84112 USA. RP Coon, H (reprint author), Univ Utah, Med Ctr, Dept Psychiat, Utah Neurodev Genet Project, 421 Wakara Way,Suite 143, Salt Lake City, UT 84108 USA. FU NCRR NIH HHS [M01-RR00064]; PHS HHS [Z01-000046-04] NR 35 TC 82 Z9 83 U1 4 U2 40 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 MAY PY 2003 VL 112 IS 5-6 BP 567 EP 572 DI 10.1007/s00439-003-0911-y PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 677EX UT WOS:000182794900009 PM 12624758 ER PT J AU Jiao, XD Munier, FL Schorderet, DF Zografos, L Smith, J Rubin, B Hejtmancik, JF AF Jiao, XD Munier, FL Schorderet, DF Zografos, L Smith, J Rubin, B Hejtmancik, JF TI Genetic linkage of Francois-Neetens fleck (mouchetee) corneal dystrophy to chromosome 2q35 SO HUMAN GENETICS LA English DT Article AB Francois-Neetens fleck (mouchetee) corneal dystrophy is an autosomal dominant corneal dystrophy characterized by scattered small white flecks occurring at all levels of the corneal stroma. We report linkage of the CFD locus to D2S2289 (Z(max)=4.46, theta=0), D2S325 (Z(max)=3.28, theta=0), D2S317 (Z(max)=3.1, theta=0), D2S143 (Z(max)=3.8, theta=0.03), and D2S2382 (Z(max)=5.0, theta=0) on chromosome 2q35. Multipoint analysis confirmed linkage to the region between D2S117 and D2S126 with a maximum multipoint lod score of 5.0 located midway between D2S2289 and D2S325. Analysis of CFD in these same families assuming a 90% penetrance increased the maximum lod score to 6.28 at D2S157. C1 NEI, OGCSB, NIH, Bethesda, MD 20892 USA. NEI, Ophthalm Genet & Clin Serv Branch, Bethesda, MD 20892 USA. Jules Gonin Eye Hosp, Oculogenet Unit, Lausanne, Switzerland. Div Med Genet, Lausanne, Switzerland. RP Hejtmancik, JF (reprint author), NEI, OGCSB, NIH, Bldg 10,Room 10B10,10 Ctr DR MSC 1860, Bethesda, MD 20892 USA. NR 10 TC 15 Z9 15 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 MAY PY 2003 VL 112 IS 5-6 BP 593 EP 599 DI 10.1007/s00439-002-0905-1 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 677EX UT WOS:000182794900012 PM 12607114 ER PT J AU Nemesure, B Jiao, XD He, QM Leske, MC Wu, SY Hennis, A Mendell, N Redman, J Garchon, HJ Agarwala, R Schaffer, AA Hejtmancik, F AF Nemesure, B Jiao, XD He, QM Leske, MC Wu, SY Hennis, A Mendell, N Redman, J Garchon, HJ Agarwala, R Schaffer, AA Hejtmancik, F CA Barbados Family Study Grp TI A genome-wide scan for primary open-angle glaucoma (POAG): the Barbados Family Study of Open-Angle Glaucoma SO HUMAN GENETICS LA English DT Article ID NAIL-PATELLA SYNDROME; BALTIMORE EYE SURVEY; GENETIC-LINKAGE; RISK-FACTORS; LOCUS; LOCALIZATION; PREVALENCE; MUTATIONS; REGION; MAPS AB Primary open-angle glaucoma (POAG) is characterized by damage to the optic nerve with associated loss of vision. Six named genetic loci have been identified as contributing to POAG susceptibility by genetic linkage analysis of mostly Caucasian families, and two of the six causative genes have been identified. The Barbados Family Study of Open-Angle Glaucoma (BFSG) was designed to evaluate the genetic component of POAG in a population of African descent. A genome-wide scan was performed on 1327 individuals from 146 families in Barbados, West Indies. Linkage results were based on models and parameter estimates derived from a segregation analysis of these families, and on model-free analyses. Two-point LOD scores >1.0 were identified on chromosomes 1, 2, 9, 10, 11, and 14, with increased multipoint LOD scores being found on chromosomes 2, 10, and 14. Fine mapping was subsequently carried out and indicated that POAG may be linked to intervals on chromosome 2q between D2S2188 and D2S2178 and chromosome 10p between D10S1477 and D10S601. Heterogeneity testing strongly supports linkage for glaucoma to at least one of these regions and suggests possible linkages to both. Although TIGR/myocilin and optineurin mutations have been shown to be causally linked to POAG in other populations, findings from this study do not support either of these as causative genes in an Afro-Caribbean population known to have relatively high rates of POAG. C1 SUNY Stony Brook, Sch Med, Dept Prevent Med, BFS Grp, Stony Brook, NY 11794 USA. NEI, Ophthalm Genet & Visual Funct Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Dept Appl Math & Stat, Coll Arts & Sci, Stony Brook, NY 11794 USA. Hop Necker Enfants Malad, INSERM, U25, F-75743 Paris 15, France. NIH, Informat Engn Branch, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Nemesure, B (reprint author), SUNY Stony Brook, Sch Med, Dept Prevent Med, BFS Grp, Stony Brook, NY 11794 USA. RI Schaffer, Alejandro/F-2902-2012 NR 41 TC 64 Z9 68 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 MAY PY 2003 VL 112 IS 5-6 BP 600 EP 609 DI 10.1007/s00439-003-0910-z PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 677EX UT WOS:000182794900013 PM 12616399 ER PT J AU Nenguke, T Aladjem, MI Gusella, JF Wexler, NS Arnheim, N AF Nenguke, T Aladjem, MI Gusella, JF Wexler, NS Arnheim, N CA Venezuela HD Project TI Candidate DNA replication initiation regions at human trinucleotide repeat disease loci SO HUMAN MOLECULAR GENETICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CPG ISLANDS; CTG REPEAT; SOMATIC INSTABILITY; HUMAN-CELLS; ORIGIN; EXPANSION; ORIENTATION; SITES; YEAST AB The positions of DNA replication initiation regions (IRs) at three human trinucleotide repeat (TNR) disease loci were examined in order to characterize the role played by IRs in explaining the known locus-specific variation in TNR instability levels. Using three different normal cell lines, candidate IRs were identified at the HD, SCA-7 and SBMA loci. At each locus the IR is less than 3.6 kb from the CAG/CTG repeat tract. Preliminary studies with a cell line homozygous for an HD disease mutation indicated no change in the position of the candidate IR in spite of the mutation. Comparison with experimental results from model systems suggests that a complex relationship may exist between instability and the proximity and/or orientation of the repeats with respect to an IR. C1 Univ So Calif, Program Mol & Computat Biol, Los Angeles, CA 90089 USA. NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Psychiat, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Hereditary Dis Fdn, New York, NY 10032 USA. RP Arnheim, N (reprint author), Univ So Calif, Program Mol & Computat Biol, Los Angeles, CA 90089 USA. RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 NR 48 TC 26 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2003 VL 12 IS 9 BP 1021 EP 1028 DI 10.1093/hmg/ddg111 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 674WQ UT WOS:000182660500007 PM 12700170 ER PT J AU Bakalov, VK Nelson, LM AF Bakalov, VK Nelson, LM TI Adrenal antibiotics detect asymptomatic auto-immune adrenal insufficiency in young women with, premature ovarian failure SO HUMAN REPRODUCTION LA English DT Letter C1 NICHHD, Sect Womens Hlth Res, NIH, Bethesda, MD 20892 USA. RP Nelson, LM (reprint author), NICHHD, Sect Womens Hlth Res, NIH, 10 Ctr Dr,MSC 1862,Bldg 10,Room 10N262, Bethesda, MD 20892 USA. NR 1 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 MAY PY 2003 VL 18 IS 5 BP 1133 EP 1133 DI 10.1093/humrep/deg196 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 680NK UT WOS:000182984100043 ER PT J AU Beutler, KT Masilamani, S Turban, S Nielsen, J Brooks, HL Ageloff, S Fenton, RA Packer, RK Knepper, MA AF Beutler, KT Masilamani, S Turban, S Nielsen, J Brooks, HL Ageloff, S Fenton, RA Packer, RK Knepper, MA TI Long-term regulation of ENaC expression in kidney by angiotensin II SO HYPERTENSION LA English DT Article DE receptors; angiotensin II; angiotensin antagonist; sodium channels; aldosterone ID THICK ASCENDING LIMB; RAT-KIDNEY; TRANSPORTER ABUNDANCE; MEDIATED REGULATION; NA+ TRANSPORTER; COLLECTING DUCT; A6 CELLS; ALDOSTERONE; LOCALIZATION; VASOPRESSIN AB We carried out semiquantitative immunoblotting of kidney to identify apical sodium transporter proteins whose abundances are regulated by angiotensin II. In NaCl-restricted rats (0.5 mEq Na/200 g BW/d), the type 1 angiotensin II receptor (AT(1) receptor) antagonist, candesartan, (1 mg/kg of body weight per day SC for 2 days) markedly decreased the abundance of the alpha subunit of the epithelial sodium channel (ENaC). This subunit has been shown to be rate-limiting for assembly of mature ENaC complexes. In addition, systemic infusion of angiotensin II increased alphaENaC protein abundance in rat kidney cortex. The decrease in alphaENaC protein abundance in response to AT(1) receptor blockade was associated with a fall in alphaENaC mRNA abundance (real-time RT-PCR), consistent with transcriptionally mediated regulation. The effect of AT(1) receptor blockade on alphaENaC expression was not blocked by spironolactone, suggesting a direct role of the AT(1) receptor in regulation of alphaENaC gene expression. Candesartan administration was also found to increase the abundances of the beta and gamma subunits. The increase in beta and gammaENaC protein abundance was not associated with a significant increase in the renal abundances of the corresponding mRNAs, suggesting a posttranscriptional mechanism. Immunocytochemistry confirmed the increase in beta and gammaENaC protein abundance and demonstrated candesartan-induced ENaC internalization in collecting duct cells. The results support the view that the angiotensin II receptor regulates ENaC abundance, consistent with a role for angiotensin II in regulation of collecting duct function. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21] NR 40 TC 106 Z9 106 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2003 VL 41 IS 5 BP 1143 EP 1150 DI 10.1161/01.HYP.0000066129.12106.E2 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 673NA UT WOS:000182586000026 PM 12682079 ER PT J AU Kanungo, T Mao, S AF Kanungo, T Mao, S TI Stochastic language models for style-directed layout analysis of document images SO IEEE TRANSACTIONS ON IMAGE PROCESSING LA English DT Article DE bilingual dictionaries; duration hidden Markov models; physical layout analysis; stochastic regular grammar; style-directed analysis ID PERFORMANCE EVALUATION; SEGMENTATION; METHODOLOGY; RECOGNITION; ALGORITHMS AB Image segmentation is an important component of any document image analysis system. While many segmentation algorithms exist in the literature, very few i) allow users to specify the physical style, and ii) incorporate user-specified style information into the algorithm's objective function that is to be minimized. We describe a segmentation algorithm that models a document's physical structure as a hierarchical structure where each node describes a region of the document using a stochastic regular grammar. The exact form of the hierarchy and the stochastic language is specified by the user, while the probabilities associated with the transitions are estimated from groundtruth data. We demonstrate the segmentation algorithm on images of bilingual dictionaries. C1 IBM Corp, Almaden Res Ctr, San Jose, CA 95120 USA. Natl Lib Med, Commun Engn Branch, Bethesda, MD 20894 USA. RP Kanungo, T (reprint author), IBM Corp, Almaden Res Ctr, 650 Harry Rd, San Jose, CA 95120 USA. NR 30 TC 12 Z9 12 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1057-7149 J9 IEEE T IMAGE PROCESS JI IEEE Trans. Image Process. PD MAY PY 2003 VL 12 IS 5 BP 583 EP 596 DI 10.1109/TIP.2003.811487 PG 14 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 688BK UT WOS:000183412200009 PM 18237934 ER PT J AU Fitzgerald, JR Reid, SD Ruotsalainen, E Tripp, TJ Liu, MY Cole, R Kuusela, P Schlievert, PM Jarvinen, A Musser, JM AF Fitzgerald, JR Reid, SD Ruotsalainen, E Tripp, TJ Liu, MY Cole, R Kuusela, P Schlievert, PM Jarvinen, A Musser, JM TI Genome diversification in Staphylococcus aureus: Molecular evolution of a highly variable chromosomal region encoding the staphylococcal exotoxin-like family of proteins SO INFECTION AND IMMUNITY LA English DT Article ID SEQUENCE; IDENTIFICATION AB Recent genomic studies have revealed extensive variation in natural populations of many pathogenic bacteria. However, the evolutionary processes which contribute to much of this variation remain unclear. A previous whole-genome DNA microarray study identified variation at a large chromosomal region (RD13) of Staphylococcus aureus which encodes a family of proteins with homology to staphylococcal and streptococcal superantigens, designated staphylococcal exotoxin-like (SET) proteins. In the present study, RD13 was found in all 63 S. aureus isolates of divergent clonal, geographic, and disease origins but contained a high level of variation in gene content in different strains. A central variable region which contained from 6 to 10 different set genes, depending on the strain, was identified, and DNA sequence analysis suggests that horizontal gene transfer and recombination have contributed to the diversification of RD13. Phylogenetic analysis based on the RD13 DNA sequence of 18 strains suggested that loss of various set genes has occurred independently several times, in separate lineages of pathogenic S. aureus, providing a model to explain the molecular variation of RD13 in extant strains. In spite of multiple episodes of set deletion, analysis of the ratio of silent substitutions in set genes to amino acid replacements in their products suggests that purifying selection (selective constraint) is acting to maintain SET function. Further, concurrent transcription in vitro of six of the seven set genes in strain COL was detected, indicating that the expression of set genes has been maintained in contemporary strains, and Western immunoblot analysis indicated that multiple SET proteins are expressed during the course of human infections. Overall, we have shown that the chromosomal region RD13 has diversified extensively through episodes of gene deletion and recombination. The coexpression of many set genes and the production of multiple SET proteins during human infection suggests an important role in host-pathogen interactions. C1 NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Univ Helsinki, Cent Hosp, Dept Med, Div Infect Dis, Helsinki, Finland. Univ Helsinki, Cent Hosp, Div Clin Microbiol, HUCH Lab Diagnost, Helsinki, Finland. Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. RP Musser, JM (reprint author), NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 20 TC 72 Z9 78 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2003 VL 71 IS 5 BP 2827 EP 2838 DI 10.1128/IAI.71.5.2827-2838.2003 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 672BT UT WOS:000182501500060 PM 12704157 ER PT J AU Lei, BF Liu, MY Meyers, EG Manning, HM Nagiec, MJ Musser, JM AF Lei, BF Liu, MY Meyers, EG Manning, HM Nagiec, MJ Musser, JM TI Histidine and aspartic acid residues important for immunoglobulin G endopeptidase activity of the group A Streptococcus opsonophagocytosis-inhibiting mac protein SO INFECTION AND IMMUNITY LA English DT Article ID GROUP-A STREPTOCOCCUS; CYSTEINE PROTEASE; PAPAIN AB The secreted Mae protein made by serotype M1 group A Streptococcus (GAS) (designated Mac(5005)) inhibits opsonophagocytosis and killing of GAS by human polymorphonuclear neutrophils. This protein also has cysteine endopeptidase activity against human immunoglobulin G (IgG). Site-directed mutagenesis was used to identify histidine and aspartic acid residues important for Mac IgG endopeptidase activity. Replacement of His262 with Ala abolished Mac5005 IgG endopeptidase activity. Asp284Ala and Asp286Ala mutant proteins had compromised enzymatic activity, whereas 21 other Asp-to-Ala mutant proteins cleaved human IgG at the apparent wild-type level. The results suggest that His262 is an active-site residue and that Asp284 and Asp286 are important for the enzymatic activity or structure of Mac protein. These Mac mutants provide new information about structure-activity relationships in this protein and will assist study of the mechanism of inhibition of opsonophagocytosis and killing of GAS by Mac. C1 NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Musser, JM (reprint author), NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 10 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2003 VL 71 IS 5 BP 2881 EP 2884 DI 10.1128/IAI.71.5.2881-2884.2003 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 672BT UT WOS:000182501500065 PM 12704162 ER PT J AU Orwin, PM Fitzgerald, JR Leung, DYM Gutierrez, JA Bohach, GA Schlievert, PM AF Orwin, PM Fitzgerald, JR Leung, DYM Gutierrez, JA Bohach, GA Schlievert, PM TI Characterization of Staphylococcus aureus enterotoxin L SO INFECTION AND IMMUNITY LA English DT Article ID TOXIC-SHOCK-SYNDROME; CRYSTAL-STRUCTURE; SUPERANTIGEN; IDENTIFICATION; EXOTOXINS; SITE AB Staphylococcus aureus causes a wide variety of diseases. Major virulence factors of this organism include enterotoxins (SEs) that cause both food poisoning and toxic shock syndrome. Recently, a novel SE, tentatively designated SEL, was identified in a pathogenicity island from a bovine mastitis isolate. The toxin had a molecular weight of 26,000 and an isoelectric point of 8.5. Recombinant SEL shared many biological activities with SEs, including superantigenicity, pyrogenicity, enhancement of endotoxin shock, and lethality in rabbits when administered in subcutaneous miniosmotic pumps, but the protein lacked emetic activity. T cells bearing the T-cell receptor P chain variable regions 5.1, 5.2, 6.7, 16, and 22 were significantly stimulated by recombinant SEL. C1 Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Natl Jewish Med & Res Ctr, Dept Pediat, Denver, CO 80206 USA. Univ Idaho, Dept Microbiol Mol Biol & Biochem, Moscow, ID 83844 USA. RP Schlievert, PM (reprint author), Univ Minnesota, Sch Med, Dept Microbiol, Mayo Mail Code 196,420 Delaware St SE, Minneapolis, MN 55455 USA. FU NCRR NIH HHS [P20 RR015587, P51 RR000166, RR00166, RR15587]; NHLBI NIH HHS [HL36577, HL37260, P01 HL036577, R37 HL037260]; NIAID NIH HHS [AI2840, R01 AI022159, R37 AI022159, T32 AI007421]; NIAMS NIH HHS [AR41256, R01 AR041256]; PHS HHS [159] NR 15 TC 65 Z9 68 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 MAY PY 2003 VL 71 IS 5 BP 2916 EP 2919 DI 10.1128/IAI.71.5.2916-2919.2003 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 672BT UT WOS:000182501500072 PM 12704169 ER PT J AU Stephens, GL Ashwell, JD Ignatowicz, L AF Stephens, GL Ashwell, JD Ignatowicz, L TI Mutually antagonistic signals regulate selection of the T cell repertoire SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE knockout; lymphocyte development; T lymphocyte; thymus; transgenic ID MHC CLASS-II; POSITIVE SELECTION; THYMOCYTE SELECTION; GLUCOCORTICOID RECEPTOR; SELF-PEPTIDES; NEGATIVE SELECTION; INVARIANT CHAIN; THYMUS; MICE; EXPRESSION AB The sensitivity of T cells to agonist-induced death during development contrasts with their proliferative responses after agonist challenge in the periphery. The means by which TCR engagement results in these distinct outcomes is incompletely understood. It has been previously hypothesized that glucocorticoids (GC) modulate the threshold for thymocyte activation by blunting the consequences of TCR engagement. In support of this possibility, inhibition of GC production in fetal thymic organ culture was shown to result in CD4(+)CD8(+) thymocyte apoptosis. This was dependent upon MHC diversity, implying that endogenous GC might regulate antigen-specific selection. Similarly, mice expressing reduced GC receptor (GR) levels due to the presence of an antisense transgene have fewer CD4(+)CD8(+) thymocytes, which was due to an impaired transition from CD4(-)CD8(-) precursors and increased apoptosis. Here we ask how manipulating peptide diversity in the context of reduced GC signaling might affect T cell development and function. In mice with impaired GR expression there was a rescue of thymocyte cellularity and proportions as the diversity of peptides presented by self-MHC was reduced. Furthermore, whereas more CD4(+) T cells survived the selection process in mice expressing single-peptide-MHC class II complexes and reduced GR levels, these cells largely failed to recognize the same MHC molecules bound with foreign peptides. Together, these results support a role for endogenous GC in balancing TCR-mediated signals during thymic selection. C1 Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Ignatowicz, L (reprint author), Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. NR 42 TC 9 Z9 9 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 MAY PY 2003 VL 15 IS 5 BP 623 EP 632 DI 10.1093/intimm.dxg056 PG 10 WC Immunology SC Immunology GA 671RH UT WOS:000182477500007 PM 12697662 ER PT J AU Dennehy, KM Kerstan, A Bischof, A Park, JH Na, SY Hunig, T AF Dennehy, KM Kerstan, A Bischof, A Park, JH Na, SY Hunig, T TI Mitogenic signals through CD28 activate the protein kinase C theta-NF-kappa B pathway in primary peripheral T cells SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD28; co-stimulation; NF-kappa B; protein kinase C theta ID ANTIGEN RECEPTOR; TYROSINE PHOSPHORYLATION; IMMUNOLOGICAL SYNAPSE; MONOCLONAL-ANTIBODY; PKC-THETA; RESPONSE ELEMENT; IL-2 PROMOTER; TCR LIGATION; IN-VITRO; LYMPHOCYTES AB Mitogenic anti-CD28 antibody stimulates all peripheral T cells to proliferate in the absence of TCR ligation, providing an exception to the two-signal requirement of T cell responses. This antibody preferentially recognizes a mobilized signaling-competent form of CD28, normally induced following TCR ligation, thus providing a unique non-physiological tool to dissect CD28-specific signals leading to T cell proliferation. The protein kinase C (PKC)theta-NF-kappaB pathway has recently been shown to integrate TCR- and CD28-derived signals in co-stimulation. We now demonstrate that this pathway is activated by mitogenic anti-CD28 antibody stimulation. In contrast to conventional anti-CD28 antibody, mitogenic anti-CD28 antibody induced activation of phospholipase Cgamma and Ca2+ flux in peripheral rat T cells despite no or low levels of inducible tyrosine phosphorylation of TCRzeta chain, TCRzeta-associated protein of 70 kDa (ZAP-70) or linker for activation of T cells (LAT)-critical components of the TCR signaling machinery. Nevertheless, PKCtheta kinase activity in vitro was increased following mitogenic anti-CD28 antibody stimulation, as was membrane association of both PKCtheta and Bcl10. As downstream targets of PKCtheta activation, NF-kappaB components translocated to the nucleus at levels comparable to those after TCR-CD28 co-stimulation. NF-kappaB translocation was diminished by PKCtheta inhibition, as was induction of the NF-kappaB/AP-1 responsive activation marker CD69. We propose that co-stimulation is a sequential process in which appropriate TCR engagement is required to mobilize CD28 into a signaling-competent form which then activates the PKCtheta-NF-kappaB pathway necessary for IL-2 production and proliferation. C1 Univ Wurzburg, Inst Virol & Immunbiol, D-97078 Wurzburg, Germany. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Hunig, T (reprint author), Univ Wurzburg, Inst Virol & Immunbiol, D-97078 Wurzburg, Germany. RI Park, Jung Hyun /B-5712-2015 OI Park, Jung Hyun /0000-0002-9547-9055 NR 47 TC 29 Z9 30 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 MAY PY 2003 VL 15 IS 5 BP 655 EP 663 DI 10.1093/intimm/dxg063 PG 9 WC Immunology SC Immunology GA 671RH UT WOS:000182477500010 PM 12697665 ER PT J AU Brown, LM McNatt, PS Cooper, GD AF Brown, LM McNatt, PS Cooper, GD TI Ingroup romantic preferences among Jewish and non-Jewish White undergraduates SO INTERNATIONAL JOURNAL OF INTERCULTURAL RELATIONS LA English DT Article ID COLLECTIVE SELF-ESTEEM; SOCIAL IDENTITY; IN-GROUP; ETHNOCENTRISM; STEREOTYPES; PREJUDICE; BIAS; AMERICAN; IDENTIFICATION; SIMILARITY AB We hypothesized that ingroup. romantic preferences positively relate to group ties (e.g., ingroup identity and approval from friends and family) among ethnic minority groups particularly compared to ethnic majority groups. In Study. 1, Jewish undergraduates completed items regarding ingroup identity and ratings of Jewish and non-Jewish partners. Students rated ingroup members more positively than outgroup members, ratings positively correlated with identity, and identity positively predicted ingroup preferences while similarity did not. Study 2 included both White Jewish and White non-Jewish students. Social network approval and collectivism positively predicted preferences among Jewish students, while social network approval and similarity positively predicted preferences among non-Jewish students. We discuss ingroup identity's differential role in attraction between ethnic minority group members and ethnic majority group members. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA. Univ Florida, Dept Psychol, Gainesville, FL 32610 USA. RP Brown, LM (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, POB 100165, Gainesville, FL 32610 USA. NR 60 TC 4 Z9 4 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0147-1767 J9 INT J INTERCULT REL JI Int. J. Intercult. Relat. PD MAY PY 2003 VL 27 IS 3 BP 335 EP 354 DI 10.1016/S0147-1767(03)00015-4 PG 20 WC Psychology, Social; Social Sciences, Interdisciplinary; Sociology SC Psychology; Social Sciences - Other Topics; Sociology GA 683QZ UT WOS:000183162100004 ER PT J AU Bar-Gal, GK Ducos, P Horwitz, LK AF Bar-Gal, GK Ducos, P Horwitz, LK TI The application of ancient DNA analysis to identify Neolithic caprinae: A case study from the site of Hatoula, Israel SO INTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY LA English DT Article DE ancient DNA; Ovis; Capra; domestication; southern Levant ID ENZYMATIC AMPLIFICATION; DOMESTIC SHEEP; CAPRA-AEGAGRUS; GOATS; PURIFICATION; CONFIDENCE; EXTRACTION; RECOVERY; HIRCUS; BONES AB The evidence for wild sheep (Ovis orientalis) in archaeological sites from the southern Levant is examined through the application of ancient DNA analysis to specimens from the Pre-Pottery Neolithic A (8300-7500 uncal. BC) site of Hatoula, Israel. The results indicate that at least one of the bones from this site, previously identified as sheep, is in fact goat. To date this is the earliest faunal sample to have yielded DNA in the region. This study highlights the problems in applying morphological criteria to distinguish between caprine species, and illustrates how ancient DNA analysis can serve as a powerful tool in resolving questions of species attribution. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Kuvin Ctr Study Infect & Trop Dis, IL-91010 Jerusalem, Israel. Hebrew Univ Jerusalem, Dept Evolut Systemat & Ecol, Fac Life Sci, Jerusalem, Israel. RP Bar-Gal, GK (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. NR 53 TC 16 Z9 16 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1047-482X J9 INT J OSTEOARCHAEOL JI Int. J. Osteoarchaeol. PD MAY-JUN PY 2003 VL 13 IS 3 BP 120 EP 131 DI 10.1002/oa.666 PG 12 WC Anthropology; Archaeology SC Anthropology; Archaeology GA 691RE UT WOS:000183618600002 ER PT J AU Swezey, RR Aldridge, DE LeValley, SE Crowell, JA Hara, Y Green, CE AF Swezey, RR Aldridge, DE LeValley, SE Crowell, JA Hara, Y Green, CE TI Absorption, tissue distribution and elimination of 4-[H-3]-epigallocatechin gallate in beagle dogs SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE beagle dogs; EGCG; epigallocatechin gallate; tea catechins; tissue distribution ID GREEN TEA POLYPHENOLS; (-)-EPIGALLOCATECHIN GALLATE; ORAL ABSORPTION; METABOLIC-FATE; RATS; CATECHINS; MICE; INHIBITION; CELLS; IDENTIFICATION AB Polyphenols found in tea are potent antioxidants and have inhibitory activity against tumorigenicity. The purpose of the described study was to assess the absorption, tissue distribution, and elimination of epigallocatechin gallate (EGCG), the principal catechin found in green tea, in a nonrodent species. 4-[H-3]-EGCG was administered to beagle dogs by intravenous (IV) and oral routes. Following IV administration of 25 mg/kg, radioactivity in the bloodstream resided predominantly in the plasma. Distribution occurred during the first hour, and the plasma levels of total radioactivity declined with a mean half-life of approximately 7 hours. The apparent volume of distribution (0.65 l/kg) indicated wide distribution, and the total body clearance (1.01 ml/min-kg) was low. A subsequent single oral dose (250 mg/kg) was rapidly absorbed, with peak plasma levels at about 1 hour after administration, followed by elimination with a mean half-life of 8.61 hours. The mean area under the curve (AUC) for total radioactivity was approximately 20% of the value following IV administration (corrected for dose administered). Excretion of radioactivity in the feces predominated over urinary excretion following both IV and oral administration of [H-3]-EGCG. Tissue distribution was determined 1 hour after an IV dose (25 mg/kg) administered after 27 days of oral treatment with EGCG (250 mg/kg/day) to mimic chronic consumption of tea. Radioactivity was distributed to a variety of epithelial tissues; the highest concentrations were observed in the liver and gastrointestinal tract tissues. Repeat dose oral administration of EGCG resulted in significantly lower blood radioactivity compared to the concentration following a single dose. These results are generally in accord with previous studies in rodents and indicate that, after oral administration, EGCG (as parent compound and metabolites) is widely distributed to tissues where it can exert a chemopreventive effect. C1 SRI Int, Dept Drug Metab & Pharmacokinet, Menlo Pk, CA 94025 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Mitsui Norm Co Ltd, Tokyo Food Techno Co Ltd, Miyabara, Japan. RP Swezey, RR (reprint author), SRI Int, Dept Drug Metab & Pharmacokinet, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA. NR 30 TC 26 Z9 30 U1 1 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY-JUN PY 2003 VL 22 IS 3 BP 187 EP 193 DI 10.1080/10915810390201154 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 691NE UT WOS:000183611700005 PM 12851151 ER PT J AU Sparreboom, A Karlsson, MO AF Sparreboom, A Karlsson, MO TI Introduction: Role of modeling and simulation in clinical development of anticancer agents SO INVESTIGATIONAL NEW DRUGS LA English DT Editorial Material C1 NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. RP Sparreboom, A (reprint author), NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. RI Sparreboom, Alex/B-3247-2008 NR 8 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD MAY PY 2003 VL 21 IS 2 BP 139 EP 140 DI 10.1023/A:1023573610970 PG 2 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 672LG UT WOS:000182521600001 ER PT J AU Zhao, XJ Pearson, KE Stephan, DA Russell, P AF Zhao, XJ Pearson, KE Stephan, DA Russell, P TI Effects of prostaglandin analogues on human ciliary muscle and trabecular meshwork cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MELANIN-CONCENTRATING HORMONE; FIBRINOGEN-LIKE PROTEIN; OPEN-ANGLE GLAUCOMA; AQUEOUS-HUMOR; PROTHROMBINASE ACTIVITY; T-LYMPHOCYTES; GROWTH; MONKEY; GENE; MICE AB PURPOSE. To determine the effects of prostaglandin F-2alpha analogues on gene expression of human ciliary muscle (HCM) and trabecular meshwork (HTM) cells. METHODS. Cultures of HCM and HTM cells were established from five different donors treated for 9 days with 10 mug/mL of either latanoprost (free acid) or prostaglandin F,, ethanolamide and compared with control cells. The mRNA from the cells of the five individual donors was pooled and analyzed by using gene microarrays. Gene expression changes were confirmed by either real-time PCR or relative quantitative PCR. RESULTS. Approximately 12 genes showed a twofold or greater change in expression under experimental conditions. Four of these may alter outflow. Aquaporin-1 and versican were downregulated in the HCM, whereas IGF1 and fibroleukin were upregulated in HTM. Expression levels of TNFSF10 and promelanosome-concentrating hormone also increased in the treated HTM cells. The mRNA levels for the prostaglandin FP receptor were downregulated in the ciliary muscle cells. Optineurin and alphaB-crystallin levels remained unchanged, but myocilin in the HTM cells was decreased in some samples. CONCLUSIONS. Both analogues changed gene expression similarly in either HCM or HTM cells, but the changes appeared to be cell specific, perhaps indicating that other transcription factors are influential. Outflow of aqueous humor may be increased by the prostaglandin analogues by alterations in the extracellular matrix. Other changes may influence cellular metabolism, such as the increases in IGF1, tumor necrosis factor superfamily-10 and promelanosome-concentrating hormone. C1 NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. RP Russell, P (reprint author), 6 Ctr Dr,MSC 2735, Bethesda, MD 20892 USA. NR 35 TC 24 Z9 26 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 BP 1945 EP 1952 DI 10.1167/iovs.02-0920 PG 8 WC Ophthalmology SC Ophthalmology GA 672CQ UT WOS:000182503700023 PM 12714628 ER PT J AU Momma, Y Nagineni, CN Chin, MS Srinivasan, K Detrick, B Hooks, JJ AF Momma, Y Nagineni, CN Chin, MS Srinivasan, K Detrick, B Hooks, JJ TI Differential expression of chemokines by human retinal pigment epithelial cells infected with cytomegalovirus SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; IMMUNE-DEFICIENCY-SYNDROME; FAS LIGAND EXPRESSION; GENE-EXPRESSION; IMMUNODEFICIENCY SYNDROME; OCULAR MANIFESTATIONS; INTERLEUKIN-8 GENE; ENDOTHELIAL-CELLS; CC-CHEMOKINES; UP-REGULATION AB PURPOSE. To evaluate the effects of human cytomegalovirus (HCMV) infection on chemokine gene expression and secretion by human retinal pigment epithelial (HRPE) cell cultures. METHODS. HRPE cells were infected with HCMV (strain AD 169) at an MOI of 5. Culture supernatants, collected at various postinoculation days, were used for the analyses of chemokines by ELISA. The steady state levels of chemokine and chemokine receptor mRNA were analyzed by RT-PCR. Effects of interferon and MCP-1 on HCMV replication in HRPE cells were evaluated by plaque assays. RESULTS. HRPE cells infected with HCMV exhibited characteristic cytopathic effects. The reduction in the levels of monocyte chemotactic protein (MCP)-1 and -3 mRNA in HCMV-infected HRPE cells was observed in comparison to uninfected HRPE cells. In contrast, HCMV infection enhanced IL-8 mRNA levels, whereas regulated on activation normal T-cell expressed and secreted (RANTES) mRNA was not detectable in either control or infected HRPE cells. A significant decrease in MCP-1 (P < 0.01) and MCP-3 (P < 0.05), but a significant increase in IL-8 (P < 0.05), protein secretion was observed. Expression of the chemokine receptors CCR2, specific for MCP-1, and CXCR1 and CXCR2, specific for IL-8, were not altered by HCMV infection. Treatment of HRPE cultures with MCP-1 had no significant effect on HCMV replication in HRPE cells. CONCLUSIONS. HCMV infection in HRPE cells resulted in the modulation of MCP-1, MCP-3, and IL-8. Because chemokines facilitate the activation of leukocytes and their migration to the sites of inflammation, the modulation of chemokine production by the virus suggests a role for chemokines in immune evasion and/or immunopathogenesis of CMV retinitis. C1 NEI, Immunol & Virol Sect, Immunol Lab, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Hooks, JJ (reprint author), NEI, Immunol & Virol Sect, Immunol Lab, Bldg 10,Room 6N 228, Bethesda, MD 20892 USA. NR 62 TC 25 Z9 25 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 BP 2026 EP 2033 DI 10.1167/iovs.02-0980 PG 8 WC Ophthalmology SC Ophthalmology GA 672CQ UT WOS:000182503700035 PM 12714640 ER PT J AU Cannon, JP Fiscella, R Pattharachayakul, S Garey, KW De Alba, F Piscitelli, S Edward, DP Danziger, LH AF Cannon, JP Fiscella, R Pattharachayakul, S Garey, KW De Alba, F Piscitelli, S Edward, DP Danziger, LH TI Comparative toxicity and concentrations of intravitreal amphotericin B formulations in a rabbit model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOPHTHALMITIS AB PURPOSE. To determine the toxicity of various doses of intravitreal amphotericin B deoxycholate, amphotericin B lipid complex (ABLC), and liposomal amphotericin B (L-AmB). METHODS. Fifty-two rabbits were divided into two treatment groups (groups A and B). Thirteen treatments were administered intravitreally to the 104 rabbit eyes. Treatments included a control plus 10, 20, 30, and 50 mug amphotericin B deoxycholate, ABLC, and L-AmB. Eye examinations were performed before injection and on day 11 for group A and on day 18 for group B. At death, on days 13 and 21 in groups A and B, respectively, vitreous humor was aspirated and concentrations of amphotericin B were determined by high performance liquid chromatography (HPLC), followed by enucleation for histologic studies. RESULTS. Significantly more eyes treated with ABLC showed development of vitreal opacities than developed in eyes treated with amphotericin B deoxycholate or L-AmB (P < 0.05). Vitreal band formation was significantly higher in ABLC-treated eyes than in those treated with L-AmB, (P = 0.039). Vitreal inflammation was greater in eyes treated with L-AmB (75%), amphotericin B deoxycholate (78%), and ABLC (91%) than with the control (50%; P = 0.08). Retinal ganglion cell loss was greater in eyes treated with amphotericin B deoxycholate (81%), L-AmB (91%), and ABLC (97%) than with the control (38%; P = 0.003). Amphotericin B concentrations were measurable for all doses of the three formulations. CONCLUSIONS. Based on histologic data, increasing doses of an three agents appear to be associated with increasing toxicity, however based on ophthalmologic data, L-AmB appears to be less toxic than. either amphotericin B deoxycholate or ABLC. C1 Univ Illinois, Coll Pharm, Dept Pharm Practice, Chicago, IL 60612 USA. Hines VA Hosp, Dept Pharm, Hines, IL USA. Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. Prince Songkla Univ, Dept Clin Pharm, Songkhla, Thailand. Univ Houston, Dept Clin Sci & Adm, Coll Pharm, Houston, TX USA. Loyola Univ, Med Ctr, Dept Ophthalmol, Maywood, IL 60153 USA. NIH, Bethesda, MD 20892 USA. RP Danziger, LH (reprint author), Univ Illinois, Coll Pharm, Dept Pharm Practice, 833 S Wood St,M-C 886, Chicago, IL 60612 USA. OI Garey, Kevin/0000-0003-2063-7503 FU NEI NIH HHS [EY001792] NR 12 TC 34 Z9 42 U1 2 U2 3 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 MAY PY 2003 VL 44 IS 5 BP 2112 EP 2117 DI 10.1167/iovs.02-1020 PG 6 WC Ophthalmology SC Ophthalmology GA 672CQ UT WOS:000182503700045 PM 12714650 ER PT J AU Al-Khatib, SQ Li, Z Silver, P Shen, D Sen, HN Ursea, R Srivastava, SK Buggage, RR Chan, CC Nussenblatt, RB AF Al-Khatib, SQ Li, Z Silver, P Shen, D Sen, HN Ursea, R Srivastava, SK Buggage, RR Chan, CC Nussenblatt, RB TI Intravitreal injection of anti-interleukin-2 receptor in experimental autoimmune uveoretinitis (EAU) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 724 BP U216 EP U216 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800700 ER PT J AU Alam, S Jaworski, C Gordiyenko, N Rodriguez, IR AF Alam, S Jaworski, C Gordiyenko, N Rodriguez, IR TI Establishment of stably transfected human RPE cell lines over-expressing oxysterol binding proteins SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 385 BP U75 EP U75 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800361 ER PT J AU Amaral, J Becerra, P AF Amaral, J Becerra, P TI Diffusion of pigment epithelium derived factor (PEDF) through the outer blood retinal barrier SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 391 BP U76 EP U76 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800367 ER PT J AU Ambasudhan, R Wang, XF Jablonski, MM Fariss, RN Wong, PW Sieving, PA Ayyagari, R AF Ambasudhan, R Wang, XF Jablonski, MM Fariss, RN Wong, PW Sieving, PA Ayyagari, R TI Subcellular localization of ELOVL4 gene product in cultured cells and mammalian retinae and intracellular misrouting of its mutant SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. UTHSC, Retinal Degenerat Res Ctr, Memphis, TN USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Alberta, Edmonton, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 5096 BP U710 EP U710 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002557 ER PT J AU Aryankalayi, MJ Carper, DA Brown, K Stephan, DA Wawrousek, EF AF Aryankalayi, MJ Carper, DA Brown, K Stephan, DA Wawrousek, EF TI Microarray analysis of alphaA and alphaB-crystallin knockout mouse lenses SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1245 BP U325 EP U325 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801195 ER PT J AU Baer, SM Nelson, R Zela, D AF Baer, SM Nelson, R Zela, D TI A computational study of background-induced flicker enhancement in cat retinal horizontal cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Arizona State Univ, Tempe, AZ USA. NINDS, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4175 BP U458 EP U458 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001639 ER PT J AU Baffi, JZ Byrnes, GA Wolfe, JD Ponce, L Cousins, SW Csaky, KG AF Baffi, JZ Byrnes, GA Wolfe, JD Ponce, L Cousins, SW Csaky, KG TI Adult hematopoetic stem cells (HSC) provide functional hemangioblast activity during choroidal neovascularization (CNV) in mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Dept Ophthalmol, Bethesda, MD 20892 USA. Bascom Palmer Eye Inst, Miami, FL 33136 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1825 BP U422 EP U422 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801776 ER PT J AU Bai, F Xi, J Fleming, TP Wawrousek, EF Andley, UP AF Bai, F Xi, J Fleming, TP Wawrousek, EF Andley, UP TI Loss of p53-dependent checkpoint function in lens epithelial cells derived from alpha B-crystallin knockout mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Washington Univ, Sch Med, St Louis, MO 63130 USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1246 BP U325 EP U325 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801198 ER PT J AU Bettelheim, FA Neal, R Zigler, JS AF Bettelheim, FA Neal, R Zigler, JS TI Dynamic light scattering studies and proteomic analysis of the topographic distribution of components of human vitreous SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 431 BP U84 EP U84 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800407 ER PT J AU Bressler, S Bressler, NM Chandra, SR Chew, EY Clemons, TE Klein, R Seddon, JM AF Bressler, S Bressler, NM Chandra, SR Chew, EY Clemons, TE Klein, R Seddon, JM CA AREDS Res Grp TI Mortality in the Age-Related Eye Disease Study: Associations with age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04-09, 2003 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol C1 Wilmer Eye Inst, Baltimore, MD USA. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. NEI, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2056 BP U342 EP U342 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801999 ER PT J AU Brooks, BP Dagenais, SL Caulder, MS Glover, TW AF Brooks, BP Dagenais, SL Caulder, MS Glover, TW TI Characterization of a mouse model of distichiasis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NIH, NHGRI, Bethesda, MD USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4525 BP U543 EP U543 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001983 ER PT J AU Campos, MM Fariss, RN Katz, ML Robison, WG AF Campos, MM Fariss, RN Katz, ML Robison, WG TI Lipofuscin accumulation and retinal microangiopathies associated with diabetes and the oxidative stress of vitamin E deficiency SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Bethesda, MD 20892 USA. Univ Missouri, Sch Med, Columbia, MO 65211 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 455 BP U91 EP U91 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800431 ER PT J AU Caruso, RC Lopez, P Ayres, LM Kaiser-Kupfer, MI AF Caruso, RC Lopez, P Ayres, LM Kaiser-Kupfer, MI TI Fast and slow oscillations of the electro-oculogram in Stargardt's disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 5110 BP U712 EP U712 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002570 ER PT J AU Castano, ME Csaky, KG Cousins, SW AF Castano, ME Csaky, KG Cousins, SW TI Angiotensin II receptor subtypes expression in human retinal pigment epithelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Bascom Palmer Eye Inst, Miami, FL 33136 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2282 BP U392 EP U392 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802208 ER PT J AU Chan, CC Smith, JA Shen, D Ursea, RA Grossniklaus, HE AF Chan, CC Smith, JA Shen, D Ursea, RA Grossniklaus, HE TI Molecular signatures of Helicobacter pylori (H. pylori) in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Emory Univ, Ctr Eye, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2437 BP U423 EP U423 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802364 ER PT J AU Chen, J Vistica, BP Ham, DI Fariss, RN Wawrousek, EF Gery, I AF Chen, J Vistica, BP Ham, DI Fariss, RN Wawrousek, EF Gery, I TI Antigenic re-activation of murine Th1 lymphocytes enhances their capacity to induce ocular inflammation, but reduces their expression of the chemokine receptor CXCR3 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 995 BP U274 EP U274 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800971 ER PT J AU Chen, S Chu, M Fariss, RN Kutty, RK Wiggert, B AF Chen, S Chu, M Fariss, RN Kutty, RK Wiggert, B TI Neuronal differentiation of RPE cells, but not Y-79 or PC-12 cells, is induced by fenretinide and results in a time-dependent increase in Hsp70 expression SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 382 BP U75 EP U75 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800357 ER PT J AU Chew, EY Ferris, FL de Monasterio, F Thompson, DJ Kim, J Csaky, CG Woods, M Khachik, F Bone, R Landrum, J AF Chew, EY Ferris, FL de Monasterio, F Thompson, DJ Kim, J Csaky, CG Woods, M Khachik, F Bone, R Landrum, J TI Dose ranging study of lutein supplementation in persons over age 60 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Univ Maryland, Baltimore, MD 21201 USA. Florida Int Univ, Miami, FL 33199 USA. RI Khachik, Frederick/C-5055-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 968 BP U267 EP U267 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800944 ER PT J AU Chin, MS Nagineni, CN Caruso, RC Agarwal, N Detrick, B Hooks, JJ AF Chin, MS Nagineni, CN Caruso, RC Agarwal, N Detrick, B Hooks, JJ TI Autoantibodies in a patient with cone-rod degeneration triggers death of retinal ganglion (RGC-5) cells by complement mediated lysis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. Univ N Texas, Ctr Hlth Sci, Ft Worth, TX USA. Johns Hopkins Med Inst, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4613 BP U609 EP U609 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002072 ER PT J AU Christen, WG Manson, JE Glynn, RJ Gaziano, JM Chew, EY Buring, JE Hennekens, CH AF Christen, WG Manson, JE Glynn, RJ Gaziano, JM Chew, EY Buring, JE Hennekens, CH TI Age-related maculopathy (ARM) in a randomized trial of beta-carotene in men SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NEI, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Miami, FL 33152 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2111 BP U353 EP U353 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802036 ER PT J AU Clemons, TE Friberg, TR Kurinij, N Sperduto, RD AF Clemons, TE Friberg, TR Kurinij, N Sperduto, RD CA AREDS Res Grp TI Mortality in the age-related eye disease study: Associations with lens opacity and cataract surgery SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 EMMES Corp, AREDS Res Grp, Rockville, MD USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4242 BP U477 EP U477 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001703 ER PT J AU Coblentz, FE Li, A Moreira, EF Fariss, RN Rodriguez, IR AF Coblentz, FE Li, A Moreira, EF Fariss, RN Rodriguez, IR TI Intracellular localization of oxysterol binding proteins (OSBPs) in cultured human RPE cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. Informax, Bethesda, MD USA. Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1636 BP U384 EP U384 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801586 ER PT J AU Connaughton, VP Graham, D Nelson, R AF Connaughton, VP Graham, D Nelson, R TI Morphological identification of second and third order neurons in the zebrafish retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 American Univ, Dept Biol, Washington, DC 20016 USA. NINDS, Basic Neurosci Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4134 BP U449 EP U449 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001597 ER PT J AU Crouch, RK Znoiko, S Kono, M Rohrer, B Goletz, P Gresh, J Redmond, TM Ma, JX AF Crouch, RK Znoiko, S Kono, M Rohrer, B Goletz, P Gresh, J Redmond, TM Ma, JX TI Can a delivery of 11-cis retinal to the RPE65 KO mouse restore normal rod and cone function? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Med Univ S Carolina, Charleston, SC 29425 USA. NEI, Bethesda, MD 20892 USA. RI Znoyko, Sergey/E-1294-2013 OI Znoyko, Sergey/0000-0003-1265-328X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3506 BP U265 EP U265 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000969 ER PT J AU Cui, W Tomarev, SI Chepelinsky, AB Duncan, MK AF Cui, W Tomarev, SI Chepelinsky, AB Duncan, MK TI Mafs, Pax6 and Prox1 cooperate to regulate bB1 crystallin gene expression in developing lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1076 BP U290 EP U290 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801026 ER PT J AU Cusik, M Charles, MK SanGiovanni, JP Agron, E Newsome, S Ferris, FL Charles, ST AF Cusik, M Charles, MK SanGiovanni, JP Agron, E Newsome, S Ferris, FL Charles, ST TI Anatomic and visual results of surgery for stage 5 retinopathy of prematurity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. Charles Retina Inst, Memphis, TN USA. RI SanGiovanni, John Paul/A-7605-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2161 BP U368 EP U368 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802088 ER PT J AU Davis, MD Gangnon, RE Hubbard, LD Lee, LY King, WN Bressler, SB Chew, EY Klein, BEK Klein, R AF Davis, MD Gangnon, RE Hubbard, LD Lee, LY King, WN Bressler, SB Chew, EY Klein, BEK Klein, R CA AREDS Res Grp TI A severity scale for age-related macular degeneration (AMD) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Wisconsin, Madison, WI 53706 USA. Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2108 BP U353 EP U353 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802037 ER PT J AU Ding, Y Zeimer, R Knezevich, F Marks, C Vitale, S Quigley, H Freidman, DS Congdon, N Jampel, H AF Ding, Y Zeimer, R Knezevich, F Marks, C Vitale, S Quigley, H Freidman, DS Congdon, N Jampel, H TI Correlation of macular retinal thickness loss with optic disc changes in eyes with primary open-angle glaucoma: The GILS (Glaucoma Imaging Longitudinal Study) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 JHU, Wilmer Eye Inst, Baltimore, MD USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3395 BP U241 EP U241 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000858 ER PT J AU Djalilian, AR Fan, QY Nussenblatt, RB Vogel, JC Holland, EJ Chan, CC AF Djalilian, AR Fan, QY Nussenblatt, RB Vogel, JC Holland, EJ Chan, CC TI Can bone marrow stem cells trans-diffierntiate into ocular surface epithelial cells? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati Eye Inst, Cincinnati, OH 45221 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1352 BP U322 EP U322 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801301 ER PT J AU Ebong, SJ Yu, CR Carper, DA Egwuagu, CE AF Ebong, SJ Yu, CR Carper, DA Egwuagu, CE TI Regulation of the duration and intensity of growth factor signaling in the lens is mediated by suppressors of cytokine signaling SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, LI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4497 BP U538 EP U538 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001955 ER PT J AU Fan, J Donovan, AK Ledee, DR Zelenka, PS Fariss, RN Chepelinksy, AB AF Fan, J Donovan, AK Ledee, DR Zelenka, PS Fariss, RN Chepelinksy, AB TI Specific interaction between lens MIP/Aquaporin-0 and gamma E-crystallin results in gamma E-crystallin recruitment to the plasma membrane SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2135 BP U361 EP U361 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802062 ER PT J AU Franklin, AJ Jetton, TL Kohn, EC AF Franklin, AJ Jetton, TL Kohn, EC TI CAI appears to provide neuroprotection in mouse model of ischemia induced retinal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Tennessee, Chattanooga, TN USA. Univ Vermont, Burlington, VT USA. NCI, Signal Transduct Unit, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 2926 BP U79 EP U79 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000391 ER PT J AU Frederikse, PH Sun, Q Li, G Farnsworth, P Zigler, S AF Frederikse, PH Sun, Q Li, G Farnsworth, P Zigler, S TI Copper, copper binding amyloid disease proteins, and dityrosine increase in a congenital cataract model linked with oxidative stress SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 UMDNJ, NJMS, Newark, NJ USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3487 BP U260 EP U260 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000952 ER PT J AU Gao, CY Stepp, MA Zelenka, PS AF Gao, CY Stepp, MA Zelenka, PS TI Inhibition of CDK5 activity alters localization of cSRC and promotes corneal wound healing in vitro SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3271 BP U215 EP U215 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000736 ER PT J AU Ghosh, MP Zigler, JS AF Ghosh, MP Zigler, JS TI Studies on rat lenses following long term organ culture SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3492 BP U261 EP U261 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000955 ER PT J AU Gilger, BC Salmon, JH Peng, H Robinson, MR AF Gilger, BC Salmon, JH Peng, H Robinson, MR TI Suprachoroidal placement of a matrix-reservoir cyclosporine device for treatment of chronic recurrent uveitis in horses: Preliminary results SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 N Carolina State Univ, Raleigh, NC 27695 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4433 BP U524 EP U524 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001893 ER PT J AU Golestaneh, N Lo, WK Fan, J Chepelinsky, AB AF Golestaneh, N Lo, WK Fan, J Chepelinsky, AB TI Activation of the lens MIP/aquaporin 0 gene promoter during induced differentiation of lens epithelia explants by FGF2 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Morehouse Sch Med, Atlanta, GA 30310 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4484 BP U535 EP U535 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001943 ER PT J AU Gordiyenko, NV Alam, S Jaworski, C Rodriguez, I AF Gordiyenko, NV Alam, S Jaworski, C Rodriguez, I TI Identification of oxysterol binding proteins (OSBPs) and associated proteins in cultured human RPE cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 384 BP U75 EP U75 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800358 ER PT J AU Gradstein, L Danek, A Grafman, J FitzGibbon, EJ AF Gradstein, L Danek, A Grafman, J FitzGibbon, EJ TI Eye movements in chorea-acanthocytosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Lab Senorimotor Res, Bethesda, MD USA. Univ Munich, Dept Neurol, D-8000 Munich, Germany. NINDS, Cognit Neurosci Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1934 BP U313 EP U313 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801886 ER PT J AU Ham, DI Kim, SJ Chen, J Vistica, BP Fariss, RN Lee, RS Wawrousek, EF Gery, I AF Ham, DI Kim, SJ Chen, J Vistica, BP Fariss, RN Lee, RS Wawrousek, EF Gery, I TI Tolerance does develop in transgenic mice expressing a foreign antigen under control of the rhodopsin promoter SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 991 BP U273 EP U273 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800966 ER PT J AU Haque, R Chaurasia, SS Chong, NW Klein, DC Iuvone, PM AF Haque, R Chaurasia, SS Chong, NW Klein, DC Iuvone, PM TI Circadian expression of Bmal1 in chicken retina, pineal gland, and peripheral tissues SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Emory Univ, Atlanta, GA 30322 USA. Univ Leicester, Leicester, Leics, England. Natl Inst Child Hlth & Human Dev, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 2871 BP U70 EP U70 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000337 ER PT J AU Hawse, JP Huang, Q Sheets, NL Hostick, D Lempicki, R Hejtmancik, J Horwitz, J Kantorow, M AF Hawse, JP Huang, Q Sheets, NL Hostick, D Lempicki, R Hejtmancik, J Horwitz, J Kantorow, M TI Identification and functional clustering of global gene expression differences between age-related cataract and clear human lenses SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 W Virginia Univ, Morgantown, WV 26506 USA. Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. NCBI, NIH, Bethesda, MD USA. NIH, OGVFB, Bethesda, MD USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3135 BP U123 EP U123 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000604 ER PT J AU Hertle, RW Dell'Osso, LF Fitzgibbon, EJ Yang, D Thompson, D Mellow, SD AF Hertle, RW Dell'Osso, LF Fitzgibbon, EJ Yang, D Thompson, D Mellow, SD TI Horizontal rectus tenotomy in the treatment of congenital nystagmus: Results of a phase 1 study in ten patients SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Ohio State Univ, Childrens Hosp, Columbus, OH USA. Case Western Reserve Univ, Ocular Motor Neurophysiol Lab, Cleveland, OH 44106 USA. Case Western Reserve Univ, VA Med Ctr, Cleveland, OH 44106 USA. NEI, Lsr, NIH, Bethesda, MD 20892 USA. EMMES Corp, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4248 BP U479 EP U479 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001712 ER PT J AU Hjelmeland, L Ida, H Ogawa, T Wistow, G AF Hjelmeland, L Ida, H Ogawa, T Wistow, G TI Expressed sequence tag analysis of an RPE/choroid cDNA library from the C57B16 mouse SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Calif Davis, Sch Med, Davis, CA 95616 USA. NEI, Sect Mol Struct & Funct, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 480 BP U96 EP U96 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800455 ER PT J AU Hooper, LC Chin, MS Wang, Y Detrick, B Hooks, JJ AF Hooper, LC Chin, MS Wang, Y Detrick, B Hooks, JJ TI Elevated TNF-alpha and soluble TNF receptor in degeneration susceptible mice with experimental coronavirus retinopathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Immunol Lab, Bethesda, MD USA. Georgetown Univ, Ctr Med, Dept Microbiol & Immunol, Rockville, MD USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4597 BP U606 EP U606 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002056 ER PT J AU Hough, RB Piatigorsky, J AF Hough, RB Piatigorsky, J TI Cornea-preferred transcription of rabbit ALDH1A1: Importance of cis-elements mediating a hypoxic response SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 852 BP U240 EP U240 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800828 ER PT J AU Kador, PF Blessing, K Wyman, M AF Kador, PF Blessing, K Wyman, M TI The results of combretastatin in galactose-fed dogs with diabetes-like proliferative retinopathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Nebraska, Med Ctr, Coll Pharm, Omaha, NE USA. NEI, Lab Ocular Therapeut, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 558 BP U111 EP U111 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800534 ER PT J AU Khan, NW Wissinger, B Kohl, S Singh, R Sieving, PA AF Khan, NW Wissinger, B Kohl, S Singh, R Sieving, PA TI CNGB3 gene mutations: Functional deficits in patients and carriers indicate more than simple achromatopsia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. Univ Tubingen, Hosp Eye, Tubingen, Germany. NEI, NIDCD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4893 BP U669 EP U669 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002352 ER PT J AU Kim, BJ Li, Z Chan, CC Shen, D Egwuagu, C Yu, CR Nagineni, C Nussenblatt, R AF Kim, BJ Li, Z Chan, CC Shen, D Egwuagu, C Yu, CR Nagineni, C Nussenblatt, R TI GITR ligand is expressed in the eye and inhibits CD4+T cell proliferation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Howard Hughes Med Inst, NEI, Natl Inst Hlth Res Scholars Program, Bethesda, MD 20817 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 736 BP U219 EP U219 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800714 ER PT J AU Kim, H D'Amato, RJ Lutz, RJ Yuan, P Baffi, J Wolfe, JD Byrnes, G Robinson, MR Csaky, KG AF Kim, H D'Amato, RJ Lutz, RJ Yuan, P Baffi, J Wolfe, JD Byrnes, G Robinson, MR Csaky, KG TI A subconjunctival implant for delivery of cytochalasin E in a model of choroidal neovascularization: A pilot study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. NIH, Clin Ctr Pharm, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Surg Res, Boston, MA USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4429 BP U523 EP U523 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001888 ER PT J AU Knezevich, F Zeimer, R Vitale, S Ding, Y Marks, C Quigley, H Friedman, DS Congdon, N Jampel, H AF Knezevich, F Zeimer, R Vitale, S Ding, Y Marks, C Quigley, H Friedman, DS Congdon, N Jampel, H TI Image analysis to obtain macular retinal thickness summary parameters for characterizing glaucomatous ganglion cell loss: The GILS (Glaucoma Imaging Longitudinal Study) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 JHU, Wilmer Eye Inst, Baltimore, MD USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3367 BP U235 EP U235 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000828 ER PT J AU Kozlowski, K Berry, F Coca-Prados, M Ahmed, F Tomarev, SI Walter, MA AF Kozlowski, K Berry, F Coca-Prados, M Ahmed, F Tomarev, SI Walter, MA TI Regulation of the primary open-angle glaucoma gene myocilin by PITX2 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Alberta, Edmonton, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3229 BP U203 EP U203 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000696 ER PT J AU Kumar, MV Nagineni, CN Chin, MS Hooks, JJ Detrick, B AF Kumar, MV Nagineni, CN Chin, MS Hooks, JJ Detrick, B TI Double stranded RNA (poly I : C) up regulates Toll-like receptor 3 and induces interferon beta (IFN-beta) in human retinal pigment epithelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 738 BP U219 EP U219 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800715 ER PT J AU Lee, SS Talar-Williams, C Sneller, MC Lerner, R Langford, CA Cox, TA Chan, CC Smith, JA Robinson, MR AF Lee, SS Talar-Williams, C Sneller, MC Lerner, R Langford, CA Cox, TA Chan, CC Smith, JA Robinson, MR TI Tarsal-conjunctival disease associated with Wegener's granulomatosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Johns Hopkins Univ, Baltimore, MD USA. NIAID, NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3721 BP U309 EP U309 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001183 ER PT J AU Lin, D Zhou, J Zelenka, PS Boyle, DL Takemoto, DJ AF Lin, D Zhou, J Zelenka, PS Boyle, DL Takemoto, DJ TI Caveolin regulation of lens epithelial cell gap junctions through PKC gamma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Kansas State Univ, Manhattan, KS 66506 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 427 BP U84 EP U84 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800405 ER PT J AU Lopez, P Caruso, RC AF Lopez, P Caruso, RC TI The effect of stimulus size on color vision deficiencies in retinal disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Ophthalm Genet & Visual Funct Branch, NIIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4906 BP U672 EP U672 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002365 ER PT J AU Mahdi, R Jackson, SH Yu, C Egwuagu, CE AF Mahdi, R Jackson, SH Yu, C Egwuagu, CE TI Dendritic cell maturation is accompanied by a change from STAT6 to STAT1 utilization and by differential expression of suppressor of cytokine signaling (SOCS) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 743 BP U220 EP U220 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800718 ER PT J AU Mahesh, SP Li, Z Buggage, R Nussenblatt, RB AF Mahesh, SP Li, Z Buggage, R Nussenblatt, RB TI Surface expression of glucocorticoid induced TNF receptor family related (GITR) serves as a marker for non-infectious uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Immunol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4605 BP U608 EP U608 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002066 ER PT J AU Malyukova, IV Wawrousek, EF Swaminathan, S Sharan, SK Tomarev, SI AF Malyukova, IV Wawrousek, EF Swaminathan, S Sharan, SK Tomarev, SI TI Transgenic mice containing BAC clone with a point mutation in the myocilin gene as a model for glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, MCGP, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1112 BP U300 EP U300 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801064 ER PT J AU Mandal, MA Ambasudhan, R Wong, PW Gage, P Sieving, PA Ayyagari, R AF Mandal, MA Ambasudhan, R Wong, PW Gage, P Sieving, PA Ayyagari, R TI Mouse ELOVL4 - Genomic organisation, spatial and temporal expression SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. Univ Alberta, Dept Biol Sci, Edmonton, AB, Canada. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 5095 BP U710 EP U710 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002554 ER PT J AU Maraini, G Hejtmancik, JF Shiels, A Mackay, DS Aldigeri, R Jiao, X Williams, SL Sperduto, RD Reed, G AF Maraini, G Hejtmancik, JF Shiels, A Mackay, DS Aldigeri, R Jiao, X Williams, SL Sperduto, RD Reed, G TI Galactokinase gene mutations and age-related cataract. Lack of association in an Italian population SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Parma, I-43100 Parma, Italy. NEI, NIH, Bethesda, MD 20892 USA. Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63130 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4244 BP U478 EP U478 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001707 ER PT J AU Martin, DF Bressler, NM Bressler, SB Chew, EY Clemons, TE Klein, R Seddon, JM AF Martin, DF Bressler, NM Bressler, SB Chew, EY Clemons, TE Klein, R Seddon, JM CA AREDS Res Grp TI Risk factors for the incidence of advanced age-related macular degeneration in the age-related eye disease study (AREDS) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Emory Eye Ctr, Atlanta, GA USA. Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. NEI, NIH, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI 53706 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3077 BP U109 EP U109 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000544 ER PT J AU Mathers, PH Voronina, VA Lewandoski, M AF Mathers, PH Voronina, VA Lewandoski, M TI A continuing role for the Rx homeobox gene in growth of the developing optic vesicle SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 W Virginia Univ, Sch Med, Sensory Neurosci Res Ctr, Morgantown, WV 26506 USA. NCI, Genet Vertebrate Dev Sect, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1603 BP U376 EP U376 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801551 ER PT J AU Mayser, HM Narfstrom, K Bragadottir, R Rakoczy, E Redmond, TM Seeliger, MW AF Mayser, HM Narfstrom, K Bragadottir, R Rakoczy, E Redmond, TM Seeliger, MW TI Assessment of local functional improvement following gene therapy in the RPE65 null mutation dog model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Tubingen, Hosp Eye, Dept 2, Retinal Electrodiagnost Res Grp, Tubingen, Germany. Univ Missouri, Coll Vet Med, Vis Sci Grp, Dept Vet Med & Surg, Columbia, MO USA. Ullevaal Univ Hosp, Dept Ophthalmol, Oslo, Norway. Univ Western Australia, Lions Eye Inst, Perth, WA 6009, Australia. NEI, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3592 BP U283 EP U283 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001056 ER PT J AU McHenry, CL Liu, Y Feng, W Ding, X Gal, A Vollrath, D Sieving, PA Thompson, DA AF McHenry, CL Liu, Y Feng, W Ding, X Gal, A Vollrath, D Sieving, PA Thompson, DA TI MERTK R844C mutant shows reduced phosphorylation activity in transfected cells and is associated with severe rod-cone dystrophy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Michigan, Sch Med, WK Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA USA. Univ Hamburg, Klinikum Eppendorf, Inst Humangenet, Hamburg, Germany. NEI, NIDCD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3566 BP U278 EP U278 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001031 ER PT J AU Meleth, AD Reed, GF Chan, CC Byrnes, GA Shimel, K Chew, EY AF Meleth, AD Reed, GF Chan, CC Byrnes, GA Shimel, K Chew, EY TI Serum cytokines in diabetic retinopathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, Bethesda, MD USA. USN, Ctr Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3981 BP U418 EP U418 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001444 ER PT J AU Moiseyev, GP Crouch, RK Goletz, P Oatis, JE Redmond, TM Ma, JX AF Moiseyev, GP Crouch, RK Goletz, P Oatis, JE Redmond, TM Ma, JX TI Retinyl esters are the substrate for isomerohydrolase SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Med Univ S Carolina, Charleston, SC 29425 USA. NEI, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 947 BP U259 EP U259 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800923 ER PT J AU Nagineni, CN Kutty, V Detrick, B Hooks, JJ AF Nagineni, CN Kutty, V Detrick, B Hooks, JJ TI Expression of PGDF Isoforms and their receptors in human RPE and choroid fibroblasts: Regulation by TGF-beta SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 2956 BP U85 EP U85 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000423 ER PT J AU Narfstrom, K Bragadottir, R Redmond, TM Rakoczy, EP Katz, ML AF Narfstrom, K Bragadottir, R Redmond, TM Rakoczy, EP Katz, ML TI Long-term ultrastructural studies in RPE65-/- dogs with and without unilateral rAAV.RPE65 gene transfer treatment SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Coll Vet Med, Dept Med & Surg, Columbia, MO USA. Ullevaal Univ Hosp, Dept Ophthalmol, Oslo, Norway. NEI, Bethesda, MD 20892 USA. Lions Eye Inst, Perth, WA, Australia. Sch Med, Dept Ophthalmol, Columbia, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3589 BP U283 EP U283 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001052 ER PT J AU Neal, RE Lin, C Zigler, JS AF Neal, RE Lin, C Zigler, JS TI Ph exposure induces cataract formation in cultured rat lens and alters cytoskeletal protein profiles SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3491 BP U260 EP U260 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000954 ER PT J AU Nemesure, BB Jiao, X He, Q Wu, SY Hennis, A Leske, MC Agarwala, R Schaffer, AA Hejtmancik, JF AF Nemesure, BB Jiao, X He, Q Wu, SY Hennis, A Leske, MC Agarwala, R Schaffer, AA Hejtmancik, JF CA Barbados Family Study Grp TI A genome-wide scan for primary open-angle glaucoma in a Black population SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ W Indies, Bridgetown, Barbados. Minist Hlth, Bridgetown, Barbados. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1133 BP U303 EP U303 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801081 ER PT J AU Ohta, K Yamagami, S Wiggert, B Dana, RM Streilein, JW AF Ohta, K Yamagami, S Wiggert, B Dana, RM Streilein, JW TI Chemokine gene expression in iris-ciliary body during experimental autoimmune uveoretinitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Shinshu Univ, Sch Med, Dept Ophthalmol, Matsumoto, Nagano 390, Japan. Univ Tokyo, Sch Med, Dept Ophthalmol, Tokyo 113, Japan. NIH, Lab Retinal & Mol Biol, Bethesda, MD 20892 USA. Harvard Univ, Schepens Eye Res Inst, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 726 BP U216 EP U216 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800701 ER PT J AU Patronas, M Smith, JA Reed, GF Levy-Clarke, GA Buggage, RR AF Patronas, M Smith, JA Reed, GF Levy-Clarke, GA Buggage, RR TI Association between serum immunoglobulin levels and corneal abnormalities in patients with HTLV-1 related disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Georgetown Univ, Washington, DC 20057 USA. NEI, NIH, Bethesda, MD 20892 USA. Sharp Rees Stealy, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 667 BP U205 EP U205 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800645 ER PT J AU Perruccio, EM Rowlette, LLS Balko, NA Becerra, SP Borras, T AF Perruccio, EM Rowlette, LLS Balko, NA Becerra, SP Borras, T TI Dexamethasone increases expression of pigment epithelium derived factor (PEDF) in perfused human anterior segments from post-mortem donor eyes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1140 BP U305 EP U305 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801091 ER PT J AU Rakoczy, EP Lai, CM Brankov, M Redmond, MT Zhou, X Narfstrom, K AF Rakoczy, EP Lai, CM Brankov, M Redmond, MT Zhou, X Narfstrom, K TI The lessons of rAAV mediated RPE65 gene delivery from mouse and dog models of LCA SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Western Australia, Ctr Ophthal & Vis Sci, Perth, WA 6009, Australia. Lions Eye Inst, Perth, WA, Australia. NEI, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. Univ N Carolina, Gene Therapy Ctr, Virus Vector Core Facil, Chapel Hill, NC 27515 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3593 BP U283 EP U283 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001054 ER PT J AU Ray, S Fariss, R Wyatt, K Zelenka, P Wistow, G AF Ray, S Fariss, R Wyatt, K Zelenka, P Wistow, G TI A central role for iris-expressed growth factor/PDGFD in proliferation of lens epithelial cells and control of lens growth SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4501 BP U539 EP U539 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001960 ER PT J AU Reid, TW John, M Dushku, N Pearson, KE Stephan, DA Schultz, GS Baker, HV Carper, DA AF Reid, TW John, M Dushku, N Pearson, KE Stephan, DA Schultz, GS Baker, HV Carper, DA TI Microarray gene expression in ptergyia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. NEI, NIH, Bethesda, MD 20892 USA. Kaiser Permanente Med Ctr, Sacramento, CA USA. Georgetown Univ, Childrens Med Ctr, Washington, DC 20007 USA. Univ Florida, Gainesville, FL 32611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1327 BP U316 EP U316 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801276 ER PT J AU Roberts, JE He, YY Chignell, C Bilski, P Miller, DS Andley, U AF Roberts, JE He, YY Chignell, C Bilski, P Miller, DS Andley, U TI Toxicity and phototoxicity of hypericin to human lens epithelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Fordham Univ, New York, NY 10023 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 304 BP U58 EP U58 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800278 ER PT J AU Robinson, MR Yuan, P Baffi, J Byrnes, G Kim, H Lutz, R Fortman, D Csaky, KG AF Robinson, MR Yuan, P Baffi, J Byrnes, G Kim, H Lutz, R Fortman, D Csaky, KG TI 2-methoxyestradiol subconjunctival implant in a model of choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD USA. NIH, Clin Ctr Pharm, Bethesda, MD USA. NIH, Div Bioengn & Phys Sci, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3943 BP U411 EP U411 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001408 ER PT J AU Rodriguez, IR Alam, S AF Rodriguez, IR Alam, S TI Cytotoxic effects of oxidized LDL-cholesterol and oxysterols on cultured human RPE cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1638 BP U384 EP U384 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801587 ER PT J AU Russell, P Zhao, X Pearson, KE Stephan, DA AF Russell, P Zhao, X Pearson, KE Stephan, DA TI Effects of prostaglandin analogues on human ciliary muscle and trabecular meshwork cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4233 BP U475 EP U475 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001695 ER PT J AU Saika, S Ohnishi, Y Sato, M Ooshima, A Flanders, KC Anzono, M Yoo, J Liu, CY Kao, WWY Roberts, AB AF Saika, S Ohnishi, Y Sato, M Ooshima, A Flanders, KC Anzono, M Yoo, J Liu, CY Kao, WWY Roberts, AB TI TGF beta-Smad3 signaling is required for epithelial-mesenchymal transition of lens epithelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Wakayama Med Coll, Wakayama 640, Japan. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD USA. Univ Miami, Bascom Palmer Eye Inst, Miami, FL 33152 USA. Univ Cincinnati, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4505 BP U539 EP U539 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001962 ER PT J AU Samuel, W Kutty, RK Chandraratna, RAS Wiggert, B AF Samuel, W Kutty, RK Chandraratna, RAS Wiggert, B TI Fenretinide induces apoptosis in human retinal pigment epithelial (RPE) cells: The role of retinoid receptors SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Allergan Pharmaceut Inc, Dept Chem & Biol Retinoid Res, Irvine, CA 92715 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4548 BP U548 EP U548 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002008 ER PT J AU SanGiovanni, JP Chandra, SR Chew, EY Friberg, TR Klein, ML Kurinij, N Seddon, JM AF SanGiovanni, JP Chandra, SR Chew, EY Friberg, TR Klein, ML Kurinij, N Seddon, JM CA AREDS Res Grp TI Dietary omega-3 long-chain polyunsaturated fatty acids and risk for age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI 53706 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Devers Eye Inst, Portland, OR USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RI SanGiovanni, John Paul/A-7605-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2112 BP U353 EP U353 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802039 ER PT J AU Schey, KL Ball, LE Crouch, RK Garland, DL AF Schey, KL Ball, LE Crouch, RK Garland, DL TI The distribution of phosphorylated and posttranslationally modified aquaporin 0 within the normal human lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Med Univ S Carolina, Charleston, SC 29425 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4483 BP U534 EP U534 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001942 ER PT J AU Seitzman, GD Margulies, EH Gottsch, JD Stark, WJ AF Seitzman, GD Margulies, EH Gottsch, JD Stark, WJ TI Cataract surgery in patients with Fuchs' corneal dystrophy-assessment of preoperative pachmetry in predicting the relative risk of future penetrating keratoplasty SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3853 BP U333 EP U333 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001316 ER PT J AU Semina, EV Frees, K Tomarev, S Cvekl, A Murray, JC AF Semina, EV Frees, K Tomarev, S Cvekl, A Murray, JC TI Identification of promoter and other regulatory regions of Pitx3 gene SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Iowa, Iowa City, IA 52242 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Ophthalmol & Visual Sci, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 418 BP U82 EP U82 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800392 ER PT J AU Sen, HN Chan, CC Al-Khatib, SQ Ursea, R Nussenblatt, RB Buggage, RR AF Sen, HN Chan, CC Al-Khatib, SQ Ursea, R Nussenblatt, RB Buggage, RR TI Factors that influence long term survival in patients with primary intraocular lymphoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 763 BP U223 EP U223 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800737 ER PT J AU Sergeev, YY Soustov, LV Chelnokov, EV Bityurin, NM Wingfield, PT Ostrovsky, MA Hejtmancik, JF AF Sergeev, YY Soustov, LV Chelnokov, EV Bityurin, NM Wingfield, PT Ostrovsky, MA Hejtmancik, JF TI Increased sensitivity of amino-arm truncated beta A3 crystallin to UV-light induced photoaggregation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, OGVFB, NIH, Bethesda, MD 20892 USA. NIAMS, NIH, Bethesda, MD USA. Russian Acad Sci, Inst Appl Phys, Nizhnii Novgorod 603600, Russia. Russian Acad Sci, Inst Biol Phys, Moscow 142292, Russia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 298 BP U57 EP U57 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800272 ER PT J AU Shah, SM Haller, JA Campochiaro, PA Polito, A Nguyen, QD Vitale, S AF Shah, SM Haller, JA Campochiaro, PA Polito, A Nguyen, QD Vitale, S TI A randomized, prospective, controlled clinical trial of Sandostatin LAR depot in patients with cystoid macular edema SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Wilmer Eye Inst, Baltimore, MD USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4310 BP U497 EP U497 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001768 ER PT J AU Shen, D Tuaillon, N Peterson, J Lu, B Chan, CC AF Shen, D Tuaillon, N Peterson, J Lu, B Chan, CC TI Lack of ocular response to lipopolysaccharide in CCR-1 deficient mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 720 BP U215 EP U215 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800695 ER PT J AU Singer, JH Diamond, JS AF Singer, JH Diamond, JS TI Multi-vesicular release from mammalian rod bipolar cell terminals SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NINDS, Synapt Physiol Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1008 BP U277 EP U277 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800984 ER PT J AU Sinha, D O'Brien, TP Hose, S Robison, GW Garland, D Sundin, O Zigler, S AF Sinha, D O'Brien, TP Hose, S Robison, GW Garland, D Sundin, O Zigler, S TI A spontaneous mutation in rat disrupts early development of the lens leading to congenital cataract and microphthalmia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Baltimore, MD 21205 USA. NEI, LMOD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1266 BP U302 EP U302 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801217 ER PT J AU Smith, JA Sankar, V Goodman, L Leakan, R Pillemer, S Vitale, S AF Smith, JA Sankar, V Goodman, L Leakan, R Pillemer, S Vitale, S TI Evaluation of ocular, oral and immunologic disease activity measures in Sjogren's syndrome over time SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2470 BP U430 EP U430 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802395 ER PT J AU Sosne, C Xu, L Prach, L Mrock, L Kleinman, HK Letterio, J Hazlett, LD Kurpakus-Wheater, M AF Sosne, C Xu, L Prach, L Mrock, L Kleinman, HK Letterio, J Hazlett, LD Kurpakus-Wheater, M TI Thymosin beta 4 stimulated corneal laminin-5 production is not mediated by TGF-beta SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Wayne State Univ, Detroit, MI 48202 USA. NIDCR, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 861 BP U241 EP U241 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800838 ER PT J AU Srivastava, S Csaky, KG AF Srivastava, S Csaky, KG TI Fluorescein angiographic findings in choroidal neovascularization (CNV) immediately following feeder vessel closure SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4940 BP U679 EP U679 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002401 ER PT J AU Stambolian, D Bailey-Wilson, JE Neider, M Armstrong, J Nigl, K Dana, D Cotch, MF AF Stambolian, D Bailey-Wilson, JE Neider, M Armstrong, J Nigl, K Dana, D Cotch, MF TI Screening for AMD in the Amish population SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. NHGRI, IDRB, NIH, Baltimore, MD USA. Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI 53706 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1786 BP U415 EP U415 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801737 ER PT J AU Stramer, BM Austin, JS Roberts, AB Fini, ME AF Stramer, BM Austin, JS Roberts, AB Fini, ME TI Absence of myofibroblast transformation in corneas of mice deficient for the TGF-beta signaling mediator Smad3 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Miami, Sch Med, Bascom Palmer Eye Inst, Miami, FL 33152 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2145 BP U363 EP U363 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802073 ER PT J AU Strunnikova, NV Baffi, J Zhang, C Teichberg, D Becker, K Cousins, SW Csaky, KG AF Strunnikova, NV Baffi, J Zhang, C Teichberg, D Becker, K Cousins, SW Csaky, KG TI Cellular and molecular responses to sublethal oxidative injury in retinal pigment epithelial cells (RPE) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Bethesda, MD 20892 USA. NIA, DNA Array Unit, Baltimore, MD 21224 USA. Bascom Palmer Eye Inst, Miami, FL 33136 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3145 BP U125 EP U125 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000610 ER PT J AU Suner, IJ Espinosa-Heidmann, DG Tafur, CM Caicedo, AD Legra, JM Hernandez, E Csaky, KG Cousins, SW AF Suner, IJ Espinosa-Heidmann, DG Tafur, CM Caicedo, AD Legra, JM Hernandez, E Csaky, KG Cousins, SW TI The effects of nicotine in choroidal neovascularization: Characterization of nicotinic receptors in choroid and reduction of choroidal neovascularization size and severity via receptor blockade SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD USA. Bascom Palmer Eye Inst, Miami, FL 33136 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3933 BP U409 EP U409 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001397 ER PT J AU Swamynathan, SK Robison, WG Crawford, MA Piatigorsky, J AF Swamynathan, SK Robison, WG Crawford, MA Piatigorsky, J TI Gelsolin is the most abundant water-soluble protein in the corneal epithelium of Anableps anableps, the four-eyed fish SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 908 BP U251 EP U251 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800884 ER PT J AU Takase, H Yu, CR Mahdi, RM DiRusso, G Midgley, F Douek, D Egwuagu, CE Gery, I AF Takase, H Yu, CR Mahdi, RM DiRusso, G Midgley, F Douek, D Egwuagu, CE Gery, I TI Expression of uveitogenic retinal antigens in human thymi: Variability among antigens and individual thymi SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 767 BP U224 EP U224 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800742 ER PT J AU Tomarev, SI Wistow, G Raymond, V Dubois, S Malyukova, I AF Tomarev, SI Wistow, G Raymond, V Dubois, S Malyukova, I TI Gene expression profile of the human trabecular meshwork SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Lmdb, NIH, Bethesda, MD 20892 USA. NEI, Smsf, NIH, Bethesda, MD 20892 USA. CHUL, Res Ctr, Quebec City, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3166 BP U131 EP U131 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000633 ER PT J AU Troyk, PR Bradley, D Towle, V Erickson, R McCreery, D Bak, M Schmidt, E Kufta, C Cogan, S Berg, J AF Troyk, PR Bradley, D Towle, V Erickson, R McCreery, D Bak, M Schmidt, E Kufta, C Cogan, S Berg, J TI Experimental results of intracortical electrode stimulation in macaque V1 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 IIT, Pritzker Inst Biomed Sci & Engn, Chicago, IL 60616 USA. Univ Chicago, Chicago, IL 60637 USA. Huntington Med Res Inst, Pasadena, CA USA. NIH, Bethesda, MD 20892 USA. EIC Labs, Norwood, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 4203 BP U467 EP U467 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001666 ER PT J AU Tsai, JY Fariss, RN Yamamoto, T Hickman, FI AF Tsai, JY Fariss, RN Yamamoto, T Hickman, FI TI A novel transgenic mouse strain expressing green fluorescent protein (GFP) in retinal pigment epithelial (RPE) cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2288 BP U393 EP U393 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802214 ER PT J AU Tsilou, ET Chan, CC Rubin, BI Shen, D Sandrini, F Stratakis, CA Kaiser-Kupfer, M AF Tsilou, ET Chan, CC Rubin, BI Shen, D Sandrini, F Stratakis, CA Kaiser-Kupfer, M TI Eyelid myxoma in Carney complex: Prevalence, histo-pathology & genetics SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Ophth Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. NICHD, Dev Endocrinol Branch, Unit Genet & Endocrinol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2442 BP U424 EP U424 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802367 ER PT J AU Tsina, E Cornwall, MC Chen, C Koutalos, Y Crouch, RK Wiggert, B AF Tsina, E Cornwall, MC Chen, C Koutalos, Y Crouch, RK Wiggert, B TI Relationship between reduction of all-trans retinal to all-trans retinol and dark-adaptation in salamander rods SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Colorado, Sch Med, Denver, CO 80202 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 943 BP U259 EP U259 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800921 ER PT J AU Tuo, J Shen, D Tuaillon, N Chan, CC AF Tuo, J Shen, D Tuaillon, N Chan, CC TI Endotoxin-induced uveitis in cyclooxygenase 2 deficient mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 718 BP U215 EP U215 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800694 ER PT J AU Ursea, R Nussenblatt, RB Smith, JA Ayres, L Caruso, RC Sen, HN Al-Khatib, SQ Srivastava, SR Buggage, RR AF Ursea, R Nussenblatt, RB Smith, JA Ayres, L Caruso, RC Sen, HN Al-Khatib, SQ Srivastava, SR Buggage, RR TI The role of ultrasound biomicroscopy in assessment of patients with anterior segment ocular inflammatory disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2394 BP U415 EP U415 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802319 ER PT J AU Vitale, S Goodman, L Reed, GF Smith, JA AF Vitale, S Goodman, L Reed, GF Smith, JA TI Comparison of a generic (NEI-VFQ) and a disease-specific (OSDI) questionnaire in patients with Sjogren's syndrome SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1282 BP U305 EP U305 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801231 ER PT J AU Wang, X Garcia, CM Kwon, G Guo, J Wistow, G Beebe, DC AF Wang, X Garcia, CM Kwon, G Guo, J Wistow, G Beebe, DC TI Expression and regulation of gamma S-crystallin in the lens epithelium: An epithelial "stress crystallin" SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Washington Univ, St Louis, MO 63130 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2354 BP U409 EP U409 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802281 ER PT J AU Wistow, G Wyatt, K Bernstein, S Orlova, E Wang, L Slingsby, C AF Wistow, G Wyatt, K Bernstein, S Orlova, E Wang, L Slingsby, C TI Lengsin: A novel marker for terminal differentiation in the lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Ophthalmol, Bethesda, MD USA. Univ London Birkbeck Coll, Dept Crystallog, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 949 BP U261 EP U261 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800927 ER PT J AU Wolfe, JD Baffi, J Byrnes, G Csaky, KG AF Wolfe, JD Baffi, J Byrnes, G Csaky, KG TI Requirement for indocyanine green as a photodynamic agent in diode laser closure of retinal and choroidal vessels SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Lab Ocular Gene Therapy, Bethesda, MD 20892 USA. Natl Naval Hosp, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1782 BP U414 EP U414 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801732 ER PT J AU Wong, P Erickson, T McDonald, B Rengarajan, K Gentleman, S AF Wong, P Erickson, T McDonald, B Rengarajan, K Gentleman, S TI Characterization of a new retinal expressed gene with an evolutionarily conserved leucine rich coil motif SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Alberta, Edmonton, AB T6G 2M7, Canada. Emory Univ, Atlanta, GA 30322 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 2265 BP U388 EP U388 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802192 ER PT J AU Xiao, T Choudhary, S Srivastava, S Nees, D Piatigorsky, J Ansari, N AF Xiao, T Choudhary, S Srivastava, S Nees, D Piatigorsky, J Ansari, N TI Involvement of aldehyde dehydrogenase 1 in the oxidation of 4-hydroxynonenal in rat lens and human lens epithelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Louisville, Dept Med, Div Cardiol, Louisville, KY 40292 USA. NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 317 BP U62 EP U62 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800291 ER PT J AU Yang, Y Chauhan, BK Golestaneh, NC Cveklova, K Chepelinsky, AB Cvekl, A AF Yang, Y Chauhan, BK Golestaneh, NC Cveklova, K Chepelinsky, AB Cvekl, A TI Novel regulatory elements of the mouse alpha A-crystallin locus SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 429 BP U84 EP U84 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800406 ER PT J AU Yu, C Guo, Y Mahdi, RM Ebong, S Darrow, RM Organisciak, DT Egwuagu, CE AF Yu, C Guo, Y Mahdi, RM Ebong, S Darrow, RM Organisciak, DT Egwuagu, CE TI SOCS proteins have neuroprotective role in the mammalian retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Wright State Univ, Dayton, OH 45435 USA. NEI, Immunol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 5245 BP U742 EP U742 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002703 ER PT J AU Yu, SS Fariss, RN Poliakov, E Boulanger, A Gentleman, S Redmond, T AF Yu, SS Fariss, RN Poliakov, E Boulanger, A Gentleman, S Redmond, T TI Interaction of RPE65 with caveolin-1 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. NEI, LMOD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 945 BP U259 EP U259 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800922 ER PT J AU Zadnik, K Schechtman, KB Wilson, BA Barr, JT Edrington, TB McMahon, TT Everett, DF Gordon, MO AF Zadnik, K Schechtman, KB Wilson, BA Barr, JT Edrington, TB McMahon, TT Everett, DF Gordon, MO CA CLEK Study Grp TI Visual acuity loss in keratoconus SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Ohio State Univ, Coll Optometry, Columbus, OH 43210 USA. Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63130 USA. Washington Univ, Div Biostat, St Louis, MO 63130 USA. So Calif Coll Optometry, Fullerton, CA USA. Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60680 USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1308 BP U311 EP U311 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801257 ER PT J AU Zelenka, PS Ledee, D Seth, R Gao, C Fariss, R AF Zelenka, PS Ledee, D Seth, R Gao, C Fariss, R TI The Cdk5 activating protein, p39, complexes with muskelin to regulate cell adhesion on thrombospondin SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3262 BP U212 EP U212 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000725 ER PT J AU Zernant, J Jaakson, K Lewis, RA Glavac, D Caruso, R Gouras, P Simonelli, F Lupski, JR Cremers, FPM Allikmets, R AF Zernant, J Jaakson, K Lewis, RA Glavac, D Caruso, R Gouras, P Simonelli, F Lupski, JR Cremers, FPM Allikmets, R TI Molecular diagnostics of Stargardt disease by genotyping patients on the ABCR (ABCA4) microarray SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Columbia Univ, New York, NY USA. Asper Biotech, Tartu, Estonia. Baylor Coll Med, Houston, TX 77030 USA. Inst Pathol, Ljubljana, Slovenia. NEI, Bethesda, MD 20892 USA. Univ Naples 2, Naples, Italy. Univ Nijmegen, Ctr Med, Nijmegen, Netherlands. RI Cremers, Frans/A-5625-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 5107 BP U712 EP U712 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002566 ER PT J AU Zhang, C Caplen, NJ Strunnikova, N Baffi, J Chan, CC Cousins, SW Csaky, KG AF Zhang, C Caplen, NJ Strunnikova, N Baffi, J Chan, CC Cousins, SW Csaky, KG TI Regulation of c-FLIP prevents tumor necrosis factor-alpha (TNF-alpha) induced programmed cell death in human retinal pigment epithelium (hRPE) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, Bethesda, MD 20892 USA. NEI, Ocular Gene Therapy Grp, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Sascom Palmer Eye Inst, Miami, FL 33152 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 473 BP U95 EP U95 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800451 ER PT J AU Zhao, X Russell, P AF Zhao, X Russell, P TI Effects of prostaglandin analogues on the FP receptor and genes associated with glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, LMOD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 1 MA 1149 BP U307 EP U307 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801099 ER PT J AU Zoltoski, RK Novak, LA Garland, D Kuszak, JR AF Zoltoski, RK Novak, LA Garland, D Kuszak, JR TI Correlative structure/function analysis of sutures in insulin-treated diabetic rat lenses SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Illinois Coll Optometry, Chicago, IL USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2003 VL 44 SU 2 MA 3478 BP U258 EP U258 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000942 ER PT J AU Buchacz, K Rogol, AD Lindsey, JC Wilson, CM Hughes, MD Seage, GR Oleske, JM Rogers, LS AF Buchacz, K Rogol, AD Lindsey, JC Wilson, CM Hughes, MD Seage, GR Oleske, JM Rogers, LS CA Pediat AIDS Clinical Trials Grp 21 TI Delayed onset of pubertal development in children and adolescents with perinatally acquired HIV infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; puberty; perinatal; children; adolescents; adrenarche ID HUMAN-IMMUNODEFICIENCY-VIRUS; SECONDARY SEXUAL CHARACTERISTICS; RANDOMIZED CONTROLLED TRIAL; BLOOD-INSTITUTE GROWTH; ANTIRETROVIRAL THERAPY; PROTEASE INHIBITORS; HEMOPHILIA GROWTH; NATIONAL-HEART; SOMATIC GROWTH; BOYS AB Objective: To examine whether greater severity of HIV infection is associated with delayed initiation of pubertal development among perinatally HIV-infected children, and to compare sexual maturation of perinatally HIV-infected children with children in the general US population using the National Health and Nutrition Examination Survey III. Methods: In a prospective cohort study, the authors studied 983 HIV-infected children aged 6 to 18 years, who had Tanner stage assessed on at least two occasions between 1995 and 2000. Analyses were conducted separately for girls and boys to identify factors associated with onset of puberty or adrenarche (progression beyond Tanner stage 1). Results: Among children who were in Tanner stage 1 at their first assessment, 185 of 413 (45%) girls and 144 of 434 (33%) boys entered puberty during the observation period. In multivariate longitudinal regression analyses adjusted for age, race/ethnicity, time interval between study visits, and other clinical factors, girls with severe immunosuppression (CD4% <15) were significantly less likely to enter adrenarche (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.29-0.83) and puberty (OR, 0.57; 95% CI, 0.33-0.96) compared with girls who were not immunosuppressed (CD4% greater than or equal to25). For boys, those with severe immunosuppression were significantly less likely to enter adrenarche (OR, 0.52; 95% CI, 0.28-0.96) and tended to be less likely to begin puberty (OR, 0.69; 95% CI, 0.39-1.22) compared with boys who were not immunosuppressed. Qualitative comparisons suggested that HIV-infected children may experience delayed puberty and adrenarche compared with similarly aged children in the general US population. Conclusions: Immunosuppression was associated with delayed pubertal onset in perinatally HIV-infected children. Further studies of perinatally HIV-infected and uninfected children are needed to better quantify the delay in pubertal onset and to compare the pace of pubertal maturation. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Insmed Inc, Glen Allen, VA USA. Univ Alabama, Birmingham, AL USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. NICHHD, NIH, Rockville, MD USA. RP Buchacz, K (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd,MS E-45, Atlanta, GA 30333 USA. RI Oleske, James/C-1951-2016 OI Oleske, James/0000-0003-2305-5605 FU NIAID NIH HHS [1U01- AI-41110]; NICHD NIH HHS [N01-HD-3-3162] NR 46 TC 43 Z9 44 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAY 1 PY 2003 VL 33 IS 1 BP 56 EP 65 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 677KD UT WOS:000182805400009 PM 12792356 ER PT J AU Feldman, JG Gange, SJ Bacchetti, P Cohen, M Young, M Squires, JE Williams, C Goldwasser, P Anastos, T AF Feldman, JG Gange, SJ Bacchetti, P Cohen, M Young, M Squires, JE Williams, C Goldwasser, P Anastos, T TI Serum albumin is a powerful predictor of survival among HIV-1-infected women SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV trends in serum albumin; independent predictor of survival; time-dependent model; HAART ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTENSIVE-CARE; INFECTED PATIENTS; INTERAGENCY HIV; CYTOKINE LEVELS; OLDER PERSONS; AIDS; RISK; PERMEABILITY; MORTALITY AB Background: We previously reported that single measurements of albumin strongly predict survival in HIV-1-infected women independent of disease-specific markers. We now extend this to the use of serial measurements and single albumin values prior to initiation of highly active antiretroviral therapy. Design: Prospective cohort study of 1941 women enrolled at six sites in the Women's Interagency HIV Study. Results: Albumin fell 0.44 g/L/y in 1627 women who survived and at a faster rate in 397 who died (1.54 g/L/y; p < .01). In a time-dependent model adjusting for disease markers, the relative hazard (RH) was fivefold higher in patients with serum albumin <35 g/L compared with patients with serum albumin >42 g/L. The RH of serum albumin <35 g/L in women with CD4(+) lymphocyte counts greater than or equal to200 cells/muL was 8.2 [95% CI: 4.2-15.8]) versus only 3.8 [95% CI: 2.4-6.1] in those with counts <200 cells/mm(3). In a fixed-covariate Cox analysis of patients who started HAART during the study, albumin prior to HAART was associated with a higher RH (7.0 for albumin <35 g/L versus >42 g/L) than were other factors. Conclusion: Serum albumin is a strong independent predictor of mortality in HIV-1-infected women after adjustment for known disease markers and may be useful for clinical monitoring. C1 SUNY Hlth Sci Ctr, Dept Prevent Med & Community Hlth, Brooklyn, NY 11203 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Cook Cty Hosp, Chicago, IL 60612 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Univ So Calif, Los Angeles, CA USA. NIAID, Bethesda, MD 20892 USA. Brooklyn VA Med Ctr, Brooklyn, NY USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Lincoln Med & Mental Hlth Ctr, Bronx, NY 10451 USA. RP Feldman, JG (reprint author), SUNY Hlth Sci Ctr, Dept Prevent Med & Community Hlth, 450 Clarkson Ave, Brooklyn, NY 11203 USA. RI Andrade, Hugo/M-6631-2013; OI Andrade, Hugo/0000-0001-6781-6125; Gange, Stephen/0000-0001-7842-512X FU NIAID NIH HHS [U01-AI-42590, N01-AI-35161, U01-AI-31834, U01-AI-34989, U01-AI-34993, U01-AI-34994, U01-AI-35004]; NICHD NIH HHS [U01-HD-32632] NR 34 TC 38 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAY 1 PY 2003 VL 33 IS 1 BP 66 EP 73 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 677KD UT WOS:000182805400010 PM 12792357 ER PT J AU Woody, TE Gallop, R Luborsky, L Blaine, J Frank, I Salloum, IM Gastfriend, B Crits-Christoph, P AF Woody, TE Gallop, R Luborsky, L Blaine, J Frank, I Salloum, IM Gastfriend, B Crits-Christoph, P CA Cocaine Psychotherapy Study Grp TI HIV risk reduction in the National Institute on Drug Abuse Cocaine Collaborative Treatment Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE cocaine dependence; HIV risk ID ANTISOCIAL PERSONALITY-DISORDER; DEPENDENCE AB HIV risk was evaluated among 487 cocaine-dependent patients recruited from five treatment programs in a trial that examined the efficacy of four outpatient-based psychosocial treatments. Treatments were offered two to three times per week for 6 months and consisted of group drug counseling (GDC) or group counseling plus individual drug counseling (IDC), cognitive therapy (CT), or supportive-expressive therapy (SE). The average patient had used cocaine for 7 years, with 10 days of use in the last month. Crack smoking was the main route in 79%, and HIV risk was mainly due to multiple partners and unprotected sex. Treatment was associated with a decrease in cocaine use from an average of 10 days per month at baseline to 1 day per month at 6 months. Reduction in cocaine use was associated with an average 40% decrease in HIV risk across all treatment, gender, and ethnic groups, mainly as a result of fewer sexual partners and less unprotected sex. The combination of IDC and GDC was associated with an equal or even greater reduction in HIV risk than the other treatment conditions and thus shows promise as an effective HIV prevention strategy, at least for some patients. C1 Univ Penn, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NIDA, Bethesda, MD 20892 USA. Brookside Hosp, Nashua, NH USA. Harvard Univ, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Woody, TE (reprint author), Treatment Res Inst, 600 Publ Ledger Bldg,150 S Independence Mall W, Philadelphia, PA 19106 USA. NR 19 TC 0 Z9 0 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAY 1 PY 2003 VL 33 IS 1 BP 82 EP 87 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 677KD UT WOS:000182805400012 ER PT J AU Bingham, RJ AF Bingham, RJ CA Natl Inst Nursing Res TI Annotated bibliography of recent National Institute of Nursing Research findings on women's health across the life span SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article C1 Natl Inst Nursing Res, NIH, Bethesda, MD 20892 USA. RP Bingham, RJ (reprint author), Natl Inst Nursing Res, NIH, 31 Ctr Dr,MSC 2178,Bldg 31,Room 5B-10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0884-2175 J9 JOGNN JI JOGNN PD MAY-JUN PY 2003 VL 32 IS 3 BP 370 EP 377 DI 10.1111/j.1552-6909.2003.tb00168.x PG 8 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 676QY UT WOS:000182764600016 ER PT J AU Trull, TJ Widiger, TA Lynam, DR Costa, PT AF Trull, TJ Widiger, TA Lynam, DR Costa, PT TI Borderline personality disorder from the perspective of general personality functioning SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID DSM-III-R; 5-FACTOR MODEL; STRUCTURED INTERVIEW; DIMENSIONS; REPRESENT; DIAGNOSES; VALIDITY; VARIANTS; FACETS AB The authors extended previous work on the hypothesis that borderline personality disorder (BPD) can be understood as a maladaptive variant of personality traits included within the 5-factor model (FFM) of personality. In each of 3 samples, an empirically derived prototypic FFM borderline profile was correlated with individuals' FFM profiles to yield a similarity score, an FFM borderline index. Results across all samples indicated that the FFM borderline index correlated as highly with existing borderline measures as they correlated with one another, and the FFM borderline index correlated as highly with measures of dysfunction, history of childhood abuse, and parental psychopathology as did traditional measures of BPD. Findings support the hypothesis that BPD is a maladaptive variant of FFM personality traits. C1 Univ Missouri, Dept Psychol Sci, Columbia, MO 65211 USA. Univ Kentucky, Dept Psychol, Lexington, KY 40506 USA. NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. RP Trull, TJ (reprint author), Univ Missouri, Dept Psychol Sci, 106C McAlester Hall, Columbia, MO 65211 USA. RI Lynam, Donald/J-5755-2014; OI Lynam, Donald/0000-0001-8306-498X; Costa, Paul/0000-0003-4375-1712 FU NIMH NIH HHS [R01 MH 60104, R01 MH52695, R55 MH52695] NR 77 TC 110 Z9 112 U1 3 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2003 VL 112 IS 2 BP 193 EP 202 DI 10.1037/0021-843X.112.2.193 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 679LY UT WOS:000182925000002 PM 12784828 ER PT J AU Cooper, PJ Chico, ME Rodrigues, LC Ordonez, M Strachan, D Griffin, GE Nutman, TB AF Cooper, PJ Chico, ME Rodrigues, LC Ordonez, M Strachan, D Griffin, GE Nutman, TB TI Reduced risk of atopy among school-age children infected with geohelminth parasites in a rural area of the tropics SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE geohelminths; intestinal helminths; atopy; total IgE; anti-Ascaris lumbricoides IgG4; tropics; Ecuador ID ALLERGIC REACTIVITY; HELMINTH INFECTION; PREVALENCE; RESPONSES; ASTHMA; URBAN; SLUM; IGE AB Background: Childhood infections might protect against the expression of atopy. Geohelminths are among the most prevalent infections of childhood and might contribute to the low prevalence of allergic disease reported from rural areas of the tropics. Objective: We sought to establish whether geohehninth infections protect against atopy and to explore whether this protection is dependent on infection chronicity. Methods: The risk of atopy (measured by means of allergen skin test reactivity) associated with active geohelminth infections (measured by means of the presence of eggs in stool samples) or with chronic geohelminth infections (measured by means of high levels [greater than or equal to3564 IU/mL] of total serum IgE or the presence of detectable anti-Ascaris lumbricoides IgG4 antibodies) was investigated in an analytic cross-sectional study conducted among school-age children attending rural schools in Pichincha Province in Ecuador. Results: A total of 2865 children aged 5 to 19 years from 55 schools was examined. Active infection with any geohelminth and infections with A lumbricoides or Ancylostoma duodenale were associated with significant protective effects against allergen skin test reactivity. Children with the highest levels of total IgE or with anti-A lumbricoides IgG4 antibodies were protected against skin test reactivity also, and the protective effects of high IgE or anti-A lumbricoides IgG4 and or active geohelminth infections were statistically independent. Conclusion: Active infections with geohelminth parasites and the presence of serologic markers of chronic infections (high levels of total serum IgE or anti-A lumbricoides IgG4) are independent protective factors against allergen skin test reactivity among school-age children living in an endemic region of the rural tropics. C1 NIAID, LPD, NIH, Bethesda, MD 20892 USA. Hosp Pedro Vicente Maldonado, Lab Invest, Pedro Vicente Maldonado, Ecuador. London Sch Hyg & Trop Med, Infect Dis Epidemiol Unit, London WC1, England. Univ London St Georges Hosp, Sch Med, Dept Publ Hlth Sci, London SW17 0RE, England. Univ London St Georges Hosp, Sch Med, Dept Infect Dis, London SW17 0RE, England. RP Nutman, TB (reprint author), NIAID, LPD, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. OI Rodrigues, Laura Cunha/0000-0001-9008-660X NR 19 TC 167 Z9 174 U1 1 U2 10 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2003 VL 111 IS 5 BP 995 EP 1000 DI 10.1067/mai.2003.1348 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 679DA UT WOS:000182904500013 PM 12743563 ER PT J AU Cohen, SG AF Cohen, SG TI Noon and Freeman on prophylactic inoculation against hey fever SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material C1 NIAID, Natl Lib Med, NIH, Bethesda, MD USA. RP Cohen, SG (reprint author), NIAID, Natl Lib Med, NIH, Bethesda, MD USA. NR 15 TC 6 Z9 8 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2003 VL 111 IS 5 BP 1142 EP 1144 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 679DA UT WOS:000182904500041 PM 12743591 ER PT J AU Weber, HA Zart, MK Hodges, AE White, KD Barnes, SM Moody, LA Clark, AP Harris, RK Overstreet, JD Smith, CS AF Weber, HA Zart, MK Hodges, AE White, KD Barnes, SM Moody, LA Clark, AP Harris, RK Overstreet, JD Smith, CS TI Method validation for determination of alkaloid content in goldenseal root powder SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID HYDRASTIS-CANADENSIS; ISOQUINOLINE ALKALOIDS; MEDICINAL-PLANTS; BERBERINE; ACID AB A fast, practical ambient extraction methodology followed by isocratic liquid chromatography (LC) analysis with UV detection was validated for the determination of berberine, hydrastine, and canadine in goldenseal (Hydrastis canadensis L.) root powder. The method was also validated for palmatine, a major alkaloid present in the possible bioadulterants Coptis, Oregon grape root, and barberry bark. Alkaloid standard solutions were linear over the evaluated concentration ranges. The analytical method was linear for alkaloid extraction using 0.3-2 g goldenseal root powder/100 m L extraction solvent. Precision of the method was demonstrated using 10 replicate extractions of 0.5 g goldenseal root powder, with percent relative standard deviation for all 4 alkaloids less than or equal to1.6. Alkaloid recovery was determined by spiking each alkaloid into triplicate aliquots of neat goldenseal root powder. Recoveries ranged from 92.3% for palmatine to 101.9% for hydrastine. Ruggedness of the method was evaluated by performing multiple analyses of goldenseal root powder from 3 suppliers over a 2-year period. The method was also used to analyze Coptis root, Oregon grape root, barberry bark, and celandine herb, which are possible goldenseal bloadulterants. The resulting chromatographic profiles of the bioadulterants; were significantly different from that of goldenseal. The method was directly transferred to LC with mass spectrometry, which was used to confirm the presence of goldenseal alkaloids tetrahydro-berberastine, berberastine, canadaline, berberine, hydrastine, and canadine, as well as alkaloids from the bloadulterants, including palmatine, jatrorrhizine, and coptisine. C1 Midwest Res Inst, Kansas City, MO 64110 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Weber, HA (reprint author), Midwest Res Inst, 425 Volker Blvd, Kansas City, MO 64110 USA. FU NIEHS NIH HHS [N01-ES-05457, N01-ES-55385] NR 29 TC 15 Z9 15 U1 0 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2003 VL 86 IS 3 BP 476 EP 483 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 690EY UT WOS:000183535500007 PM 12852562 ER PT J AU Esposito, D Gerard, GF AF Esposito, D Gerard, GF TI The Escherichia coli fis protein stimulates bacteriophage lambda integrative recombination in vitro SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DNA INVERSION; GROWTH-PHASE; PHAGE LAMBDA; BINDING; IDENTIFICATION; CHROMOSOME; EXPRESSION; INVITRO AB The Escherichia coli nucleoid-associated protein Fis was previously shown to be involved in bacteriophage lambda site-specific recombination in vivo, enhancing the levels of both integrative recombination and excisive recombination. While purified Fis protein was shown to stimulate in vitro excision, Fis appeared to have no effect on in vitro integration reactions even though a 15-fold drop in lysogenization frequency had previously been observed in fis mutants. We demonstrate here that E. coli Fis protein does stimulate integrative lambda recombination in vitro but only under specific conditions which likely mimic natural in vivo recombination more closely than the standard conditions used in vitro. In the presence of suboptimal concentrations of Int protein, Fis stimulates the rate of integrative recombination significantly. In addition, Fis enhances the recombination of substrates with nonstandard topologies which may be more relevant to the process of in vivo phage lambda recombination. These data support the hypothesis that Fis may play an essential role in lambda recombination in the host cell. C1 Invitrogen Corp, Frederick, MD 21704 USA. RP Esposito, D (reprint author), NCI, Frederick Canc Res & Dev Ctr, Prot Express Lab, SAIC Frederick Inc, Bldg 325,POB B, Frederick, MD 21702 USA. NR 18 TC 14 Z9 15 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2003 VL 185 IS 10 BP 3076 EP 3080 DI 10.1128/JB.185.10.3076-3080.2003 PG 5 WC Microbiology SC Microbiology GA 675HA UT WOS:000182686900013 PM 12730167 ER PT J AU Stewart, PE Chaconas, G Rosa, P AF Stewart, PE Chaconas, G Rosa, P TI Conservation of plasmid maintenance functions between linear and circular plasmids in Borrelia burgdorferi SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; OSPC GENE; FACTOR-H; BIDIRECTIONAL REPLICATION; TELOMERE RESOLUTION; PROPHAGE N-15; STRAIN B31; ORIGIN; DNA; INFECTIVITY AB The Lyme disease agent Borrelia burgdorferi maintains both linear and circular plasmids that appear to be essential for mammalian infection. Recent studies have characterized the circular plasmid regions that confer autonomous replication, but the genetic elements necessary for linear plasmid maintenance have not been experimentally identified. Two vectors derived from linear plasmids lp25 and lp28-1 were constructed and shown to replicate autonomously in B. burgdorferi. These vectors identify internal regions of linear plasmids necessary for autonomous replication in B. burgdorferi. Although derived from linear plasmids, the vectors are maintained in circular form in B. burgdorferi, indicating that plasmid maintenance functions are conserved, regardless of DNA form. Finally, derivatives of these vectors indicate that paralogous gene family 49 is apparently not required for either circular or linear plasmid replication. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. RP Stewart, PE (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 48 TC 32 Z9 34 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2003 VL 185 IS 10 BP 3202 EP 3209 DI 10.1128/JB.185.10.3202-3209.2003 PG 8 WC Microbiology SC Microbiology GA 675HA UT WOS:000182686900026 PM 12730180 ER PT J AU Gronthos, S Zannettino, ACW Hay, SJ Shi, ST Graves, SE Kortesidis, A Simmons, PJ AF Gronthos, S Zannettino, ACW Hay, SJ Shi, ST Graves, SE Kortesidis, A Simmons, PJ TI Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow SO JOURNAL OF CELL SCIENCE LA English DT Article DE bone marrow stroma; mesenchymal stem cells; STRO-1; bone; cartilage; adipose; CFU-F ID IN-VIVO; OSTEOBLAST DIFFERENTIATION; TELOMERASE EXPRESSION; TRANSCRIPTION FACTOR; MONOCLONAL-ANTIBODY; TRANSPLANTATION; FIBROBLASTS; PRECURSORS; CULTURES; VITRO AB Previous studies have provided evidence for the existence of adult human bone marrow stromal stem cells (BMSSCs) or mesenchymal stem cells. Using a combination of cell separation techniques, we have isolated an almost homogeneous population of BMSSCs from adult human bone marrow. Lacking phenotypic characteristics of leukocytes and mature stromal elements, BMSSCs are noncycling and constitutively express telomerase activity in vivo. This mesenchymal stem cell population demonstrates extensive proliferation and retains the capacity for differentiation into bone, cartilage and adipose tissue in vitro. In addition, clonal analysis demonstrated that individual BMSSC colonies exhibit a differential capacity to form new bone in vivo. These data are consistent with the existence of a second population of bone marrow stem cells in addition to those for the hematopoietic system. Our novel selection protocol provides a means to generate purified populations of BMSSCs for use in a range of different tissue engineering and gene therapy strategies. C1 Inst Med & Vet Sci, Div Haematol, Mesenchymal Stem Cell Grp, Adelaide, SA, Australia. Matthew Roberts Fdn Lab, Inst Med & Vet Sci, Myeloma & Mesenchymal Res Grp, Adelaide, SA, Australia. Univ Adelaide, Dept Orthopaed & Trauma, Adelaide, SA, Australia. Natl Inst Dental & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Royal Melbourne Hosp, Dept Orthopaed, Melbourne, Vic, Australia. Peter MacCallum Canc Inst, Stem Cell Lab, Melbourne, Vic, Australia. RP Gronthos, S (reprint author), Inst Med & Vet Sci, Div Haematol, Mesenchymal Stem Cell Grp, Adelaide, SA, Australia. RI Graves, Stephen/A-9463-2016 OI Graves, Stephen/0000-0002-1629-319X NR 49 TC 623 Z9 691 U1 3 U2 31 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 MAY 1 PY 2003 VL 116 IS 9 BP 1827 EP 1835 DI 10.1242/jcs.00369 PG 9 WC Cell Biology SC Cell Biology GA 679CN UT WOS:000182903600019 PM 12665563 ER PT J AU Cappola, AR Xue, QL Ferrucci, L Guralnik, JM Volpato, S Fried, LP AF Cappola, AR Xue, QL Ferrucci, L Guralnik, JM Volpato, S Fried, LP TI Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CARDIOVASCULAR RISK MARKERS; FACTOR BINDING PROTEIN-3; C-REACTIVE PROTEIN; BODY-COMPOSITION; MUSCLE STRENGTH; TRANSGENIC MICE; IGF-I; HORMONE; AGE; MEN AB The physiology of age-related functional decline is poorly understood, but may involve hormones and inflammation. We hypothesized that older women with both low IGF-I and high IL-6 levels are at high risk for disability and death. We assessed walking speed and disability in 718 women enrolled in the Women's Health and Aging Study I, a 3-yr cohort study with 5-yr mortality follow-up. Women with IGF-I levels in the lowest quartile and IL-6 levels in the highest quartile had significantly greater limitation in walking and disability in mobility tasks and instrumental activities of daily living than those with neither risk factor ( adjusted odds ratios, 10.77, 5.14, and 3.66). Women with both risk factors were at greater risk for death ( adjusted relative risk, 2.10) as well as incident walking limitation, mobility disability, and disability in activities of daily living compared with those with high IGF-I and low IL-6 levels. The combination of low IGF-I and high IL-6 levels confers a high risk for progressive disability and death in older women, suggesting an aggregate effect of dysregulation in endocrine and immune systems. The joint effects of IGF-I and IL-6 may be important targets for treatments to prevent or minimize disability associated with aging. C1 Univ Maryland, Dept Med, Baltimore, MD 21201 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. INRCA Geriatr Dept, Lab Clin Epidemiol, Florence, Italy. NIA, Dept Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. RP Cappola, AR (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Div Endocrinol Diabet & Metab, 932 Blockley Hall, Philadelphia, PA 19104 USA. EM acappola@cceb.med.upenn.edu RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 FU NIA NIH HHS [N01-AG-1-2112, R01-AG-19905] NR 42 TC 165 Z9 166 U1 2 U2 5 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 MAY 1 PY 2003 VL 88 IS 5 BP 2019 EP 2025 DI 10.1210/jc.2002-021694 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 673TD UT WOS:000182595500014 PM 12727948 ER PT J AU Vgontzas, AN Zoumakis, M Bixler, EO Lin, HM Prolo, P Vela-Bueno, A Kales, A Chrousos, GP AF Vgontzas, AN Zoumakis, M Bixler, EO Lin, HM Prolo, P Vela-Bueno, A Kales, A Chrousos, GP TI Impaired nighttime sleep in healthy old versus young adults is associated with elevated plasma interleukin-6 and cortisol levels: Physiologic and therapeutic implications SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 83rd Annual Meeting of the Endocrine-Society CY JUN 20-23, 2001 CL DENVER, CO SP Endocrine Soc ID PITUITARY-ADRENAL AXIS; EXCESSIVE DAYTIME SLEEPINESS; CLINICAL IMPLICATIONS; CHRONIC INSOMNIA; STRESS SYSTEM; TIME-SERIES; DISORDERS; AGE; MEN; CYTOKINES AB IL-6 and TNFalpha secretion is increased by sleep loss or restriction. IL-6 secretion progressively increases with age, yet its association with decreased quality and quantity of sleep in old adults is unknown. This study examined the alteration of 24-h secretory pattern of IL-6, TNFalpha, and cortisol in 15 young and 13 old normal sleepers who were recorded in the sleep laboratory for four consecutive nights. Serial 24-h plasma measures of IL-6, TNFalpha, and cortisol were obtained during the fourth day, and daytime sleepiness was assessed with the multiple sleep latency test. Old adults, compared with young subjects, slept poorly at night ( wake time and percentage stage 1 sleep were increased, whereas their percentage slow wave sleep and percentage sleep time were decreased, P < 0.05). Accordingly, their daytime sleep latency was longer than in young adults ( P < 0.05). The mean 24-h IL-6 and cortisol levels were significantly higher in old than young adults ( P < 0.05). In both groups, IL-6 and cortisol plasma concentrations were positively associated with total wake time, with a stronger association of IL-6 and cortisol with total wake time in the older individuals ( P < 0.05); their combined effect was additive. IL-6 had a negative association with rapid eye movement ( REM) sleep only in the young ( P < 0.05), but cortisol was associated negatively with REM sleep both in the young and old, with a stronger effect in the young. We conclude that in healthy adults, age-related alterations in nocturnal wake time and daytime sleepiness are associated with elevations of both plasma IL-6 and cortisol concentrations, but REM sleep decline with age is primarily associated with cortisol increases. C1 Penn State Univ, Coll Med, Dept Psychiat H073, Sleep Res & Treatment Ctr, Hershey, PA 17033 USA. Penn State Univ, Coll Med, Dept Psychiat & Hlth Evaluat Sci, Hershey, PA 17033 USA. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Vgontzas, AN (reprint author), Penn State Univ, Coll Med, Dept Psychiat H073, Sleep Res & Treatment Ctr, 500 Univ Dr, Hershey, PA 17033 USA. EM axv3@psu.edu NR 37 TC 123 Z9 125 U1 0 U2 8 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 MAY 1 PY 2003 VL 88 IS 5 BP 2087 EP 2095 DI 10.1210/jc.2002-021176 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 673TD UT WOS:000182595500026 PM 12727959 ER PT J AU Agnello, D Lankford, CSR Bream, J Morinobu, A Gadina, M O'Shea, JJ Frucht, DM AF Agnello, D Lankford, CSR Bream, J Morinobu, A Gadina, M O'Shea, JJ Frucht, DM TI Cytokines and transcription factors that regulate T helper cell differentiation: New players and new insights SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Review DE T helper (T-H) cells; differentiation; T(H)1 cells; T(H)2 cells; interferon-gamma; interleukin (IL)-4; IL-12; IL-23; IL-27; Stat1; Stat4; Stat6; GATA-3; c-Maf; NFATs ID IFN-GAMMA-PRODUCTION; INDUCED AIRWAY HYPERRESPONSIVENESS; STAT4 SERINE PHOSPHORYLATION; ACTIVATED PROTEIN-KINASE; MOUSE IL-12 RECEPTOR; DEVELOPING TH1 CELLS; NF-KAPPA-B; CUTTING EDGE; GENE-EXPRESSION; INTERFERON-GAMMA AB The differentiation of naive CD4(+) T cells into subsets of T helper cells is a pivotal process with major implications for host defense and the pathogenesis of immune-mediated diseases. Though the basic paradigm was discovered more than 15 years ago, new discoveries continue to be made that offer fresh insights into the regulation of this process (1). T helper (T-H)1 cells produce interferon (IFN)-gamma, promoting cell-mediated immunity and control of intracellular pathogens. We now know that T(H)1 differentiation is regulated by transcription factors such as T-bet, Stat1, and Stat4, as well as cytokines such as IL-12, IL-23, IL-27, type I IFNs, and IFN-gamma. In contrast, T(H)2 cells produce IL-4, which promotes allergic responses and is important in host defense against helminths. The transcription factors Stat6, GATA-3, c-Maf, NFATs, and the cytokine IL-4 promote T(H)2 differentiation. These key regulators of T-H differentiation are the subject of this review. C1 NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20802 USA. US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Queens Univ Belfast, Dept Microbiol & Immunol, Belfast, Antrim, North Ireland. RP O'Shea, JJ (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bldg 10,Room 9N262,10 Ctr Dr,MSC 1820, Bethesda, MD 20802 USA. NR 174 TC 231 Z9 250 U1 0 U2 7 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 2003 VL 23 IS 3 BP 147 EP 161 DI 10.1023/A:1023381027062 PG 15 WC Immunology SC Immunology GA 666FR UT WOS:000182166900001 PM 12797537 ER PT J AU Gravitt, PE Hildesheim, A Herrero, R Schiffman, M Sherman, ME Bratti, MC Rodriguez, AC Morera, LA Cardenas, F Bowman, FP Shah, KV Crowley-Nowick, PA AF Gravitt, PE Hildesheim, A Herrero, R Schiffman, M Sherman, ME Bratti, MC Rodriguez, AC Morera, LA Cardenas, F Bowman, FP Shah, KV Crowley-Nowick, PA TI Correlates of IL-10 and IL-12 concentrations in cervical secretions SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE mucosal; cervix, secretions ID HUMAN-PAPILLOMAVIRUS INFECTION; T-CELLS; CYTOKINE; CANCER; WOMEN; RISK; IMMUNIZATION; COLLECTION; CARCINOMA; LESIONS AB Interindividual variations in host immune responses to HPV infection are thought to be important determinants of viral persistence and progression to cervical intraepithelial neoplasia and cancer. However, few studies have measured local immune markers at the site of infection (e.g., the cervical mucosa). We sought to determine biologic correlates of IL-10 and IL-12 concentrations in cervical secretions. Cervical secretions were passively collected using a WeckCel sponge from 247 women participating in a natural history study of human papillomavirus infection as part of an immunologic ancillary study. IL-10 and IL-12 concentrations were determined using standard ELISA assays. In general, IL-10 and IL-12 levels were significantly intercorrelated (Pearson's correlation coefficient=0.6) but had somewhat different determinants. Significant increases (P<0.05) in IL-10 concentrations were observed for nonovulatory phases of the menstrual cycle, postmenopausal status, recent use of oral contraceptives (OC), low secretion volume, macrolevels of heme contamination, and high vaginal pH. Increasing IL-10 levels were also observed among smokers, women with increasing numbers of lifetime sex partners, and women who report having less frequent sex (less than once per week), however, these results were not statistically significant. Significantly higher IL-12 concentrations were observed among recent OC users, women with low secretion volume, and women with a high vaginal pH. There was a non-statistically significant observation of increasing IL-12 levels among nonsmokers, women with increasing numbers of lifetime and recent pregnancies, and increasing levels of heme contamination. We failed to observe a significant association between HPV and IL-10 or IL-12 levels in this cross-sectional sample. Future analyses of cervical cytokine levels and HPV infection should control for the inherent variation of local cytokine levels due to hormonal influences, hemoglobin contamination, pH, and cervical secretion volume differences. C1 NCI, Interdisciplinary Studies Sect, Environm Epidemiol Branch, DCEG, Rockville, MD 20852 USA. Proyecto Epidemiol Guanacaste, Guanacaste, Costa Rica. Harvard Univ, Sch Med, Brigham & Womens Hosp, Fearing Res Lab,Dept Obstet Gynecol & Reprod Biol, Boston, MA USA. Johns Hopkins Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. RP Hildesheim, A (reprint author), NCI, Interdisciplinary Studies Sect, Environm Epidemiol Branch, DCEG, 6120 Execut Blvd,EPS 7059,Room 7062, Rockville, MD 20852 USA. NR 26 TC 30 Z9 31 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 2003 VL 23 IS 3 BP 175 EP 183 DI 10.1023/A:1023305827971 PG 9 WC Immunology SC Immunology GA 666FR UT WOS:000182166900003 PM 12797539 ER PT J AU Ashcroft, GS Mills, SJ Lei, KJ Gibbons, L Jeong, MJ Taniguchi, M Burow, M Horan, MA Wahl, SM Nakayama, T AF Ashcroft, GS Mills, SJ Lei, KJ Gibbons, L Jeong, MJ Taniguchi, M Burow, M Horan, MA Wahl, SM Nakayama, T TI Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MODIFIED TETRACYCLINE CMT-8; RECEPTOR-ALPHA; FACTOR MIF; INFLAMMATORY RESPONSE; OVARIECTOMIZED RATS; BETA; EXPRESSION; ENDOTOXEMIA; PROTECTION; DEFICIENCY AB Characteristic of both chronic wounds and acute wounds that fail to heal are excessive leukocytosis and reduced matrix deposition. Estrogen is a major regulator of wound repair that can reverse age-related impaired wound healing in human and animal models, characterized by a dampened inflammatory response and increased matrix deposited at the wound site. Macrophage migration inhibitory factor (MIF) is a candidate proinflammatory cytokine involved in the hormonal regulation of inflammation. We demonstrate that MIF is upregulated in a distinct spatial and temporal pattern during wound healing and its expression is markedly elevated in wounds of estrogen-deficient mice as compared with intact animals. Wound-healing studies in mice rendered null for the MIF gene have demonstrated that in the absence of MIF, the excessive inflammation and delayed-healing phenotype associated with reduced estrogen is reversed. Moreover, in vitro assays have shown a striking estrogen-mediated decrease in MIF production by activated murine macrophages, a process involving the estrogen receptor. We suggest that estrogen inhibits the local inflammatory response by downregulating MIF, suggesting a specific target for future therapeutic intervention in impaired wound-healing states. C1 Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. Chiba Univ, Grad Sch Med, Dept Med Immunol, Chiba, Japan. Chiba Univ, Grad Sch Med, Dept Mol Immunol, Chiba, Japan. Tulane Med Sch, New Orleans, LA USA. RP Ashcroft, GS (reprint author), Univ Manchester, Sch Biol Sci, 3-239 Stopford Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England. RI Mills, Stuart/L-4889-2014; Nakayama, Toshinori/E-1067-2017 OI Mills, Stuart/0000-0002-2462-7081; NR 42 TC 182 Z9 187 U1 3 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2003 VL 111 IS 9 BP 1309 EP 1318 DI 10.1172/KCO200316288 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 673XD UT WOS:000182605400009 PM 12727922 ER PT J AU Wada, T Konno, A Schurman, SH Garabedian, EK Anderson, SM Kirby, M Nelson, DL Candotti, F AF Wada, T Konno, A Schurman, SH Garabedian, EK Anderson, SM Kirby, M Nelson, DL Candotti, F TI Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID IN-VIVO REVERSION; SEVERE COMBINED IMMUNODEFICIENCY; ADENOSINE-DEAMINASE DEFICIENCY; INHERITED MUTATION; FANCONI-ANEMIA; WASP GENE; REVERTANT MOSAICISM; CELL LINES; DNA; MECHANISM AB Revertant mosaicism due to true back mutations or second-site mutations has been identified in several inherited disorders. The occurrence of revertants is considered rare, and the underlying genetic mechanisms remain mostly unknown. Here we describe somatic mosaicism in two brothers affected with Wiskott-Aldrich syndrome (WAS). The original mutation causing disease in this family is a single base insertion (1305insG) in the WAS protein (WASP) gene, which results in frameshift and abrogates protein expression. Both patients, however, showed expression of WASP in a fraction of their T cells that were demonstrated to carry a second-site mutation causing the deletion of 19 nucleotides from nucleotide 1299 to 1316. This deletion abrogated the effects of the original mutation and restored the WASP reading frame. In vitro expression studies indicated that mutant protein encoded by the second-site mutation was expressed and functional, since it was able to bind to cellular partners and mediate T cell receptor/CD3 downregulation. These observations were consistent with evidence of in vivo selective advantage of WASP-expressing lymphocytes. Molecular analysis revealed that the sequence surrounding the deletion contained two 4-bp direct repeats and that a hairpin structure could be formed by five GC pairs within the deleted fragment. These findings strongly suggest that slipped mispairing was the cause of this second-site mutation and that selective accumulation of WASP-expressing T lymphocytes led to revertant mosaicism in these patients. C1 NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Candotti, F (reprint author), NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Bldg 49,Room 3A20,MSC 4442, Bethesda, MD 20892 USA. OI Schurman, Shepherd/0000-0002-9133-7906 NR 38 TC 51 Z9 53 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2003 VL 111 IS 9 BP 1389 EP 1397 DI 10.1172/JCI200315485 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 673XD UT WOS:000182605400018 PM 12727931 ER PT J AU Lum, JJ Cohen, OJ Nie, ZL Weaver, JG Gomez, TS Yao, XJ Lynch, D Pilon, AA Hawley, N Kim, JE Chen, ZX Montpetit, M Sanchez-Dardon, J Cohen, EA Badley, AD AF Lum, JJ Cohen, OJ Nie, ZL Weaver, JG Gomez, TS Yao, XJ Lynch, D Pilon, AA Hawley, N Kim, JE Chen, ZX Montpetit, M Sanchez-Dardon, J Cohen, EA Badley, AD TI Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; BLOOD MONONUCLEAR-CELLS; VIRAL PROTEIN-R; LYMPHOCYTE APOPTOSIS; T-CELLS; PROGRESSION; REPLICATION; EXPRESSION; DEFECTS; CD4(+) AB The absence of immune defects that occurs in the syndrome of long-term nonprogressive (LTNP) HIV infection offers insights into the pathophysiology of HIV-induced immune disease. The (H[F/S]RIG)(2) domain of viral protein R (Vpr) induces apoptosis and may contribute to HIV-induced T cell depletion. We demonstrate a higher frequency of R77Q Vpr mutations in patients with LTNP than in patients with progressive disease. In addition, T cell infections using vesicular stomatitis virus G (VSV-G) pseudotyped HIV-1 Vpr R77Q result in less (P = 0.01) T cell death than infections using wild-type Vpr, despite similar levels of viral replication. Wild-type Vpr-associated events, including procaspase-8 and -3 cleavage, loss of mitochondrial transmembrane potential (Deltapsi(m)), and DNA fragmentation factor activation are attenuated by R77Q Vpr. These data highlight the pathophysiologic role of Vpr in HIV-induced immune disease and suggest a novel mechanism of LTNP. C1 Mayo Clin & Mayo Fdn, Div Infect Dis, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Sect Immunol Res, Rochester, MN 55905 USA. Univ Ottawa, Ottawa Hlth Res Inst, Ottawa, ON, Canada. NIAID, NIH, Bethesda, MD 20892 USA. Univ Montreal, Dept Microbiol & Immunol, Lab Retrovirol Humaine, Montreal, PQ H3C 3J7, Canada. Immunex Corp, Seattle, WA USA. Hlth Canada, Natl HIV AIDS Labs, Ottawa, ON K1A 0L2, Canada. RP Badley, AD (reprint author), Mayo Clin & Mayo Fdn, Div Infect Dis, 200 1st St SW, Rochester, MN 55905 USA. RI badley, andrew/O-9022-2014 NR 29 TC 159 Z9 171 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2003 VL 111 IS 10 BP 1547 EP 1554 DI 10.1172/JCI200316233 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 680KK UT WOS:000182976400015 PM 12750404 ER PT J AU Brambilla, D Jennings, C Aldrovandi, G Bremer, J Comeau, AM Cassol, SA Dickover, R Jackson, JB Pitt, J Sullivan, JL Butcher, A Grosso, L Reichelderfer, P Fiscus, SA AF Brambilla, D Jennings, C Aldrovandi, G Bremer, J Comeau, AM Cassol, SA Dickover, R Jackson, JB Pitt, J Sullivan, JL Butcher, A Grosso, L Reichelderfer, P Fiscus, SA TI Multicenter evaluation of use of dried blood and plasma spot specimens in quantitative assays for human immunodeficiency virus RNA: Measurement, precision, and RNA stability SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; FILTER-PAPER; TYPE-1 RNA; SUBTYPE-B; QUANTIFICATION; TRANSMISSION; INFECTION; SAMPLES; INFANTS; HIV-1 AB Eleven laboratories evaluated the use of dried blood and plasma spots for quantitation of human immunodeficiency virus (HIV) RNA by two commercially available RNA assays, the Roche Amplicor HIV-1 Monitor and the bioMerieux NucliSens HIV-1 QT assays. The recovery of HIV RNA was linear over a dynamic range extending from 4,000 to 500,000 HIV type I RNA copies/ml. The Monitor assay appeared to have a broader dynamic range and seemed more sensitive at lower concentrations. However, the NucliSens assay gave more consistent results and could be performed without modification of the kit. HIV RNA was stable in dried whole blood or plasma stored at room temperature or at -70degreesC for up to I year. Dried blood and dried plasma spots can be used as an easy and inexpensive means for the collection and storage of specimens under field conditions for the diagnosis of HIV infection and the monitoring of antiretroviral therapy. C1 Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 28599 USA. New England Res Ctr, Waltham, MA USA. Rush Presbyterian Hosp, Chicago, IL USA. Univ Alabama, Birmingham, AL USA. Africa Ctr Durban, Durban, South Africa. Univ Calif Los Angeles, Los Angeles, CA USA. Johns Hopkins Univ, Baltimore, MD USA. Columbia Univ, New York, NY USA. Univ Massachusetts, Worcester, MA 01605 USA. Roche Mol Syst, Pleasanton, CA USA. bioMerieux, Durham, NC USA. Natl Inst Child Hlth & Dev, Bethesda, MD USA. RP Fiscus, SA (reprint author), Univ N Carolina, Dept Microbiol & Immunol, 709 Mary Ellen Jones Bldg, Chapel Hill, NC 28599 USA. FU NIAID NIH HHS [U01 AI032907, AI42845, AI32907, AI35712, N01AI85354, P30 AI042845]; NICHD NIH HHS [HD-05-3328] NR 18 TC 102 Z9 105 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2003 VL 41 IS 5 BP 1888 EP 1893 DI 10.1128/JCM.41.5.1888-1893.2003 PG 6 WC Microbiology SC Microbiology GA 679QY UT WOS:000182934500013 PM 12734222 ER PT J AU Ito, Y Grivel, JC Margolis, L AF Ito, Y Grivel, JC Margolis, L TI Real-time PCR assay of individual human immunodeficiency virus type 1 variants in coinfected human lymphoid tissues SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID T-CELL DEPLETION; BIOLOGICAL PHENOTYPE; CHEMOKINE RECEPTORS; CXCR4-TROPIC HIV-1; INFECTION; PROGRESSION; TROPISM; DISEASE; ISOLATE; AIDS AB In the course of infection, human immunodeficiency virus type 1 (IHV-1) mutates, diverging into a "swarm" of viral quasispecies, and the predominance of CCR5- or CXCR4-utilizing quasispecies is strongly associated with the pattern of disease progression. Quantification of CCR5- and CXCR4-utilizing viruses in viral swarms is important in the investigation of the mechanisms of this phenomenon. Here, we report on a new real-time PCR-based methology for the evaluation of replication of individual CCR5- and CXCR4-utilizing variants. The assay is highly reproducible, with a coefficient of variation of <3%, and it accurately estimates the numbers of virus-specific RNA copies even when their difference in the mixture is 2 orders of magnitude. We demonstrate that replications of CCR5- and CXCR4-utilizing variants can be evaluated and distinguished in experimentally coinfected human lymphoid tissue. The assay we developed may facilitate study of the mechanisms of the R5-to-X4 switch in viral swarms in human tissues infected with HIV-1. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Margolis, L (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 9D58,10 Ctr Dr, Bethesda, MD 20892 USA. NR 32 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2003 VL 41 IS 5 BP 2126 EP 2131 DI 10.1128/JCM.41.5.2126.2131.2003 PG 6 WC Microbiology SC Microbiology GA 679QY UT WOS:000182934500049 PM 12734258 ER PT J AU Bertario, L Russo, A Sala, P Varesco, L Giarola, M Mondini, P Pierotti, M Spinelli, P Radice, P AF Bertario, L Russo, A Sala, P Varesco, L Giarola, M Mondini, P Pierotti, M Spinelli, P Radice, P CA Hereditary Colorectal Tumor Reg TI Multiple approach to the exploration of genotype-phenotype correlations in familial adenomatous polyposis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID APC GENE-MUTATIONS; SOMATIC MUTATIONS; DESMOID TUMORS; MODIFIER GENES; COLI; GERMLINE; LESIONS; PREDISPOSITION; CANCER; CHRPE AB Purpose: Familial adenomatous polyposis (FAP), caused by a mutation in the APC gene, is a colorectal cancer predisposition syndrome associated with several other clinical conditions. The severity of the FAP is related to the position of the inherited mutation in the APC gene. We analyzed a large series of FAP patients to identify associations among major clinical manifestations and to correlate the mutation site with specific disease manifestations. Materials and Methods: APC mutations were identified in 953 FAP patients from 187 families. We used unconditional logistic regression models and a method involving generalized estimating equations to investigate the association between genotype and phenotype. We used multiple correspondence analysis to represent the interrelationships of a multiway contingency table of the considered variables. Results: APC germline mutations were located between codons 156 and 2011 of the APC gene. Mutations spanning the region between codons 543 and 1309 were variable, but strongly associated with congenital hypertrophy of retinal pigment epithelium. Mutations between codons 1310 and 2011 were associated with a six-fold risk of desmoid tumors relative to the low-risk reference region (159 to 495). Mutations at codon 1309 were associated with early development of colorectal cancer. Mutations between codons 976 and 1067 were associated with a three- to four-fold increased risk of duodenal adenomas. The cumulative frequency of extracolonic manifestations was highest for mutations between codons 976 and 1067, followed by mutations between 1310 and 2011. Conclusion: Analysis of the relation between APC mutation site and phenotype identifies subgroups of FAP patients at high risk for major extracolonic disease, which is useful for surveillance and prevention. C1 NCI, Dept Expt Oncol, Div Predict & Prevent Med, I-20133 Milan, Italy. NCI, Endoscopy Div, I-20133 Milan, Italy. Natl Canc Inst, Div Expt Oncol, Genoa, Italy. Local Hlth Author Milan, Epidemiol Unit, Milan, Italy. RP Bertario, L (reprint author), NCI, Dept Expt Oncol, Div Predict & Prevent Med, Via Venezian 1, I-20133 Milan, Italy. RI Radice, Paolo/O-3119-2013; OI Pierotti, Marco Alessandro/0000-0002-7431-8332 NR 42 TC 111 Z9 118 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2003 VL 21 IS 9 BP 1698 EP 1707 DI 10.1200/JCO.2003.09.118 PG 10 WC Oncology SC Oncology GA 673MQ UT WOS:000182585100008 PM 12721244 ER PT J AU Adjei, AA Mauer, A Bruzek, L Marks, RS Hillman, S Geyer, S Hanson, LJ Wright, JJ Erlichman, C Kaufmann, SH Vokes, EE AF Adjei, AA Mauer, A Bruzek, L Marks, RS Hillman, S Geyer, S Hanson, LJ Wright, JJ Erlichman, C Kaufmann, SH Vokes, EE TI Phase II study of the farnesyl transferase inhibitor r115777 in patients with advanced non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FARNESYLTRANSFERASE INHIBITORS; CLINICAL-TRIALS; RAS PROTEIN; IN-VITRO; PATHWAY; ASSOCIATION; SCH66336; THERAPY; KINASE; TARGET AB Purpose: This phase 11 study was undertaken to define the efficacy and pharmacadynamics of RI 15777, a farnesyl transferase inhibitor, in the first-line treatment of patients with advanced non-small-cell lung cancer. Patients and Methods: Forty-four patients with measurable stage IIIB (pleural effusion) or stage IV disease received 193 courses of treatment (median, 2.0; range, I to 22) with R115777 300 mg administered orally twice daily for 21 of every 28 days. Buccal mucosa samples and peripheral blood mononuclear cells (PBMCs) were collected before and after 8 days of treatment to evaluate inhibition of farnesyl transferase in Vivo. Results: No objective complete or partial responses were documented. Seven patients (16%; 95% confidence interval [CI], 8% to 31%) had disease stabilization for greater than 6 months. Median survival was 7.7 months (95% Cl, 6.5 to 10.5) and time to progression was 2.7 months (95% Cl, 1.9 to 3.1). The most severe toxicity was neutropenic (9% grade 3, 7% grade 4) and the most common toxicities were anemia (50% grade 1 or 2, 5% grade 3) and anorexic (50% grade 1 or 2, 2% grade 3). Mild peripheral neuropathy occurred in 25% of patients. Evidence of farnesyl transferase inhibition was documented in 83% of patients. Conclusion: Single-agent 11115777 was well tolerated in patients with advanced NSCLC, but demonstrated minimal clinical activity. Inhibition of farnesylation in vivo was consistently documented. On the basis of promising results of farnesyl transferase inhibitor combinations with standard chemotherapy agents, future studies of this agent in NSCLC should be in combination with systemic chemotherapy. C1 Mayo Clin & Mayo Fdn, Div Med Oncol, Dept Oncol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Med, Rochester, MN 55905 USA. Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Chicago, Ctr Canc Res, Chicago, IL 60637 USA. Natl Canc Inst, Bethesda, MD USA. RP Adjei, AA (reprint author), Mayo Clin & Mayo Fdn, Div Med Oncol, Dept Oncol, 200 1st St SW, Rochester, MN 55905 USA. RI Geyer, Susan/E-3112-2011 FU NCI NIH HHS [CA69912, N01-CM-17102-02, P30-CA-14599-27] NR 37 TC 99 Z9 103 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2003 VL 21 IS 9 BP 1760 EP 1766 DI 10.1200/JCO.2003.09.075 PG 7 WC Oncology SC Oncology GA 673MQ UT WOS:000182585100017 PM 12721252 ER PT J AU Parnes, HL Cirrincione, C Aisner, J Berry, DA Allen, SL Abrams, J Chuang, E Cooper, MR Perry, MC Duggan, DB Szatrowski, TP Henderson, IC Norton, L AF Parnes, HL Cirrincione, C Aisner, J Berry, DA Allen, SL Abrams, J Chuang, E Cooper, MR Perry, MC Duggan, DB Szatrowski, TP Henderson, IC Norton, L TI Phase III study of cyclophosphamide, doxorubicin, and fluorouracil (CAF) plus leucovorin versus CAF for metastatic breast cancer: Cancer and Leukemia Group B 9140 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLORECTAL-CARCINOMA; FOLINIC ACID; CHEMOTHERAPY; 5-FLUOROURACIL; TRIAL; ADENOCARCINOMA; COMBINATION; MODULATION; WOMEN; LIFE AB Purpose : To determine whether biochemical modulation with LV (leucovorin) enhances the efficacy of CAF (cyclophosphamide, doxorubicin, and fluorouracil) against metastatic breast cancer. Patients and Methods: Women with histologically confirmed stage IV breast cancer, Cancer and Leukemia Group B (CALGB) performance status 0 to 2, and no prior chemotherapy for metastatic disease were randomly assigned to receive CAF (cyclophosphamide 500 mg/m(2) day 1, doxorubicin 40 mg/m(2) day 1, and fluorouracil [FU] 200 mg/m(2) intravenous bolus days 1 to 5) with or without LV (LV 200 mg/m(2) over 30 minutes days 1 to 5 given I hour before FU). Results: Two hundred forty-two patients were randomly assigned to treatment, 124 patients had visceral crisis and 40 patients had a CALGB performance status score of 2. The median follow-up was 6 years. The two study arms were similar with regard to serious adverse events; four patients died from treatment-related causes, two patients on each study arm. Predictive variables for time to treatment failure and survival were visceral disease and performance status. The overall response rate was 29% for CAF versus 28% for CAF plus LV. The median time to treatment failure (9 months) and median survival (1.7 years) did not differ by treatment arm. Conclusion: Modulation of CAF with LV improved neither response rates nor survival among women with metastatic breast cancer, compared with CAF alone. Multivariate analyses confirmed the prognostic importance of performance status and visceral crisis. However, the overall and complete response rates, response durations, time to treatment failure, and survival were the same in the two treatment arms. (C) 2003 by American Society of Clinical Oncology. C1 NCI, Div Canc Prevent, NIH, Rockville, MD 20852 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. CALGB Stat Ctr, Durham, NC USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Inst Canc Res, New Brunswick, NJ USA. Hoffman LaRoche Inc, Nutley, NJ USA. Cornell Univ, Weill Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY USA. SUNY Upstate Med Ctr, Syracuse, NY USA. N Shore Univ Hosp, Manhasset, NY USA. Univ Missouri, Ellis Fischel Canc Ctr, Columbia, MO USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Parnes, HL (reprint author), NCI, Div Canc Prevent, NIH, 6130 Execut Plaza,EPN Room 2100, Rockville, MD 20852 USA. OI Norton, Larry/0000-0003-3701-9250; Allen, Steven/0000-0002-3482-3182 FU NCI NIH HHS [CA31946] NR 25 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2003 VL 21 IS 9 BP 1819 EP 1824 DI 10.1200/JCO.2003.05.119 PG 6 WC Oncology SC Oncology GA 673MQ UT WOS:000182585100024 PM 12721259 ER PT J AU Abraham, J Agrawal, M Bakke, S Rutt, A Edgerly, M Balis, FM Widemann, B Davis, L Damle, B Sonnichsen, D Lebwohl, D Bates, S Kotz, H Fojo, T AF Abraham, J Agrawal, M Bakke, S Rutt, A Edgerly, M Balis, FM Widemann, B Davis, L Damle, B Sonnichsen, D Lebwohl, D Bates, S Kotz, H Fojo, T TI Phase I trial and pharmacokinetic study of BMS-247550, an epothilone B analog, administered intravenously on a daily schedule for five days SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MICROTUBULE-STABILIZING AGENTS; CLINICAL-TRIALS; BREAST-CANCER; PACLITAXEL; DESIGN; TAXOL AB Purpose : The epothilones are a novel class of nontaxane microtubule-stabilizing agents. BMS-247550 is a semisynthetic analog of the natural product epothilone B. We conducted a phase I study administering BMS-247550 as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. Patients and Methods: Twenty-one patients received BMS-247550 without filgrastim in the first cycle. An additional six patients were enrolled at a starting dose of 8 mg/m(2)/d with filgrastim support. Twenty-one of the 27 patients had received prior paclitaxel, docetaxel, or both. Results: One hundred seven cycles were administered to 27 patients. The maximum-tolerated dose was 6 mg/m(2) Of BMS-247550 administered as a I-hour intravenous infusion daily for 5 consecutive days every 21 days. Dose-limiting toxicity at a dose of 8 mg/m(2)/d was neutropenia with or without filgrastim support. Nonhematologic grade 3 toxicities included fatigue (seven cycles), stomatitis (two cycles), and anorexia (one cycle). The mean terminal half-life of BMS-247550 was 16.8 +/- 6.0 hours, the volume of distribution at steady-state was 798 375 L, and the clearance was 712 +/- 247 mL/min. Objective responses were observed in patients with breast, cervical, and basal cell cancer. Reductions in CA-125 levels were noted in patients with ovarian cancer. Conclusion: The recommended phase 11 dose of BMS-247550 on the daily schedule for 5 days is 6 mg/m(2)/d. Neutropenia was dose limiting, but higher doses were tolerated by a large fraction of patients with filgrastim support. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting. (C) 2003 by American Society of Clinical Oncology. C1 NCI, Canc Res Ctr, Bethesda, MD 20892 USA. W Virginia Univ, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. RP Fojo, T (reprint author), NCI, Canc Res Ctr, Blg 10,Rm 12N2265,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 26 TC 107 Z9 109 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2003 VL 21 IS 9 BP 1866 EP 1873 DI 10.1200/JCO.2003.03.063 PG 8 WC Oncology SC Oncology GA 673MQ UT WOS:000182585100030 PM 12721265 ER PT J AU Leverich, GS Altshuler, LL Frye, MA Suppes, T Keck, PE McElroy, SL Denicoff, KD Obrocea, G Nolen, WA Kupka, R Walden, J Grunze, H Perez, S Luckenbaugh, DA Post, RM AF Leverich, GS Altshuler, LL Frye, MA Suppes, T Keck, PE McElroy, SL Denicoff, KD Obrocea, G Nolen, WA Kupka, R Walden, J Grunze, H Perez, S Luckenbaugh, DA Post, RM TI Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar Network SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CHILDHOOD SEXUAL ABUSE; STRESSFUL LIFE EVENTS; MAJOR DEPRESSION; LITHIUM TREATMENT; EMOTIONAL ABUSE; MOOD DISORDERS; FAMILY HISTORY; RISK-FACTORS; BEHAVIOR; ILLNESS AB Background: Clinical factors related to suicide and suicide attempts have been studied much more extensively in unipolar depression compared with bipolar disorder. We investigated demographic and course-of-illness variables to better understand the incidence and potential clinical correlates of serious suicide attempts in 648 outpatients with bipolar disorder. Method: Patients with bipolar I or II disorder (DSM-IV criteria) diagnosed with structured interviews were evaluated using self-rated and clinician-rated questionnaires to assess incidence and correlates of serious suicide attempts prior to study entry. Clinician prospective ratings of illness severity were compared for patients with and without a history of suicide attempt. Results: The 34% of patients with a history of suicide attempts, compared with those without such a history, had a greater positive family history of drug abuse and suicide (or attempts); a greater personal history of early traumatic stressors and more stressors both at illness onset and for the most recent episode: more hospitalizations for depression; a course of increasing severity of mania; more Axis I, II, and III comorbidities; and more time ill on prospective follow-up. In a hierarchical logistic regression, a history of sexual abuse, lack of confidant prior to illness onset, more prior hospitalizations for depression, suicidal thoughts when depressed, and cluster B personality disorder remained significantly associated with a serious suicide attempt. Conclusion: Our retrospective findings, supplemented by prospective follow-up, indicate that a history of suicide attempts is associated with a more difficult course of bipolar disorder and the occurrence of more psychosocial stressors at many different time domains. Greater attention to recognizing those at highest risk for suicide attempts and therapeutic efforts aimed at some of the correlates identified here could have an impact on bipolar illness-related morbidity and mortality. C1 NIMH, Biol Psychiat Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. VA Med Ctr, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Bipolar Disorder Clin, Dept Psychiat, Dallas, TX USA. Univ Texas, SW Med Ctr, Res Program, Dept Psychiat, Dallas, TX USA. Univ Cincinnati, Coll Med, Dept Psychiat, Biol Psychiat Program, Cincinnati, OH USA. Univ Utrecht, Med Ctr, Utrecht, Netherlands. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Univ Freiburg, Dept Psychiat & Psychotherapy, Freiburg, Germany. Univ Munich, Psychiat Clin, Munich, Germany. RP NIMH, Biol Psychiat Branch, Dept Hlth & Human Serv, NIH, Bldg 10,Room 3S 239,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. EM levericg@intra.nimh.nih.gov RI Nolen, Willem/E-9006-2014 FU NIMH NIH HHS [R01 MH079261] NR 82 TC 200 Z9 207 U1 2 U2 12 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2003 VL 64 IS 5 BP 506 EP 515 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 682WC UT WOS:000183114500003 PM 12755652 ER PT J AU Cote, LR Bornstein, MH AF Cote, LR Bornstein, MH TI Cultural and parenting cognitions in acculturating cultures 1. Cultural comparisons and developmental continuity and stability SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Review DE parenting; cognitions; acculturation; Japanese American; Latin American ID UNITED-STATES; SOCIAL-BEHAVIOR; CHILD-BEHAVIOR; MOTHERS; SELF; AMERICAN; JAPAN; ATTRIBUTIONS; KNOWLEDGE; FAMILIES AB This longitudinal study evaluated cultural differences and developmental continuity and stability in cultural cognitions (acculturation, individualism, collectivism) and parenting cognitions (attributions, self-perceptions, and knowledge) in 86 Japanese American and South American acculturating mothers when their children were 5 and 20 months of age. South American mothers were more collectivistic than Japanese American mothers. Cultural group and attribution differences emerged for mothers' parenting attributions in successful situations, whereas child age and attribution differences emerged for parenting attributions in unsuccessful situations. Japanese American mothers' feelings of competence increased over time. South American mothers were more satisfied in the parenting role than Japanese American mothers. Mothers' knowledge of parenting increased over time in both groups. Mothers' cultural cognitions were stable, as were Japanese-American mothers' parenting cognitions. This study provides insight into the differential influence of cultural background on the acculturation of cultural and parenting cognitions in two U.S. acculturating groups. C1 NICHHD, Bethesda, MD 20892 USA. RP Cote, LR (reprint author), NICHHD, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. NR 108 TC 20 Z9 20 U1 1 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD MAY PY 2003 VL 34 IS 3 BP 323 EP 349 DI 10.1177/0022022103253185 PG 27 WC Psychology, Social SC Psychology GA 672NN UT WOS:000182527200006 ER PT J AU Bornstein, MH Cote, LR AF Bornstein, MH Cote, LR TI Cultural and parenting cognitions in acculturating cultures 2. Patterns of prediction and structural coherence SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Review DE parenting; acculturation; Japanese American; Latin American; cognitions ID MOTHER-INFANT INTERACTION; SOUTH-AMERICAN FAMILIES; UNITED-STATES; JAPANESE-AMERICAN; MATERNAL-BEHAVIOR; ETHNIC-GROUPS; ATTRIBUTIONS; SELF; KNOWLEDGE; SOCIALIZATION AB This longitudinal study evaluated prediction and coherence in cultural (acculturation, individualism, collectivism) and parenting cognitions (attributions, self-perceptions, knowledge) in 86 Japanese American and South American acculturating mothers. Mothers' cultural cognitions when their infants were 5 months old predicted some parenting cognitions 15 months later, particularly among Japanese American mothers. Coherence among mothers' attributions obtained in both cultural groups when their infants were both 5 and 20 months of age and among Japanese American mothers' self-perceptions of parenting at both time periods. Although a few relations across types of parenting cognitions were found, domains of parenting cognitions were relatively independent. This study provides insight into the nature and structure of cultural and parenting cognitions in two U.S. acculturating groups. C1 NICHHD, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. NR 102 TC 14 Z9 15 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD MAY PY 2003 VL 34 IS 3 BP 350 EP 373 DI 10.1177/0022022103253186 PG 24 WC Psychology, Social SC Psychology GA 672NN UT WOS:000182527200007 ER PT J AU de Sereday, MS Damiano, MM Gonzalez, CD Bennett, PH AF de Sereday, MS Damiano, MM Gonzalez, CD Bennett, PH TI Diagnostic criteria for gestational diabetes in relation to pregnancy outcome SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE gestational diabetes; diagnostic criteria; macrosomia; cut-off points; predictive value ID GLUCOSE-TOLERANCE AB Objectives: To determine which of the American Diabetes Association (ADA) or World Health Organization (WHO) plasma glucose criteria for gestational diabetes mellitus (GDM) best predicts poor fetal outcome. To determine whether an alternative cut-off point would result in increased predictive value and greater diagnostic effectiveness in pregnancies at high risk for GDM. Research design and methods: A sample of 473 successive apparently normal pregnant women attending the Obstetric Department were screened for GDM using both the ADA and the WHO criteria. Between 26 and 30 weeks of gestation, they underwent, on subsequent days, a screening test with a 50-g oral glucose load and two oral glucose tolerance tests (OGTTs) with 75 and 100 g of glucose according to the WHO and the ADA recommendations, respectively. From this group, we identified 99 women at high risk for GDM, who did not attend their pregnancy follow-up and whose delivery records were recovered at our hospital or in neighbouring hospitals. This unusual situation enabled us to study the natural history and outcome of their pregnancy in spite of not receiving special management usually provided to such women. As macrosomia was expected to be the most frequent undesirable foetal outcome, sensitivity and specificity calculations have been based on this outcome. Results: The study population (n = 99) had a median parity of two and 14% had abnormal results in the 2-h, 75-g load test (WHO) vs. 6% in the 100-g test (ADA). Optimal cut-off points for each test were lower than those recommended for diagnosis by the ADA and the WHO. The optimal sensitivity for the 1-h, 50-g test was 66.7% (cut-off 137 mg/dl), and for the 2-h, 75-g test (cut-off 119 mg/dl). The best specificity and positive predictive value was for this last test with a cut-off point of 140 mg/dl in the second hour. Conclusions: The standard 2-h cut-off value of 140 mg/dl for the 75-g test, as now recommended by WHO, was optimal for predicting macrosomia. Based on the sensitivity and specificity for macrosomia, the 1-h, 50-g screening test had an optimal cut-off point of 137 mg/dl (vs. 140 mg/dl recommended by ADA). The 2-h, 75-g OGTT value using a cut-off point of 119 mg/dl had equivalent sensitivity, specificity, and positive predictive value. In contrast, the 100-g OGTT had much lower levels of sensitivity, but higher specificity and higher positive predictive value. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Argentine Diabet Soc, Buenos Aires, DF, Argentina. Pedro Fiorito Hosp, Endocrinol & Diabet Unit, Buenos Aires, DF, Argentina. Univ Buenos Aires, Dept Pharmacol, Sch Med, Buenos Aires, DF, Argentina. NIH, Phoenix, AZ USA. RP de Sereday, MS (reprint author), Rodriguez Pena 1838-1,Piso 4, RA-1014 Buenos Aires, DF, Argentina. NR 13 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAY-JUN PY 2003 VL 17 IS 3 BP 115 EP 119 DI 10.1016/S1056-8727(02)00173-3 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 679LQ UT WOS:000182924200001 PM 12738394 ER PT J AU Nilsson, O Chrysis, D Pajulo, I Boman, A Holst, M Rubinstein, J Ritzen, EM Savendahl, L AF Nilsson, O Chrysis, D Pajulo, I Boman, A Holst, M Rubinstein, J Ritzen, EM Savendahl, L TI Localization of estrogen receptors-alpha and -beta and androgen receptor in the human growth plate at different pubertal stages SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID HORMONE-RELATED PROTEIN; SEX STEROIDS; CONSTITUTIONAL DELAY; CARTILAGE CELLS; INDIAN HEDGEHOG; BONE-FORMATION; EXPRESSION; RAT; RABBIT; CHONDROCYTES AB Sex steroids are required for a normal pubertal growth spurt and fusion of the human epiphyseal growth plate. However, the localization of sex steroid receptors in the human pubertal growth plate remains controversial. We have investigated the expression of estrogen receptor (ER) alpha, ERbeta and androgen receptor (AR) in biopsies of proximal tibial growth plates obtained during epiphyseal surgery in 16 boys and eight girls. All pubertal stages were represented (Tanner stages 1-5). ERalpha, ERbeta and AR were visualized with immunohistochemistry and the number of receptor-positive cells was counted using an image analysis system. Percent receptor-positive chondrocytes were assessed in the resting, proliferative and hypertrophic zones and evaluated for sex differences and pubertal trends. Both ERalpha- and ERbeta-positive cells were detected at a greater frequency in the resting and proliferative zones than in the hypertrophic zone (64 +/- 2%, 64 +/- 2% compared with 38 +/- 3% for ERalpha, and 63 3%, 66 +/- 3% compared with 53 3% for ERbeta), whereas AR, was more abundant in the resting (65 +/- 3%) and hypertrophic zones (58 +/- 3%) than in the proliferative zone (41 +/- 3%). No sex difference in the patterns of expression was detected. For ERalpha and AR, the percentage of receptor-positive cells was similar at all Tanner pubertal stages, whereas ERbeta showed a slight decrease in the proliferative zone during pubertal development (P<0(.)05). In summary, our findings suggest that ERalpha, ERbeta and AR are expressed in the human growth plate throughout pubertal development, with no difference between the sexes. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Dept Woman & Child Hlth, Pediat Endocrinol Unit, Stockholm, Sweden. Tampere Univ Hosp, Dept Pediat Surg, Tampere, Finland. Karolinska Inst, Dept Surg Sci, Stockholm, Sweden. Columbia Univ, New York, NY 10032 USA. RP Nilsson, O (reprint author), NICHD, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. NR 43 TC 79 Z9 82 U1 2 U2 3 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD MAY PY 2003 VL 177 IS 2 BP 319 EP 326 DI 10.1677/joe.0.1770319 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 681YV UT WOS:000183063900015 PM 12740020 ER PT J AU Walsh, PJ Mayer, GD Medina, M Bernstein, ML Barimo, JF Mommsen, TP AF Walsh, PJ Mayer, GD Medina, M Bernstein, ML Barimo, JF Mommsen, TP TI A second glutamine synthetase gene with expression in the gills of the gulf toadfish (Opsanus beta) SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE glutamine synthetase; toadfish; ureotely; ornithine-urea cycle; ammonia detoxification; Opsanus beta; ammonia excretion; gill; ORF; UTR ID PULSATILE UREA EXCRETION; CARBAMOYL-PHOSPHATE; NITROGEN-METABOLISM; BOSTRICHTHYS-SINENSIS; BATRACHOIDID FISHES; MESSENGER-RNA; LIVER; MUSCLE; CYCLE; PURIFICATION AB We characterized the expression of the nitrogen metabolism enzyme glutamine synthetase [GSase; L-glutamate: ammonia ligase (ADP-forming), E.C. 6.3.1.2] in tissues of the gulf toadfish Opsanus beta subjected to unconfined (ammonotelic) and confined (ureotelic) conditions. Enzymological results demonstrate that mass-specific GSase activities rank, in the order of brain > liver > stomach approximate to kidney > intestine > gill > heart/spleen > muscle. When tissue mass is used to calculate a glutamine synthetic potential, the liver has the greatest, followed by muscle > stomach and intestine, with minor. contributions from the remaining tissues. Additionally, during confinement stress, GSase activity increases significantly only in liver (fivefold) and muscle (twofold), tissues that previously showed significant expression of the other enzymes of urea synthesis. Western analyses of samples on SDS gels demonstrated that GSase-specific protein content reflected enzyme activity, and all tissues except muscle had a single, similarly sized GSase subunit of 49.4 kDa; muscle showed staining of two bands of 36.8 and 98.9 kDa, which may possibly result from another gene product or post-translational modification. RT-PCR and RACE-PCR revealed the presence of a second GSase cDNA from gill tissue that shares only 73% nucleotide and amino acid sequence similarity with the GSase cDNA previously cloned from liver, and that lacks a mitochondrial leader-targeting sequence. RT-PCR and restriction digestion experiments demonstrated that mRNA from the original 'liver' GSase is expressed in all tissues examined (liver, gill, stomach, intestine, kidney, brain and muscle), whereas the new 'gill' form shows expression primarily, in the gill. Gill GSase activity shows apparently exclusive expression in the soluble compartment, while other tissues expressing the 'liver' form show both cytoplasmic and mitochondrial activities. Phylogenetic analysis of a number of GSases demonstrates that the toadfish gill GSase has a greater affinity for a clade that includes the Xenopus GSase genes and one of two Fugu GSase genes, than it has for a clade containing the toadfish liver GSase and other described teleost GSase genes. The results are discussed in the context of a prior hypothesis on an ammonia-trapping mechanism in the gill of the toadfish. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. Joint Genome Inst, Genomic Divers Lab, Walnut Creek, CA 94598 USA. Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada. RP Walsh, PJ (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, 4600 Rickenbacker Causeway, Miami, FL 33149 USA. RI Mayer, Gregory/K-4496-2012; Mayer, Gregory/A-8459-2017 OI Mayer, Gregory/0000-0002-2652-9856; Mayer, Gregory/0000-0002-2652-9856 FU NIEHS NIH HHS [ES07320, ES 05705] NR 35 TC 35 Z9 37 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 MAY PY 2003 VL 206 IS 9 BP 1523 EP 1533 DI 10.1242/jeb.00251 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 677JQ UT WOS:000182804100019 PM 12654891 ER PT J AU Sugimoto, Y Tsukahara, S Sato, S Suzuki, M Nunoi, H Malech, HL Gottesman, MM Tsuruo, T AF Sugimoto, Y Tsukahara, S Sato, S Suzuki, M Nunoi, H Malech, HL Gottesman, MM Tsuruo, T TI Drug-selected co-expression of P-gtycoprotein and gp91 in vivo from an MDR1-bicistronic retrovirus vector Ha-MDR-IRES-gp91 SO JOURNAL OF GENE MEDICINE LA English DT Article DE P-glycoprotein; drug resistance; chronic granulomatous disease; gene therapy; hematopoietic stem cell; bicistronic retrovirus vector ID MULTIDRUG-RESISTANCE GENE; STEM-CELL TRANSPLANTATION; CHRONIC GRANULOMATOUS-DISEASE; THYMIDINE KINASE GENE; HEMATOPOIETIC-CELLS; BONE-MARROW; MEDIATED TRANSFER; EX-VIVO; MULTIDRUG-RESISTANCE-1 GENE; TRANSGENIC MICE AB Background Retroviral transduction of human hematopoietic stem cells is an attractive strategy in gene therapy; however, transduction efficiency and duration of transgene expression may not be satisfactory in current protocols. Co-expression of a human multidrug resistance gene (MDR1) with a therapeutic gene affords selectable growth advantage to genetically modified cells. Methods A bicistronic retrovirus vector, Ha-MDR-IRES-gp91, was constructed for the co-expression of MDR1 and gp91, a gene responsible for X-linked chronic granulomatous disease (X-CGD). Drug-selected co-expression of P-glycoprotein and gp91 was evaluated in transduced cells. Results Epstein-Barr virus-transformed B cells from X-CGD patients transduced with Ha-MDR-IRES-gp91 co-expressed human P-glycoprotein and gp91, and acquired superoxide-generating activity. Human CD34-positive cells from an X-CGD patient were transduced with Ha-MDR-IRES-gp91 and subsequently treated with 2 ng/ml vincristine. After 13 days, 20% of Ha-MDR-IRES-gp91-transduced cells were P-glycoprotein- and gp91-positive by FACS analysis. The superoxide-generating activity of the transduced population was 27% of that of normal cells. Mice transplanted with Ha-MDR-IRES-gp91-transduced bone marrow cells showed co-expression of P-glycoprotein and gp91 in peripheral blood mononuclear cells. By administering paclitaxel, the proportions of P-glycoprotein- and gp91-positive cells were increased in all the four mice examined. When mice transplanted with Ha-MDR-IRESgp91-transduced cells were repeatedly administered paclitaxel, the ratios of P-glycoprotein- and gp91-positive cells were maintained for over 1 year. Conclusions These results suggest that MDR1-bicistronic vectors may be useful to select the transduced hematopoietic cells in vivo. This may lead to the sustained expression of transgenes in the blood cells of patients treated with stem cell gene therapy. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Div Mol Biotherapy, Toshima Ku, Tokyo 1708455, Japan. Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Div Expt Chemotherapy, Tokyo 1708455, Japan. Miyazaki Med Coll, Dept Pediat, Miyazaki 8891692, Japan. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan. RP Sugimoto, Y (reprint author), Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Div Mol Biotherapy, Toshima Ku, 1-37-1 Kami Ikebukuro, Tokyo 1708455, Japan. NR 30 TC 15 Z9 17 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAY PY 2003 VL 5 IS 5 BP 366 EP 376 DI 10.1002/jgm.362 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 689KZ UT WOS:000183493100002 PM 12731085 ER PT J AU Rakoczy, EP Lai, CM Brankov, M Redmond, MT Zhou, X Narfstrom, K AF Rakoczy, EP Lai, CM Brankov, M Redmond, MT Zhou, X Narfstrom, K TI rAAV mediated RPE65 gene therapy of mouse and dog models of Leber's Congenital Amaurosis SO JOURNAL OF GENE MEDICINE LA English DT Meeting Abstract CT 3rd Meeting of the Australasian-Gene-Therapy-Society CY APR 30-MAY 02, 2003 CL QUEENSLAND INST MED RES BRISBANE, BRISBANE, AUSTRALIA SP Australasian Gene Therapy Soc HO QUEENSLAND INST MED RES BRISBANE C1 Lions Eye Inst, Nedlands, WA 6009, Australia. NEI, Retinal Cell & Mol Biol Lab, Bethesda, MD USA. Univ N Carolina, Gene Therapy Ctr, Virus Vector Cort Facil, Chapel Hill, NC 27515 USA. Univ Missouri, Columbia, MO USA. Univ Western Australia, Ctr Ophthalmol & Vis Sci, Nedlands, WA 6009, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAY PY 2003 VL 5 IS 5 MA O6 BP S5 EP S5 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 689KZ UT WOS:000183493100016 ER PT J AU Nascimbeni, M Rehermann, B AF Nascimbeni, M Rehermann, B TI Chronic HCV infection and the clonality of intrahepatic T cells SO JOURNAL OF HEPATOLOGY LA English DT Editorial Material ID HEPATITIS-C VIRUS; PERIPHERAL-BLOOD; CYTOTOXIC LYMPHOCYTES; PEPTIDE RECOGNITION; ANTIGEN RECEPTOR; IMMUNE-RESPONSE; ELDERLY HUMANS; HUMAN LIVER; SPECIFICITY; EXPANSIONS C1 NIDDK, Liver Dis Sect, DDB, NIH,DHHS, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), NIDDK, Liver Dis Sect, DDB, NIH,DHHS, 10 Ctr Dr,Room 9B16, Bethesda, MD 20892 USA. NR 40 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAY PY 2003 VL 38 IS 5 BP 677 EP 680 DI 10.1016/S0168-8278(03)00121-1 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 680GQ UT WOS:000182968300018 PM 12713882 ER PT J AU Shillingford, JM Miyoshi, K Robinson, GW Bierie, B Cao, YX Karin, M Hennighausen, L AF Shillingford, JM Miyoshi, K Robinson, GW Bierie, B Cao, YX Karin, M Hennighausen, L TI Proteotyping of mammary tissue from transgenic and gene knockout mice with immunohistochemical markers: a tool to define developmental lesions SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE proteotyping; mammary; development; immunohistochemistry; markers ID GLAND DEVELOPMENT; SECRETORY EPITHELIUM; STAT3; DIFFERENTIATION; ACTIVATION; PROLIFERATION; COTRANSPORTER; DISRUPTION; INVOLUTION; APOPTOSIS AB Through the use of transgenic and gene knockout mice, several studies have identified specific genes required for the functional development of mammary epithelium. Although histological and milk protein gene analyses can provide useful information regarding functional differentiation, they are limited in their ability to precisely define the molecular lesions. For example, mice that carry a mutation in one of the subunits of the IkappaB kinase, IKKalpha, cannot lactate despite the presence of histologically normal alveolar compartment and the expression of milk protein genes. To further define and understand such lesions on a molecular level, we sought evidence for proteins that are differentially expressed during mammary gland development with a view to generating a tissue proteotype. Using database screens and immunolnistochemical analyses, we have identified three proteins that exhibit distinct profiles. Here, using mouse models as test biological systems, we demonstrate the development and application of mammary tissue proteotyping and its use in the elucidation of specific developmental lesions. We propose that the technique of proteotyping will have wide applications in the analyses of defects in other mouse models. C1 NIDDK, Lab Genet & Physiol, Bethesda, MD 20892 USA. Univ Tokushima, Sch Dent, Dept Biochem, Tokushima, Japan. Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. RP Shillingford, JM (reprint author), NIDDK, Lab Genet & Physiol, Bethesda, MD 20892 USA. EM jonshi@helix.nih.gov RI Robinson, Gertraud/I-2136-2012 NR 25 TC 40 Z9 41 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAY PY 2003 VL 51 IS 5 BP 555 EP 565 PG 11 WC Cell Biology SC Cell Biology GA 674HK UT WOS:000182631200001 PM 12704203 ER PT J AU Riley, JP Rosenberg, SA Parkhurst, MR AF Riley, JP Rosenberg, SA Parkhurst, MR TI Stimulation of tumor-reactive T lymphocytes using mixtures of synthetic peptides derived from tumor-associated antigens with diverse MHC binding affinities SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE reverse immunology; T lymphocytes; tumor-associated antigen; MHC binding affinity; immunotherapy; cancer; peptides ID HUMAN DENDRITIC CELLS; TYROSINASE-RELATED PROTEIN-2; RECOMBINANT VACCINIA VIRUS; MELANOMA ANTIGEN; CLASS-I; CTL EPITOPES; PHASE-I; ANTITUMOR IMMUNITY; CANCER ANTIGENS; GENE-EXPRESSION AB The use of reverse immunology may be necessary to identify new tumor-associated antigens, particularly for cancers, against which tumor-reactive T cell populations have been difficult to establish. One approach has been to screen peptides derived from a candidate antigen with high major histocompatibility complex (MHC) binding affinities for the induction of tumor-reactive T lymphocytes in vitro. However, many candidate antigens that are overexpressed in tumors are nonmutated self-proteins, and unlike foreign or mutated proteins, immunodominant epitopes may not be expressed at high density on the surface of tumor cells. Therefore, to identify tumor-associated epitopes, it may be necessary to screen large panels of peptides with wide ranges of MHC binding affinities. The current methodology of stimulating peripheral blood lymphocytes (PBL) from donors expressing the MHC molecule of interest with individual peptides is impractical for screening such large panels. Therefore, we evaluated the use of mixtures of peptides with variable MHC binding affinities for the induction of tumor-reactive T lymphocytes with the melanoma antigens gp 100 and an alternate isoform of tyrosinase-related protein 2 (TRP2-6b) as models. A mixture of 10 known human leukocyte antigen (HLA)-A*0201-restricted peptides from gp100 induced melanoma-reactive cytotoxic T lymphoycte (CTL) from multiple patients with metastatic melanoma. The majority of these T cell populations recognized the known immunodominant epitopes gp100:209-217 and gp100:280-288, even though the HLA-A*0201 binding affinities of these peptides were much lower than other peptides in the mixture. Similarly, melanoma-reactive CTL were generated with a mixture of HLA-A*0201-restricted peptides from TRP2-6b, and these responses were directed against the previously identified tumor-associated epitopes TRP2-6b:180-188, TRP2-6b:288-296 and TRP2-6b:403-411. These results suggest that the use of peptide mixtures may facilitate the identification of new tumor-associated antigens through the application of reverse immunology. Published by Elsevier Science B.V. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Parkhurst, MR (reprint author), NCI, Surg Branch, NIH, Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC003811-33] NR 71 TC 6 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAY 1 PY 2003 VL 276 IS 1-2 BP 103 EP 119 DI 10.1016/S0022-1759(03)00078-4 PG 17 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 680BV UT WOS:000182957200010 PM 12738363 ER PT J AU Niederberger, N Holmberg, K Alam, SM Sakati, W Naramura, M Gu, H Gascoigne, NRJ AF Niederberger, N Holmberg, K Alam, SM Sakati, W Naramura, M Gu, H Gascoigne, NRJ TI Allelic exclusion of the TCR alpha-chain is an active process requiring TCR-mediated signaling and c-Cbl SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; THYMIC POSITIVE SELECTION; ANTIGEN RECEPTOR; DEVELOPMENTAL REGULATION; TRANSGENIC MICE; DOWN-MODULATION; EXPRESSION; PROTEIN; GENES; DEGRADATION AB Phenotypic allelic exclusion at the TCRalpha locus is developmentally regulated in thymocytes. Many immature thymocytes express two cell surface alpha-chain species. Following positive selection, the vast majority of mature thymocytes and peripheral T cells display a single cell surface alpha-chain. A posttranslational mechanism occurring at the same time as positive selection and TCR upregulation leads to this phenotypic allelic exclusion. Different models have been proposed to explain the posttranslational regulation of the alpha-chain allelic exclusion. In this study, we report that allelic exclusion is not regulated by competition between distinct alpha-chains for a single beta-chain, as proposed by the dueling alpha-chain model, nor by limiting CD3 zeta-chain in mature TCRhigh thymocytes. Our data instead favor the selective retention model where the positive selection signal through the TCR leads to phenotypic allelic exclusion by specifically maintaining cell surface expression of the selected alpha-chain while the nonselected alpha-chain is internalized. The use of inhibitors specific for Lck and/or other Src kinases indicates a role for these protein tyrosine kinases in the signaling events leading to the down-regulation of the nonselectable alpha-chain. Loss of the ubiquitin ligase/TCR signaling adapter molecule c-Cbl, which is important in TCR down-modulation and is a negative regulator of T cell signaling, leads to increased dual alpha-chain expression on the cell surface of double-positive thymocytes. Thus, not only is there an important role for TCR signaling in causing alpha-chain allelic exclusion, but differential ubiquitination by c-Cbl may be an important factor in causing only the nonselected alpha-chain to be down-modulated. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA. RP Gascoigne, NRJ (reprint author), Scripps Res Inst, Dept Immunol, IMM1 R310,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Niederberger, Nathalie/B-1860-2008 FU NIGMS NIH HHS [R01 GM48002] NR 43 TC 18 Z9 19 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2003 VL 170 IS 9 BP 4557 EP 4563 PG 7 WC Immunology SC Immunology GA 672NX UT WOS:000182528100020 PM 12707333 ER PT J AU Verthelyi, D Gursel, M Kenney, RT Lifson, JD Liu, SY Mican, J Klinman, DM AF Verthelyi, D Gursel, M Kenney, RT Lifson, JD Liu, SY Mican, J Klinman, DM TI CpG oligodeoxynucleotides protect normal and SIV-infected macaques from Leishmania infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN IMMUNE CELLS; BACTERIAL-DNA; CUTANEOUS LEISHMANIASIS; PERIPHERAL-BLOOD; INNATE IMMUNITY; HIV-1 INFECTION; CUTTING EDGE; IN-VIVO AB Oligodeoxynucleotides containing CpG motifs (CpG ODNs) mimic microbial DNA and activate effectors of the innate immune response, which limits the spread of pathogens and promotes an adaptive immune response. CpG ODNs have been shown to protect mice from infection with intracellular pathogens. Unfortunately, CpG motifs that optimally stimulate humans are only weakly active in mice, mandating the use of nonhuman primates to monitor the activity and safety of "human" CpG ODNs in vivo. This study demonstrates that CpG ODN treatment of rhesus macaques significantly reduces the severity of the lesions caused by a challenge with Leishmania. Leishmania superinfection is common in immunocompromised hosts, particularly those infected with HIV. This study shows that PBMCs from HIV-infected subjects respond to stimulation with CpG ODNs. To determine whether CpG ODNs can protect retrovirus-infected primates, SIV-infected macaques were treated with CpG ODNs and then challenged with Leishmania. Both lesion size and parasite load were significantly reduced in the CpG-treated animals. These findings support the clinical development of CpG ODNs as immunoprotective agents in normal and HIV-infected patients. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. NCI, AIDS Vaccine Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. NIAID, Immunoregulat Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Verthelyi, D (reprint author), Bldg 29A,Room 3B19,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Gursel, Mayda /H-1812-2012 FU NCI NIH HHS [N01-CO-12400] NR 44 TC 78 Z9 87 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2003 VL 170 IS 9 BP 4717 EP 4723 PG 7 WC Immunology SC Immunology GA 672NX UT WOS:000182528100038 PM 12707351 ER PT J AU Dudley, ME AF Dudley, ME TI To bead or not to bead SO JOURNAL OF IMMUNOTHERAPY LA English DT Editorial Material DE adoptive cell transfer therapy; artificial; APC; CD3 ID CYTOTOXIC T-CELLS; TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; ADOPTIVE TRANSFER; TRANSPLANT RECIPIENTS; MONOCLONAL-ANTIBODIES; PHASE-I; ACTIVATION; PREVENTION; INFUSION AB To bead or not to bead, that is the question posed by Ito et al. in this issue of the Journal of Immunotherapy. The generation of tumor-reactive T cells remains a major impediment to the wider application of adoptive cell transfer (ACT) therapy for the treatment of patients with cancer. Ito et al. used lymph nodes of mice draining implanted sarcomas as an enriched source of tumor antigen-specific cells. They investigated the ex vivo activation of the lymph node cells by artificial antigen presenting cells (aAPCs) for the production of therapeutic T cell cultures. The optimal aAPC consisted of magnetic beads coated with anti-CD3 and anti-CD28 antibodies. Shortterm ex vivo culture with the aAPCs led to a selective expansion and/or activation of tumor antigen specific CD4(+) cells. These results lay a solid foundation for the clinical application of bead-based T cell activation, and promote efforts to develop the therapeutic strategy of in vivo immunization, ex vivo T cell activation, and adoptive cell transfer. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Dudley, ME (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B-08,10 Ctr Dr, Bethesda, MD 20892 USA. NR 24 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2003 VL 26 IS 3 BP 187 EP 189 DI 10.1097/00002371-200305000-00002 PG 3 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 682MM UT WOS:000183095800002 PM 12806272 ER PT J AU Liu, K Rosenberg, SA AF Liu, K Rosenberg, SA TI Interleukin-2-independent proliferation of human melanoma-reactive T lymphocytes transduced with an exogenous IL-2 gene is stimulation dependent SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE cytokines; cytotoxic T lymphocytes; gene therapy; immunotherapy; retroviral transduction ID TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; SIGNALING PATHWAYS; ADOPTIVE TRANSFER; C-MYC; RECEPTOR; CANCER; BCL-2; INDUCTION; GROWTH AB A major obstacle limiting the efficacy of adoptive T-cell transfer (adoptive immunotherapy) to treat patients with cancer is the short survival of the transferred cells. These in vitro activated T cells depend on the growth factor, interleukin (IL)-2, and may undergo apoptosis in vivo when they are transferred. The authors previously reported that the need for an exogenous source of IL-2 could be abrogated in vitro by retrovirally transducing antitumor T lymphocytes with an exogenous IL-2 gene. Here they report that this growth of IL-2 transductants depended on restimulation of the T-cell receptor complex and appeared to be regulated at the transcriptional level of the transduced IL-2 gene. The transduced IL-2 transcript was barely detectable in IL-2-transductants just before they died without restimulation, and they expressed a low level of the CD25 molecule, the alpha chain of the IL-2 trimeric receptor complex. Melanoma-specific tumor-infiltrating lymphocytes (either bulk or CD8(+) cells alone), when transduced with an IL-2 retroviral vector, could produce IL-2 upon tumor stimulation and proliferated after the destruction of autologous tumor cells in the absence of added IL-2. Control vector-transduced tumor-infiltrating lymphocytes failed to do so under the same conditions. These findings provide a foundation for the development of clinical efforts to adoptively transfer melanoma-specific tumor-infiltrating lymphocytes transduced with an IL-2 retroviral vector for the treatment of patients with metastatic melanoma to evaluate the fate and therapeutic effect of these IL-2 gene-modified antitumor T lymphocytes in vivo. C1 NCI, Canc Res Ctr, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Liu, K (reprint author), NCI, Canc Res Ctr, Surg Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 2B08, Bethesda, MD 20892 USA. OI Liu, Kebin/0000-0003-1965-7240 FU Intramural NIH HHS [Z01 SC003811-33] NR 22 TC 26 Z9 28 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2003 VL 26 IS 3 BP 190 EP 201 DI 10.1097/00002371-200305000-00003 PG 12 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 682MM UT WOS:000183095800003 PM 12806273 ER PT J AU Cermelli, C Berti, R Soldan, SS Mayne, M D'ambrosia, JM Ludwin, SK Jacobson, S AF Cermelli, C Berti, R Soldan, SS Mayne, M D'ambrosia, JM Ludwin, SK Jacobson, S TI High frequency of human herpesvirus 6 DNA in multiple sclerosis plaques isolated by laser microdissection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 4th International Conference on Human Herpesvirus 6, 7, and 8 CY MAY 10-12, 2001 CL PARIS, FRANCE ID POLYMERASE CHAIN-REACTION; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HHV-6 INFECTION; FEBRILE CONVULSIONS; BRAIN-TISSUE; VARIANT; VIRUS; HUMAN-HERPESVIRUS-6; ASSOCIATION; LESIONS AB The frequency of human herpesvirus 6 (HHV-6) DNA was assessed in autopsy material from multiple sclerosis (MS) plaques and normal-appearing white matter (NAWM) from brains of persons with MS, healthy brains, and brains of persons with other neurologic diseases. Specific areas from formalin-fixed, paraffin-embedded brain tissue samples were isolated by laser microscope. DNA was extracted from laser microdissected brain material, and HHV-6 genomic sequences were amplified by nested polymerase chain reaction. We analyzed 44 NAWM samples and 64 MS plaques from 13 patients with MS, 46 samples from 13 patients with non-MS neurologic disorders, and 41 samples from 12 healthy control brains. Of the 44 NAWM samples, 7 (15.9%) were positive for HHV-6 DNA sequences, versus 37 (57.8%) of 64 MS plaques (P<.0005). HHV-6 DNA was detected in 10 (21.7%) of 46 samples from patients with non-MS neurologic disorders and in 11 ( 26.8%) of 41 samples from patients without known neurologic disease. Although the frequency of HHV-6 DNA did not differ significantly by sample type, HHV-6 DNA was significantly more common in MS plaques, suggesting that HHV-6 may play a role in MS pathogenesis. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Biostat Branch, NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Neuropharmacol & Mol Biol, Silver Spring, MD USA. George Washington Univ, Inst Biomed Sci, Dept Genet, Washington, DC USA. Univ Modena & Reggio Emilia, Dept Hyg Microbiol & Biostat, Modena, Italy. Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada. Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada. RP Jacobson, S (reprint author), NINDS, Neuroimmunol Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 5B-16, Bethesda, MD 20892 USA. RI Cermelli, Claudio/L-1501-2016 OI Cermelli, Claudio/0000-0003-3396-0000 NR 38 TC 71 Z9 72 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 MAY 1 PY 2003 VL 187 IS 9 BP 1377 EP 1387 DI 10.1086/368166 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 668CX UT WOS:000182273700004 PM 12717618 ER PT J AU Liu, CL Carrington, M Kaslow, RA Gao, XJ Rinaldo, CR Jacobson, LP Margolick, JB Phair, J O'Brien, SJ Detels, R AF Liu, CL Carrington, M Kaslow, RA Gao, XJ Rinaldo, CR Jacobson, LP Margolick, JB Phair, J O'Brien, SJ Detels, R TI Association of polymorphisms in human leukocyte antigen class I and transporter associated with antigen processing genes with resistance to human immunodeficiency virus type 1 infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 14th International AIDS Conference CY JUL 07-12, 2002 CL BARCELONA, SPAIN ID MULTICENTER AIDS COHORT; CYTOTOXIC T-LYMPHOCYTES; HIV-1 INFECTION; HOMOSEXUAL-MEN; DISEASE PROGRESSION; SERONEGATIVE MEN; CELL RESPONSES; VIRAL LOAD; HLA-A; PEPTIDE AB To examine the relationship of human leukocyte antigen (HLA) class I and transporter associated with antigen processing (TAP) genes with resistance to human immunodeficiency virus type 1 (HIV-1) infection, 100 HIV-seronegative men who had been exposed repeatedly to HIV-1 were compared with 184 men who had seroconverted to HIV positive and had lower risk. In the univariate analysis, the HLA-A2 supertype, excluding A*0201 (HLA-A2/6802 supertype; odds ratio [OR], 4.45; 95% confidence interval [CI], 1.33-4.84; P = .009) was associated with resistance to HIV-1 infection; the effect was the result of the presence of the A*0205 subgroup alleles. Susceptibility was associated in univariate analysis with the B*35 Px alleles (OR, 0.29; 95% CI, 0.08-0.99; P = .037), which suggests that differential preferences for amino acids at the C terminus may influence peptide-binding capacity. TAP2 Ala665 was also associated with resistance (OR, 2.26; 95% CI, 1.35-3.79; P = . 002), perhaps because of its higher efficiency in transporting peptides, thus eliciting a greater CD8(+) T cell response, or because of linkage disequilibrium. In multivariate logistic analysis, only the A*0205 subgroup (OR, 5.56; 95% CI, 1.34-23.10; P = .018) and the TAP2 Ala665 (OR, 2.22; 95% CI, 1.28-3.84; P = .005) were associated with resistance. C1 Univ Calif Los Angeles, Dept Epidemiol, Sch Publ Hlth, Los Angeles, CA 90095 USA. SAIC, Basic Res Program, Frederick, MD USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Howard Brown Hlth Ctr, Chicago, IL 60611 USA. RP Detels, R (reprint author), Univ Calif Los Angeles, Dept Epidemiol, Sch Publ Hlth, Box 951772, Los Angeles, CA 90095 USA. NR 50 TC 46 Z9 49 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2003 VL 187 IS 9 BP 1404 EP 1410 DI 10.1086/374394 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 668CX UT WOS:000182273700007 PM 12717621 ER PT J AU Yeh, LH Alayash, AI AF Yeh, LH Alayash, AI TI Redox side reactions of haemoglobin and cell signalling mechanisms SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE blood substitutes; haemoglobin; hypoxia-inducible factor; signalling pathways ID HYPOXIA-INDUCIBLE FACTOR-1; HEME DEGRADATION; HYDROGEN-PEROXIDE; OXYGEN CARRIERS; BOVINE HEMOGLOBIN; BLOOD SUBSTITUTES; TRANSDUCTION; ACTIVATION; METHEMOGLOBIN; OXIDANTS AB Cell-free chemically modified or recombinant haemoglobins developed as oxygen therapeutics are designed to correct oxygen deficit caused by ischaemia in a variety of clinical settings. Oxidative processes, which are in some cases enhanced when modifications are introduced that lower oxygen affinity, can limit the safety of these proteins. Direct cytotoxic effects associated with haemoglobins have been ascribed to the redox reactions between haemoglobin and biological peroxides [i.e. hydrogen peroxide (H2O2), lipid peroxides (LOOH) and peroxynitrite (ONOO-)]. Biochemical changes at the cellular, tissue and organ levels have been documented to occur in response to haemoglobin oxidative reactions. These peroxides have been implicated as regulators of redox sensitive cell signalling pathways. The effects of reactions between haemoglobin and biologically relevant peroxides may be more subtle than oxidative damage and may thus involve perturbation of redox sensitive signalling pathways. In this review, a brief outline of the role of cell-free haemoglobin in oxidative and cell-signalling pathways and the implications of these reactions on the safety and efficacy evaluation of haemoglobin-based oxygen carries are presented. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, 8800 Rockville Pike,NIH Bldg 29,Rm 112, Bethesda, MD 20892 USA. NR 33 TC 19 Z9 20 U1 0 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD MAY PY 2003 VL 253 IS 5 BP 518 EP 526 DI 10.1046/j.1365-2796.2003.01152.x PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 668YA UT WOS:000182323100004 PM 12702029 ER PT J AU Pursley, RH Kakareka, J Salem, G Devasahayam, N Subramanian, S Tschudin, RG Krishna, MC Pohida, TJ AF Pursley, RH Kakareka, J Salem, G Devasahayam, N Subramanian, S Tschudin, RG Krishna, MC Pohida, TJ TI Stochastic excitation and Hadamard correlation spectroscopy with bandwidth extension in RF FT-EPR SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE EPR; Fourier transform; Hadamard transform; noise excitation; correlation spectroscopy ID ELECTRON-PARAMAGNETIC-RESONANCE; DATA-ACQUISITION SYSTEM; DISCRETE ANALYSIS; NMR; TRANSFORM; SOLIDS AB The application of correlation spectroscopy employing stochastic excitation and the Hadamard transform to time-domain Fourier transform electron paramagnetic resonance (FT-EPR) spectroscopy in the radiofrequency (RF) band is described. An existing, time-domain FT-EPR spectrometer system with a Larmor frequency (L-f) of 300 MHz was used to develop this technique by incorporating a pseudo-random pulse sequence generator to output the maximum length binary sequence (MLBS, 10- and I I-bit). Software developed to control the EPR system setup, acquire the signals, and post process the data, is outlined. The software incorporates the Hadamard transform algorithm to perform the required cross-correlation of the acquired signal and the MLBS after stochastic excitation. To accommodate the EPR signals, bandwidth extension was accomplished by sampling at a rate many times faster than the RF pulse repetition rate, and subsequent digital signal processing of the data. The results of these experiments showed that there was a decrease in the total acquisition time, and an improved free induction decay (FID) signal-to-noise (SIN) ratio compared to the conventional coherent averaging approach. These techniques have the potential to reduce the RF pulse power to the levels used in continuous wave (CW) EPR while retaining the advantage of time-domain EPR methods. These methods have the potential to facilitate the progression to in vivo FT-EPR imaging of larger volumes. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Ctr Informat Technol, Div Computat Biosci, Signal Proc & Instrumentat Sect, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Div Intramural Res, Lab Chem Phys, NIH, Bethesda, MD 20892 USA. RP Pursley, RH (reprint author), Ctr Informat Technol, Div Computat Biosci, Signal Proc & Instrumentat Sect, NIH, 12 S Dr,Bldg 12A-2025, Bethesda, MD 20892 USA. OI Kakareka, John/0000-0003-0072-0035 FU Intramural NIH HHS [Z99 CT999999] NR 23 TC 13 Z9 14 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAY PY 2003 VL 162 IS 1 BP 35 EP 45 DI 10.1016/S1090-7807(03)00050-8 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 687JD UT WOS:000183372400002 PM 12762981 ER PT J AU Choyke, PL Dwyer, AJ Knopp, MV AF Choyke, PL Dwyer, AJ Knopp, MV TI Functional tumor imaging with dynamic contrast-enhanced magnetic resonance imaging SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Review DE angiogenesis; magnetic resonance imaging; contrast agent; pharmacokinetic modeling; dynamic ID ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER; GD-DTPA; CAPILLARY-PERMEABILITY; VASCULAR-PERMEABILITY; T-1-WEIGHTED MRI; TRACER KINETICS; MAMMARY-TUMORS; BLOOD-FLOW; ANGIOGENESIS AB Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is the acquisition of serial MRI images before, during, and after the administration of an MR contrast agent. Unlike conventional enhanced MRI, which simply provides a snapshot of enhancement at one point in time, DCE-MRI permits a fuller depiction of the wash-in and wash-out contrast kinetics within tumors, and thus provides insight into the nature of the bulk tissue properties. Such data is readily amenable to two-compartment pharmacokinetic modeling from which parameters based on the rates of exchange between the compartments can be generated. These parameters can be used to generate color-encoded images that aid in the visual assessment of tumors. DCE-MRI is used currently to characterize masses, stage tumors, and noninvasively monitor therapy. While DCE-MRI is in clinical use, there are also a number of limitations, including overlap between malignant and benign inflammatory tissue, failure to resolve microscopic disease, and the inconsistent predictive value of enhancement pattern with regard to clinical outcome. Current research focuses on improving understanding of the meaning of DCE-MRI at a molecular level, evaluating macromolecular and targeted contrast agents, and combining DCE-MRI with other physiologic imaging techniques such as positron emission tomography. Efforts to standardize DCE-MRI acquisition, analysis, and reporting methods will allow wider dissemination of this useful functional imaging technique. C1 NIH, Dept Radiol, Bethesda, MD 20892 USA. Ohio State Univ, Dept Radiol, Columbus, OH 43210 USA. RP Choyke, PL (reprint author), NIH, Dept Radiol, Bldg 10,Room 1C660, Bethesda, MD 20892 USA. NR 63 TC 244 Z9 253 U1 5 U2 30 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAY PY 2003 VL 17 IS 5 BP 509 EP 520 DI 10.1002/jmri.10304 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 674HF UT WOS:000182630800001 PM 12720260 ER PT J AU Petersen, EF Fishbein, KW Laouar, L Spencer, RGS Wenz, JF AF Petersen, EF Fishbein, KW Laouar, L Spencer, RGS Wenz, JF TI Ex vivo magnetic resonance microscopy of an osteochondral transfer SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE OATS; MRI; cartilage; osteochondral transfer; formalin; gadolinium ID HUMAN ARTICULAR-CARTILAGE; SPATIAL VARIATION; KNEE; MRI; T2 AB A 49-year-old woman with right knee pain and a chondral defect on the medial femoral condyle underwent an osteochondral transfer. The patient initially had pain relief, but then sustained a twisting injury and had progressive chondromalacia and pain on the affected side. She subsequently underwent a total knee replacement, and the tissue from the osteochondral transfer (OATS) site was harvested for analysis. In vitro MR micromraging of the excised joint segment revealed undamaged, full-thickness cartilage on the OATS plug, intact cartilage on the posterior condyle, and severely thinned and damaged cartilage on the anterior condyle. Alcian blue-stained sections revealed that proteoglycans were present throughout the OATS core but were nearly absent in the native cartilage. Quantitative T-1 data acquired after equilibration with Gd-DTPA indicated a distribution of matrix fixed charge in the OATS plug and anterior tissue that agreed well with histology and literature observations, while the posterior native cartilage appeared to have fixed charge similar to that of the OATS tissue. Histology revealed poor graft integration between OATS and native cartilage, with a distinct layer of fibrous tissue at the posterior interface. MRI images, by comparison, showed a hypointense feature at the posterior interface but uniform intensity across the anterior interface. Quantitative T-2, magnetization transfer and T-1 data acquired with and without gadolinium contrast showed dependences on depth, location, and pathology that were consistent with measurements reported in the literature for articular cartilage. C1 Johns Hopkins Bayview Med Ctr, Dept Orthoped Surg, Johns Hopkins Cartilage Restorat Ctr, Baltimore, MD 21224 USA. Univ Alberta, Dept Pathol & Med, Edmonton, AB, Canada. NIA, NIH, Gerontol Res Ctr, NMR Unit, Baltimore, MD 21224 USA. RP Wenz, JF (reprint author), Johns Hopkins Bayview Med Ctr, Dept Orthoped Surg, Johns Hopkins Cartilage Restorat Ctr, Baltimore, MD 21224 USA. OI Fishbein, Kenneth/0000-0002-6353-4603 NR 19 TC 16 Z9 18 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAY PY 2003 VL 17 IS 5 BP 603 EP 608 DI 10.1002/jmri.10305 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 674HF UT WOS:000182630800012 PM 12720271 ER PT J AU Policastro, PF Schwan, TG AF Policastro, PF Schwan, TG TI Experimental infection of Ixodes scapularis larvae (acari : ixodidae) by immersion in low passage cultures of Borrelia burgdorferi SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE tick; spirochete; Lyme disease; Peromyscus leucopus; Barbour-Stoenner-Kelly medium ID LYME-DISEASE SPIROCHETE; WHITE-FOOTED MICE; VECTOR TICKS; GENE-EXPRESSION; AMBLYOMMA-VARIEGATUM; TRANSMISSION; CULTIVATION; ACQUISITION; DISSEMINATION; MIGRATION AB We describe a procedure for the introduction of Borrelia burgdorferi, the spirochetal agent of Lyme disease, into larvae of the tick vector Ixodes scapularis. Internalized spirochetes were observed in larvae examined after 15 or 45 min immersion at 32degreesC in liquid culture suspensions of low passage B. burgdorferi strain B31. Larval ticks immersed in low passage strain B31 were able to feed to repletion on white-footed mice. Midguts of larvae contained many spirochetes 1 wk postengorgement, while larvae incubated with high passage strain B31 were free of detectable spirochetes at the same interval. Larvae incubated with low passage strain B31 were competent to transmit the pathogen to mice, as shown by serology, reisolation of B. burgdorferi from mice, and xenodiagnosis. Ticks maintained the infection transstadially to the nymphal stage and transmitted the infection to naive mice, replicating an essential aspect of natural infection. This method requires no special equipment and allows artificial infection of large numbers of ticks at the larval stage. it will facilitate studies of the contribution of specific B, burgdorferi genetic loci to tick colonization. C1 NIAID, NIH, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. RP Policastro, PF (reprint author), NIAID, NIH, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, 903 S 4th St, Hamilton, MT 59840 USA. NR 58 TC 53 Z9 53 U1 0 U2 2 PU ENTOMOL SOC AMER PI LANHAM PA 9301 ANNAPOLIS RD, LANHAM, MD 20706 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD MAY PY 2003 VL 40 IS 3 BP 364 EP 370 DI 10.1603/0022-2585-40.3.364 PG 7 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 681CJ UT WOS:000183019100019 PM 12943118 ER PT J AU Naz, S Alasti, F Mowjoodi, A Riazuddin, S Sanati, MH Friedman, TB Griffith, AJ Wilcox, ER Riazuddin, S AF Naz, S Alasti, F Mowjoodi, A Riazuddin, S Sanati, MH Friedman, TB Griffith, AJ Wilcox, ER Riazuddin, S TI Distinctive audiometric profile associated with DFNB21 alleles of TECTA SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID SYNDROMIC HEARING-LOSS; AUTOSOMAL-DOMINANT; TECTORIAL MEMBRANE; MESSENGER-RNA; MUTATIONS; PROTEINS; IMPAIRMENT; NONSENSE; DOMAIN; FAMILY C1 Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. NIH, Mol Genet Lab, Natl Inst Deafness & Commun Disorders, Rockville, MD 20850 USA. Natl Res Ctr Genet Engn & Biotechnol, Tehran, Iran. RP Riazuddin, S (reprint author), Natl Ctr Excellence Mol Biol, Canal Bank Rd, Lahore 53700, Pakistan. EM riaz@lhr.comsats.net.pk OI Naz, Sadaf/0000-0002-1912-0235 FU NIDCD NIH HHS [Z01DC000060-01, Z01DC000035-06, Z01 DC000039-06] NR 18 TC 32 Z9 34 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD MAY PY 2003 VL 40 IS 5 BP 360 EP 363 DI 10.1136/jmg.40.5.360 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 677TK UT WOS:000182823500011 PM 12746400 ER PT J AU Cheadle, C Vawter, MP Freed, WJ Becker, KG AF Cheadle, C Vawter, MP Freed, WJ Becker, KG TI Analysis of microarray data using Z score transformation SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID GENE-EXPRESSION PROFILE; CDNA MICROARRAYS; CELLS AB High-throughput cDNA microarray technology allows for the simultaneous analysis of gene expression levels for thousands of genes and as such, rapid, relatively simple methods are needed to store, analyze, and cross-compare basic microarray data. The application of a classical method of data normalization, Z score transformation, provides a way of standardizing data across a wide range of experiments and allows the comparison of microarray data independent of the original hybridization intensities. Data normalized by Z score transformation can be used directly in the calculation of significant changes in gene expression between different samples and conditions. We used Z scores to compare several different methods for predicting significant changes in gene expression including fold changes, Z ratios, Z and t statistical tests. We conclude that the Z score transformation normalization method accompanied by either Z ratios or Z tests for significance estimates offers a useful method for the basic analysis of microarray data. The results provided by these methods can be as rigorous and are no more arbitrary than other test methods, and, in addition, they have the advantage that they can be easily adapted to standard spreadsheet programs. C1 NIA, DNA Array Unit, Res Resources Branch, NIH, Baltimore, MD 21221 USA. NIDA, Cellular Neurobiol Branch, Baltimore, MD USA. Univ Calif Irvine, Coll Med, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. RP Becker, KG (reprint author), NIA, DNA Array Unit, Res Resources Branch, NIH, 333 Cassell Dr, Baltimore, MD 21221 USA. OI Becker, Kevin/0000-0002-6794-6656 NR 20 TC 364 Z9 371 U1 0 U2 13 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAY PY 2003 VL 5 IS 2 BP 73 EP 81 DI 10.1016/S1525-1578(10)60455-2 PG 9 WC Pathology SC Pathology GA 671YK UT WOS:000182492800002 PM 12707371 ER PT J AU Davies-Coleman, MT Dzeha, TM Gray, CA Hess, S Pannell, LK Hendricks, DT Arendse, CE AF Davies-Coleman, MT Dzeha, TM Gray, CA Hess, S Pannell, LK Hendricks, DT Arendse, CE TI Isolation of homodolastatin 16, a new cyclic depsipeptide from a Kenyan collection of Lyngbya majuscula SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MARINE CYANOBACTERIA; BIOLOGICAL-ACTIVITY; NATURAL-PRODUCTS; BRINE SHRIMP; DOLASTATIN-16; DIVERSE; CANCER AB An examination of an organic extract of the cyanobacterium Lyngbya majuscula, collected from Wasini Island off the southern Kenyan coast, led to the isolation of the known cyclic depsipeptide antanapeptin A (1), recently isolated from a Madagascan collection of L. majuscula, and a new bioactive cyclic depsipeptide, homodolastatin 16 (2). The structures of these two compounds were determined from NMR and mass spectrometry data. Homodolastatin 16, a higher homologue of the potential anticancer agent dolastatin 16, exhibited moderate activity against oesophageal and cervical cancer cell lines. C1 Rhodes Univ, Dept Chem, Grahamstown, South Africa. NIDDKD, Struct Mass Spect Facil, NIH, Bethesda, MD 20892 USA. Univ Cape Town, Dept Biochem Med, Rondebosch, South Africa. RP Davies-Coleman, MT (reprint author), Rhodes Univ, Dept Chem, Grahamstown, South Africa. EM M.Davies-Coleman@ru.ac.za RI Hess, Sonja/K-4842-2013 OI Hess, Sonja/0000-0002-5904-9816 FU NCI NIH HHS [1-U19-CA67775-07] NR 24 TC 42 Z9 43 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAY PY 2003 VL 66 IS 5 BP 712 EP 715 DI 10.1021/np030014t PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 682AP UT WOS:000183067900030 PM 12762816 ER PT J AU McCarron, RM Ohara, Y Golech, S Lenz, F Spatz, M AF McCarron, RM Ohara, Y Golech, S Lenz, F Spatz, M TI Adrenergic modulation of TNFalpha-induced ICAM-1 expression by human brain endothelium SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 USN, Med Res Ctr, Silver Spring, MD USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 SU 1 BP 5 EP 5 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800020 ER PT J AU Mattson, MP Cutler, R Zhang, S Lu, C Wang, Y Cheng, A AF Mattson, MP Cutler, R Zhang, S Lu, C Wang, Y Cheng, A TI Lipid rafts in neuronal plasticity and neurodegenerative disorders SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 SU 1 BP 23 EP 23 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800078 ER PT J AU Armstrong, RC Nielsen, JA Vana, AC Hudson, LD AF Armstrong, RC Nielsen, JA Vana, AC Hudson, LD TI Regulation of oligodendrocyte lineage cell differentiation: nuclear organization and functional analysis of MYT1 SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 SU 1 BP 26 EP 26 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800092 ER PT J AU Sapko, MT Guidetti, P Yu, P Tagle, DA Schwarcz, R AF Sapko, MT Guidetti, P Yu, P Tagle, DA Schwarcz, R TI A mouse with reduced brain kynurenic acid shows increased susceptibilty to intrastriatal quinolinic acid SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 Maryland Psychiat Res Ctr, Baltimore, MD USA. NIHGR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 SU 1 BP 34 EP 34 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800122 ER PT J AU Lahiri, DK Maloney, B Ge, YW Vrize, FWD Hardy, J AF Lahiri, DK Maloney, B Ge, YW Vrize, FWD Hardy, J TI Characterization of polymorphisms in the APP gene promoter involved in Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. NIA, Lab Neurogenet, NIH, Bethesda, MD USA. RI Maloney, Bryan/C-4924-2011 OI Maloney, Bryan/0000-0003-2364-9649 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 SU 1 BP 45 EP 45 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800160 ER PT J AU Gao, J Stoklosa, J Hammer, JA Quarles, RH AF Gao, J Stoklosa, J Hammer, JA Quarles, RH TI Signal transduction pathways by which myelin-associated glycoprotein (MAG) affects the axonal cytoskeleton SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 NINDS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 SU 1 BP 50 EP 50 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800177 ER PT J AU Kashiwaya, Y Veech, RL AF Kashiwaya, Y Veech, RL TI Ketosis alters mitochondrial energy metabolism rescuing neuronal culture models of Alzheimer's and Parkinson's disease. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 NIAAA, LMBB, DHHS, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 SU 1 BP 62 EP 62 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800222 ER PT J AU Mattson, MP Duan, W Guo, Z Wan, R AF Mattson, MP Duan, W Guo, Z Wan, R TI Lessen thy meals: why it benefits the brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 NIA, Neurosci Lab, Ctr Gerontol Res, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 SU 1 BP 62 EP 62 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800223 ER PT J AU Stevens, B Fields, RD AF Stevens, B Fields, RD TI Differential activity-dependent roles of ATP and adenosine in axon-Schwann cell communication SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 SU 1 BP 86 EP 86 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800305 ER PT J AU Sapko, MT Guidetti, P Yu, P Tagle, DA Schwarcz, R AF Sapko, MT Guidetti, P Yu, P Tagle, DA Schwarcz, R TI A mouse with reduced brain kynurenic acid shows increased susceptibilty to intrastriatal quinolinic acid SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. NIHGR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 SU 1 BP 90 EP 90 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800319 ER PT J AU Rao, M AF Rao, M TI Progenitor cells for therapy SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 SU 1 BP 102 EP 102 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800365 ER PT J AU Kawahara, Y Kwak, S Sun, H Ito, K Hashida, H Aizawa, H Jeong, SY Kanazawa, I AF Kawahara, Y Kwak, S Sun, H Ito, K Hashida, H Aizawa, H Jeong, SY Kanazawa, I TI Human spinal motoneurons express low relative abundance of GluR2 mRNA: an implication for excitotoxicity in ALS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE ALS; AMPA receptor; excitotoxicity; GluR2; quantitative RT-PCR; RNA editing ID AMYOTROPHIC-LATERAL-SCLEROSIS; AMPA RECEPTOR SUBUNIT; CA2+ PERMEABILITY; MESSENGER-RNAS; MOTOR-NEURONS; GLUTAMATE RECEPTORS; NEOCORTICAL NEURONS; HIPPOCAMPAL-NEURONS; ACID RECEPTORS; ION FLOW AB AMPA receptor-mediated neurotoxicity is currently the most plausible hypothesis for the etiology of amyotrophic lateral sclerosis (ALS). The mechanism initiating this type of neuronal death is believed to be exaggerated Ca2+-influx through AMPA receptors, which is critically determined by the presence or absence of the glutamate receptor subunit 2 (GluR2) in the assembly. We have provided the first quantitative measurements of the expression profile of AMPA receptor subunits mRNAs in human single neurons by means of quantitative RT-PCR with a laser microdissector. Among the AMPA subunits, GluR2 shared the vast majority throughout the neuronal subsets and tissues examined. Furthermore, both the expression level and the proportion of GluR2 mRNA in motoneurons were the lowest among all neuronal subsets examined, whereas those in motoneurons of ALS did not differ from the control group, implying that selective reduction of the GluR2 subunit cannot be a mechanism of AMPA receptor-mediated neurotoxicity in ALS. However, the low relative abundance of GluR2 might provide spinal motoneurons with conditions that are easily affected by changes of AMPA receptor properties including deficient GluR2 mRNA editing in ALS. C1 Univ Tokyo, Grad Sch Med, Dept Neurol, Bunkyo Ku, Tokyo 1138655, Japan. Asahikawa Med Coll, Dept Internal Med 1, Asahikawa, Hokkaido 078, Japan. NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Tokyo, Japan. RP Kwak, S (reprint author), Univ Tokyo, Grad Sch Med, Dept Neurol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. NR 49 TC 72 Z9 73 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 IS 3 BP 680 EP 689 DI 10.1046/j.1471-4159.2003.01703.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 667XJ UT WOS:000182259900014 PM 12694394 ER PT J AU Bosetti, F Weerasinghe, GR Rosenberger, TA Rapoport, SI AF Bosetti, F Weerasinghe, GR Rosenberger, TA Rapoport, SI TI Valproic acid down-regulates the conversion of arachidonic acid to eicosanoids via cyclooxygenase-1 and-2 in rat brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE arachidonic acid; bipolar disorder; brain; cyclo-oxygenase; prostaglandin; valproic acid ID BIPOLAR DISORDER; PHOSPHOLIPASE A(2); PSYCHIATRIC-DISORDERS; SIGNAL-TRANSDUCTION; TREATMENT DECREASES; MOLECULAR-BIOLOGY; CHRONIC LITHIUM; PROTEIN-KINASE; PROSTAGLANDIN; METABOLISM AB Sodium valproate, a mood stabilizer, when chronically administered to rats (200 mg/kg i.p. daily for 30 days) significantly reduced the brain protein levels of cyclooxygenase (COX)-1 and COX-2, without altering the mRNA levels of these enzymes. COX activity was decreased, as were the brain concentrations of 11-dehydrothromboxane B-2 and prostaglandin E-2 (PGE(2)), metabolites of arachidonic acid (AA) produced via COX. In contrast, the brain protein level of 5-lipoxygenase and the concentration of its AA metabolite leukotriene B-4 were unchanged. In view of published evidence that lithium chloride administered chronically to rats, like chronic valproate, reduces AA turnover within brain phospholipids, and that lithium post-transcriptionally down-regulates COX-2 but not COX-1 protein level and enzyme activity, these observations suggest that mood stabilizers generally modulate the release and recycling of AA within brain phospholipids, and the conversion of AA via COX-2 to PGE(2) and related eicosanoids. If targeting this part of the 'AA cascade' accounts for their therapeutic action, non-steroidal anti-inflammatory drugs or selective COX-2 inhibitors might prove effective in bipolar disorder. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bosetti, F (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 10,Room 6N202, Bethesda, MD 20892 USA. NR 57 TC 82 Z9 84 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 IS 3 BP 690 EP 696 DI 10.1046/j.1471-4159.2003.01701.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 667XJ UT WOS:000182259900015 PM 12694395 ER PT J AU Chong, NW Chaurasia, SS Haque, R Klein, DC Iuvone, PM AF Chong, NW Chaurasia, SS Haque, R Klein, DC Iuvone, PM TI Temporal-spatial characterization of chicken clock genes: circadian expression in retina, pineal gland, and peripheral tissues SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Bmal1; circadian rhythm; MOP4; peripheral oscillators; pineal gland; retina ID SEROTONIN N-ACETYLTRANSFERASE; HYDROXYLASE MESSENGER-RNA; SUPRACHIASMATIC NUCLEUS; MELATONIN SYNTHESIS; MOLECULAR-BASES; IN-VITRO; RHYTHMS; MOUSE; LOOP; SYSTEM AB The molecular core of the vertebrate circadian clock is a set of clock genes, whose products interact to control circadian changes in physiology. These clock genes are expressed in all tissues known to possess an endogenous self-sustaining clock, and many are also found in peripheral tissues. In the present study, the expression patterns of two clock genes, cBmal1 and cMOP4, were examined in the chicken, a useful model for analysis of the avian circadian system. In two tissues which contain endogenous clocks - the pineal gland and retina - circadian fluctuations of both cBmal1 and cMOP4 mRNAs were observed to be synchronous; highest levels occurred at Zeitgeber time 12. Expression of these genes is also rhythmic in several peripheral tissues; however, the phases of these rhythms differ from those in the pineal gland and retina: in the liver the peaks of cMOP4 and cBmal1 mRNAs are delayed 4-8 h and in the heart they are advanced by 4 h, relative to those in the pineal gland and retina. These results provide the first temporal characterization of cBmal1 and cMOP4 mRNAs in avian tissues: their presence in avian peripheral tissues indicates they may influence temporal features of daily rhythms in biochemical, physiological, and behavioral functions at these sites. C1 Univ Leicester, Glenfield Gen Hosp, Dept Med, Div Cardiol,Clin Sci Wing, Leicester LE3 9QP, Leics, England. Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, Bethesda, MD 20892 USA. RP Chong, NW (reprint author), Univ Leicester, Glenfield Gen Hosp, Dept Med, Div Cardiol,Clin Sci Wing, Leicester LE3 9QP, Leics, England. FU NEI NIH HHS [EY 04864, R01 EY004864] NR 60 TC 45 Z9 47 U1 2 U2 8 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 IS 4 BP 851 EP 860 DI 10.1046/j.1471-4159.2003.01723.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 671QW UT WOS:000182476400003 PM 12716417 ER PT J AU Baptista, MJ O'Farrell, C Daya, S Ahmad, R Miller, DW Hardy, J Farrer, MJ Cookson, MR AF Baptista, MJ O'Farrell, C Daya, S Ahmad, R Miller, DW Hardy, J Farrer, MJ Cookson, MR TI Co-ordinate transcriptional regulation of dopamine synthesis genes by alpha-synuclein in human neuroblastoma cell lines SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE oligonucleotide expression array; Parkinson's disease; quantitative real-time RT-PCR; alpha-synuclein ID PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; IN-VITRO; TYROSINE-HYDROXYLASE; MOUSE MODEL; WILD-TYPE; EXPRESSION; MUTATION; MUTANT; MICE AB Abnormal accumulation of alpha-synuclein in Lewy bodies is a neuropathological hallmark of both sporadic and familial Parkinson's disease (PD). Although mutations in alpha-synuclein have been identified in autosomal dominant PD, the mechanism by which dopaminergic cell death occurs remains unknown. We investigated transcriptional changes in neuroblastoma cell lines transfected with either normal or mutant (A30P or A53T) alpha-synuclein using microarrays, with confirmation of selected genes by quantitative RT-PCR. Gene products whose expression was found to be significantly altered included members of diverse functional groups such as stress response, transcription regulators, apoptosis-inducing molecules, transcription factors and membrane-bound proteins. We also found evidence of altered expression of dihydropteridine reductase, which indirectly regulates the synthesis of dopamine. Because of the importance of dopamine in PD, we investigated the expression of all the known genes in dopamine synthesis. We found co-ordinated downregulation of mRNA for GTP cyclohydrolase, sepiapterin reductase (SR), tyrosine hydroxylase (TH) and aromatic acid decarboxylase by wild-type but not mutant alpha-synuclein. These were confirmed at the protein level for SR and TH. Reduced expression of the orphan nuclear receptor Nurr1 was also noted, suggesting that the co-ordinate regulation of dopamine synthesis is regulated through this transcription factor. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Mayo Clin, Neurogenet Lab, Jacksonville, FL 32224 USA. RP Baptista, MJ (reprint author), NIA, Neurogenet Lab, NIH, Bldg 10 Room 6C103,MSC1589,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Hardy, John/C-2451-2009 FU NINDS NIH HHS [NS 40256] NR 58 TC 81 Z9 87 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2003 VL 85 IS 4 BP 957 EP 968 DI 10.1046/j.1471-4159.2003.01742.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 671QW UT WOS:000182476400013 PM 12716427 ER PT J AU Kasckow, J Mulchahey, JJ Aguilera, G Pisarska, M Nikodemova, M Chen, HC Herman, JP Murphy, EK Liu, Y Rizvi, TA Dautzenberg, FM Sheriff, S AF Kasckow, J Mulchahey, JJ Aguilera, G Pisarska, M Nikodemova, M Chen, HC Herman, JP Murphy, EK Liu, Y Rizvi, TA Dautzenberg, FM Sheriff, S TI Corticotropin-releasing hormone (CRH) expression and protein kinase a mediated CRH receptor signalling in an immortalized hypothalamic cell line SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE hypothalamus; corticotropin-releasing hormone; receptor; SV40 large T antigen; CREB; stress ID MESSENGER-RIBONUCLEIC-ACID; ADENYLATE-CYCLASE ACTIVITY; CENTRAL-NERVOUS-SYSTEM; PARAVENTRICULAR NUCLEUS; RAT HYPOTHALAMUS; CYCLIC-AMP; GENE-EXPRESSION; FACTOR TYPE-1; C-FOS; BRAIN AB Corticotropin-releasing hormone (CRH) is a 41 amino acid neuropeptide which plays an important role in the stress response in the hypothalamus. We describe the development of an immortalized hypothalamic cell line which expresses CRH. We hypothesized that this cell line would possess the relevant characteristics of parvocellular CRH-expressing neurones such as glucocorticoid receptor (GR) expression and vasopressin (VP) coexpression. For production of hypothalamic cells, embryonic day 19 rat pup hypothalami were dissected and dissociated into tissue culture dishes. They were immortalized by retrovirus-mediated transfer of the SV40 large T antigen gene at 3 days of culture and then screened for expression of CRH following dilution cloning. One cell line was chosen (IVB) which exhibited CRH-like immunoreactivity (CRH-LI) and expressed CRH, VP and CRH1 receptor RNA via the reverse transcriptase-polymerase chain reaction. In addition, the cell line expressed the neuronal marker, microtubule-associated protein-2. We verified that the CRH-LI from IVB cell lysates coeluted with CRH standard via reversed-phase high-performance liquid chromatography (HPLC). Furthermore, oxidation of the lysate converted its HPLC profile to that identical with oxidized CRH standard. In addition, IVB cells exhibited high affinity binding to CRH. Incubation of IVB cells with CRH lead to increases in cAMP levels and protein kinase A activity in a concentration-dependent manner. Incubation of IVB cells with CRH also resulted in increases in phospho-cyclic-AMP response element binding protein (CREB) imunostaining as detected by immunocytochemical analysis. Finally, CRH treatment of IVB cell lines has been linked to CREB-mediated gene expression as determined via the PathDetect CREB trans -reporting system. The characteristics of IVB cells, such as CRH and VP coexpression, GR expression and a biologically active CRH-R1-mediated signalling pathway, suggest that this neuronal cell line may serve as model of parvocellular CRH neurones. C1 Univ Cincinnati, Sch Med, Dept Psychiat, Cincinnati, OH 45267 USA. Cincinnati VAMC, Psychiat Serv 116A, Cincinnati, OH USA. Univ Cincinnati, Neurosci Program, Cincinnati, OH USA. Phase 2 Discovery Inc, Cincinnati, OH USA. NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD USA. Univ Cincinnati, Coll Med, Dept Surg, Cincinnati, OH 45267 USA. Axovan Ltd, Innovat Ctr, Allschwil, Switzerland. RP Kasckow, J (reprint author), Univ Cincinnati, Sch Med, Dept Psychiat, 231 Bethesda Ave ML 559, Cincinnati, OH 45267 USA. RI Herman, James/D-4960-2015 OI Herman, James/0000-0003-3571-2406 NR 44 TC 36 Z9 36 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD MAY PY 2003 VL 15 IS 5 BP 521 EP 529 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 666RH UT WOS:000182189900009 PM 12694378 ER PT J AU Quezado, MM Santi, M Ronchetti, R Perez, J Clark, B Ghatak, N AF Quezado, MM Santi, M Ronchetti, R Perez, J Clark, B Ghatak, N TI Analysis of chromosome 7 in intracranial and spinal cord ependymomas by chromogenic in situ hybridization (CISH). SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 79th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 19-22, 2003 CL ORLANDO, FLORIDA SP Amer Assoc Neuropatholgists C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Washington, DC USA. Virginia Commonwealth Univ, MCV Hosp, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2003 VL 62 IS 5 MA 29 BP 545 EP 545 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 680CQ UT WOS:000182959100039 ER PT J AU Santi, M Quezado, M Cassarino, D Evangelista, R Ghatak, N AF Santi, M Quezado, M Cassarino, D Evangelista, R Ghatak, N TI Intramedullary heterotopic adrenocortical oncocytoma of the conus medullaris. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 79th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 19-22, 2003 CL ORLANDO, FL SP Amer Assoc Neuropathologists C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. Natl Canc Inst, NIH, Bethesda, MD USA. BIOPSE Labs, Fortaleza, Ceara, Brazil. MCV Hosp, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2003 VL 62 IS 5 MA 144 BP 574 EP 574 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 680CQ UT WOS:000182959100156 ER PT J AU Wolters, A Sandbrink, F Schlottmann, A Kunesch, E Stefan, K Cohen, LG Benecke, R Classen, J AF Wolters, A Sandbrink, F Schlottmann, A Kunesch, E Stefan, K Cohen, LG Benecke, R Classen, J TI A temporally asymmetric Hebbian rule governing plasticity in the human motor cortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LONG-TERM DEPRESSION; TRANSCRANIAL MAGNETIC STIMULATION; PAIRED ASSOCIATIVE STIMULATION; TIMING-DEPENDENT PLASTICITY; METHYL-D-ASPARTATE; SYNAPTIC PLASTICITY; VISUAL-CORTEX; PYRAMIDAL CELLS; HIPPOCAMPAL-NEURONS; IFCN COMMITTEE AB Synaptic plasticity is conspicuously dependent on the temporal order of the pre- and postsynaptic activity. Human motor cortical excitability can be increased by a paired associative stimulation ( PAS) protocol. Here we show that it can also be decreased by minimally changing the interval between the two associative stimuli. Corticomotor excitability of the abductor pollicis brevis (APB) representation was tested before and after repetitively pairing of single right median nerve simulation with single pulse transcranial magnetic stimulation (TMS) delivered over the optimal site for activation of the contralateral APB. Following PAS, depression of TMS-evoked motor-evoked potentials (MEPs) was induced only when the median nerve stimulation preceded the TMS pulse by 10 ms, while enhancement of cortical excitability was induced using an interstimulus interval of 25 ms, suggesting an important role of the sequence of cortical events triggered by the two stimulation modalities. Experiments using F-wave studies and electrical brain stem stimulation indicated that the site of the plastic changes underlying the decrease of MEP amplitudes following PAS ( 10 ms) was within the motor cortex. MEP amplitudes remained depressed for approximately 90 min. The decrease of MEP amplitudes was blocked when PAS( 10 ms) was performed under the influence of dextromethorphan, an N-methyl-D-aspartate-receptor antagonist, or nimodipine, an L-type voltage-gated calcium-channel antagonist. The physiological profile of the depression of human motor cortical excitability following PAS( 10 ms) suggests long-term depression of synaptic efficacy to be involved. Together with earlier findings, this study suggests that strict temporal Hebbian rules govern the induction of long-term potentiation/long-term depression-like phenomena in vivo in the human primary motor cortex. C1 Univ Wurzburg, Neurol Klin, Dept Neurol, Human Cort Physiol & Motor Control Lab, D-97080 Wurzburg, Germany. Univ Rostock, Dept Neurol, Human Cort Physiol Lab, D-18147 Rostock, Germany. NINDS, Human Cort Physiol Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Classen, J (reprint author), Univ Wurzburg, Neurol Klin, Dept Neurol, Human Cort Physiol & Motor Control Lab, Josef Schneider Str 11, D-97080 Wurzburg, Germany. NR 55 TC 307 Z9 310 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2003 VL 89 IS 5 BP 2339 EP 2345 DI 10.1152/jn.00900.2002 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 676FT UT WOS:000182741200001 PM 12612033 ER PT J AU Petit, L Beauchamp, MS AF Petit, L Beauchamp, MS TI Neural basis of visually guided head movements studied with fMRI SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; SACCADIC EYE-MOVEMENTS; POSTERIOR PARIETAL CORTEX; VESTIBULAR CORTEX; FUNCTIONAL-ANATOMY; HUMAN BRAIN; CINGULATE CORTEX; CORTICAL CONTROL; CEREBRAL-CORTEX; WORKING-MEMORY AB We used event-related fMRI to measure brain activity while subjects performed saccadic eye, head, and gaze movements to visually presented targets. Two distinct patterns of response were observed. One set of areas was equally active during eye, head, and gaze movements and consisted of the superior and inferior subdivisions of the frontal eye fields, the supplementary eye field, the intraparietal sulcus, the precuneus, area MT in the lateral occipital sulcus and subcortically in basal ganglia, thalamus, and the superior colliculus. These areas have been previously observed in functional imaging studies of human eye movements, suggesting that a common set of brain areas subserves both oculomotor and head movement control in humans, consistent with data from single-unit recording and microstimulation studies in nonhuman primates that have described overlapping eye- and head-movement representations in oculomotor control areas. A second set of areas was active during head and gaze movements but not during eye movements. This set of areas included the posterior part of the planum temporale and the cortex at the temporoparietal junction, known as the parieto-insular vestibular cortex ( PIVC). Activity in PIVC has been observed during imaging studies of invasive vestibular stimulation, and we confirm its role in processing the vestibular cues accompanying natural head movements. Our findings demonstrate that fMRI can be used to study the neural basis of head movements and show that areas that control eye movements also control head movements. In addition, we provide the first evidence for brain activity associated with vestibular input produced by natural head movements as opposed to invasive caloric or galvanic vestibular stimulation. C1 NIMH, LBC, Bethesda, MD 20892 USA. Univ Caen, CEA, Grp Imagerie Neurofonct, CNRS,UMR 6095, F-14032 Caen, France. Univ Paris 05, Ctr Cyceron, Caen, France. RP Beauchamp, MS (reprint author), NIMH, LBC, 10 Ctr Dr MSC 1366,Bldg 10,Room 4C104, Bethesda, MD 20892 USA. RI GINSPAN, All/B-8714-2008; Petit, Laurent/D-6583-2011; OI Petit, Laurent/0000-0003-2499-5367; Beauchamp, Michael/0000-0002-7599-9934 NR 71 TC 53 Z9 54 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2003 VL 89 IS 5 BP 2516 EP 2527 DI 10.1152/jn.00988.2002 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 676FT UT WOS:000182741200021 PM 12611944 ER PT J AU Maltenfort, MG Burke, RE AF Maltenfort, MG Burke, RE TI Spindle model responsive to mixed Fusimotor inputs and testable predictions of beta feedback effects SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CAT MUSCLE-SPINDLES; STATIC GAMMA-AXONS; IA FIBERS; SKELETOFUSIMOTOR INNERVATION; DECEREBRATED CATS; SKELETAL-MUSCLE; MOTONEURONS; AFFERENTS; STIMULATION; LOCOMOTION AB Skeletofusimotor (beta) motoneurons innervate both extrafusal muscle units and muscle fibers within muscle spindle stretch receptors. By receiving excitation from group Ia muscle spindle afferents and driving the muscle spindle afferents that excite them, they form a positive feedback loop of unknown function. To study it, we developed a computationally efficient model of group Ia afferent behavior, capable of responding to multiple fusimotor inputs, that matched experimental data. This spindle model was then incorporated into a simulation of group Ia feedback during ramp/hold and triangular stretches with and without closure of the beta loop, assuming that gamma and beta fusimotor drives of the same type (static or dynamic) have identical effects on spindle afferent firing. The effects of beta feedback were implemented by driving a fusimotor input with a delayed and filtered fraction of the spindle afferent output. During triangular stretches, feedback through static beta motoneurons enhanced Ia afferent firing during shortening of the spindle. In contrast, closure of a dynamic beta loop increased Ia firing during lengthening. The strength of beta feedback, estimated as a "loop gain" was comparable to experimental estimates. The loop gain increased with velocity and amplitude of stretch but decreased with increased superimposed gamma fusimotor rates. The strongest loop gains were seen when the beta loop and the gamma bias were of different types ( static vs. dynamic). C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP Burke, RE (reprint author), NINDS, Neural Control Lab, NIH, Bldg 49,Rm 3A50, Bethesda, MD 20892 USA. NR 60 TC 7 Z9 7 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2003 VL 89 IS 5 BP 2797 EP 2809 DI 10.1152/jn.00942.2002 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 676FT UT WOS:000182741200044 PM 12740414 ER PT J AU Romieu, P Martin-Fardon, R Bowen, WD Maurice, T AF Romieu, P Martin-Fardon, R Bowen, WD Maurice, T TI sigma(1) receptor-related neuroactive steroids modulate cocaine-induced reward SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cocaine; neuroactive steroids; locomotor activity; reward; convulsions; sigma(1) receptor ID CONDITIONED PLACE PREFERENCE; METHYL-D-ASPARTATE; RAT NUCLEUS-ACCUMBENS; GABA-A RECEPTOR; PREGNENOLONE SULFATE; THERAPEUTIC OPPORTUNITIES; DOPAMINE RELEASE; NEUROSTEROIDS; LIGANDS; PROGESTERONE AB The sigma(1) receptor is critically involved in the rewarding effect of cocaine, as measured using the conditioned place preference (CPP) procedure in mice. Neuroactive steroids exert rapid neuromodulatory effects in the brain by interacting with GABA(A), NMDA, and sigma(1) receptors. At the sigma(1) receptor level, 3beta-hydroxy-5-androsten-17-one [dehydroepiandrosterone (DHEA)] and 3beta-hydroxy-5-pregnen-20-one ( pregnenolone) act as agonists, whereas 4-pregnene-3,20-dione ( progesterone) is an efficient antagonist. The present study sought to investigate the action of neuroactive steroids in acquisition of cocaine-induced CPP in C57BL/6 mice. None of these steroids induced CPP alone. However, pretreatment with DHEA or pregnenolone ( 5 - 20 mg/kg, s.c.) during conditioning with cocaine ( 10 mg/kg, i.p.) increased the conditioned score. On the contrary, pretreatment with either progesterone ( 10 or 20 mg/kg, s.c.) or finasteride ( 25 mg/kg, twice a day), a 5alpha-reductase inhibitor, blocked acquisition of cocaine (20 mg/kg)-induced CPP. A crossed pharmacology was observed between steroids and sigma(1) ligands. The sigma(1) antagonist N-[2-(3,4-dichlorophenyl) ethyl]- N- methyl-2-(dimethylamino) ethylamine blocked cocaine-induced CPP and its potentiation by DHEA or pregnenolone. Progesterone blocked cocaine-induced CPP and its potentiation by the sigma(1) agonist igmesine. These results showed that neuroactive steroids play a role in cocaine-induced appetence, through their interaction with the sigma(1) receptor. Therefore, neuroendocrine control of cocaine addiction may not involve solely glucocorticoids. The importance of neuroactive steroids as factors of individual vulnerability to drug addiction should, thus, be considered. C1 Univ Montpellier 2, CNRS, UMR 5102, F-34095 Montpellier 5, France. Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA 92307 USA. NIDDKD, Unit Receptor Biochem & Pharmacol, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Maurice, T (reprint author), Univ Montpellier 2, CNRS, UMR 5102, Pl Eugene Bataillon, F-34095 Montpellier 5, France. NR 47 TC 66 Z9 73 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 2003 VL 23 IS 9 BP 3572 EP 3576 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 675MX UT WOS:000182700100003 PM 12736327 ER PT J AU King, SL Marks, MJ Grady, SR Caldarone, BJ Koren, AO Mukhin, AG Collins, AC Picciotto, MR AF King, SL Marks, MJ Grady, SR Caldarone, BJ Koren, AO Mukhin, AG Collins, AC Picciotto, MR TI Conditional expression in corticothalamic efferents reveals a developmental role for nicotinic acetylcholine receptors in modulation of passive avoidance behavior SO JOURNAL OF NEUROSCIENCE LA English DT Article DE nicotine; learning; transgenic mice; nicotinic acetylcholine receptors; brain; prenatal ID DEFICIT HYPERACTIVITY DISORDER; MOUSE-BRAIN SYNAPTOSOMES; PRENATAL NICOTINE; MATERNAL SMOKING; POSTNATAL-DEVELOPMENT; RB-86(+) EFFLUX; GABA RELEASE; MUTANT MICE; RAT; PREGNANCY AB Prenatal nicotine exposure has been linked to attention deficit hyperactivity disorder and cognitive impairment, but the sites of action for these effects of nicotine are still under investigation. High-affinity nicotinic acetylcholine receptors (nAChRs) contain the beta2 subunit and modulate passive avoidance (PA) learning in mice. Using an inducible, tetracycline-regulated transgenic system, we generated lines of mice with expression of high-affinity nicotinic receptors restored in specific neuronal populations. One line of mice shows functional beta2 subunit-containing nAChRs localized exclusively in corticothalamic efferents. Functional, presynaptic nAChRs are present in the thalamus of these mice as detected by nicotine-elicited rubidium efflux assays from synaptosomes. Knock-out mice lacking high-affinity nAChRs show elevated baseline PA learning, whereas normal baseline PA behavior is restored in mice with corticothalamic expression of these nAChRs. In contrast, nicotine can enhance PA learning in adult wild-type animals but not in corticothalamic-expressing transgenic mice. When these transgenic mice are treated with doxycycline in adulthood to switch off nAChR expression, baseline PA is maintained even after transgene expression is abolished. These data suggest that high-affinity nAChRs expressed on corticothalamic neurons during development are critical for baseline PA performance and provide a potential neuroanatomical substrate for changes induced by prenatal nicotine exposure leading to long-term behavioral and cognitive deficits. C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06508 USA. Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. NIDA, Brain Imaging Ctr, Intramural Res Program, Baltimore, MD 21224 USA. RP Picciotto, MR (reprint author), Yale Univ, Sch Med, Dept Psychiat, 34 Pk St,3 Floor Res, New Haven, CT 06508 USA. RI Picciotto, Marina/F-8747-2012 OI Picciotto, Marina/0000-0002-4404-1280 FU NIDA NIH HHS [DA00197, DA00436, DA03194, DA10455, DA14241, DA84733] NR 49 TC 59 Z9 61 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 2003 VL 23 IS 9 BP 3837 EP 3843 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 675MX UT WOS:000182700100030 PM 12736354 ER PT J AU Brown, PL Wise, RA Kiyatkin, EA AF Brown, PL Wise, RA Kiyatkin, EA TI Brain hyperthermia is induced by methamphetamine and exacerbated by social interaction SO JOURNAL OF NEUROSCIENCE LA English DT Article DE brain temperature; hyperthermia; metabolic neural activation; nucleus accumbens; hippocampus; social interaction ID DOPAMINERGIC NEUROTOXICITY; TEMPERATURE; AMPHETAMINE; TOXICITY; MICE; CELLS; MOUSE; RATS; ENVIRONMENT; GLUTAMATE AB Hyperthermia is a symptom of methamphetamine (METH) intoxication and a factor implicated in neurotoxicity during chronic METH use. To characterize the thermic response to METH, it was injected once daily into rats at increasing doses (0, 1, 3, and 9 mg/kg, s.c.) while brain [nucleus accumbens (NAcc), hippocampus] and body (deep temporal muscle) temperatures were continuously monitored. METH produced dose-dependent hyperthermia, with brain structures ( especially the NAcc) showing a more rapid and pronounced temperature increase than the muscle. At the highest dose, brain and body temperatures increased 3.5-4.0degreesC above basal levels and remained elevated for 3-5 hr. Stressful and other high-activity situations such as interaction with a conspecific female are also known to induce a significant hyperthermic response in the rat. A combination of social interaction and METH administration was tested for additive effects. Male rats were exposed daily to a conspecific female for a total of 120 min, and METH was injected at the same doses 30 min after the initial contact with the female. An initial hyperthermic response (similar to1.5degreesC) to social interaction was followed by a large and prolonged hyperthermic response (3.5-5.0degreesC, 5-7 hr at 9 mg/kg) to METH, which was again stronger in brain structures ( especially in the NAcc) than in the muscle. Although the combined effect of the hyperthermic events was not additive, METH administration during social interaction produced stronger and longer-lasting increases in brain and body temperature than that induced by drug alone, heating the brain in some animals near its biological limit (>41degreesC). C1 NIDA, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. RI Wise, Roy/A-6465-2012 NR 34 TC 51 Z9 52 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 2003 VL 23 IS 9 BP 3924 EP 3929 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 675MX UT WOS:000182700100038 PM 12736362 ER PT J AU Oldfield, EH AF Oldfield, EH TI Cushing disease SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID TERM FOLLOW-UP; PITUITARY SURGERY; POSTOPERATIVE EVALUATION; TRANSSPHENOIDAL SURGERY; HORMONE TEST; PREDICTION; RELAPSE C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 8 TC 14 Z9 15 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 2003 VL 98 IS 5 BP 948 EP 951 DI 10.3171/jns.2003.98.5.0948 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 674CJ UT WOS:000182619000007 PM 12744352 ER PT J AU Denslow, N Michel, ME Temple, MD Hsu, CY Saatman, K Hayes, RL AF Denslow, N Michel, ME Temple, MD Hsu, CY Saatman, K Hayes, RL TI Application of proteomics technology to the field of neurotrauma SO JOURNAL OF NEUROTRAUMA LA English DT Article DE brain trauma; mass spectroscopy; proteomics; spinal cord trauma ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; HUMAN GENES; PROTEIN; NEUROSCIENCE; SEQUENCE; NETWORK; DEATH AB Near-completion of the Human Genome Project has stimulated scientists to begin looking for the next step in unraveling normal and abnormal functions within biological systems. Consequently, there is new focus on the role of proteins in these processes. Proteomics is a burgeoning field that may provide a valuable approach to evaluate the post-traumatic central nervous system (CNS). Although we cannot provide a comprehensive assessment of all methods for protein analysis, this report summarizes some of the newer proteomic technologies that have propelled this field into the limelight and that are available to most researchers in neurotrauma. Three technical approaches (two-dimensional gel electrophoresis, direct analysis by mass spectrometry, including two-dimensional chromatography coupled to mass spectrometry and isotope coded affinity tags, and antibody technologies) are reviewed, and their advantages and disadvantages presented. A discussion of proteomic technology in the context of brain and spinal cord trauma follows, addressing current and future challenges. Proteomics will likely be very useful for developing diagnostic predictors after CNS injury and for mapping changes in proteins after injury in order to identify new therapeutic targets. Neurotrauma results in complex alterations to the biological systems within the nervous system, and these changes evolve over time. Exploration of the "new nervous system" that follows injury will require methods that can both fully assess and simplify this complexity. C1 NINDS, Repair & Plast Program, Bethesda, MD 20982 USA. Univ Florida, Biotechnol Program, Gainesville, FL USA. Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Univ Penn, Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA. Univ Florida, Coll Med, McKnight Brain Inst, Gainesville, FL USA. RP Michel, ME (reprint author), NINDS, Repair & Plast Program, 6001 Execut Blvd,Rm 2227, Bethesda, MD 20982 USA. OI Hsu, Chung Y./0000-0002-5632-2733 NR 20 TC 38 Z9 43 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD MAY PY 2003 VL 20 IS 5 BP 401 EP 407 DI 10.1089/089771503765355487 PG 7 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 682MY UT WOS:000183096900001 PM 12803973 ER PT J AU Ichise, M Liow, JS Lu, JQ Takano, A Modell, K Toyama, H Suhara, T Innis, RB Carson, RE AF Ichise, M Liow, JS Lu, JQ Takano, A Modell, K Toyama, H Suhara, T Innis, RB Carson, RE TI Quantification of central serotonin transporter binding potential and relative tracer delivery by using multilinear reference tissue models for human [C-11]DASB PET studies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. Natl Inst Radiol Sci, Brain Imaging Project, Anagawa, Chiba, Japan. NIH, PET Dept, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 35 BP 11P EP 12P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600036 ER PT J AU Herholz, K Zuendorf, G Kerrouche, N Rapoport, SI Silverman, DH AF Herholz, K Zuendorf, G Kerrouche, N Rapoport, SI Silverman, DH TI Comparison of dementia diagnoses derived from principal component analyses (PCA) of FDG-PET data with diagnoses based on autopsies of human brain. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Univ Cologne, Max Planck Inst Neurol Res, D-5000 Cologne 41, Germany. Inst Nat Sante Recherche Med, Caen, France. NIA, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Ahmanson Biolog Imaging Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 51 BP 16P EP 17P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600052 ER PT J AU Utsunomiya, K Narabayashi, I Ogura, Y Komori, T Adachi, I Stundzia, A Dufort, P Ichise, M AF Utsunomiya, K Narabayashi, I Ogura, Y Komori, T Adachi, I Stundzia, A Dufort, P Ichise, M TI Quantitative global assessment of cerebral perfusion changes via 3D perfusion isosurfaces in patients with Alzheimer's disease using Iodine-123-IMP SPECT and autoradiography protocol. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Osaka Med Coll, Takatsuki, Osaka 569, Japan. Adv Biol Corp, Toronto, ON, Canada. NIMH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 53 BP 17P EP 17P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600054 ER PT J AU Giovacchini, G Toczek, MT Lang, L Fraser, C Herscovitch, P Eckelman, WC Theodore, WH Carson, RE AF Giovacchini, G Toczek, MT Lang, L Fraser, C Herscovitch, P Eckelman, WC Theodore, WH Carson, RE TI 5-HT1A receptors in temporal lobe epilepsy (TLE): An [F-18]FCWAY PET study with partial volume correction (PVC). SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 NIH, PET Dept, Bethesda, MD 20892 USA. Natl Inst Neurolog Disorders & Stroke, Clin Epilepsy Sect, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 62 BP 20P EP 20P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600063 ER PT J AU Fujita, M Southwick, SM DeNucci, C Zoghbi, SS Dillon, MS Baldwin, RM Bozkurt, A Kugaya, A Seibyl, JP Innis, RB AF Fujita, M Southwick, SM DeNucci, C Zoghbi, SS Dillon, MS Baldwin, RM Bozkurt, A Kugaya, A Seibyl, JP Innis, RB TI Central type benzodiazepine receptors in Gulf War veterans with posttraumatic stress disorder. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Yale Univ, West Haven, CT USA. NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT 06520 USA. Inst Neurodegener Disorders, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 119 BP 38P EP 38P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600120 ER PT J AU Buvat, I Hapdey, S Carson, JM Sundaram, SK Libutti, SK Yang, JC Carasquillo, JA Whatley, M Sellers, D Bacharach, SL AF Buvat, I Hapdey, S Carson, JM Sundaram, SK Libutti, SK Yang, JC Carasquillo, JA Whatley, M Sellers, D Bacharach, SL TI Non-parametric simplified kinetic method for characterization of tumor metabolism in FDG PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 CHU Pitie Salpetriere, U494 INSERM, Paris, France. NIH, Dept Nucl Med, Bethesda, MD USA. RI Sundaram, Senthil/B-3905-2013 OI Sundaram, Senthil/0000-0002-0382-0536 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 201 BP 62P EP 63P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600202 ER PT J AU Wong, DF Lee, JS Maini, A Zhou, Y Kuwabara, H Endres, C Brasic, J Dogan, S Schretlen, D Alexander, M Kimes, A Ernst, M Jasinski, D London, ED Zukin, S AF Wong, DF Lee, JS Maini, A Zhou, Y Kuwabara, H Endres, C Brasic, J Dogan, S Schretlen, D Alexander, M Kimes, A Ernst, M Jasinski, D London, ED Zukin, S TI Cue induced cocaine craving and dopamine release: Methodology and correlates. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIDA, IRP, Baltimore, MD USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Columbia Univ, New York, NY USA. RI Brasic, James/B-3503-2008 OI Brasic, James/0000-0002-3948-4853 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 215 BP 67P EP 67P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600216 ER PT J AU Lee, KS Zhang, L Jones, DW Gorey, JG Weinberger, DR AF Lee, KS Zhang, L Jones, DW Gorey, JG Weinberger, DR TI Estrogen upregulates sigma receptor binding activity in the hippocampus of rat. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 NIH, NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 224 BP 70P EP 70P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600225 ER PT J AU Sundaram, SK Carrasquillo, JA Carson, JM Whatley, M Sellers, D Libutti, SK Yang, JC Bacharach, SL AF Sundaram, SK Carrasquillo, JA Carson, JM Whatley, M Sellers, D Libutti, SK Yang, JC Bacharach, SL TI Relationship between blood flow and FDG metabolism in renal cell cancer: Implications for therapy? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; Sundaram, Senthil/B-3905-2013 OI Sundaram, Senthil/0000-0002-0382-0536 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 266 BP 82P EP 82P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600267 ER PT J AU Liow, J Seidel, J Johnson, CA Toyama, H Green, MV Innis, RB AF Liow, J Seidel, J Johnson, CA Toyama, H Green, MV Innis, RB TI A single slice rebinning/2D exact positioning OSEM reconstruction for the NIH ATLAS small animal PET scanner. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. Natl Inst Hlth, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD USA. Natl Inst Hlth, Comput Inst & Technol, Bethesda, MD USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 529 BP 163P EP 163P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600530 ER PT J AU Kobayashi, H Mandler, R Brechbiel, MW Waldmann, TA AF Kobayashi, H Mandler, R Brechbiel, MW Waldmann, TA TI Conjugation of Herceptin with geldanamycin leads to enhanced therapy of tumors in part due to respectable internalization rate. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 NIH, Natl Canc Inst, Metab Branch, Bethesda, MD 20892 USA. NIH, Natl Canc Inst, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 577 BP 177P EP 177P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600578 ER PT J AU Shimoji, K Ravasi, L Soto-Montenegro, ML Schmidt, K Esaki, T Seidel, J Jagoda, E Riboldi, S Sokoloff, L Green, MV Eckelman, WC AF Shimoji, K Ravasi, L Soto-Montenegro, ML Schmidt, K Esaki, T Seidel, J Jagoda, E Riboldi, S Sokoloff, L Green, MV Eckelman, WC TI Measurement of cerebral glucose metabolic rates in the anesthetized rat by dynamic scanning with the ATLAS small animal PET scanner and arterial blood sampling SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 NIH, Ctr Clin, Positron Emmiss Tomography Dept, Bethesda, MD 20892 USA. NIMH, NIH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nucl Med, Bethesda, MD 20892 USA. Hosp Gen Gregorio Maranon, Lab Imagen, Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 779 BP 213P EP 214P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600696 ER PT J AU Toyama, H Ichise, M Liow, J Modell, K Vines, D Esaki, T Cook, M Seidel, J Sokoloff, L Green, MV Innis, RB AF Toyama, H Ichise, M Liow, J Modell, K Vines, D Esaki, T Cook, M Seidel, J Sokoloff, L Green, MV Innis, RB TI Absolute quantification of regional cerebral glucose utilization in mice by [F-18]FDG small animal PET scanning and 2-[C-14]DG autoradiography. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 781 BP 214P EP 214P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600698 ER PT J AU Shimoji, K Ravasi, L Esaki, T Soto-Montenegro, ML Schmidt, K Seidel, J Green, MV Sokoloff, L Eckelman, WC AF Shimoji, K Ravasi, L Esaki, T Soto-Montenegro, ML Schmidt, K Seidel, J Green, MV Sokoloff, L Eckelman, WC TI Use of [F-18]FDG and atlas small animal PET scanner to study functional activation in the somatosensory cortex by whisker stimulation in unanesthetized rats SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 NIH, Ctr Clin, Positron Emmiss Tomography Dept, Bethesda, MD 20892 USA. NIMH, NIH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nucl Med, Bethesda, MD 20892 USA. Hosp Gen Univ Gregorio Maranon, Lab Imagen, Med Cirugia Expt, Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 784 BP 215P EP 215P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600701 ER PT J AU Alexander, M Rothman, RB Endres, C Rauseo, P Brasic, JR Maini, A Dannals, RF Zukin, SR Wong, DF AF Alexander, M Rothman, RB Endres, C Rauseo, P Brasic, JR Maini, A Dannals, RF Zukin, SR Wong, DF TI A dose-response PET study of the noradrenergic and dopaminergic effects of amphetamine-like stimulants in baboons SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA. Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. RI Brasic, James/B-3503-2008 OI Brasic, James/0000-0002-3948-4853 NR 0 TC 1 Z9 1 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 805 BP 221P EP 221P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600722 ER PT J AU Jagoda, EM Contoreggi, C Lee, MJ Kao, CK Szajek, LP Gold, PW Chrousos, GP Jacobson, AE Rice, KC Eckelman, WC AF Jagoda, EM Contoreggi, C Lee, MJ Kao, CK Szajek, LP Gold, PW Chrousos, GP Jacobson, AE Rice, KC Eckelman, WC TI Regional rat brain distribution of [Br-76]MJL-1-109-2, a non-peptide corticotrophin-releasing hormone type 1 receptor (CRHR1) ligand, using in vitro autoradiography SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 NIH, PET Dept, Bethesda, MD 20892 USA. NIH, IRP NIDA, Bethesda, MD 20892 USA. NIH, LMC NIDDK, Bethesda, MD 20892 USA. NIH, CNE NIMH, Bethesda, MD 20892 USA. NIH, NICHD, Pediatric & Reproduct Endocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 813 BP 224P EP 224P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600730 ER PT J AU Erlandsson, K Fujita, M Innis, RB Ell, PJ Pilowsky, LS AF Erlandsson, K Fujita, M Innis, RB Ell, PJ Pilowsky, LS TI The effect of lipophilic metabolites on reference tissue modelling of [(123)I]epidepride SPET data. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL New Orleans, LA SP Soc Nucl Med C1 UCL, Inst Nucl Med, London WC1E 6BT, England. NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. Kings Coll London, Inst Psychiat, London WC2R 2LS, England. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 917 BP 254P EP 255P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600834 ER PT J AU Lang, L Vuong, B Ma, Y Channing, MA Eckelman, WC AF Lang, L Vuong, B Ma, Y Channing, MA Eckelman, WC TI The automated radiosynthesis of [F-18]FCWAY. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 1056 BP 295P EP 295P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600973 ER PT J AU Kim, HS Han, ES Sato, N Park, LS Wong, KJ Carrasquillo, JA Paik, CH AF Kim, HS Han, ES Sato, N Park, LS Wong, KJ Carrasquillo, JA Paik, CH TI Synthesis and evaluation of [I-125]-labeled biotinylated dendrimer for antibody pretargeting. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 1091 BP 305P EP 305P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729601008 ER PT J AU Han, ES Kim, HS Sato, N Park, LS Wong, KJ Yu, S Carrasquillo, JA Paik, CH AF Han, ES Kim, HS Sato, N Park, LS Wong, KJ Yu, S Carrasquillo, JA Paik, CH TI Synthesis and in vivo evaluation of Tc-99m-tricarbonyl-labeled DTPA- and EDTA-norbiotinamide. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 1112 BP 310P EP 311P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729601029 ER PT J AU Kurdziel, KA Fey, G Channing, M Voung, B Eckelman, WC Salem, N Herscovitch, P AF Kurdziel, KA Fey, G Channing, M Voung, B Eckelman, WC Salem, N Herscovitch, P TI Human radiation dosimetry estimates for C-11 docosahexaenoic acid (DHA): A promising PET tracer for evaluation of alcoholism and affective disorders. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Virginia Commonwealth Univ, MCV, Richmond, VA USA. NIH, Ctr Clin, PET, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 1152 BP 321P EP 321P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729601069 ER PT J AU Yao, Z Dai, W Perry, J Brechbiel, MW Sung, C AF Yao, Z Dai, W Perry, J Brechbiel, MW Sung, C TI Effect of albumin fusion on the biodistribution of interleukin-2. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Human Genome Sci Inc, Preclin Dev, Rockville, MD USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 1330 BP 373P EP 373P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729601247 ER PT J AU Gangloff, A Kesner, AL Hsueh, WA Kiesewetter, DO Eckelman, W Czernin, J Pegram, M Beryt, M Silverman, DH AF Gangloff, A Kesner, AL Hsueh, WA Kiesewetter, DO Eckelman, W Czernin, J Pegram, M Beryt, M Silverman, DH TI Biodistribution and microPET imaging studies of the chemotherapy analogue and p-glycoprotein substrate [F-18]-fluoropaclitaxel SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Univ Calif Los Angeles, Ctr Med, Ahmanson Biol Imaging Ctr, Los Angeles, CA 90024 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2003 VL 44 IS 5 SU S MA 1333 BP 374P EP 374P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729601250 ER PT J AU Romero, R Chaiworapongsa, T Espinoza, J AF Romero, R Chaiworapongsa, T Espinoza, J TI Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Meeting on Nutrition as A Preventive Strategy Against Adverse Pregnancy Outcomes CY JUL 18-19, 2002 CL MERTON COLL, OXFORD, ENGLAND HO MERTON COLL DE intrauterine infection; prematurity; fetal inflammation; vitamins C and E; rupture of membranes ID AMNIOTIC-FLUID INTERLEUKIN-6; TUMOR-NECROSIS-FACTOR; POLYMERASE-CHAIN-REACTION; UMBILICAL-CORD PLASMA; PREMATURE RUPTURE; INTRAAMNIOTIC INFECTION; UREAPLASMA-UREALYTICUM; CHLAMYDIA-TRACHOMATIS; GENETIC AMNIOCENTESIS; CLINICAL-SIGNIFICANCE AB Prematurity is the leading cause of perinatal morbidity and mortality worldwide. Intrauterine infection has emerged as a major cause of premature labor and delivery. It has been estimated that 25% of all preterm deliveries occur to mothers who have microbial invasion of the amniotic cavity, although these infections are mostly subclinical in nature. This article describes the pathways leading to intrauterine infection, microbiology, frequency and clinical consequences of infection. The pathophysiology of the fetal inflammatory response syndrome is reviewed, as is its relationship to long-term handicap, such as cerebral palsy and bronchopulmonary dysplasia. A possible role for two micronutrients, vitamins C and E, in the prevention of the preterm prelabor rupture of membranes and the consequences of fetal inflammation is considered. Research needs are listed. C1 NICHHD, Perinatol Res Branch, DHHS, NIH, Bethesda, MD 20892 USA. RP Romero, R (reprint author), NICHHD, Perinatol Res Branch, DHHS, NIH, Bethesda, MD 20892 USA. NR 97 TC 63 Z9 69 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2003 VL 133 IS 5 SU 2 BP 1668S EP 1673S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 681AC UT WOS:000183011400012 PM 12730483 ER PT J AU Cogswell, ME Weisberg, P Spong, C AF Cogswell, ME Weisberg, P Spong, C TI Cigarette smoking, alcohol use and adverse pregnancy outcomes: Implications for micronutrient supplementation SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Meeting on Nutrition as A Preventive Strategy Against Adverse Pregnancy Outcomes CY JUL 18-19, 2002 CL MERTON COLL, OXFORD, ENGLAND HO MERTON COLL DE cigarette smoking; alcohol use; pregnancy; vitamins; minerals ID MATERNAL ETHANOL INGESTION; FETAL GROWTH-RETARDATION; METALLOTHIONEIN-NULL MICE; RETINOL-BINDING PROTEIN; LOW-BIRTH-WEIGHT; VITAMIN-A; FOLIC-ACID; ZINC-DEFICIENCY; BETA-CAROTENE; PLASMA-LEVELS AB This literature review examines whether smoking or alcohol: use during pregnancy increases maternal micronutrient requirements and whether smoking or alcohol use interacts with micronutrient deficiencies to affect pregnancy outcomes, Studies suggest that vitamin C requirements increase for pregnant smokers. Studies also indicate that beta-carotene, vitamin B-12, vitamin B-6 and folate concentrations appear lower in pregnant smoker's than in pregnant nonsmokers, although it is unclear whether lower serum concentrations are due to increased requirements, lower dietary or supplement intakes or other factors. Experimental animal studies suggest that iron supplementation partially ameliorates impaired fetal growth caused by cadmium, a heavy metal inhaled from cigarette smoke, but studies in humans have not substantiated cadmium's effect on fetal growth, Animal studies also suggest chronic alcohol consumption at levels of 20-50% of energy intake during pregnancy may mobilize fetal vitamin A concentration from the liver and result in increases in vitamin A in fetal organs and subsequent defects. Evidence is lacking, however, on whether zinc metabolism is altered by alcohol intake during pregnancy. Health care practitioners should consider increasing nutrient levels in pregnant women who do not meet the Recommended Dietary Allowances through their diet. Future studies that examine the nutrient levels of women exposed to cigarette smoke and alcohol should control for dietary intake. In addition, randomized controlled studies of the health impact of micronutrient supplementation in pregnant women should consider stratification by exposure to cigarette smoke and alcohol use. C1 Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr & Phys Act, Atlanta, GA 30341 USA. Emory Clin, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. NICHHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. RP Cogswell, ME (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr & Phys Act, Atlanta, GA 30341 USA. NR 103 TC 43 Z9 44 U1 1 U2 7 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2003 VL 133 IS 5 SU 2 BP 1722S EP 1731S PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 681AC UT WOS:000183011400019 PM 12730490 ER PT J AU Khasar, SG Green, PG Gear, RW Isenberg, W Levine, JD AF Khasar, SG Green, PG Gear, RW Isenberg, W Levine, JD TI Gonadal hormones do not account for sexual dimorphism in vagal modulation of nociception in the rat SO JOURNAL OF PAIN LA English DT Article DE hyperalgesia; nociception; sex hormones; vagotomy ID MECHANICAL HYPERALGESIA; MESSENGER-RNA; SPINAL-CORD; NEURONS; PAIN AB Subdiaphragmatic vagotomy produces a decrease in mechanical nociceptive threshold that is greater in male rats and an enhancement of bradykinin hyperalgesia that is greater in female rats. To examine the role of gonadal hormones in these sex differences, we evaluated the effect of gonadectomy, with or without gonadal hormone replacement, on vagal modulation of nociceptive threshold and bradykinin hyperalgesia by using the Randall-Selitto paw withdrawal test. Gonadectomy (before sexual maturation) plus vagotomy decreased nociceptive threshold in male rats more than either lesion alone, whereas neither lesion nor in combination had an effect on nociceptive threshold in female rats. Testosterone or dihydrotestosterone replacement in gonadectomized plus vagotomized males and 17beta-estradiol in females did not significantly alter nociceptive threshold compared to vagotomy plus gonadectomy, respectively. Combined vagotomy and gonadectomy unexpectedly almost completely abolished bradykinin hyperalgesia, whereas gonadectomy alone had no effect on bradykinin hyperalgesia in both sexes. Testosterone replacement in vagotomized males and 17beta-estradiol in vagotomized females reversed the effect of gonadectomy. Dihydrotestosterone replacement in vagotomized males also reversed the effect of gonadectomy on bradykinin hyperalgesia, although to a lesser degree than testosterone. We conclude that although gonadal hormones and other gonadal-dependent mechanisms influence nociception, they do not account for sexual dimorphism in vagal modulation of mechanical nociceptive threshold or bradykinin hyperalgesia. (C) 2003 by the American Pain Society. C1 Univ Calif San Francisco, NIH, Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH, Pain Ctr, Box 0440,C-522, San Francisco, CA 94143 USA. RI Green, Paul/C-5943-2011 FU NINR NIH HHS [NR004880] NR 15 TC 8 Z9 8 U1 0 U2 2 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 MAY PY 2003 VL 4 IS 4 BP 190 EP 196 DI 10.1016/S1526-5900(03)00560-1 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 687EC UT WOS:000183362200004 PM 14622703 ER PT J AU Tsao, JCI Zeltzer, LK AF Tsao, JCI Zeltzer, LK TI Sex differences in pain-related symptoms and self-initiated school nurse visits among pre-adolescents SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE pain; school nurse visits; adolescents; sex differences; somatization; functional symptoms ID COLD PRESSOR PAIN; NEONATAL CIRCUMCISION; GENDER DIFFERENCES; CARE; SOMATIZATION; CHILDREN; VACCINATION; RESPONSES AB We examined sex differences in self-initiated school nurse visits and pain-associated symptoms in 5 7 pre-adolescents (36 girls), aged 9-11, with a brief, pain-focused version of the Children's Somatization Inventory (CSI). Using sequential multiple regression, pain Symptom scores, sex, and their interaction were analyzed in relation to nurse visits prospectively collected for 1 year. Neither sex, nor pain scores alone, predicted total nurse visits. For girls only, higher pain symptom scores predicted increased total visits and increased visits for complaints with documented physical findings. For both sexes, higher pain symptom scores predicted more visits for complaints without documented physical findings. A complex relationship between sex, pain-related symptoms, and self-initiated nurse visits was found in this pre-adolescent sample. Our findings suggest pain-focused symptom measures may be useful in studies of early predictors of adult pain-related healthcare utilization. (C) 2003 U. S. Cancer Pain Relief Committee. Published by Elsevier. All rights reserved. C1 Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA. Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL 32610 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Pediat Pain Program, Los Angeles, CA 90024 USA. RP Tsao, JCI (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, Box 100165 HSC, Gainesville, FL 32610 USA. OI Zeltzer, Lonnie/0000-0001-9306-9450 NR 25 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAY PY 2003 VL 25 IS 5 BP 472 EP 480 DI 10.1016/S0885-3924(03)00076-9 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 675FH UT WOS:000182682300016 PM 12727046 ER PT J AU Hillard, PJA Nelson, LM AF Hillard, PJA Nelson, LM TI Adolescent girls, the menstrual cycle, and bone health SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 16th Annual National Cooperative Growth Study (NCGS)/13th Annual National Cooperative Somatropin Surveillance Investigator Meeting (NCSS) CY OCT 17-20, 2002 CL CHICAGO, ILLINOIS DE amenorrhea; oligomenorrhea; menstrual cycle; adolescents; bone density; osteoporosis; osteopenia; estradiol ID FEMALE ATHLETE TRIAD; PREMATURE OVARIAN FAILURE; ANOREXIA-NERVOSA; YOUNG-WOMEN; SECONDARY AMENORRHEA; MINERAL DENSITY; DIETARY CALCIUM; OSTEOPENIA; OSTEOPOROSIS; MASS AB In adolescent girls, amenorrhea is sometimes viewed as a variant of normal; in fact, however, during the first gynecologic year, the 95(th) percentile for cycle length is 90 days. Although early menstrual cycles are frequently anovulatory and may be somewhat irregular, girls with menses coming less frequently than every 90 days may have significant pathology associated with hypoestrogenism. Hypoestrogenism is a known risk factor for the development of osteoporosis. Causes of oligomenorrhea and amenorrhea include the relatively common conditions of hyperandrogenism, eating disorders, and exercise-induced amenorrhea, as well as uncommon conditions such as pituitary tumor, gonadal dysgenesis, and premature ovarian failure. Even functional hypothalamic oligomenorrhea has been linked to reduced bone density. Attention to menstrual irregularity and the earlier diagnosis of conditions causing it may lead to interventions that will benefit life-long bone health. C1 NICHHD, Gynecol Endocrinol Unit, Sect Womens Hlth Res, Dev Endocrinol Branch,NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Dept Ob Gyn, Cincinnati, OH USA. Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. RP Nelson, LM (reprint author), NICHHD, Gynecol Endocrinol Unit, Sect Womens Hlth Res, Dev Endocrinol Branch,NIH, 10 Ctr Dr,MSC 1862,Bldg 10,Room 10N262, Bethesda, MD 20892 USA. NR 52 TC 8 Z9 10 U1 1 U2 4 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD MAY PY 2003 VL 16 SU 3 BP 673 EP 681 PG 9 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 687XK UT WOS:000183402100012 ER PT J AU Toretsky, JA Everly, EM Padilla-Nash, HM Chen, A Abruzzo, LV Eskenazi, AE Frantz, C Ried, T Stamberg, J AF Toretsky, JA Everly, EM Padilla-Nash, HM Chen, A Abruzzo, LV Eskenazi, AE Frantz, C Ried, T Stamberg, J TI Novel translocation in acute megakaryoblastic leukemia (AML-M7) SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE acute myeloid leukemia; cytogenetics; megakaryocytic leukemia; spectral karyotyping; translocation ID ACUTE MYELOID-LEUKEMIA; ACUTE MEGAKARYOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; CHROMOSOMAL TRANSLOCATIONS; MYELODYSPLASTIC SYNDROME; MYELOMONOCYTIC LEUKEMIA; PROGNOSTIC-SIGNIFICANCE; FUSION GENE; CELL-LINE AB The authors report a unique translocation in a patient with M7 acute myeloid leukemia and review the literature. A 22-month-old girl without Down syndrome was diagnosed with acute myeloid leukemia, subtype M7 (AML-M7), and died with relapsed disease following bone marrow transplantation. Tumor cells were evaluated using cytogenetics (including spectral karyotyping), immunohistochemistry, and flow cytometry. The patient was found to have a previously unreported complex translocation as follows: 50,XX,der(1)t(1;5)(p36?.1;p15?.1),del(5)(p15?.1), +6,+der(6;7)(?;?),der(7)t(6;7)(?;p22)[2],der(9)t(6;9) (?;p21)t(9;14)(q34;q11.2-q13),+10,t(12;16)(p 13;q24),-14[2], del(14)(q13)[2],+der(19)t(1;19)(?;p13.3),+22[cp 4]. AML-M7 in non-Down syndrome patients is a rare disease that requires improved prognostic markers. C1 Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. NIH, Genet Branch, Ctr Canc Res, Natl Canc Inst, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA USA. Johns Hopkins Sch Med, Baltimore, MD USA. RP Toretsky, JA (reprint author), Georgetown Univ, Sch Med, 3970 Reservoir Rd NW, Washington, DC 20007 USA. FU NCI NIH HHS [CA 88004-01] NR 42 TC 5 Z9 5 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 MAY PY 2003 VL 25 IS 5 BP 396 EP 402 DI 10.1097/00043426-200305000-00009 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 677KC UT WOS:000182805300009 PM 12759627 ER PT J AU Alter, BP Elghetany, MT AF Alter, BP Elghetany, MT TI The CCC system: Is it really the answer to pediatric MDS? SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Letter ID LEUKEMIA GROUP-B; MYELODYSPLASTIC SYNDROME; CANCER C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77550 USA. RP Alter, BP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. NR 7 TC 4 Z9 5 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 MAY PY 2003 VL 25 IS 5 BP 426 EP 427 DI 10.1097/00043426-200305000-00016 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 677KC UT WOS:000182805300016 PM 12759634 ER PT J AU Ippolito, E Bray, EW Corsi, A De Maio, F Exner, UG Robey, PG Grill, F Lala, R Massobrio, M Pinggera, O Riminucci, M Snela, S Zambakidis, C Bianco, P AF Ippolito, E Bray, EW Corsi, A De Maio, F Exner, UG Robey, PG Grill, F Lala, R Massobrio, M Pinggera, O Riminucci, M Snela, S Zambakidis, C Bianco, P TI Natural history and treatment of fibrous dysplasia of bone: a multicenter clinicopathologic study promoted by the European Pediatric Orthopaedic Society SO JOURNAL OF PEDIATRIC ORTHOPAEDICS-PART B LA English DT Article DE fibrous dysplasia; McCune-Albright syndrome; GNAS1 mutations; orthopedic surgery; intramedullary nailing; pathology ID MCCUNE-ALBRIGHT-SYNDROME; ACTIVATING G(S)ALPHA MUTATION; STIMULATORY G-PROTEIN; INTRAVENOUS PAMIDRONATE; GENE; CELLS; DYSFUNCTION; LESIONS AB A multicenter study on fibrous dysplasia of bone (FD) was promoted by the European Pediatric Orthopaedic Society in 1999 in order to gain insight into the natural history of the disease and to evaluate current diagnostic and therapeutic approaches. We collected and reviewed clinical, radiographic, pathological, and molecular genetic data when possible, from a total of 64 cases diagnosed as either monostotic FD (MFD), polyostotic FD (PFD), or McCune-Albright syndrome (MAS), evaluated or treated in 11 participating centers. Results from the initial analysis of the series indicate five main points: (1) Significant diagnostic pitfalls affect the diagnosis of MFD and, to a lesser extent, PFD in orthopedic centers and allied radiology and pathology facilities, which may be circumvented by the adoption of stringent diagnostic criteria, and in some cases by the analysis of FD-associated GNAS1 mutations. (2) MFD carries a significant risk for fracture in the face of limited disease in the proximal femur, whereas its tendency to progress is restricted to a minority of cases, and long-term outcome is usually satisfactory, regardless of treatment, in non-progressive cases. (3) The profile of tibial disease, both in MFD and in PFD, is markedly different from that of femoral disease. (4) As expected, MAS patients have the most extensive disease and the most complicated course, regularly experience multiple fractures, and require adequate surgical treatment. It appears that conservative treatment of femoral fracture, or curettage and cancellous bone grafting, or fixation with screws and plates are not indicated for the treatment of femoral fractures in these patients and should all be discouraged. Internal fixation with intramedullary nails provides stabilization of extensively affected bones, and prevents further fractures and major deformities, and thus providing a better option both for acute and elective surgery in patients with extensive involvement of the femur or of other limb long bones. (5) Evaluation of patients with FD at orthopedic centers should include, but rarely does, a thorough evaluation of endocrine profile and phosphate metabolism, and proper pathological and radiographic assessment. (C) 2003 Lippincott Williams Wilkins. C1 Univ Roma Tor Vergata, Dept Orthoped Surg, Rome, Italy. Shriners Hosp Children, Greenville, SC USA. Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. Univ Roma La Sapienza, Dept Orthoped Surg, Rome, Italy. Balgrist Orthoped Univ, Ctr Hlth, Zurich, Switzerland. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Orthopad Spital Speising GmbH, Vienna, Austria. Regina Margherita Hosp, Div Pediat Endocrinol, Turin, Italy. Szpital Wojewodski, Rzeszow, Poland. P&A Kiriakou Childrens Hosp Athens, Athens, Greece. Univ Roma La Sapienza, Dept Pathol & Expt Med, Rome, Italy. RP Ippolito, E (reprint author), Univ Roma Tor Vergata, Dept Orthoped Surg, Rome, Italy. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [E.1029] NR 42 TC 72 Z9 80 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1060-152X J9 J PEDIATR ORTHOP B JI J. Pediatr. Orthop.-Part B PD MAY PY 2003 VL 12 IS 3 BP 155 EP 177 DI 10.1097/01.bpb.0000064021.41829.94 PG 23 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 681JP UT WOS:000183033300001 PM 12703030 ER PT J AU Lash, LH Hines, RN Gonzalez, FJ Zacharewski, TR Rothstein, MA AF Lash, LH Hines, RN Gonzalez, FJ Zacharewski, TR Rothstein, MA TI Genetics and susceptibility to toxic chemicals: Do you (or should you) know your genetic profile? SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID EXPRESSION PROFILES; TARGETED DISRUPTION; EPOXIDE HYDROLASE; MICROARRAY DATA; HUMAN LIVER; ACETAMINOPHEN; PHARMACOGENETICS; METABOLISM; REVEALS; CYP1A2 AB This review is based on a symposium/roundtable session, sponsored by the Division of Toxicology of the American Society for Pharmacology and Experimental Therapeutics, that was held at the 2002 Experimental Biology meeting in New Orleans, LA. The focus is on the role of pharmacogenomics in determining individual susceptibility to chemically induced toxicity. An individual's risk of disease from exposure to toxic chemicals is determined by a complex interplay between genetics, physiology, and concurrent or prior exposures to drugs and other chemicals. The first section of the review defines the basics of pharmacogenetics and pharmacogenomics and assesses the current state of the science. Selected applications to specific enzyme systems are summarized by way of example. New, state-of-the-art approaches to studying genetic determinants of susceptibility, including analytical methods and transgenic technology, are then discussed. Finally, ethical and legal concerns with the application of this knowledge and methodology to human health will be discussed. C1 Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. Med Coll Wisconsin, Dept Pediat, Birth Defects Res Ctr, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Pharmacol Toxicol, Milwaukee, WI 53226 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. Michigan State Univ, Natl Food Safety & Toxicol Ctr, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. Univ Louisville, Sch Med, Inst Bioeth Hlth Policy & Law, Louisville, KY 40292 USA. RP Lash, LH (reprint author), Wayne State Univ, Sch Med, Dept Pharmacol, 540 E Canfield Ave, Detroit, MI 48201 USA. OI Lash, Lawrence/0000-0003-3239-4481; Hines, Ronald/0000-0002-3094-4200 NR 47 TC 7 Z9 8 U1 0 U2 2 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 MAY PY 2003 VL 305 IS 2 BP 403 EP 409 DI 10.1124/jpet.102.039925 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 669GL UT WOS:000182343500001 PM 12606672 ER PT J AU Hoffler, U El-Masri, HA Ghanayem, BI AF Hoffler, U El-Masri, HA Ghanayem, BI TI Cytochrome P450 2E1 (CYP2E1) is the principal enzyme responsible for urethane metabolism: Comparative studies using CYP2E1-null and wild-type mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the Society-of-Toxicology CY MAR 17-21, 2002 CL NASHVILLE, TENNESSEE SP Society Toxicol ID ETHYL CARBAMATE URETHANE; VINYL CARBAMATE; HYDROLASE-A; RATS; CARCINOGENICITY; INHIBITION; TOXICITY AB Urethane ([carbonyl-C-14] ethyl carbamate) is a fermentation by-product in alcoholic beverages and foods and is classified as reasonably anticipated to be a human carcinogen. Early studies indicated that while CYP2E1 is involved, esterases are the primary enzymes responsible for urethane metabolism. Using CYP2E1-null ( KO) mice, current studies were undertaken to elucidate CYP2E1's contribution to urethane metabolism. [Carbonyl-C-14] urethane was administered by gavage to male CYP2E1-null and wild-type mice at 10 or 100 mg/kg and its metabolism and disposition were investigated. CO2 was confirmed as the main metabolite of urethane. Significant inhibition of urethane metabolism to CO2 occurred in CYP2E1-null versus wild-type mice. Pharmacokinetic modeling of (CO2)-C-14 exhalation data revealed that CYP2E1 is responsible for approximately 96% of urethane metabolism to CO2 in wild-type mice. The contributions of other enzymes to urethane metabolism merely account for the remaining 4%. The half-life of urethane in wild-type and CYP2E1-null mice was estimated at 0.8 and 22 h, respectively. Additionally, the concentration of urethane-derived radioactivity in blood and tissues was dose-dependent and significantly higher in CYP2E1-null mice. High-performance liquid chromatography analysis showed only urethane in the plasma and liver extracts of CYP2E1-null mice. Because the lack of CYP2E1 did not completely inhibit urethane metabolism, the disposition of 10 mg/kg urethane was compared in mice pretreated with the P450 inhibitor, 1-aminobenzotriazole or the esterase inhibitor, paraoxon. Unlike paraoxon, 1-aminobenzotriazole resulted in significant inhibition of urethane metabolism to CO2 in both genotypes. In conclusion, this work demonstrated that CYP2E1, not esterase, is the principal enzyme responsible for urethane metabolism. C1 NIEHS, Lab Pharmacol & Chem, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. Meharry Med Coll, Dept Pharmacol, Nashville, TN 37208 USA. Agcy Tox Subst & Dis Registry, Div Toxicol, Computat Toxicol Lab, Atlanta, GA USA. RP Ghanayem, BI (reprint author), NIEHS, Lab Pharmacol & Chem, Environm Toxicol Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 30 TC 35 Z9 36 U1 0 U2 4 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 MAY PY 2003 VL 305 IS 2 BP 557 EP 564 DI 10.1124/jpet.102.049072 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 669GL UT WOS:000182343500020 PM 12704224 ER PT J AU He, LP Cleemann, L Soldatov, NM Morad, A AF He, LP Cleemann, L Soldatov, NM Morad, A TI Molecular determinants of cAMP-mediated regulation of the Na+-Ca2+ exchanger expressed in human cell lines SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID SODIUM-CALCIUM EXCHANGER; CARDIAC NA+/CA2+ EXCHANGER; PIG VENTRICULAR MYOCYTES; FUNCTIONAL EXPRESSION; SARCOPLASMIC-RETICULUM; DEPENDENT REGULATION; MEMBRANE PATCHES; XENOPUS OOCYTES; INWARD CURRENT; ISOFORMS NCX1 AB The cardiac Na+-Ca2+ exchanger (NCX1) is one of the major sarcolemmal Ca2+ transporters of cardiomyocytes. Structure-function studies suggest that beta-adrenergic inhibition of NCX1, as reported for frog, but not mammalian hearts, may be associated with a unique splice variant of frog cardiac NCX1 where insertion of an extra exon completes the coding of a nucleotide binding P-loop. To test the involvement of the P-loop in cAMP-mediated regulation of NCX1 we used four stably transfected human cell lines (a previously established line of baby hamster kidney (BHK) cells and three new lines of human embryonic kidney (HEK) cells) expressing: (1) wild-type dog NCX1 (dog NCX1); (2) wild-type frog NCX1 (frog NCX1); (3) chimeric frog-dog NCX1 incorporating the completed P-loop from the frog NCX1 into the dog NCX1 sequence (frog/dog NCX1); and (4) a mutated frog NCX1 where a putative protein kinase A (PKA) site was disrupted by substitution of a single serine residue with glycine (S374G frog NCX1). Structural expression of these NCX1 constructs was confirmed using Western blot analysis of extracted proteins and immunofluorescence imaging. The NCX1-generated current (INa-Ca) was reliably measured in cells expressing dog (2.0 +/- 0.15 pA pF(-1)), frog (0.6 +/- 0.1 pA pF(-1)) and frog/dog (0.6 +/- 0.1 pA pF(-1)) NCX1, but less so in those expressing S374G frog NCX1 (0.3 +/- 0.1 pA pF(-1)). Addition of 100 muM 8-bromoadenosine 3',5' cyclic monophosphate (8-Br-cAMP) suppressed INa-Ca of frog and frog/dog NCX1 by 60-80 %. The suppression of INa-Ca was smaller and transient in cells expressing S374G frog NCX1, and absent in cells expressing dog NCX1. Intracellular Ca2+ (Ca-i(2+)) -transients, activated by rapid withdrawal of Na+, were also downregulated in the frog and frog/dog NCX1 and to a smaller and transient extent in S374G frog NCX1. Our findings suggest that the suppressive effect of beta-adrenergic agonists requires the presence of the P-loop domain of the frog NCX1, and provide evidence that the putative PFA site, present in both dog and frog NCX1, might also be critical in the cAMP-mediated regulation of the exchanger. C1 Georgetown Univ, Washington, DC 20007 USA. NIA, NIH, Baltimore, MD 21224 USA. RP Cleemann, L (reprint author), Georgetown Univ, 4000 Reservoir Rd NW, Washington, DC 20007 USA. FU PHS HHS [R01 16152] NR 58 TC 22 Z9 22 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAY 1 PY 2003 VL 548 IS 3 BP 677 EP 689 DI 10.1113/jphysiol.2002.036426 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 690VR UT WOS:000183571600006 PM 12626672 ER PT J AU Pianta, RC AF Pianta, RC TI Untitled SO JOURNAL OF SCHOOL PSYCHOLOGY LA English DT Editorial Material C1 Univ Virginia, NICHD Study Early Childcare, Charlottesville, VA 22908 USA. RP Pianta, RC (reprint author), Univ Virginia, NICHD Study Early Childcare, POB 800784, Charlottesville, VA 22908 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-4405 J9 J SCHOOL PSYCHOL JI J. Sch. Psychol. PD MAY-JUN PY 2003 VL 41 IS 3 BP 165 EP 166 DI 10.1016/S0022-4405(03)00042-6 PG 2 WC Psychology, Educational SC Psychology GA 682HN UT WOS:000183085800001 ER PT J AU Zimmerman, SB AF Zimmerman, SB TI Underlying regularity in the shapes of nucleoids of Escherichia coli: Implications for nucleoid organization and partition SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE chromosome; Escherichia coli; flexible doublet model; nucleoid; partition; spheroplast ID BACTERIAL CHROMOSOME SEGREGATION; PROTEIN-SYNTHESIS; CELL-DIVISION; DNA; CHLORAMPHENICOL; LOCALIZATION; CONDENSATION; REPLICATION; TRANSERTION; MICROSCOPY AB The genomic DNA of Escherichia coli is localized in one or a few compact nucleoids. Nucleoids in rapidly grown cells appear in complex shapes; the relationship of these shapes to underlying arrangements of the DNA is of structural interest and of potential importance in gene localization and nucleoid partition studies. To help assess this variation in shape, limited three-dimensional information on individual nucleoids was obtained by DNA fluorescence microscopy of cells as they reoriented in solution or by optical sectioning. These techniques were also applied to enlarged nucleoids within swollen cells or spheroplasts. The resulting images indicated that much of the apparent variation was due to imaging from different directions and at different focal planes of more regular underlying nucleoid shapes. Nucleoid images could be transformed into compact doublet shapes by exposure of cells to chloramphenicol or puromycin, consistent with a preexisting bipartite nucleoid structure. Isolated nucleoids and nucleoids in stationary-phase cells also assumed a doublet shape, supporting such a structure. The underlying structure is suggested to be two subunits joined by a linker. Both the subunits and the linker appear to deform to accommodate the space available within cells or spheroplasts ("flexible doublet" model). (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zimmerman, SB (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 46 TC 12 Z9 12 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 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD MAY PY 2003 VL 142 IS 2 BP 256 EP 265 DI 10.1016/S1047-8477(02)00637-8 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 675ZT UT WOS:000182728000004 PM 12713953 ER PT J AU Fraser, RDB Steinert, PM Parry, DAD AF Fraser, RDB Steinert, PM Parry, DAD TI Structural changes in trichocyte keratin intermediate filaments during keratinization SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE hair; surface lattice; compaction; packing; protofilaments; protofibrils; ring-core structure; keratin ID CROSS-LINKING; MICROSCOPY AB The so-called hard alpha-keratins, such as quill and hair, have a composite structure in which intermediate filaments (IF) are embedded in a sulfur-rich matrix. Recent studies of these trichocyte keratin IF have revealed that substantial changes in the molecular architecture take place when oxidation of the cysteine residues occurs as part of the terminal differentiation/keratinization process. Recent cryoelectron microscope studies suggest that the IF has a tubular structure prior to keratinization, but transmission electron micrographs of thin sections of fully keratinized fibers exhibit a "ring-core" structure. In the present contribution we develop a generic model for the IF in the reduced state based on cross-linking studies and discuss two possibilities for the way in which this structure may be modified during the keratinization process. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Massey Univ, Inst FUndamental Sci, Palmerston North, New Zealand. NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Parry, DAD (reprint author), Massey Univ, Inst FUndamental Sci, Private Bag 11-222, Palmerston North, New Zealand. NR 35 TC 12 Z9 12 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD MAY PY 2003 VL 142 IS 2 BP 266 EP 271 DI 10.1016/S1047-8477(02)00636-6 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 675ZT UT WOS:000182728000005 PM 12713954 ER PT J AU Argenziano, G Soyer, HP Chimenti, S Talamini, R Corona, R Sera, F Binder, M Cerroni, L De Rosa, G Ferrara, G Hofmann-Wellenhof, R Landthater, M Menzies, SW Pehamberger, H Piccolo, D Rabinovitz, HS Schiffner, R Staibano, S Stolz, W Bartenjev, I Blum, A Braun, R Cabo, H Carli, P De Giorgi, V Fleming, MG Grichnik, JM Grin, CM Halpern, AC Johr, R Katz, B Kenet, RO Kittler, H Kreusch, J Malvehy, J Mazzocchetti, G Oliviero, M Ozdemir, F Peris, K Perotti, R Perusquia, A Pizzichetta, MA Puig, S Rao, B Rubegni, P Saida, T Scalvenzi, M Seidenari, S Stanganelli, I Tanaka, M Westerhoff, K Wolf, IH Braun-Falco, O Kerl, H Nishikawa, T Wolff, K AF Argenziano, G Soyer, HP Chimenti, S Talamini, R Corona, R Sera, F Binder, M Cerroni, L De Rosa, G Ferrara, G Hofmann-Wellenhof, R Landthater, M Menzies, SW Pehamberger, H Piccolo, D Rabinovitz, HS Schiffner, R Staibano, S Stolz, W Bartenjev, I Blum, A Braun, R Cabo, H Carli, P De Giorgi, V Fleming, MG Grichnik, JM Grin, CM Halpern, AC Johr, R Katz, B Kenet, RO Kittler, H Kreusch, J Malvehy, J Mazzocchetti, G Oliviero, M Ozdemir, F Peris, K Perotti, R Perusquia, A Pizzichetta, MA Puig, S Rao, B Rubegni, P Saida, T Scalvenzi, M Seidenari, S Stanganelli, I Tanaka, M Westerhoff, K Wolf, IH Braun-Falco, O Kerl, H Nishikawa, T Wolff, K TI Dermoscopy of pigmented skin lesions: Results of a consensus meeting via the Internet SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID EPILUMINESCENCE MICROSCOPY; SURFACE MICROSCOPY; CLINICAL-DIAGNOSIS; MALIGNANT-MELANOMA; EARLY RECOGNITION; PATTERN-ANALYSIS; ABCD RULE; DERMATOSCOPY; FEATURES; RATERS AB Background: There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. Objective: The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. Methods: Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. kappa Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. Results: Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean kappa value: 0.53). Conclusion: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens Lip a new territory for diagnosing and managing pigmented skin lesions. C1 Graz Univ, Dept Dermatol, A-8036 Graz, Austria. Univ Naples 2, Dept Dermatol, Naples, Italy. Univ Roma Tor Vergata, Rome, Italy. Univ Vienna, A-1010 Vienna, Austria. Univ Ljubljana, Ctr Clin, Ljubljana, Slovenia. Univ Tubingen, D-72074 Tubingen, Germany. Univ Hosp Geneva, Geneva, Switzerland. Univ Buenos Aires, Hosp Clin, RA-1053 Buenos Aires, DF, Argentina. Univ Florence, I-50121 Florence, Italy. Med Coll Wisconsin, Milwaukee, WI USA. Univ Connecticut, Sch Med, Storrs, CT 06268 USA. Univ Luebeck, Lubeck, Germany. Univ Barcelona, E-08007 Barcelona, Spain. Ege Univ, Fac Med, Izmir, Turkey. Univ Siena, I-53100 Siena, Italy. Shinshu Univ, Sch Med, Matsumoto, Nagano, Japan. Univ Modena, I-41100 Modena, Italy. Keio Univ, Sch Med, Tokyo 108, Japan. Univ Munich, D-80539 Munich, Germany. NYU, Sch Med, Ctr Med, New York, NY USA. NCI, Bethesda, MD 20892 USA. Univ Naples Federico II, Inst Pathol, Ist Dermopatico Immacolata, Naples, Italy. Gaetano Rummo Gen Hosp, Pathol Anat Serv, Sydney, NSW, Australia. Univ Sydney, Skin Canc Res Inst, Sydney, NSW 2006, Australia. Royal Prince Alfred Hosp, Sydney, NSW, Australia. Univ Miami, Sch Med, Dept Dermatol, Coral Gables, FL 33124 USA. Duke Univ, Ctr Med, Div Dermatol, Dept Med, Durham, NC 27706 USA. Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, New York, NY USA. Univ Miami, Pigmented Les Clin, Dept Dermatol & Cutaneous, Sch Med, Coral Gables, FL 33124 USA. Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. New York Presbyterian Hosp, Dept Med, New York, NY USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Dermatol, Newark, NJ 07103 USA. RP Soyer, HP (reprint author), Graz Univ, Dept Dermatol, Auenbruggerpl 8, A-8036 Graz, Austria. RI Sera, Francesco/C-8176-2011; Soyer, H. Peter/E-6000-2010; Rubegni, Pietro/J-8734-2016; Karabulut, Erman/G-6679-2011; OI Soyer, H. Peter/0000-0002-4770-561X; Rubegni, Pietro/0000-0002-4128-3145; SCALVENZI, Massimiliano/0000-0002-9912-3611; DE ROSA, Gaetano/0000-0002-3635-5853; Peris, Ketty/0000-0002-5237-0463; KITTLER, HARALD/0000-0002-0051-8016; Argenziano, Giuseppe/0000-0003-1413-8214; Puig, Susana/0000-0003-1337-9745 NR 35 TC 533 Z9 541 U1 3 U2 27 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2003 VL 48 IS 5 BP 679 EP 693 DI 10.1067/mjd.2003.281 PG 15 WC Dermatology SC Dermatology GA 680KT UT WOS:000182977200004 PM 12734496 ER PT J AU Yabroff, KR Mangan, P Mandelblatt, J AF Yabroff, KR Mangan, P Mandelblatt, J TI Effectiveness of interventions to increase Papanicolaou smear use SO JOURNAL OF THE AMERICAN BOARD OF FAMILY PRACTICE LA English DT Review ID PREVENTIVE HEALTH-CARE; RANDOMIZED CONTROLLED TRIAL; MEXICAN-AMERICAN WOMEN; CANCER-SCREENING-TESTS; PUBLIC HOSPITAL EMERGENCY; INNER-CITY WOMEN; LOW-INCOME WOMEN; CERVICAL-CANCER; PAP SMEAR; BREAST-CANCER AB Background. Many women fail to adhere to Papanicolaou smear screening guidelines. Although many interventions have been developed to increase screening, the effectiveness of different types of interventions; is unclear. Methods: We performed a systematic review of interventions to increase Papanicolaou smear use published between 1980 and April 2001 and included concurrently or randomized controlled studies with defined outcomes. Interventions were classified as targeted to patients, providers, patients and providers, or health care systems and as behavioral, cognitive, sociologic, or a combination based on the expected action of the intervention. Effect sizes and 95% confidence intervals were calculated for each intervention. Results: Forty-six studies with 63 separate interventions were included. Most interventions increased Papanicolaou smear use, although in many cases the increase was not statistically significant. Behavioral interventions targeted to patients (eg, mailed or telephone reminders) increased Papanicolaou smear use by up to 18.8%; cognitive and sociologic interventions were only marginally effective, although a single culturally specific, sociologic intervention using a lay health worker increased use by 18.0% (95% confidence interval [CI]: 7.6, 28.4). Provider-targeted interventions were heterogeneous. Interventions that targeted both patients and providers did not appear to be any more effective than interventions targeted to either patients or providers alone. One of the most effective interventions, which introduced a system change by integrating a nurse-practitioner and offered same-day screening, increased screening by 32.7% (95% CI: 20.5, 44.9). Conclusions: Overall, most interventions increased Papanicolaou smear use, although there was tremendous variability in their effectiveness. Selection of intervention strategies will depend on provider and patient population characteristics and feasibility of implementation. (J Am Board Fain Pract 2003; 16:188-203.) C1 Georgetown Univ, Med Ctr, Canc Control Program, Lombardi Canc Ctr, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. RP Yabroff, KR (reprint author), NCI, Hlth Serv & Econ Branch, Applied Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. OI Yabroff, K. Robin/0000-0003-0644-5572 FU NIA NIH HHS [R01-AG15340] NR 138 TC 25 Z9 26 U1 9 U2 10 PU AMER BOARD FAMILY PRACTICE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 0893-8652 J9 J AM BOARD FAM PRACT JI J. Am. Board Fam. Pract. PD MAY-JUN PY 2003 VL 16 IS 3 BP 188 EP 203 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 676JW UT WOS:000182749000001 PM 12755245 ER PT J AU Reuben, DB Keeler, E Seeman, TE Sewall, A Hirsch, SH Guralnik, JM AF Reuben, DB Keeler, E Seeman, TE Sewall, A Hirsch, SH Guralnik, JM TI Identification of risk for high hospital use: Cost comparisons of four strategies and performance across subgroups SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE healthcare costs; risk identification; screening; hospital use ID CASE-MANAGEMENT; SELF-REPORT; MEDICARE; ENROLLEES; OUTCOMES; TRIAL; CARE AB OBJECTIVES: To determine the relative costs of four risk-identification strategies and compare their performance in predicting hospital use by different subgroups of older persons based on age, sex, and prior hospital use. DESIGN: Prospective validation study and cost-comparison analysis. SETTING: Community-based. PARTICIPANTS: Five thousand one hundred thirty-eight participants of the sixth wave of three sites of the Established Populations for Epidemiologic Studies of the Elderly. MEASUREMENTS: Four strategies (prior hospitalization data only, a 10-item self-report screen alone, self-report combined with two laboratory tests, and sequential self-report plus as-needed use of laboratory tests when the self-report screen is inconclusive) and 3-year Medicare Part A hospital cost data. RESULTS: Assuming that interventions based on screening would yield a total benefit of $1,000 per true-positive case and a cost of $400 for each false-positive case, the sequential strategy was slightly less expensive than the self-report only strategy; both were considerably less expensive than the combined or hospitalization-only strategies. Accuracy as measured by the area under the receiver operating characteristic curve for the sequential strategy was comparable for all subgroups (between 0.62 and 0.70) but was least accurate for those who had high prior use and for those aged 85 and older. CONCLUSION: A sequential screening strategy that administers laboratory tests selectively is slightly less expensive than one that uses only self-report items. This strategy is also accurate in both sexes, in those with various degrees of prior use, and in the oldest old. C1 Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA. RAND Corp, Santa Monica, CA USA. Sewall Inc, Bethesda, MD USA. NIA, Bethesda, MD 20892 USA. RP Reuben, DB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. FU NIA NIH HHS [AG16677] NR 14 TC 6 Z9 6 U1 2 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2003 VL 51 IS 5 BP 615 EP 620 DI 10.1034/j.1600-0579.2003.00204.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 673JU UT WOS:000182577900004 PM 12752835 ER PT J AU Rantanen, T Volpato, S Ferrucci, L Heikkinen, E Fried, LP Guralnik, JM AF Rantanen, T Volpato, S Ferrucci, L Heikkinen, E Fried, LP Guralnik, JM TI Handgrip strength and cause-specific and total mortality in older disabled women: Exploring the mechanism SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE handgrip strength; muscle strength; predictor of mortality; older disabled women ID C-REACTIVE PROTEIN; BODY-MASS INDEX; MUSCLE STRENGTH; SERUM-ALBUMIN; GRIP STRENGTH; PHYSICAL-ACTIVITY; SKELETAL-MUSCLE; MEN; PREDICTORS; RISK AB OBJECTIVES: To examine the association between muscle strength and total and cause-specific mortality and the plausible contributing factors to this association, such as presence of diseases commonly underlying mortality, inflammation, nutritional deficiency, physical inactivity, smoking, and depression. DESIGN: Prospective population-based cohort study with mortality surveillance over 5 years. SETTING: Elderly women residing in the eastern half of Baltimore, Maryland, and part of Baltimore County. PARTICIPANTS: Nine hundred nineteen moderately to severely disabled women aged 65 to 101 who participated in handgrip strength testing at baseline as part of the Women's Health and Aging Study. MEASUREMENTS: Cardiovascular disease (CVD), cancer, respiratory disease, other measures (not CVD, respiratory, or cancer), total mortality, handgrip strength, and interleukin-6. RESULTS: Over the 5-year follow-up, 336 deaths occurred: 149 due to CVD, 59 due to cancer, 38 due to respiratory disease, and 90 due to other diseases. The unadjusted relative risk (RR) of CVD mortality was 3.21 (95% confidence interval (CI) = 2.00-5.14) in the lowest and 1.88 (95% CI = 1.11-3.21) in the middle compared with the highest tertile of handgrip strength. The unadjusted RR of respiratory mortality was 2.38 (95% CI = 1.09-5.20) and other mortality 2.59 (95% CI = 1.59-4.20) in the lowest versus the highest grip-strength tertile. Cancer mortality was not associated with grip strength. After adjusting for age, race, body height, and weight, the RR of CVD mortality decreased to 2.17 (95% CI = 1.26-3.73) in the lowest and 1.56 (95% CI = 0.89-2.71) in the middle, with the highest grip-strength tertile as the reference. Further adjustments for multiple diseases, physical inactivity, smoking, interleukin-6, C-reactive protein, serum albumin, unintentional weight loss, and depressive symptoms did not materially change the risk estimates. Similar results were observed for all-cause mortality. CONCLUSION: In older disabled women, handgrip strength was a powerful predictor of cause-specific and total mortality. Presence of chronic diseases commonly underlying death or the mechanisms behind decline in muscle strength in chronic disease, such as inflammation, poor nutritional status, disuse, and depression, all of which are independent predictors of mortality, did not explain the association. Handgrip strength, an indicator of overall muscle strength, may predict mortality through mechanisms other than those leading from disease to muscle impairment. Grip strength tests may help identify patients at increased risk of deterioration of health. C1 Univ Jyvaskyla, Dept Hlth Sci, FIN-40014 Jyvaskyla, Finland. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Natl Res Inst, Dept Geriatr, Florence, Italy. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Rantanen, T (reprint author), Univ Jyvaskyla, Dept Hlth Sci, POB 35, FIN-40014 Jyvaskyla, Finland. RI VOLPATO, STEFANO/H-2977-2014; Rantanen, Taina/O-6579-2016 OI VOLPATO, STEFANO/0000-0003-4335-6034; Rantanen, Taina/0000-0002-1604-1945 NR 28 TC 260 Z9 267 U1 4 U2 30 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2003 VL 51 IS 5 BP 636 EP 641 DI 10.1034/j.1600-0579.2003.00207.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 673JU UT WOS:000182577900007 PM 12752838 ER PT J AU Weeber, M Vos, R Klein, H de Jong-van den Berg, LTW Aronson, AR Molema, G AF Weeber, M Vos, R Klein, H de Jong-van den Berg, LTW Aronson, AR Molema, G TI Generating hypotheses by discovering implicit associations in the literature: A case report of a search for new potential therapeutic uses for thalidomide. SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID CHRONIC HEPATITIS-C; MESSENGER-RNA EXPRESSION; NECROSIS-FACTOR-ALPHA; ACUTE-PANCREATITIS; CYTOKINE PRODUCTION; MYASTHENIA-GRAVIS; TNF-ALPHA; MULTIPLE-SCLEROSIS; MONONUCLEAR-CELLS; VIRUS-INFECTION AB The availability of scientific bibliographies through online databases provides a rich source of information for scientists to support their research. However, the risk of this pervasive availability is that an individual researcher may fail to find relevant information that is outside the direct scope of interest. Following Swanson's ABC model of disjoint but complementary structures in the biomedical literature, we have developed a discovery support tool to systematically analyze the scientific literature in order to generate novel and plausible hypotheses. In this case report, we employ the system to find potentially new target diseases for the drug thalidomide. We find solid bibliographic evidence suggesting that thalidomide might be useful for treating acute pancreatitis, chronic hepatitis C, Helicobacter pylori-induced gastritis, and myasthenia gravis. However, experimental and clinical evaluation is needed to validate these hypotheses and to assess the trade-off between therapeutic benefits and toxicities. C1 Univ Groningen, Int Drug Explorat, Dept Social Pharm & Pharmacoepidemiol, Groningen, Netherlands. Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD USA. Univ Masstricht, Dept Hlth Eth & Philosophy, Hlth Res Inst, Maastricht, Netherlands. Univ Groningen, Inst Drug Explorat, Med Biol Sect, Dept Pathol & Lab Med, Groningen, Netherlands. RP Weeber, M (reprint author), Erasmus Univ, Dept Med Informat, Erasmus MC, NL-3000 DR Rotterdam, Netherlands. OI Molema, Grietje/0000-0002-4147-6676 NR 52 TC 98 Z9 102 U1 1 U2 7 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY-JUN PY 2003 VL 10 IS 3 BP 252 EP 259 DI 10.1197/jamia.M1158 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 675AE UT WOS:000182670200004 PM 12626374 ER PT J AU Nguyen, DM Schrump, WD Tsai, WS Chen, A Stewart, JH Steiner, F Schrump, DS AF Nguyen, DM Schrump, WD Tsai, WS Chen, A Stewart, JH Steiner, F Schrump, DS TI Enhancement of depsipeptide-mediated apoptosis of lung or esophageal cancer cells by flavopiridol: Activation of the mitochondria-dependent death-signaling pathway SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; PHASE-I TRIAL; KINASE-INHIBITOR; LEUKEMIA-CELLS; REFRACTORY NEOPLASMS; UP-REGULATION; CYCLE ARREST; FR901228; DIFFERENTIATION; DYSFUNCTION AB Objective: Treating cancer cells with depsipeptide, a novel antitumor agent currently in a phase II clinical trial, causes potent upregulation of p2l/WAF1 expression and cell arrest at G1 and G2 checkpoints. p21/WAF1 upregulation, however, impedes the ability of depsipeptide to induce significant apoptosis. This study was designed to determine whether flavopiridol, a synthetic cyclin-dependent kinase inhibitor known to inhibit p21 expression in tumor cells, could enhance depsipeptide-mediated apoptosis in cultured lung and esophageal cancer cells. Methods: Lung or esophageal cancer cells were exposed to depsipeptide, flavopiridol, or a combination of depsipeptide and flavopiridol. Cytotoxicity and apoptosis were quantitated by means of (4,5-dimethylthiazo-2-yl)-2,5-diphenyl tetrazolium bromide and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-based assays, respectively. Cytosolic cytochrome c levels, caspase 9 activity, mitochondrial membrane depolarization, and dependence of apoptosis on caspase 9 in treated cells were studied to determine the role of the mitochondria in mediating apoptosis induced by this drug combination. Results: Flavopiridol completely abolished depsipeptide-mediated dose-dependent upregulation of p21/WAF1 expression. Combining flavopiridol with depsipeptide resulted in a 3- to 8-fold reduction of depsipeptide inhibitory concentration of 50% values that was closely paralleled by synergistic enhancement of apoptosis (4- to 10-fold higher than levels of cell death induced by either drug alone) in all cancer cell lines. The essential role of mitochondria in mediating cell death was indicated by robust translocation of cytochrome c from the mitochondria into the cytosol, 2.5- to 5-fold activation of caspase 9, severe disruption of mitochondrial inner membrane potential, and complete inhibition of apoptosis by the selective caspase 9 inhibitor. More important, this drug combination was not toxic to primary normal epithelial cells derived from the airway or skin. Conclusion: The depsipeptide plus flavopiridol combination exhibits powerful and selective cytocidal activity against cancer but not normal cells. Apoptosis induced by this combination is mediated by the mitochondria-dependent death pathway. C1 NCI, Sect Thorac Oncol, Surg Branch, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. RP Nguyen, DM (reprint author), NCI, Sect Thorac Oncol, Surg Branch, Canc Res Ctr,NIH, 10 Ctr Dr,Room 2B07, Bethesda, MD 20892 USA. FU NCI NIH HHS [K08 CA131482] NR 22 TC 38 Z9 38 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2003 VL 125 IS 5 BP 1132 EP 1142 DI 10.1067/mtc.2003.180 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 685MC UT WOS:000183266600022 PM 12771887 ER PT J AU Snyder, C Harlan, L Knopf, K Potosky, A Kaplan, R AF Snyder, C Harlan, L Knopf, K Potosky, A Kaplan, R TI Patterns of care for the treatment of bladder cancer SO JOURNAL OF UROLOGY LA English DT Article DE bladder; bladder neoplasms; patient care; risk factors; SEER Program ID RACIAL-DIFFERENCES; ADJUVANT THERAPY; CARCINOMA; MANAGEMENT; PRESERVATION; PROSTATE; AGE AB Purpose: We examined bladder cancer patterns of care and differences in treatments administered to patients by age, race/ethnicity and gender using a population based sample. Material and Methods: A random sample of bladder cancer patients diagnosed in 1995 without upper urinary tract involvement in 8 Surveillance, Epidemiology and End Results registries were included. Tumor stage and grade were used to assign patients to risk groups and patterns of care were investigated. Descriptive analyses and logistic regression models examined differences in care based on patient age, race/ethnicity and gender. Results: Of the 669 patients 485 patients had superficial disease, including 222 at low, 151 at intermediate and 112 at high risk, while 154 had muscle invasive disease. Of the patients with superficial bladder cancer 73.4% underwent transurethral bladder resection only. Those with muscle invasive disease were most commonly treated with transurethral bladder resection only (49.1%) or cystectomy only (31%). Intravesical chemotherapy in patients with superficial tumors and aggressive treatment with cystectomy and/or systemic chemotherapy in those with muscle invasive disease increased in relation to risk classification, as may have been expected. However, multivariate analyses suggested an influence of co-morbidities on intravesical therapy in patients with superficial tumors and an influence of patient age and geographic region on aggressive treatment for muscle invasive disease. Conclusions: No differences in treatment were identified based on patient race/ethnicity or gender. Treatment for superficial disease is primarily influenced by risk category and co-morbidities, while treatment for muscle invasive disease is influenced by patient age and geographic region. C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Anne Arundel Oncol Ctr, Annapolis, MD USA. RP Snyder, C (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NR 19 TC 56 Z9 56 U1 1 U2 2 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 MAY PY 2003 VL 169 IS 5 BP 1697 EP 1701 DI 10.1097/01.ju.0000056727.30546.b7 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 667WM UT WOS:000182257600011 PM 12686811 ER PT J AU Jung, YT Kozak, CA AF Jung, YT Kozak, CA TI Generation of novel syncytium-inducing and host range variants of ecotropic Moloney murine leukemia virus in Mus spicilegus SO JOURNAL OF VIROLOGY LA English DT Article ID RECEPTOR; RETROVIRUSES; GLYCOPROTEIN; SEQUENCE; PROTEIN; DOMAIN; MICE AB Mus spicilegus is an Eastern European wild mouse species that has previously been reported to harbor an unusual infectious ecotropic murine leukemia virus (MLV) and proviral envelope genes of a novel MLV subgroup. In the present study, M. spicilegus neonates were inoculated with Moloney ecotropic MLV (MoMLV). All 17 inoculated mice produced infectious ecotropic virus after 8 to 14 weeks, and two unusual phenotypes distinguished the isolates from MoMLV. First, most of the M. spicilegus isolates grew to equal titers on M. dunni and SC-1 cells, although MoMLV does not efficiently infect M. dunni cells. The deduced amino acid sequence of a representative clone differed from MoMLV by insertion of two serine residues within the VRA of SUenv. Modification of a molecular clone of MoMLV by the addition of these serines produced a virus that grows to high titer in M. dunni cells, establishing a role for these two serine residues in host range. A second unusual phenotype was found in only one of the M. spicilegus isolates, Sp1574. Sp1574 produces large syncytia of multinucleated giant cells in M. dunni cells, but its replication is restricted in other mouse cell lines. Sequencing and mutagenesis demonstrated that syncytium formation could be attributed to a single amino acid substitution within VRA, S82F. Thus, viruses with altered growth properties are selected during growth in M. spicilegus. The mutations associated with the host range and syncytium-inducing variants map to a key region of VRA known to govern interactions with the cell surface receptor, suggesting that the associated phenotypes may result from altered interactions with the unusual ecotropic virus mCAT1 receptor carried by M. dunni. C1 NIAID, NIH, LMM, Bethesda, MD 20892 USA. RP Kozak, CA (reprint author), NIAID, NIH, LMM, Bldg 4,Room 329,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA. NR 23 TC 11 Z9 11 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 MAY PY 2003 VL 77 IS 9 BP 5065 EP 5072 DI 10.1128/JVI.77.9.5065-5072.2003 PG 8 WC Virology SC Virology GA 668MF UT WOS:000182297200005 PM 12692209 ER PT J AU Jinno-Oue, A Wilt, SG Hanson, C Dugger, NV Hoffman, PM Masuda, M Ruscetti, SK AF Jinno-Oue, A Wilt, SG Hanson, C Dugger, NV Hoffman, PM Masuda, M Ruscetti, SK TI Expression of inducible nitric oxide synthase and elevation of tyrosine nitration of a 32-kilodalton cellular protein in brain capillary endothelial cells from rats infected with a neuropathogenic murine leukemia virus SO JOURNAL OF VIROLOGY LA English DT Article ID NERVOUS-SYSTEM; NITROTYROSINE IMMUNOREACTIVITY; OXIDATIVE DAMAGE; PEROXYNITRITE; NEURODEGENERATION; TROPISM; TLR4; PHOSPHORYLATION; PURIFICATION; INACTIVATION AB PVC-211 murine leukemia virus (MuLV) is a neuropathogenic variant of Friend MuLV (F-MuLV) which causes a rapidly progressive spongiform neurodegenerative disease in rodents. The primary target of PVC-211 MuLV infection in the brain is the brain capillary endothelial cell (BCEC), which is resistant to F-MuLV infection. Previous studies have shown that changes in the envelope gene of PVC-211 MuLV confer BCEC tropism to the virus. However, little is known about how infection of BCECs by PVC-211 MuLV induces neurological disease. Previous results suggest that nitric oxide (NO), which has been implicated as a potential neurotoxin, is involved in PVC-211 MuLV-induced neurodegeneration. In this study, we show that expression of inducible nitric oxide synthase (iNOS), which produces NO from L-arginine, is induced in BCECs from PVC-211 MuLV-infected rats. Furthermore, elevated levels of a 32-kDa cellular protein modified by 3-nitrotyrosine, which is a hallmark of NO production, were observed in virus-infected BCECs. BCECs from rats infected with BCEC-tropic but nonneuropathogenic PVF-e5 MuLV; which is a chimeric virus between PVC-211 MuLV and F-MuLV, fail to induce either iNOS expression or elevation of tyrosine nitration of a 32-kDa protein. These results suggest that expression of iNOS and nitration of tyrosine residues of a 32-kDa protein in PVC-211 MuLV-infected BCECs may play an important role in neurological disease induction. C1 NCI, Basic Res Lab, Frederick, MD 21702 USA. Univ Maryland, Res Serv, Dept Vet Affairs Med Ctr, Baltimore, MD 21201 USA. Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA. Dokkyo Univ, Sch Med, Dept Microbiol, Mibu, Tochigi 3210293, Japan. RP Ruscetti, SK (reprint author), NCI, Basic Res Lab, Bldg 469,Room 205, Frederick, MD 21702 USA. NR 46 TC 6 Z9 7 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 MAY PY 2003 VL 77 IS 9 BP 5145 EP 5151 DI 10.1128/JVI.77.9.5145-5151.2003 PG 7 WC Virology SC Virology GA 668MF UT WOS:000182297200013 PM 12692217 ER PT J AU Best, SM Shelton, JF Pompey, JM Wolfinbarger, JB Bloom, ME AF Best, SM Shelton, JF Pompey, JM Wolfinbarger, JB Bloom, ME TI Caspase cleavage of the nonstructural protein NS1 mediates replication of Aleutian mink disease parvovirus SO JOURNAL OF VIROLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; MINUTE VIRUS; IN-VIVO; NUCLEOCAPSID PROTEIN; ADULT MINK; APOPTOSIS; INFECTION; IDENTIFICATION; MICE; LOCALIZATION AB Virus-induced apoptosis of infected cells can limit both the time and the cellular machinery available for virus replication. Hence, many viruses have evolved strategies to specifically inhibit apoptosis. However, Aleutian mink disease parvovirus (ADV) is the first example of a DNA virus that not only induces apoptosis but also utilizes caspase activity to facilitate virus replication. To determine the function of caspase activity during ADV replication, virus-infected cell lysates or purified ADV proteins were incubated with various purified caspases. Caspases cleaved the major nonstructural protein of ADV (NS1) at two caspase recognition sequences, whereas ADV structural proteins could not be cleaved. Importantly, the NS1 products could be identified in ADV-infected cells but were not present in infected cells pretreated with caspase inhibitors. By mutating putative caspase cleavage sites (D to E), we mapped the two cleavage sites to amino acid residues NS1:227 (INTD down arrow S) and NS1:285 (DQTD down arrow S). Replication of ADV containing either of these mutations was reduced 10(3)- to 10(4)-fold compared to that of wild-type virus, and a construct containing both mutations was replication defective. Immunofluorescent studies revealed that cleavage was required for nuclear localization of NS1. The requirement for caspase activity during permissive replication suggests that limitation of caspase activation and apoptosis in vivo may be a novel approach to restricting virus replication. C1 NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Bloom, ME (reprint author), NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 39 TC 39 Z9 43 U1 0 U2 11 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 MAY PY 2003 VL 77 IS 9 BP 5305 EP 5312 DI 10.1128/JVI.77.9.5305-5312.2003 PG 8 WC Virology SC Virology GA 668MF UT WOS:000182297200028 PM 12692232 ER PT J AU Nicola, AV McEvoy, AM Straus, SE AF Nicola, AV McEvoy, AM Straus, SE TI Roles for endocytosis and low pH in herpes simplex virus entry into HeLa and chinese hamster ovary cells SO JOURNAL OF VIROLOGY LA English DT Article ID RECEPTOR-RELATED PROTEIN-1; GLYCOPROTEIN-D; POLIOVIRUS RECEPTOR; MONOCLONAL-ANTIBODIES; SURFACE RECEPTORS; MEMBRANE-FUSION; HEPARAN-SULFATE; PSEUDORABIES VIRUS; SEMLIKI FOREST; VERO CELLS AB Herpes simplex virus (HSV) infection of many cultured cells, e.g., Vero cells, can be initiated by receptor binding and pH-neutral fusion with the cell surface. Here we report that a major pathway for HSV entry into the HeLa and CHO-K1 cell lines is dependent on endocytosis and exposure to a low pH. Enveloped virions were readily detected in HeLa or receptor-expressing CHO cell vesicles by electron microscopy at <30 min postinfection. As expected, images of virus fusion with the Vero cell surface were prevalent. Treatment with energy depletion or hypertonic medium, which inhibits endocytosis, prevented uptake of HSV from the HeLa and CHO cell surface relative to uptake from the Vero cell surface. Incubation of HeLa and CHO cells with the weak base ammonium chloride or the ionophore monensin, which elevate the low pH of organelles, blocked HSV entry in a dose-dependent manner. Noncytotoxic concentrations of these agents acted at an early step during infection by HSV type 1 and 2 strains. Entry mediated by the HSV receptor HveA, nectin-1, or nectin-2 was also blocked. As analyzed by fluorescence microscopy, lysosomotropic agents such as the vacuolar H+-ATPase inhibitor bafilomycin A1 blocked the delivery of virus capsids to the nuclei of the HeLa and CHO cell lines but had no effect on capsid transport in Vero cells. The results suggest that HSV can utilize two distinct entry pathways, depending on the type of cell encountered. C1 NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Nicola, AV (reprint author), 10 Ctr Dr,Room 11N228, Bethesda, MD 20892 USA. NR 61 TC 204 Z9 210 U1 1 U2 15 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 MAY PY 2003 VL 77 IS 9 BP 5324 EP 5332 DI 10.1128/JVI.77.9.5324-5332.2003 PG 9 WC Virology SC Virology GA 668MF UT WOS:000182297200030 PM 12692234 ER PT J AU Teysset, L Dang, VD Kim, MK Levin, HL AF Teysset, L Dang, VD Kim, MK Levin, HL TI A long terminal repeat-containing retrotransposon of Schizosaccharomyces pombe expresses a Gag-like protein that assembles into virus-like particles which mediate reverse transcription SO JOURNAL OF VIROLOGY LA English DT Article ID ROUS-SARCOMA VIRUS; MAJOR HOMOLOGY REGION; MURINE LEUKEMIA VIRUSES; NUCLEAR-PORE FACTOR; DNA STRAND TRANSFER; FISSION YEAST; NUCLEOCAPSID PROTEIN; RIBONUCLEOPROTEIN PARTICLE; DROSOPHILA-MELANOGASTER; MUTATIONAL ANALYSIS AB The Tf1 element of Schizosaccharomyces pombe is a long terminal repeat-containing retrotransposon that encodes functional protease, reverse transcriptase, and integrase proteins. Although these proteins are known to be necessary for protein processing, reverse transcription, and integration, respectively, the function of the protein thought to be Gag has not been determined. We present here the first electron microscopy of Tf1 particles. We tested whether the putative Gag of Tf1 was required for particle formation, packaging of RNA, and reverse transcription. We generated deletions of 10 amino acids in each of the four hydrophilic domains of the protein and found that all four mutations reduced transposition activity. The N-terminal deletion removed a nuclear localization signal and inhibited nuclear import of the transposon. The two mutations in the center of Gag destabilized the protein and resulted in no virus-like particles. The C-terminal deletion caused a defect in RNA packaging and, as a result, low levels of cDNA. The electron microscopy of cells expressing a truncated Tf1 showed that Gag alone was sufficient for the formation of virus-like particles. Taken together, these results indicate that Tf1 encodes a Gag protein that is a functional equivalent of the Gag proteins of retroviruses. C1 NICHHD, Lab Gene Regulat & Dev, Sect Eukaryot Transposable Elements, NIH, Bethesda, MD 20892 USA. RP NICHHD, Lab Gene Regulat & Dev, Sect Eukaryot Transposable Elements, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. EM Henry_Levin@nih.gov NR 67 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2003 VL 77 IS 9 BP 5451 EP 5463 DI 10.1128/JVI.77.9.5451-5463.2003 PG 13 WC Virology SC Virology GA 668MF UT WOS:000182297200042 PM 12692246 ER PT J AU Caughey, B Raymond, LD Raymond, GJ Maxson, L Silveira, J Baron, GS AF Caughey, B Raymond, LD Raymond, GJ Maxson, L Silveira, J Baron, GS TI Inhibition of protease-resistant prion protein accumulation in vitro by curcumin SO JOURNAL OF VIROLOGY LA English DT Article ID CONGO RED; AGENT REPLICATION; INCUBATION PERIOD; PRP ACCUMULATION; DEXTRAN SULFATE; SCRAPIE; INFECTION; MOUSE AB Inhibition of the accumulation of protease-resistant prion protein (PrP-res) is a prime strategy in the development of potential transmissible spongiform encephalopathy (TSE) therapeutics. Here we show that curcumin (diferoylmethane), a major component of the spice turmeric, potently inhibits PrP-res accumulation in scrapie agent-infected neuroblastoma cells (50% inhibitory concentration, similar to10 nM) and partially inhibits the cell-free conversion of PrP to PrP-res. In vivo studies showed that dietary administration of curcumin had no significant effect on the onset of scrapie in hamsters. Nonetheless, other studies have shown that curcumin is nontoxic and can penetrate the brain, properties that give curcumin advantages over inhibitors previously identified as potential prophylactic and/or therapeutic anti-TSE compounds. C1 NIAID, Rocky Mt Lab, Lab Persistent Viral Dis, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Lab, Lab Persistent Viral Dis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 14 TC 59 Z9 62 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 MAY PY 2003 VL 77 IS 9 BP 5499 EP 5502 DI 10.1128/JVI.77.9.5499-5502.2003 PG 4 WC Virology SC Virology GA 668MF UT WOS:000182297200047 PM 12692251 ER PT J AU Ott, DE Coren, LV Chertova, EN Gagliardi, TD Nagashima, K Sowder, RC Poon, DTK Gorelick, RJ AF Ott, DE Coren, LV Chertova, EN Gagliardi, TD Nagashima, K Sowder, RC Poon, DTK Gorelick, RJ TI Elimination of protease activity restores efficient virion production to a human immunodeficiency virus type 1 nucleocapsid deletion mutant SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; ROUS-SARCOMA VIRUS; VITRO ASSEMBLY PROPERTIES; POLYMERASE CHAIN-REACTION; RETROVIRAL GAG PROTEINS; VIRAL GENOMIC RNA; IN-VITRO; ZINC-FINGER; PARTICLE-PRODUCTION; BASIC RESIDUES AB The nucleocapsid (NC) region of human immunodeficiency virus type 1 (HIV-1) Gag is required for specific genomic RNA packaging. To determine if NC is absolutely required for virion formation, we deleted all but seven amino acids from NC in a full-length NL4-3 proviral clone. This construct, DelNC, produced approximately four- to sixfold fewer virions than did the wild type, and these virions were noninfectious (less than 10(-6) relative to the wild type) and severely genomic RNA deficient. Immunoblot and high-pressure liquid chromatography analyses showed that all of the mature Gag proteins except NC were present in the mutant virion preparations, although there was a modest decrease in Gag processing. DelNC virions had lower densities and were more heterogeneous than wild-type particles, consistent with a defect in the interaction assembly or I domain. Electron microscopy showed that the DelNC virions displayed a variety of aberrant morphological forms. Inactivating the protease activity of DelNC by mutation or protease inhibitor treatment restored virion production to wild-type levels. DelNC-protease mutants formed immature-appearing particles that were as dense as wild-type virions without incorporating genomic RNA. Therefore, protease activity combined with the absence of NC causes the defect in DelNC virion production, suggesting that premature processing of Gag during assembly causes this effect. These results show that HIV-1 can form particles efficiently without NC. C1 NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Res Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Ott, DE (reprint author), NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 78 TC 40 Z9 41 U1 0 U2 2 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 MAY PY 2003 VL 77 IS 10 BP 5547 EP 5556 DI 10.1128/JVI.77.10.5547.2003 PG 10 WC Virology SC Virology GA 674HJ UT WOS:000182631100001 PM 12719547 ER PT J AU Kaur, A Kassis, N Hale, CL Simon, M Elliott, M Gomez-Yafal, A Lifson, JD Desrosiers, RC Wang, F Barry, P Mach, M Johnson, RP AF Kaur, A Kassis, N Hale, CL Simon, M Elliott, M Gomez-Yafal, A Lifson, JD Desrosiers, RC Wang, F Barry, P Mach, M Johnson, RP TI Direct relationship between suppression of virus-specific immunity and emergence of cytomegalovirus disease in simian AIDS SO JOURNAL OF VIROLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSES; INFECTED RHESUS-MACAQUES; ALLOGENEIC BONE-MARROW; LIVED PLASMA-CELLS; IMMUNODEFICIENCY-VIRUS; DIFFERENTIATION; INDIVIDUALS; ANTIBODIES; GENERATION; RECIPIENTS AB Although opportunistic infections like cytomegalovirus (CMV) are common sequelae of end-stage AIDS, the immune events leading to CMV reactivation in human immunodeficiency virus (HIV)-infected individuals are not well defined. The role of cellular and humoral CMV-specific immune responses in immune control of latent CMV infection was evaluated prospectively in a cohort of 11 simian immunodeficiency virus (SIV)-infected CMV-seropositive rhesus macaques, 6 of whom had histologic evidence of CMV disease at death. Macaques with CMV disease differed from macaques without CMV disease in having significantly higher levels of plasma SIV RNA and CMV DNA and significantly lower titers of anti-CMV binding antibodies (Abs) at the time of death. A significant decline in anti-CMV Abs and CMV-specific CD4(+) and CD8(+) T lymphocytes over time was observed in the macaques with CMV disease, but not in the macaques without CMV disease. Reduction in CMV-specific CD8(+) T lymphocytes and anti-CMV neutralizing Abs was significantly correlated with a decline in CMV-specific CD4(+) T lymphocytes. Although declines in CMV-specific T lymphocytes alone were sufficient for reactivation of low-level CMV viremia, high-level viremia (> 1,000 copies of CMV DNA per ml of plasma) was observed when anti-CMV neutralizing and binding Abs had also declined. Thus, the occurrence of CMV reactivation-associated disease in AIDS is associated with suppression of both cellular and humoral CMV-specific immune responses. The underlying mechanism may be a dysfunction of memory B and CD8(+) T lymphocytes associated with SIV-induced impairment of CMV-specific CD4(+) T-cell help. C1 Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, Sch Med, New England Primate Res Ctr, Div Pathol, Southborough, MA 01772 USA. Harvard Univ, Sch Med, New England Primate Res Ctr, Div Microbiol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Therion Biol, Cambridge, MA 02142 USA. NCI, SAIC Frederick, AIDS Vaccine Program, Frederick, MD 21702 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. Univ Erlangen Nurnberg, Inst Klin & Mol Virol, D-91058 Erlangen, Germany. RP Kaur, A (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, 1 Pine Hill Dr, Southborough, MA 01772 USA. FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NCRR NIH HHS [P51 RR000168, K26 RR000168, RR00168]; NIAID NIH HHS [AI43890, AI45314, R01 AI043890] NR 31 TC 48 Z9 50 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 MAY PY 2003 VL 77 IS 10 BP 5749 EP 5758 DI 10.1128/JVI.77.10.5749-5758.2003 PG 10 WC Virology SC Virology GA 674HJ UT WOS:000182631100022 PM 12719568 ER PT J AU Gaddis, NC Chertova, E Sheehy, AM Henderson, LE Malim, MH AF Gaddis, NC Chertova, E Sheehy, AM Henderson, LE Malim, MH TI Comprehensive investigation of the molecular defect in vif-deficient human immunodeficiency virus type 1 virions SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-DEPENDENT REQUIREMENT; VIRAL MATRIX PROTEIN; IN-VIVO REPLICATION; AP-1 BINDING-SITE; REVERSE TRANSCRIPTION; HIV-1 PROTEASE; DNA-SYNTHESIS; NONPERMISSIVE CELLS; RESTRICTIVE CELLS; NONDIVIDING CELLS AB Replication of human immunodeficiency virus type 1 (HIV-1) in primary blood lymphocytes, certain T-cell lines (nonpermissive cells), and most likely in vivo is highly dependent on the virally encoded Vif protein. Evidence suggests that Vif acts late in the viral life cycle during assembly, budding, and/or maturation to counteract the antiviral activity of the CEM15 protein and possibly other antiviral factors. Because HIV-1 virions produced in the absence of Vif are severely restricted at a postentry, preintegration step of infection, it is presumed that such virions differ from wild-type virions in some way. In the present study, we established a protocol for producing large quantities of vif-deficient HIV-1 (HIV-1/Deltavif) from an acute infection of nonpermissive T cells and performed a thorough examination of the defect in these virions. Aside from the expected lack of Vif, we observed no apparent abnormalities in the packaging, modification, processing, or function of proteins in Deltavif virions. In addition, we found no consistent defect in the ability of Deltavif virions to perform intravirion reverse transcription under a variety of assay conditions, suggesting that the reverse transcription complexes in these particles can behave normally under cell-free conditions. Consistent with this finding, neither the placement of the primer tRNA(3)(Lys) nor its ability to promote reverse transcription in an in vitro assay was affected by a lack of Vif. Based on the inability of this comprehensive analysis to uncover molecular defects in Deltavif virions, we speculate that such defects are likely to be subtle and/or rare. C1 Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. NCI, SAIC Frederick, AIDS Vaccine Program, Frederick, MD 21702 USA. Univ London Kings Coll, Guys Kings & St Thomas Sch Med, Dept Infect Dis, London SE1 9RT, England. RP Malim, MH (reprint author), Univ London Kings Coll, GKT Guys Hosp, Guys Kings & St Thomas Sch Med, Dept Infect Dis, 3rd Floor,New Guys House, London SE1 9RT, England. OI Gaddis, Nathan/0000-0001-5205-7138; Malim, Michael/0000-0002-7699-2064 FU NCI NIH HHS [N01CO12400]; NIAID NIH HHS [AI10460, F32 AI010460, AI46246] NR 69 TC 58 Z9 58 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 MAY PY 2003 VL 77 IS 10 BP 5810 EP 5820 DI 10.1128/JVI.77.10.5810-5820.2003 PG 11 WC Virology SC Virology GA 674HJ UT WOS:000182631100028 PM 12719574 ER PT J AU Fisher, TS Darden, T Prasad, VR AF Fisher, TS Darden, T Prasad, VR TI Mutations proximal to the minor groove-binding track of human immunodeficiency virus type 1 reverse transcriptase differentially affect utilization of RNA versus DNA as template SO JOURNAL OF VIROLOGY LA English DT Article ID DOUBLE-STRANDED DNA; VERTICAL-SCANNING MUTAGENESIS; NUCLEIC ACID INTERACTIONS; DRUG-RESISTANT MUTANTS; POLYMERASE ACTIVE-SITE; PRIMER GRIP REGION; ANGSTROM RESOLUTION; CRITICAL TRYPTOPHAN; CRYSTAL-STRUCTURE; IN-VITRO AB Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), like all retroviral RTs, is a versatile DNA polymerase that can copy both RNA and DNA templates. In spite of extensive investigations into the structure-function of this enzyme, the structural basis for this dual template specificity is poorly understood. Biochemical studies with two mutations in HIV-1 RT that affect residues contacting the template-primer now provide some insight into this specialized property. The mutations are N255D and N265D, both adjoining the minor groove-binding track, in the thumb region. The N265D substitution led to a loss of processive polymerization on DNA but not on RNA, whereas N255D drastically reduced processive synthesis on both templates. This differential template usage was accompanied by a rapid dissociation of the N265D variant on DNA but not RNA templates, whereas the N255D variant rapidly dissociated from both templates. Molecular dynamics modeling suggested that N265D leads to a loss of template strand-specific hydrogen bonding, indicating that this is a key determinant of the differential template affinity. The N255D substitution caused local changes in conformation and a consequent loss of interaction with the primer, leading to a loss of processive synthesis with both templates. We conclude that N265 is part of a subset of template-enzyme contacts that enable RT to utilize DNA templates in addition to RNA templates and that such residues play an important role in facilitating processive DNA synthesis on both RNA and DNA templates. C1 Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Prasad, VR (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, 1300 Morris Pk Ave,Rm GB 401, Bronx, NY 10461 USA. FU NIAID NIH HHS [R01 AI030861, R01 AI30861]; NIGMS NIH HHS [T32 GM007491, T32-GM07491] NR 46 TC 18 Z9 18 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 MAY PY 2003 VL 77 IS 10 BP 5837 EP 5845 DI 10.1128/JVI.77.10.5837-5845.2003 PG 9 WC Virology SC Virology GA 674HJ UT WOS:000182631100031 PM 12719577 ER PT J AU Rea, TD Psaty, BM Heckbert, SR Cushman, M Meilahn, E Olson, JL Lemaitre, RN Smith, NL Sotoodehnia, N Chaves, PHM AF Rea, TD Psaty, BM Heckbert, SR Cushman, M Meilahn, E Olson, JL Lemaitre, RN Smith, NL Sotoodehnia, N Chaves, PHM TI Hormone replacement therapy and the risk of incident congestive heart failure: The cardiovascular health study SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID PRESSURE-OVERLOAD HYPERTROPHY; CORONARY-ARTERY DISEASE; C-REACTIVE PROTEIN; POSTMENOPAUSAL WOMEN; OLDER ADULTS; SECONDARY PREVENTION; NATRIURETIC PEPTIDE; GENDER DIFFERENCES; BODY-MASS; ESTROGEN AB Background: The development of congestive heart failure (CHF) in older persons is related to a variety of mechanisms. Hormone replacement therapy (HRT) affects several of the pathways that may be important in the development of CHF. We hypothesized that HRT would be associated with a decreased risk of incident CHF. Methods: Using Cox proportional-hazards regression, we assessed the risk of incident CHF (n = 304) associated with time-dependent past and current use of HRT compared to never use. The Cardiovascular Health Study is a prospective cohort study of community-dwelling adults aged 65 years and older. This analysis included female participants without a history of CHF at baseline (n = 3223). Results: At baseline, 62% were never users, 26% were past users, and 12% were current users of HRT. Compared with never users, the multivariable relative risk (RR) of CHF was 1.01 (95% confidence interval [95% CI] 0.76,1.34) for past users and 1.34 (0.93,1.94) for current users. Results were similar among most treatment and clinical subgroups, except that the association of current HRT with CHF appeared to depend on body mass index (BMD or osteoporosis status. The RR was 0.82 (0.43,1.60) for normal weight women, 1.65 (0.95,2.88) for overweight women, and 2.22 (1.06,4.67) for obese women (p = 0.01 for interaction). Similarly, the RR was 0.15 (0.04,0.65) for women with osteoporosis and 1.82 (1.25,2.65) for women without osteoporosis (p = 0.001 for interaction). Conclusions: Overall, HRT was not associated with the risk of incident CHF, although BMI and osteoporosis appeared to modify the association of HRT with CHF. The risk of CHF was lower in patients with lower BMI or osteoporosis. C1 Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. Univ Vermont, Dept Med, Burlington, VT USA. Univ Vermont, Dept Pathol, Burlington, VT USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. NHLBI, Bethesda, MD 20892 USA. Johns Hopkins Ctr Aging & Hlth, Baltimore, MD USA. RP Rea, TD (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Metropolitan Pk,E Tower,1730 Minor Ave, Seattle, WA 98101 USA. NR 63 TC 2 Z9 2 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD MAY PY 2003 VL 12 IS 4 BP 341 EP 350 DI 10.1089/154099903765448853 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 683JN UT WOS:000183145100005 PM 12804341 ER PT J AU Priyadarshi, S Valentine, B Han, C Fedorova, OV Bagrov, AY Liu, J Periyasamy, SM Kennedy, D Malhotra, D Xie, ZJ Shapiro, JI AF Priyadarshi, S Valentine, B Han, C Fedorova, OV Bagrov, AY Liu, J Periyasamy, SM Kennedy, D Malhotra, D Xie, ZJ Shapiro, JI TI Effect of green tea extract on cardiac hypertrophy following 5/6 nephrectomy in the rat SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-Society-of-Nephrology CY OCT 10-17, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Nephrol DE sodium; potassium; ATPase; ventricular dysfunction; myocardial calcium ID CHRONIC-RENAL-FAILURE; NA+/K+-ATPASE; INHIBITOR AB Background. Left ventricular hypertrophy commonly complicates chronic renal failure. We have observed that at least one pathway of left ventricular hypertrophy appears to involve signaling through reactive oxygen species (ROS). Green tea is a substance that appears to have substantial antioxidant activity, yet is safe and is currently widely used. We, therefore, studied whether green tea supplementation could attenuate the development of left ventricular hypertrophy in an animal model of chronic renal failure. Methods. Male Sprague-Dawley rats were subjected to sham or remnant kidney surgery and given green tea extract (0.1% and 0.25%) or plain drinking water for the next 4 weeks. Heart weight, body weight, and cardiac Na-K-ATPase activity were measured at the end of this period. To further test our hypothesis, we performed studies in cardiac myocytes isolated from adult male Sprague-Dawley rats. We measured the generation of ROS using the oxidant sensitive dye dichlorofluorescein (DCF) as well as (H-3)phenylalanine incorporation following exposure to cardiac glycosides with and without green tea extract. Results. Administration of green tea extract at 0.25% resulted in attenuation of left ventricular hypertrophy, hypertension, and preserved cardiac Na-K-ATPase activity in rats subjected to remnant kidney surgery (all P < 0.01). In subsequent studies performed in isolated cardiac myocytes, both ouabain and marinobufagenin (MBG) were both found to increase ROS production and (H-3)phenylalanine incorporation at concentrations substantially below their inhibitor concentration (IC) 50 for the sodium pump. Addition of green tea extract prevented increases in ROS production as well as (H-3)phenylalanine incorporation in these isolated cardiac myocytes. Conclusion. Green tea extract appears to block the development of cardiac hypertrophy in experimental renal failure. Some of this effect may be related to the attenuation of hypertension, but a direct effect on cardiac myocyte ROS production and growth was also identified. Clinical studies of green tea extract in chronic renal failure patients may be warranted. C1 Med Coll Ohio, Dept Med, Toledo, OH 43614 USA. Med Coll Ohio, Dept Pharmacol, Toledo, OH 43614 USA. Chinese Acad Prevent Med Sci, Inst Nutr & Food Hyg, Beijing, Peoples R China. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Shapiro, JI (reprint author), Med Coll Ohio, Dept Med, 3120 Glendale Ave, Toledo, OH 43614 USA. FU NHLBI NIH HHS [HL67963, HL57144, HL63238] NR 25 TC 54 Z9 57 U1 0 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2003 VL 63 IS 5 BP 1785 EP 1790 DI 10.1046/j.1523-1755.2003.00914.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 664BG UT WOS:000182041400019 PM 12675854 ER PT J AU Stamatelou, KK Francis, ME Jones, CA Nyberg, LM Curhan, GC AF Stamatelou, KK Francis, ME Jones, CA Nyberg, LM Curhan, GC TI Time trends in reported prevalence of kidney stones in the United States: 1976-1994 SO KIDNEY INTERNATIONAL LA English DT Article DE kidney stones; prevalence; temporal trends ID DIETARY CALCIUM; GEOGRAPHIC VARIABILITY; NEPHROLITHIASIS; RISK; UROLITHIASIS; EPIDEMIOLOGY; POPULATION; HYPERCALCIURIA; HYPERTENSION; NUTRIENTS AB Background. A body of evidence establishes that the occurrence of kidney stone disease has increased in some communities of industrialized countries. Information on recent temporal trends in the United States is lacking and population-based data on epidemiologic patterns are limited. Study objective was to determine whether kidney stone disease prevalence increased in the United States over a 20-year period and the influence of region, race/ethnicity, and gender on stone disease risk. Methods. We measured the prevalence of kidney stone disease history from the United States National Health and Nutrition Examination Survey (II and III), population-based, cross-sectional studies, involving 15,364 adult United States residents in 1976 to 1980 and 16,115 adult United States residents in 1988 to 1994. Results. Disease prevalence among 20- to 74-year-old United States residents was greater in 1988 to 1994 than in 1976 to 1980 (5.2% vs. 3.8%, P < 0.05), greater in males than females, and increased with age in each time period. Among 1988 to 1994 adults, non-Hispanic African Americans had reduced risk of disease compared to non-Hispanic Caucasians (1.7% vs. 5.9%, P < 0.05), and Mexican Americans (1.7% vs. 2.6%, P < 0.05). Also, age-adjusted prevalence was highest in the South (6.6%) and lowest in the West (3.3%). Findings were consistent across gender and multivariate adjusted odds ratios for stone disease history, including all demographic variables, as well as diuretic use, tea or coffee consumption, and dietary intake of calcium, protein, and fat did not materially change the results. Conclusion. Prevalence of kidney stone disease history in the United States population increased between 1980 and 1994. A history of stone disease was strongly associated with race/ethnicity and region of residence. C1 Blue Cross Hosp, Renal Unit, Athens, Greece. Social & Sci Syst, Silver Spring, MD USA. Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. NIDDKD, Urol Program, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Stamatelou, KK (reprint author), 40 E Adistasis Str Vrilissia, Athens 15235, Greece. NR 29 TC 629 Z9 653 U1 3 U2 23 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2003 VL 63 IS 5 BP 1817 EP 1823 DI 10.1046/j.1523-1755.2003.00917.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 664BG UT WOS:000182041400023 PM 12675858 ER PT J AU Hironaka, K Factor, VM Calvisi, DF Conner, EA Thorgeirsson, SS AF Hironaka, K Factor, VM Calvisi, DF Conner, EA Thorgeirsson, SS TI Dysregulation of DNA repair pathways in a transforming growth factor alpha/c-myc transgenic mouse model of accelerated hepatocarcinogenesis SO LABORATORY INVESTIGATION LA English DT Article ID BASE EXCISION-REPAIR; TRANSCRIPTION-COUPLED REPAIR; OXIDE SYNTHASE EXPRESSION; CELL-CYCLE CHECKPOINT; STRAND BREAK REPAIR; MISMATCH REPAIR; C-MYC; ATAXIA-TELANGIECTASIA; HEPATOCELLULAR-CARCINOMA; V(D)J RECOMBINATION AB Previous work from our laboratory has implicated oxidative DNA damage and genetic instability in the etiology of transforming growth factor-alpha (TGFalpha)/c-myc-associated hepatocarcinogenesis. In contrast, oxidative DNA damage was lower in c-myc single-transgenic mice, consistent with less chromosomal damage and with later and more benign tumor formation. We examined whether defects in the DNA repair pathways contribute to the acceleration of liver cancer in TGFalpha/c-myc mice. A cDNA expression array containing 140 known genes and multiplex RT-PCR were used to compare the basal levels of expression of DNA repair genes at the dysplastic stage. Thirty-five percent (8/23) and 43% (10/23) of DNA repair genes were constitutively up-regulated in 10-week-old TGFalpha/c-myc and c-myc transgenic livers, respectively, compared with wild-type controls. The commonly up-regulated genes were OGG1 and NTH1 of base excision repair; ERCC5, RAD23A, and RAD23B of nucleotide excision repair; and RAD50, RAD52, and RAD54 involved in DNA strand break repair. Additional treatment with a peroxisome proliferator, Wy-14,643, known to increase the level of oxidants in the liver, failed to induce a further increase in the expression level of DNA repair enzymes in TGFalpha/c-myc but not in c-myc or wild-type livers. Moreover, expression of several genes, including Ku80, PMS2, and ATM, was decreased in TGFalpha/c-myc livers, suggesting a fault or inefficient activation of the DNA repair pathway upon induction of oxidative stress. Together, the results show that DNA damage response is attenuated in TGFalpha/c-myc mice, creating a condition that may contribute to acceleration of liver cancer in this model. C1 NCI, Canc Res Ctr, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Canc Res Ctr, Expt Carcinogenesis Lab, NIH, 37 Convent Dr,Bldg 37,Room 4146A, Bethesda, MD 20892 USA. NR 65 TC 27 Z9 27 U1 0 U2 1 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 MAY PY 2003 VL 83 IS 5 BP 643 EP 654 DI 10.1097/01.LAB.0000067483.89649.11 PG 12 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 682WE UT WOS:000183114700005 PM 12746474 ER PT J AU Warner, HR Sierra, F AF Warner, HR Sierra, F TI Models of accelerated ageing can be informative about the molecular mechanisms of ageing and/or age-related pathology SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE accelerated ageing; molecular mechanisms; age-related pathology ID LIFE-SPAN; CAENORHABDITIS-ELEGANS; GROWTH-HORMONE; STRESS RESISTANCE; MUTANT MICE; IN-VIVO; SENESCENCE; LONGEVITY; PROTEIN; GENE AB During the past ten years considerable progress has been made in discovering genes that regulate longevity by identifying single gene mutations that lead to increased longevity. The initial success in nematodes was quickly followed by comparable success in fruit flies and mice. In contrast, mutations that cause a decrease in longevity have been largely discounted as unlikely to be informative about aging mechanisms. However, the recent creation of several mutant mouse models that develop a variety of aging-like phenotypes and die prematurely, suggests that such models may be useful in understanding aging mechanisms, particularly as they relate to progressive tissue and organ dysfunction. A possible common feature of these models may be an imbalance between loss of cells by apoptosis and subsequent cell replacement, leading gradually to a net loss of cells in multiple tissues. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 NIA, Biol Ageing Program, Bethesda, MD 20892 USA. RP Warner, HR (reprint author), NIA, Biol Ageing Program, Bethesda, MD 20892 USA. NR 40 TC 28 Z9 28 U1 0 U2 0 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 PY 2003 VL 124 IS 5 BP 581 EP 587 DI 10.1016/S0047-6374(03)00008-3 PG 7 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 682ZB UT WOS:000183121300002 PM 12735898 ER PT J AU Graakjaer, J Bischoff, C Korshohn, L Holstebroe, S Vach, W Bohr, VA Christensen, K Kolvraa, S AF Graakjaer, J Bischoff, C Korshohn, L Holstebroe, S Vach, W Bohr, VA Christensen, K Kolvraa, S TI The pattern of chromosome-specific variations in telomere length in humans is determined by inherited, telomere-near factors and is maintained throughout life SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE chromosome-specific variations; telomere length; FISH ID HUMAN-DIPLOID FIBROBLASTS; POLY(ADP-RIBOSE) POLYMERASE; P53 PROTEIN; HUMAN-CELLS; IN-VIVO; END; ACTIVATION; REPEATS; AGE; ELONGATION AB In this study the telomere length distribution on individual chromosome arms in humans has been characterized. Using fluorescent in situ hybridisation (FISH) followed by computer-assisted analysis of digital images, we show that the distribution of telomere length on individual chromosome arms is not random, but that humans have a common telomere profile. This profile exists in both lymphocytes, amniocytes and fibroblasts, and is conserved during life until about the age of 100. We find that the length of the telomeres generally follows the length of the chromosomes and that the chromosome specific differences in telomere length are determined by factors located very distally on the chromosome arms. In addition to the common profile, we also find that each individual has specific characteristics. Based on analysis of both monozygotic and dizygotic twins, we find that these characteristics are partly inherited. For each chromosome, age-related chromosome loss correlates negatively with telomere length. This suggests that decrease in telomere length may be an element in age-related genome instability. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Aarhus Univ, Inst Human Genet, DK-8000 Aarhus C, Denmark. Univ So Denmark, Dept Stat & Demog, DK-5000 Odense C, Denmark. DAKO, DK-2600 Glostrup, Denmark. NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. Univ So Denmark, Inst Publ Hlth, Epidemiol Sect, DK-5000 Odense C, Denmark. RP Kolvraa, S (reprint author), Aarhus Univ, Inst Human Genet, Bartholin Bldg,Vilhelm Meyers Alle, DK-8000 Aarhus C, Denmark. EM steen@humgen.au.dk RI Christensen, Kaare/C-2360-2009; Vach, Werner/F-2512-2011 OI Christensen, Kaare/0000-0002-5429-5292; Vach, Werner/0000-0003-1865-8399 FU PHS HHS [08761] NR 55 TC 74 Z9 74 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD MAY PY 2003 VL 124 IS 5 BP 629 EP 640 DI 10.1016/S0047-6374(03)00081-2 PG 12 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 682ZB UT WOS:000183121300007 PM 12735903 ER PT J AU Breneman, J Collins, MH Glod, J AF Breneman, J Collins, MH Glod, J TI Correspondence: Highly conformal radiotherapy for craniopharyngioma: (Potentially) throwing the baby out with the bathwater - Reply SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Letter C1 NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Dept Radiol, Div Radiat Oncol, Cincinnati, OH 45221 USA. Childrens Hosp, Med Ctr, Dept Pathol, Cincinnati, OH 45229 USA. RP Glod, J (reprint author), NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD MAY PY 2003 VL 40 IS 5 BP 341 EP 341 DI 10.1002/mpo.10238 PG 1 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 662KQ UT WOS:000181946200019 ER PT J AU Egan, CA Lazarova, Z Darling, TN Yee, C Yancey, KB AF Egan, CA Lazarova, Z Darling, TN Yee, C Yancey, KB TI Anti-epiligrin cicatricial pemphigoid - Clinical findings, immunopothogenesis, and significant associations SO MEDICINE LA English DT Article ID SUBEPIDERMAL BULLOUS DISEASES; BASAL-CELL CARCINOMA; GASTRIC-CARCINOMA; IGG AUTOANTIBODIES; LAMININ-5 ALPHA-3-BETA-3-GAMMA-2; DIFFERENTIAL EXPRESSION; ALPHA-SUBUNIT; NEONATAL MICE; AUTOIMMUNE; CANCER AB We report the clinical and immunopathologic findings in a cohort of 35 patients with anti-epiligrin cicatricial pemphigoid (AECP). These patients have a mucosal predominant subepithelial blistering disease that is clinically indistinguishable from other forms of cicatricial pemphigoid. The mucosal surfaces of the mouth and eye are most commonly involved. The skin is also involved in most patients, but usually this is less severe than mucosal involvement. AECP is characterized by the binding of circulating IgG autoantibodies to the dermal side of I M NaCl split human skin on indirect immunofluorescence microscopy. These IgG antibasement membrane autoantibodies target laminin 5, a heterotrimeric protein consisting of alpha3, beta3, and gamma2 subunits. IgG autoantibodies predominantly target the G domain within the a subunit. The presence of circulating IgG autoantibodies are specific for the diagnosis of AECP and are not seen in patients with other autoimmune blistering diseases or normal volunteers. Furthermore, we expand on data previously reported on the finding of an increased relative risk for solid cancer in patients with AECP, especially in the first year after blister onset. The majority of cancers documented in a cohort of 35 patients assembled over 12 years of study were adenocarcinomas that were at an advanced stage at their time of detection. This circumstance is thought to account for a high incidence of mortality among AECP patients who develop an associated cancer. AECP patients also demonstrate a significant risk for mortality as a consequence of treatment with systemic immunosuppressives. The current longitudinal study suggests that only a minority of AECP patients go into remission. C1 NCI, Dermatol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Egan, CA (reprint author), Beaumont Hosp, Dept Dermatol, Beaumont Rd, Dublin 9, Ireland. OI Darling, Thomas/0000-0002-5161-1974 NR 59 TC 54 Z9 55 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAY PY 2003 VL 82 IS 3 BP 177 EP 186 DI 10.1097/00005792-200305000-00004 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 679EC UT WOS:000182907000004 PM 12792304 ER PT J AU Thiel, M Caldwell, CC Sitkovsky, MV AF Thiel, M Caldwell, CC Sitkovsky, MV TI The critical role of adenosine A(2A) receptors in downregulation of inflammation and immunity in the pathogenesis of infectious diseases SO MICROBES AND INFECTION LA English DT Review DE adenosine; receptor; sepsis; infectious disease ID NECROSIS-FACTOR-ALPHA; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; TRIGGERED RESPIRATORY BURST; HUMAN ENDOTHELIAL-CELLS; HUMAN-NEUTROPHILS; CYCLIC-AMP; EXTRACELLULAR ADENOSINE; ENDOGENOUS ADENOSINE; HUMAN MONOCYTES; NITRIC-OXIDE AB Adenosine can be described as a retaliatory metabolite, the production and release of which is usually enhanced under adverse environmental conditions. Binding via specific receptors, adenosine activates endogenous protective mechanisms aiming at the restoration of tissue homeostasis. While adenosinergic downregulation of tissue damage is beneficial in acute inflammation, chronic suppression of the immune system by adenosine may account for immunoparalysis in long-term septic patients. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Klinikum Grosshadern, Anesthesiol Clin, D-81377 Munich, Germany. RP Sitkovsky, MV (reprint author), NIAID, Immunol Lab, NIH, 10-11N311,10 Ctr Dr, Bethesda, MD 20892 USA. OI Caldwell, Charles/0000-0003-1692-4550 NR 99 TC 91 Z9 95 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD MAY PY 2003 VL 5 IS 6 BP 515 EP 526 DI 10.1016/S1286-4579(03)00068-6 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 716WA UT WOS:000185051500009 PM 12758281 ER PT J AU Eddy, EM Toshimori, K O'Brien, DA AF Eddy, EM Toshimori, K O'Brien, DA TI Fibrous sheath of mammalian spermatozoa SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Review DE AKAP; signal transduction; glycolysis; sperm motility; GAPDS; cytoskeleton ID PROTEIN-KINASE-A; GLUTATHIONE-S-TRANSFERASE; PORIN-BINDING DOMAIN; MESSENGER-RIBONUCLEIC-ACID; TYPE-1 HEXOKINASE LACKING; SOLUBLE ADENYLYL-CYCLASE; MOUSE SPERM CAPACITATION; OUTER DENSE FIBERS; SMALL GTPASE RHO; MALE GERM-CELLS AB The fibrous sheath is a unique cytoskeletal structure surrounding the axoneme and outer dense fibers and defines the extent of the principal piece,region of the sperm flagellum. It consists of two longitudinal columns connected by closely arrayed semicircular ribs that assemble from distal to proximal throughout spermiogenesis. The fibrous sheath is believed to influence the degree of flexibility, plane of flagellar motion, and the shape of the flagellar beat. Nearly half of the protein in fibrous sheaths isolated from mouse sperm is AKAP4. This protein and two others, AKAP3 and TAKAP-80, have anchoring sites for cAMP-dependent protein kinase. AKAP3 also anchors ropporin, a spermatogenic cell-specific protein that is linked through rhophilin to the small GTPase Rho. Other proteins associated with the fibrous sheath include two enzymes in the glycolytic pathway. Glyceraldehyde 3-phosphate dehydrogenase-s (GAPDS) is the product of a gene expressed only in spermatogenic cells, while hexokinase type 1-s (HK1-S) is derived from alternative transcripts present only in spermatogenic cells. Most of the other glycolytic enzymes in sperm have unique structural or functional properties. The fibrous sheath also contains a spermatogenic cell-specific member of the L-class glutathione S-transferase family (GSTM5) and an intermediate filament-like protein (FS39). These and other observations indicate that the fibrous sheath functions as a scaffold for proteins in signaling pathways that might be involved in regulating sperm maturation, motility, capacitation, hyperactivation, and/or acrosome reaction and for enzymes in the glycolytic pathway that provide energy for the hyperactivated motility of sperm that allows them to penetrate the zona pellucida. Published 2003 Wiley-Liss, Inc. C1 NIEHS, Reprod & Dev Toxicol Lab, Gamete Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. Miyazaki Med Coll, Dept Anat & Reprod Cell Biol, Miyazaki 8891629, Japan. Univ N Carolina, Sch Med, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. RP Eddy, EM (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Gamete Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. FU NICHD NIH HHS [U54 HD35041, U54 HD035041] NR 129 TC 175 Z9 186 U1 1 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-910X J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD MAY 1 PY 2003 VL 61 IS 1 BP 103 EP 115 DI 10.1002/jemt.10320 PG 13 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA 670AQ UT WOS:000182385000010 PM 12672126 ER PT J AU Engels, EA Pittaluga, S Whitby, D Rabkin, C Aoki, Y Jaffe, ES Goedert, JJ AF Engels, EA Pittaluga, S Whitby, D Rabkin, C Aoki, Y Jaffe, ES Goedert, JJ TI Immunoblastic lymphoma in persons with AIDS-associated Kaposi's sarcoma: A role for Kaposi's sarcoma-associated herpesvirus SO MODERN PATHOLOGY LA English DT Article ID PRIMARY EFFUSION LYMPHOMA; MULTICENTRIC CASTLEMANS-DISEASE; CAVITY-BASED LYMPHOMAS; DNA-SEQUENCES; HIV-INFECTION; VIRAL PROTEIN; VIRUS; EXPRESSION; ENTITY; P53 AB Kaposi's sarcoma-associated herpesvirus, the viral agent of Kaposi's sarcoma, is associated with two lymphoproliferative disorders: primary effusion lymphoma and multicentric Castleman's disease. To identify other lymphoproliferative conditions linked with Kaposi's sarcoma-associated herpesvirus, we studied non-Hodgkin's lymphomas arising in individuals with AIDS-associated Kaposi's sarcoma. Formalin-fixed tissues from 24 such lymphomas were examined. As expected, two primary effusion lymphomas were Kaposi's sarcoma-associated herpesvirus-positive, with immunohistochemistry demonstrating the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen in the nuclei of all neoplastic cells. Additionally, three of seven evaluable cases of the immunoblastic variant of diffuse large B-cell lymphoma (inummoblastic lymphoma) showed similar latency-associated nuclear antigen staining. These Kaposi's sarcoma-associated herpesvirus-positive inummoblastic lymphomas resembled primary effusion lymphoma histologically but were not known to involve body cavities (sites included lymph nodes, soft tissues of the neck, and spleen). Notably, 5-20% of the neoplastic cells in the Kaposi's sarcoma-associated herpesvirus-positive inummoblastic lymphomas also showed cytoplasmic staining for viral interleukin-6, a biologically active cytokine homologue found in primary effusion lymphoma. We conclude that Kaposi's sarcoma-associated herpesvirus is present in some inummoblastic lymphomas in persons with AIDS-associated Kaposi's sarcoma. C1 NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NCI, Viral Epidemiol Sect, AIDS Vaccine Program, Frederick, MD 21701 USA. NCI, Viral Epidemiol Branch, Div Canc & Epidemiol & Genet, Rockville, MD USA. NCI, Hematopathol Sect, Pathol Lab, Canc Res Ctr, Rockville, MD USA. RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8010, Bethesda, MD 20892 USA. NR 19 TC 40 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 2003 VL 16 IS 5 BP 424 EP 429 DI 10.1097/01.MP.0000056629.62148.55 PG 6 WC Pathology SC Pathology GA 682XM UT WOS:000183117700004 PM 12748248 ER PT J AU Howcroft, TK Raval, A Weissman, JD Gegonne, A Singer, DS AF Howcroft, TK Raval, A Weissman, JD Gegonne, A Singer, DS TI Distinct transcriptional pathways regulate basal and activate major histocompatibility complex class I expression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MHC CLASS-I; RNA-POLYMERASE-II; CORE PROMOTER ELEMENT; BINDING PROTEIN; GENE-EXPRESSION; TATA-BOX; NUCLEAR FACTOR; CPG ISLANDS; DNA-BINDING; B GENE AB Transcription of major histocompatibility complex (MHC) class I genes is regulated by both tissue-specific (basal) and hormone/cytokine (activated) mechanisms. Although promoter-proximal regulatory elements have been characterized extensively, the role of the core promoter in mediating regulation has been largely undefined. We report here that the class I core promoter consists of distinct elements that are differentially utilized in basal and activated transcription pathways. These pathways recruit distinct transcription factor complexes to the core promoter elements and target distinct transcription initiation sites. Class I transcription initiates at four major sites within the core promoter and is clustered in two distinct regions: "upstream" (-14 and -18) and "downstream" (+12 and +1). Basal transcription initiates predominantly from the upstream start site region and is completely dependent upon the general transcription factor TAF1 (TAF(II)250). Activated transcription initiates predominantly from the downstream region and is TAF1 (TAF(II)250) independent. USF1 augments transcription initiating through the upstream start sites and is dependent on TAR (TAF(II)250), a finding consistent with its role in regulating basal class I transcription. In contrast, transcription activated by the interferon mediator CIITA is independent of TAF1 (TAF(II)250) and focuses initiation on the downstream start sites. Thus, basal and activated transcriptions of an MHC class I gene target distinct core promoter domains, nucleate distinct transcription initiation complexes and initiate at distinct sites within the promoter. We propose that transcription initiation at the core promoter is a dynamic process in which the mechanisms of core promoter function differ depending on the cellular environment. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Howcroft, TK (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Rm 4B-17,10 Ctr Dr,MSC 1360, Bethesda, MD 20892 USA. NR 65 TC 25 Z9 25 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 MAY PY 2003 VL 23 IS 10 BP 3377 EP 3391 DI 10.1128/MCB.23.10.3377-3391.2003 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 675LJ UT WOS:000182696100001 PM 12724398 ER PT J AU Meetei, AR Sechi, S Wallisch, M Yang, DF Young, MK Joenje, H Hoatlin, ME Wang, WD AF Meetei, AR Sechi, S Wallisch, M Yang, DF Young, MK Joenje, H Hoatlin, ME Wang, WD TI A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SYNDROME GENE-PRODUCT; TOPOISOMERASE III-ALPHA; DNA MISMATCH REPAIR; SYNDROME PROTEIN; CANCER PREDISPOSITION; POSITIONAL CLONING; COLON-CANCER; HELICASE; BRCA2; BLM AB Bloom syndrome (BS) is a genetic disorder associated with dwarfism, immunodeficiency, reduced fertility, and an elevated risk of cancer. To investigate the mechanism of this disease, we isolated from human HeLa extracts three complexes containing the helicase defective in BS, BLM. Interestingly, one of the complexes, termed BRAFT, also contains five of the Fanconi anemia (FA) complementation group proteins (FA proteins). FA resembles BS in genomic instability and cancer predisposition, but most of its gene products have no known biochemical activity, and the molecular pathogenesis of the disease is poorly understood. BRAFT displays a DNA-unwinding activity, which requires the presence of BLM because complexes isolated from BLM-deficient cells lack such an activity. The complex also contains topoisomerase IIIalpha and replication protein A, proteins that are known to interact with BLM and could facilitate unwinding of DNA. We show that BLM complexes isolated from an FA cell line have a lower molecular mass. Our study provides the first biochemical characterization of a multiprotein FA complex and suggests a connection between the BLM and FA pathways of genomic maintenance. The findings that FA proteins are part of a DNA-unwinding complex imply that FA proteins may participate in DNA repair. C1 NIA, Genet Lab, Mass Spectrometry Unit, NIH, Baltimore, MD 21224 USA. Oregon Hlth & Sci Univ, Div Mol Med, Portland, OR 97201 USA. City Hope Natl Med Ctr, Beckman Res Inst, Div Immunol, Duarte, CA 91010 USA. Free Univ Amsterdam, Med Ctr, Dept Clin Genet & Human Genet, NL-1081 BT Amsterdam, Netherlands. RP Wang, WD (reprint author), NIA, Genet Lab, Mass Spectrometry Unit, NIH, 333 Cassell Dr,TRIAD Ctr Rm 3000, Baltimore, MD 21224 USA. NR 51 TC 243 Z9 257 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2003 VL 23 IS 10 BP 3417 EP 3426 DI 10.1128/MCB.23.10.3417-3426.2003 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 675LJ UT WOS:000182696100004 PM 12724401 ER PT J AU Galbraith, JA Terasaki, M AF Galbraith, JA Terasaki, M TI Controlled damage in thick specimens by multiphoton excitation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PLASMA-MEMBRANE DISRUPTIONS; STARFISH OOCYTES; CELL-CYCLE; FLUORESCENCE MICROSCOPY; MEIOSIS REINITIATION; GROWTH CONE; IN-VIVO; LASER; ZEBRAFISH; NUCLEAR AB Controlled damage by light energy has been a valuable tool in studies of cell function. Here, we show that the Ti:Sapphire laser in a multiphoton microscope can be used to cause localized damage within unlabeled cells or tissues at greater depths than previously possible. We show that the damage is due to a multiphoton process and made wounds as small as 1 mum in diameter 20 mum from the surface. A characteristic fluorescent scar allows monitoring of the damage and identifies the wound site in later observations. We were able to lesion a single axon within a bundle of nerves, locally interrupt organelle transport within one axon, cut dendrites in a zebrafish embryo, ablate a mitotic pole in a sea urchin egg, and wound the plasma membrane and nuclear envelope in starfish oocytes. The starfish nucleus collapsed similar to1 h after wounding, indicating that loss of compartmentation barrier makes the structure unstable; surprisingly, the oocyte still completed meiotic divisions when exposed to maturation hormone, indicating that the compartmentalization and translocation of cdk1 and its regulators is not required for,this process. Multiphoton excitation provides a new means for producing controlled damage deep within tissues or living organisms. C1 Marine Biol Lab, Woods Hole, MA 02543 USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Dept Physiol, Farmington, CT 06032 USA. RP Marine Biol Lab, Woods Hole, MA 02543 USA. EM terasaki@neuron.uchc.edu FU NIGMS NIH HHS [R01 GM060389, R01-GM60389] NR 42 TC 30 Z9 30 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 2003 VL 14 IS 5 BP 1808 EP 1817 DI 10.1091/mbc.E02-03-0163 PG 10 WC Cell Biology SC Cell Biology GA 679ED UT WOS:000182907100009 PM 12802057 ER PT J AU Huang, YE Iijima, M Parent, CA Funamoto, S Firtel, RA Devreotes, P AF Huang, YE Iijima, M Parent, CA Funamoto, S Firtel, RA Devreotes, P TI Receptor-mediated regulation of PI3Ks confines PI(3,4,5)P-3 to the leading edge of chemotaxing cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ADENYLYL-CYCLASE; LIVING CELLS; PHOSPHATIDYLINOSITOL 3,4-BISPHOSPHATE; PHOSPHOINOSITIDE 3-KINASE-GAMMA; CHEMOATTRACTANT RECEPTOR; CYTOSOLIC REGULATOR; SIGNAL-TRANSDUCTION; PI 3-KINASE; DICTYOSTELIUM; PROTEIN AB Recent studies have demonstrated that PH domains specific for PI(3,4,5)P-3 accumulate at the leading edge of a number of migrating cells and that PI3Ks and PTEN associate with the membrane at the front and back, respectively, of chemotaxing Dictyostelium discoideum cells. However, the dependence of chemoattractant induced changes in PI(3,4,5)p(3) on PI3K and PTEN activities have not been defined. We find that bulk PI(3,4,5)p3 levels increase transiently upon chemoattractant stimulation, and the changes are greater and more prolonged in pten(-) cells. PI3K activation increases within 5 s of chemoattractant addition and then declines to a low level of activity identically in wild-type and pten(-) cells. Reconstitution of the PI3K activation profile can be achieved by mixing membranes from stimulated pi3k1(-)/pi3k2(-) cells with cytosolic PI3Ks from unstimulated cells. These studies show that significant control of chemotaxis occurs upstream of the PI3Ks and that regulation of the PI3Ks and PTEN cooperate to shape the temporal and spatial localization of PI(3,4,5)p(3). C1 Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. NCI, Cellular & Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA. RP Devreotes, P (reprint author), Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. FU NIGMS NIH HHS [GM34933, R01 GM034933]; PHS HHS [29007] NR 42 TC 128 Z9 132 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 2003 VL 14 IS 5 BP 1913 EP 1922 DI 10.1091/mbc.E02-10-0703 PG 10 WC Cell Biology SC Cell Biology GA 679ED UT WOS:000182907100016 PM 12802064 ER PT J AU Schmidt, M Varma, A Drgon, T Bowers, B Cabib, E AF Schmidt, M Varma, A Drgon, T Bowers, B Cabib, E TI Septins, under Cla4p regulation, and the chitin ring are required for neck integrity in budding yeast SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CELL-WALL; SYNTHETIC LETHAL; ACTOMYOSIN RING; SYNTHASE-III; CYTOKINESIS; PROTEIN; MUTANTS; SEPTUM; CYCLE AB CLA4, encoding a protein kinase of the PAK type, and CDC11, encoding a septin, were isolated in a screen for synthetic lethality with CHS3, which encodes the chitin synthase III catalytic moiety. Although Ste20p shares some essential function with Cla4p, it did not show synthetic lethality with Chs3p. cla4 and cdc11 mutants exhibited similar morphological and septin localization defects, including aberrant and ectopic septa. Myo1p, which requires septins for localization, formed abnormally wide rings in cla4 mutants. In cultures started with unbudded cells, an inhibitor of Chs3p activity, nikkomycin Z, aggravated the abnormalities of cla4 and cdc11 mutants and gave rise to enlarged necks at the mother-bud junction, leading to cell death. It is concluded that Cla4p is required for the correct localization and/or assembly of the septin ring and that both the septin ring and the Chs3p-requiring chitin ring at the mother-bud neck cooperate in maintaining the neck constricted throughout the cell cycle, a vital function in budding yeast. C1 NIDDKD, Lab Biochem & Genet, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, Bethesda, MD 20892 USA. RP NIDDKD, Lab Biochem & Genet, Bethesda, MD 20892 USA. EM enricoc@bdg10.niddk.nih.gov NR 41 TC 50 Z9 50 U1 0 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 2003 VL 14 IS 5 BP 2128 EP 2141 DI 10.1091/mbc.E02-08-0547 PG 14 WC Cell Biology SC Cell Biology GA 679ED UT WOS:000182907100032 PM 12802080 ER PT J AU Hall, JM Korach, KS AF Hall, JM Korach, KS TI Stromal cell-derived factor 1, a novel target of estrogen receptor action, mediates the mitogenic effects of estradiol in ovarian and breast cancer cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID CXC CHEMOKINE PBSF/SDF-1; FACTOR-I; PROGESTERONE RECEPTORS; REPLACEMENT THERAPY; HORMONE RECEPTORS; MESSENGER-RNA; HIV-1 ENTRY; PS2 GENE; EXPRESSION; LIGAND AB Recent clinical studies estimate that 60-70% of human ovarian and breast cancers overexpress the estrogen receptor (ER). However, despite the established mitogenic effects of estrogen in these tumors, proliferative markers of hormone action are limited. In the current study, we report that the growth stimulatory cytokine stromal cell-derived factor 1 (SDF-1) is a bona fide target of estrogen action in ERalpha-positive human ovarian and breast cancer cells. Notably, estradiol treatment of BG-1 (ovarian carcinoma) and MCF-7 (breast carcinoma) cells leads to rapid and robust induction of the SDF-1 alpha and beta isoforms. This response is blocked by the pure ER antagonist ICI 182,780 and is not apparent in ER-negative ovarian cells, indicating that SDF-1 regulation is ERalpha mediated. Treatment with the protein synthesis inhibitor cycloheximide had no effect on estradiol induction of induction of SDF-1 mRNA levels mRNA levels, demonstrating that SDF-1 is a direct target of ERalpha. SDF-1 protein levels, although undetectable under basal conditions, were strikingly increased by hormone both intracellularly and in the media of cultured BG-1 and MCF-7 cells. In cell proliferation assays, the mitogenic effects of estradiol were neutralized by addition of an SDF-1 antibody and mimicked by the addition of exogenous SDF-1 protein, indicating that SDF-1 mediates the proliferative actions of hormone. Furthermore, activation of the SDF-1 receptor CXCR4 stimulated BG-1 and MCF-7 cell proliferation in a manner comparable to estradiol. Taken together, these results demonstrate a novel estrogen-mediated paracrine pathway for inducing cancer cell proliferation and suggest that SDF-1 and CXCR4 may represent novel therapeutic targets in ERalpha-positive ovarian and breast tumors. C1 NIEHS, Receptor Biol Sect, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), NIEHS, Receptor Biol Sect, POB 12233,MD B3-02, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 46 TC 191 Z9 204 U1 1 U2 7 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 MAY PY 2003 VL 17 IS 5 BP 792 EP 803 DI 10.1210/me.2002.0438 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 671CK UT WOS:000182447500002 PM 12586845 ER PT J AU Suzuki, H Zhang, XY Forrest, D Willingham, MC Cheng, SY AF Suzuki, H Zhang, XY Forrest, D Willingham, MC Cheng, SY TI Marked potentiation of the dominant negative, action of a mutant thyroid hormone receptor beta in mice by the ablation of one wild-type beta allele SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GENERALIZED RESISTANCE; BINDING DOMAIN; ISOFORMS; GENE; MUTATION; LIVER; SENSITIVITY; EXPRESSION; MECHANISM; KINDREDS AB Mutations in the thyroid hormone receptor (TR) beta gene result in resistance to thyroid hormone (RTH), characterized by reduced sensitivity of tissues to thyroid hormone. To understand which physiological TR pathways are affected by mutant receptors, we crossed mice with a dominantly negative TRbeta mutation (TRbetaPV) with mice carrying a TRbeta null mutation (TRbeta(-/-)) to determine the consequences of the TRbetaPV mutation in the absence of wild-type TRbeta. TRbeta(PV/-) mice are distinct from TRbeta(+/-) mice that did not show abnormalities in thyroid function tests. TRbeta(PV/-) mice are also distinct from TRbeta(PV/+) and TRbeta(-/-) mice in that the latter shows mild dysfunction in the pituitary-thyroid axis, whereas the former exhibit very severe abnormalities, including extensive papillary hyperplasia of the thyroid epi-thelium, indistinguishable from that observed in TRbeta(PV/PV) mice. Similar to TRbeta(PV/PV) mice, TRbeta(PV/-) mice exhibited impairment in weight gain. Moreover, the abnormal;regulation patterns of T-3-target genes in the tissues of TRbeta(PV/-) and TRbeta(PV/PV) mice were strikingly similar. Using TR isoforms and PV-specific antibodies in gel shift assays, we found that in vivo, PV competed with TRalpha1 for binding to thyroid hormone response elements in TRbeta(PV/-) mice as effectively as in TRbeta(PV/PV) mice. Thus, the actions of mutant TRbeta are markedly potentiated by the ablation of the second TRbeta allele, suggesting that interference with wild-type TRalpha1-mediated gene regulation by mutant TRbeta leads to severe RTH. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27157 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. FU NIDCD NIH HHS [DC-03441] NR 30 TC 9 Z9 9 U1 0 U2 0 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 MAY PY 2003 VL 17 IS 5 BP 895 EP 907 DI 10.1210/me.2002.0326 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 671CK UT WOS:000182447500010 PM 12576488 ER PT J AU Mudd, SH Braverman, N Pomper, M Tezcan, K Kronick, J Jayakar, P Garganta, C Ampola, MG Levy, HL McCandless, SE Wiltse, H Stabler, SP Allen, RH Wagner, C Borschel, MW AF Mudd, SH Braverman, N Pomper, M Tezcan, K Kronick, J Jayakar, P Garganta, C Ampola, MG Levy, HL McCandless, SE Wiltse, H Stabler, SP Allen, RH Wagner, C Borschel, MW TI Infantile hypermethioninemia and hyperhomocysteinemia due to high methionine intake: a diagnostic trap SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE hypermethioninemia; hyperhomocysteinemia; methionine; homocysteine; cystathionine; S-adenosylmethionine; infant; diet; cerebral edema; inferior colliculi ID GLYCINE N-METHYLTRANSFERASE; LOW-BIRTH-WEIGHT; FOLATE-DEFICIENCY; S-ADENOSYLMETHIONINE; PROTEIN INTAKE; AMINO-ACIDS; BLOOD SPOTS; PLASMA; COBALAMIN; ENCEPHALOPATHY AB Studies were carried out to identify the cause of combined severe hypermethioninemia and moderate hyperhomocysteinemia in a cluster of 10 infants ascertained between 1999 and early 2001. Although several were thought initially to have cystathionine synthase (CBS) deficiency and treated accordingly, CBS deficiency and other known genetic causes of hypermethioninemia were ruled out by assay of CBS activity in fibroblasts of four patients and by assays of plasma cystathionine and S-adenosylmethionine. Retrospective data on dietary methionine intakes and plasma concentrations of methionine and related metabolites established that the hypermethioninemia in nine of the 10 babies was related to ingestion of an infant protein hydrolysate formula, the methionine content of which had been increased from May 1998 to February 2001. The formula in question has now been reformulated and is no longer available. The 10th infant manifested similar metabolic abnormalities while receiving TPN containing excessive methionine. Brain MRI abnormalities indicative of cerebral edema, most marked in the cerebral cortex and posterior brainstem, occurred in two patients near times of extreme hypermethioninemia. Metabolic and MRI abnormalities resolved when the methionine intake decreased. A third infant had a normal MRI 1 day after the formula was changed. The possible relationship between extreme hypermethioninemia and cerebral edema is discussed and a working hypothesis offered to explain the relative sensitivity of the inferior colliculi, based upon the facts that this is the region most active in glucose utilization and that Na+,K+-ATPase is inhibited by methionine and related metabolites. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIMH, DIRP LMB, Mol Biol Lab, Bethesda, MD 20892 USA. Mckusick Nathans Inst Genet Med, CMSC 1004, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neuroradiol, Baltimore, MD 21205 USA. Connecticut Childrens Med Ctr, Hartford, CT 06106 USA. Dalhousie Univ, Dept Pediat, 1WK Hlth Ctr, Halifax, NS B3J 3G9, Canada. Miami Childrens Hosp, Dept Genet, Miami, FL 33155 USA. Yale Univ, Sch Med, Dept Genet, Biochem Dis Detect Lab, New Haven, CT 06520 USA. Tufts Univ, New England Med Ctr, Dept Pediat, Boston, MA 02111 USA. Childrens Hosp, Boston, MA 02115 USA. Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA. Univ Nebraska, Med Ctr, Dept Pediat, Omaha, NE 68198 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. VA Med Ctr, Nashville, TN 37232 USA. Abbott Labs, Ross Prod Div, Columbus, OH 43215 USA. RP Mudd, SH (reprint author), NIMH, DIRP LMB, Mol Biol Lab, Bldg 36,Room 1B-08,36 Convent Dr,MSC 4034, Bethesda, MD 20892 USA. EM shm@codon.nih.gov NR 30 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAY PY 2003 VL 79 IS 1 BP 6 EP 16 DI 10.1016/S1096-7192(03)00066-0 PG 11 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 685XG UT WOS:000183289200002 ER PT J AU Osawa, H Niiya, T Onuma, H Murakami, A Ochi, M Nishimiya, T Ogura, T Kato, K Shimizu, I Fujii, Y Ohashi, J Yamada, K Liang, SJ Manganiello, VC Fujita-Yamaguchi, Y Makino, H AF Osawa, H Niiya, T Onuma, H Murakami, A Ochi, M Nishimiya, T Ogura, T Kato, K Shimizu, I Fujii, Y Ohashi, J Yamada, K Liang, SJ Manganiello, VC Fujita-Yamaguchi, Y Makino, H TI Systematic search for single nucleotide polymorphisms in the 5 ' flanking region of the human phosphodiesterase 3B gene: absence of evidence for major effects of identified polymorphisms on susceptibility to Japanese type 2 diabetes SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE PDE3B gene; 5 ' flanking region; single nucleotide polymorphism; linkage disequilibrium; insulin resistance; type 2 diabetes ID ADIPOSE-TISSUE; INSULIN-SECRETION; EXPRESSION; OBESE; ACTIVATION; MOUSE; RESTORATION; ADIPOCYTES; FREQUENCY; KINASE AB The activation of phosphodiesterase 3B (PDE3B) reduces free fatty acid output from adipocytes. A reduced PDE3B gene expression could lead to insulin resistance. To determine whether there are polymorphisms associated with type 2 diabetes in PDE3B gene promoter. this 5' flanking region was isolated. The transcription initiation site was located 206 bp upstream from the translation start site. Sequences of 2 kb of the 5' flanking region for 24 type 2 diabetic Japanese subjects were initially analyzed using PCR direct sequencing, and the regions including the identified polymorphisms were then examined. In 98 controls and 98 type 2 diabetic subjects, -1947T > C, -567G > A, -465G > T, -458T > C, and -1727_-1726insTCAATT were found. Only -465G > T and this insertion had more than 5% frequencies. Since a complete linkage disequilibrium existed between them, -465G > T was further analyzed along with a previously identified +1389G > A in the coding region, in a total of 200 controls and 207 type 2 diabetic subjects. These allele frequencies were not significantly different between these two groups (controls vs. cases; -465G > T, 12.0% vs. 10.1%, P = 0.435; +1389G > A, 30.3% vs. 33.3%, P = 0.408). These genotype distributions were not significantly different between these two groups. The T/T genotype at -465 was rare although this frequency could be higher in type 2 diabetes (4/207 subjects) than controls (0/200 subjects). The linkage disequilibrium existed between -465G > T and +1389G >A, and the estimated haplotype frequencies defined by these SNPs were not significantly different between the cases and controls. Thus, the identified polymorphisms are unlikely to have major effects on susceptibility to Japanese type 2 diabetes. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Ehime Univ, Sch Med, Dept Lab Med, Shigenobu, Ehime 7910295, Japan. Univ Tokyo, Grad Sch Med, Sch Int Hlth, Dept Human Genet, Tokyo, Japan. Fukui Med Univ, Dept Biochem, Fukui, Japan. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Beckman Res Inst, Duarte, CA USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD USA. Tokai Univ, Sch Engn, Dept Appl Biochem, Tokyo 151, Japan. RP Osawa, H (reprint author), Ehime Univ, Sch Med, Dept Lab Med, Shigenobu, Ehime 7910295, Japan. RI OHASHI, JUN/G-5907-2015 NR 27 TC 4 Z9 4 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAY PY 2003 VL 79 IS 1 BP 43 EP 51 DI 10.1016/S1096-7192(03)00035-0 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 685XG UT WOS:000183289200006 PM 12765845 ER PT J AU Wolford, JK Konheim, YL Colligan, PB Bogardus, C AF Wolford, JK Konheim, YL Colligan, PB Bogardus, C TI Association of a F479L variant in the cytosolic phospholipase A2 gene (PLA2G4A) with decreased glucose turnover and oxidation rates in Pima Indians SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE chromosome 1q; single nucleotide polymorphisms (SNPs); candidate gene analysis; glucose oxidation; lipid oxidation; type 2 diabetes mellitus; arachidonic acid ID PROLIFERATOR-ACTIVATED RECEPTORS; DIABETES-SUSCEPTIBILITY GENES; ARACHIDONIC-ACID; 3T3-L1 ADIPOCYTES; FATTY-ACIDS; PPAR-GAMMA; INDEPENDENT REPLICATION; INSULIN-RESISTANCE; BETA-CELL; MELLITUS AB Phospholipase A2, Group IVA (PLA2G4A) belongs to the class of cytosolic calcium-dependent phospholipases (cPLA2s) that preferentially cleave arachidonic acid (AA) from membrane glycerophospholipids. AA and AA metabolites play key roles in glucose disposal and insulin secretion. PLA2G4A is located on Chromosome 1q, where a number of groups have reported linkage to type 2 diabetes mellitus. We have screened the PLA2G4A gene and identified a C --> G variant, which predicts a phenylalanine to leucine substitution. In logistic regression analyses adjusted for age, sex, ethnicity, and birth year, we found a trend toward association between this SNP and diabetes [OR= 1.53 (0.97-2.40); p = 0.06]. Individuals with the variant genotype had lower mean basal endogenous glucose output (1.8 +/- 0.03 vs. 1.9 +/- 0.01 mg/kgEMBS/min,- p = 0.04) and lower mean basal glucose oxidation (1.2 +/- 0.11 vs. 1.4 +/- 0.03 mg/kgEMBS/min; p = 0.005) compared to individuals with the wild-type genotype. During a low dose insulin infusion, non-diabetic individuals with the variant genotype had a lower mean glucose oxidation (1.9 0.11 vs. 2.0 +/- 0.03 mg/kgEMBS/min; p = 0.04) and total glucose turnover rate (2.5 +/- 0.22 vs. 2.6 +/- 0.06 mg/kg EMBS/min; p = 0.01) compared to subjects with the wild-type genotype. In addition, under basal conditions, individuals with the variant genotype had a higher mean lipid oxidation rate compared to individuals with the wild-type genotype (0.77 +/- 0.25 vs. 0.67 +/- 0.23 mg/ kgEMBS/min; p = 0.02). These results provide evidence supporting a role for the eicosanoid biosynthesis pathway in type 2 diabetes mellitus pathophysiology. (C) 2003 Elsevier Science (USA). All rights reserved. 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. NR 42 TC 7 Z9 7 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAY PY 2003 VL 79 IS 1 BP 61 EP 66 DI 10.1016/S1096-7192(03)00051-9 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 685XG UT WOS:000183289200008 PM 12765847 ER PT J AU Fields, KA Mead, DJ Dooley, CA Hackstadt, T AF Fields, KA Mead, DJ Dooley, CA Hackstadt, T TI Chlamydia trachomatis type III secretion: evidence for a functional apparatus during early-cycle development SO MOLECULAR MICROBIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; YERSINIA YOP PROTEINS; INCLUSION MEMBRANE; SALMONELLA-TYPHIMURIUM; SURFACE PROJECTIONS; ELECTRON-MICROSCOPY; NEEDLE COMPLEX; SHIGELLA-FLEXNERI; ENDOCYTIC PATHWAY; GENE-EXPRESSION AB The obligate intracellular bacterium Chlamydia trachomatis occupies a parasitophorous vacuole termed an inclusion. During its intracellular developmental cycle, C. trachomatis maintains this intracellular niche, presumably by expressing a type III secretion system, which deploys a set of host cell-interactive proteins including inclusion membrane-localized proteins termed Incs. Some Incs are expressed and secreted by 2 h (early cycle) after infection, whereas the expression of type III-specific genes is not detectable until 6-12 h (mid-cycle). To resolve this paradox, we investigated the presence of a type III apparatus on elementary bodies (EBs) that might function early in infection. We demonstrate the existence of the type III secretory apparatus by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) and immunoblot analyses of purified EB extracts. Immunoblots using polyclonal antibodies specific for the core apparatus component CdsJ identified this protein in both EB and reticulate body (RB) extracts. Furthermore, CdsJ-specific signals were detected by immunoblot of whole infected-culture extracts and by indirect immunofluorescence of infected monolayers at times before the detection of cdsJ -specific message. Finally, expression of IncC, expressed by 2 h after infection during C. trachomatis infections, in Yersinia pseudotuberculosis resulted in its secretion via the Yersinia type III apparatus. Based on these data, we propose a model in which type III secretion pores are present on EBs and mediate secretion of early Incs and possible additional effectors. Mid-cycle expression of type III genes would then replenish secretion apparatus on vegetative RBs and serve as a source of secretion pores for subsequently formed EBs. C1 NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. NR 65 TC 124 Z9 127 U1 1 U2 6 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2003 VL 48 IS 3 BP 671 EP 683 DI 10.1046/j.1365-2958.2003.03462.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 666TC UT WOS:000182191700008 PM 12694613 ER PT J AU Repoila, F Majdalani, N Gottesman, S AF Repoila, F Majdalani, N Gottesman, S TI Small non-coding RNAs, co-ordinators of adaptation processes in Escherichia coli: the RpoS paradigm SO MOLECULAR MICROBIOLOGY LA English DT Review ID DSRA-RNA; SALMONELLA-TYPHIMURIUM; COMPARATIVE GENOMICS; SIGNAL-TRANSDUCTION; SIGMA(S) SUBUNIT; LEUO EXPRESSION; NONCODING RNAS; GENES; TRANSLATION; PROTEIN AB Adaptation to the changing environment requires both the integration of external signals and the co-ordination of internal responses. Around 50 non-coding small RNAs (sRNAs) have been described in Escherichia coli ; the levels of many of these vary with changing environmental conditions. This suggests that they play a role in cell adaptation. In this review, we use the regulation of RpoS (sigma(38)) translation as a paradigm of sRNA-mediated response to environmental conditions; rpoS is currently the only known gene regulated post-transcriptionally by at least three sRNAs. DsrA and RprA stimulate RpoS translation in response to low temperature and cell surface stress, respectively, whereas OxyS represses RpoS translation in response to oxidative shock. However, in addition to regulating RpoS translation, DsrA represses the translation of HNS (a global regulator of gene expression), whereas OxyS represses the translation of FhlA (a transcriptional activator), allowing the cell to co-ordinate different pathways involved in cell adaptation. Environmental cues affect the synthesis and stability of specific sRNAs, resulting in specific sRNA-dependent translational control. C1 NIH, Mol Biol Lab, Bethesda, MD 20892 USA. INRA, INVT, UMR960, Mol Microbiol Lab, F-31076 Toulouse, France. RP Gottesman, S (reprint author), NIH, Mol Biol Lab, 9000 Rockville Pike,Bldg 37,Room 5132, Bethesda, MD 20892 USA. OI Repoila, Francis/0000-0001-5149-9698 NR 43 TC 168 Z9 177 U1 2 U2 22 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2003 VL 48 IS 4 BP 855 EP 861 DI 10.1046/j.1365-2958.2003.03454.x PG 7 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 676ZN UT WOS:000182782600001 PM 12753181 ER PT J AU Gao, ZG Kim, SK Gross, S Chen, AS Blaustein, JB Jacobson, KA AF Gao, ZG Kim, SK Gross, S Chen, AS Blaustein, JB Jacobson, KA TI Identification of essential residues involved in the allosteric modulation of the human A(3) adenosine receptor SO MOLECULAR PHARMACOLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; MUSCARINIC ACETYLCHOLINE-RECEPTORS; PROTEIN-COUPLED RECEPTOR; MUTATIONAL ANALYSIS; ANTAGONIST BINDING; AGONIST BINDING; DERIVATIVES; SODIUM; ENHANCEMENT; ACTIVATION AB We examined the effects on allosteric modulation and ligand binding of the mutation of amino acid residues of the human A(3) adenosine receptor (A(3)AR) that are hypothesized to be near one of three loci: the putative sodium binding site, the putative ligand binding site, and the DRY motif in transmembrane helical domain 3. The effects of three heterocyclic allosteric modulators [ the imidazoquinoline 2-cyclopentyl-4-phenylamino-1H-imidazo[4,5-c]quinoline (DU124183), the pyridinylisoquinoline 4-methoxy-N-[7-methyl-3-(2-pyridinyl)-1-isoquinolinyl]benzamide (VUF5455), and the amiloride analog 5-(N,N-hexamethylene)amiloride] on the dissociation of the agonist radioligand, N-6-(4-amino-3-[I-125]iodobenzyl)-5'-N-methylcarboxamidoadenosine, were compared at wild-type (WT) and mutant A(3)ARs. The F182A(5.43) and N274A(7.45) mutations eliminated the allosteric effects of all three modulators but had little effect on agonist binding. The N30A(1.50) and D58N(2.50) mutations abolished the allosteric effects of DU124183 and VUF5455, but not HMA, whereas the D107N(3.49) mutation abolished the effects of DU124183, but not HMA or VUF5455. The T94A(3.36), H95A(3.37), K152A(EL2), W243A(6.48), L244A(6.49), and S247A(6.52) mutations did not influence allosteric effects of the modulators. Sodium ions (100 mM), which modulate agonist binding at a variety of receptors, caused an similar to80% inhibition of agonist binding in WT A(3)ARs but did not show any effect on D58N(2.50), D107N(3.49), and F182A(5.43) mutant receptors. In contrast, NaCl induced a modest increase of agonist binding in N30A(1.50) and N274A(7.45) mutant receptors. NaCl decreased the dissociation rate of the antagonist radioligand [H-3]8-ethyl-4-methyl-2-phenyl-(8R)-4,5,7,8-tetrahydro-1H-imidazo[2.1-i]purin-5-one (PSB-11) at the WT A(3)ARs, but not the D58N(2.50) mutant receptor. The results were interpreted using a rhodopsin-based molecular model of the A(3)AR to suggest multiple binding modes of the allosteric modulators. C1 NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH,Dept Hlth & Human Serv, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z99 DK999999, Z01 DK031116-20] NR 40 TC 53 Z9 53 U1 0 U2 7 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 MAY PY 2003 VL 63 IS 5 BP 1021 EP 1031 DI 10.1124/mol.63.5.1021 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 667NQ UT WOS:000182238900008 PM 12695530 ER PT J AU Agnete, S Huszthy, PC Thorsen, F Halbert, C Miller, AD James, W Robert, K Rolf, B Eystein, LP Hoover, F AF Agnete, S Huszthy, PC Thorsen, F Halbert, C Miller, AD James, W Robert, K Rolf, B Eystein, LP Hoover, F TI Transduction and penetration of human breast cancer by multiple adeno-associated viral vector serotypes SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Haukeland Univ Hosp, Dept Oncol, Gene Therapy Program, N-5021 Bergen, Norway. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Univ Penn, Wistar Inst, Philadelphia, PA 19104 USA. NIH, Bethesda, MD 20892 USA. RI Huszthy, Peter Csaba/H-1414-2016 OI Huszthy, Peter Csaba/0000-0003-0184-8989 NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 485 BP S190 EP S190 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300484 ER PT J AU Becker, PS Khan, NN LaMarca, ME Soukharev, S Chrzanowski, C Faryna, D Ginns, EI AF Becker, PS Khan, NN LaMarca, ME Soukharev, S Chrzanowski, C Faryna, D Ginns, EI TI Gene transfer studies in a novel murine model of Gaucher disease SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ Massachusetts, Div Gene Therapy, Dept Med, Sch Med, Worcester, MA 01605 USA. Univ Massachusetts, Brudnick Neuropsychiat Res Inst, Dept Psychiat, Sch Med, Worcester, MA 01605 USA. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1021 BP S394 EP S394 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301020 ER PT J AU Bishop, CL Ramalho, M McBride, AA Higgins, CF Krauzewicz, N AF Bishop, CL Ramalho, M McBride, AA Higgins, CF Krauzewicz, N TI Understanding transcriptional regulation of exogenously delivered DNA SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London, England. NCI, NIAID, Div Basic Sci, Lab Viral Dis,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1150 BP S443 EP S443 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301149 ER PT J AU Bosticardo, M Novelli, F Casanova, JL Candotti, F AF Bosticardo, M Novelli, F Casanova, JL Candotti, F TI Reconstitution of the IL-12 signaling pathway in IL-12 receptor beta-1 (IL-12R beta 1) KO mice upon transplantation of retrovirally transduced hematopoietic stem cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Osped San Giovanni Battista Torino, Ctr Oncol Ematol Subalpino, Ctr Ric Med Sperimentale, Turin, Italy. Hop Necker Enfants Malad, Unite Clin Immunol & Hematol Pediat, Paris, France. NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1061 BP S409 EP S409 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301060 ER PT J AU Brenner, S Whiting-Theobald, N Sechler, J Murphy, PM Rudikoff, AG Malech, HL AF Brenner, S Whiting-Theobald, N Sechler, J Murphy, PM Rudikoff, AG Malech, HL TI CXCR4-transgene over-expression in peripheral blood CD34(+) cells enhances migration towards SDF-1 alpha and preserves engraftment potential of cultured NOD/SCID repopulating cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RI Brenner, Sebastian/D-7456-2013 NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 276 BP S109 EP S109 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300277 ER PT J AU Candotti, F Podsakoff, G Schurman, SH Muul, LM Engel, BC Carbonaro, DA Jagadeesh, GJ Hematti, P Tuschong, LM Carter, CS Ramsey, WJ Choi, C Smogorzewska, M Hershfield, MS Read, EJ Tisdale, JF Dunbar, CE Kohn, DB AF Candotti, F Podsakoff, G Schurman, SH Muul, LM Engel, BC Carbonaro, DA Jagadeesh, GJ Hematti, P Tuschong, LM Carter, CS Ramsey, WJ Choi, C Smogorzewska, M Hershfield, MS Read, EJ Tisdale, JF Dunbar, CE Kohn, DB TI Corrective gene transfer into bone marrow CD34+cells for adenosine deaminase (ADA) deficiency: Results in four patients after one year of follow-up SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NIH, Bethesda, MD 20892 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1163 BP S448 EP S449 PN 2 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301162 ER PT J AU Cresawn, KO Raben, N Plotz, PH Byrne, BJ AF Cresawn, KO Raben, N Plotz, PH Byrne, BJ TI Inhibitory antibody response and neonatal tolerization in a mouse model of rAAV-mediated cross-correction of Glycogen Storage Disease Type II SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ Florida, Powell Gene Therapy Ctr, Gainesville, FL USA. Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL USA. NIAMS, Arthritis & Rheumatism Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 211 BP S83 EP S83 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300212 ER PT J AU Di Pasquale, G Scudiero, D Monks, A Chiorini, JA AF Di Pasquale, G Scudiero, D Monks, A Chiorini, JA TI Identification of PDGFR as a receptor for AAV5 transduction SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NIH, GTTB, Bethesda, MD 20892 USA. NCI, SAIC Frederick, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 862 BP S334 EP S334 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300861 ER PT J AU Dick, AJ Hill, JM Raman, VK Guttman, MA Peters, DC Thompson, RB Pessanha, BSS Martin, B Dunbar, CE McVeigh, ER Lederman, RJ AF Dick, AJ Hill, JM Raman, VK Guttman, MA Peters, DC Thompson, RB Pessanha, BSS Martin, B Dunbar, CE McVeigh, ER Lederman, RJ TI MRI for the delivery and surveillance of mesenchymal stem cells injected at the border of recent myocardial infarction in swine SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. Osiris Therapeut, Baltimore, MD USA. NHLBI, Hematol Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 860 BP S333 EP S333 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300859 ER PT J AU Fan, QY Yee, C Vogel, J AF Fan, QY Yee, C Vogel, J TI A murine model to assess bone marrow stem cell plasticity in reconstituting differentiated keratinocytes following bone marrow transplant SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1040 BP S401 EP S401 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301039 ER PT J AU Goldsmith, ME Alley, MC Waud, WR Fok, P Bates, S Fojo, T AF Goldsmith, ME Alley, MC Waud, WR Fok, P Bates, S Fojo, T TI Coxsackie-adenovirus receptor (CAR) levels are increased in two human melanoma xenograft mouse model systems by treatment with the histone deacetylase inhibitor FK228 SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NCI, CCR, Canc Therapeut Branch, Bethesda, MD USA. NCI, Frederick Canc Res & Dev Ctr, Biol Testing Branch, DTP,DCTD,NIH, Frederick, MD USA. So Res Inst, Birmingham, AL 35255 USA. NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1109 BP S427 EP S428 PN 2 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301108 ER PT J AU Griesenbach, U Kitson, C Garcia, SE Painter, H Farley, R Chow, YH Edbrooke, M Cheng, S Hu, J Hyde, S Geddes, D Caplen, N Alton, E AF Griesenbach, U Kitson, C Garcia, SE Painter, H Farley, R Chow, YH Edbrooke, M Cheng, S Hu, J Hyde, S Geddes, D Caplen, N Alton, E TI Gene silencing through RNA interference and antisense strategies in the lung SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Gene Therapy, London, England. GlaxoSmithKline, Stevenage, Herts, England. Univ Oxford, Nuffield Dept Clin Lab Sci, Gene Med Grp, Oxford, England. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Genzyme Corp, Framingham, MA 01701 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1009 BP S389 EP S389 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301008 ER PT J AU Hanawa, H Hematti, P Persons, DA Dunbar, CE Nienhuis, AW AF Hanawa, H Hematti, P Persons, DA Dunbar, CE Nienhuis, AW TI Development of an SIV-based lentiviral vector system for transduction of rhesus, primitive hematopoietic cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 St Jude Childrens Res Hosp, Dept Hematol Oncol, Div Exp Hematol, Memphis, TN 38105 USA. NHBLI, Hematol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 MAY PY 2003 VL 7 IS 5 MA 385 BP S151 EP S151 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300385 ER PT J AU Harding, T Donahue, B Wang, J Koprivnikar, K Yendluri, S Tu, GH Cordier, L Colbern, G VanRoey, M Gonzalez, M Jooss, K Fine, H AF Harding, T Donahue, B Wang, J Koprivnikar, K Yendluri, S Tu, GH Cordier, L Colbern, G VanRoey, M Gonzalez, M Jooss, K Fine, H TI AAV vectors for brain cancer gene therapy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Cell Genesys Inc, Foster City, CA USA. NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 225 BP S89 EP S89 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300226 ER EF