FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Buffalo, EA Bertini, G Ungerleider, LG Desimone, R AF Buffalo, EA Bertini, G Ungerleider, LG Desimone, R TI Impaired filtering of distracter stimuli by TE neurons following V4 and TEO lesions in macaques SO CEREBRAL CORTEX LA English DT Article DE extrastriate cortex; inferotemporal cortex; monkey; spatial attention; vision ID EXTRASTRIATE AREA V4; SELECTIVE VISUAL-ATTENTION; INFERIOR TEMPORAL NEURONS; INFEROTEMPORAL CORTEX; CORTICAL CONNECTIONS; SHAPE-DISCRIMINATION; SPATIAL INTERACTION; PERIPHERAL-VISION; NEURAL MECHANISMS; MONKEYS AB Directing attention to a behaviorally relevant visual stimulus can overcome the distracting effects of other nearby stimuli. Correspondingly, physiological studies indicate that attention serves to filter distracting stimuli from receptive fields (RFs) in several extrastriate areas. Moreover, a recent study demonstrated that lesions of extrastriate areas V4 and TEO produce impairments in attentional filtering. A critical remaining question concerns why lesions of ventral stream areas cause attentional filtering impairments. To address this question, we tested the effects of restricted area V4 and TEO lesions on both behavioral performance and the responses of downstream neurons in area TE. The lesions impaired behavioral discrimination thresholds and altered neuronal selectivity for target stimuli in the presence of distracters. With attention to the target, but in the absence of V4 and/or TEO inputs, TE neurons responded as though attentional inputs could no longer be used to filter distracters from their RFs. This presumably occurred because top-down attentional signals were no longer able to filter distracters from the RFs of the cells that provide TE with major input. Consistent with this interpretation, increasing the spatial separation between targets and distracters, such that they no longer fell within a typical V4 RF dimension, restored both behavioral performance and neuronal selectivity in the portion of TE RFs affected by the V4 lesion. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Buffalo, EA (reprint author), NIMH, Neuropsychol Lab, 49 Convent Dr, Bethesda, MD 20892 USA. EM ebuffalo@nih.gov NR 57 TC 19 Z9 19 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD FEB PY 2005 VL 15 IS 2 BP 141 EP 151 DI 10.1093/cercor/bhh117 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 886BD UT WOS:000226200500003 PM 15269106 ER PT J AU Jacobson, KA Ohno, M Duong, HT Kim, SK Tchilibon, S Cesnek, M Holy, A Gao, ZG AF Jacobson, KA Ohno, M Duong, HT Kim, SK Tchilibon, S Cesnek, M Holy, A Gao, ZG TI A neoceptor approach to unraveling microscopic interactions between the human A(2A) adenosine receptor and its agonists SO CHEMISTRY & BIOLOGY LA English DT Article ID NUCLEIC-ACIDS; DERIVATIVES; SELECTIVITY; INHIBITION; BINDING; POTENT; MUTAGENESIS; MODULATION; EFFICACY; AFFINITY AB Strategically mutated neoceptors, e.g., with anionic residues in TMs 3 and 7 intended for pairing with positively charged amine-modified nucleosides, were derived from the antiinflammatory A(2A) adenosine receptor (AR). Adenosine derivatives functionalized at the 5', 2, and N-6 positions were synthesized. The T88D mutation selectively enhanced the binding of the chain-length-optimized 5'-(2-aminoethyl)uronamide but not 5'-(2-hydroxyethyl)uronamide, suggesting a critical role of the positively charged amine. Combination of this modification with the N-6(2-methylbenzyl) group enhanced affinity at the Q89D- and N181 D- but not the T88D-A(2A)AR. Amino groups placed near the 2- or N-6-position only slightly affected the binding to mutant receptors. The 5'-hydrazide MRS3412 was 670-and 161-fold enhanced, in binding and functionally, respectively, at the Q89D-A(2A)AR compared to the wild-type. Thus, we identified and modeled pairs of A(2A)AR-derived neoceptor-neoligand, which are pharmacologically orthogonal with respect to the native species. C1 NIDDKD, Mol Recognit Sect, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. Inst Organ Chem & Biochem, Prague 16610 6, Czech Republic. RP NIDDKD, Mol Recognit Sect, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Cesnek, Michal/G-5612-2014 OI Jacobson, Kenneth/0000-0001-8104-1493; Cesnek, Michal/0000-0003-0486-8942 FU Intramural NIH HHS [Z01 DK031115-24] NR 40 TC 33 Z9 33 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 EI 1879-1301 J9 CHEM BIOL JI Chem. Biol. PD FEB PY 2005 VL 12 IS 2 BP 237 EP 247 DI 10.1016/j.chembiol.12.010 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903HT UT WOS:000227417300013 PM 15734651 ER PT J AU Meschia, JF Case, D Brown, RD Silliman, S Brott, TG Worrall, BB Frankel, M Hardy, J Rich, SS Strecker, KD AF Meschia, JF Case, D Brown, RD Silliman, S Brott, TG Worrall, BB Frankel, M Hardy, J Rich, SS Strecker, KD TI Sex differences in stroke subtypes in the ischemic stroke genetics study SO CIRCULATION LA English DT Meeting Abstract CT 2nd International Conference on Women Heart Disease and Stroke CY FEB 16-19, 2005 CL Orlando, FL C1 Mayo Clin, Jacksonville, FL 32224 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Mayo Clin, Rochester, MN USA. Univ Florida, Jacksonville, FL USA. Univ Virginia, Charlottesville, VA USA. Emory Univ, Atlanta, GA 30322 USA. NIA, 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 2005 VL 111 IS 4 BP E86 EP E86 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 893AW UT WOS:000226692600257 ER PT J AU Taubenheim, AM AF Taubenheim, AM TI Mobilizing communities to embrace the "Red Dress": Lessons from The Heart Truth campaign SO CIRCULATION LA English DT Meeting Abstract CT 2nd International Conference on Women Heart Disease and Stroke CY FEB 16-19, 2005 CL Orlando, FL C1 NHLBI, 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 2005 VL 111 IS 4 BP E81 EP E81 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 893AW UT WOS:000226692600232 ER PT J AU Lee, YS Vortmeyer, AO Lubensky, IA Vogel, TWA Ikejiri, B Ferlicot, S Benoit, G Giraud, S Oldfield, EH Linehan, WM Teh, BT Richard, S Zhuang, ZP AF Lee, YS Vortmeyer, AO Lubensky, IA Vogel, TWA Ikejiri, B Ferlicot, S Benoit, G Giraud, S Oldfield, EH Linehan, WM Teh, BT Richard, S Zhuang, ZP TI Coexpression of erythropoietin and erythropoietin receptor in Von Hippel-Lindau disease-associated renal cysts and renal cell carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID HEMANGIOBLASTOMA; CANCER; TUMOR; HISTOGENESIS; DIAGNOSIS; INSIGHTS; LESIONS; GENE AB Von Hippel-Lindau (VHL) disease is characterized by multiple tumors in specific target organs. The tumors at different sites share distinct morphologic and genetic characteristics but their cell of origin is unknown. We show that VHL disease-associated renal clear cell carcinomas (RCC) consistently coexpress erythropoietin (Epo) and Epo receptor (EpoR). In addition, coexpression of Epo and EpoR is detected in many renal cysts, providing further evidence that renal cysts are potential precursors for RCC. In conjunction with VHL gene deficiency, coexpression of Epo and EpoR in renal cysts and tumors may reflect a developmental arrest in immature mesenchymal cells. Such arrest may lead to autocrine stimulation, cell proliferation, and renal tumor development, similar to tumorigenesis of VHL disease-associated hemangioblastomas. C1 NINDS, Mol Pathogenesis Unit, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Pathol Lab, Le Kremlin Bicetre, France. Serv Urol, Le Kremlin Bicetre, France. EPHE, Lab Genet Oncol, Le Kremlin Bicetre, France. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. Andel Res Inst, Grand Rapids, MI USA. Hop Bicetre, Serv Urol, Paris, France. Hop Necker Enfants Malad, Serv Nephrol, Paris, France. RP Zhuang, ZP (reprint author), NINDS, Mol Pathogenesis Unit, Surg Neurol Branch, NIH, Bldg 10,Room 5D37,10 Ctr Dr, Bethesda, MD 20892 USA. NR 26 TC 41 Z9 45 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2005 VL 11 IS 3 BP 1059 EP 1064 PG 6 WC Oncology SC Oncology GA 893SV UT WOS:000226740400014 PM 15709172 ER PT J AU Lebowitz, PF Eng-Wong, J Widemann, BC Balis, FM Jayaprakash, N Chow, C Clark, G Gantz, SB Venzon, D Zujewski, JA AF Lebowitz, PF Eng-Wong, J Widemann, BC Balis, FM Jayaprakash, N Chow, C Clark, G Gantz, SB Venzon, D Zujewski, JA TI A phase I trial and pharmacokinetic study of tipifarnib, a farnesyltransferase inhibitor, and tamoxifen in metastatic breast cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID FARNESYL TRANSFERASE INHIBITOR; TUMOR-CELL-LINES; ENDOCRINE THERAPY; R115777; GROWTH; RESISTANCE; RECEPTORS; EFFICACY AB Purpose: Farnesyltransferase (FTase) inhibitors, which were designed to inhibit oncogenic Ras, act synergistically with tamoxifen in preclinical breast cancer models. We studied the safety and toxicity of tipifarnib in combination with tamoxifen in metastatic breast cancer. The pharmacokinetics and pharmacodynamics of tipifarnib were also assessed. Patients and Methods: Patients with metastatic, hormone receptor- positive breast cancer were enrolled. Two cohorts of patients were treated with tipifarnib at either 200 or 300 mg p.o. twice daily for 21 of 28 days. Tamoxifen (20 mg once daily) was started after 1 week of tipifarnib monotherapy to perform pharmacokinetics and FTase inhibition levels in peripheral blood mononuclear cells with tipifarnib alone and with tipifarnib and tamoxifen. Results: A total of 12 heavily pretreated patients with prior progression on hormonal therapy were enrolled. Minimal toxicity was observed at the 200-mg dose level of tipifarnib. At the 300-mg dose, all six patients required dose reduction of tipifarnib due to toxicities that included grade 2 nausea, rash, and fatigue and grade 3 diarrhea and neutropenia. Tipifarnib pharmacokinetic and pharmacodynamic variables were similar in the presence and absence of tamoxifen. Average FTase inhibition was 42% at 200 mg and 54% at 300 mg in peripheral blood mononuclear cells. Of the 12 patients treated, there were two partial responses and one stable disease for >6 months. Conclusions: Tipifarnib (200 mg twice daily for 21 of 28 days) and tamoxifen (20 mg once daily) can be given safely with minimal toxicity. Tamoxifen does not have a significant effect on tipifarnib pharmacokinetics. C1 NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Canc & Cell Biol Lab, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Lebowitz, PF (reprint author), NCI, Med Oncol Clin Res Unit, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM peter.lebowitz@nih.gov RI Venzon, David/B-3078-2008 NR 20 TC 19 Z9 20 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2005 VL 11 IS 3 BP 1247 EP 1252 PG 6 WC Oncology SC Oncology GA 893SV UT WOS:000226740400037 PM 15709195 ER PT J AU Khatami, M AF Khatami, M TI Cyclooxygenase inhibitor ketorolac or mast cell stabilizers: Immunologic challenges in cancer therapy SO CLINICAL CANCER RESEARCH LA English DT Letter ID ALLERGIC CONJUNCTIVITIS; FLUORESCEINYL OVALBUMIN C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Khatami, M (reprint author), NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2005 VL 11 IS 3 BP 1349 EP 1351 PG 3 WC Oncology SC Oncology GA 893SV UT WOS:000226740400052 PM 15709209 ER PT J AU Mulshine, J AF Mulshine, J TI Cyclooxygenase inhibitor ketorolac or mast cell stabilizers: Immunologic challenges in cancer therapy - Response SO CLINICAL CANCER RESEARCH LA English DT Letter C1 Ctr Canc Res, NC NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Mulshine, J (reprint author), Ctr Canc Res, NC NIH, Ctr Clin, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mulshinj@mail.nih.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2005 VL 11 IS 3 BP 1351 EP 1351 PG 1 WC Oncology SC Oncology GA 893SV UT WOS:000226740400053 ER PT J AU Bowen, RAR Chan, Y Cohen, J Rehak, NN Hortin, GL Csako, G Remaley, AT AF Bowen, RAR Chan, Y Cohen, J Rehak, NN Hortin, GL Csako, G Remaley, AT TI Effect of blood collection tubes on total triiodothyronine and other laboratory assays SO CLINICAL CHEMISTRY LA English DT Article ID SERUM-SEPARATOR TUBES; CLINICAL-CHEMISTRY; IONIZED MAGNESIUM; THERAPEUTIC DRUGS; QUALITY-CONTROL; DRAWING TUBES; STABILITY; ANALYTES; ANALYZER; GELS AB Background: Increased total triiodothyronine (TT3) assay results in apparently euthyroid patients triggered an investigation of the effect of blood collection tubes on serum TT3 and other laboratory assays. Methods: We examined potential assay interference for three types of tubes: plastic Greiner Bio-One(TM) Vacuette(TM); glass Becton Dickinson (BD) Vacutainer(TM); and plastic BD Vacutainer SST(TM) tubes. Serum samples from apparently healthy volunteers (age range, 30-60 years; 15 males and 34 females) were collected in different tube types and analyzed in 17 immunoassays (n = 49), 30 clinical chemistry tests (n = 20), and 33 immunology assays (n = 15). Tube effects were also examined by adding pooled serum to different tube types. Results: TT3 values, when measured by the IMMULITE(TM) 2000 but not the AxSYM(TM) analyzer, were significantly higher (P < 0.0001) for SST (2.81 nmol/L) than either glass (2.15 nmol/L) or Vacuette (2.24 nmol/L) tubes. The effect was large enough to substantially shift the distribution of patient values, increasing the percentage of values above the reference interval from 11.3% to 35.8%. The degree of interference from SST tubes on TT3 differed among various tube lots and could be attributed to a tube additive shared by other plastic tubes. Results from several other tests statistically differed among tube types, but differences we're not considered to be clinically significant. Conclusions: Assay interferences from blood collection tubes represent challenges to clinical laboratories because they are not detected by the usual quality-control or proficiency testing programs. Laboratories can, however, address this problem by monitoring distribution of patients' results. (C) 2005 American Association for Clinical Chemistry. C1 NIH, Clin Chem Serv, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Remaley, AT (reprint author), NIH, Clin Chem Serv, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Rm 2C-433,10 Ctr Dr, Bethesda, MD 20892 USA. EM aremaley@nih.gov NR 30 TC 48 Z9 51 U1 0 U2 5 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 2005 VL 51 IS 2 BP 424 EP 433 DI 10.1373/clinchem.2004.043349 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 893KK UT WOS:000226717600021 PM 15576427 ER PT J AU Singh, RJ Grebe, SK Yue, BF Rockwood, AL Cramer, JC Gombos, Z Eisenhofer, G AF Singh, RJ Grebe, SK Yue, BF Rockwood, AL Cramer, JC Gombos, Z Eisenhofer, G TI Precisely wrong? Urinary fractionated metanephrines and peer-based laboratory proficiency testing SO CLINICAL CHEMISTRY LA English DT Letter ID MASS-SPECTROMETRY; PHEOCHROMOCYTOMA; NORMETANEPHRINE C1 Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Mayo Clin, Dept Med, Rochester, MN 55905 USA. ARUP Inst Clin & Expt Pathol, Salt Lake City, UT USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD USA. Berkshire Hlth Syst, Dept Pathol & Lab Med, Pittsfield, MA USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD USA. RP Singh, RJ (reprint author), Mayo Clin, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55905 USA. EM Singh.Ravinder@mayo.edu NR 3 TC 11 Z9 12 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 2005 VL 51 IS 2 BP 472 EP 473 DI 10.1373/clinchem.2004.043802 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 893KK UT WOS:000226717600033 PM 15681566 ER PT J AU Park, HJ Lee, SJ Jin, HS Lee, JO Go, SH Jang, HS Moon, SK Lee, SC Chun, YM Lee, HK Choi, JY Jung, SC Griffith, AJ Koo, SK AF Park, HJ Lee, SJ Jin, HS Lee, JO Go, SH Jang, HS Moon, SK Lee, SC Chun, YM Lee, HK Choi, JY Jung, SC Griffith, AJ Koo, SK TI Genetic basis of hearing loss associated with enlarged vestibular aqueducts in Koreans SO CLINICAL GENETICS LA English DT Article DE DFNB4; non-syndromic deafness; Pendred syndrome; SLC26A4 ID PENDRED-SYNDROME GENE; PDS MUTATIONS; DEAFNESS; IDENTIFICATION; TRANSPORTERS; FREQUENCIES; CELLS; EAR AB Sensorineural hearing loss associated with enlargement of the vestibular aqueduct (EVA) can be associated with mutations of the SLC26A4 gene. In western populations, less than one-half of the affected individuals with EVA have two mutant SLC26A4 alleles, and EVA is frequently caused by unknown genetic or environmental factors alone or in combination with a single SLC26A4 mutation as part of a complex trait. In this study, we ascertained 26 Korean probands with EVA and performed nucleotide sequence analysis to detect SLC26A4 mutations. All subjects had bilateral EVA, and 20 of 26 were sporadic (simplex) cases. Fourteen different mutations were identified, including nine novel mutations. Five mutations were recurrent and accounted for 80% of all mutant alleles, providing a basis for the design and interpretation of cost-efficient mutation detection algorithms. Two mutant alleles were identified in 21 (81%), one mutant allele was detected in three (11%), and zero mutant allele was detected in two (8%) of 26 probands. The high proportion of Korean probands with two SLC26A4 mutations may reflect a reduced frequency of other genetic or environmental factors causing EVA in comparison to western populations. C1 Natl Inst Hlth, Dept Biomed Sci, Div Genet Dis, Seoul 122701, South Korea. Natl Inst Hlth, Soree Ear Clin, Seoul 122701, South Korea. Ajou Univ, Sch Med, Dept Otolaryngol, Suwon, South Korea. Yonsei Univ, Coll Med, Dept Otorhinolaryngol, Seoul, South Korea. Ewha Womans Univ, Coll Med, Dept Biochem, Dept Biochem Coll, Seoul, South Korea. Natl Inst Deafness & Other Communicable Disorders, NIH, Rockville, MD USA. RP Koo, SK (reprint author), Natl Inst Hlth, Dept Biomed Sci, Div Genet Dis, 5 Nokbun Dong, Seoul 122701, South Korea. EM skkoo@nih.go.kr OI Jung, Sung-Chul/0000-0002-3174-8965 FU NIDCD NIH HHS [Z01 DC 000060-03] NR 25 TC 72 Z9 92 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD FEB PY 2005 VL 67 IS 2 BP 160 EP 165 DI 10.1111/j.1399-0004.2004.00386.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 892HN UT WOS:000226641100007 PM 15679828 ER PT J AU Anderson, J Fleming, SD Rehrig, S Tsokos, GC Basta, M Shea-Donohue, T AF Anderson, J Fleming, SD Rehrig, S Tsokos, GC Basta, M Shea-Donohue, T TI Intravenous immunoglobulin attenuates mesenteric ischemia-reperfusion injury SO CLINICAL IMMUNOLOGY LA English DT Article DE complement; IVIG; ischemia-reperfusion; neutrophil; inflammation; rat ID INTESTINAL ISCHEMIA; ISCHEMIA/REPERFUSION INJURY; CAPILLARY LEAK; COMPLEMENT; RAT; INFLAMMATION; MODULATION; FRAGMENTS; DAMAGE AB Intravenous immunoglobulin (IVIG) has been found useful in the treatment of various clinical entities and its effect has been associated with inhibition of complement-mediated tissue damage. The aim of this study was to determine the ability of IVIG to protect against mesenteric ischemia-reperfusion (IR)-induced local and remote injury. Rats received vehicle or IVIG (150-600 mg/kg) 5 min prior to sham operation or 30 min of superior mesenteric artery occlusion, followed by 5, 120, or 240 min of reperfusion. IVIG reduced IR-induced mucosal injury without altering IR-induced increases in PMN infiltration or LTB4 generation. At 5 min post IR, the deposition of IgG and C3 in the lamina propria and surface epithelial cells was attenuated by IVIG. The increased capillary leak, evident at 240 min, was inhibited by IVIG and coincided with a reduction in C3 deposition in lung tissue. The beneficial effects of IVIG may be related to the ability to scavenge deleterious products. Published by Elsevier Inc. C1 Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA. Univ Maryland, Dept Med, Baltimore, MD 21201 USA. USDA ARS, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Dept Cellular Injury, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. MD Inst Res, Dept Surg, Walter Reed Army Forest Glen, Silver Spring, MD 20910 USA. RP Shea-Donohue, T (reprint author), Univ Maryland, Sch Med, Mucosal Biol Res Ctr, 20 Penn St,HSF 2,Room 349, Baltimore, MD 21201 USA. EM tdonohue@medicine.umaryland.edu OI rehrig, scott/0000-0002-1287-9708; Basta, Milan/0000-0001-5958-9241 NR 29 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD FEB PY 2005 VL 114 IS 2 BP 137 EP 146 DI 10.1016/j.clim.2004.08.018 PG 10 WC Immunology SC Immunology GA 889KA UT WOS:000226440700006 PM 15639647 ER PT J AU Cortez, KJ Groll, AH Walsh, TJ AF Cortez, KJ Groll, AH Walsh, TJ TI Resources for medical mycology on the World Wide Web SO CLINICAL INFECTIOUS DISEASES LA English DT Article AB Searching the World Wide Web for information on medical mycology can be challenging. We provide the reader with an organized overview of the available resources on the Internet, including authoritative sites from academic institutions, professional societies, government agencies, and personal sites. This article reviews clinically relevant Internet resource directories, comprehensive sites of interest to clinicians, clinical trials in medical mycology, clinically relevant Web sites devoted to specific fungal pathogens and their infections, genomic resources in medical mycology, culture collections, images of fungi on the World Wide Web, medical mycology lecture and teaching materials, environmental health and safety information, and a listing of Web sites of medical mycology professional societies. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Munster, Childrens Hosp, Infect Res Program, Ctr Bone Marrow Transplantat, Munster, Germany. Univ Munster, Childrens Hosp, Dept Hematol Oncol, Munster, Germany. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Rm 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2005 VL 40 IS 3 BP 437 EP 450 PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JM UT WOS:000227492500016 PM 15668869 ER PT J AU Slobounov, S Hallett, M Stanhope, S Shibasaki, H AF Slobounov, S Hallett, M Stanhope, S Shibasaki, H TI Role of cerebral cortex in human postural control: an EEG study SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE postural stability in human; cortical control; motor-related cortical potentials (MRCP); neural detectors; EEG gamma activity ID MOVEMENT-RELATED POTENTIALS; FOOT MOVEMENT; TIME; COORDINATION; LOCALIZATION; ACTIVATION; HANDEDNESS; FREQUENCY; RESPONSES; RHYTHMS AB Objective: it was our primary objective to provide evidence supporting the existence of neural detectors for postural instability that could trigger the compensatory adjustments to avoid falls. Methods: Twelve young healthy subjects performed self-initiated oscillatory and discrete postural movements in the anterior-posterior (AP) directions with maximal range of motion predominantly at ankle joint. Movements were recorded by the system and included force plate and EMG. and EEG measures from 25 electrode sites. The center of pressure dynamics and stability index were calculated, and EEG potentials both in voltage and frequency domains were extracted by averaging and Morlet wavelet techniques, respectively. Results: The initiation of self-paced postural movement was preceded by slow negative DC shift, similar to movement-related cortical potentials (MRCP) accompanying voluntary limb movement. A burst of gamma activity preceded the initiation of compensatory backward postural movement when balance was in danger. This was evident for both oscillatory and discrete AP postural movements. The spatial distribution of EEG patterns in postural actions approximated that previously observed during the postural perceptual tasks. Conclusions: The results suggest an important role of the higher cortical structures in regulation of posture equilibrium in dynamic stances. Postural reactions to prevent falls may be triggered by central command mechanisms identified by a burst of EEG gamma activity. Significance: The results from this study contribute to our understanding of neurophysiological mechanisms underlying the cortical control of human upright posture in normal subjects. (C) 2004 Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology. C1 Penn State Univ, Dept Kinesiol, University Pk, PA 16802 USA. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Slobounov, S (reprint author), Penn State Univ, Dept Kinesiol, 19 Recreat Hall, University Pk, PA 16802 USA. EM sms18@psu.edu NR 47 TC 60 Z9 61 U1 2 U2 15 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD FEB PY 2005 VL 116 IS 2 BP 315 EP 323 DI 10.1016/j.clinph.2004.09.007 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 897SQ UT WOS:000227025800012 PM 15661110 ER PT J AU Paradee, CV Rapport, LJ Hanks, RA Levy, JA AF Paradee, CV Rapport, LJ Hanks, RA Levy, JA TI Circadian preference and cognitive functioning among rehabilitation inpatients SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article ID CEREBRAL BLOOD-FLOW; MORNINGNESS-EVENINGNESS PREFERENCE; INDIVIDUAL-DIFFERENCES; RHYTHM QUESTIONNAIRES; TYMPANIC TEMPERATURE; ALZHEIMERS-DISEASE; BODY-TEMPERATURE; COMPLEX FIGURE; MEMORY; PERFORMANCE AB The influence of circadian preference was examined among 56 morning-oriented rehabilitation inpatients with cognitive (n = 28) and noncognitive (n = 28) impairments. Each individual was tested twice: morning (preferred time) and evening (nonpreferred time); sessions and test batteries were counterbalanced to control for practice effects. Standard measures assessed attention, language, memory, visuospatial, and executive functions. Persons with cognitive impairment showed disproportionate vulnerability to the effects of circadian preference and time of testing, performing more poorly at nonpreferred than preferred times. Substantial effects (eta(2) .12 to .48) were found on tests of executive functioning and tasks incorporating similar higher-order demands (e.g., complex figure copy). Results are supported by tympanic temperature changes during a vigilance task, an index of cerebral blood flow in response to cognitive challenge. Cognitive reserve theory is suggested as an explanation for the differential effects. These findings may have implications for inpatient therapeutic interventions and discharge planning. C1 Wayne State Univ, Detroit, MI 48202 USA. Rehabil Inst Michigan, Detroit, MI USA. NIH, Washington, DC USA. RP Paradee, CV (reprint author), Wayne State Univ, 71 W Warren, Detroit, MI 48202 USA. EM cparadee@comcast.net NR 68 TC 10 Z9 10 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD FEB PY 2005 VL 19 IS 1 BP 55 EP 72 DI 10.1080/13854040490524173 PG 18 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 912YF UT WOS:000228115300004 PM 15814478 ER PT J AU Di Prospero, NA Sumner, C Atkinson, A Fischbeck, K Taylor, JP AF Di Prospero, NA Sumner, C Atkinson, A Fischbeck, K Taylor, JP TI Safety, tolerability, and pharmacokinetics of idebenone in a dose-escalation trial in patients with Friedreich's ataxia. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 NIH, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P68 EP P68 DI 10.1016/j.clpt.2004.12.150 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500255 ER PT J AU Edwards, D Chugani, DC Chugani, HT Chehab, J Malian, M Aranda, JV AF Edwards, D Chugani, DC Chugani, HT Chehab, J Malian, M Aranda, JV TI Buspirone pharmacokinetics in autistic children. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 Wayne State Univ, Childrens Hosp Michigan, NICHD, PPRU Network, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P31 EP P31 DI 10.1016/j.clpt.2004.12.009 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500114 ER PT J AU Eldadah, B Pechnik, S Holmes, C Goldstein, DS AF Eldadah, B Pechnik, S Holmes, C Goldstein, DS TI Propranolol tor neurocardiogenic syncope with sympathoadrenal imbalance. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P55 EP P55 DI 10.1016/j.clpt.2004.12.100 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500205 ER PT J AU Kim, H Dionne, RA AF Kim, H Dionne, RA TI Haplotype structures of cyclooxygenase genes in human ethnic populations. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P64 EP P64 DI 10.1016/j.clpt.2004.12.137 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500242 ER PT J AU Lee, Y Kim, H Rodriguez, C Dionne, RA AF Lee, Y Kim, H Rodriguez, C Dionne, RA TI Effects of a dual cox-1/-2 inhibitor and a selective cox-2 inhibitor on pro-inflammatory gene expression in a clinical model of tissue injury. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P9 EP P9 DI 10.1016/j.clpt.2004.11.035 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500030 ER PT J AU Ma, Q Forrest, A Rosenkranz, S Para, MF Adams, E Yarasheski, KE Reichman, RC Morse, GD AF Ma, Q Forrest, A Rosenkranz, S Para, MF Adams, E Yarasheski, KE Reichman, RC Morse, GD TI Optimal multi-drug PK sampling strategies (OSS) for efavirenz (EFV) & indinavir (IDV). SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 SUNY Buffalo, Buffalo, NY USA. Harvard Univ, Cambridge, MA 02138 USA. Ohio State Univ, Columbus, OH 43210 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Univ Rochester, Rochester, NY 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P42 EP P42 DI 10.1016/j.clpt.2004.12.052 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500157 ER PT J AU Mager, DE Shirey, JD Cox, D Fitzgerald, DJ Abernethy, DR AF Mager, DE Shirey, JD Cox, D Fitzgerald, DJ Abernethy, DR TI Neural network model of orbofiban pharmacodynamics from sparse Phase-II data SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 SUNY Buffalo, Buffalo, NY 14260 USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Coll Dublin, Royal Coll Surg Ireland, Dublin 2, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P92 EP P92 DI 10.1016/j.clpt.2004.12.244 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500347 ER PT J AU Mittal-Parikh, PD Kim, H Brahim, J Rowan, J Dionne, RA AF Mittal-Parikh, PD Kim, H Brahim, J Rowan, J Dionne, RA TI The association between cyclooxygenase gene polymorphisms and acute post-surgical pain in humans. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 NIDCR, PNMB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P20 EP P20 DI 10.1016/j.clpt.2004.11.079 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500074 ER PT J AU Preston, KL Schmittner, J Schroeder, JR Epstein, DH AF Preston, KL Schmittner, J Schroeder, JR Epstein, DH TI Menstrual function during methadone maintenance (MM). SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 NIDA, Intramural Res Program, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P65 EP P65 DI 10.1016/j.clpt.2004.12.140 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500245 ER PT J AU Reed, M Konstan, M O'Riordan, M Blumer, J AF Reed, M Konstan, M O'Riordan, M Blumer, J TI Pharmacokinetics (PK) and absolute bioavailability (F) of linezolid (L) in cystic fibrosis (CF) patients (PTS). SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 Case Western Reserve Univ, NICHHD, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P30 EP P30 DI 10.1016/j.clpt.2004.12.006 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500111 ER PT J AU Schmittner, J Schroeder, JR Epstein, DH Preston, KL AF Schmittner, J Schroeder, JR Epstein, DH Preston, KL TI Adverse events in a behavioral treatment trial in methadone maintenance. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 Natl Inst Drug Abuse, IRP, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P71 EP P71 DI 10.1016/j.clpt.2004.12.164 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500268 ER PT J AU Wang, XM Wu, TX Lee, YS Dionne, RA AF Wang, XM Wu, TX Lee, YS Dionne, RA TI Gene expression in the arachidonic acid pathway due to tissue injury and inflammation, an NSAID, and COXIB in a clinical model of pain. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P8 EP P8 DI 10.1016/j.clpt.2004.11.034 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500029 ER PT J AU Zack, JZ Forrest, A Ma, Q Rosenkranz, S Para, MF Adams, E Reichman, RC Yaresheski, K Morse, GD AF Zack, JZ Forrest, A Ma, Q Rosenkranz, S Para, MF Adams, E Reichman, RC Yaresheski, K Morse, GD TI Optimal sparse pharmacokinetic (PK) sampling strategies (OSS) for multi-drug antiretroviral (ARV) regimens SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 SUNY Buffalo, Buffalo, NY 14260 USA. Harvard Univ, Cambridge, MA 02138 USA. Ohio State Univ, Columbus, OH 43210 USA. NIAID, Bethesda, MD 20892 USA. Univ Rochester, Rochester, NY 14627 USA. Washington Univ, St Louis, MO 63130 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P90 EP P90 DI 10.1016/j.clpt.2004.12.236 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500339 ER PT J AU Zack, JZ Forrest, A Okusanya, OO Rosenkranz, S Para, MF Adams, E Yaresheski, K Reichman, RC Morse, GD AF Zack, JZ Forrest, A Okusanya, OO Rosenkranz, S Para, MF Adams, E Yaresheski, K Reichman, RC Morse, GD TI Compartmental analysis of saquinavir (SQV) pharmacokinetics (PK). SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 SUNY Buffalo, Buffalo, NY 14260 USA. Harvard Univ, Cambridge, MA 02138 USA. Ohio State Univ, Columbus, OH 43210 USA. Washington Univ, NIAID, St Louis, MO 63130 USA. Univ Rochester, Rochester, NY 14627 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P79 EP P79 DI 10.1016/j.clpt.2004.12.195 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500298 ER PT J AU Yoo, TS Ackerman, MJ AF Yoo, TS Ackerman, MJ TI Open source software for medical image processing and visualization SO COMMUNICATIONS OF THE ACM LA English DT Article C1 NIH, 3D Informat Program, Natl Lib Med, Bethesda, MD 20892 USA. RP NIH, 3D Informat Program, Natl Lib Med, Bethesda, MD 20892 USA. EM tyoo@mail.nih.gov; ackerman@nlm.nih.gov NR 12 TC 7 Z9 7 U1 0 U2 1 PU ASSOC COMPUTING MACHINERY PI NEW YORK PA 2 PENN PLAZA, STE 701, NEW YORK, NY 10121-0701 USA SN 0001-0782 EI 1557-7317 J9 COMMUN ACM JI Commun. ACM PD FEB PY 2005 VL 48 IS 2 BP 55 EP 59 DI 10.1145/1042091.1042120 PG 5 WC Computer Science, Hardware & Architecture; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA 889RH UT WOS:000226459600016 ER PT J AU Fontenot, MB Padgett, EE Dupuy, AM Lynch, CR De Petrillo, PB Higley, JD AF Fontenot, MB Padgett, EE Dupuy, AM Lynch, CR De Petrillo, PB Higley, JD TI The effects of fluoxetine and buspirone on self-injurious and stereotypic behavior in adult male rhesus macaques SO COMPARATIVE MEDICINE LA English DT Article ID CEREBROSPINAL-FLUID MONOAMINE; ELECTROCHEMICAL DETECTION; MACACA-MULATTA; MONKEYS; AGGRESSION; NEUROBIOLOGY; POPULATION; DEPRESSION; DISORDER; STRESS AB The effects of two serotonergic agents-fluoxetine, a serotonin (5-HT) reuptake inhibitor, and buspirone, a 5-HT 1(a) agonist-on rates of self-injurious and stereotypic behavior were examined in 15 adult male Macaca mulatta. All animals received a placebo for 2 weeks followed by either buspirone or fluoxetine for 12 weeks. Behavior was monitored using a focal sampling technique throughout the study and for 2 weeks post-study. Cerebrospinal fluid (CSF) samples and body weights were obtained pre-study, at the ends of placebo and treatment phases, and post-study. Fluoxetine and buspirone were significantly effective in reducing rates of self-biting during treatment weeks I to 8 and self-directed stereotypic behavior during weeks 5 to 12 and post-treatment. No significant effect of either treatment on hair-plucking, stereotypic pacing, saluting, or head tossing was identified. The duration of neutral behavior increased, and rates of scratching and yawning decreased in the buspirone-treated condition. In the fluoxetine-treated condition, rates of yawning, scratching, and self-directed grooming were higher overall compared with those of buspirone-treated animals, and rates of scratching increased significantly (P < 0.05) in weeks 9 to 12; these findings suggest that animals in the fluoxetine-treated condition experienced higher levels of anxiety throughout the study. In both treatment conditions, concentrations of CSF 5-HIAA (5-HT metabolite) were significantly lower (P < 0.05) than placebo concentrations. Fluoxetine and buspirone may be efficacious for treatment of self-injurious and self-directed stereotypic behavior in macaques. Further studies are required to determine the optimal dosages and treatment length. C1 Univ Louisiana Lafayette, New Iberia Res Ctr, New Iberia, LA 70560 USA. NIH, Sect Clin & Biochem Pharmacol, Poolesville, MD 20837 USA. NIH, Clin Studies Lab, Anim Ctr, Poolesville, MD 20837 USA. RP Fontenot, MB (reprint author), Univ Louisiana Lafayette, New Iberia Res Ctr, 4401 W Admiral Doyle Dr, New Iberia, LA 70560 USA. NR 44 TC 25 Z9 26 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD FEB PY 2005 VL 55 IS 1 BP 67 EP 74 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 936TQ UT WOS:000229878700012 PM 15766212 ER PT J AU Horwitz, B AF Horwitz, B TI Integrating neuroscientific data across spatiotemporal scales SO COMPTES RENDUS BIOLOGIES LA English DT Article; Proceedings Paper CT International Colloquium on New Approaches to Neurosciences and Diseases of the Central Nervous System CY MAY 10-12, 2004 CL Paris, FRANCE SP French Acad Sci Med DE brain; audition; vision; neural modeling; neural networks; IRMf ID CEREBRAL BLOOD-FLOW; PARKINSONS-DISEASE; NETWORK ANALYSIS; WORKING-MEMORY; SYNAPTIC ACTIVITY; AUDITORY-CORTEX; VISUAL PATHWAYS; HUMAN GENOME; PET; PRIMATE AB A major challenge confronting neuroscientists is associated with the multiple spatial and temporal scales of investigation of neural structure and function. I shall discuss the use of computational neural modeling as one method to bridge some of the different spatial and temporal levels. This approach will be illustrated using large-scale, neurobiologically realistic network models of auditory and visual pattern recognition that relate neuronal dynamics to fMRI data. It will be demonstrated that the models are capable of exhibiting the salient features of both electrophysiological neuronal activities and fMRI values that are in agreement with empirically observed data. (C) 2004 Academie des sciences. Published by Elsevier SAS. All rights reserved. C1 NIDCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. RP Horwitz, B (reprint author), NIDCD, Brain Imaging & Modeling Sect, NIH, Bldg 10,Rm 6C420 MSC 1591, Bethesda, MD 20892 USA. EM horwitz@helix.nih.gov NR 42 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 1631-0691 EI 1768-3238 J9 CR BIOL JI C. R. Biol. PD FEB PY 2005 VL 328 IS 2 BP 109 EP 118 DI 10.1016/j.crvi.2004.10.015 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 904HG UT WOS:000227486100002 PM 15770997 ER PT J AU Warden, D Rush, AJ Trivedi, M Ritz, L Stegman, D Wisniewski, SR AF Warden, D Rush, AJ Trivedi, M Ritz, L Stegman, D Wisniewski, SR TI Quality improvement methods as applied to a multicenter effectiveness trial - STAR*D SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE quality improvement; efficiency in clinical trials; depression; multicenter clinical trials; improving recruitment and retention in clinical trials; improving outcomes collection in clinical trials ID DEPRESSIVE SYMPTOMATOLOGY IDS; REPORT QIDS-SR; PSYCHOMETRIC EVALUATION; MAJOR DEPRESSION; QUICK INVENTORY; HEALTH-CARE; MANAGEMENT; ASSURANCE; IMPLEMENTATION; SYSTEM AB In multicenter clinical trials, important aspects of trial performance (e.g., the number of participants who enter the trial within the required time frame, the number of participants who remain in the trial, and/or the completeness of the outcome data collected) directly affect the extent to which the study can achieve its aims. Obtaining the maximum amount of data from the maximum number of participants at each step in the trial increases the likelihood of identifying real differences in outcome. These aspects of trial performance can, therefore, be considered intermediate performance goals of the study since success in achieving each of them is directly related to success in achieving study aims. A quality improvement system was introduced to improve efficiency and performance in the multicenter Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Four intermediate performance goals were targeted for quality improvement efforts: (1) initial enrollment of subjects, (2) collection of entry/exit primary outcome data, (3) retention of subjects to enter subsequent "levels" of the trial, and (4) collection of blood samples for genetics studies. The identification of numerical targets for these goals provides a basis for monitoring performance and for implementing attempts to improve performance, since success in achieving each goal is directly related to success in achieving the study aims. This paper describes the background, rationale, development, and potential utility of implementing a quality improvement system to improve the performance and efficiency of the trial. © 2004 Elsevier Inc. All rights reserved. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75235 USA. NIMH, Bethesda, MD 20892 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. RP Warden, D (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. EM Diane.Warden@UTSouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 58 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD FEB PY 2005 VL 26 IS 1 BP 95 EP 112 DI 10.1016/j.cct.2004.11.011 PG 18 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 926JB UT WOS:000229118400009 PM 15837455 ER PT J AU Frattali, C AF Frattali, C TI What's in a name? Commentary on Szekely et al. (2005), timed action and object naming SO CORTEX LA English DT Editorial Material ID VERBS; NOUNS; REPRESENTATION; IMAGEABILITY; BRAIN C1 NIH, BC NCD, Speech Language Pathol Sect, WG Magnuson Clin Ctr,Rehabil Med Dept, Bethesda, MD 20892 USA. RP Frattali, C (reprint author), NIH, BC NCD, Speech Language Pathol Sect, WG Magnuson Clin Ctr,Rehabil Med Dept, Bldg 10,Rm 6S 235, Bethesda, MD 20892 USA. EM carol_frattali@nih.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU MASSON DIVISIONE PERIODICI PI MILAN PA VIA FRATELLI BRESSAN 2, 20126 MILAN, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD FEB PY 2005 VL 41 IS 1 BP 3 EP 5 DI 10.1016/S0010-9452(08)70173-4 PG 3 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 881UM UT WOS:000225894900002 PM 15633702 ER PT J AU Masur, H Carlet, J Gerlach, H Dellinger, RP AF Masur, H Carlet, J Gerlach, H Dellinger, RP TI Surviving Sepsis Campaign Guidelines: Selective decontamination of the digestive tract still neglected - The authors reply SO CRITICAL CARE MEDICINE LA English DT Letter ID PREVENTION C1 NIH, Bethesda, MD 20892 USA. Fdn Hop St Joseph, Paris, France. Vivantes Klinikum Neukoelln, Berlin, Germany. Cooper Hosp Univ Med Ctr, Camden, NJ 08103 USA. RP Masur, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2005 VL 33 IS 2 BP 463 EP 464 DI 10.1097/01.CCM.0000153606.37258.74 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 898LE UT WOS:000227077500036 ER PT J AU Zimmerman, JL Neukoelln, VK Masur, H Carlet, J Dellinger, RP AF Zimmerman, JL Neukoelln, VK Masur, H Carlet, J Dellinger, RP TI Doing antithrombin III An injustice? The authors reply SO CRITICAL CARE MEDICINE LA English DT Letter ID SEVERE SEPSIS; CONTROLLED TRIAL; MULTICENTER; ANTIBODY C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Vivantes Klinikum Neukoelln, Dept Anesthesiol & Crit Care Med, Berlin, Germany. NIH, Bethesda, MD 20892 USA. Fdn Hop St Joseph, Serv Reanimat Polyvalente, Paris, France. Cooper Univ Hosp, Sect Crit Care Med, Camden, NJ USA. RP Zimmerman, JL (reprint author), Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NR 5 TC 0 Z9 0 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 FEB PY 2005 VL 33 IS 2 BP 465 EP 466 DI 10.1097/01.CCM.0000153603.61299.15 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 898LE UT WOS:000227077500040 ER PT J AU Fouts, HN Hewlett, BS Lamb, ME AF Fouts, HN Hewlett, BS Lamb, ME TI Parent-offspring weaning conflicts among the Bofi farmers and foragers of Central Africa SO CURRENT ANTHROPOLOGY LA English DT Article ID PREINDUSTRIAL SOCIETIES; ECOLOGY; BEHAVIOR; BREAST; CHILD; ANTHROPOLOGY; PERSPECTIVE; ATTACHMENT; GROWTH; COST AB Parent-offspring conflict theory suggests that the reproductive interests of parents and children may conflict when parents want to have another child and an existing child wants continued parental attention and resources. This conflict leads toddlers to throw temper tantrums and use other psychological weapons to maintain parental investment. Few studies employing this theory have considered both the cultural and the biological contexts of weaning. Using systematic qualitative and quantitative data collected among the Bofi farmers and foragers of Central Africa, we examined the influence of cultural schemas and practices, nursing patterns, child's age, maternal pregnancy, and maternal work patterns on children's responses to the cessation of nursing. As predicted by the theory, Bofi farmer children exhibited high levels of fussing and crying when abruptly weaned while Bofi forager children showed no marked signs of distress. Differences in child care practices associated with the cessation of nursing contributed to this variation, and these practices are linked to broader differences in cultural schemas and social relations. These findings are used to discuss intersections between culture and biology and to show that parent-offspring conflict theory can accommodate a diversity of contexts. C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD 20892 USA. Washington State Univ, Pullman, WA 99164 USA. Univ Cambridge, Cambridge CB2 1TN, England. RP Fouts, HN (reprint author), NICHHD, Sect Social & Emot Dev, Rockledge 1 Ctr,6705 Rockledge Dr,Suite 8048, Bethesda, MD 20892 USA. EM foutsh@mail.nih.gov NR 99 TC 37 Z9 38 U1 2 U2 13 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0011-3204 EI 1537-5382 J9 CURR ANTHROPOL JI Curr. Anthropol. PD FEB PY 2005 VL 46 IS 1 BP 29 EP 50 DI 10.1086/425659 PG 22 WC Anthropology SC Anthropology GA 902JU UT WOS:000227352100002 ER PT J AU Hoffmann, S He, SK Jin, ML Masiero, L Wiedemann, P Ryan, SJ Kohn, EC AF Hoffmann, S He, SK Jin, ML Masiero, L Wiedemann, P Ryan, SJ Kohn, EC TI Carboxyamido-triazole modulates retinal pigment epithelial and choroidal endothelial cell attachment, migration, proliferation, and MMP-2 secretion of choroidal endothelial cells SO CURRENT EYE RESEARCH LA English DT Article; Proceedings Paper CT 101st Annual Meeting of the German-Ophthalmological-Society CY SEP 25-28, 2003 CL Berlin, GERMANY SP German Ophthalmol Soc DE age-related macular degeneration; choroidal endothelial cell; choroidal neovascularization; retinal pigment epithelial cell; signal transduction therapy ID FIBROBLAST-GROWTH-FACTOR; FOCAL ADHESION KINASE; PHOSPHOLIPASE C-GAMMA; CALCIUM INFLUX; IN-VITRO; NEOVASCULAR MEMBRANES; SIGNAL-TRANSDUCTION; MACULAR DEGENERATION; EXTRACELLULAR-MATRIX; TYROSINE KINASE AB Purpose: To determine the effect of the calcium signaling modulating drug carboxyamido-triazole (CAI) on substeps of exudative age-related macular degeneration (AMD) in vitro. Materials and Methods: Zymography and ELISA determined the effect of CAI on MMP- 2 production of choroidal endothelial cells (CECs) stimulated by bFGF and VEGF. The effects of CAI on attachment of retinal pigment endothelial (RPE) cells/ CECs onto fibronectin, laminin, collagen IV, and migration toward fibronectin were investigated. Proliferation induced by serum and bFGF (10 mu g/ ml) with and without CAI (0.1 - 10 mu M) was measured by cell counting and H-3-uptake. Viability and apoptosis of the exposed cells was assessed by an MTT and an apoptosis assay. Results: CAI inhibited serum- and bFGF- induced proliferation, cell attachment onto fibronectin and collagen IV, but only CEC attachment onto laminin. Inhibition of MMP- 2 production was observed (10 mu M CAI). CAI reduced the cellular viability by apoptosis induction. Conclusions: CAI inhibits substeps of exudative macular degeneration and may be of value for the treatment of the disease. C1 Univ Leipzig, Dept Ophthalmol, D-7010 Leipzig, Germany. Univ So Calif, Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. NCI, Pathol Lab, Mol Signaling Sect, Bethesda, MD 20892 USA. Univ So Calif, Keck Sch Med, Doheny Eye Inst, Beckman Macula Res Ctr,Dept Ophthalmol, Los Angeles, CA USA. RP Hoffmann, S (reprint author), Univ Saugen Klin Leipzig, Liebigstr 10-14, D-04103 Leipzig, Germany. EM HoffmS@web.de FU NEI NIH HHS [EY03040] NR 56 TC 7 Z9 8 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD FEB PY 2005 VL 30 IS 2 BP 103 EP 113 DI 10.1080/02713680490894595 PG 11 WC Ophthalmology SC Ophthalmology GA 913UZ UT WOS:000228182000003 PM 15814468 ER PT J AU Lin, HW Schneider, ME Kachar, B AF Lin, HW Schneider, ME Kachar, B TI When size matters: the dynamic regulation of stereocilia lengths SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID PARALLEL ACTIN BUNDLES; NEURONAL GROWTH CONE; HAIR-CELLS; MYOSIN-X; UNCONVENTIONAL MYOSIN; MOLECULAR TREADMILL; FILOPODIA FORMATION; ENA/VASP PROTEINS; BARBED-END; TIP LINKS AB Stereocilia, the mechanosensitive protrusions in hair cells, are organized into rows of graded heights forming precisely uniform staircase patterns. The actin turnover process in stereocilia follows a treadmill model in which the rate of treadmilling is scaled to the stereocilium's length. Myosin XVa, which is present at the site of actin polymerization at concentrations proportional to the length of the actin filament bundles, plays a combined role with the treadmill machinery in regulating the steady state length of these actin protrusions, together with other myosins localized alongside the actin bundles. C1 Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Kachar, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. EM kacharb@nidcd.nih.gov NR 40 TC 51 Z9 52 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD FEB PY 2005 VL 17 IS 1 BP 55 EP 61 DI 10.1016/j.ceb.2004.12.005 PG 7 WC Cell Biology SC Cell Biology GA 894YW UT WOS:000226828500009 PM 15661519 ER PT J AU Gaydos, CA Quinn, TC AF Gaydos, CA Quinn, TC TI Urine nucleic acid amplification tests for the diagnosis of sexually transmitted infections in clinical practice SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE self-sampling; STIs; urine/vagina ID LIGASE CHAIN-REACTION; CHLAMYDIA-TRACHOMATIS INFECTION; PELVIC-INFLAMMATORY-DISEASE; HUMAN-PAPILLOMAVIRUS DNA; FEMALE-ARMY-RECRUITS; NEISSERIA-GONORRHOEAE INFECTIONS; MICROTRAK ENZYME-IMMUNOASSAY; DIRECT FLUORESCENT-ANTIBODY; ADMINISTERED VAGINAL SWABS; GENITAL-TRACT INFECTION AB Purpose of review With the advent of highly sensitive and specific nucleic acid amplification assays, this report will demonstrate that self-collected genital specimens, such as urine or even vaginal swabs can be accurately used to diagnose sexually transmitted infections. Recent findings Use of self collected samples can eliminate the necessity of a clinician to perform a pelvic examination for women or collect a urethral swab for men, thus extending the diagnostic capability for sexually transmitted infections to non-clinic screening venues. As many sexually transmitted infections are asymptomatic, this ability to use self-sampling greatly increases the numbers of patients that can be screened, and has the potential to augment public health programs designed to control the epidemic of sexually transmitted infections in the community. Patient collected samples are highly acceptable, highly accurate, and are becoming widely used. Self-sampling also allows clinicians to easily screen patients in the clinic, who are not presenting for pelvic or urogenital examinations, for sexually transmitted infections. Summary Highly accurate molecular tests and easily obtained selfcollected urogenital samples represent the ideal combination for obtaining the public health goal of decreasing the sexually transmitted infection epidemic among sexually active persons in the United States today. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Gaydos, CA (reprint author), 1159 Ross,720 Rutland Ave, Baltimore, MD 21205 USA. EM cgaydos@jhmi.edu RI Gaydos, Charlotte/E-9937-2010 NR 148 TC 20 Z9 23 U1 5 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD FEB PY 2005 VL 18 IS 1 BP 55 EP 66 DI 10.1097/00001432-200502000-00010 PG 12 WC Infectious Diseases SC Infectious Diseases GA 900QC UT WOS:000227228400009 PM 15647701 ER PT J AU Laabs, T Carulli, D Geller, HM Fawcett, JW AF Laabs, T Carulli, D Geller, HM Fawcett, JW TI Chondroitin sulfate proteoglycans in neural development and regeneration SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD-INJURY; NEURITE OUTGROWTH; GLIAL SCAR; AXONAL REGENERATION; ASTROCYTE BOUNDARY; VISUAL-CORTEX; SENSORY AXONS; WHITE-MATTER; GROWTH AB Proteoglycans are of two main types, chondroitin sulfate (CSPGs) and heparin sulfate (HSPGs). The CSPGs act mainly as barrier-forming molecules, whereas the HSPGs stabilise the interactions of receptors and ligands. During development CSPGs pattern cell migration, axon growth pathways and axon terminations. Later in development and in adulthood CSPGs associate with some classes of neuron and control plasticity. After damage to the nervous system, CSPGs are the major axon growth inhibitory component of the glial scar tissue that blocks successful regeneration. CSPGs have a variety of roles in the nervous system, including binding to molecules and blocking their action, presenting molecules to cells and axons, localising active molecules to particular sites and presenting growth factors to their receptors. C1 Univ Cambridge, Ctr Brain Repair, Cambridge, England. NHLBI, NIH, Bethesda, MD 20892 USA. RP Fawcett, JW (reprint author), Univ Cambridge, Ctr Brain Repair, Robinson Way, Cambridge, England. EM jf108@cam.ac.uk OI Carulli, Daniela/0000-0003-1365-7063; Geller, Herbert/0000-0002-7048-6144; Fawcett, James/0000-0002-7990-4568 NR 42 TC 171 Z9 175 U1 1 U2 13 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD FEB PY 2005 VL 15 IS 1 BP 116 EP 120 DI 10.1016/j.conb.2005.01.014 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 906KQ UT WOS:000227640000017 ER PT J AU Antachopoulos, C Walsh, TJ AF Antachopoulos, C Walsh, TJ TI New agents for invasive mycoses in children SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE invasine fungal infections; echinocandins; triazoles; Candida; Aspergillus; pediatrics ID IN-VITRO ACTIVITIES; LIPOSOMAL AMPHOTERICIN-B; EXPERIMENTAL PULMONARY ASPERGILLOSIS; CHRONIC GRANULOMATOUS-DISEASE; PERSISTENTLY NEUTROPENIC RABBITS; REFRACTORY FUNGAL-INFECTIONS; LIPOPEPTIDE ANTIFUNGAL AGENT; CLINICALLY IMPORTANT MOLDS; ACUTE MYELOID-LEUKEMIA; GUINEA-PIG MODEL AB Purpose of review Invasive fungal infections are an important cause of morbidity and mortality in immunocompromised children of all ages. This review summarizes information on new antifungal agents, including current data on their clinical use in children, as well as alternative strategies such as antifungal combination and immunomodulation therapy. Recent findings Novel antifungal agents, such as the echinocandins and the second-generation triazoles, were recently introduced that exhibit promising efficacy against Candida spp., Aspergillus spp., and other opportunistic fungal pathogens. These compounds are generally well tolerated and show substantial efficacy as salvage treatment and equal or even superior efficacy compared with older azoles or amphotericin B as first-line or empiric therapy for fungal infections. Clinical studies of pharmacokinetics and efficacy of the new agents in the pediatric population are, however, limited. Summary the response rates observed with the recently introduced drugs, although superior in some cases compared with older antifungal agents, are still far from satisfactory. The development of new antifungal compounds as well as the use of alternative approaches of combination therapy and immunomodulation should be pursued through well-designed laboratory and clinical studies in pediatric patients. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, CRC 1-5750,10 Ctr Dr, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 132 TC 18 Z9 21 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD FEB PY 2005 VL 17 IS 1 BP 78 EP 87 DI 10.1097/01.mop.0000150630.83442.e1 PG 10 WC Pediatrics SC Pediatrics GA 890IO UT WOS:000226505100016 PM 15659969 ER PT J AU Hickman, AB Dyda, F AF Hickman, AB Dyda, F TI Binding and unwinding: SF3 viral helicases SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID ADENOASSOCIATED VIRUS TYPE-2; LARGE T-ANTIGEN; EUKARYOTIC DNA-REPLICATION; LARGE TUMOR-ANTIGEN; CRYSTAL-STRUCTURE; DOUBLE HEXAMERS; SIMIAN-VIRUS-40 ORIGIN; NUCLEASE DOMAIN; E1 HELICASE; PROTEIN AB The SF3 helicases, distinct from the more prevalent SF1 and SF2 helicases, were originally identified in the genomes of small DNA and RNA viruses. The first crystal structures of SF3 helicases have been determined, revealing a closer structural relationship to AAA+ proteins than to RecA, consistent with their participation in replication initiation. In conjunction with origin-binding domains, SF3 helicases are responsible for distorting DNA before replication forks can be assembled. At these forks, the SF3 helicases act as replicative helicases. The simian virus 40 SF3 helicase forms a hexameric ring, anticipated to be characteristic of the entire superfamily. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dyda, F (reprint author), NIDDKD, Mol Biol Lab, NIH, 5 Ctr Dr MSC 0560, Bethesda, MD 20892 USA. EM dyda@helix.nih.gov NR 51 TC 64 Z9 65 U1 0 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD FEB PY 2005 VL 15 IS 1 BP 77 EP 85 DI 10.1016/j.sbi.2004.12.001 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 905UU UT WOS:000227596800012 PM 15718137 ER PT J AU Biragyn, A AF Biragyn, A TI Defensins - Non-antibiotic use for vaccine development SO CURRENT PROTEIN & PEPTIDE SCIENCE LA English DT Review DE antimicrobial peptides; dendritic cells; vaccine carrier ID REGULATORY T-CELLS; ANTIBACTERIAL PEPTIDE LL-37; AIRWAY EPITHELIAL-CELLS; DENDRITIC CELLS; IMMUNE-RESPONSES; INNATE IMMUNITY; MAST-CELLS; ANTIMICROBIAL PEPTIDES; ADAPTIVE IMMUNITY; MEDIATED SUPPRESSION AB Vaccines should elicit protective and long lasting immune memory, which depends on well choreographed responses between innate and acquired immunity. Defensins are small host defense peptides of innate immunity hitherto reported to have antimicrobial activity, which also orchestrate chemotaxis and activation of effector immune cells, including immature dendritic cells. This review analyzes the biological meaning of the immunomodulatory and immunoenhancing features of defensins and their use for the development of novel vaccines to combat cancer and clinically relevant diseases. C1 NIA, Immunol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Biragyn, A (reprint author), NIA, Immunol Lab, Gerontol Res Ctr, NIH, Rm 4B09,5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM biragyna@grc.nia.nih.gov NR 89 TC 27 Z9 31 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2037 J9 CURR PROTEIN PEPT SC JI Curr. Protein Pept. Sci. PD FEB PY 2005 VL 6 IS 1 BP 53 EP 60 DI 10.2174/1389203053027601 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 893KT UT WOS:000226718500006 PM 15638768 ER PT J AU Fan, T Hagan, JP Kozlov, SV Stewart, CL Muegge, K AF Fan, T Hagan, JP Kozlov, SV Stewart, CL Muegge, K TI Lsh controls silencing of the imprinted Cdkn1c gene SO DEVELOPMENT LA English DT Article DE chromatin structure; DNA methylation; gene imprinting; Lsh ID DEPENDENT KINASE INHIBITOR; TUMOR-SUPPRESSOR GENE; DNA METHYLATION; EPIGENETIC REGULATION; FAMILY-MEMBER; SNF2 FAMILY; MOUSE; P57(KIP2); MECHANISMS; EXPRESSION AB Epigenetic regulation, such as DNA methylation plays an important role in the control of imprinting. Lsh, a member of the SNF2 family of chromatin remodeling proteins, controls DNA methylation in mice. To investigate whether Lsh affects imprinting, we examined CpG methylation and allelic expression of individual genes in Lsh-deficient embryos. We report here that loss of Lsh specifically alters expression of the Cdkn1c gene (also known as p57((Kip2))) but does not interfere with maintenance of imprints at the H19, Igf2, Igf2r, Zac1 and Meg9 genes. The reactivation of the silenced paternal Cdkn1c allele correlates closely with a loss of CpG methylation at the 5' DMR at the Cdkn1c promoter, whereas KvDMR1 and DMRs of other imprinted genes were not significantly changed. Chromatin immunoprecipitations demonstrate a direct association of Lsh with the 5' DMR at the Cdkn1c promoter, but not with Kv DMR1 or other imprinted loci. These data suggest that methylation of the 5' DMR plays an important role in the imprinting of the Cdkn1c gene. Furthermore, it suggests that Lsh is not required for maintenance of imprinting marks in general, but is only crucial for imprinting at distinct genomic sites. C1 NCI, SAIC Frederick, Basic Res Program, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. NCI, Canc & Dev Biol Lab, Ft Detrick, MD 21702 USA. RP Muegge, K (reprint author), NCI, SAIC Frederick, Basic Res Program, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. EM muegge@ncifcrf.gov OI Hagan, John/0000-0003-0295-4898 FU PHS HHS [N01-C0-12400] NR 44 TC 45 Z9 47 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 FEB PY 2005 VL 132 IS 4 BP 635 EP 644 DI 10.1242/dev.01612 PG 10 WC Developmental Biology SC Developmental Biology GA 903LJ UT WOS:000227427100002 PM 15647320 ER PT J AU Smith, GH AF Smith, GH TI Label-retaining epithelial cells in mouse mammary gland divide asymmetrically and retain their template DNA strands SO DEVELOPMENT LA English DT Article DE mammary; stem cell; asymmetric division; autoradiography ID STEM-CELLS; POPULATION; CARCINOGENESIS; SEGREGATION; EXPRESSION; CYCLE; UNIT; SKIN AB It has been postulated that the stem cells of somatic tissues protect themselves from mutation and cancer risk by selective segregation of their template DNA strands. Self-renewing mammary epithelial stem cells that were originated during allometric growth of the mammary ducts in pubertal females were labeled using [H-3]-thymidine ((3)HTdR). After a prolonged chase during which much of the branching duct morphogenesis was completed, (3)HTdRlabel retaining epithelial cells (LREC) were detected among the epithelium of the maturing glands. Labeling newly synthesized DNA in these glands with a different marker, 5-bromodeoxyuridine (5BrdU), resulted in the appearance of doubly labeled nuclei in a large percentage of the LREC. By contrast, label-retaining cells within the stroma did not incorporate 5BrdU during the pulse, indicating that they were not traversing the cell cycle. Upon chase, the second label (5BrdU) was distributed from the double-labeled LREC to unlabeled mammary cells while (3)HTdR was retained. These results demonstrate that mammary LREC selectively retain their (3)HTdR-labeled template DNA strands and pass newly synthesized 5BrdU-Iabeled DNA to their progeny during asymmetric divisions. Similar results were obtained in mammary transplants containing selfrenewing, lacZ-positive epithelial cells suggesting that cells capable of expansive self-renewal may repopulate new mammary stem cell niches during the allometric growth of new mammary ducts. C1 NCI, Canc Res Ctr, Lab Mammary Gland Biol & Tumorigenesis, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, Canc Res Ctr, Lab Mammary Gland Biol & Tumorigenesis, Bethesda, MD 20892 USA. EM gs4d@nih.gov NR 20 TC 205 Z9 218 U1 0 U2 8 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 FEB PY 2005 VL 132 IS 4 BP 681 EP 687 DI 10.1242/dev.01609 PG 7 WC Developmental Biology SC Developmental Biology GA 903LJ UT WOS:000227427100006 PM 15647322 ER PT J AU Odenwald, WF AF Odenwald, WF TI Changing fates on the road to neuronal diversity SO DEVELOPMENTAL CELL LA English DT Editorial Material ID DEVELOPING NERVOUS-SYSTEM; CELL-FATE; DROSOPHILA; ORDER; BIRTH AB One of the longstanding goals of neurobiologists is to describe, in molecular terms, how a neural progenitor cell (NPC) can generate an ordered series of uniquely fated neurons and glia. Recent studies reveal that many, or all, neural-subtype identities can be linked to sequentially changing regulatory programs within NPCs. Two new studies, in this issue of Developmental Cell, provide novel insights into the molecular details of how Drosophila NPCs transition from one offspring identity program to the next. C1 NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA. RP Odenwald, WF (reprint author), NINDS, Neural Cell Fate Determinants Sect, NIH, 900 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD FEB PY 2005 VL 8 IS 2 BP 133 EP 134 DI 10.1016/j.devcel.2005.01.005 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 895PN UT WOS:000226875500001 PM 15691753 ER PT J AU Stern, SE Williams, K Ferrannini, E DeFronzo, RA Bogardus, C Stern, MP AF Stern, SE Williams, K Ferrannini, E DeFronzo, RA Bogardus, C Stern, MP TI Identification of individuals with insulin resistance using routine clinical measurements SO DIABETES LA English DT Article ID PIMA-INDIANS; NORMAL-DISTRIBUTIONS; CARDIOVASCULAR RISK; GLUCOSE; SENSITIVITY; MODEL; ATHEROSCLEROSIS; PARENTS; DISEASE; MIXTURE AB Insulin resistance is a treatable precursor of diabetes and potentially of cardiovascular disease as well. To identify insulin-resistant patients, we developed decision rules from measurements of obesity, fasting glucose, insulin, lipids, and blood pressure and family history in 2,321 (2,138 nondiabetic) individuals studied with the euglycemic insulin clamp technique at 17 European sites; San Antonio, Texas; and the Pima Indian reservation. The distribution of whole-body glucose disposal appeared to be bimodal, with an optimal insulin resistance cutoff of <28 mumol/min (.) kg lean body mass. Using recursive partitioning, we developed three types of classification tree models: the first, based on clinical measurements and all available laboratory determinations, had an area under the receiver operator characteristic curve (aRoC) of 90.0% and generated a simple decision rule: diagnose insulin resistance if any of the following conditions are met: BMI>28.9 kg/m(2), homeostasis model assessment of insulin resistance (HOMA-IR) >4.65, or BMI > 27.5 kg/m(2) and HOMA-IR > 3.60. The fasting serum insulin concentrations corresponding to these HOMA-IR cut points were 20.7 and 16.3 muU/ml, respectively. This rule had a sensitivity and specificity of 84.9 and 78.7%, respectively. The second model, which included clinical measurements but no laboratory determinations, had an aROC of 85.0% and generated a decision rule that had a sensitivity and specificity of 78.7 and 79.6%, respectively. The third model, which included clinical measurements and lipid measurements but not insulin (and thus excluded HOMA-IR as well), had a similar aROC (85.1%), sensitivity (81.3%), and specificity (76.3%). Thus, insulin-resistant individuals can be identified using simple decision rules that can be tailored to specific needs. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. Australian Natl Univ, Sch Finance & Appl Stat, Canberra, ACT, Australia. CNR, Inst Clin Physiol, I-56100 Pisa, Italy. Univ Texas, Hlth Sci Ctr, Div Diabet, Dept Med, San Antonio, TX 78285 USA. NIDDK, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ USA. RP Stern, MP (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Epidemiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM stern@uthscsa.edu NR 28 TC 164 Z9 176 U1 2 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2005 VL 54 IS 2 BP 333 EP 339 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 891XD UT WOS:000226613400005 PM 15677489 ER PT J AU Kanaya, AM Fyr, CLW de Reheneire, N Shorr, RI Schwartz, AV Goodpaster, BH Newman, AB Harris, T Barrett-Connor, E AF Kanaya, AM Fyr, CLW de Reheneire, N Shorr, RI Schwartz, AV Goodpaster, BH Newman, AB Harris, T Barrett-Connor, E TI Predicting the development of diabetes in older adults - The derivation and validation of a prediction rule SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; INSULIN-RESISTANCE; LIFE-STYLE; HIGH-RISK; MELLITUS; PREVENTION; DIAGNOSIS; CLASSIFICATION; WOMEN AB OBJECTIVE - To create a simple prediction rule that could perforin as well as the 2-h postchallenge plasma glucose (PCPG) test to predict those at risk for diabetes. We created a 0 prediction rule in one sample and prospectively validated it for incident diabetes in a separate cohort. RESEARCH DESIGN AND METHODS - A cross-sectional analysis with data from the Rancho Bernardo Study (age 67 +/- 11 years) to derive I rule predicting abnormal PCPG greater than or equal to140 mg/dl, using demographic, clinical, and laboratory data of nondiabetic participants with fasting plasma glucose (FPG) <126 mg/dl. Data from the Health, Aging and Body Composition Study (age 74 +/- 3 years) were used to prospectively validate this rule for incident diabetes and compare it with the predictive ability of the PCPG test. RESULTS - Of 1,549 RBS participants, 514 (33%) had PCPG greater than or equal to140 mg/dl. Female sex, age, triglycerides, and FPG were most significantly associated With abnormal PCPG. Based on standardized beta-coefficients, we allotted I point for female sex, triglycerides greater than or equal to150 mg/dl, or FPG 95-104 mg/dl. Age greater than or equal to70 years or FPG 105-115 mg/dl were given 2 points, and FPG 116-125 mg/dl received 3 points. In the validation cohort., this simple prediction rule was as good as the 2-h PCPG Lest for predicting incident diabetes (C-statistic: 0.71 for both). CONCLUSIONS - Advanced age, female sex, FPG, and triglycerides were able to predict adults at risk for diabetes equally well as the 2-h PCPG test. Using this rule, clinicians may better identify, older persons who Should receive intensive lifestyle intervention to prevent type 2 diabetes. Diabetes Care 28:404-408, 2005. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. RP Kanaya, AM (reprint author), 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. EM alkak@itsa.ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [5R01 AG07181, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, P30-AG15272]; NIAMS NIH HHS [5 K12 AR47659]; NIDDK NIH HHS [5R01 DK31801] NR 21 TC 67 Z9 70 U1 0 U2 4 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 FEB PY 2005 VL 28 IS 2 BP 404 EP 408 DI 10.2337/diacare.28.2.404 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 891WY UT WOS:000226612900028 PM 15677800 ER PT J AU Stumvoll, M Tataranni, PA Bogardus, C AF Stumvoll, M Tataranni, PA Bogardus, C TI The hyperbolic law - a 25-year perspective SO DIABETOLOGIA LA English DT Editorial Material ID BETA-CELL FUNCTION; GLUCOSE ALLOSTASIS; INSULIN; TOLERANCE C1 Univ Leipzig, Dept Med 3, D-04301 Leipzig, Germany. NIDDKD, Obes & Diabet Clin Res Sect, US Dept HHS, NIH, Phoenix, AZ USA. RP Stumvoll, M (reprint author), Univ Leipzig, Dept Med 3, Philipp Rosenthal Str 27, D-04301 Leipzig, Germany. EM michael.stumvoll@medizin.uni-leipzig.de NR 12 TC 17 Z9 17 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 2005 VL 48 IS 2 BP 207 EP 209 DI 10.1007/s00125-004-1657-3 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 903SW UT WOS:000227446900001 PM 15666135 ER PT J AU Snijder, MB Visser, M Dekker, JM Goodpaster, BH Harris, TB Kritchevsky, SB De Rekeneire, N Kanaya, AM Newman, AB Tylavsky, FA Seidell, JC AF Snijder, MB Visser, M Dekker, JM Goodpaster, BH Harris, TB Kritchevsky, SB De Rekeneire, N Kanaya, AM Newman, AB Tylavsky, FA Seidell, JC CA Hlth ABC Study TI Low subcutaneous thigh fat is a risk factor for unfavourable glucose and lipid levels, independently of high abdominal fat. The Health ABC Study SO DIABETOLOGIA LA English DT Article DE subcutaneous fat; thigh; visceral fat; glucose; lipids; waist circumference; hip circumference; elderly; ethnicity ID TYPE-2 DIABETES-MELLITUS; VISCERAL ADIPOSE-TISSUE; X-RAY ABSORPTIOMETRY; LEG MUSCLE MASS; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; HIP CIRCUMFERENCES; OPPOSITE ASSOCIATIONS; COMPUTED-TOMOGRAPHY; REGIONAL ADIPOSITY AB Aims: We investigated whether low subcutaneous thigh fat is an independent risk factor for unfavourable glucose and lipid levels, and whether these associations differ between sexes, and between white and black adults. Our secondary aim was to investigate which body composition characteristics ( lean tissue, fat tissue) are reflected by anthropometric measures ( waist and thigh circumference). Methods: Anthropometric measurements and computed tomography of the abdomen and of the thigh were performed for all participants of the Health, Aging and Body Composition Study, who were aged 70 - 79 years. Fasting glucose, triglycerides and HDL-cholesterol, and 2- h postload glucose were determined. Results: After excluding those already diagnosed with diabetes or dyslipidaemia, we analysed data from 2,106 participants. After adjustment for abdominal subcutaneous and visceral fat, and intermuscular thigh fat, larger thigh subcutaneous fat area was statistically significantly associated with lower ln- transformed triglycerides [ standardised beta ( 95% CI) - 0.12 (- 0.20 to - 0.04) in men and - 0.13 (- 0.21 to - 0.05) in women] and higher ln- HDL- cholesterol [ 0.10 ( 0.02 to 0.19) and 0.09 ( 0.01 to 0.18), respectively]. The associations with lower glucose levels were strong in men [- 0.11 (- 0.20 to - 0.02) for fasting and - 0.14 (- 0.23 to - 0.05) for postload glucose], but not statistically significant in women [- 0.02 (- 0.10 to 0.07) and - 0.04 (- 0.13 to 0.05), respectively]. There were no differences in the associations between white and black persons. Waist circumference was more strongly associated with abdominal subcutaneous fat, and this association became stronger with increasing BMI, whereas the association with visceral fat became weaker. Thigh circumference was equally dependent on thigh fat and thigh muscle in men, whereas in women the fat component was the main contributor. Conclusion: Larger subcutaneous thigh fat is independently associated with more favourable glucose ( in men) and lipid levels ( in both sexes) after accounting for abdominal fat depots, which are associated with unfavourable glucose and lipid levels. Anthropometric measures reflect different fat depots at different levels of BMI at the abdomen, and reflect both fat and lean tissue at the thigh. These results emphasise the importance of accurate measures of regional body composition when investigating potential health risks. C1 VU Univ Med Ctr, Inst Res Extramural Med, NL-1081 BT Amsterdam, Netherlands. Vrije Univ Amsterdam, Fac Earth & Life Sci, Inst Hlth Sci, Amsterdam, Netherlands. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC 27157 USA. Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94115 USA. Univ Tennessee, Memphis Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38105 USA. RP Snijder, MB (reprint author), VU Univ Med Ctr, Inst Res Extramural Med, Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. EM marieke.snijder@falw.vu.nl RI seidell, jacob/N-7427-2013; Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2106, N01-AG-6-2101, N01-AG-6-2103] NR 40 TC 171 Z9 171 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 2005 VL 48 IS 2 BP 301 EP 308 DI 10.1007/s00125-004-1637-7 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 903SW UT WOS:000227446900015 PM 15660262 ER PT J AU Ng, CL Waterman, D Koonin, EV Antson, AA Ortiz-Lombardia, M AF Ng, CL Waterman, D Koonin, EV Antson, AA Ortiz-Lombardia, M TI Crystal structure of Mil (Mth680): internal duplication and similarity between the Imp4/Brix domain and the anticodon-binding domain of class IIa aminoacylt-RNA synthetases SO EMBO REPORTS LA English DT Article DE Imp4 domain; Brix domain; RNA binding; Methanothermobacter; crystal structure ID RIBOSOMAL-RNA; SACCHAROMYCES-CEREVISIAE; PROTEIN; BIOGENESIS; RIBONUCLEOPROTEIN; SUBUNIT; IMP4P; REFINEMENT; PROCESSOME; COMPONENTS AB Proteins of the Imp4/Brix superfamily are involved in ribosomal RNA processing, an essential function in all cells. We report the first structure of an Imp4/Brix superfamily protein, the Mil (for Methanothermobacter thermautotrophicus Imp4-like) protein (gene product Mth680), from the archaeon M. thermautotrophicus. The amino- and carboxy-terminal halves of Mil show significant structural similarity to one another, suggesting an origin by means of an ancestral duplication. Both halves show the same fold as the anticodon-binding domain of class IIa aminoacyl-tRNA synthetases, with greater conservation seen in the N-terminal half. This structural similarity, together with the charge distribution in Mil, suggests that Imp4/Brix superfamily proteins could bind single-stranded segments of RNA along a concave surface formed by the N-terminal half of their beta-sheet and a central alpha-helix. The crystal structure of Mil is incompatible with the presence, in the Imp4/Brix domain, of a helix-turn-helix motif that was proposed to comprise the RNA-binding moiety of the Imp4/Brix proteins. C1 Univ York, Dept Chem, York Struct Biol Lab, York YO10 5YW, N Yorkshire, England. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Ortiz-Lombardia, M (reprint author), Univ York, Dept Chem, York Struct Biol Lab, York YO10 5YW, N Yorkshire, England. EM mol1@york.ac.uk RI Ng, Chyan Leong/E-9689-2014; Antson, Alfred/N-2551-2016 OI Ng, Chyan Leong/0000-0001-8590-7418; Antson, Alfred/0000-0002-4533-3816 NR 34 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD FEB PY 2005 VL 6 IS 2 BP 140 EP 146 DI 10.1038/sj.embor.7400328 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 897CR UT WOS:000226982100010 PM 15654320 ER PT J AU Wang, WG Martindale, JL Yang, XL Chrest, FJ Gorospe, M AF Wang, WG Martindale, JL Yang, XL Chrest, FJ Gorospe, M TI Increased stability of the p16 mRNA with replicative senescence SO EMBO REPORTS LA English DT Article DE INK4a; mRNA turnover; AUF1; post-transcriptional regulation ID AU-RICH ELEMENT; GENE-EXPRESSION; BINDING-PROTEINS; IN-VIVO; HNRNP D; HUR; FIBROBLASTS; TURNOVER; ISOFORMS; DECAY AB Expression of p16(INK4a) is elevated during ageing and replicative senescence. Here, we report the presence of an instability determinant within the 3'-untranslated region (UTR) of the p16 messenger RNA in WI-38 human diploid fibroblasts. The p16 3'UTR was found to be a specific target of AUF1, an RNA-binding protein implicated in promoting mRNA decay. Both AUF1 levels and AUF1-p16 mRNA associations were strikingly more abundant in early-passage than late-passage fibroblast cultures. Moreover, short interfering RNA-based reductions in AUF1 levels increased the stability of p16 3'UTR-containing transcripts, elevated the expression of p16 and accentuated the senescence phenotype. Together, our findings show that p16 mRNA turnover decreases during replicative senescence and that the instability-conferring region is located within the 3'UTR of p16, as well as identifying AUF1 as a critical mediator of these regulatory events. C1 NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA. NIA, Res Resources Branch, IRP, NIH, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov FU NIA NIH HHS [Z01 AG000511-08] NR 31 TC 57 Z9 62 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD FEB PY 2005 VL 6 IS 2 BP 158 EP 164 DI 10.1038/sj.embor.7400346 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 897CR UT WOS:000226982100013 PM 15678155 ER PT J AU Moon, H Filippova, G Loukinov, D Pugacheva, E Chen, Q Smith, ST Munhall, A Grewe, B Bartkuhn, M Arnold, R Burke, LJ Renkawitz-Pohl, R Ohlsson, R Zhou, JM Renkawitz, R Lobanenkov, V AF Moon, H Filippova, G Loukinov, D Pugacheva, E Chen, Q Smith, ST Munhall, A Grewe, B Bartkuhn, M Arnold, R Burke, LJ Renkawitz-Pohl, R Ohlsson, R Zhou, JM Renkawitz, R Lobanenkov, V TI CTCF is conserved from Drosophila to humans and confers enhancer blocking of the Fab-8 insulator SO EMBO REPORTS LA English DT Article DE Drosophila; CTCF; enhancer blocking; Fab-8; abdominal-B ID THYROID-HORMONE RECEPTOR; CHROMATIN DOMAIN BOUNDARY; PROTEIN CTCF; BITHORAX COMPLEX; ERYTHROID-CELLS; CONTROL REGION; PROMOTER; GENE; SILENCER; ELEMENT AB Eukaryotic transcriptional regulation often involves regulatory elements separated from the cognate genes by long distances, whereas appropriately positioned insulator or enhancer-blocking elements shield promoters from illegitimate enhancer action. Four proteins have been identified in Drosophila mediating enhancer blocking - Su(Hw), Zw5, BEAF32 and GAGA factor. In vertebrates, the single protein CTCF, with 11 highly conserved zinc fingers, confers enhancer blocking in all known chromatin insulators. Here, we characterize an orthologous CTCF factor in Drosophila with a similar domain structure, binding site specificity and transcriptional repression activity as in vertebrates. In addition, we demonstrate that one of the insulators (Fab-8) in the Drosophila Abdominal-B locus mediates enhancer blocking by dCTCF. Therefore, the enhancer-blocking protein CTCF and, most probably, the mechanism of enhancer blocking mediated by this remarkably versatile factor are conserved from Drosophila to humans. C1 NIAID, Sect Mol Pathol, Immunopathol Lab, NIH, Rockville, MD 20852 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. Wistar Inst Anat & Biol, Div Mol Genet, Philadelphia, PA 19104 USA. Univ Marburg, Fachbereich Biol Zool Entwicklungsbiol, D-35039 Marburg, Germany. Univ Giessen, Inst Genet, D-35392 Giessen, Germany. Uppsala Univ, Evolut Biol Ctr, Dept Genet & Dev, S-75236 Uppsala, Sweden. RP Renkawitz, R (reprint author), NIAID, Sect Mol Pathol, Immunopathol Lab, NIH, Rockville, MD 20852 USA. EM renkawitz@gen.bio.uni-giessen.de; vlobanenkov@niaid.nih.gov OI Lobanenkov, Victor/0000-0001-6665-3635 NR 32 TC 138 Z9 144 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD FEB PY 2005 VL 6 IS 2 BP 165 EP 170 DI 10.1038/sj.embor.7400334 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 897CR UT WOS:000226982100014 PM 15678159 ER PT J AU Temple, JL Wray, S AF Temple, JL Wray, S TI Bovine serum albumin-estrogen compounds differentially alter gonadotropin-releasing hormone-1 neuronal activity SO ENDOCRINOLOGY LA English DT Article ID BREAST-CANCER CELLS; PROTEIN-KINASE-C; LHRH NEURONS; EXPLANT CULTURES; RECEPTOR-BETA; IN-VITRO; MEMBRANE-RECEPTOR; ESTRADIOL; 17-BETA-ESTRADIOL; BRAIN AB Steroid hormones regulate a host of physiological processes and behaviors. These actions can occur by genomic mechanisms involving gene transcription or by nongenomic mechanisms proposed to involve receptors associated with the plasma membrane. BSA-conjugated steroid hormones have been extensively used to elucidate signal transduction pathways for these hormones. We have previously shown, using calcium imaging, that 17beta-estradiol (E2) significantly increases GnRH-1 neuronal activity. During the course of these experiments, it became apparent that three different BSA-estrogen compounds have been used in a variety of cell types: 17beta-estradiol 6-O-carboxymethyloxime-BSA (E2-6-BSA); 1,3,5(10)-estratrien-3,16alpha, 17beta-triol-6-one 6-O-carboxymethyloxime-BSA (E-6-BSA); and 1,3,5(10)-estratrien-3,17beta-diol 17-hemisuccinate-BSA (E2-17-BSA). The effects of these compounds on GnRH-1 neuronal activity were compared using calcium imaging. E-6-BSA and E2-17-BSA, but not E2-6-BSA, significantly increased all parameters of GnRH-1 neuronal activity. In addition, the effects of these two BSA compounds were reversed by the estrogen receptor antagonist ICI 182,780 but not by inhibition of gene transcription. The effects of E2-17-BSA, but not E-6-BSA were reversed by treatment with pertussis toxin, which blocks G protein-coupled receptors. These data indicate that these compounds cannot be used interchangeably and clearly have different binding properties and/or different effects on target tissues. C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, 36 Convent Dr,MSC 4156,Bldg 35,Room 3A1012, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov OI wray, susan/0000-0001-7670-3915 NR 29 TC 39 Z9 39 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2005 VL 146 IS 2 BP 558 EP 563 DI 10.1210/en.2004-1117 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 887HA UT WOS:000226295300006 PM 15539555 ER PT J AU Goehl, TJ Ramos, KS AF Goehl, TJ Ramos, KS TI Note form the editors - Toxicogenomics SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Louisville, Hlth Sci Ctr, Louisville, KY 40292 USA. RP Goehl, TJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM goehl@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2005 VL 113 IS 2 BP A85 EP A85 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 899TY UT WOS:000227169400002 ER PT J AU Galperin, MY AF Galperin, MY TI Life is not defined just in base pairs SO ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MINIMAL-GENE-SET; GENOME SEQUENCE; BACTERIUM C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 22 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD FEB PY 2005 VL 7 IS 2 BP 149 EP 152 DI 10.1111/j.1462-2920.2005.00774.x PG 4 WC Microbiology SC Microbiology GA 888LX UT WOS:000226376800001 PM 15658982 ER PT J AU Longnecker, MP Klebanoff, MA Dunson, DB Guo, XG Zhen, C Zhou, HB Brock, JW AF Longnecker, MP Klebanoff, MA Dunson, DB Guo, XG Zhen, C Zhou, HB Brock, JW TI Maternal serum level of the DDT metabolite DDE in relation to fetal loss in previous pregnancies SO ENVIRONMENTAL RESEARCH LA English DT Article DE DDT; abortion; spontaneous; epidemiology; reproductive history ID POLYCHLORINATED-BIPHENYLS PCBS; DICHLORODIPHENYL DICHLOROETHENE DDE; SPONTANEOUS-ABORTION; CHLORINATED HYDROCARBONS; MALARIA CONTROL; HUMAN-MILK; WOMEN; INSECTICIDES; ASSOCIATION; PESTICIDES AB Use of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) continues in about 25 countries. This use has been justified partly by the belief that it has no adverse consequences on human health. Evidence has been increasing, however, for adverse reproductive effects of DDT, but additional data are needed. Pregnant women who enrolled in the Collaborative Perinatal Project (United States, 1959-1965) were asked about their previous pregnancy history; blood samples were drawn and the serum frozen. In 1997-1999, the sera of 1717 of these women who had previous pregnancies were analyzed for 1,1-dichloro-2,2-bis(p-chloropbenyl)ethylene (DDE), the major breakdown product of DDT. The odds of previous fetal loss was examined in relation to DDE level in logistic regression models. Compared with women whose DDE level was < 15 mug/L, the adjusted odds ratios of fetal loss according to category of DDE were as follows: 15-29 mug/L, 1.1; 30-44 mug/L, 1.4; 45-59 mug/L, 1.6; and 60 + mug/L, 1.2. The adjusted odds ratio per 60 mug/L increase was 1.4 (95% confidence interval 1.1-1.6). The results were consistent with an adverse effect of DDE on fetal loss, but were inconclusive owing to the possibility that previous pregnancies ending in fetal loss decreased serum DDE levels less than did those carried to term. Published by Elsevier Inc. C1 NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Natl Inst Child Hlth & Human Dev, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, NIH, Rockville, MD USA. NIEHS, Biostat Branch, Res Triangle Pk, NC USA. Analyt Sci Inc, Stat & Publ Hlth Res Div, Durham, NC USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, POB 12233 MD A3-05, Res Triangle Pk, NC 27709 USA. EM longnecker@niehs.nih.gov OI Longnecker, Matthew/0000-0001-6073-5322 NR 44 TC 48 Z9 51 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD FEB PY 2005 VL 97 IS 2 BP 127 EP 133 DI 10.1016/S0013-9351(03)00108-7 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 879EV UT WOS:000225700100002 PM 15533328 ER PT J AU Mendola, P Robinson, LK Buck, GM Druschel, CM Fitzgerald, EF Sever, LE Vena, JE AF Mendola, P Robinson, LK Buck, GM Druschel, CM Fitzgerald, EF Sever, LE Vena, JE TI Birth defects risk associated with maternal sport fish consumption: potential effect modification by sex of offspring SO ENVIRONMENTAL RESEARCH LA English DT Article DE birth defects; effect modifiers (epidemiology); endocrine system; environmental pollutants; pregnancy ID BODY BURDEN LEVELS; GREAT-LAKES FISH; CONGENITAL-MALFORMATIONS; INFANTS BORN; BREAST-MILK; EXPOSURE; WOMEN; HYPOSPADIAS; ANOMALIES; HEALTH AB Contaminated sport fish consumption may result in exposure to various reproductive and developmental toxicants, including pesticides and other suspected endocrine disruptors. We investigated the relation between maternal sport fish meals and risk of major birth defects among infants born to members of the New York State (NYS) Angler Cohort between 1986 and 1991 (n = 2237 births). Birth defects (n = 125 cases) were ascertained from both newborn medical records and the NYS Congenital Malformations Registry. For sport fish meals eaten during pregnancy, the odds ratio (OR) for all major malformations combined was slightly elevated for less than or equal to1 meal/month (OR=1.26, 95% confidence interval (Cl): 0,84, 1.89) and greater than or equal to2 meals/month (OR=1.51, CI=0.74, 3.09), with no meals during pregnancy as the reference category. Higher ORs were consistently observed among male offspring compared with females. For greater than or equal to 2 meals/month, the risk for males was significantly elevated (males: OR = 3.01, CI: 1.2, 7.5; females: OR = 0.73, CI: 0.2, 2.4). Exposure during pregnancy and effect modification by infants sex could be important considerations for future studies of birth outcomes associated with endocrine disruptors. Published by Elsevier Inc. C1 US EPA, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Univ Buffalo, Dept Pediat, Buffalo, NY USA. NICHHD, Div Epidemiol Stat & Prevent, Rockville, MD USA. New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA. New York City Dept Hlth, Bur Environm & Occupat Hlth, Albany, NY USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. Univ Buffalo, Dept Social & Prevent Med, Buffalo, NY USA. RP Mendola, P (reprint author), US EPA, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. EM mendola.pauline@epa.gov RI Fitzgerald, Edward/F-4087-2010; OI Mendola, Pauline/0000-0001-5330-2844; Buck Louis, Germaine/0000-0002-1774-4490 NR 26 TC 12 Z9 13 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD FEB PY 2005 VL 97 IS 2 BP 134 EP 141 DI 10.1016/j.envres.2003.10.008 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 879EV UT WOS:000225700100003 PM 15533329 ER PT J AU Senn, KM McGuinness, BM Buck, GM Vena, JE Anderson, S Rogers, BT AF Senn, KM McGuinness, BM Buck, GM Vena, JE Anderson, S Rogers, BT TI Longitudinal study of babies born to mothers enrolled in a preconception prospective pregnancy study: study design and methodology, New York State Angler Cohort Study SO ENVIRONMENTAL RESEARCH LA English DT Article DE child health; cohort study; development; halogenated aromatic hydrocarbons; neurodevelopment; organochlorine pesticides; polychlorinated biphenyls ID POLYCHLORINATED-BIPHENYLS; FUNCTIONAL INDEPENDENCE; CHILDRENS HEALTH; GREAT-LAKES; EXPOSURE; FISH; NEUROTOXICITY; CONSUMPTION; CONGENERS; GROWTH AB Persistent environmental chemicals such as organochlorine pesticides and polychlorinated biphenyls (PCBs) have been associated with alterations in fetal development and child health including subtle differences in developmental status. Previous prospective studies have ascertained prenatal or postnatal exposures but none have been designed to assess exposures at critical windows including preconception. To address this gap, we followed infants born to mothers recruited prior to conception in the New York State Prospective Pregnancy Study to assess feasibility issues including acceptability of a relatively invasive study protocol during the child's first 2 years of life. Longitudinal measurements on health, development, and growth were obtained from 53 live-born infants; 49 families consented to standardized in-home neurodevelopmental and psychosocial evaluations at 12 and 24 months of age. Nineteen participating parents consented to the collection of blood from infants for lead thyroid and PCB levels. Despite the intensive data collection protocol over 2 years coupled with the mothers having completed an intensive prospective pregnancy protocol, we found parents readily open to continued participation in a longitudinal study involving their children. Suggestions for conducting in-home assessments include use of a consistent contact nurse, comprehensive parent-friendly developmental assessment tools with some interim assessment by parent report, and periodic team visits. Published by Elsevier Inc. C1 Womens & Childrens Hosp, Robert Warner Rehabil Ctr, Div Dev Pediat & Rehabil, Buffalo, NY 14209 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. NICHHD, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA. Oregon Hlth & Sci Univ, Child Dev & Rehabil Ctr, Portland, OR 97201 USA. RP Senn, KM (reprint author), Womens & Childrens Hosp, Robert Warner Rehabil Ctr, Div Dev Pediat & Rehabil, Buffalo, NY 14209 USA. EM Ksenn@KaleidaHealth.Org OI Buck Louis, Germaine/0000-0002-1774-4490 NR 39 TC 9 Z9 10 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 0013-9351 J9 ENVIRON RES JI Environ. Res. PD FEB PY 2005 VL 97 IS 2 BP 163 EP 169 DI 10.1016/j.envres.2004.08.001 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 879EV UT WOS:000225700100006 PM 15533332 ER PT J AU Vupputuri, S Longnecker, MP Daniels, JL Guo, XG Sandler, DP AF Vupputuri, S Longnecker, MP Daniels, JL Guo, XG Sandler, DP TI Blood mercury level and blood pressure among US women: results from the National Health and Nutrition Examination Survey 1999-2000 SO ENVIRONMENTAL RESEARCH LA English DT Article DE blood pressure; mercury; fatty acids; women; cross-sectional studies ID CORONARY-HEART-DISEASE; METHYLMERCURY EXPOSURE; MYOCARDIAL-INFARCTION; DOCOSAHEXAENOIC ACID; FISH CONSUMPTION; ADIPOSE-TISSUE; FINNISH MEN; RISK; POPULATION; DEATH AB Exposure to mercury has been linked to elevations in blood pressure (BP), though few data are available. We examined the cross-sectional relationship between blood mercury concentration and BP in a representative US sample of 1240 women, aged 16-49 years, from the National Health and Nutrition Examination Survey 1999-2000. We found no association overall between mercury and BP in multivariate models. We stratified our data by dietary fish intake (presumably reflecting the consumption of long-chain n-3 fatty acids that may reduce BP) resulting in 759 fish consumers and 481 non-fish consumers. We found that for each 1.3 mug/L (interquartile distance) increase in mercury, systolic BP significantly increased by 1.83 mm Hg (95% CI: 0.36, 3.30) among non-fish consumers. A similar pattern was seen for diastolic BP, although it was non-significant. While an adverse effect of mercury exposure at background levels on BP was not present overall, an adverse association was present among non-fish-consuming young and middle-aged women. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Cardiovasc Dis Program,Bank Amer Ctr, Chapel Hill, NC 27514 USA. NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC USA. Constella Grp Inc, Stat & Publ Hlth Res Div, Durham, NC USA. RP Vupputuri, S (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Cardiovasc Dis Program,Bank Amer Ctr, 137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA. EM suma@email.unc.edu OI Longnecker, Matthew/0000-0001-6073-5322; Sandler, Dale/0000-0002-6776-0018 NR 33 TC 61 Z9 61 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD FEB PY 2005 VL 97 IS 2 BP 195 EP 200 DI 10.1016/j.envres.2004.05.001 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 879EV UT WOS:000225700100009 PM 15533335 ER PT J AU Whitcomb, BW Schisterman, EF Buck, GM Weiner, JM Greizerstein, H Kostyniak, PJ AF Whitcomb, BW Schisterman, EF Buck, GM Weiner, JM Greizerstein, H Kostyniak, PJ TI Relative concentrations of organochlorines in adipose tissue and serum among reproductive age women SO ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE adipose tissue; endometriosis; limits of detection; organochlorine pesticides; polychlorinated biphenyls ID POLYCHLORINATED BIPHENYL CONGENERS; BREAST-CANCER RISK; AROMATIC-HYDROCARBONS; VIETNAM VETERANS; PCB CONGENERS; NEW-YORK; ENDOMETRIOSIS; EXPOSURE; PESTICIDES; DIOXINS AB Much of the available literature focusing on organochlorine exposure and human health effects has relied upon serum for quantifying exposure despite adipose tissue being the purported "gold standard". The accuracy of exposure status is dependent upon serum being a valid and reliable proxy for adipose tissue regardless of compound under study and served as the impetus for study. Serum and omentum fat concentrations for 62 polychlorinated biphenyls (PCBs) and 7 organochlorine pesticides (OCPs) were determined using gas chromatography with electron capture and compared to assess their relative abundance and correlation among 15 women aged 18-40 years undergoing laparoscopy. The relation between concentration in serum and fat was determined by linear regression. Of the 20 organochlorines (OCs) (29%) present in both serum and fat samples, moderate linear correlations (r > 0.6) were observed between lipid-adjusted serum and fat concentrations for PCBs #138, 153, 180, 188, 194, 206, and DDE. Forty-nine OCs were present in adipose samples but measured below the LOD in serum samples. Our findings underscore the potential for discrepant human health results associated with OC exposure on the basis of medium used for quantification purposes, especially for less ubiquitous compounds or when study samples include individuals with relatively low exposures. These data support earlier findings and argue for concerted methodological work aimed at developing standardized laboratory methods for epidemiologic studies. (C) 2004 Elsevier B.V. All rights reserved. C1 NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. SUNY Buffalo, Sch Med & Biomed Sci, Dept Social Med, Buffalo, NY 14214 USA. SUNY Buffalo, Sch Med & Biomed Sci, Dept Prevent Med, Buffalo, NY 14214 USA. RP Schisterman, EF (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd, Rockville, MD 20852 USA. EM schistee@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X; Buck Louis, Germaine/0000-0002-1774-4490 NR 56 TC 24 Z9 24 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1382-6689 EI 1872-7077 J9 ENVIRON TOXICOL PHAR JI Environ. Toxicol. Pharmacol. PD FEB PY 2005 VL 19 IS 2 BP 203 EP 213 DI 10.1016/j.etap.2004.04.009 PG 11 WC Environmental Sciences; Pharmacology & Pharmacy; Toxicology SC Environmental Sciences & Ecology; Pharmacology & Pharmacy; Toxicology GA 892IC UT WOS:000226642800002 PM 21783478 ER PT J AU Quimby, BB Arnaoutov, A Dasso, M AF Quimby, BB Arnaoutov, A Dasso, M TI Ran GTPase regulates Mad2 localization to the nuclear pore complex SO EUKARYOTIC CELL LA English DT Article ID CELL-CYCLE PROGRESSION; SPINDLE CHECKPOINT; BINDING PROTEIN; BUDDING YEAST; IN-VIVO; TRANSPORT; RAN/TC4; NTF2 AB In yeast and mammalian cells, the spindle assembly checkpoint proteins Mad1p and Mad2p localize to the nuclear pore complex (NPC) during interphase. Deletion of MAD1 or MAD2 did not affect steady-state nucleocytoplasmic distribution of a classical nuclear localization signal-containing reporter, a nuclear export signal-containing reporter, or Ran localization. We utilized cells with conditional mutations in the yeast Ran GTPase pathway to examine the relationship between Ran and targeting of checkpoint regulators to the NPC. Mutations that disrupt the concentration of Ran in the nucleus displaced Mad2p but not Mad1p from the NPC. The displacement of Mad2p in M-phase cells was correlated with activation of the spindle checkpoint. Our observations demonstrate that Mad2p localization at NPCs is sensitive to nuclear levels of Ran and suggest that release of Mad2p from NPCs is closely linked with spindle assembly checkpoint activation in yeast. This is the first evidence indicating that Ran affects the localization of Mad2p to the NPC. C1 NICHD, LGRD, NIH, Bethesda, MD 20892 USA. RP Quimby, BB (reprint author), NICHD, LGRD, NIH, Bldg 18T,Rm 106,18 Lib Dr, Bethesda, MD 20892 USA. EM quimbyb@mail.nih.gov OI Dasso, Mary/0000-0002-5410-1371 FU Intramural NIH HHS [Z01 HD008740-06] NR 22 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD FEB PY 2005 VL 4 IS 2 BP 274 EP 280 DI 10.1128/EC.4.2.274-280.2005 PG 7 WC Microbiology; Mycology SC Microbiology; Mycology GA 901BK UT WOS:000227257800006 PM 15701789 ER PT J AU Song, YT Wu, YX Jung, GM Tutar, Y Eisenberg, E Greene, LE Masison, DC AF Song, YT Wu, YX Jung, GM Tutar, Y Eisenberg, E Greene, LE Masison, DC TI Role for Hsp70 chaperone in Saccharomyces cerevisiae prion seed replication SO EUKARYOTIC CELL LA English DT Article ID YEAST PRION; PSI+ PRION; GUANIDINE-HYDROCHLORIDE; PROTEIN HSP104; FUSION PROTEIN; GENE DELETION; PROPAGATION; URE3; SUP35; TRANSLATION AB The Saccharomyces cerevisiae [PSI+] prion is a misfolded form of Sup35p that propagates as self-replicating cytoplasmic aggregates. Replication is believed to occur through breakage of transmissible [PSI+] prion particles, or seeds, into more numerous pieces. In [PSI+] cells, large Sup35p aggregates are formed by coalescence of smaller sodium dodecyl sulfate-insoluble polymers. It is uncertain if polymers or higher-order aggregates or both act as prion seeds. A mutant Hsp70 chaperone, Ssa1-21p, reduces the number of transmissible [PSI+] seeds per cell by 10-fold but the overall amount of aggregated Sup35p by only two- to threefold. This discrepancy could be explained if, in SSA1-21 cells, [PSI+] seeds are larger or more of the aggregated Sup35p does not function as a seed. To visualize differences in aggregate size, we constructed a Sup35-green fluorescent protein (GFP) fusion (NGMC) that has normal Sup35p function and can propagate like [PSI+]. Unlike GFP fusions lacking Sup35p's essential C-terminal domain, NGMC did not form fluorescent foci in log-phase [PSI+] cells. However, using fluorescence recovery after photobleaching and size fractionation techniques, we find evidence that NGMC is aggregated in these cells. Furthermore, the aggregates were larger in SSA1-21 cells, but the size of NGMC polymers was unchanged. Possibly, NGMC aggregates are bigger in SSA1-21 cells because they contain more polymers. Our data suggest that Ssa1-21p interferes with disruption of large Sup35p aggregates, which lack or have limited capacity to function as seed, into polymers that function more efficiently as [PSI+] seeds. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Masison, DC (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM masisond@helix.nih.gov NR 52 TC 72 Z9 79 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD FEB PY 2005 VL 4 IS 2 BP 289 EP 297 DI 10.1128/EC.4.2.289-297.2005 PG 9 WC Microbiology; Mycology SC Microbiology; Mycology GA 901BK UT WOS:000227257800008 PM 15701791 ER PT J AU Gannoun-Zaki, L Jost, A Mu, JB Deitsch, KW Wellems, TE AF Gannoun-Zaki, L Jost, A Mu, JB Deitsch, KW Wellems, TE TI A silenced Plasmodium falciparum var promoter can be activated in vivo through spontaneous deletion of a silencing element in the intron SO EUKARYOTIC CELL LA English DT Article ID GENE FAMILY; MALARIA; ERYTHROCYTES; EXPRESSION AB Introns of Plasmodium falciparum var genes act as transcriptional silencing elements that help control antigenic variations. In transfected episomes, intron silencing of a drug-selectable marker under var promoter control is reversed by the spontaneous deletion of key intron regions. The resulting promoter activation does not affect the transcription of chromosomal var genes. C1 NIAID, LMVR, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Dept Immunol & Microbiol, New York, NY USA. RP Wellems, TE (reprint author), NIAID, LMVR, NIH, 12735 Twinbrook Pkwy,Room 3E-10D, Bethesda, MD 20892 USA. EM tew@helix.nih.gov NR 10 TC 40 Z9 42 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD FEB PY 2005 VL 4 IS 2 BP 490 EP 492 DI 10.1128/EC.4.2.490-492.2005 PG 3 WC Microbiology; Mycology SC Microbiology; Mycology GA 901BK UT WOS:000227257800029 PM 15701812 ER PT J AU Sundstrom, J Vasan, RS AF Sundstrom, J Vasan, RS TI Relations of plasma total TIMP-1 levels to cardiovascular risk factors and echocardiographic measures: the Framingham Heart Study: reply SO EUROPEAN HEART JOURNAL LA English DT Letter ID ATHEROSCLEROSIS C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Univ Uppsala, Dept Publ Hlth & Caring Sci, Uppsala, Sweden. Boston Univ, Sch Med, Dept Prevent Med, Cardiol Sect, Boston, MA 02118 USA. RP Sundstrom, J (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM vasan@bu.edu OI Sundstrom, Johan/0000-0003-2247-8454 NR 3 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD FEB PY 2005 VL 26 IS 4 BP 418 EP 419 DI 10.1093/eurheartj/ehi106 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 923EP UT WOS:000228892300017 ER PT J AU Torrent-Guasp, F Kocica, MJ Corno, AF Komeda, M Carreras-Costa, F Flotats, A Cosin-Aguillar, J Wen, H AF Torrent-Guasp, F Kocica, MJ Corno, AF Komeda, M Carreras-Costa, F Flotats, A Cosin-Aguillar, J Wen, H TI Towards new understanding of the heart structure and function SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Review DE ventricle; anatomy; myocardium; physiology ID CARDIAC CONDUCTION SYSTEM; VENTRICULAR MUSCLE BAND; FIBER ORIENTATION; MYOCARDIAL ARCHITECTURE; SPATIAL ORIENTATION; FAILURE; WALL; SYSTOLE; MICROSTRUCTURE; PROPAGATION AB Structure and function in any organ are inseparable categories, both in health and disease. Whether we are ready to accept, or not, many questions in cardiovascular medicine are still pending, due to our insufficient insight in the basic science. Even so, any new concept encounters difficulties, mainly arising from our inert attitude, which may result either in unjustified acceptance or denial. The ventricular myocardial band concept, developed over the last 50 years, has revealed unavoidable coherence and mutual coupling of form and function in the ventricular myocardium. After more than five centuries long debate on macroscopic structure of the ventricutar myocardium, this concept has provided a promising ground for its final understanding. Recent validations of the ventricutar myocardial band, reviewed here, as well as future research directions that are pointed out, should initiate much wider scientific interest, which would, in turn, lead to reconciliation of some exceeded concepts about developmental, electrical, mechanical and energetical events in human heart. The benefit of this, of course, would be the most evident in the clinical arena. (C) 2004 Elsevier B.V. All rights reserved. C1 UC Clin Ctr Serbia, Inst Cardiovasc Dis, Clin Cardiac Surg, YU-11000 Belgrade, Serbia Monteneg, Serbia Monteneg. Alder Hey Childrens Hosp, Liverpool L12 2AP, Merseyside, England. Kyoto Univ, Grad Sch Med, Dept Cardiovasc Surg, Kyoto, Japan. Hosp Sant Pau, Dept Cardiol, Cardiac Imaging Unit, Barcelona, Spain. Hosp Sant Pau, Dept Nucl Med, Barcelona, Spain. Hosp La Fe, Ctr Invest, Cardiocirculatory Unit, E-46009 Valencia, Spain. NHLBI, NIH, Cardiac Energet Lab, Bethesda, MD 20892 USA. RP UC Clin Ctr Serbia, Inst Cardiovasc Dis, Clin Cardiac Surg, 8th Kosta Todorovic St, YU-11000 Belgrade, Serbia Monteneg, Serbia Monteneg. EM kocica@sezampro.yu RI Kocica, Mladen/G-4646-2015; Wen, Han/G-3081-2010 OI Kocica, Mladen/0000-0002-1391-5053; Wen, Han/0000-0001-6844-2997 NR 101 TC 106 Z9 143 U1 2 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1010-7940 EI 1873-734X J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD FEB PY 2005 VL 27 IS 2 BP 191 EP 201 DI 10.1016/j.ejects.2004.11.026 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 902CG UT WOS:000227328300003 PM 15691670 ER PT J AU Hartman, TJ Baer, DJ Graham, LB Stone, WL Gunter, EW Parker, CE Albert, PS Dorgan, JF Clevidence, BA Campbell, WS Tomer, KB Judd, JT Taylor, PR AF Hartman, TJ Baer, DJ Graham, LB Stone, WL Gunter, EW Parker, CE Albert, PS Dorgan, JF Clevidence, BA Campbell, WS Tomer, KB Judd, JT Taylor, PR TI Moderate alcohol consumption and levels of antioxidant vitamins and isoprostanes in postmenopausal women SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE alcohol; antioxidants; oxidative stress; isoprostanes ID IN-VIVO FORMATION; BREAST-CANCER; LIPID-PEROXIDATION; CIGARETTE-SMOKING; E SUPPLEMENTATION; OXIDATIVE STRESS; OXIDANT STRESS; RAT-LIVER; F-2-ISOPROSTANES; RISK AB Background: Although alcohol intake has been positively associated with breast cancer risk in epidemiologic studies, the mechanisms mediating this association are speculative. Objective: The Postmenopausal Women's Alcohol Study was designed to explore the effects of moderate alcohol consumption on potential risk factors for breast cancer. In the present analysis, we evaluated the relationship of alcohol consumption with antioxidant nutrients and a biomarker of oxidative stress. Design: Participants (n = 53) consumed a controlled diet plus each of three treatments (15 or 30 g alcohol/day or a no-alcohol placebo beverage), during three 8-week periods in random order. We measured the antioxidants, vitamin E (alpha (alpha)- and gamma (gamma)-tocopherols), selenium, and vitamin C in fasting blood samples which were collected at the end of diet periods, treated and frozen for assay at the end of the study. We also measured 15-F-2t-IsoP isoprostane, produced by lipid peroxidation, which serves as an indicator of oxidative stress and may serve as a biomarker for conditions favorable to carcinogenesis. Results: After adjusting for BMI (all models) and total serum cholesterol (tocopherol and isoprostane models) we observed a significant 4.6% decrease (P = 0.02) in alpha-tocopherol and a marginally significant 4.9% increase (P = 0.07) in isoprostane levels when women consumed 30 g alcohol/day (P = 0.06 and 0.05 for overall effect of alcohol on alpha-tocopherol and isoprostanes, respectively). The other antioxidants were not significantly modified by the alcohol treatment. Conclusions: These results suggest that moderate alcohol consumption increases some biomarkers of oxidative stress in postmenopausal women. C1 Penn State Univ, University Pk, PA 16802 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. E Tennessee State Univ, Johnson City, TN 37614 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Hartman, TJ (reprint author), Penn State Univ, University Pk, PA 16802 USA. EM tjh9@psu.edu RI Tomer, Kenneth/E-8018-2013; Stone, William/B-6499-2008 OI Stone, William/0000-0002-6829-0417 NR 45 TC 24 Z9 24 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD FEB PY 2005 VL 59 IS 2 BP 161 EP 168 DI 10.1038/sj.ejcn.1602051 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 893AC UT WOS:000226690200002 PM 15367922 ER PT J AU Nathanson, N Mathieson, BJ AF Nathanson, N Mathieson, BJ TI Development of an AIDS vaccine: A daunting epidemiological challenge SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID SIMIAN IMMUNODEFICIENCY VIRUS; HIV-1 INFECTION; GASTROINTESTINAL-TRACT; T-LYMPHOCYTES; PROTECTION; SUPERINFECTION; EVOLUTION; DEPLETION; EFFICACY; ESCAPE C1 Univ Penn, Dept Microbiol, Philadelphia, PA USA. Univ Penn, Dept Neurol, Philadelphia, PA USA. NIH, Off AIDS Res, Bethesda, MD USA. RP Nathanson, N (reprint author), Univ Penn, Dept Microbiol, Philadelphia, PA USA. EM nathansn@mail.med.upenn.edu NR 22 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD FEB PY 2005 VL 20 IS 2 BP 123 EP 126 DI 10.1007/s10654-004-6919-3 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 898MZ UT WOS:000227082200001 PM 15792276 ER PT J AU Blankenburg, S Konig, IR Moessner, R Laspe, P Thoms, KM Krueger, U Khan, SG Westphal, G Volkenandt, M Neumann, C Ziegler, A Kraemer, KH Reich, K Emmert, S AF Blankenburg, S Konig, IR Moessner, R Laspe, P Thoms, KM Krueger, U Khan, SG Westphal, G Volkenandt, M Neumann, C Ziegler, A Kraemer, KH Reich, K Emmert, S TI No association between three xeroderma pigmentosum group C and one group G gene polymorphisms and risk of cutaneous melanoma SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE DNA repair; xeroderma pigmentosum; XPC; XPG (ERCC5); cutaneous melanoma ID SINGLE NUCLEOTIDE POLYMORPHISMS; DNA-REPAIR GENE; XPG GENE; CANCER AB Xeroderma pigmentosum (XP) patients exhibit a 1000-fold increased risk for developing skin cancers including malignant melanoma. We investigated the role of three variant alleles of the DNA repair gene XPC and one variant allele of the XPG gene in a hospital-based case-control study of 294 Caucasian patients from Germany with malignant melanoma and 375 healthy control individuals from the same area matched by sex. The polymorphisms G1580A (XPC exon 8; Arg492His), T1601C (XPC exon 8; Val499Ala), G2166A (XPC exon 10; Arg687Arg), and C3507G ( XPG exon 15; Asp1104His) were not in linkage disequilibrium. The allele frequencies ( cases: controls) were for 1580A 6.29%: 5.63%, for 1601C 79.08%: 78.28%, for 2166A 26.19%: 28.13%, and for 3507G 79.86%: 78.61%. We found no association of the homozygous 1580A, 1601C, 2166A, and 3507G genotypes with increased risks of melanoma: OR 1.254 (95% CI: 0.486 - 3.217), OR 1.108 ( 95% CI: 0.629 - 1.960), OR 0.817 ( 95% CI: 0.490 - 1.358), and OR 1.168 ( 95% CI: 0.670 - 2.044), respectively. Exploratory analyses of subgroups of melanoma patients compared to all controls indicated no association of these genotypes with increased risks for development of multiple primary melanomas (n = 28), a negative family history for melanoma ( n = 277), melanomas in individuals with a low number of nevi ( n = 273), melanomas in individuals older than 55 years ( n = 142), and melanomas thicker than 1 mm ( n = 126). C1 Univ Gottingen, Dept Dermatol, D-37075 Gottingen, Germany. Univ Hosp Schleswig Holstein, Inst Med Biometry & Stat, Lubeck, Germany. NCI, Basic Res Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Gottingen, Dept Occupat & Social Med, D-3400 Gottingen, Germany. Univ Munich, Dept Dermatol, D-8000 Munich, Germany. RP Emmert, S (reprint author), Univ Gottingen, Dept Dermatol, Von Siebold Str 3, D-37075 Gottingen, Germany. EM semmert@gwdg.de RI Konig, Inke/A-4544-2009; OI Ziegler, Andreas/0000-0002-8386-5397 FU Intramural NIH HHS [Z01 BC004517-31] NR 11 TC 33 Z9 34 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD FEB PY 2005 VL 13 IS 2 BP 253 EP 255 DI 10.1038/sj.ejhg.5201296 PG 3 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 888ZR UT WOS:000226413600020 PM 15494739 ER PT J AU Vacchio, MS Williams, JA Hodes, RJ AF Vacchio, MS Williams, JA Hodes, RJ TI A novel role for CD28 in thymic selection: Elimination of CD28/B7 interactions increases positive selection SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T lymphocyte; thymus; costimulation; repertoire development; cellular differentiation ID T-CELL-RECEPTOR; NEGATIVE SELECTION; CD4(+)CD8(+) THYMOCYTES; CD28-DEFICIENT MICE; CLONAL DELETION; IN-VIVO; COSTIMULATION; ANTIGEN; DIFFERENTIATION; EXPRESSION AB While the importance of the CD28/B7 costimulation pathway is well established for mature T cells, the role of CD28 in thymocyte selection is less well defined. The role of CD28 in both negative and positive selection was assessed using H-Y-specific TCR-transgenic (Tg) RAG-2-deficient (H-Yrag) mice. Negative selection in male H-Yrag mice was not affected by deficiency in CD28 or B7. Surprisingly, absence of CD28 or B7 in H-Yrag females resulted in increased numbers of CD8 single-positive (SP) thymocytes. The CD8 SP thymocytes found in these females were mature and functionally competent. Furthermore, double-positive (DP) thymocytes from CD28-knockout (CD28KO) or B7.1/B7.2 double-KO (B7DKO) females had higher levels of both CD5 and TCR than those from WT females, consistent with a stronger selecting signal. CD28KO H-Yrag fetal thymic organ cultures also had elevated numbers of thymic CD8 SP cells, reflecting increased thymic differentiation and not recirculation of peripheral T cells. Finally, increased selection of mature CD4 and CD8 SP T cells was observed in non-TCR-Tg CD28KO and B7DKO mice, indicating that this function of CD28-B7 interaction is not unique to a TCR-Tg model. Together these findings demonstrate a novel negative regulatory role for CD28 in inhibiting differentiation of SP thymocytes, probably through inhibition of thymic selection. C1 Natl Canc Inst, Expt Immunol Branch, NIH, Bethesda, MD USA. NIA, NIH, Bethesda, MD 20892 USA. RP Vacchio, MS (reprint author), Bldg 10,Rm 4B10 MSC1360,10 Ctr Dr, Bethesda, MD 20892 USA. EM Vacchio@nih.gov NR 34 TC 16 Z9 16 U1 1 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 FEB PY 2005 VL 35 IS 2 BP 418 EP 427 DI 10.1002/eji.200424918 PG 10 WC Immunology SC Immunology GA 900AH UT WOS:000227187300012 PM 15657954 ER PT J AU Rusnak, M Gainer, H AF Rusnak, M Gainer, H TI Differential effects of forskolin on tyrosine hydroxylase gene transcription in identified brainstem catecholaminergic neuronal subtypes in organotypic culture SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE A1; A2; cAMP; GABA; locus coeruleus; tetrodotoxin; tyrosine hydroxylase hnRNA ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CILIARY NEUROTROPHIC FACTOR; DEPENDENT PROTEIN-KINASE; LOCUS-COERULEUS NEURONS; CENTRAL-NERVOUS-SYSTEM; CAMP RESPONSE ELEMENT; NORADRENERGIC NEURONS; NOREPINEPHRINE BIOSYNTHESIS; SUPRACHIASMATIC NUCLEUS; INDUCIBLE TRANSCRIPTION AB The regulation of gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, was studied in brainstem noradrenergic nuclei, locus coeruleus (LC), A2 and A1, in vitro. Several novel experimental approaches employed in this study included: (i) the development of a slice-explant model in which these brainstem nuclei maintained a high survival of the noradrenergic neurons, an organotypic topology and the coexpression of two identifying markers in addition to TH, i.e. norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2); (ii) quantitative analysis of TH transcription in these nuclei was made using a labelled intronic probe to measure TH heteronuclear RNA (hnRNA) and (iii) the use of tetrodotoxin in the media to eliminate spontaneous neural activity in these nuclei, thereby providing a basal state as the starting point for the study of TH transcription under various pharmacological perturbations. In the presence of TTX, the adenylcyclase stimulator, forskolin, produced a 155% increase in LC, a 130% increase in A1, and a 220% increase in A2 in TH hnRNA as compared to control nuclei. This effect of forskolin was abolished in the LC and A1 by the PKA inhibitor, H89 (5 mu m), but not by the MAP kinase pathway (MEK) inhibitor, PD98059 (75 mu m). In contrast, the robust increase in TH transcription produced by forskolin in A2 neurons, was completely inhibited by PD98059, and only partially inhibited by H89, showing that induced TH transcription is mediated by different kinase pathways in specific central noradrenergic neuronal subtypes. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Rusnak, M (reprint author), NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. EM gainerh@ninds.nih.gov NR 55 TC 19 Z9 19 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 2005 VL 21 IS 4 BP 889 EP 898 DI 10.1111/j.1460-9568.2005.03913.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 906OX UT WOS:000227652600006 PM 15787695 ER PT J AU Oliveira, MCG Parada, CA Ferraz, MC Veiga, A Rodrigues, LR Barros, SP Tambeli, CH AF Oliveira, MCG Parada, CA Ferraz, MC Veiga, A Rodrigues, LR Barros, SP Tambeli, CH TI Evidence for the involvement of endogenous ATP and P2X receptors in TMJ pain SO EUROPEAN JOURNAL OF PAIN LA English DT Article DE P2X receptors; TMJ; inflammation; pain; alpha,beta-meATP ID RAT SENSORY NEURONS; INFLAMMATORY PAIN; MAST-CELLS; KNEE-JOINT; NOCICEPTIVE BEHAVIOR; HISTAMINE-SECRETION; NEUROPATHIC PAIN; FORMALIN TEST; ACTIVATION; RELEASE AB Evidence is accumulating which supports a role for ATP in the initiation of pain by acting on P2X receptors expressed on nociceptive afferent nerve terminals. To investigate whether these receptors play a role in temporomandibular (TMJ) pain, we studied the presence of functional P2X receptors in rat TMJ by examining the nociceptive behavioral response to the application of the selective P2X receptor agonist alpha,beta-methylene ATP (alpha,beta-meATP) into the TMJ region of rat. The involvement of endogenous ATP in the development of TMJ inflammatory hyperalgesia was also determined by evaluating the effect of the general P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) on carrageenan-induced TMJ inflammatory hyperalgesia. Application of alpha,beta-meATP into the TMJ region of rats produced significant nociceptive responses that were significantly reduced by the co-application of lidocaine N-ethyl bromide quaternary salt, QX-314, (2%) or of the P2 receptor antagonist PPADS. Co-application of PPADS with carrageenan into the TMJ significantly reduced inflammatory hyperalgesia. The results indicate that functional P2X receptors are present in the TMJ and suggest that endogenous ATP may play a role in TMJ inflammatory pain mechanisms possibly by acting primarily in these receptors. (C) 2004 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. C1 Univ Campinas, UNICAMP, Fac Dent Piracicaba, Dept Physiol,Lab Orofacial Pain, Piracicaba, SP, Brazil. NIH Pain Ctr, San Francisco, CA 94143 USA. USP, Fac Med Ribeirao Preto, Dept Pharmacol, Sao Paulo, Brazil. Univ Campinas, Fac Dent Piracicaba, Dept Morphol, Div Histol, Campinas, Brazil. RP Tambeli, CH (reprint author), NIH Pain Ctr, 521 Parnassus Ave,Box 0440,Room C-522, San Francisco, CA 94143 USA. EM tambeli@fop.unicamp.br RI Parada, Carlos Amilcar/C-3974-2012; Tambeli, Claudia/D-4356-2012; Oliveira-Fusaro, Maria Claudia/D-4328-2012 OI Oliveira-Fusaro, Maria Claudia/0000-0001-7676-2317 NR 57 TC 44 Z9 44 U1 1 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1090-3801 J9 EUR J PAIN JI Eur. J. Pain PD FEB PY 2005 VL 9 IS 1 BP 87 EP 93 DI 10.1016/j.ejpain.2004.04.006 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 891UD UT WOS:000226605600013 PM 15629879 ER PT J AU Fishbein, D Hyde, C Eldreth, D London, ED Matochik, J Ernst, M Isenberg, N Steckley, S Schech, B Kimes, A AF Fishbein, D Hyde, C Eldreth, D London, ED Matochik, J Ernst, M Isenberg, N Steckley, S Schech, B Kimes, A TI Cognitive performance and autonomic reactivity in abstinent drug abusers and nonusers SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE executive cognition; drug abuse; decision-making; skin conductance; prefrontal cortex ID SUBSTANCE USE DISORDER; HUMAN PREFRONTAL CORTEX; DECISION-MAKING; HEART-RATE; NEUROCOGNITIVE DEFICITS; AGGRESSIVE-BEHAVIOR; FUTURE CONSEQUENCES; PREDICTING RELAPSE; COLLEGE-STUDENTS; FAMILY-HISTORY AB In this study the authors compared the performance of abstinent drug abusers (n = 21) and nonuser control participants (n = 20) in neurocognitive and emotional functions by use of the Rogers Decision Making Task, Gambling Task, Emotional Stroop, impulsivity continuous performance task (CPT), and vigilance CPT. Skin conductance (SC) and heart rate (HR) monitoring was synchronized with task performance. Groups showed similar performance for vigilance, impulsivity, and emotional interference; however, drug abusers showed stronger SC responses. Drug abusers performed more poorly on the Gambling and Rogers Decision Making Tasks. When making risky decisions, drug abusers showed significantly less increase in SC activity than controls and exhibited lower HRs throughout performance on all tasks. In conclusion, complex tasks involving decision making, sensitivity to consequences, and emotional regulation discriminated between drug abusers and controls. C1 RTI Int, Baltimore, MD 21224 USA. NIDA, Intramural Res Program, Bethesda, MD 20892 USA. John F Kennedy Med Ctr, New York, NY USA. Cornell Univ, Weill Med Coll, Funct Neuroimaging Lab, Ithaca, NY 14853 USA. BioAssessments, Elkton, MD USA. Univ Calif Los Angeles, Brain Res Inst, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA. RP Fishbein, D (reprint author), RTI Int, 6801 Eastern Ave,Suite 203, Baltimore, MD 21224 USA. EM dfishbein@rti.org NR 86 TC 32 Z9 36 U1 4 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD FEB PY 2005 VL 13 IS 1 BP 25 EP 40 DI 10.1037/1064-1297.13.1.25 PG 16 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 898UD UT WOS:000227100800004 PM 15727501 ER PT J AU Bauer, B Hartz, AMS Fricker, G Miller, DS AF Bauer, B Hartz, AMS Fricker, G Miller, DS TI Modulation of p-glycoprotein transport function at the blood-brain barrier SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review DE ATP-binding cassette; central nervous system pharmacotherapy; endothelin; nuclear receptors; regulation ID PREGNANE-X-RECEPTOR; RENAL PROXIMAL TUBULE; CAPILLARY ENDOTHELIAL-CELLS; MULTIDRUG-RESISTANCE; ABC TRANSPORTERS; MDR1A EXPRESSION; GENE-EXPRESSION; UP-REGULATION; IN-VITRO; RAT AB The central nervous system (CNS) effects of many therapeutic drugs are blunted because of restricted entry into the brain. The basis for this poor permeability is the brain capillary endotheliurn, which comprises the blood-brain barrier. This tissue exhibits very low paracellular (tight-junctional) permeability and expresses potent, multispecific, drug export pumps. Together, these combine to limit use of pharmacotherapy to treat CNS disorders such as brain cancer and bacterial or viral infections. Of all the xenobiotic efflux pumps highly expressed in brain capillary endothelial cells, p-glycoprotein handles the largest fraction of commonly prescribed drugs and thus is an obvious target for manipulation. Here we review recent studies focused on understanding the mechanisms by which pglycoprotein activity in the blood-brain barrier can be modulated. These include (i) direct inhibition by specific competitors, (ii) functional modulation, and (iii) transcriptional modulation. Each has the potential to specifically reduce p-glycoprotein function and thus selectively increase brain permeability of pglycoprotein substrates. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Heidelberg, Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany. RP Miller, DS (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. EM miller@niehs.nih.gov NR 78 TC 82 Z9 85 U1 1 U2 6 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD FEB PY 2005 VL 230 IS 2 BP 118 EP 127 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 903MV UT WOS:000227431000006 PM 15673560 ER PT J AU Freed, WJ Zhang, P Sanchez, JF Dillon-Carter, O Coggiano, M Errico, SL Lewis, BD Truckenmiller, ME AF Freed, WJ Zhang, P Sanchez, JF Dillon-Carter, O Coggiano, M Errico, SL Lewis, BD Truckenmiller, ME TI Truncated N-terminal mutants of SV40 large T as minimal immortalizing agents for CNS antigen cells SO EXPERIMENTAL NEUROLOGY LA English DT Article DE immortalization; SV40 large T antigen; T155g; T155c; plasmid; telomerase; telomere; growth arrest; T64-7b; cell line; cell cycle; oncogene ID SIMIAN-VIRUS-40 LARGE-T; MOUSE EMBRYO FIBROBLASTS; TUMOR-SUPPRESSOR GENE; J-DOMAIN; SIMIAN VIRUS-40; SV40-TRANSFORMED CELLS; PROTEIN PHOSPHATASE-2A; TELOMERASE EXPRESSION; GROWTH ARREST; P53 BINDING AB Immortalized central nervous system (CNS) cell lines are useful as in vitro models for innumerable purposes such as elucidating biochemical pathways, studies of effects of drugs, and ultimately, such cells may also be useful for neural transplantation. The SV40 large T (LT) oncoprotein, commonly used for immortalization, interacts with several cell cycle regulatory factors, including binding and inactivating p53 and retinoblastoma family cell-cycle regulators. In an attempt to define the minimal requirements of SV40 T antigen for immortalizing cells of CNS origin, we constructed T155c, encoding the N-terminal 155 amino acids of LT. The p53 binding region is known to reside in the C-terminal region of LT. An additional series of mutants was produced to further narrow the molecular targets for immortalization, and plasmid vectors were constructed for each. In a p53 temperature sensitive cell line model, T64-7B, expression of T155c and all constructs having mutations outside of the first 82 amino acids were capable of overriding cell-cycle block at the non-permissive growth temperature. Several cell lines were produced from fetal rat mesencephalic and cerebral cortical cultures using the T155c construct. The E107K construct contained a mutation in the Rb binding region, but was nonetheless capable of overcoming cell cycle block in T64-7B cell and immortalizing primary cultured cells. Cells immortalized with T155c were often highly dependent on the presence of bFGF for growth. Telomerase activity, telomere length, growth rates, and integrity of the p53 gene in cells immortalized with T155c did not change over 100 population doublings in culture, indicating that cells immortalized with T155c were generally stable during long periods of continuous culture. Published by Elsevier Inc. C1 NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Freed, WJ (reprint author), NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wfreed@intra.nida.nih.gov FU NIDA NIH HHS [Z01 DA000410-08] NR 76 TC 3 Z9 3 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 2005 VL 191 SU 1 BP S45 EP S59 DI 10.1016/j.expneurol.2004.08.019 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 893LP UT WOS:000226720900005 PM 15629761 ER PT J AU Robertson, SM Penzak, SR Pau, AK AF Robertson, SM Penzak, SR Pau, AK TI Drug interactions in the management of HIV infection SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE AIDS; cytochrome P450; drug interactions; drug metabolism; HIV; non-nucleoside reverse transcriptase inhibitors; nucleoside reverse transcriptase inhibitors; P-glycoprotein; pharmacokinetics; protease inhibitors ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEASE INHIBITOR THERAPY; REVERSE-TRANSCRIPTASE INHIBITORS; INDUCED CARBAMAZEPINE TOXICITY; HUMAN CYTOCHROMES P450; PHARMACOKINETIC INTERACTION; LIVER-TRANSPLANTATION; P-GLYCOPROTEIN; IN-VITRO; COMBINATION THERAPY AB The availability of antiretroviral therapy has significantly reduced the morbidity and mortality of HIV infection. In addition, improved treatment of opportunistic infections and comorbidities common to patients with HIV is further prolonging the lives of patients. Improvement in the treatment of HIV has led to a significant increase in the number of medications which caregivers are able to utilise to manage HIV/AIDS. Antiretroviral medications, as well as many of the drugs used in the management of opportunistic infections and primary care (e.g., macrolide antibiotics, azole antifungals, cholesterol-lowering medications), are particularly prone to drug interactions. The interpretation of clinically significant interactions is complicated by the rate at which new information on drug metabolism and transport is becoming available. Management of drug interactions in HIV is further confounded by conflicting study results and differences between documented and theoretical interactions. The mechanisms and significance of interactions involving antiretrovirals, drugs used for opportunistic infections, and other medications commonly used in HIV patients will be reviewed. C1 NIAID, NIH, Off Clin Res, Bethesda, MD 20892 USA. Natl Inst Hlth, Clin Pharmacokinet Res Lab, Clin Ctr Pharm Dept, Bethesda, MD USA. RP Pau, AK (reprint author), NIAID, NIH, Off Clin Res, Bldg 10,Room 11C103, Bethesda, MD 20892 USA. EM apau@nih.gov NR 208 TC 11 Z9 11 U1 0 U2 0 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD FEB PY 2005 VL 6 IS 2 BP 233 EP 253 DI 10.1515/14656566.6.2.233 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 900BD UT WOS:000227189500007 PM 15757420 ER PT J AU Romeo, MJ Espina, V Lowenthal, M Espina, BH Petricoin, EF Liotta, LA AF Romeo, MJ Espina, V Lowenthal, M Espina, BH Petricoin, EF Liotta, LA TI CSF proteome: a protein repository for potential biomarker identification SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE 2D gel electrophoresis; biomarkers; central nervous system; cerebrospinal fluid; ELISA; immunoblotting; isoelectric focusing; MALDI; mass spectrometry; neurodegenerative; protein; proteomics ID HUMAN CEREBROSPINAL-FLUID; NEURON-SPECIFIC ENOLASE; TRAUMATIC BRAIN-INJURY; STANFORD MICROARRAY DATABASE; CREUTZFELDT-JAKOB-DISEASE; FLIGHT-MASS SPECTROMETRY; ALZHEIMERS-DISEASE; 2-DIMENSIONAL ELECTROPHORESIS; PARKINSONS-DISEASE; TAU-PROTEIN AB Proteomic analysis is not limited to the analysis of serum or tissues. Synovial, peritoneal, pericardial and cerebrospinal fluid represent unique proteomes for disease diagnosis and prognosis. In particular, cerebrospinal fluid serves as a rich source of putative biomarkers that are not solely limited to neurologic disorders. Peptides, proteolytic fragments and antibodies are capable of crossing the blood-brain barrier, thus providing a repository of pathologic information. Proteomic technologies such as immunoblotting, Isoelectric focusing, 2D gel electrophoresis and mass spectrometry have proven useful for deciphering this unique proteome. Cerebrospinal fluid proteins are generally less abundant than their corresponding serum counterparts, necessitating the development and use of sensitive analytical techniques. This review highlights some of the promising areas of cerebrospinal fluid proteomic research and their clinical applications. C1 NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Our Lady Good Counsel High Sch, Wheaton, MD USA. US FDA, Ctr Biol Evaluat & Res, Off Cellular & Genet Therapy, Bethesda, MD 20892 USA. RP Romeo, MJ (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, 9000 RockvillePike,Bldg 10,Room 2A33, Bethesda, MD 20892 USA. EM romeoma@mail.nih.gov; espinav@mail.nih.gov; lowenthm@mail.nih.gov; beespina@yahoo.com; petricoin@cber.fda.gov; lance@helix.nih.gov OI Espina, Virginia/0000-0001-5080-5972 NR 105 TC 82 Z9 88 U1 1 U2 11 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD FEB PY 2005 VL 2 IS 1 BP 57 EP 70 DI 10.1586/14789450.2.1.57 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 939ZZ UT WOS:000230114700006 PM 15966853 ER PT J AU Chertov, O Simpson, JT Biragyn, A Conrads, TP Veenstra, TD Fisher, RJ AF Chertov, O Simpson, JT Biragyn, A Conrads, TP Veenstra, TD Fisher, RJ TI Enrichment of low-molecular-weight proteins from biofluids for biomarker discovery SO EXPERT REVIEW OF PROTEOMICS LA English DT Review ID DIFFERENTIAL PEPTIDE DISPLAY; MASS-SPECTROMETRY; OVARIAN-CANCER; SERUM; BLOOD; TOLERANCE; ANTIGEN; CELLS AB The dramatic progress in mass spectrometry-based methods of protein identification has triggered a new quest for disease-associated biomarkers. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and its variant surface-enhanced laser desorption/ionization mass spectrometry, provide effective means to explore the less studied Information slice of the human serum proteome - low-molecular-weight proteins and peptides. These low-molecular-weight proteins and peptides are promising for the detection of important biomarkers. Due to the significant experimental problems imposed by high-abundance and high-molecular-weight proteins, it is important to effectively remove these species prior to mass spectrometry analysis of the low-molecular-weight serum and plasma proteomes. In this review, the advantages afforded by recently introduced methods for prefractionation of serum, as they pertain to the detection and identification of biomarkers, will be discussed. C1 NCI, Prot Chem Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. NIA, Immunol Lab, Baltimore, MD 21224 USA. NCI, SAIC Frederick Inc, Mass Spectrometry Ctr, Biomed Proteom Program, Ft Detrick, MD 21702 USA. RP Chertov, O (reprint author), NCI, Prot Chem Lab, SAIC Frederick Inc, POB B, Frederick, MD 21701 USA. EM oleg@ncifcrf.gov; jsimpson@ncifcrf.gov; biragyna@grc.nia.nih.gov; conrads@ncifcrf.gov; veenstra@ncifcrf.gov; fisger@ncifcrf.gov RI Fisher, Robert/B-1431-2009 FU NCI NIH HHS [N01-CO-12400] NR 23 TC 42 Z9 44 U1 1 U2 5 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD FEB PY 2005 VL 2 IS 1 BP 139 EP 145 DI 10.1586/14789450.2.1.139 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 939ZZ UT WOS:000230114700012 PM 15966859 ER PT J AU Krasnova, IN Ladenheim, B Cadet, JL AF Krasnova, IN Ladenheim, B Cadet, JL TI Amphetamine induces apoptosis of medium spiny striatal projection neurons via the mitochondria-dependent pathway SO FASEB JOURNAL LA English DT Article DE striatum; caspase-3; Bax; striatal dopaminergic terminals ID METHAMPHETAMINE-INDUCED NEUROTOXICITY; INNERVATED BRAIN-REGIONS; SUBSTITUTED AMPHETAMINES; INDUCED TOXICITY; C57BL/6J MOUSE; CELL-DEATH; IN-VIVO; DOPAMINE; BAX; P53 AB Amphetamine ( AMPH) is a psychostimulant whose chronic abuse may cause impairments in attention and memory in humans. These cognitive deficits might be related to neurotoxic effects of the drug. One such toxic effect is the well-described destruction of striatal dopaminergic terminals in mammals. In the present study, we investigated the possibility that AMPH might also cause neuronal apoptosis in the rodent striatum. Administration of a dose of the drug ( 10 mg/kg, 4 times, every 2 h) that is toxic to dopaminergic terminals resulted in the appearance of striatal cells that were positive for cleaved caspase-3 and for terminal deoxynucleotidyl transferase- mediated biotin- dUTP nick-end labeling ( TUNEL), observations that are indicative of an ongoing apoptotic process. Dual immunofluorescence staining revealed that cleaved caspase-3-positive cells express calbindin and DARPP-32, but not somatostatin, parvalbumin, or cholinergic markers. In addition, AMPH also caused increased expression of p53 and Bax at both transcript and protein levels; in contrast, Bcl-2 levels were decreased after the AMPH injections. Moreover, Bax knockout mice showed resistance to AMPH-induced apoptotic cell death but not to AMPH-induced destruction of dopaminergic terminals. When taken together, these observations indicate that injections of doses of AMPH that are known to destroy striatal dopamine terminals can also cause apoptotic death of postsynaptic medium spiny projection neurons via mitochondria-dependent mechanisms. C1 NIDA, Mol Neuropsychiat Branch, Intramural Res Program, DHHS,NIH, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Branch, Intramural Res Program, DHHS,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM JCADET@intra.nida.nih.gov NR 71 TC 46 Z9 46 U1 1 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 FEB PY 2005 VL 19 IS 2 BP 851 EP + DI 10.1096/fj.04-2881fje PG 22 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905TE UT WOS:000227591900006 PM 15731293 ER PT J AU Le, YY Ye, RD Gong, WH Li, JX Iribarren, P Wang, JM AF Le, YY Ye, RD Gong, WH Li, JX Iribarren, P Wang, JM TI Identification of functional domains in the formyl peptide receptor-like 1 for agonist-induced cell chemotaxis SO FEBS JOURNAL LA English DT Article DE chemotaxis; formyl peptide receptor; formyl peptide receptor-like 1; structure-function ID PROTEIN-COUPLED RECEPTOR; LIGAND-BINDING; CHEMOATTRACTANT RECEPTOR; ESCHERICHIA-COLI; FPRL1; 7-TRANSMEMBRANE; NEUTROPHILS; ACTIVATION; CDNA AB Formyl peptide receptor-like 1 (FPRL1) is a seven transmembrane domain, G protein-coupled receptor that interacts with a variety of exogenous and host-derived agonists. In order to identify domains crucial for ligand recognition by FPRL1, we used chimeric receptors with segments in FPRL1 replaced by corresponding amino acid sequences derived from the prototype formyl peptide receptor FPR. The chimeric receptors were stably transfected into human embryonic kidney epithelial cells and the capacity of the cells to migrate in response to formyl peptide receptor agonists was evaluated. Our results showed that multiple domains in FPRL1 are involved in the receptor response to chemotactic agonists with the sixth transmembrane domain and the third extracellular loop playing a prominent role. Interestingly, the N-terminus and a segment between the fourth transmembrane domain and the third intracellular loop of FPRL1 are important for receptor interaction with a 42 amino acid amyloid beta peptide (Abeta(42)), an Alzheimer's disease-associated FPRL1 agonist, but not with MMK-1, a synthetic FPRL1 agonist, suggesting that diverse agonists may use different domains in FPRL1. Considering the potential importance of FPRL1 in inflammation and neurodegenerative diseases, the identification of functional domains in this receptor will provide valuable information for the design of specific receptor antagonists. C1 NCI Frederick, Mol Immunoregulat Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. Chinese Acad Sci, Inst Nutr Sci, Shanghai, Peoples R China. Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL USA. NCI Frederick, Basic Res Program, Ctr Canc Res, Ft Detrick, MD 21702 USA. RP Wang, JM (reprint author), NCI Frederick, Mol Immunoregulat Lab, Ctr Canc Res, Bldg 560,Rm 31-40, Ft Detrick, MD 21702 USA. EM wangji@mail.ncifcrf.gov RI Ye, Richard/O-5223-2016 OI Ye, Richard/0000-0002-2164-5620 FU PHS HHS [N01-C0-12400] NR 22 TC 26 Z9 27 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD FEB PY 2005 VL 272 IS 3 BP 769 EP 778 DI 10.1111/j.1742-4658.2004.04514.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 902LU UT WOS:000227359400013 PM 15670157 ER PT J AU Brinton, LA Moghissi, KS Scoccia, B Westhoff, CL Lamb, EJ AF Brinton, LA Moghissi, KS Scoccia, B Westhoff, CL Lamb, EJ TI Ovulation induction and cancer risk SO FERTILITY AND STERILITY LA English DT Review DE ovulation induction; fertility drugs; infertility; cancer risk; epidemiology ID IN-VITRO FERTILIZATION; EPITHELIAL OVARIAN-CANCER; OF-THE-LITERATURE; HOSPITAL DISCHARGE DIAGNOSIS; HORMONE-REPLACEMENT THERAPY; GRANULOSA-CELL TUMOR; BREAST-CANCER; FERTILITY DRUGS; INFERTILE WOMEN; UNITED-STATES AB Objective: To review and critique the literature regarding ovulation induction and cancer risk. Design: Identification of relevant clinical and epidemiological literature through PubMed and other sources. Conclusion(s): Ovulation and associated hormonal changes have suggested potential links, but more definitive analytic investigations have been difficult to interpret given the small numbers, short follow-up, and imprecise information on drugs or indications for usage. Prospective studies have been limited by inabilities to control for other cancer predictors (including parity), while selective recall has been a concern for retrospective studies. Reports of large increases in ovarian cancer risk associated with fertility medications have not been replicated by more recent investigations. Some findings, based on small numbers, suggest slight increases in risk associated with fertility drugs among nulligravid women or after extended follow-up of for certain tumor subtypes, but further expectation is needed. Fewer studies have assessed relationships with hormonally related cancers, but limited findings supported the need for further monitoring of long-term effects for breast and endometrial cancers. Findings regarding other cancers are extremely limited but should be pursued for cancers showing evidence of hormonal influences, including colon cancers and melanomas. C1 NCI, Hormonal & Reprod Epidemiol Branch, Rockville, MD 20852 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Univ Illinois, Dept Obstet & Gynecol, Chicago, IL 60612 USA. Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. Stanford Univ, Dept Obstet & Gynecol, Stanford, CA 94305 USA. RP Brinton, LA (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, 6120 Execut Blvd,Room 7068, Rockville, MD 20852 USA. EM brinton@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 99 TC 66 Z9 69 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 FEB PY 2005 VL 83 IS 2 BP 261 EP 274 DI 10.1016/j.fertnstert.2004.09.016 PG 14 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 898DD UT WOS:000227055400001 PM 15705362 ER PT J AU Cho, HY Reddy, SP DeBiase, A Yamamoto, M Kleeberger, SR AF Cho, HY Reddy, SP DeBiase, A Yamamoto, M Kleeberger, SR TI Gene expression profiling of NRF2-mediated protection against oxidative injury SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE microarray; lung; hyperoxia; transcription factor; antioxidant; free radicals ID INDUCED LUNG INJURY; PROTEIN-KINASE-C; EXTRACELLULAR-MATRIX; SUPEROXIDE-DISMUTASE; PULMONARY INJURY; OXYGEN-TOXICITY; PHORBOL ESTER; HYPEROXIA; MICE; NRF2 AB Nuclear factor E2 p45-related factor 2 (NRF2) contributes to cellular protection against oxidative insults and chemical carcinogens via transcriptional activation of anitioxidant/detoxifying enzymes. To understand the molecular basis of NRF2-mediated protection against oxidative lung injury, pulmonary gene expression profiles were characterized in Nrf2-disrupted (Nrf2(-/-)) and wild-type (Nrf2(-/-)) mice exposed to hyperoxia or air. Genes expressed constitutively higher in Nrf2(+/+) mice than in Nrf2(-/-) mice included antioxidant defense enzyme and immune cell receptor genes. Higher basal expression of heat shock protein and structural genes was detected in Nrf2(-/-) mice relative to Nrf2(+/+) mice. Hyperoxia enhanced expression of 175 genes (greater than or equal to twofold) and decreased expression of 100 genes (greater than or equal to50%) in wild-type mice. Hyperoxia-induced upregulation of many well-known/new antioxidant/defense genes (e.g. Txnrd 1, Ex, Cp-2) and other novel genes (e.g., Pkc-alpha, Tcf-3, Ppar-gamma) was markedly greater in Nrf2(+/+) mice than in Nrf2(-/-) mice. In contrast, induced expression of genes encoding extracellular matrix and cytoskeletal proteins was higher in Nrf2(-/-) mice than in Nrf2(+/+) mice. These NRF2-dependent gene products might have key roles in protection against hyperoxic lung injury. Results from our global gene expression profiles provide putative downstream molecular mechanisms of oxygen tissue toxicity. (C) 2004 Elsevier Inc. All rights reserved. C1 Johns Hopkins Med Inst, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. NIEHS, NIH, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. George Washington Univ, Childrens Natl Med Ctr, Washington, DC 20010 USA. Univ Tsukuba, Inst Basic Med Sci, Tsukuba, Ibaraki 305, Japan. Univ Tsukuba, Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki 305, Japan. RP Cho, HY (reprint author), Johns Hopkins Med Inst, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. EM cho2@niehs.nih.gov RI Yamamoto, Masayuki/A-4873-2010 FU NCI NIH HHS [CA-44530]; NHLBI NIH HHS [HL-073996, HL-57142, HL-66109, U01 HL-66614-01]; NIEHS NIH HHS [ES-03819, ES-09606] NR 46 TC 147 Z9 158 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD FEB 1 PY 2005 VL 38 IS 3 BP 325 EP 343 DI 10.1016/j.freeradbiomed.2004.10.013 PG 19 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 889VX UT WOS:000226472000004 PM 15629862 ER PT J AU Smith, KF Dobson, AP McKenzie, FE Real, LA Smith, DL Wilson, ML AF Smith, KF Dobson, AP McKenzie, FE Real, LA Smith, DL Wilson, ML TI Ecological theory to enhance infectious disease control and public health policy SO FRONTIERS IN ECOLOGY AND THE ENVIRONMENT LA English DT Review ID PARASITE POPULATION INTERACTIONS; IMMUNODEFICIENCY VIRUS HIV; MATHEMATICAL-MODELS; NEEDLE EXCHANGE; MOUTH EPIDEMIC; COMMUNITY SIZE; TRANSMISSION DYNAMICS; MEASLES EPIDEMICS; GREAT-BRITAIN; DRUG-USERS AB Through the work of international public health organizations and advancements in the biological and technological sciences, substantial progress has been made in our ability to prevent, control, locally eliminate, and in one case eradicate infectious diseases. Yet each successful control or local elimination has been met with the emergence of new pathogens, the evolution of novel strains, or different epidemiological circumstances that have limited or reversed control methods. To respond to the increasing threat of emerging infectious diseases and bioterrorism it is vital that we design and implement efficient programs that prevent and control infectious pathogen transmission. The theoretical tools of ecology and epidemiology may be the cornerstone in constructing future programs aimed at preventing and controlling infectious diseases throughout the world. C1 Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA. Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. NCI, Fogarty Int Ctr, Bethesda, MD 20892 USA. Emory Univ, Ctr Dis Ecol, Atlanta, GA 30322 USA. Univ Michigan, Dept Epidemiol, Sch Publ Hlth, Ann Arbor, MI 48109 USA. RP Smith, KF (reprint author), Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA. EM k_smith@lifesci.ucsb.edu RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 FU Intramural NIH HHS [Z99 TW999999] NR 67 TC 35 Z9 42 U1 2 U2 27 PU ECOLOGICAL SOC AMER PI WASHINGTON PA 1707 H ST NW, STE 400, WASHINGTON, DC 20006-3915 USA SN 1540-9295 J9 FRONT ECOL ENVIRON JI Front. Ecol. Environ. PD FEB PY 2005 VL 3 IS 1 BP 29 EP 37 DI 10.1890/1540-9295(2005)003[0029:ETTEID]2.0.CO;2 PG 9 WC Ecology; Environmental Sciences SC Environmental Sciences & Ecology GA 896TA UT WOS:000226955300005 PM 19838319 ER PT J AU Kamakaka, RT Biggins, S AF Kamakaka, RT Biggins, S TI Histone variants: deviants? SO GENES & DEVELOPMENT LA English DT Review ID CHROMATIN-REMODELING COMPLEX; INACTIVE X-CHROMOSOME; RNA-POLYMERASE-II; KINETOCHORE-MICROTUBULE ATTACHMENT; FUNCTIONAL HUMAN CENTROMERE; NUCLEOSOME CORE PARTICLE; CELL-CYCLE PROGRESSION; ESSENTIAL CHARGE PATCH; HIGHER-ORDER STRUCTURE; EXPRESSION IN-VIVO AB Histones are a major component of chromatin, the protein-DNA complex fundamental to genome packaging, function, and regulation. A fraction of histones are nonallelic variants that have specific expression, localization, and species-distribution patterns. Here we discuss recent progress in understanding how histone variants lead to changes in chromatin structure and dynamics to carry out specific functions. in addition, we review histone variant assembly into chromatin, the structure of the variant chromatin, and post-translational modifications that occur on the variants. C1 NIH, UCT, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. RP NIH, UCT, Bethesda, MD 20892 USA. EM Rohinton@helix.nih.gov NR 154 TC 219 Z9 228 U1 3 U2 11 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD FEB 1 PY 2005 VL 19 IS 3 BP 295 EP 310 DI 10.1101/gad.1272805 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 894NZ UT WOS:000226800100001 PM 15687254 ER PT J AU Chatterjee, N Kalaylioglu, Z Carroll, RJ AF Chatterjee, N Kalaylioglu, Z Carroll, RJ TI Exploiting gene-environment independence in family-based case-control studies: Increased power for detecting associations, interactions and joint effects SO GENETIC EPIDEMIOLOGY LA English DT Article DE case-control studies; case-only designs; conditional likelihood; conditional logistic regression; family-based studies; gene-environment independence; gene-environment interactions; genetic epidemiology; matched case-control studies; population stratification ID CASE-PARENTS DESIGN; TRANSMISSION/DISEQUILIBRIUM TEST; CANDIDATE GENES; GENOTYPE; SIBLINGS; LINKAGE; EXPOSURE; MODELS AB Family-based case-control studies are popularly used to study the effect of genes and gene-environment interactions in the etiology of rare complex diseases. We consider methods for the analysis of such studies under the assumption that genetic susceptibility (G) and environmental exposures (E) are independently distributed of each other within families in the source population. Conditional logistic regression, the traditional method of analysis of the data, fails to exploit the independence assumption and hence can be inefficient. Alternatively, one can estimate the multiplicative interaction between G and E more efficiently using cases only, but the required population-based G-E independence assumption is very stringent. In this article, we propose a novel conditional likelihood framework for exploiting the within-family G-E independence assumption. This approach leads to a simple and yet highly efficient method of estimating interaction and various other risk parameters of scientific interest. Moreover, we show that the same paradigm also leads to a number of alternative and even more efficient methods for analysis of family-based case-control studies when parental genotype information is available on the case-control study participants. Based on these methods, we evaluate different family-based study designs by examining their relative efficiencies to each other and their efficiencies compared to a population-based case-control design of unrelated subjects. These comparisons reveal important design implications. Extensions of the methodologies for dealing with complex family studies are also discussed. (C) 2004 Wiley-Liss, Inc. C1 US Dept HHS, NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Informat Management Syst, Rockville, MD USA. Texas A&M Univ, College Stn, TX USA. RP Chatterjee, N (reprint author), US Dept HHS, NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS Room 8038, Rockville, MD 20852 USA. EM chattern@mail.nih.gov FU NCI NIH HHS [CA-57030]; NIEHS NIH HHS [P30-ES09106] NR 28 TC 38 Z9 38 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD FEB PY 2005 VL 28 IS 2 BP 138 EP 156 DI 10.1002/gepi.20049 PG 19 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 891GB UT WOS:000226568200004 PM 15593088 ER PT J AU Gibbs, PEM McDonald, J Woodgate, R Lawrence, CW AF Gibbs, PEM McDonald, J Woodgate, R Lawrence, CW TI The relative roles in vivo of Saccharomyces cerevisiae Pol eta, Pol xi, Rev1 protein and Pol32 in the bypass and mutation induction of an abasic site, T-T (64) photoadduct and T-T cis-syn cyclobutane dimer SO GENETICS LA English DT Article ID DNA-POLYMERASE-ZETA; ESCHERICHIA-COLI; TRANSLESION REPLICATION; INDUCED MUTAGENESIS; ULTRAVIOLET-LIGHT; YEAST; DAMAGE; GENE; PHOTOPRODUCT; DISRUPTION AB We have investigated the relative roles in vivo of Saccharomyces cerevisiae DNA polymerase eta, DNA polymerase zeta, Rev1 protein, and the DNA polymerase delta subunit, Pol32, in the bypass of an abasic site, T-T (6-4) photoadduct and T-T cis-syn cyclobutane dimer, by transforming strains deleted for RAD30, REV3, REV1, or POL32 with duplex plasmids carrying one of these DNA lesions located within a 28-nucleotide single-stranded region. DNA polymerase eta was found to be involved only rarely in the bypass of the T-T (6-4) photoadduct or the abasic sites in the sequence context used, although, as expected, it was solely responsible for the bypass of the T-T dimer. We argue that DNA polymerase, rather than DNA polymerase 8 as previously suggested, is responsible for insertion in bypass events other than those in which polymerase eta performs this function. However, DNA polymerase 8 is involved indirectly in mutagenesis, since the strain lacking its Pol32 subunit, known to be deficient in mutagenesis, shows as little bypass of the T-T (6-4) photoadduct or the abasic sites as those deficient in Pol zeta or Rev1. In contrast, bypass of the T-T dimer in the pol32 Delta strain occurs at the wild-type frequency. C1 Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, Bethesda, MD 20892 USA. RP Lawrence, CW (reprint author), Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, 601 Elmwood Ave, Rochester, NY 14642 USA. EM christopher_lawrence@urmc.rochester.edu FU NIGMS NIH HHS [GM60652] NR 38 TC 125 Z9 128 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD FEB PY 2005 VL 169 IS 2 BP 575 EP 582 DI 10.1534/genetics.104.034611 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 907EC UT WOS:000227697200008 PM 15520252 ER PT J AU Zhang, JH Hunter, KW Gandolph, M Rowe, WL Finney, RP Kelley, JM Edmonson, M Buetow, KH AF Zhang, JH Hunter, KW Gandolph, M Rowe, WL Finney, RP Kelley, JM Edmonson, M Buetow, KH TI A high-resolution multistrain haplotype analysis of laboratory mouse genome reveals three distinctive genetic variation patterns SO GENOME RESEARCH LA English DT Article ID INBRED STRAINS; Y-CHROMOSOME; MICE; BLOCKS; ORIGIN; COMMON; CROSS AB Understanding of the structure and the origin of genetic variation patterns in the laboratory inbred mouse provides insight into the utility of the mouse model for Studying human complex diseases and strategies for disease gene mapping. In order to address this issue, we have constructed a multistrain, high-resolution haplotype map for the 99-Mb mouse Chromosome 16 using similar to70,000 single nucleotide polymorphism (SNP) markers derived from whole-genome shotgun sequencing of five laboratory inbred strains. We discovered that large polymorphic blocks (i.e., regions where only two haplotypes, thus One SNP conformation, are found in the five strains), large monomorphic blocks (i.e., regions where the five strains share the same haplotype), and fragmented blocks (i.e., regions of greater complexity not resembling at all the first two categories) span 50%, 18%, and 32% of the chromosome, respectively. The haplotype map has 98% accuracy in predicting mouse genotypes in two other studies. Its predictions are also confirmed by experimental results obtained from resequencing of 40-kb genomic sequences at 21 distinct genomic loci in 13 laboratory inbred strains and 12 wild-derived strains. We demonstrate that historic recombination, intra-subspecies variations and inter-subspecies variations have all contributed to the formation of the three distinctive genetic signatures. The results Suggest that the controlled complexity of the laboratory inbred strains may provide a means for uncovering the biological factors that have shaped genetic variation patterns. C1 NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. RP Zhang, JH (reprint author), NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. EM jinghuiz@mail.nih.gov NR 16 TC 27 Z9 27 U1 0 U2 0 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 FEB PY 2005 VL 15 IS 2 BP 241 EP 249 DI 10.1101/gr.2901705 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 894AP UT WOS:000226762500006 PM 15687287 ER PT J AU Greene, E Entezam, A Kumari, D Usdin, K AF Greene, E Entezam, A Kumari, D Usdin, K TI Ancient repeated DNA elements and the regulation of the human frataxin promoter SO GENOMICS LA English DT Article DE frataxin promoter; Alu; MIR; L2 elements ID HUMAN ALU ELEMENTS; HERPES-SIMPLEX-VIRUS; FRIEDREICH-ATAXIA; RNA-POLYMERASE; TRIPLET REPEATS; TRANSCRIPTION; METHYLATION; EXPRESSION; SUBFAMILIES; EXPANSION AB Friedreich ataxia results from frataxin insufficiency caused by repeat expansion in intron 1 of the frataxin gene. Since the coding sequence is unchanged, the potential exists to ameliorate symptoms by increasing frataxin promoter activity. We therefore defined the minimal frataxin promoter in humans. Despite the fact that frataxin is an essential gene, its promoter is not well conserved in mammals, in part because it has been the frequent target of retroelement insertions. Most of the activity of the human frataxin promoter can be attributed to these retroelements, illustrating how these elements, considered parasitic by some, have been co-opted to drive critical genes. Individuals with the milder French Acadian form and those with the classic form of the disease have no biologically relevant sequence differences in the promoter or 3' UTR, suggesting that some other region of the gene, perhaps the repeat itself, is responsible for the difference in disease severity. Published by Elsevier Inc. C1 NIDDKD, Sect Genome Struct & Funct, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIDDKD, Sect Genome Struct & Funct, Mol & Cellular Biol Lab, NIH, Bldg 8,Room 202,8 Ctr Dr ,MSC 0830, Bethesda, MD 20892 USA. EM ku@helix.nih.gov NR 41 TC 15 Z9 15 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 0888-7543 J9 GENOMICS JI Genomics PD FEB PY 2005 VL 85 IS 2 BP 221 EP 230 DI 10.1016/j.ygeno.2004.10.013 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 895EI UT WOS:000226843300007 PM 15676280 ER PT J AU Wang, GQ Abnet, CC Shen, Q Lewin, KJ Sun, XD Roth, MJ Qiao, YL Mark, SD Dong, ZW Taylor, PR Dawsey, SM AF Wang, GQ Abnet, CC Shen, Q Lewin, KJ Sun, XD Roth, MJ Qiao, YL Mark, SD Dong, ZW Taylor, PR Dawsey, SM TI Histological precursors of oesophageal squamous cell carcinoma: results from a 13 year prospective follow up study in a high risk population SO GUT LA English DT Article ID VITAMIN MINERAL SUPPLEMENTATION; NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; CANCER INCIDENCE; CHINA; LINXIAN; LESIONS; DYSPLASIA; IRAN AB Background: Oesophageal squamous cell carcinoma (OSCC) has a very poor prognosis, which is largely due to late diagnosis. Successful early detection strategies will require identification of clinically relevant precursor lesions that can be targets for screening and treatment. Aims: To identify the clinically relevant histological precursors of OSCC. Subjects: A cohort of 682 endoscoped patients from a high risk rural population in Linxian, China. Methods: Subjects were endoscoped and biopsied at baseline and followed for 13.5 years. We estimated the relative risk of developing OSCC for each of the initial histological diagnoses using Cox proportional hazards regression models. Results: A total of 114 (16.7%) patients developed OSCC during the follow up period. After adjusting for potential confounding factors, relative risks (95% confidence intervals) for incidence of this tumour, by initial histological diagnosis, were: normal 1.0 ( reference), oesophagitis 0.8 (0.2 - 3.2), basal cell hyperplasia 1.9 ( 0.8 - 4.5), mild dysplasia 2.9 (1.6 - 5.2), moderate dysplasia 9.8 (5.3 - 18.3), severe dysplasia 28.3 (15.3 - 52.3), and carcinoma in situ 34.4 (16.6 - 71.4). Conclusions: In this study, squamous dysplasia and carcinoma in situ were the only histological lesions associated with a significantly increased risk of developing OSCC within 13.5 years after endoscopy. There was no evidence that oesophagitis predisposed to this tumour. Increasing grades of dysplasia were strongly associated with increasing risk, indicating that the histological grading was clinically meaningful. The follow up experience of severe dysplasia and carcinoma in situ was equivalent, suggesting that this distinction is not clinically relevant. Documenting these precursor lesions of OSCC should assist in the development of effective prevention, early detection, and treatment strategies for this disease. C1 NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Henan Med Univ, Zhengzhou, Peoples R China. Univ Calif Los Angeles, Ctr Hlth Sci, Dept Pathol, Los Angeles, CA 90024 USA. RP Dawsey, SM (reprint author), NCI, Canc Prevent Studies Branch, Ctr Canc Res, 6116 Execut Blvd,Suite 705, Bethesda, MD 20892 USA. EM dawseys@mail.nih.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 FU NCI NIH HHS [N01-CP-40540, N01-SC-91030]; PHS HHS [263-MQ-731789, 263-MQ-822420] NR 26 TC 133 Z9 149 U1 1 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD FEB PY 2005 VL 54 IS 2 BP 187 EP 192 DI 10.1136/gut.2004.046631 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 886RP UT WOS:000226246300007 PM 15647178 ER PT J AU Trimble, EL Harlan, LC Clegg, LX AF Trimble, EL Harlan, LC Clegg, LX TI Untreated cervical cancer in the United States SO GYNECOLOGIC ONCOLOGY LA English DT Article DE cervical cancer; FIGO; SEER program ID CONCURRENT CHEMOTHERAPY; TREATMENT TRIALS; CLINICAL-TRIALS; OLDER PATIENTS; WOMEN; AGE; HEALTH; CARE; PARTICIPATION; SURVIVAL AB Objective. To evaluate treatment patterns, including lack of treatment, among, women diagnosed with cervical cancer in the United States. Methods. Using the National Cancer Institute's (NCI's) Surveillance, Epidemiology, and End Results (SEER) program. we identified 13,715 women diagnosed with invasive cervical cancer between 1992 and 1999 and eligible for inclusion in the study. Results. Nearly 9% of women diagnosed with invasive cervical cancer received no therapy for their disease. Lack of therapy was associated with a later stage of disease at diagnosis, older age, and unmarried status. More than 16% of women aged 65 and older with stage IIB/IV cervical cancer received no therapy for their disease. Conclusion. We must educate women diagnosed with cervical cancer and their families about the importance of treatment for potential cure and control of symptoms. We must identify and overcome obstacles that may prevent adherence to treatment recommendations. These may include comorbidity, access to cancer treatment, inability to pay for treatment, and inadequate social support. Published by Elsevier Inc. C1 NCI, Surg Sect, Bethesda, MD 20892 USA. RP Trimble, EL (reprint author), NCI, Surg Sect, 6130 Execut Blvd,Suite 741,MSC 7436, Bethesda, MD 20892 USA. EM tt6m@nih.gov NR 23 TC 17 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2005 VL 96 IS 2 BP 271 EP 277 DI 10.1016/j.ygyno.2004.09.062 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 892FX UT WOS:000226636600002 PM 15661207 ER PT J AU Lutchman, G Ghany, M AF Lutchman, G Ghany, M TI Pushing the treatment envelope for chronic hepatitis C - Is more necessarily better? SO HEPATOLOGY LA English DT Editorial Material ID ALPHA-2A PLUS RIBAVIRIN; PEGINTERFERON-ALPHA-2A 40KD; TREATMENT DURATION; VIRUS-INFECTION; NAIVE PATIENTS; COMBINATION; THERAPY; INTERFERON; COPEGUS(R); PEGASYS(R) C1 NIDDK, NIH, Liver Dis Branch, Bethesda, MD 20892 USA. RP Ghany, M (reprint author), NIDDK, NIH, Liver Dis Branch, Bldg 10,Room 9B-06,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM marcg@intra.niddk.nih.gov NR 14 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2005 VL 41 IS 2 BP 234 EP 236 DI 10.1002/hep.20605 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 892GK UT WOS:000226637900003 PM 15657958 ER PT J AU Baumert, TF Yang, C Schurmann, P Kock, J Ziegler, C Grullich, C Nassal, M Liang, TJ Blum, HE von Weizsacker, F AF Baumert, TF Yang, C Schurmann, P Kock, J Ziegler, C Grullich, C Nassal, M Liang, TJ Blum, HE von Weizsacker, F TI Hepatitis B virus mutations associated with fulminant hepatitis induce apoptosis in primary Tupaia hepatocytes SO HEPATOLOGY LA English DT Article ID CORE PROMOTER; EXPERIMENTAL-INFECTION; ENHANCED REPLICATION; VIRAL REPLICATION; LIVER-DISEASE; TREE SHREWS; E-ANTIGEN; IN-VIVO; PROTEIN; GENE AB Hepatitis B virus (HBV) core promoter mutations have been implicated in the pathogenesis of fulminant hepatitis B. Due to the limited availability of primary human hepatocytes, the functional characterization of HBV mutants has been performed predominantly in transformed cells, which may not represent ideal model systems for studying virus-cell interactions. We and others have shown that primary hepatocytes of the tree shrew Tupaia belangeri support HBV infection and replication. In this study, we used primary Tupaia hepatocytes to analyze the phenotype of two HBV core promoter mutations that have been associated with a clinical outbreak of fatal fulminant hepatitis. Similar to previous findings in human hepatoma cells, the HBV core promoter mutations resulted in enhanced viral replication and core expression. Surprisingly, however, the presence of the mutations had a marked effect on hepatocyte viability not previously observed in hepatoma cells. Reduced cell viability was found to be due to the induction of apoptosis, as evidenced by caspase-3 activation and nuclear fragmentation. In conclusion, HBV mutants exhibit a novel phenotype in primary hepatocytes distinctly different from previous findings in hepatoma cell lines. This phenotype may have important implications for the understanding of the fulminant clinical course associated with HBV mutations. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/J pages/0270-9139/ suppmatlindex.html). C1 Univ Freiburg, Dept Med 2, D-79106 Freiburg, Germany. Univ Freiburg, Dept Med 1, D-79106 Freiburg, Germany. NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Baumert, TF (reprint author), Univ Freiburg, Dept Med 2, Hugstetter Str 55, D-79106 Freiburg, Germany. EM Thomas.Baumert@uniklinik-freiburg.de NR 50 TC 40 Z9 50 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2005 VL 41 IS 2 BP 247 EP 256 DI 10.1002/hep.20553 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 892GK UT WOS:000226637900005 PM 15660384 ER PT J AU Bradford, BU Kono, H Isayama, F Kosyk, O Wheeler, MD Akiyama, TE Bleye, L Krausz, KW Gonzalez, FJ Koop, DR Rusyn, I AF Bradford, BU Kono, H Isayama, F Kosyk, O Wheeler, MD Akiyama, TE Bleye, L Krausz, KW Gonzalez, FJ Koop, DR Rusyn, I TI Cytochrome P450 CYP2E1, but not nicotinamide adenine dinucleotide phosphate oxidase, is required for ethanol-induced oxidative DNA damage in rodent liver SO HEPATOLOGY LA English DT Article ID BASE EXCISION-REPAIR; HEPATOCELLULAR-CARCINOMA; PEROXISOME PROLIFERATORS; MITOCHONDRIAL-DNA; FREE-RADICALS; MOUSE-LIVER; IN-VIVO; ALCOHOL; DISEASE; INJURY AB The occurrence of malignant tumors of the upper gastrointestinal tract and liver is, based largely on epidemiological evidence, causally related to the consumption of ethanol. It is widely recognized that oxidants play a key role in alcohol-induced liver injury; however, it is unclear how oxidants may be involved in DNA damage. We asked whether nicotinamide adenine dinucleotide phosphate oxidase, cytochrome P450 CYP2E1, or both are responsible for the production of DNA damage. The rodent Tsukamoto-French model of intragastric ethanol infitsion was used. Wistar rats, Cyp2e1-, p47(phax)-null, and hCyp2e1 transgenic mice were used. The abundance of oxidative DNA adducts, mutagenic apurinic/apyrimidinic sites, and expression of base excision DNA repair genes was determined. In rats and wild-type mice, ethanol treatment for 4 weeks led to an increase in oxidative DNA damage and induction of expression of the base excision DNA repair genes that are known to remove oxidative DNA lesions. No increase in either of the endpoints was observed in ethanol-treated Cyp2e1-null mice, whereas the magnitude of response in p47(phax)-null mice and transgenic hCyp2e1 was identical to that in wild types. The increase in expression of DNA repair genes was completely abolished by treatment with the P450 inhibitor 1-aminobenzotriazole. In conclusion, the data support the hypothesis that oxidative stress to DNA is induced in liver by ethanol. Furthermore, although it was shown that nicotinamide adenine dinucleotide phosphate oxidase-derived oxidants are critical for the development of ethanol-induced liver injury, CYP2E1 is required for the induction of oxidative stress to DNA, and thus may play a key role in ethanol-associated hepatocarcinogenesis. C1 Univ N Carolina, Dept Environm Sci & Engn, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC 27599 USA. Yamanashi Univ, Dept Surg 1, Tamaho, Yamanashi, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Sch Publ Hlth, 357 Rosenau Hall, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Rusyn, Ivan/S-2426-2016 FU NIDDK NIH HHS [DK56350]; NIEHS NIH HHS [ES11391, ES11660, ES10126] NR 48 TC 79 Z9 81 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2005 VL 41 IS 2 BP 336 EP 344 DI 10.1002/hep.20532 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 892GK UT WOS:000226637900015 PM 15660387 ER PT J AU Barouch, DH Nabel, GJ AF Barouch, DH Nabel, GJ TI Adenovirus vector-based vaccines for human immunodeficiency virus type 1 SO HUMAN GENE THERAPY LA English DT Review ID SIGNIFICANT GENE-EXPRESSION; CELLULAR IMMUNE-RESPONSES; CYTOTOXIC T-LYMPHOCYTES; RECOMBINANT ADENOVIRUS; DENDRITIC CELLS; VIRAL-ANTIGENS; RHESUS-MONKEYS; IN-VIVO; NEUTRALIZING ANTIBODIES; TRANSGENE EXPRESSION AB Recombinant adenovirus (rAd) vectors have received considerable attention for gene therapy because of their high transduction efficiency. However, recombinant gene expression from rAd vectors elicits rapid and potent immune responses to foreign transgene products. Such immunogenicity limits the duration of transgene expression and poses a major challenge to the use of rAd vectors for gene therapy. In contrast, the inherent immunogenicity of these vectors is a desirable feature for vaccine development. The immunogenicity and protective efficacy of rAd vector-based vaccines have now been demonstrated in a number of animal models, and rAd vaccines for a variety of pathogens are currently being explored in early-phase clinical trials. In this review, we describe progress in the development of rAd vector-based vaccines with a focus on human immunodeficiency virus type 1. C1 Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Barouch, DH (reprint author), Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Res E Room 113,330 Brookline Ave, Boston, MA 02215 USA. EM dbarouch@bidmc.harvard.edu NR 81 TC 129 Z9 133 U1 0 U2 2 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD FEB PY 2005 VL 16 IS 2 BP 149 EP 156 DI 10.1089/hum.2005.16.149 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 905BZ UT WOS:000227543900001 PM 15761255 ER PT J AU Berman, JJ AF Berman, JJ TI Pathology data integration with extensible Markup Language SO HUMAN PATHOLOGY LA English DT Article DE XML; pathology informatics; data integration; data standards ID INSTITUTIONS; SYSTEMS AB It is impossible to overstate the importance of XML (eXtensible Markup Language) as a data organization tool. With XML, pathologists can annotate all of their data (clinical and anatomic) in a format that can transform every pathology report into a database, without compromising narrative structure. The purpose of this manuscript is to provide an overview of XML for pathologists. Examples will demonstrate how pathologists can use XML to annotate individual data elements and to structure reports in a common format that can be merged with other XML files or queried using standard XML tools. This manuscript gives pathologists a glimpse into how XML allows pathology data to be linked to other types of biomedical data and reduces our dependence on centralized proprietary databases. Published by Elsevier Inc. C1 NCI, Canc Diagnosis Program, NIH, Bethesda, MD 20892 USA. RP Berman, JJ (reprint author), NCI, Canc Diagnosis Program, NIH, Bethesda, MD 20892 USA. EM bermanj@mail.nih.gov NR 33 TC 12 Z9 12 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2005 VL 36 IS 2 BP 139 EP 145 DI 10.1016/j.humpath.2004.10.013 PG 7 WC Pathology SC Pathology GA 905UL UT WOS:000227595800002 PM 15754290 ER PT J AU Arraztoa, JA Zhou, J Marcu, D Cheng, C Bonner, R Chen, M Xiang, C Brownstein, M Maisey, K Imarai, M Bondy, C AF Arraztoa, JA Zhou, J Marcu, D Cheng, C Bonner, R Chen, M Xiang, C Brownstein, M Maisey, K Imarai, M Bondy, C TI Identification of genes expressed in primate primordial oocytes SO HUMAN REPRODUCTION LA English DT Article DE embryogenesis; fertility; folliculogenesis; microarray; oogenesis ID TISSUE TRANSGLUTAMINASE; CELL-CYCLE; PROTEIN; OVARY; FERTILITY; FOLLICLES AB Background: The factors involved in oocyte survival and transition from quiescence to the growing phenotype remain unknown. Herein we report genes that are differentially expressed in the primordial oocyte revealed by DNA arrays. Methods: Primordial oocytes were captured selectively in rhesus monkey ovary sections using laser capture microdissection. The RNA was extracted and amplified in two rounds by T7-based linear RNA amplification, fluorescence labelled and then hybridized to human cDNA arrays containing 7680 elements. RNA from human placenta served as a reference sample. Results: Ninety-five genes were found to be consistently expressed at a higher level in primordial oocytes. Expression of several of these genes in the oocyte has been reported before, e.g. deleted in azoospermia (DAZ), prohibitin and transglutaminase 2. Oocyte expression of several novel transcripts revealed on array hybridization, such as gene 33, ubiquitin-conjugating enzyme E2A, G(1) to S phase transition 1, growth arrest and DNA damage-inducible (GADD), and dendritic cell-derived ubiquitin-like protein (DC-UbP) was confirmed by in situ hybridization. Some array-identified gene products [integrin beta3, alpha-tubulin, regulatory telomere elongation protein (RAP1) and cellular repressor of EIA-stimulated genes (CREG protein)] were detected in human oocytes by immunofluorescence. Bioinformatic analysis of the oocyte-enriched transcripts reveals a functional profile summarized as follows: cell cycle (14%); transporter (13%); signal transduction (10%); cytoskeletal (7%); transcription factor (5%); immune response (5%); apoptosis-related (5%); RNA processing (5%); and the remainder of miscellaneous categories. Conclusions: These observations may contribute to the elucidation of molecular pathways involved in oocyte survival and maturation. C1 NICHD, DEB, Bethesda, MD USA. NCI, Pathol Lab, Bethesda, MD USA. NIMH, Genet Lab, NIH, Bethesda, MD USA. Univ Santiago, Biochem Lab, Santiago, Chile. RP Bondy, C (reprint author), NIH, Bldg 10-10N262,10 Ctr Dr, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov RI Bonner, Robert/C-6783-2015 NR 25 TC 20 Z9 21 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD FEB PY 2005 VL 20 IS 2 BP 476 EP 483 DI 10.1093/humrep/deh498 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 891WI UT WOS:000226611300025 PM 15576398 ER PT J AU Franks, PW AF Franks, PW TI White-Coat hypertension and risk of stroke - Do the data really tell us what we need to know? SO HYPERTENSION LA English DT Editorial Material ID BLOOD-PRESSURE C1 NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ 85014 USA. RP Franks, PW (reprint author), NIDDK, Diabet Epidemiol & Clin Res Sect, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM pfranks@niddk.nih.gov OI Franks, Paul/0000-0002-0520-7604 NR 12 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB PY 2005 VL 45 IS 2 BP 183 EP 184 DI 10.1161/01.HYP.0000151621.03913.f3 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 891PS UT WOS:000226593600006 PM 15583073 ER PT J AU Franks, PW AF Franks, PW TI Comparing the roles of physical activity and fitness in arterial stiffness: How important is exposure measurement error? SO HYPERTENSION LA English DT Letter ID CARDIORESPIRATORY FITNESS C1 NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ 85016 USA. RP Franks, PW (reprint author), NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ 85016 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB PY 2005 VL 45 IS 2 BP E1 EP E1 DI 10.1161/01.HYP.0000151326.48642.6c PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 891PS UT WOS:000226593600028 PM 15583074 ER PT J AU Krieger, A Susil, RC Menard, C Coleman, JA Fichtinger, G Atalar, E Whitcomb, LL AF Krieger, A Susil, RC Menard, C Coleman, JA Fichtinger, G Atalar, E Whitcomb, LL TI Design of a novel MRI compatible manipulator for image guided prostate interventions SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE biomedical imaging; cancer; magnetic resonance imaging; medical diagnosis; medical treatment ID MAGNETIC-RESONANCE; CANCER; SYSTEM; BIOPSY; FEASIBILITY; DIAGNOSIS AB This paper reports a novel remotely actuated manipulator for access to prostate tissue under magnetic resonance imaging guidance (APT-MRI) device, designed for use in a standard high-field MRI scanner. The device provides three-dimensional MRI guided needle placement with millimeter accuracy under physician control. Procedures enabled by this device include MRI guided needle biopsy, fiducial marker placements, and therapy delivery. Its compact size allows for use in both standard cylindrical and open configuration MRI scanners. Preliminary in vivo canine experiments and first clinical trials are reported. C1 Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. NCI, Radiat Oncol Branch, NIH, DHHS, Frederick, MD USA. Bilkent Univ, Dept Elect & Elect Engn, TR-06533 Bilkent, Turkey. RP Krieger, A (reprint author), Johns Hopkins Univ, Dept Mech Engn, 123 Latrobe Hall,3400 N Charles St, Baltimore, MD 21218 USA. EM llw@jhu.edu RI Atalar, Ergin/D-3184-2012; OI Atalar, Ergin/0000-0002-6874-6103; Coleman, Jonathan/0000-0002-6428-7835 FU NHLBI NIH HHS [R01 HL61672, R01 HL061672, R01 HL57483, R01 HL057483]; NIBIB NIH HHS [R01 EB002963-05, R01 EB02963, R01 EB002963] NR 19 TC 172 Z9 178 U1 0 U2 19 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD FEB PY 2005 VL 52 IS 2 BP 306 EP 313 DI 10.1109/TBME.2004.840497 PG 8 WC Engineering, Biomedical SC Engineering GA 889ML UT WOS:000226447000017 PM 15709668 ER PT J AU Rosenzweig, SD Holland, SM AF Rosenzweig, SD Holland, SM TI Defects in the interferon-gamma and interleukin-12 pathways SO IMMUNOLOGICAL REVIEWS LA English DT Review ID NF-KAPPA-B; ANHIDROTIC ECTODERMAL DYSPLASIA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; RECEPTOR-1 GENE POLYMORPHISM; CALMETTE-GUERIN INFECTION; SMALL DELETION HOTSPOT; IFN-GAMMA; MYCOBACTERIAL INFECTION; IMMUNE-RESPONSES; PROMOTER POLYMORPHISMS AB The interferon-gamma (IFN-gamma)/interleukin-12 (IL-12) pathway is a pivotal player in the immune system and is central to controlling mycobacterial infections. We highlight the most recent and relevant advances in understanding this pathway and their repercussions on basic and clinical science. Human mutations in IFN-gamma receptor-1 (IFN-gammaR1), IFN-gammaR2, IL-12p40, IL-12 receptor-beta1, signal transducer and activator of transcription-1, and nuclear factor-kappaB essential modulator are analyzed in the context of genetic susceptibility to mycobacterial diseases. A diagnostic and therapeutic approach is described. The IFN-gamma/IL-12 pathway is central in immune control of both environmental and autochthonous challenges, as reflected in human mutations and animal models. Besides being crucial for mycobacterial control, the IFN-gamma/IL-12 pathway is also involved in the pathogenesis of autoimmune disease as well as tumor development and control. Genotype-phenotype correlations have been established for certain genes in this pathway, some of which have therapeutic implications. C1 Hosp Nacl Pediat Juan P Garrahan, Dept Pediat, Div Immunol, Buenos Aires, DF, Argentina. NIAID, Lab Clin Infect Dis, DHHS, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), Bldg 10,CRC B3-4141 10 Ctr Dr MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov NR 90 TC 108 Z9 111 U1 0 U2 5 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2005 VL 203 BP 38 EP 47 DI 10.1111/j.0105-2896.2005.00227.x PG 10 WC Immunology SC Immunology GA 888TZ UT WOS:000226398400004 PM 15661020 ER PT J AU Pesu, M Candotti, F Husa, M Hofmann, SR Notarangelo, LD O'Shea, JJ AF Pesu, M Candotti, F Husa, M Hofmann, SR Notarangelo, LD O'Shea, JJ TI Jak3, severe combined immunodeficiency, and a new class of immunosuppressive drugs SO IMMUNOLOGICAL REVIEWS LA English DT Review ID RECEPTOR-GAMMA-CHAIN; BONE-MARROW-TRANSPLANTATION; COMBINED IMMUNE-DEFICIENCY; STEM-CELL TRANSPLANTATION; PROTEIN-TYROSINE KINASES; MICE LACKING JAK3; THYMIC STROMAL LYMPHOPOIETIN; DEFECTIVE LYMPHOID DEVELOPMENT; TRANSDUCING ADAPTER MOLECULE; MEDIATED GENE-TRANSFER AB The recent elucidation of the multiple molecular mechanisms underlying severe combined immunodeficiency (SCID) is an impressive example of the power of molecular medicine. Analysis of patients and the concomitant generation of animal models mimicking these disorders have quickly provided great insights into the pathophysiology of these potentially devastating illnesses. In this review, we summarize the discoveries that led to the understanding of the role of cytokine receptors and a specific tyrosine kinase, Janus kinase 3 (Jak3), in the pathogenesis of SCID. We discuss how the identification of mutations of Jak3 in autosomal recessive SCID has facilitated the diagnosis of these disorders, offered new insights into the biology of this kinase, permitted new avenues for therapy, and provided the rationale for a generation of a new class of immunosuppressants. C1 NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NIH, Howard Hughes NIH Scholars Program, Bethesda, MD 20892 USA. Univ Brescia, Dept Pediat, Inst Mol Med Angelo Nocivelli, Brescia, Italy. RP NIAMSD, Mol Immunol & Inflammat Branch, Bldg 10,Room 9N252, Bethesda, MD 20892 USA. EM osheajo@mail.nih.gov RI Husa, Matthew/G-4850-2012; Pesu, marko/L-6344-2013; Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 167 TC 70 Z9 73 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2005 VL 203 BP 127 EP 142 DI 10.1111/j.0105-2896.2005.00220.x PG 16 WC Immunology SC Immunology GA 888TZ UT WOS:000226398400010 PM 15661026 ER PT J AU Nichols, KE Ma, CS Cannons, JL Schwartzberg, PL Tangye, SG AF Nichols, KE Ma, CS Cannons, JL Schwartzberg, PL Tangye, SG TI Molecular and cellular pathogenesis of X-linked lymphoproliferative disease SO IMMUNOLOGICAL REVIEWS LA English DT Review ID EPSTEIN-BARR-VIRUS; LYMPHOCYTIC ACTIVATION MOLECULE; NATURAL-KILLER-CELLS; GENE-PRODUCT SAP; NF-KAPPA-B; COMMON VARIABLE IMMUNODEFICIENCY; FATAL INFECTIOUS-MONONUCLEOSIS; PROTEIN-TYROSINE-PHOSPHATASE; DOMAIN-CONTAINING PROTEINS; IFN-GAMMA PRODUCTION AB X-linked lymphoproliferative disease (XLP) is an inherited immune defect caused by mutations in the Src homology 2 domain-containing gene 1A, which encodes the adapter protein, signaling lymphocytic activation molecule (SLAM)-associated protein (SAP). SAP is expressed in T cells, natural killer (NK) cells, and NKT cells, where it binds to the cytoplasmic domain of the surface receptor SLAM (CD150) and the related receptors, 2B4 (CD244), CD84, Ly9 (CD229), NK-T-B-antigen, and CD2-like receptor-activating cytotoxic T cells. SAP also binds to the Src family tyrosine kinase Fyn and recruits it to SLAM, which leads to the generation of downstream phosphotyrosine signals. While the roles of the SLAM family receptors are only beginning to be understood, experiments suggest that these molecules regulate important aspects of lymphocyte function, such as proliferation, cytokine secretion, cytotoxicity, and antibody production. Thus, in XLP patients who lack functional SAP, the SLAM family receptors may not signal properly. This property likely contributes to the phenotypes of XLP, including fulminant infectious mononucleosis, lymphoma, and hypogammaglobulinemia. Further studies of SAP and the SLAM family receptors will provide insights into XLP and elucidate the signaling events regulating lymphocyte ontogeny and function. C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Centenary Inst Canc Med & Cell Biol, Newtown, NSW, Australia. NHGRI, NIH, Bethesda, MD 20892 USA. RP Nichols, KE (reprint author), Childrens Hosp Philadelphia, ARC 910B, Philadelphia, PA 19104 USA. EM nicholsk@email.chop.edu RI Ma, Cindy/B-2340-2012; Tangye, Stuart/H-4023-2014 FU NIAID NIH HHS [U01AI30070] NR 169 TC 143 Z9 151 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2005 VL 203 BP 180 EP 199 DI 10.1111/j.0105-2896.2005.00230.x PG 20 WC Immunology SC Immunology GA 888TZ UT WOS:000226398400014 PM 15661030 ER PT J AU Grimbacher, B Holland, SM Puck, JM AF Grimbacher, B Holland, SM Puck, JM TI Hyper-IgE syndromes SO IMMUNOLOGICAL REVIEWS LA English DT Review ID HYPERIMMUNOGLOBULIN-E SYNDROME; INFECTION JOBS SYNDROME; COLD STAPHYLOCOCCAL ABSCESSES; INTERLEUKIN-4 RECEPTOR; RECURRENT INFECTIONS; CYTOKINE IMBALANCE; INTERFERON-GAMMA; PATIENT; IMMUNOGLOBULIN; TRANSPLANTATION AB The hyper-immunoglobulin E (IgE) syndromes (HIES) are primary immunodeficiencies characterized by the clinical triad of recurrent staphylococcal abscesses, recurrent cyst-forming pneumonia, and an elevated serum IgE level of >2000 IU/ml. Most cases are sporadic; however, multiplex families displaying autosomal dominant (AD) and autosomal recessive (AR) inheritance have been described. In most sporadic and AD cases, the HIES clinical triad is part of a multisystem disorder including abnormalities of the soft tissue, skeletal, and dental systems. In contrast, those with AR-HIES have severe molluscum contagiosum and other viral infections and may develop severe neurological complications. Unlike patients with sporadic HIES and AD-HIES, those with AR-HIES lack skeletal or dental involvement and do not develop lung cysts. Additional variants of HIES are discussed in this review. The etiology of HIES is still unresolved. Recent research points toward a skewed T helper 1 (Th1) cell/Th2 cell ratio and the involvement of chemokines. Therapy for HIES is directed at prevention and management of infections by using sustained systemic antibiotics and antifungals along with topical therapy for eczema and drainage of abscesses. Anti-staphylococcal antibiotic prophylaxis is useful. Interferons, immunoglobulin supplementation, or low-dose cyclosporine A have been reported to benefit selected patients, but they are not generally indicated. C1 Univ Freiburg, Sch Med, Dept Rheumatol & Clin Immunol, D-79106 Freiburg, Germany. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Grimbacher, B (reprint author), Univ Freiburg, Sch Med, Dept Rheumatol & Clin Immunol, Hugstetter Str 55, D-79106 Freiburg, Germany. EM grimbacher@medizin.ukl.uni-freiburg.de NR 53 TC 123 Z9 128 U1 1 U2 7 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2005 VL 203 BP 244 EP 250 DI 10.1111/j.0105-2896.2005.00228.x PG 7 WC Immunology SC Immunology GA 888TZ UT WOS:000226398400018 PM 15661034 ER PT J AU Hayman, JR Southern, TR Nash, TE AF Hayman, JR Southern, TR Nash, TE TI Role of sulfated glycans in adherence of the microsporidian Encephalitozoon intestinalis to host cells in vitro SO INFECTION AND IMMUNITY LA English DT Article ID SURFACE HEPARAN-SULFATE; DEVELOPMENTAL EXPRESSION; TOXOPLASMA-GONDII; PROTEOGLYCANS; BINDING; PROTEIN; INFECTION; INVASION; RECEPTOR; PATIENT AB Microsporidia are obligate intracellular opportunistic protists that infect a wide variety of animals, including humans, via environmentally resistant spores. Infection requires that spores be in close proximity to host cells so that the hollow polar tube can pierce the cell membrane and inject the spore contents into the cell cytoplasm. Like other eukaryotic microbes, microsporidia may use specific mechanisms for adherence in order to achieve target cell proximity and increase the likelihood of successful infection. Our data show that Encephalitozoon intestinalis exploits sulfated glycans such as the cell surface glycosaminoglycans (GAGs) in selection of and attachment to host cells. When exogenous sulfated glycans are used as inhibitors in spore adherence assays, E. intestinalis spore adherence is reduced by as much as 88%. However. there is no inhibition when nonsulfated glycans are used, suggesting that E. intestinalis spores utitize sulfated host cell glycans in adherence. These studies were confirmed by exposure of host cells to xylopyranoside. which limits host cell surface GAGs, and sodium chlorate, which decreases surface sulfation. Spore adherence studies with CHO mutant cell lines that are deficient in either surface GAGs or surface heparan sulfate also confirmed the necessity of sulfated glycans. Furthermore, when spore adherence is inhibited. host cell infection is reduced. indicating a direct association between spore adherence and infectivity. These data show that E. iniestinalis specifically adheres to target cells by way of sulfated host cell surface GAGs and that this mechanism serves to enhance infectivity. C1 E Tennessee State Univ, James H Quillen Coll Med, Dept Microbiol, Johnson City, TN 37614 USA. NIAID, NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Hayman, JR (reprint author), E Tennessee State Univ, James H Quillen Coll Med, Dept Microbiol, Box 70579, Johnson City, TN 37614 USA. EM hayman@etsu.edu FU NIAID NIH HHS [AI 055267, R21 AI055267] NR 44 TC 45 Z9 49 U1 1 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 FEB PY 2005 VL 73 IS 2 BP 841 EP 848 DI 10.1128/IAI.73.2.841-848.2005 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 893PM UT WOS:000226731700021 PM 15664924 ER PT J AU Nguyen, JC Murphy, ME Nutman, TB Neafie, RC Maturo, S Burke, DS Turiansky, GW AF Nguyen, JC Murphy, ME Nutman, TB Neafie, RC Maturo, S Burke, DS Turiansky, GW TI Cutaneous onchocerciasis in an American traveler SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID VOLVULUS; IVERMECTIN; WORMS AB A case report of cutaneous onchocercias acquired during travels to Africa is presented. The salient epidemiologic, clinical, diagnostic, and therapeutic aspects are reviewed. Clinical and laboratory differences between onchocerciasis patients who are inhabitants of endemic areas and those who are occasional visitors to such areas are discussed. Parasitic infections, including onchocerciasis, should be considered in the differential diagnosis of pruritic eruptions in patients with a history of foreign travel to Africa, Central and South America. C1 Stanford Univ, Sch Med, Walter Reed Army Med Ctr, Dermatol Serv, Washington, DC 20307 USA. NIH, Helminth Immunol Sect, Bethesda, MD 20892 USA. NIH, Clin Parasitol Unit, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Parasit Dis Pathol Branch, Washington, DC 20306 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Turiansky, GW (reprint author), Stanford Univ, Sch Med, Walter Reed Army Med Ctr, Dermatol Serv, 6900 Georgia Ave NW, Washington, DC 20307 USA. EM george.turiansky@na.amedd.army.mil OI /0000-0002-5704-8094 NR 18 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD FEB PY 2005 VL 44 IS 2 BP 125 EP 128 DI 10.1111/j.1365-4632.2004.02203.x PG 4 WC Dermatology SC Dermatology GA 900RZ UT WOS:000227233300009 PM 15689210 ER PT J AU Lindroos, MM Soini, SL Kukko-Lukjanov, TK Korpi, ER Lovinger, D Holopainen, IE AF Lindroos, MM Soini, SL Kukko-Lukjanov, TK Korpi, ER Lovinger, D Holopainen, IE TI Maturation of cultured hippocampal slices results in increased excitability in granule cells SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE rat; hippocampus; in vitro maturation; granule cells ID DENTATE GYRUS; RAT HIPPOCAMPUS; STATUS EPILEPTICUS; SYNAPTIC CONNECTIONS; FEBRILE SEIZURES; TEMPORAL-LOBE; ORGANIZATION; INHIBITION; MODEL; REORGANIZATION AB The preparation of hippocampal slices results in loss of input neurons to dentate granule cells, which leads to the reorganization of their axons, the mossy fibers, and alters their functional properties in long-term cultures, but its temporal aspects in the immature hippocampus are not known. In this study, we have focused on the early phase of this plastic reorganization process by analyzing granule cell function with field potential and whole cell recordings during the in vitro maturation of hippocampal slices (from I to 17 days in vitro, prepared from 6 to 7-day-old rats), and their morphology using extracellular biocytin labelling technique. Acute slices from postnatal 14-22-day-old rats were analyzed to detect any differences in the functional properties of granule cells in these two preparations. In field potential recordings, small synaptically-evoked responses were detected at 2 days in vitro, and their amplitude increased during the culture time. Whole cell voltage clamp recordings revealed intensive spontaneous excitatory postsynaptic currents, and the susceptibility to stimulus-evoked bursting increased with culture time. In acutely prepared slices, neither synaptically-evoked responses in field potential recordings nor any bursting in whole cell recordings were detected. The excitatory activity was under the inhibitory control of gamma-aminobutyric acid type A receptor. Extracellularily applied biocytin labelled dentate granule cells, and revealed sprouting and aberrant targeting of mossy fibers in cultured slices. Our results suggest that reorganization of granule cell axons takes place during the early in vitro maturation of hippocampal slices, and contributes to their increased excitatory activity resembling that in the epileptic hippocampus. Cultured immature hippocampal slices could thus serve as an additional in vitro model to elucidate mechanisms of synaptic plasticity and cellular reactivity in response to external damage in the developing hippocampus. (C) 2004 ISDN. Published by Elsevier Ltd. All rights reserved. C1 Univ Turku, Dept Pharmacol, FIN-20520 Turku, Finland. Univ Turku, Dept Clin Pharmacol, FIN-20520 Turku, Finland. Univ Turku, Dept Physiol, FIN-20520 Turku, Finland. Biomedicum Helsinki, Inst Biomed, FIN-00014 Helsinki, Finland. NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. RP Holopainen, IE (reprint author), Univ Turku, Dept Pharmacol, Itainen Pitakatu 4, FIN-20520 Turku, Finland. EM irma.holopainen@utu.fi OI Korpi, Esa R./0000-0003-0683-4009 NR 35 TC 14 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD FEB PY 2005 VL 23 IS 1 BP 65 EP 73 DI 10.1016/j.ijdevneu.2004.08.003 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 907XW UT WOS:000227752500008 PM 15730888 ER PT J AU Mai, V Kant, AK Flood, A Lacey, JV Schairer, C Schatzkin, A AF Mai, V Kant, AK Flood, A Lacey, JV Schairer, C Schatzkin, A TI Diet quality and subsequent cancer incidence and mortality in a prospective cohort of women SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diet; cancer; dietary pattern; mortality; diet quality; women ID MAJOR CHRONIC DISEASE; GUIDELINES-FOR-AMERICANS; COLORECTAL-CANCER; BREAST-CANCER; LIFE-STYLE; UNITED-STATES; RISK; PATTERNS; ADHERENCE; SURVIVAL AB Background We have previously reported on the utility of the Recommended Foods Score (RFS), a measure of overall diet quality, in detecting associations between diet and mortality in a cohort of older women. Using additional follow-up, we have now extended our analysis to detailed studies of associations between RFS and the mortality and incidence from common cancers. Methods The RFS, the sum of 23 recommended food items consumed at least weekly, was computed from a 62-item food frequency questionnaire completed at baseline by 42 254 women with a mean age of 61 years. Multivariate adjusted relative risk (RR) of cancer mortality and incidence of the cancers for which we were able to obtain data in relation to quartiles of RFS were examined using proportional hazards regression analyses after a median follow-up period of 9.5 years. Results We observed that RFS was inversely associated with total mortality (RR = 0.8; P < 0.001) cancer mortality (RR = 0.74; P < 0.001) as well as mortality from cancers of the breast (RR = 0.75; P < 0.06), colon/rectum (RR = 0.49; P < 0.01) and lung (RR = 0.54; P < 0.001). The risk of incident lung cancer (RR = 0.62; P < 0.001) was reduced in women in the highest vs the lowest quartile of RFS; for incident cancers of the breast, colorectum, endometrium, ovaries, and bladder, there was no RFS association. Conclusion A dietary pattern reflecting a higher RFS was associated with decreased overall mortality in women, specifically cancers of the lung, colon/rectum, and to a lesser extent breast. Incidence was only decreased for lung cancers. These observations are consistent with the hypothesis that a high RFS dietary pattern, or associated lifestyle factors, might affect cancer progression and survival. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55454 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Mai, V (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, 10 S Pine St,MSTF 9-34, Baltimore, MD 21201 USA. EM vmai@epi.umaryland.edu NR 24 TC 49 Z9 50 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD FEB PY 2005 VL 34 IS 1 BP 54 EP 60 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 899FF UT WOS:000227129600014 PM 15649959 ER PT J AU McKenzie, FE AF McKenzie, FE TI Polyparasitism SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Letter DE Diet; cancer; dietary pattern; mortality; diet quality; women ID ASCARIS-LUMBRICOIDES; TRICHURIS-TRICHIURA; INTESTINAL PARASITES; INFECTIONS; PLASMODIUM; PREVALENCE; COMMUNITY; EPIDEMIOLOGY; MORBIDITY; HOOKWORM C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP McKenzie, FE (reprint author), NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. EM em225k@nih.gov FU Intramural NIH HHS [Z99 TW999999] NR 16 TC 17 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD FEB PY 2005 VL 34 IS 1 BP 221 EP 222 DI 10.1093/ije/dyh399 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 899FF UT WOS:000227129600042 PM 15659470 ER PT J AU Iwao, N Iwao, S Muller, DC Koda, M Ando, F Shimokata, H Kobayashi, F Andres, R AF Iwao, N Iwao, S Muller, DC Koda, M Ando, F Shimokata, H Kobayashi, F Andres, R TI Differences in the relationship between lipid CHD risk factors and body composition in Caucasians and Japanese SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE racial difference; BMI; waist circumference; lipids; coronary risk factor ID DENSITY-LIPOPROTEIN CHOLESTEROL; ABDOMINAL SAGITTAL DIAMETER; WAIST-HIP RATIO; FAT DISTRIBUTION; CARDIOVASCULAR RISK; MASS INDEX; MONICA PROJECT; 19 POPULATIONS; CIRCUMFERENCE; FATNESS AB OBJECTIVES: To examine differences in the relationship between fat distribution and lipid coronary risk factors in Caucasian and Japanese population and further to determine whether the cut-points for body mass index (BMI) and waist circumference (WC) proposed by WHO and NHLBI are applicable to Japanese population as a predictor of a lipid risk factor abnormality or not. RESEARCH METHODS AND PROCEDURES: Subjects were 895 participants of the Baltimore Longitudinal Study of Aging in the US (BLSA) and 1705 participants of the Longitudinal Study of Aging by the National Institutes for Longevity Science in Japan (NILS-LSA). Subjects were divided into four demographic groups as younger (age < 65 y) men and women, and older (age &GE; 65 y) men and women. Blood total cholesterol, triglycerides, LDL- and HDL-cholesterol and anthropometry were measured. Regression coefficients of BMI and WC on risk factors, sensitivity and specificity of the BMI and WC cut-points for blood lipid abnormality, and mean values of blood lipids at BMI or WC cut-points were computed in both populations. RESULTS: Height, weight, WC and BMI were significantly greater in the BLSA than those in the NILS-LSA subjects. Total cholesterol, HDL- and LDL-cholesterol were significantly greater in the NILS-LSA than in the BLSA subjects. Sensitivities of BMI and WC cut-points were much lower in the NILS-LSA than in the BLSA subjects. Specificities of BMI and WC cut-points were higher in the NILS-LSA than in the BLSA subjects. Mean values of triglycerides, total cholesterol, HDL- and LDL- cholesterol at BMI = 25 were significantly greater in the NILS-LSA than in the BLSA subjects. At the WC cut-point (94 cm for men, 80 cm for women), mean values of all lipids were significantly greater in the NILS-LSA than in the BLSA subjects with the exception of triglycerides in younger women. CONCLUSIONS: The Japanese subjects have smaller BMI and WC, worse total and LDL-cholesterol levels and better HDL-cholesterol levels compared to Caucasians. Sensitivities of BMI and WC for predicting lipid risk factor abnormality are much lower in Japanese. The cut-points for BMI and WC proposed by WHO and NHLBI may be too high for predicting an abnormality in triglycerides, total and LDL-cholesterol in Japanese. For detecting an abnormal HDL-cholesterol level, the BMI and WC cut-points may not be as beneficial for the Japanese population as for Caucasians. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Natl Inst Longev Sci, Dept Epidemiol, Aichi, Japan. Aichi Med Univ, Sch Med, Inst Med Sci Aging, Dept Hlth & Psychosocial Med, Nagakute, Aichi 48011, Japan. RP Andres, R (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM andresr@grc.nia.nih.gov NR 33 TC 15 Z9 16 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD FEB PY 2005 VL 29 IS 2 BP 228 EP 235 DI 10.1038/sj.ijo.0802615 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 887RD UT WOS:000226322300012 PM 15570315 ER PT J AU Smith, AW Baum, A Wing, RR AF Smith, AW Baum, A Wing, RR TI Stress and weight gain in parents of cancer patients SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE chronic stress; weight change; physical activity; cancer ID PSYCHOLOGICAL ADJUSTMENT; DEPRESSIVE SYMPTOMS; PERCEIVED STRESS; EATING BEHAVIOR; CHILDREN; PREDICTORS; CORTISOL; EXERCISE; ANXIETY; HUNGER AB OBJECTIVE: To investigate the effects of chronic stress on weight changes and related behavioral changes in parents with a child who had just been diagnosed with cancer compared to parents with healthy children. DESIGN: Longitudinal case-control study with assessments occurring over a three-month period following the child's diagnosis of cancer. SUBJECTS: In total, 49 parents of healthy children and 49 parents of cancer patients aged 19-58 y. MEASUREMENTS: Body weight, diet, physical activity, self-reported mood and stress. RESULTS: Parents of cancer patients were more likely to gain weight, and experienced significantly greater weight gain over the 3 months than parents of healthy children. The magnitude of weight gain was related to the degree of psychological distress that the parents experienced. Parents of cancer patients reported lower levels of physical activity and lower caloric intake than parents of healthy children, with the most marked differences between groups occurring in the area of physical activity. CONCLUSION: Findings suggest that a major stressor, such as a child's diagnosis of cancer, is associated with weight gain. Further research is needed to determine how long these weight gains persist and whether other types of stress also produce weight gains. Such studies should focus not only on the effect of stress on eating behavior but also on physical activity. C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. RP Smith, AW (reprint author), NCI, Execut Plaza N,Suite 4001,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM smithas@mail.nih.gov NR 33 TC 25 Z9 25 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD FEB PY 2005 VL 29 IS 2 BP 244 EP 250 DI 10.1038/sj.ijo.0802835 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 887RD UT WOS:000226322300014 PM 15654361 ER PT J AU Okada, H Kimura, MT Tan, DF Fujiwara, K Igarashi, J Makuuchi, M Hui, AM Tsurumaru, M Nagase, H AF Okada, H Kimura, MT Tan, DF Fujiwara, K Igarashi, J Makuuchi, M Hui, AM Tsurumaru, M Nagase, H TI Frequent trefoil factor 3 (TFF3) overexpression and promoter hypomethylation in mouse and human hepatocellular carcinomas SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE hepatocellular carcinoma; trefoil factor 3 (TFF3); DNA methylation; expression regulation; epigenetic regulation ID COMPARATIVE GENOMIC HYBRIDIZATION; GENE-EXPRESSION; HUMAN BREAST; PEPTIDES; CELLS; PS2; IDENTIFICATION; PROGRESSION; ESTROGEN; RECEPTOR AB Expression profiling analysis revealed ectopic high expression of mouse TFF3 in non-tumor liver tissues from the hepatocellular carcinoma (HCC) Susceptible PWK/Rbrc strain. TFF3 is a member of the trefoil factor family peptides, which are small secreted proteins regulating mucosal regeneration and repair, and which are overexpressed during inflammatory processes and cancer progression. We. therefore. analyzed the TFF3 expression extensively in mouse and human HCCs. Expression of the mouse TFF3 gene was significantly increased in 6 out of 7 HCCs from a PWK spontaneous tumor model and in all 7 HCCs front an SV40T antigen-induced transgenic MT-D2C57BL/6 model. In humans. 8 of 20 HCCs (40%) had overexpression of TFF3 in both mRNA level and protein level. We then analyzed DNA methylation patterns of the TFF3 promoter region to evaluate expression regulation of promoter methylation. In mouse HCCs, we demonstrated that two CpGs, at positions -992 and +109, were hypomethylated in 13 of 14 mouse HCCs. In human HCCs, hypomethylation at CpG -260 was associated with TFF3 overexpression (p=0.04). These results indicate that TFF3 overexpression may be a critical process in mouse and human hepatocellular carcinogenesis, and the specific promoter CpG hypomethylation may be one of the regulation mechanisms of TFF3 overexpression in HCCs. C1 Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA. Juntendo Univ, Dept Surg, Grad Sch Med, Tokyo 1138421, Japan. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Juntendo Univ, Hepato Biliary Pancreat Surg Div, Dept Surg, Grad Sch Med, Tokyo 1138655, Japan. RP Nagase, H (reprint author), Roswell Pk Canc Inst, Dept Canc Genet, Elm & Carlton St, Buffalo, NY 14263 USA. EM Hiroki.Nagase@RoswellPark.org RI 幕内, 雅敏/A-2140-2012 FU NCI NIH HHS [CA16056, P30 CA016056]; NIEHS NIH HHS [ES012249-01, R01 ES012249, R01 ES012249-01A1, R01 ES012249-02] NR 35 TC 29 Z9 30 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 2005 VL 26 IS 2 BP 369 EP 377 PG 9 WC Oncology SC Oncology GA 889ZM UT WOS:000226481500009 PM 15645121 ER PT J AU Wallner, PE Coleman, CN Brechbiel, M Milencic, D Tripuraneni, P AF Wallner, PE Coleman, CN Brechbiel, M Milencic, D Tripuraneni, P TI In response to Dr. Order SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter C1 21st Century Oncol Inc, Ft Myers, FL USA. NCI, Radiat Res Program, Bethesda, MD 20892 USA. Scripps Clin, La Jolla, CA USA. RP Wallner, PE (reprint author), 21st Century Oncol Inc, Ft Myers, FL 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2005 VL 61 IS 2 BP 631 EP 631 DI 10.1016/j.ijrobp.2004.11.004 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 893DT UT WOS:000226700200044 ER PT J AU Inbar, Y Wolfson, HJ Nussinov, R AF Inbar, Y Wolfson, HJ Nussinov, R TI Multiple docking for protein structure prediction SO INTERNATIONAL JOURNAL OF ROBOTICS RESEARCH LA English DT Article DE protein structure prediction; multiple docking; combinatorial assembly; self-reconfigurable chain-type system ID SHAPE COMPLEMENTARITY; GENETIC ALGORITHM; HYDROGEN-EXCHANGE; GLOBULAR-PROTEINS; FOLDING UNITS; RECOGNITION; ELECTROSTATICS; RESTRAINTS; INTERFACES; SEQUENCES AB Protein structure prediction and protein docking prediction are two related problems in molecular biology. We suggest the use of multiple docking in the process of protein structure prediction. Once reliable structural models are predicted to disjoint fragments of the protein target sequence, a combinatorial assembly may be used to predict their native arrangement. Here, we present CombDock, a combinatorial docking algorithm for the structural units assembly problem. We have tested the algorithm on various examples using both domains and domain substructures as input. Inaccurate models of the structural units were also used, to test the robustness of the algorithm. The algorithm was able to predict a near-native arrangement of the input structural units in almost all of the cases, showing that the combinatorial approach succeeds in overcoming the inexact shape complementarity caused by the inaccuracy of the models. C1 Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, SAIC Frederick Inc,Basic Res Program, Frederick, MD 21702 USA. RP Inbar, Y (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. EM inbaryuv@tau.ac.il RI Wolfson, Haim/A-1837-2011 NR 64 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0278-3649 J9 INT J ROBOT RES JI Int. J. Robot. Res. PD FEB-MAR PY 2005 VL 24 IS 2-3 BP 131 EP 150 DI 10.1177/0278364905050358 PG 20 WC Robotics SC Robotics GA 903FB UT WOS:000227409900003 ER PT J AU Pezawas, L Angst, J Kasper, S AF Pezawas, L Angst, J Kasper, S TI Recurrent brief depression revisited SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Article ID GENERAL HEALTH-CARE; PSYCHIATRIC-DISORDERS; SUICIDAL-BEHAVIOR; AFFECTIVE-ILLNESS; PSYCHOLOGICAL-PROBLEMS; MAJOR DEPRESSION; COMMUNITY SAMPLE; CONTROLLED TRIAL; ZURICH; MOOD AB Recurrent Brief Depressive Disorder (RBD) is a well-defined and prevalent mood disorder with an increased risk of suicidal behavior and significant clinical impairment in the community and general practice. Occurring at least monthly with depressive episodes lasting only a few days defines recurrent Brief Depressive Disorder. The lifetime co-occurrence of both RBD and Major Depressive Disorder (MDD), called Combined Depression ( CD), substantially increases the risk for attempted suicide, even more than that known for 'pure' MDD. The diagnostic criteria for RBD found in the ICD-10 and DSM-IV are helpful in research and clinical routine as well as several methodological issues, which make clinical diagnostic and drug response evaluation of RBD very different from MDD. Formal differences in the course of RBD and MDD require different designs for drug treatment studies. Denials of disorder, specific methodological requirements, and highly selected patient samples have probably been responsible for false negative results in double blind, placebo-controlled treatment studies. Although several authors reported successful treatment of RBD with different compounds in about 60 patients, it is still not possible to deduce a treatment algorithm for RBD to date. Obviously future treatment studies without the limitations of previous studies are clearly required for RBD. Results of ongoing studies will soon provide the first data on the biological underpinnings of RBD. C1 NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. Med Univ Vienna, Dept Gen Psychiat, Vienna, Austria. Zurich Univ Psychiat Hosp, Zurich, Switzerland. RP Pezawas, L (reprint author), NIMH, Genes Cognit & Psychosis Program, NIH, 10 Ctr Dr 4S235, Bethesda, MD 20892 USA. EM lukaspezawas@mail.nih.gov RI Pezawas, Lukas/A-2367-2011 OI Pezawas, Lukas/0000-0002-1329-6352 NR 51 TC 15 Z9 16 U1 1 U2 3 PU ROUTLEDGE TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD FEB PY 2005 VL 17 IS 1 BP 63 EP 70 DI 10.1080/00207390500064650 PG 8 WC Psychiatry SC Psychiatry GA 920CZ UT WOS:000228668000008 PM 16194772 ER PT J AU Chan, CC Fischette, M Shen, DF Mahesh, SP Nussenblatt, RB Hochman, J AF Chan, CC Fischette, M Shen, DF Mahesh, SP Nussenblatt, RB Hochman, J TI Murine model of primary Intraocular lymphoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID B-CELL; MALIGNANT-LYMPHOMA; EXPRESSION; DIAGNOSIS; ANTERIOR; FEATURES; BRAIN; EYES AB PURPOSE. Primary intraocular lymphoma ( PIOL) is a subtype of central nervous system lymphoma. Although this lymphoma is rare, its incidence has tripled in the past 15 years. Currently, the only available model is a murine metastatic malignant lymphoma that occurs after intraperitoneal inoculation of Rev-2-T-6 lymphoma cells into newborn syngeneic mice. The current study was conducted to develop a new experimental model for PIOL. METHODS. Rev-2-T-6 cells (0.5 x 10(5) or 1.0 x 10(5)) were inoculated into the vitreous of adult BALB/c mice. Mice were monitored clinically every other day and under fundoscopic examination weekly. They were euthanatized on weeks 3, 5, 6, 7, or 8, after inoculation. All eyes were processed for histology. Immunohistochemistry was performed with an antibody (p14) specific for Rev-2-T-6 cells. Cytokine mRNA expression (IL-2, - 4, - 6, - 10, and IFN-gamma and CC chemokine receptor-1 [CCR1]) was assayed in the lymphoma cells by microdissection and RT-PCR. IL-10 and - 6 levels in the vitreous were measured by ELISA. RESULTS. Within 2 to 4 weeks, tumor cells from the vitreous migrate through the retina and gather between the RPE cell and retina. Rarely ( > 2 months after inoculation), Rev-2-T-6 cells may break through the RPE and infiltrate the choroid and sclera. Tumor localization was confirmed by immunohistochemistry. The intraocular lymphoma cells produce high levels of IL-10, IFN-gamma, and CCR1 transcripts. A high level of IL-10 was detected in the vitreous inoculated with Rev-2-T-6 cells. CONCLUSIONS. The data suggest that RPE cells constitute a barrier to the spread of intraocular lymphoma. Intravitreal injection of Rev-2-T-6 cells is a novel model of PIOL in immune-competent hosts that will aid in understanding the molecular mechanisms of the disease. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Inst Life Sci, Dept Cell & Anim Biol, IL-91904 Jerusalem, Israel. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov FU Intramural NIH HHS [Z01 EY000222-22] NR 22 TC 18 Z9 18 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 FEB PY 2005 VL 46 IS 2 BP 415 EP 419 DI 10.1167/iovs.04-0869 PG 5 WC Ophthalmology SC Ophthalmology GA 890WP UT WOS:000226542100003 PM 15671263 ER PT J AU Klein, AP Duggal, P Lee, KE Klein, R Bailey-Wilson, JE Klein, BEK AF Klein, AP Duggal, P Lee, KE Klein, R Bailey-Wilson, JE Klein, BEK TI Support for polygenic influences on ocular refractive error SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID BEAVER DAM EYE; HIGH MYOPIA MAPS; SEGREGATION ANALYSIS; ADULT-ONSET; POPULATION; LOCUS; PREVALENCE; SCAN; AGGREGATION; FAMILIES AB PURPOSE. Refractive errors, myopia, and hyperopia are common conditions requiring corrective lenses. The familial clustering of myopia has been well established. Several chromosomal regions have been linked to high myopia (12q, 17q, and 18q), to quantitative refraction among twins (3q, 4q, 8p, and 11p), and to families with moderate myopia (22q). This study examined the familial aggregation and pattern of inheritance of ocular refraction in an adult population, by using data from the Beaver Dam Eye Study. METHODS. Familial correlations were examined and segregation analysis was performed on the average refractive error measurements in the right and left eyes after adjustment for age, sex, and education. Analyses were based on 2138 individuals in 620 extended pedigrees with complete data on age, sex, education, and spherical equivalent. RESULTS. Substantial positive correlation was found between siblings (0.33), parents and offspring (0.17), and cousins (0.10) and lower correlation among avuncular pairs (0.08) after adjustment for age, sex, and years of education. The results of this segregation analysis do not support the involvement of a single major locus throughout the entire range of refractive error. However, models allowing for familial correlation, attributable in part to polygenic effects, provided a better fit to the observed data than models without a polygenic component, suggesting that several genes of modest effect may influence refractive error, possibly in conjunction with environmental factors. CONCLUSIONS. These results support the involvement of genetic factors in the etiology of refractive error and are consistent with reports of linkage to multiple regions of the genome. C1 Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA. NHGRI, Stat Genet Sect, Inherited Dis Res Branch, Baltimore, MD USA. RP Klein, BEK (reprint author), Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, 610 N Walnut St,Room 409, Madison, WI 53726 USA. EM kleinb@epi.ophth.wisc.edu OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCRR NIH HHS [RR3655]; NEI NIH HHS [R03 EY13438, U10 EY06594] NR 31 TC 36 Z9 38 U1 0 U2 1 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 FEB PY 2005 VL 46 IS 2 BP 442 EP 446 DI 10.1167/iovs.04-0794 PG 5 WC Ophthalmology SC Ophthalmology GA 890WP UT WOS:000226542100007 PM 15671267 ER PT J AU Duggal, P Klein, AP Lee, KE Iyengar, SK Klein, R Bailey-Wilson, JE Klein, BEK AF Duggal, P Klein, AP Lee, KE Iyengar, SK Klein, R Bailey-Wilson, JE Klein, BEK TI A genetic contribution to intraocular pressure: The Beaver Dam Eye Study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPEN-ANGLE GLAUCOMA; GENOME-WIDE SCAN; INFLUENCING BLOOD-PRESSURE; AGE-RELATED MACULOPATHY; QUANTITATIVE TRAIT; LINKAGE ANALYSIS; REGION; LOCUS; IDENTIFICATION; HYPERTENSION AB PURPOSE. To investigate a potential genetic contribution to intraocular pressure (IOP), we performed a complex segregation analysis on 2337 individuals in 620 extended pedigrees ascertained through a population-based cohort, the Beaver Dam Eye Study (BDES). IOP is a principal risk factor for primary open-angle glaucoma (POAG) a leading cause of blindness worldwide. METHODS. Segregation analysis is an analytical method that provides statistical evidence supporting the involvement of a major gene or polygenes in a particular phenotype. Detailed medical histories and eye examinations were performed on all participants. From the two eyes, the higher IOP measurement was used as a continuous trait after adjustment for covariates. A genome-wide scan (GWS) using affected sib pair linkage analysis was performed on 218 sibling pairs. RESULTS. In this segregation analysis the model that allowed for an unmeasured major environmental effect plus a polygenic/ multifactorial effect provided the best fit and was the most parsimonious model. The lack of an adequate fit for the Mendelian single-gene models is consistent with a multifactorial model of inheritance that may include multiple genes and environmental factors that contribute to IOP. The results of the GWS yielded two novel loci as potential linkage regions for IOP on chromosomes 6 (P = 0.008) and 13 (P = 0.0007). Neither of these regions has previously been identified in GWS of POAG. CONCLUSIONS. The segregation and familial correlation analyses of IOP suggest a polygenetic component with environmental influences. The pilot linkage study further confirms the heterogeneity of IOP with the identification of two novel genetic loci. C1 Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med, Madison, WI 53726 USA. NHGRI, Stat Genet Sect, Inherieted Dis Res Branch, NIH, Baltimore, MD USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. RP Klein, BEK (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med, 610 N Walnut St,4th Floor WARF, Madison, WI 53726 USA. EM kleinb@epi.ophth.wisc.edu OI Bailey-Wilson, Joan/0000-0002-9153-2920 NR 43 TC 39 Z9 39 U1 0 U2 1 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 FEB PY 2005 VL 46 IS 2 BP 555 EP 560 DI 10.1167/iovs.04-0729 PG 6 WC Ophthalmology SC Ophthalmology GA 890WP UT WOS:000226542100022 PM 15671282 ER PT J AU Riazuddin, SA Yasmeen, A Zhang, QJ Yao, WL Sabar, MF Ahmed, Z Riazuddin, S Hejtmancik, JF AF Riazuddin, SA Yasmeen, A Zhang, QJ Yao, WL Sabar, MF Ahmed, Z Riazuddin, S Hejtmancik, JF TI A new locus for autosomal recessive nuclear cataract mapped to chromosome 19q13 in a Pakistani family SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID DOMINANT CONGENITAL CATARACT; ZONULAR PULVERULENT CATARACT; ADULT I-PHENOTYPE; NONSENSE MUTATION; GENE; ASSOCIATION; BLINDNESS; LINKAGE; BLOOD; MAPS AB PURPOSE. To identify the disease locus of autosomal recessive congenital nuclear cataracts in a consanguineous Pakistani family. METHODS. A large Pakistani family with multiple individuals affected by autosomal recessive congenital cataracts was ascertained. Patients were examined, blood samples were collected, and DNA was isolated. A genome- wide scan was performed using 382 polymorphic microsatellite markers on genomic DNA from affected and unaffected family members. Two- point lod scores were calculated, and haplotypes were formed by inspection. RESULTS. In the genome- wide scan, a maximum lod score of 2.89 was obtained for marker D19S414 on 19q13. Fine mapping using D19S931, D19S433, D19S928, D19S225, D19S416, D19S213, D19S425, and D19S220 markers from the Genethon database showed that markers in a 14.3- cM ( 12.66- Mb) interval flanked by D19S928 and D19S420 cosegregated with the cataract locus. Lack of homozygosity further suggests that the cataract locus may lie in a 7- cM ( 4.3- Mb) interval flanked by D19S928 proximally and D19S425 distally. On fine mapping, a maximum lod score of 3.09 was obtained with D19S416 at theta = 0. CONCLUSIONS. Linkage analysis identified a new locus for autosomal recessive congenital nuclear cataracts on chromosome 19q13 in a consanguineous Pakistani family. C1 NEI, OGVFB, NIH, Bethesda, MD 20892 USA. Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. RP Hejtmancik, JF (reprint author), NEI, OGVFB, NIH, Bldg 10,Room 10B10,10 Ctr Dr MSC 1860, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov RI SHEIKH, RIAZUDDIN/L-2406-2015 NR 29 TC 30 Z9 30 U1 0 U2 1 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 FEB PY 2005 VL 46 IS 2 BP 623 EP 626 DI 10.1167/iovs.04-0955 PG 4 WC Ophthalmology SC Ophthalmology GA 890WP UT WOS:000226542100031 PM 15671291 ER PT J AU Kim, H Csaky, KG Gilger, BC Dunn, JP Lee, SS Tremblay, M de Monasterio, F Tansey, G Yuan, P Bungay, PM Lutz, RJ Robinson, MR AF Kim, H Csaky, KG Gilger, BC Dunn, JP Lee, SS Tremblay, M de Monasterio, F Tansey, G Yuan, P Bungay, PM Lutz, RJ Robinson, MR TI Preclinical evaluation of a novel episcleral cyclosporine implant for ocular graft-versus-host disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID BONE-MARROW TRANSPLANTATION; KERATOCONJUNCTIVITIS SICCA; DRUG-DELIVERY; DRY EYE; RABBIT; SCLERA; FIBROBLASTS; DIFFUSION; RELEASE; TISSUES AB PURPOSE. To develop a local drug delivery system that provides therapeutic cyclosporine levels to treat lacrimal gland graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. METHODS. Episcleral cyclosporine implants were manufactured with a silicone- based matrix design, and in vitro release rates were determined. Preclinical evaluation included toxicology ( clinical examination, serial electroretinography, and histopathology) in normal rabbits and dogs, pharmacokinetics in normal rabbits, and pharmacodynamics in a canine model of aqueous tear deficiency and keratoconjunctivitis sicca. RESULTS. The cyclosporine implants showed sustained release of drug over time with in vitro assays. Histopathology showed normal ocular tissues in both dogs and rabbits 6 months after implantation. The cyclosporine implant produced lacrimal gland drug levels 1 to 2 log units higher than those reported with a variety of topical cyclosporine formulations and oral administration. The cyclosporine implant was effective in a canine model of keratoconjunctivitis sicca, with all animals able to discontinue topical cyclosporine and maintain normal Schirmer scores over a 6- month follow- up. CONCLUSIONS. This preclinical evaluation showed that the episcleral cyclosporine implant was safe, delivered potentially therapeutic cyclosporine levels to the lacrimal gland, and showed efficacy in a clinically relevant model of keratoconjunctivitis sicca. The episcleral cyclosporine implant shows promise in reducing the morbidity associated with lacrimal gland graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. In addition, continuous release of cyclosporine in the subconjunctival space with the episcleral implant was an effective means of delivering drug to the ocular surface and may have potential in treating other ocular inflammatory diseases. C1 NEI, NIH, Bethesda, MD 20892 USA. N Carolina State Univ, Coll Vet Med, Raleigh, NC USA. Johns Hopkins Univ Hosp, Wilmer Eye Inst, Baltimore, MD 21287 USA. NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. RP Robinson, MR (reprint author), NEI, NIH, 10-10S229,10 Ctr Dr,MSC 1863, Bethesda, MD 20892 USA. EM robinsonm@nei.nih.gov NR 48 TC 26 Z9 29 U1 0 U2 5 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 FEB PY 2005 VL 46 IS 2 BP 655 EP 662 DI 10.1167/iovs.04-1076 PG 8 WC Ophthalmology SC Ophthalmology GA 890WP UT WOS:000226542100036 PM 15671296 ER PT J AU Van Rompay, KKA Abel, K Lawson, JR Singh, RP Schmidt, KA Evans, T Earl, P Harvey, D Franchini, G Tartaglia, J Montefiori, D Hattangadi, S Moss, B Marthas, ML AF Van Rompay, KKA Abel, K Lawson, JR Singh, RP Schmidt, KA Evans, T Earl, P Harvey, D Franchini, G Tartaglia, J Montefiori, D Hattangadi, S Moss, B Marthas, ML TI Attenuated poxvirus-based simian immunodeficiency virus (SIV) vaccines given in infancy partially protect infant and juvenile macaques against repeated oral challenge with virulent SIV SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE pediatric; HIV; AIDS; macaque; infant; breast-feeding; transmission; vaccine; poxvirus ID NEWBORN RHESUS MACAQUES; TO-CHILD TRANSMISSION; CD8(+) LYMPHOCYTES; CANARYPOX VACCINE; IMMUNE-RESPONSES; BREAST-MILK; PROLONGS SURVIVAL; HIV-1 INFECTION; TYPE-1; TENOFOVIR AB An infant macaque model was developed to test pediatric vaccine candidates aimed at reducing HIV transmission through breast-feeding. Infant macaques were given multiple immunizations during the first 3 weeks of life with recombinant poxvirus vaccines expressing simian immunodeficiency virus (SIV) structural proteins Gag, Pol, and Env (ALVAC-SIV or modified vaccinia virus Ankara [MVA]-SIV). After repeated daily oral inoculations with virulent SIVmac251 at 4 weeks of age, significantly fewer ALVAC-SIV-immunized infants were infected compared with unimmunized infants. Monkeys not infected after oral challenge in infancy were rechallenged at 16 months of age or older by repeated weekly oral SIV exposure; unimmunized animals were infected after fewer SIV exposures than were animals vaccinated with ALVAC-SIV or MVA-SIV When infected, ALVAC-SIV- and MVA- SIV-vaccinated animals also ha reduced viremia compared with unimmunized animals. The results of these investigations suggest that immunization of human infants wit poxvirus-based HIV vaccine candidates may offer protection against early and late HIV infection through breastfeeding. C1 Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. Univ Calif Davis, Div Infect Dis, Sch Med, Davis, CA 95616 USA. Univ Calif Davis, Div Biostat, Dept Epidemiol & Prevent Med, Sch Med, Davis, CA 95616 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Aventis Pasteur Ltd, Toronto, ON, Canada. Duke Univ, Med Ctr, Durham, NC USA. RP Marthas, ML (reprint author), Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. EM mlmarthas@ucdavis.edu FU NCRR NIH HHS [RR00169, RR16001]; NIAID NIH HHS [AI46320, AI39109] NR 57 TC 72 Z9 74 U1 0 U2 2 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 FEB 1 PY 2005 VL 38 IS 2 BP 124 EP 134 DI 10.1097/00126334-200502010-00002 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 893RL UT WOS:000226736800002 PM 15671796 ER PT J AU Chan, K Puck, JM AF Chan, K Puck, JM TI Development of population-based newborn screening for severe combined immunodeficiency SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE SCID; newborn screening; TREC; T-cell receptor excision circle; T-cell maturation; early intervention; primary immunodeficiency; cost-effectiveness; bone marrow transplant; dried blood spots ID STEM-CELL TRANSPLANTATION; GENE-THERAPY; THYMIC FUNCTION; MUTATIONS; DEFICIENCY; CD45; AGE; RECONSTITUTION; EXPRESSION; SURVIVAL AB Background: Severe combined immunodeficiency (SCID) is a treatable, inherited lack of cellular and Immoral immunity caused by diverse mutations in several different genes and leading to death in infancy unless immune reconstitution is provided. Currently no population screening exists for SCID, but early diagnosis would improve outcome. Objective: Because all patients with SCID make few or no T cells, we asked whether the absence of T-cell receptor excision circles (TRECs), DNA episomes in newly formed T cells, could identify SCID regardless of genotype. Methods: DNA isolated from dried blood spots was assayed by real-time PCR to quantitate TRECs. Control PCR was performed on a segment of the P-actin gene. After pilot studies with adult and cord blood control subjects, blood from SCID patients was spotted onto filters and tested, followed by screening of actual blood spots from the Maryland Newborn Screening Program. Finally, newborn blood spots were recovered and tested from 2 infants after their diagnosis of SCID. Results: In contrast to filters from the newborn screening program, which had a mean of 1020 TRECs in two 3-mm punches, samples from 23 infants with SCID had < 30 TRECs. The newborn screening filter was retrieved from a state laboratory for one of these infants plus another infant who had died of SCID previously; although both samples had detectable R-actin DNA, neither had TRECs. Conclusion: TRECs are a stable analyte that can identify T-cell lymphopenia in newborn dried blood spots so that infants with SCID can receive early, life-saving treatment. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med Epidemiol & Publ Hlth, New Haven, CT 06520 USA. RP Puck, JM (reprint author), NHGRI, NIH, 49 Convent Dr,Bldg 49,Room 4A14, Bethesda, MD 20892 USA. EM JPuck@mail.nih.gov NR 51 TC 145 Z9 154 U1 3 U2 8 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 FEB PY 2005 VL 115 IS 2 BP 391 EP 398 DI 10.1016/j.jaci.2004.10.012 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 897YU UT WOS:000227043600029 PM 15696101 ER PT J AU Egwuagu, CE Yu, CR Li, ZQ Nussenblatt, RB AF Egwuagu, CE Yu, CR Li, ZQ Nussenblatt, RB TI SOCS5 mRNA levels in peripheral blood mononuclear cells (PBMC): a potential bio-marker for monitoring response of uveitis patients to Daclizumab therapy SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE uveitis; SOCS; SOCS5; Daclizumab therapy; bio-marker; JAK/STAT ID NEGATIVE REGULATION; POSTERIOR UVEITIS; BINDING PROTEIN; CYTOKINE; ACTIVATION; SUPPRESSOR; INTERMEDIATE; MAINTENANCE; LENS AB Uveitis is an intraocular inflammatory disease mediated by Th1 lymphocytes. Therapy for severe uveitis is frequently long-term immunosuppression using systemic corticosteroids and cytotoxic agents, but side effects make long-term therapy difficult. Long-term humanized anti-interleukin-2 (IL-2) receptor alpha (Daclizumab) therapy has few side effects and is as effective as standard immunosuppression for treating severe uveitis. However, it is necessary to carefully monitor levels of activated T cells in the eye to allow prompt re-institution of standard immuno suppressive therapy to non-responders to Daclizumab therapy. Suppressors of cytokine signaling (SOCS) are feedback regulators of Th1/Th2 cytokines. SOCS5 and SOCS3 are preferentially expressed in Th1 and Th2 cells, respectively, and are thought to be lineage markers for T-helper cells. In this study, we have investigated whether SOCS3 or SOCS5 expression can serve as surrogate markers of T-cell levels in the eye. Compared to healthy volunteers, SOCS5 mRNA is significantly elevated in PBMC of uveitis patients while SOCS3 is decreased. However, after Daclizumab therapy SOCS5 mRNA level is significantly decreased, suggesting that SOCS5 mRNA can be used as diagnostic tool to monitor therapeutic response of uveitis patients. Our data also suggest that SOCS5 may serve as a new therapeutic target for uveitis and other autoimmune diseases. Published by Elsevier Ltd. C1 NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Clin Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, Immunol Lab, NIH, Bldg 10,Room 10N116,10 Ctr Dr, Bethesda, MD 20892 USA. EM egwuaguc@nei.nih.gov NR 23 TC 8 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD FEB PY 2005 VL 24 IS 1 BP 39 EP 46 DI 10.1016/j.jaut.2004.11.006 PG 8 WC Immunology SC Immunology GA 905TJ UT WOS:000227592600005 PM 15725575 ER PT J AU Gerbaud, P Petzold, L Therond, P Anderson, WB Evain-Brion, D Raynaud, F AF Gerbaud, P Petzold, L Therond, P Anderson, WB Evain-Brion, D Raynaud, F TI Differential regulation of Cu, Zn- and Mn-superoxide dismutases by retinoic acid in normal and psoriatic human fibroblasts SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE psoriasis; superoxide dismutases; free radicals; fibroblasts; retinoic acid ID DEPENDENT PROTEIN-KINASE; OXIDATIVE STRESS; OXYGEN RADICALS; MESSENGER-RNA; CELLS; EXPRESSION; ALPHA; SKIN; SOD; IDENTIFICATION AB Superoxide dismutases' (SODs) expression is altered in several diseases including Alzheimer, atherosclerosis, cancer and psoriasis. Previously, we reported a marked increase in Mn-SOD and Cu,Zn-SOD functional activity in human dermal psoriatic fibroblasts. As retinoic acid (RA) has been used in the treatment of psoriasis and a mechanism for its beneficial effects is not understood, we investigated the effects of RA on SOD mRNA and protein expression levels in human normal and psoriatic fibroblasts. Prior to RA exposure, Cu,Zn-SOD protein and mRNA levels were similar in normal compared to psoriatic fibroblasts while Mn-SOD protein and mRNA levels were increased in psoriatic cells. However, in contrast to normal fibroblasts, exposure of psoriatic fibroblasts to 1 mu M RA down-regulated Mn-SOD mRNA, and also decreased Mn-SOD activity by similar to 80% with no change in Mn-SOD protein levels. In contrast, Cu,Zn-SOD protein and enzymatic activity were modestly reduced by RA treatment in both normal and psoriatic fibroblasts. Furthermore, RA treatment of psoriatic fibroblasts also caused a decrease in Cu,Zn-SOD steady-state mRNA levels. These results indicate that RA can serve as a regulatory agent to down-regulate the steady-state levels of both Mn-SOD and Cu,Zn-SOD in psoriatic cells. These findings offer a new model for the antiinflammatory activity of RA when used in the treatment of psoriasis. (c) 2004 Elsevier Ltd. All rights reserved. C1 Inst Andre Lwoff, CNRS, UPR 9045, Villejuif, France. Univ Paris 05, INSERM, U 427, Fac Sci Pharmaceut & Biol Paris, F-75270 Paris, France. Hop Bicetre, Serv Biochim, Le Kremlin Bicetre, France. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Raynaud, F (reprint author), Inst Andre Lwoff, CNRS, UPR 9045, 7 Rue Guy Moquet,BP 8-94, Villejuif, France. EM raynaud@vjf.cnrs.fr NR 46 TC 2 Z9 3 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD FEB PY 2005 VL 24 IS 1 BP 69 EP 78 DI 10.1016/j.jaut.2004.10.003 PG 10 WC Immunology SC Immunology GA 905TJ UT WOS:000227592600009 PM 15725579 ER PT J AU Nagano, K Read, EK Murakami, Y Masuda, T Noguchi, T Yoshimura, F AF Nagano, K Read, EK Murakami, Y Masuda, T Noguchi, T Yoshimura, F TI Trimeric structure of major outer membrane proteins homologous to OmpA in Porphyromonas gingivalis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; BACTEROIDES-GINGIVALIS; DISULFIDE BOND; IDENTIFICATION; VIRULENCE; SEQUENCE; ANTIGENS; ANAEROBE; PORINS AB The major outer membrane proteins Pgm6 (41 kDa) and Pgm7 (40 kDa) of Porphyromonas gingivalis ATCC 33277 are encoded by open reading frames pg0695 and pg0694, respectively, which form a single operon. Pgm6 and Pgm7 (Pgm6/7) have a high degree of similarity to Escherichia coli OmpA in the C-terminal region and are predicted to form eight-stranded beta-barrels in the N-terminal region. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Pgm6/7 appear as bands with apparent molecular masses of 40 and 120 kDa, with and without a reducing agent, suggesting a monomer and trimer, respectively. To verify the predicted trimeric structure and function of Pgm6/7, we constructed three mutants with pg0695, pg0694, or both deleted. The double mutant produced no Pgm6/7. The single-deletion mutants appeared to contain less Pgm7 and Pgm6 and to form homotrimers that migrated slightly faster (115 kDa) and slower (130 kDa), respectively, than wild-type Pgm6/7 under nonreducing conditions. N-terminal amino acid sequencing and mass spectrometry analysis of partially digested Pgm6/7 detected only fragments from Pgm6 and Pgm7. Two-dimensional, diagonal electrophoresis and chemical cross-linking experiments with or without a reducing agent clearly showed that Pgm6/7 mainly form stable heterotrimers via intermolecular disulfide bonds. Furthermore, growth retardation and arrest of the three mutants and increased permeability of their outer membranes indicated that Pgm6/7 play an important role in outer membrane integrity. Based on results of liposome swelling experiments, these proteins are likely to function as a stabilizer of the cell wall rather than as a major porin in this organism. C1 Aichi Gakuin Univ, Dept Microbiol, Sch Dent, Nagoya, Aichi 4648650, Japan. Aichi Gakuin Univ, Dept Periodontol, Sch Dent, Nagoya, Aichi 4648650, Japan. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Yoshimura, F (reprint author), Aichi Gakuin Univ, Dept Microbiol, Sch Dent, Nagoya, Aichi 4648650, Japan. EM fuminobu@dpc.aichi-gakuin.ac.jp NR 50 TC 31 Z9 31 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 2005 VL 187 IS 3 BP 902 EP 911 DI 10.1128/JB.187.3.902-911.2005 PG 10 WC Microbiology SC Microbiology GA 893FR UT WOS:000226705200011 PM 15659668 ER PT J AU Demirel, MC Keskin, O AF Demirel, MC Keskin, O TI Protein interactions and fluctuations in a proteomic network using an elastic network model SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID DYNAMICS; STABILITY; MOTIONS; SLOW AB A set of protein conformations are analyzed by normal mode analysis. An elastic network model is used to obtain fluctuation and cooperativity of residues with low amplitude fluctuations across different species. Slow modes that are associated with the function of proteins have common features among different protein structures. We show that the degree of flexibility of the protein is important for proteins to interact with other proteins and as the species gets more complex its proteins become more flexible. In the complex organism. higher cooperativity arises due to protein structure and connectivity. C1 Penn State Univ, Coll Engn, University Pk, PA 16802 USA. Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Istanbul, Turkey. Koc Univ, Coll Engn, TR-34450 Istanbul, Turkey. NCI, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. RP Demirel, MC (reprint author), Penn State Univ, Coll Engn, University Pk, PA 16802 USA. EM melikdemirel@psu.edu RI Demirel, Melik/E-4495-2010 NR 22 TC 15 Z9 15 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD FEB PY 2005 VL 22 IS 4 BP 381 EP 386 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 887OW UT WOS:000226316400001 PM 15588102 ER PT J AU Collins, MT Kushner, H Reynolds, JC Chebli, C Kelly, MH Gupta, A Brillante, B Leet, AI Riminucci, M Robey, PG Bianco, P Wientroub, S Chen, CC AF Collins, MT Kushner, H Reynolds, JC Chebli, C Kelly, MH Gupta, A Brillante, B Leet, AI Riminucci, M Robey, PG Bianco, P Wientroub, S Chen, CC TI An instrument to measure skeletal burden and predict functional outcome in fibrous dysplasia of bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE fibrous dysplasia; outcomes(s); instrument; disease burden; McCune-Albright syndrome; GNAS ID MCCUNE-ALBRIGHT-SYNDROME; STIMULATORY G-PROTEIN; PRECOCIOUS PUBERTY; DYSFUNCTION; MUTATIONS; GENE; PIGMENTATION; DISEASE; IMAGE AB An instrument to measure skeletal burden in fibrous dysplasia was developed. Biological and clinical relevance was shown by correlating skeletal burden scores with bone markers, quality of life, and ambulatory status. Childhood scores predict adult ambulatory status, and scores were unaffected when bone markers decreased with bisphosphonate treatment or aging. C1 NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Biomed Comp Res Inst, Philadelphia, PA USA. NIH, Dept Nucl Med, Dept Hlth & Human Serv, Bethesda, MD USA. Univ Maryland, Dept Orthopaed Surg, Baltimore, MD 21201 USA. NIH, Warren G Magnuson Clin Ctr, Dept Nursing Serv, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Orthoped, Div Pediat Orthoped, Baltimore, MD USA. Sperimentale Univ Laquila, Dipartimento Med, Laquila, Italy. Parco Sci Biomed San Raffaele, Rome, Italy. Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, Rome, Italy. Tel Aviv Univ, Sackler Fac Med, Tel Aviv Med Ctr, Dana Childrens Hosp,Dept Pediat Orthopaed Surg, IL-69978 Tel Aviv, Israel. RP Collins, MT (reprint author), NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, 30 Convent Dr,MSC 4320, Bethesda, MD 20892 USA. EM mc247k@nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 24 TC 41 Z9 42 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2005 VL 20 IS 2 BP 219 EP 226 DI 10.1359/JBMR.041111 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 889RT UT WOS:000226460800006 PM 15647815 ER PT J AU Hillion, JA Takahashi, K Maric, D Ruetzler, C Barker, JL Hallenbeck, JM AF Hillion, JA Takahashi, K Maric, D Ruetzler, C Barker, JL Hallenbeck, JM TI Development of an ischemic tolerance model in a PC12 cell line SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE apoptosis; OGD; PC12; preconditioning ID RAT CORTICAL-NEURONS; IN-VITRO; GROWTH-FACTOR; PARKINSONS-DISEASE; DRUG DISCOVERY; HYPOXIC STRESS; TNF-ALPHA; APOPTOSIS; PROTEIN; DEATH AB Although ischemic tolerance has been described in a variety of primary cell culture systems, no similar in vitro models have been reported with any cell line. A model of ischemic preconditioning in the rat pheochromocytoma PC12 cell line is described here. When compared to nonpreconditioned cells, preexposure of PC12 cells to 6 hours of oxygen and glucose deprivation (OGD) significantly increased cell viability after 15 hours of OGD 24 hours later. Flow cytometry analysis of cells labeled with specific markers for apoptosis, Annexin V, and Hoechst 33342, and of DNA content, revealed that apoptosis is involved in OGD-induced PC12 cell death and that preconditioning of the cells mainly counteracts the effect of apoptosis. Immunocytochemistry of caspase-3, a central executioner in the apoptotic process, further confirmed the activation of apoptotic pathways in OGD-induced PC12 cell death. This model may be useful to investigate the cellular mechanisms involved in neuronal transient tolerance following ischemia. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Hillion, JA (reprint author), NINDS, Stroke Branch, NIH, 36 Convent Dr MSC 4128,Bldg 36,Room 4B16, Bethesda, MD 20892 USA. EM hillionj@ninds.nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 43 TC 70 Z9 78 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 2005 VL 25 IS 2 BP 154 EP 162 DI 10.1038/sj.jcbfm.9600003 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 893SS UT WOS:000226740100002 PM 15647748 ER PT J AU Vitiello, B AF Vitiello, B TI Pharmacoepidemiology and pediatric psychopharmacology research SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Editorial Material ID CHILDREN C1 NIMH, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Room 7147,6001 Execut Blvd,MSC 9633, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov NR 3 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FEB PY 2005 VL 15 IS 1 BP 10 EP 11 DI 10.1089/cap.2005.15.10 PG 2 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 907RW UT WOS:000227736600003 PM 15741781 ER PT J AU Bloch, M Rubinow, DR Schmidt, PJ Lotsikas, A Chrousos, GP Cizza, G AF Bloch, M Rubinow, DR Schmidt, PJ Lotsikas, A Chrousos, GP Cizza, G TI Cortisol response to ovine corticotropin-releasing hormone in a model of pregnancy and parturition in euthymic women with and without a history of postpartum depression SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-ADRENAL AXIS; PSYCHOSOCIAL STRESS; GENE-EXPRESSION; MENSTRUAL-CYCLE; 3RD TRIMESTER; LEPTIN LEVELS; PLASMA; RISK AB Hypothalamic-pituitary-adrenal axis abnormalities have been reported in depressed women and those with postpartum blues, compared with nondepressed women. We investigated the effect of gonadal steroids on the hormonal response to ovine CRH in women with (n = 5) and without (n = 7) a past history of postpartum depression (PPD) by creating an endocrine model of pregnancy and the postpartum. Ovine CRH (1 mug/kg) stimulation tests were performed in the baseline follicular phase, during hormone add-back (leuprolide acetate plus supraphysiologic doses of estradiol and progesterone-mimicking pregnancy), and after precipitous withdrawal of hormone replacement (mimicking the puerperium). Significant phase by time (P < 0.005) and phase by diagnosis (P < 0.05) interactions were observed, reflecting increased stimulated cortisol during the supraphysiologic phase, particularly in subjects with a history of PPD. Cortisol area under the curve also showed a significant phase by diagnosis effect (P < 0.05). Significant increases during the supraphysiologic phase were also seen for urinary free cortisol (P < 0.05), cortisol area under the curve (P < 0.001), and plasma corticosteroid-binding globulin (P < 0.05). Our data show that in humans, as in animals, supraphysiologic gonadal steroid levels enhance pituitary-adrenal axis activity, and, further, that women with a history of PPD have an enhanced sensitivity of the pituitary-adrenal axis to gonadal steroids. C1 NIMH, Behav Endocrinol Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. Tel Aviv Sourasky Med Ctr, Dept Psychiat, IL-64239 Tel Aviv, Israel. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Rubinow, DR (reprint author), NIMH, Behav Endocrinol Branch, NIH, US Dept HHS, Bldg 10,Room 3N238,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA. EM rubinowd@intra.nimh.nih.gov NR 27 TC 54 Z9 55 U1 1 U2 6 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 FEB PY 2005 VL 90 IS 2 BP 695 EP 699 DI 10.1210/jc.2004-1388 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 895HD UT WOS:000226850700014 PM 15546899 ER PT J AU Moeller, LC Dumitrescu, AM Walker, RL Meltzer, PS Refetoff, S AF Moeller, LC Dumitrescu, AM Walker, RL Meltzer, PS Refetoff, S TI Thyroid hormone responsive genes in cultured human fibroblasts SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ELEMENT-BINDING PROTEIN; HUMAN-SKIN FIBROBLASTS; RECEPTOR-BETA GENE; KNOCKOUT MICE; FIBRONECTIN SYNTHESIS; EXPRESSION; RESISTANCE; TRANSCRIPTION; ACTIVATION; SUPPRESSION AB Human skin fibroblasts are readily accessible cells for propagation in culture without transformation that can serve for direct pathophysiology studies in subjects with inherited diseases. We thus examined by quantitative fluorescent cDNA microarray analysis the effect of thyroid hormone (TH) on the expression of more than 15,000 genes in fibroblasts of two normal individuals. Fibroblasts from two subjects with resistance to thyroid hormone (RTH) due to mutations in the TH receptor-beta gene were used to confirm the specificity of the hormonal effect by the ability to discriminate between normal cells and cells with a defect in TH action. Microarray analysis identified 148 genes induced by 1.4-fold or more and five genes repressed to 0.7 or less 24 h after treatment with 2 X 10(-9) M T(3). Taking into account duplicate genes, these represented 91 up-regulated and five down-regulated genes, respectively. Confirmation by real-time PCR was obtained in eight of 10 induced and two of three repressed genes that were tested. Further evidence for T(3)-specific induction was provided by a graded dose response absent in fibroblasts from the patients with RTH. The following genes not previously known to be induced by TH were identified and validated: aldo-keto reductase family 1 C1-3, collagen type VI alpha3, member RAS oncogene family brain antigen RAB3B, platelet phosphofructokinase, hypoxia-inducible factor-1alpha, and enolase 1alpha. These genes as well as three known to be TH regulated in other species and found in this study also in human cells (glucose transporter 1, solute carrier family 16 member 3, and basic transcription element-binding protein 1) have a variety of regulatory functions in development and metabolism. TH seems to induce these genes by initiating either genomic or nongenomic mechanisms. Surprisingly, TH-mediated down-regulation of fibroblast growth factor 7 and alcohol dehydrogenase 1B persisted in fibroblasts from patients with RTH. This first systematic study of TH-mediated gene expression in normal human cells identifies several new TH-responsive genes and demonstrates that skin fibroblasts are suitable for the study of TH action in health and disease. C1 Univ Chicago, Dept Med, Committees Genet & Mol Med, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Committees Genet & Mol Med, Chicago, IL 60637 USA. Univ Chicago, Dept Human Genet, Committees Genet & Mol Med, Chicago, IL 60637 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Refetoff, S (reprint author), Univ Chicago, Dept Med, Committees Genet & Mol Med, MC3090,5841 S Maryland Ave, Chicago, IL 60637 USA. EM refetoff@uchicago.edu OI Moeller, Lars/0000-0002-9330-9036 FU NCRR NIH HHS [RR00055]; NIDDK NIH HHS [DK 15070] NR 42 TC 44 Z9 46 U1 1 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 FEB PY 2005 VL 90 IS 2 BP 936 EP 943 DI 10.1210/jc.2004-1768 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 895HD UT WOS:000226850700052 PM 15507505 ER PT J AU Fauci, AS Challberg, MD AF Fauci, AS Challberg, MD TI Host-based antipoxvirus therapeutic strategies: turning the tables SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID ERBB SIGNALING NETWORK; VACCINIA VIRUS; GROWTH-FACTOR; SMALLPOX; BIOTERRORISM AB The potential threat of the smallpox virus as a bioterror weapon has long been recognized, and the need for developing suitable countermeasures has become especially acute following the events of September 2001. Traditional antiviral agents interfere with viral proteins or functions. In a new study, Yang et al. focus instead on host cellular pathways used by the virus. A drug that interferes with the cellular ErbB-1 signal transduction pathway, activated by smallpox growth factor, sheds new light on how the virus replicates in the cell (see the related article beginning on page 379). Drugs that target the ErbB-signaling pathways represent a promising new class of antiviral agents. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, Bldg 31,Room 7A03,9000 Rockville Pike, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 22 TC 15 Z9 16 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2005 VL 115 IS 2 BP 231 EP 233 DI 10.1172/JCI200524270 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 895ML UT WOS:000226867300007 PM 15690079 ER PT J AU LeRoith, D Nissley, P AF LeRoith, D Nissley, P TI Knock your SOCS off! SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID GROWTH-FACTOR-I; CYTOKINE SIGNALING-2; HORMONE; MICE; RECEPTOR; SUPPRESSOR; ENHANCEMENT; MUTATION; STAT5B; SHP-2 AB The growth hormone/IGF-1-signaling (GH/IGF-1-signaling) system is involved in numerous physiological processes during normal growth and development and also in the aging process. Understanding the regulation of this system is therefore of importance to the biologist. Studies conducted over the past decade have shown that the JAK/STAT pathways are involved in GH signaling to the nucleus. More recently, evidence has been presented that a member of the SOCS family, SOCS2, is a negative regulator of GH signaling. This story began several years ago with the dramatic demonstration of gigantism in the SOCS2-knockout mouse. A more specific definition of the role of SOCS2 in GH signaling is provided in this issue of the JCI (see the related article beginning on page 397) by the demonstration that the overgrowth phenotype of the SOCS2(-/-) mouse is dependent upon the presence of endogenous GH and that administration of GH to mice lacking both endogenous GH and SOCS2 produced excessive growth. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Diabet Branch, NIH, Room 8D12,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM derek@helix.nih.gov NR 20 TC 29 Z9 29 U1 1 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2005 VL 115 IS 2 BP 233 EP 236 DI 10.1172/JCI200524228 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 895ML UT WOS:000226867300008 PM 15690080 ER PT J AU O'Connor, OA Wright, J Moskowitz, C Muzzy, J MacGregor-Cortelli, B Stubblefield, M Straus, D Portlock, C Hamlin, P Choi, E Dumetrescu, O Esseltine, D Trehu, E Adams, J Schenkein, D Zelenetz, AD AF O'Connor, OA Wright, J Moskowitz, C Muzzy, J MacGregor-Cortelli, B Stubblefield, M Straus, D Portlock, C Hamlin, P Choi, E Dumetrescu, O Esseltine, D Trehu, E Adams, J Schenkein, D Zelenetz, AD TI Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NF-KAPPA-B; CHRONIC LYMPHOCYTIC-LEUKEMIA; DRUG-RESISTANCE; APOPTOSIS; CANCER; PS-341; EXPRESSION; ARREST; TRIAL; MALIGNANCIES AB Purpose To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent and mantle-cell lymphoma (MCL). Patients and Methods Patients with indolent and MCL were eligible. Bortezomib was given at a dose of 1.5 mg/m(2) on days 1, 4, 8, and 11. Patients were required to have received no more than three prior chemotherapy regimens, with at least I month since the prior treatment, 3 months from prior rituximab, and 7 days from prior corticosteroids; absolute neutrophil count more than 1,500/muL (500/muL if documented bone marrow involvement); and platelet count more than 50,000/muL. Results Twenty-six patients were registered, of whom 24 were assessable. Ten patients had follicular lymphoma, 11 had MCL, three had small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL), and two had marginal zone lymphoma. The overall response rate was 58%, with one complete remission (CR), one unconfirmed CR (CRu), and four partial remissions (PR) among patients with follicular non-Hodgkin's lymphoma (NHL). All responses were durable, lasting from 3 to 24+ months. One patient with MCL achieved a CRu, four achieved a PR, and four had stable disease. One patient with MCL maintained his remission for 19 months. Both patients with marginal zone lymphoma achieved PR lasting 8+ and 11+ months, respectively. Patients with SILL or CLL have yet to respond. Overall, the drug was well tolerated, with only one grade 4 toxicity (hyponatremia). The most common grade 3 toxicities were lymphopenia (n = 14) and thrombocytopenia (n = 7). Conclusion These data suggest that bortezomib was well tolerated and has significant single-agent activity in patients with certain subtypes of NHL. C1 Mem Sloan Kettering Canc Ctr, Dept Med, Lymphoma & Dev Chemotherapy Serv, Div Hematol Oncol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Rehabil Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. Millennium Pharmaceut, Cambridge, MA USA. Natl Canc Inst, Drug Dev Branch, Bethesda, MD USA. RP O'Connor, OA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Lymphoma & Dev Chemotherapy Serv, Div Hematol Oncol, 1275 York Ave,Box 329, New York, NY 10021 USA. EM oconnoro@mskcc.org OI Zelenetz, Andrew/0000-0003-1403-6883 FU NCI NIH HHS [UO1 CA 69913] NR 38 TC 403 Z9 416 U1 0 U2 11 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 FEB 1 PY 2005 VL 23 IS 4 BP 676 EP 684 DI 10.1200/JCO.2005.02.050 PG 9 WC Oncology SC Oncology GA 893SG UT WOS:000226738900006 PM 15613699 ER PT J AU Marshall, JL Gulley, JL Arlen, PM Beetham, PK Tsang, KY Slack, R Hodge, JW Doren, S Grosenbach, DW Hwang, J Fox, E Odogwu, L Park, S Panicali, D Schlom, J AF Marshall, JL Gulley, JL Arlen, PM Beetham, PK Tsang, KY Slack, R Hodge, JW Doren, S Grosenbach, DW Hwang, J Fox, E Odogwu, L Park, S Panicali, D Schlom, J TI Phase I study of sequential vaccinations with fowlpox-CEA(6D)-TRICOM alone and sequentially with vaccinia-CEA(6D)-TRICOM, with and without granulocyte-macrophage colony-stimulating factor, in patients with carcinoembryonic antigen-expressing carcinomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; CYTOTOXIC T-LYMPHOCYTE; ADVANCED COLORECTAL-CANCER; TUMOR-ASSOCIATED ANTIGENS; IMMUNE-RESPONSES; COSTIMULATORY MOLECULE; ANTITUMOR-ACTIVITY; DENDRITIC CELLS; PEPTIDE; GENE AB Purpose Our previous clinical experience with vaccinia and replication-defective avipox recombinant carcinoembryonic antigen (CEA) vaccines has demonstrated safety and clinical activity with a correlation between CEA-specific immune response and survival. Preclinical evidence demonstrated that the addition of the transgenes for three T-cell costimulatory molecules (B7-1, ICAM-1, LFA-3, designated TRICOM) results in a significant improvement in antigen-specific T-cell responses and antitumor activity. We describe here the first trial in humans of the CEA-TRICOM vaccines (also including an enhancer agonist epitope within the CEA gene). Patients and Methods Fifty-eight patients with advanced CEA-expressing cancers were accrued to eight cohorts that involved vaccinations with the following: replication-defective fowlpox recombinant (rF)-CEA(6D)-TRlCOM; primary vaccination with recombinant vaccinia (rV)-CEA(6D)-TRICOM plus rF-CEA(6D)-TRICOM booster vaccinations; and rV-CEA(6D)-TRICOM and then rF-CEA(6D)-TRICOM, plus granulocyte-macrophage colony-stimulating factor (GM-CSF) with vaccines, or with divided doses of vaccine with GM-CSF. Vaccines were administered every 28 days for six doses and then once every 3 months. Reverting to treatments every 28 days was allowed if patients progressed on the 3-month schedule. Results In this phase I study, no significant toxicity was observed. Twenty-three patients (40%) had stable disease for at least 4 months, with 14 of these patients having prolonged stable disease (> 6 months). Eleven patients had decreasing or stable serum I and one patient had a pathologic complete response. Enhanced CEA-specific T-cell responses were observed in the majority of patients tested. Conclusion We demonstrated that the CEA-TRICOM vaccines are safe and can generate significant CEA-specific immune responses, and they seem to have clinical benefit in some patients with advanced cancer. C1 Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. Natl Canc Inst, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD USA. Therion Biol Corp, Cambridge, MA USA. RP Marshall, JL (reprint author), Georgetown Univ, Med Ctr, Lombardi Canc Ctr, 3800 Reservoir Rd NW, Washington, DC 20007 USA. EM marshalj@georgetown.edu RI Hodge, James/D-5518-2015; Gulley, James/K-4139-2016 OI Hodge, James/0000-0001-5282-3154; Gulley, James/0000-0002-6569-2912 NR 40 TC 197 Z9 211 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 FEB 1 PY 2005 VL 23 IS 4 BP 720 EP 731 DI 10.1200/JCO.2005.10.206 PG 12 WC Oncology SC Oncology GA 893SG UT WOS:000226738900011 PM 15613691 ER PT J AU Irwin, ML McTiernan, A Baumgartner, RN Baumgartner, KB Bernstein, L Gilliland, FD Ballard-Barbash, R AF Irwin, ML McTiernan, A Baumgartner, RN Baumgartner, KB Bernstein, L Gilliland, FD Ballard-Barbash, R TI Changes in body fat and weight after a breast cancer diagnosis: Influence of demographic, prognostic, and lifestyle factors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECEIVING ADJUVANT CHEMOTHERAPY; PHYSICAL-ACTIVITY LEVELS; PROSPECTIVE COHORT; ENERGY-BALANCE; US ADULTS; WOMEN; GAIN; SURVIVAL; OBESITY; THERAPY AB Purpose Obese women and women who gain weight after a breast cancer diagnosis are at a greater risk for breast cancer recurrence and death compared with lean women and women who do not gain weight after diagnosis. In this population-based study, we assessed weight and body fat changes from during the first year of diagnosis to during the third year after diagnosis, and whether any changes in weight and body fat varied by demographic, prognostic, and lifestyle factors in 514 women with incident Stage 0-IIIA breast cancer. Methods Patients were participants in the Health, Eating, Activity, and Lifestyle (HEAL) study. Weight and body fat (via dual-energy x-ray absorptiometry scans) were measured during the baseline visit and 2 years later at a follow-up visit. Analysis of covariance methods were used to obtain mean weight and body fat changes adjusted for potential cofounders. Results Women increased their weight and percent body fat by 1.7 +/- 4.7 kg and 2.1% +/- 3.9%, respectively, from during their first year of diagnosis to during their third year of diagnosis. A total of 68% and 74% of patients gained weight and body fat, respectively. Greater increases in weight were observed among women diagnosed with a higher disease stage, younger age, being postmenopausal, and women who decreased their physical activity from diagnosis to up to 3 years after diagnosis (P for trend < .05). Conclusion Weight and body fat increased in the postdiagnosis period. Future research should focus on the effect of physical activity on weight and fat loss and breast cancer prognosis. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ New Mexico, Dept Internal Med, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Irwin, ML (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, POB 208034, New Haven, CT 06520 USA. EM melinda.irwin@yale.edu FU NCI NIH HHS [N01 PC067010, N01 CN005228, N01 PC035138-22, N01-CN-05228, N01-CN-75036-20, T32 CA009661, T32 CA09661]; NCRR NIH HHS [M01 RR000037, M01-RR-00037]; NICHD NIH HHS [N01-HD-3-3175] NR 44 TC 134 Z9 141 U1 0 U2 8 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 FEB 1 PY 2005 VL 23 IS 4 BP 774 EP 782 DI 10.1200/JCO.2005.04.036 PG 9 WC Oncology SC Oncology GA 893SG UT WOS:000226738900017 PM 15681521 ER PT J AU Singh, S Parulekar, W Murray, N Feld, R Evans, WK Tu, D Shepherd, FA AF Singh, S Parulekar, W Murray, N Feld, R Evans, WK Tu, D Shepherd, FA TI Influence of sex on toxicity and treatment outcome in small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CROSS-RESISTANT CHEMOTHERAPY; SOUTHWEST-ONCOLOGY-GROUP; PROGNOSTIC-FACTORS; COLORECTAL-CANCER; BODY-WEIGHT; GENDER; SURVIVAL; WOMEN; PHARMACOKINETICS; CARCINOMA AB Purpose Female sex has been shown consistently to be a favorable prognostic factor in small-cell lung cancer (SCLC). Studies have shown that women with other tumor types experience greater treatment toxicity, but there have been few studies of sex-related toxicity in SCLC. Patients and Methods This was a sex-based retrospective analysis of four SCLC trials conducted by the National Cancer Institute of Canada Clinical Trials Group between 1987 and 1999. The 1,006 patients (648 males and 358 females) received similar chemotherapy consisting of cyclophosphamide-doxorubicin-vincristine and etoposide-cisplatin. Toxicities examined included myelosuppression, stomatitis, vomiting, and infection. Other end points included dose reductions and omissions, response, and survival. Results Women experienced significantly more hematologic toxicity than men (grade 3 and 4 anemia, 16.3% v 7.6%, respectively, P < .001; grade 3 and 4 leukopenia, 80.4% v69.2%, respectively, P = .0001). However, toxic death rates were similar for men and women (1.5% v 1.1%, respectively, P = .58). Women also had significantly more stomatitis and vomiting of all grades. Despite increased toxicity, 76% of females versus 73.4% of males received all six treatment cycles (P = .38), but 52% of females versus 43.4% of males had treatment delayed for 2 weeks or more (P = .022). Only 31.8% of females and 28.2% of males had at least one cycle of chemotherapy dose reduction (P = .23). The overall response rate was 80.3% for females and 66.9% for males (P < .0001), and the median survival time was 1.31 years for females compared with only 0.91 year for males (P < .0001). Conclusion Women experience more chemotherapy-related toxicity in the treatment of SCLC, but they also have increased response rates and survival. C1 Princess Margaret Hosp, Dept Med, Div Med Oncol, Toronto, ON M5G 2M9, Canada. Univ Toronto, Toronto, ON, Canada. NCI, Clin Trials Grp, Kingston, ON, Canada. Queens Univ, Kingston, ON, Canada. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. RP Shepherd, FA (reprint author), Princess Margaret Hosp, Dept Med, Div Med Oncol, Ste 5-104,610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM frances.shepherd@uhn.on.ca NR 40 TC 43 Z9 49 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2005 VL 23 IS 4 BP 850 EP 856 DI 10.1200/JCO.2005.03.171 PG 7 WC Oncology SC Oncology GA 893SG UT WOS:000226738900026 PM 15681530 ER PT J AU Adlam, ALR Vargha-Khadem, F Mishkin, M de Haan, M AF Adlam, ALR Vargha-Khadem, F Mishkin, M de Haan, M TI Deferred imitation of action sequences in developmental amnesia SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID LONG-TERM RECALL; MEMORY; CHILDREN; INFANCY; EVENTS; INJURY AB The aims of this study were to investigate whether patients with developmental amnesia (DA) associated with bilateral hippocampal volume reduction show an impairment in incidental nonverbal recall of action sequences, and whether the severity of this memory impairment is influenced by the sequence structure (causal vs. arbitrary). Like adult-onset cases of amnesia (McDonough, Mandler, McKee, & Squire, 1995), patients with DA did not differ significantly from their age-, sex-, and IQ-matched controls in spontaneous production of the sequences prior to modeling but recalled fewer target actions and action pairs than the control group after a 24-hour delay, independent of sequence structure. Unlike the patients with adult-onset amnesia, however, the patients with DA showed some memory for both types of sequences after a 24-hour delay. This difference in severity of memory impairment might reflect differences in extent of pathology and/or age at injury. C1 Inst Child Hlth, London, England. NIMH, Bethesda, MD 20892 USA. RP Adlam, ALR (reprint author), MRC, Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge CB2 2EF, England. RI de Haan, Michelle/C-5070-2008; Adlam, Anna/F-8400-2010; Vargha-Khadem, Faraneh/C-2558-2008; OI Adlam, Anna/0000-0001-7212-4051 NR 31 TC 44 Z9 44 U1 0 U2 1 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD FEB PY 2005 VL 17 IS 2 BP 240 EP 248 DI 10.1162/0898929053124901 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 896LB UT WOS:000226934500005 PM 15811236 ER PT J AU Kralik, JD AF Kralik, JD TI Inhibitory control and response selection in problem solving: How cotton-top Tamarins (Saguinus oedipus) overcome a bias for selecting the larger quantity of food SO JOURNAL OF COMPARATIVE PSYCHOLOGY LA English DT Article ID CHIMPANZEES PAN-TROGLODYTES; FUNCTIONAL DESIGN-FEATURES; CARD SORTING TEST; PREFRONTAL CORTEX; SYMBOLIC REPRESENTATIONS; NUMBER; (SAGUINUS-OEDIPUS)/; DISCRIMINATION; PERFORMANCE; CONTINGENCY AB When presented with a choice between I and 3 pieces of food in a type of reversed contingency task, 4 Cotton-top tamarins (Saguinus oedipus) consistently chose the 3 pieces of food and received nothing, even though the choice of I piece would have yielded 3. However, in a task in which the tamarins received the I piece of food when they chose it, all subjects learned to select 1 over 3. Thus, the tamarins' prior failure on the reversed contingency task did not result entirely from an inherent inability to suppress the prepotent response of reaching to the larger of 2 quantities of food. After the experience of selecting the smaller quantity and receiving it, all of the tamarins solved the version of the reversed contingency task that they failed initially. These results suggest that the tamarins' initial failure may have reflected a difficulty with selecting an alternative response option. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Kralik, JD (reprint author), NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. EM jeraldkralik@mail.nih.gov FU NCRR NIH HHS [P51RR00168-36] NR 34 TC 26 Z9 26 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7036 J9 J COMP PSYCHOL JI J. Comp. Psychol. PD FEB PY 2005 VL 119 IS 1 BP 78 EP 89 DI 10.1037/0735-7036.119.1.78 PG 12 WC Behavioral Sciences; Psychology; Psychology, Multidisciplinary; Zoology SC Behavioral Sciences; Psychology; Zoology GA 902NZ UT WOS:000227365100009 PM 15740432 ER PT J AU Corbetta, S Baccarelli, A Aroldi, A Vicentini, L Fogazzi, GB Eller-Vainicher, C Ponticelli, C Beck-Peccoz, P Spada, A AF Corbetta, S Baccarelli, A Aroldi, A Vicentini, L Fogazzi, GB Eller-Vainicher, C Ponticelli, C Beck-Peccoz, P Spada, A TI Risk factors associated to kidney stones in primary hyperparathyroidism SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE primary hyperparathyroidism; nephrolithiasis; hypercalciuria; oxaluria ID CALCIUM-OXALATE UROLITHIASIS; PARATHYROID SURGERY; HYPEROXALURIA; NEPHROLITHIASIS; PATHOGENESIS; MAGNESIUM; EXCRETION; DISEASE; URINE; URATE AB Nephrolithiasis is the most important clinical manifestation of primary hyperparathyroidism (PHPT), although nowadays this disorder is often asymptomatic. Clinical or biochemical differences between PHPT patients with and without nephrolithiasis have not been clearly identified in most of the previous studies. The aim of the study was to investigate clinical and biochemical parameters in kidney stone former (SF) and non-stone former (NSF) patients with PHPT in order to identify potential risk factors. Serum and plasma samples from 55 consecutive patients (43 females, 12 males) with PHPT were collected after overnight fasting; 24-h urine collection and a fresh sample of urine for sediment analysis were obtained from all patients. Clinical data were recorded in all. Out of 55 patients, 22 had kidney stones, which were symptomatic in 73%. SFs showed circulating PTH, total and ionized calcium, 1,25 dihydroxyvitamin D-3, urinary calcium excretion and 24-h urine oxalate levels significantly higher than NSFs. Hypercalciuria was often concomitant with massive quantities of calcium oxalate crystals in urine sediment. Hypercalciuria and relatively high oxaluria were associated with stone formation with an odds ratio (OR) of 4.0 and 7.0, respectively, which rose to 33.5 when they coexisted. Hypomagnesuria and hypocitraturia were common in at least one third of all PHPT patients, but they were not associated to an increased OR. As expected, they were positively correlated with urine calcium excretion, suggesting that calcium, magnesium and citrate are commonly regulated at renal level. In conclusion, hypercalciuria, higher oxalate excretion and severe PHPT are associated with kidney stones in PHPT. (c) 2005, Editrice Kurtis. C1 Univ Milan, IRCCS, Fdn Osped Maggiore, Ist Sci Endocrine, I-20122 Milan, Italy. Univ Milan, Osped Maggiore, IRCCS, Div Nephrol, I-20122 Milan, Italy. Univ Milan, Osped Maggiore, IRCCS, Div Endocrine Surg, I-20122 Milan, Italy. Natl Canc Inst, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD USA. RP Corbetta, S (reprint author), Univ Milan, IRCCS, Fdn Osped Maggiore, Ist Sci Endocrine, Via F Sforza 35, I-20122 Milan, Italy. EM sabrina.corbetta@unimi.it RI Corbetta, Sabrina/H-5457-2011; OI Corbetta, Sabrina/0000-0001-8140-3175; Baccarelli, Andrea/0000-0002-3436-0640 NR 33 TC 20 Z9 25 U1 1 U2 1 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD FEB PY 2005 VL 28 IS 2 BP 122 EP 128 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 921AC UT WOS:000228735600005 PM 15887857 ER PT J AU Orlic, D AF Orlic, D TI Bone marrow mobilization for myocardial repair: Where do things stand? SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Meeting Abstract CT 18th International Congress on Endovascular Interventions CY FEB 13-17, 2005 CL Scottsdale, AZ SP Int Soc Endovasc Specialists C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD FEB PY 2005 VL 12 SU 1 BP 33 EP 34 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 898EP UT WOS:000227059300058 ER PT J AU Swenson, KE Eveland, RL Gladwin, MT Swenson, ER AF Swenson, KE Eveland, RL Gladwin, MT Swenson, ER TI Nitric oxide (NO) in normal and hypoxic vascular regulation of the spiny dogfish, Squalus acanthias SO JOURNAL OF EXPERIMENTAL ZOOLOGY PART A-COMPARATIVE EXPERIMENTAL BIOLOGY LA English DT Article ID PERIPHERAL NERVOUS-SYSTEM; MYKISS CORONARY SYSTEM; BLOOD-FLOW REGULATION; RAINBOW-TROUT; CARBONIC-ANHYDRASE; DORSAL AORTA; SYNTHASE; ACETYLCHOLINE; VESSELS; SHARK AB Nitric oxide (NO) is a potent vasodilator in terrestrial vertebrates, but whether vascular endothelial-derived NO plays a role in vascular regulation in fish remains controversial. To explore this issue, a study was made of spiny dogfish sharks (Squalus acanthias) in normoxia and acute hypoxia (60 min exposure to seawater equilibrated with 3% oxygen) with various agents known to alter NO metabolism or availability. In normoxia, nitroprusside (a NO donor) reduced blood pressure by 20%, establishing that vascular smooth muscle responds to NO. L-arginine, the substrate for NO synthase, had no hemodynamic effect. Acetylcholine, which stimulates endothelial NO and prostaglandin production in mammals, reduced blood pressure, but also caused marked bradycardia. L-NAME, an inhibitor of all NO synthases, caused a small 10% rise in blood pressure, but cell-free hemoglobin (a potent NO scavenger and hypertensive agent in mammals) had no effect. Acute hypoxia caused a 15% fall in blood pressure, which was blocked by L-NAME and cell-free hemoglobin. Serum nitrite, a marker of NO production, rose with hypoxia, but not with L-NAME. Results suggest that NO is not an endothelial-derived vasodilator in the normoxic elasmobranch. The hypertensive effect of L-NAME may represent inhibition of NO production in the CNS and nerves regulating blood pressure. In acute hypoxia, there is a rapid up-regulation of vascular NO production that appears to be responsible for hypoxic vasodilation. (C) 2005 Wiley-Liss, Inc. C1 Univ Washington, Div Pulm & Crit Care Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Swenson, ER (reprint author), VA Puget Sound Hlth Care Syst, Pulm Div S111 Pulm, 1660 S Columbian Way, Seattle, WA 98108 USA. EM eswenson@u.washington.edu NR 39 TC 17 Z9 18 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1548-8969 J9 J EXP ZOOL PART A JI J. Exp. Zool. Part A PD FEB 1 PY 2005 VL 303A IS 2 BP 154 EP 160 DI 10.1002/jez.a.145 PG 7 WC Zoology SC Zoology GA 894XV UT WOS:000226825800006 PM 15662661 ER PT J AU Lee, CK Christensen, LL Magee, JC Ojo, AO Leichtman, AB Bridges, ND AF Lee, C. K. Christensen, L. L. Magee, J. C. Ojo, A. O. Leichtman, A. B. Bridges, N. D. TI Chronic renal failure in a 10-year national cohort of pediatric heart transplant recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 [Lee, C. K.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Bridges, N. D.] NIAID, NIH, Bethesda, MD 20892 USA. [Christensen, L. L.] SRTR URREA, Ann Arbor, MI USA. [Magee, J. C.; Ojo, A. O.; Leichtman, A. B.] Univ Michigan, SRTR, Ann Arbor, MI 48109 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2005 VL 24 IS 2 SU S MA 220 BP S114 EP S114 DI 10.1016/j.healun.2004.11.243 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA V50KP UT WOS:000203407500220 ER PT J AU Gannot, G Gillespie, JW Chuaqui, RF Tangrea, MA Linehan, WM Emmert-Buck, MR AF Gannot, G Gillespie, JW Chuaqui, RF Tangrea, MA Linehan, WM Emmert-Buck, MR TI Histomathematical analysis of clinical specimens: Challenges and progress SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE histomathematics; histopathology; mathematics; immunohistochemistry; prostate cancer ID PROSTATE-CANCER; IMAGE-ANALYSIS; EXPRESSION; TISSUE; PROTEIN; SECRETION AB Proteomic analysis of clinical tissue specimens is a difficult undertaking. Described here is a multiplex study of protein expression levels in histological sections of human prostate that addresses many of the associated challenges. Whole-mount sections from 10 prostatectomy specimens were studied using 15 antibodies, immunohistochemical staining, digital imaging, and mathematical analysis of the data sets. The approach was successful in stratifying cell lineages present in the samples based on proteomic patterns, including differentiating normal epithelium from cancer. This strategy likely will be a useful method for extending the number of proteins that can be analyzed in clinical cancer specimens using currently available laboratory techniques. C1 NCI, Pathogenesis Unit, Ctr Adv Technol, Pathol Lab,NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenesis Unit, Ctr Adv Technol, Pathol Lab,NIH, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM mbuck@helix.nih.gov NR 23 TC 6 Z9 6 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD FEB PY 2005 VL 53 IS 2 BP 177 EP 185 DI 10.1369/jhc.4A6457.2005 PG 9 WC Cell Biology SC Cell Biology GA 894HF UT WOS:000226780900004 PM 15684330 ER PT J AU Olivera, A Rivera, J AF Olivera, A Rivera, J TI Sphingolipids and the balancing of immune cell function: Lessons from the mast cell SO JOURNAL OF IMMUNOLOGY LA English DT Review ID FC-EPSILON-RI; PROTEIN-COUPLED RECEPTORS; AFFINITY IGE RECEPTOR; SPHINGOSINE KINASE; PHOSPHOLIPASE-D; LYMPHOCYTE TRAFFICKING; LYSOPHOSPHATIDIC ACID; CALCIUM MOBILIZATION; HL-60 CELLS; LYN KINASE AB Recent studies reveal that metabolites of sphingomyelin are critically important for initiation and maintenance of diverse aspects of immune cell activation and function. The conversion of sphingomyelin to ceramide, sphingosine, or sphingosine-1-phoshate (S1P) provides inter-convertible metabolites with distinct biological activities. Whereas ceramide and sphingosine function to induce apoptosis and to dampen mast cell responsiveness, S1P junctions as a chemoattractant and can up-regulate some effector responses. Many of the S1P effects are mediated through S1P receptor family members (S1P(1-5)). S1P(1), which is required for thymocyte emigration and lymphocyte recirculation, is also essential for Ag-induced mast cell chemotaxis, whereas S1P, is important for mast cell degranulation. S1P is released to the extracellular milieu by Ag-stimulated mast cells, enhancing inflammatory cell functions. Modulation of S1P receptor expression profiles, and of enzymes involved in sphingolipid metabolism, particularly. sphingosine kinases, are key in balancing mast cell and immune cell responses. Current efforts are unraveling the complex underlying mechanisms regulating the sphingolipid pathway. Pharmacological intervention of these key processes may hold promise for controlling unwanted immune responses. C1 NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Olivera, A (reprint author), NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bldg 10,Room 9N228, Bethesda, MD 20892 USA. EM oliveraa@mail.nih.gov; juan_rivera@nih.gov NR 62 TC 77 Z9 80 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 FEB 1 PY 2005 VL 174 IS 3 BP 1153 EP 1158 PG 6 WC Immunology SC Immunology GA 891HG UT WOS:000226571300003 PM 15661867 ER PT J AU Dombroski, D Houghtling, RA Labno, CM Precht, P Takesono, A Caplen, NJ Billadeau, DD Wange, RL Burkhardt, JK Schwartzberg, PL AF Dombroski, D Houghtling, RA Labno, CM Precht, P Takesono, A Caplen, NJ Billadeau, DD Wange, RL Burkhardt, JK Schwartzberg, PL TI Kinase-independent functions for Itk in TCR-induced regulation of Vav and the actin cytoskeleton SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; X-LINKED AGAMMAGLOBULINEMIA; TEC FAMILY KINASES; APC CONTACT SITE; TYROSINE KINASE; ANTIGEN RECEPTOR; GENE-EXPRESSION; ACTIVATION; CALCIUM; RECRUITMENT AB The Tee family kinase Itk is an important regulator of Ca2+ mobilization and is required for in vivo responses to Th-2-inducing agents. Recent data also implicate Itk in TCR-induced regulation of the actin cytoskeleton. We have evaluated the requirements for Itk function in TCR-induced actin polarization. Reduction of Itk expression via small interfering RNA treatment of the Jurkat human T lymphoma cell line or human peripheral blood T cells disrupted TCR-induced actin polarization, a defect that correlated with decreased recruitment of the Vav guanine nucleotide exchange factor to the site of Ag contact. Vav localization and actin polarization could be rescued by re-expression of either wild-type or kinase-inactive murine Itk but not by Itk containing mutations affecting the pleckstrin homology or Src homology 2 domains. Additionally.. we find that Itk is constitutively associated with Vav. Loss of Itk expression did not alter gross patterns of Vav tyrosine phosphorylation but appeared to disrupt the interactuons of Vav with SLP-76. Expression of membrane-targeted Vav, Vav-CAAX, can rescue the small interfering RNA to Itk-induced phenotype, implicating the alteration in Vav localization as directly contributing to the actin polarization defect. These data suggest a kinase-independent scaffolding function for Itk in the regulation of Vav localization and TCR-induced actin polarization. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Oncol Res, Rochester, MN 55905 USA. Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Schwartzberg, PL (reprint author), NHGRI, NIH, 4A38,49 Convent Dr, Bethesda, MD 20892 USA. EM pams@nhgri.nih.gov RI Caplen, Natasha/H-2768-2016 OI Caplen, Natasha/0000-0002-0001-9460 NR 47 TC 86 Z9 90 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2005 VL 174 IS 3 BP 1385 EP 1392 PG 8 WC Immunology SC Immunology GA 891HG UT WOS:000226571300032 PM 15661896 ER PT J AU Chang, CC Campoli, M Restifo, NP Wang, XH Ferrone, S AF Chang, CC Campoli, M Restifo, NP Wang, XH Ferrone, S TI Immune selection of hot-spot beta(2)-microglobulin gene mutations, HLA-A2 allospecificity loss, and antigen-processing machinery component down-regulation in melanoma cells derived from recurrent metastases following immunotherapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I ANTIGEN; BETA-2-MICROGLOBULIN MESSENGER-RNA; MHC CLASS-I; MONOCLONAL-ANTIBODIES; TUMOR ESCAPE; EXPRESSION; CHAIN; SPECIFICITY; MOLECULES; SURFACE AB Scanty information is available about the mechanisms underlying HLA class I Ag abnormalities in malignant cells exposed to strong T cell-mediated selective pressure. In this study, we have characterized the molecular defects underlying HLA class I Ag loss in five melanoma cell lines derived from recurrent metastases following initial clinical responses to T cell-based immunotherapy. Point mutations in the translation initiation codon (ATG-->ATA) and in codon 31 (TCA-->TGA) of the beta(2)-microglobulin (beta(2)M) gene were identified in the melanoma cell lines 1074MEL and 1174MEL, respectively. A hot-spot CT dinucleotide deletion within codon 13-15 was found in the melanoma cell lines 1106NIEL, 1180MEL, and 1259MEL. Reconstitution of beta(2)m expression restored HLA class I Ag expression in the five melanoma cell lines; however, the HLA-A and HLA-B,-C gene products were differentially expressed by 1074MEL, 1106MEL, and 1259MEL cells. In addition, in 1259MEL cells, the Ag-processing machinery components calnexin, calreticulin, and low m.w. polypeptide 10 are down-regulated, and HLA-A2 Ags are selectively lost because of a single cytosine deletion in the HLA-A2 gene exon 4. Our results in conjunction with those in the literature suggest the emergence of a preferential beta(2)M gene mutation in melanoma cells following strong T cell-mediated immune selection. Furthermore, the presence of multiple HLA class I Ag defects within a tumor cell population may reflect the accumulation of multiple escape mechanisms developed by melanoma cells to avoid distinct sequential T cell-mediated selective events. C1 Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Ferrone, S (reprint author), Roswell Pk Canc Inst, Dept Immunol, Elm & Carlton St, Buffalo, NY 14263 USA. EM soldano.ferrone@roswellpark.org RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01]; NCI NIH HHS [P30 CA16056, P30 CA016056, R01 CA067108, R01 CA67108, T32 CA85183, T32 CA085183] NR 46 TC 52 Z9 53 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2005 VL 174 IS 3 BP 1462 EP 1471 PG 10 WC Immunology SC Immunology GA 891HG UT WOS:000226571300041 PM 15661905 ER PT J AU Wagner, D Maser, J Lai, B Cai, ZH Barry, CE Bentrup, KHZ Russell, DG Bermudez, LE AF Wagner, D Maser, J Lai, B Cai, ZH Barry, CE Bentrup, KHZ Russell, DG Bermudez, LE TI Elemental analysis of Mycobacterium avium-, Mycobacterium tuberculosis-, and Mycobacterium smegmatis-containing phagosomes indicates pathogen-induced microenvironments within the host cell's endosomal system SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IRON TRANSPORT; SUPEROXIDE-DISMUTASE; MOUSE MACROPHAGES; VIRULENCE; TRANSFERRIN; INFECTION; NRAMP1; ACIDIFICATION; ACTIVATION; EXPRESSION AB Mycobacterium avium and Mycobacterium tuberculosis are human pathogens that infect and replicate within macrophages Both organisms live in phagosomes that fail to fuse with lysosomes and have adapted their lifestyle to accommodate the changing environment within the endosomal system. Among the many environmental factors that could influence. expression of bacterial genes are the concentrations of single elements within the phagosomes. We used a novel hard x-ray microprobe with suboptical spatial resolution to analyze characteristic x-ray fluorescence of 10 single elements inside phagosomes of macrophages infected with M. tuberculosis and M avium or with avirulent M. smegmatis. The iron concentration decreased over time in phagosomes of macrophages infected with Mycobacterium smegmatis but increased in those infected with pathogenic mycobacteria. Autoradiography of infected macrophages incubated with Fe-59-loaded transferrin demonstrated that the bacteria could acquire iron delivered via the endocytic-route, confirming the. results obtained in the x-ray microscopy. In addition. the concentrations of chlorine, calcium, potassium, manganese, copper, and zinc were shown to differ between the vacuole of pathogenic mycobacteria and M smegmatis. Differences in the concentration of several elements between M. avium and M. tuberculosis vacuoles were also observed. Activation of macrophages with recombinant IFN-gamma or TNF-alpha before infection altered the concentrations of elements in the, phagosome, which was not observed in cells activated following infection. Siderophore knockout M. tuberculosis vacuoles exhibited retarded acquisition of iron ' compared with phagosomes with wild-type M. tuberculosis. This is a unique approach to define the environmental conditions within the pathogen-containing compartment. C1 Kuzell Inst Arthritis & Infect Dis, San Francisco, CA 94115 USA. Univ Freiburg, Dept Internal Med 2 Infect Dis, Freiburg, Germany. Argonne Natl Lab, Expt Fac Div, Argonne, IL 60439 USA. NIH, Tuberculosis Res Sect, Host Def Lab, Rockville, MD 20852 USA. Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Ithaca, NY 14853 USA. RP Bermudez, LE (reprint author), Oregon State Univ, Coll Vet Med, Dept Biomed Sci, 105 Magruder Hall, Corvallis, OR 97331 USA. EM Luiz.Bermudez@oregonstate.edu RI Russell, David/D-4533-2009; Barry, III, Clifton/H-3839-2012; Wagner, Dirk/G-4598-2013; Maser, Jorg/K-6817-2013; Wagner, Dirk/D-9778-2016 OI Wagner, Dirk/0000-0002-3271-5815 FU Intramural NIH HHS [Z01 AI000783-11]; NIAID NIH HHS [R01-AI 47010] NR 41 TC 189 Z9 195 U1 0 U2 15 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2005 VL 174 IS 3 BP 1491 EP 1500 PG 10 WC Immunology SC Immunology GA 891HG UT WOS:000226571300044 PM 15661908 ER PT J AU Cataisson, C Pearson, AJ Torgerson, S Nedospasov, SA Yuspa, SH AF Cataisson, C Pearson, AJ Torgerson, S Nedospasov, SA Yuspa, SH TI Protein kinase C alpha-mediated chemotaxis of neutrophils requires NF-kappa B activity but is independent of TNF alpha signaling in mouse skin in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; TRANSGENIC MICE; FACTOR RECEPTOR; DEFICIENT MICE; T-LYMPHOCYTES; EPIDERMAL-KERATINOCYTES; INCONTINENTIA PIGMENTI; PKC-THETA; INFLAMMATION; ACTIVATION AB Protein kinase C (PKC) isoforms are major regulators of cutaneous homeostasis and mediate inflammation in response to 12-O-tetradecanoylphorbol-13-acetate (TPA). We have previously reported that transgenic mice overexpressing PKCalpha in the skin exhibit severe intraepidermal neutrophilic inflammation and keratinocyte apoptosis when treated topically with TPA. Activation of PKCalpha increases the production of TNFalpha and the transcription of chemotactic factors (MIP-2, KC, S100A8/A9), vascular endothelial growth factor, and GM-CSF in K5-PKCalpha keratinocytes. In response to PKCalpha activation, NF-kappaB translocates to the nucleus and this is associated with IkappaB phosphorylation and degradation. Preventing IkappaB degradation reduces both the expression of inflammation-associated genes and chemoattractant release. To determine whether TNFalpha mediated NF-kappaB translocation and subsequent expression of proinflammatory factors, K5-PKCalpha mice were treated systemically with a dimeric soluble form of p75 TNFR (etanercept) or crossed with mice deficient for both TNFR isoforms, and keratinocytes were cultured in the presence of TNFalpha-neutralizing Abs. The in vivo treatment and TNFR deficiency did not prevent inflammation, and the in vitro treatment did not prevent NF-kappaB nuclear translocation after TPA. Together these results implicate PKCa as a regulator of a subset of cutaneous cytokines and chemokines responsible for intraepidermal inflammation independent of TNFalpha. PKCalpha inhibition may have therapeutic benefit in some human inflammatory skin disorders. C1 NCI, Ctr Canc Res, Lab Cellular Carcinogenesis & Tumor Promot, Bethesda, MD 20892 USA. SAIC, Basic Res Program, Ft Detrick, MD 21702 USA. NCI, Canc Res Ctr, Mol Immunoregulat Lab, Frederick, MD 21701 USA. RP Yuspa, SH (reprint author), NCI, Ctr Canc Res, Lab Cellular Carcinogenesis & Tumor Promot, 37 Convent Dr,MSC-4255,Bldg 37,Room 4068, Bethesda, MD 20892 USA. EM yuspas@mail.nih.gov RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 FU NCI NIH HHS [N01-CO-12400] NR 55 TC 54 Z9 55 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2005 VL 174 IS 3 BP 1686 EP 1692 PG 7 WC Immunology SC Immunology GA 891HG UT WOS:000226571300068 PM 15661932 ER PT J AU Edghill-Smith, Y Bray, M Whitehouse, CA Miller, D Mucker, E Manischewitz, J King, LR Robert-Guroff, M Hryniewicz, A Venzon, D Meseda, C Weir, J Nalca, A Livingston, V Wells, J Lewis, MG Huggins, J Zwiers, SH Golding, H Franchini, G AF Edghill-Smith, Y Bray, M Whitehouse, CA Miller, D Mucker, E Manischewitz, J King, LR Robert-Guroff, M Hryniewicz, A Venzon, D Meseda, C Weir, J Nalca, A Livingston, V Wells, J Lewis, MG Huggins, J Zwiers, SH Golding, H Franchini, G TI Smallpox vaccine does not protect Macaques with AIDS from a lethal Monkeypox virus challenge SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Trans-Natl Institutes of Health/United States Food and Drug Administration Intramural Biodefense Symposium CY APR 22-23, 2004 CL Bethesda, MD ID EXPRESSION; MVA AB It is unknown whether smallpox vaccination would protect human immunodeficiency virus type 1 (HIV-1) infected individuals, because helper CD4(+) cells, the targets of HIV-1 infection, are necessary for the induction of both adaptive CD8(+) cell and B cell responses. We have addressed this question in macaques and have demonstrated that, although smallpox vaccination is safe in immunodeficient macaques when it is preceded by immunization with highly attenuated vaccinia strains, the macaques were not protected against lethal monkeypox virus challenge if their CD4(+) cell count was <300 cells/mm(3). The lack of protection appeared to be associated with a defect in vaccinia-specific immunoglobulin (Ig) switching from IgM to IgG. Thus, vaccination strategies that bypass CD4(+) cell help are needed to elicit IgG antibodies with high affinity and adequate tissue distribution and to restore protection against smallpox in severely immunocompromised individuals. C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. NCI, Immune Biol Retroviral Infect Sect, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NIAID, Biodef Clin Res Branch, Off Clin Res, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. So Res Inst, Frederick, MD USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, 41-D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov RI Venzon, David/B-3078-2008 FU NIAID NIH HHS [N01-AI-15451] NR 18 TC 47 Z9 49 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 FEB 1 PY 2005 VL 191 IS 3 BP 372 EP 381 DI 10.1086/427265 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 885BH UT WOS:000226130500008 PM 15633096 ER PT J AU Cui, XZ Li, Y Moayeri, M Choi, GH Subramanian, GM Li, XM Haley, M Fitz, Y Feng, J Banks, SM Leppla, SH Eichacker, PQ AF Cui, XZ Li, Y Moayeri, M Choi, GH Subramanian, GM Li, XM Haley, M Fitz, Y Feng, J Banks, SM Leppla, SH Eichacker, PQ TI Late treatment with a protective antigen-directed monoclonal antibody improves hemodynamic function and survival in a lethal toxin-infused rat model of anthrax sepsis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BACILLUS-ANTHRACIS; INHALATIONAL ANTHRAX; FACTOR CLEAVES; TNF-ALPHA; MACROPHAGES; EXPOSURE; KINASE; COMPONENTS; PATIENTS/; APOPTOSIS AB Background. In animal models, treatment with 5H3, a fully human protective antigen-directed monoclonal antibody (PA-MAb), improved survival when administered close to the time of Bacillus anthracis lethal toxin (LeTx) bolus or live bacterial challenge. However, treatment with PA-MAb would be most valuable clinically if it were beneficial even when administered after the onset of shock and lethality due to LeTx. Methods. We investigated the effects of PA-MAb versus placebo administered in rats (n = 324) at the time of or 3, 6, 9, or 12 h after the initiation of a 24-h LeTx infusion. Results. In rats receiving placebo, mean arterial blood pressure (MBP) and heart rate (HR) were decreased in nonsurvivors, compared with those in survivors, at 6 h and then worsened further, with lethality first evident at 8 h (median, 16 h; range, 8-152 h). At each treatment time, survival rates were greater for PA-MAb than for placebo, although improvement was decreased at later treatment times (P = .001, for the effect of time). Compared with placebo, PA-MAb significantly increased MBP during the 12 h after the initiation of treatment, but the increase was greatest for treatment at 3 h; similarly, PA-MAb significantly increased HR at all treatment times. Conclusion. In this rat model, improvements in outcome due to PA-MAb were significant when it was administered up to 6 h (and approached significance when administered up to 12 h) after initial exposure to LeTx. Clinically, PA-MAb may be beneficial even when administered after the onset of shock and lethality due to LeTx. C1 NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Human Genome Sci, Rockville, MD USA. RP Cui, XZ (reprint author), NIH, Crit Care Med Dept, Ctr Clin, Bldg 10,Room 7D43, Bethesda, MD 20892 USA. EM cxizhong@mail.cc.nih.gov NR 34 TC 54 Z9 54 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 FEB 1 PY 2005 VL 191 IS 3 BP 422 EP 434 DI 10.1086/427189 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 885BH UT WOS:000226130500014 PM 15633102 ER PT J AU Richmond, B Huizing, M Knapp, J Koshoffer, A Zhao, Y Gahl, WA Boissy, RE AF Richmond, B Huizing, M Knapp, J Koshoffer, A Zhao, Y Gahl, WA Boissy, RE TI Melanocytes derived from patients with Hermansky-Pudlak Syndrome types 1, 2, and 3 have distinct defects in cargo trafficking SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE pigmentation; albinism; tyrosinase; lysosomes; translocation ID LYSOSOME-RELATED ORGANELLES; TYROSINASE-RELATED PROTEIN-1; MELANOSOME BIOGENESIS; PULMONARY-FIBROSIS; AP-3 ADAPTER; COMPLEX; GENE; AUTOPHAGY; MECHANISMS; MUTATIONS AB Hermansky-Pudlak Syndrome (HIPS) is a genetically heterogeneous disorder in which mutations in one of several genes interrupts biogenesis of melanosomes, platelet dense bodies, and lysosomes. Affected patients have oculocutaneous albinism, a bleeding diathesis, and sometimes develop granulomatous colitis or pulmonary fibrosis. In order to assess the role of HPS genes in melanosome biogenesis, melanocytes cultured from patients with HPS subtypes 1, 2, or 3 were assessed for the localization of various melanocyte proteins. Tyrosinase, Tyrp1, and Dct/Tyrp2 were atypically and distinctly expressed in HPS-1 and HPS-3 melanocytes, whereas only tyrosinase showed an atypical distribution in HPS-2 melanocytes. The HPS1 and AP3B1 (i.e., HPS-2) gene products showed no expression in HPS-1 and HPS-2 melanocytes, respectively, whereas HPS-3 melanocytes exhibited normal expression for both proteins. In normal human melanocytes, the HPS1 protein was expressed as an approximately 80 kDa molecule with both granular and reticular intracellular profiles. In HPS-1, lysosome associated membrane protein 1 (LAMP1), and LAMP3 were localized to abnormal large granules; in HPS-2, all LAMPs exhibited a normal granular expression; and in HPS-3, LAMP1, and LAMP3 exhibited a distinct less granular and more floccular pattern. In contrast, the expressions of Rab 27, transferrin, and cKit were unaffected in all three HPS genotypes. These data demonstrate that the three initially identified subtypes of human HPS exhibit distinct defects in the trafficking of various melanocyte-specific proteins. C1 Univ Cincinnati, Dept Dermatol, Coll Med, Cincinnati, OH 45267 USA. NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Boissy, RE (reprint author), Univ Cincinnati, Dept Dermatol, Coll Med, POB 670592, Cincinnati, OH 45267 USA. EM boissyre@email.uc.edu RI Koshoffer, Amy/N-2278-2014; 何, 敏仪/E-6352-2015 OI Koshoffer, Amy/0000-0001-8130-103X; FU NIAMS NIH HHS [R01 AR045429, 5 R01 AR45429] NR 63 TC 39 Z9 40 U1 0 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 2005 VL 124 IS 2 BP 420 EP 427 DI 10.1111/j.0022-202X.2004.23585.x PG 8 WC Dermatology SC Dermatology GA 892UC UT WOS:000226674500020 PM 15675963 ER PT J AU Pryor, SP Madeo, AC Reynolds, JC Sarlis, NJ Arnos, KS Nance, WE Yang, Y Zalewski, CK Brewer, CC Butman, JA Griffith, AJ AF Pryor, SP Madeo, AC Reynolds, JC Sarlis, NJ Arnos, KS Nance, WE Yang, Y Zalewski, CK Brewer, CC Butman, JA Griffith, AJ TI SLC26A4/PDS genotype-phenotype correlation in hearing loss with enlargement of the vestibular aqueduct (EVA): evidence that Pendred syndrome and non-syndromic EVA are distinct clinical and genetic entities SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID CONGENITAL DEAFNESS; RECESSIVE DEAFNESS; MOLECULAR ANALYSIS; PDS GENE; ASSOCIATION; MUTATIONS; GOITRE; PERCHLORATE; POPULATION; FAMILIES C1 NIDCD, Hearing Sect, NIH, Rockville, MD 20850 USA. NIDCD, Off Clin Director, NIH, Rockville, MD 20850 USA. NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Gallaudet Univ, Dept Biol, Washington, DC 20002 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Human Genet, Richmond, VA 23298 USA. NIDCD, Sect Gene Struct & Funct, Mol Genet Lab, NIH, Rockville, MD 20850 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Griffith, AJ (reprint author), NIDCD, Hearing Sect, NIH, 5 Res Court,Room 2A-01, Rockville, MD 20850 USA. EM griffita@nidcd.nih.gov RI Butman, John/A-2694-2008; Madeo, Anne/K-2880-2012; OI Butman, John/0000-0002-1547-9195 FU NIDCD NIH HHS [1-Z01-DC-000060, 1-Z01-DC-000064] NR 30 TC 135 Z9 150 U1 0 U2 4 PU B M J 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 FEB PY 2005 VL 42 IS 2 BP 159 EP 165 DI 10.1136/jmg.2004.024208 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 893VJ UT WOS:000226748100011 PM 15689455 ER PT J AU Lee, JS Tartaglia, M Gelb, BD Fridrich, K Sachs, S Stratakis, CA Muenke, M Robey, PG Collins, MT Slavotinek, A AF Lee, JS Tartaglia, M Gelb, BD Fridrich, K Sachs, S Stratakis, CA Muenke, M Robey, PG Collins, MT Slavotinek, A TI Phenotypic and genotypic characterisation of Noonan-like/multiple giant cell lesion syndrome SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID TYROSINE-PHOSPHATASE SHP-2; SH2 DOMAIN; MUTATIONS; PTPN11; CHERUBISM; SPECTRUM; PATIENT; BINDING; SH-PTP2; MUTANT C1 NIDCR, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bethesda, MD USA. Ist Super Sanita, Dipartimento Biol Cellulare & Neurosci, I-00161 Rome, Italy. Mt Sinai Sch Med, Dept Pediat, New York, NY USA. Mt Sinai Sch Med, Dept Human Genet, New York, NY USA. Harvard Univ, Sch Med, Dept Cell Biol, LHRRB, Boston, MA USA. SUNY, Dept Oral & Maxillofacial Surg, New York, NY USA. NICHD, Dev Endocrinol Branch, NIH, DHHS, Bethesda, MD USA. NHGRI, Med Genet Branch, NIH, DHHS, Bethesda, MD USA. RP Lee, JS (reprint author), Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, 521 Parnassus Ave,C522, San Francisco, CA 94143 USA. EM jslee@itsa.ucsf.edu RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU NHLBI NIH HHS [HL074728, HL71207]; NICHD NIH HHS [HD01294]; Telethon [GGP04172] NR 26 TC 36 Z9 37 U1 0 U2 1 PU B M J 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 FEB PY 2005 VL 42 IS 2 AR e11 DI 10.1136/jmg.2004.024091 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 893VJ UT WOS:000226748100021 PM 15689434 ER PT J AU Pine, SR Yin, CH Matloub, YH Sabaawy, HE Sandoval, C Levendoglu-Tugal, O Ozkaynak, MF Jayabose, S AF Pine, SR Yin, CH Matloub, YH Sabaawy, HE Sandoval, C Levendoglu-Tugal, O Ozkaynak, MF Jayabose, S TI Detection of central nervous system leukemia in children with acute lymphoblastic leukemia by real-time polymerase chain reaction SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID MINIMAL RESIDUAL DISEASE; LOW LEUKOCYTE COUNTS; CEREBROSPINAL-FLUID; GENE REARRANGEMENTS; QUANTITATIVE PCR; CANCER GROUP; DIAGNOSIS; BLASTS; CELLS AB Accurate detection of central nervous system (CNS) involvement in children with newly diagnosed acute lymphoblastic leukemia (ALL) could have profound prognostic and therapeutic implications. We examined various cerebrospinal fluid (CSF) preservation methods to yield adequate DNA stability for polymerase chain reaction (PCR) analysis and developed a quantitative real-time PCR assay to detect occult CNS leukemia. Sixty CSF specimens were maintained in several storage conditions for varying amounts of time, and we found that preserving CSF in 1:1 serum free RPMI tissue culture medium offers the best stability of DNA for PCR analysis. Sixty CSF samples (30 at diagnosis and 30 at the end of induction therapy) from 30 children with ALL were tested for CNS leukemic involvement by real-time PCR using patient-specific antigen receptor gene rearrangement primers. Six of thirty patient diagnosis samples were PCR-positive at levels ranging from 0.5 to 66% leukemic blasts in the CSF. Four of these patients had no clinical or cytomorphological evidence of CNS leukemia involvement at that time. All 30 CSF samples drawn at the end of induction therapy were PCR-negative. The data indicate that real-time PCR analysis of CSF is an excellent tool to assess occult CNS leukemia involvement in patients with ALL and can possibly be used to refine CNS status classification. C1 New York Med Coll, Dept Pediat Hematol Oncol, Valhalla, NY 10595 USA. Univ Wisconsin, Dept Pediat Hematol Oncol, Madison, WI 53706 USA. NCI, Natl Canc Inst, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Pine, SR (reprint author), New York Med Coll, Dept Pediat Hematol Oncol, Room 401 BSB, Valhalla, NY 10595 USA. EM sharon_pine@nymc.edu NR 13 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD FEB PY 2005 VL 7 IS 1 BP 127 EP 132 DI 10.1016/S1525-1578(10)60018-9 PG 6 WC Pathology SC Pathology GA 908XQ UT WOS:000227823900017 PM 15681484 ER PT J AU Zheng, Q Bobich, JA Vidugiriene, J McFadden, SC Thomas, F Roder, J Jeromin, A AF Zheng, Q Bobich, JA Vidugiriene, J McFadden, SC Thomas, F Roder, J Jeromin, A TI Neuronal calcium sensor-1 facilitates neuronal exocytosis through phosphatidylinositol 4-kinase SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE glutamate; neuronal calcium sensor-1; neurotransmitter release; norepinephrine; phosphatidylinositol 4-kinase ID CA2+ SIGNAL-TRANSDUCTION; ADRENAL CHROMAFFIN CELLS; CANINE KIDNEY-CELLS; BINDING-PROTEIN; PC12 CELLS; SUBCELLULAR-DISTRIBUTION; CA2+-BINDING PROTEIN; MEMBRANE ASSOCIATION; PLASMA-MEMBRANE; NERVOUS-SYSTEM AB This work tested the theory that neuronal calcium sensor-1 (NCS-1) has effects on neurotransmitter release beyond its actions on membrane channels. We used nerve-ending preparations where membrane channels are bypassed through membrane permeabilization made by mechanical disruption or streptolysin-O. Nerve ending NCS-1 and phosphatidylinositol 4-kinase (PI4K) are largely or entirely particulate, so their concentrations in nerve endings remain constant after breaching the membrane. Exogenous, myristoylated NCS-1 stimulated nerve ending phosphatidylinositol 4-phosphate [PI(4)P] synthesis, but non-myristoylated-NCS-1 did not. The N-terminal peptide of NCS-1 interfered with PI(4)P synthesis, and with spontaneous and Ca2+-evoked release of both [H-3]-norepinephrine (NA) and [C-14]-glutamate (glu) in a concentration-dependent manner. An antibody raised against the N-terminal of NCS-1 inhibited perforated nerve ending PI(4)P synthesis, but the C-terminal antibody had no effects. Antibodies against the N- and C-termini of NCS-1 caused significant increases in mini/spontaneous/stimulation-independent release of [H-3]-NA from perforated nerve endings, but had no effect on [C-14]-glu release. These results support the idea that NCS-1 facilitates nerve ending neurotransmitter release and phosphoinositide production via PI4K and localizes these effects to the N-terminal of NCS-1. Combined with previous work on the regulation of channels by NCS-1, the data are consistent with the hypothesis that a NCS-1-PI4K (NP, neuropotentiator) complex may serve as an essential linker between lipid and protein metabolism to regulate membrane traffic and co-ordinate it with ion fluxes and plasticity in the nerve ending. C1 Baylor Coll Med, Div Neurosci, Houston, TX 77030 USA. Texas Christian Univ, Dept Chem, Ft Worth, TX 76129 USA. Promega Corp, Res & Dev, Madison, WI USA. NHLBI, NIH, Bethesda, MD 20892 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. RP Jeromin, A (reprint author), Baylor Coll Med, Div Neurosci, Houston, TX 77030 USA. EM jeromin@ltp.enusc.bcm.tmc.edu RI Roder, John/G-6468-2013 NR 62 TC 29 Z9 32 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 FEB PY 2005 VL 92 IS 3 BP 442 EP 451 DI 10.1111/j.1471-4159.2004.02897.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 888VI UT WOS:000226401900002 PM 15659215 ER PT J AU Hope, BT Crombag, HS Jedynak, JP Wise, RA AF Hope, BT Crombag, HS Jedynak, JP Wise, RA TI Neuroadaptations of total levels of adenylate cyclase, protein kinase A, tyrosine hydroxylase, cdk5 and neurofilaments in the nucleus accumbens and ventral tegmental area do not correlate with expression of sensitized or tolerant locomotor responses to cocaine SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE adenylate cyclase; cdk5; neurofilaments; protein kinase A; tyrosine hydroxylase ID MESOLIMBIC DOPAMINE SYSTEM; CYCLIC-AMP SYSTEM; BEHAVIORAL SENSITIZATION; DENDRITIC SPINES; MOLECULAR-BASIS; CHOLERA-TOXIN; RAT-BRAIN; RECEPTOR; INHIBITION; MORPHINE AB Neuroadaptations induced by high-dose cocaine treatment have been hypothesized to persist after the cessation of drug treatment and mediate the expression of sensitization and tolerance to cocaine. We looked for evidence of these neuroadaptations in rats receiving more modest behaviorally effective cocaine treatments. Rats were exposed to either a sensitizing regimen of seven once-daily injections of 15 mg/kg cocaine or a tolerance-producing regimen involving a continuous infusion of the same daily dose. We assessed enzyme activity levels of protein kinase A and adenylate cyclase, and protein levels of tyrosine hydroxylase, cdk5 and neurofilaments in the nucleus accumbens and ventral tegmental area. Only protein kinase A activity levels were altered by cocaine treatment, but this alteration persisted for only 7 days, whereas a sensitized locomotor response was still evident at 21 days. Although behavioral tolerance to cocaine was seen the day after the termination of treatment, none of the molecular measures was altered on this or any other day. Thus, although increased protein kinase A activity can temporarily modulate sensitized responses to cocaine, alterations in total levels of the molecules assessed in our study do not correlate with the expression of sensitized or tolerant locomotor responses to cocaine. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,US Dept HHS, Baltimore, MD 21224 USA. RP Hope, BT (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,US Dept HHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bhope@intra.nida.nih.gov RI Wise, Roy/A-6465-2012; Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 NR 43 TC 30 Z9 30 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 FEB PY 2005 VL 92 IS 3 BP 536 EP 545 DI 10.1111/j.1471-4159.2004.02891.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 888VI UT WOS:000226401900011 PM 15659224 ER PT J AU Renaud, S Hays, AP Brannagan, TH Sander, HW Edgar, M Weimer, LH Olarte, MR Dalakas, MC Xiang, ZY Danon, MJ Latov, N AF Renaud, S Hays, AP Brannagan, TH Sander, HW Edgar, M Weimer, LH Olarte, MR Dalakas, MC Xiang, ZY Danon, MJ Latov, N TI Gene expression profiling in chronic inflammatory demyelinating polyneuropathy SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE CIDP; vasculitic neuropathy; nerve biopsy; microarray; SCD; TAC1; AIF-1 ID DENSITY OLIGONUCLEOTIDE ARRAYS; FACTOR-I; NAD(P)H-QUINONE OXIDOREDUCTASE; SUBSTANCE-P; MACROPHAGES/MICROGLIAL CELLS; ALZHEIMERS-DISEASE; CEREBRAL-ISCHEMIA; QUINONE REDUCTASE; RAT; DIAGNOSIS AB Gene expression in archived frozen sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) was compared to that in vasculitic nerve biopsies (VAS) and to normal nerve (NN) by DNA microarray technology. Hierarchical clustering analysis demonstrated distinct gene expression patterns distinguishing these disease groups. Of particular interest were: (1) Tachykinin precursor 1, which may be involved in pain mediation; (2) Stearoyl-CoA-desaturase, which may be a marker for remyelination and (3) the Allograft Inflammatory Factor 1 (AIF-1), a modulator of immune response during macrophage activation. Differential gene expression may help distinguish between CIDP, VAS and NN in sural nerve biopsies and identify genes that may be involved in disease pathogenesis. (C) 2004 Elsevier B.V. All rights reserved. C1 Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Cornell Univ, Dept Pathol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Pathol, New York, NY 10021 USA. Cornell Univ, Dept Neurol, New York, NY 10021 USA. NINDS, Neuromuscular Dis Sect, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Microarray Core Facil, New York, NY 10021 USA. Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. RP Univ Basel Hosp, Dept Neurol, Petersgraben 4, CH-4031 Basel, Switzerland. EM susanne.renaud@unibas.ch OI Sander, Howard/0000-0002-9654-7849 NR 47 TC 32 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 EI 1872-8421 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD FEB PY 2005 VL 159 IS 1-2 BP 203 EP 214 DI 10.1016/j.jneuroim.2004.10.021 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 895SB UT WOS:000226882300025 PM 15652421 ER PT J AU Mikolaenko, I Pletnikova, O Kawas, CH O'Brien, R Resnick, SM Crain, B Troncoso, JC AF Mikolaenko, I Pletnikova, O Kawas, CH O'Brien, R Resnick, SM Crain, B Troncoso, JC TI Alpha-synuclein lesions in normal aging, Parkinson disease, and Alzheimer disease: Evidence from the Baltimore Longitudinal Study of Aging (BLSA) SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE alpha-synucleinopathy; aging; Alzheimer disease; Lewy body; Lewy neurite; Parkinson disease ID LEWY-BODY-DISEASE; MULTIPLE SYSTEM ATROPHY; ARGYROPHILIC GLIAL INCLUSIONS; FORMIC-ACID PRETREATMENT; A-BETA COMPONENT; CYTOPLASMIC INCLUSIONS; COGNITIVE IMPAIRMENT; NACP/ALPHA-SYNUCLEIN; CLINICAL-DIAGNOSIS; PRECURSOR PROTEIN AB Alpha-synuclein (alpha-synuclein) lesions are characteristic of idiopathic Parkinson disease (PD) and other alpha-synucleinopathies. To study the frequency of alpha-synuclein lesions in normal aging and how frequently they coexist with lesions of Alzheimer disease (AD), we examined the autopsy brains from normal and demented subjects in the Baltimore Longitudinal Study of Aging (BLSA) (n = 117). We found that the overall frequency of alpha-synuclein lesions was 25%, with 100% in 7 cases of PD, 31.5% in 56 cases with AD lesions, and 8.3% among 36 older control brains. Among brains with AD lesions, the frequency of alpha-synuclein pathology was higher in those with higher scores for neuritic plaques, but not in those with higher scores for neurofibrillary tangles. Our observations indicate that alpha-synuclein lesions are uncommon in aged control subjects. Finally, the coexistence of Abeta amyloid and alpha-synuclein pathology in AD brains suggests that the pathogenic mechanism/s leading to the accumulation of Abeta and alpha-synuclein may be similar. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Div Neuropathol, Baltimore, MD 21205 USA. Univ Calif Irvine, Inst Brain Aging & Dementia, Irvine, CA USA. NIA, Lab Personal & Cognit, Intramural Res Program, Baltimore, MD 21224 USA. RP Troncoso, JC (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, 558 Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM troncoso@jhmi.edu FU NIA NIH HHS [AG 05146] NR 78 TC 67 Z9 68 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD FEB PY 2005 VL 64 IS 2 BP 156 EP 162 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 898WK UT WOS:000227106700008 PM 15751230 ER PT J AU Kaelin-Lang, A Sawaki, L Cohen, LG AF Kaelin-Lang, A Sawaki, L Cohen, LG TI Role of voluntary drive in encoding an elementary motor memory SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID USE-DEPENDENT PLASTICITY; TRANSCRANIAL MAGNETIC STIMULATION; PAIRED ASSOCIATIVE STIMULATION; CORTICOMOTOR EXCITABILITY; MUSCLE RESPONSES; CORTEX; MODULATION; REPRESENTATION; MECHANISMS; MOVEMENT AB Motor training consisting of repetitive thumb movements results in encoding of motor memories in the primary motor cortex. It is not known if proprioceptive input originating in the training movements is sufficient to produce this effect. In this study, we compared the ability of training consisting of voluntary ( active) and passively-elicited ( passive) movements to induce this form of plasticity. Active training led to successful encoding accompanied by characteristic changes in corticomotor excitability, while passive training did not. These results support a pivotal role for voluntary motor drive in coding motor memories in the primary motor cortex. C1 NIH, Human Cort Physiol Sect, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NIH, Human Cort Physiol Sect, Bldg 10,Room 5N234,10 Ctr Dr,MSC 1430, Bethesda, MD 20892 USA. EM COHENL@ninds.nih.gov NR 32 TC 74 Z9 75 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2005 VL 93 IS 2 BP 1099 EP 1103 DI 10.1152/jn.00143.2004 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 887YS UT WOS:000226342000041 PM 15456807 ER PT J AU Mah, LWY Arnold, MC Grafman, J AF Mah, LWY Arnold, MC Grafman, J TI Deficits in social knowledge following damage to ventromedial prefrontal cortex SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID FRONTAL-LOBE DAMAGE; DECISION-MAKING; RIGHT-HEMISPHERE; ACQUIRED SOCIOPATHY; HEAD-INJURY; COGNITION; PATIENT; MIND; DISTURBANCE; EXCISIONS AB Patients with damage to the frontal lobes frequently exhibit impaired social behavior, but it is not clear which specific processes are disrupted. The authors investigated the ability to interpret nonverbal emotional expression in patients with lesions involving ventromedial (N=20) or dorsolateral prefrontal cortex (N=9) and in healthy volunteers (N=23). As hypothesized, only patients with ventromedial prefrontal lesions showed impaired task performance relative to normal comparison subjects. These results suggest that deficits in social knowledge, namely difficulty interpreting nonverbal emotional expression, contribute to the aberrant social behavior observed following ventromedial prefrontal cortex lesions. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Rm 5C205,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 39 TC 39 Z9 39 U1 3 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FEB PY 2005 VL 17 IS 1 BP 66 EP 74 DI 10.1176/appi.neuropsych.17.1.66 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 902RP UT WOS:000227374500009 PM 15746485 ER PT J AU Chen, ZG Silva, AC Yang, JH Shen, J AF Chen, ZG Silva, AC Yang, JH Shen, J TI Elevated endogenous GABA level correlates with decreased fMRI signals in the rat brain during acute inhibition of GABA transaminase SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE functional imaging; in vivo spectroscopy; vigabatrin; gabaculine ID GAMMA-VINYL GABA; CEREBRAL-BLOOD-FLOW; AMINOBUTYRIC ACID GABA; IN-VIVO; FUNCTIONAL MRI; VIGABATRIN; RELEASE; GABACULINE; CORTEX; ANTICONVULSANT AB Vigabatrin and gabaculine, both highly specific inhibitors of GABA (gamma-aminobutyric acid) transaminase, cause significant elevation of endogenous GABA levels in brain. The time course of GABA concentration after acute GABA transaminase inhibition was measured quantitatively in the alpha-chloralose-anesthetized rat brain using in vivo selective homonuclear polarization transfer spectroscopy. The blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging (fMRI) has been considered to be coupled tightly to neuronal activation via the metabolic demand of associated glutamate transport. Correlated with the rise in endogenous GABA level after vigabatrin or gabaculine treatment, the intensity of BOLD-weighted fMRI signals in rat somatosensory cortex during forepaw stimulation was found to be reduced significantly. These results are consistent with previous findings that inhibition of GABA transaminase leads to augmented GABA release and potentiation of GABAergic inhibition. (C) 2004 Wiley-Liss, Inc. C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NINDS, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov RI Silva, Afonso/A-7129-2009 NR 62 TC 43 Z9 44 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 1 PY 2005 VL 79 IS 3 BP 383 EP 391 DI 10.1002/jnr.20364 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 892FG UT WOS:000226634800014 PM 15619231 ER PT J AU Benveniste, H Fowler, JS Rooney, W Ding, YS Baumann, AL Moller, DH Du, CW Backus, W Logan, J Carter, P Coplan, JD Biegon, A Rosenblum, L Scharf, B Gatley, JS Volkow, ND AF Benveniste, H Fowler, JS Rooney, W Ding, YS Baumann, AL Moller, DH Du, CW Backus, W Logan, J Carter, P Coplan, JD Biegon, A Rosenblum, L Scharf, B Gatley, JS Volkow, ND TI Maternal and fetal C-11-cocaine uptake and kinetics measured in vivo by combined PET and MRI in pregnant nonhuman primates SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE C-11-cocaine; maternal-fetal exchange; PET; MRI; primate ID DOPAMINE TRANSPORTER; BLOOD-FLOW; COCAINE; PHARMACOKINETICS; DISPOSITION; FETUS; SHEEP; RAT AB Cocaine use during pregnancy has been shown to be deleterious to the infant. This may reflect reduction of flow to placenta or effects on the fetal brain. Methods to assess pharmacokinetics of drugs of abuse in vivo would be useful to investigate the mechanisms underlying the fetal adverse effects. We recently reported that combined MRI and PET technology allows the measurement of radioisotope distribution in maternal and fetal organs in pregnant Macaca radiata. Here, we evaluate the utility of PET to measure the uptake and distribution of C-11-cocaine in the third-trimester fetus. Methods: Six pregnant M. radiata weighing 3.8-9.0 kg were anesthetized and MR images were acquired on a 4-T MRI instrument. In all 6 animals, dynamic PET scans were subsequently acquired using 148-259 MBq of C-11-cocaine. Time-activity curves for both maternal and fetal organs were obtained simultaneously with the pregnant animal positioned transverse in the PET scanner. Distribution volume ratios for maternal and fetal brain for C-11-cocaine were calculated. Results: Coregistration of PET and MR images allowed identification of fetal organs and brain regions and demonstrated that C-11-cocaine or its labeled metabolites readily cross the placenta and accumulate mainly in fetal liver and to a lesser extent in the brain. Time to reach peak C-11 uptake in brain was shorter for the mother than for the fetus. The distribution volume ratios of the maternal striatum were higher than those of the fetus. Placenta was clearly visible on the early time frames and showed more rapid uptake and clearance than other fetal tissues. Conclusion: The pregnant M. radiata model allows the noninvasive measurement of radioisotope pharmacokinetics in maternal and fetal brain and other organs simultaneously. Although the uptake of radioactivity into the fetal brain after the injection of C-11-cocaine is lower and slower than in the maternal brain, a measurable quantity of C-11-cocaine (or its labeled metabolites) accumulates in the fetal brain at early times after injection. The highest accumulation of C-11 occurs in the fetal liver. Rapid radioisotope accumulation and clearance in the placenta offer potential as an input function for kinetic modeling for future studies of binding site availability. C1 Brookhaven Natl Lab, Dept Med, Upton, NY 11793 USA. SUNY Stony Brook, Dept Anesthesiol, Stony Brook, NY 11794 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. Suny Downstate Med Ctr, Dept Psychiat, Brooklyn, NY 11203 USA. NIAAA, NIH, Bethesda, MD USA. RP Benveniste, H (reprint author), Brookhaven Natl Lab, Dept Med, Bldg 490,30 Bell ASve, Upton, NY 11793 USA. EM Benveniste@bnl.gov FU NIDA NIH HHS [1R21DA0015545] NR 23 TC 22 Z9 22 U1 1 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 FEB PY 2005 VL 46 IS 2 BP 312 EP 320 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 896JD UT WOS:000226929500037 PM 15695792 ER PT J AU Denomme, J Stark, KD Holub, BJ AF Denomme, J Stark, KD Holub, BJ TI Directly quantitated dietary (n-3) fatty acid intakes of pregnant Canadian women are lower than current dietary recommendations SO JOURNAL OF NUTRITION LA English DT Article DE (n-3) fatty acids; dietary intakes; pregnant women; direct quantitation; docosahexaenoic acid ID ALPHA-LINOLENIC ACID; HORMONE REPLACEMENT THERAPY; DOCOSAHEXAENOIC ACID; CARDIOVASCULAR-DISEASE; FETAL BABOONS; RISK-FACTOR; FISH-OIL; BRAIN; CONSUMPTION; ACCRETION AB During pregnancy, (n-3) PUFA are incorporated into fetal brain and retinal lipids. Docosahexaenoic acid [DHA, 22:6(n-3)], in particular, is required physiologically for optimal development and function of the central nervous system. Maternal intake of (n-3) PUFA must be sufficient to maintain maternal tissues stores and meet fetal accruement. Recommendations for pregnant women include an Acceptable Macronutrient Distribution Range (AMDR) of 0.6-1.2% of energy for (n-3) PUFA intake in the current Dietary Reference Intakes, and greater than or equal to300 mg/d of DHA suggested by the International Society for the Study of Fatty Acids and Lipids working group. The present study directly quantitated the (n-3) PUFA intake, including DHA, of pregnant, Canadian women (n = 20) in their 2nd and 3rd trimester. Fatty acid intakes were quantitated in triplicate by lipid extraction and GLC of 3-d duplicate food collections calibrated with an internal standard before homogenization. Total fat intakes were also estimated using dietary analysis software from simultaneous 3-d food records to corroborate biochemical analyses. The mean (n-3) PUFA intake was 0.57 +/- 0.06% of energy, with 65% of the women below the AMDR. The mean DHA intake was 82 +/- 33 mg/d, with 90% of the women consuming <300 mg/d. Nutritional education of pregnant women to ensure adequate intakes of (n-3) PUFA for optimal health of mother and child and the inclusion of DHA in prenatal vitamins may be pertinent. C1 Univ Guelph, Dept Human Biol & Nutrit Sci, Guelph, ON N1G 2W1, Canada. NIAAA, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RP Holub, BJ (reprint author), Univ Guelph, Dept Human Biol & Nutrit Sci, Guelph, ON N1G 2W1, Canada. EM bholub@uoguelph.ca RI Stark, Ken/I-1347-2016 OI Stark, Ken/0000-0001-7828-4072 NR 62 TC 93 Z9 95 U1 2 U2 9 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2005 VL 135 IS 2 BP 206 EP 211 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 894GU UT WOS:000226779700010 PM 15671214 ER PT J AU Hartman, TJ Albert, PS Snyder, K Slattery, ML Caan, B Paskett, E Iber, F Kikendall, JW Marshall, J Shike, M Weissfeld, J Brewer, B Schatzkin, A Lanza, E AF Hartman, TJ Albert, PS Snyder, K Slattery, ML Caan, B Paskett, E Iber, F Kikendall, JW Marshall, J Shike, M Weissfeld, J Brewer, B Schatzkin, A Lanza, E CA Polyp Prevention Study Grp TI The association of calcium and vitamin D with risk of colorectal adenomas SO JOURNAL OF NUTRITION LA English DT Article DE calcium; vitamin D; Polyp Prevention Trial; colorectal adenomas ID COLON-CANCER; UNITED-STATES; DAIRY-PRODUCTS; LOW-FAT; DIETARY INTERVENTION; SUPPLEMENTAL CALCIUM; HYPERPLASTIC POLYPS; OLDER WOMEN; LARGE-BOWEL; D-RECEPTOR AB The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber, high-fruit and vegetable, low-fat diet on the recurrence of adenomatous polyps in the large bowel. Detailed dietary intake and supplement use data were collected at baseline and at each of 4 annual study visits. Adenoma recurrence was ascertained by complete colonoscopy at baseline and after 1 and 4 y. Recurrence was found in 754 of the 1905 trial participants. We evaluated the association between calcium and vitamin D intake and adenomatous polyp recurrence after adjusting for intervention group, age, gender, nonsteroidal anti-inflammatory drug use, total energy intake, and the interaction of gender and intervention group. Vitamin D models were also adjusted for the location of the clinic site. Dietary variables were adjusted for total energy intake via the residual method. There were no overall significant associations between adenoma recurrence and dietary calcium intake [odds ratio (OR) for the 5th compared with the lowest quintile = 0.91; 95% Cl = 0.67-1.23; P-trend = 0.68], total calcium intake (OR = 0.86; 95% Cl = 0.62-1.18; P-trend = 0.20), or dietary vitamin D intake (OR = 0.93; 95% Cl = 0.69-1.25; P-trend = 0.43) averaged over follow-up. Total vitamin D intake was weakly inversely associated with adenoma recurrence (OR = 0.84; 95% Cl = 0.62-1.13; P-trend = 0.03). Supplemental calcium and vitamin D use during follow-up also were inversely associated with adenoma recurrence (OR for any compared with no use = 0.82; 95% Cl = 0.68-0.99; and OR = 0.82; 95% Cl = 0.68-0.99; for calcium and vitamin D, respectively). Slightly stronger associations were noted for the prevention of multiple recurrences. Our analyses did not suggest a significant effect modification between total calcium and total vitamin D intake (P = 0.14) on risk for adenoma recurrence. This trial cohort provides some evidence that calcium and vitamin D may be inversely associated with adenoma recurrence. C1 Penn State Univ, Dept Nutrit Sci, University Pk, PA 16802 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Informat Management Serv Inc, Rockville, MD USA. Univ Utah, Salt Lake City, UT 84112 USA. Kaiser Fdn Res Inst, Oakland, CA USA. Ohio State Univ, Columbus, OH 43210 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Natl Naval Med Res Inst, Bethesda, MD USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. WESTAT Corp, Rockville, MD 20850 USA. NCI, Nutrit Epidemiol Branch, Div Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Lab Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA. RP Hartman, TJ (reprint author), Penn State Univ, Dept Nutrit Sci, University Pk, PA 16802 USA. EM tjhg@psu.edu NR 49 TC 63 Z9 64 U1 2 U2 8 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2005 VL 135 IS 2 BP 252 EP 259 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 894GU UT WOS:000226779700018 PM 15671222 ER PT J AU Kim, YS Milner, JA AF Kim, YS Milner, JA TI Targets for indole-3-carbinol in cancer prevention SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Review DE indole-3-carbinol; estrogen receptor; aryl hydrocarbon receptor; Spl ID HUMAN BREAST-CANCER; CELL-CYCLE ARREST; TRANSCRIPTION FACTOR INTERACTIONS; ACTIVATED PROTEIN-KINASE; ESTROGEN-RECEPTOR-ALPHA; DNA ADDUCT FORMATION; INDUCE APOPTOSIS; GENE-EXPRESSION; 3,3'-DIINDOLYLMETHANE DIM; MAMMARY CARCINOGENESIS AB Mounting preclinical and clinical evidence indicate that indole-3-carbinol (I3C), a key bioactive food component in cruciferous vegetables, has multiple anticarcinogenic and antitumorigenic properties. Evidence that p21, p27, cyclin-dependent kinases, retinoblastoma, Bax/Bcl-2, cytochrome P-450 1Al and GADD153 are targets for I3C already exists. Modification of nuclear transcription factors including Sp1, estrogen receptor, nuclear factor kappaB and aryl hydrocarbon receptor may represent a common site of action to help explain downstream cellular responses to dietary I3C and, ultimately, to its anticancer properties. While the current information is intriguing, future I3C research needs to focus on why these changes in nuclear transcription factors occur and how they relate to phenotypic responses and the quantity and duration of exposure to I3C and its dimer 3,3'-diindolylmethane. Published by Elsevier Inc. C1 NCI, Div Canc Prevent, Nutr Sci Res Grp, Bethesda, MD 20892 USA. RP NCI, Div Canc Prevent, Nutr Sci Res Grp, Bethesda, MD 20892 USA. EM yk47s@nih.gov NR 71 TC 110 Z9 114 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 EI 1873-4847 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD FEB PY 2005 VL 16 IS 2 BP 65 EP 73 DI 10.1016/j.jnutbio.2004.10.007 PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 899NW UT WOS:000227152400001 PM 15681163 ER PT J AU Zylicz, Z Krajnik, M van Sorge, AA Costantini, M AF Zylicz, Z Krajnik, M van Sorge, AA Costantini, M TI Re: Paroxetine in the treatment of severe non-dermatological pruritus - Authors' response SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Letter C1 Ctr Comprehens Canc, Nijmegen, Netherlands. Ludwig Rydgier Univ Med Sci, Bydgoszcz, Poland. Rijnstate Hosp, Arnhem, Netherlands. Natl Canc Inst, Genoa, Italy. RP Zylicz, Z (reprint author), Ctr Comprehens Canc, Nijmegen, Netherlands. RI Krajnik, Malgorzata/G-8923-2014 NR 4 TC 0 Z9 0 U1 1 U2 1 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 FEB PY 2005 VL 29 IS 2 BP 115 EP 116 DI 10.1016/j.jpainsymman.2004.12.004 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 907RS UT WOS:000227736200004 ER PT J AU Voss, JG AF Voss, JG TI Predictors and correlates of fatigue in HIV/AIDS SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE fatigue; depression; HIV/AIDS; hierarchical regression ID QUALITY-OF-LIFE; HIV DISEASE; SYMPTOMS; HEALTH; AIDS; MEN; RELIABILITY; PREVALENCE; SEVERITY; TRIAL AB Variation in the intensity of fatigue according to selected demographic, cultural, and health/illness variables was explored in 372 patients with HIV/AIDS, and the contribution of fatigue to physical and mental health in this population was investigated within the UCSF Symptom Management Model (UCSF-SMM). The sample included 73% African Americans and 63% males. Moderate to severe fatigue intensity was reported by 58% of the total sample. Women, Hispanics, the disabled and those with inadequate income or insurance reported higher fatigue intensity scores. Two hierarchical regression models explored the contributions of fatigue to physical and mental health. Fatigue contributed 2% to the total variance (37.4%) in physical health, but did not contribute as an independent predictor of the total variance (23.2%) in mental health. The results of this study imply the need for further gender and ethnic-specific fatigue research, as well as symptom cluster research. (c) 2005 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. RP Voss, JG (reprint author), NINDS, NIH, Neuromuscular Dis Sect, Bldg 10,Room 4N252,10 Ctr Dr, Bethesda, MD 20892 USA. FU NINR NIH HHS [T32NR07081] NR 31 TC 37 Z9 38 U1 4 U2 8 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 FEB PY 2005 VL 29 IS 2 BP 173 EP 184 DI 10.1016/j.jpainsymman.2004.05.006 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 907RS UT WOS:000227736200012 PM 15733809 ER PT J AU Kim, Y Howerth, EW Shin, NS Kwon, SW Terrell, SP Kim, DY AF Kim, Y Howerth, EW Shin, NS Kwon, SW Terrell, SP Kim, DY TI Disseminated visceral coccidiosis and cloacal cryptosporidiosis in a Japanese white-naped crane (Grus vipio) SO JOURNAL OF PARASITOLOGY LA English DT Article AB A 4-mo-old male Japanese white-naped crane (Grus vipio) kept in an outdoor exhibit at the Everland Zoological Gardens in Korea became depressed and developed anorexia, weight loss, and diarrhea. Death of this bird was associated with an overwhelming systemic infection by an intracellular coccidian parasite, which resulted in necrosis and granulomatous inflammation in a number of major organs, including the intestine, liver, spleen, and kidney. Coccidian parasite-laden macrophages were Commonly found in the blood vessels of these organs. Using electron microscopy and polymerase chain reaction assays, the parasite, was identified as Eimeria sp. The bird was also infected with Cryptosporidium sp., which suggests an immunosuppressed state. although the cause of such suppression was not identified. Our findings suggest that an initial Eimeria sp. intestinal infection spread to other organs through the blood vessels, with the immunosuppressed state possibly contributing to a rapid hematogenous transmission. To our knowledge, this is the first report of disseminated visceral coccidiosis caused by Eimeria sp. in a captive Japanese white-naped crane. C1 Seoul Natl Univ, Coll Vet Med, Dept Vet Pathol, Seoul 151742, South Korea. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Georgia, Coll Vet Med, Dept Pathol, Athens, GA 30605 USA. Seoul Natl Univ, Coll Vet Med, Dept Wild Anim Med, Seoul 151742, South Korea. Everland Zool Gardens, Yongin 449715, South Korea. Walt Disney World Anim Programs, Bay Lake, FL 32830 USA. RP Kim, DY (reprint author), Seoul Natl Univ, Coll Vet Med, Dept Vet Pathol, Seoul 151742, South Korea. EM daeyong@plaza.snu.ac.kr NR 6 TC 6 Z9 6 U1 0 U2 9 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD FEB PY 2005 VL 91 IS 1 BP 199 EP 201 DI 10.1645/GE-378R PG 3 WC Parasitology SC Parasitology GA 907QN UT WOS:000227733100041 PM 15856903 ER PT J AU Susin, C Kingman, A Albandar, JM AF Susin, C Kingman, A Albandar, JM TI Effect of partial recording protocols on estimates of prevalence of periodontal disease SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE clinical protocols; dental records; periodontal attachment loss; periodontal diseases/diagnosis; observer bias ID ADULTS 30 YEARS; ATTACHMENT LOSS; UNITED-STATES; RISK INDICATORS; PARTIAL-MOUTH; OLDER; POPULATION; SEVERITY; HALF; CPITN AB Background: The aim of this study was to assess the degree of underreporting in the estimates of prevalence of periodontal attachment loss due to different partial recording protocols (PRP) in epidemiological studies, and to derive a correction factor to adjust for this bias. Methods: The study sample included 1,460 dentate persons 14 to 103 years old who were examined clinically to assess the clinical attachment loss at six sites per tooth. Seven PRP based on full-mouth or half-mouth designs were assessed, and the bias and sensitivity in the assessment of attachment loss prevalence for these protocols were assessed. Results: All partial protocols underestimated the prevalence of attachment loss. Bias estimates for any full-mouth PRP were smaller than those for the corresponding site-combination PRP for the half-mouth design. The PRP using the mesio-buccal (MB), mid-buccal (B), and disto-lingual (DL) sites of teeth in all four quadrants showed the smallest bias and highest sensitivity of prevalence estimates among the seven PRP evaluated, uniformly across the range of attachment loss severity level. The three site PRP incorporating the DL site produced less bias than the three site PRP including the disto-buccal (DB) site. There was a 3% to 12% gain in sensitivity for 2 to 5 mm attachment loss thresholds for the three site half-mouth PRP compared with the two site MB, B half-mouth PRP. Conclusions: The bias in the assessment of attachment loss is influenced by the partial recording design and the type and number of sites assessed, and is also influenced by the severity of attachment loss in the study population. These factors should be considered when selecting a partial recording method in large surveys. Furthermore, inflation factors designed to adjust for the bias due to the use of partial systems should be calculated and reported so that comparisons of results with other surveys are more meaningful. C1 Temple Univ, Sch Dent, Dept Periodontol, Periodontol Diagnost Res Lab, Philadelphia, PA 19140 USA. Univ Bergen, Fac Dent, Bergen, Norway. Univ Luterana Brasil, Dept Periodontol, Canoas, Brazil. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Albandar, JM (reprint author), Temple Univ, Sch Dent, Dept Periodontol, Periodontol Diagnost Res Lab, 3223 N Broad St, Philadelphia, PA 19140 USA. EM Jasim.Albandar@temple.edu RI Susin, Cristiano/B-9822-2008; OI Albandar, Jasim M./0000-0001-7801-3811 NR 21 TC 90 Z9 94 U1 0 U2 4 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD FEB PY 2005 VL 76 IS 2 BP 262 EP 267 DI 10.1902/jop.2005.76.2.262 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 912NK UT WOS:000228085500015 PM 15974851 ER PT J AU Miyata, M Tozawa, A Otsuka, H Nakamura, T Nagata, K Gonzalez, FJ Yamazoe, Y AF Miyata, M Tozawa, A Otsuka, H Nakamura, T Nagata, K Gonzalez, FJ Yamazoe, Y TI Role of farnesoid X receptor in the enhancement of canalicular bile acid output and excretion of unconjugated bile acids: A mechanism for protection against cholic acid-induced liver toxicity SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SALT EXPORT PUMP; ORPHAN NUCLEAR RECEPTOR; P-GLYCOPROTEIN; MOUSE-LIVER; CHOLESTASIS; EXPRESSION; SISTER; MICE; SULFOTRANSFERASE; IDENTIFICATION AB Mice lacking the farnesoid X receptor (FXR) involved in the maintenance of hepatic bile acid levels are highly sensitive to cholic acid-induced liver toxicity. Serum aspartate aminotransferase (AST) activity was elevated 15.7-fold after feeding a 0.25% cholic acid diet, whereas only slight increases in serum AST (1.7- and 2.5-fold) were observed in wild-type mice fed 0.25 and 1% cholic acid diet, respectively. Bile salt export pump mRNA and protein levels were increased in wild-type mice fed 1% cholic acid diet (2.1- and 3.0-fold) but were decreased in FXR-null mice fed 0.25% cholic acid diet. The bile acid output rate was 2.0- and 3.7-fold higher after feeding of 0.25 and 1.0% cholic acid diet in wild-type mice, respectively. On the other hand, no significant increase in bile acid output rate was observed in FXR-null mice fed 0.25% cholic acid diet in contrast to a significant decrease observed in mice fed a 1.0% cholic acid diet in spite of the markedly higher levels of hepatic tauro-conjugated bile acids. Unconjugated cholic acid was not detected in the bile of wild-type mice fed a control diet, but it was readily detected in wild-type mice fed 1% cholic acid diet. The ratio of biliary unconjugated cholic acid to total cholic acid ( unconjugated cholic acid and tauro-conjugated cholic acid) reached 30% under conditions of hepatic taurine depletion. These results suggest that the cholic acid-induced enhancement of canalicular bile acid output rates and excretion of unconjugated bile acids are involved in adaptive responses for prevention of cholic acid-induced toxicity. C1 Tohoku Univ, Grad Sch Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Aoba Ku, Sendai, Miyagi 9808578, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Miyata, M (reprint author), Tohoku Univ, Grad Sch Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Aoba Ku, Sendai, Miyagi 9808578, Japan. EM miyata@mail.pharm.tohoku.ac.jp NR 38 TC 25 Z9 26 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2005 VL 312 IS 2 BP 759 EP 766 DI 10.1124/jpet.104.076158 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 888IJ UT WOS:000226367100040 PM 15466244 ER PT J AU Bird, GS Putney, JW AF Bird, GS Putney, JW TI Capacitative calcium entry supports calcium oscillations in human embryonic kidney cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CYTOPLASMIC FREE CALCIUM; PROTEIN-KINASE-C; CA2+ ENTRY; TRPC3 CHANNELS; HEK293 CELLS; RELEASE; HEPATOCYTES; PATHWAYS; ACTIVATION; MECHANISMS AB Treatment of human epithelial kidney (HEK293) cells with low concentrations of the muscarinic agonist methacholine results in the activation of complex and repetitive cycling of intracellular calcium ([Ca2+](i)), known as [Ca2+](i) oscillations. These oscillations occur with a frequency that depends on the concentration of methacholine, whereas the magnitude of the [Ca2+](i) spikes does not. The oscillations do not persist in the absence of extracellular Ca2+, leading to the conclusion that entry of Ca2+ across the plasma membrane plays a significant role in either their initiation or maintenance. However, treatment of cells with high concentrations of GdCl3, a condition which limits the flux of calcium ions across the plasma membrane in both directions, allows sustained [Ca2+], oscillations to occur. This suggests that the mechanisms that both initiate and regenerate [Ca2+](i) Oscillations are intrinsic to the intracellular milieu and do not require entry of extracellular Ca2+. This would additionally suggest that, under normal conditions, the role of calcium entry is to sustain [Ca2+](i) oscillations. By utilizing relatively specific pharmacological manoeuvres we provide evidence that the Ca2+ entry that supports Ca2+ oscillations occurs through the store-operated or capacitative calcium entry pathway. However, by artificial introduction of a non-store-operated pathway into the cells (TRPC3 channels), we find that other Ca2+ entry mechanisms can influence oscillation frequency in addition to the store-operated channels. C1 NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Bird, GS (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM bird@niehs.nih.gov NR 29 TC 75 Z9 78 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB 1 PY 2005 VL 562 IS 3 BP 697 EP 706 DI 10.1113/jphysiol.2004.077289 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 894GK UT WOS:000226778700007 PM 15513935 ER PT J AU Rana, ZA Gundersen, K Buonanno, A Vullhorst, D AF Rana, ZA Gundersen, K Buonanno, A Vullhorst, D TI Imaging transcription in vivo: distinct regulatory effects of fast and slow activity patterns on promoter elements from vertebrate troponin I isoform genes SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID MYOSIN HEAVY-CHAIN; MUSCLE FIBER-TYPE; ADULT SKELETAL-MUSCLE; TRANSGENIC MICE; NERVE-ACTIVITY; ELECTRICAL-ACTIVITY; RAT MUSCLES; NEUROMUSCULAR-JUNCTIONS; CONTRACTILE PROPERTIES; DEPENDENT REGULATION AB Firing patterns typical of slow motor units activate genes for slow isoforms of contractile proteins, but it remains unclear if there is a distinct pathway for fast isoforms or if their expression simply occurs in the absence of slow activity. Here we first show that denervation in adult soleus and EDL muscles reverses the postnatal increase in expression of troponin I (TnI) isoforms, suggesting that high-level transcription of both genes in mature muscles is under neural control. We then use a combination of in vivo transfection, live muscle imaging and fluorescence quantification to investigate the role of patterned electrical activity in the transcriptional control of troponin I slow (TnIs) and fast (TnIf) regulatory sequences by directly stimulating denervated muscles with pattern that mimic fast and slow motor units. Rat soleus muscles were electroporated with green fluorescent protein (GFP) reporter constructs harbouring 2.7 and 2.1 kb of TnIs and TnIf regulatory sequences, respectively. One week later, electrodes were implanted and muscles stimulated for 12 days. The change in GFP fluorescence of individual muscle fibres before and after the stimulation was used as a measure for transcriptional responses to different patterns of action potentials. Our results indicate that the response of TnI promoter sequences to electrical stimulation is consistent with the regulation of the endogenous genes. The TnIf and TnIs enhancers were activated by matching fast and slow activity patterns, respectively. Removal of nerve-evoked activity by denervation, or stimulation with a mismatching pattern reduced transcriptional activity of both enhancers. These results strongly suggest that distinct signalling pathways couple both fast and slow patterns of activity to enhancers that regulate transcription from the fast and slow troponin I isoforms. C1 NICHD, Mol Neurobiol Sect, NICHHD, Bethesda, MD USA. Univ Oslo, Dept Mol Biosci, Oslo, Norway. RP Vullhorst, D (reprint author), NICHD, Mol Neurobiol Sect, NICHHD, Bethesda, MD USA. EM vullhord@mail.nih.gov NR 62 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB 1 PY 2005 VL 562 IS 3 BP 815 EP 828 DI 10.1113/jphysiol.2004.075333 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 894GK UT WOS:000226778700015 PM 15528243 ER PT J AU Gougelet, A Bouclier, C Marsaud, V Maillard, S Mueller, SO Korach, KS Renoir, JM AF Gougelet, A Bouclier, C Marsaud, V Maillard, S Mueller, SO Korach, KS Renoir, JM TI Estrogen receptor alpha and beta subtype expression and transactivation capacity are differentially affected by receptor-, hsp90- and immunophilin-ligands in human breast cancer cells SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 16th International Symposium of the Journal-of-Steroid-Biochemistry-and-Molecular-Biology CY JUN 05-08, 2004 CL Seefeld, AUSTRIA SP Journal Steroid Biochem & Mol Biol, Inst Rech Pierre Fabre DE estrogen receptors; breast cancer cells; anti-estrogens; proteasome; transactivation; hsp90-inhibitors; immunosuppressants ID HSP90 MOLECULAR CHAPERONE; HEAT-SHOCK-PROTEIN; ER-ALPHA; TRANSCRIPTIONAL ACTIVITY; TARGET PROMOTER; GENE-EXPRESSION; MESSENGER-RNA; PROTEASOME; BINDING; MECHANISMS AB In MCF-7 (estrogen receptor (ER)+) and in MDA-MB-231 (ER-) cells stably transfected with either estrogen receptor a (ER alpha) or P (ER beta) subtype (MDA-MB-231 stably transfected with the mouse ER alpha cDNA (MERA) and MDA-MB-231 stably transfected with the human ER beta cDNA (HERB), respectively) N-term heat shock protein of 90 kDa (hsp90) ligands (geldanamycin and radicicol) and C-term hsp90 ligands (novobiocin) decrease the basal and estradiol (E-2)-induced transcription activity of ER on an estrogen responsive element (ERE)-LUC reporter construct concomitantly with or I h after E2 treatment. All hsp90 ligands induced an E-2- and MG132-inhibited decrease of both ER cell content. However, the kinetics of these degradations are slower than those induced by the selective estrogen receptor down-regulator RU 58668 (RU). This suggests that inhibition of the hsp90 ATPase activity targets both ERs to the 26S proteasome and that hsp90 interacts with both ER subtypes. Rapamycin (Rapa) and cyclosporin A (CsA), ligands of immunophilins FK506 binding protein (FKBP52) and cyclophilin of 40 kDa (CYP40) interacting in separate ER-hsp90 complexes, both induced a proteasomal-mediated degradation of ERs but not of their cognate immunophilin. Moreover, they also decrease the E-2-induced luciferase transcription but weaker than RU and hsp90 ligands. Fluorescence activated cell sorter (FACS) analysis revealed a blockade of cell progression by RU and 4-hydroxy-tamoxifen at the G(1) phase of the cell cycle and an induction of apoptosis in MCF-7 cells. Rapa and mainly CsA (but not FK506) and hsp90 ligands promote by their own apoptosis in MCF-7, in MERA, and in HERB cells and in MDA-MB-231 ER-null cells. These data suggest that (1) hsp90, as for all steroid receptors, acts as a molecular chaperone for ER beta; (2) ER-ligands (except tamoxifen), hsp90- and immunophilin-ligands (except FK506) target the two ER subtypes to a proteasome-mediated proteolysis via different signalling pathways; (3) hsp90- and immunophilin-ligands Rapa and CsA, alone or in association with anti-estrogens such as RU, may constitute a potential therapeutic strategy for breast cancer treatment. (c) 2005 Elsevier Ltd. All rights reserved. C1 UMR CNRS 8612, F-92296 Chatenay Malabry, France. Merck KGaA, Inst Toxicol, Darmstadt, Germany. NIEHS, Res Triangle Pk, NC 27709 USA. RP Renoir, JM (reprint author), UMR CNRS 8612, 5 Rue JB Clement, F-92296 Chatenay Malabry, France. EM michel.renoir@cep.u-psud.fr RI Gougelet, Angelique/E-2071-2017; OI Gougelet, Angelique/0000-0001-7464-9804; Korach, Kenneth/0000-0002-7765-418X NR 59 TC 31 Z9 32 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD FEB PY 2005 VL 94 IS 1-3 BP 71 EP 81 DI 10.1016/j.jsbmb.2005.01.018 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 930VP UT WOS:000229445500008 PM 15862952 ER PT J AU Vitiello, B Aman, MG Scahill, L McCracken, JT McDougle, CJ Tierney, E Davies, M Arnold, LE AF Vitiello, B Aman, MG Scahill, L McCracken, JT McDougle, CJ Tierney, E Davies, M Arnold, LE TI Research knowledge among parents of children participating in a randomized clinical trial SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ethics; clinical trials ID INFORMED-CONSENT; UNDERSTAND AB Objective: Parental permission is required for child research, but parents' understanding of research aims and procedures has not been well documented. Parental research knowledge was assessed during a clinical trial in autism. Method: Parents of 101 children (age 5-17 years) with autism participating in a placebo-controlled trial of risperidone were given a questionnaire at the end of the study. Results: Of the 95 parents completing the questionnaire, 99% knew of possible placebo assignment and that testing the medication efficacy was the main purpose of the investigators; 96% to 98% knew that research involved both risks and potential benefits, identified the study medication, and knew of their right to withdraw at any time; 90% to 95% knew of the medication's main side effects; 87% reported having been informed of possible alternatives to research participation; and 72% were aware that treatment was randomly assigned (whereas 27% reported that treatment was chosen based on individual needs to ensure best care). Parents with a college degree were more likely to recognize the random nature of treatment assignment. Conclusions: Overall, parents were highly knowledgeable of the main research components. About one fourth, however, seemed unaware that treatment was randomly determined and not personalized, suggesting that therapeutic misconception may affect some otherwise well-informed parents. C1 NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA USA. Indiana Univ, Div Child & Adolescent Psychiat, Indianapolis, IN 46204 USA. Kennedy Krieger Inst, Baltimore, MD USA. Columbia Univ, New York State Psychiat Inst, New York, NY 10027 USA. RP Vitiello, B (reprint author), NIMH, Child & Adolescent Treatment & Prevent Intervent, Room 7147,6001 Execut Blvd,MSC 9633, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov OI Scahill, Lawrence/0000-0001-5073-1707 FU NIMH NIH HHS [K24MH10805, N01MH80011, N01MH70010, N01MH70001, N01MH70009] NR 13 TC 20 Z9 20 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 2005 VL 44 IS 2 BP 145 EP 149 DI 10.1097/00004583-200502000-00006 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 893HP UT WOS:000226710200006 PM 15689727 ER PT J AU Liang, C Kraemer, KH Morris, A Schiffmann, R Price, VH Menefee, E DiGiovanna, JJ AF Liang, C Kraemer, KH Morris, A Schiffmann, R Price, VH Menefee, E DiGiovanna, JJ TI Characterization of tiger tail banding and hair shaft abnormalities in trichothiodystrophy SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID DEFICIENT BRITTLE HAIR; XERODERMA-PIGMENTOSUM; BASAL TRANSCRIPTION; MUTATIONS; PATTERN AB Background: Tiger tail banding under polarizing light microscopy and hair shaft abnormalities are associated with trichothiodystrophy (TTD), a rare disorder with a wide spectrum of clinical presentations. Objective: To characterize the frequency, specificity, and extent of tiger tail banding and hair shaft abnormalities in the spectrum of TTD patients. Methods: We developed a standardized procedure for microscopic hair examination and studied hairs from 14 TTD and 4 xeroderma pigmentosum (XP)-TTD patients for tiger tail banding and hair shaft abnormalities. For comparison we examined hairs from 173 control donors consisting of 15 normals, 13 XP patients, 11 family members of XP or TTD patients, 101 patients with various cornification disorders, and 33 leukodystrophy patients. Amino acid analysis performed on hair from the TTD and XP-TTD patients showed low sulfur content. Results: Using a rotating microscope stage, all hairs in each TTD sample showed tiger tail banding under polarized light in association with a variety of hair shaft abnormalities (trichoschisis, trichorrhexis nodosa-like defects, surface irregularities, and ribboning). None of the control hairs showed tiger tail banding, and 5 of 173 controls had weathering hair shaft abnormalities. Conclusions: In patients with clinical features suggestive of TTD, tiger tail banding seen in all hairs with polarizing microscopy, in conjunction with certain hair shaft abnormalities, provides a reliable diagnostic test. C1 NCI, DNA Repair Sect, Bethesda, MD 20892 USA. Univ Calif San Francisco, NINDS, NIH, Dept Dermatol,Hair Res Ctr, San Francisco, CA 94143 USA. Brown Med Sch, Dept Dermatol, Div Dermatopharmacol, Providence, RI USA. RP Liang, C (reprint author), NCI, DNA Repair Sect, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 14 TC 28 Z9 28 U1 0 U2 1 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 FEB PY 2005 VL 52 IS 2 BP 224 EP 232 DI 10.1016/j.jaad.2004.09.013 PG 9 WC Dermatology SC Dermatology GA 893EF UT WOS:000226701400004 PM 15692466 ER PT J AU Eberting, CLD Javor, E Gorden, P Turner, ML Cowen, EW AF Eberting, CLD Javor, E Gorden, P Turner, ML Cowen, EW TI Insulin resistance, acanthosis nigricans, and hypertriglyceridemia SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CONGENITAL GENERALIZED LIPODYSTROPHY; OBESE GENE; THERAPY C1 NCI, Dermatol Branch, CCR, Bethesda, MD 20892 USA. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. RP Cowen, EW (reprint author), NCI, Dermatol Branch, CCR, NCI Bldg 10,Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov NR 16 TC 7 Z9 8 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2005 VL 52 IS 2 BP 341 EP 344 DI 10.1016/j.jaad.2004.10.867 PG 4 WC Dermatology SC Dermatology GA 893EF UT WOS:000226701400019 PM 15692481 ER PT J AU Telep, JD Raval, AN Guttman, MA Ozturk, C Jones, M Thompson, RB Wright, VJ Schenke, WH DeSilva, R Aviles, RJ Raman, VK Slack, MC Lederman, RJ AF Telep, JD Raval, AN Guttman, MA Ozturk, C Jones, M Thompson, RB Wright, VJ Schenke, WH DeSilva, R Aviles, RJ Raman, VK Slack, MC Lederman, RJ TI Real-time MRI guided aortic coarctation stent repair is safe and feasible in a swine model SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RI Thompson, Richard/E-9821-2011; Ozturk, Cengizhan/A-6177-2016 OI Ozturk, Cengizhan/0000-0002-6966-0774 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 12A EP 12A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808200051 ER PT J AU Plehn, JF Owens, DS McAreavey, D Bacharach, SL Arai, AE Fananapazir, L Tripodi, D Mohiddin, SA AF Plehn, JF Owens, DS McAreavey, D Bacharach, SL Arai, AE Fananapazir, L Tripodi, D Mohiddin, SA TI Is MRI-determined LV mass associated with ventricular filling and exercise capacity in non-obstructive hypertrophic cardiomyopathy? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 129A EP 129A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808200563 ER PT J AU Shizukuda, Y Nguyen, T Bolan, CD Sachdev, V Tripodi, D Inez, E Yau, Y Leitman, SF Finkel, T Rosing, DR AF Shizukuda, Y Nguyen, T Bolan, CD Sachdev, V Tripodi, D Inez, E Yau, Y Leitman, SF Finkel, T Rosing, DR TI Role of oxidative stress in diastolic function in patients with hereditary hemochromatosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 129A EP 129A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808200561 ER PT J AU Domanski, M Jablonski, KA Rice, M Fowler, S Pfeffer, M Braunwald, E AF Domanski, M Jablonski, KA Rice, M Fowler, S Pfeffer, M Braunwald, E TI Obesity as a risk factor for major adverse cardiovascular events in patients with stable coronary disease and preserved left ventricular function SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 NHLBI, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 204A EP 204A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808200891 ER PT J AU Shizukuda, Y Bolan, CD Tripodi, DJ Sachdev, V Nguyen, T Inez, E Yau, YY Leitman, SF Rosing, DR AF Shizukuda, Y Bolan, CD Tripodi, DJ Sachdev, V Nguyen, T Inez, E Yau, YY Leitman, SF Rosing, DR TI Altered diastolic function in asymptornatic patients who were newly diagnosed with hereditary hemochromatosis: Utilization of strain rate imaging SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 255A EP 255A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808201104 ER PT J AU Wen, H Bennett, E Plehn, JF AF Wen, H Bennett, E Plehn, JF TI MRI assessment of myocardial elasticity using displacement imaging and phase-contrast velocity mapping SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 NHLBI, NIH, Bethesda, MD 20892 USA. RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 259A EP 260A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808201123 ER PT J AU Padmanabhan, S Sachdev, V Hsu, LY Stanislav, S Arai, AE AF Padmanabhan, S Sachdev, V Hsu, LY Stanislav, S Arai, AE TI Longitudinal, myocardial and transmitral velocities by phase-contrast cardiac magnetic resonance imaging: Correlation with Doppler echocardiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 NHLBI, NIH, LCE, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 260A EP 260A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808201126 ER PT J AU Paterson, DI Natanzon, A Pessahna, B Arai, AE AF Paterson, DI Natanzon, A Pessahna, B Arai, AE TI Detection of right ventricular infarction by cardiac magnetic resonance imaging SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 288A EP 288A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808201250 ER PT J AU Raval, AN Karmarkar, PV Guttman, MA Ozturk, C DeSilva, R Aviles, RJ McVeigh, ER Atalar, E Lederman, RJ AF Raval, AN Karmarkar, PV Guttman, MA Ozturk, C DeSilva, R Aviles, RJ McVeigh, ER Atalar, E Lederman, RJ TI Interactive real-time magnetic resonance-guided atrial septal puncture and atrial balloon septostomy are feasible in swine SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 NHLBI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. RI Atalar, Ergin/D-3184-2012; Ozturk, Cengizhan/A-6177-2016 OI Atalar, Ergin/0000-0002-6874-6103; Ozturk, Cengizhan/0000-0002-6966-0774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 328A EP 329A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808201422 ER PT J AU Paul, JD Powell, TM Thompson, M Benjamin, M Rodrigo, M McCoy, JP Zalos, G Press, B Murphy, M Hill, JM Csako, G Cannon, RO AF Paul, JD Powell, TM Thompson, M Benjamin, M Rodrigo, M McCoy, JP Zalos, G Press, B Murphy, M Hill, JM Csako, G Cannon, RO CA Natl Inst Hlth TI Importance of endothelial progenitor cell activation to improvement in endothelial function in coronary artery disease patients undergoing cardiac rehabilitation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 Natl Inst Hlth, Bethesda, MD USA. Suburban Hosp, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 385A EP 385A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808201662 ER PT J AU Koh, KK Han, SH Quon, MJ Chung, WJ Shin, MS Ahn, TH Choi, IS Shin, EK AF Koh, KK Han, SH Quon, MJ Chung, WJ Shin, MS Ahn, TH Choi, IS Shin, EK TI Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of patients with combined hyperlipidemia SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 Gachon Med Sch, Inchon, South Korea. NIH, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 394A EP 394A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808201705 ER PT J AU Koh, KK Han, SH Quon, MJ Kang, WC Shin, MS Choi, S AF Koh, KK Han, SH Quon, MJ Kang, WC Shin, MS Choi, S TI Comparative metabolic effects of fenofibrate and atorvastatin in patients with combined hyperlipiderma SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 Gachon Med Sch, Inchon, South Korea. NIH, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 396A EP 396A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808201713 ER PT J AU Koh, KK Han, SH Quon, MJ Kang, WC Shin, MS Shin, EK AF Koh, KK Han, SH Quon, MJ Kang, WC Shin, MS Shin, EK TI Vascular and metabolic effects of fenofibrate in hypertriglyceridemic patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 Gachon Med Sch, Inchon, South Korea. NIH, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 428A EP 428A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808201856 ER PT J AU Tabak, LA AF Tabak, LA TI Practice-based research - Author's response SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Tabak, LA (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD FEB PY 2005 VL 136 IS 2 BP 146 EP 146 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 898TA UT WOS:000227097900006 ER PT J AU Stables, GJ Young, EM Howerton, MW Yaroch, AL Kuester, S Solera, MK Cobb, K Nebeling, L AF Stables, GJ Young, EM Howerton, MW Yaroch, AL Kuester, S Solera, MK Cobb, K Nebeling, L TI Small school-based effectiveness trials increase vegetable and fruit consumption among youth SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID RESOURCE TEACHERS; US ADULTS; GIMME 5; HEALTH; PROGRAM; CHILDREN; OUTCOMES; ADOLESCENTS; CANCER; RISK AB This article profiles a research initiative of state health agency-initiated 5 A Day school-based interventions. Four of the seven projects reviewed had significant results, with an average effect size of 0.4 servings of vegetables and fruit. Results are comparable with the largerscale, well-controlled, and more costly 5 A Day For Better Health efficacy trials. These comparable findings underscore the value of assessing effectiveness of interventions in real-world settings to potentially enable wide-scale implementation of tested strategies. These small effectiveness trials show that school-based interventions are feasible to implement using current and effective strategies, and may facilitate translation of health promotion research to practice. The projects fostered valuable research/practice partnerships at the community level. Limitations across studies included heterogeneity in research methods, participant attrition, and variability in reporting data. Further research is needed to develop standardized, cost-effective dietary assessment methodology for viable dissemination research in community settings. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. GJS Associates, Potomac, MD USA. NCI, 5 A Day Better Hlth Program, Bethesda, MD 20892 USA. NCI, Hlth Promot Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Tennessee, Dept Nutr, Knoxville, TN 37996 USA. Johns Hopkins Univ, Sch Med, Dept Canc Prevent & Control, Baltimore, MD USA. NCI, Behav Res Program, Hlth Promot Res Branch, Bethesda, MD 20892 USA. NCI, Hlth Promot Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Nutr & Phys Act, Atlanta, GA USA. Ctr Dis Control & Prevent, 5 Day Better Hlth Program, Old Saybrook, CT USA. RP Stables, GJ (reprint author), 12740 Lamp Post Lane, Potomac, MD 20854 USA. EM gstables@comcast.net NR 30 TC 16 Z9 16 U1 2 U2 5 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD FEB PY 2005 VL 105 IS 2 BP 252 EP 256 DI 10.1016/j.jada.2004.11.031 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 893QA UT WOS:000226733100017 PM 15668684 ER PT J AU Simonsick, EM Guralnik, JM Volpato, S Balfour, J Fried, LP AF Simonsick, EM Guralnik, JM Volpato, S Balfour, J Fried, LP TI Just get out the door! Importance of walking outside the home for maintaining mobility: Findings from the Women's Health and Aging Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aged; walking; women; mobility; physical activity ID DISABLED OLDER WOMEN; LOWER-EXTREMITY FUNCTION; BODY-MASS INDEX; PHYSICAL-ACTIVITY; ELDERLY-PEOPLE; ADULTS; EXERCISE; DISEASE; RISK; DISABILITY AB OBJECTIVES: To determine the association between volitional walking behavior and change in walking ability and lower extremity function over 1 year in functionally limited older women. DESIGN: Longitudinal cohort study. SETTING: Data were collected in participant's homes in Baltimore, Maryland. PARTICIPANTS: One thousand two cognitively intact community-resident female Medicare beneficiaries aged 65 and older enrolled in the Women's Health and Aging Study. MEASUREMENTS: Reported walking behavior and change in reported walking difficulty, usual and rapid gait speed, and lower extremity physical performance score over 1 year. RESULTS: Of 800 functionally limited women who could walk unassisted at baseline and were alive and contacted 1 year later, 226 (28%) walked regularly, at least eight blocks per week. These women exhibited better health and functioning than nonwalkers (e.g., lower prevalence of depressive and fatigue symptoms and cardiovascular disease and higher mean ankle-arm index, forced expiratory volume in the first second, and gait speed). One year later, independent of initial functional status, social-psychological and behavioral factors, and health conditions, walkers were 1.8 times (95% confidence interval=1.2-2.7; P=.002) more likely to maintain reported walking ability and showed less decline in customary walking speed (0.009 m/s vs -0.070 m/s; P=.001) and functional performance score (-0.17 vs -0.73; P=.01) than women who walked less than eight blocks. CONCLUSION: The strength, consistency, and specificity of the association between walking behavior and maintenance of mobility provide strong evidence that even a small amount of regular walking can confer short-term protection from further mobility loss in functionally limited women. The observation that most women capable of walking at least eight blocks per week were not doing so indicates the need to get more women "out the door" and to encourage those who walk a little to walk a little more. C1 Harbor Hosp, NIA, Clin Res Branch, ASTRA, Baltimore, MD 21225 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. RP Simonsick, EM (reprint author), Harbor Hosp, NIA, Clin Res Branch, ASTRA, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM simonsickel@grc.nia.nih.gov RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 FU NIA NIH HHS [N01-AG-12112] NR 38 TC 131 Z9 133 U1 5 U2 19 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 FEB PY 2005 VL 53 IS 2 BP 198 EP 203 DI 10.1111/j.1532-5415.2005.53103.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 889VW UT WOS:000226471900003 PM 15673341 ER PT J AU Arnold, AM Psaty, BM Kuller, LH Burke, GL Manolio, TA Fried, LP Robbins, JA Kronmal, RA AF Arnold, AM Psaty, BM Kuller, LH Burke, GL Manolio, TA Fried, LP Robbins, JA Kronmal, RA TI Incidence of cardiovascular disease in older Americans: The Cardiovascular Health Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cardiovascular disease; incidence; congestive heart failure; coronary heart disease; stroke ID CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; SUBCLINICAL DISEASE; PRIMARY PREVENTION; RISK-FACTORS; STROKE; TRENDS; PREDICTORS; ATHEROSCLEROSIS; MINNESOTA AB OBJECTIVES: To estimate incidence rates of major cardiovascular disease (CVD) in older Americans. DESIGN: Longitudinal cohort study using prospectively collected data on cardiovascular events. SETTING: Four U.S. communities in the Cardiovascular Health Study (CHS). PARTICIPANTS: Five thousand eight hundred eighty-eight participants in CHS, aged 65 or older at enrollment, including 3,393 women (581 African American) and 2,495 men (343 African American). MEASUREMENTS: At semiannual contacts, participants reported any occurrence of clinical CVD. Medical records were obtained and adjudicated to confirm diagnosis of CVD. RESULTS: During 10 years of follow-up, incidence of coronary heart disease (CHD) per 1,000 person-years was 39.6 (95% confidence interval (CI)=36.4-43.1) in men and 22.3 (95% CI=20.4-24.2) in women. Cumulative event rates for CHD and myocardial infarction for women aged 75 and older at baseline were similar to those for men aged 65 to 74. The overall incidence of stroke was similar for men and women (14.7 (95% CI=13.0-16.6) and 13.7 (95% CI=12.4-15.1) per 1,000 person-years, respectively), but the risk of stroke increased with age more rapidly in women, resulting in a greater cumulative event rate for stroke in women than in men aged 75 and older. The incidence of congestive heart failure increased 9% with each year of age over 65 and was greater than 6% per year in Caucasian men and women aged 85 and older at baseline. Rates were similar in African Americans and Caucasians. CONCLUSION: The occurrence of new CVD in older Americans is high, indicating that preventive efforts need to be maintained into older ages. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Hlth Policy, Baltimore, MD 21205 USA. Univ Calif Davis, Dept Internal Med, Sacramento, CA 95817 USA. RP Arnold, AM (reprint author), Collaborat Hlth Studies Coordinating Ctr, Bldg 29,Suite 310,6200 NE 74th St, Seattle, WA 98155 USA. EM arnolda@u.washington.edu FU NHLBI NIH HHS [N01 HC-85080, N01 HC-85081, N01 HC-85082, N01 HC-85079, N01 HC-85083, N01 HC-85084, N01 HC-85085, N01 HC-85086, N01 HC15103, N01-HC-35129] NR 35 TC 62 Z9 63 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 2005 VL 53 IS 2 BP 211 EP 218 DI 10.1111/j.1532-5415.2005.53105.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 889VW UT WOS:000226471900005 PM 15673343 ER PT J AU Zhan, CL Correa-de-Araujo, R Bierman, AS Sangl, J Miller, MR Wickizer, SW Stryer, D AF Zhan, CL Correa-de-Araujo, R Bierman, AS Sangl, J Miller, MR Wickizer, SW Stryer, D TI Suboptimal prescribing in elderly outpatients: Potentially harmful drug-drug and drug-disease combinations SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE prescription drugs; drug interactions; medication errors; aged ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INAPPROPRIATE MEDICATION USE; HEART-VALVE REPLACEMENT; EXPLICIT CRITERIA; HIGH-RISK; WARFARIN; ASPIRIN; PREVENTION; THERAPY; PEOPLE AB OBJECTIVES: To assess the prevalence and correlates of potentially harmful drug-drug combinations and drug-disease combinations prescribed for elderly patients at outpatient settings. DESIGN: Retrospective analysis of the 1995-2000 National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS). SETTING: Physician offices and hospital outpatient departments. PARTICIPANTS: Outpatient visits by patients aged 65 and older in the NAMCS and NHAMCS (n=70,203). MEASUREMENTS: Incidences of six drug-drug combinations and 50 drug-disease combinations that can place elderly patients at risk for adverse events according to expert consensus panels. RESULTS: Overall, 0.74% (95% confidence interval (CI)=0.65-0.83) of visits with two or more prescriptions had at least one inappropriate drug-drug combination, and 2.58% (95% CI=2.44-2.72) of visits with at least one prescription had one or more inappropriate drug-disease combinations. Of visits with a prescription of warfarin, 6.60% (95% CI=5.46-7.74) were prescribed a drug with potentially harmful interaction. Of patients with benign prostatic hypertrophy, 4.06% (95% CI=3.06-5.06) had at least one of six drugs that should be avoided. The number of drugs prescribed is most predictive of inappropriate drug-drug and drug-disease combinations. CONCLUSION: Potentially harmful drug-drug and drug-disease combinations occur in various degrees in outpatient care in the elderly population. Targeting combinations such as those involving warfarin that are high in prevalence and potential harm offers a practical approach to improving prescribing and patient safety. C1 Agcy Healthcare Res & Qual, Dept Hlth & Human Serv, Ctr Qual Improvement & Patient Safety, Rockville, MD 20850 USA. Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. NCI, NIH, Frederick, MD 21701 USA. RP Zhan, CL (reprint author), Agcy Healthcare Res & Qual, Dept Hlth & Human Serv, Ctr Qual Improvement & Patient Safety, 540 Gaither Rd, Rockville, MD 20850 USA. EM czhan@ahrq.gov NR 31 TC 54 Z9 55 U1 3 U2 7 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 FEB PY 2005 VL 53 IS 2 BP 262 EP 267 DI 10.1111/j.1532-5415.2005.53112.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 889VW UT WOS:000226471900012 PM 15673350 ER PT J AU LaMascus, AM Bernard, MA Barry, P Salerno, J Weiss, J AF LaMascus, AM Bernard, MA Barry, P Salerno, J Weiss, J TI Bridging the workforce gap for our aging society: How to increase and improve knowledge and training. Report of an expert panel SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE healthcare workforce; workforce gap; geriatric trained workers; geriatric training ID UNITED-STATES AB The healthcare workforce is currently unprepared for the increasing number of older persons and the complexities of their healthcare needs. Too few healthcare workers are adequately trained in geriatrics, and developers of educational curricula across healthcare disciplines have been slow to incorporate or require geriatric training. In April 2003, leaders in geriatrics met in Washington, D.C., to discuss and recommend solutions to the growing shortage of an appropriately trained workforce for geriatric research, education, and patient care. After considering data, presenting statistics, and offering insights into the future, the conference concluded by formulating recommendations to meet specific challenges. This report is a summary of the conference proceedings and recommendations, and it serves as a reminder that demographic trends and an everexpanding geriatric knowledge base demand not only attention, but also action. C1 Univ Oklahoma, Coll Med, Reynolds Dept Geriatr, Oklahoma City, OK 73104 USA. Merck Inst Aging & Hlth, Washington, DC USA. NIA, Bethesda, MD 20892 USA. Bur Hlth Profess, Div Interdisciplinary Community Based Programs, Hlth Resources Serv Adm, Rockville, MD USA. RP Bernard, MA (reprint author), Univ Oklahoma, Coll Med, Reynolds Dept Geriatr, 921 NE 13th 11G, Oklahoma City, OK 73104 USA. EM marie-bernard@ouhsc.edu NR 19 TC 19 Z9 19 U1 0 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 FEB PY 2005 VL 53 IS 2 BP 343 EP 347 DI 10.1111/j.1532-5415.2005.53137.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 889VW UT WOS:000226471900025 PM 15673363 ER PT J AU Jackson, SN Wang, HYJ Woods, AS AF Jackson, SN Wang, HYJ Woods, AS TI Direct tissue analysis of phospholipids in rat brain using MALDI-TOFMS and MALDI-ion mobility-TOFMS SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID ASSISTED-LASER-DESORPTION/IONIZATION; FLIGHT MASS-SPECTROMETRY; DESORPTION; SPHINGOMYELIN; SEPARATION; PEPTIDES; DISEASE; GAS; MS AB After water, lipids are the most common biomolecules found in the brain (12%). A brief perusal of the physiology, anatomy, and pathophysiology of the brain illustrates the importance of lipids. Recent advances in mass spectrometry have allowed the direct probing of tissues. However, most studies have focused on proteins. In the present work, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and MALDI-ion mobility (IM)-TCFMS were employed for direct analysis of phospholipids in rat brain tissue. Molecular ions (MH+) corresponding to phosphatidylcholines, phosphatidylethanolamines, and sphingomyelin, were recorded. When studying pharmacology, we learn that many therapeutic compounds are stored in the body's adipose tissue. MALDI-TOFMS and MALDI-IM-TOFMS were thus used to analyze rat brain tissue with chlorisondamine added directly onto the tissue slice. With both techniques, noncovalent complexes between the tissue phospholipids and chlorisondamine were detected. In addition, MALDI-IM-TOFMS of noncovalent complexes between phospholipids and chlorisondamine displayed a mobility between that of an isobaric lipid and peptide. (C) 2004 American Society for Mass Spectrometry. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Ionwerks Inc, Houston, TX USA. RP Woods, AS (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov FU NIDA NIH HHS [N43DA-2-7727] NR 28 TC 117 Z9 120 U1 1 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD FEB PY 2005 VL 16 IS 2 BP 133 EP 138 DI 10.1016/j.jasms.2004.10.002 PG 6 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 897JI UT WOS:000226999700001 PM 15694763 ER PT J AU Matoba, S Hwang, PM Nguyen, T Shizukuda, Y AF Matoba, S Hwang, PM Nguyen, T Shizukuda, Y TI Evaluation of pulsed Doppler tissue velocity imaging for assessing systolic function of murine global heart failure SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID ADRIAMYCIN-INDUCED CARDIOMYOPATHY; DOXORUBICIN-INDUCED APOPTOSIS; STRAIN-RATE ECHOCARDIOGRAPHY; LEFT-VENTRICULAR FUNCTION; ANESTHETIZED MICE; CARDIAC-FUNCTION; IN-VIVO; DYSFUNCTION; PROTECTS; CARDIOTOXICITY AB The feasibility of Doppler tissue imaging (DTI) for assessing global systolic function has not been determined in small animals, particularly at near-conscious heart rates. Therefore, we compared DTI measurements with conventional M-mode-derived fractional shortening in murine global left ventricular systolic dysfunction induced by intraperitoneal doxorubicin (Dox) injection. In all, 13 female C57BL mice received 20 mg/kg of Dox and 12 mice received saline injection (controls). DTI signals were obtained from the inferior wall through parasternal short-axis views. The heart rate was kept at near-conscious level throughout DTI measurements (approximately 500/min). Left ventricular systolic dysfunction was detectable by measurements of fractional shortening from 4 to 14 days after Dox administration. Among DTI measurements, peak systolic velocity and time to peak systolic velocity decreased from 4 to 14 days after Dox injection. Our results indicate that these new DTI measurements appear feasible to assess global left ventricular systolic dysfunction in mice. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Shizukuda, Y (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10,Room 7B15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. EM shizukuy@nhlbi.nih.gov NR 23 TC 10 Z9 10 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD FEB PY 2005 VL 18 IS 2 BP 148 EP 154 DI 10.1016/j.echo.2004.08.038 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 896YZ UT WOS:000226972000008 PM 15682052 ER PT J AU Foley, RN Murray, AM Li, SL Herzog, CA McBean, AM Eggers, PW Collins, AJ AF Foley, RN Murray, AM Li, SL Herzog, CA McBean, AM Eggers, PW Collins, AJ TI Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States medicare population, 1998 to 1999 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; HEART-FAILURE; INSUFFICIENCY; MORTALITY; OUTCOMES; STRATIFICATION; DYSFUNCTION; INHIBITORS; CREATININE AB Knowledge of the excess risk posed by specific cardiovascular syndromes could help in the development of strategies to reduce premature mortality among patients with chronic kidney disease (CKD). The rates of atherosclerotic vascular disease, congestive heart failure, renal replacement therapy, and death were compared in a 5% sample of the United States Medicare population in 1998 and 1999 (n = 1,091,201). Patients were divided into the following groups: 1, no diabetes, no CKD (79.7%); 2, diabetes, no CKD (16.5%); 3, CKD, no diabetes (2.2%); and 4, both CKD and diabetes (1.6%). During the 2 yr of follow-up, the rates (per 100 patient-years) in the four groups were as follows: atherosclerotic vascular disease, 14.1, 25.3, 35.7, and 49.1; congestive heart failure, 8.6, 18.5, 30.7, and 52.3; renal replacement therapy, 0.04, 0.2, 1.6, and 3.4; and death, 5.5, 8.1, 17.7, and 19.9, respectively (P < 0.0001). With use of Cox regression, the corresponding adjusted hazards ratios were as follows: atherosclerotic vascular disease, 1, 1.30, 1.16, and 1.41 (P < 0.0001); congestive heart failure, 1, 1.44, 1.28, and 1.79 (P < 0.0001); renal replacement therapy, 1, 2.52, 23.1, and 38.9 (P < 0.0001); and death, 1, 1.21, 1.38, and 1.56 (P < 0.0001). On a relative basis, patients with CKD were at a much greater risk for the least frequent study outcome, renal replacement therapy. On an absolute basis, however, the high death rates of patients with CKD may reflect accelerated rates of atherosclerotic vascular disease and congestive heart failure. C1 United States Renal Data Syst, Coordinating Ctr, Minneapolis, MN 55404 USA. Minneapolis Med Res Fdn Inc, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN 55455 USA. Hennepin Cty Med Ctr, Div Geriatr Med, Dept Med, Minneapolis, MN 55415 USA. Hennepin Cty Med Ctr, Div Cardiol, Dept Med, Minneapolis, MN 55415 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Foley, RN (reprint author), United States Renal Data Syst, Coordinating Ctr, 914 S 8th St,Suite D-253, Minneapolis, MN 55404 USA. EM RFoley@usrds.org FU NIDDK NIH HHS [N01-DK-9-2343] NR 24 TC 474 Z9 501 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2005 VL 16 IS 2 BP 489 EP 495 DI 10.1681/ASN.2004030203 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 896UM UT WOS:000226959400026 PM 15590763 ER PT J AU Potlog-Nahari, C Armstrong, A Stratton, P Giri, N Alter, BP AF Potlog-Nahari, C Armstrong, A Stratton, P Giri, N Alter, BP TI Fanconi Anemia: An inherited DNA repair syndrome associated with premature ovarian failure. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 19 BP 91A EP 91A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329100020 ER PT J AU Al-Hendy, A Chiorini, J Di Pasquale, G AF Al-Hendy, A Chiorini, J Di Pasquale, G TI Towards gene therapy for uterine fibroids: Adeno-associated virus can infect human and rat Leiomyoma cells. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 23 BP 92A EP 93A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329100024 ER PT J AU Bromer, JG Parker, CY Mayers, CM Segars, JH Catherino, WH AF Bromer, JG Parker, CY Mayers, CM Segars, JH Catherino, WH TI TGF-Beta receptor II is overexpressed in human leiomyomata. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 Georgetown Univ Hosp, Washington, DC 20007 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 24 BP 93A EP 93A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329100025 ER PT J AU Parker, CY Leppert, PC Segars, JH Catherino, WH AF Parker, CY Leppert, PC Segars, JH Catherino, WH TI Transforming growth factor beta3 overexpression results in altered extracellular matrix gene transcription in uterine fibroids. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 32 BP 95A EP 96A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329100033 ER PT J AU Parker, CY Bromer, JG Segars, JH Catherino, WH AF Parker, CY Bromer, JG Segars, JH Catherino, WH TI Uterine fibroid development involves activation of the transforming growth factor (TGF)beta signaling pathway. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ Hosp, Dept Obstet & Gynecol, Washington, DC 20007 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 33 BP 96A EP 96A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329100034 ER PT J AU Espinoza, J Nien, JK Edwin, SS Medina, L Gomez, R Mazor, M Romero, R AF Espinoza, J Nien, JK Edwin, SS Medina, L Gomez, R Mazor, M Romero, R TI A low placental growth factor concentration in maternal plasma at 23-24 weeks of gestation in patients with an abnormal uterine artery doppler velocimetry increases the risk of fetal growth restriction. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NICHD, Perinatal Res Branch, DHHS, Bethesda, MD USA. Hosp Dr Sotero del Rio, CEDIP, Dept Ob Gyn, Santiago, Chile. Wayne State Univ, Dept Ob Gyn, Detroit, MI 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 94 BP 115A EP 115A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329100095 ER PT J AU Ramirez, MM AF Ramirez, MM TI The MFMU cesarean registry: Clinical management of women with antepartum fetal demise after prior cesarean delivery. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 191 BP 146A EP 146A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329100192 ER PT J AU Richani, K Soto, E Romero, R Espinoza, J Chaiworapongsa, T Nien, JK Edwin, SS Kim, YM Hong, JS Goncalves, LF Mazor, M AF Richani, K Soto, E Romero, R Espinoza, J Chaiworapongsa, T Nien, JK Edwin, SS Kim, YM Hong, JS Goncalves, LF Mazor, M TI Preeclampsia and SGA differ in the maternal plasma complement split products profile. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. NICHD, NIH, DHHS, Perinatal Res Branch, Bethesda, MD USA. Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 198 BP 148A EP 148A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329100199 ER PT J AU Espinoza, J Nien, JK Edwin, SS Medina, L Gomez, R Mazor, M Romero, R AF Espinoza, J Nien, JK Edwin, SS Medina, L Gomez, R Mazor, M Romero, R TI Identification of patients at risk for the development of early onset preeclampsia with uterine artery Doppler velocimetry and the determination of plasma angiogenic and anti-angiogenic factors SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Hosp Dr Sotero del Rio, CEDIP, Dept Obstet & Gynecol, Santiago, Chile. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 206 BP 150A EP 151A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329100207 ER PT J AU Leach, RE Kilburn, BA Petkova, A Romero, R Armant, DR AF Leach, RE Kilburn, BA Petkova, A Romero, R Armant, DR TI A positive feedback loop induced by hypoxia regulates trophoblast secretion of heparin binding EGF-like growth factor (HB-EGF). SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 Univ Illinois, Chicago, IL USA. Wayne State Univ, Detroit, MI USA. NICHD, Perintal Res Branch, Intramural Div, NIH,DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 300 BP 180A EP 181A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329100301 ER PT J AU Kim, GJ Kim, YM Cushenberry, E Nien, JK Kim, CJ Yoon, BH Espinoza, J Mazor, M Romero, R AF Kim, GJ Kim, YM Cushenberry, E Nien, JK Kim, CJ Yoon, BH Espinoza, J Mazor, M Romero, R TI Decreased expression of silencing of cytokine signaling (SOCS) proteins by trophoblast in spontaneous human parturition at term. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. Seoul Natl Univ, Dept Pathol, Seoul 151, South Korea. Seoul Natl Univ, Dept Obstet & Gynecol, Seoul 151, South Korea. 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 455 BP 230A EP 231A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329100456 ER PT J AU Vink, J Roberson, R Woodard, J Endres, M Toso, L Spong, CY AF Vink, J Roberson, R Woodard, J Endres, M Toso, L Spong, CY TI In utero alcohol exposure decreases VIP immunoreactivity in adult cortex in fetal alcohol syndrome. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NICHD, UNit Perinatal & Dev Neurobiol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S BP 238A EP 238A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101019 ER PT J AU Wadell, JL McLean, K McDaniel, K Mayers, C Venere, M Driggers, P Tiulpakov, A Mukhopandhyay, M Gorivodsky, M Westphal, H Segars, J AF Wadell, JL McLean, K McDaniel, K Mayers, C Venere, M Driggers, P Tiulpakov, A Mukhopandhyay, M Gorivodsky, M Westphal, H Segars, J TI Molecular characterization of the role of BRX in cardiac morphogenesis. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIH, Lab Mammalian Genes & Dev, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 481 BP 238A EP 238A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101020 ER PT J AU Toso, L Poggi, S Roberson, R Park, J Abebe, D Spong, CY AF Toso, L Poggi, S Roberson, R Park, J Abebe, D Spong, CY TI Prevention of alcohol-induced learning deficits in fetal alcohol syndrome mediated through NMDA receptors. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 UPDN, NICHD, NIH, Bethesda, MD USA. Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 512 BP 248A EP 248A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101051 ER PT J AU Sheehan, KM Fishman, DA Liotta, LA Petricoin, EF Wulfkuhle, JD AF Sheehan, KM Fishman, DA Liotta, LA Petricoin, EF Wulfkuhle, JD TI Mapping the molecular network of metastatic ovarian carcinoma: Theranostics using proteomics. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NCI, FDA, Clin Prote Program, Pathol Lab, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 628 BP 285A EP 285A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101167 ER PT J AU Srinivasan, S Petricoin, EF Liotta, LA Fishman, DA AF Srinivasan, S Petricoin, EF Liotta, LA Fishman, DA TI Effects of autotaxin (atx) mediated invasion of ovarian epithelial cells on protein signaling cascades. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NIH, Dept Therapeut Prot, CBER, FDA,Clin Prote Program, Bethesda, MD 20892 USA. NCI, Pathol Lab, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 630 BP 285A EP 286A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101169 ER PT J AU Wang, HY Parry, S Macones, G Sammel, M Kuivaniemi, H Tromp, G Romero, R Shriver, M Strauss, JF AF Wang, HY Parry, S Macones, G Sammel, M Kuivaniemi, H Tromp, G Romero, R Shriver, M Strauss, JF TI An african-american specific polymorphism in the promoter of the fetal SERPINH1 gene encoding Hsp47 is a risk factor for PPROM. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 Univ Penn, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Hutzel Hosp, NICHD, Perinatol Res Branch, Detroit, MI 48201 USA. Penn State Univ, Dept Anthropol, University Pk, PA 16802 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 643 BP 289A EP 290A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101182 ER PT J AU Abrahams, VM Straszewski-Chavez, SL Bole-Aldo, P Romero, R Mor, G AF Abrahams, VM Straszewski-Chavez, SL Bole-Aldo, P Romero, R Mor, G TI Trophoblast cells regulate an immune response through TLR-4 induced cytokine production. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 Yale Univ, Dept Obstet Gynecol & Reprod Sci, Sch Med, New Haven, CT USA. NICHD, NIH, Perinatol Res Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 695 BP 306A EP 306A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101234 ER PT J AU Aagaard-Tillery, K AF Aagaard-Tillery, K CA Maternal-Fetal Med Units Network TI Does granting permission to retain DNA samples for future genetic studies identify a biased population? SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 Univ Utah, Salt Lake City, UT USA. NICHHD, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 716 BP 313A EP 313A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101255 ER PT J AU Moldenhauer, JS AF Moldenhauer, JS TI Fetal gender and pregnancy outcomes in women with asthma. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 726 BP 316A EP 316A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101265 ER PT J AU Soto, E Richani, K Romero, R Espinoza, J Chaiworapongsa, T Nien, JK Edwin, SS Kim, YM Hong, JS Goncalves, LF Mazor, M AF Soto, E Richani, K Romero, R Espinoza, J Chaiworapongsa, T Nien, JK Edwin, SS Kim, YM Hong, JS Goncalves, LF Mazor, M TI Acute pyelonepritis during pregnancy is characterised by an excess of the complement split product C5a. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. NICHD, Perinatol Res Branch, DHHS, NIH, Bethesda, MD USA. Wayne State Univ, Dept Pathol, Detroit, MI 48202 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 729 BP 317A EP 317A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101268 ER PT J AU Gustofson, RL Kim, N Liu, S Stratton, P AF Gustofson, RL Kim, N Liu, S Stratton, P TI Right lower quadrant pain and appendiceal abnormalities in women with endometriosis. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NICHHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 745 BP 322A EP 322A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101284 ER PT J AU Chou, D Ma, YJ Nien, JK Romero, R Parry, S AF Chou, D Ma, YJ Nien, JK Romero, R Parry, S TI Cytomegalovirus: A common cause of failed placental invasion and spontaneous preterm labor? SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 Ctr Res Reprod & Womens Hlth, Philadelphia, PA USA. NICHHD, Perinatol Res Branch, DHHS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 766 BP 328A EP 328A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101305 ER PT J AU Bytautiene, E Vedernikov, Y Saade, G Romero, R Garfield, R AF Bytautiene, E Vedernikov, Y Saade, G Romero, R Garfield, R TI Endogenous mast cell degranulation increases tension of isolated human chorionic plate vessels. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. NICHD, Perinatol Res Branch, NIH, Detroit, MI 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 782 BP 333A EP 333A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101321 ER PT J AU Hendler, I AF Hendler, I TI The preterm prediction study: The association between corticotropin releasing hormone (CRH), maternal body mass index (BMI) and spontaneous preterm birth (SPB). SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NICHHD, Maternal Fetal Med Units Network, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 852 BP 355A EP 355A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101390 ER PT J AU Esplin, MS AF Esplin, MS TI The use of proteomic analysis to identify markers of preterm birth. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NICHHD, Maternal Fetal Med Units Network, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 856 BP 356A EP 356A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101394 ER PT J AU Aquino, JA Fishman, DA Coukos, G Liotta, LA Petricoin, EF Wulfkuhle, JD AF Aquino, JA Fishman, DA Coukos, G Liotta, LA Petricoin, EF Wulfkuhle, JD TI Multiplexed kinase substrate and signal transduction profiling of human ovarian cancer: Towards patient tailored therapeutics. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NCI, FDA Clin Proteom Program, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY USA. Univ Penn, Philadelphia, PA 19104 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 902 BP 370A EP 370A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101440 ER PT J AU North, CS Pollio, DE Pfefferbaum, B Megivern, D Vythilingam, M Westerhaus, ET Martin, GJ Hong, BA AF North, CS Pollio, DE Pfefferbaum, B Megivern, D Vythilingam, M Westerhaus, ET Martin, GJ Hong, BA TI Capitol hill staff workers' experiences of bioterrorism: Qualitative findings from focus groups SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID ILLNESS; ADULTS; URBAN AB Little systematic information is available on mental health issues related to bioterrorism. Five focus groups were conducted with Capitol Hill office staff (n = 28 total participants) to learn about their experience of the anthrax incident on October 15, 2001. More than 2,000 verbal passages were coded into categories and themes by using qualitative analysis software. Issues emerging from the discussions included difficulties utilizing customary social supports, concerns over potential long-term dangers created by efforts to eradicate the anthrax, and nonadherence to antianthrax medication regimens. Nonadherence to antibiotic prophylaxis is of immediate concern for response to future bioterrorist events as well as infectious disease epidemics. Other topics that warrant attention are social support and mental health interventions. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63130 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Oklahoma City, OK 73190 USA. NIMH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. RP North, CS (reprint author), Washington Univ, Sch Med, Dept Psychiat, 660 S Euclid Ave,Campus Box 8134, St Louis, MO 63110 USA. EM NorthC@psychiatry.wustl.edu FU NIMH NIH HHS [MH40025] NR 25 TC 11 Z9 11 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2005 VL 18 IS 1 BP 79 EP 88 DI 10.1002/jts.20006 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 926WM UT WOS:000229154400010 PM 16281199 ER PT J AU Lee, W Goncalves, LF Espinoza, J Romero, R AF Lee, W Goncalves, LF Espinoza, J Romero, R TI Inversion mode - A new volume analysis tool for 3-dimensional ultrasonography SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE fetus; inversion mode; pregnancy; 3-dimensional ultrasonography ID SPATIOTEMPORAL IMAGE CORRELATION; FETAL HEART; ULTRASOUND AB Objectives. The main goal was to introduce the inversion mode as a new image analysis tool for the examination of fluid-filled structures using 3-dimensional ultrasonography during pregnancy. Methods. Three-dimensional ultrasonography was performed on fetuses having fluid collections of noncardiac origin, Threshold adjustment was used to visually assign full transparency to voxels that were associated with fluid. A new postprocessing tool, called the inversion mode, was activated to transform this region of interest into opaque voxels. The morphologic appearance of fluid collections and their anatomic relationship to other organs were shown in this manner. Results. Diagnostic features were shown by this technique in several fetuses with problems that included pleural effusion, duodenal atresia, urinary tract abnormalities, and hydrocephaly. Furthermore, the inversion mode also permitted surface reconstruction of an irregular pleural effusion that had close resemblance to results with the Virtual Organ Computer-Aided Analysis rotational slice technique. Acoustic shadowing was also documented as a potential technical limitation of this method. Conclusions. The inversion mode can display scattered or contiguous fluid-filled structures in ways that can be very difficult or impossible to accurately characterize with conventional ultrasonography. It may be particularly helpful for the evaluation of multiple fluid-filled cysts or irregular fluid collections in the fetus. C1 William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48073 USA. NICHHD, Perinatol Res Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Lee, W (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3601 W 13th Mile Rd, Royal Oak, MI 48073 USA. EM wlee@beaumont.edu NR 10 TC 40 Z9 45 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD FEB PY 2005 VL 24 IS 2 BP 201 EP 207 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 891MS UT WOS:000226585800010 PM 15661951 ER PT J AU Goin, JE Salem, R Carr, BI Dancey, JE Soulen, MC Geschwind, JFH Goin, K Van Buskirk, M Thurston, K AF Goin, JE Salem, R Carr, BI Dancey, JE Soulen, MC Geschwind, JFH Goin, K Van Buskirk, M Thurston, K TI Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: A risk-stratification analysis SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID Y-90 MICROSPHERES; CONTROLLED-TRIAL; UNITED-STATES; CHEMOEMBOLIZATION AB PURPOSE: To present the findings of a risk-stratification survival analysis with use of data collected on a heterogeneous group of patients with hepatocellular carcinoma (HCC) treated with TheraSphere. MATERIALS AND METHODS: Baseline, treatment, and follow-up data were collected and analyzed from 121 Thera Sphere-treated patients. Survival analyses were performed to identify those variables most strongly associated with 3-month mortality. The presence of any of the identified risk variables resulted in the assignment of a patient to the high-risk category. RESULTS: Five liver reserve and two non-liver reserve variables were identified and used to stratify patients into lowor high-risk groups. Sixteen of the 33 patients assigned to the high-risk group (49%) did not survive the first 3 months after treatment, compared with six of the 88 patients assigned to the low-risk group (7%; Fisher exact test, P < .0001). Median survival for the low- and high-risk groups were 466 days and 108 days, respectively (hazard ratio, 6.0; P < .0001). Eleven of 12 patients who experienced a treatment-related major complication ending in death were included in the high-risk group. No single variable explained the major complication relationship to treatment. CONCLUSION: Patients with HCC who are being considered for treatment with TheraSpheres should be evaluated for the presence of the risk variables described herein. The absence of these variables is predictive of improved survival (median of 466 days) compared with patients at high risk (median of 108 days). C1 NW Mem Hosp, Dept Radiol, Div Intervent Radiol, Chicago, IL 60611 USA. DataMedix Corp, Brookhaven, PA USA. Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplant Inst, Pittsburgh, PA USA. Univ Penn, Med Ctr, Div Intervent Radiol, Philadelphia, PA 19104 USA. NCI, Invest Drug Branch, Div Canc Treatment & Diag, Rockville, MD USA. Johns Hopkins Univ Hosp, Div Cardiovasc & Intervent Radiol, Baltimore, MD 21287 USA. RP Salem, R (reprint author), NW Mem Hosp, Dept Radiol, Div Intervent Radiol, 676 N St Clair,Suite 800, Chicago, IL 60611 USA. EM r-salem@northwestern.edu NR 27 TC 66 Z9 66 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 2005 VL 16 IS 2 BP 195 EP 203 DI 10.1097/01.RVI.0000142602.79459.90 PN 1 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 907IL UT WOS:000227710000006 PM 15713920 ER PT J AU Goin, JE Salem, R Carr, BI Dancey, JE Soulen, MC Geschwind, JFH Goin, K Van Buskirk, M Thurston, K AF Goin, JE Salem, R Carr, BI Dancey, JE Soulen, MC Geschwind, JFH Goin, K Van Buskirk, M Thurston, K TI Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: Factors associated with liver toxicities SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID RADIATION-THERAPY; PROGNOSTIC SYSTEM; CHEMOEMBOLIZATION; Y-90; HEPATITIS; CANCERS; DISEASE; MODEL; CLIP AB PURPOSE: Intraarterial injection of yttrium 90 microspheres (TheraSpheres) is used in the treatment of hepatocellular carcinoma (HCC). This article presents an analysis of the incidence of liver toxicities (liver-related events) and pretreatment factors associated with liver toxicities after TheraSphere treatment. PATIENTS AND METHODS: Eighty-eight TheraSphere-treated patients with low 90-day mortality risk were selected for analysis, with liver toxicities coded with use of standard oncology criteria. Descriptive and inferential statistical methods were applied to estimate the incidence of liver toxicities and to evaluate the influence of liver radiation dose and various pretreatment factors on the risk of their occurrence. RESULTS: Sixty-eight liver toxicities occurred in 37 of the 88 patients (42%). Thirty-two patients (36%) experienced 50 liver toxicities after the first treatment and nine of 23 patients (39%) who received a second treatment experienced 18 liver toxicities. Pretreatment total bilirubin and liver radiation dose were found to be associated with the risk of at least one liver toxicity and with the time to first occurrence of a liver toxicity after first treatment. Pretreatment total bilirubin also was associated with liver toxicities after the second treatment. Most of the toxicities resolved; however, those that did not resolve were attributed to tumor progression or advancing cirrhosis. CONCLUSIONS: The risk of liver toxicities in patients with unresectable HCC treated with TheraSpheres increases with increasing pretreatment total bilirubin level and liver radiation dose to a maximum of 150 Gy for a single administration. The toxicities attributed to treatment resolved over time, and none of the patients studied had confirmed radiation-induced liver disease. Consequently, doses as high as 150 Gy on a single administration and as high as 268 Gy on repeated administrations were well tolerated. C1 NW Mem Hosp, Dept Radiol, Chicago, IL 60611 USA. DataMedix Corp, Brookhaven, PA USA. Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA. Hosp Univ Penn, Div Intervent Radiol, Philadelphia, PA 19104 USA. NCI, Invest Grug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD USA. Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. RP Salem, R (reprint author), NW Mem Hosp, Dept Radiol, 676 N St Clair,Suite 800, Chicago, IL 60611 USA. EM r-salem@northwestern.edu NR 31 TC 112 Z9 113 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 2005 VL 16 IS 2 BP 205 EP 213 DI 10.1097/01.RVI.00001142592.89564.F9 PN 1 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 907IL UT WOS:000227710000007 PM 15713921 ER PT J AU Chang, KO Sosnovtsev, SS Belliot, G Wang, QH Saif, LJ Green, KY AF Chang, KO Sosnovtsev, SS Belliot, G Wang, QH Saif, LJ Green, KY TI Reverse genetics system for porcine enteric calicivirus, a prototype Sapovirus in the Caliciviridae SO JOURNAL OF VIROLOGY LA English DT Article ID FELINE CALICIVIRUS; INTESTINAL CONTENTS; SERIAL PROPAGATION; GNOTOBIOTIC PIGS; CYCLIC-AMP; BILE-ACIDS; WILD-TYPE; VIRUS; IDENTIFICATION; PATHOGENESIS AB A porcine enteric calicivirus (PEC), strain Cowden in the genus Sapovirus of the Caliciviridae family, can be propagated in a porcine kidney continuous cell line (LLC-PK) in the presence of bile acids in the cell culture medium. A full-length cDNA copy of the Cowden PEC genome was cloned into a plasmid vector directly downstream from the T7 RNA polymerase promoter, and capped RNA transcripts derived from this clone were infectious when transfected into LLC-PK cells. The recovery of PEC after transfection of RNA transcripts was dependent on the presence of bile acids, consistent with our recent identification of a bile acid-mediated signaling pathway required for PEC replication (Chang et al., Proc. Natl. Acad. Sci. USA 101:8733-87:88, 2004). Recovery of virus was verified by detection of PEC antigen in transfected cells by immunofluorescence and enzyme-linked immunosorbent assays, direct observation of recovered viral particles by electron microscopy, and partial sequence analysis of their genomes (first 1,070 nucleotides) to differentiate them from tissue culture-adapted parental virus. The recovered virus retained its ability to infect piglets when administered by the oral route and showed an attenuated phenotype similar to that of the tissue culture-adapted parental virus. This reverse genetics system for PEC provides a new tool to study the molecular basis of replication and pathogenesis for caliciviruses associated with diarrheal disease. C1 NIAID, LID, Natl Inst Hlth, DHHS, Bethesda, MD 20892 USA. Ohio State Univ, Dept Vet Prevent Med, Food Anim Hlth Res Program, Wooster, OH USA. RP Chang, KO (reprint author), NIAID, LID, Natl Inst Hlth, DHHS, Bldg 50,Room 6316,9000 Rockeville Pike, Bethesda, MD 20892 USA. EM kchang@niaid.nih.gov FU NIAID NIH HHS [R01AI 49716] NR 26 TC 40 Z9 40 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 FEB PY 2005 VL 79 IS 3 BP 1409 EP 1416 DI 10.1128/JVI.79.3.1409-1416.2005 PG 8 WC Virology SC Virology GA 892FB UT WOS:000226634300008 PM 15650167 ER PT J AU Zheng, PS Brokaw, J McBride, AA AF Zheng, PS Brokaw, J McBride, AA TI Conditional mutations in the mitotic chromosome binding function of the bovine papillomavirus type 1 E2 protein SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSCRIPTIONAL ACTIVATION; REPLICATION FUNCTIONS; TRANSACTIVATION DOMAIN; NUCLEAR ANTIGEN-1; DNA-REPLICATION; AMINO-ACIDS; PLASMIDS; PHOSPHORYLATION; MAINTENANCE; ATTACHMENT AB The papillomavirus E2 protein is required for viral transcriptional regulation, DNA replication and genome segregation. We have previously shown that the E2 transactivator protein and BPV1 genomes are associated with mitotic chromosomes; E2 links the genomes to cellular chromosomes to ensure efficient segregation to daughter nuclei. The transactivation domain of the E2 protein is necessary and sufficient for association of the E2 protein with mitotic chromosomes. To determine which residues of this 200-amino-acid domain are important for chromosomal interaction, E2 proteins with amino acid substitutions in each conserved residue of the transactivation domain were tested for their ability to associate with mitotic chromosomes. Chromatin binding was assessed by using immunofluorescence on both spread and directly fixed mitotic chromosomes. E2 proteins defective in the transactivation and replication functions were unable to associate with chromosomes, and those that were competent in these functions were attached to mitotic chromosomes. However, several mutated proteins that were defective for chromosomal interaction could associate with chromosomes after treatment with agents that promote protein folding or when cells were incubated at lower temperatures. These results indicate that precise folding of the E2 transactivation domain is crucial for its interaction with mitotic chromosomes and that this association can be modulated. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Rm 137,4 Ctr Dr,MSC 0455, Bethesda, MD 20892 USA. EM amcbride@nih.gov OI McBride, Alison/0000-0001-5607-5157 NR 34 TC 18 Z9 19 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 FEB PY 2005 VL 79 IS 3 BP 1500 EP 1509 DI 10.1128/JVI.79.3.1500-1509.2005 PG 10 WC Virology SC Virology GA 892FB UT WOS:000226634300017 PM 15650176 ER PT J AU Morcock, DR Thomas, JA Gagliardi, TD Gorelick, RJ Roser, JD Chertova, EN Bess, JW Ott, DE Sattentau, QJ Frank, I Pope, M Lifson, JD Henderson, LE Crise, BJ AF Morcock, DR Thomas, JA Gagliardi, TD Gorelick, RJ Roser, JD Chertova, EN Bess, JW Ott, DE Sattentau, QJ Frank, I Pope, M Lifson, JD Henderson, LE Crise, BJ TI Elimination of retroviral infectivity by N-ethylmaleimide with preservation of functional envelope glycoproteins SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 NUCLEOCAPSID PROTEIN; CYTOMEGALOVIRUS UL80 PROTEASE; VESICULAR STOMATITIS-VIRUS; GREEN FLUORESCENT PROTEIN; DISULFIDE BOND FORMATION; ACID-CHAPERONE ACTIVITY; MURINE LEUKEMIA-VIRUS; HUMAN DENDRITIC CELLS; INTEGRATION IN-VITRO AB The zinc finger motifs in retroviral nucleocapsid (NC) proteins are essential for viral replication. Disruption of these Cys-X-2-Cys-X-4-His-X-4-Cys zinc-binding structures eliminates infectivity. To determine if N-ethylmaleimide (NEM) can inactivate human immunodeficiency virus type 1 (HIV-1) or simian immunodeficiency virus (SIV) preparations by alkylating cysteines of NC zinc fingers, we treated infectious virus with NEM and evaluated inactivation of infectivity in cell-based assays. Inactivation was rapid and proportional to the NEM concentration. NEM treatment of HIV-1 or SIV resulted in extensive covalent modification of NC and other internal virion proteins. In contrast, viral envelope glycoproteins, in which the cysteines are disulfide bonded, remained intact and functional, as assayed by high-performance liquid chromatography, fusion-from-without analyses, and dendritic cell capture. Quantitative PCR assays for reverse transcription intermediates showed that NEM and 2,2'-dipyridyl disulfide (aldrithiol-2), a reagent which inactivates retroviruses through oxidation of cysteines in internal virion proteins such as NC, blocked HIV-1 reverse transcription prior to the formation of minus-strand strong-stop products. However, the reverse transcriptase from NEM-treated virions remained active in exogenous template assays, consistent with a role for NC in reverse transcription. Since disruption of NC zinc finger structures by NEM blocks early postentry steps in the retroviral infection cycle, virus preparations with modified NC proteins may be useful as vaccine immunogens and probes of the role of NC in viral replication. C1 Natl Canc Inst, SAIC Frerick, AIDS Vaccine Program, Frederick, MD 21702 USA. Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 2JD, England. Populat Council, Biomed Res Ctr, New York, NY USA. RP Crise, BJ (reprint author), Natl Canc Inst, SAIC Frerick, AIDS Vaccine Program, Bldg 535,5th Floor,POB B, Frederick, MD 21702 USA. EM criseb@ncifcrf.gov RI Bess, Jr., Julian/B-5343-2012; OI Thomas, James/0000-0002-2509-490X FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [R01 AI040877, AI40877, AI52048, P01 AI052048, R37 AI040877]; NICHD NIH HHS [HD41752, P01 HD041752] NR 65 TC 29 Z9 31 U1 0 U2 4 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 FEB PY 2005 VL 79 IS 3 BP 1533 EP 1542 DI 10.1128/JVI.79.3.1533-1542.2005 PG 10 WC Virology SC Virology GA 892FB UT WOS:000226634300020 PM 15650179 ER PT J AU Huang, YW Haqshenas, G Kasorndorkbua, C Halbur, PG Emerson, SU Meng, XJ AF Huang, YW Haqshenas, G Kasorndorkbua, C Halbur, PG Emerson, SU Meng, XJ TI Capped RNA transcripts of full-length cDNA clones of swine hepatitis e virus are replication competent when transfected into Huh7 cells and infectious when intrahepatically inoculated into pigs SO JOURNAL OF VIROLOGY LA English DT Article ID CROSS-SPECIES INFECTION; UNITED-STATES; BLOOD-DONORS; PREVALENCE; TRANSMISSION; ANTIBODY; STRAINS; RISK; SEROREACTIVITY; ATTENUATION AB Swine hepatitis E virus (swine HEV), the first animal strain of HEV to be isolated, is a zoonotic agent. We report here the construction and in vitro and in vivo characterizations of infectious cDNA clones of swine HEV. Eight overlapping fragments spanning the entire genome were amplified by reverse transcription-PCR and assembled into a full-length cDNA clone, clone C, which contained 14 mutations compared to the consensus sequence of swine HEV. RNA transcripts from clone C were not infectious, as determined by intrahepatic inoculation into pigs and by in vitro transfection of Huh7 cells. Multiple site-based site-directed mutagenesis was performed to generate three new cDNA clones (pSHEV-1, pSHEV-2, and pSHEV-3) which differed from each other. The transfection of capped RNA transcripts into human liver Huh7 cells resulted in the synthesis of both ORF2 capsid and ORF3 proteins, indicating that the cDNA clones were replication competent. Each of the three clones resulted in active swine HEV infections after the intrahepatic inoculation of pigs with capped RNA transcripts. The patterns of seroconversion, viremia, and fecal virus shedding for pigs inoculated with RNA transcripts from clones pSHEV-2 and pSHEV-3 were similar to each other and to those for pigs inoculated with wild-type swine HEV, suggesting that the nucleotide differences between these two cDNA clones were not critical for replication. Pigs inoculated with RNA transcripts from clone pSHEV-1, which contained three nonsilent mutations in the ORF2 capsid gene, had a delayed appearance of seroconversion and fecal virus shedding and had undetectable viremia. The availability of these infectious cDNA clones affords us an opportunity to understand the mechanisms of cross-species infection by constructing chimeric human and swine HEVs. C1 Virginia Polytech Inst & State Univ, Coll Vet Med, Ctr Mol Med & Infect Dis, Blacksburg, VA 24061 USA. Iowa State Univ, Coll Vet Med, Ames, IA USA. NIAID, Infect Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Meng, XJ (reprint author), Virginia Polytech Inst & State Univ, Coll Vet Med, Ctr Mol Med & Infect Dis, 1410 Prices Fork Rd, Blacksburg, VA 24061 USA. EM xjmeng@vt.edu RI Huang, Yaowei/B-1468-2009; Meng, X.J./B-8769-2009 OI Huang, Yaowei/0000-0001-9755-8411; Meng, X.J./0000-0002-2739-1334 FU NIAID NIH HHS [AI01653, AI46505, AI50611, R01 AI050611] NR 36 TC 38 Z9 46 U1 0 U2 4 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 FEB PY 2005 VL 79 IS 3 BP 1552 EP 1558 DI 10.1128/JVI.79.3.1552-1558.2005 PG 7 WC Virology SC Virology GA 892FB UT WOS:000226634300022 PM 15650181 ER PT J AU Rhodes, TD Nikolaitchik, O Chen, JB Powell, D Hu, WS AF Rhodes, TD Nikolaitchik, O Chen, JB Powell, D Hu, WS TI Genetic recombination of human immunodeficiency virus type 1 in one round of viral replication: Effects of genetic distance, target cells, accessory genes, and lack of high negative interference in crossover events SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; RETROVIRAL RECOMBINATION; STRAND TRANSFER; REVERSE-TRANSCRIPTASE; NUCLEOCAPSID PROTEIN; TRANSFER MECHANISM; INTERNAL REGIONS; HIV-1 INFECTION; DNA-SYNTHESIS; RATES AB Recombination is a major mechanism that generates variation in populations of human immunodeficiency virus type 1 (HIV-1). Mutations that confer replication advantages, such as drug resistance, often cluster within regions of the HIV-1 genome. To explore how efficiently HIV-1 can assort markers separated by short distances, we developed a flow cytometry-based system to study recombination. Two HIV-1-based vectors were generated, one encoding the mouse heat-stable antigen gene and green fluorescent protein gene (GFP), and the other encoding the mouse Thy-1 gene and GFP. We generated derivatives of both vectors that contained nonfunctional GFP inactivated by different mutations. Recombination in the region between the two inactivating mutations during reverse transcription could yield a functional GFP. With this system, we determined that the recombination rates of markers separated by 588, 300, 288, and 103 bp in one round of viral replication are 56, 38, 31, and 12%, respectively, of the theoretical maximum measurable recombination rate. Statistical analyses revealed that at these intervals, recombination rates and marker distances have a near-linear relationship that is part of an overall quadratic fit. Additionally, we examined the segregation of three markers within 600 bp and concluded that HIV-1 crossover events do not exhibit high negative interference. We also examined the effects of target cells and viral accessory proteins on recombination rate. Similar recombination rates were observed when human primary CD4(+) T cells and a human T-cell line were used as target cells. We also found equivalent recombination rates in the presence and absence of accessory genes vif, vpr, vpu, and nef. These results illustrate the power of recombination in generating viral population variation and predict the rapid assortment of mutations in the HIV-1 genome in infected individuals. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. NCI, Data Management Serv Inc, Frederick, MD 21702 USA. W Virginia Univ, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535,Room 336, Frederick, MD 21702 USA. EM whu@ncifcrf.gov RI Chen, Jianbo/N-3737-2014 OI Chen, Jianbo/0000-0001-6491-6577 NR 47 TC 64 Z9 65 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 FEB PY 2005 VL 79 IS 3 BP 1666 EP 1677 DI 10.1128/JVI.79.3.1666-1677.2005 PG 12 WC Virology SC Virology GA 892FB UT WOS:000226634300033 PM 15650192 ER PT J AU Nakata, H Maeda, K Miyakawa, T Shibayama, S Matsuo, M Takaoka, Y Ito, M Koyanagi, Y Mitsuya, H AF Nakata, H Maeda, K Miyakawa, T Shibayama, S Matsuo, M Takaoka, Y Ito, M Koyanagi, Y Mitsuya, H TI Potent anti-R5 human immunodeficiency virus type 1 effects of a CCR5 antagonist, AK602/ONO4128/GW873140, in a novel human peripheral blood mononuclear cell nonobese diabetic-SCID, interleukin-2 receptor gamma-chain-knocked-out AIDS mouse model SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SELECTIVE ANTI-HIV-1 ACTIVITY; PROTEASE INHIBITOR PI; CD4(+) T-CELLS; HIV-1 INFECTION; IN-VITRO; DENDRITIC CELLS; SMALL-MOLECULE; LIGAND TRAIL; MICE AB We established human peripheral blood mononuclear cell (PBMC)-transplanted R5 human immunodeficiency virus type 1 isolate JR-FL (HIV-1(JR-FL))-infected, nonobese diabetic-SCID, interleukin 2 receptor T-chain-knocked-out (NOG) mice, in which massive and systemic HIV-1 infection occurred. The susceptibility of the implanted PBMC to the infectivity and cytopathic effect of R5 HIV-1 appeared to stem from hyperactivation of the PBMC, which rapidly proliferated and expressed high levels of CCR5. When a novel spirodiketopiperazine-containing CCR5 inhibitor, AK602/ONO4128/GW873140 (molecular weight, 614), was administered to the NOG mice 1 day after R5 HIV-1 inoculation, the replication and cytopathic effects of R5 HIV-1 were significantly suppressed. In saline-treated mice (n = 7), the mean human CD4(+)/CD8(+) cell ratio was 0.1 on day 16 after inoculation, while levels in mice (n = 8) administered AK602 had a mean value of 0.92, comparable to levels in uninfected mice (n = 7). The mean number of HIV-RNA copies in plasma in saline-treated mice were similar to10(6)/ml on day 16, while levels in AK602-treated mice were 1.27 X 10(3)/ml (P = 0.001). AK602 also significantly suppressed the number of proviral DNA copies and serum p24 levels (P = 0.001). These data suggest that the present NOG mouse system should serve as a small-animal AIDS model and warrant that AK602 be further developed as a potential therapeutic for HIV-1 infection. C1 Kumamoto Univ, Grad Sch Med, Dept Infect Dis, Kumamoto 8608556, Japan. Ono Pharmaceut Co Ltd, Osaka, Japan. Cent Inst Expt Anim, Kawasaki, Kanagawa, Japan. Tohoku Univ, Grad Sch Med, Dept Virol, Sendai, Miyagi 980, Japan. Natl Canc Inst, Expt Retrovirol Sect, HIV AIDS Malignancy Branch, Bethesda, MD USA. RP Mitsuya, H (reprint author), Kumamoto Univ, Grad Sch Med, Dept Infect Dis, 1-1-1 Honjo, Kumamoto 8608556, Japan. EM hmitsuya@helix.nih.gov NR 35 TC 48 Z9 50 U1 0 U2 3 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 FEB PY 2005 VL 79 IS 4 BP 2087 EP 2096 DI 10.1128/JVI.79.4.2087-2096.2005 PG 10 WC Virology SC Virology GA 894DZ UT WOS:000226772100012 PM 15681411 ER PT J AU Smulevitch, S Michalowski, D Zolotukhin, AS Schneider, R Bear, J Roth, P Pavlakis, GN Felber, BK AF Smulevitch, S Michalowski, D Zolotukhin, AS Schneider, R Bear, J Roth, P Pavlakis, GN Felber, BK TI Structural and functional analysis of the RNA transport element, a member of an extensive family present in the mouse genome SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL MESSENGER-RNA; POSTTRANSCRIPTIONAL CONTROL ELEMENT; SIMIAN RETROVIRUS TYPE-1; REV-RESPONSIVE ELEMENT; ROUS-SARCOMA-VIRUS; SECONDARY STRUCTURE; NUCLEAR EXPORT; MUTATIONAL ANALYSIS; MAMMALIAN-CELLS AB We previously identified an RNA transport element (RTE), present in a subclass of rodent intracisternal A particle retroelements (F. Nappi, R. Schneider, A. Zolotukhin, S. Smulevitch, D. Michalowski, J. Bear, B. Felber, and G. Pavlakis, J. Virol. 75:4558-4569, 2001), that is able to replace Rev-responsive element regulation in human immunodeficiency virus type 1. RTE-directed mRNA export is mediated by a still-unknown cellular factor(s), is independent of the CRM1 nuclear export receptor, and is conserved among vertebrates. Here we show that this RTE folds into an extended RNA secondary structure and thus does not resemble any known RTEs. Computer searches revealed the presence of 105 identical elements and more than 3,000 related elements which share at least 70% sequence identity with the RTE and which are found on all mouse chromosomes. These related elements are predicted to fold into RTE-like structures. Comparison of the sequences and structures revealed that the RTE and related elements can be divided into four groups. Mutagenesis of the RTE revealed that the minimal element contains four internal stem-loops, which are indispensable for function in mammalian cells. In contrast, only part of the element is essential to mediate RNA transport in microinjected Xenopus laevis oocyte nuclei. Importantly, the minimal RTE able to promote RNA transport has key structural features which are preserved in all the RTE-related elements, further supporting their functional importance. Therefore, RTE function depends on a complex secondary structure that is important for the interaction with the cellular export factor(s). C1 NCI Frederick, Vaccine Branch, Human Retrovirus Pathogenesis Sect, Ft Detrick, MD 21702 USA. NCI Frederick, Human Retrovirus Sect, Ft Detrick, MD 21702 USA. GSF Forschungszentrum Umwelt & Gesundheit GMBH, AG BIODV, Inst Expt Genet, Oberschleissheim, Germany. RP Felber, BK (reprint author), NCI Frederick, Vaccine Branch, Human Retrovirus Pathogenesis Sect, Bldg 535,Rm 110, Ft Detrick, MD 21702 USA. EM felber@ncifcrf.gov NR 38 TC 15 Z9 15 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 FEB PY 2005 VL 79 IS 4 BP 2356 EP 2365 DI 10.1128/JVI.79.4.2356-2365.2005 PG 10 WC Virology SC Virology GA 894DZ UT WOS:000226772100037 PM 15681436 ER PT J AU Belliot, G Sosnovtsev, SV Chang, KO Babu, V Uche, U Arnold, JJ Cameron, CE Green, KY AF Belliot, G Sosnovtsev, SV Chang, KO Babu, V Uche, U Arnold, JJ Cameron, CE Green, KY TI Norovirus proteinase-polymerase and polymerase are both active forms of RNA-dependent RNA polymerase SO JOURNAL OF VIROLOGY LA English DT Article ID HEMORRHAGIC-DISEASE VIRUS; FELINE CALICIVIRUS GENOME; NORWALK-LIKE VIRUS; IN-VITRO; ESCHERICHIA-COLI; CLEAVAGE SITES; NONSTRUCTURAL POLYPROTEIN; POLIOVIRUS RNA; GASTROENTERITIS OUTBREAKS; 3C-LIKE PROTEASE AB In vitro mapping studies of the MD145 norovirus (Caliciviridae) ORF1 polyprotein identified two stable cleavage products containing the viral RNA-dependent RNA polymerase (RdRp) domains: ProPol (a precursor comprised of both the proteinase and polymerase) and Pol (the mature polymerase). The goal of this study was to identify the active form (or forms) of the norovirus polymerase. The recombinant ProPol (expressed as Pro(-)Pol with an inactivated proteinase domain to prevent autocleavage) and recombinant Pol were purified after synthesis in bacteria and shown to be active RdRp enzymes. In addition, the mutant His-E1189A-ProPol protein (with active proteinase but with the natural ProPol cleavage site blocked) was active as an RdRp, confirming that the norovirus ProPol precursor could possess two enzymatic activities simultaneously. The effects of several UTP analogs on the RdRp activity of the norovirus and feline calicivirus Pro-Poll enzymes were compared and found to be similar. Our data suggest that the norovirus ProPol is a bifunctional enzyme during virus replication. The availability of this recombinant ProPol enzyme might prove useful in the development of antiviral drugs for control of the noroviruses associated with acute gastroenteritis. C1 NIAID, NIH, DHHS, LID, Bethesda, MD 20892 USA. Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. RP Belliot, G (reprint author), NIAID, NIH, DHHS, LID, Bldg 50,Room 6316,9000 Rockville Pike, Bethesda, MD 20892 USA. EM gbelliot@niaid.nih.gov NR 49 TC 37 Z9 42 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 FEB PY 2005 VL 79 IS 4 BP 2393 EP 2403 DI 10.1128/JVI.79.4.2393-2403.2005 PG 11 WC Virology SC Virology GA 894DZ UT WOS:000226772100041 PM 15681440 ER PT J AU McGivern, DR Collins, PL Fearns, R AF McGivern, DR Collins, PL Fearns, R TI Identification of internal sequences in the 3 ' leader region of human respiratory syncytial virus that enhance transcription and confer replication processivity SO JOURNAL OF VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; VIRAL-RNA POLYMERASE; SENDAI-VIRUS; ANTIGENOMIC PROMOTERS; MESSENGER-RNA; NUCLEOTIDE-SEQUENCES; GENOME RNA; GENE-START; N-PROTEIN; INITIATION AB Previous studies of respiratory syncytial virus have shown that the 44-nucleotide (nt) leader (Le) region is sufficient to initiate RNA replication, producing antigenome RNA, and that the Le and adjoining gene start (GS) signal of the first gene are sufficient to initiate transcription, producing mRNA. A cis-acting element necessary for both transcription and replication was mapped within the first 11 nt at the 3' end of Le. In the present study the remainder of the Le region was mapped to identify sequences important for transcription and replication. A series of minigenomes with mutant Le sequences was generated, and their ability to direct transcription and replication was determined by Northern blot analysis, which examined full-length antigenome and mRNA, and by primer extension analysis, which examined antigenome and mRNA initiation. With regard to transcription, nt 36 to 43, located immediately upstream of the GS signal, were found to be necessary for optimal levels of mRNA synthesis, although the GS signal in conjunction with the 3'-terminal region of Le was sufficient to direct accurate mRNA synthesis initiation. With regard to replication, the first 15 nt of Le were found to be sufficient to direct initiation of antigenome synthesis, but nt 16 to 34 were required in addition for efficient encapsidation and production of full-length antigenome. Analysis of transcripts produced from di- and tricistronic minigenomes indicated that a significant proportion of abortive replicases continue RNA synthesis to the end of the first gene and then continue in a transcription mode along the remainder of the genome. C1 Univ Dundee, Div Pathol & Neurosci, Dundee DD1 9SY, Scotland. NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Fearns, R (reprint author), Univ Dundee, Sch Med, Ninewells Hosp, Div Pathol & Neurosci, Dundee DD1 9SY, Scotland. EM r.fearns@dundee.ac.uk OI Fearns, Rachel/0000-0003-0783-7498; McGivern, David/0000-0003-3497-5087 NR 41 TC 26 Z9 26 U1 0 U2 4 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 FEB PY 2005 VL 79 IS 4 BP 2449 EP 2460 DI 10.1128/JVI.79.4.2449-2460.2005 PG 12 WC Virology SC Virology GA 894DZ UT WOS:000226772100047 PM 15681446 ER PT J AU Fernandez-Llama, P Ageloff, S Fernandez-Varo, G Ros, J Wang, XY Garra, N Esteva-Font, C Ballarin, J Barcelo, P Arroyo, V Stokes, JB Knepper, MA Jimenez, W AF Fernandez-Llama, P Ageloff, S Fernandez-Varo, G Ros, J Wang, XY Garra, N Esteva-Font, C Ballarin, J Barcelo, P Arroyo, V Stokes, JB Knepper, MA Jimenez, W TI Sodium retention in cirrhotic rats is associated with increased renal abundance of sodium transporter proteins SO KIDNEY INTERNATIONAL LA English DT Article DE NKCC2; NCC; ENaC; aldosterone ID THICK ASCENDING LIMB; NA-CL COTRANSPORTER; ALDOSTERONE-ESCAPE PHENOMENON; LONG-TERM REGULATION; SYSTEMIC HEMODYNAMICS; RECEPTOR ANTAGONIST; ASCITES FORMATION; LIVER-CIRRHOSIS; ANGIOTENSIN-II; DIETARY NACL AB Background. Liver cirrhosis with ascites is associated with a decrease in renal sodium excretion and therefore sodium retention. Methods. In this paper, we utilize transporter-specific antibodies to address the hypothesis that dysregulation of one or more sodium transporters or channels is associated with sodium chloride (NaCl) retention in a rat model of cirrhosis induced by repeated exposure to carbon tetrachloride. Age-matched controls and cirrhotic rats were pair fed to ensure identical NaCl and water intake for 4 days prior to euthanasia for quantitative immunoblotting studies. Results and Conclusion. The rats manifested marked extracellular fluid volume expansion with massive ascites. Plasma aldosterone levels were markedly elevated. Analysis of immunoblots revealed marked increases in the abundances of both of the major aldosterone-sensitive apical transport proteins of the renal tubule, namely the thiazide-sensitive NaCl cotransporter NCC and the epithelial sodium channel alpha subunit (alpha-ENaC). These results are consistent with an important role for hyperaldosteronism in the pathogenesis of sodium retention and ascites formation in cirrhosis. In addition, we observed a large decrease in cortical NHE3 abundance (proximal tubule) and a large increase in NKCC2 abundance (thick ascending limb), potentially shifting premacula densa sodium absorption from proximal tubule to loop of Henle (which powers urinary concentration and dilution). C1 Fdn Puigvert, Renal & Hypertens Unit, Barcelona 08025, Spain. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Inst Invest Biomed August Pi & Sunyer, Hormonal Lab, Barcelona, Spain. Inst Reina Sofia Invest Nefrol, Madrid, Spain. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. VA Med Ctr, Iowa City, IA USA. RP Fernandez-Llama, P (reprint author), Fdn Puigvert, Renal & Hypertens Unit, Cartagena 340-350, Barcelona 08025, Spain. EM pfernandezllama@fundacio-puigvert.es RI Arroyo, Vicente/F-9189-2015 OI Arroyo, Vicente/0000-0002-2728-1848 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-01282]; NIDDK NIH HHS [DK-96001] NR 42 TC 29 Z9 30 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2005 VL 67 IS 2 BP 622 EP 630 DI 10.1111/j.1523-1755.2005.67118.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 889CH UT WOS:000226420600023 PM 15673309 ER PT J AU Eisenhofer, G Huysmans, F Pacak, K Walther, MM Sweep, FCGJ Lenders, JWM AF Eisenhofer, G Huysmans, F Pacak, K Walther, MM Sweep, FCGJ Lenders, JWM TI Plasma metanephrines in renal failure SO KIDNEY INTERNATIONAL LA English DT Article DE normetanephrine; metanephrine; norepinephrine; epinephrine; renal failure; dialysis; pheochromocytoma ID BIOCHEMICAL-DIAGNOSIS; CATECHOLAMINE METABOLISM; CHROMOGRANIN-A; PHEOCHROMOCYTOMA; HEMODIALYSIS; NORMETANEPHRINE; COMBINATION; DISEASE; PATIENT AB Background. Diagnosis of pheochromocytoma in renal failure poses a diagnostic dilemma due to lack of reliability of conventional urinary measurements of catecholamine excess. Measurements of the plasma metanephrines, normetanephrine and metanephrine (the O-methylated metabolites of norepinephrine and epinephrine), provide an alternative diagnostic test. The metanephrines may be measured as free metabolites or after a deconjugation step where measurements reflect mainly sulfate-conjugated metabolites. The influence of renal insufficiency states on these various measurements is unclear. Methods. Plasma free and deconjugated metanephrines and catecholamines in 17 patients on dialysis with end-stage renal disease and 19 patients with renal insufficiency (creatinine clearance, 5-78 mL/min) were compared with levels in 89 hypertensives, 68 healthy normotensives, and 51 patients with von Hippel-Lindau syndrome. Results. Patients with renal failure had up to two-fold higher plasma concentrations of catecholamines and free metanephrines, and more than 12-fold higher plasma concentrations of deconjugated metanephrines than comparison groups. Plasma free metanephrines and catecholamines were, respectively, within the 95% confidence intervals of reference groups in 75% and 42% of the dialysis patients, and in 74% and 68% of patients with renal insufficiency. In contrast, no dialysis patient and only half the renal insufficiency patients had plasma levels of deconjugated metanephrines within the reference intervals. Plasma levels of deconjugated metanephrines, but not free metanephrines, showed strong inverse relationships with creatinine clearance. Conclusion. Plasma concentrations of free metanephrines are relatively independent of renal function and are, therefore, more suitable for diagnosis of pheochromocytoma among patients with renal failure than measurements of deconjugated metanephrines. C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. St Radboud Univ Med Ctr, Dept Nephrol, Nijmegen, Netherlands. St Radboud Univ Med Ctr, Dept Chem Endocrinol, Nijmegen, Netherlands. St Radboud Univ Med Ctr, Dept Gen Internal Med, Nijmegen, Netherlands. RP Eisenhofer, G (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10,Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. EM ge@box-g.nih.gov RI Sweep, C.G.J./H-8096-2014; Lenders, J.W.M./L-4487-2015 NR 34 TC 30 Z9 31 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2005 VL 67 IS 2 BP 668 EP 677 DI 10.1111/j.1523-1755.2005.67123.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 889CH UT WOS:000226420600029 PM 15673315 ER PT J AU Weber, MA Schnyder-Candrian, S Schnyder, B Quesniaux, V Poli, V Stewart, CL Ryffel, B AF Weber, MA Schnyder-Candrian, S Schnyder, B Quesniaux, V Poli, V Stewart, CL Ryffel, B TI Endogenous leukemia inhibitory factor attenuates endotoxin response SO LABORATORY INVESTIGATION LA English DT Article DE LPS; LIF-deficient mice; endotoxic shock; LIF; TNF; IL-6; acute phase ID TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA; D-GALACTOSAMINE; SEPTIC SHOCK; FACTOR-ALPHA; PASSIVE-IMMUNIZATION; FACTOR PROTECTS; STEM-CELLS; FACTOR LIF; MICE AB Leukemia inhibitory factor (LIF) is induced in inflammation and likely plays a regulatory role. Using LIF-deficient mice ( LIF -/-), we report here that endogenous LIF has a protective role in endotoxic shock and host defence. LIF -/- mice have heightened sensitivity to LPS in a LPS/D-galactosamine (D-Gal) sensitization model compared to wild-type mice ( LIF+/+), enhanced thrombocytopenia and leukopenia, with increased hepatic necrosis, neutrophil sequestration in the lung and accelerated mortality. These findings correlated with 10-fold higher tumour necrosis factor-alpha (TNFalpha) and interleukin-6 ( IL-6) serum levels and reduced IL-10 production in LIF -/- mice in response to LPS. Therefore, endogenous LIF attenuates the endotoxic shock response, enhances the expression of basal acute phase proteins and IL-10 production, which downregulates TNFalpha synthesis and release and thereby confers partial protection to endotoxemia. C1 CNRS, F-45071 Orleans, France. NCI, Canc & Dev Biol Lab, FCRDC, Frederick, MD USA. Univ Turin, Dipartimento Genet Biol & Biochim, I-10124 Turin, Italy. RP Ryffel, B (reprint author), CNRS, 3B Rue Ferrollerie,GEM2358, F-45071 Orleans, France. EM bryffel@cnrs-orelans.fr RI Poli, Valeria/A-9215-2012 OI Poli, Valeria/0000-0002-3739-3966 NR 43 TC 21 Z9 22 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2005 VL 85 IS 2 BP 276 EP 284 DI 10.1038/labinvest.3700216 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 893LG UT WOS:000226719900014 PM 15702085 ER PT J AU Risitano, AM Maciejewski, JP Muranski, P Wlodarski, M O'Keefe, C Sloand, EM Young, NS AF Risitano, AM Maciejewski, JP Muranski, P Wlodarski, M O'Keefe, C Sloand, EM Young, NS TI Large granular lymphocyte (LGL)-like clonal expansions in paroxysmal nocturnal hemoglobinuria (PNH) patients SO LEUKEMIA LA English DT Article DE paroxysmal nocturnal hemoglobinuria; bone marrow failure; LGL-disease; T-cell receptor; complementarity determining region 3 ID ACQUIRED APLASTIC-ANEMIA; MARROW FAILURE SYNDROMES; T-CELL REPERTOIRE; MOLECULAR ANALYSIS; IN-VIVO; A GENE; RECEPTOR; DISEASE; MECHANISMS; DISORDERS AB In paroxysmal nocturnal hemoglobinuria (PNH), clonal expansion of glycosylphosphatidylinositol-anchored proteins (GPI-AP)-deficient cells leads to a syndrome characterized by hemolytic anemia, marrow failure, and venous thrombosis. PNH is closely related to aplastic anemia and may share its immune pathophysiology. In vivo expansion of dominant T-cell clones can reflect an antigen-driven immune response but may also represent autonomous proliferation, such as in large granular lymphocytic (LGL)-leukemia. T-cell clonality can be assessed by a combination of T-cell receptor (TCR) flow cytometry and complementarity-determining-region-3 (CDR3) molecular analysis. We studied 24 PNH patients for evidence of in vivo dominant T-cell responses by flow cytometry; TCR-Vbeta-specific expansions were identified in all patients. In four cases, extreme expansions of one Vbeta-subset of CD8+/CD28-/CD56+ ( effector) phenotype mimicked subclinical LGL-disease. The monoclonality of these expansions was inferred from unique CDR3-size peak distributions and sequencing of dominant clonotypes. We conclude that the molecular analysis of TCR-beta chain may demonstrate clonal LGL-like expansions at unexpected frequency in PNH patients. Our observations blur the classical boundaries between different bone marrow failure syndromes such as AA, PNH, and LGL, and support the hypothesis that in PNH, the mutant clone may expand as a result of an immune-escape from antigen-driven lymphocyte attack on hematopoietic progenitors. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Taussig Canc Ctr, Expt Hematol & Hematopoiesis Div, Cleveland, OH USA. RP Risitano, AM (reprint author), Univ Naples Federico II, Div Hematol, Via Pansini 5, I-80131 Naples, Italy. EM amrisita@unina.it RI Muranski, Pawel/E-5572-2010; OI Wlodarski, Marcin/0000-0001-6638-9643 NR 35 TC 34 Z9 34 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 2005 VL 19 IS 2 BP 217 EP 222 DI 10.1038/sj.leu.2403617 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 890HI UT WOS:000226501900010 PM 15668701 ER PT J AU Sen, PN Basser, PJ AF Sen, PN Basser, PJ TI Modeling diffusion in white matter in the brain: A composite porous medium SO MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT 7th International Conference on Magnetic Resonance in Porous Media (MRPM7) CY JUL 04-08, 2004 CL Palaiseau, FRANCE DE diffusion; white matter; myelin; axon; brain; conductivity; tensor; model; MRI ID TRANSPORT-PROPERTIES; CYLINDERS AB We model diffusion in white matter fascicles as a problem of diffusion in an array of identical thick-walled cylindrical tubes immersed in an outer medium and arranged periodically in a regular lattice. The diffusing molecules have different diffusion coefficients and concentrations (or densities) within the tubes' inner core, membrane, myclin sheath, and within the outer medium. For an impermeable myelin sheath, diffusing molecules within the inner core are completely restricted, while molecules in the outer medium are hindered due to the tortuosity of the array of impenetrable tubes. (c) 2005 Elsevier Inc. All rights reserved. C1 Schlumberger Doll Res Ctr, Ridgefield, CT 06877 USA. NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Sen, PN (reprint author), Schlumberger Doll Res Ctr, Old Quarry Rd, Ridgefield, CT 06877 USA. EM psen@ridgefield.oilfield.slb.com RI Basser, Peter/H-5477-2011 NR 11 TC 21 Z9 21 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD FEB PY 2005 VL 23 IS 2 SI SI BP 215 EP 220 DI 10.1016/j.mri.2004.11.014 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920AD UT WOS:000228658400015 PM 15833615 ER PT J AU Shapiro, EM Skrtic, S Koretsky, AP AF Shapiro, EM Skrtic, S Koretsky, AP TI Sizing it up: Cellular MRI using micron-sized iron oxide particles SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; iron oxide; cells; contrast agents; particles ID STEM-CELLS; IN-VIVO; TRANSFECTION AGENTS; RAT; TRACKING; MIGRATION; STROKE AB There is rapidly increasing interest in the use of MRI to track cell migration in intact animals. Currently, cell labeling is usually accomplished by endocytosis of nanometer-sized, dextrancoated iron oxide particles. The limitations of using nanometersized particles, however, are that millions of particles are required to achieve sufficient contrast, the label can be diluted beyond observability by cell division, and the label is biodegradable. These problems make it difficult to label cells other than macrophages in vivo, and to conduct long-term engraftment studies. It was recently demonstrated that micron-sized iron oxide particles (MPIOs) can be taken up by a number of cell types. In this study we examined the MRI properties of single MPIOs with sizes of 0.96, 1.63, 2.79, 4.50, and 5.80 mum. Furthermore, the capacity of cells to endocytose these MPIOs was investigated, and the MRI properties of the labeled cells at 7.0 and 11.7 Tesla were measured as a function of image resolution and echo time (TE). Cells labeled with MPlOs generally contained iron levels of similar to100 pg, which is approximately threefold higher than those obtained with the best strategies to label cells using nanometer-sized particles. On occasion, some cells had levels as high as similar to400 pg. We demonstrate that these large particles and the cells labeled with them can be detected by spin echo (SE)-based imaging methods. These measurements indicate that MPIOs should be useful for improving cell tracking by MRI. Published 2005 Wiley-Liss, Inc. C1 Natl Inst Neurol Disorders & Stroke, NIH, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. RP Shapiro, EM (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. EM ShapiroE@ninds.nih.gov RI Koretsky, Alan/C-7940-2015; OI Koretsky, Alan/0000-0002-8085-4756; Skrtic, Stanko/0000-0002-1950-5418 FU Intramural NIH HHS [Z01 NS003047-01] NR 22 TC 209 Z9 216 U1 1 U2 24 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD FEB PY 2005 VL 53 IS 2 BP 329 EP 338 DI 10.1002/mrm.20342 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 892LC UT WOS:000226651100011 PM 15678543 ER PT J AU Lancaster, M Rouse, J Hunter, KW AF Lancaster, M Rouse, J Hunter, KW TI Modifiers of mammary tumor progression and metastasis on mouse Chromosomes 7, 9, and 17 SO MAMMALIAN GENOME LA English DT Article ID DROSOPHILA-MELANOGASTER; SUBSTITUTION ANALYSIS; BREAST-CANCER; EXPRESSION; STRAINS; CELLS; MODEL; PROLIFERATION; INEFFICIENCY; DORMANCY AB Tumor progression, the growth and dissemination of primary tumor to secondary sites, is of critical clinical importance since the vast majority of patients succumb to metastatic disease rather than to the primary tumor. Many factors are likely to influence this process, including the primary oncogenic events, environmental exposures and stress and progressive stochastic mutations. Previously, our laboratory demonstrated that an additional factor, the genetic background on which tumors arose, had a significant effect on metastatic efficiency. Using a highly metastatic transgene-induced mammary tumor model, a locus modulating metastatic efficiency, Mtes1, was localized on proximal mouse Chromosome 19. In addition, a number of additional suggestive loci were observed on several other chromosomes. To confirm the presence of these additional loci before initiating cloning strategies, chromosomal substitution strains have been constructed and assayed for modification of the cancer phenotypes. Using the chromosomal substitution strains, an additional modifier modulating tumor latency was confirmed, as well as three new modifier genes that alter the kinetics of tumor progression. Identification and analysis of these loci will likely present interesting and novel information about cancer heterogeneity in the human population. C1 NCI, Lab Populat Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hunter, KW (reprint author), NCI, Lab Populat Genet, Ctr Canc Res, NIH, Bldg 41,Room D702,41 Lib Dr, Bethesda, MD 20892 USA. EM hunterk@mail.nih.gov NR 25 TC 22 Z9 24 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 2005 VL 16 IS 2 BP 120 EP 126 DI 10.1007/s00335-004-2432-y PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 893VT UT WOS:000226749300007 PM 15859357 ER PT J AU Hadley, EC Rossi, WK AF Hadley, EC Rossi, WK TI Exceptional survival in human populations: National Institute on Aging perspectives and programs SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT Conference on Old Age - Searching for Human Longevity Genes CY DEC 01-04, 2003 CL ISRAEL DE National Institute on Aging (NIA); longevity assurance genes; health span; active life expectancy ID HUMAN LONGEVITY; CENTENARIANS; MORTALITY; SIBLINGS AB Identifying the factors that contribute to long and healthy life can lead to improved interventions that can help delay or prevent the onset of major aging-related diseases and disabilities and increase the time that older persons spend in good health. Studies on longevity and other exceptional survival outcomes can contribute to this knowledge. The National Institute on Aging (NIA) supports a considerable amount of basic, behavioral, demographic, epidemiologic, and clinical research on these topics, including a large research program on longevity assurance genes, primarily in laboratory animals, and in biodemographic aspects of longevity in humans and other species. This article describes NIA's activities regarding one important aspect of research on longevity and related phenotypes: exceptional survival phenotypes in humans, including exceptional longevity, health span, and active life expectancy. Published by Elsevier Ireland Ltd. C1 NIA, NIH, Geriatr & Clin Gerontol Program, Bethesda, MD 20892 USA. RP Hadley, EC (reprint author), NIA, NIH, Geriatr & Clin Gerontol Program, Gateway Bldg,Suite 3C307,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM ehadley@nih.gov NR 16 TC 15 Z9 15 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 FEB PY 2005 VL 126 IS 2 BP 231 EP 234 DI 10.1016/j.mad.2004.08.014 PG 4 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 891EN UT WOS:000226564200003 PM 15621201 ER PT J AU Warner, HR AF Warner, HR TI Longevity genes: from primitive organisms to humans SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT Conference on Old Age - Searching for Human Longevity Genes CY DEC 01-04, 2003 CL ISRAEL DE aging; longevity; stress resistance; caloric restriction; insulin-signaling ID SUPEROXIDE DISMUTASE/CATALASE MIMETICS; DROSOPHILA LIFE-SPAN; HEAT-SHOCK FACTOR; CAENORHABDITIS-ELEGANS; STRESS RESISTANCE; OXIDATIVE STRESS; INSULIN-RECEPTOR; C-ELEGANS; CALORIC RESTRICTION; SIGNALING PATHWAY AB Recent results indicate that the longevity of both invertebrates and vertebrates can be altered through genetic manipulation and pharmacological intervention. Most of these interventions involve alterations of one or more of the following: insulin/IGF-I signaling pathway, caloric intake, stress resistance and nuclear structure. How longevity regulation relates to aging per se is less clear, but longevity increases are usually accompanied by extended periods of good health. How these results will translate to primate aging and longevity remains to be shown. Published by Elsevier Ireland Ltd. C1 NIA, Biol Aging Program, Bethesda, MD 20892 USA. RP Warner, HR (reprint author), NIA, Biol Aging Program, Gateway Bldg,Room 2C31, Bethesda, MD 20892 USA. EM warnerh@nia.nih.gov NR 90 TC 38 Z9 54 U1 1 U2 9 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 FEB PY 2005 VL 126 IS 2 BP 235 EP 242 DI 10.1016/j.mad.2004.08.015 PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 891EN UT WOS:000226564200004 PM 15621202 ER PT J AU Yabroff, KR Klabunde, CN Myers, R Brown, ML AF Yabroff, KR Klabunde, CN Myers, R Brown, ML TI Physician recommendations for follow-up of positive fecal occult blood tests SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE follow-up studies; fecal occult blood test; colorectal neoplasms; mass screening; physician's role; physician's practice patterns ID COMPLETE DIAGNOSTIC EVALUATION; PRIMARY-CARE PHYSICIANS; COLORECTAL-CANCER; SCREENING RECOMMENDATIONS; NATIONAL-SURVEY; SELF-REPORT; ADHERENCE; INTERVENTIONS; METAANALYSIS; SERVICES AB Following a positive fecal occult blood test (FOBT), physician recommendation of complete diagnostic evaluation (CDE) is an important first step to ensure identification and treatment of preinvasive or invasive colorectal cancer. Physicians may not recommend CDE, however, potentially compromising the effectiveness of colorectal cancer screening programs and the quality of care for individual patients. The authors used a theoretical model of health behavior and two national physician samples to explore factors associated with recommendations for CDE. Overall, 63 percent of the sample of physicians providing primary care and 76 percent of the gastroenterologist and general surgeon sample reported recommending CDE. Variables representing the theoretical model constructs Of physician background, experience, and practice patterns; practice environment; physician psychosocial representations; and patient characteristics were significantly associated with recommendations of CDE. Development of interventions to improve recommendations of CDE is an important area for future research. C1 NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP Yabroff, KR (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. EM yabroffr@mail.nih.gov OI Myers, Ronald E./0000-0002-8059-7390; Yabroff, K. Robin/0000-0003-0644-5572 NR 39 TC 12 Z9 12 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD FEB PY 2005 VL 62 IS 1 BP 79 EP 110 DI 10.1177/1077558704271725 PG 32 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 889TD UT WOS:000226464600004 PM 15643030 ER PT J AU Musso, C Cochran, E Javor, E Young, J DePaoli, AM Gorden, P AF Musso, C Cochran, E Javor, E Young, J DePaoli, AM Gorden, P TI The long-term effect of recombinant methionyl human leptin therapy on hyperandrogenism and menstrual function in female and pituitary function in male and female hypoleptinemic lipodystrophic patients SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; INSULIN-RESISTANCE; REPRODUCTIVE FUNCTION; REPLACEMENT THERAPY; CLINICAL-COURSE; GROWTH-HORMONE; ONSET; PUBERTY; PATHOGENESIS; DEFICIENCY AB Lipodystrophy patients are hypoleptinemic and insulin resistant. Women have enlarged polycystic ovaries, hyperandrogenism, and amenorrhea. We have determined the role of correction of hypoleptinemia on these metabolic and neuroendocrine parameters. Ten females and 4 males with generalized lipodystrophy were treated with recombinant methionyl human leptin (r-metHuLeptin) in physiologic doses in an open-labeled study for a period of 12 and 8 months, respectively. In the female group, serum free testosterone decreased from 39.6 +/- 11 to 18.9 +/- 4.5 ng/dL (P < 0.01) and serum sex hormone binding globulin increased from 14 +/- 2.5 to 25 +/- 4.8 nmol/L (P < 0.02). Luteinizing hormone (LH) responses to LH releasing hormone were more robust after therapy and significantly changed in the youngest group of 3 female patients (P < 0.01). Ovarian ultrasound showed a polycystic ovarian disease pattern in all patients and did not change after therapy. Eight of the 10 patients had amenorrhea prior to therapy and all 8 developed normal menses after therapy. In the male group, serum testosterone tended to increase from 433 +/- 110 to 725 +/- 184 ng/dL (P = 0.1) and sex hormone binding globulin also increased from 18.25 +/- 2.6 to 27 +/- 1.7 nmol/L (P < 0.04) following r-metHuLeptin therapy. Serum LH response to LH releasing hormone did not show significant changes. Five additional hypoleptinemic male subjects with minimal metabolic abnormalities underwent normal pubertal development without receiving r-metHuLeptin therapy. In both genders, insulin-like growth factor increased significantly and there were no differences in growth hormone, thyroid, or adrenal hormone levels following r-metHuLeptin therapy. Glycemic parameters significantly improved after r-metHuLeptin therapy in both groups. Hypoglycemic medications were discontinued in 7 of 12 patients and dramatically reduced in 5 patients. r-metHuLeptin therapy plays an important role in insulin sensitivity. In females, it plays an additional role in normalizing menstrual function. This is likely to occur both from increasing insulin sensitivity and from restoring LH pulsatility. The persistent hypoleptinemic state in these subjects did not inhibit pubertal development. (C) 2005 Elsevier Inc. All rights reserved. C1 NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Gorden, P (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM carlam@intra.niddk.nih.gov; phillipg@intra.niddk.nih.gov NR 29 TC 60 Z9 63 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD FEB PY 2005 VL 54 IS 2 BP 255 EP 263 DI 10.1016/j.metabol.2004.08.021 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 899JU UT WOS:000227141500018 PM 15690321 ER PT J AU Shen, JS Snapp, EL Lippincott-Schwartz, J Prywes, R AF Shen, JS Snapp, EL Lippincott-Schwartz, J Prywes, R TI Stable binding of ATF6 to BiP in the endoplasmic reticulum stress response SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID UNFOLDED-PROTEIN RESPONSE; TRANSCRIPTION FACTOR ATF6; ER STRESS; MOLECULAR CHAPERONES; TRANSLATIONAL CONTROL; MEMBRANE-PROTEIN; QUALITY-CONTROL; MESSENGER-RNA; HEAVY-CHAINS; IN-VITRO AB Endoplasmic reticulum (ER) stress-induced activation of ATF6. an ER membrane-bound transcription factor, requires a dissociation step from its inhibitory regulator. BiP. It has been generally postulated that dissociation of the BiP-ATF6 complex is a result of the competitive binding of misfolded proteins generated during ER stress. Here we present evidence against this model and for an active regulatory mechanism for dissociation of the complex. Contradictory to the competition model that is based on dynamic binding of BiP to ATF6, our data reveal relatively stable binding. First, the complex was easily isolated, in contrast to many chaperone complexes that require chemical cross-linking. Second, ATF6 bound at similar levels to wild-type BiP and a BiP mutant form that binds substrates stably because of a defect in its ATPase activity. Third. ER stress specifically induced the dissociation of BiP from ER stress transducers while the competition model would predict dissociation from any specific substrate. Fourth, the ATF6-BiP complex was resistant to ATP-induced dissociation in vitro when isolated without detergents, suggesting that cofactors stabilize the complex. In favor of an active dissociation model, one specific region within the ATF6 lumenal domain was identified as a specific ER stress-responsive sequence required for ER stress-triggered BiP release. Together, our results do not support a model in which competitive binding of misfolded proteins causes dissociation of the BiP-ATF6 complex in stressed cells. We propose that stable BiP binding is essential for ATF6 regulation and that ER stress dissociates BiP from ATF6 by actively restarting the BiP ATPase cycle. C1 Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD USA. RP Prywes, R (reprint author), Columbia Univ, Dept Biol Sci, Fairchild 813B,MC 2420,1212 Amsterdam Ave, New York, NY 10027 USA. EM mrp6@columbia.edu OI SHEN, JINGSHI/0000-0001-9595-1148 FU NCI NIH HHS [CA 50329, R01 CA050329] NR 51 TC 111 Z9 120 U1 2 U2 11 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 FEB PY 2005 VL 25 IS 3 BP 921 EP 932 DI 10.1128/MCB.25.3.921-932.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 892LU UT WOS:000226652900006 PM 15657421 ER PT J AU Yang, Q Zheng, YL Harris, CC AF Yang, Q Zheng, YL Harris, CC TI POT1 and TRF2 cooperate to maintain telomeric integrity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID END-BINDING-PROTEIN; NORMAL HUMAN-CELLS; MAMMALIAN TELOMERES; HUMAN-CHROMOSOMES; DNA-DAMAGE; CANCER; LENGTH; SENESCENCE; COMPLEX; LOCALIZATION AB Mammalian telomeric DNA contains duplex TTAGGG repeats and single-stranded overhangs. POT1 (protection of telomeres 1) is a telomere-specific single-stranded DNA-binding protein, highly conserved in eukaryotes. The biological function of human POT1 is not well understood. In the present study, we demonstrate that POT1 plays a key role in telomeric end protection. The reduction of POT1 by RNA interference led to the loss of telomeric single-stranded overhangs and induced apoptosis, chromosomal instability, and senescence in cells. POT1 and TRF2 interacted with each other to form a complex with telomeric DNA. A dominant negative TRF2, TRF2 (DeltaBDeltaM), bound to POT1 and prevented it from binding to telomeres. POT1 overexpression protected against TRF2(DeltaBDeltaM) -induced loss of telomeric single-stranded overhangs, chromosomal instability, and senescence. These results demonstrate that POTI and TRF2 share in part in the same pathway for telomere capping and suggest that POT1 binds to the telomeric single-stranded DNA in the D-loop and cooperates with TRF2 in t-loop maintenance. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Rm 3068,37 Convent Dr, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov NR 60 TC 111 Z9 124 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 FEB PY 2005 VL 25 IS 3 BP 1070 EP 1080 DI 10.1128/MCB.25.3.1070-1080.2005 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 892LU UT WOS:000226652900018 PM 15657433 ER PT J AU Salerno, M Palmieri, D Bouadis, A Halverson, D Steeg, PS AF Salerno, M Palmieri, D Bouadis, A Halverson, D Steeg, PS TI Nm23-H1 metastasis suppressor expression level influences the binding properties, stability, and function of the kinase suppressor of Ras1 (KSR1) Erk scaffold in breast carcinoma cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEOSIDE-DIPHOSPHATE KINASE; ACTIVATED PROTEIN-KINASE; CANCER-CELLS; SIGNAL-TRANSDUCTION; IN-VITRO; MELANOMA-CELLS; ADENOCARCINOMA CELLS; ENZYMATIC-ACTIVITY; GENE-EXPRESSION; ALPHA-ISOFORM AB Metastatic disease is a significant contributor to cancer patient mortality. We previously reported that the Kinase Suppressor of Ras1 (KSR1) scaffold protein for the Erk mitogen-activated protein kinase pathway coimmunoprecipitated the metastasis suppressor protein Nm23-H1. We now hypothesize that altered expression levels of Nm23-H1 influence the binding properties, stability, and function of the KSR1 scaffold. Increased coimmunoprecipitation of Hsp90 with KSR1 was observed in either stable or transient transfectants of nm23-H1 in MDA-MB-435 human breast carcinoma cells. Similar trends were also observed in the cytoplasmic and nuclear fractions of cells. Cells expressing high levels of Nm23-H1 exhibited increased KSR1 degradation in the presence of either cycloheximide or an Hsp90-directed drug currently in clinical trial, 17-allylamino-17-demethoxygeldanamycin (17-AAG). In agreement with KSR1 degradation data, high-Nm23-H1-expression cells were preferentially inhibited in anchorage-independent colonization assays by 17-AAG. KSR1 scaffold binding patterns are dynamic in both the cytoplasmic and nuclear compartments, modulated by metastasis suppressor expression. Metastasis suppressor expression levels can impact traditional signaling pathways, such as the Erk pathway, resulting in altered tumor cell sensitivity to cancer therapeutics. C1 NCI, Womens Canc Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Salerno, M (reprint author), NCI, Womens Canc Sect, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. EM maxsal@mail.nih.gov RI Palmieri, Diane/B-4258-2015 NR 82 TC 54 Z9 59 U1 1 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 FEB PY 2005 VL 25 IS 4 BP 1379 EP 1388 DI 10.1128/MCB.25.4.1379-1388.2005 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 896AW UT WOS:000226908000014 PM 15684389 ER PT J AU Garrett, FE Emelyanov, AV Sepulveda, MA Flanagan, P Volpi, S Li, FB Loukinov, D Eckhardt, LA Lobanenkov, VV Birshtein, BK AF Garrett, FE Emelyanov, AV Sepulveda, MA Flanagan, P Volpi, S Li, FB Loukinov, D Eckhardt, LA Lobanenkov, VV Birshtein, BK TI Chromatin architecture near a potential 3 ' end of the Igh locus involves modular regulation of histone modifications during B-Cell development and in vivo occupancy at CTCF sites SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENHANCER-BLOCKING ACTIVITY; BETA-GLOBIN LOCUS; VIRTUALLY IDENTICAL ENHANCERS; IMPRINTING CONTROL REGION; HEAVY-CHAIN ENHANCER; C-MYC EXPRESSION; NF-KAPPA-B; GENE SEGMENTS; PROTEIN CTCF; TRANSCRIPTIONAL ACTIVATION AB The murine Igh locus has a 3' regulatory region (3' RR) containing four enhancers (hs3A, hs1,2, hs3B, and hs4) at DNase I-hypersensitive sites. The 3' RR exerts long-range effects on class switch recombination (CSR) to several isotypes through its control of germ line transcription. By measuring levels of acetylated histones H3 and H4 and of dimethylated H3 (K4) with chromatin immunoprecipitation assays, we found that early in B-cell development, chromatin encompassing the enhancers of the 3' RR began to attain stepwise modifications typical of an open conformation. The hs4 enhancer was associated with active chromatin initially in pro- and pre-B cells and then together with hs3A, hs1,2, and hs3B in B and plasma cells. Historic modifications were similar in resting splenic B cells and in splenic B cells induced by lipopolysaccharide to undergo CSR. From the pro-B-cell stage onward, the similar to11-kb region immediately downstream of hs4 displayed H3 and H4 modifications indicative of open chromatin. This region contained newly identified DNase I-hypersensitive sites and several CTCF target sites, some of which were occupied in vivo in a developmentally regulated manner. The open chromatin environment of the extended 3' RR in mature B cells was flanked by regions associated with dimethylated K9 of histone H3. Together, these data suggest that 3' RR elements are located within a specific chromatin subdomain that contains CTCF binding sites and developmentally regulated modules. C1 Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. CUNY Hunter Coll, Dept Biol Sci, New York, NY 10021 USA. CUNY, Grad Sch, New York, NY USA. NIAID, Mol Pathol Sect, Immunopathol Lab, NIH, Rockville, MD USA. RP Birshtein, BK (reprint author), Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. EM birshtei@aecom.yu.edu RI Li, Fubin/H-1285-2012 FU NCI NIH HHS [5 F31 CA76942, F31 CA076942, P30 CA013330, P30CA13330, T32 CA009173, T32 CA09173]; NIAID NIH HHS [R01 AI030653-16, AI13509, AI30653, R01 AI013509, R01 AI030653, R37 AI013509] NR 87 TC 78 Z9 79 U1 0 U2 4 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 FEB PY 2005 VL 25 IS 4 BP 1511 EP 1525 DI 10.1128/MCB.25.4.1511-1525.2005 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 896AW UT WOS:000226908000025 PM 15684400 ER PT J AU Chung, S Hedlund, E Hwang, M Kim, DW Shin, BS Hwang, DY Kang, UJ Isacson, O Kim, KS AF Chung, S Hedlund, E Hwang, M Kim, DW Shin, BS Hwang, DY Kang, UJ Isacson, O Kim, KS TI The homeodomain transcription factor Pitx3 facilitates differentiation of mouse embryonic stem cells into AHD2-expressing dopaminergic neurons SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; VENTRAL MESENCEPHALON; RAT MODEL; NURR1; GENE; EXPRESSION; MIDBRAIN; SURVIVAL; FETAL AB The A9 dopaminergic (DA) neuronal group projecting to the dorsal striatum is the most vulnerable in Parkinson's disease (PD). We genetically engineered mouse embryonic stem (ES) cells to express the transcription factors Nurr1 or Pitx3. After in vitro differentiation of Pitx3-expressing ES cells, the proportion of DA neurons expressing aldehyde dehydrogenase 2 (AHD2) increased, while the total number of DA neurons remained the same. The highest levels of AHD2 expression were observed in mouse A9 DA neurons projecting to the dorsal striatum. Furthermore, real-time PCR analyses of in vitro differentiated Pitx3-expressing ES cells revealed that genes highly expressed in A9 DA neurons were up-regulated. When transplanted into the mouse striatum, PRA-expressing cells generated an increased proportion of AHD2-expressing DA neurons. Contrastingly, in Nurr1-expressing ES cells, increases of all midbrain DA markers were observed, resulting in a higher total number of DA neurons in vitro and in vivo, whereas the proportion of AHD2-expressing DA neurons was not changed. Our data, using gain-of-function analysis of ES cells, suggest that Pitx3 may be important for specification and/or maintenance of A9-like neuronal properties, while Nurr1 influences overall midbrain DA specification. These findings may be important for modifying ES cells to generate an optimal cell source for transplantation therapy of PD. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, McLean Hosp, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02178 USA. Harvard Univ, Sch Med, McLean Hosp, Mol Neurobiol Labs, Belmont, MA 02178 USA. Harvard Univ, Sch Med, McLean Hosp, Neuroregenerat Labs, Belmont, MA 02178 USA. Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. RP Isacson, O (reprint author), Harvard Univ, Sch Med, McLean Hosp, Udall Parkinsons Dis Res Ctr Excellence, MRC 216,115 Mill St, Belmont, MA 02178 USA. EM isacson@hms.harvard.edu; kskim@mclean.harvard.edu OI Hedlund, Eva/0000-0001-6347-0075 FU NIMH NIH HHS [MH48866]; NINDS NIH HHS [NS044439, P50NS39793, P50 NS039793-06A1, NS32080] NR 42 TC 99 Z9 101 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD FEB PY 2005 VL 28 IS 2 BP 241 EP 252 DI 10.1016/j.mcn.2004.09.008 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 895OW UT WOS:000226873800004 PM 15691706 ER PT J AU Xu, XH Meier-Schellersheim, M Jiao, XM Nelson, LE Jin, T AF Xu, XH Meier-Schellersheim, M Jiao, XM Nelson, LE Jin, T TI Quantitative imaging of single live cells reveals spatiotemporal dynamics of multistep signaling events of chemoattractant gradient sensing in Dictyostelium SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; NUCLEOTIDE EXCHANGE FACTOR; G-PROTEIN; LIVING CELLS; NEUTROPHIL CHEMOTAXIS; LEUKOCYTE CHEMOTAXIS; MEDIATED ACTIVATION; ADENYLYL-CYCLASE; EUKARYOTIC CELLS; LEADING-EDGE AB Activation of G-protein-coupled chemoattractant receptors triggers dissociation of Galpha and Gbetagamma subunits. These subunits induce intracellular responses that can be highly polarized when a cell experiences a gradient of chemoattractant. Exactly how a cell achieves this amplified signal polarization is still not well understood. Here, we quantitatively measure temporal and spatial changes of receptor occupancy, G-protein activation by FRET imaging, and PIP, levels by monitoring the dynamics of PHCrac-GFP translocation in single living cells in response to different chemoattractant fields. Our results provided the first direct evidence that G-proteins are activated to different extents on the cell surface in response to asymmetrical stimulations. A stronger, uniformly applied stimulation triggers not only a stronger G-protein activation but also a faster adaptation of downstream responses. When naive cells (which have not experienced chemoattractant) were abruptly exposed to stable cAMP gradients, G-proteins were persistently activated throughout the entire cell surface, whereas the response of PHCrac-GFP translocation surprisingly consisted of two phases, an initial transient and asymmetrical translocation around the cell membrane, followed by a second phase producing a highly polarized distribution of PHCrac-GFP. We propose a revised model of gradient sensing, suggesting an important role for locally controlled components that inhibit PI3Kinase activity. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NIAID, Immunol Labs, NIH, Rockville, MD 20852 USA. RP Jin, T (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM tjin@niaid.nih.gov NR 63 TC 87 Z9 88 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 FEB PY 2005 VL 16 IS 2 BP 676 EP 688 DI 10.1091/mbc.E04-07-0544 PG 13 WC Cell Biology SC Cell Biology GA 891EH UT WOS:000226563600020 PM 15563608 ER PT J AU Bova, GS Eltoum, IA Kiernan, JA Siegal, GP Frost, AR Best, CJM Gillespie, JW Su, GH Emmert-Buck, MR AF Bova, GS Eltoum, IA Kiernan, JA Siegal, GP Frost, AR Best, CJM Gillespie, JW Su, GH Emmert-Buck, MR TI Optimal molecular profiling of tissue and tissue components - Defining the best processing and microdissection methods for biomedical applications SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE tissue processing; tissue fixation; tissue staining; molecular profiling; microdissection; laser capture microdissection; proteomics; DNA analysis; RNA analysis; cytology; phenotype-genotype correlation ID LASER-CAPTURE MICRODISSECTION; GENE-EXPRESSION; PROTEOMIC ANALYSIS; ARCHIVAL TISSUE; ASSISTED MICRODISSECTION; ARRAY HYBRIDIZATION; GENOMIC DNA; SECTIONS; RNA; CELLS AB Isolation of well-preserved pure cell populations is a prerequisite for sound studies of the molecular basis of any tissue-based biological phenomenon. This article reviews current methods for obtaining anatomically specific signals from molecules isolated from tissues, a basic requirement for productive linking of phenotype and genotype. The quality of samples isolated from tissue and used for molecular analysis is often glossed over or omitted from publications, making interpretation and replication of data difficult or impossible. Fortunately, recently developed techniques allow life scientists to better document and control the quality of samples used for a given assay, creating a foundation for improvement in this area. Tissue processing for molecular studies usually involves some or all of the following steps: tissue collection, gross dissection/identification, fixation, processing/embedding, storage/archiving, sectioning, staining, microdissection/annotation, and pure analyte labeling/identification and quantification. We provide a detailed comparison of some current tissue microdissection technologies, and provide detailed example protocols for tissue component handling upstream and downstream from microdissection. We also discuss some of the physical and chemical issues related to optimal tissue processing, and include methods specific to cytology specimens. We encourage each laboratory to use these as a starting point for optimization of their overall process of moving from collected tissue to high quality, appropriately anatomically tagged scientific results. In optimized protocols is a source of inefficiency in current life science research. Improvement in this area will significantly increase life science quality and productivity. The article is divided into introduction, materials, protocols, and notes sections. Because many protocols are covered in each of these sections, information relating to a single protocol is not contiguous. To get the greatest benefit from this article, readers are advised to read through the entire article first, identify protocols appropriate to their laboratory for each step in their workflow, and then reread entries in each section pertaining to each of these single protocols. C1 Johns Hopkins Univ Hosp, PELICAN Lab, Dept Pathol, Baltimore, MD 21287 USA. Johns Hopkins Univ Hosp, PELICAN Lab, Dept Oncol, Baltimore, MD 21287 USA. Johns Hopkins Univ Hosp, PELICAN Lab, Inst Med Genet, Baltimore, MD 21287 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama, UAB Comprehens Canc Ctr, Birmingham, AL 35294 USA. Univ Western Ontario, Dept Anat & Cell Biol, London, ON, Canada. NCI, Pathogenet Unit, NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Bethesda, MD 20892 USA. Columbia Univ, Coll Phys & Surg, Dept Otolaryngol, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. RP Bova, GS (reprint author), Johns Hopkins Univ Hosp, PELICAN Lab, Dept Pathol, Carnegie 628, Baltimore, MD 21287 USA. EM gbov@jhmi.edu OI Kiernan, John/0000-0002-3324-1092 NR 46 TC 13 Z9 14 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD FEB PY 2005 VL 29 IS 2 BP 119 EP 152 DI 10.1385/MB:29:2:119 PG 34 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 905UK UT WOS:000227595700004 PM 15699569 ER PT J AU Hu, J Colburn, NH AF Hu, J Colburn, NH TI Histone deacetylase inhibition down-regulates cyclin D1 transcription by inhibiting nuclear factor-kappa B/p65 DNA binding SO MOLECULAR CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; NF-KAPPA-B2 P100; CANCER-THERAPY; IKK COMPLEX; KINASE IKK; ACETYLATION; ACTIVATION; PHOSPHORYLATION; EXPRESSION; INDUCTION AB Histone deacetylase (HDAC) inhibitors are emerging as a promising new class of cancer therapeutic agents. HDAC inhibitors relieve the deacetylation of histone proteins. However, little is known about the nonhistone targets of HDAC inhibitors and their roles in gene regulation. In this study, we addressed the molecular basis of the down-regulation of the nuclear factor-kappaB (NF-kappaB)-responsive gene cyclin D1 by the HDAC inhibitor trichostatin A in mouse JB6 cells. Cyclin D1 plays a critical role in cell proliferation and tumor progression. Trichostatin A inhibits cyclin D1 expression in a NF-kappaB-dependent manner in JB6 cells. Electrophoretic mobility shift assay studies showed that trichostatin A treatment prevents p65 dimer binding to NF-kappaB sites on DNA. Moreover, a chromatin immunoprecipitation assay shows that trichostatin A treatment inhibits endogenous cyclin Ell gene transcription by preventing p65 binding to the cyclin D1 promoter. However, acetylation of p65 is not affected by trichostatin A treatment. Instead, trichostatin A enhances p52 acetylation and increases p52 protein level by enhancing p100 processing. This is the first report that trichostatin A, a HDAC inhibitor, activates p100 processing and relieves the repression of p52 acetylation. The enhanced acetylation of p52 in the nuclei may operate to cause nuclear retention of p65 by increasing the p52/p65 interaction and preventing IkappaBalpha-p65 binding. The enhanced p52 acetylation coincides with decreased p65 DNA binding, suggesting a potential role of p52 acetylation in NF-kappaB regulation. Together, the results provide the first demonstration that HDAC inhibitor trichostatin A inhibits cyclin D1 gene transcription through targeting transcription factor NFkappaB/p65 DNA binding. NF-kappaB is therefore identified as a transcription factor target of trichostatin A treatment. C1 NCI, Gene Regulat Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA. RP Hu, J (reprint author), NCI, Gene Regulat Sect, Lab Canc Prevent, Ctr Canc Res, Bldg 567,Room 188, Frederick, MD 21702 USA. EM huji@ncifcrf.gov RI Hu, Jing/M-3130-2014 NR 52 TC 72 Z9 74 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD FEB PY 2005 VL 3 IS 2 BP 100 EP 109 DI 10.1158/1541-7786.MCR-04-0070 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 899LB UT WOS:000227144800005 PM 15755876 ER PT J AU Caron, RW Yacoub, A Li, M Zhu, XY Mitchell, C Hong, Y Hawkins, W Sasazuki, T Shirasawa, S Kozikowski, AP Dennis, PA Hagan, MP Grant, S Dent, P AF Caron, RW Yacoub, A Li, M Zhu, XY Mitchell, C Hong, Y Hawkins, W Sasazuki, T Shirasawa, S Kozikowski, AP Dennis, PA Hagan, MP Grant, S Dent, P TI Activated forms of H-RAS and K-RAS differentially regulate membrane association of PI3K, PDK-1, and AKT and the effect of therapeutic kinase inhibitors on cell survival SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID IONIZING-RADIATION CAUSES; GROWTH-FACTOR RECEPTOR; CARCINOMA-CELLS; PHOSPHOINOSITIDE 3-KINASE; PROSTATE CARCINOMA; SIGNALING PATHWAY; PROTEIN KINASE-1; RAF-1 ACTIVATION; DNA-SYNTHESIS; B ACTIVATION AB The abilities of mutated active RAS proteins to modulate cell survival following exposure to ionizing radiation and small molecule kinase inhibitors were examined. Homologous recombination in HCT116 cells to delete the single allele of K-RAS D13 resulted in a cell line that exhibited an similar to75% reduction in basal extracellular signal-regulated kinase 1/2, AKT, and c-jun-NH2-kinase 1/2 activity. Transfection of cells lacking K-RAS D13 with H-RAS V12 restored extracellular signal-regulated kinase 1/2 and AKT activity to basal levels but did not restore c-jun-NH2-kinase 1/2 phosphorylation. In cells expressing H-RAS V12, radiation caused prolonged intense activation of AKT. Inhibition of H-RAS V12 function, blockade of phosphatidylinositol 3-kinase (PI3K) function using small interfering RNA/small-molecule inhibitors, or expression of dominant-negative AKT abolished radiation-induced AKT activation, and radiosensitized these cells. Inhibition of PI3K function did not significantly radiosensitize parental HCT116 cells. Inhibitors of the AKT PH domain including perifosine, SH-(5, 23-25) and ml-(14-16) reduced the plating efficiency of H-RAS V12 cells in a dose-dependent fashion. Inhibition of AKT function using perifosine enhanced radiosensitivity in H-RAS V12 cells, whereas the SH and ml series of AKT PH domain inhibitors failed to promote radiation toxicity. In HCT116 H-RAS V12 cells, PI3K, PDK-1, and AKT were membrane associated, whereas in parental cells expressing K-RAS D13, only PDK-1 was membrane bound. In H-RAS V12 cells, membrane associated PDK-1 was phosphorylated at Y373/376, which was abolished by the Src family kinase inhibitor PP2. Inhibition of PDK-1 function using the PH domain inhibitor OSU-03012 or using PP2 reduced the plating efficiency of H-RAS V12 cells and profoundly increased radiosensitivity. OSU-03012 and PP2 did not radiosensitize and had modest inhibitory effects on plating efficiency in parental cells. A small interfering RNA generated against PDK1 also radiosensitized HCT116 cells expressing H-RAS V12. Collectively, our data argue that molecular inhibition of AKT and PDK-1 signaling enhances the radiosensitivity of HCT116 cells expressing H-RAS V12 but not K-RAS D13. Small-molecule inhibitory agents that blocked stimulated and/or basal PDK-1 and AKT function profoundly reduced HCT116 cell survival but had variable effects at enhancing tumor cell radiosensitivity. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Dept Hematol Oncol, Richmond, VA 23298 USA. Int Med Ctr Japan, Dept Pathol, Tokyo, Japan. NCI, Bethesda, MD 20892 USA. Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL USA. Consejo Nacl Invest Cient & Tecn, Inst Med & Bio Expt Cuyo, Mendoza, Argentina. RP Dent, P (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, 401 Coll St, Richmond, VA 23298 USA. EM pdent@hsc.vcu.edu FU NCI NIH HHS [P01-CA72955, R01-CA63753, R01-CA77141, R01-CA88906]; NIDDK NIH HHS [R01-DK52825] NR 43 TC 58 Z9 62 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD FEB PY 2005 VL 4 IS 2 BP 257 EP 270 PG 14 WC Oncology SC Oncology GA 898OL UT WOS:000227086000008 PM 15713897 ER PT J AU Karsan, A Pollet, I Yu, LR Chan, KC Conrads, TP Lucas, DA Andersen, R Veenstra, T AF Karsan, A Pollet, I Yu, LR Chan, KC Conrads, TP Lucas, DA Andersen, R Veenstra, T TI Quantitative proteomic analysis of sokotrasterol sulfate-stimulated primary human endothelial cells SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID ISCHEMIC-HEART-DISEASE; GROWTH-FACTOR; THERAPEUTIC ANGIOGENESIS; MASS-SPECTROMETRY; EXPRESSION; CANCER; MOLECULE; DIFFERENTIATION; VEGF; GENE AB The endothelium forms a continuous monolayer at the interface between blood and tissue and contributes significantly to the sensing and transducing of signals between blood and tissue. New blood vessel formation, or angiogenesis, is initiated by the activation of endothelial cells and is an important process required for various pathological and physiological situations. This study used cleavable isotope-coded affinity tag reagents combined with mass spectrometry to investigate the molecular basis of a recently discovered angiogenesis-promoting steroid, sokotrasterol sulfate. Changes in the relative abundances of over 1000 proteins within human endothelial cells treated with sokotrasterol sulfate and vehicle-treated cells were identified and quantitated using this technique. A method that examines the entire ensemble of quantitative measurements was developed to identify proteins that showed a statistically significant change in relative abundance resulting from treatment with sokotrasterol sulfate. A total of 93 proteins was significantly up-regulated, and 37 were down-regulated in response to sokotrasterol sulfate stimulation of endothelial cells. Among the up-regulated proteins, several were identified that are novel to endothelial cells and are likely involved in cell communication and morphogenesis. These findings are consistent with a role for sokotrasterol sulfate in endothelial sprouting. C1 British Columbia Canc Agcy, Dept Med Biophys & Pathol & Lab Med, Vancouver, BC V5Z 1L3, Canada. NCI, Lab Proteom & Anal Technol, SAIC Frederick Inc, NIH, Frederick, MD 21702 USA. Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z4, Canada. RP Karsan, A (reprint author), British Columbia Canc Res Ctr, Dept Med Biophys, Vancouver, BC V5Z 1L3, Canada. EM akarsan@bccrc.ca RI Tang, Macy/B-9798-2014; Karsan, Aly/K-2067-2015 FU NCI NIH HHS [N01 CO 12400] NR 40 TC 10 Z9 12 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD FEB PY 2005 VL 4 IS 2 BP 191 EP 204 DI 10.1074/mcp.M400152-MCP200 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 902UF UT WOS:000227381300008 PM 15611527 ER PT J AU Cho, SY Kagan, BL Blackford, JA Szapary, D Simons, SS AF Cho, SY Kagan, BL Blackford, JA Szapary, D Simons, SS TI Glucocorticoid receptor ligand binding domain is sufficient for the modulation of glucocorticoid induction properties by homologous receptors, coactivator transcription intermediary factor 2, and Ubc9 SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HUMAN ESTROGEN-RECEPTOR; TYROSINE AMINOTRANSFERASE GENE; UBIQUITIN-CONJUGATING ENZYME; HUMAN PROGESTERONE-RECEPTOR; CARBOXYL-TERMINAL REGIONS; PARTIAL AGONIST ACTIVITY; ACTIVATION FUNCTION 2; ANDROGEN RECEPTOR; NUCLEAR RECEPTOR; TRANSACTIVATION DOMAIN AB Several factors modulate the position of the dose-response curve of steroid receptor-agonist complexes and the partial agonist activity of antagonist complexes, thereby causing differential gene activation by circulating hormones and unequal gene repression during endocrine therapies with antisteroids. We now ask whether the modulatory activity of three factors (homologous receptor, coactivator transcription intermediary factor 2, and Ubc9) requires the same or different domains of glucocorticoid receptors (GRs). In all cases, we find that neither the amino terminal half of the receptor, which contains the activation function-1 activation domain, nor the DNA binding domain is required. This contrasts with the major role of activation function-1 in determining the amount of gene expression and partial agonist activity of antisteroids with most steroid receptors. However, the situation is more complicated with Ubc9, where GR N-terminal sequences prevent the actions of Ubc9, but not added GR or transcription intermediary factor 2, at low GR concentrations. Inhibition is relieved by deletion of these sequences or by replacement with the comparable region of progesterone receptors but not by overexpression of the repressive sequences. These results plus the binding of C-terminal GR sequences to the suppressive N-terminal domain implicate an intramolecular mechanism for the inhibition of Ubc9 actions at low GR concentrations. A shift from noncooperative to cooperative steroid binding at high GR concentrations suggests that conformational changes reposition the inhibitory N-terminal sequence to allow Ubc9 interaction with elements of the ligand binding domain. Collectively, these results indicate a dominant role of GR C-terminal sequences in the modulation of the dose-response curve and partial agonist activity of GR complexes. They also reveal mechanistic differences both among individual modulators and between the ability of the same factors to regulate the total amount of gene expression. C1 NIDDKD, LMCB, Steroid Hormones Sect, NIH, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDKD, LMCB, Steroid Hormones Sect, NIH, Bldg 8,Room B2A-07, Bethesda, MD 20892 USA. EM steroids@helix.nih.gov NR 84 TC 40 Z9 40 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 2005 VL 19 IS 2 BP 290 EP 311 DI 10.1210/me.2004-0134 PG 22 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 890WZ UT WOS:000226543200002 PM 15539428 ER PT J AU El-Gharbawy, AH AF El-Gharbawy, AH TI Hyperinsulinism/Hyperammonemia Syndrome: A synopsis SO MOLECULAR GENETICS AND METABOLISM LA English DT Editorial Material ID GLUTAMATE-DEHYDROGENASE GENE; HYPERAMMONEMIA-SYNDROME; REGULATORY MUTATIONS; CHILDREN C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP El-Gharbawy, AH (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 12 TC 4 Z9 4 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2005 VL 84 IS 2 BP 101 EP 103 DI 10.1016/j.ymgme.2004.12.013 PG 3 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 901RP UT WOS:000227299900001 PM 15773041 ER PT J AU Correa-Cerro, LS Porter, FD AF Correa-Cerro, LS Porter, FD TI 3 beta-hydroxysterol Delta(7)-reductase and the Smith-Lemli-Opitz syndrome SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE Smith-Lemi-Opitz syndrome; 7-dehydrocholesterol reductase; inborn error of cholesterol synthesis ID 7-DEHYDROCHOLESTEROL REDUCTASE GENE; PERIODIC FEVER SYNDROME; STEROL-SENSING DOMAIN; LAMIN-B RECEPTOR; ANTLEY-BIXLER-SYNDROME; DEFECTIVE CHOLESTEROL-BIOSYNTHESIS; HUMAN DELTA-7-STEROL REDUCTASE; CLEAVAGE-ACTIVATING PROTEIN; HMG COA REDUCTASE; HYPERIMMUNOGLOBULINEMIA-D AB In the final step of cholesterol synthesis, 7-dehydrocholesterol reductase (DHCR7) reduces the double bond at C7-8 of 7-dehydrocholesterol to yield cholesterol. Mutations of DHCR7 cause Smith-Lemli-Opitz syndrome (SLOS). Over 100 different mutations of DHCR7 have been identified in SLOS patients. SLOS is a classical multiple malformation, mental retardation syndrome, and was the first human malformation syndrome shown to result from an inborn error of cholesterol synthesis. This paper reviews the biochemical, molecular, and mutational aspects of DHCR7. Published by Elsevier Inc. C1 NICHHD, Unit Mol Dysmorphol, Heritable Disorders Branch, Dept HHS,NIH, Bethesda, MD 20892 USA. RP Porter, FD (reprint author), NICHHD, Unit Mol Dysmorphol, Heritable Disorders Branch, Dept HHS,NIH, Bld 10,Rm 9S241,10 Ctr Dr, Bethesda, MD 20892 USA. EM fdporter@helix.nih.gov NR 131 TC 58 Z9 58 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2005 VL 84 IS 2 BP 112 EP 126 DI 10.1016/j.ymgme.2004.09.017 PG 15 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 901RP UT WOS:000227299900003 PM 15670717 ER PT J AU Ortaldo, JR Young, HA AF Ortaldo, JR Young, HA TI Mouse Ly49 NK receptors: balancing activation and inhibition SO MOLECULAR IMMUNOLOGY LA English DT Article; Proceedings Paper CT 20th International Natural Killer Cell Workshop CY APR 24-28, 2004 CL Noordwijkerhout, NETHERLANDS DE NK cells; synergy; Ly49; inhibition ID NATURAL-KILLER-CELLS; TYROSINE PHOSPHATASE; IFN-GAMMA; T-CELLS; LY-49D; MHC; EXPRESSION; IL-12; PHOSPHORYLATION; CYTOTOXICITY AB Previous studies from numerous laboratories have demonstrated that inhibitory class I binding NK receptors dominate functional interactions in vitro. Our previous studies have shown that in addition to lysis, a major consequence of triggering the murine activating NK receptor Ly49D is the expression of cytokines and chemokines. We have recently shown that the activating Ly49D murine NK cell receptor can potently synergize during co-stimulation with IL- 12 and IL- 18 for selective production of IFN-gamma. Activation both in vitro and in vivo and synergistic production of IFN-gamma by Ly49D expressing NK cells results from cytokine stimulation combined with co-receptor ligation. In addition, EL- 12 is capable of overriding the inhibitory receptor blockade for cytokine production, both in vitro and in vivo. Our current studies will expand this finding of IL- 12 synergy to other receptors in the NK repertoire and evaluate potential biochemical mechanisms involved in this synergy. These findings place NK cells and their activating Ly49 receptors as important initiators of microbial, antiviral and anti-tumor immunity and provide a mechanism for the release of activating Ly49 receptors from an inhibitory receptor blockade. Discussion of how activation of the innate immune system provides important initiators of adaptive immune responses by receptor cross-linking and cytokine co-receptor engagement will ensue. Published by Elsevier Ltd. C1 NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21702 USA. RP Ortaldo, JR (reprint author), NCI, Expt Immunol Lab, Canc Res Ctr, 560-31-90, Frederick, MD 21702 USA. EM ortaldo@ncifcrf.gov NR 28 TC 26 Z9 31 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD FEB PY 2005 VL 42 IS 4 BP 445 EP 450 DI 10.1016/j.molimm.2004.07.024 PG 6 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 899KB UT WOS:000227142200009 PM 15607796 ER PT J AU Borrego, F Masilamani, M Kabat, J Sanni, TB Coligan, JE AF Borrego, F Masilamani, M Kabat, J Sanni, TB Coligan, JE TI The cell biology of the human natural killer cell CD94/NKG2A inhibitory receptor SO MOLECULAR IMMUNOLOGY LA English DT Article; Proceedings Paper CT 20th International Natural Killer Cell Workshop CY APR 24-28, 2004 CL Noordwijkerhout, NETHERLANDS DE CD94/NKG2A; HLA-E; NK synapse; lipid raft; endocytosis; trafficking ID ACTIVATING RECEPTORS; LIGAND-BINDING; IMMUNE SYNAPSE; LIPID RAFTS; NK CELLS; POLARIZATION; CYTOSKELETON; SIGNAL; NKG2A; SELF AB To avoid destruction of normal bystander cells, natural killer (NK) cells must provide a continuous supply of functional inhibitory receptors to their cell surface. After interaction with its ligand HLA-E, which is expressed on normal cells, the C-type lectin inhibitory receptor CD94/NKG2A suppresses activation signaling processes. CD94/NKG2A receptors continuously recycle from the cell surface through endosomal compartments and back again in a process that requires energy and the cytoskeleton. This steady state process appears to be largely unaffected by exposure to ligand. CD94/NKG2A receptors move freely within the plasma membrane and accumulate at the site of contact with the ligand bearing target cells (or monoclonal antibodies (mAb) coated beads). As expected, ligated CD94/NKG2A receptors are less mobile than the nonligated receptors, and the lipid raft marker cholera toxin B is excluded from the CD94/NKG2A enriched target cell contact sites. Also, methylcyclodextrin does not interfere with CD94/NKG2A accumulation at these contact sites. The constant renewal of CD94/NKG2A receptors at the cell surface and their free mobility within the plasma membrane likely facilitates and insures inhibitory capacity. Published by Elsevier Ltd. C1 NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. RP Borrego, F (reprint author), NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Twinbrook 2,Room 205,12441 Parklawn Dr, Rockville, MD 20852 USA. EM Fborrego@niaid.nih.gov OI Masilamani, Madhan/0000-0001-8181-8848 NR 26 TC 36 Z9 38 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD FEB PY 2005 VL 42 IS 4 BP 485 EP 488 DI 10.1016/j.molimm.2004.07.031 PG 4 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 899KB UT WOS:000227142200016 PM 15607803 ER PT J AU Lee, H Chang, YC Kwon-Chung, KJ AF Lee, H Chang, YC Kwon-Chung, KJ TI TUP1 disruption reveals biological differences between MATa and MAT alpha strains of Cryptococcus neoformans SO MOLECULAR MICROBIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CANDIDA-ALBICANS; NEUROSPORA-CRASSA; SEX-CHROMOSOMES; PHEROMONE GENE; LOCUS; VIRULENCE; EXPRESSION; YEAST; REPRESSOR AB Cryptococcus neoformans exists in two mating types MATa and MATalpha. Although the morphology, growth characteristics and genetic segregation patterns among MATa and MATalpha strains are indistinguishable in the laboratory, the predominance of MATalpha strains in nature suggests that MATalpha strains are better suited for survival in nature. We disrupted the TUP1 gene, a global repressor, to find the possible biological differences in congenic MATalpha and MATa cells of C. neoformans. Disruption of TUP1 affected neither the yeast nor the hyphal cell morphology but resulted in a similar reduction of mating frequencies in both MATalpha and MATa cells. Disruption of TUP1, however, functionally manifested itself in several mating type-dependent phenotypes: (i) MATalpha cells became more sensitive to 0.8 M KCl while MATa cells showed no change in sensitivity, (ii) a temperature-dependent growth reduction was exhibited at both 30degreesC and 25degreesC in MATa but a similar growth reduction was not observed in MATalpha cells until the temperature was lowered to 25degreesC and (iii) the transcriptional level of genes in several different biological pathways was markedly altered in a mating type-dependent manner. This work is the first case in which non-mating-related biological differences are observed between two congenic mating partners in yeast. C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM June_Kwon-Chung@nih.gov NR 49 TC 17 Z9 17 U1 1 U2 1 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 FEB PY 2005 VL 55 IS 4 BP 1222 EP 1232 DI 10.1111/j.1365-2958.2004.04458.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 893GQ UT WOS:000226707700021 PM 15686566 ER PT J AU Baek, SJ Kim, JS Moore, SM Lee, SH Martinez, J Eling, TE AF Baek, SJ Kim, JS Moore, SM Lee, SH Martinez, J Eling, TE TI Cyclooxygenase inhibitors induce the expression of the tumor suppressor gene EGR-1, which results in the up-regulation of NAG-1, an antitumorigenic protein SO MOLECULAR PHARMACOLOGY LA English DT Article ID DRUG-ACTIVATED GENE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BETA SUPERFAMILY MEMBER; COLON-CANCER CELLS; GROWTH-FACTOR-BETA; COLORECTAL-CANCER; MORPHOGENETIC PROTEIN; PROSTATE-CANCER; CARCINOMA CELLS; DNA-DAMAGE AB Nonsteroidal anti-inflammatory drugs ( NSAIDs) have been shown to have chemopreventive activity, but the mechanisms involved are not clearly understood. Although NSAIDs inhibit cyclooxygenase activity, they also increase the expression of a divergent member of the transforming growth factor-beta superfamily, termed NSAID-activated gene 1 (NAG-1), a protein with an antitumorigenic and proapoptotic activity that could in part be linked to the chemoprevention activity of NSAIDs. NAG-1 is induced by some NSAIDs, but the mechanisms responsible are not clear. In this report, we have identified a cis-acting element responsive to NSAIDs located within the -73 to -51 region of the NAG-1 promoter. This region contains overlapping EGR-1 and Sp1 binding sites, and mutations in this region suggest that the transcription factors have an important role in NSAID-induced NAG-1 expression. EGR-1 was found to play a critical role in the induction of NAG-1 by sulindac sulfide and other NSAIDs. NSAIDs increase EGR-1 protein expression that occurs before the induction of NAG-1 expression, supporting the hypothesis that EGR-1 is necessary for NSAID-induced NAG-1 expression. Thus, NSAIDs induce the expression of EGR-1, a tumor suppressor gene, providing a novel mechanism to explain, in part, the antitumorigenic properties of some NSAIDs. NAG-1 seems to be an important downstream target protein of this transcription factor, EGR-1, and may mediate the chemopreventive activity of some NSAIDs. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Computat Biol & Risk Anal, NIH, Res Triangle Pk, NC 27709 USA. Univ Tennessee, Coll Vet Med, Dept Pathobiol, Lab Environm Carcinogenesis, Knoxville, TN 37901 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Eling@niehs.nih.gov OI Baek, Seung/0000-0001-7866-7778 FU NIEHS NIH HHS [K22-ES011657] NR 48 TC 108 Z9 116 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 2005 VL 67 IS 2 BP 356 EP 364 DI 10.1124/mol.104.005108 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 888ZK UT WOS:000226412900002 PM 15509713 ER PT J AU Antony, S Kohlhagen, G Agama, K Jayaraman, M Cao, SS Durrani, FA Rustum, YM Cushman, M Pommier, Y AF Antony, S Kohlhagen, G Agama, K Jayaraman, M Cao, SS Durrani, FA Rustum, YM Cushman, M Pommier, Y TI Cellular topoisomerase I inhibition and antiproliferative activity by MJ-III-65 (NSC 706744), an indenoisoquinoline topoisomerase I poison SO MOLECULAR PHARMACOLOGY LA English DT Article ID DNA STRAND BREAKS; CAMPTOTHECIN DERIVATIVES; BIOLOGICAL EVALUATION; CLEAVAGE COMPLEXES; MAMMALIAN-CELLS; FILTER ELUTION; RESISTANT; VITRO; HOMOCAMPTOTHECIN; VIVO AB To overcome camptothecin's (CPT) lactone instability, reversibility of the drug-target interaction, and drug resistance, attempts to synthesize compounds that are CPT-like in their specificity and potency yet display a unique profile have been underway. In this pursuit, we have identified one of the idenoisoquinoline derivatives, MJ-III-65 (NSC 706744; 6-[3-(2-hydroxyethyl)amino-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline) with both similarities and differences from CPT. MJ-III- 65 traps topoisomerase I (Top1) reversibly like CPT but with different DNA sequence preferences. Consistent with Top1 poisoning, protein-linked DNA breaks were detected in cells treated with MJ-III-65 at nanomolar concentrations. These MJ-III-65-induced protein-linked DNA breaks were resistant to reversal after an hour of drug removal, compared with CPT, which completely reversed. Studies in human cells in culture found MJ-III-65 to be cytotoxic. Furthermore, limited cross-resistance was observed in camptothecin-resistant cell lines. MJ-III-65 also exhibits antitumor activity in mouse tumor xenografts. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Roswell Pk Canc Inst, Grace Canc Drug Ctr, Buffalo, NY 14263 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov FU NCI NIH HHS [U01-CA89566]; OHS HRSA HHS [ST32-CA09634] NR 36 TC 54 Z9 54 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 2005 VL 67 IS 2 BP 523 EP 530 DI 10.1124/mol.104.003889 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 888ZK UT WOS:000226412900020 PM 15531731 ER PT J AU Trebak, M Hempel, N Wedel, BJ Smyth, JT Bird, GS Putney, JW AF Trebak, M Hempel, N Wedel, BJ Smyth, JT Bird, GS Putney, JW TI Negative regulation of TRPC3 channels by protein kinase C-mediated phosphorylation of serine 712 SO MOLECULAR PHARMACOLOGY LA English DT Article ID TRANSIENT RECEPTOR; CALCIUM-ENTRY; PLASMA-MEMBRANE; FUNCTIONAL-CHARACTERIZATION; INOSITOL TRISPHOSPHATE; COUPLED RECEPTOR; CATION CHANNELS; CA2+ ENTRY; ACTIVATION; EXPRESSION AB TRPC3 is a nonselective cation channel member of the "canonical" transient receptor potential ( TRPC) family whose members are activated by phospholipase C-coupled receptors. TRPC3 can be activated by the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol (OAG) in a protein kinase C-independent manner. On the other hand, phorbol 12-myristate 13-acetate (PMA) inhibits OAG-mediated TRPC3 channel activation, suggesting that phosphorylation of TRPC3 by protein kinase C is a mechanism of receptor-mediated negative feedback. Here, we show PMA-induced phosphorylation of TRPC3 channels in vivo. We demonstrate by site-directed mutagenesis that a single site containing Ser(712) and conserved among all members of the TRPC family is essential for protein kinase C-mediated negative regulation of TRPC3. In human embryonic kidney 293 cells expressing a TRPC3 mutant in which Ser(712) was replaced by alanine (S712A), PMA failed to block channel activation, whereas wild-type TRPC3 activity was completely inhibited. Phosphorylation of the S712A TRPC3 mutant was not stimulated in response to PMA treatment. Furthermore, S712A TRPC3 mutant-mediated Ca2+ entry after methacholine activation was significantly greater than that of wild-type TRPC3. These findings demonstrate a dual role for phospholipase C-generated diacylglycerol, which serves as a signal for TRPC3 activation as well as a signal for negative feedback via protein kinase C-mediated phosphorylation. C1 NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Reprod & Dev Toxicol Lab, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Trebak, M (reprint author), NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM trebak@niehs.nih.gov RI Trebak, Mohamed/E-7405-2014; Hempel, Nadine/F-1700-2014 OI Hempel, Nadine/0000-0002-5574-8783 NR 34 TC 87 Z9 94 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 2005 VL 67 IS 2 BP 558 EP 563 DI 10.1124/mol.104.007252 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 888ZK UT WOS:000226412900024 PM 15533987 ER PT J AU Shibasaki, H Hallett, M AF Shibasaki, H Hallett, M TI Electrophysiological studies of myoclonus SO MUSCLE & NERVE LA English DT Article DE electrophysiology; jerk-locked back averaging; magnetoencephalography; myoclonus; transcranial magnetic stimulation ID CORTICAL REFLEX MYOCLONUS; SOMATOSENSORY-EVOKED-POTENTIALS; EPILEPSIA PARTIALIS CONTINUA; TRANSCRANIAL MAGNETIC STIMULATION; CORTICOBASAL DEGENERATION; NEGATIVE MYOCLONUS; SCALP TOPOGRAPHY; PROPRIOSPINAL MYOCLONUS; PHYSIOLOGICAL FEATURES; CO2-LASER STIMULATION AB As myoclonus is often associated with abnormally increased excitability of cortical structures, electrophysiological studies provide useful information for its diagnosis and classification, and about its generator mechanisms. The electroencephalogram-electromyogram polygraph reveals the most important information about the myoclonus of interest. Jerk-locked back-averaging and evoked potential studies combined with recording of the long-latency, long-loop reflexes are useful to investigate the pathophysiology of myoclonus further, especially that of cortical myoclonus. Recent advances in magnetoencephalography and transcranial magnetic stimulation have contributed significantly to the understanding of some of the cortical mechanisms underlying myoclonus. Elucidation of physiological mechanisms underlying myoclonus in individual patients is important for selecting the most appropriate treatment. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Shibasaki, H (reprint author), Amer Assoc Neuromuscular & Electodiagnost Med, 421 1st Ave SW,Suite 300 E, Rochester, MN 55902 USA. EM aanem@aanem.org NR 93 TC 87 Z9 96 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD FEB PY 2005 VL 31 IS 2 BP 157 EP 174 DI 10.1002/mus.20234 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 894OZ UT WOS:000226802800002 PM 15547927 ER PT J AU Shaukat, A Bakri, F Young, P Hahn, T Ball, D Baer, MR Wetzler, M Slack, JL Loud, P Czuczman, M McCarthy, PL Walsh, TJ Segal, BH AF Shaukat, A Bakri, F Young, P Hahn, T Ball, D Baer, MR Wetzler, M Slack, JL Loud, P Czuczman, M McCarthy, PL Walsh, TJ Segal, BH TI Invasive filamentous fungal infections in allogeneic hematopoietic stem cell transplant recipients after recovery from neutropenia: Clinical, radiologic, and pathologic characteristics SO MYCOPATHOLOGIA LA English DT Article DE Aspergillus; filamentous fungal infection; histology; transplantation ID BONE-MARROW-TRANSPLANTATION; PULMONARY ASPERGILLOSIS; RISK-FACTORS; CIRCULATING GALACTOMANNAN; MOLD INFECTIONS; AMPHOTERICIN-B; DIAGNOSIS; GRANULOCYTOPENIA; EPIDEMIOLOGY; VALIDATION AB Invasive filamentous fungal infection (IFFI) is an important cause of mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. We reviewed 22 consecutive cases of IFFI in allogeneic HSCT recipients at Roswell Park Cancer Institute. IFFI was diagnosed after neutrophil recovery in 21 patients (95%). All had received corticosteroids within 1 month prior to IFFI diagnosis. Fourteen (64%) presented with dyspnea, and only 7 (32%) were febrile. Aspergillus species were isolated in 18 (82%) cases. Thirty day mortality after IFFI diagnosis was associated with a higher mean daily dose of corticosteroids (P=0.02) and receiving OKT3 (P=0.01) within 1 month prior to IFFI diagnosis and serum creatinine >2 mg/dl at the time of diagnosis (P=0.004). Histopathologic material from biopsy or autopsy was available in 15 patients (68%). In 8 (53%), the predominant lung histopathology was an acellular coagulative necrosis and hyphal angioinvasion was observed in some of these cases. These findings have generally been observed in neutropenic patients but not in non-neutropenic HSCT recipients. The predominance of coagulative necrosis in our series may reflect the high doses of corticosteroids used to treat graft-versus-host disease (GVHD), which may have disabled leukocyte trafficking and hyphal killing. C1 New York State Dept Hlth, Roswell Pk Canc Inst, Div Infect Dis, Dept Med, Buffalo, NY 14263 USA. SUNY Buffalo, Dept Med, Sch Med & Biochem Sci, Buffalo, NY 14260 USA. New York State Dept Hlth, Roswell Pk Canc Inst, Dept Diagnost Radiol, Buffalo, NY 14263 USA. NCI, Immocompromised Host Sect, Pediat Branch, NIH, Bethesda, MD 20892 USA. RP Segal, BH (reprint author), New York State Dept Hlth, Roswell Pk Canc Inst, Div Infect Dis, Dept Med, Elm & Carolton St, Buffalo, NY 14263 USA. EM brahm.segal@roswellpark.org RI Bakri, Faris/M-7862-2016 OI Bakri, Faris/0000-0001-5447-5245 NR 21 TC 50 Z9 57 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-486X J9 MYCOPATHOLOGIA JI Mycopathologia PD FEB PY 2005 VL 159 IS 2 BP 181 EP 188 DI 10.1007/s11046-004-5495-0 PG 8 WC Mycology SC Mycology GA 907GR UT WOS:000227704600001 PM 15770441 ER PT J AU Belyantseva, IA Boger, ET Naz, S Frolenkov, GI Sellers, JR Ahmed, ZM Griffith, AJ Friedman, TB AF Belyantseva, IA Boger, ET Naz, S Frolenkov, GI Sellers, JR Ahmed, ZM Griffith, AJ Friedman, TB TI Myosin-XVa is required for tip localization of whirlin and differential elongation of hair-cell stereocilia SO NATURE CELL BIOLOGY LA English DT Article ID ACTIN-FILAMENTS; UNCONVENTIONAL MYOSIN; MOLECULAR TREADMILL; DEAFNESS DFNB3; BIRD COCHLEA; BUNDLES; MOUSE; ORGANIZATION; CYTOSKELETON; MICROVILLI AB Stereocilia are microvilli-derived mechanosensory organelles that are arranged in rows of graded heights on the apical surface of inner-ear hair cells(1). The 'staircase'-like architecture of stereocilia bundles is necessary to detect sound and head movement, and is achieved through differential elongation of the actin core of each stereocilium to a predetermined length(2,3). Abnormally short stereocilia bundles that have a diminished staircase are characteristic of the shaker 2 (Myo15a(sh2)) and whirler (Whrn(wi)) strains of deaf mice(4-6). We show that myosin-XVa is a motor protein that, in vivo, interacts with the third PDZ domain of whirlin through its carboxy-terminal PDZ-ligand. Myosin-XVa then delivers whirlin to the tips of stereocilia. Moreover, if green fluorescent protein (GFP)-Myo15a is transfected into hair cells of Myo15a(sh2) mice, the wild-type pattern of hair bundles is restored by recruitment of endogenous whirlin to the tips of stereocilia. The interaction of myosin-XVa and whirlin is therefore a key event in hair-bundle morphogenesis. C1 Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, NIH, Rockville, MD 20850 USA. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. Natl Inst Deafness & Other Commun Disorders, Sect Gene Struct & Funct, NIH, Rockville, MD 20850 USA. NHLBI, Lab Mol Physiol, Bethesda, MD 20890 USA. Natl Inst Deafness & Other Commun Disorders, Hearing Sect, NIH, Rockville, MD 20850 USA. RP Friedman, TB (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, NIH, Rockville, MD 20850 USA. EM friedman@nidcd.nih.gov OI Naz, Sadaf/0000-0002-1912-0235; Frolenkov, Gregory/0000-0002-9810-5024 NR 30 TC 161 Z9 166 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD FEB PY 2005 VL 7 IS 2 BP 148 EP U60 DI 10.1038/ncb1219 PG 12 WC Cell Biology SC Cell Biology GA 893LC UT WOS:000226719500011 PM 15654330 ER PT J AU Meshel, AS Wei, Q Adelstein, RS Sheetz, MP AF Meshel, AS Wei, Q Adelstein, RS Sheetz, MP TI Basic mechanism of three-dimensional collagen fibre transport by fibroblasts SO NATURE CELL BIOLOGY LA English DT Article ID MYOSIN HEAVY-CHAIN; CELL-MIGRATION; II-B; MATRIX; EXPRESSION; REORGANIZATION; CYTOSKELETON; CONTRACTION; LOCOMOTION; RECEPTORS AB Collagen remodelling by fibroblasts has a crucial role in organizing tissue structures that are essential to motility during wound repair, development and regulation of cell growth. However, the mechanism of collagen fibre movement in three-dimensional (3D) matrices is not understood. Here, we show that fibroblast lamellipodia extend along held collagen fibres, bind, and retract them in a 'hand-over-hand' cycle, involving alpha2beta1 integrin. Wild-type fibroblasts move collagen fibres three to four times farther per cycle than fibroblasts lacking myosin II-B (myosin II- B-/-). Similarly, myosin II-B-/- fibroblasts contract 3D collagen gels threefold less than controls. On two-dimensional (2D) substrates, however, rates of collagen bead and cell movement are not affected by loss of myosin II- B. Green fluorescent protein (GFP)-tagged myosin II- B, but not II- A, restores normal function in knockout cells and localizes to cell processes, whereas myosin II- A is more centrally located. Additionally, GFP - myosin II- B moves out to the periphery and back during hand-over-hand fibre movement, whereas on 2D collagen, myosin II- B is more centrally distributed. Thus, we suggest that cyclic myosin II- B assembly and contraction in lamellipodia power 3D fibre movements. C1 Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Sheetz, MP (reprint author), Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. EM ms2001@columbia.edu OI Adelstein, Robert/0000-0002-8683-2144 NR 30 TC 182 Z9 183 U1 4 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD FEB PY 2005 VL 7 IS 2 BP 157 EP U70 DI 10.1038/ncb1216 PG 10 WC Cell Biology SC Cell Biology GA 893LC UT WOS:000226719500012 PM 15654332 ER PT J AU Lin, TX Chao, C Saito, S Mazur, SJ Murphy, ME Appella, E Xu, Y AF Lin, TX Chao, C Saito, S Mazur, SJ Murphy, ME Appella, E Xu, Y TI P53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression SO NATURE CELL BIOLOGY LA English DT Article ID WILD-TYPE P53; DNA-DAMAGE; ES CELLS; TRANSCRIPTIONAL REPRESSION; CELLULAR-DIFFERENTIATION; RESPONSES; APOPTOSIS; PHOSPHORYLATION; PLURIPOTENCY; MUTATION AB The tumour suppressor p53 becomes activated in response to upstream stress signals, such as DNA damage, and causes cell-cycle arrest or apoptosis(1). Here we report a novel role for p53 in the differentiation of mouse embryonic stem cells (ESCs). p53 binds to the promoter of Nanog, a gene required for ESC self-renewal(2,3), and suppresses Nanog expression after DNA damage. The rapid down-regulation of Nanog mRNA during ESC differentiation correlates with the induction of p53 transcriptional activity and Ser 315 phosphorylation. The importance of Ser 315 phosphorylation was revealed by the finding that induction of p53 activity is impaired in p53(S315A) knock-in ESCs during differentiation, leading to inefficient suppression of Nanog expression. The decreased inhibition of Nanog expression in p53(S315A) ESCs during differentiation is due to an impaired recruitment of the co-repressor mSin3a to the Nanog promoter. These findings indicate an alternative mechanism for p53 to maintain genetic stability in ESCs, by inducing the differentiation of ESCs into other cell types that undergo efficient p53-dependent cell-cycle arrest and apoptosis. C1 Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Dept Pharmacol, Philadelphia, PA 19111 USA. RP Xu, Y (reprint author), Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM yangxu@ucsd.edu RI Lin, Tongxiang/I-4695-2013 OI Lin, Tongxiang/0000-0001-7033-6982 FU NCI NIH HHS [CA94254] NR 23 TC 497 Z9 526 U1 5 U2 39 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD FEB PY 2005 VL 7 IS 2 BP 165 EP U80 DI 10.1038/ncb1211 PG 10 WC Cell Biology SC Cell Biology GA 893LC UT WOS:000226719500013 PM 15619621 ER PT J AU Cannon, RO AF Cannon, RO TI Mechanisms, management and future directions for reperfusion injury after acute myocardial infarction SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Review DE myocardial infarction; myocardial ischemia; preconditioning; reperfusion injury; superoxide anions ID GLUCOSE-INSULIN-POTASSIUM; TISSUE-PLASMINOGEN ACTIVATOR; ANTI-C5 COMPLEMENT ANTIBODY; STUNNED MYOCARDIUM; CARDIAC MYOCYTES; NITRIC-OXIDE; CORONARY ANGIOPLASTY; VENTRICULAR-FUNCTION; ISCHEMIC-MYOCARDIUM; ADJUNCTIVE THERAPY AB Animal models of sustained ischemia have shown exacerbation of myocardial injury during reperfusion, mediated largely by cytotoxic effects of free radical generation, complement activation, shifts in substrate use and inflammation. On the basis of current understanding of the pathogenesis of reperfusion injury, numerous therapies have shown a reduction in infarct size and improved ventricular function in animal models. Clinical trial experience has, however, so far been disappointing for the use of these therapies in patients with acute myocardial infarction (MI), being associated with no or inconsistent benefit to left-ventricular function, complications of MI or survival. The growing emphasis on early revascularization with primary coronary intervention and stenting in the management acute MI, with the potential for more complete drug delivery to injured myocardium, could provide greater opportunities for pharmacologic cardioprotection as adjunctive therapy in the future. C1 NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. Cardiovasc Branch, Clin Cardiol Sect, Bethesda, MD USA. RP Cannon, RO (reprint author), NHLBI, Div Intramural Res, NIH, Bldg 10 CRC,Room 5-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM cannonr@njh.gov NR 55 TC 59 Z9 63 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1743-4297 J9 NAT CLIN PRACT CARD JI Nat. Clin. Pract. Cardiovasc. Med. PD FEB PY 2005 VL 2 IS 2 BP 88 EP 94 DI 10.1038/ncpcardio0096 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 925QS UT WOS:000229068300012 PM 16265379 ER PT J AU Singh, AS Chau, CH Price, DK Figg, WD AF Singh, AS Chau, CH Price, DK Figg, WD TI Mechanisms of disease: polymorphisms of androgen regulatory genes in the development of prostate cancer SO NATURE CLINICAL PRACTICE UROLOGY LA English DT Review DE androgen receptor; metabolism; polymorphisms; prostate cancer; testosterone ID RECEPTOR GENE; BINDING DOMAIN; CLINICAL PRESENTATION; AFRICAN-AMERICANS; INCREASED RISK; SRD5A2 GENE; CYP1B1 GENE; MUTATIONS; CYP3A4; ASSOCIATION AB Androgens are of primary importance in the etiology of prostate cancer, and binding of the androgen dihydrotestosterone to the androgen receptor is thought to stimulate prostate growth. It has been proposed that polymorphisms within key androgen regulatory genes may contribute to an individual's risk of developing prostate cancer. Attributing single polymorphisms to complex, late-onset, chronic diseases such as prostate cancer is probably not feasible, but identification of genes that increase risk will contribute to larger-scale multigenic risk assessment. Here, we review the current status of our knowledge of associations between important androgen regulatory gene polymorphisms and prostate cancer risk. C1 NCI, Mol Pharmacol Sect, Canc Res Ctr, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Canc Res Ctr, Bldg 10,Room 5A01,MSC 1910,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 52 TC 14 Z9 14 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1743-4270 J9 NAT CLIN PRACT UROL JI Nat. Clin. Pract. Urol. PD FEB PY 2005 VL 2 IS 2 BP 101 EP 107 DI 10.1038/ncpuro0091 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 926JD UT WOS:000229118600012 PM 16474655 ER PT J AU Staats, B Qi, LQ Beerman, M Sicotte, H Burdett, LA Packer, B Chanock, SJ Yeager, M AF Staats, B Qi, LQ Beerman, M Sicotte, H Burdett, LA Packer, B Chanock, SJ Yeager, M TI Genewindow: an interactive tool for visualization of genomic variation SO NATURE GENETICS LA English DT Letter C1 NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20877 USA. NCI, Intramural Res Support Program, SAIC Frederick, FCRDC, Frederick, MD 21702 USA. NCI, Sect Gen Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Yeager, M (reprint author), NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20877 USA. EM yeagerm@mail.nih.gov NR 4 TC 19 Z9 20 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2005 VL 37 IS 2 BP 109 EP 110 DI 10.1038/ng0205-109 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 893AB UT WOS:000226690100002 PM 15678133 ER PT J AU Sen, R AF Sen, R TI A move to exclude SO NATURE IMMUNOLOGY LA English DT Editorial Material ID HEAVY-CHAIN GENE; PRE-B CELLS; ALLELIC EXCLUSION; KAPPA LOCUS; ACTIVATION; PAX5; REARRANGEMENTS; RECOMBINATION; EXPRESSION AB It is not clear how lymphocytes establish monoallelic gene expression of antigen receptor genes. New data linking local chromatin modifications with nuclear movements provide a framework for deciphering this process. C1 NIA, Mol & Cellular Biol Lab, Baltimore, MD 21224 USA. RP Sen, R (reprint author), NIA, Mol & Cellular Biol Lab, Baltimore, MD 21224 USA. EM rs465z@nih.gov NR 12 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2005 VL 6 IS 2 BP 128 EP 130 DI 10.1038/ni0205-128 PG 4 WC Immunology SC Immunology GA 889UL UT WOS:000226468100007 PM 15662439 ER PT J AU Tai, XG Cowan, M Feigenbaum, L Singer, A AF Tai, XG Cowan, M Feigenbaum, L Singer, A TI CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2 SO NATURE IMMUNOLOGY LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; NEGATIVE SELECTION; CD4(+)CD8(+) THYMOCYTES; CYTOPLASMIC DOMAIN; SURFACE MOLECULES; CLONAL DELETION; CUTTING EDGE; ANTIGEN 4; CD4(+)CD25(+); RECEPTOR AB Efficient generation of regulatory T cells (T-reg cells) in the thymus requires CD28 costimulation, but it is not known why. Here, molecular mapping of CD28 costimulation showed that T-reg cell generation requires a motif that binds the tyrosine kinase Lck, precisely the same motif that is required for CD28 costimulation of interleukin 2 production. Nevertheless, CD28 costimulation provides more than interleukin 2 to developing T-reg cells, as CD28 costimulation of T cell receptor-signaled double-positive thymocytes induced expression of Foxp3, considered to be the T-reg 'master gene', as well as GITR and CTLA-4, two proteins expressed on T-reg cells. Thus, CD28 costimulation directly signals developing thymocytes to express Foxp3 and to initiate the T-reg cell differentiation program. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Singer, A (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM singera@nih.gov NR 49 TC 352 Z9 369 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2005 VL 6 IS 2 BP 152 EP 162 DI 10.1038/ni1160 PG 11 WC Immunology SC Immunology GA 889UL UT WOS:000226468100018 PM 15640801 ER PT J AU Domi, A Moss, B AF Domi, A Moss, B TI Engineering of a vaccinia virus bacterial artificial chromosome in Escherichia coli by bacteriophage lambda-based recombination SO NATURE METHODS LA English DT Article ID INFECTIOUS VIRUS; MAMMALIAN-CELLS; VECTORS; CLONING; GENOME; DNA; VACCINATION; SYSTEM AB The large capacity of vaccinia virus (VAC) for added DNA, cytoplasmic expression and broad host range make it a popular choice for gene delivery, despite the burdensome need for multiple plaque purifications to isolate recombinants. Here we describe how a bacterial artificial chromosome (BAC) containing the entire VAC genome can be engineered in Escherichia coli by homologous recombination using bacteriophage.-encoded enzymes. The engineered VAC genomes can then be used to produce clonally pure recombinant viruses in mammalian cells without the need for plaque purification. C1 NIAID, NIH, Viral Dis Lab, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, NIH, Viral Dis Lab, 4 Ctr Dr, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 15 TC 19 Z9 20 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD FEB PY 2005 VL 2 IS 2 BP 95 EP 97 DI 10.1038/NMETH734 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 893XJ UT WOS:000226754100009 PM 15782205 ER PT J AU Ji, YY Pang, PT Feng, LY Lu, B AF Ji, YY Pang, PT Feng, LY Lu, B TI Cyclic AMP controls BDNF-induced TrkB phosphorylation and dendritic spine formation in mature hippocampal neurons SO NATURE NEUROSCIENCE LA English DT Article ID NEUROTROPHIC FACTOR; EXCITATORY SYNAPSES; POSTSYNAPTIC DENSITIES; SYNAPTIC-TRANSMISSION; SURFACE EXPRESSION; PRIMARY CULTURES; FULL-LENGTH; CAMP; POTENTIATION; RELEASE AB Synaptic actions of brain-derived neurotrophic factor (BDNF) are 'gated' by cyclic AMP (cAMP), but the underlying molecular mechanisms remain unclear. Here we report that cAMP regulates BDNF function in mature hippocampal neurons by modulating the signaling and trafficking of its receptor TrkB. cAMP gated the TrkB tyrosine kinase with three characteristic features: BDNF-induced TrkB phosphorylation was attenuated by inhibitors of cAMP signaling, it was potentiated by cAMP analogs, and activation of the cAMP pathway alone had no effect. In addition, cAMP facilitated trafficking of TrkB to dendritic spines, possibly by promoting its interaction with synaptic scaffolding protein PSD-95. Norepinephrinergic and dopaminergic agonists, which elevate intracellular cAMP concentration, also enhanced TrkB phosphorylation and its translocation to spines. cAMP gated long-term modulation by BDNF of spine density, but not the number of primary dendrites. These results reveal a specific role of cAMP in controlling BDNF actions in the brain, and provide new insights into the molecular mechanism underlying cAMP gating. C1 NICHHD, NIH, Sect Neural Dev & Plast, Bethesda, MD 20892 USA. Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai, Peoples R China. Chinese Univ Hong Kong, Dept Physiol, Shatin, Hong Kong, Peoples R China. RP Lu, B (reprint author), NICHHD, NIH, Sect Neural Dev & Plast, 35 Lincoln Dr, Bethesda, MD 20892 USA. EM bailu@mail.nih.gov RI Lu, Bai/A-4018-2012 NR 43 TC 175 Z9 182 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD FEB PY 2005 VL 8 IS 2 BP 164 EP 172 DI 10.1038/nn1381 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 892GN UT WOS:000226638200015 PM 15665879 ER PT J AU Lu, L Hope, BT Dempsey, J Liu, SY Bossert, JM Shaham, Y AF Lu, L Hope, BT Dempsey, J Liu, SY Bossert, JM Shaham, Y TI Central amygdala ERK signaling pathway is critical to incubation of cocaine craving SO NATURE NEUROSCIENCE LA English DT Article ID MESOLIMBIC DOPAMINE SYSTEM; VENTRAL TEGMENTAL AREA; REWARD-RELATED STIMULI; MAP KINASE CASCADE; SEEKING BEHAVIOR; SYNAPTIC PLASTICITY; EXCITOTOXIC LESIONS; BASOLATERAL AMYGDALA; NEUROTROPHIC FACTOR; REGULATED KINASE AB Using a rat model of craving and relapse, we have previously found time-dependent increases in cue-induced cocaine seeking over the first months of withdrawal from cocaine, suggesting that drug craving incubates over time. Here, we explored the role of the amygdala extracellular signal-regulated kinase (ERK) signaling pathway in this incubation. Cocaine seeking induced by exposure to cocaine cues was substantially higher after 30 withdrawal days than after 1 withdrawal day. Exposure to these cues increased ERK phosphorylation in the central, but not the basolateral, amygdala after 30 d, but not 1 d, of withdrawal. After 30 d of withdrawal from cocaine, inhibition of central, but not basolateral, amygdala ERK phosphorylation decreased cocaine seeking. After 1 d of withdrawal, stimulation of central amygdala ERK phosphorylation increased cocaine seeking. Results suggest that the incubation of cocaine craving is mediated by time-dependent increases in the responsiveness of the central amygdala ERK pathway to cocaine cues. C1 NIDA, NIH, Dept HHS, Intramural Res Program,Behav Neurosci Branch, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, NIH, Dept HHS, Intramural Res Program,Behav Neurosci Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014 OI Hope, Bruce/0000-0001-5804-7061; NR 50 TC 264 Z9 268 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD FEB PY 2005 VL 8 IS 2 BP 212 EP 219 DI 10.1038/nn1383 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 892GN UT WOS:000226638200021 PM 15657599 ER PT J AU Ransohoff, DF AF Ransohoff, DF TI Opinion - Bias as a threat to the validity of cancer molecular-marker research SO NATURE REVIEWS CANCER LA English DT Article ID SERUM PROTEOMIC PATTERNS; DISCOVERY-BASED RESEARCH; ESTROGEN PLUS PROGESTIN; CORONARY-HEART-DISEASE; BREAST-CANCER; OVARIAN-CANCER; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIALS; CONSORT STATEMENT; DNA MICROARRAYS AB Claims that molecular markers can accurately diagnose cancer have recently been disputed; some prominent results have not been reproduced and bias has been proposed to explain the original observations. As new '-omics' fields are explored to assess molecular markers for cancer, bias will increasingly be recognized as the most important 'threat to validity' that must be addressed in the design, conduct and interpretation of such research. C1 Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Ransohoff, DF (reprint author), Univ N Carolina, Dept Med, CB 7080,Bioinformat Bldg 4103, Chapel Hill, NC 27599 USA. EM ransohof@med.unc.edu NR 63 TC 321 Z9 330 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD FEB PY 2005 VL 5 IS 2 BP 142 EP 149 DI 10.1038/nrc1550 PG 8 WC Oncology SC Oncology GA 893LQ UT WOS:000226721000015 PM 15685197 ER PT J AU Rosa, PA Tilly, K Stewart, PE AF Rosa, PA Tilly, K Stewart, PE TI The burgeoning molecular genetics of the Lyme disease spirochaete SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID OUTER-SURFACE PROTEIN; BURGDORFERI-SENSU-STRICTO; IXODES-SCAPULARIS ACARI; BORRELIA-BURGDORFERI; CIRCULAR PLASMID; CRYSTAL-STRUCTURE; MAMMALIAN HOST; MOTILITY OPERON; STRAIN B31; OSPC GENE AB Lyme disease is the most commonly reported vector-borne disease in North America and Europe, yet we know little about which components of the causative agent, Borrelia burgdorferi, are critical for infection or virulence. Molecular genetics has provided a powerful means by which to address these topics in other bacterial pathogens. Certain features of B. burgdorferi have hampered the development of an effective system of genetic analysis, but basic tools are now available and their application has begun to provide information about the identities and roles of key bacterial components in both the tick vector and the mammalian host. Increased genetic analysis of B. burgdorferi should advance our understanding of the infectious cycle and the pathogenesis of Lyme disease. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Rosa, PA (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM prosa@niaid.nih.gov NR 165 TC 115 Z9 118 U1 6 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD FEB PY 2005 VL 3 IS 2 BP 129 EP 143 DI 10.1038/nrmicro1068 PG 15 WC Microbiology SC Microbiology GA 893AL UT WOS:000226691200012 PM 15685224 ER PT J AU Vargha-Khadem, F Gadian, DG Copp, A Mishkin, M AF Vargha-Khadem, F Gadian, DG Copp, A Mishkin, M TI FOXP2 and the neuroanatomy of speech and language SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID INHERITED SPEECH; TRANSCRIPTIONAL REPRESSORS; BRAIN ABNORMALITIES; CEREBELLAR LOOPS; FORKHEAD-DOMAIN; PURE ANARTHRIA; BASAL GANGLIA; DISORDER; EXPRESSION; MOTOR AB That speech and language are innate capacities of the human brain has long been widely accepted, but only recently has an entry point into the genetic basis of these remarkable faculties been found. The discovery of a mutation in FOXP2 in a family with a speech and language disorder has enabled neuroscientists to trace the neural expression of this gene during embryological development, track the effects of this gene mutation on brain structure and function, and so begin to decipher that part of our neural inheritance that culminates in articulate speech. C1 Univ London, Inst Child Hlth, London WC1N 1EH, England. Great Ormond St Hosp Children, London WC1N 1EH, England. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Vargha-Khadem, F (reprint author), Univ London, Inst Child Hlth, 30 Guildford St, London WC1N 1EH, England. EM fkhadem@ich.ucl.ac.uk RI Copp, Andrew/C-4174-2008; Gadian, David/C-4961-2008; Vargha-Khadem, Faraneh/C-2558-2008; Galantucci, Bruno/E-5770-2010 OI Copp, Andrew/0000-0002-2544-9117; NR 43 TC 198 Z9 202 U1 5 U2 65 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD FEB PY 2005 VL 6 IS 2 BP 131 EP 138 DI 10.1038/nrn1605 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 893LJ UT WOS:000226720200015 PM 15685218 ER PT J AU Liu, W Lippincott-Schwartz, J AF Liu, W Lippincott-Schwartz, J TI Illuminating COPII coat dynamics SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material ID TRANSPORT VESICLES; PROTEINS; GOLGI AB A FRET-based approach to monitor the assembly of membrane-associated COPII coat proteins provides new insights into how the COPII-cargo complex is maintained on the membrane during continuous rounds of Sar1p-GTP hydrolysis. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Liu, W (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM jlippin@helix.nih.gov NR 9 TC 8 Z9 8 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD FEB PY 2005 VL 12 IS 2 BP 106 EP 107 DI 10.1038/nsmb0205-106 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 893VW UT WOS:000226749600004 PM 15702068 ER PT J AU Xu, WP Yuan, XT Xiang, ZX Mimnaugh, E Marcu, M Neckers, L AF Xu, WP Yuan, XT Xiang, ZX Mimnaugh, E Marcu, M Neckers, L TI Surface charge and hydrophobicity determine ErbB2 binding to the Hsp90 chaperone complex SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID ATPASE ACTIVITY; KINASE DOMAIN; MOLECULAR CHAPERONE; TYROSINE KINASE; CLIENT PROTEIN; NEU ONCOGENE; CO-CHAPERONE; GELDANAMYCIN; DEGRADATION; CDC37 AB The molecular chaperone Hsp90 modulates the function of specific cell signaling proteins. Although targeting Hsp90 with the antibiotic inhibitor geldanamycin (GA) may be a promising approach for cancer treatment, little is known about the determinants of Hsp90 interaction with its client proteins. Here we identify a loop within the N lobe of the kinase domain of ErbB2 that determines Hsp90 binding. The amino acid sequence of the loop determines the electrostatic and hydrophobic character of the protein's surface, which in turn govern interaction with Hsp90. A point mutation within the loop that alters ErbB2 surface properties disrupts Hsp90 association and confers GA resistance. Notably, the immature ErbB2 point mutant remains sensitive to GA, suggesting that mature and nascent client kinases may use distinct motifs to interact with the Hsp90 chaperone complex. C1 NCI, Urol Oncol Branch, Ctr Canc Res, Rockville, MD 20850 USA. NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Rockville, MD 20850 USA. EM len@helix.nih.gov NR 42 TC 85 Z9 89 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD FEB PY 2005 VL 12 IS 2 BP 120 EP 126 DI 10.1038/nsmb885 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 893VW UT WOS:000226749600008 PM 15643424 ER PT J AU Bauer, B Hartz, AMS Fricker, G Miller, DS AF Bauer, B Hartz, AMS Fricker, G Miller, DS TI Nuclear receptors regulate transport and metabolism at the blood-brain barrier SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 46th Spring Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und -Toxikologie CY MAR 15-17, 2005 CL Mainz, GERMANY SP Deutsche Gesellsch Experimentelle Klinische Pharmakolog Toxikolog C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Heidelberg, Inst Pharmacol & Mol Biotechnol, D-69120 Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2005 VL 371 SU 1 MA 6 BP R2 EP R2 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 925IM UT WOS:000229046800007 ER PT J AU Hartz, AMS Bauer, B Fricker, G Miller, DS AF Hartz, AMS Bauer, B Fricker, G Miller, DS TI Inflammatory mediators alter P-glycoprotein function and expression at the blood-brain barrier SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 46th Spring Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und -Toxikologie CY MAR 15-17, 2005 CL Mainz, GERMANY SP Deutsche Gesellsch Experimentelle Klinische Pharmakolog Toxikolog C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Heidelberg, Inst Pharmacol & Mol Biotechnol, D-69120 Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2005 VL 371 SU 1 MA 7 BP R2 EP R2 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 925IM UT WOS:000229046800008 ER PT J AU Piekorz, RP vom Dahl, S Pexa, K Kurig, B Wetzel, W Spicher, K Haussinger, D Birnbaumer, L Numberg, B AF Piekorz, RP vom Dahl, S Pexa, K Kurig, B Wetzel, W Spicher, K Haussinger, D Birnbaumer, L Numberg, B TI G alpha(i3) selectively regulates autophagic proteolysis in mouse liver SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 46th Spring Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und -Toxikologie CY MAR 15-17, 2005 CL Mainz, GERMANY SP Deutsche Gesellsch Experimentelle Klinische Pharmakolog Toxikolog C1 Univ Klinikum Dusseldorf, Inst Biochem & Molekularbiol 2, D-40225 Dusseldorf, Germany. Univ Klinikum Dusseldorf, Klin Gastroenterol, D-40225 Dusseldorf, Germany. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2005 VL 371 SU 1 MA 177 BP R43 EP R43 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 925IM UT WOS:000229046800178 ER PT J AU Reichel, V Miller, DS Masereeuw, R Fricker, G AF Reichel, V Miller, DS Masereeuw, R Fricker, G TI Functional analysis of multidrug resistance protein 4 (MRP4) in renal proximal tubules SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 46th Spring Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und -Toxikologie CY MAR 15-17, 2005 CL Mainz, GERMANY SP Deutsche Gesellsch Experimentelle Klinische Pharmakolog Toxikolog C1 Univ Heidelberg, Inst Pharm & Mol Biotechnol, Heidelberg, Germany. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ Nijmegen, Inst Pharmacol, Nijmegen, Netherlands. Mt Desert Isl Biol Lab, Salsbury Cove, ME USA. RI Masereeuw, Roos/N-3582-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2005 VL 371 SU 1 MA 17 BP R4 EP R4 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 925IM UT WOS:000229046800018 ER PT J AU Rieg, T Steigele, H Schnermann, J Richter, K Osswald, H Vallon, V AF Rieg, T Steigele, H Schnermann, J Richter, K Osswald, H Vallon, V TI Absence of caffeine and theophylline induced diuresis and natriuresis in adenosine A(1) receptor (A1AR) knock out mice SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 46th Spring Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und -Toxikologie CY MAR 15-17, 2005 CL Mainz, GERMANY SP Deutsche Gesellsch Experimentelle Klinische Pharmakolog Toxikolog C1 Univ Tubingen, Dept Pharmacol & Toxicol, D-72076 Tubingen, Germany. NIDDK, NIH, Bethesda, MD USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Pharmacol, San Diego, CA 92103 USA. VASDHS, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2005 VL 371 SU 1 MA 379 BP R90 EP R90 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 925IM UT WOS:000229046800379 ER PT J AU Rocco, MV Cheung, AK Greene, T Eknoyan, G AF Rocco, MV Cheung, AK Greene, T Eknoyan, G CA HEMO Study Grp TI The HEMO Study: applicability and generalizability SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Editorial Material DE clinical trial; dialysis dose; dialysis flux; haemodialysis; hospitalizations; mortality ID NATIONAL COOPERATIVE DIALYSIS; HEMODIALYSIS-PATIENTS; MORTALITY; SURVIVAL; VIEWPOINT; SELECTION C1 Wake Forest Univ, Sch Med, Dept Internal Med Nephrol, Winston Salem, NC 27157 USA. Vet Affairs Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Baylor Coll Med, Houston, TX 77030 USA. NIDDK, Bethesda, MD USA. RP Rocco, MV (reprint author), Wake Forest Univ, Sch Med, Dept Internal Med Nephrol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mrocco@wfubmc.edu NR 27 TC 9 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD FEB PY 2005 VL 20 IS 2 BP 278 EP 284 DI 10.1093/ndt/gfh304 PG 7 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 897IP UT WOS:000226997600005 PM 15615811 ER PT J AU Yasar, S Corrada, M Brookmeyer, R Kawas, C AF Yasar, S Corrada, M Brookmeyer, R Kawas, C TI Calcium channel blockers and risk of AD: the Baltimore Longitudinal Study of Aging SO NEUROBIOLOGY OF AGING LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the American-Geriatrics-Society/American-Federation-for-Aging-Research CY MAY 18, 2000 CL NASHVILLE, TN SP Amer Geriatr Soc, Amer Federat Aging Res DE Alzheimer's disease; calcium channel blocker; dihydropyridine; longitudinal study; prevention ID ALZHEIMERS-DISEASE; BLOOD-PRESSURE; COGNITIVE FUNCTION; DEMENTIA; SMOKING; NIMODIPINE; PREVENTION; ROTTERDAM; TOXICITY; NEURONS AB Objective: To investigate the association between use of calcium channel blockers (CCB), dihydropyridine (DHP) or nondihydropyridine (nonDHP) type CCB and risk of developing Alzheimer's Disease (AD) or mortality. There is evidence suggesting that calcium plays a key role in changes in the brain leading to AD. Previous reports suggest a possible role for CCB in the treatment of AD. However, there are some indications that CCB increase mortality in patients with cardiac disease. Methods: Subjects were 1092 participants in the Baltimore Longitudinal Study of Aging (BLSA) older than 60 years of age. Data on CCB use was collected prospectively for up to 19 years. Cox proportional hazards regression was used to estimate relative risks (RR) and confidence intervals (CI) of AD and mortality associated with use of CCB or use of only DHP or nonDHP-CCB. Analyses were adjusted for gender, education, smoking, blood pressure and history of heart problems. Results: Use of DHP-CCB was not associated with a significantly reduced risk of AD compared to non-users, although the estimate of the RR was low with DHP-CCB (RR = 0.30, 95% CI = 0.07-1.25, P = 0.10). Use of nonDHP-CCB was not associated with reduced risk of AD and the estimate of the RR risk was close to one (RR = 0.82, 95% CI = 0.37-1.83, P = 0.63). In addition, there was no increase in mortality among users of DHP-CCB (RR = 0.64, 95% CI = 0.32-1.29, P = 0.21) or nonDHP-CCB (RR = 1.10, 95% CI = 0.65-1.87, P = 0.72). Conclusion: Users of DHP-CCB and nonDHP-CCB in this study did not have a significantly reduced risk of AD. (C) 2004 Elsevier Inc. All rights reserved. C1 Johns Hopkins Sch Med, Div Geriatr Med & Gerontol, Dept Med, Baltimore, MD 21224 USA. Univ Calif Irvine, Inst Brain Aging & Dementia, Irvine, CA 92697 USA. Johns Hopkins Univ, Bloomberg Sch Publ Med, Dept Biostat, Baltimore, MD 21205 USA. NIA, NIH, DHHS,Baltimore Longitudinal Study Aging, Cognit Sect,Lab Personal & Cognit, Baltimore, MD 21224 USA. RP Johns Hopkins Sch Med, Div Geriatr Med & Gerontol, Dept Med, 5505 Hopkins Bayview Cir, Baltimore, MD 21224 USA. EM syasar@jhmi.edu OI corrada, maria/0000-0002-8168-8593 FU NIA NIH HHS [AG05146, AG08325] NR 37 TC 50 Z9 54 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2005 VL 26 IS 2 BP 157 EP 163 DI 10.1016/j.neurobiolaging.2004.03.009 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 885TC UT WOS:000226178800002 PM 15582745 ER PT J AU Beason-Held, LL Golski, S Kraut, MA Esposito, G Resnick, SM AF Beason-Held, LL Golski, S Kraut, MA Esposito, G Resnick, SM TI Brain activation during encoding and recognition of verbal and figural information in older adults SO NEUROBIOLOGY OF AGING LA English DT Article DE positron emission tomography; functional imaging; neuroimaging; brain function; age; aging; spatial; memory ID POSITRON-EMISSION-TOMOGRAPHY; VOXEL-BASED MORPHOMETRY; MEDIAL TEMPORAL-LOBE; AGE-RELATED-CHANGES; EPISODIC MEMORY; ALZHEIMERS-DISEASE; FUNCTIONAL NEUROANATOMY; WORKING-MEMORY; VISUAL MEMORY; RETRIEVAL AB Positron emission tomography (PET) patterns of cerebral blood flow associated with verbal and figural memory are described in relation to their value as functional probes for studying longitudinal changes that occur in the aging brain. Relative to a matching control task, verbal and figural encoding increase blood flow in prefrontal cortex (PFC), anterior cingulate, insular, lateral and medial temporal, occipital cortex and the cerebellum. Additionally, medial temporal regions exhibited greater activity during figural encoding relative to verbal encoding. During recognition, blood flow increases in prefrontal, cingulate, insular, and lateral temporal and Broca's areas. Analysis of hemispheric asymmetry reveals that the prefrontal cortex exhibits regionally dependent results. Prefrontal region BA 10 demonstrates more bilateral activation during encoding and retrieval, whereas BA 46 shows right greater than left activation during both encoding and retrieval. Overall, the two tasks activate diverse regions within the frontal, temporal and occipital lobes of the brain, including areas that show age-related structural changes, proving their usefulness in the longitudinal assessment of brain function in the elderly. (C) 2004 Elsevier Inc. All rights reserved. C1 NIA, LPC, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. RP Beason-Held, LL (reprint author), NIA, LPC, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM heldlo@grc.nia.nih.gov NR 50 TC 16 Z9 17 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2005 VL 26 IS 2 BP 237 EP 250 DI 10.1016/j.neurobiolaging.2004.03.014 PG 14 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 885TC UT WOS:000226178800008 PM 15582751 ER PT J AU Pelled, D Trajkovic-Bodennec, S Lloyd-Evans, E Sidransky, E Schiffmann, R Futerman, AH AF Pelled, D Trajkovic-Bodennec, S Lloyd-Evans, E Sidransky, E Schiffmann, R Futerman, AH TI Enhanced calcium release in the acute neuronopathic form of Gaucher disease SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Gaucher disease; lysosomal storage disease; glucocerebrosidase; glucosylceramide; glucosylphingosine; calcium; neuronopathic ID NEUTRAL GLYCOSPHINGOLIPIDS; BRAIN MICROSOMES; MECHANISMS; RETICULUM; GLUCOSYLCERAMIDE; PHENOTYPE; NEURONS; TYPE-3; MODEL AB Gaucher disease is an inherited metabolic disorder caused by defective activity of the lysosomal enzyme, glucocerebrosidase, resulting in accumulation of the lipids, glucosylceramide (GlcCer), and glucosylsphingosine (GlcSph). Little is known about the mechanism leading from lipid accumulation to disease, particularly in the acute and subacute neuronopathic forms of Gaucher disease, types 2 and 3, respectively. Recent work from our laboratory has shown, in animal models, that GlcCer enhances agonist-induced calcium release from intracellular stores via the ryanodine receptor, which results in neuronal cell death. We now test whether calcium release is altered in human brain tissue obtained post-mortem from Gaucher disease patients. Agonist-induced calcium release via the ryanodine receptor was significantly enhanced (P < 0.05) in brain microsomes from the acute neuronopathic form of Gaucher disease (type 2) (43 +/- 6% of the calcium in microsomes) compared to the subacute (type 3) (27 +/- 3%) and the non-neuronopathic (type 1) (28 +/- 6%) forms, and controls (18 +/- 3%), and correlated with levels of GlcCer accumulation. These findings suggest that defective calcium homeostasis may be a mechanism responsible for neuropathophysiology in acute neuronopathic Gaucher disease, and may potentially offer new therapeutic approaches for disease management. (C) 2004 Elsevier Inc. All rights reserved. C1 Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Futerman, AH (reprint author), Weizmann Inst Sci, Dept Biol Chem, 1 Herzl St, IL-76100 Rehovot, Israel. EM tony.futerman@weizmann.ac.il OI Pelled, Dori/0000-0002-8643-1850; Futerman, Anthony/0000-0003-0013-0115 NR 26 TC 74 Z9 77 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD FEB PY 2005 VL 18 IS 1 BP 83 EP 88 DI 10.1016/j.nbd.2004.09.004 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 889OO UT WOS:000226452500007 PM 15649698 ER PT J AU de Zwart, JA Silva, AC van Gelderen, P Kellman, P Fukunaga, M Chu, RX Koretsky, AP Frank, JA Duyn, JH AF de Zwart, JA Silva, AC van Gelderen, P Kellman, P Fukunaga, M Chu, RX Koretsky, AP Frank, JA Duyn, JH TI Temporal dynamics of the BOLD fMRI impulse response SO NEUROIMAGE LA English DT Article DE BOLD fMRI; binary m-sequence; hemodynamic response; vascular dispersion ID CEREBRAL-BLOOD-FLOW; HUMAN VISUAL-CORTEX; EVENT-RELATED FMRI; FUNCTIONAL MRI; HEMODYNAMIC-RESPONSE; HUMAN-BRAIN; NEURONS PROJECT; RAT-BRAIN; OXYGENATION; RESOLUTION AB Using computer simulations and high-resolution fMRI experiments in humans (n = 6) and rats (n = 8) we investigated to what extent BOLD fMRI temporal resolution is limited by dispersion in the venous vasculature. For this purpose, time-to-peak (TTP) and full-width at half-maximum (FWHM) of the BOLD impulse response (IR) function were determined. In fMRI experiments, a binary in-sequence probe method was used to obtain high-sensitivity model-free single-pixel estimates of IR. Simulations of posteapillary flow suggested that flow-related dispersion leads to a TTP and FWHM increase, which can amount to several seconds in larger pial veins. fMRI experiments showed substantial spatial variation in IR timing within human visual cortex, together with a correlation between TTP and FWHM. Averaged across the activated regions and across subjects, TTP and FWHM were 4.51 +/- 0.52 and 4.04 +/- 0.42 s, respectively. In regions of interest (ROI) weighted toward the larger venous structures, TTP and FWHM increased to 5.07 +/- 0.64 and 4.32 +/- 0.48 s, respectively. In rat somatosensory cortex, TTP and FWHM were substantially shorter than in humans (2.73 +/- 0.60 and 2.28 +/- 0.63 s, respectively). These results are consistent with a substantial macrovascular dispersive contribution to BOLD IR in humans, and furthermore suggest that neurovascular coupling is a relatively rapid process, with a resolution below 2.3 s FWHM. Published by Elsevier Inc. C1 NINDS, Adv MRI Sect, LFMI, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NIH, Lab Diagnost Radiol Res, CC, Bethesda, MD 20892 USA. RP de Zwart, JA (reprint author), NINDS, Adv MRI Sect, LFMI, NIH, Bldg 10,Room B1D-728,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Jacco.deZwart@nih.gov RI Duyn, Jozef/F-2483-2010; Silva, Afonso/A-7129-2009; Fukunaga, Masaki/F-6441-2013; Koretsky, Alan/C-7940-2015 OI Fukunaga, Masaki/0000-0003-1010-2644; Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS002989-08] NR 59 TC 46 Z9 47 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2005 VL 24 IS 3 BP 667 EP 677 DI 10.1016/j.neuroimage.2004.09.013 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 891NT UT WOS:000226588500007 PM 15652302 ER PT J AU Rodd, ZA Bell, RL Zhang, Y Murphy, JM Goldstein, A Zaffaroni, A Li, TK McBride, WJ AF Rodd, ZA Bell, RL Zhang, Y Murphy, JM Goldstein, A Zaffaroni, A Li, TK McBride, WJ TI Regional heterogeneity for the intracranial self-administration of ethanol and acetaldehyde within the ventral tegmental area of alcohol-preferring (P) rats: Involvement of dopamine and serotonin SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ventral tegmental area; intracranial self-administration; ethanol reinforcement; acetaldehyde reinforcement; serotonin-3 receptor; dopamine D2 receptor ID WISTAR RATS; NUCLEUS-ACCUMBENS; 5-HT3 RECEPTOR; BRAIN CATALASE; NEURONS; ANTAGONISTS; METABOLISM; INFUSION; MICE; 3-AMINO-1,2,4-TRIAZOLE AB The meso-limbic dopamine (DA) system has an important role in regulating alcohol drinking. Previous findings from our laboratory indicated that Wistar rats self-administered ethanol ( EtOH) directly into the posterior, but not anterior, ventral tegmental area (VTA), and that coadministration of a DA D-2,D-3 receptor agonist or a serotonin-3 (5-HT3) receptor antagonist blocked EtOH self-administration. In addition, we reported that alcohol-preferring (P) rats self-administered acetaldehyde (ACD), the first metabolite of EtOH, into the posterior VTA. The objectives of this study were to compare the reinforcing effects of EtOH and ACD within the VTA of P rats to examine the possibility that the reinforcing effects of EtOH within the VTA may be mediated by its conversion to ACD. Adult female P rats were stereotaxically implanted with guide cannulae aimed at either the posterior or anterior VTA. At 1 week after surgery, rats were placed in standard two-lever ( active and inactive) experimental chambers for a total of seven to eight sessions. The 4-h sessions were conducted every other day. The results indicated that ( a) 75 - 300 mg% ( 17 - 66 mM) EtOH and 6 - 90 mM ACD were self- administered into the posterior, but not anterior, VTA; (b) the self- administration of 150 mg% EtOH was not altered by coinfusion of a catalase inhibitor; (c) coadministration of the D-2/3 agonist quinpirole (100 muM) blocked the self- infusions of 150 mg% EtOH and 23 muM ACD into the posterior VTA; and (d) coadministration of 200 muM ICS205,930 (5-HT3 receptor antagonist) prevented the self- infusion of 150 mg% EtOH, whereas concentrations of ICS 205,930 up to 400 muM had no effect on the self- infusion of 23 muM ACD into the posterior VTA. Overall, the results of this study indicate that EtOH and ACD can independently produce reinforcing effects within the posterior VTA, and that activation of DA neurons mediates these effects. Furthermore, activation of 5-HT3 receptors within the posterior VTA is involved in the self- infusion of EtOH, but not ACD. C1 Indiana Univ Purdue Univ, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. Indiana Univ Purdue Univ, Indiana Univ, Sch Med, Dept Biochem, Indianapolis, IN 46202 USA. Indiana Univ Purdue Univ, Purdue Sch Sci, Dept Psychol, Indianapolis, IN 46202 USA. Stanford Univ, Stanford, CA 94305 USA. Technofyn Associates, Palo Alto, CA USA. NIAAA, Bethesda, MD USA. RP Rodd, ZA (reprint author), Indiana Univ, Sch Med, Inst Psychiat Res, 791 Union Dr, Indianapolis, IN 46202 USA. EM zrodd@iupui.edu RI Rodd, Zachary/L-1580-2015 OI Rodd, Zachary/0000-0002-8105-1920 FU NIAAA NIH HHS [AA07611, AA12262, AA14437] NR 43 TC 94 Z9 97 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2005 VL 30 IS 2 BP 330 EP 338 DI 10.1038/sj.npp.1300561 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 891GS UT WOS:000226569900012 PM 15383830 ER PT J AU Bart, G Kreek, MJ Ott, J LaForge, KS Proudnikov, D Pollak, L Heilig, M AF Bart, G Kreek, MJ Ott, J LaForge, KS Proudnikov, D Pollak, L Heilig, M TI Increased attributable risk related to a functional mu-opioid receptor gene polymorphism in association with alcohol dependence in central Sweden SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE alcohol dependence; single-nucleotide polymorphism; opioid system; endogenous; association study; opioid receptor ID SUBSTANCE DEPENDENCE; FAMILY-HISTORY; DRUG-DEPENDENCE; BETA-ENDORPHIN; KNOCKOUT MICE; MALE TWINS; ABUSE; NALTREXONE; OPRM1; AXIS AB The mu-opioid receptor (MOR), through its effects on reward and stress-responsivity, modulates alcohol intake in both animal and human laboratory studies. We have previously demonstrated that the frequently occurring A118G single-nucleotide polymorphism ( SNP) in exon 1 of the MORgene (OPRM1), which encodes an amino-acid substitution, is functional and receptors encoded by the variant 118G allele bind the endogenous opioid peptide beta-endorphin with three-fold greater affinity than prototype receptors. Other groups subsequently reported that this variant alters stress-responsivity in normal volunteers and also increases the therapeutic response to naltrexone ( a mu-preferring opioid antagonist) in the treatment of alcohol dependence. We compared frequencies of genotypes containing an 118G allele in 389 alcohol-dependent individuals and 170 population-based controls without drug or alcohol abuse or dependence. The A118G SNP was present in the Hardy - Weinberg equilibrium with an overall frequency of the 118G allele of 10.9%. There was a significant overall association between genotypes with an 118G allele and alcohol dependence ( p = 0.0074). The attributable risk for alcohol dependence in subjects with an 118G allele was 11.1%. There was no difference in A118G genotype between type 1 and type 2 alcoholics. In central Sweden, the functional variant 118G allele in exon 1 of OPRM1 is associated with an increased attributable risk for alcohol dependence. C1 Rockefeller Univ, Lab Biol Addict Dis, New York, NY 10021 USA. Karolinska Inst, Stockholm, Sweden. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. NIAAA, Clin Sci Lab, NIH, Bethesda, MD USA. RP Bart, G (reprint author), Rockefeller Univ, Lab Biol Addict Dis, 1230 York Ave, New York, NY 10021 USA. EM bartg@rockefeller.edu OI Heilig, Markus/0000-0003-2706-2482 FU NIDA NIH HHS [K05-DA00049, P60-DA05130, R01-DA12848]; NIMH NIH HHS [MH044292] NR 48 TC 123 Z9 129 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2005 VL 30 IS 2 BP 417 EP 422 DI 10.1038/sj.npp.1300598 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 891GS UT WOS:000226569900021 PM 15525999 ER PT J AU Panlilio, LV Yasar, S Nemeth-Coslett, R Katz, JL Henningfield, JE Solinas, M Heishman, SJ Schindler, CW Goldberg Sr AF Panlilio, LV Yasar, S Nemeth-Coslett, R Katz, JL Henningfield, JE Solinas, M Heishman, SJ Schindler, CW Goldberg, SR TI Human cocaine-seeking behavior and its control by drug-associated stimuli in the laboratory SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cocaine; stimulants; self-administration; reinforcement schedule; human; intravenous drug abuse ID INDUCED DOPAMINE OVERFLOW; 2ND-ORDER SCHEDULES; FOOD PRESENTATION; ACUTE TOLERANCE; ENVIRONMENTAL DETERMINANTS; OPERANT ACQUISITION; INTRAVENOUS COCAINE; CIGARETTE-SMOKING; NUCLEUS-ACCUMBENS; TAKING BEHAVIOR AB Second-order schedules of drug self-administration were developed to incorporate the effects of drug-related environmental stimuli into an animal model of drug abuse, making it more similar to human situations. Ironically, little is known about how human subjects behave under these schedules. In this study, human volunteers with a history of cocaine use worked on a second-order schedule in which every 100th lever response produced an auditory - visual brief stimulus ( 2 s). The first stimulus produced after 1 h was extended to 10 s and paired with an intravenous injection of cocaine ( 25 mg). Up to three injections were allowed per session. In different phases of the experiment, presentation of the brief stimulus was discontinued and/or saline solution ( placebo) was injected instead of cocaine. Injections of cocaine were found to maintain responding even when the brief stimulus was not presented. Placebo injections alone did not maintain responding. In contrast, the brief stimulus maintained high levels of responding under placebo conditions, even though self-reports indicated that subjects could clearly discriminate that they were not receiving cocaine. These results demonstrate that drug-related environmental stimuli can maintain persistent drug seeking during periods of drug unavailability. As this procedure directly measures the effects of stimuli on drug seeking, it may provide a valuable complement to indirect measures, such as self-reports of craving, that are often used with human subjects. The similarity of the response patterns in humans and animals also supports the use of second-order schedules in animals as a valid model of human drug seeking. C1 NIDA, Preclin Pharmacol Sect, US Dept HHS, Intramural Res Program,NIH,IRP, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. NIDA, Behav Neurosci Sect, Baltimore, MD USA. NIDA, Clin Neurobiol Branch, Baltimore, MD USA. NIDA, Medicat Discovery Branch, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Pinney Associates, Bethesda, MD USA. NIDA, Clin Pharmacol & Therapeut Branch, Baltimore, MD USA. RP Goldberg Sr (reprint author), NIDA, Preclin Pharmacol Sect, US Dept HHS, Intramural Res Program,NIH,IRP, 5500 Nathan Shock Dr, Baltimore, MD USA. EM sgoldber@nih.gov RI Solinas, Marcello/M-3500-2016; OI Solinas, Marcello/0000-0002-0664-5964; Katz, Jonathan/0000-0002-1068-1159 NR 60 TC 31 Z9 31 U1 4 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2005 VL 30 IS 2 BP 433 EP 443 DI 10.1038/sj.npp.1300599 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 891GS UT WOS:000226569900023 PM 15536497 ER PT J AU Maestripieri, D Lindell, SG Ayala, A Gold, PW Higley, JD AF Maestripieri, D Lindell, SG Ayala, A Gold, PW Higley, JD TI Neurobiological characteristics of rhesus macaque abusive mothers and their relation to social and maternal behavior SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Article; Proceedings Paper CT International Conference on Insividual Differences in Behavior and Physiology CY OCT, 2003 CL Erice, ITALY DE infant abuse; CRH; monoamine metabolites; anti-social behavior; rhesus macaques ID POSTTRAUMATIC-STRESS-DISORDER; CORTICOTROPIN-RELEASING-FACTOR; CSF MONOAMINE METABOLITE; LIVING PIGTAIL MACAQUES; INFANT ABUSE; MALTREATED CHILDREN; BRAIN-DEVELOPMENT; PHYSICAL ABUSE; MONKEYS; CHILDHOOD AB Previous studies have reported hyperactivation of catecholaminergic systems and elevated concentrations of corticotropin-releasing-hormone (CRH) in the cerebrospinal fluid (CSF) of child maltreatment victims or combat veterans with post-traumatic stress disorder (PTSD). This study investigated the CSF concentrations of CRH and monoamine metabolites in rhesus macaque mothers that physically abused their infants and had themselves been abused as infants. Ten abusive mothers and 10 controls served as study subjects. All animals were sampled for CSF during pregnancy and the postpartum period. Focal observations of social and maternal behavior were also made. Abusive mothers had significantly higher CSF concentrations of CRH and 5-HIAA than controls. Across both subjects and controls, higher CRH, 5-HIAA and MHPG concentrations were associated with anti-social behavior patterns including a high frequency of maternal aggression, infant rejection, and a low frequency of contacts received from other individuals. These findings are consistent with those of previous primate and human studies and suggest that the neurobiological alterations associated with infant abuse may play an important role in the occurrence of maladaptive behavior in adulthood, including the perpetuation of infant abuse across generations. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Chicago, Inst Mind & Biol, Chicago, IL 60637 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. Natl Inst Alcohol & Alcoholism, Primate Unit, Clin Studies Lab, Bethesda, MD USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Maestripieri, D (reprint author), Univ Chicago, Inst Mind & Biol, 5730 S Woodlawn Ave, Chicago, IL 60637 USA. EM dario@uchicago.edu FU NCRR NIH HHS [RR-00165]; NIMH NIH HHS [K02-MH63097, R01-MH57249, R01-MH62577] NR 37 TC 55 Z9 56 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD FEB PY 2005 VL 29 IS 1 BP 51 EP 57 DI 10.1016/j.neubiorev.2004.05.004 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 899NO UT WOS:000227151500004 PM 15652254 ER PT J AU Lejuez, CW Aklin, WM Bornovalova, MA Moolchan, ET AF Lejuez, CW Aklin, WM Bornovalova, MA Moolchan, ET TI Differences in risk-taking propensity across inner-city adolescent ever- and never-smokers SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SUBSTANCE USE DISORDERS; SENSATION SEEKING; AFRICAN-AMERICAN; CIGARETTE-SMOKING; ALCOHOL-USE; TASK BART; SUSTAINED ATTENTION; YOUNG ADULTHOOD; 5-FACTOR MODEL; DRUG-USE AB Because adolescent smoking is a significant public health concern, potential value lies in understanding and identifying the psychological factors that distinguish ever- and never-smokers. To that end, we examined the relationship between risk-taking propensity as measured by the Balloon Analogue Risk Task and ever-smoking (i.e., even one puff) versus never-smoking in a sample of 125 predominantly African American high-school adolescents (M=15.1, SD=1.5). Results indicated that ever-smokers and never-smokers differed on risk-taking propensity; further risk-taking propensity was related to smoking status above and beyond both demographic variables and a measure of self-reported impulsive sensation seeking. We discuss these results in relation to the potential utility of a multimethod assessment approach (i.e., self-report measures and behavioral tasks) to identify adolescents' risk-taking susceptibilities and engagement in smoking and other risk-taking behaviors. C1 Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. RP Lejuez, CW (reprint author), Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. EM clejuez@psyc.umd.edu FU NIDA NIH HHS [DA014699] NR 65 TC 69 Z9 69 U1 4 U2 14 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD FEB PY 2005 VL 7 IS 1 BP 71 EP 79 DI 10.1080/14622200412331328484 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 919UE UT WOS:000228642300007 PM 15804679 ER PT J AU Ryzhikov, NN Seneca, N Krasikova, RN Gomzina, NA Shchukin, E Fedorova, OS Vassiliev, DA Gulyas, B Hall, H Savic, I Halldin, C AF Ryzhikov, NN Seneca, N Krasikova, RN Gomzina, NA Shchukin, E Fedorova, OS Vassiliev, DA Gulyas, B Hall, H Savic, I Halldin, C TI Preparation of highly specific radioactivity [F-18]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE [F-18]flumazenil; Ro 15-1788; nucleophilic fluorination; central benzodiazepine receptors; PET; brain ID CENTRAL BENZODIAZEPINE RECEPTORS; HUMAN BRAIN; BINDING-SITES; PET; FLUOROETHYLFLUMAZENIL; RADIOLIGANDS; FLUMAZENIL AB A straightforward method for the preparation of no-carrier-added (n.c.a.) [F-18]flumazenil via standard nucleophilic radiotluorination of the corresponding nitro-analog Ro 15-2344 has been developed. The labeling was performed by employing the (KF)-F-18/kryptofix complex in DNIF at 160 degrees C for 30 min and equimolar ratio [K/K2.2.2]F-+18(-)/precursor. Under these conditions, an F-18 incorporation rate into flumazenil was in the range of 55-60%. The final product was isolated by HPLC purification within a total synthesis time of 75 min and a radiochemical yield of about 30% (EOB). Human post-mortem whole-hemisphere autoradiography of brain sections demonstrated selective uptake of the radioligand in the areas of high density of the central benzodiazepine receptors (BZR). PET studies in a cynomolgus monkey and metabolite studies by HPLC demonstrated similar results by [F-18]flumazenil as for [C-11]flumazenil. In blocking experiments, almost all radioactivity was inhibited by the addition of unlabeled flumazenil. [F-18]Flumazenil is a suitable radioligand for PET assessment of the BZR. (c) 2005 Elsevier Inc. All rights reserved. C1 Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. Russian Acad Sci, Inst Human Brain, St Petersburg 197376, Russia. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Halldin, C (reprint author), Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. EM christer.haildin@cns.ki.se RI Gulyas, Balazs/F-9508-2015; Krasikova, Raisa/A-2561-2014 NR 26 TC 52 Z9 53 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD FEB PY 2005 VL 32 IS 2 BP 109 EP 116 DI 10.1016/j.nucmedbio.2004.11.001 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 907BF UT WOS:000227689100001 PM 15721755 ER PT J AU Garcia-Palmieri, MR Crespo, CJ Mc Gee, D Sempos, C Smit, E Sorlie, PD AF Garcia-Palmieri, MR Crespo, CJ Mc Gee, D Sempos, C Smit, E Sorlie, PD TI Wide pulse pressure is an independent predictor of cardiovascular mortality in Puerto Rican men SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES LA English DT Article ID CORONARY-HEART-DISEASE; NUTRITION EXAMINATION SURVEY; OLDER HYPERTENSIVE PATIENTS; URBAN-RURAL DIFFERENCES; 3RD NATIONAL-HEALTH; BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; RISK-FACTOR; MEAN PRESSURE; UNITED-STATES AB Background and aim: Emerging evidence suggests that pulse pressure is an independent predictor of risk for cardiovascular mortality. New studies in diverse populations are needed to further establish the applicability of this finding. Thus, the purpose of this study is to examine the relationship between pulse pressure and cardiovascular mortality in a cohort of Puerto Rican men after 12 years of follow-up. Methods and results: The Puerto Rico Heart Health Program is a study of coronary disease risk factors in men aged 35-79 years at baseline who had an initial examination during the years 1962-1965. It was attended by 9824 subjects representing 80% of the total age-specific mate residents in 4 rural and 3 urban areas of Puerto Rico. Cardiovascular risk factors including systolic and diastolic blood pressures were monitored prospectively. This study includes 9106 men free of overt CHID at baseline who were stratified by quartiles of pulse pressure in mmHg: quartile 1, &LE; 38, quartile 2, 39-46; quartile 3, 47-56; and quartile 4, &GE; 57. The odds ratio of cardiovascular mortality was calculated using logistic regression analysis. After adjusting for age, education, smoking status, hypercholesterolemic status, physical activity, diabetic status and mean arterial pressure, we found that those in the highest quartile of pulse pressure (pulse pressure > = 57) had significantly higher cardiovascular mortality than those in the lowest quartile (reference group) (OR = 1.38 95% CI = 1.01-1.88). Conclusion: Our findings showed that a wide pulse pressure is independently associated with cardiovascular mortality in this group of Puerto Rican men. © 2005 Elsevier Ltd. All rights reserved. C1 SUNY Buffalo, Univ Buffalo, Dept Social & Prevent Med, Sch Med, Buffalo, NY 14214 USA. Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. Florida State Univ, Dept Stat, Tallahassee, FL 32306 USA. NHLBI, Bethesda, MD 20892 USA. RP Crespo, CJ (reprint author), SUNY Buffalo, Univ Buffalo, Dept Social & Prevent Med, Sch Med, 270 Farber Hall, Buffalo, NY 14214 USA. EM mgarcia@rcm.upr.edu; ccrespo@buffalo.edu FU NCI NIH HHS [P20CA96256-01A1, R03CA103475-01] NR 42 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0939-4753 J9 NUTR METAB CARDIOVAS JI Nutr. Metab. Carbiovasc. Dis. PD FEB PY 2005 VL 15 IS 1 BP 71 EP 78 DI 10.1016/j.numecd.2004.08.002 PG 8 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition & Dietetics SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; Nutrition & Dietetics GA 923IG UT WOS:000228903000012 PM 15871854 ER PT J AU Petrini, JR Callaghan, WM Klebanoff, M Green, NS Lackritz, EM Howse, JL Schwarz, RH Damus, K AF Petrini, JR Callaghan, WM Klebanoff, M Green, NS Lackritz, EM Howse, JL Schwarz, RH Damus, K TI Estimated effect of 17 alpha-hydroxyprogesterone caproate on preterm birth in the United States SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 9th Annual Maternal and Child Health Epidemiology Conference CY DEC, 2003 CL Tempe, AZ ID PREVENTION AB OBJECTIVE: A multicenter, randomized placebo-controlled trial among women with singleton pregnancies and a history of spontaneous preterm birth found that weekly injections of 17 alpha-hydroxyprogesterone caproate (17P), initiated between 16 and 20 weeks of gestation, reduced preterm birth by 33%. The current study estimated both preterm birth recurrence and the potential reduction in the national preterm. birth rate. METHODS: Using 2002 national birth certificate data, augmented by vital statistics from 2 states, we estimated the number of singleton births delivered to women eligible for 17P through both a history of spontaneous preterm. birth and prenatal care onset within the first 4 months of pregnancy. The number and rate of recurrent spontaneous preterm births were estimated. To predict effect, the reported 33% reduction in spontaneous preterm birth attributed to 17P therapy was applied to these estimates. RESULTS: In 2002, approximately 30,000 recurrent preterm births occurred to women eligible for 17P, having had a recurrent preterm birth rate of 22.5%. If 17P therapy were delivered to these women, nearly 10,000 spontaneous preterm births would have been prevented, thereby reducing the overall United States preterm birth rate by approximately 2%, from 12.1% to 11.8% (P < .001), with higher reductions in targeted groups of eligible pregnant women. CONCLUSION: Use of 17P could reduce preterm birth among eligible women, but would likely have a modest effect on the national preterm birth rate. Additional research is urgently needed to identify other populations who might benefit from 17P, evaluate new methods for early detection of women at risk, and develop additional prevention strategies. C1 Natl Off, White Plains, NY 10605 USA. Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA. Ctr Dis Control & Prevent, Maternal & Infant Hlth Branch, Div Reprod Hlth, Dept Hlth & Human Sci, Atlanta, GA USA. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA. Albert Einstein Coll Med, Dept Pediat & Cell Biol, Bronx, NY 10467 USA. RP Petrini, JR (reprint author), Natl Off, 1375 Mamaroneck Ave, White Plains, NY 10605 USA. EM jpetrini@marchofdimes.com OI Green, Nancy/0000-0002-9877-1561 NR 9 TC 67 Z9 67 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2005 VL 105 IS 2 BP 267 EP 272 DI 10.1097/01.AOG.0000150560.24297.4f PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 893DX UT WOS:000226700600008 PM 15684150 ER PT J AU Chen, J Vistica, BP Wiggert, B Chan, CC Gery, I AF Chen, J Vistica, BP Wiggert, B Chan, CC Gery, I TI The immunomodulator vasoactive intestinal peptide (VIP) does not affect experimental autoimmune uveitis (EAU) in B10.RIII mice SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE experimental autoimmune uveitis (EAU); immunopathogenic mechanisms; immunosuppression; mouse strains; vasoactive intestinal peptide (VIP) ID ENDOTOXIN-INDUCED UVEITIS; TH1 RESPONSES; DISEASE; UVEORETINITIS; MACROPHAGES; PERTUSSIS; PROTEIN; CELLS; IRBP; EYE AB Purpose: Vasoactive intestinal peptide (VIP) exhibits immunomodulatory activities both in vivo and in vitro, including efficient inhibition of murine experimental arthritis. In this study, we investigated the effects of VIP treatment on the induction of experimental automimune uveoretinitis (EAU). Methods: EAU was induced in B10.RIII mice by immunization with interphotoreceptor retinoid-binding protein (IRBP) using routine methods, but without treatment with pertussis toxin (PTX). VIP was injected i.p. at different doses into mice on alternate days. Mice were tested by conventional methods for ocular inflammation, antibody levels, lymphocyte proliferation, and cytokine release by cultured lymphocytes. Results: Treatment with VIP, at different doses, had essentially no effect on the development of EAU or antibody production in the B10.RIII mice. The treatment did have variable effects on the low interferon-gamma production by lymphocytes of these mice. Conclusion: Unlike its inhibitory effect in the experimental arthritis system, VIP did not modulate the development of EAU in B10.RIII mice. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Chen, J (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N112, Bethesda, MD 20892 USA. NR 17 TC 10 Z9 10 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD FEB PY 2005 VL 13 IS 1 BP 13 EP 17 DI 10.1080/09273940490912399 PG 5 WC Ophthalmology SC Ophthalmology GA 914ZR UT WOS:000228267900002 PM 15804764 ER PT J AU Longo, DL AF Longo, DL TI Follicular lymphoma: Expanding therapeutic options - The Ganti/Bociek/Bierman et al article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 NIA, Baltimore, MD 21224 USA. RP Longo, DL (reprint author), NIA, Baltimore, MD 21224 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD FEB PY 2005 VL 19 IS 2 BP 235 EP + PG 3 WC Oncology SC Oncology GA 052EB UT WOS:000238213100017 ER PT J AU Baker, H Patel, V Molinolo, AA Shillitoe, EJ Ensley, JF Yoo, GH Meneses-Garcia, A Myers, JN El-Naggar, AK Gutkind, JS Hancock, WS AF Baker, H Patel, V Molinolo, AA Shillitoe, EJ Ensley, JF Yoo, GH Meneses-Garcia, A Myers, JN El-Naggar, AK Gutkind, JS Hancock, WS TI Proteome-wide analysis of head and neck squamous cell carcinomas using laser-capture microdissection and tandem mass spectrometry SO ORAL ONCOLOGY LA English DT Article DE oral cancer; microdissection; proteome; biomarkers; drug targets; mass spectrometry ID PLACENTAL GROWTH-FACTOR; ORAL-CANCER; PREDICTIVE FACTORS; SHOCK-PROTEIN; EXPRESSION; WNT; DIFFERENTIATION; IDENTIFICATION; PROGRESSION; ACTIVATION AB Remarkable progress has been made to identify genes expressed in squamous cell carcinomas of the head and neck (HNSCC). However, limited information is available on their corresponding protein products, whose expression, post-translational modifications, and activity are ultimately responsible for the malignant behavior of this tumor type. We have combined laser-capture microdissection (LCM) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify proteins expressed in histologically normal squamous epithelium and matching SCC. The protein fraction from approximately 10,000-15,000 normal and tumor cells was solubilized, digested with trypsin, and the resulting peptides were analyzed by LC-MS/MS. Database searching of the resulting sequence information identified 30-55 proteins per sample. Keratins were the most abundant proteins in both normal and tumor tissues. Among the proteins differentially expressed, keratin 13 was much Lower in tumors, whereas heat-shock (Hsp) family members were highly expressed in neoplastic cells. Wnt-6 and Wnt-14 were identified in both normal and tumor tissues, respectively, and placental growth factor (PIGF) was detected only in tumors. Immunohistochemical analysis of HNSCC tissues revealed tack of keratin 13 in tumor tissues, and strong staining in normal epithelia, and high expression of Hsp90 in tumors. Our study, by combining LCM and proteomic technologies, underscores the advantages of this approach to investigate complex changes at the protein Level in HNSCC, thus complementing existing and emerging genomic technologies. These efforts may likely result in the identification of new biomarkers for HNSCC that can be used to diagnose disease, predict susceptibility, and monitor progression in individual patients. Published by Elsevier Ltd. C1 Natl Inst Craniofacial & Dent Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Northeastern Univ, Dept Chem & Chem Biol, Barnett Inst, Boston, MA 02115 USA. SUNY Coll Med, Dept Microbiol & Immunol, Syracuse, NY 13210 USA. Wayne State Univ, Karmanos Canc Ctr, Dept Internal Med, Detroit, MI 48201 USA. Wayne State Univ, Dept Otolaryngol Head & Neck Surg, Univ Hlth Ctr 5E, Detroit, MI 48201 USA. Natl Inst Cancerol, Dept Pathol, Mexico City, DF, Mexico. Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. RP Gutkind, JS (reprint author), Natl Inst Craniofacial & Dent Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. EM sg39v@nih.gov; wi.hancock@neu.edu RI Gutkind, J. Silvio/A-1053-2009 NR 46 TC 62 Z9 65 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD FEB PY 2005 VL 41 IS 2 BP 183 EP 199 DI 10.1016/j.oraloncology.2004.08.009 PG 17 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 898TG UT WOS:000227098500011 PM 15695121 ER PT J AU Strigo, IA Duncan, GH Bushnell, MC Boivin, M Wainer, I Rosas, MER Persson, J AF Strigo, IA Duncan, GH Bushnell, MC Boivin, M Wainer, I Rosas, MER Persson, J TI The effects of racemic ketamine on painful stimulation of skin and viscera in human subjects SO PAIN LA English DT Article DE nociception NMDA-R; psychophysics; heat; pressure; analgesia ID D-ASPARTATE RECEPTOR; HEALTHY MALE-VOLUNTEERS; DORSAL-HORN NEURONS; LOW-DOSE KETAMINE; C-FOS EXPRESSION; NMDA RECEPTORS; SECONDARY HYPERALGESIA; COLORECTAL DISTENSION; ANTAGONIST KETAMINE; POSTOPERATIVE PAIN AB Evidence suggests that NMDA receptors may have a differential role in the modulation of visceral and somatic pain. Specifically, animal data indicate an analgesic role of NMDA-R antagonists in acute visceral but not acute somatic pain. In humans analgesic effects are documented in acute somatic pain, while the role of NMDA-R antagonists in acute visceral pain is still questionable. We, therefore, conducted a study in humans comparing the analgesic effects of ketamine in an experimental model of visceral and cutaneous pain. In a double-blind, randomized. cross-over study, 11 healthy volunteers (3M, 8F) participated in two experimental sessions in which they evaluated perceptions induced by balloon distention of the distal esophagus and contact heat on the upper chest during continuous computer-controlled i.v. infusion of either ketamine (60 and 120 ng/mL) or saline. Two stimulus intensities producing non-painful and painful sensation were used for each stimulus modality. Subjects reported maximum pain intensity and unpleasantness on visual analog scales (VAS). For noxious visceral stimulation, low dose ketamine produced significant attenuation of both pain intensity and unpleasantness. In contrast, for noxious cutaneous stimulation, ketamine reduced pain unpleasantness, but not perceived intensity. In addition, ketamine did not alter the perception of innocuous stimuli in either modality. Our results confirm the analgesic effects of low-dose ketamine, with minimal side effects. on acute visceral pain and indicate a similar but smaller effect on acute cutaneous pain. A decrease in the unpleasantness but not in the intensity of cutaneous pain may reflect the differential effect of NMDA-R antagonists for the two pain states observed in animal models. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 McGill Univ, Dept Anesthesia, Ctr Res Pain, Montreal, PQ H3A 2B2, Canada. Univ Montreal, Ctr Rech Sci Neurol, Fac Med Dent, Dept Stomatol, Montreal, PQ H3C 3J7, Canada. Univ Montreal, Dept Gastroenterol, Montreal, PQ H3C 3J7, Canada. NIA, Gerontol Ctr, NIH, Baltimore, MD 21224 USA. Karolinska Inst, Dept Anesthesiol & Intens Care, Stockholm, Sweden. Karolinska Inst, Dept Clin Pharmacol, Stockholm, Sweden. RP Strigo, IA (reprint author), McGill Univ, Dept Anesthesia, Ctr Res Pain, 3640 Univ St, Montreal, PQ H3A 2B2, Canada. EM irina.strigo@mail.mcgill.ca RI strigo, irina/L-9882-2016 OI strigo, irina/0000-0002-8799-716X NR 59 TC 42 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD FEB PY 2005 VL 113 IS 3 BP 255 EP 264 DI 10.1016/j.pain.2004.10.023 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 896JL UT WOS:000226930300003 PM 15661431 ER PT J AU Wiley, JM Seibel, NL Walsh, TJ AF Wiley, JM Seibel, NL Walsh, TJ TI Efficacy and safety of amphotericin B lipid complex in 548 children and adolescents with invasive fungal infections SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE amphotericin B; Abelcet; mycoses; fungal infections; aspergillosis; candidiasis; organ transplantation; hematopoietic; stem cell transplantation ID TRANSPLANT RECIPIENTS; PEDIATRIC-PATIENTS; ASPERGILLOSIS; CANCER; VORICONAZOLE; EXPERIENCE; THERAPY AB Background: The safety and efficacy of amphotericin B lipid complex injection (ABELCET; Enzon Pharmaceuticals, Piscataway, NJ) was assessed in 548 children and adolescents 0-20 years of age who were enrolled in the Collaborative Exchange of Antifungal Research (CLEAR) registry. To our knowledge, this is the largest series of pediatric patients treated for invasive mycoses with a single ag, ent. All patients had cancer or had received a bone marrow, cord blood or solid organ transplant and were treated with amphotericin B lipid complex for documented or suspected fungal infection, Methods: The CLEAR database was queried for all patients 0-20 years of age from 1996 to 2000. Data gathered included demographic variables, underlying disease type, reasons for the use of amphotericin B lipid complex injection, dosing information, clinical response and renal effects. Results: Most patients were either intolerant of or refractory to conventional antifungal therapy, and almost one-half were neutropenic at treatment onset. Of the 548 patients, 300 (54.7%) were transplant recipients and 393 (71.7%) had received one or more concomitant nephrotoxins. Candida and Aspergillits were the most commonly isolated species in patients with proven or probable infections. Response data were evaluable for 255 of the 285 patients with documented single or multiple pathogens. A Complete (Cured) or partial (improved) response was achieved in 54.9% of patients, with an additional 16.9% of patients having a stable outcome. Among patients with proven Aspergilhis infection, the response rates (cured + improved) were 40.5 and 37.5% in transplant and nontransplant patients, respectively. When stable responses were added, the response rates were 48.6 and 71.9%, respectively. There were few clinically significant deleterious effects on renal function. There was no significant difference between the rates of newhemodialysis versus baseline hemodialysis. Elevations in serum creatinine of > 1.5 x baseline and > 2.5 x baseline values were seen in 24.8 and 8.8% of all patients, respectively. Conclusions: The safety and efficacy data from this large pediatric population support the use of amphotericin B lipid complex injection for treatment of invasive fungal infections in imunocompromised children and adolescents, including the high risk subgroup of transplant recipients. The overall response rate and safety profile in pediatric patients who were largely intolerant of or refractory to conventional antifungal therapy were consistent with earlier reported findings of smaller trials. C1 Sinai Hosp, Dept Pediat, Div Hematol Oncol, Baltimore, MD 21215 USA. Sinai Hosp Baltimore, Div Hematol Oncol, Baltimore, MD USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Wiley, JM (reprint author), Sinai Hosp, Dept Pediat, Div Hematol Oncol, 2401 Belvedere Ave, Baltimore, MD 21215 USA. EM jwiley@lifebridgehealth.org NR 16 TC 52 Z9 56 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD FEB PY 2005 VL 24 IS 2 BP 167 EP 174 DI 10.1097/01.inf.0000153183.51258.b8 PG 8 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 898WH UT WOS:000227106400013 PM 15702047 ER PT J AU Raju, TNK Ariagno, RL Higgins, R Van Marter, LJ AF Raju, TNK Ariagno, RL Higgins, R Van Marter, LJ TI Research in Neonatology for the 21st Century: Executive summary of the National Institute of Child Health and Human Development-American Academy of Pediatrics Workshop. Part I: Academic issues SO PEDIATRICS LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; PREMATURE-INFANTS; BIRTH; CARE; INTESTINE; DELIVERY AB This article presents the executive summary of the presentations and discussions at the Workshop on Research in Neonatology sponsored by the National Institute of Child Health and Human Development and the American Academy of Pediatrics Section on Perinatal Pediatrics convened in January 2004. In this article, the scientific aspects are summarized, highlighting the current knowledge gaps and identifying research priorities with a focus on emerging technologies. In a separate article, issues concerning workforce needs and shortages and board-certification requirements are presented. Full-length articles on the presented topics will be published in the Journal of Perinatology. C1 NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, Bethesda, MD 20892 USA. Stanford Univ, Dept Pediat, Div Neonatal & Dev Med, Stanford, CA 94305 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Raju, TNK (reprint author), NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, 6100 Execut Blvd,Room 4B03, Bethesda, MD 20892 USA. EM rajut@mail.nih.gov NR 42 TC 7 Z9 9 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 2005 VL 115 IS 2 BP 468 EP 474 DI 10.1542/peds.2004-2556 PG 7 WC Pediatrics SC Pediatrics GA 893NB UT WOS:000226725000047 PM 15687457 ER PT J AU Ariagno, RL Van Marter, LJ Higgins, R Raju, TNK AF Ariagno, RL Van Marter, LJ Higgins, R Raju, TNK TI Neonatology Research for the 21st Century: Executive summary of the National Institute of Child Health and Human Development-American Academy of Pediatrics Workshop. Part II: Training issues SO PEDIATRICS LA English DT Article ID CARE AB This is the second part of the executive summary based on the presentations and discussions at a workshop on research in neonatology sponsored by the National Institute of Child Health and Human Development and the American Academy of Pediatrics held in January 2004. In this article, neonatology fellowship training requirements and workforce issues are addressed, and the reasons for the shortage of physician-scientists, particularly of the underrepresented minority ethnic groups, are highlighted. Full-length articles from the presented topics are yet to be published. C1 NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, Stanford, CA 94305 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Raju, TNK (reprint author), NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, 6100 Execut Blvd,Room 4B03, Bethesda, MD 20892 USA. EM rajut@mail.nih.gov NR 14 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 2005 VL 115 IS 2 BP 475 EP 479 DI 10.1542/peds.2004-2559 PG 5 WC Pediatrics SC Pediatrics GA 893NB UT WOS:000226725000048 PM 15687458 ER PT J AU Beblo, S Stark, KD Murthy, M Janisse, J Rockett, H Whitty, JE Buda-Abela, M Martier, SS Sokol, RJ Hannigan, JH Salem, N AF Beblo, S Stark, KD Murthy, M Janisse, J Rockett, H Whitty, JE Buda-Abela, M Martier, SS Sokol, RJ Hannigan, JH Salem, N TI Effects of alcohol intake during pregnancy on docosahexaenoic acid and arachidonic acid in umbilical cord vessels of black women SO PEDIATRICS LA English DT Article DE docosahexaenoic acid; arachidonic acid; nutrition; essential fatty acids; pregnancy; alcohol; fetal alcohol syndrome ID POLYUNSATURATED FATTY-ACIDS; RHESUS-MONKEYS; FOOD FREQUENCY; RISK-DRINKING; HUMAN PLACENTA; ENERGY-INTAKE; ETHANOL; EXPOSURE; CONSUMPTION; PATTERN AB Objective. Alcohol influences the intake and metabolism of several nutrients including long-chain polyunsaturated fatty acids (LC-PUFAs). The LC-PUFAs docosahexaenoic acid (DHA) and arachidonic acid ( AA) are particularly crucial for intrauterine growth and brain development. We hypothesized that alcohol consumption adversely affects LC-PUFA levels in pregnant women and their newborn infants. Methods. Pregnant black women ( N = 208) presenting at a core city antenatal clinic were screened and recruited. Shortly before delivery, maternal plasma was collected. After delivery, umbilical arteries and veins were dissected from the cords, total lipids were extracted from the vessel tissues and maternal plasma, and fatty acid levels were assayed by gas chromatography. For statistical analysis, subjects were categorized according to absolute alcohol intake per day (AAD) and absolute alcohol intake per drinking day (AADD) around the time of conception, with smoking and other potential confounders included in the analyses. Results. Significant differences in fatty acid composition of total lipid extracts were detected in umbilical cord vessels among the AADD groups: abstainers ( AADD = 0), moderate drinkers ( AADD < 130 g), and heavy drinkers ( AADD &GE; 130 g). DHA and AA content in the arterial umbilical vessel wall was &SIM; 14% and &SIM; 10% higher in the moderate ( n = 127) and heavy ( n = 32) alcohol groups, respectively, than in abstainers ( n = 49). A small, nonsignificant increase ( &SIM; 3%) was seen in the umbilical vein for AA but not for DHA. Alcohol intake was positively correlated to both DHA and AA concentrations in the arterial vessel wall but to neither in the venous wall nor maternal plasma. Maternal plasma DHA was positively correlated with both umbilical arteries and vein DHA, but there were no significant correlations for AA between maternal plasma and either umbilical vessel. Conclusions. Our findings indicate that alcohol intake during pregnancy is associated with altered DHA and AA status in fetal tissues. Although differences may be due to either metabolism and/or distribution, it is most likely a result of a direct influence of alcohol on fetal metabolism. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Salem, N (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 5625 Fishers Lane,Room 3N-07, Rockville, MD 20852 USA. EM nsalem@niaaa.nih.gov RI Stark, Ken/I-1347-2016 OI Stark, Ken/0000-0001-7828-4072 FU NIAAA NIH HHS [N01-AA83019] NR 65 TC 7 Z9 7 U1 1 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 2005 VL 115 IS 2 BP E194 EP E203 DI 10.1542/peds.2004-0202 PG 10 WC Pediatrics SC Pediatrics GA 893NB UT WOS:000226725000011 PM 15687427 ER PT J AU Harvey, BK Hoffer, BJ Wang, Y AF Harvey, BK Hoffer, BJ Wang, Y TI Stroke and TGF-beta proteins: glial cell line-derived neurotrophic factor and bone morphogenetic protein SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE transforming growth factor-beta; glial cell line-derived neurotrophic factor; bone morphogenetic protein; stroke; ischemia; gene theraphy ID MIDBRAIN DOPAMINERGIC-NEURONS; CEREBRAL-ARTERY OCCLUSION; SERINE/THREONINE KINASE RECEPTORS; ISCHEMIC BRAIN-INJURY; TRANSIENT GLOBAL-ISCHEMIA; ADENOVIRUS-MEDIATED GDNF; CENTRAL-NERVOUS-SYSTEM; DORSAL NEURAL-TUBE; GROWTH-FACTOR-BETA; MICE LACKING GDNF AB Recent studies have indicated that proteins in the transforming growth factor-beta, superfamily alter damage induced by various neuronal injuries. Of these proteins, glial cell line-derived neurotrophic factor (GDNF) and bone morphogenetic protein-7 (BMP-7) have unique protective and regenerative effects in stroke animals. Delivery of GDNF or BMP-7 to brain tissue reduced cerebral infarction and improved motor functions in stroke animals. Pretreatment with these factors reduced caspase-3 activity and DNA fragmentation in the ischemic brain region. suggesting that antiapoptotic effects are involved. Beside the protective effects. BMP-7 given after stroke improves locomotor function. These regenerative effects of BMP-7 may involve the enhancement of dendritic growth and remodeling. In this review, we illustrate the neuroprotective and neuroregenerative properties of GDNF and BMP-7 and emphasize their therapeutic potential for stroke. (C) 2004 Elsevier Inc. All rights reserved. C1 NIDA, Neural Protect & Regenerat Sect, Mol Neuropsychiat Branch, NIH, Baltimore, MD 21124 USA. RP Wang, Y (reprint author), NIDA, Neural Protect & Regenerat Sect, Mol Neuropsychiat Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21124 USA. EM ywang@intra.nida.nih.gov RI Harvey, Brandon/A-5559-2010 NR 160 TC 56 Z9 60 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD FEB PY 2005 VL 105 IS 2 BP 113 EP 125 DI 10.1016/j.pharmthera.2004.09.003 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 896JR UT WOS:000226930900003 PM 15670622 ER PT J AU Chen, JT Wesley, R Shamburek, RD Pucino, F Csako, G AF Chen, JT Wesley, R Shamburek, RD Pucino, F Csako, G TI Meta-analysis of natural therapies for hyperlipidemia: Plant sterols and stanols versus policosanol SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Eastern States Conference for Pharmacy Residents and Preceptors CY MAY 01-03, 2003 CL Baltimore, MD DE hyperlipidemia; policosanol; plant sterols; plant stanols; natural therapy; cholesterol; hypercholesterolemia; LDL ID LOW-DENSITY-LIPOPROTEIN; SERUM-CHOLESTEROL CONCENTRATIONS; SITOSTANOL-ESTER MARGARINE; SUCCESSIVE DOSE INCREASES; CORONARY-HEART-DISEASE; LOW-FAT DIET; II HYPERCHOLESTEROLEMIA; LIPID PROFILE; HEALTHY-VOLUNTEERS; DOUBLE-BLIND AB Study Objective. To compare the efficacy and safety of plant sterols and stanols as well as policosanol in the treatment of coronary heart disease, as measured by a reduction in low-density lipoprotein cholesterol (LDL) levels. Design. Systematic review and meta-analysis of randomized controlled trials. Patients. A total of 4596 patients from 52 eligible studies. Measurements and Main Results. We searched MEDLINE, EMBASE, the Web of Science, and the Cochrane Library from January 1967-June 2003 to identify pertinent studies. Reduction of LDL levels was the primary end point; effects on other lipid parameters and withdrawal of study patients due to adverse effects were the secondary end points. Weighted estimates of percent change in LDL were -11.0% for plant sterol and stanol esters 3.4 g/day (range 2-9 g/day [893 patients]) versus -2.3% for placebo (769 patients) in 23 eligible studies, compared with -23.7% for policosanol 12 mg/day (range 5-40 mg/day [1528 patients]) versus -0.11% for placebo (1406 patients) in 29 eligible studies. Cumulative p values were significantly different from placebo for both (p<0.0001). The net LDL reduction in the treatment groups minus that in the placebo groups was greater with policosanol than plant sterols and stanols (-24% versus -10%, p<0.0001). Policosanol also affected total cholesterol, high-density lipoprotein cholesterol (HDL), and triglyceride levels more favorably than plant sterols and stanols. Policosanol caused a clinically significant decrease in the LDL:HDL ratio. Pooled withdrawal rate due to adverse effects and combined relative risk for patients who withdrew were 0% and 0.84, respectively (95% confidence interval [CI] 0.36-1.95, p=0.69), for plant sterols and stanols across 20 studies versus 0.86% and 0.31, respectively (95% CI 0.20-0.48, p<0.0001), for policosanol across 28 studies. Conclusion. Plant sterols and stanols and policosanol are well tolerated and safe; however, policosanol is more effective than plant sterols and stanols for LDL level reduction and more favorably alters the lipid profile, approaching antilipemic drug efficacy. C1 Purdue Univ, Sch Pharm & Pharmacal Sci, W Lafayette, IN 47907 USA. NHLBI, Dept Pharm, Bethesda, MD 20892 USA. NHLBI, Biostat & Clin Epidemiol Serv, Bethesda, MD 20892 USA. NHLBI, Dept Lab Med, Bethesda, MD 20892 USA. NHLBI, Mol Dis Branch, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Warren G Magnuson Clin Ctr, Bethesda, MD USA. RP Chen, JT (reprint author), Purdue Univ, Dept Pharm Practice, R Heine Pharm Bldg,Room 502D,575 Stadium Mall Dr, W Lafayette, IN 47907 USA. EM jtchen@pharmacy.purdue.edu NR 86 TC 57 Z9 61 U1 5 U2 11 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD FEB PY 2005 VL 25 IS 2 BP 171 EP 183 DI 10.1592/phco.25.2.171.56942 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 894MR UT WOS:000226796500004 PM 15767233 ER PT J AU McCardle, P Chhabra, V AF McCardle, P Chhabra, V TI Motivation and commitment in the interest of science and our children SO PHI DELTA KAPPAN LA English DT Editorial Material C1 NICHD, Ctr Res Mothers & Children, NIH, Washington, DC USA. RP McCardle, P (reprint author), NICHD, Ctr Res Mothers & Children, NIH, Washington, DC USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU PHI DELTA KAPPA PI BLOOMINGTON PA 8TH AND UNION P O BOX 789, BLOOMINGTON, IN 47402 USA SN 0031-7217 J9 PHI DELTA KAPPAN JI Phi Delta Kappan PD FEB PY 2005 VL 86 IS 6 BP 448 EP 451 PG 4 WC Education & Educational Research SC Education & Educational Research GA 897ZA UT WOS:000227044200008 ER PT J AU Bisova, K Krylov, DM Umen, JG AF Bisova, K Krylov, DM Umen, JG TI Genome-wide annotation and expression profiling of cell cycle regulatory genes in Chlamydomonas reinhardtii SO PLANT PHYSIOLOGY LA English DT Review ID CDK-ACTIVATING KINASE; RETINOBLASTOMA PROTEIN HOMOLOG; BRIGHT YELLOW-2 CELLS; RNA-POLYMERASE-II; E2F FAMILY-MEMBER; DEPENDENT KINASES; ARABIDOPSIS-THALIANA; FISSION YEAST; TRANSCRIPTION FACTORS; E2F-REGULATED GENES AB Eukaryotic cell cycles are driven by a set of regulators that have undergone lineage-specific gene loss, duplication, or divergence in different taxa. It is not known to what extent these genomic processes contribute to differences in cell cycle regulatory programs and cell division mechanisms among different taxonomic groups. We have undertaken a genome-wide characterization of the cell cycle genes encoded by Chlamydomonas reinhardtii, a unicellular eukaryote that is part of the green algal/land plant clade. Although Chlamydomonas cells divide by a noncanonical mechanism termed multiple fission, the cell cycle regulatory proteins from Chlamydomonas are remarkably similar to those found in higher plants and metazoans, including the proteins of the RB-E2F pathway that are absent in the fungal kingdom. Unlike in higher plants and vertebrates where cell cycle regulatory genes have undergone extensive duplication, most of the cell cycle regulators in Chlamydomonas have not. The relatively small number of cell cycle genes and growing molecular genetic toolkit position Chlamydomonas to become an important model for higher plant and metazoan cell cycles. C1 Salk Inst Biol Studies, La Jolla, CA 92037 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Umen, JG (reprint author), Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM umen@salk.edu RI Bisova, Katerina/H-2625-2014; Umen, James/K-9120-2013 OI Bisova, Katerina/0000-0003-1997-0894; Umen, James/0000-0003-4094-9045 NR 130 TC 74 Z9 81 U1 1 U2 14 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD FEB PY 2005 VL 137 IS 2 BP 475 EP 491 DI 10.1104/pp.104.054155 PG 17 WC Plant Sciences SC Plant Sciences GA 899AI UT WOS:000227116900007 PM 15710686 ER PT J AU Bhan, MK Berkley, S DeWilde, M Esparza, J Fauci, AS Gayle, H Johnston, MI Kaleebu, P Kazatch-Kine, MD Klausner, RD Lander, ES Makgoba, MW Mocumbi, P Piot, P Quintana-Trias, O Snow, W Walport, MJ Wigzell, H AF Bhan, MK Berkley, S DeWilde, M Esparza, J Fauci, AS Gayle, H Johnston, MI Kaleebu, P Kazatch-Kine, MD Klausner, RD Lander, ES Makgoba, MW Mocumbi, P Piot, P Quintana-Trias, O Snow, W Walport, MJ Wigzell, H CA Coordinating Comm Global HIV AIDS TI The global HIV/AIDS vaccine enterprise: Scientific strategic plan SO PLOS MEDICINE LA English DT Editorial Material ID HIV VACCINES; AIDS VACCINE; INFECTION; TRANSMISSION; IMMUNITY; ESCAPE; NEUTRALIZATION; RESPONSES; MACAQUES; CELLS C1 Bill & Melinda Gates Fdn, Seattle, WA USA. Dept Biotechnol, New Delhi, India. Int AIDS Vaccine Initiat, New York, NY USA. Aventis Pasteur, Swiftwater, PA USA. NIH, Bethesda, MD 20892 USA. Uganda Virus Res Inst, Entebbe, Uganda. Agence Natl Rech SIDA, Paris, France. MIT, Cambridge, MA USA. Univ KwaZulu Natal, Durban, South Africa. European & Dev Countries Clin Trials Partnership, The Hague, Netherlands. UN Programme HIV AIDS, Geneva, Switzerland. Commiss European Communities, B-1049 Brussels, Belgium. AIDS Vaccines Advocacy Coalit, New York, NY USA. Wellcome Trust Res Labs, London, England. Karolinska Inst, Stockholm, Sweden. RP Esparza, J (reprint author), Bill & Melinda Gates Fdn, Seattle, WA USA. EM josee@gatesfoundation.org OI Walport, Mark/0000-0001-7220-5273 NR 28 TC 6 Z9 7 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD FEB PY 2005 VL 2 IS 2 BP 111 EP 121 AR e25 DI 10.1371/journal.pmed.0020025 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 909JR UT WOS:000227856700015 ER PT J AU Shu, S Liu, X Korn, ED AF Shu, S Liu, X Korn, ED TI Blebbistatin and blebbistatin-inactivated myosin II inhibit myosin II-independent processes in Dictyostelium SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE phagocytosis; macropinocytosis; cell streaming; development ID HEAVY-CHAIN GENE; ACANTHAMOEBA MYOSIN; MOTOR DOMAIN; CYTOKINESIS; DISRUPTION; MECHANISM; VII AB Blebbistatin, a cell-permeable inhibitor of class-II myosins, was developed to provide a tool for studying the biologic roles of myosin II. Consistent with this use, we find that blebbistatin inhibits three myosin II-dependent processes in Dictyostelium (growth in suspension culture, capping of Con A receptors, and development to fruiting bodies) and does not inhibit growth on plates, which does not require myosin II. As expected, macropinocytosis (myosin I-dependent), contractile vacuole activity (myosin V-dependent), and phagocytosis (myosin VII-dependent) none of which requires myosin II, are not inhibited by blebbistatin in myosin II-null cells, but, unexpectedly, blebbistatin does inhibit macropinocytosis and phagocytosis by cells expressing myosin II. Expression of catalytically inactive myosin II in myosin II-null cells also inhibits macropinocytosis and phagocytosis. Both blebbistatin-inhibited myosin II and catalytically inactive myosin II form cytoplasmic aggregates, which may be why they inhibit myosin II-independent processes, but neither affects the distribution of actin filaments in vegetative cells or actin and myosin distribution in dividing or polarized cells. Blebbistatin also inhibits cell streaming and plaque expansion in myosin II-null cells. Our results are consistent with myosin II being the only Dictyostelium myosin that is inhibited by blebbistatin but also show that blebbistatin-inactivated myosin II inhibits some myosin II-independent processes and that blebbistatin inhibits other activities in the absence of myosin II. C1 NHLBI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Korn, ED (reprint author), NIH, Bldg 50,Room 2517, Bethesda, MD 20892 USA. EM edk@nih.gov RI Korn, Edward/F-9929-2012 NR 26 TC 68 Z9 68 U1 2 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 2005 VL 102 IS 5 BP 1472 EP 1477 DI 10.1073/pnas.0409528102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 895QF UT WOS:000226877300041 PM 15671182 ER PT J AU Reina-San-Martin, B Nussenzweig, MC Nussenzweig, A Difilippantonio, S AF Reina-San-Martin, B Nussenzweig, MC Nussenzweig, A Difilippantonio, S TI Genomic instability, endoreduplication, and diminished Ig class-switch recombination in B cells lacking Nbs1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NIJMEGEN BREAKAGE SYNDROME; CYTIDINE DEAMINASE AID; URACIL-DNA GLYCOSYLASE; S-MU REGION; SOMATIC HYPERMUTATION; MRE11 COMPLEX; TARGETED DISRUPTION; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; ANTIBODY DIVERSITY AB Mre11, Rad50, and Nbs1 form an evolutionarily conserved protein complex (Mre11-Rad50-Nbs1, MRN) that has been proposed to function as a DNA damage sensor. Hypomorphic mutations in Mre11 and Nbs1 result in the human ataxia-telangiectasia-like disorder and Nijmegen breakage syndrome (NBS), respectively. In contrast, complete inactivation of Mre11, Rad50, or Nbs1 leads to early embryonic lethality, suggesting that the hypomorphic mutations may fail to reveal some of the essential functions of MRN. Here, we use Cre-loxP-mediated recombination to restrict Nbs1 deletion to B lymphocytes. We find that disruption of Nbs1 results in the accumulation of high levels of spontaneous DNA damage, impaired proliferation, and chromosomal endoreduplication. Moreover, we show that Ig class-switch recombination (CSR) Is diminished in Nbs1-deficient B cells. The CSR defect is B cell-intrinsic, independent of switch-region transcription, and a consequence of inefficient recombination at the DNA level. Our findings reveal that Nbs1 is critical for efficient Ig CSR and maintenance of the integrity of chromosomal structure and number. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM andre_nussenzweig@nih.gov RI Reina-San-Martin, Bernardo/I-9484-2016 OI Reina-San-Martin, Bernardo/0000-0003-2083-6166 NR 60 TC 95 Z9 98 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 2005 VL 102 IS 5 BP 1590 EP 1595 DI 10.1073/pnas.0406289102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 895QF UT WOS:000226877300061 PM 15668392 ER PT J AU Vorup-Jensen, T Carman, CV Shimaoka, M Schuck, P Svitel, J Springer, TA AF Vorup-Jensen, T Carman, CV Shimaoka, M Schuck, P Svitel, J Springer, TA TI Exposure of acidic residues as a danger signal for recognition of fibrinogen and other macromolecules by integrin alpha x beta(2) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE plasmin; scavenger receptor ID CD11B A-DOMAIN; CRYSTAL-STRUCTURE; CR3 CD11B/CD18; IMMUNE-SYSTEM; I-DOMAIN; ADHESION; RECEPTORS; BINDING; LIGAND; AFFINITY AB The structural integrity of tissue proteins is damaged in processes ranging from remodeling of the extracellular matrix to destruction by microbial pathogens. Leukocytes play a prominent role in tissue surveillance and repair. However, it remains enigmatic what features of structurally decayed proteins prompt recognition by leukocyte cell-surface receptors. Here, we report that adhesion of human neutrophil granulocytes to fibrinogen is greatly increased by plasmin digestion in a mode where alpha(X)beta(2) dominates the integrin-dependent binding. The bacterial protease subtilisin also enhances binding by alpha(X)beta(2). The a(X) ligand binding domain has an unusually high affinity for carboxyl groups, with K-D at approximate to100 muM. Our findings implicate enhanced accessibility of negatively charged residues in structurally decayed proteins as a pattern recognition motif for alpha(X)beta(2) integrin. Comparisons among integrins show relevance of these findings to the large number of ligands recognized by alpha(M)beta(2) and alpha(X)beta(2) but not alpha(L)beta(2). The observations suggest that the pericellular proteolysis at the leading edge of neutrophils not only facilitates passage through the extracellular matrix but also manufactures binding sites for alpha(X)beta(2). C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM springer@cbr.med.harvard.edu RI Carman, Christopher/L-8108-2016; OI Carman, Christopher/0000-0001-7358-2548; Schuck, Peter/0000-0002-8859-6966; Vorup-Jensen, Thomas/0000-0002-4140-6563 FU NCI NIH HHS [R01 CA031799, CA31799] NR 42 TC 59 Z9 60 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 2005 VL 102 IS 5 BP 1614 EP 1619 DI 10.1073/pnas.0409057102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 895QF UT WOS:000226877300065 PM 15665082 ER PT J AU Celli, J Salcedo, SP Gorvel, JP AF Celli, J Salcedo, SP Gorvel, JP TI Brucella coopts the small GTPase Sar1 for intracellular replication SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE macrophage; secretory pathway; endoplasmic reticulum; pathogenesis ID TO-GOLGI TRANSPORT; ENDOPLASMIC-RETICULUM; EXIT SITES; COPII; IDENTIFICATION; PROTEIN; VECTOR; VIRB; TRAFFICKING; COMPARTMENT AB The pathogen Brucella abortus resides inside macrophages within a unique, replication-permissive organelle that is derived from the endoplasmic reticulum (ER). Although dependent on the Brucella type IV secretion system VirB, the mechanisms governing the biogenesis of this compartment remain elusive. Here, we investigated a putative role of the early secretory pathway in ER membrane accretion by the Brucella-containing vacuoles (BCVs). We show that BCVs interact with ER exit sites (ERES), and blockade of Sar1 activity, which disrupts ERES, prevents intracellular replication of Brucella. In cells expressing the dominant interfering form Sar1[T39N], BCVs do not acquire ER membranes, suggesting that they are unable to mature into replicative organelles. By contrast, treatments that block subsequent secretory events do not affect bacterial replication. We propose that Sar1-dependent ERES functions, but not subsequent secretory events, are essential for the biogenesis of the Brucella replicative compartment and, thus, bacterial replication. These results assign an essential role for Sar1 in pathogenesis of an intracellular bacterium. C1 Univ Mediterranee, CNRS, INSERM, Ctr Immunol Marseille Luminy, F-13288 Marseille 09, France. RP Celli, J (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM jcelli@niaid.nih.gov RI salcedo, suzana/C-2853-2014; OI salcedo, suzana/0000-0001-5149-7756; Gorvel, Jean-Pierre/0000-0002-2829-9804 NR 25 TC 101 Z9 107 U1 2 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 2005 VL 102 IS 5 BP 1673 EP 1678 DI 10.1073/pnas.0406873102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 895QF UT WOS:000226877300075 PM 15632218 ER PT J AU Sumby, P Barbian, KD Gardner, DJ Whitney, AR Welty, DM Long, RD Bailey, JR Parnell, MJ Hoe, NP Adams, GG DeLeo, FR Musser, JM AF Sumby, P Barbian, KD Gardner, DJ Whitney, AR Welty, DM Long, RD Bailey, JR Parnell, MJ Hoe, NP Adams, GG DeLeo, FR Musser, JM TI Extracellular deoxyribonuclease made by group A Streptococcus assists pathogenesis by enhancing evasion of the innate immune response SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE virulence factor; Streptococcus pyogenes; neutrophil extracellular traps ID COMPLETE GENOME SEQUENCE; SEROTYPE M3 STRAIN; PYOGENES; PROTEIN; EXPRESSION; DNASE; DIVERSITY; INFECTION; TOXIN AB Many pathogenic bacteria produce extracellular DNase, but the benefit of this enzymatic activity is not understood. For example, all strains of the human bacterial pathogen group A Streptococcus (GAS) produce at least one extracellular DNase, and most strains make several distinct enzymes. Despite six decades of study, it is not known whether production of DNase by GAS enhances virulence. To test the hypothesis that extracellular DNase is required for normal progression of GAS infection, we generated seven isogenic mutant strains in which the three chromosomal- and prophage-encoded DNases made by a contemporary serotype M1 GAS strain were inactivated. Compared to the wild-type parental strain, the isogenic triple-mutant strain was significantly less virulent in two mouse models of invasive infection. The triple-mutant strain was cleared from the skin injection site significantly faster than the wild-type strain. Preferential clearance of the mutant strain was related to the differential extracellular killing of the mutant and wild-type strains, possibly through degradation of neutrophil extracellular traps, innate immune structures composed of chromatin and granule proteins. The triple-mutant strain was also significantly compromised in its ability to cause experimental pharyngeal disease in cynomolgus macaques. Comparative analysis of the seven DNase mutant strains strongly suggested that the prophage-encoded SdaD2 enzyme is the major DNase that contributes to virulence in this clone. We conclude that extracellular DNase activity made by GAS contributes to disease progression, thereby resolving a long-standing question in bacterial pathogenesis research. C1 Baylor Coll Med, Ctr Human Bacterial Pathogenesis Res, Dept Pathol, Houston, TX 77030 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Musser, JM (reprint author), Baylor Coll Med, Ctr Human Bacterial Pathogenesis Res, Dept Pathol, 1 Baylor Plaza, Houston, TX 77030 USA. EM musser@bcm.tmc.edu OI DeLeo, Frank/0000-0003-3150-2516 NR 37 TC 188 Z9 199 U1 1 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 2005 VL 102 IS 5 BP 1679 EP 1684 DI 10.1073/pnas.0406641102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 895QF UT WOS:000226877300076 PM 15668390 ER PT J AU Takahashi, S Ohshima, T Cho, A Sreenath, T Iadarola, MJ Pant, HC Kim, Y Nairn, AC Brady, RO Greengard, P Kulkarni, AB AF Takahashi, S Ohshima, T Cho, A Sreenath, T Iadarola, MJ Pant, HC Kim, Y Nairn, AC Brady, RO Greengard, P Kulkarni, AB TI Increased activity of cyclin-dependent kinase 5 leads to attenuation of cocaine-mediated dopamine signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cocaine addiction; phosphorylation; striatum ID ELEMENT-BINDING PROTEIN; GENE-EXPRESSION; DELTA-FOSB; MOLECULAR-BASIS; PHOSPHORYLATION; BRAIN; DARPP-32; NEURONS; CDK5; PLASTICITY AB Cocaine, a drug of abuse, increases synaptic dopamine levels in the striatum by blocking doparmine reuptake at axon terminals. Cyclin-dependent kinase 5 (Cdk5) and its activator p35, proteins involved in phosphorylation of substrates in postmitotic neurons, have been found to be up-regulated after chronic exposure to cocaine. To further examine the effects of Cdk5 and p35 induction on striatal dopamine signaling, we generated two independent transgenic mouse lines in which Cdk5 or p35 was overexpressed specifically in neurons. We report here that increased Cdk5 activity, as a result of p35 but not of Cdk5 overexpression, leads to attenuation of cocaine-mediated dopamine signaling. Increased Cdk5-mediated phosphorylation of dopamine and cAMP-regulated phosphoprotein, molecular mass 32 kDa (DARPP-32) at Thr-75, was accompanied by decreased phosphorylation of DARPP-32 at Thr-34. Increased Cdk5-mediated phosphorylation of extracellular signal-regulated kinase kinase 1 at Thr-286 was accompanied by decreased activation of extracellular signal-regulated kinase 1/2. These effects contributed to attenuation of cocaine-induced phosphorylation of cAMP response element-binding protein as well as a lesser induction of c-fos in the striatum. These results support the idea that Cdk5 activity is involved in altered gene expression after chronic exposure to. cocaine and hence impacts the long-lasting changes in neuronal function underlying cocaine addiction. C1 Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RIKEN, Dev Neurobiol Lab, Brain Sci Inst, Wako, Saitama 3510198, Japan. Natl Inst Dent & Craniofacial Res, Gene Targeting Facil, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA. RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, 30 Convent Dr, Bethesda, MD 20892 USA. EM ak40m@nih.gov OI Nairn, Angus/0000-0002-7075-0195 FU NIDA NIH HHS [P01 DA010044, DA10044]; NIDCR NIH HHS [Z01 DE000664, Z01DE00664-05] NR 28 TC 56 Z9 60 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 2005 VL 102 IS 5 BP 1737 EP 1742 DI 10.1073/pnas.0409456102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 895QF UT WOS:000226877300086 PM 15665076 ER PT J AU Yusof, AM Hu, NJ Wlodawer, A Hofmann, A AF Yusof, AM Hu, NJ Wlodawer, A Hofmann, A TI Structural evidence for variable oligomerization of the N-terminal domain of cyclase-associated protein (CAP) SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE ASP-56; CAP; crystal structure; MCH1; protein crystallography; protein-protein interactions; Srv2 ID ELECTRON-DENSITY MAPS; ADENYLYL-CYCLASE; SACCHAROMYCES-CEREVISIAE; DICTYOSTELIUM-DISCOIDEUM; ACTIN POLYMERIZATION; CELL POLARITY; YEAST; PROFILIN; COFILIN; COMPLEX AB Cyclase-associated protein (CAP) is a highly conserved and widely distributed protein that links the nutritional response signaling to cytoskeleton remodeling. In yeast, CAP is a component of the adenylyl cyclase complex and helps to activate the Ras-mediated catalytic cycle of the cyclase. While the N-terminal domain of CAP (N-CAP) provides a binding site for adenylyl cyclase, the C-terminal domain (C-CAP) possesses actin binding activity. Our attempts to crystallize full-length recombinant CAP from Dictyostelium discoideum resulted in growth of orthorhombic crystals containing only the N-terminal domain (residues 42-227) due to auto-proteolytic cleavage. The structure was solved by molecular replacement with data at 2.2 Angstrom resolution. The present crystal structure allows the characterization of a head-to-tail N-CAP dimer in the asymmetric unit and a crystallographic side-to-side dimer. Comparison with previously published structures of N-CAP reveals variable modes of dimerization of this domain, but the presence of a common interface for the side-to-side dimer. (C)2004 Wiley-Liss, Inc. C1 Univ Edinburgh, Inst Struct & Mol Biol, Sch Biol Sci, Edinburgh EH9 3JR, Midlothian, Scotland. NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA. RP Hofmann, A (reprint author), Univ Edinburgh, Inst Struct & Mol Biol, Sch Biol Sci, Kings Bldg,Mayfield Rd, Edinburgh EH9 3JR, Midlothian, Scotland. EM Andreas.Hofmann@ed.ac.uk RI Hofmann, Andreas/B-9515-2008 OI Hofmann, Andreas/0000-0003-4408-5467 NR 42 TC 18 Z9 20 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD FEB 1 PY 2005 VL 58 IS 2 BP 255 EP 262 DI 10.1002/prot.20314 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 886PZ UT WOS:000226242100001 PM 15558566 ER PT J AU Nelson, EE Leibenluft, E McClure, EB Pine, DS AF Nelson, EE Leibenluft, E McClure, EB Pine, DS TI The social re-orientation of adolescence: a neuroscience perspective on the process and its relation to psychopathology SO PSYCHOLOGICAL MEDICINE LA English DT Review ID EMOTIONAL FACIAL EXPRESSIONS; MAJOR DEPRESSIVE DISORDER; ORBITOFRONTAL CORTEX; GENDER-DIFFERENCES; BIOLOGICAL MOTION; SEXUAL-BEHAVIOR; LIFE EVENTS; INBREEDING AVOIDANCE; AMYGDALA RESPONSE; ANXIETY DISORDER AB Background. Many changes in social behavior take place during adolescence. Sexuality and romantic interests emerge during this time, and adolescents spend more time with peers and less time with parents and family. While such changes in social behavior have been well documented in the literature, relatively few neurophysiological explanations for these behavioral changes have been presented. Method. In this article we selectively review studies documenting (a) the neuronal circuits that are dedicated to the processing of social information; (b) the changes in social behavior that take place during adolescence; (c) developmental alterations in the adolescent brain; and (a) links between the emergence of mood and anxiety disorders in adolescence and changes in brain physiology occurring at that time. Results. The convergence of evidence from this review indicates a relationship between development of brain physiology and developmental changes in social behavior. Specifically, the surge of gonadal steroids at puberty induces changes within the limbic system that alters the emotional attributions applied to social stimuli while the gradual maturation of the prefrontal cortex enables increasingly complex and controlled responses to social information. Conclusions. Observed alterations in adolescent social behavior reflect developmental changes in the brain social information processing network. We further speculate that dysregulation of the social information processing network in this critical period may contribute to the onset of mood and anxiety disorders during adolescence. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Nelson, EE (reprint author), NIMH, Mood & Anxiety Disorders Program, Bldg 106-C,5413 W Cedar Lane, Bethesda, MD 20892 USA. EM nelsone@intra.nimh.nih.gov RI Nelson, Eric/B-8980-2008 OI Nelson, Eric/0000-0002-3376-2453 NR 105 TC 354 Z9 359 U1 18 U2 180 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD FEB PY 2005 VL 35 IS 2 BP 163 EP 174 DI 10.1017/S0033291704003915 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 959EI UT WOS:000231499500001 PM 15841674 ER PT J AU Hahn, B Stolerman, IP AF Hahn, B Stolerman, IP TI Modulation of nicotine-induced attentional enhancement in rats by adrenoceptor antagonists SO PSYCHOPHARMACOLOGY LA English DT Article DE nicotine; attention; serial reaction time; noradrenaline; prazosin; propranolol ID REACTION-TIME-TASK; LOCUS-COERULEUS NEURONS; NOREPINEPHRINE RELEASE; COGNITIVE PERFORMANCE; D-AMPHETAMINE; HUMAN BRAIN; RECEPTORS; DOPAMINE; CORTEX; VIGILANCE AB Rationale: Understanding the neuropharmacological mechanisms mediating attentional enhancement by nicotine would help a targeted search for nicotinic compounds with retained therapeutic but reduced unwanted side-effects. Previous studies suggested that the dopamine-releasing effects of nicotine may not be of primary importance for its attention-enhancing properties. Objectives: The present study examined the role of noradrenergic neurotransmission for the effects of nicotine on different response indices of an attentional paradigm. Methods: The effects of systemic injections of the alpha(1)-adrenoceptor antagonist prazosin that also displays significant affinity at alpha(2B) and alpha(2C)-adrenoceptors and the beta-adrenoceptor antagonist propranolol were tested in both the presence and absence of nicotine in rats trained in a version of the five-choice serial reaction time task. Results: Nicotine generally enhanced the accuracy of signal detection, reduced omission errors and shortened response latencies. At the largest doses tested, both prazosin (1 mg/kg) and propranolol (10 mg/kg) impaired performance. For propranolol, these effects depended on the rate of target signal presentation. The two compounds differentially modulated the effects of nicotine. Propranolol (6 mg/kg and 10 mg/kg) but not prazosin reduced its effects on omission errors and accuracy. By contrast, prazosin (0.5 mg/kg) reversed the nicotine-induced reductions in response latency. Conclusions: The data provide the first evidence that beta-adrenoceptors are involved in mediating the effects of nicotine on signal detection, while activation of alpha-adrenoceptors may contribute to its effects on response speed. This is a further indication that, from among nicotine's wide range of neuropharmacological effects, specific facets can be dissociated that are responsible for its attention-enhancing properties. C1 NIDA, Neuroimaging Res Branch, NIH, IRP, Baltimore, MD 21224 USA. Inst Psychiat, Sect Behav Pharmacol, London SE5 8AF, England. RP Hahn, B (reprint author), NIDA, Neuroimaging Res Branch, NIH, IRP, 5500 Nathan Schock Dr, Baltimore, MD 21224 USA. EM bhahn@intra.nida.nih.gov RI Hahn, Britta/G-4593-2012; OI Stolerman, Ian/0000-0002-2703-5137 NR 56 TC 16 Z9 16 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 2005 VL 177 IS 4 BP 438 EP 447 DI 10.1007/s00213-004-1969-5 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 884RU UT WOS:000226104500010 PM 15252705 ER PT J AU Likhtarov, I Kovgan, L Vavilov, S Chepurny, M Bouville, A Luckyanov, N Jacob, P Voilleque, P Voigt, G AF Likhtarov, I Kovgan, L Vavilov, S Chepurny, M Bouville, A Luckyanov, N Jacob, P Voilleque, P Voigt, G TI Post-chornobyl thyroid cancers in ukraine. Report 1: Estimation of thyroid doses SO RADIATION RESEARCH LA English DT Article ID SHORT-LIVED RADIOIODINES; ACCIDENT; CHILDREN; BYELARUS; I-131; RISK AB About 1.8 EBq of (131)I was released into the atmosphere during the Chornobyl accident that occurred in Ukraine on April 26, 1986. More than 10% of this activity was deposited on the territory of Ukraine. Beginning 4-5 years after the accident, an increase in the incidence of thyroid cancer among children, believed to be caused in part by exposure to (131)I, has been observed in different regions of Ukraine. A three-level system of thyroid dose estimation was developed for the reconstruction of thyroid doses from (131)I for the entire population of Ukrainian children aged 1 to 18 at the time of accident: (1) At the first level, individual doses were estimated for the approximately 99,000 children and adolescents with direct measurements of radioactivity in the thyroid (so-called direct thyroid measurements) performed in May-June of 1986; (2) at the second level, group doses by year of age and by gender were estimated for the population of 748 localities (with 208,400 children aged 1-18 in 1986) where direct thyroid measurements of good quality were performed on some of the residents; and (3) at the third level, group doses by age and by gender were estimated for the population of the localities where no thyroid measurements were made in 1986. The third-level doses were then aggregated over the population of each oblast. Data, models and procedures required for each level of thyroid dose estimation are described in the paper. At the first level, individual doses were found to range up to 27,000 mGy, with geometric and arithmetic means of 100 and 300 mGy, respectively. At the second level, group doses were found to be highest for the younger children (aged 1 to 4 years); doses for the older children (aged 16 to 18 years) were 3.5 times smaller. At the third level, average population-weighted doses were found to exceed 35 mGy in the five northern oblasts closer to the Chornobyl reactor site; to be in the 14- to 34-mGy range in seven other oblasts, Kyiv city and Crimea; and to be less than 13 mGy in all other oblasts. (C) 2005 by Radiation Research Society. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,Radiat Epidemiol Branch,NIH, Bethesda, MD 20892 USA. Ukraine Acad Med Sci, Radiat Protect Inst, Sci Ctr Radiat Med, UA-04050 Kiev, Ukraine. MJP Risk Assessment Inc, Denver, CO 80230 USA. IAEA, Agcy Labs Seibersdorf, A-1400 Vienna, Austria. RP Bouville, A (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,Radiat Epidemiol Branch,NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM bouvilla@mail.nih.gov NR 37 TC 38 Z9 38 U1 1 U2 4 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD FEB PY 2005 VL 163 IS 2 BP 125 EP 136 DI 10.1667/RR3291 PG 12 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 892WF UT WOS:000226680000001 PM 15658887 ER PT J AU Yankaskas, BC Taplin, SH Ichikawa, L Geller, BM Rosenberg, RD Carney, PA Kerlikowske, K Ballard-Barbash, R Cutter, GR Barlow, WE AF Yankaskas, BC Taplin, SH Ichikawa, L Geller, BM Rosenberg, RD Carney, PA Kerlikowske, K Ballard-Barbash, R Cutter, GR Barlow, WE TI Association between mammography timing and measures of screening performances in the United States SO RADIOLOGY LA English DT Article ID HORMONE REPLACEMENT THERAPY; BREAST-CANCER; PROGRAM; WOMEN; SPECIFICITY; SENSITIVITY; SERVICE; EUROPE; ACCURACY; OUTCOMES AB PURPOSE: To evaluate whether there is an association between the number of months since previous mammography (MSPM), and performance measures (sensitivity, specificity, recall rate, cancer detection rated and positive predictive value) in women who underwent U.S. community-based screening mammography. MATERIALS AND METHODS: Data from seven registries (Breast Cancer Surveillance Consortium) and mammographic data and cancer outcome in regard to 1 213 754 screening mammographic', examinations performed in 680 641 women who were 40-89 years old for the years 1996-2000 were used in this study. These who were 40 data are submitted annually in a,standard format to a central statistical coordinating center that is subject to institutional, review board approval, quality control, and confidentiality standards. Performance measures were calculated for first and subsequent screening mammography. For subsequent mammography, performance measures were calculated according to categories of MSPM (9-15, 16-20, 21-27, and greater than or equal to28 months). Receiver operating characteristic and multivariable logistic regression analyses were conducted to test association between the number of MSPM and performance measures. RESULTS: With increasing MSPM in each category from 9-15 to 28 months or more and for first mammographic. examinations, respectively, there was increased sensitivity 70.9%, 75.70%, 85.4%, 82.5%, and 88.6%), decreased specificity (93.3%, 92.7%, 91.6%, 91.0%, and 85.9%), increased recall rate (7.0%, 7.6%, 8.8% 9.4%, and 14.7%), and increased cancer detection rates (3.2, 3.5, 4.5, 4.6, and 6.1 per 1000 mammographic examinations). When the category of 9-15 here MSPM was compared with that of 21-27 MSPM there was a slight increase in positive predictive value from 4.6% to 5.1%. Confidence intervals were narrow and did not overlap. Age affected these associations for all performance measures except sensitivity. CONCLUSION: Performance measures increased as MSPM increased, except for specificity, which decreased. Time between mammograms is an important factor to consider when audits are reviewed or screening performance measures are compared. C1 Univ N Carolina, Dept Radiol, Chapel Hill, NC 27599 USA. NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Vermont, Burlington, VT USA. Univ New Mexico, Dept Radiol, Albuquerque, NM 87131 USA. Norris Cotton Canc Ctr, Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH USA. Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. UCSF, Dept Med, San Francisco, CA USA. Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. Cooper Inst, Denver, CO USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Yankaskas, BC (reprint author), Univ N Carolina, Dept Radiol, CB 7515,106 Mason Farm Rd, Chapel Hill, NC 27599 USA. EM bcy@med.unc.edu NR 44 TC 70 Z9 71 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2005 VL 234 IS 2 BP 363 EP 373 DI 10.1148/radiol.2342040048 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 890AD UT WOS:000226483200010 PM 15670994 ER PT J AU Yuh, EL Shulman, SG Mehta, SA Xie, JW Chen, LL Frenkel, V Bednarski, MD Li, KCP AF Yuh, EL Shulman, SG Mehta, SA Xie, JW Chen, LL Frenkel, V Bednarski, MD Li, KCP TI Delivery of systemic chemotherapeutic agent to tumors by using focused ultrasound: Study in a murine model SO RADIOLOGY LA English DT Article ID HUMAN BREAST-CANCER; DRUG-DELIVERY; IN-VIVO; SOLID TUMORS; LIPOSOMAL DOXORUBICIN; ANTITUMOR-ACTIVITY; PROSTATE-CANCER; XENOGRAFT MODEL; THERAPY; HYPERTHERMIA AB PURPOSE: To quantitatively determine the delivery of systemic liposomal doxorubicin to tumors treated with pulsed high-intensity focused ultrasound and to study the mechanism underlying this delivery in a murine model. MATERIALS AND METHODS: All animal work was performed in compliance with guidelines and approval of institutional animal care committee. C3H mice received subcutaneous injections in the flank of a-cell suspension of SCC7, a murine squamous cell carcinoma cell line; mice (n = 32) in drug delivery study received unilateral injections, whereas mice (n = 10) in mechanistic study received bilateral injections. Tumors were treated when they reached 1 cm(3) in volume. In the drug delivery study, doxorubicin hydrochloride liposomes were injected into the tail vein: Mice received therapy with doxorubicin injections and high-intensity focused ultrasound, doxorubicin injections alone, or neither form of therapy (controls). Tumors were removed, and the,doxorubicin content was assayed with fluorescent spectrophotometry. In the mechanistic study, all mice received an injection of 500-kDa dextran-fluorescein isothyocyanate into the tail vein, and half of them were exposed to high-intensity focused ultrasound prior to injection. Contralateral tumors served as controls for each group. Extravasation of dextranfluorescein isothyocyanate was observed by using in vivo confocal microscopy. RESULTS: Mean doxorubicin concentration in tumors treated with pulsed high-intensity focused ultrasound was 9.4 mug . g(-1) +/- 2.1 (standard deviation), and it was significantly higher (124% [9.4 mug . g(-1)/4.2 mug . g(-1)]) than in those that were not treated with high-intensity focused ultrasound (4.2 mug . g(-1) +/- 0.95) (P <.001, unpaired two-tailed Student t test). Extravasation of dextran-fluorescein isothyocyanate was observed in the vasculature of tumors treated with high-intensity focused ultrasound but not in that of untreated tumors. CONCLUSION: Pulsed high-intensity focused ultrasound is an effective method of targeting systemic drug delivery to tumor tissue. Potential mechanisms for producing the observed enhancement are discussed. C1 NIH, Dept Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Radiol, Lucas Magnet Resonance Imaging & Sprectroscopy Re, Stanford, CA 94305 USA. RP Frenkel, V (reprint author), NIH, Dept Radiol, Warren Grant Magnuson Clin Ctr, 10 Ctr Dr,Bldg 10,Room 1C657, Bethesda, MD 20892 USA. EM vfrenkel@cc.nih.gov NR 51 TC 83 Z9 88 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 2005 VL 234 IS 2 BP 431 EP 437 DI 10.1148/radiol.2342030889 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 890AD UT WOS:000226483200017 PM 15671000 ER PT J AU Graves, E Hitt, A Pariza, MW Cook, ME McCarthy, DO AF Graves, E Hitt, A Pariza, MW Cook, ME McCarthy, DO TI Conjugated linoleic acid preserves gastrocnemius muscle mass in mice bearing the colon-26 adenocarcinoma SO RESEARCH IN NURSING & HEALTH LA English DT Article DE colon-26 adenocarcinoma; cancer cachexia; mice; tumor necrosis factor; conjugated linoleic acid ID NF-KAPPA-B; GASTROINTESTINAL CANCER-PATIENTS; WEIGHT-LOSS; DIETARY SUPPLEMENTATION; PROSTAGLANDIN E-2; TUMOR-GROWTH; CACHEXIA; RATS; CYCLOOXYGENASE-2; EXPRESSION AB Cancer cachexia is a syndrome of weight loss, muscle wasting, fatigue, and anorexia that occurs in Patients with advanced or recurrent sol id tumor disease. Tumor necrosis factor-alpha (TNFalpha) and prostaglandin E2 (PGE2) have been implicated in the biology of cachexia and serve as possible targets for treatment of this condition. Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid that alters the synthesis of PGE2 and reduces the negative effects of TNF on body weight of healthy mice. We hypothesized that a diet supplemented with .5% CLA might reduce muscle wasting in mice bearing the colon-26 adenocarcinoma, an animal model of cancer cachexia. CLA preserved gastrocnemius muscle mass and reduced TNF receptors in muscle of tumor-bearing mice. These data suggest that CLA may preserve muscle mass by reducing the catabolic effects of TNF on skeletal muscle. (C) 2004 Wiley Periodicals, Inc. C1 NINR, NIH, Bethesda, MD USA. Univ Wisconsin, Coll Agr, Madison, WI USA. RP McCarthy, DO (reprint author), Room K6-326,600 Highland Ave, Madison, WI 53792 USA. RI McCarthy, Donna/A-3291-2013 NR 45 TC 21 Z9 21 U1 2 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD FEB PY 2005 VL 28 IS 1 BP 48 EP 55 DI 10.1002/nur.20052 PG 8 WC Nursing SC Nursing GA 887MJ UT WOS:000226309900006 PM 15625711 ER PT J AU Hitt, A Graves, E McCarthy, DO AF Hitt, A Graves, E McCarthy, DO TI Indomethacin preserves muscle mass and reduces levels of E3 ligases and TNF receptor type 1 in the gastrocnemius muscle of tumor-bearing mice SO RESEARCH IN NURSING & HEALTH LA English DT Article DE cancer cachexia; mice; indomethacin; ubiquitin ligase; colon-26 adeno-carcinoma; muscle wasting; Western blotting ID PROTEASOME PROTEOLYTIC PATHWAY; EXPERIMENTAL CANCER CACHEXIA; NF-KAPPA-B; SKELETAL-MUSCLE; PROTEIN-METABOLISM; MEDICAL-CENTER; MURINE MODEL; WEIGHT-LOSS; UBIQUITIN; EXPRESSION AB Tumor-induced skeletal muscle wasting involves tumor necrosis factor (TNF) and the ubiquitin-proteasome pathway of muscle protein degradation. In this study, growth of the colon-26 adenocarcinoma in mice was associated with diminished gastrocnemius muscle mass and increased muscle levels of actin, ubiquitin-conjugated proteins, free ubiquitin, E3 ubiquitin ligases, and the type 1 TNF receptor (TNFR1). Indomethacin at 1 or 5 mg/kg/day reduced tumor growth and muscle levels of TNFR1. However, only the 5 mg dose of indomethacin reduced muscle wasting and muscle levels of the E3 ligases and actin. These data suggest that the beneficial effects of indomethacin in the treatment of tumor-induced skeletal muscle wasting may involve inhibition of TNF- and ubiquitin-mediated pathways of muscle protein degradation. These data also demonstrate that E3 ligases, which are involved in disuse atrophy, also are associated with tumor-induced skeletal muscle wasting. (C) 2004 Wiley Periodicals, Inc. C1 NINR, NIH, Bethesda, MD USA. RP McCarthy, DO (reprint author), K6-326,600 Highland Ave, Madison, WI 53792 USA. RI McCarthy, Donna/A-3291-2013 NR 47 TC 18 Z9 18 U1 2 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD FEB PY 2005 VL 28 IS 1 BP 56 EP 66 DI 10.1002/nur.20057 PG 11 WC Nursing SC Nursing GA 887MJ UT WOS:000226309900007 PM 15625704 ER PT J AU Shi, Q AF Shi, Q TI Melatonin is involved in sex change of the ricefield eel, Monopterus albus zuiew SO REVIEWS IN FISH BIOLOGY AND FISHERIES LA English DT Article DE environmental factor; melatonin; pineal complex; ricefield eel; sex change; teleost ID CIRCULATING MELATONIN; PINEAL ORGAN; REVERSAL; RETINA; GLAND; BASS AB The ricefield eel (Monopterus albus Zuiew), a burrowing eel-like synbranchoid teleost, undergoes a natural sex change from female to male during its life history. Since the teleost pineal gland and its melatoninergic output have been suggested as regulators in seasonal reproduction and sexual maturation in many fish species, it is reasonable to postulate that melatonin may play important roles in the ricefield eel's sex-change process. This hypothesis was tested by examining secretional characteristics and reproductive effects of melatonin in the ricefield eel. Results indicate that serum melatonin (mainly secreted from the pineal complex, retinae and gastrointestinal tract) is involved in sex change of this species. It seems that, within a reproductive cycle, relatively lower mid-night serum melatonin (MNSM) levels are necessary for natural spawning, but relatively higher MNSM levels after spawning permit initiation of the sex-change process. A putative model is presented to clarify the involvement of melatonin in natural sex change of the ricefield eel, although the precise mechanisms are still under further investigation. C1 Zhongshan Univ, Sch Life Sci, Inst Aquat Econ Anim, Guangzhou 510275, Peoples R China. NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Shi, Q (reprint author), Zhongshan Univ, Sch Life Sci, Inst Aquat Econ Anim, Guangzhou 510275, Peoples R China. EM shiq@mail.nih.gov NR 34 TC 10 Z9 12 U1 3 U2 14 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0960-3166 J9 REV FISH BIOL FISHER JI Rev. Fish. Biol. Fish. PD FEB PY 2005 VL 15 IS 1-2 BP 23 EP 36 DI 10.1007/s11160-005-7848-2 PG 14 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 990EG UT WOS:000233725400002 ER PT J AU Khaliq, AA Smego, RA AF Khaliq, AA Smego, RA TI Barber shaving and blood-borne disease transmission in developing countries SO SAMJ SOUTH AFRICAN MEDICAL JOURNAL LA English DT Editorial Material ID C VIRUS-INFECTION; HEPATITIS-B; PREVALENCE; INJECTIONS; RISK C1 NIAID, Int Res TB Res Sect, NIH, Rockville, MD USA. Univ Oklahoma, Hlth Sci Ctr, Dept Hlth Policy & Adm, Coll Publ Hlth, Oklahoma City, OK USA. RP Smego, RA (reprint author), NIAID, Int Res TB Res Sect, NIH, Rockville, MD USA. EM rsmego@niaid.nih.gov NR 15 TC 15 Z9 17 U1 0 U2 0 PU MED ASSOC S AFRICA PI JOHANNESBURG PA MED HOUSE CENTRAL SQ 7430 PINELANDS PRIV BAG X1, JOHANNESBURG, SOUTH AFRICA SN 0256-9574 J9 SAMJ S AFR MED J JI SAMJ S. Afr. Med. J. PD FEB PY 2005 VL 95 IS 2 BP 94 EP + PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 899QV UT WOS:000227160600010 PM 15751200 ER PT J AU Song, X Tao, YG Tan, YN Lee, LM Deng, XY Wu, Q Cao, Y AF Song, X Tao, YG Tan, YN Lee, LM Deng, XY Wu, Q Cao, Y TI Heterodimer formation between c-Jun and Jun B proteins mediated by Epstein Barr virus encoded latent membrane protein 1 SO SCIENCE IN CHINA SERIES C-LIFE SCIENCES LA English DT Article DE Epstein barr virus; latent membrane protein 1; jun B; c-Jun; heterodimer; DNA binding; JNK; JIP ID NF-KAPPA-B; TRANSCRIPTION FACTORS; DNA-BINDING; CELLS; JNK; PHOSPHORYLATION; EXPRESSION; PATHWAY; DIFFERENTIATION; OVEREXPRESSION AB Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) may trigger the transcription factor AP-1 including c-Jun and c-fos. In this report, using a Tet-on LMP1 HNE2 cell line which is a dual-stable LMP1 integrated nasopharyngeal carcinoma (NPC) cell line and the expression of LMP1 in which could be regulated by the Tet-on system, we show that Jun B can efficiently form a new heterodimeric complex with the c-Jun protein under the regulation of LMP1, phosphorylation of c-Jun (ser 63, ser 73) and Jun B is involved in the process of the new heterodimeric formation. We also find that this heterodimeric form can bind to the AP-1 consensus sequence. Transfection studies suggest that JNK interaction protein (JIP) could inhibit the heterodimer formation of c-Jun and Jun B through blocking the AP-1 signaling pathway triggered by LMP1. The interaction and function between c-Jun protein and Jun B protein increase the repertoire of possible regulatory complexes by LMP1 that could play an important role in the regulation of transcription of specific cellular genes in the process of genesis of nasopharyngeal carcinoma. C1 Cent S Univ, Xiangya Sch Med, Inst Canc Res, Changsha 410078, Peoples R China. Natl Canc Inst, SAIC Frederick, Lab Mol Technol, Ft Detrick, MD 21702 USA. Xiamen Univ, Sch Life Sci, Key Lab Minist Educ Cell Biol & Tumor Cell Engn, Xiamen 361005, Peoples R China. RP Cao, Y (reprint author), Cent S Univ, Xiangya Sch Med, Inst Canc Res, Changsha 410078, Peoples R China. EM ycao98@public.cs.hn.cn RI Cao, Ya/C-6801-2008; Wu, Q/G-4646-2010 NR 42 TC 3 Z9 3 U1 0 U2 0 PU SCIENCE CHINA PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1006-9305 J9 SCI CHINA SER C JI Sci. China Ser. C-Life Sci. PD FEB PY 2005 VL 48 IS 1 BP 70 EP 80 DI 10.1360/03yc0218 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 913YE UT WOS:000228190700009 PM 15844359 ER PT J AU Pierce, S Harder, T AF Pierce, S Harder, T TI Spatial organization in immune cell signaling SO SEMINARS IN IMMUNOLOGY LA English DT Editorial Material C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 2ET, England. RP Pierce, S (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM spierce@nih.gov; thomas.harder@path.ox.ac.uk NR 0 TC 0 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD FEB PY 2005 VL 17 IS 1 BP 1 EP 2 DI 10.1016/j.smim.2004.09.009 PG 2 WC Immunology SC Immunology GA 892PB UT WOS:000226661400001 PM 15582484 ER PT J AU Heller, T Rehermann, B AF Heller, T Rehermann, B TI Acute hepatitis C: A multifaceted disease SO SEMINARS IN LIVER DISEASE LA English DT Review DE acute; liver; hepatitis C virus; treatment; interferon; T cell; immune response ID T-LYMPHOCYTE RESPONSE; NON-B-HEPATITIS; CELLULAR IMMUNE-RESPONSES; INTERFERON-ALPHA THERAPY; VIRUS ENVELOPE PROTEIN; ACUTE HCV INFECTION; ACUTE NON-A; VIRAL CLEARANCE; NONSTRUCTURAL PROTEIN-3; NATURAL-HISTORY AB Although acute hepatitis C virus (HCV) infection is a rare disease and typically not associated with severe clinical symptoms, it has become a disease of significant interest for clinical investigators, virologists, and immunologists alike. In the same way that acute hepatitis C provided a window of opportunity for understanding the clinical and virological aspects of HCV infection as the field was being established, it is now clear that it can provide a window into further understanding the early interaction of the virus with the host immune response. The acute phase of infection is usually considered to be the first 6 months; however, rather than defining acute HCV by the time that has passed after initial infection, it can also be defined as the biological state in which spontaneous clearance is still possible. C1 NIDDK, Liver Dis Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), NIDDK, Liver Dis Branch, NIH, US Dept HHS, Bldg 10,Room 9B16,10 Ctr Dr, Bethesda, MD 20892 USA. EM Rehermann@nih.gov NR 90 TC 46 Z9 46 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD FEB PY 2005 VL 25 IS 1 BP 7 EP 17 DI 10.1055/s-2005-864778 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 902KJ UT WOS:000227354400001 PM 15731994 ER PT J AU Kleiner, DE AF Kleiner, DE TI The liver biopsy in chronic hepatitis C: A view from the other side of the microscope SO SEMINARS IN LIVER DISEASE LA English DT Review DE liver biopsy; chronic hepatitis C; progression; therapeutic response ID CHRONIC VIRAL-HEPATITIS; HEMOCHROMATOSIS GENE-MUTATIONS; BODY-MASS INDEX; INTERFERON-ALPHA THERAPY; CHRONIC ACTIVE HEPATITIS; VIRUS-INFECTION; FIBROSIS PROGRESSION; CONTROLLED-TRIAL; IRON REDUCTION; HFE MUTATIONS AB The liver biopsy has long been the gold standard for the evaluation of the state of liver disease in patients with chronic hepatitis C. Although a liver biopsy continues to be a recommended part of the work-up of this disease, its routine use is challenged by the increasing effectiveness of therapy and by surrogate biochemical tests that give information about the stage of disease. Nevertheless, recent studies have shown that histological features other than stage may have predictive value for disease progression and therapeutic response to interferon-based regimens. Pathologists can increase the relevance and utility of the liver biopsy in chronic hepatitis C by the systematic reporting of steatosis and iron accumulation in addition to stage and grade, and by identifying certain potential confounding liver diseases, such as steatohepatitis and hereditary hemochromatosis. Clinicians can then make best use of the information derived from the liver biopsy to help them advise patients on the natural history of their disease and the therapeutic options that are available. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Kleiner, DE (reprint author), NCI, Pathol Lab, Bldg 10,Room 2N212, Bethesda, MD 20892 USA. EM kleinerd@mail.nih.gov OI Kleiner, David/0000-0003-3442-4453 NR 95 TC 40 Z9 45 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD FEB PY 2005 VL 25 IS 1 BP 52 EP 64 DI 10.1055/s-2005-864781 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 902KJ UT WOS:000227354400004 PM 15731997 ER PT J AU Wei, CL Miura, T Robson, P Lim, SK Xu, XQ Lee, MYC Gupta, S Stanton, L Luo, YQ Schmitt, J Thies, S Khrebtukova, I Zhou, DX Liu, ET Ruan, YJ Rao, M Lim, B AF Wei, CL Miura, T Robson, P Lim, SK Xu, XQ Lee, MYC Gupta, S Stanton, L Luo, YQ Schmitt, J Thies, S Khrebtukova, I Zhou, DX Liu, ET Ruan, YJ Rao, M Lim, B TI Transcriptome profiling of human and murine ESCs identifies divergent paths required to maintain the stem cell state SO STEM CELLS LA English DT Article DE embryonic stem cells; murine and human; transcriptome; massively parallel signature sequencing (MPSS) ID GENE-EXPRESSION; MOLECULAR SIGNATURE; SPEMANN ORGANIZER; HUMAN BLASTOCYSTS; FREE CULTURE; IN-VITRO; LINES; MOUSE; DIFFERENTIATION; PROTEINS AB Human embryonic stem cells (hESCs) are an important however, identified only a small (core) set of conserved source of stem cells in regenerative medicine, and much remains unknown about their molecular characteristics. To develop a detailed genomic profile of ESC lines in two different species, we compared transcriptomes of one murine and two different hESC lines by massively parallel signature sequencing (MPSS). Over 2 million signature tags from each line and their differentiating embryoid bodies were sequenced. Major differences and conserved similarities between species identified by MPSS were validated by reverse transcription polymerase chain reaction (RT-PCR) and microarray. The two hESC lines were similar overall, with differences that are attributable to alleles and propagation. Human-mouse comparisons, genes that included genes known to be important in ESC biology, as well as additional novel genes. Identified were major differences in leukemia inhibitory factor, transforming growth factor-beta, and Wnt and fibroblast growth factor signaling pathways, as well as the expression of genes encoding metabolic, cytoskeletal, and matrix proteins, many of which were verified by RT-PCR or by comparing them with published databases. The study reported here underscores the importance of cross-species comparisons and the versatility and sensitivity of MPSS as a powerful complement to current array technology. C1 Genome Inst Singapore, Singapore 138672, Singapore. NIA, Baltimore, MD 21224 USA. Neurosci Lab, Baltimore, MD USA. Harvard Univ, Sch Med, Inst Med, Beth Israel Deaconess Med Ctr,Div Canc Biol, Boston, MA USA. Natl Univ Singapore, Dept Biol Sci, Singapore, Singapore. Lynx Therapeut Inc, Hayward, CA USA. Embryo Stem Cell Int, Singapore, Singapore. Geron Corp, Menlo Pk, CA USA. RP Lim, B (reprint author), Genome Inst Singapore, 60 Biopolis St,Genome 02-01, Singapore 138672, Singapore. EM raomah@grc.nia.nih.gov; limbl@gis.a-star.edu.sg RI Liu, Edison/C-4141-2008; Robson, Paul/A-3464-2009 OI Robson, Paul/0000-0002-0191-3958 FU NIDDK NIH HHS [DK47636] NR 55 TC 141 Z9 155 U1 0 U2 5 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD FEB PY 2005 VL 23 IS 2 BP 166 EP 185 DI 10.1634/stemcells.2004.0162 PG 20 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 897FJ UT WOS:000226989100003 PM 15671141 ER PT J AU Philip, D Chen, SS Fitzgerald, W Orenstein, J Margolis, L Kleinman, HK AF Philip, D Chen, SS Fitzgerald, W Orenstein, J Margolis, L Kleinman, HK TI Complex extracellular matrices promote tissue-specific stem cell differentiation SO STEM CELLS LA English DT Article DE matrigel; basement membrane; extracellular matrix; gland formation; chondrogenesis ID BASEMENT-MEMBRANE; GROWTH-FACTORS; COMPONENTS; LAMININ; CHONDROCYTES; EXPRESSION; LINE AB Most cells in tissues contact an extracellular matrix on at least one surface. These complex mixtures of interacting proteins provide structural support and biological signals that regulate cell differentiation and may be important for stem cell differentiation. In this study, we have grown a rhesus monkey embryonic stem cell line in the presence of various extracellular matrix components in monolayer, in a NASA-developed rotating wall vessel bioreactor in vitro, and subcutaneously in vivo. We find that individual components of the extracellular matrix, such as laminin-1 or collagen 1, do not influence the growth or morphology of the cells. In contrast, a basement membrane extract, Matrigel, containing multiple extracellular matrix components, induces the cells within 4 days to form immature glandular- and tubular-like structures, many of which contain a lumen with polarized epithelium and microvilli. Such structures were seen in vitro when the cells were grown in the bioreactor and when the cells were injected into mice. These tubular- and glandular-like structures were polarized epithelia based on immunostaining for laminin and cytokeratin. The cell aggregates and tumors also contained additional mixed populations of cells, including mesenchymal cells and neuronal cells, based on immunostaining with vimentin and neuronal markers. An extract of cartilage, containing multiple cartilage matrix components, promoted chondrogenesis in vivo where alcian blue-stained cartilage nodules could be observed. Some of these nodules stained with von Kossa, indicating that they had formed calcified cartilage. We conclude that extracellular matrices can promote the differentiation of embryonic stem cells into differentiated cells and structures that are similar to the tissue from which the matrix is derived. Such preprogramming of cell differentiation with extracellular matrices may be useful in targeting stem cells to repair specific damaged organs. C1 NICHD, NASA, Ctr Dimens Tissue Culture 3, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Cell Biol Sect, Bethesda, MD USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. NICHHD, Lab Cellular & Mol Biophys, Bethesda, MD USA. RP Margolis, L (reprint author), NICHD, NASA, Ctr Dimens Tissue Culture 3, NIH, Bldg 10D58, Bethesda, MD 20892 USA. EM margolis@helix.nih.gov NR 21 TC 103 Z9 111 U1 0 U2 6 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD FEB PY 2005 VL 23 IS 2 BP 288 EP 296 DI 10.1634/stemcells.2002.0109 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 897FJ UT WOS:000226989100013 PM 15671151 ER PT J AU Lo, EH Moskowitz, MA Jacobs, TP AF Lo, EH Moskowitz, MA Jacobs, TP TI Exciting, radical, suicidal - How brain cells die after stroke SO STROKE LA English DT Article ID ACTIVATED PROTEIN-C; FOCAL CEREBRAL-ISCHEMIA; GLUTATHIONE DEPLETION; NEURONAL APOPTOSIS; DEATH; ERYTHROPOIETIN; KINASE; NEUROPROTECTION; 12-LIPOXYGENASE; PROTECTION C1 Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Program Neurosci, Sch Med, Charlestown, MA USA. Harvard Univ, Neurovasc Regulat & Stroke Lab, Sch Med,Dept Radiol, Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Charlestown, MA USA. NINDS, NIH, Bethesda, MD 20892 USA. Harvard Univ, Neuroprotect Res Lab, Dept Radiol, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Lo, EH (reprint author), Harvard Univ, Neuroprotect Res Lab, Sch Med, MGH E 149-2401, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu RI Moskowitz, Michael/D-9916-2011 NR 35 TC 113 Z9 119 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 189 EP 192 DI 10.1161/01.STR.0000153069.96296.fd PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 890JN UT WOS:000226507600005 PM 15637315 ER PT J AU Baron, JC Warach, S AF Baron, JC Warach, S TI Imaging SO STROKE LA English DT Article ID ACUTE ISCHEMIC-STROKE; INTRACEREBRAL HEMORRHAGE; MOTOR RECOVERY; CORTEX ACTIVATION; ARTERY OCCLUSION; MRI; BRAIN; THROMBOLYSIS; REORGANIZATION; TOMOGRAPHY C1 Univ Cambridge, Dept Neurol, Cambridge, England. NINDS, NIH, Bethesda, MD 20892 USA. RP Baron, JC (reprint author), Addenbrookes Hosp, Dept Neurol, Hills Rd,Box 83, Cambridge CB2 2QQ, England. EM jcb54@cam.ac.uk OI baron, jean-claude/0000-0002-5264-2588 NR 36 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 196 EP 199 DI 10.1161/01.STR.0000154559.03784.db PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 890JN UT WOS:000226507600007 PM 15637311 ER PT J AU Merino, JG Lattimore, SU Warach, S AF Merino, JG Lattimore, SU Warach, S TI Telephone assessment of stroke outcome is reliable SO STROKE LA English DT Letter ID INTERVIEW C1 NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA. RP Merino, JG (reprint author), NINDS, Sect Stroke Diagnost & Therapeut, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. OI Merino, Jose/0000-0002-6676-0008 NR 7 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 232 EP 233 DI 10.1161/01.STR.0000153055.43138.2f PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 890JN UT WOS:000226507600028 PM 15637321 ER PT J AU Ardelt, AA McCullough, LD Korach, KS Wang, MM Munzenmaier, DH Hurn, PD AF Ardelt, AA McCullough, LD Korach, KS Wang, MM Munzenmaier, DH Hurn, PD TI Estradiol regulates angiopoietin-1 mRNA expression through estrogen receptor-alpha in a rodent experimental stroke model SO STROKE LA English DT Article DE angiogenesis; cerebrovascular accident; endothelial growth factors ID ENDOTHELIAL GROWTH-FACTOR; CEREBRAL-ARTERY OCCLUSION; RANDOMIZED CONTROLLED-TRIAL; BLOOD-BRAIN-BARRIER; ISCHEMIA-REPERFUSION; POSTMENOPAUSAL WOMEN; ANGIOGENESIS; VEGF; BETA; RATS AB Background and Purpose - Female, compared with male, animals are protected from cerebral ischemic injury. Physiological concentrations of 17beta-estradiol (E2) reduce damage in experimental stroke. E2 augments angiogenesis in reproductive organs and noncerebral vascular beds. We hypothesized that E2 protects brain in stroke through modulation of angiogenesis. We quantified molecular markers of angiogenesis and capillary density before and after unilateral middle cerebral artery occlusion (MCAO). Methods - Female animals were ovariectomized, treated with 25 mug E2 or placebo implants, and subjected to 2-hour MCAO and 22 hours of reperfusion. Brain angiopoietin-1 (Ang-1), Ang-2, Tie-1, Tie-2, vascular endothelial growth factor ( VEGF), VEGF R1, and VEGF R2 mRNA levels were determined by RNAse protection assays, and CD31-positive vessels were counted. Results - E2, but not ischemia, upregulated cerebral Ang-1 mRNA by 49%. Capillary density was higher in the brains of E2-treated animals. In estrogen receptor-alpha knockout (ERKO) mice, E2-mediated induction of Ang-1 mRNA was absent relative to wild-type littermates. Conclusions - These results suggest that E2 increases Ang-1 and enhances capillary density in brain under basal conditions, priming the MCA territory for survival after experimental focal ischemia. C1 Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. RP Ardelt, AA (reprint author), Johns Hopkins Univ Hosp, Div Neurosci Crit Care, Meyer 8-140,600 N Wolfe St, Baltimore, MD 21287 USA. EM aardelt1@jhmi.edu OI Korach, Kenneth/0000-0002-7765-418X FU NINDS NIH HHS [NS33668]; NINR NIH HHS [NR03521] NR 55 TC 55 Z9 76 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 337 EP 341 DI 10.1161/01.STR.0000153795.38388.72 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 890JN UT WOS:000226507600050 PM 15637314 ER PT J AU Hjort, N Butcher, K Davis, SM Kidwell, CS Koroshetz, WJ Rother, J Schellinger, PD Warach, S Ostergaard, L AF Hjort, N Butcher, K Davis, SM Kidwell, CS Koroshetz, WJ Rother, J Schellinger, PD Warach, S Ostergaard, L CA UCLA Thrombolysis Investigators TI Magnetic resonance imaging criteria for thrombolysis in acute cerebral infarct SO STROKE LA English DT Review DE diffusion magnetic resonance imaging; magnetic resonance imaging; perfusion magnetic resonance imaging; stroke management; thrombolysis ID TISSUE-PLASMINOGEN ACTIVATOR; ACUTE ISCHEMIC-STROKE; PERFUSION-WEIGHTED MRI; HIGH-RESOLUTION MEASUREMENT; ACUTE HEMISPHERIC STROKE; TRACER BOLUS PASSAGES; BLOOD-FLOW; CT ANGIOGRAPHY; ARTERY OCCLUSION; APPARENT DIFFUSION AB Background and Purpose - Magnetic resonance imaging (MRI) selection of stroke patients eligible for thrombolytic therapy is an emerging application. Although the efficacy of therapy within 3 hours after onset of symptoms with intravenous (IV) tissue plasminogen activator (tPA) has been proven for patients selected with computed tomography (CT), no randomized, double-blinded MRI trial has been published yet. Summary of Review - MRI screening of acute stroke patients before thrombolytic therapy is performed in some cerebrovascular centers. In contrast to the CT trials, MRI pilot studies demonstrate benefit of therapy up to 6 hours after onset of symptoms. This article reviews the literature that has lead to current controlled MRI-based thrombolysis trials. We examined the MRI criteria applied in 5 stroke centers. Along with the personal views of clinicians at these centers, the survey reveals a variety of clinical and MRI technical aspects that must be further investigated: the therapeutic consequence of microbleeds, the use of magnetic resonance angiography, dynamic time windows, and others. Conclusion - MRI is an established application in acute evaluation of stroke patients and may suit as a brain clock, replacing the currently used epidemiological time clock when deciding whether to initiate thrombolytic therapy. MRI criteria for thrombolytic therapy are applied in some cerebrovascular centers, but the results of ongoing clinical trials must be awaited before it is possible to reach consensus. C1 Aarhus Univ Hosp, Ctr Funct Integrat Neurosci, Dept Neuroradiol, DK-8000 Aarhus C, Denmark. Royal Melbourne Hosp, Dept Neurol, Parkville, Vic 3050, Australia. Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Hamburg, Hosp Eppendorf, Dept Neurol, D-20246 Hamburg, Germany. Dept Neurol, Heidelberg, Germany. NINDS, NIH, Bethesda, MD 20892 USA. RP Hjort, N (reprint author), Aarhus Univ Hosp, Ctr Funct Integrat Neurosci, Dept Neuroradiol, Norrebrogade 44, DK-8000 Aarhus C, Denmark. EM niels@pet.auh.dk RI Bonefeld, Birgit/B-7936-2010; Ostergaard, Leif/A-9281-2008; Davis, Stephen/L-5260-2013 OI Ostergaard, Leif/0000-0003-2930-6997; Davis, Stephen/0000-0003-0962-2300 NR 63 TC 152 Z9 163 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 388 EP 397 DI 10.1161/01.STR.0000152268.47919.be PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 890JN UT WOS:000226507600058 PM 15618445 ER PT J AU Nentwich, LM Chalela, JA Luby, ML Warach, S AF Nentwich, LM Chalela, JA Luby, ML Warach, S CA HEME-ER Investigators TI Clinical predictors of false-negative diffusion-weighted imaging in the emergency assessment of suspected ischemic stroke SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 NINDS, 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 431 EP 431 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800067 ER PT J AU Bykowski, JL Warach, S Latour, LL AF Bykowski, JL Warach, S Latour, LL TI Prevalence of multiple cortical lesions in acute stroke patients visualized by high-resolution diffusion-weighted imaging SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 443 EP 444 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800130 ER PT J AU Khatri, P Rajajee, V Taylor, RA Katz, JM Haymore, J Chalela, J Geers, A Segal, AZ Kolansky, DM Kasner, SE AF Khatri, P Rajajee, V Taylor, RA Katz, JM Haymore, J Chalela, J Geers, A Segal, AZ Kolansky, DM Kasner, SE CA Treatment Acute Stroke Cardiac TI Thrombolysis for strokes after cardiac catheterization SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 Univ Cincinnati, Cincinnati, OH USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Iowa, Iowa City, IA USA. Cornell Univ, New York, NY USA. Washington Adventist Hosp, Washington, DC USA. Natl Inst Hlth, Washington, DC USA. Univ Penn, Philadelphia, PA 19104 USA. RI Kasner, Scott/C-6109-2011 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 450 EP 451 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800166 ER PT J AU Meschia, JF Brott, TG Brown, RD Crook, RJ Kissela, B Brown, WM Rich, SS Case, LD Evans, EW Hague, S Singleton, A Hardy, J AF Meschia, JF Brott, TG Brown, RD Crook, RJ Kissela, B Brown, WM Rich, SS Case, LD Evans, EW Hague, S Singleton, A Hardy, J TI Failure to confirm that either phosphodiesterase 4D or 5-lipoxygenase activating protein is a major risk factor gene for ischemic stroke SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 Mayo Clin, Jacksonville, AL USA. Mayo Clin, Rochester, MN USA. Univ Cincinnati, Cincinnati, OH USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NIA, Bethesda, MD 20892 USA. RI Singleton, Andrew/C-3010-2009 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 457 EP 457 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800201 ER PT J AU DeGraba, TJ Hoehn, G Nyquist, P Hamm, T Sufferdini, A AF DeGraba, TJ Hoehn, G Nyquist, P Hamm, T Sufferdini, A TI Serum biomarkers in patents with carotid atherosclerosis using proteomic techniques SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 NINDS, Natl Naval Med Ctr, USUHS, Bethesda, MD 20892 USA. NIH, Ctr Clin, CCMD, Bethesda, MD 20892 USA. Fairfax Hosp, INOVA, Fairfax, VA USA. Henry M Jackson Fdn, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 459 EP 459 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800208 ER PT J AU Worrall, BB Brott, TG Brown, RD Brown, WM Rich, SS Arepalli, S Duckworth, J Wavrant-De Vrieze, F Singleton, A Hardy, J Meschia, JF AF Worrall, BB Brott, TG Brown, RD Brown, WM Rich, SS Arepalli, S Duckworth, J Wavrant-De Vrieze, F Singleton, A Hardy, J Meschia, JF TI Interleukin-1 receptor antagonist gene polymorphism in ischemic stroke SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 Univ Virginia, Hlth Syst, Charlottesville, VA 22903 USA. Mayo Clin, Jacksonville, FL 32224 USA. Mayo Clin, Rochester, MN USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NIA, Bethesda, MD 20892 USA. RI Singleton, Andrew/C-3010-2009 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 459 EP 460 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800212 ER PT J AU Simak, J Gelderman, MP Yu, H Wright, V Alberts-Grill, N Stranix, JT Baird, AE AF Simak, J Gelderman, MP Yu, H Wright, V Alberts-Grill, N Stranix, JT Baird, AE TI Circulating endothelial microparticles in acute stroke: Relation to clinical severity, lesion volume, and outcome SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NINDS, NIH, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 475 EP 475 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800290 ER PT J AU Merino, JG Lattimore, S Warach, S AF Merino, JG Lattimore, S Warach, S TI Telephone assessment of stroke outcome is reliable SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 NINDS, 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 480 EP 480 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800316 ER PT J AU Wright, VL Olan, WJ Dick, BW Latour, LL Yla, H Alberts-Grill, NM Baird, AE AF Wright, VL Olan, WJ Dick, BW Latour, LL Yla, H Alberts-Grill, NM Baird, AE TI Rapid detection of vascular disease from the aortic arch to the circle of Willis by contrast-enhanced MR angiography: Prospective evaluation SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 NINDS, NIH, SNU, Bethesda, MD 20892 USA. Suburban Hosp, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 482 EP 483 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800328 ER PT J AU Kidwell, CS Chalela, J Saver, JL Hill, M Butman, J Starkman, S Latour, L Warach, S AF Kidwell, CS Chalela, J Saver, JL Hill, M Butman, J Starkman, S Latour, L Warach, S CA HEME Investigators TI Prospective comparison of CT vs DWI for detection of acute cerebral ischemia: Results of a multicenter study SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 Washington Hosp Ctr, Washington, DC 20010 USA. Univ Calif Los Angeles, Med Ctr, Washington, DC USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Univ Calgary, Foothills Hosp, Calgary, AB, Canada. NINDS, NIH, Bethesda, MD 20892 USA. RI Butman, John/A-2694-2008; Hill, Michael/C-9073-2012 OI Hill, Michael/0000-0002-6269-1543 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 485 EP 485 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800340 ER PT J AU Latour, LL Hilton, S Warach, S AF Latour, LL Hilton, S Warach, S TI Evolution of ischemia over 14 minutes visualized by DWI in hyperacute stroke patients SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 486 EP 486 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800348 ER PT J AU Luby, M Warach, S AF Luby, M Warach, S TI Intra-rater reliability of quantitative ischemic lesion volumes on diffusion-weighted, mean transit time, and FLAIR MRI SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 NINDS, 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 487 EP 487 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800352 ER PT J AU Azok, J Hoehn, G Yu, H Wright, VL Hammer, P Adexe, G Jeffries, N Moore, DF Guccione, S Li, K Baird, AE AF Azok, J Hoehn, G Yu, H Wright, VL Hammer, P Adexe, G Jeffries, N Moore, DF Guccione, S Li, K Baird, AE TI Protein expression profiling of plasma separates stroke patients from age- and sex-matched controls: Implications for discovery of novel biomarkers for stroke SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 NIH, CC, Bethesda, MD USA. NINDS, NIH, SNU, Bethesda, MD 20892 USA. Univ Manitoba, Winnipeg, MB, Canada. 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 488 EP 488 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800357 ER PT J AU Lyden, PD Raman, R Liu, L Groha, J Broderick, J Olson, S Shaw, S Spilker, J Meyer, B Emr, M Warren, M Mader, J AF Lyden, PD Raman, R Liu, L Groha, J Broderick, J Olson, S Shaw, S Spilker, J Meyer, B Emr, M Warren, M Mader, J TI Reliability of NHSS training and certification in DVD format SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 Univ Calif San Diego, San Diego, CA 92103 USA. Univ Texas, Houston, TX USA. Univ Cincinnati, Cincinnati, OH USA. NINDS, 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 493 EP 493 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800382 ER PT J AU Ardelt, A McCullough, L Korach, K Wang, M Munzenmaier, D Hurn, P AF Ardelt, A McCullough, L Korach, K Wang, M Munzenmaier, D Hurn, P TI Estradiol modulates anglopoietin-1 and capillary density in a rodent stroke model SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. NIH, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Oregon Hlth & Sci Univ, Portland, OR 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 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 514 EP 514 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800490 ER PT J AU Alberts-Grill, NM Nadareishvili, Z Yu, H Maric, D Stranix, JT Wright, VL Hallenbeck, JM Barker, J Baird, AE AF Alberts-Grill, NM Nadareishvili, Z Yu, H Maric, D Stranix, JT Wright, VL Hallenbeck, JM Barker, J Baird, AE TI Delayed expansion of proinflammatory CD(3+)CD(4+)CD28(-) lymphocytes following ischemic stroke SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 517 EP 517 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800506 ER PT J AU Li, YL Huang, YP Swaminathan, CP Smith-Gill, SJ Mariuzza, RA AF Li, YL Huang, YP Swaminathan, CP Smith-Gill, SJ Mariuzza, RA TI Magnitude of the hydrophobic effect at central versus peripheral sites in protein-protein interfaces SO STRUCTURE LA English DT Article ID CAVITY-CREATING MUTATIONS; ANTILYSOZYME ANTIBODY HYHEL-63; HOT-SPOTS; BINDING-ENERGY; HUMAN LYSOZYME; RECOGNITION; ANTIGEN; STABILITY; COMPLEXES; SURFACES AB Hydrophobic interactions are essential for stabilizing protein-protein complexes, whose interfaces generally consist of a central cluster of hot spot residues surrounded by less important peripheral residues. According to the O-ring hypothesis, a condition for high affinity binding is solvent exclusion from interacting residues. This hypothesis predicts that the hydrophobicity at the center is significantly greater than at the periphery, which we estimated at 21 cal mol(-1) Angstrom(-2). To measure the hydrophobicity at the center, structures of an antigen-anti body complex where a buried phenylalanine was replaced by smaller hydrophobic residues were determined. By correlating structural changes with binding free energies, we estimate the hydrophobicity at this central site to be 46 cal mol(-1) Angstrom(-2), twice that at the periphery. This context dependence of the hydrophobic effect explains the clustering of hot spots at interface centers and has implications for hot spot prediction and the design of small molecule inhibitors. C1 Univ Maryland, Inst Biotechnol, WM Keck Lab Struct Biol, Ctr Adv Res Biotechnol, Rockville, MD 20859 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Mariuzza, RA (reprint author), Univ Maryland, Inst Biotechnol, WM Keck Lab Struct Biol, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20859 USA. EM mariuzza@carb.nist.gov FU NIGMS NIH HHS [GM52801] NR 48 TC 35 Z9 35 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD FEB PY 2005 VL 13 IS 2 BP 297 EP 307 DI 10.1016/j.str.2004.12.012 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 898KT UT WOS:000227076400015 PM 15698573 ER PT J AU Gundisch, D Koren, AO Horti, AG Pavlova, OA Kimes, AS Mukhin, AG London, ED AF Gundisch, D Koren, AO Horti, AG Pavlova, OA Kimes, AS Mukhin, AG London, ED TI In vitro characterization of 6-[F-18]fluoro-A85380, a high-affinity ligand for alpha 4 beta 2*nicotinic acetylcholine receptors SO SYNAPSE LA English DT Article DE 6-[F-18]fluoro-A-85380; nicotine; epibatidine; cytisine; receptor binding; nicotinic acetylcholine receptor ID NEURONAL NICOTINIC RECEPTORS; POSITRON-EMISSION-TOMOGRAPHY; HUMAN BRAIN; CHROMAFFIN CELLS; MUTANT MICE; PET TRACER; RAT-BRAIN; BINDING; SUBUNIT; RADIOLIGAND AB Nicotinic acetylcholine receptors are involved in tobacco dependence and several other neuropathologies (e.g., Alzheimer's disease, Parkinson's disease), as well as in attention, learning, and memory. Performing in vivo imaging of these receptors in humans holds great promise for understanding their role in these conditions. Recently, three radiohalogenated analogs of 3-(2(S)-azetidinylmethoxy)pyridine (A-85380) were used successfully for the in vivo visualization of alpha4beta2* nicotinic receptors in the human brain with PET/SPECT. Herein, we present the results of the in vitro characterization of one of these radioligands, 6-[F-18]fluoro-3-(2(S)-azetidinylmethoxy)-pyridine (6-[F-18]fluoro-A-85380), which is a fluoro-analog of the potent nonopioid analgesic ABT-594. In human postmortem cortical tissue, 6- [F-18]fluoro-A-85380 reversibly binds with high affinity to a single population of sites (K-d = 59 pM at 37degreesC, B-max = 0.7 pmol/g tissue). The binding is fully reversible and is characterized at 37degreesC by T-1/2assoc = 2.2 min (at a ligand concentration of 39 pM) and by T-1/2dissoc = 3.6 min. 6-Fluoro-A-85380 exhibits clear selectivity for alpha4beta2* over the other major mammalian nicotinic receptor subtypes: alpha7, alpha3beta4, and muscle-type. These results suggest that 6-[F-18]fluoro-A-85380 is a promising radioligand for in vivo imaging of brain alpha4beta2* nicotinic receptors. Published 2004 Wiley-Liss, Inc. C1 Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, DHHS,Intramural Res Program, Baltimore, MD 21224 USA. RP Mukhin, AG (reprint author), Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, DHHS,Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM amukhin@intra.nida.nih.gov NR 55 TC 20 Z9 20 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD FEB PY 2005 VL 55 IS 2 BP 89 EP 97 DI 10.1002/syn.20096 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 882DK UT WOS:000225918700003 PM 15529332 ER PT J AU Weinstein, ND Marcus, SE Moser, RP AF Weinstein, ND Marcus, SE Moser, RP TI Smokers' unrealistic optimism about their risk SO TOBACCO CONTROL LA English DT Article ID CIGARETTE SMOKERS; CANCER; PERCEPTIONS; SUSCEPTIBILITY; IMMUNITY; SMOKING; DISEASE AB Objective: Past studies have produced ambiguous or inconsistent results when testing whether smokers actually underestimate their own risks of experiencing tobacco related illness. Whereas smokers claim that they are less at risk than the average smoker on self administered questionnaires, this unrealistic optimism has not been found in telephone or face-to-face interviews. We avoided the measurement problems of past studies and examined responses to a number of new questions to assess different aspects of smokers' perceptions. Methodology: A US national telephone survey ( n = 6369; 1245 current smokers) posed a variety of questions designed to examine beliefs about the risks of smoking. For key questions, separate samples of smokers were asked either about their own risk or about the risk of the average smoker. Results: Smokers underestimated their relative risk compared to non-smokers and, contrary to previous interview surveys, believed they have a lower risk of developing lung cancer than the average smoker. Furthermore, their perceived risk of lung cancer and of cancer in general barely increases with the number of cigarettes smoked per day, and their estimates of their risk of cancer are actually slightly lower than their estimates of their risk of lung cancer. Substantial proportions of smokers and former smokers agree with several myths, more than half agreeing that exercise undoes most smoking effects. Conclusion: Smokers underestimate their risk of lung cancer both relative to other smokers and to nonsmokers and demonstrate other misunderstandings of smoking risks. Smoking cannot be interpreted as a choice made in the presence of full information about the potential harm. C1 Rutgers State Univ, Dept Human Ecol, New Brunswick, NJ 08901 USA. NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Weinstein, ND (reprint author), Rutgers State Univ, Dept Human Ecol, Cook Off Bldg,55 Dudley Rd, New Brunswick, NJ 08901 USA. EM neilw@aesop.rutgers.edu RI Reis, Aline/G-9573-2012 NR 34 TC 174 Z9 177 U1 2 U2 17 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD FEB PY 2005 VL 14 IS 1 BP 55 EP 59 DI 10.1136/tc.2004.008375 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 906TU UT WOS:000227667200015 PM 15735301 ER PT J AU Cunningham, ML Lehman-McKeeman, L AF Cunningham, ML Lehman-McKeeman, L TI Applying toxicogenomics in mechanistic and predictive toxicology SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material ID DRUG-INDUCED PHOSPHOLIPIDOSIS C1 NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. Bristol Myers Squibb Co, Discovery Toxicol, Princeton, NJ 08543 USA. RP Cunningham, ML (reprint author), NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM cunning1@niehs.nih.gov NR 10 TC 7 Z9 8 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2005 VL 83 IS 2 BP 205 EP 206 DI 10.1093/toxsci/kfi047 PG 2 WC Toxicology SC Toxicology GA 888JY UT WOS:000226371400001 PM 15678597 ER PT J AU Nyska, A Murphy, E Foley, JF Collins, BJ Petranka, J Howden, R Hanlon, P Dunnick, JK AF Nyska, A Murphy, E Foley, JF Collins, BJ Petranka, J Howden, R Hanlon, P Dunnick, JK TI Acute hemorrhagic myocardial necrosis and sudden death of rats exposed to a combination of ephedrine and caffeine SO TOXICOLOGICAL SCIENCES LA English DT Article DE ephedrine; caffeine; cardiotoxicity; apoptosis; coagulative necrosis; ischemia ID MA-HUANG EPHEDRA; DIETARY-SUPPLEMENTS; REPERFUSION INJURY; INFARCTION; ALKALOIDS; APOPTOSIS; PHARMACOKINETICS; VASOSPASM; ISCHEMIA; HISTONE AB Because of possible side effects of herbal medicines containing ephedrine and guarana-derived caffeine, including increased risk of stroke, myocardial infarction, and sudden death, the Food and Drug Administration recently banned the sale of ephedra-containing products, specifically over-the-counter dietary supplements. We report cardiac in 7- and 14-week-old male F344 rats exposed by gavage to ephedrine(25 mg/kg) and caffeine (30 mg/kg) administered in combination for one or two days. The ephedrine-caffeine dosage was approximately 12- and 1.4-fold, respectively, above average human exposure, based on a mg/m(2) body surface-area comparison. Several (5/7) of the exposed 14-week-old rats died or were sacrificed in extremis 4-5 h after the first dosing. In these hearts, changes were observed chiefly in the interventricular septum but also left and right ventricular walls. Massive interstitial hemorrhage, with degeneration of myofibers, occurred at the subendocardial myocardium of the left ventricle and interventricular septum. Immunostaining for cleaved caspase-3 and hyperphosphorylated H2A.X, a histone variant that becomes hyperphosphorylated during apoptosis, indicated multifocal generalized positive staining of degenerating myofibers and fragmenting nuclei, respectively. The Barbeito-Lopez trichrome stain revealed generalized patchy yellow myofibers consistent with degeneration and/or coagulative necrosis. In ephedrine-caffeine-treated animals terminated after the second dosing, foci of myocardial degeneration and necrosis were already infiltrated by mixed inflammatory cells. The myocardial necrosis may occur secondarily to intense diffuse vasoconstriction of the coronary arterial system with decreased myocardial perfusion. Our work shows the direct relationship between combined ephedrine and caffeine exposure and cardiac pathology. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, 111 TW Alexander Dr,MD B3-06, Res Triangle Pk, NC 27709 USA. EM nvska@niehs.nih.gov NR 44 TC 25 Z9 25 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2005 VL 83 IS 2 BP 388 EP 396 DI 10.1093/toxsci/kfi034 PG 9 WC Toxicology SC Toxicology GA 888JY UT WOS:000226371400021 PM 15537744 ER PT J AU Volodin, AA Voloshin, ON Camerini-Otero, RD AF Volodin, AA Voloshin, ON Camerini-Otero, RD TI Homologous recombination and RecA protein: towards a new generation of tools for genome manipulations SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID SEQUENCE-SPECIFIC MODIFICATION; ENDONUCLEASE RARE CLEAVAGE; MEDIATED STRAND EXCHANGE; ESCHERICHIA-COLI; GENE-TRANSFER; ANTIGENIC VARIATION; PAIRING SEQUENCES; MISMATCH REPAIR; DNA-SEQUENCE; LOW FIDELITY AB Homologous recombination (HR) is one of the central processes of DNA metabolism, combining roles in both cell housekeeping and the evolution of genomes. In eukaryotes, HR underlies meiosis and ensures genome stability. The complete sequencing of numerous bacterial genomes; has shown that HR has a substantial role in the evolution of microorganisms, especially pathogens. HIR systems from different species and their isolated components are finding an expanding field of applications in modern genetic engineering and bio- and nanotechnologies. Recently, much progress has been made in our understanding of HR mechanisms in eukaryotes and the practical applications of HR systems. C1 Russian Acad Sci, Inst Mol Genet, Moscow 123182, Russia. NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Volodin, AA (reprint author), Russian Acad Sci, Inst Mol Genet, Kurchatov Sq, Moscow 123182, Russia. EM volodin@img.ras.ru RI Volodin, Alexander/B-9656-2012 NR 78 TC 12 Z9 12 U1 2 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD FEB PY 2005 VL 23 IS 2 BP 97 EP 102 DI 10.1016/j.tibtech.2004.12.005 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 898NE UT WOS:000227082700010 PM 15661347 ER PT J AU Sprague, BL McNally, JG AF Sprague, BL McNally, JG TI FRAP analysis of binding: proper and fitting SO TRENDS IN CELL BIOLOGY LA English DT Review ID FLUORESCENCE CORRELATION SPECTROSCOPY; INTERACTIONS IN-VIVO; LIVING CELLS; PROTEIN DYNAMICS; PHOTOBLEACHING RECOVERY; LATERAL DIFFUSION; TRANSLATIONAL DIFFUSION; ANOMALOUS DIFFUSION; MONTE-CARLO; MOBILITY AB Dynamic molecular interactions are fundamental to all cellular processes. In vivo analyses of these interactions are frequently done using fluorescence recovery after photobleaching (FRAP). Proper interpretation of FRAP data yields information about the binding interactions of fluorescently tagged molecules, including the number of binding states and the binding strength of each state. This binding information can be gleaned from appropriate models of the process underlying a FRAP recovery. Continued application and development of these approaches promise to provide crucial information for a quantitative description of the molecular networks that regulate cellular function. C1 NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. EM mcnallyj@exchange.nih.gov RI Sprague, Brian/A-8923-2009 NR 65 TC 298 Z9 303 U1 5 U2 59 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD FEB PY 2005 VL 15 IS 2 BP 84 EP 91 DI 10.1016/j.tcb.2004.12.001 PG 8 WC Cell Biology SC Cell Biology GA 901RE UT WOS:000227298800005 PM 15695095 ER PT J AU Glazko, GV Koonin, EV Rogozin, IB AF Glazko, GV Koonin, EV Rogozin, IB TI Molecular dating: ape bones agree with chicken entrails SO TRENDS IN GENETICS LA English DT Editorial Material ID LONG-BRANCH ATTRACTION; DIVERGENCE TIMES; RATE EVOLUTION; PHYLOGENY; MIOCENE; SIVAPITHECUS; PRECISION; ORANGUTAN; RADIATION; SEQUENCES AB Molecular time estimates, especially those that employed the 310 million years ago (Mya) date of mammal-bird divergence as the calibration point, were criticized in recent publications. In this article, we estimate the divergence time of primates and rodents, primates and artiodactyls and the different great ape species by using two independent calibration-time ranges and maximally conservative error estimates. We observed a variation of approximately +/- 15-20% for most of the molecular time estimates in the 10-100 Mya range. The estimated range of the primate-rodent divergence time, 84-121 Mya, includes the date obtained with the 310 million years calibration point (110 Mya). We conclude that molecular time estimates remain useful tools of evolutionary biology, although utmost caution is required when interpreting the results. C1 Stowers Inst Med Res, Kansas City, MO 64110 USA. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Glazko, GV (reprint author), Stowers Inst Med Res, 1000 E 50th St, Kansas City, MO 64110 USA. EM gvg@Stowers-Institute.org NR 37 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD FEB PY 2005 VL 21 IS 2 BP 89 EP 92 DI 10.1016/j.tig.2004.12.006 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 898ND UT WOS:000227082600006 PM 15661354 ER PT J AU Klebanoff, CA Khong, HT Antony, PA Palmer, DC Restifo, NP AF Klebanoff, CA Khong, HT Antony, PA Palmer, DC Restifo, NP TI Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy SO TRENDS IN IMMUNOLOGY LA English DT Review ID VERSUS-HOST-DISEASE; VIVO ANTITUMOR-ACTIVITY; TOTAL-BODY IRRADIATION; IN-VIVO; HOMEOSTATIC PROLIFERATION; CUTTING EDGE; DENDRITIC CELLS; CANCER-IMMUNOTHERAPY; METASTATIC MELANOMA; EFFECTOR FUNCTION AB Lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells boosts antitumor immunotherapeutic activity in mouse and in humans. In the most recent clinical trials, lymphodepletion together with ACT has an objective response rate of 50% in patients with solid metastatic tumors. The mechanisms underlying this recent advance in cancer immunotherapy are beginning to be elucidated and include: the elimination of cellular cytokine 'sinks' for homeostatic gamma(c)-cytokines, such as interieukin-7 [IL-7), IL-15 and possibly IL-21, which activate and expand tumor-reactive T cells; the impairment of CD4(+)CD25(+) regulatory T (Treg) cells that suppress tumor-reactive T cells; and the induction of tumor apoptosis and necrosis in conjunction with antigen-presenting cell activation. Knowledge of these factors could be exploited therapeutically to improve the in vivo function of adoptively transferred, tumor-reactive T cells for the treatment of cancer. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. Univ S Alabama, Canc Res Inst, Mobile, AL 36688 USA. RP Palmer, DC (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM palmerd@mail.nih.gov RI Restifo, Nicholas/A-5713-2008; Klebanoff, Christopher/B-8088-2008; Palmer, Douglas/B-9454-2008; Klebanoff, Christopher/D-9581-2011; OI Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 84 TC 193 Z9 203 U1 4 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD FEB PY 2005 VL 26 IS 2 BP 111 EP 117 DI 10.1016/j.it.2004.12.003 PG 7 WC Immunology SC Immunology GA 900OZ UT WOS:000227225500009 PM 15668127 ER PT J AU Ulrich, LE Koonin, EV Zhulin, IB AF Ulrich, LE Koonin, EV Zhulin, IB TI One-component systems dominate signal transduction in prokaryotes SO TRENDS IN MICROBIOLOGY LA English DT Review ID CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; PROTEIN; 2-COMPONENT; DOMAINS; RECEPTORS; EVOLUTION; BACTERIA; DATABASE; GENOMES AB Two-component systems that link environmental signals to cellular responses are viewed as the primary mode of signal transduction in prokaryotes. By analyzing information encoded by 145 prokaryotic genomes, we found that the majority of signal transduction systems consist of a single protein that contains input and output domains but lacks phosphotransfer domains typical of two-component systems. One-component systems are evolutionarily older, more widely distributed among bacteria and archaea, and display a greater diversity of domains than two-component systems. C1 Georgia Inst Technol, Sch Biol, Ctr Bioinformat & Computat Biol, Atlanta, GA 30332 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Zhulin, IB (reprint author), Georgia Inst Technol, Sch Biol, Ctr Bioinformat & Computat Biol, Atlanta, GA 30332 USA. EM igor.zhulin@biology.gatech.edu RI Zhulin, Igor/A-2308-2012 OI Zhulin, Igor/0000-0002-6708-5323 FU NIGMS NIH HHS [R01 GM072285, GM 72285, R01 GM072285-01] NR 29 TC 223 Z9 235 U1 2 U2 26 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD FEB PY 2005 VL 13 IS 2 BP 52 EP 56 DI 10.1016/j.tim.2004.12.006 PG 5 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 901RC UT WOS:000227298600004 PM 15680762 ER PT J AU Kronenwett, U Huwendiek, S Castro, J Ried, T Auer, G AF Kronenwett, U Huwendiek, S Castro, J Ried, T Auer, G TI Characterisation of breast fine-needle aspiration biopsies by centrosome aberrations and genomic instability SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast tumours; DCIS; FNAB; image cytometry; SSI; centrosome aberrations ID NUCLEAR-DNA CONTENT; PROGNOSTIC-SIGNIFICANCE; GAMMA-TUBULIN; CELL-CYCLE; MICROTUBULE NUCLEATION; CANCER; TUMORS; DUPLICATION; LESIONS; ADENOCARCINOMAS AB Recent studies have suggested that aneuploidy in malignant tumours could be a consequence of centrosome aberrations. Using immunofluorescence analysis with an antibody against gamma-tubulin and DNA image cytometry, we measured centrosome aberrations and DNA ploidy patterns in fine-needle aspiration biopsies (FNABs) of 58 breast lesions. Benign lesions did not show any centrosome aberrations. DNA diploid carcinomas showed a mean percentage of cells with centrosomal defects of 2.1%. The aneuploid invasive carcinomas could be divided into two subgroups by their significantly ( P = 0.0003) different percentage of cells with centrosome aberrations (2.0 and 10.3%, respectively) and their significantly ( P = 0.0003) different percentage of cells with nonmodal DNA content values determined by the Stemline Scatter Index (SSI), a measure of genomic instability. The percentage of cells with centrosome aberrations demonstrated a positive, linear correlation with the corresponding SSI ( r = 0.82, P<0.0001) and loss of tissue differentiation ( r = 0.78, P<0.0001). Our results indicate the percentage of cells with centrosome aberrations as being sufficient to divide the investigated tumours into three significantly different groups: benign lesions with no centrosomal aberrations, and two malignant tumour types with mean values of 2.1 and 9.6% of centrosomal defects, respectively. Together, these results demonstrate that centrosome aberrations correlate with genomic instability and loss of tissue differentiation. Furthermore, this study shows the feasibility of centrosomal analysis in FNAB of the breast and suggests centrosomal aberrations as possessing diagnostic and prognostic value. C1 Karolinska Hosp & Inst, Dept Oncol & Pathol, Div Cellular & Mol Anal, CCK, S-17176 Stockholm, Sweden. NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kronenwett, U (reprint author), Karolinska Hosp & Inst, Dept Oncol & Pathol, Div Cellular & Mol Anal, CCK, R8-04, S-17176 Stockholm, Sweden. EM Ulrike.Kronenwett@cck.ki.se NR 35 TC 23 Z9 27 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 31 PY 2005 VL 92 IS 2 BP 389 EP 395 DI 10.1038/sj.bjc.6602246 PG 7 WC Oncology SC Oncology GA 890XF UT WOS:000226543800030 PM 15558069 ER PT J AU Hose, S Zigler, JS Sinha, D AF Hose, S Zigler, JS Sinha, D TI A novel rat model to study the functions of macrophages during normal development and pathophysiology of the eye SO IMMUNOLOGY LETTERS LA English DT Article DE macrophage; apoptosis; necrosis; phagocytosis; lens; retina; hyaloid vessels ID TUNICA-VASCULOSA-LENTIS; TRANSGENIC MICE; GROWTH-FACTOR; APOPTOSIS; REGRESSION; INDUCTION; CELLS AB Several studies have shown that macrophages play an active role in the initiation and completion of the programmed cell death process during development. Macrophages are called professional phagocytes, as their primary role is phagocytosis. The process of phagocytosis is complex and to date only poorly defined. It has also been postulated that macrophages around the developing lens likely migrate into the neural retina and differentiate into microglia after completion of their role as debris removers. We have identified ED1 immunopositive macrophages and CD11b/18 (OX-42) immunopositive macrophage-like cells in the vitreous chamber and sub-retinal space of a rat spontaneous mutation that we have termed Nuc1. The mutation appears to affect the programmed cell death process and is highly eye specific in its effects. While ED1 and ED2-immunopositive macrophages have previously been found surrounding the developing lens and are thought to play a role in the programmed regression of the tunica vasculosa lentis (part of the vascular structure present on the posterior surface of the lens during development), OX-42-immunopositive cells have not previously been identified in the vitreous chamber under normal or pathological conditions. Macrophage subpopulations surrounding the lens may differentiate into OX-42(+) cells in Nucl following the release of lens material into the vitreous after the posterior capsule ruptures. In Nuc1 homozygotes, the posterior lens capsule ruptures before birth, causing lens material to be extruded into the vitreous compartment and damaging the tunica vasculosa lentis. Alternatively, OX-42(+) cells may be recruited due to an inflammatory response both in the vitreous compartment and sub-retinal space. Inflammation is known to have an enhanced influx of phagocytic cells. Our data suggests that subpopulations of macrophages perform distinct functions in inducing apoptosis and phagocytic activity during normal conditions and in disease. (C) 2004 Elsevier B.V. All rights reserved. C1 Johns Hopkins Univ, Dept Ophthalmol, Sch Med, Baltimore, MD 21287 USA. NEI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. RP Sinha, D (reprint author), Johns Hopkins Univ, Dept Ophthalmol, Sch Med, 600 N Wolfe St Jefferson 3-127A, Baltimore, MD 21287 USA. EM debasish@jhmi.edu NR 15 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JAN 31 PY 2005 VL 96 IS 2 BP 299 EP 302 DI 10.1016/j.imlet.2004.09.017 PG 4 WC Immunology SC Immunology GA 889MR UT WOS:000226447600019 PM 15585337 ER PT J AU Kim, IY Kim, MM Kim, SJ AF Kim, IY Kim, MM Kim, SJ TI Transforming growth factor-beta: Biology and clinical relevance SO JOURNAL OF BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE TGF-beta; Smad; cell cycle; tumor suppressor; signal; wound healing ID CELL-CYCLE ARREST; EPITHELIAL-MESENCHYMAL TRANSITIONS; GASTRIC-CANCER CELLS; MICE LACKING SMAD3; II RECEPTOR GENE; TGF-BETA; MICROSATELLITE INSTABILITY; INFLAMMATORY RESPONSE; TRANSGENIC MICE; DOWN-REGULATION AB Transforming growth factor-beta is a pleiotropic growth factor that has enthralled many investigators for approximately two decades. In addition to many reports that have clarified the basic mechanism of transforming growth factor-beta signal transduction, numerous laboratories have published on the clinical implication/application of transforming growth factor-beta. To name a few, dysregulation of transforming growth factor-beta signaling plays a role in carcinogenesis, autoimmunity, angiogenesis, and wound healing. In this report, we will review these clinical implications of transforming growth factor-beta. C1 Univ Calif Irvine, Dept Urol, Orange, CA 92868 USA. Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Kim, IY (reprint author), Univ Calif Irvine, Dept Urol, Orange, CA 92868 USA. EM kimi@uci.edu NR 75 TC 68 Z9 72 U1 0 U2 4 PU SPRINGER SINGAPORE PTE LTD PI SINGAPORE PA #04-01 CENCON I, 1 TANNERY RD, SINGAPORE 347719, SINGAPORE SN 1225-8687 J9 J BIOCHEM MOL BIOL JI J. Biochem. Mol. Biol. PD JAN 31 PY 2005 VL 38 IS 1 BP 1 EP 8 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 892XJ UT WOS:000226683000001 PM 15715939 ER PT J AU Dayer, AG Cleaver, KM Abouantoun, T Cameron, HA AF Dayer, AG Cleaver, KM Abouantoun, T Cameron, HA TI New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors SO JOURNAL OF CELL BIOLOGY LA English DT Article ID LOCAL-CIRCUIT NEURONS; DENTATE GYRUS; CEREBRAL-CORTEX; VISUAL-CORTEX; HIPPOCAMPAL NEUROGENESIS; CORTICAL NEUROGENESIS; NEUROTROPHIC FACTOR; NG2-POSITIVE CELLS; PROGENITOR CELLS; RAT AB Ongoing neurogenesis in the adult mammalian dentate gyrus and olfactory bulb is generally accepted, but its existence in other adult brain regions is highly controversial. We labeled newly born cells in adult rats with the S-phase marker bromodeoxyuridine (BrdU) and used neuronal markers to characterize new cells at different time points after cell division. In the neocortex and striatum, we found BrdU-labeled cells that expressed each of the eight neuronal markers. Their size as well as staining for gamma-aminobutyric acid (GABA), glutamic acid decarboxylase 67, calretinin and/or calbindin, suggest that new neurons in both regions are GABAergic interneurons. BrdU and doublecortin-immuno-reactive (BrdU+/DCX+) cells were seen within the striatum, suggesting migration of immature neurons from the subventricular zone. Surprisingly, no DCX+ cells were found within the neocortex. NG2 immunoreactivity in some new neocortical neurons suggested that they may instead be generated from the NG2+ precursors that reside within the cortex itself. C1 NIMH, Unit Neuroplast, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Cameron, HA (reprint author), NIMH, Unit Neuroplast, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM heathercameron@mail.nih.gov RI Messier, Claude/A-2322-2008; Cameron, Heather/E-6221-2011; OI Messier, Claude/0000-0002-4791-1763; Cameron, Heather/0000-0002-3245-5777; Dayer, Alexandre/0000-0002-4490-9780 NR 58 TC 262 Z9 272 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 31 PY 2005 VL 168 IS 3 BP 415 EP 427 DI 10.1083/jcb.200407053 PG 13 WC Cell Biology SC Cell Biology GA 896HP UT WOS:000226925500008 PM 15684031 ER PT J AU Xiao, Z Prieto, D Conrads, TP Veenstra, TD Issaq, HJ AF Xiao, Z Prieto, D Conrads, TP Veenstra, TD Issaq, HJ TI Proteomic patterns: their potential for disease diagnosis SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE proteomic patterns; SELDI; cancer; biomarker discovery ID ENHANCED LASER DESORPTION/IONIZATION; FLIGHT MASS-SPECTROMETRY; NIPPLE ASPIRATE FLUID; CANCER-CELL-LINES; PROSTATE-CANCER; OVARIAN-CANCER; SELDI-TOF; ALZHEIMERS-DISEASE; BREAST-CANCER; CEREBROSPINAL-FLUID AB Alterations in proteins abundance, structure, or function, act as useful indicators of pathological abnormalities prior to development of clinical symptoms and as such are often useful diagnostic and prognostic biomarkers. The underlying mechanism of diseases such as cancer are, however, quite complicated in that often multiple dysregulated proteins are involved. It is for this reason that recent hypotheses suggest that detection of panels of biomarkers may provide higher sensitivities and specificities for disease diagnosis than is afforded with single markers. Recently, a novel approach based on the analysis of protein patterns has emerged that may provide a more effective means to diagnose diseases, such as ovarian and prostate cancer. The method is based on the use of surface-enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry (TOF-MS) to detect differentially captured proteins from clinical samples, such as serum and plasma. This analysis results in the detection of "proteomic" patterns that have been shown in recent investigations to distinguish diseased and unaffected subjects to varying degrees. This review will discuss the basics of SELDI protein chip technology and highlight its recent applications in disease biomarker discovery with emphasis on cancer diagnosis. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 SAIC Frederick Inc, Lab Proteom & Analyt Technol, NCI, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), SAIC Frederick Inc, Lab Proteom & Analyt Technol, NCI, POB 8, Frederick, MD 21702 USA. EM issaqh@ncifcrf.gov FU NCI NIH HHS [N01 CO 12400] NR 66 TC 132 Z9 146 U1 2 U2 10 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JAN 31 PY 2005 VL 230 IS 1-2 BP 95 EP 106 DI 10.1016/j.mce.2004.10.010 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 896OZ UT WOS:000226944700012 PM 15664456 ER PT J AU Boguna, M Pajevic, S Basser, PJ Weiss, GH AF Boguna, M Pajevic, S Basser, PJ Weiss, GH TI A model for noise effects on fibre tract trajectories in diffusion tensor imaging: theory and simulations SO NEW JOURNAL OF PHYSICS LA English DT Article ID HUMAN BRAIN; WATER DIFFUSION; MATTER; MRI; CONNECTIVITY; ORIENTATION; PATHWAYS; TRACKING AB In vivo diffusion tensor data obtained with diffusion tensor magnetic resonance imaging (DT-MRI) can be used to estimate fibre tract trajectories in white matter in the brain. Such data can, for example, be used to visualize and study the connectivity and continuity of neural pathways in the central and peripheral nervous systems. This paper discusses a toy model which is used to assess limitations on the reliability of computed trajectories imposed by MRI noise. The analysis is based on a two-dimensional random walk model for which a very good approximate solution is available. The suggested theoretical approach to analyse this model is shown to be in excellent agreement with simulations. C1 NIH, Math & Stat Comp Lab, DCB, CIT, Bethesda, MD 20892 USA. Univ Barcelona, Dept Fis Fonamental, Barcelona, Spain. NICHD, Sect Tissue Biophys & Biomimet, LIMB, NIH, Bethesda, MD 20892 USA. RP Weiss, GH (reprint author), NIH, Math & Stat Comp Lab, DCB, CIT, Bldg 10, Bethesda, MD 20892 USA. EM ghw@helix.nih.gov RI Boguna, Marian/B-7795-2011; Basser, Peter/H-5477-2011 OI Boguna, Marian/0000-0001-7833-3487; NR 36 TC 1 Z9 1 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1367-2630 J9 NEW J PHYS JI New J. Phys. PD JAN 31 PY 2005 VL 7 AR 24 DI 10.1088/1367-2630/7/1/024 PG 10 WC Physics, Multidisciplinary SC Physics GA 892VQ UT WOS:000226678500013 ER PT J AU Hummer, G AF Hummer, G TI Position-dependent diffusion coefficients and free energies from Bayesian analysis of equilibrium and replica molecular dynamics simulations SO NEW JOURNAL OF PHYSICS LA English DT Article ID SYSTEMS; RECONSTRUCTION; KINETICS; MODELS AB Bayesian inference is used to obtain self-consistent estimates of free energies and position-dependent diffusion coefficients along complex reaction coordinates from molecular dynamics simulation trajectories. Effectively, exact solutions for the dynamics of a diffusive model are matched globally to the observed molecular dynamics data. The approach is first tested for a simple one-dimensional diffusion model, and then applied to the dihedral-angle dynamics of a peptide fragment dissolved in water. Both long equilibrium molecular dynamics simulations and short, appropriately initialized, replica simulations are used to sample the short-time dynamics of the peptide-water system. In both cases, accurate estimates of free energies and diffusion coefficients are obtained. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM Gerhard.Hummer@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 29 TC 195 Z9 195 U1 6 U2 49 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1367-2630 J9 NEW J PHYS JI New J. Phys. PD JAN 31 PY 2005 VL 7 AR 34 DI 10.1088/1367-2630/7/1/034 PG 14 WC Physics, Multidisciplinary SC Physics GA 892VQ UT WOS:000226678500003 ER PT J AU Toyooka, N Nemoto, H Kawasaki, M Garraffo, HM Spande, TF Daly, JW AF Toyooka, N Nemoto, H Kawasaki, M Garraffo, HM Spande, TF Daly, JW TI Enantioselective syntheses of two 5, 9E diastereomers of 223V, an alkaloid from the poison frog Dendrobates pumilio SO TETRAHEDRON LA English DT Article DE enantioselective syntheses; diastereomers; alkaloid ID INDOLIZIDINE ALKALOIDS; (-)-INDOLIZIDINE 209B; ASYMMETRIC-SYNTHESIS; STEREOSELECTIVE-SYNTHESIS; (+/-)-INDOLIZIDINES 167B; DYNEMICIN-A; 207A; 8-METHYLINDOLIZIDINES; DECAHYDROQUINOLINES; QUINOLIZIDINES AB Enantioselective syntheses of two 5, 9E diastereomers (1 and 2) of 223V (3) are described. Neither corresponded on GC-MS and GC-FTIR analyses to alkaloid 223I, previously tentatively proposed to be a 5,8-disubstituted indolizidine of the unusual 5, 9E relative stereochemistry. Synthetic (-)-(5, 9Z)-5-n-propyl-8-n-butylindolizidine (3) corresponds on GC-MS and GC-FTIR analyses to the natural indolizidine 223V found in a pumilio from 'Split Hill', Panama. (C) 2004 Elsevier Ltd. All rights reserved. C1 Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Toyama 9300194, Japan. Toyama Prefectural Univ, Dept Liberal Arts & Sci, Fac Engn, Toyama 9390398, Japan. NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Toyooka, N (reprint author), Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Sugitani 2630, Toyama 9300194, Japan. EM toyooka@ms.toyama-ac.jp NR 26 TC 15 Z9 15 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD JAN 31 PY 2005 VL 61 IS 5 BP 1187 EP 1198 DI 10.1016/j.tet.2004.11.060 PG 12 WC Chemistry, Organic SC Chemistry GA 891EZ UT WOS:000226565400018 ER PT J AU Vlangos, CN Wilson, M Blancato, J Smith, ACM Elsea, SH AF Vlangos, CN Wilson, M Blancato, J Smith, ACM Elsea, SH TI Diagnostic FISH probes for del(17)(p11.2p11.2) associated with Smith-Magenis syndrome should contain the RAI1 gene SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article; Proceedings Paper CT 23rd David W Smith Workshop on Malformations and Morphogenesis CY AUG 07-11, 2002 CL Greenville, SC DE Smith-Magenis syndrome; fluorescent in situ hybridization; microdeletion; RAI1 ID INTERSTITIAL DELETION; 17P11.2 DELETIONS; ALAGILLE-SYNDROME; CIRCADIAN-RHYTHM; HUMAN JAGGED1; MUTATIONS; (17)(P11.2P11.2); MELATONIN; BEHAVIOR; CHILDREN AB Smith-Magenis syndrome (SMS) is a mental retardation syndrome with distinctive behavioral characteristics, dysmorphic features, and congenital anomalies usually associated with an interstitial deletion of chromosome 17p11.2. While high quality G-banding will identify most SMS patients, fluorescent in situ hybridization (FISH) is the recommended test for confirmation of an SMS diagnosis. Recently, haploinsufficiency of the RAI1 gene due to deletion or mutation was determined to be the likely cause of SMS. All diagnostic FISH probes available commercially contain the FLII gene and are approximately 580 kb centromeric to RAI1. We present two patients with SMS who have interstitial deletions at 17p11.2 but are not deleted for currently available commercial FISH probes that include FLII; both patients have deletions that are demonstrated with probes containing the RAI1 gene. We recommend that for diagnostic accuracy, all future FISH tests for SMS be performed with probes containing the RAI1 gene, as some atypical deletions in the region critical to the SMS phenotype will otherwise be missed. (C) 2004 Wiley-Liss, Inc. C1 Virginia Commonwealth Univ, Dept Pediat, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23298 USA. Michigan State Univ, Genet Grad Program, E Lansing, MI 48824 USA. Childrens Hosp Westmead, Dept Clin Genet, Westmead, NSW, Australia. Georgetown Univ, Inst Mol & Human Genet, Washington, DC 20057 USA. Natl Human Genome Res Inst, Med Genet Branch, HHS, NIH, Bethesda, MD USA. RP Elsea, SH (reprint author), Virginia Commonwealth Univ, Dept Pediat, POB 980441,12-018 Sanger Hall, Richmond, VA 23298 USA. EM selsea@vcu.edu FU NHGRI NIH HHS [01-HG-0109]; NICHD NIH HHS [HD38534] NR 20 TC 23 Z9 26 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN 30 PY 2005 VL 132A IS 3 BP 278 EP 282 DI 10.1002/ajmg.a.30461 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 885UC UT WOS:000226181500011 PM 15690371 ER PT J AU Korn, EL Albert, PS McShane, LM AF Korn, EL Albert, PS McShane, LM TI Assessing surrogates as trial endpoints using mixed models SO STATISTICS IN MEDICINE LA English DT Article DE clinical trials; fixed effects; meta-analysis; random effects; surrogate endpoints; surrogates outcomes ID RANDOMIZED CLINICAL-TRIALS; ADVANCED OVARIAN-CANCER; PROPORTION; ENDPOINTS; SURVIVAL; VALIDATION; MARKER; METAANALYSES; CHEMOTHERAPY; DISCRETE AB Having a surrogate for a definitive endpoint in a clinical trial can sometimes be useful when it is impractical, invasive or very time consuming to obtain the definitive endpoint. This paper discusses methods for assessing whether the surrogate-endpoint results of a trial can be used in place of definitive-endpoint results. It is important when examining this trial-level surrogacy to include the possibility of trial-level effects and to distinguish whether the treatment arms are naturally ordered, e.g. A vs A+B rather than A vs B. Methods using mixed models of trial-level summaries are discussed and compared to fixed-effects models and to the possibility of using models of individual-level data. We give estimators for definitive-endpoint results of a trial that are predicted from the surrogate-endpoint results of the trial and a set of results from previous trials in which both the definitive and surrogate trial results were available. Graphical displays are also suggested. Two sets of trial results previously analysed for trial-level surrogacy are used as examples. Published in 2004 by John Wiley Sons, Ltd. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, EPN 8128, Bethesda, MD 20892 USA. EM korne@ctep.nci.nih.gov NR 26 TC 40 Z9 42 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2005 VL 24 IS 2 BP 163 EP 182 DI 10.1002/sim.1779 PG 20 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 886UE UT WOS:000226257400001 PM 15515150 ER PT J AU Korn, EL Albert, PS McShane, LM AF Korn, EL Albert, PS McShane, LM TI Rejoinder to commentary by Dr Freedman of 'Assessing surrogates as trial endpoints using mixed models' SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, EPN-8128, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2005 VL 24 IS 2 BP 187 EP 190 DI 10.1002/sim.2020 PG 4 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 886UE UT WOS:000226257400003 ER PT J AU Kashuba, ADM Tierney, C Downey, GF Acosta, EP Vergis, EN Klingman, K Mellors, JW Eshleman, SH Scott, TR Collier, AC AF Kashuba, ADM Tierney, C Downey, GF Acosta, EP Vergis, EN Klingman, K Mellors, JW Eshleman, SH Scott, TR Collier, AC TI Combining fosamprenavir with lopinavir/ritonavir substantially reduces amprenavir and lopinavir exposure: ACTG protocol A5143 results SO AIDS LA English DT Article; Proceedings Paper CT 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 14-17, 2003 CL CHICAGO, IL DE amprenavir; fosamprenavir; lopinavir; ritonavir; pharmacokinetics; drug interactions; protease inhibitors; salvage treatment ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; PROTEASE INHIBITOR; P-GLYCOPROTEIN; PHARMACOKINETIC INTERACTION; RITONAVIR; COMBINATION; RESISTANCE; SALVAGE; EXPRESSION AB Objective: To evaluate fosamprenavir/lopinavir (LPV)/ritonavir (RTV), fosamprenavir/RTV, or LPV/RTV in antiretroviral treatment-experienced patients. Lack of drug interaction data prompted a pharmacokinetic substudy to minimize subject risk. Design: Multi-center, open-label, selectively randomized, steady-state pharmacokinetic study in HIV-infected subjects. Methods: A planned independent interim review occurred after at least eight subjects were randomized to each arm. Subjects received twice daily LPV/RTV 400/100 mg (arm A; n = 8); fosamprenavir/RTV 700/100 mg (arm B; n = 8) or LPV/RTV/fosamprenavir 400/100/700 mg (arm C; n = 17). Plasma samples were collected over 12 h between study weeks 2 and 4. Pharmacokinetic parameters were compared based on a one-sided t-test on log-transformed data with a Peto stopping boundary (P < 0.001). Results: Amprenavir mean area under the curve over 12 h (AUC(0-12 h)) and concentration at 12 h (C-12 h) (mu g/ml) were, respectively, 42.7 mu g x h/ml (range, 33.1-55.1) and 2.4 mu g/ml (range, 1.4-3.2) in arm B and 17.4 mu g x h/ml (range, 4.6-41.3) and 0.9 mu g/ml (range, 0.2-2.7) in arm C: geometric mean ratio (GMR) arm C:B was 0.36 [99.9% upper confidence boundary (UCB), 0.64] and 0.31 (99.9% h UCB, 0.61), respectively (P <= 0.0001). Lopinavir AUC(0-12 h) and C-12 h were, respectively, 95.3 mu g x h/ml (range, 60.3-119.3) and 6.3 mu g/ml (range, 2.2-9.2) in arm A and 54.4 mu g x h/ml (range, 23.5-112.2) and 3.0 mu g/ml (range, 0.4-7.9) in arm C: GMR arm C:A of 0.52 (99.9% UCB, 0.89) and 0.39 (99.9% UCB, 0.98), respectively (P <= 0.0008). Ritonavir exposure was not significantly different between arms. Conclusion: APV and LPV exposures are significantly reduced using LPV/RTV/fosamprenavir, possibly increasing the risk of virologic failure. Consequently, A5143 was closed to enrollment. (c) 2005 Lippincott Williams & Wilkins. C1 Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, SDAC, Boston, MA USA. Univ Alabama Birmingham, Div Clin Pharmacol, Birmingham, AL 35294 USA. Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. DAIDS, TRP, HIV Res Branch, NIAID,NIH, Bethesda, MD USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Kashuba, ADM (reprint author), Univ N Carolina, Sch Pharm, Kerr Hall,CB 7360, Chapel Hill, NC 27599 USA. EM akashuba@unc.edu FU NCRR NIH HHS [M01-RR-0037]; NIAID NIH HHS [AI54980, AI32775, AI38855, AI27664] NR 40 TC 45 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 28 PY 2005 VL 19 IS 2 BP 145 EP 152 DI 10.1097/00002030-200501280-00006 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 904EH UT WOS:000227478400006 PM 15668539 ER PT J AU Chen, L Trujillo, KM Van Komen, S Roh, DH Krejci, L Lewis, LK Resnick, MA Sung, P Tomkinson, AE AF Chen, L Trujillo, KM Van Komen, S Roh, DH Krejci, L Lewis, LK Resnick, MA Sung, P Tomkinson, AE TI Effect of amino acid substitutions in the Rad50 ATP binding domain on DNA double strand break repair in yeast SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DAMAGE RESPONSE; NUCLEASE ACTIVITIES; PROTEIN COMPLEX; MRE11 COMPLEX; RECOMBINATION; PATHWAY; ENDS; IDENTIFICATION; MAINTENANCE AB The Saccharomyces cerevisiae Rad50-Mre11-Xrs2 complex plays a central role in the cellular response to DNA double strand breaks. Rad50 has a globular ATPase head domain with a long coiled-coil tail. DNA binding by Rad50 is ATP-dependent and the Rad50-Mre11-Xrs2 complex possesses DNA unwinding and endonuclease activities that are regulated by ATP. Here we have examined the role of the Rad50 Walker type A ATP binding motif in DNA double strand break repair by a combination of genetic and biochemical approaches. Replacement of the conserved lysine residue within the Walker A motif with alanine, glutamate, or arginine results in the same DNA damage sensitivity and homologous recombination defect as the rad50 deletion mutation. The Walker A mutations also cause a deficiency in non-homologous end-joining. As expected, complexes containing the rad50 Walker A mutant proteins are defective in ATPase, ATP-dependent DNA unwinding, and ATP-stimulated endonuclease activities. Although the DNA end-bridging activity of the Rad50-Mre11-Xrs2 complex is ATP-independent, the end-bridging activity of complexes containing the rad50 Walker A mutant proteins is salt-sensitive. These results provide a molecular explanation for the observed in vivo defects of the rad50 Walker mutant strains and reveal a novel ATP-independent function for Rad50 in DNA end-bridging. C1 Univ Maryland, Sch Med, Dept Radiat Oncol, Radiat Oncol Res Lab, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Texas, Hlth Sci Ctr, Dept Mol Med, Inst Biotechnol, San Antonio, TX 78245 USA. Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. SW Texas State Univ, Dept Chem & Biochem, San Marcos, TX 78666 USA. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Univ Maryland, Sch Med, Dept Radiat Oncol, Radiat Oncol Res Lab, 655 W Baltimore St, Baltimore, MD 21201 USA. EM atomkinson@som.umaryland.edu RI Krejci, Lumir/B-7842-2009 OI Krejci, Lumir/0000-0002-4732-1405 FU NIEHS NIH HHS [R01 ES07061]; NIGMS NIH HHS [R01 GM47251] NR 47 TC 28 Z9 29 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 28 PY 2005 VL 280 IS 4 BP 2620 EP 2627 DI 10.1074/jbc.M410192200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 889NG UT WOS:000226449100031 PM 15546877 ER PT J AU Gozansky, EK Louis, JM Caffrey, MC Clore, GM AF Gozansky, EK Louis, JM Caffrey, MC Clore, GM TI Mapping the binding of the tail of the CXCR4 receptor n-terminal extracellular to stromal cell-derived factor-1 alpha SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE chemokine; SDF-1 alpha; CXCR4 receptor; chemical shift mapping; solution structure ID MACROMOLECULAR STRUCTURE DETERMINATION; NMR STRUCTURE REFINEMENT; CRYSTAL-STRUCTURE; FACTOR-I; HIV-1; PROTEINS; LIGAND; SDF-1; LESTR/FUSIN; VALIDATION AB The solution structure of monomeric stromal cell-derived factor-1alpha (SDF-1alpha), the natural ligand for the CXCR4 G-coupled receptor, has been solved by multidimensional heteronuclear NMR spectroscopy. The structure has a characteristic chemokine fold and is in excellent agreement with the individual subunits observed in the crystal structures of dimeric SDF-1alpha. Using various peptides derived from. the N-terminal extracellular tail of the CXCR4 receptor, we show that the principal determinants of binding reside in the N-terminal 17 residues of CXCR4, with a major contribution from the first six residues. From N-15/H-1(N) chemical shift pertubation studies we show that the interaction surface on SDF-1alpha is formed by the undersurface parallel beta-sheet bounded by the N-terminal loop of the three-stranded anti on one side and the C-terminal helix on the other. This surface overlaps with but is not identical to that mapped on several other chemokines for the binding of equivalent peptides derived from their respective receptors. Published by Elsevier Ltd. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 35 TC 45 Z9 47 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 28 PY 2005 VL 345 IS 4 BP 651 EP 658 DI 10.1016/j.jmb.2004.11.003 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 881ZW UT WOS:000225909100002 PM 15588815 ER PT J AU Le Foll, B Diaz, J Sokoloff, P AF Le Foll, B Diaz, J Sokoloff, P TI Neuroadaptations to hyperdopaminergia in dopamine D-3 receptor-deficient mice SO LIFE SCIENCES LA English DT Article DE grooming; knock-out mice; autoreceptor; in situ hybridization; synaptosomes; substance P; dopamine; drug; abuse; cues; D-3 receptor; cocaine; morphine; nicotine ID INSITU HYBRIDIZATION HISTOCHEMISTRY; RAT-BRAIN; COCAINE-SEEKING; IN-VIVO; NUCLEUS-ACCUMBENS; GENE-EXPRESSION; MESSENGER-RNA; D2 RECEPTORS; FUNCTIONAL-CHARACTERIZATION; AUTORECEPTOR FUNCTION AB The dopamine D-3 receptor (D3R) has been implicated in schizophrenia, drug addiction, depression and Parkinson's disease. The D3R is localized post-synaptically on nucleus accumbens neurons, but is also an autoreceptor on dopaminergic neurons in the mesencephalon. Its functional role as autoreceptor is highly debated, but supported by the elevated basal extracellular dopamine levels found in D3R-deficient mice. To investigate the functional role of the D3R in vivo, we used mice with a targeted disruption of the D3R gene. We found a higher basal level of grooming in D3R-deficient mice, compared to their wild-type littermates. This behavior, which is under the control of D1R stimulation, may be related to an increased dopaminergic tone, since no changes in the gene expression of dopamine D-1 and D-2 receptors were noticed in the striatum of these mice. D3R-deficient mice displayed other neuroadaptive changes, including decreased tyrosine hydroxylase, increased dopamine transporter mRNAs and increased dopamine reuptake in striatum. The level of tyrosine hydroxylase protein was unchanged in the striatum, as preprodynorphin and preproenkephalin gene expressions. All the changes identified in D3R-deficient mice cannot explain hyperdopaminergia, but, on the contrary, tend to attenuate this phenotype. These results support a distinct role for D2R and D3R as autoreceptors: the D2R is the release-regulating and firing rate-regulating autoreceptor, whereas the D3R may control basal dopamine levels in the striatum, by an unknown mechanism, which does not involve regulation of dopamine transporters or tyrosine hydroxylase. This hyperdopaminergia phenotype of D3R-deficient mice may explain their hyperactivity to drug-paired environmental cues. (C) 2004 Elsevier Inc. All rights reserved. C1 INSERM, Unite Neurobiol & Pharmacol Mol, U573, Ctr Paul Broca, F-75014 Paris, France. Univ Paris 05, Physiol Lab, F-75006 Paris, France. RP Le Foll, B (reprint author), NIDA, NIH, Intramural Res Program, Behav Neurosci Branch,Preclin Pharmacol Sect, POB 5180,5500 Nathan Shock Dr,Bldg C,Room 435, Baltimore, MD 21224 USA. EM blefoll@intra.nida.nih.gov RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 FU NIDA NIH HHS [R01-DA11534] NR 84 TC 35 Z9 36 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JAN 28 PY 2005 VL 76 IS 11 BP 1281 EP 1296 DI 10.1016/j.lfs.2004.09.018 PG 16 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 893IJ UT WOS:000226712200009 PM 15642598 ER PT J AU Teeling, EC Springer, MS Madsen, O Bates, P O'Brien, SJ Murphy, WJ AF Teeling, EC Springer, MS Madsen, O Bates, P O'Brien, SJ Murphy, WJ TI A molecular phylogeny for bats illuminates biogeography and the fossil record SO SCIENCE LA English DT Article ID EOCENE BAT; CHIROPTERA; ECHOLOCATION; SEQUENCES AB Bats make up more than 20% of extant mammals, yet their evolutionary history is largely unknown because of a limited fossil record and conflicting or incomplete phylogenies. Here, we present a highly resolved molecular phylogeny for all extant bat families. Our results support the hypothesis that megabats are nested among four major microbat lineages, which originated in the early Eocene [52 to 50 million years ago (Mya)], coincident with a significant global rise in temperature, increase in plant diversity and abundance, and the zenith of Tertiary insect diversity. Our data suggest that bats originated in Laurasia, possibly in North America, and that three of the major microbat lineages are Laurasian in origin, whereas the fourth is Gondwanan. Combining principles of ghost lineage analysis with molecular divergence dates, we estimate that the bat fossil record underestimates (unrepresented basal branch length, UBBL) first occurrences by, on average, 73% and that the sum of missing fossil history is 61%. C1 NCI, Lab Genom Divers, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. Univ Coll Dublin, Dept Zool, Dublin 4, Ireland. Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA. Radboud Univ Nijmegen, Dept Biochem, NL-6500 HB Nijmegen, Netherlands. Harrison Inst, Ctr Systemat & Biodivers Res, Sevenoaks TN13 3AQ, Kent, England. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. RP Teeling, EC (reprint author), NCI, Lab Genom Divers, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM emma.teeling@ucd.ie; mark.springer@ucr.edu; obrien@mail.ncifcrf.gov RI Robertson, Linda/D-1157-2010; Raleva, Sofiya/A-3114-2011; Madsen, Ole/E-3730-2012; Ho, Hilary/F-3029-2011 OI Madsen, Ole/0000-0001-8082-7881; FU NCI NIH HHS [N01-CO-12400] NR 29 TC 483 Z9 514 U1 38 U2 258 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 28 PY 2005 VL 307 IS 5709 BP 580 EP 584 DI 10.1126/science.1105113 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 893BJ UT WOS:000226694000047 PM 15681385 ER PT J AU Munro, TA Rizzacasa, MA Roth, BL Toth, BA Yan, F AF Munro, TA Rizzacasa, MA Roth, BL Toth, BA Yan, F TI Studies toward the pharmacophore of salvinorin A, a potent kappa opioid receptor agonist SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MINT SALVIA-DIVINORUM; NEOCLERODANE DITERPENOIDS; SAGE; CONVERSION; LACTONES; ETHERS AB Salvinorin A (1), from the sage Salvia divinorum, is a potent and selective K opioid receptor (KOR) agonist. We screened other salvinorins and derivatives for binding affinity and functional activity at opioid receptors. Our results suggest that the methyl ester and furan ring are required for activity but that the lactone and ketone functionalities are not. Other salvinorins showed negligible binding affinity at the KOR. None of the compounds bound to mu or delta opioid receptors. C1 Univ Melbourne, Sch Chem, Melbourne, Vic 3010, Australia. Case Western Reserve Univ, Sch Med, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. RP Rizzacasa, MA (reprint author), Univ Melbourne, Sch Chem, Melbourne, Vic 3010, Australia. EM masr@unimelb.edu.au RI Munro, Thomas/B-2712-2009; Roth, Bryan/F-3928-2010 OI Munro, Thomas/0000-0002-3366-7149; FU NIDA NIH HHS [R01DA017204, R01 DA017204-05, R01 DA017204]; NIMH NIH HHS [K02MH01366, K02 MH001366-10, K02 MH001366] NR 24 TC 77 Z9 79 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 27 PY 2005 VL 48 IS 2 BP 345 EP 348 DI 10.1021/jm049438q PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 891OZ UT WOS:000226591700002 PM 15658846 ER PT J AU Li, TY Fujita, Y Tsuda, Y Miyazaki, A Ambo, A Sasaki, Y Jinsmaa, Y Bryant, SD Lazarus, LH Okada, Y AF Li, TY Fujita, Y Tsuda, Y Miyazaki, A Ambo, A Sasaki, Y Jinsmaa, Y Bryant, SD Lazarus, LH Okada, Y TI Development of potent mu-opioid receptor ligands using unique tyrosine analogues of endomorphin-2 SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DMT-TIC PHARMACOPHORE; AROMATIC-AMINO-ACIDS; ASYMMETRIC-SYNTHESIS; METHIONINE-ENKEPHALIN; ANTAGONIST PROPERTIES; NUCLEOPHILIC GLYCINE; MEDIATED ANALGESIA; DELTA; AGONIST; SELECTIVITY AB Six analogues of tyrosine, which contained alkyl groups at positions 2', 3', and 6', either singly or in combination on the tyramine ring, were investigated for their effect on the opioid activity of [Xaa(1)]endomorphin-2 (EM-2). The opioid analogues displayed the following characteristics: (i) high mu-opioid receptor affinity [K-i(mu) = 0.063-2.29 nM] with selectivity [K-i(delta)/Ki(mu)] ranging from 46 to 5347; (ii) potent functional mu-opioid agonism [GPI assay (IC50 = 0.623-0.924 nM)1 and with a correlation between delta-opioid receptor affinities and functional bioactivity using MVD; (iii) intracerebroventricular administration of [Dmt(1)]- (14) and [Det(1)]EM-2 (10) produced a dose-response antinociception in mice, with the former analogue more active than the latter; and (iv) a marked shift occurred from the trans-orientation at the Tyr(1)-Pro(2) bond to a cis-conformer compared to that observed previously with [Dmt(1)]EM-2 (14) (Okada et al. Bioorg. Med. Chem. 2003, 11, 1983-1984) except [Mmt(1)]EM-2 (7). The active profile of the [Xaa(1)]EM-2 analogues indicated that significant modifications on the tyramine ring are possible while high biological activity is maintained. C1 NIEHS, Med Chem Grp, LPC, Res Triangle Pk, NC 27709 USA. Tohoku Pharmaceut Univ, Aoba Ku, Sendai, Miyagi 9818558, Japan. Kobe Gakuin Univ, Fac Pharmaceut Sci, Grad Sch Food & Med Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, High Technol Res Ctr, Nishi Ku, Kobe, Hyogo 6512180, Japan. RP Lazarus, LH (reprint author), NIEHS, Med Chem Grp, LPC, Res Triangle Pk, NC 27709 USA. EM lazarus@niehs.nih.gov; okada@pharm.kobegakuin.ac.jp NR 51 TC 37 Z9 42 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 27 PY 2005 VL 48 IS 2 BP 586 EP 592 DI 10.1021/jm049384k PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 891OZ UT WOS:000226591700027 PM 15658871 ER PT J AU Krause, RM AF Krause, RM TI Maclyn McCarty (1911-2005) - Obituary SO NATURE LA English DT Biographical-Item C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Krause, RM (reprint author), NIAID, NIH, 16 Ctr Dr, Bethesda, MD 20892 USA. EM richard_krause@nih.gov NR 1 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 0028-0836 J9 NATURE JI Nature PD JAN 27 PY 2005 VL 433 IS 7024 BP 372 EP 372 DI 10.1038/433372a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 890XZ UT WOS:000226546200028 PM 15674278 ER PT J AU Walsh, TJ Donowitz, GR dePauw, BE AF Walsh, TJ Donowitz, GR dePauw, BE TI Caspofungin versus liposomal amphotericin B for empirical therapy - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID INVASIVE ASPERGILLOSIS; RANDOMIZED-TRIAL C1 NCI, Bethesda, MD 20892 USA. Univ Virginia Hlth Syst, Charlottesville, VA 22908 USA. Univ Hosp St Radboud, NL-6525 GA Nijmegen, Netherlands. RP Walsh, TJ (reprint author), NCI, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 27 PY 2005 VL 352 IS 4 BP 413 EP 414 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 890UH UT WOS:000226535900022 ER PT J AU Huh, JI Calvo, A Stafford, J Cheung, M Kumar, R Philp, D Kleinman, HK Green, JE AF Huh, JI Calvo, A Stafford, J Cheung, M Kumar, R Philp, D Kleinman, HK Green, JE TI Inhibition of VEGF receptors significantly impairs mammary cancer growth in C3(1)/Tag transgenic mice through antiangiogenic and nonantiangiogenic mechanisms SO ONCOGENE LA English DT Article DE antiangiogenesis; VEGFR tyrosine kinase inhibitor; mammary cancer; C3(1)/Tag transgenic mice ID BONE-MARROW MICROENVIRONMENT; MULTIPLE-MYELOMA CELLS; TYROSINE KINASE; MOUSE MODEL; MONOCLONAL-ANTIBODY; ENDOTHELIAL-CELLS; BREAST-CANCER; THERAPY; ANTIGEN; ENDOSTATIN AB Cancer growth and progression is often critically influenced by the production of vascular endothelial growth factor ( VEGF), a key mediator of angiogenesis. VEGF produced by tumor cells stimulates endothelial cell growth through the binding and activation of the KDR/Flk-1 receptor (VEGFR-2) on endothelial cells. Recently, some human breast cancer epithelial cells have been shown to express VEGF receptors, suggesting a potential autocrine-mediated growth stimulation of a subset of cancers by VEGF. We demonstrate that mammary tumors in the C3(1)/Tag transgenic model express VEGF and VEGF receptors and tumor growth is stimulated by this autocrine mechanism. GW654652, an indazolylpyrimidine, is a VEGFRs tyrosine kinase inhibitor that dramatically reduces both angiogenesis and tumor cell growth in this model, as demonstrated using both in vitro and in vivo assays. GW654652 significantly decreased cell proliferation and induced apoptosis in human umbilical vein endothelial cells and M6 mammary tumor cells derived from C3(1)/Tag ( Tag: simian virus 40 T-antigen) transgenic mice. A 75% reduction in VEGF-induced angiogenesis was observed with GW654652 using the chick chorioallantoic membrane assay, whereas GW654652 produced an approximately 85% reduction in angiogenesis as assessed by the Matrigel(TM) plug assay. A profound inhibitory effect on tumor growth in the C3(1)/Tag transgenic model of human breast cancer was observed with oral administration of GW654652 as measured by delayed tumor onset, decreased multiplicity, reduced tumor volume, and extended animal survival. The antitumor effects of GW654652 were associated with reduced tumor vascularization and no apparent toxicity. Tumor growth, however, rapidly advanced following cessation of treatment. This is the first demonstration that a VEGF receptor inhibitor, GW654652, has a strong inhibitory effect on angiogenesis and tumor progression in a transgenic model of mammary cancer, suggesting that this is a useful approach for preclinical testing of such agents. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Cell Biol Sect, NIH, Bethesda, MD USA. GlaxoSmithKline, Res Triangle Pk, NC USA. RP Green, JE (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bldg 41,Room C629,41 Medlars Dr, Bethesda, MD 20892 USA. EM jegreen@nih.gov NR 38 TC 40 Z9 40 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 27 PY 2005 VL 24 IS 5 BP 790 EP 800 DI 10.1038/sj.onc.1208221 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 891JM UT WOS:000226577100005 PM 15592523 ER PT J AU Akpinar, E Keary, JM Kurlander, R Hale, DA AF Akpinar, E Keary, JM Kurlander, R Hale, DA TI Measurement of chimerism in cynomolgus monkeys using human-specific short tandem repeat-based assay SO TRANSPLANTATION LA English DT Article DE short tandem repeats; mixed chimerism; nonhuman primate; cynomolgus; microsatellite ID TRANSPLANTATION; TOLERANCE; MARKERS AB Prectinical testing of a mixed chimerism mediated organ transplant tolerance strategy, in a cynomolgus macaque model, would be facilitated by the establishment of a reliable technique for quantitative assessment of chimerism. Among various techniques used for measurement of chimerism in humans, microsatellite DNA profiling has been considered the most versatile one that can discriminate between two individuals. We adopted a commercially available short tandem repeat profiling methodology to cynomolgus monkeys using two human specific alleles, TPOX and CSF I PO. Polymerase chain reaction (PCR) was used to amplify these alleles, and the analysis of the PCR products was performed by capillary electrophoresis. Of 54 cynomolgus macaques investigated, only one pair with the same ABO blood type demonstrated identity at both alleles. This implies that this technique should interfere minimally with the assignment of donor-recipient pairs based upon molecular tissue typing or mixed lymphocyte cultures. C1 NIDDKD, NIH, Transplantat Branch, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. RP Hale, DA (reprint author), Room 5-5-750,Bldg 10,Ctr Dr, Bethesda, MD 20892 USA. EM douglash@intra.niddk.nih.gov RI AKPINAR, Edip/C-3402-2014 OI AKPINAR, Edip/0000-0003-1445-8680 NR 11 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 27 PY 2005 VL 79 IS 2 BP 236 EP 239 DI 10.1097/01.TP.0000148916.95656.93 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 891FH UT WOS:000226566200016 PM 15665773 ER PT J AU Corner, FI Lippincott, CK Masbad, JJ Parent, CA AF Corner, FI Lippincott, CK Masbad, JJ Parent, CA TI The PI3K-mediated activation of CRAC independently regulates adenylyl cyclase activation and chemotaxis SO CURRENT BIOLOGY LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAINS; PROTEIN-MEDIATED ACTIVATION; CHEMOATTRACTANT RECEPTOR; LEADING-EDGE; DICTYOSTELIUM; ROLES; CELLS; LOCALIZATION; PI(3,4,5)P-3; AKT/PKB AB The ability of a cell to detect an external chemical signal and initiate a program of directed migration along a gradient comprises the fundamental process called chemotaxis [1]. Investigations in Dictyostelium discoideum and neutrophils have established that pleckstrin homology (PH) domain-containing proteins that bind to the PI3K products PI(3,4)P-2 and PI(3,4,5)P-3, such as CRAC (cytosolic regulator of adenylyl cyclase) and Akt/PKB, translocate specifically to the leading edge of chemotaxing cells [2-4]. CRAC is essential for the chemoattractant-mediated activation of the adenylyl cyclase ACA [5], which converts ATP into cAMP, the primary chemoattractant for D. discoideum. The mechanisms by which CRAC activates ACA remain to be determined. We now show that in addition to its essential role in the activation of ACA, CRAC is involved in regulating chemotaxis. Through mutagenesis, we show that these two functions are independently regulated downstream of Pl3K. A CRAC mutant that has lost the capacity to bind PI3K products does not support chemotaxis and shows minimal ACA activation. Finally, overexpression of CRAC and various CRAC mutants show strong effects on ACA activation with little effect on chemotaxis. These findings establish that chemoattractant-mediated activation of PI3K is important for the CRAC-dependent regulation of both chemotaxis and adenylyl cyclase activation. C1 NCI, Cellular & Mol Biol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NIGMS, PRAT, Res Fellowship Program, NIH, Bethesda, MD 20892 USA. RP NCI, Cellular & Mol Biol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. EM parentc@helix.nih.gov NR 20 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD JAN 26 PY 2005 VL 15 IS 2 BP 134 EP 139 DI 10.1016/j.cub.2005.01.007 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 895JZ UT WOS:000226858600024 ER PT J AU Venkatesh, K Chivatakarn, O Lee, H Joshi, PS Kantor, DB Newman, BA Mage, R Rader, C Giger, RJ AF Venkatesh, K Chivatakarn, O Lee, H Joshi, PS Kantor, DB Newman, BA Mage, R Rader, C Giger, RJ TI The Nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor selective for myelin-associated glycoprotein SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neuron; axon; neurite outgrowth; myelin; MAG; Nogo receptor; ganglioside ID INHIBITS AXONAL REGENERATION; LIPID RAFTS MEDIATE; NEURITE OUTGROWTH; BLOCKS INHIBITION; BINDING PARTNER; GENE-TRANSFER; SPINAL-CORD; GROWTH; MAG; GANGLIOSIDES AB The Nogo-66 receptor (NgR1) is a promiscuous receptor for the myelin inhibitory proteins Nogo/Nogo-66, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp). NgR1, an axonal glycoprotein, is the founding member of a protein family composed of the structurally related molecules NgR1, NgR2, and NgR3. Here we show that NgR2 is a novel receptor for MAG and acts selectively to mediate MAG inhibitory responses. MAG binds NgR2 directly and with greater affinity than NgR1. In neurons NgR1 and NgR2 support MAG binding in a sialic acid-dependent Vibrio cholerae neuraminidase-sensitive manner. Forced expression of NgR2 is sufficient to impart MAG inhibition to neonatal sensory neurons. Soluble NgR2 has MAG antagonistic capacity and promotes neuronal growth on MAG and CNS myelin substrate in vitro. Structural studies have revealed that the NgR2 leucine-rich repeat cluster and the NgR2 "unique" domain are necessary for high-affinity MAG binding. Consistent with its role as a neuronal MAG receptor, NgR2 is an axon-associated glycoprotein. In postnatal brain NgR1 and NgR2 are strongly enriched in Triton X-100-insoluble lipid rafts. Neural expression studies of NgR1 and NgR2 have revealed broad and overlapping, yet distinct, distribution in the mature CNS. Taken together, our studies identify NgRs as a family of receptors ( or components of receptors) for myelin inhibitors and provide insights into how interactions between MAG and members of the Nogo receptor family function to coordinate myelin inhibitory responses. C1 Univ Rochester, Sch Med & Dent, Ctr Aging & Dev Biol, Grad Program Neurosci, Rochester, NY 14642 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Giger, RJ (reprint author), Univ Rochester, Sch Med & Dent, Ctr Aging & Dev Biol, Grad Program Neurosci, 601 Elmwood Ave, Rochester, NY 14642 USA. EM Roman_Giger@URMC.Rochester.edu FU NINDS NIH HHS [NS047333, T32 NS07489] NR 61 TC 155 Z9 159 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 26 PY 2005 VL 25 IS 4 BP 808 EP 822 DI 10.1523/JNEUROSCI.4464-04.2005 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 891JL UT WOS:000226577000005 PM 15673660 ER PT J AU Smolka, MN Schumann, G Wrase, J Grusser, SM Flor, H Mann, K Braus, DF Goldman, D Buchel, C Heinz, A AF Smolka, MN Schumann, G Wrase, J Grusser, SM Flor, H Mann, K Braus, DF Goldman, D Buchel, C Heinz, A TI Catechol-O-methyltransferase val(158)met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE gene; catecholamine; emotion; amygdala; prefrontal; fMRI; COMT ID OBSESSIVE-COMPULSIVE DISORDER; LOW-ACTIVITY ALLELE; FUNCTIONAL POLYMORPHISM; GENETIC-VARIATION; BIPOLAR DISORDER; NEURAL CIRCUITS; PANIC DISORDER; ASSOCIATION; ANXIETY; COMT AB Catechol-O-methyltransferase (COMT) degrades the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. A functional polymorphism in the COMT gene (val(158)met) accounts for a fourfold variation in enzyme activity. The low-activity met(158) allele has been associated with improved working memory but with higher risk for anxiety-related behaviors. Using functional magnetic resonance imaging, we assessed the effects of COMT genotype on brain activation by standardized affective visual stimuli ( unpleasant, pleasant, and neutral) in 35 healthy subjects. The analysis of genotype effects was restricted to brain areas with robust activation by the task. To determine gene - dose effects, the number of met(158) alleles (0, 1, or 2) was correlated with the blood oxygen level-dependent (BOLD) response elicited by pleasant or unpleasant stimuli compared with neutral stimuli. COMT genotype had no significant impact on brain activation by pleasant stimuli but was related to the neural response to unpleasant stimuli: reactivity to unpleasant stimuli was significantly positively correlated with the number of met(158) alleles in the limbic system ( left hippocampus, right amygdala, right thalamus), connected prefrontal areas ( bilateral ventrolateral prefrontal cortex, right dorsolateral prefrontal cortex), and the visuospatial attention system ( bilateral fusiform gyrus, left inferior parietal lobule). Genotype explained up to 38% of interindividual variance in BOLD response elicited by unpleasant stimuli. We conclude that ( 1) genetic variations can account for a substantial part of interindividual variance in task-related brain activation and that ( 2) increased limbic and prefrontal activation elicited by unpleasant stimuli in subjects with more met(158) alleles might contribute to the observed lower emotional resilience against negative mood states. C1 Cent Inst Mental Hlth, D-68159 Mannheim, Germany. Charite Univ Med Berlin, Dept Psychiat, D-10117 Berlin, Germany. Charite Univ Med Berlin, Med Psychol Charite, D-10117 Berlin, Germany. Univ Hamburg, Dept Psychiat, NeuroImage Nord, D-20246 Hamburg, Germany. Univ Hamburg, Dept Neurol, D-20246 Hamburg, Germany. NIAAA, NIH, Bethesda, MD 20892 USA. RP Heinz, A (reprint author), Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Charite Campus Mitte,Schumannstr 20-21, D-10117 Berlin, Germany. EM andreas.heinz@charite.de RI Smolka, Michael/B-4865-2011; Goldman, David/F-9772-2010; OI Smolka, Michael/0000-0001-5398-5569; Goldman, David/0000-0002-1724-5405; Flor, Herta/0000-0003-4809-5398 NR 59 TC 285 Z9 295 U1 3 U2 23 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 JAN 26 PY 2005 VL 25 IS 4 BP 836 EP 842 DI 10.1523/JNEUROSCI.1792-04.2005 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 891JL UT WOS:000226577000008 PM 15673663 ER PT J AU Shell, SM Hess, S Kvaratskhelia, M Zou, Y AF Shell, SM Hess, S Kvaratskhelia, M Zou, Y TI Mass spectrometric identification of lysines involved in the interaction of human replication protein a with single-stranded DNA SO BIOCHEMISTRY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; BINDING DOMAIN; FUNCTIONAL-ANALYSIS; RPA-BINDING; XPA; COMPLEX; DAMAGE; SUBUNIT; RECOGNITION; MECHANISM AB Human replication protein A (hRPA), a heterotrimeric single-stranded DNA (ssDNA) binding protein, is required for many cellular pathways including DNA damage repair, recombination, and replication as well as the ATR-mediated DNA damage response. While extensive effort has been devoted to understanding the structural relationships between RPA and ssDNA, information is currently limited to the RPA domains, the trimerization core, and a partial cocrystal structure. In this work, we employed a mass spectrometric protein footprinting method of single amino acid resolution to investigate the interactions of the entire heterotrimeric hRPA with ssDNA. In particular, we monitored surface accessibility of RPA lysines with NHS-biotin modification in the contexts of the free protein and the nucleoprotein complex. Our results not only indicated excellent agreement with the available crystal structure data for RPA70 DBD-AB-ssDNA complex but also revealed new protein contacts in the nucleoprotein complex. In addition to two residues, K263 and K343 of p70, previously identified by cocrystallography as direct DNA contacts, we observed protection of five additional lysines (K183, K259, K489, K577, and K588 of p70) upon ssDNA binding to RPA. Three residues, K489, K577, and K588, are located in ssDNA binding domain C and are likely to establish the direct contacts with cognate DNA. In contrast, no ssDNA-contacting lysines were identified in DBD-D. In addition, two lysines, K183 and K259, are positioned outside the putative ssDNA binding cleft. We propose that the protection of these lysines could result from the RPA interdomain structural reorganization induced by ssDNA binding. C1 E Tennessee State Univ, James H Quillen Coll Med, Dept Biochem & Mol Biol, Johnson City, TN 37614 USA. NIDDKD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Ohio State Univ, Coll Pharm, Hlth Sci Ctr, Ctr Retrovirus Res, Columbus, OH 43210 USA. Ohio State Univ, Coll Pharm, Hlth Sci Ctr, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Zou, Y (reprint author), E Tennessee State Univ, James H Quillen Coll Med, Dept Biochem & Mol Biol, Johnson City, TN 37614 USA. EM zouy@etsu.edu RI Hess, Sonja/K-4842-2013 OI Hess, Sonja/0000-0002-5904-9816 FU NCI NIH HHS [CA86927, R01 CA086927, R56 CA086927] NR 36 TC 36 Z9 36 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 25 PY 2005 VL 44 IS 3 BP 971 EP 978 DI 10.1021/bi048208a PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 889CN UT WOS:000226421200015 PM 15654753 ER PT J AU Lefrancois, S Canuel, M Zeng, JB Morales, CR AF Lefrancois, S Canuel, M Zeng, JB Morales, CR TI Inactivation of sortilin (a novel lysosomal sorting receptor) by dominant negative competition and RNA interference SO BIOLOGICAL PROCEDURES ONLINE LA English DT Article DE sortilin; sphingolipid activator proteins ID SPHINGOLIPID ACTIVATOR PROTEINS; TRANSPORT; SAPOSINS; GENETICS; CELLS; GGA2 AB To assess the role of sortilin in the sorting and trafficking of sphingolipid activator proteins (SAPs) the function of sortilin was abolished by a dominant-negative mutant and by the use of RNAi. Mutant sortilin lacking the carboxyl-terminal region that contains the sorting signal abolished the trafficking of SAPs to the lysosomes. Both sortilin and SAPs were retained in the Golgi apparatus. The use of chemically synthesized siRNA effectively blocked the trafficking of SAPs to the lysosomes as well. Additionally, we created a stable COS-7 cell line transfected with the pSilencer 3.1 H1 neo vector containing a selected siRNA template oligonucleotide (small hairpin interference RNA) where the levels of sortilin were greatly suppressed. The elimination of sortilin by this method will permit to determine whether or not sortilin is involved in a general mechanism of lysosomal sorting that involves the trafficking of various soluble lysosomal proteins other than SAPs. C1 McGill Univ, Dept Anat & Cell Biol, Montreal, PQ, Canada. RP Lefrancois, S (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, 9000 Rockville Pike,Bldg 18T,Room 101, Bethesda, MD 20892 USA. EM lefrancs@mail.nih.gov RI Morales, Carlos/H-1055-2011 NR 19 TC 9 Z9 10 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1480-9222 J9 BIOL PROCED ONLINE JI Biol. Proced. Online PD JAN 25 PY 2005 VL 7 BP 17 EP 25 DI 10.1251/bpo101 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 995OO UT WOS:000234113900001 ER PT J AU Kim, I Darwin, WD Huestis, MA AF Kim, I Darwin, WD Huestis, MA TI Simultaneous determination of nicotine, cotinine, norcotinine, and trans-3 '-hydroxycotinine in human oral fluid using solid phase extraction and gas chromatography-mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE nicotine; cotinine; trans-3 '-hydroxycotinine; norcotinine; oral fluid ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TOBACCO-SMOKE EXPOSURE; SALIVA COTININE; CIGARETTE-SMOKING; URINARY COTININE; PLASMA; 3-HYDROXYCOTININE; METABOLISM; ANTIBODIES; CAFFEINE AB Nicotine is rapidly and extensively metabolized in humans. We present an analytical method to simultaneously quantify nicotine, cotinine, norcotinine. and trans-3'-hydroxycotinine in human oral fluid. Solid phase extraction (SPE) and GC/MS/EI with selected ion monitoring (SIM) were utilized. Linearity ranged from 5 to 1000 ng/mL of oral fluid; correlation coefficients for calibration curves were >0.99. Recoveries were 90-115% nicotine, 76-117% cotinine, 88-101% norcotinine, and 67-77% trans-3'-hydroxycotinine. Intra-assay precision and accuracy ranged from 1.6 to 5.7% and 1.6 to 17.8%, respectively. Inter-assay precision and accuracy ranged from 4.3 to 10.2% and 0 to 12.8%, respectively. Suitable precision and accuracy were achieved for the simultaneous determination of nicotine and three metabolites in the oral fluid of smokers. This assay is applicable to pharmacokinetic studies of nicotine, cotinine, and trans-3'-hydroxycotinine from tobacco smokers and can be utilized for routine monitoring of tobacco smoke exposure. 3-Hydroxycotinine requires additional investigation to determine its usefulness as a biomarker for tobacco smoke exposure. (C) 2004 Elsevier B.V. All rights reserved. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov NR 31 TC 44 Z9 48 U1 3 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD JAN 25 PY 2005 VL 814 IS 2 BP 233 EP 240 DI 10.1016/j.jchromb.2004.10.034 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 889JD UT WOS:000226438400005 PM 15639444 ER PT J AU Choo, RE Murphy, CM Jones, HE Huestis, MA AF Choo, RE Murphy, CM Jones, HE Huestis, MA TI Determination of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, 2-ethyl-5-methyl-3,3-diphenylpyraline and methadol in meconium by liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE methadone; meconium; LC-APCI-MS/MS ID STEREOSELECTIVE DETERMINATION; QUANTITATIVE-DETERMINATION; ENANTIOSELECTIVE ANALYSIS; PRIMARY METABOLITE; HUMAN PLASMA; COCAINE; URINE; IMMUNOASSAY; ENANTIOMERS; SALIVA AB This paper details a validated liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS/MS) method for the quantification of methadone, and its metabolites 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), 2-ethyl-5-methyl-3,3-diphenylpyraline (EMDP) and methadol in human meconium. Limits of detection (LOD) were determined to be 1.0 ng/g for methadone, EDDP and EMDP and 2.5 ng/g for methadol. The limits of quantitation (LOQ) for methadone, EDDP, EMDP were 5 and 25 ng/g for methadol. Linearity ranged from 5.0 to 500 ng/g. Following solid-phase extraction, no matrix effect was observed. This method proved to be suitable for the quantification of methadone, EDDP and EMDP and the semi-quantitation of methadol in meconium. Literature review revealed no other published LC-APCI-MS/MS method for the detection of methadone and its three main metabolites in meconium specimens. Published by Elsevier B.V. C1 NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Ctr Addict & Pregnancy, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU NIDA NIH HHS [DA12403-02] NR 23 TC 26 Z9 27 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD JAN 25 PY 2005 VL 814 IS 2 BP 369 EP 373 DI 10.1016/j.jchromb.2004.10.068 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 889JD UT WOS:000226438400022 PM 15639461 ER PT J AU Fan, JG Fariss, RN Purkiss, AG Slingsby, C Sandilands, A Quinlan, R Wistow, G Chepelinsky, AB AF Fan, JG Fariss, RN Purkiss, AG Slingsby, C Sandilands, A Quinlan, R Wistow, G Chepelinsky, AB TI Specific interaction between lens MIP/Aquaporin-0 and two members of the gamma-crystallin family SO MOLECULAR VISION LA English DT Article ID MAJOR INTRINSIC PROTEIN; EYE LENS; WATER PERMEABILITY; CHANNEL PROTEINS; GENE FAMILY; RAT LENS; EVOLUTIONARY RELATIONSHIPS; CONGENITAL CATARACTS; MOUSE LENS; MIP AB Purpose: Major Intrinsic Protein (MIP)/Aquaporin 0 is required for lens transparency and is specifically expressed in lens fiber cell membranes. We have demonstrated previously that in the rat lens MIP interacts specifically with gammaE-crystallin, resulting in its recruitment to the plasma membrane. Our goal was to examine the interaction or lack of interaction between MIP and all members of the gamma-crystallin family and to provide evidence for a physiological role these interactions may play in gamma-crystallin or MIP function. Methods: Full length MIP was expressed as untagged, enhanced green fluorescent protein (EGFP) tagged, or myc tagged proteins. Members of the gamma-crystallin family were expressed as red fluorescent protein (HcRed) tagged proteins in the rabbit kidney epithelial cell line RK13. Co-localization of tagged proteins was analyzed by confocal fluorescence microscopy. Results: Confocal fluorescence microscopy demonstrated that gammaE- and gammaF-crystallin co-localize specifically with full length MIP in mammalian cells while other gamma-crystallins, including gammaA-, gammaB-, gammaC-, gammaD-, and gammaS-crystallin do not. As a result of this interaction, either gammaE- or gammaF-crystallin was recruited to the plasma membrane from the cytoplasm. MIP does not interact with the Elo mutant of gammaE-crystallin, which has been linked to a dominant cataract phenotype in mice. Conclusions: These experiments demonstrate that MIP interacts selectively with gammaE- and gammaF-crystallin, and not with other gamma-crystallins. This raises the possibility of MIP playing a structural role in the organization of gamma-crystallins in rodent lens fibers and/or that gammaE- and gammaF-crystallin may have a specific role in MIP function in the rodent lens. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA. NEI, Sect Mol Struct & Funct, NIH, Bethesda, MD 20892 USA. Univ Durham, Sch Biol & Biomed Sci, Durham, England. Univ London Birkbeck Coll, Sch Crystallog, London, England. RP Chepelinsky, AB (reprint author), NEI, Mol & Dev Biol Lab, NIH, 7 Mem Dr,MSC 0704,Bldg 7,Room 105, Bethesda, MD 20892 USA. EM abc@helix.nih.gov RI Quinlan, Roy/A-1348-2012 OI Quinlan, Roy/0000-0003-0644-4123 NR 65 TC 20 Z9 20 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD JAN 25 PY 2005 VL 11 IS 8-9 BP 76 EP 87 PG 12 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 893ZP UT WOS:000226759900002 PM 15692460 ER PT J AU Ravina, B Eidelberg, D Ahlskog, JE Albin, RL Brooks, DJ Carbon, M Dhawan, V Feigin, A Fahn, S Guttman, M Gwinn-Hardy, K McFarland, H Innis, R Katz, RG Kieburtz, K Kish, SJ Lange, N Langston, JW Marek, K Morin, L Moy, C Murphy, D Oertel, WH Oliver, G Palesch, Y Powers, W Seibyl, J Sethi, KD Shults, CW Sheehy, P Stoessl, AJ Holloway, R AF Ravina, B Eidelberg, D Ahlskog, JE Albin, RL Brooks, DJ Carbon, M Dhawan, V Feigin, A Fahn, S Guttman, M Gwinn-Hardy, K McFarland, H Innis, R Katz, RG Kieburtz, K Kish, SJ Lange, N Langston, JW Marek, K Morin, L Moy, C Murphy, D Oertel, WH Oliver, G Palesch, Y Powers, W Seibyl, J Sethi, KD Shults, CW Sheehy, P Stoessl, AJ Holloway, R TI The role of radiotracer imaging in Parkinson disease SO NEUROLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; STRIATAL DOPAMINE TRANSPORTER; RANDOMIZED CONTROLLED-TRIAL; SURROGATE END-POINTS; QUALITY-OF-LIFE; DIFFERENTIAL-DIAGNOSIS; F-18 FLUORODEOXYGLUCOSE; INITIAL TREATMENT; SUBSTANTIA-NIGRA; LEVODOPA AB Radiotracer imaging (RTI) of the nigrostriatal dopaminergic system is a widely used but controversial biomarker in Parkinson disease (PD). Here the authors review the concepts of biomarker development and the evidence to support the use of four radiotracers as biomarkers in PD: [F-18] fluorodopa PET, (+)-[C-11] dihydrotetrabenazine PET, [I-123] beta-CIT SPECT, and [F-18] fluorodeoxyglucose PET. Biomarkers used to study disease biology and facilitate drug discovery and early human trials rely on evidence that they are measuring relevant biologic processes. The four tracers fulfill this criterion, although they do not measure the number or density of dopaminergic neurons. Biomarkers used as diagnostic tests, prognostic tools, or surrogate endpoints must not only have biologic relevance but also a strong linkage to the clinical outcome of interest. No radiotracers fulfill these criteria, and current evidence does not support the use of imaging as a diagnostic tool in clinical practice or as a surrogate endpoint in clinical trials. Mechanistic information added by RTI to clinical trials may be difficult to interpret because of uncertainty about the interaction between the interventions and the tracer. C1 NINDS, Ctr Neurosci, NIH, Bethesda, MD 20892 USA. N Shore Long Isl Jewish Hlth Syst, Inst Med Res, Ctr Neurosci, Manhasset, NY USA. Mayo Clin, Dept Neurol, Rochester, MN USA. Univ Michigan, Dept Neurol, Ann Arbor, MI USA. Ann Arbor VAMC GRECC, Ann Arbor, MI USA. Univ London Imperial Coll Sci Technol & Med, Fac Med, London, England. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Ctr Addict & Mental Hlth, Human Neurochem Pathol Lab, Toronto, ON, Canada. NIMH, NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Univ Rochester, Dept Neurol, Rochester, NY 14627 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Parkinsons Inst, Sunnyvale, CA USA. Inst Neurodegenerat Disorders, New Haven, CT USA. Univ Marburg, Dept Neurol, Marburg, Germany. Med Univ S Carolina, Dept Biometry, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Epidemiol, Charleston, SC 29425 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. Univ British Columbia, Pacific Parkinsons Res Ctr, Vancouver, BC V5Z 1M9, Canada. RP Ravina, B (reprint author), NINDS, Ctr Neurosci, NIH, Room 2225,6001 Execut Blvd, Bethesda, MD 20892 USA. EM ravinab@ninds.nih.gov RI Gwinn, Katrina/C-2508-2009; Eidelberg, David/F-5214-2011; OI Brooks, David/0000-0003-2602-2518 NR 60 TC 201 Z9 206 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 25 PY 2005 VL 64 IS 2 BP 208 EP 215 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 890JJ UT WOS:000226507200007 PM 15668415 ER PT J AU den Heijer, T Launer, LJ Prins, ND van Dijk, EJ Vermeer, SE Hofman, A Koudstaal, PJ Breteler, MMB AF den Heijer, T Launer, LJ Prins, ND van Dijk, EJ Vermeer, SE Hofman, A Koudstaal, PJ Breteler, MMB TI Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe SO NEUROLOGY LA English DT Review ID SILENT BRAIN INFARCTS; ALZHEIMERS-DISEASE; ROTTERDAM SCAN; COGNITIVE DECLINE; RISK-FACTORS; FOLLOW-UP; NEUROFIBRILLARY TANGLES; KUNGSHOLMEN PROJECT; VASCULAR DEMENTIA; POPULATION AB Background: Blood pressure level is associated with the risk of clinical Alzheimer disease ( AD), yet the underlying mechanisms are unclear. High blood pressure levels may cause cerebral small-vessel pathology, which contributes to cognitive decline in patients with AD. Alternatively, in persons with high blood pressure, increased numbers of neurofibrillary tangles and amyloid plaques at autopsy have also been observed, suggesting direct links between blood pressure and AD. Objective: To investigate the association of blood pressure and markers of small-vessel disease ( white matter lesions [WMLs] on MRI) with hippocampal and amygdalar atrophy on MRI - potential in vivo indicators of Alzheimer pathology. Methods: In 1995 to 1996, 511 nondemented elderly subjects ( age 60 to 90) underwent MRI. The extent of WMLs was assessed, and volumes of the hippocampus and amygdala were measured. Blood pressure levels were assessed at the time of MRI and 5 years before the MRI. Results: Higher diastolic blood pressure 5 years before MRI predicted more hippocampal atrophy in persons untreated for hypertension ( per SD increase - 0.10 mL [95% CI - 0.19 to - 0.02, p = 0.02]). Conversely, in persons treated for hypertension, a low diastolic blood pressure was associated with more severe atrophy. Persons with more WMLs on MRI more often had severe atrophy of the hippocampus and amygdala. Conclusion: Blood pressure and indicators of small-vessel disease in the brain may be associated with atrophy of structures affected by Alzheimer pathology. C1 Erasmus Med Ctr, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands. Erasmus Med Ctr, Dept Neurol, NL-3000 DR Rotterdam, Netherlands. NIA, Neuroepidemiol Sect, Bethesda, MD 20892 USA. RP Breteler, MMB (reprint author), Erasmus Med Ctr, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands. EM m.breteler@erasmusmc.nl RI van Dijk, Ewoud/J-7951-2012; Breteler, Monique /J-5058-2014 NR 51 TC 111 Z9 111 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 25 PY 2005 VL 64 IS 2 BP 263 EP 267 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 890JJ UT WOS:000226507200016 PM 15668423 ER PT J AU Edwards-Lee, T Ringman, JM Chung, J Werner, J Morgan, A Hyslop, PS Thompson, P Dutton, R Mlikotic, A Rogaeva, E Hardy, J AF Edwards-Lee, T Ringman, JM Chung, J Werner, J Morgan, A Hyslop, PS Thompson, P Dutton, R Mlikotic, A Rogaeva, E Hardy, J TI An African American family with earlyonset Alzheimer disease and an APP (T714I) mutation SO NEUROLOGY LA English DT Article ID PRESENILIN-1 MUTATION; PATHOLOGY; DEMENTIA AB The occurrence of an APP T174I mutation is described in a large American family of African descent with Alzheimer disease. The clinical characteristics were an unusually early onset of disease (early 30s), similar to a previously reported age at onset of this mutation in an Austrian family. Distinct from that family, seizures and myoclonus were prominent features of the disease in this kindred. C1 NIH, Neurogenet Lab, NIA, Bethesda, MD 20892 USA. Harbor UCLA Med Ctr, Dept Neurol, Torrance, CA 90509 USA. Harbor UCLA Med Ctr, Dept Psychiat, Torrance, CA 90509 USA. Harbor UCLA Med Ctr, Dept Radiol, Torrance, CA 90509 USA. Univ Calif Los Angeles, Dept Neurol, Lab Neuroimaging, Los Angeles, CA 90024 USA. Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON, Canada. Univ Hlth Network, Dept Med, Div Neurol, Toronto, ON, Canada. RP Hardy, J (reprint author), NIH, Neurogenet Lab, NIA, Bldg 35,Rm 1A1015, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Hardy, John/C-2451-2009 FU NIA NIH HHS [K08 AG 22228] NR 10 TC 26 Z9 28 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 25 PY 2005 VL 64 IS 2 BP 377 EP 379 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 890JJ UT WOS:000226507200042 PM 15668448 ER PT J AU Ogasawara, Y Lacourciere, GM Ishii, K Stadtman, TC AF Ogasawara, Y Lacourciere, GM Ishii, K Stadtman, TC TI Characterization of potential selenium-binding proteins in the selenophosphate synthetase system SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE 3-mercaptopyruvate sulfurtransferase; glyceraldehyde-3-phosphate dehydrogenase; rhodanese; selenodiglutathione; selenium delivery ID SELD GENE-PRODUCT; ESCHERICHIA-COLI; SELENOCYSTEINE; METABOLISM; ENZYME; GLUTATHIONE; RHODANESE; SEQUENCE; LYASE; ACID AB Selenophosphate, an activated form of selenium that can serve as a selenium donor, is generated by the selD gene product, selenophosphate synthetase (SPS). Selenophosphate is required by several bacteria and by mammals for the specific synthesis of Secys-tRNA, the precursor of selenocysteine in selenoenzymes. Although free selenide can be used in vitro for synthesis of selenophosphate, the physiological system that donates selenium to SIPS is incompletely characterized. To detect potential selenium-delivery proteins, two known sulfurtransferases and glyceraidehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) were analyzed for ability to bind and transfer selenium. Rhodanese (EC 2.8.1.1) was shown to bind selenium tightly, with only part of the selenium being available as substrate for SIPS in the presence of added reductant. 3-Mercaptopyruvate sulfurtransferase (3-MST; EC 2.8.1.2) and GAPDH also bound selenium supplied as selenodiglutathione formed from SeO32- and glutathione. Selenium bound to 3-MST and GAPDH was released more readily than that from rhodanese and also was more available as a substrate for SIPS. Although rhodanese retained tightly bound selenium under aerobic conditions, the protein gradually became insoluble, whereas GAPDH containing bound selenium was stable at neutral pH for a long period. These results indicate that 3-MST and GAPDH have more suitable potentials as a physiological selenium-delivery protein than rhodanese. In the presence of a selenium-binding protein, a low level of selenodiglutathione formed from SeO32- and glutathione could effectively replace the high concentrations of selenide routinely used as substrate in the SIPS in vitro assays. C1 Meiji Pharmaceut Univ, Dept Environm Biol, Nishitokyo, Tokyo 2048588, Japan. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Ogasawara, Y (reprint author), Meiji Pharmaceut Univ, Dept Environm Biol, 2-522-1 Noshio, Nishitokyo, Tokyo 2048588, Japan. EM yo@my-pharm.ac.jp NR 22 TC 27 Z9 32 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 25 PY 2005 VL 102 IS 4 BP 1012 EP 1016 DI 10.1073/pnas.0409042102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 891YW UT WOS:000226617900012 PM 15653770 ER PT J AU Ganguly, S Weller, JL Ho, A Chemineau, P Malpaux, B Klein, DC AF Ganguly, S Weller, JL Ho, A Chemineau, P Malpaux, B Klein, DC TI Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE pineal; circadian; cAMP; kinase ID 14-3-3 PROTEINS; PHOTONEUROENDOCRINE TRANSDUCTION; PINEAL-GLAND; ENZYME; RHYTHM; BINDING; PHOSPHORYLATION; COMPLEX; METABOLISM AB The nocturnal increase in circulating melatonin in vertebrates is regulated by the activity of arylalkylamine N-acetyltransferase (AANAT), the penultimate enzyme in the melatonin pathway (serotonin --> N-acetylserotonin --> melatonin). Large changes in activity are linked to cyclic AMP-dependent protein kinase-mediated phosphorylation of AANAT T31. Phosphorylation of T31 promotes binding of AANAT to the dimeric 14-3-3 protein, which activates AANAT by increasing arylalkylamine affinity. In the current study, a putative second AANAT cyclic AMP-dependent protein kinase phosphorylation site, S205, was found to be approximate to55% phosphorylated at night, when T31 is approximate to40% phosphorylated. These findings indicate that ovine AANAT is dual-phosphorylated. Moreover, light exposure at night decreases T31 and S205 phosphorylation, consistent with a regulatory role of both sites. AANAT peptides containing either T31 or S205 associate with 114-3-3zeta in a phosphorylation-dependent manner; binding through phosphorylated (p)T31 is stronger than that through pS205, consistent with the location of only pT31 in a mode I binding motif, one of two recognized high-affinity 14-3-3-binding motifs AANAT protein binds to 114-3-3zeta through pT31 or pS205. Two-site binding lowers the K-m for arylalkylamine substrate to approximate to30 muM. In contrast, single-site pS205 binding increases the K-m to approximate to1,200 muM. Accordingly, the switch from dual to single pS205 binding of AANAT to 14-3-3 changes the K-m for substrates by approximate to40-fold. pS205 seems to be part of a previously unrecognized 14-3-3-binding motif-pS/pT (X1-2)-COOH, referred to here as mode III. C1 NICHHD, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. Univ Alberta, Dept Physiol, Edmonton, AB T6G 2H7, Canada. Univ Tours, Unite Mixte Rech Physiol Reprod & Comportements, Inst Natl Rech Agron, CNRS,Haras Nationaux, F-37380 Nouzilly, France. RP Klein, DC (reprint author), NICHHD, Sect Neuroendocrinol, NIH, Bldg 49,Room 6A82, Bethesda, MD 20892 USA. EM kleind@mail.nih.gov NR 28 TC 119 Z9 124 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 25 PY 2005 VL 102 IS 4 BP 1222 EP 1227 DI 10.1073/pnas.0406871102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 891YW UT WOS:000226617900048 PM 15644438 ER PT J AU Mozaffarian, D Longstreth, WT Lemaitre, RN Manolio, TA Kuller, LH Burke, GL Siscovick, DS AF Mozaffarian, D Longstreth, WT Lemaitre, RN Manolio, TA Kuller, LH Burke, GL Siscovick, DS TI Fish consumption and stroke risk in elderly individuals - The cardiovascular health study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; DIETARY; PLATELET; DISEASE AB Background: Associations between fish consumption and stroke risk have been inconsistent, possibly because of the differences in types of fish meals consumed. Additionally, such relationships have not been specifically evaluated in the elderly, in whom disease burden may be high and diet less influential. Methods: Among 4775 adults 65 years or older (range, 65-98 years) and free of known cerebrovascular disease at baseline in 1989-1990, usual dietary intake was assessed using a food frequency questionnaire. In a subset consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches (fish burgers), correlated with plasma phospholipid long-chain n-3 fatty acid levels. Incident strokes were prospectively ascertained. Results: During 12 years of follow-up, participants experienced 626 incident strokes, including 529 ischemic strokes. In multivariate analyses, tuna/other fish consumption was inversely associated with total stroke (P=.04) and ischemic stroke (P=.02), with 27% lower risk of ischemic stroke with an intake of 1 to 4 times per week (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.98) and 30% lower risk with intake of 5 or more times per week (HR, 0.70; 95% CI, 0.50-0.99) compared with an intake of less than once per month. In contrast, fried fish/fish sandwich consumption was positively associated with total stroke (P=.006) and ischemic stroke (P=.003), with a 44% higher risk of ischemic stroke with consumption of more than once per week (HR, 1.44; 95% CI, 1.12-1.85) compared with consumption of less than once per month. Fish consumption was not associated with hemorrhagic stroke. Conclusions: Among elderly individuals, consumption of tuna or other broiled or baked fish is associated with lower risk of ischemic stroke, while intake of fried fish or fish sandwiches is associated with higher risk. These results suggest that fish consumption may influence stroke risk late in life; potential mechanisms and alternate explanations warrant further study. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Cardiovasc Res Unit, Seattle, WA 98195 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. RP Mozaffarian, D (reprint author), 665 Huntington Ave,Bldg 2,Room 315, Boston, MA 02115 USA. EM dmozaffa@hsph.harvard.edu RI Mozaffarian, Dariush/B-2276-2008 FU NHLBI NIH HHS [N01HC85086, K08 HL075628, N01 HC015103, N01 HC035129, N01-HC-85079, N01-HC-85086, N01HC85079]; NIDDK NIH HHS [DK07703, T32 DK007703] NR 31 TC 102 Z9 111 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 24 PY 2005 VL 165 IS 2 BP 200 EP 206 DI 10.1001/archinte.165.2.200 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 889PS UT WOS:000226455500010 PM 15668367 ER PT J AU Svarovsky, SA Szekely, Z Barchi, JJ AF Svarovsky, SA Szekely, Z Barchi, JJ TI Synthesis of gold nanoparticles bearing the Thomsen-Friedenreich disaccharide: a new multivalent presentation of an important tumor antigen SO TETRAHEDRON-ASYMMETRY LA English DT Article ID GLYCOPEPTIDE BUILDING-BLOCKS; SOLID-PHASE SYNTHESIS; T-ANTIGEN; BINDING PROPERTIES; CONCANAVALIN-A; HUMAN BREAST; CANCER; GLYCONANOPARTICLES; DERIVATIVES; VACCINES AB Herein we describe the synthesis gold nanoshells encapsulated with up to 90 units of the Thomsen-Friedenreich (TF) tumor-associated carbohydrate antigen (TACA) disaccharide (Galbeta1-3GaINAc-alpha-O-Ser/Thr) as well as the assembly of a suitably linked designer glycopeptide as a precursor to similar multivalent presentations on gold. The TF-coated nanoparticles are highly stable, water soluble, and easily handled. Improvements in the linker technology used to attach the disaccharide to the particles led to a robust multivalent platform for the presentation of this important carbohydrate. The antigen retains all recognition characteristics while displayed on this template as shown by several in vitro assays. This area of research could lead to the development of novel therapeutic agents that inhibit protein-carbohydrate interactions. Published by Elsevier Ltd. C1 Ctr Canc Res, Lab Med Chem, NCI, Ft Detrick, MD 21702 USA. Ctr Canc Res, Struct Biophys Lab, NCI, Ft Detrick, MD 21702 USA. RP Barchi, JJ (reprint author), Ctr Canc Res, Lab Med Chem, NCI, 376 Boyles St, Ft Detrick, MD 21702 USA. EM barchi@helix.nih.gov RI Barchi Jr., Joseph/N-3784-2014 NR 56 TC 47 Z9 48 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0957-4166 J9 TETRAHEDRON-ASYMMETR JI Tetrahedron: Asymmetry PD JAN 24 PY 2005 VL 16 IS 2 BP 587 EP 598 DI 10.1016/j.tetasy.2004.12.003 PG 12 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic; Chemistry, Physical SC Chemistry GA 897KK UT WOS:000227002600032 ER PT J AU Wu, XW Brooks, BR AF Wu, XW Brooks, BR TI Isotropic periodic sum: A method for the calculation of long-range interactions SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; PARTICLE MESH EWALD; SYSTEMS; WATER; PROGRAM AB This work presents an accurate and efficient approach to the calculation of long-range interactions for molecular modeling and simulation. This method defines a local region for each particle and describes the remaining region as images of the local region statistically distributed in an isotropic and periodic way, which we call isotropic periodic images. Different from lattice sum methods that sum over discrete lattice images generated by periodic boundary conditions, this method sums over the isotropic periodic images to calculate long-range interactions, and is referred to as the isotropic periodic sum (IPS) method. The IPS method is not a lattice sum method and eliminates the need for a reciprocal space sum. Several analytic solutions of IPS for commonly used potentials are presented. It is demonstrated that the IPS method produces results very similar to that of Ewald summation, but with three major advantages, (1) it eliminates unwanted symmetry artifacts raised from periodic boundary conditions, (2) it can be applied to potentials of any functional form and to fully and partially homogenous systems as well as finite systems, and (3) it is more computationally efficient and can be easily parallelized for multiprocessor computers. Therefore, this method provides a general approach to an efficient calculation of long-range interactions for various kinds of molecular systems. (C) 2005 American Institute of Physics. C1 NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Wu, XW (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wuxw@nhlbi.nih.gov NR 23 TC 89 Z9 92 U1 0 U2 12 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JAN 22 PY 2005 VL 122 IS 4 AR 044107 DI 10.1063/1.1836733 PG 18 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 894QP UT WOS:000226807000010 PM 15740235 ER PT J AU Laugel, B Boulter, JM Lissin, N Vuidepot, A Li, Y Gostick, E Crotty, LE Douek, DC Hemelaar, J Price, DA Jakobsen, BK Sewell, AK AF Laugel, B Boulter, JM Lissin, N Vuidepot, A Li, Y Gostick, E Crotty, LE Douek, DC Hemelaar, J Price, DA Jakobsen, BK Sewell, AK TI Design of soluble recombinant T cell receptors for antigen targeting and T cell inhibition SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TCR CROSS-REACTIVITY; MONOCLONAL-ANTIBODIES; LIGAND RECOGNITION; HIGH-AFFINITY; IN-VIVO; NEUROLOGICAL DISEASE; STRUCTURAL FEATURES; PHENOTYPIC ANALYSIS; MULTIPLE-SCLEROSIS; MOLECULAR MIMICRY AB The use of recombinant T cell receptors (TCRs) to target therapeutic interventions has been hindered by the naturally low affinity of TCR interactions with peptide major histocompatibility complex ligands. Here, we use multimeric forms of soluble heterodimeric alphabeta TCRs for specific detection of target cells pulsed with cognate peptide, discrimination of quantitative changes in antigen display at the cell surface, identification of virus-infected cells, inhibition of antigen-specific cytotoxic T lymphocyte activation, and identification of cross-reactive peptides. Notably, the A6 TCR specific for the immunodominant HLA A2-restricted human T cell leukemia virus type 1 Tax(11-19) epitope bound to HLA A2-HuD(87-95) (K-D 120 muM by surface plasmon resonance), an epitope implicated as a causal antigen in the paraneoplastic neurological degenerative disorder anti-Hu syndrome. A mutant A6 TCR that exhibited dramatically increased affinity for cognate antigen (K-D 2.5 nM) without enhanced cross-reactivity was generated; this TCR demonstrated potent biological activity even as a monomeric molecule. These data provide insights into TCR repertoire selection and delineate a framework for the selective modification of TCRs in vitro that could enable specific therapeutic intervention in vivo. C1 Univ Oxford, T Cell Modulat Grp, Peter Medawar Bldg Pathogen Res, Oxford OX1 3SY, England. Univ Wales Coll Med, Dept Med Biochem & Immunol, Cardiff CF14 4XN, S Glam, Wales. Avidex Ltd, Abingdon OX14 4RX, Oxon, England. NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Oxford Magdalen Coll, Oxford OX1 4AU, England. RP Sewell, AK (reprint author), Univ Oxford, T Cell Modulat Grp, Peter Medawar Bldg Pathogen Res, S Parks Rd, Oxford OX1 3SY, England. EM andy.sewell@ndm.ox.ac.uk RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Sewell, Andrew/0000-0003-3194-3135; Crotty Alexander, Laura/0000-0002-5091-2660 NR 70 TC 53 Z9 55 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 21 PY 2005 VL 280 IS 3 BP 1882 EP 1892 DI 10.1074/jbc.M409427200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 887YP UT WOS:000226341700022 PM 15531581 ER PT J AU Kruth, HS Jones, NL Huang, W Zhao, B Ishii, I Chang, J Combs, CA Malide, D Zhang, WY AF Kruth, HS Jones, NL Huang, W Zhao, B Ishii, I Chang, J Combs, CA Malide, D Zhang, WY TI Macropinocytosis is the endocytic pathway that mediates macrophage foam cell formation with native low density lipoprotein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MONOCYTE-DERIVED MACROPHAGES; EXOGENOUS SOLUBLE-ANTIGEN; DENDRITIC CELLS; GROWTH-FACTOR; CONSTITUTIVE MACROPINOCYTOSIS; HORSERADISH-PEROXIDASE; MANNOSE RECEPTOR; MEMBRANE RUFFLES; APOLIPOPROTEIN-E; DOWN-REGULATION AB Previously, we reported that fluid-phase endocytosis of native LDL by PMA-activated human monocyte-derived macrophages converted these macrophages into cholesterol-enriched foam cells (Kruth, H. S., Huang, W., Ishii, I., and Zhang, W. Y. ( 2002) J. Biol. Chem. 277, 34573 - 34580). Uptake of fluid by cells can occur either by micropinocytosis within vesicles (<0.1 mu m diameter) or by macropinocytosis within vacuoles (similar to 0.5 - 5.0 mu m) named macropinosomes. The current investigation has identified macropinocytosis as the pathway for fluid-phase LDL endocytosis and determined signaling and cytoskeletal components involved in this LDL endocytosis. The phosphatidylinositol 3-kinase inhibitor, LY294002, which inhibits macropinocytosis but does not inhibit micropinocytosis, completely blocked PMA- activated macrophage uptake of fluid and LDL. Also, nystatin and filipin, inhibitors of micropinocytosis from lipid-raft plasma membrane domains, both failed to inhibit PMA- stimulated macrophage cholesterol accumulation. Time-lapse video phase-contrast microscopy and time-lapse digital confocal-fluorescence microscopy with fluorescent DiI-LDL showed that PMA- activated macrophages took up LDL in the fluid phase by macropinocytosis. Macropinocytosis of LDL depended on Rho GTPase signaling, actin, and microtubules. Bafilomycin A1, the vacuolar H+-ATPase inhibitor, inhibited degradation of LDL and caused accumulation of undegraded LDL within macropinosomes and multivesicular body endosomes. LDL in multivesicular body endosomes was concentrated > 40-fold over its concentration in the culture medium consistent with macropinosome shrinkage by maturation into multivesicular body endosomes. Macropinocytosis of LDL taken up in the fluid phase without receptor-mediated binding of LDL is a novel endocytic pathway that generates macrophage foam cells. Macropinocytosis in macrophages and possibly other vascular cells is a new pathway to target for modulating foam cell formation in atherosclerosis. C1 NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27157 USA. NHLBI, Light Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. RP NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10,Rm 5N-113,10 Ctr Dr MSC 1422, Bethesda, MD 20892 USA. EM kruthh@nhlbi.nih.gov RI Huang, Wei/E-3270-2011 FU NHLBI NIH HHS [HL-41990] NR 72 TC 129 Z9 135 U1 1 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 21 PY 2005 VL 280 IS 3 BP 2352 EP 2360 DI 10.1074/jbc.M407167200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 887YP UT WOS:000226341700072 PM 15533943 ER PT J AU Fontanini, A Chies, R Snapp, EL Ferrarini, M Fabrizi, GM Brancolini, C AF Fontanini, A Chies, R Snapp, EL Ferrarini, M Fabrizi, GM Brancolini, C TI Glycan-independent role of calnexin in the intracellular retention of Charcot-Marie-Tooth 1A Gas3/PMP22 mutants SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERIPHERAL MYELIN PROTEIN-22; ARREST-SPECIFIC GENE; ENDOPLASMIC-RETICULUM; QUALITY-CONTROL; MOLECULAR CHAPERONE; MEMBRANE-PROTEINS; CELL-SURFACE; IN-VITRO; PMP22; MUTATIONS AB Missense point mutations in Gas3/PMP22 are responsible for the peripheral neuropathies Charcot-Marie-Tooth 1A and Dejerine Sottas syndrome. These mutations induce protein misfolding with the consequent accumulation of the proteins in the endoplasmic reticulum and the formation of aggresomes. During folding, Gas3/PMP22 associates with the lectin chaperone calnexin. Here, we show that calnexin interacts with the misfolded transmembrane domains of Gas3/PMP22, fused to green fluorescent protein, in a glycan-independent manner. In addition, photobleaching experiments in living cells revealed that Gas3/PMP22-green fluorescent protein mutants are mobile but diffuse at almost half the diffusion coefficient of wild type protein. Our results support emerging models for a glycan-independent chaperone role for calnexin and for the mechanism of retention of misfolded membrane proteins in the endoplasmic reticulum. C1 Univ Udine, Dipartimento Sci & Tecnol Biomed, Sez Biol, I-33100 Udine, Italy. Univ Udine, MATI Ctr Excellence, I-33100 Udine, Italy. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Policlin GB Rossi, Dept Neurol & Visual Sci, Sect Clin Neurol, I-37134 Verona, Italy. RP Brancolini, C (reprint author), Univ Udine, Dipartimento Sci & Tecnol Biomed, Sez Biol, Piazza Kolbe 4, I-33100 Udine, Italy. EM cbrancolini@makek.dstb.uniud.it OI BRANCOLINI, Claudio/0000-0002-6597-5373 NR 59 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 21 PY 2005 VL 280 IS 3 BP 2378 EP 2387 DI 10.1074/jbc.M405104200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 887YP UT WOS:000226341700075 PM 15537650 ER PT J AU Masuda, J Maynard, DA Nishimura, M Uedac, T Kowalak, JA Markey, SP AF Masuda, J Maynard, DA Nishimura, M Uedac, T Kowalak, JA Markey, SP TI Fully automated micro- and nanoscale one- or two-dimensional high-performance liquid chromatography system for liquid chromatography-mass spectrometry compatible with non-volatile salts for ion exchange chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE proteomics; two-dimensional high performance liquid chromatography (2D-HPLC); electrospray ionization (ESI); mass spectrometry (MS) ID PROTEINS; IDENTIFICATION; PROTEOME; PEPTIDES AB A one- or two-dimensional high performance liquid chromatography system for electrospray ionization mass spectrometers has been developed that is optimized for ion exchange and reversed phase separations. A unique and simple valve configuration permits the use of a variety of non-volatile salts; ammonium sulfate was used in an example of strong cation exchange separations. The system was designed and evaluated for both micro- and nanoflow chromatography. The peptide detection limit was similar to100 fmol for micro- and 20 fmol for nanoflow, demonstrating the concentration and mass sensitivity improvements expected with nanoelectrospray ionization. The 1D/2D-HPLC MS system is fully automated for routine peptide analyses, compatible with direct injection of proteolytic digests, and exhibits chromatographic reproducibility and sensitivity. Software permits operator selection of either a 1D or 2D configuration with corresponding system parameters as required for individual samples. The hardware elements and resulting performance are described in this paper. Published by Elsevier B.V. C1 NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. Shimadzu Sci Instruments Inc, Columbia, MD 21046 USA. Shimadzu Co Ltd, Kyoto 6048511, Japan. RP Markey, SP (reprint author), NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. EM markeys@mail.nih.gov NR 18 TC 33 Z9 34 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JAN 21 PY 2005 VL 1063 IS 1-2 BP 57 EP 69 DI 10.1016/j.chroma.2004.11.084 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 887IS UT WOS:000226299800007 PM 15700457 ER PT J AU Boyer, PL Julias, JG Marquez, VE Hughes, SH AF Boyer, PL Julias, JG Marquez, VE Hughes, SH TI Fixed conformation nucleoside analogs effectively inhibit excision-proficient HIV-1 reverse transcriptases SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE retrovirus; reverse transcriptase; delayed chain termination; nucleoside analog; drug resistance ID DOUBLE-STRANDED DNA; MOLECULAR-MECHANISMS; ANGSTROM RESOLUTION; PRIMER UNBLOCKING; DRUG-RESISTANCE; MUTATIONS; COMPLEX; INSERTIONS; PUCKER; AZTMP AB An important mechanism of resistance to nucleoside analogs is the enhanced excision of the analog after it has been incorporated. Excision requires that the analog be located at the 3' terminus of the primer. We have developed nucleoside analogs that do not block DNA synthesis at the point of incorporation, but only after additional normal dNTPs have been added to the DNA. Such delayed chain terminators" should be relatively resistant to excision and therefore effective against drug-resistant HIV-1 reverse transcriptases (RTs) that are proficient at excision. We tested a class of nucleoside analogs in which a pseudosugar ring is locked in either the North or the South conformation. These analogs have a 3' OH present on the pseudosugar ring, which allows extension of the primer strand after the analog is incorporated. We asked whether these, analogs would inhibit polymerization by HIV-1 RT in assays using purified HIV-1 RT and in cell-based assays. HIV-1 RT did not effectively incorporate the analogs in which the pseudosugar is in the South conformation. The North conformation analogs are readily incorporated into the primer; the primer can be extended for two or three additional nucleotides before extension is inhibited. This block to polymerization is not complete; larger extension products are detectable at longer incubation times. Experiments with purified excision-proficient HIV-1 RT mutants suggest that the North conformation analogs are relatively resistant to excision. These analogs can also block the replication of viruses containing excision-proficient RTs. Although the fixed-conformation nucleotides are probably not suitable for development as drugs, other nucleoside analogs that cause delayed chain termination may complement the nucleoside analogs already approved for HIV-1 therapy. (C) 2004 Elsevier Ltd. All rights reserved. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. NCI, Med Chem Lab, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 539, Frederick, MD 21702 USA. EM hughes@ncifcrf.gov FU NCI NIH HHS [N0I-CO-12400] NR 17 TC 43 Z9 44 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 21 PY 2005 VL 345 IS 3 BP 441 EP 450 DI 10.1016/j.jmb.2004.10.021 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880JS UT WOS:000225786700003 PM 15581889 ER PT J AU Joshi, BV Moon, HR Fettinger, JC Marquez, VE Jacobson, KA AF Joshi, BV Moon, HR Fettinger, JC Marquez, VE Jacobson, KA TI A new synthetic route to (north)-methanocarba nucleosides designed as A(3) adenosine receptor agonists SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID CARBOCYCLIC NUCLEOSIDES; MOLECULAR-CLONING; ACTIVATION; LIGANDS; PHARMACOLOGY; DERIVATIVES; SELECTIVITY; POTENT AB DIAGRAM Activation of the A(3) adenosine receptor (AR) is associated with cerebroprotective, cardioprotective. and anticancer effects. Among potent and selective A(3) AR agonists are novel methanocarba adenosine analogues in which the conformation of a pseudo-ribose moiety is locked in the North (N) hemisphere of the pseudorotational cycle. 5'-Uronamide (N)-methanocarba nucleosides, such as MRS1898 and MRS2346, are examples of full agonists of the human A3 AR. An improved convergent approach from easily accessible 2,3-O-isopropyhdene-D-erythrose (2b),. and the combination of a strategic intramolecular cyclopropanation step plus the acid-catalyzed isomerization of an isopropylidene group, provided a suitable pseudosugar precursor (23) for the synthesis of MRS1898, MRS2346, and related analogues. This new synthetic route uses readily available building, blocks and opens the way for the preparation of a variety of targets on a reasonable scale. C1 NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20748 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. EM marquezv@dc73a.nci.nih.gov; kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 31 TC 21 Z9 21 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JAN 21 PY 2005 VL 70 IS 2 BP 439 EP 447 DI 10.1021/jo0487606 PG 9 WC Chemistry, Organic SC Chemistry GA 887NU UT WOS:000226313600006 PM 15651784 ER PT J AU Janas, AM Cunningham, SC Duffy, KB Devan, BD Greig, NH Holloway, HW Yu, QS Markowska, AL Ingram, DK Spangler, EL AF Janas, AM Cunningham, SC Duffy, KB Devan, BD Greig, NH Holloway, HW Yu, QS Markowska, AL Ingram, DK Spangler, EL TI The cholinesterase inhibitor, phenserine, improves Morris water maze performance of scopolamine-treated rats SO LIFE SCIENCES LA English DT Article DE Alzheimer's disease; muscarinic receptors; acetylcholine; memory; learning; cognitive enhancement ID 14-UNIT T-MAZE; ALZHEIMERS-DISEASE; LEARNING IMPAIRMENT; AGED RATS; EPTASTIGMINE; RECEPTOR; THERAPY; TACRINE; TRIALS AB Male Fischer-344 rats (n = 38) at 5 months old were tested in a Morris water maze to determine if treatment with the cholinesterase inhibitor, phenserine (PHEN), would overcome a learning impairment induced by scopolamine (SCOP), a muscarinic cholinergic receptor antagonist. Each rat was randomly assigned to one of five groups to receive two intraperitoneal injections 60 and 30 min, prior to testing, respectively, as follows: (1) saline-saline (SAL); (2) saline-1.0 mg/kg (SCOP); (3) 2 mg/kg PHEN- SCOP (PHEN2); (4) 4 mg/kg PHEN-SCOP (PHEN4); and (5) 1 mg/kg PHEN-SAL (PHEN1). Maze testing occurred across 5 days with 4 days of acquisition trials (4 trials per day) and a fifth day consisting of a single 120 sec probe trial. PHEN1 and SAL were combined into one control (CON) group for purposes of statistical analysis for both acquisition and probe trials as comparison of the two groups revealed that they did not significantly differ on any measure. SCOP-treated rats were significantly impaired compared to CON in learning the location of the submerged platform as measured by latency to locate the platform and the distance traversed to find the platform across days of testing. The PHEN4 group had significantly lower latencies and traveled a shorter distance to reach the submerged platform when compared to SCOP on the fourth day of trials while the PHEN2 group traveled more directly to the submerged platform but did not have shorter latencies than the SCOP group. For probe trials, CON rats swam closer to the target area (a measure of proximity to the removed platform) than did all other groups, and the PHEN4 group swam in an area more proximate to the target area than did the SCOP-treated group. These findings demonstrate the ability of this drug to improve learning when cholinergic function has been impaired in a spatial memory task. Published by Elsevier Inc. C1 NIA, Lab Expt Gerontol, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. NIA, LNS, Drug Design & Dev Sect,Gerontol Res Ctr, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. NIA, Off Extramural Res & Sci Review, NIH, Bethesda, MD 20892 USA. RP Spangler, EL (reprint author), NIA, Lab Expt Gerontol, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM spanglere@grc.nia.nih.gov NR 26 TC 19 Z9 19 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JAN 21 PY 2005 VL 76 IS 10 BP 1073 EP 1081 DI 10.1016/j.lfs.2004.06.028 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 886LG UT WOS:000226228200001 PM 15620572 ER PT J AU Dougherty, MK Muller, J Ritt, DA Zhou, M Zhou, XZ Copeland, TD Conrads, TP Veenstra, TD Lu, KP Morrison, DK AF Dougherty, MK Muller, J Ritt, DA Zhou, M Zhou, XZ Copeland, TD Conrads, TP Veenstra, TD Lu, KP Morrison, DK TI Regulation of raf-1 by direct feedback phosphorylation SO MOLECULAR CELL LA English DT Article ID DEPENDENT PROLINE ISOMERIZATION; PROLYL ISOMERASE PIN1; PROTEIN-KINASE; SIGNALING PATHWAY; MAP KINASE; IN-VITRO; B-RAF; ACTIVATION; CANCER; CELLS AB The Raf-1 kinase is an important signaling molecule, functioning in the Ras pathway to transmit mitogenic, differentiative, and oncogenic signals to the downstream kinases MEK and ERK. Because of its integral role in cell signaling, Raf-1 activity must be precisely controlled. Previous studies have shown that phosphorylation is required for Raf-1 activation, and here, we identify six phosphorylation sites that contribute to the downregulation of Raf-1 after mitogen stimulation. Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli. The hyperphosphorylated/desensitized Raf-1 is subsequently dephosphorylated and returned to a signaling-competent state through interactions with the protein phosphatase PP2A and the prolyl isomerase Pin1. These findings elucidate a critical Raf-1 regulatory mechanism that contributes to the sensitive, temporal modulation of Ras signaling. C1 Natl Canc Inst, Lab Prot Dynam & Signaling, Ft Detrick, MD 21702 USA. Sci Applicat Int Corp, Lab Proteom & Analyt Technol, Ft Detrick, MD 21702 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Morrison, DK (reprint author), Natl Canc Inst, Lab Prot Dynam & Signaling, Ft Detrick, MD 21702 USA. EM dmorrison@ncifcrf.gov FU NIGMS NIH HHS [R01GM58556] NR 45 TC 323 Z9 334 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 21 PY 2005 VL 17 IS 2 BP 215 EP 224 DI 10.1016/j.molcel.2004.11.055 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 891QR UT WOS:000226596100009 PM 15664191 ER PT J AU Maag, D Fekete, CA Gryczynski, Z Lorsch, JR AF Maag, D Fekete, CA Gryczynski, Z Lorsch, JR TI A conformational change in the eukaryotic translation preinitiation complex and release of eIF1 signal recognition of the start codon SO MOLECULAR CELL LA English DT Article ID INITIATION-FACTOR EIF1; SACCHAROMYCES-CEREVISIAE; PROTEIN-SYNTHESIS; RIBOSOMAL-SUBUNIT; GTP HYDROLYSIS; TRANSFER-RNA; SELECTION; NIP1/C; 1A AB During eukaryotic translation initiation, ribosomal 43S complexes scan mRNAs for the correct AUG codon at which to begin translation. Start codon recognition triggers GTP hydrolysis, committing the complex to engagement at that point on the mRNA. While fidelity at this step is essential, the nature of the codon recognition event and the mechanism by which it activates GTP hydrolysis are poorly understood. Here we report the changes that occur within the 43S-mRNA complex in response to AUG codon recognition. eIF1 and eIF1 A are key players in assembly of 43S.mRNA complexes capable of locating initiation codons. We observed FRET between these two factors when bound to the 40S subunit. Using steady-state FRET, anisotropy, and kinetic analyses, we demonstrate that start codon recognition results in a conformational change and release of eIF1 from the ribosome. These rearrangements probably play a role in triggering GTP hydrolysis and committing the complex to downstream events. C1 Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Biochem, Ctr Fluorescene Spect, Baltimore, MD 21201 USA. RP Lorsch, JR (reprint author), Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. EM jlorsch@jhmi.edu OI Lorsch, Jon/0000-0002-4521-4999 FU NIGMS NIH HHS [GM62128] NR 28 TC 118 Z9 121 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 21 PY 2005 VL 17 IS 2 BP 265 EP 275 DI 10.1016/j.molcel.2004.11.051 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 891QR UT WOS:000226596100013 PM 15664195 ER PT J AU Hwang, ES Szabo, SJ Schwartzberg, PL Glimcher, LH AF Hwang, ES Szabo, SJ Schwartzberg, PL Glimcher, LH TI T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3 SO SCIENCE LA English DT Article ID TEC FAMILY KINASES; TYROSINE PHOSPHORYLATION; LINEAGE COMMITMENT; SIGNALING PATHWAYS; MICE LACKING; DNA-BINDING; ITK; DIFFERENTIATION; ASTHMA AB Cell Lineage specification depends on both gene activation and gene silencing, and in the differentiation of T helper progenitors to Th1 or Th2 effector cells, this requires the action of two opposing transcription factors, T-bet and GATA-3. T-bet is essential for the development of Th1 cells, and GATA-3 performs an equivalent role in Th2 development. We report that T-bet represses Th2 lineage commitment through tyrosine kinase-mediated interaction between the two transcription factors that interferes with the binding of GATA-3 to its target DNA. These results provide a novel function for tyrosine phosphorylation of a transcription factor in specifying alternate fates of a common progenitor cell. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM lglimche@hsph.harvard.edu FU NIAID NIH HHS [AI48126, AI56296] NR 22 TC 287 Z9 319 U1 2 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 21 PY 2005 VL 307 IS 5708 BP 430 EP 433 DI 10.1126/science.1103336 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 890DQ UT WOS:000226492300049 PM 15662016 ER PT J AU Tran, GD Sun, XD Abnet, CC Fan, JH Dawsey, SM Dong, ZW Mark, SD Qiao, YL Taylor, PR AF Tran, GD Sun, XD Abnet, CC Fan, JH Dawsey, SM Dong, ZW Mark, SD Qiao, YL Taylor, PR TI Prospective study of risk factors for esophageal and gastric cancers in the Linxian General Population Trial cohort in China SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE gastric cardia cancer; gastric noncardia cancer; cohort studies; diet; smoking ID SQUAMOUS-CELL CARCINOMA; REPUBLIC-OF-CHINA; FAMILIAL AGGREGATION; ALCOHOL-DRINKING; SHANXI-PROVINCE; INCIDENCE AREA; SMOKING; MEN; VEGETABLES; TOBACCO AB Esophageal cancer incidence and mortality rates in Linxian, China are among the highest in the world. We examined risk factors for esophageal squamous cell carcinoma (ESCC), gastric cardia cancer (GCC), and gastric noncardia cancer (GNCC) in a population-based, prospective study of 29,584 adults who participated in the Linxian General Population Trial. All study participants completed a baseline questionnaire that included questions on demographic characteristics, personal and family history of disease, and lifestyle factors. After 15 years of follow-up, a total of 3,410 incident upper gastrointestinal cancers were identified, including 1,958 ESCC, 1,089 GCC and 363 GNCC. Cox proportional hazard models were used to estimate risks. Increased age and a positive family history of esophageal cancer (including ESCC or GCQ were significantly associated with risk at all 3 cancer sites. Additional risk factors for ESCC included being born in Linxian, increased height, cigarette smoking and pipe smoking; for GCC, male gender, consumption of moldy breads and pipe smoking; and for GNCC, male gender and cigarette smoking. Protective factors for ESCC included formal education, water piped into the home, increased consumption of meat, eggs and fresh fruits and increased BMI; for GCC, formal education, water piped into the home, increased consumption of eggs and fresh fruits and alcohol consumption; and for GNCC, increased weight and BMI. General socioeconomic status (SES) is a common denominator. in many of these factors and improving SES is a promising approach for reducing the tremendous burden of upper gastrointestinal cancers in Linxian. C1 NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Dept Epidemiol, Beijing 100021, Peoples R China. RP Taylor, PR (reprint author), NCI, Canc Prevent Studies Branch, Ctr Canc Res, 6116 Execut Blvd,Suite 705, Bethesda, MD 20892 USA. EM ptaylor@mail.nih.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 36 TC 304 Z9 325 U1 1 U2 16 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 20 PY 2005 VL 113 IS 3 BP 456 EP 463 DI 10.1002/ijc.20616 PG 8 WC Oncology SC Oncology GA 881WR UT WOS:000225900600017 PM 15455378 ER PT J AU Srinivasan, R Linehan, WM AF Srinivasan, R Linehan, WM TI Targeted for destruction: The molecular basis for development of novel therapeutic strategies in renal cell cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID TYROSINE KINASE; XIAP; CARCINOMAS; INHIBITOR; MUTATIONS; EFFICACY; PROTEINS; KIDNEY; SAFETY; GENE C1 NCI, Urol Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Srinivasan, R (reprint author), NCI, Urol Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NR 21 TC 2 Z9 3 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 JAN 20 PY 2005 VL 23 IS 3 BP 410 EP 412 DI 10.1200/JCO.2005.09.907 PG 3 WC Oncology SC Oncology GA 891OS UT WOS:000226591000003 PM 15572728 ER PT J AU Hotte, SJ Winquist, EW Lamont, E MacKenzie, M Vokes, E Chen, EX Brown, S Pond, GR Murgo, A Siu, LL AF Hotte, SJ Winquist, EW Lamont, E MacKenzie, M Vokes, E Chen, EX Brown, S Pond, GR Murgo, A Siu, LL TI Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: A Princess Margaret Hospital phase II consortium study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 12th Annual European Conference on Clinical Oncology (ECCO) CY SEP 21-25, 2003 CL Copenhagen, DENMARK ID GASTROINTESTINAL STROMAL TUMORS; CARCINOMA; MALIGNANCIES; CISPLATIN; MUTATIONS; PROTEIN; DISEASE; NECK; HEAD AB Purpose This study aimed to assess the antitumor activity of imatinib in adenoid cystic carcinoma (ACC) of the salivary gland expressing c-kit. A high level of c-kit expression has been identified in more than 90% of ACCs. Imatinib specifically inhibits autophosphorylation of the bcr-abl, platelet-derived growth factor receptor beta, and c-kit tyrosine kinases. Patients and Methods In a single-arm, two-stage, phase II clinical trial, adult patients with unresectable or metastatic ACC measurable by Response Evaluation Criteria in Solid Tumors Group criteria and expressing c-kit by immunohistochemistry were treated with imatinib 400 mg orally bid. Response was assessed every 8 weeks. Results Sixteen patients have been enrolled onto the study; 10 were female. Median age was 47 years (range, 31 to 69 years). Median Eastern Cooperative Oncology Group performance status was 1 (range, 0 to 2). Fourteen patients had lung metastases, 14 had prior radiotherapy, and six had prior chemotherapy. Toxicities occurring in at least 50% of patients included fatigue, nausea, vomiting, diarrhea, anorexia, edema, dyspnea, and/or headache, usually of mild to moderate severity. In 15 patients assessable for response, no objective responses have been observed. Nine patients had stable disease as best response. Six patients had progressive disease after two cycles. Conclusion Because of the lack of activity, the study has been stopped after the first stage and additional evaluation of imatinib in this population is not warranted. Overexpression of wild-type c-kit was not sufficient for clinical benefit from imatinib in ACC. Accrual to this study was rapid for a relatively rare cancer, encouraging additional efforts to identify more effective systemic therapy for these patients. C1 Univ Chicago, Princess Margaret Hosp, Phase Consortium 2, Bethesda, MD USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Hotte, SJ (reprint author), Hamilton Hlth Sci, Juravinski Canc Ctr, 699 Concession St, Hamilton, ON L8V 5C2, Canada. EM sebastien.hotte@hrcc.on.ca FU NCI NIH HHS [N01 CM 17102-01, N01 CM 17107-01] NR 20 TC 150 Z9 152 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2005 VL 23 IS 3 BP 585 EP 590 DI 10.1200/JCO.2005.06.125 PG 6 WC Oncology SC Oncology GA 891OS UT WOS:000226591000025 PM 15659505 ER PT J AU Buchanan, DR O'Mara, AM Kelaghan, JW Minasian, LM AF Buchanan, DR O'Mara, AM Kelaghan, JW Minasian, LM TI Quality-of-life assessment in the symptom management trials of the National Cancer Institute - Supported Community Clinical Oncology Program SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 10th Annual Conference of the International-Society-for-Quality-of-Life-Research CY NOV 12-15, 2003 CL Prague, CZECH REPUBLIC SP Int Soc Qual Life Res ID VALIDATION; SURVIVORS; INDEX AB Purpose To examine how quality of life (QOL) is prospectively conceptualized, defined, and measured in the symptom management clinical trials supported by the National Cancer Institute Community Clinical Oncology Program (CCOP). Methods All QOL research objectives, rationales, assessment instruments, symptoms treated, and types of interventions from the CCOP symptom management portfolio of clinical trials were extracted and analyzed. Results QOL assessments were proposed in 68 (52%) of the 130 total CCOP symptom management trials initiated since 1987. A total of 22 global QOL instruments were identified. Both the frequency of symptom management trials and the frequency of QOL assessment have increased significantly over time. The Functional Assessment of Cancer Therapy and Uniscale instruments were the most widely used QOL instruments, included in 55% of trials assessing QOL. The conceptual framework for QOL inclusion was limited to univariate relationships between symptom relief and global improvements in QOL. No consistent associations were found between QOL assessment and either the symptoms targeted or types of interventions. Conclusion To advance the state of the science, research protocols need to provide more explicit rationales for assessing QOL in symptom management trials and for the selection of the QOL instrument(s) to be used. Conceptual frameworks that specify the hypothesized links between the specific symptom(s) being managed, interactions with other symptoms, different domains of QCL, and global QOL also need to be more precisely described. Methodologic and conceptual advances in QOL symptom management trials are critical to fulfill the promise of alleviating suffering and improving the QOL of cancer patients. C1 NCI, Commun Oncol & Prevent Trials Res Grp, Div Canc Prevent, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Buchanan, DR (reprint author), NCI, Commun Oncol & Prevent Trials Res Grp, Div Canc Prevent, NIH,Dept Hlth & Human Serv, 6130 Execut Blvd,Room EPN 2149, Bethesda, MD 20892 USA. EM buchanad@mail.nih.gov NR 26 TC 48 Z9 48 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 JAN 20 PY 2005 VL 23 IS 3 BP 591 EP 598 DI 10.1200/JCO.2005.12.181 PG 8 WC Oncology SC Oncology GA 891OS UT WOS:000226591000026 PM 15659506 ER PT J AU Belyakov, AV Kieninger, M Cachau, RE Ventura, ON Oberhammer, H AF Belyakov, AV Kieninger, M Cachau, RE Ventura, ON Oberhammer, H TI Molecular structure and internal rotation in 2,3,5,6-tetrafluoroanisole as studied by gas-phase electron diffraction and quantum chemical calculations SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID AB-INITIO CALCULATIONS; METHYL VINYL ETHER; CONSISTENT BASIS-SETS; CONFORMATIONAL PROPERTIES; CORRELATION-ENERGY; MICROWAVE-SPECTRUM; ORBITAL METHODS; MP2 ENERGY; DENSITY; ANISOLE AB The geometric structure of 2, 3,5,6-tetrafluoroanisole and the potential function for internal rotation around the C(sp(2))-O bond were determined by gas electron diffraction (GED) and quantum chemical calculations. Analysis of the GED intensities with a static model resulted in near-perpendicular orientation of the O-CH3 bond relative to the benzene plane with a torsional angle around the C(sp(2))-O bond of tau(C-O) = 67(15)degrees With a dynamic model, a wide single-minimum potential for internal rotation around the C(sp(2))-O bond with perpendicular orientation of the methoxy group [tau(C-O) = 90degrees] and a barrier of 2.7 +/- 1.6 kcal/mol at planar orientation [tau(C-O) = 0degrees] was derived. Calculated potential functions depend strongly on the computational method (HF, MP2, or B3LYP) and converge adequately only if large basis sets are used. The electronic energy curves show internal structure, with local minima appearing because of the interplay between electron delocalization, changes in the hybridization around the oxygen atom, and the attraction between the positively polarized hydrogen atoms in the methyl group and the fluorine atom at the ortho position. The internal structure of the electronic energy curves mostly disappears if zero-point energies and thermal Corrections are added. The calculated free energy barrier at 298 K is 2.0 +/- 1.0 kcal/mol. in good agreement with the experimental determination. C1 Univ Tubingen, Inst Phys & Theoret Chem, D-7207 Tubingen, Germany. St Petersburg State Technol Inst, St Petersburg 190013, Russia. CCPG, Fac Quim, Montevideo 11800, Uruguay. SAIC Frederick Inc, Natl Canc Inst, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. RP Oberhammer, H (reprint author), Univ Tubingen, Inst Phys & Theoret Chem, Morgenstelle 8, D-7207 Tubingen, Germany. EM heinz.oberhammer@uni-tuebingen.de RI Belyakov, Alexander/N-9314-2015 OI Belyakov, Alexander/0000-0001-8575-8248 NR 39 TC 9 Z9 9 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD JAN 20 PY 2005 VL 109 IS 2 BP 394 EP 399 DI 10.1021/jp06975d PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 887NN UT WOS:000226312900013 PM 16833358 ER PT J AU Plotkin, JB Dushoff, J Fraser, HB AF Plotkin, JB Dushoff, J Fraser, HB TI Evolutionary genomics - Detecting selection needs comparative data - Codon volatility does not detect selection - Reply SO NATURE LA English DT Editorial Material ID MYCOBACTERIUM-TUBERCULOSIS; POPULATION; MUTATION C1 Harvard Soc Fellows, Cambridge, MA 02138 USA. Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08540 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Plotkin, JB (reprint author), Harvard Soc Fellows, 7 Divin Ave, Cambridge, MA 02138 USA. EM jplotkin@fas.harvard.edu RI Plotkin, Joshua/E-6947-2013 NR 14 TC 6 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 20 PY 2005 VL 433 IS 7023 BP E7 EP E8 DI 10.1038/nature03224 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 888NK UT WOS:000226381300033 ER PT J AU Lou, H Kim, SK Zaitsev, E Snell, CR Lu, B Loh, YP AF Lou, H Kim, SK Zaitsev, E Snell, CR Lu, B Loh, YP TI Sorting and activity-dependent secretion of BDNF require interaction of a specific motif with the sorting receptor carboxypeptidase E SO NEURON LA English DT Article ID NERVE GROWTH-FACTOR; PRIMARY SENSORY NEURONS; NEUROTROPHIC FACTOR; HIPPOCAMPAL-NEURONS; CORTICAL-NEURONS; SYNAPTIC MODULATION; PATHWAY; CELLS; PROOPIOMELANOCORTIN; IDENTIFICATION AB Activity-dependent secretion of BDNF is important in mediating synaptic plasticity, but how it is achieved is unclear. Here we uncover a sorting motif receptor-mediated mechanism for regulated secretion of BDNF. X-ray crystal structure analysis revealed a putative sorting Motif, l(16)E(18)l(105)D(106), in BDNF, which when mutated at the acidic residues resulted in missorting of proBDNF to the constitutive pathway in AtT-20 cells. A V20E mutation to complete a similar motif in NGF redirected a significant proportion of it from the constitutive to the regulated pathway. Modeling and binding studies showed interaction of the acidic residues in the BDNF motif with two basic residues in the sorting receptor, carboxypeptidase E (CPE). S-35 labeling experiments demonstrated that activity dependent secretion of BDNF from cortical neurons was obliterated in CPE knockout mice. Thus, we have identified a mechanism whereby a specific Motif l(16)E(18)l(105)D(106) interacts with CPIE to sort proBDNF into regulated pathway vesicles for activity-dependent secretion. C1 NICHHD, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. Medivir UK Ltd, Saffron Walden CB10 1XL, Essex, England. RP Loh, YP (reprint author), NICHHD, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov RI Lu, Bai/A-4018-2012 NR 52 TC 98 Z9 106 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JAN 20 PY 2005 VL 45 IS 2 BP 245 EP 255 DI 10.1016/j.neuron.2004.12.037 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 889OE UT WOS:000226451500011 PM 15664176 ER PT J AU Bardy, GH Lee, KL Mark, DB Poole, JE Packer, DL Boineau, R Domanski, M Troutman, C Anderson, J Johnson, G McNulty, SE Clapp-Channing, N Davidson-Ray, LD Fraulo, ES Fishbein, DP Luceri, RM Ip, JH AF Bardy, GH Lee, KL Mark, DB Poole, JE Packer, DL Boineau, R Domanski, M Troutman, C Anderson, J Johnson, G McNulty, SE Clapp-Channing, N Davidson-Ray, LD Fraulo, ES Fishbein, DP Luceri, RM Ip, JH CA SCD-HeFT Investigators TI Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NONISCHEMIC DILATED CARDIOMYOPATHY; RANDOMIZED-TRIAL; VENTRICULAR ARRHYTHMIAS; MYOCARDIAL-INFARCTION; CLINICAL-TRIALS; HIGH-RISK AB BACKGROUND: Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure (CHF). Treatment with amiodarone or an implantable cardioverter-defibrillator (ICD) has been proposed to improve the prognosis in such patients. METHODS: We randomly assigned 2521 patients with New York Heart Association (NYHA) class II or III CHF and a left ventricular ejection fraction (LVEF) of 35 percent or less to conventional therapy for CHF plus placebo (847 patients), conventional therapy plus amiodarone (845 patients), or conventional therapy plus a conservatively programmed, shock-only, single-lead ICD (829 patients). Placebo and amiodarone were administered in a double-blind fashion. The primary end point was death from any cause. RESULTS: The median LVEF in patients was 25 percent; 70 percent were in NYHA class II, and 30 percent were in class III CHF. The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent. The median follow-up was 45.5 months. There were 244 deaths (29 percent) in the placebo group, 240 (28 percent) in the amiodarone group, and 182 (22 percent) in the ICD group. As compared with placebo, amiodarone was associated with a similar risk of death (hazard ratio, 1.06; 97.5 percent confidence interval, 0.86 to 1.30; P=0.53) and ICD therapy was associated with a decreased risk of death of 23 percent (0.77; 97.5 percent confidence interval, 0.62 to 0.96; P=0.007) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population. Results did not vary according to either ischemic or nonischemic causes of CHF, but they did vary according to the NYHA class. CONCLUSIONS: In patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favorable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23 percent. C1 Seattle Inst Cardiac Res, Seattle, WA 98103 USA. Univ Washington, Seattle, WA 98195 USA. Duke Univ, Durham, NC USA. Mayo Clin, Rochester, MN USA. NHLBI, Bethesda, MD 20892 USA. Florida Arrhythmia Consultants, Ft Lauderdale, FL USA. Ingham Med Ctr, Lansing, MI USA. RP Bardy, GH (reprint author), Seattle Inst Cardiac Res, 7900 E Greenlake Dr N,300, Seattle, WA 98103 USA. EM gbardy@sicr.org RI Tang, Anthony/E-6203-2014; omidvari, elham/Q-6686-2016; OI Mark, Daniel/0000-0001-6340-8087 FU NHLBI NIH HHS [UO1 HL55297, UO1 HL55496, UO1 HL55766] NR 19 TC 2995 Z9 3097 U1 4 U2 69 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 20 PY 2005 VL 352 IS 3 BP 225 EP 237 DI 10.1056/NEJMoa043399 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 888JP UT WOS:000226370500003 PM 15659722 ER PT J AU Kehn, K de la Fuente, C Strouss, K Berro, R Jiang, H Brady, J Mahieux, R Pumfery, A Bottazzi, ME Kashanchi, F AF Kehn, K de la Fuente, C Strouss, K Berro, R Jiang, H Brady, J Mahieux, R Pumfery, A Bottazzi, ME Kashanchi, F TI The HTLV-I Tax oncoprotein targets the retinoblastoma protein for proteasomal degradation SO ONCOGENE LA English DT Review DE tax; HTLV-I; Rb; proteasome; cell cycle; tumorigenesis ID T-CELL LEUKEMIA; VIRUS TYPE-I; PAPILLOMAVIRUS TYPE-16 E7; TUMOR-SUPPRESSOR PROTEIN; ONCOGENE PRODUCT TAX; KAPPA-B-ALPHA; GENE-PRODUCT; CYCLE PROGRESSION; TRANSCRIPTIONAL ACTIVATION; ADENOVIRUS E1A AB Human T-cell leukemia virus type-I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL), is estimated to affect 10 - 20 million people worldwide. The transforming ability of HTLV-I has been largely attributed to the viral protein Tax, which modulates the activity of several well-known cell cycle regulators. An important cell cycle regulator, the retinoblastoma (Rb) protein, is often inactivated in many cancers including virally induced cancers. Upon examination of Rb status, we observed a decrease in Rb protein expression in HTLV-1-infected cell lines as well as in ex vivo ATL patient samples. Transient transfection assays indicated that decreased Rb protein levels were Tax dependent. Here, we demonstrate for the first time that Tax directly associates with Rb. This interaction was localized within the B pocket of Rb and the C-terminus of Tax (aa 245 - 353). Within the C-terminus of Tax, we have identified an LXCXE-like motif, that when mutated resulted in the loss of Tax/Rb interaction. Furthermore, through the use of proteasome inhibitors, such as MG-132, in vivo and proteasome degradation assays in vitro, we found that Tax destabilizes the hypo-phosphorylated( active) form of Rb via the proteasome pathway. Therefore, we propose a model whereby Tax targets Rb to the proteasome by acting as a molecular bridge bringing Rb into contact with the proteasome for degradation. C1 George Washington Univ, Sch Med, Dept Biochem & Mol Biol, Washington, DC 20037 USA. NCI, Virus Tumor Biol Sect, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Inst Pasteur, Dept SIDA & Retrovirus, Unite Epidemiol & Physiopathol Virus Oncogenes, F-75724 Paris, France. George Washington Univ, Med Ctr, Dept Microbiol & Trop Med, Washington, DC 20037 USA. Inst Genom Res TIGR, Rockville, MD 20850 USA. RP Kashanchi, F (reprint author), George Washington Univ, Sch Med, Dept Biochem & Mol Biol, 2300 Eye St NW,Ross Hall,Rm 552, Washington, DC 20037 USA. EM bcmfxk@gwumc.edu RI Kehn-Hall, Kylene/I-5752-2013 FU NIAID NIH HHS [AI061560, AI44357, AI43894] NR 101 TC 70 Z9 72 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 20 PY 2005 VL 24 IS 4 BP 525 EP 540 DI 10.1038/sj.onc.1208105 PG 16 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 889CF UT WOS:000226420400001 PM 15580311 ER PT J AU Boulanger, CA Wagner, KU Smith, GH AF Boulanger, CA Wagner, KU Smith, GH TI Parity-induced mouse mammary epithelial cells are pluripotent, self-renewing and sensitive to TGF-beta 1 expression SO ONCOGENE LA English DT Article DE mammary; transplantation; stem cells; TGF-beta 1; cell fate; pregnancy ID GLAND; DIFFERENTIATION; CARCINOGENESIS; MORPHOGENESIS; POPULATION; SENESCENCE; PREGNANCY AB A parity-induced mammary population, marked by beta-galactosidase expression conditionally activated through cre-lox recombinase originates in WAP-Cre/Rosa-lox-STOP- lox-LacZ (WAP-Cre/Rosa-LacZ) female mice during pregnancy, lactation and involution. During subsequent pregnancies, these parity-induced mammary epithelial cells (PI-MEC) proliferated to produce new secretory acini composed of secretory luminal cells and myoepithelium. In serial transplantation assays, PI-MEC were able to self-renew over several transplant generations and to contribute significantly to the resulting mammary outgrowths. In limiting dilution transplantation, they proliferated to produce both luminal and myoepithelial cells, comprised both lobule-limited and duct-limited epithelial outgrowths, and differentiated into all the cellular subtypes recognized in murine mammary epithelium. TGF-beta1 expression from the whey acidic protein promoter (WAP) in triply transgenic females did not prevent the appearance of PI-MEC after pregnancy despite the absence of full lactation or their ability to proliferate and produce progeny with diverse cellular fates in situ upon subsequent pregnancies. However, in transplants from triple transgenic parous females, the WAP-TGF-beta1-positive PI-MEC did not contribute to the newly recapitulated mammary outgrowths, suggesting that they were incapable of expansive cellular proliferation (self-renewal). This result is consistent with our earlier publication that WAP-TGF-beta1 expression in mammary epithelium induces premature stem cell senescence in mammary transplants and decreases mammary cancer risk in mouse mammary tumor virus (MMTV)-infected females even after multiple pregnancies. C1 NCI, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. Univ Nebraska, Sch Med, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. RP Smith, GH (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Bldg 10,Room 5B56,9000 Rockville Pike, Bethesda, MD 20892 USA. EM gs4d@nih.gov RI Wagner, Kay-Uwe/B-6044-2009 NR 19 TC 133 Z9 134 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 20 PY 2005 VL 24 IS 4 BP 552 EP 560 DI 10.1038/sj.onc.1208185 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 889CF UT WOS:000226420400003 PM 15580303 ER PT J AU Klimes, I Weston, K Gasperikova, D Kovacs, P Kvetnansky, R Jezova, D Dixon, R Thompson, JR Sebokova, E Samani, NJ AF Klimes, I Weston, K Gasperikova, D Kovacs, P Kvetnansky, R Jezova, D Dixon, R Thompson, JR Sebokova, E Samani, NJ TI Mapping of genetic determinants of the sympathoneural response to stress SO PHYSIOLOGICAL GENOMICS LA English DT Article DE catecholamine; stress; genetics; quantitative trait loci ID BLOOD-PRESSURE; LINKAGE; HYPERTENSION; TRAITS; LOCI; RATS AB Activation of the sympathoadrenal system ( SAS, comprising the sympathetic nervous system and the adrenal medulla) in response to stressful stimuli is an important defense mechanism as well as a contributor to several cardiovascular diseases. There is variability in the SAS response to stress, although the extent to which this is genetically regulated is unclear. Some rodent models, including the hereditary hypertriglyceridemic (hHTg) rat, are hyperresponsive to stress. We investigated whether quantitative trait loci (QTLs) that affect sympathoadrenal response to stress could be identified. Second filial generation rats (n = 189) derived from a cross of the hHTg rat and the Brown Norway rat had plasma norepinephrine ( NE) and epinephrine (Epi) levels, indices of activation of the sympathoneural and adrenal medulla components, respectively, measured in the resting state and in response to an immobilization stress. Responses were assessed early (20 min) and late ( 20 min) after the application of the stress. A genome scan was conducted using 153 microsatellite markers. Two QTLs (maximum peak LOD scores of 4.17 and 3.52, respectively) influencing both the early and late plasma NE response to stress were found on chromosome 10. Together, the QTLs accounted for similar to 20% of the total variation in both the early and late NE responses in the F-2 rats. Interestingly, the QTLs had no effect on plasma Epi response to stress. These findings provide evidence for a genetic determination of the response of a specific component of the SAS response to stress. Genetically determined variation in sympathetic nervous system response to stress may contribute to cardiovascular diseases. C1 Slovak Acad Sci, Inst Expt Endocrinol, Diabet & Nutr Res Lab, Bratislava, Slovakia. Slovak Acad Sci, Inst Expt Endocrinol, Stress Res Lab, Bratislava, Slovakia. Slovak Acad Sci, Inst Expt Endocrinol, Lab Pharmacol Neuroendocrinol, Bratislava, Slovakia. Univ Leicester, Dept Cardiovasc Sci, Cardiol Grp, Leicester LE1 7RH, Leics, England. NIDDKD, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England. RP Samani, NJ (reprint author), Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Cardiol Grp, Clin Sci Wing,Groby Rd, Leicester LE3 9QP, Leics, England. EM njs@le.ac.uk NR 20 TC 8 Z9 8 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JAN 20 PY 2005 VL 20 IS 2 BP 183 EP 187 DI 10.1152/physiolgenomics.00054.2004 PG 5 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 908RD UT WOS:000227806000005 PM 15547139 ER PT J AU Miranda, KM Dutton, AS Ridnour, LA Foreman, CA Ford, E Paolocci, N Katori, T Tocchetti, CG Mancardi, D Thomas, DD Espey, MG Houk, KN Fukuto, JM Wink, DA AF Miranda, KM Dutton, AS Ridnour, LA Foreman, CA Ford, E Paolocci, N Katori, T Tocchetti, CG Mancardi, D Thomas, DD Espey, MG Houk, KN Fukuto, JM Wink, DA TI Mechanism of aerobic decomposition of Angeli's salt (sodium trioxodinitrate) at physiological pH SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NEUTRAL AQUEOUS-SOLUTION; NITRIC-OXIDE NO; NITROXYL ANION; SUPEROXIDE-DISMUTASE; NITROSYL HYDRIDE; CARDIOVASCULAR-SYSTEM; ISCHEMIA-REPERFUSION; BIOLOGICAL-SYSTEMS; PULSE-RADIOLYSIS; CENTER-DOT AB The recent determination that Angeli's salt may have clinical application as a nitrogen oxide donor for treatment of cardiovascular diseases such as heart failure has led to renewed interest in the mechanism and products of thermal decomposition of Angeli's salt under physiological conditions. In this report, several mechanisms are evaluated experimentally and by quantum mechanical calculations to determine whether HNO is in fact released from Angeli's salt in neutral, aerobic solution. The mechanism of product autoxidation is also considered. C1 Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Hlth Sci Ctr, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. Johns Hopkins Med Inst, Div Cardiol, Dept Med, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Dept Biomed Engn, Baltimore, MD 21287 USA. RP Miranda, KM (reprint author), Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. EM kmiranda@email.arizona.edu; wink@box-w.nih.gov RI Miranda, Katrina/B-7823-2009; Liu, Peng/D-1233-2013; OI tocchetti, carlo gabriele/0000-0001-5983-688X; MANCARDI, Daniele/0000-0003-3809-6047 FU NIGMS NIH HHS [GM 59446] NR 81 TC 71 Z9 74 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 19 PY 2005 VL 127 IS 2 BP 722 EP 731 DI 10.1021/ja045480x PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 887RZ UT WOS:000226324500056 PM 15643898 ER PT J AU Lippman, SM Goodman, PJ Klein, EA Parnes, HL Thompson, IM Kristal, AR Santella, RM Probstfield, JL Moinpour, CM Albanes, D Taylor, PR Minasian, LM Hoque, A Thomas, SM Crowley, JJ Gaziano, JM Stanford, JL Cook, ED Fleshner, NE Lieber, MM Walther, PJ Khuri, FR Karp, DD Schwartz, GG Ford, LG Coltman, CA AF Lippman, SM Goodman, PJ Klein, EA Parnes, HL Thompson, IM Kristal, AR Santella, RM Probstfield, JL Moinpour, CM Albanes, D Taylor, PR Minasian, LM Hoque, A Thomas, SM Crowley, JJ Gaziano, JM Stanford, JL Cook, ED Fleshner, NE Lieber, MM Walther, PJ Khuri, FR Karp, DD Schwartz, GG Ford, LG Coltman, CA TI Designing the selenium and vitamin E cancer prevention trial (SELECT) SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; ALPHA-TOCOPHEROL SUPPLEMENTATION; PROSTATE-SPECIFIC ANTIGEN; BETA-CAROTENE; LUNG-CANCER; CELL-LINES; GAMMA-TOCOPHEROL; REDUCED RISK; MALE SMOKERS; IN-VITRO AB Prostate cancer continues to be a major health threat, especially among African American men. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), which opened on July 25, 2001, was planned to study possible agents for the prevention of prostate cancer in a population of 32 400 men in the United States, including Puerto Rico, and Canada. SELECT is a phase III randomized, placebo-controlled trial of selenium (200 mug/day from L-selenomethionine) and/or vitamin E (400 IU/day of all rac (alpha-tocopheryl acetate) supplementation for a minimum of 7 years (maximum of 12 years) in non-African American men at least 55 years of age and African American men at least 50 years of age. SELECT is a large, simple trial that conforms as closely as possible with community standards of care. This commentary discusses the design problems the SELECT investigators had to resolve in developing the trial, including the role of prostate cancer screening, the best forms and doses of the study agents, and estimation of the event (prostate cancer) rate of men on the placebo arm. C1 Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Natl Canc Inst, Bethesda, MD USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Columbia Univ, Coll Phys & Surg, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA. Boston VA Healthcare Syst, Boston, MA USA. Canadian Urol Oncol Grp, Toronto, ON, Canada. N Cent Canc Treatment Grp, Rochester, MN USA. Canc & Leukemia Grp B, Chicago, IL USA. Radiat Therapy Oncol Grp, Philadelphia, PA USA. Eastern Cooperat Oncol Grp, Brookline, MA USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. SW Oncol Grp Operat Off, San Antonio, TX USA. RP Lippman, SM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, 1515 Holcombe Blvd,Rm HMB 11-192,Box 236, Houston, TX 77030 USA. EM slippman@mdanderson.org RI Kristal, Alan/A-8779-2008; Albanes, Demetrius/B-9749-2015; OI Kristal, Alan/0000-0002-7329-1617 FU NCI NIH HHS [CA37429] NR 87 TC 207 Z9 212 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 19 PY 2005 VL 97 IS 2 BP 94 EP 102 DI 10.1093/jnci/dji009 PG 9 WC Oncology SC Oncology GA 891RX UT WOS:000226599500007 PM 15657339 ER PT J AU Bianco, C Strizzi, L Ebert, A Chang, C Rehman, A Normanno, N Guedez, L Salloum, R Ginsburg, E Sun, YP Khan, N Hirota, M Wallace-Jones, B Wechselberger, C Vonderhaar, BK Tosato, G Stetler-Stevenson, WG Sanicola, M Salomon, DS AF Bianco, C Strizzi, L Ebert, A Chang, C Rehman, A Normanno, N Guedez, L Salloum, R Ginsburg, E Sun, YP Khan, N Hirota, M Wallace-Jones, B Wechselberger, C Vonderhaar, BK Tosato, G Stetler-Stevenson, WG Sanicola, M Salomon, DS TI Role of human cripto-1 in tumor angiogenesis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MAMMARY EPITHELIAL-CELLS; CERVICAL-CARCINOMA CELLS; GROWTH-FACTOR-BETA; ENDOTHELIAL-CELLS; TYROSINE PHOSPHORYLATION; VERTEBRATE DEVELOPMENT; GENE FAMILY; IN-VIVO; RECEPTORS; MIGRATION AB Background: Human cripto-1 (CR-1) promotes cell transformation and increases migration and invasion of various mouse and human epithelial cell lines. We investigated whether CR-1 also stimulates angiogenesis. Methods: We used human umbilical vein endothelial cells (HUVECs) to measure in vitro migration with fibronectin-coated Boyden chambers, invasion with Matrigel-coated Boyden chambers, proliferation with a tetrazolium salt, and differentiation with an in vitro Matrigel assay. We investigated new blood vessel formation in vivo by use of Matrigel-filled silicone cylinders implanted under the skin of nude mice and by use of a breast cancer xenograft model with CR-1-transfected or control Neo-transfected MCF-7 human breast cancer cells. We also used a blocking anti-CR-1 monoclonal antibody to investigate the role of CR-1 in angiogenesis in vivo and in vitro. All statistical tests were two-sided. Results: CR-1 stimulated HUVEC proliferation, migration, and invasion and induced HUVEC differentiation into vascular-like structures on Matrigel. In vivo recombinant CR-1 protein induced microvessel formation in Matrigel-filled silicone cylinders, and microvessel formation was statistically significantly inhibited with a blocking anti-CR-1 monoclonal antibody (CR-1 and antibody = 127% of microvessel formation compared with that in untreated control cylinders and CR-1 alone = 259%; difference = 132%, 95% confidence interval [CI] = 123% to 140%; P < .001). Tumors formed by CR-1-transfected MCF-7 cells in the cleared mammary fat pad of nude mice had higher microvessel density than tumors formed by control Neo-transfected MCF-7 cells (CR-1-transfected cells = 4.66 vessels per field and Neo-transfected cells = 2.33 vessels per field; difference = 2.33 vessels per field, 95% CI = 1.2 to 2.8; P = .004). Conclusion: CR-1 appears to have an important role in the multistep process of angiogenesis. C1 NCI, Mol & Cellular Endocrinol Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Extracellular Matrix Sect, Pathol Lab, Expt Transplantat & Immunol Branch,NIH, Bethesda, MD 20892 USA. Dept Gynecol, Berlin, Germany. Univ Michigan, Dept Mol & Cellular Biol, Ann Arbor, MI 48109 USA. ITN, Fdn Pascale, Div Haematol Oncol, Naples, Italy. ITN, Fdn Pascale, Dept Expt Oncol, Naples, Italy. Upper Austrian Res GmbH Zentrum, Linz, Austria. Biogen Idec Inc, Cambridge, MA USA. RP Salomon, DS (reprint author), NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res,NIH, Bldg 10,Rm 5B39, Bethesda, MD 20892 USA. EM salomond@mail.nih.gov RI Stetler-Stevenson, William/H-6956-2012; Guedez, Liliana/H-4951-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Normanno, Nicola/0000-0002-7158-2605 NR 35 TC 45 Z9 48 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 19 PY 2005 VL 97 IS 2 BP 132 EP 141 DI 10.1093/jnci/dji011 PG 10 WC Oncology SC Oncology GA 891RX UT WOS:000226599500011 PM 15657343 ER PT J AU Schiffman, M Khan, MJ Solomon, D Herrero, R Wacholder, S Hildesheim, A Rodriguez, AC Bratti, MC Wheeler, CM Burk, RD AF Schiffman, M Khan, MJ Solomon, D Herrero, R Wacholder, S Hildesheim, A Rodriguez, AC Bratti, MC Wheeler, CM Burk, RD TI A study of the impact of adding HPV types to cervical cancer screening and triage tests SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ATYPICAL SQUAMOUS-CELLS; HUMAN-PAPILLOMAVIRUS TYPES; INTRAEPITHELIAL NEOPLASIA; UNDETERMINED SIGNIFICANCE; MANAGEMENT STRATEGIES; RANDOMIZED-TRIAL; HIGH-RISK; WOMEN; DNA; METAANALYSIS AB Use of human papillomavirus (HPV) testing in cervical cancer prevention is increasing rapidly. A DNA test for 13 HPV types that can cause cervical cancer is approved in the United States for co-screening with cytology of women greater than or equal to30 years old and for triage of women of all ages with equivocal cytology. However, most infections with HPV are benign. We evaluated trade-offs between specificity and sensitivity for approximately 40 HPV types in predicting cervical intraepithelial neoplasia 3 and cancer in two prospective studies: a population-based screening study that followed 6196 women aged 30-94 years from Costa Rica for 7 years and a triage study that followed 3363 women aged 18-90 years with equivocal cytology in four U.S. centers for 2 years. For both screening and triage, testing for more than about 10 HPV types decreased specificity more than it increased sensitivity. The minimal increases in sensitivity and in negative predictive value achieved by adding HPV types to DNA tests must be weighed against the projected burden to thousands of women falsely labeled as being at high risk of cervical cancer. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Howard Hughes Med Inst, Div Canc Prevent, NIH,DHHS, Bethesda, MD USA. Proyecto Epidemiol Guanacaste, Guanacaste, Costa Rica. Univ New Mexico, Hlth Sci Ctr, Sch Med, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Sch Med, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Schiffman, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,Room 7066,EPS MSC 7234, Bethesda, MD 20892 USA. EM schiffmm@mail.nih.gov FU NCI NIH HHS [CN-55154, CN-55105, CN-55153, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159, N01-CP-21081, N01-CP-33061, N01-CP-40542, N01-CP-506535] NR 19 TC 93 Z9 98 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 19 PY 2005 VL 97 IS 2 BP 147 EP 150 DI 10.1093/jnci/dji014 PG 4 WC Oncology SC Oncology GA 891RX UT WOS:000226599500013 PM 15657345 ER PT J AU Nadel, MR Shapiro, JA Klabunde, CN Seeff, LC Uhler, R Smith, RA Ransohoff, DF AF Nadel, MR Shapiro, JA Klabunde, CN Seeff, LC Uhler, R Smith, RA Ransohoff, DF TI A national survey of primary care physicians' methods for screening for fecal occult blood SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CANCER-SOCIETY GUIDELINES; COLORECTAL-CANCER; CLINICAL GUIDELINES; SELF-REPORT; FOLLOW-UP; SURVEILLANCE; MORTALITY; UPDATE; SIGMOIDOSCOPY; RATIONALE AB Background: Screening with the fecal occult blood test (FOBT) has been shown to reduce colorectal cancer incidence and mortality in randomized, controlled trials. Although the test is simple, implementation requires adherence to specific techniques of testing and follow-up of abnormal results. Objective: To examine how FOBT and follow-up are conducted in community practice across the United States. Design: Cross-sectional national surveys of primary care physicians and the public. Setting: The Survey of Colorectal Cancer Screening Practices in Health Care Organizations and the 2000 National Health Interview Survey. Participants: 1147 primary care physicians who ordered or performed FOBT and 11 365 adults 50 years of age or older who responded to questions about FOBT use. Measurements: Self-reported data on details of FOBT implementation and follow-up of positive results. Results: Although screening guidelines recommend home tests, 32.5% (95% Cl, 29.8% to 35.3%) of physicians used only the less accurate method of single-sample in-office testing; another 41.2% (Cl, 38.3% to 44.0%) used both types of test. Follow-up of positive test results showed considerable nonadherence to guidelines, with 29.7% (Cl, 27.1% to 32.4%) of physicians recommending repeating FOBT. Furthermore, sigmoidoscopy, rather than total colon examination, was commonly recommended to work up abnormal findings. Nearly one third of adults who reported having FOBT said they had only an in-office test, and nearly one third of those who reported abnormal FOBT results reported no follow-up diagnostic procedures. Limitations: The study was based on self-reports. Data from the National Health Interview Survey may underestimate the prevalence of in-office testing and inadequate follow-up. Conclusions: mortality reductions demonstrated with FOBT in clinical trials may not be realized in community practice because of the common use of in-office tests and inappropriate follow-up of positive results. Education of providers and system-level interventions are needed to improve the quality of screening implementation. C1 Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. Amer Canc Soc, Atlanta, GA 30329 USA. NCI, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. RP Nadel, MR (reprint author), Ctr Dis Control & Prevent, 4770 Buford Highway,Mailstop K-55, Atlanta, GA 30341 USA. EM mrn1@cdc.gov FU NCI NIH HHS [N01-PC-85169]; PHS HHS [99FED06571] NR 39 TC 129 Z9 131 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 18 PY 2005 VL 142 IS 2 BP 86 EP 94 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 915LQ UT WOS:000228306100002 PM 15657156 ER PT J AU Sakamoto, T Limouze, J Combs, CA Straight, AF Sellers, JR AF Sakamoto, T Limouze, J Combs, CA Straight, AF Sellers, JR TI Blebbistatin, a myosin II inhibitor, is photoinactivated by blue light SO BIOCHEMISTRY LA English DT Article ID RABBIT SKELETAL-MUSCLE; ACTIN AB Blebbistatin is a small molecule inhibitor discovered in a screen for inhibitors of nonmuscle myosin IIA. Blebbistatin inhibits the actin-activated MgATPase activity and in vitro motility of class II myosins. In cells, it has been shown to inhibit contraction of the cytokinetic ring. Blebbistatin has some photochemical properties that may affect its behavior in cells. In particular, we have found that exposure to light at wavelengths below 488 nm rapidly inactivates the inhibitory action of blebbistatin using the in vitro motility of myosin as an assay. In addition, the inhibition of cytokinetic ring contraction can be reversed by exposure of the cells to blue light. This property may be useful in locally reversing the action of blebbistatin treatment in a cell. However, caution should be exercised as free radicals may be produced upon irradiation of blebbistatin that could result in cell damage. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Light Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. RP Sellers, JR (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Room 8N202, Bethesda, MD 20892 USA. EM sellersj@nhlbi.nih.gov OI Straight, Aaron/0000-0001-5885-7881 NR 14 TC 85 Z9 85 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 18 PY 2005 VL 44 IS 2 BP 584 EP 588 DI 10.1021/bi0483357 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 888BA UT WOS:000226348000016 PM 15641783 ER PT J AU Rinfret, S Cohen, DJ Lamas, GA Fleischmann, KE Weinstein, MC Orav, J Schron, E Lee, KL Goldman, L AF Rinfret, S Cohen, DJ Lamas, GA Fleischmann, KE Weinstein, MC Orav, J Schron, E Lee, KL Goldman, L TI Cost-effectiveness of dual-chamber pacing compared with ventricular pacing for sinus node dysfunction SO CIRCULATION LA English DT Article DE pacing; pacemakers; sinoatrial node; cost-benefit analysis; quality of life ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; ACUTE MYOCARDIAL-INFARCTION; MODE SELECTION TRIAL; QUALITY-OF-LIFE; TERM-FOLLOW-UP; ATRIAL-FIBRILLATION; SINGLE-CHAMBER; CARDIAC-PACEMAKERS; CANADIAN TRIAL; HEART-FAILURE AB Background - Compared with single-chamber ventricular pacing, dual-chamber pacing can reduce adverse events and, as a result, improve quality of life in patients paced for sick sinus syndrome. It is not clear, however, how these benefits compare with the increased cost of dual-chamber pacemakers. Methods and Results - We used 4-year data from a 2010-patient, randomized trial to estimate the incremental cost-effectiveness of dual-chamber pacing compared with ventricular pacing and then projected these findings over the patients' lifetimes by using a Markov model that was calibrated to the first 5 years of in-trial data. To assess the stability of the findings, we performed 1000 bootstrap analyses and multiple sensitivity analyses. During the first 4 years of the trial, dual-chamber pacemakers increased quality-adjusted life expectancy by 0.013 year per subject at an incremental cost-effectiveness ratio of $53 000 per quality-adjusted year of life gained. Over a lifetime, dual-chamber pacing was projected to increase quality-adjusted life expectancy by 0.14 year with an incremental cost-effectiveness ratio of approximate to$6800 per quality-adjusted year of life gained. In bootstrap analyses, dual-chamber pacing was cost-effective in 91.9% of simulations at a threshold of $50 000 per quality-adjusted year of life and in 93.2% of simulations at a threshold of $100 000. Its cost-effectiveness ratio was also below this threshold in numerous sensitivity analyses that varied key estimates. Conclusions - For patients with sick sinus syndrome requiring pacing, dual-chamber pacing increases quality-adjusted life expectancy at a cost that is generally considered acceptable. C1 Beth Israel Deaconess Med Ctr, Div Cardiol, Dept Med, Boston, MA 02215 USA. Univ Montreal, Dept Med, CHUM, Montreal, PQ H3C 3J7, Canada. Harvard Univ, Sch Med, Boston, MA USA. Mt Sinai Med Ctr, Div Cardiol, Miami Beach, FL 33140 USA. Miami Heart Inst, Miami Beach, FL 33140 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Duke Clin Res Inst, Durham, NC USA. Duke Univ, Sch Med, Durham, NC USA. RP Cohen, DJ (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiol, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM dcohen@caregroup.harvard.edu FU NHLBI NIH HHS [UO1HL55981] NR 42 TC 24 Z9 24 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 18 PY 2005 VL 111 IS 2 BP 165 EP 172 DI 10.1161/01.CIR.0000151810.69732.41 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 888HW UT WOS:000226365800009 PM 15630030 ER PT J AU Moore, DF Li, H Jeffries, N Wright, V Cooper, RA Elkahloun, A Gelderman, MP Zudaire, E Blevins, G Yu, H Goldin, E Baird, AE AF Moore, DF Li, H Jeffries, N Wright, V Cooper, RA Elkahloun, A Gelderman, MP Zudaire, E Blevins, G Yu, H Goldin, E Baird, AE TI Using peripheral blood mononuclear cells to determine a gene expression profile of acute ischemic stroke - A pilot investigation SO CIRCULATION LA English DT Article DE cerebral infarction; genes; ischemia; stroke ID CEREBRAL-ISCHEMIA; MULTIPLE-SCLEROSIS; NEURONAL APOPTOSIS; GENOMIC RESPONSES; HYPOXIA; DISEASE; PROTEIN; HYPOGLYCEMIA; PATHOGENESIS; MICROARRAY AB Background - Direct brain biopsy is rarely indicated during acute stroke. This study uses peripheral blood mononuclear cells (PBMCs) to determine whether a systemic gene expression profile could be demonstrated in patients with acute ischemic stroke. Methods and Results - Using oligonucleotide microarrays, we compared the gene expression profile of an index cohort of 20 patients with confirmed ischemic stroke on neuroimaging studies with that of 20 referent subjects. Validation studies used quantitative real-time polymerase chain reaction to measure the levels of 9 upregulated genes in the index cohort, and an independent cohort of 9 patients and 10 referent subjects was prospectively studied to determine the accuracy of the Prediction Analysis for Microarrays list to classify stroke. After correction for multiple comparisons with the Bonferroni technique, 190 genes were significantly different between the stroke and referent groups. Broad classes of genes included white blood cell activation and differentiation (approximate to60%), genes associated with hypoxia and vascular repair, and genes potentially associated with an altered cerebral microenvironment. Real-time polymerase chain reaction confirmed increased mRNA expression in 9 of 9 upregulated stroke-associated genes in the index cohort. A panel of 22 genes derived from the Prediction Analysis for Microarrays algorithm in the index cohort classified stroke in the validation cohort with a sensitivity of 78% and a specificity of 80%. Control for the Framingham stroke risk score revealed only a partial dependence of the stroke gene expression profile in PBMCs on vascular risk. Conclusions - This study demonstrated an altered gene expression profile in PBMCs during acute ischemic stroke. Some genes with altered expression were consistent with an adaptive response to central nervous system ischemia. C1 NINDS, Stroke Neurosci Unit, NIH, Bethesda, MD 20892 USA. NINDS, Biostat Branch, NIH, Bethesda, MD 20892 USA. NINDS, Micro Array Core Facil, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Lab Cellular Hematol, CBER, Rockville, MD 20857 USA. NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. RP Moore, DF (reprint author), NINDS, Stroke Neurosci Unit, NIH, 10 Ctr Dr,MSC1294,Room 3N258, Bethesda, MD 20892 USA. EM bairda@ninds.nih.gov NR 37 TC 119 Z9 124 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 18 PY 2005 VL 111 IS 2 BP 212 EP 221 DI 10.1161/01.CIR.0000152105.79665.C6 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 888HW UT WOS:000226365800016 PM 15630028 ER PT J AU Weichsel, A Maes, EM Andersen, JF Valenzuela, JG Shokhireva, TK Walker, FA Montfort, WR AF Weichsel, A Maes, EM Andersen, JF Valenzuela, JG Shokhireva, TK Walker, FA Montfort, WR TI Heme-assisted S-nitrosation of a proximal thiolate in a nitric oxide transport protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE crystal structure; heme protein; nitrophorin; S-nitrosocysteine; S-nitroso ID ELECTRON-PARAMAGNETIC-RESONANCE; BLOODSUCKING INSECT; RHODNIUS-PROLIXUS; CRYSTALLOGRAPHIC ANALYSIS; SALIVARY NITROPHORIN; CIMEX-LECTULARIUS; BINDING; COMPLEXES; LIGAND; NITROSOTHIOLS AB Certain bloodsucking insects deliver nitric oxide (NO) while feeding, to induce vasoclilation and inhibit blood coagulation. We have expressed, characterized, and determined the crystal structure of the Cimexlectularius (bedbug) nitrophorin,the protein responsible for NO storage and delivery, to understand how the insect successfully handles this reactive molecule. Surprisingly, NO binds not only to the ferric nitrophorin heme, but it can also be stored as an S-nitroso (SNO) conjugate of the proximal heme cysteine (Cys-60) when present at higher concentrations. EPR- and UV-visible spectroscopies, and a crystallographic structure determination to 1.75-Angstrom resolution, reveal SNO formation to proceed with reduction of the heme iron, yielding an Fe-NO complex. Stopped-flow kinetic measurements indicate that an ordered reaction mechanism takes place: initial NO binding occurs at the ferric heme and is followed by heme reduction, Cys-60 release from the heme iron, and SNO formation. Release of NO occurs through a reversal of these steps. These data provide, to our knowledge, the first view of reversible metal-assisted SNO formation in a protein and suggest a mechanism for its role in NO release from ferrous heme. This mechanism and Cimex nitrophorin structure are completely unlike those of the nitrophorins from Rhodnius prolixus, where NO protection is provided by a large conformational change that buries the heme nitrosyl complex, highlighting the remarkable evolution of proteins that assist insects in bloodfeeding. C1 Univ Arizona, Dept Biochem & Mol Biophys, Tucson, AZ 85721 USA. Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Montfort, WR (reprint author), Univ Arizona, Dept Biochem & Mol Biophys, Tucson, AZ 85721 USA. EM montfort@email.arizona.edu RI Walker, Frances/O-4395-2016 FU NHLBI NIH HHS [HL54826, HL62969, R01 HL054826, R01 HL062969] NR 46 TC 97 Z9 98 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 18 PY 2005 VL 102 IS 3 BP 594 EP 599 DI 10.1073/pnas.0406549102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 889IF UT WOS:000226436000015 PM 15637157 ER PT J AU Yang, ZY Werner, HC Kong, WP Leung, K Traggiai, E Lanzavecchia, A Nabel, GJ AF Yang, ZY Werner, HC Kong, WP Leung, K Traggiai, E Lanzavecchia, A Nabel, GJ TI Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE angiotensin-converting enzyme 2; enhancement; immunoglobulin G; pseudovirus ID ANGIOTENSIN-CONVERTING ENZYME-2; SARS-CORONAVIRUS; PROTECTIVE IMMUNITY; SPIKE GLYCOPROTEIN; GENOME SEQUENCE; CELL-LINES; S-PROTEIN; RECEPTOR; VIRUS; ENTRY AB Molecular characterization of the severe acute respiratory syndrome coronavirus has revealed genetic diversity among isolates. The spike (S) glycoprotein, the major target for vaccine and immune therapy, shows up to 17 substitutions in its 1,255-aa sequence; however, the biologic significance of these changes is unknown. Here, the functional effects of S mutations have been determined by analyzing their affinity for a viral receptor, human angiotensin-converting enzyme 2 (hACE-2), and their sensitivity to Ab neutralization with viral pseudotypes. Although minor differences among eight strains transmitted during human outbreaks in early 2003 were found, substantial functional changes were detected in S derived from a case in late 2003 from Guangdong province [S(GD03T0013)] and from two palm civets, S(SZ3) and S(SZ16). S(GD03T0013) depended less on the hACE-2 receptor and was markedly resistant to Ab inhibition. Unexpectedly, Abs that neutralized most human S glycoproteins enhanced entry mediated by the civet virus 5 glycoproteins. The mechanism of enhancement involved the interaction of Abs with conformational epitopes in the hACE-2-binding domain. Finally, improved immunogens and mAbs that minimize this complication have been defined. These data show that the entry of severe acute respiratory syndrome coronaviruses can be enhanced by Abs, and they underscore the need to address the evolving diversity of this newly emerged virus for vaccines and immune therapies. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Inst Biomed Res, CH-6500 Bellinzona, Switzerland. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC-3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov RI traggiai, elisabetta/A-2316-2009 NR 25 TC 105 Z9 116 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 18 PY 2005 VL 102 IS 3 BP 797 EP 801 DI 10.1073/pnas.0409065102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 889IF UT WOS:000226436000050 PM 15642942 ER PT J AU Jayanthi, S Deng, XL Ladenheim, B McCoy, MT Cluster, A Cai, NS Cadet, JL AF Jayanthi, S Deng, XL Ladenheim, B McCoy, MT Cluster, A Cai, NS Cadet, JL TI Calcineurin/NFAT-induced up-regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE calcium; neurodegeneration; gelsolin; Egr ID T-CELLS; INDUCED NEUROTOXICITY; TRANSCRIPTION FACTORS; CD95 LIGAND; EXPRESSION; NFAT; FOS; JUN; CALCIUM; ABUSERS AB Methamphetamine [METH ("speed")] is an abused psychostimulant that can cause psychotic, cognitive, and psychomotor impairment in humans. These signs and symptoms are thought to be related to dysfunctions in basal ganglionic structures of the brain. To identify possible molecular bases for these clinical manifestations, we first used cDNA microarray technology to measure METH-induced transcriptional responses in the striatum of rats treated with an apoptosis-inducing dose of the drug. METH injection resulted in increased expression of members of the Jun, Egr, and Nur77 subfamilies of transcription factors (TFs), changes that were confirmed by quantitative PCR. Because pathways linked to these factors are involved in the up-regulation of Fas ligand (FasL), FasL mRNA was quantified and found to be increased. Immunohistochemical studies also revealed METH-induced increased FasL protein expression in striatal GABAergic neurons that express enkephalin. Moreover, there were METH-mediated increases in calcineurin, as well as shuttling of nuclear factor of activated T cells (NFAT)c3 and NFATc4 from the cytosol to the nucleus of METH-treated rats, mechanisms also known to be involved in FasL regulation. Furthermore, METH induced cleavage of caspase-3 in FasL- and Fas-containing neurons. Finally, the METH-induced changes in the FasL-Fas death pathway were attenuated by pretreatment with the dopamine D1 receptor antagonist, SCH23390, which also caused attenuation of METH-induced apoptosis. These observations indicate that METH causes some of its neurodegenerative effects, in part, via stimulation of the Fas-mediated cell death pathway consequent to FasL up-regulation mediated by activation of multiple TFs. C1 NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov NR 49 TC 135 Z9 139 U1 3 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 18 PY 2005 VL 102 IS 3 BP 868 EP 873 DI 10.1073/pnas.0404990102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 889IF UT WOS:000226436000062 PM 15644446 ER PT J AU Stadtman, ER Van Remmen, H Richardson, A Wehr, NB Levine, RL AF Stadtman, ER Van Remmen, H Richardson, A Wehr, NB Levine, RL TI Methionine oxidation and aging SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Review DE methionine sulfoxide; methionine; methionine sulfoxide reductase; aging ID MANGANESE SUPEROXIDE-DISMUTASE; RADICAL-CATION COMPLEXES; SULFOXIDE REDUCTASE GENE; PROTEIN OXIDATION; TRABECULAR MESHWORK; CATARACTOUS LENSES; ESCHERICHIA-COLI; ALPHA-SYNUCLEIN; ENZYME-ACTIVITY; HUMAN-EYE AB It is well established that many amino acid residues of proteins are susceptible to oxidation by various forms of reactive oxygen species (ROS), and that oxidatively modified proteins accumulate during aging, oxidative stress, and in a number of age-related diseases. Methionine residues and cysteine residues of proteins are particularly sensitive to oxidation by ROS. However, unlike oxidation of other amino acid residues, the oxidation of these sulfur amino acids is reversible. Oxidation of methionine residues leads to the formation of both R- and S-stereoisomers of methionine sulfoxide (MetO) and most cells contain stereospecific methionine sulfoxide reductases (Msr's) that catalyze the thioredoxin-dependent reduction of MetO residues back to methionine residues. We summarize here results of studies, by many workers, showing that the MetO content of proteins increases with age in a number of different aging models, including replicative senescence and erythrocyte aging, but not in mouse tissues during aging. The change in levels of MetO may reflect alterations in any one or more of many different mechanisms, including (i) an increase in the rate of ROS generation; (ii) a decrease in the antioxidant capacity; (iii) a decrease in proteolytic activities that preferentially degrade oxidized proteins; or (iv) a decrease in the ability to convert MetO residues back to Met residues, due either to a direct loss of Msr enzyme levels or indirectly to a loss in the availability of the reducing equivalents (thioredoxin, thioredoxin reductase, NADPH generation) involved. The importance of Msr activity is highlighted by the fact that aging is associated with a loss of Msr activities in a number of animal tissues, and mutations in mice leading to a decrease in the Msr levels lead to a decrease in the maximum life span, whereas overexpression of Msr leads to a dramatic increase in the maximum life span. Published by Elsevier B.V. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev Studies, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NIH, Bldg 50,Room 2140, Bethesda, MD 20892 USA. EM EarlStadtman@nih.gov RI Levine, Rodney/D-9885-2011 NR 47 TC 210 Z9 217 U1 2 U2 34 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD JAN 17 PY 2005 VL 1703 IS 2 BP 135 EP 140 DI 10.1016/j.bbapap.2004.08.010 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 899GE UT WOS:000227132100005 PM 15680221 ER PT J AU Wood, MJ Prieto, JH Komives, EA AF Wood, MJ Prieto, JH Komives, EA TI Structural and functional consequences of methionine oxidation in thrombomodulin SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Review DE anticoagulant; protein C; thrombin; coagulation; NMR; EGF domain ID EGF-LIKE DOMAIN; ALPHA-1-PROTEINASE INHIBITOR; COFACTOR ACTIVITY; PROTEIN-C; COAGULATION; ACTIVATION; MECHANISM; RESIDUES; BINDING; ROLES AB Thrombomodulin (TM) is an endothelial cell surface glycoprotein that is responsible for switching the catalytic activity of thrombin away from fibrinogen cleavage (pro-coagulant) and towards protein C cleavage (anticoagulant). Although TM is a large protein, only the fourth and fifth epidermal growth factor-like (EGF-like) domains are required for anticoagulant function. These two domains must work together, and the linker between the two domains contains a single methionine residue, Met 388. Oxidation of Met 388 is deleterious for TM activity. Structural studies, both X-ray and NMR, of wild type and variants at position 388 show that Met 388 provides a key linkage between the two domains. Oxidation of the methionine has consequences for the structure of the fifth domain, which binds to thrombin. Oxidation also appears to disrupt the interdomain contacts resulting in structural and dynamic changes. The functional consequences of oxidation of Met 388 include decreased anticoagulant activity. Oxidative stress from several causes is reflected in lower serum levels of activated protein C and a higher thrombotic tendency, and this is thought to be linked to the oxidation of Met 388 in TM. Thus, TM structure and function are altered in a subtle but functionally critical way upon oxidation of Met 388. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Komives, EA (reprint author), Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM ekomives@ucsd.edu FU NHLBI NIH HHS [R01 HL047463]; NIDDK NIH HHS [T32 DK007233] NR 24 TC 29 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD JAN 17 PY 2005 VL 1703 IS 2 BP 141 EP 147 DI 10.1016/j.bbapap.2004.090007 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 899GE UT WOS:000227132100006 PM 15680222 ER PT J AU Burnett, JC Schmidt, JJ McGrath, CF Nguyen, TL Hermone, AR Panchal, RG Vennerstrom, JL Kodukula, K Zaharevitz, DW Gussio, R Bavari, S AF Burnett, JC Schmidt, JJ McGrath, CF Nguyen, TL Hermone, AR Panchal, RG Vennerstrom, JL Kodukula, K Zaharevitz, DW Gussio, R Bavari, S TI Conformational sampling of the botulinum neurotoxin serotype a light chain: implications for inhibitor binding SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE molecular dynamics; molecular modeling; pharmacophore; metalloprotease ID TOXIN TYPE-A; NEUROTRANSMITTER RELEASE; CLOSTRIDIAL NEUROTOXINS; STRUCTURAL-ANALYSIS; CRYSTAL-STRUCTURE; PROTEASE ACTIVITY; TETANUS; VAMP/SYNAPTOBREVIN; SYNAPTOBREVIN; MANAGEMENT AB Botulinum neurotoxins (BoNTs) are the most potent of the known biological toxins, and consequently are listed as category A biowarfare agents. Currently, the only treatments against BoNTs include preventative antitoxins and long-term supportive care. Consequently, there is an urgent need for therapeutics to counter these enzymes-post exposure. In a previous study, we identified a number of small, nonpeptidic lead inhibitors of BoNT serotype A light chain (BoNT/A LC) metalloprotease activity, and we identified a common pharmacophore for these molecules. In this study, we have focused on how the dynamic movement of amino acid residues in and surrounding the substrate binding cleft of the BoNT/A LC might affect inhibitor binding modes. The X-ray crystal structures of two BoNT/A LCs (PDB refcodes = 3BTA and 1E1H) were examined. Results from these analyses indicate that the core structural features of the examined BoNT/A LCs, including alpha-helices and beta-sheets, remained relatively unchanged during 1 ns dynamics trajectories. However, conformational flexibility was observed in surface loops bordering the substrate binding clefts in both examined structures. Our analyses indicate that these loops may possess the ability to decrease the solvent accessibility of the substrate binding cleft, while at the same time creating new residue contacts for the inhibitors. Loop movements and conformational/positional analyses of residues within the substrate binding cleft are discussed with respect to BoNT/A LC inhibitor binding and our common pharmacophore for inhibition. The results from these studies may aid in the future identification/development of more potent small molecule inhibitors that take advantage of new binding contacts in the BoNT/A LC. Published by Elsevier Ltd. C1 USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. NCI, Dev Therapeut Program, Ft Detrick, MD 21702 USA. Univ Nebraska, Med Ctr, Coll Pharm, Nebraska Med Ctr 986025, Omaha, NE 68198 USA. Sarnoff Corp, Off Technol & Strategy Innovat & Acquisit, Princeton, NJ 08543 USA. RP Gussio, R (reprint author), USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. EM gussio@ncifcrf.gov; sina.bavari@amedd.army.mil FU NCI NIH HHS [Y3-CM-100505] NR 36 TC 33 Z9 34 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 JAN 17 PY 2005 VL 13 IS 2 BP 333 EP 341 DI 10.1016/j.bmc.2004.10.026 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 887ZK UT WOS:000226343800005 PM 15598556 ER PT J AU Pourshams, A Saadatian-Elahi, M Nouraie, M Malekshah, AF Rakhshani, N Salahi, R Yoonessi, A Semnani, S Islami, F Sotoudeh, M Fahimi, S Sadjadi, AR Nasrollahzadeh, D Aghcheli, K Kamangar, F Abnet, CC Saidi, F Sewram, V Strickland, PT Dawsey, SM Brennan, P Boffetta, P Malekzadeh, R AF Pourshams, A Saadatian-Elahi, M Nouraie, M Malekshah, AF Rakhshani, N Salahi, R Yoonessi, A Semnani, S Islami, F Sotoudeh, M Fahimi, S Sadjadi, AR Nasrollahzadeh, D Aghcheli, K Kamangar, F Abnet, CC Saidi, F Sewram, V Strickland, PT Dawsey, SM Brennan, P Boffetta, P Malekzadeh, R TI Golestan cohort study of oesophageal cancer: feasibility and first results SO BRITISH JOURNAL OF CANCER LA English DT Article DE oesophageal cancer; cohort; Golestan; turkmen; Iran ID SQUAMOUS-CELL CARCINOMA; RISK-FACTORS; IRAN; OPIUM; MUTAGENS; POPULATION; PYROLYSIS; EXPOSURE; CHINA/ AB To investigate the incidence of oesophageal cancer (EC) in the Golestan province of North-East Iran, we invited 1349 rural and urban inhabitants of Golestan province aged 35 - 80 to undergo extensive lifestyle interviews and to provide biological samples. The interview was repeated on a subset of 130 participants to assess reliability of questionnaire and medical information. Temperature at which tea was consumed was measured on two occasions by 110 subjects. Samples of rice, wheat and sorghum were tested for fumonisin contamination. An active follow-up was carried out after 6 and 12 months. A total of 1057 subjects ( 610 women and 447 men) participated in this feasibility study (78.4% participation rate). Cigarette smoking, opium and alcohol use were reported by 163 (13.8%), 93 (8.8%) and 39 (3.7%) subjects, respectively. Tobacco smoking was correlated with urinary cotinine (kappa = 0.74). Most questionnaire data had kappa > 0.7 in repeat measurements; tea temperature measurement was reliable (kappa = 0.71). No fumonisins were detected in the samples analysed. During the follow-up six subjects were lost (0.6%), two subjects developed EC ( one dead, one alive); in all, 13 subjects died ( with cause of death known for 11, 84.6%). Conducting a cohort study in Golestan is feasible with reliable information obtained for suspected risk factors; participants can be followed up for EC incidence and mortality. C1 Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran 14114, Iran. Int Agcy Res Canc, F-69372 Lyon, France. Golestan Univ Med Sci, Gorgan, Iran. NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. MRC, PROMEC Unit, Tygerberg, South Africa. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Malekzadeh, R (reprint author), Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, N Kargar Ave, Tehran 14114, Iran. EM malek@ams.ac.ir RI Abnet, Christian/C-4111-2015; Semnani, Shahryar/N-2270-2016; OI Abnet, Christian/0000-0002-3008-7843; Semnani, Shahryar/0000-0002-8768-6142; Malekzadeh, Reza/0000-0003-1043-3814 NR 27 TC 47 Z9 47 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 17 PY 2005 VL 92 IS 1 BP 176 EP 181 DI 10.1038/sj.bjc.6602249 PG 6 WC Oncology SC Oncology GA 890HE UT WOS:000226501500029 PM 15597107 ER PT J AU Jordan, IK Marino-Ramirez, L Koonin, EV AF Jordan, IK Marino-Ramirez, L Koonin, EV TI Evolutionary significance of gene expression divergence SO GENE LA English DT Article; Proceedings Paper CT Annual Scientific Meeting on Structural Approaches to Sequence Evolution CY JUL 05-10, 2004 CL Dresden, GERMANY SP Phys Komplexer Syst, Max-Planck Inst DE molecular evolution; neutral theory; human; mouse; genomics ID PROTEIN-PROTEIN INTERACTIONS; DUPLICATE GENES; SUBSTITUTION RATES; NEUTRAL EVOLUTION; SIMPLE DEPENDENCE; NUMBER; MOUSE; DISPENSABILITY; MICROARRAY; EVOLVE AB Recent large-scale studies of evolutionary changes in gene expression among mammalian species have led to the proposal that gene expression divergence may be neutral with respect to organismic fitness. Here, we employ a comparative analysis of mammalian gene sequence divergence and gene expression divergence to test the hypothesis that the evolution of gene expression is predominantly neutral. Two models of neutral gene expression evolution are considered: I-purely neutral evolution (i.e., no selective constraint) of gene expression levels and patterns and 2-neutral evolution accompanied by selective constraint. With respect to purely neutral evolution, levels of change in gene expression between human-mouse orthologs are correlated with levels of gene sequence divergence that are determined largely by purifying selection. In contrast, evolutionary changes of tissue-specific gene expression profiles do not show such a correlation with sequence divergence. However, divergence of both gene expression levels and profiles are significantly lower for orthologous human-mouse gene pairs than for pairs of randomly chosen human and mouse genes. These data clearly point to the action of selective constraint on gene expression divergence and are inconsistent with the purely neutral model; however, there is likely to be a neutral component in evolution of gene expression, particularly, in tissues where the expression of a given gene is low and functionally irrelevant. The model of neutral evolution with selective constraint predicts a regular, clock-like accumulation of gene expression divergence. However, relative rate tests of the divergence among human-mouse-rat orthologous gene sets reveal clock-like evolution for gene sequence divergence, and to a lesser extent for gene expression level divergence, but not for the divergence of tissue-specific gene expression profiles. Taken together, these results indicate that gene expression divergence is subject to the effects of purifying selective constraint and suggest that it might also be substantially influenced by positive Darwinian selection. (C) 2004 Elsevier B.V. All rights reserved. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Jordan, IK (reprint author), NIH, Natl Ctr Biotechnol Informat, 8600 Rockville Pike,Bldg 38A Room 5N511-M, Bethesda, MD 20894 USA. EM jordan@ncbi.nlm.nih.gov RI Marino-Ramirez, Leonardo/I-5759-2013 OI Marino-Ramirez, Leonardo/0000-0002-5716-8512 FU Intramural NIH HHS [Z99 LM999999] NR 44 TC 100 Z9 102 U1 0 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD JAN 17 PY 2005 VL 345 IS 1 BP 119 EP 126 DI 10.1016/j.gene.2004.11.034 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 900FY UT WOS:000227202000015 PM 15716085 ER PT J AU Misteli, T AF Misteli, T TI Going in GTP cycles in the nucleolus SO JOURNAL OF CELL BIOLOGY LA English DT Editorial Material ID CELLS AB Proteins are directed to cellular compartments by specific localization signals. A GTP-driven cycle has now been identified as a mechanism for protein targeting to the nucleolus. The involvement of a GTP switch suggests that nucleolar localization can be regulated and may be responsive to extracellular stimuli via signaling pathways. The uncovered mechanism also implies that localization is determined by increased retention rather than directed targeting. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov NR 9 TC 24 Z9 27 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 17 PY 2005 VL 168 IS 2 BP 177 EP 178 DI 10.1083/jcb.200412038 PG 2 WC Cell Biology SC Cell Biology GA 896JB UT WOS:000226929300001 PM 15657389 ER PT J AU Tsai, RYL McKay, RDG AF Tsai, RYL McKay, RDG TI A multistep, GTP-driven mechanism controlling the dynamic cycling of nucleostemin SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CELL-PROLIFERATION; RIBOSOMAL-SUBUNIT; BINDING-PROTEIN; ACTINOMYCIN-D; CANCER-CELLS; BIOGENESIS; NUCLEOLUS; P53; DIFFERENTIATION; NUCLEOPLASM AB Nucleostemin (NS) was identified as a stem cell- and cancer cell-enriched nucleolar protein that controls the proliferation of these cells. Here, we report the mechanism that regulates its dynamic shuttling between the nucleolus and nucleoplasm. The nucleolar residence of nucleostemin involves a transient and a long-term binding by the basic and GTP-binding domains, and a dissociation mechanism mediated by the COOH-terminal region. This cycle is propelled by the GTP binding state of nucleostemin. We propose that a rapid nucleostemin cycle is designed to translate extra- and intra-cellular signals into the amount of nucleostemin in the nucleolus in a bidirectional and fast manner. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Texas A&M Univ, Hlth Sci Ctr, Alkek Inst Biosci & Technol, Ctr Canc Biol & Nutr, Houston, TX 77030 USA. RP Tsai, RYL (reprint author), NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM rtsai@ibt.tamhsc.edu FU NCI NIH HHS [R01 CA113750, R01 CA113750-01] NR 22 TC 113 Z9 125 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 17 PY 2005 VL 168 IS 2 BP 179 EP 184 DI 10.1083/jcb.200409053 PG 6 WC Cell Biology SC Cell Biology GA 896JB UT WOS:000226929300002 PM 15657390 ER PT J AU Croft, DR Coleman, ML Li, SX Robertson, D Sullivan, T Stewart, CL Olson, MF AF Croft, DR Coleman, ML Li, SX Robertson, D Sullivan, T Stewart, CL Olson, MF TI Actin-myosin-based contraction is responsible for apoptotic nuclear disintegration SO JOURNAL OF CELL BIOLOGY LA English DT Article ID RHO-ASSOCIATED KINASE; PROTEIN-KINASE; ENVELOPE BREAKDOWN; SIGNALING PATHWAY; PLASMA-MEMBRANE; STRESS FIBERS; LAMIN KINASE; IN-VIVO; ROCK-I; PHOSPHORYLATION AB Membrane blebbing during the apoptotic execution phase results from caspase-mediated cleavage and activation of ROCK I. Here, we show that ROCK activity, myosin light chain (MLC) phosphorylation, MLC ATPase activity, and an intact actin cytoskeleton, but not microtubular cytoskeleton, are required for disruption of nuclear integrity during apoptosis. Inhibition of ROCK or MLC ATPase activity, which protect apoptotic nuclear integrity, does not affect caspase-mediated degradation of nuclear proteins such as lamins A, 131, or C. The conditional activation of ROCK I was sufficient to tear apart nuclei in lamin A/C null fibroblasts, but not in wild-type fibroblasts. Thus, arpoptotic nuclear disintegration requires actin-myosin contractile force and lamin proteolysis, making apoptosis analogous to, but distinct from, mitosis where nuclear disintegration results from microtubule-based forces and from lamin phosphorylation and depolymerization. C1 Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Inst Canc Res, Breakthrough Tony Robins Breast Canc Res Ctr, London SW3 6JB, England. NCI, Canc & Dev Biol Lab, Canc Res Ctr, Frederick, MD 21701 USA. RP Olson, MF (reprint author), Beatson Inst Canc Res, Garscube Estate, Glasgow G61 1BD, Lanark, Scotland. EM m.olson@beatson.gla.ac.uk RI Olson, Michael/A-3240-2011; Coleman, Mathew/C-1676-2014; OI Coleman, Mathew/0000-0001-6020-9023; Olson, Michael/0000-0003-3428-3507 FU NCI NIH HHS [CA030721, R01 CA030721] NR 48 TC 103 Z9 107 U1 2 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 17 PY 2005 VL 168 IS 2 BP 245 EP 255 DI 10.1083/jcb.200409049 PG 11 WC Cell Biology SC Cell Biology GA 896JB UT WOS:000226929300009 PM 15657395 ER PT J AU Lo, CG Xu, Y Proia, RL Cyster, JG AF Lo, CG Xu, Y Proia, RL Cyster, JG TI Cyclical modulation of sphingosine-1-phosphate receptor 1 surface expression during lymphocyte recirculation and relationship to lymphoid organ transit SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SPHINGOSINE 1-PHOSPHATE RECEPTOR-1; SPLENIC WHITE PULP; T-CELL CHEMOTAXIS; MIGRATION; FTY720; TRAFFICKING; EGRESS; RATS; SEQUESTRATION; EMIGRATION AB Sphingosine-1-phosphate receptor 1 (S1P(1)) was recently shown to be required for lymphocyte egress from lymphoid organs. Here we have examined the relationship between S1P(1) abundance on the cell and egress efficiency. Using an integrin neutralization approach to separate the processes of entry and exit, we show that pertussis toxin treatment reduces lymphocyte egress from lymph nodes. Retrovirally mediated S1P(1) overexpression is sufficient to reduce B cell accumulation in the splenic white pulp and to promote egress of activated T cells from lymph nodes, whereas S1P(1)(+/-) cells have reduced lymph node exit efficiency. Furthermore, lymphocyte S1P(1) is down-regulated in the blood, up-regulated in lymphoid organs, and down-regulated again in the lymph. We propose that cyclical ligand-induced modulation of S1P(1) on circulating lymphocytes contributes to establishing their lymphoid organ transit time. C1 Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Cyster, JG (reprint author), Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. EM cyster@itsa.ucsf.edu RI Proia, Richard/A-7908-2012 FU NIAID NIH HHS [AI45073, R01 AI045073] NR 43 TC 181 Z9 183 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 17 PY 2005 VL 201 IS 2 BP 291 EP 301 DI 10.1084/jem.20041509 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 893NJ UT WOS:000226726200016 PM 15657295 ER PT J AU Engel, LS Hill, DA Hoppin, JA Lubin, JH Lynch, CF Pierce, J Samanic, C Sandler, DP Blair, A Alavanja, MC AF Engel, LS Hill, DA Hoppin, JA Lubin, JH Lynch, CF Pierce, J Samanic, C Sandler, DP Blair, A Alavanja, MC TI Pesticide use and breast cancer risk among farmers' wives in the agricultural health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE agriculture; agrochemicals; breast neoplasms; fungicides; industrial; herbicides; insecticides; pesticides; risk ID ENVIRONMENTAL ORGANOCHLORINE EXPOSURE; POLYCHLORINATED-BIPHENYLS; ADIPOSE-TISSUE; SERUM ORGANOCHLORINES; ENDOCRINE DISRUPTORS; FISCHER-344 RATS; FEMALE FARMERS; NORTH-CAROLINA; METHYL-BROMIDE; WOMENS HEALTH AB The authors examined the association between pesticide use and breast cancer incidence among farmers' wives in a large prospective cohort study in Iowa and North Carolina. Participants were 30,454 women with no history of breast cancer prior to cohort enrollment in 1993-1997. Information on pesticide use and other information was obtained by self-administered questionnaire at enrollment from the women and their husbands. Through 2000, 309 incident breast cancer cases were identified via population-based cancer registries. Rate ratios were calculated for individual pesticides using Poisson regression, controlling for confounding factors. Breast cancer standardized incidence ratios were 0.87 (95% confidence interval: 0.74, 1.02) for women who reported ever applying pesticides and 1.05 (95% confidence interval: 0.89, 1.24) for women who reported never applying pesticides. There was some evidence of increased risk associated with use of 2,4,5-trichloro-phenoxypropionic acid (2,4,5-TP) and possibly use of dieldrin, captan, and 2,4,5-trichlorophenoxyacetic acid (2,4,5-TP), but small numbers of cases among those who had personally used the pesticides precluded firm conclusions. The authors found no clear association of breast cancer risk with farm size or washing of clothes worn during pesticide application, but risk was modestly elevated among women whose homes were closest to areas of pesticide application. Further follow-up of this cohort should help clarify the relation between pesticide exposure and breast cancer risk. C1 Mem Sloan Kettering Canc Ctr, Epidemiol Serv, Dept Epidemiol & Biostat, New York, NY 10021 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. Battelle Ctr Publ Hlth Res & Evaluat, Durham, NC USA. RP Engel, LS (reprint author), Mem Sloan Kettering Canc Ctr, Epidemiol Serv, Dept Epidemiol & Biostat, 307 E 63rd St,3rd Floor, New York, NY 10021 USA. EM engell@mskcc.org OI Sandler, Dale/0000-0002-6776-0018; Engel, Lawrence/0000-0001-9268-4830 NR 86 TC 66 Z9 72 U1 1 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 15 PY 2005 VL 161 IS 2 BP 121 EP 135 DI 10.1093/aje/kwi022 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 885WZ UT WOS:000226189300005 PM 15632262 ER PT J AU Kleinerman, RA Linet, MS Hatch, EE Tarone, RE Black, PM Selker, RG Shapiro, WR Fine, HA Inskip, PD AF Kleinerman, RA Linet, MS Hatch, EE Tarone, RE Black, PM Selker, RG Shapiro, WR Fine, HA Inskip, PD TI Self-reported electrical appliance use and risk of adult brain tumors SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE adult; brain neoplasms; case-control studies; electromagnetic fields; meningioma; questionnaires; risk ID ELECTROMAGNETIC-FIELD EXPOSURES; NERVOUS-SYSTEM TUMORS; VOLTAGE POWER-LINES; MAGNETIC-FIELDS; CANCER; LEUKEMIA; COHORT; HOME AB Electrical appliances produce the highest intensity exposures to residential extremely low frequency electromagnetic fields. The authors investigated whether appliances may be associated with adult brain tumors in a hospital-based case-control study at three centers in the United States from 1994 to 1998. A total of 410 glioma, 178 meningioma, and 90 acoustic neuroma cases and 686 controls responded to a self-administered questionnaire about 14 electrical appliances. There was little evidence of association between brain tumors and curling iron, heating pad, vibrating massager, electric blanket, heated water bed, sound system, computer, television, humidifier, microwave oven, and electric stove. Ever use of hair dryers was associated with glioma (odds ratio = 1.7, 95% confidence interval: 1.1, 2.5), but there was no evidence of increasing risk with increasing amount of use. In men, meningioma was associated with electric shaver use (odds ratio = 10.9, 95% confidence interval: 2.3, 50), and odds ratios increased with cumulative minutes of use, although they were based on only two nonexposed cases. Recall bias for appliances used regularly near the head or chance may provide an alternative explanation for the observed associations. Overall, results indicate that extremely low frequency electromagnetic fields from commonly used household appliances are unlikely to increase the risk of brain tumors. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Western Penn Hosp, Div Neurosurg, Pittsburgh, PA 15224 USA. St Josephs Hosp, Barrow Neurol Inst, Dept Neurol, Phoenix, AZ USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. NINDS, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Kleinerman, RA (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7044, Rockville, MD 20852 USA. EM kleinerr@mail.nih.gov OI Kleinerman, Ruth/0000-0001-7415-2478; Hatch, Elizabeth/0000-0001-7901-3928 NR 35 TC 11 Z9 13 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 15 PY 2005 VL 161 IS 2 BP 136 EP 146 DI 10.1093/aje/kwi013 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 885WZ UT WOS:000226189300006 PM 15632263 ER PT J AU Reynolds, HY AF Reynolds, HY TI Lung inflammation and fibrosis - An alveolar macrophage-centered perspective from the 1970s to 1980s SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE cytokines-chemokines; effector immune function ID IDIOPATHIC PULMONARY-FIBROSIS; ATTRACTANT ACTIVATION PROTEIN; NEUTROPHIL CHEMOTACTIC FACTOR; INFLUENZA-A NUCLEOPROTEIN; BRONCHIAL LAVAGE; IN-VITRO; PSEUDOMONAS-AERUGINOSA; BRONCHOALVEOLAR LAVAGE; RESPIRATORY-TRACT; INHIBITOR PEPTIDE C1 NHLBI, Div Lung Dis, Rockledge Ctr 2, NIH,Dept Hlth & Human Sci, Bethesda, MD 20892 USA. Penn State Univ, Coll Med, Hershey, PA USA. RP Reynolds, HY (reprint author), NHLBI, Div Lung Dis, Rockledge Ctr 2, NIH,Dept Hlth & Human Sci, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM reynoldh@mail.nih.gov NR 60 TC 39 Z9 43 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2005 VL 171 IS 2 BP 98 EP 102 DI 10.1164/rccm.200406-788PP PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 886UO UT WOS:000226258400003 PM 15557133 ER PT J AU Speer, O Back, N Buerklen, T Brdiczka, D Koretsky, A Wallimann, T Eriksson, O AF Speer, O Back, N Buerklen, T Brdiczka, D Koretsky, A Wallimann, T Eriksson, O TI Octameric mitochondrial creatine kinase induces and stabilizes contact sites between the inner and outer membrane SO BIOCHEMICAL JOURNAL LA English DT Article DE adenine nucleotide translocator (ANT); electron microscopy; micro-compartment; mitochondrion; octameric mitochondrial creatine kinase; outer membrane pore ID PERMEABILITY TRANSITION PORE; ADENYLATE TRANSLOCATOR; ENERGY-METABOLISM; MUSCLE-CELLS; BRAIN-TYPE; ISOENZYMES; COMPLEXES; TRANSPORT; BINDING; LOCALIZATION AB We have investigated the role of the protein ubiquitous mitochondrial creatine kinase (uMtCK) in the formation and stabilization of inner and outer membrane contact sites. Using liver mitochondria isolated from transgenic mice, which, unlike control animals, express uMtCK in the liver, we found that the enzyme was associated with the mitochondrial membranes and, in addition, was located in membrane-coated matrix inclusions. In mitochondria isolated from uMtCK transgenic mice, the number of contact sites increased 3-fold compared with that observed in control mitochondria. Furthermore, uMtCK-containing mitochondria were more resistant to detergent-induced lysis than wild-type mitochondria. We conclude that octameric uMtCK induces the formation of mitochondrial contact sites, leading to membrane cross-linking and to an increased stability of the mitochondrial membrane architecture. C1 Swiss Fed Inst Technol, Inst Cell Biol, ETH Honggerberg, ETH Zurich, CH-8093 Zurich, Switzerland. Univ Helsinki, Inst Biomed, FIN-00014 Helsinki, Finland. Univ Konstanz, Dept Life Sci, D-78457 Constance, Germany. NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA. RP Speer, O (reprint author), Univ Zurich, Inst Mol Biol, Winterhurerstr 190, CH-8053 Zurich, Switzerland. EM Oliver.Speer@molbio.unizh.ch RI Wallimann, Theo/C-6047-2008; Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS003047-01] NR 38 TC 49 Z9 52 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PLACE, LONDON W1B 1QW, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 15 PY 2005 VL 385 BP 445 EP 450 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 892PM UT WOS:000226662500014 PM 15294016 ER PT J AU Li, GR Liu, YX Tzeng, NS Cui, G Block, ML Wilson, B Qin, LY Wang, TG Liu, B Liu, J Hong, JS AF Li, GR Liu, YX Tzeng, NS Cui, G Block, ML Wilson, B Qin, LY Wang, TG Liu, B Liu, J Hong, JS TI Protective effect of dextromethorphan against endotoxic shock in mice SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE DM; LPS/GalN; liver injury; inflammation; ROS; gene expression ID TUMOR-NECROSIS-FACTOR; LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; GALACTOSAMINE-SENSITIZED MICE; LIVER-FAILURE; DOPAMINERGIC-NEURONS; OXIDATIVE STRESS; HEPATOCYTE APOPTOSIS; REACTIVE OXYGEN; OXIDANT STRESS; HEPATIC-INJURY AB Dextromethorphan (DM) is a dextrorotatory morphinan and an over-the-counter non-opioid cough suppressant. We have previously shown that DM protects against LPS-induced dopaminergic neurodegeneration through inhibition of microglia activation. Here, we investigated protective effects of DM against endotoxin shock induced by lipopolysaccharide/D-galactosamine (LPS/GalN) in mice and the mechanism underlying its protective effect. Mice were given multiple injections of DM (12.5 mg/kg, s.c.) 30 min before and 2, 4 It after an injection of LPS/GalN (20 mug/700 mg/kg). DM administration decreased LPS/GalN-induced mortality and hepatotoxicity, as evidenced by increased survival rate, decreased serum alanine aminotransferase activity and improved pathology. Furthermore, DM was also effective when it was given 30 min after LPS/GalN injection. The protection was likely associated with reduced serum and liver tumor necrosis factor alpha (TNF-alpha) levels. DM also attenuated production of superoxide and intracellular reactive oxygen species in Kupffer cells and neutrophils. Real-time RT-PCR analysis revealed that DM administration suppressed the expression of a variety of inflammation-related genes such as macrophage inflammatory protein-2, CXC chemokine, thrombospondin-1, intercellular adhesion molecular-1 and interleukin-6. DM also decreased the expression of genes related to cell-death pathways, such as the DNA damage protein genes GADD45 and GADD153. In summary, DM is effective in protecting mice against LPS/GaIN-induced hepatotoxicity, and the mechanism is likely through a faster TNF-a clearance, and decrease of superoxide production and inflammation and cell-death related components. This study not only extends neuroprotective effect of DM, but also suggests that DM may be a novel compound for the therapeutic intervention for sepsis. (C) 2004 Elsevier Inc. All rights reserved. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NCI,NIHS, Res Triangle Pk, NC 27709 USA. Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan. Univ N Carolina, Pathol & Lab Med, Chapel Hill, NC 27513 USA. NCI, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect, NIEHS,NIHS, Res Triangle Pk, NC 27709 USA. RP Li, GR (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NCI,NIHS, POB 12233,Mail Drop F1-01, Res Triangle Pk, NC 27709 USA. EM guorongl@med.unc.edu RI liu, Bin/A-7695-2009 NR 38 TC 35 Z9 38 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JAN 15 PY 2005 VL 69 IS 2 BP 233 EP 240 DI 10.1016/j.bcp.2004.10.003 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 890VS UT WOS:000226539800004 PM 15627475 ER PT J AU Newman, TK Syagailo, YV Barr, CS Wendland, JR Champoux, M Graessle, M Suomi, SJ Higley, JD Lesch, KP AF Newman, TK Syagailo, YV Barr, CS Wendland, JR Champoux, M Graessle, M Suomi, SJ Higley, JD Lesch, KP TI Monoamine oxidase A gene promoter variation and rearing experience influences aggressive behavior in rhesus monkeys SO BIOLOGICAL PSYCHIATRY LA English DT Article DE MAOA; promoter; VNTR; rearing; aggression; rhesus ID SYSTEM SEROTONERGIC RESPONSIVITY; REGULATORY POLYMORPHISM; CONDUCT DISORDER; ASSOCIATION; GENOTYPE; STRESS; REGION; BRAIN; MICE; MAOA AB Background: Allelic variation of the monoamine oxidase A (MAOA) gene has been implicated in conduct disorder and antisocial, aggressive behavior in humans when associated with early adverse experiences. We tested the hypothesis that a repeat polymorphism in the rhesus macaque MAOA gene promoter region influences aggressive behavior in male subjects. Methods: Forty-five unrelated male monkeys raised with or without their mothers were tested for competitive and social group aggression. Functional activity of the MAOA gene promoter polymorphism was determined and genotypes scored for assessing genetic and environmental influences on aggression. Results: Transcription of the MAOA gene in rhesus monkeys is modulated by an orthologous polymorphism (rhMAOA-LPR) in its upstream regulatory region. High- and low-activity alleles of the rhMAOA-LPR show a genotype X environment interaction of aggressive behavior, such that mother reared male monkeys with the low-activity-associated allele had higher aggression scores. Conclusions: These results suggest that the behavioral expression of allelic variation in MAOA activity is sensitive to social experiences early in development and that its functional outcome might depend on social context. C1 NIAAA, Clin Studies Lab, Poolesville, MD USA. Natl Child Hlth & Human Dev, Comparat Ethol Lab, Poolesville, MD USA. Univ Wurzburg, Dept Psychiat & Psychotherpay, Clin Mol Psychobiol, Wurzburg, Germany. RP Newman, TK (reprint author), NIAAA, NIH, Neurogenet Lab, 5625 Fishers Lane,Room 3S-32, Rockville, MD 20852 USA. EM tknewman@mail.nih.gov RI Wendland, Jens/A-1809-2012; Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 31 TC 161 Z9 170 U1 1 U2 25 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 JAN 15 PY 2005 VL 57 IS 2 BP 167 EP 172 DI 10.1016/j.biopsych.2004.10.012 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 888BQ UT WOS:000226349600009 PM 15652876 ER PT J AU Alter, BP AF Alter, BP TI Diamond-Blackfan anemia: a "cultural" diagnosis SO BLOOD LA English DT Editorial Material ID ERYTHROPOIESIS AB In vitro erythroid cultures may be necessary to detect nonpenetrant Diamond-Blackfan anemia. C1 NIH, Bethesda, MD 20892 USA. RP Alter, BP (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 6 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 JAN 15 PY 2005 VL 105 IS 2 BP 435 EP 436 DI 10.1182/blood-2004-10-4062 PG 2 WC Hematology SC Hematology GA 885ZX UT WOS:000226197000004 ER PT J AU Hegde, U Filie, A Little, RF Janik, JE Grant, N Steinberg, SM Dunleavy, K Jaffe, ES Abati, A Stetler-Stevenson, M Wilson, WH AF Hegde, U Filie, A Little, RF Janik, JE Grant, N Steinberg, SM Dunleavy, K Jaffe, ES Abati, A Stetler-Stevenson, M Wilson, WH TI High incidence of occult leptomeningeal disease detected by flow cytometry in newly diagnosed aggressive B-cell lymphomas at risk for central nervous system involvement: the role of flow cytometry versus cytology SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; DOSE-ADJUSTED EPOCH; CEREBROSPINAL-FLUID; LYMPHOPROLIFERATIVE DISORDERS; CHEMOTHERAPY; RITUXIMAB; LEUKEMIA; THERAPY; RELAPSE AB We assessed the cerebrospinal fluid (CSF) by flow cytometry and cytology in 51 newly diagnosed and 9 treated aggressive B-cell lymphomas at risk for central nervous system (CNS) involvement to examine the utility of flow cytometry, incidence of CSIF disease, and clinical surrogates of CNS spread. Multicolor flow cytometry using multiple antibody panels for light chains and B- and T-cell antigens identified neoplastic clones that constituted as little as 0.2% of total CSF lymphocytes. Among 51 newly diagnosed patients, 11 (22%) had occult CSF involvement. All 11 were detected by flow cytometry but only 1 by cytology (P = .002). Among 9 treated patients, CSF involvement was detected by flow cytometry alone in 2 and also by cytology in 1 case. CSIF chemistry and cell counts were similar in patients with and without CSIF lymphoma. Only the number of extranocial sites was associated with occult CSF lymphoma in newly diagnosed patients by univariate (P = .006) or logistic regression analysis (P = .012). We hypothesize that the biologic phenotype associated with colonization of extranocial sites leads to CNS spread, possibly related to the microenvironment. Patients at risk for CNS spread should undergo staging CSF evaluation by flow cytometry. (C) 2005 by The American Society of Hematology. C1 NCI, Expt Transplantat & Immunol Branch, CCR, NIH, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Expt Transplantat & Immunol Branch, CCR, NIH, Bldg 10,Rm 12-N-226, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov NR 24 TC 167 Z9 172 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2005 VL 105 IS 2 BP 496 EP 502 DI 10.1182/blood-2004-05-1982 PG 7 WC Hematology SC Hematology GA 885ZX UT WOS:000226197000019 PM 15358629 ER PT J AU Qin, HX Shire, NJ Keenan, ED Rouster, SD Eyster, ME Goederl, JJ Koziel, MJ Sherman, KE AF Qin, HX Shire, NJ Keenan, ED Rouster, SD Eyster, ME Goederl, JJ Koziel, MJ Sherman, KE CA Multicenter Hemophilia Cohort Stud TI HCV quasispecies evolution: association with proggession to end-stage liver disease in hemophiliacs infected with HCV or HCV/HIV SO BLOOD LA English DT Article ID HEPATITIS-C-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; INTERFERON-ALPHA THERAPY; HYPERVARIABLE REGION 1; CORE PROTEIN; TRANSGENIC MICE; COINFECTED PATIENTS; NON-A; TRANSPLANTATION; DIVERSIFICATION AB Patients with inherited bleeding disorders who received clotting factor concentrates before 1987 have high rates of hepatitis C virus (HCV) or HCV/HIV infection. We evaluated HCV quasispecies evolution in longitudinally collected specimens comparing those from patients with progression to end-stage liver disease (ESLD; cases) to those with compensated chronic hepatitis (controls). Plasma samples were obtained from the National Cancer Institute Multicenter Hemophilia Cohort Study. Controls were matched for age, sex, infection duration, and presence/ absence of HIV. Samples from early infection were compared to those obtained after onset of ESLD in the cases. The first hypervariable (HVR1) and core protein-coding regions were amplified, subcloned. and sequenced. Complexity and diversity were determined. More than 700 subclones from 10 pairs of patients (8 with HIV) followed over approximately 9.3 years were evaluated. HVR1 complexity narrowed over time in the cases, whereas it increased in controls (P = .01). Similar age, sex, infection duration, and presence/ absence of HIV. Samples from early infection were compared to those obtained after onset of ESLD in the cases. The first hypervariable (HVR1) and core protein-coding regions were amplified, subcloned. and sequenced. Complexity and diversity were determined. More than 700 subclones from 10 pairs of patients (8 with HIV) followed over approximately 9.3 years were evaluated. HVR1 complexity narrowed over time in the cases, whereas it increased in controls (P = .01). Similar trends were observed for diversity within HVR1 and the core region (P = .04). HCV-infected patients with inherited bleeding disorders undergo quasispecies evolution over time. Evolution patterns differ for progressors and nonprogressors. Further understanding of these mechanisms may help identity factors related to progression rate and treatment response. (C) 2005 by The American Society of Hematology. C1 Univ Cincinnati, Coll Med, Div Digest Dis, Cincinnati, OH 45267 USA. Penn State Univ, Hershey, PA USA. NCI, Viral Epidemiol Branch, Rockville, MD USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Sherman, KE (reprint author), Univ Cincinnati, Coll Med, Div Digest Dis, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM kenneth.sherman@uc.edu FU NCRR NIH HHS [C06 RR016499, M01 RR08084, M01 RR010732]; NIAID NIH HHS [R01 AI49508] NR 54 TC 44 Z9 46 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 JAN 15 PY 2005 VL 105 IS 2 BP 533 EP 541 DI 10.1182/blood-2004-04-1452 PG 9 WC Hematology SC Hematology GA 885ZX UT WOS:000226197000024 PM 15374882 ER PT J AU Kulka, M Metcalfe, DD AF Kulka, M Metcalfe, DD TI High-resolution tracking of cell division demonstrates differential effects of T(H)1 and T(H)2 cytokines on SCF-dependent human mast cell production in vitro: correlation with apoptosis and Kit expression SO BLOOD LA English DT Article ID FC-GAMMA-RI; MESSENGER-RNA; EPSILON-RI; IFN-GAMMA; IL-4; ACTIVATION; RECEPTOR; AGGREGATION; INHIBITION; RESPONSES AB T-helper 1 (T(H)1) (interferon-gamma [IFN-gamma]) and T(H)2 (interleukin-4 [IL-4] and IL-5) cytokines have been variably reported to alter human mast cell numbers in complex culture systems. The effects of these cytokines on the kinetics of cell division and cell death are unknown, and their effect on mast cell behavior is relevant to anticipate the consequences of in vivo strategies that alter cytokine levels.. To determine the effect of these cytokines on stem cell factor (SCF)-dependent human mast cell production, we used high-resolution tracking of cell division and correlated the results with cell apoptosis, expression of Kit, and mast cell degranulation. When IFN-gamma, IL-5, or IL-4 was administered over 8 weeks, we found each cytokine decreased the mast number through a different mechanism. IFN-gamma inhibited early progenitor cell division, IL-4 clown-regulated early Kit expression, and IL-5 blocked later cell division. Further, IL-4 and IFN-gamma had the greatest suppressive effect on degranulation and FCepsilonRI expression. When these cytokines were administered to mature mast cells, IFN-gamma and IL-5 had no effect on degranulation and cell division, but IL-4 induced division and potentiated FCepsilonRI-mediated degranulation. Thus, exposure of human mast cells to IL-4, IL-5, and IFN-gamma during growth and differentiation generally down-regulated mast cell number and function, whereas IL-4 increased mature mast cell division and degranulation. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, MSC 1881,Bldg 10,Rm 11C205,10 Ctr Dr, Bethesda, MD 20892 USA. EM dmetcalfe@niaid.nih.gov NR 26 TC 31 Z9 32 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2005 VL 105 IS 2 BP 592 EP 599 DI 10.1182/blood-2004-07-2838 PG 8 WC Hematology SC Hematology GA 885ZX UT WOS:000226197000033 PM 15367434 ER PT J AU Nemeth, MJ Cline, AP Anderson, SM Garrett-Beal, LJ Bodine, DM AF Nemeth, MJ Cline, AP Anderson, SM Garrett-Beal, LJ Bodine, DM TI Hmgb3 deficiency deregulates proliferation and differentiation of con-m-ion lymphoid and myeloid progenitors SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; TRANSCRIPTION FACTOR GATA-2; C-MYB; PROTEIN HMG1; V(D)J CLEAVAGE; MICE LACKING; DNA; EXPRESSION; BINDING; GENE AB Hmgb3 is an X-linked member of a family of chromatin-binding proteins that is expressed in primitive hematopoietic cells capable of long-term hematopoietic repopulation. To examine the role of Hmgb3 in adult hematopoiesis, we generated Hmgb3-deficient (Hmgb3(-/Y)) mice, which are viable but erythrocythemic. Hmgb3(-/Y) mice contain normal numbers of hematopoietic stem cells (HSCs), which generate fewer than normal numbers of common lymphoid progenitors (CLPs) and common myeloid progenitors (CIMPs) and greater than normal numbers of more mature progenitors. Although fewer Hmgb3(-/Y) primitive progenitor cells are in the G(2)/M cell cycle phase, bromodeoxyuridine (BrdU) incorporation demonstrated enhanced proliferation compared with their wild-type counterparts. Hmgb3(-/Y) HSCs have increased levels of Gata-2 and c-myb mRNA. We propose that Hmgb3 deficiency leads to a failure of HSCs to expand into normal numbers of CLPs and CMPs. This defect is compensated for by the ability of Hmgb3(-/Y) progenitors to expand rapidly and differentiate into normal numbers of hematopoietic cells. C1 NHGRI, Genet & Mol Biol Branch, Hematopoiesis Sect, Bethesda, MD 20892 USA. RP Bodine, DM (reprint author), NHGRI, Genet & Mol Biol Branch, Hematopoiesis Sect, 49 Convent Dr,Rm 3A04, Bethesda, MD 20892 USA. EM tedyaz@nhgri.nih.gov NR 33 TC 36 Z9 36 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 JAN 15 PY 2005 VL 105 IS 2 BP 627 EP 634 DI 10.1182/blood-2004-07-2551 PG 8 WC Hematology SC Hematology GA 885ZX UT WOS:000226197000037 PM 15358624 ER PT J AU Kobayashi, H Dubois, S Sato, N Sabzevari, H Sakai, Y Waldmann, TA Tagaya, Y AF Kobayashi, H Dubois, S Sato, N Sabzevari, H Sakai, Y Waldmann, TA Tagaya, Y TI Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance SO BLOOD LA English DT Article ID CD8(+) T-CELLS; NATURAL-KILLER-CELLS; ANTITUMOR-ACTIVITY; IN-VIVO; MEMORY; INTERLEUKIN-15; MICE; RECEPTOR; PROLIFERATION; EXPRESSION AB Interleukin 15 (IL-15) is a critical factor for the proliferation and activation of natural killer (NK) and CD8 T cells. Recently, we demonstrated that IL-15Ralpha expressed on monocytes/dendritic cells captures and presents IL-15 to neighboring cells in trans (trans-presentation of IL-15) through cell-cell contact. In the current study, we provide evidence that the IL-15 presented in trans, but not soluble IL-15 at physiologic concentrations, augments the killing activity mediated by NK cells in vitro. In addition, transfection of IL-15Ralpha into a colon carcinoma cell line (MC38) enabled these cells to present IL-15 in trans to NK cells and augmented their killing activity. resulting in the efficient lysis of MC38 cells by NK cells in vitro. Furthermore. these transfected MC38 cells no longer form fatal pulmonary metastases in mice. It was also shown that NK cells play an important role in the rejection of MC38 cells under these circumstances. These results collectively suggest that the IL-15 trans-presentation mechanism operates in vivo to augment the tumor immune surveillance mechanism. Furthermore. our observation provides the scientific basis for a novel strategy to prevent cancer development/metastasis. C1 NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Tagaya, Y (reprint author), 10 Ctr Dr,10-4B47, Bethesda, MD 20892 USA. EM ytagaya@helix.nih.gov NR 36 TC 143 Z9 151 U1 2 U2 14 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 JAN 15 PY 2005 VL 105 IS 2 BP 721 EP 727 DI 10.1182/blood-2003-12-4187 PG 7 WC Hematology SC Hematology GA 885ZX UT WOS:000226197000050 PM 15367431 ER PT J AU Iwasaki, M Kuwata, T Yamazaki, Y Jenkins, NA Copeland, NG Osato, M Ito, Y Kroon, E Sauvageau, G Nakamura, T AF Iwasaki, M Kuwata, T Yamazaki, Y Jenkins, NA Copeland, NG Osato, M Ito, Y Kroon, E Sauvageau, G Nakamura, T TI Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model SO BLOOD LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; FC-RECEPTOR; CHROMOSOMAL TRANSLOCATION; INSERTIONAL MUTAGENESIS; MOTOR COMPLEX; HOMEOBOX GENE; DYNEIN MOTOR; NUP98 GENE; IN-VITRO; MICE AB The chromosomal translocation t(7; 11)(p15;p15), observed in human myeloid leukemia, results in a NUP98 and HOXA9 gene fusion. We generated a transgenic mouse line that specifically expressed the chimeric NUP98-HOXA9 gene in the myeloid lineage. While only 20% of the transgenic mice progressed to leukemia after a latency period, myeloid progenitor cells from nonleukemic transgenic mice still exhibited increased proliferative potential. This suggested that the NUP98-HOXA9 fusion induced a preleukemic phase, and other factors were required for complete leukemogenesis. NUP98-HOXA9 expression promoted the onset of retrovirus-Induced BXH2 myeloid leukemia. This phenomenon was used to identify cooperative disease genes as common integration sites (CISs). Meis1, a known HOX cofactor, was identified as a CIS with a higher integration frequency in transgenic than in wild-type BXH2 mice. By the same means we identified further 4 candidate cooperative genes, Dnalc4, Fcgr2b, Fcrl, and Con1. These genes cooperated with NUP98-HOXA9 in transforming NIH 3T3 cells. The system described here is a powerful tool to identify cooperative oncogenes and will assist in the clarification of the multistep process of carcinogenesis. (C) 2005 by The American Society of Hematology. C1 Japanese Fdn Canc Res, Dept Carcinogenesis, Toshima Ku, Inst Canc, Tokyo 1708455, Japan. NCI, Frederick Canc Res & Dev Ctr, Mouse Canc Genet Program, Frederick, MD USA. Inst Mol & Cell Biol, Singapore, Singapore. Oncol Res Inst, Singapore, Singapore. Clin Res Inst Montreal, Lab Mol Genet Hemopoiet Stern Cells, Montreal, PQ H2W 1R7, Canada. RP Nakamura, T (reprint author), Japanese Fdn Canc Res, Dept Carcinogenesis, Toshima Ku, Inst Canc, 1-37-1 Kami Ikebukuro, Tokyo 1708455, Japan. EM takuro-ind@umin.ac.jp RI ASTAR, IMCB/E-2320-2012; Osato, Motomi/N-5056-2014 OI Osato, Motomi/0000-0003-3982-9054 NR 53 TC 53 Z9 53 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2005 VL 105 IS 2 BP 784 EP 793 DI 10.1182/blood-2004-04-1508 PG 10 WC Hematology SC Hematology GA 885ZX UT WOS:000226197000058 PM 15454493 ER PT J AU Anderson, WF AF Anderson, WF TI Breast carcinoma in men - A population-based study SO CANCER LA English DT Letter ID CANCER C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Anderson, WF (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 5 TC 4 Z9 5 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 JAN 15 PY 2005 VL 103 IS 2 BP 432 EP 433 DI 10.1002/cncr.20797 PG 2 WC Oncology SC Oncology GA 888MQ UT WOS:000226379000028 PM 15578682 ER PT J AU Suh, KS Mutoh, M Gerdes, M Crutchley, JM Mutoh, T Edwards, LE Dumont, RA Sodha, P Cheng, C Glick, A Yuspa, SH AF Suh, KS Mutoh, M Gerdes, M Crutchley, JM Mutoh, T Edwards, LE Dumont, RA Sodha, P Cheng, C Glick, A Yuspa, SH TI Antisense suppression of the chloride intracellular channel family induces apoptosis, enhances tumor necrosis factor alpha-induced apoptosis, and inhibits tumor growth SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; MOLECULAR-CLONING; ION-CHANNEL; COLORECTAL-CANCER; ANION CHANNEL; DNA-DAMAGE; CELL-DEATH; EXPRESSION; PROTEIN; INDUCTION AB mtCLIC/CLIC4 is a p53 and tumor necrosis factor alpha (TNFalpha) regulated intracellular chloride channel protein that localizes to cytoplasm and organelles and induces apoptosis when overexpressed in several cell types of mouse and human origin. CLIC4 is elevated during TNFalpha-induced apoptosis in human osteosarcoma cell lines. In contrast, inhibition of NFkappaB results in an increase in TNFalpha-mediated apoptosis with a decrease in CLIC4 protein levels. Cell lines expressing an inducible CLIC4-antisense construct that also reduces the expression of several other chloride intracellular channel (CLIC) family proteins were established in the human osteosarcoma lines SaOS and U2OS cells and a malignant derivative of the mouse squamous papilloma line SP1 Reduction of CLIC family proteins by antisense expression caused apoptosis in these cells. Moreover, CLIC4-antisense induction increased TNFa-mediated apoptosis in both the SaOS and U2OS derivative cell lines without altering TNFalpha-induced NFkappaB activity. Reducing CLIC proteins in tumor grafts of SPI cells expressing a tetracycline-regulated CLIC4-antisense substantially inhibited tumor growth and induced tumor apoptosis. Administration of TNFalpha. i.p. modestly enhanced the antitumor effect of CLIC reduction in vivo. These results suggest that CLIC proteins could serve as drug targets for cancer therapy, and reduction of CLIC proteins could enhance the activity of other anticancer drugs. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Room 3B25,MSC 4255,37 Convent Dr, Bethesda, MD 20892 USA. EM yuspns@mail.nih.gov NR 41 TC 41 Z9 43 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2005 VL 65 IS 2 BP 562 EP 571 PG 10 WC Oncology SC Oncology GA 887VV UT WOS:000226334500026 PM 15695400 ER PT J AU Samuni, AM Kasid, U Chuang, EY Suy, S DeGraff, W Krishna, MC Russo, A Mitchell, JB AF Samuni, AM Kasid, U Chuang, EY Suy, S DeGraff, W Krishna, MC Russo, A Mitchell, JB TI Effects of hypoxia on radiation-responsive stress-activated protein kinase, p53, and caspase 3 signals in TK6 human lymphoblastold cells SO CANCER RESEARCH LA English DT Article ID NATIONAL-CANCER-INSTITUTE; RAT CARDIAC MYOCYTES; INDUCED APOPTOSIS; IONIZING-RADIATION; DNA-DAMAGE; DEPENDENT PATHWAY; TUMOR HYPOXIA; INDUCTION; INSTABILITY; ASSOCIATION AB Despite significant evidence of a role of hypoxia in cellular resistance to ionizing radiation-induced toxicity, the underlying molecular mechanisms remain unclear. This study focused on the influence of hypoxia on radiation-induced signals in TK6 human lymphoblastoid cells. Hypoxic (<10 ppm oxygen) and aerobic cells were exposed to equilethal doses of ionizing radiation, radiation dose ratio, 3:1 (hypoxia:air). Hypoxia alone or radiation treatment under aerobic or hypoxic conditions led to increased levels of phospho-p44/42 mitogen-activated protein kinase. Levels of phospho-p38 mitogen-activated protein kinase did not change as a result of either hypoxia or irradiation. Hypoxia alone had no effect on expression of phospho-stress-activated protein kinase (SAPK), wild-type p53, or cleaved caspase 3. Irradiation under aerobic conditions resulted in an increase in the phospho-SAPK signal, whereas hypoxia suppressed the irradiation-induced increase in the level of phospho-SAPK. Both hypoxic and aerobic cells showed increases in p53 levels in response to radiation. Hypoxia blocked radiation-induced cleavage of caspase 3 and poly-ADP-ribose polymerase. Irradiation of aerobic and hypoxic TK6 cells using 6 and 18 Gy, respectively, resulted in a similar and significant increase in fraction of apoptotic cells within 24 hours postirradiation. In contrast, basal levels of apoptosis were observed at 24 hours postirradiation in aerobic and hypoxic TNH32 cells, a p53 null derivative of TK6 cells. These results suggest that radiation-induced apoptosis under hypoxia occurs independent of phospho-SAPK and caspase 3, and the p53 response is an obligatory apoptotic signal in TK6 cells. C1 NCI, NIH, Canc Res Ctr, Radiat Biol Branch, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Radiat Med, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. RP Mitchell, JB (reprint author), NCI, NIH, Canc Res Ctr, Radiat Biol Branch, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. EM jbm@helix.nih.gov NR 59 TC 19 Z9 22 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2005 VL 65 IS 2 BP 579 EP 586 PG 8 WC Oncology SC Oncology GA 887VV UT WOS:000226334500028 PM 15695402 ER PT J AU Moraitis, D Du, BH De Lorenzo, MS Boyle, JO Weksler, BB Cohen, EG Carew, JF Altorki, NK Kopelovich, L Subbaramaiah, K Dannenberg, AJ AF Moraitis, D Du, BH De Lorenzo, MS Boyle, JO Weksler, BB Cohen, EG Carew, JF Altorki, NK Kopelovich, L Subbaramaiah, K Dannenberg, AJ TI Levels of cyclooxygenase-2 are increased in the oral mucosa of smokers: Evidence for the role of epidermal growth factor receptor and its ligands SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; COLON-CANCER CELLS; PROSTAGLANDIN E-2; LUNG-CANCER; EPITHELIAL-CELLS; PHORBOL ESTER; FACTOR-ALPHA; CHEMOPREVENTIVE ACTIVITY; CIGARETTE-SMOKE; TRANSGENIC MICE AB Cyclooxygenase-2 (COX-2) is a promising pharmacologic target for preventing aerodigestive malignancies. In this study, we investigated the effects of tobacco smoke on the expression of COX-2 in oral mucosa. An -4-fold increase in amount of COX-2 mRNA was observed in the oral mucosa of active smokers versus never smokers. Thus, a series of in vitro studies were carried out to elucidate the mechanism by which tobacco smoke induced COX-2. Treatment of a nontumorigenic oral epithelial cell line (MSK-Leuk1) with a saline extract of tobacco smoke (TS) stimulated COX-2 transcription, resulting in increased amounts of COX-2 mRNA, COX-2 protein, and prostaglandin E2 (PGE2) synthesis. Exposure of cells to TS also caused an increase in epidermal growth factor receptor (EGFR) tyrosine kinase activity. Both an inhibitor of EGFR tyrosine kinase activity and a neutralizing anti-EGFR antibody blocked TS-mediated induction of COX-2. To define the mechanism by which TS activated EGFR, the release of amphiregulin and transforming growth factor alpha, two ligands of the EGFR, was measured. Exposure to TS caused a rapid increase in the release of both ligands. TS also markedly induced the expression of mRNAs for amphiregulin and transforming growth factor a. Importantly, increased expression of both ligands was also detected in the oral mucosa of active smokers. Taken together, these results suggest that activation of EGFR signaling contributes to the elevated levels of COX-2 found in the oral mucosa of smokers. Moreover, these findings strengthen the rationale for determining whether inhibitors of COX-2 or EGER tyrosine kinase activity can reduce the risk of tobacco smoke-related malignancies of the aerodigestive tract. C1 New York Presbyterian Cornell, Weill Med Coll, Dept Med, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Otorhinolaryngol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Cardiothorac Surg, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, Head & Neck Serv, New York, NY USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Dannenberg, AJ (reprint author), New York Presbyterian Cornell, Weill Med Coll, Dept Med, 525 E 68th St,Room F-206, New York, NY 10021 USA. EM ajdannen@med.cornell.edu FU NCI NIH HHS [1R01 CA82578, P01 CA106451, N01-CN-35107, T32 CA09685] NR 55 TC 80 Z9 86 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2005 VL 65 IS 2 BP 664 EP 670 PG 7 WC Oncology SC Oncology GA 887VV UT WOS:000226334500038 PM 15695412 ER PT J AU Doolittle, ND Abrey, LE Bleyer, WA Brem, S Davis, TP Dore-Duffy, P Drewes, LR Hall, WA Hoffman, JM Korfel, A Martuza, R Muldoon, LL Peereboom, D Peterson, DR Rabkin, SD Smith, Q Stevens, GHJ Neuwelt, EA AF Doolittle, ND Abrey, LE Bleyer, WA Brem, S Davis, TP Dore-Duffy, P Drewes, LR Hall, WA Hoffman, JM Korfel, A Martuza, R Muldoon, LL Peereboom, D Peterson, DR Rabkin, SD Smith, Q Stevens, GHJ Neuwelt, EA TI New frontiers in translational research in neuro-oncology and the blood-brain barrier: Report of the Tenth Annual Blood-Brain Barrier Disruption Consortium Meeting SO CLINICAL CANCER RESEARCH LA English DT Article ID NERVOUS-SYSTEM LYMPHOMA; IRON-OXIDE PARTICLES; PRIMARY CNS LYMPHOMA; RAT-BRAIN; N-ACETYLCYSTEINE; GROWTH-FACTOR; TUMOR-MODEL; ANGIOGENESIS; SURVIVAL; METHOTREXATE AB The blood-brain barrier (BBB) presents a major obstacle to the treatment of malignant brain tumors and other central nervous system (CNS) diseases. For this reason, a meeting partially funded by an NIH R13 grant was convened to discuss recent advances and future directions in translational research in neuro-oncology and the BBB. Cell biology and transport across the BBB. delivery of agents to the CNS. neuroimaging, angiogenesis, immunotherapy and gene therapy, as well as glioma, primary CNS lymphoma. and metastases to the CNS were. discussed. Transport across the BBB relates to the neurovascular unit. which consists not only of endothelial cells but also of pericyte. glia. and neuronal elements. C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. MD Anderson Canc Ctr, Div Pediat, Houston, TX USA. MD Anderson Canc Ctr, Div Community Oncol, Houston, TX USA. H Lee Moffitt Canc Ctr, Dept Neurooncol & Neurosurg, Tampa, FL USA. Univ Arizona, Sch Med, Dept Pharmacol, Program Neurosci & Physiol Sci, Tucson, AZ USA. Wayne State Univ, Dept Neurol, Detroit, MI USA. Univ Minnesota, Sch Med, Dept Biochem & Mol Biol, Duluth, MN 55812 USA. Univ Minnesota, Dept Neurosurg, Minneapolis, MN 55455 USA. NCI, Canc Imaging Program, Bethesda, MD 20892 USA. Charite Campus Benjamin Franklin, Dept Hematol Oncol & Transfus Med, Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. Cleveland Clin Fdn, Dept Hematol & Med Oncol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Adult Neurooncol Brain Tumor Inst, Cleveland, OH 44195 USA. Univ Chicago, Sch Med, Dept Physiol & Biophys, Chicago, IL 60637 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg,E Mol Neurosur Lab, Charlestown, MA USA. Texas Tech Univ, Dept Pharmaceut Sci, Amarillo, TX USA. RP Neuwelt, EA (reprint author), Oregon Hlth Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk,Rd L603, Portland, OR 97201 USA. EM neuwelte@ohsu.edu RI rabkin, samuel/C-2443-2012; davis, thomas/F-3244-2015 OI rabkin, samuel/0000-0003-2344-2795; davis, thomas/0000-0001-8465-4973 FU NCI NIH HHS [4R13 CA 86959-04] NR 48 TC 26 Z9 28 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2005 VL 11 IS 2 BP 421 EP 428 PG 8 WC Oncology SC Oncology GA 889IZ UT WOS:000226438000003 PM 15701824 ER PT J AU Dobbin, KK Beer, DG Meyerson, M Yeatman, TJ Gerald, WL Jacobson, JW Conley, B Buetow, KH Heiskanen, M Simon, RN Minna, JD Girard, L Misek, DE Taylor, JMG Hanash, S Naoki, K Hayes, DN Ladd-Acosta, C Enkemann, SA Viale, A Giordano, TJ AF Dobbin, KK Beer, DG Meyerson, M Yeatman, TJ Gerald, WL Jacobson, JW Conley, B Buetow, KH Heiskanen, M Simon, RN Minna, JD Girard, L Misek, DE Taylor, JMG Hanash, S Naoki, K Hayes, DN Ladd-Acosta, C Enkemann, SA Viale, A Giordano, TJ TI Interlaboratory comparability study of cancer gene expression analysis using oligonucleotide microarrays SO CLINICAL CANCER RESEARCH LA English DT Article ID B-CELL LYMPHOMA; MOLECULAR CLASSIFICATION; PREDICT SURVIVAL; ADENOCARCINOMA; LUNG; REPRODUCIBILITY AB A key step in bringing gene expression data into clinical practice is the conduct of large studies to confirm preliminary models. The performance of such confirmatory studies and the transition to clinical practice requires that microarray data from different laboratories are comparable and reproducible. We designed a study to assess the comparability of data front four laboratories that will conduct a larger microarray profiling confirmation project in lung adenocarcinomas. To test the feasibility of combining data across laboratories, frozen tumor tissues, cell line pellets, and purified RNA samples were analyzed at each of the four laboratories. Samples of each type and several subsamples from each tumor and each cell line were blinded before being distributed. The laboratories followed a common protocol for all steps of tissue processing, RNA extraction. and microarrav analysis using Affymetrix Human Genome U133A arrays. High within-laboratory and between-laboratory correlations were observed on the purified RNA samples. the cell tines. and the frozen tumor tissues. Intraclass correlation within laboratories was only slightly stronger than between laboratories, and the intraclass correlation tended to be weakest for genes expressed at low levels and showing small variation. Finally, hierarchical cluster analysis revealed that the repeated samples clustered to-ether regardless of the laboratory in which the experiments were done. The findings indicate that under properly controlled conditions it is feasible to perform complete tumor microarray analysis, from tissue processing to hybridization and scanning, at multiple independent laboratories for a single study. C1 NCI, Canc Diag Program, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NCI, Ctr Bioinformat, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Pediat, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Dept Surg, Tampa, FL USA. Univ S Florida, Inst Res, Tampa, FL USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Mol Biol, New York, NY 10021 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA. MIT, Ctr Genome, Whitehead Inst, Cambridge, MA 02139 USA. RP Dobbin, KK (reprint author), NCI, Div Canc Treatment & Diag, Rockville, MD 20852 USA. EM dobbinke@mail.nih.gov RI Meyerson, Matthew/E-7123-2012; OI Hayes, D. Neil/0000-0001-6203-7771; Giordano, Thomas/0000-0003-0641-8873 FU NCI NIH HHS [U19 CA 84593, P50 CA 70907, U01 CA 84995, U01 CA 84999, U01 CA 85052] NR 18 TC 120 Z9 127 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2005 VL 11 IS 2 BP 565 EP 572 PG 8 WC Oncology SC Oncology GA 889IZ UT WOS:000226438000021 PM 15701842 ER PT J AU Yue, W Wang, JP Li, YB Bocchinfuso, WP Korach, KS Devanesan, PD Rogan, E Cavalieri, E Santen, RJ AF Yue, W Wang, JP Li, YB Bocchinfuso, WP Korach, KS Devanesan, PD Rogan, E Cavalieri, E Santen, RJ TI Tamoxifen versus aromatase inhibitors for breast cancer prevention SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 4th International Conference on Recent Advances and Future Directions in Endocrine Manipulation of Breast Cancer CY JUL 21-22, 2004 CL Cambridge, MA ID ESTROGEN-RECEPTOR-ALPHA; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; EPITHELIAL-CELLS; INITIATION; ESTRADIOL; RISK; MICE; CARCINOGENS; MUTATIONS AB Long-term exposure to estradiol is associated with an increased risk of breast cancer, but the mechanisms responsible are not firmly established. The prevailing theory postulates that estrogens increase the rate of cell proliferation by stimulating estrogen receptor (ER)-mediated transcription, thereby increasing the number of errors occurring during DNA replication. An alternative theory suggests that estradiol is metabolized to quinone derivatives, which directly remove base pairs from DNA through a process called depurination. Error-prone DNA repair then results in point mutations. We postulate that both processes act in an additive or synergistic fashion. If correct, aromatase inhibitors would block both processes, whereas antiestrogens would only inhibit receptor-mediated effects. Accordingly, aromatase inhibitors would be more effective in preventing breast cancer than antiestrogens. Our initial studies showed that catechol-estrogen metabolites are formed in MCF-7 human breast cancer cells in culture. We then used an animal model that allows dissociation of ER-mediated function from the effects of estradiol metabolites and showed formation of genotoxic estradiol metabolites. We also examined the incidence of tumors formed in these ERalpha knockout mice bearing the Wnt-1 transgene. The absence of estradiol markedly reduced the incidence of tumors and delayed their onset. In aggregate, our results support the concept that metabolites of estradiol may act in concert with ER-mediated mechanisms to induce breast cancer. These findings support the possibility that aromatase inhibitors might be more effective than antiestrogens in preventing breast cancer. C1 Univ Virginia, Hlth Syst, Charlottesville, VA 22908 USA. NIEHS, Res Triangle Pk, NC 27709 USA. PPD Discovery, Morrisville, NC USA. Univ Nebraska, Med Ctr, Eppley Inst, Omaha, NE 68198 USA. RP Santen, RJ (reprint author), Univ Virginia, Hlth Syst, POB 801416, Charlottesville, VA 22908 USA. EM rjs5y@virginia.edu NR 32 TC 18 Z9 18 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2005 VL 11 IS 2 SU S BP 925S EP 930S PN 2 PG 6 WC Oncology SC Oncology GA 890QE UT WOS:000226525100011 PM 15701888 ER PT J AU De Langhe, SP Sala, FG Del Moral, PM Fairbanks, TJ Yamada, KM Warburton, D Burns, RC Bellusci, S AF De Langhe, SP Sala, FG Del Moral, PM Fairbanks, TJ Yamada, KM Warburton, D Burns, RC Bellusci, S TI Dickkopf-1 (DKK1) reveals that fibronectin is a major target of Wnt signaling in branching morphogenesis of the mouse embryonic lung SO DEVELOPMENTAL BIOLOGY LA English DT Article DE lung; Dickkopf-1; Wnt signaling; fibronectin; branching morphogenesis; smooth muscle; vascular development ID CONVERGENT EXTENSION MOVEMENTS; HAIR FOLLICLE DEVELOPMENT; PROTEIN-KINASE-A; BETA-CATENIN; WNT/BETA-CATENIN; STEM-CELLS; INTESTINAL EPITHELIUM; EXPRESSION; DIFFERENTIATION; PATHWAY AB Members of the Dickkopf (Dkk) family of secreted proteins are potent inhibitors of Wnt/beta-catenin signaling. In this study we show that Dkk1, -2, and -3 are expressed distally in the epithelilium, while Kremen1, the needed co-receptor, is expressed throughout the epithelium of the developing lung. Using TOPGAL mice [DasGupta, R., Fuchs, E., 1999. Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development 126, 4557-4568] to monitor the Win pathway, we show that canonical Writ signaling is dynamic in the developing lung and is active throughout the epithelium and in the proximal smooth muscle cells (SMC) until E12.5. However, from E13.5 onwards, TOPGAL activity is absent in the SMC and is markedly reduced in the distal epithelium coinciding with the onset of Dkk-1 expression in the distal epithelium. To determine the role of Win signaling in early lung development, E11.5 organ cultures were treated with recombinant DKK1. Treated lungs display impaired branching, characterized by failed cleft formation and enlarged terminal buds, and show decreased a-smooth muscle actin (alpha-SMA) expression as well as defects in the formation of the pulmonary vasculature. These defects coincide with a pattern of decreased fibronectin (FN) deposition. DKK1-induced morphogenetic defects can be mimicked by inhibition of FN and overcome by addition of exogenous FN, suggesting an involvement of FN in Wnt-regulated morphogenetic processes. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ So Calif, Keck Sch Med, Dept Surg, Dev Biol Program, Los Angeles, CA 90027 USA. Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA. Natl Inst Dental & Craniofacial Res, NIH, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. RP Bellusci, S (reprint author), Univ So Calif, Keck Sch Med, Dept Surg, Dev Biol Program, 4650 W Sunset Blvd,804 SRT,MS 35, Los Angeles, CA 90027 USA. EM sbellusci@chla.usc.edu OI Yamada, Kenneth/0000-0003-1512-6805 FU NHLBI NIH HHS [R01 HL074832-01, R01 HL75773-01] NR 52 TC 119 Z9 121 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 15 PY 2005 VL 277 IS 2 BP 316 EP 331 DI 10.1016/j.ydbio.2004.09.023 PG 16 WC Developmental Biology SC Developmental Biology GA 886KI UT WOS:000226225700004 PM 15617677 ER PT J AU Kuzin, A Brody, T Moore, AW Odenwald, WF AF Kuzin, A Brody, T Moore, AW Odenwald, WF TI Nerfin-1 is required for early axon guidance decisions in the developing Drosophila CNS SO DEVELOPMENTAL BIOLOGY LA English DT Review DE Nerfin-1; EIN domain Zn-finger proteins; axon guidance; CNS development ID CENTRAL-NERVOUS-SYSTEM; GROWTH CONE GUIDANCE; FINGER TRANSCRIPTION FACTOR; PROTEIN-TYROSINE KINASE; LONG-RANGE GUIDANCE; EMBRYONIC CNS; GENETIC-ANALYSIS; ROBO RECEPTORS; NEURONAL PRECURSORS; SEGMENTATION GENES AB Many studies have focused on the mechanisms of axon guidance; however, little is known about the transcriptional control of the navigational components that carryout these decisions. This report describes the functional analysis of Nerfin-1, a nuclear regulator of axon guidance required for a subset of early pathfinding events in the developing Drosophila CNS. Nerfin-1 belongs to a highly conserved subfamily of Zn-finger proteins with cognates identified in nematodes and man. We show that the neural precursor gene prospero is essential for nerfin-1 expression. Unlike nerfin-1 mRNA, which is expressed in many neural precursor cells. the encoded Nerfin-1 protein is only detected in the nuclei of neuronal precursors that will divide just once and then transiently in their nascent neurons. Although nerfin-1 null embryos have no discernible alterations in neural lineage development nor in neuronal or glial identities. CNS pioneering neurons require nerfin-1 function for early axon guidance decisions. Furthermore, nerfin-1 is required for the proper development of commissural and connective axon fascicles. Our studies also show that Nerfin-1 is essential for the proper expression of roho2, wnt5, derailed, G-oalpha47A, Lar, and futsch, genes whose encoded proteins participate in these early navigational events. Published by Elsevier Inc. C1 NINDS, NIH, Neural Cell Fate Determinants Sect, Bethesda, MD 20892 USA. RIKEN, Brain Sci Inst, Mol Neuropathol Grp, Wako, Saitama 35101, Japan. RP Kuzin, A (reprint author), NINDS, NIH, Neural Cell Fate Determinants Sect, Bldg 35,Room 1B-1014,35 Convent Dr,MSC 4160, Bethesda, MD 20892 USA. EM alex.kuzin@ninds.nih.gov; ward@codon.nih.gov RI Moore, Adrian/A-3339-2013 NR 112 TC 28 Z9 28 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 15 PY 2005 VL 277 IS 2 BP 347 EP 365 DI 10.1016/j.ydbio.2004.09.027 PG 19 WC Developmental Biology SC Developmental Biology GA 886KI UT WOS:000226225700006 PM 15617679 ER PT J AU Ishibashi, M Bottone, FG Taniura, S Kamitani, H Watanabe, T Eling, TE AF Ishibashi, M Bottone, FG Taniura, S Kamitani, H Watanabe, T Eling, TE TI The cyclooxygenase inhibitor indomethacin modulates gene expression and represses the extracellular matrix protein laminin gamma 1 in human glioblastoma cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE nonsteroidal anti-inflammatory drug; NSAID; laminin gamma 1; cyclooxygenase; COX; glioblastoma; invasion ID HUMAN GLIOMAS; IN-VITRO; MALIGNANT GLIOMA; ASPIRIN USE; LAMININ; CHAIN; METASTASIS; RISK; ACTIVATION; SECRETION AB The induction of cyclooxygenase-2 (COX-2) expression is associated with more aggressive gliomas and poor survival. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX activity and have antitumorigenic properties. In this report, our initial aim was to determine if indomethacin would alter gene expression as measured by suppression subtractive hybridization (SSH). Three up-regulated and four down-regulated genes by indomethacin treatment were identified. Laminin gamma1, an extracellular matrix molecule, was the most significantly repressed gene. The repression of laminin gamma1 by indomethacin was confirmed by Northern and Western blot analyses and occurred in a concentration- and time-dependent manner at the protein level. Among several NSAIDs tested, only sulindac sulfide and indomethacin suppressed laminin gamma1 protein expression, and this repression was observed in both COX-expressing and -deficient cell lines, suggesting that laminin gamma1 repression by COX inhibitors was independent of COX. Indomethacin, at a concentration that represses laminin gamma1, inhibited glioblastoma cell invasion that was partially restored with additional human laminin protein containing gamma1 chain. The repression of laminin gamma1 by NSAIDs may be related to attenuation of invasion of brain tumors. These findings are important in understanding the chemopreventive activity of some NSAIDs and could be relevant for designing therapeutic strategies against glioblastoma. Published by Elsevier Inc. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Tottori Univ, Fac Med, Inst Neurol Sci, Dept Neurosurg, Yonago, Tottori 6838504, Japan. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM eling@niehs.nih.gov NR 27 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 15 PY 2005 VL 302 IS 2 BP 244 EP 252 DI 10.1016/j.yexer.2004.09.021 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 880AA UT WOS:000225759500010 PM 15561105 ER PT J AU Ramirez, DC Mejiba, SEG Mason, RP AF Ramirez, DC Mejiba, SEG Mason, RP TI Mechanism of hydrogen peroxide-induced Cu,Zn-superoxide dismutase-centered radical formation as explored by immuno-spin trapping: the role of copper- and carbonate radical anion-mediated oxidations SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE superoxide dismutase; hydrogen peroxide; 5,5-dimethyl-l-pyrroline N-oxide; copper-catalyzed oxidation; carbonate radical anion; Cu,ZN-superoxide; dismutase radical-derived nitrone adduct; dityrosine; immuno-spin trapping ID ZINC SUPEROXIDE-DISMUTASE; HYDROXYL RADICALS; DNA-DAMAGE; BICARBONATE; H2O2; PROTEIN; ENZYME; INACTIVATION; GENERATION; REDUCTION AB We have reinvestigated the biochemistry of H2O2-induced Cu,Zn-superoxide dismutase (SOD1)-centered radicals, detecting them by immuno-spin trapping. These radicals are involved in H2O2-induced structural and functional damage to SOD1, and their mechanism of generation depends on copper and/or (bi)carbonate (i.e., CO2, CO3-2, or HCO3-). First, in the absence of DTPA and (bi)carbonate, Cu(II) was partially released and rebound at His, Cys, and Tyr residues in SOD I with the generation of protein-copper-bound oxidants outside the SOD1 active site by reaction with excess H2O2. These species produced immuno-spin trapping-detectable SOD1-centered radicals associated with H2O2-incluced active site (similar to5 and similar to10 kDa fragments) and non-active site (smearing between 3 and 16 kDa) copper-dependent backbone oxidations and subsequent fragmentation of SOD1. Second, in the presence of DTPA, which inhibits H2O2-induced SODI non-active site fragmentation, (bi)carbonate scavenged the enzyme-bound oxidant at the SOD1 active site to produce the carbonate radical anion, CO3(.-), thus protecting against active site SOD1 fragmentation. CO3.- diffiises and produces side chain oxidations forming DMPO-trappable radical sites outside the enzyme active site. Both mechanisms for generating immuno-spin trapping-detectable SOD1-centered radicals were susceptible to inhibition by cyanide and enhanced at high pH values. In addition, (bi)carbonate enhanced H2O2-induced SOD1 turnover as demonstrated by an enhancement in oxygen evolution and SOD1 inactivation. These results help clarify the free radical chemistry involved in the functional and structural oxidative damage to SOD1 by H2O2 with the intermediacy of copper- and CO3.-- mediated oxidations. Published by Elsevier Inc. C1 NIEHS, NIH, Lab Pharmacol & Chem, Res Triangle Pk, NC 27713 USA. RP Ramirez, DC (reprint author), NIEHS, NIH, Lab Pharmacol & Chem, Room F037-MD F0-02,111 TW Alexander Dr, Res Triangle Pk, NC 27713 USA. EM ramirezl@nichs.nih.gov RI RAMIREZ, DARIO/K-3312-2013 OI RAMIREZ, DARIO/0000-0001-6725-3326 NR 55 TC 43 Z9 45 U1 0 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN 15 PY 2005 VL 38 IS 2 BP 201 EP 214 DI 10.1016/j.freeradbiomed.2004.10.008 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 886KM UT WOS:000226226100005 PM 15607903 ER PT J AU Hutchin, ME Kariapper, MST Grachtchouk, M Wang, AQ Wei, LB Cummings, D Liu, JH Michael, LE Glick, A Dlugosz, AA AF Hutchin, ME Kariapper, MST Grachtchouk, M Wang, AQ Wei, LB Cummings, D Liu, JH Michael, LE Glick, A Dlugosz, AA TI Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle SO GENES & DEVELOPMENT LA English DT Article DE tumorigenesis; Hedgehog signaling; Gli2; basal cell carcinoma; hair follicle; organogenesis ID FOLLICLE STEM-CELLS; SONIC-HEDGEHOG; TRANSGENIC MICE; IN-VIVO; NEOPLASTIC PHENOTYPE; GENE-EXPRESSION; TUMOR PHENOTYPE; RAS TRANSGENE; HUMAN HOMOLOG; FLOOR PLATE AB Temporally and spatially constrained Hedgehog (Hh) signaling regulates cyclic growth of hair follicle epithelium while constitutive Hh signaling drives the development of basal cell carcinomas (BCCs), the most common cancers in humans. Using mice engineered to conditionally express the Hh effector Gli2, we show that continued Hh signaling is required for growth of established BCCs. Transgene inactivation led to BCC regression accompanied by reduced tumor cell proliferation and increased apoptosis, leaving behind a small subset of nonproliferative cells that could form tumors upon transgene reactivation. Nearly all BCCs arose from hair follicles, which harbor cutaneous epithelial stem cells, and reconstitution of regressing tumor cells with an inductive mesenchyme led to multilineage differentiation and hair follicle formation. Our data reveal that continued Hh signaling is required for proliferation and survival of established BCCs, provide compelling support for the concept that these tumors represent an aberrant form of follicle organogenesis, and uncover potential limitations to treating BCCs using Hh pathway inhibitors. C1 Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. Univ Michigan, Cellular & Mol Biol Grad Program, Ann Arbor, MI 48109 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Dlugosz, AA (reprint author), Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. EM dlugosza@umich.edu FU NCI NIH HHS [CA87837, R01 CA087837, P30 CA046592, CA46592]; NIAMS NIH HHS [AR45973, R01 AR045973, T32 AR007197, AR07197] NR 70 TC 151 Z9 156 U1 0 U2 7 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 JAN 15 PY 2005 VL 19 IS 2 BP 214 EP 223 DI 10.1101/gad.1258705 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 888KN UT WOS:000226372900005 PM 15625189 ER PT J AU Clark, K Pankov, R Travis, MA Askari, JA Mould, AP Craig, SE Newham, P Yamada, KM Humphries, MJ AF Clark, K Pankov, R Travis, MA Askari, JA Mould, AP Craig, SE Newham, P Yamada, KM Humphries, MJ TI A specific alpha(5)beta(1)-integrin conformation promotes directional integrin translocation and fibronectin matrix formation SO JOURNAL OF CELL SCIENCE LA English DT Article DE integrin; fibronectin; conformation; monoclonal antibody; matrix assembly ID MONOCLONAL-ANTIBODY; CELL-ADHESION; BINDING-SITE; LIGAND-BINDING; PLATELET GPIIB; IIIA COMPLEX; ACTIVATION; EPITOPE; DOMAINS; SUBUNIT AB Integrin adhesion receptors are structurally dynamic proteins that adopt a number of functionally relevant conformations. We have produced a conformation-dependent anti-alpha(5) monoclonal antibody (SNAKA51) that converts alpha(5)beta(1) integrin into a ligand-competent form and promotes fibronectin binding. In adherent fibroblasts, SNAKA51 preferentially bound to integrins in fibrillar adhesions. Clustering of integrins expressing this activation epitope induced directional translocation of alpha(5)beta(1), mimicking fibrillar adhesion formation. Priming of alpha(5)beta(1), integrin by SNAKA51 increased the accumulation of detergent-resistant fibronectin in the extracellular matrix, thus identifying an integrin conformation that promotes matrix assembly. The SNAKA51 epitope was mapped to the calf-1/calf-2 domains. We propose that the action of the antibody causes the legs of the integrin to change conformation and thereby primes the integrin to bind ligand. These findings identify SNAKA51 as the first anti-integrin antibody to selectively recognize a subset of adhesion contacts, and they identify an integrin conformation associated with integrin translocation and fibronectin matrix formation. C1 Univ Manchester, Sch Biol Sci, Wellcome Trust, Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Humphries, MJ (reprint author), Univ Manchester, Sch Biol Sci, Wellcome Trust, Ctr Cell Matrix Res, Michael Smith Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England. EM martin.humphries@man.ac.uk RI Pankov, Roumen/B-3284-2014; Travis, Mark/E-9643-2015; OI Pankov, Roumen/0000-0002-3157-3659; Travis, Mark/0000-0002-8485-2272; Humphries, Martin/0000-0002-4331-6967 FU Wellcome Trust [074941] NR 45 TC 64 Z9 65 U1 0 U2 6 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 JAN 15 PY 2005 VL 118 IS 2 BP 291 EP 300 DI 10.1242/jcs.01623 PG 10 WC Cell Biology SC Cell Biology GA 898UT UT WOS:000227102400004 PM 15615773 ER PT J AU Nath, K Boorech, JL Beckham, YM Burns, MM Elinson, RP AF Nath, K Boorech, JL Beckham, YM Burns, MM Elinson, RP TI Status of RNAs, localized in Xenopus laevis oocytes, in the frogs Rana pipiens and Eleutherodactylus coqui SO JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION LA English DT Article ID GERM-CELL DEVELOPMENT; T-BOX GENES; IN-SITU HYBRIDIZATION; DAZ-LIKE GENE; MESODERM FORMATION; MATERNAL VEGT; TRANSCRIPTION FACTOR; EXPRESSION CLONING; LARVAL CHARACTERS; DROSOPHILA EMBRYO AB Early development in the frog model, Xenopus laevis, is governed by RNAs, localized to the vegetal cortex of the oocyte. These RNAs include Xdazl RNA, which is involved in primordial germ cell formation, and VegT RNA, which specifies the mesoderm and endoderm. In order to determine whether orthologues of these RNAs are localized and have similar functions in other frogs, we cloned RpDazl and RpVegT from Rana pipiens, a frog that is phylogenetically distant from X laevis. RNAs from both genes are localized to the vegetal cortex of the R. pipiens oocyte, indicating that the vegetal localization is likely the basal state. The animal location of EcVegT RNA in Eleutherodactylus coqui that we found previously is then a derived state, probably due to the great increase in egg size required for direct development of this species. To answer the question of function, we injected RpVegT or EcVegT RNAs into X laevis embryos, and assayed animal caps for gene expression. Both of these RNAs induced the expression of endodermal, mesodermal, and organizer genes, showing that the function of RpVegT and EeVegT as mesoendodermal determinants is conserved in frogs. The RNA localizations and the function of VegT orthologues in germ layer specification may be synapomorphies for anuran amphibians. (C) 2005 Wiley-Liss, Inc. C1 Duquesne Univ, Dept Biol Sci, Pittsburgh, PA 15282 USA. NIH, Bethesda, MD 20892 USA. Univ Washington, Friday Harbor Labs, Ctr Cell Dynam, Friday Harbor, WA 98250 USA. Univ Virginia, Dept Biol, Charlottesville, VA 22903 USA. RP Elinson, RP (reprint author), Duquesne Univ, Dept Biol Sci, Pittsburgh, PA 15282 USA. EM elinson@duq.edu NR 63 TC 20 Z9 20 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-5007 J9 J EXP ZOOL PART B JI J. Exp. Zool. Part B PD JAN 15 PY 2005 VL 304B IS 1 BP 28 EP 39 DI 10.1002/jez.b.21020 PG 12 WC Evolutionary Biology; Developmental Biology; Zoology SC Evolutionary Biology; Developmental Biology; Zoology GA 895FK UT WOS:000226846100003 PM 15515051 ER PT J AU Vaidya, SV Stepp, SE McNerney, ME Lee, JK Bennett, M Lee, KM Stewart, CL Kumar, V Mathew, PA AF Vaidya, SV Stepp, SE McNerney, ME Lee, JK Bennett, M Lee, KM Stewart, CL Kumar, V Mathew, PA TI Targeted disruption of the 2B4 gene in mice reveals an in vivo role of 2B4 (CD244) in the rejection of B16 melanoma cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; LINKED LYMPHOPROLIFERATIVE DISEASE; CYTOTOXIC T-LYMPHOCYTES; ESTROGEN-INDUCED ACTIVATION; ANTIGEN-PRESENTING CELLS; CUTTING EDGE; RECEPTOR 2B4; 2B4/CD48 INTERACTIONS; TUMOR REJECTION AB Murine 2B4 (CD244) is a cell surface receptor expressed on all NK cells, gammadelta-T cells, a subset, of CD8(+) T cells, and all CD14(+) monocytes. 2114 binds to CD48 with high affinity, and cross-linking 2134 with anti-2B4 Ab in vitro causes activation of NK cells. To study its physiological role, we have generated, by gene targeting, mice deficient in the expression of this cell surface molecule. The expression of lymphoid cell surface markers on PBMC and splenocytes of mice homozygous for the mutation in 2B4 (2B4(-/-)) is identical to that in wild-type mice. However, thymocytes from female 2B4(-/-) mice, but not male 2B4(-/-) mice, have an increase in the immature CD4(-)/CD8(-) population. To investigate the in vivo role of 2B4, wild-type and 2B4(-/-) mice were injected with CD48(+) and CD48(-) metastatic B16 melanoma cells. Wild-type mice rejected CD48(+) melanoma poorly compared with CD48(-) tumor cells, suggesting that ligation of 2B4 by CD48 on melanoma cells is inhibitory. In keeping with this, male 2B4(-/-) mice showed enhanced ability to reject CD48(+) melanoma cells. However, female 2B4(-/-) mice poorly rejected both CD48(+) and CD48(-) melanoma cells, revealing a gender-specific and CD48-independent defect in mice lacking 2B4. In vitro and in vivo experiments reveal a complex role of NK cells in gender specificity. C1 Univ N Texas, Hlth Sci Ctr, Dept Mol Biol & Immunol, Ft Worth, TX 76107 USA. Univ N Texas, Hlth Sci Ctr, Canc Res Inst, Ft Worth, TX 76107 USA. Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Univ Chicago, Comm Immunol, Chicago, IL 60637 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. NCI, Div Basic Sci, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Mathew, PA (reprint author), Univ N Texas, Hlth Sci Ctr, Dept Mol Biol & Immunol, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA. EM pmathew@hsc.unt.edu FU NCI NIH HHS [CA85753] NR 70 TC 65 Z9 65 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2005 VL 174 IS 2 BP 800 EP 807 PG 8 WC Immunology SC Immunology GA 888FV UT WOS:000226360500029 PM 15634901 ER PT J AU Ogilvie, RL Abelson, M Hau, HH Vlasova, I Blackshear, PJ Bohjanen, PR AF Ogilvie, RL Abelson, M Hau, HH Vlasova, I Blackshear, PJ Bohjanen, PR TI Tristetraprolin down-regulates IL-2 gene expression through AU-rich element-mediated mRNA decay SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-ACTIVATION; HUMAN LYMPHOCYTES-T; CODING REGION; INTERLEUKIN-2; DEADENYLATION; STABILITY; BINDING; HUR; STABILIZATION; PATHWAY AB Posttranscriptional regulation of IL-2 gene expression at the level of mRNA decay is mediated by an AU-rich element (.ARE,) found in the 3'-untranslated region. We hypothesized that the ARE-binding protein tristetraprolin (TTP) regulates T lymphocyte IL-2 mRNA decay by interacting with the IL-2 ARE and targeting the transcript for decay. rTTP protein expressed in HeLa cells bound specifically to the IL-2 ARE with high affinity in a gel shift assay. In primary human T lymphocytes, TTP mRNA and protein expression were induced by TCR and CD28 coreceptor stimulation. Using a gel shift assay, we identified a cytoplasmic RNA-binding activity that was induced by TCR and CD28 coreceptor stimulation and bound specifically to the IL-2 ARE sequence. Using anti-TTP Abs, we showed by supershift that this inducible activity contained TTP. We also showed that insertion of the IL-2 ARE sequence into the 3'-untranslated region of a P-globin reporter construct conferred TTP-dependent mRNA destabilization on the beta-globin reporter. To determine whether TTP also regulates IL-2 gene expression in vivo, we examined IL-2 expression in primary cells from wild-type and TTP knockout mice. Compared with their wild-type counterparts. TCR- and CD28-activated splenocytes and T cells from TTP knockout mice overexpressed IL-2 mRNA and protein. Also. IL-2 mRNA was more. stable in activated splenocytes from TTP knockout mice compared with wild-type mice.-Taken together, these data suggest that TTP functions to down-regulate IL-2 gene expression through ARE-mediated mRNA decay. C1 Univ Minnesota, Dept Microbiol, Microbiol Immunol & Canc Biol Grad Program, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Microbiol, Dept Med, Minneapolis, MN 55455 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Bohjanen, PR (reprint author), Univ Minnesota, Dept Microbiol, Microbiol Immunol & Canc Biol Grad Program, Mayo Mail Code 196,420 Delaware St, Minneapolis, MN 55455 USA. EM bohja001@tc.umn.edu RI Bohjanen, Paul/B-2329-2015 OI Bohjanen, Paul/0000-0002-2772-3597 FU NIAID NIH HHS [1R01AI49494, K02 AI052170, K08 AI001517, KO2AI152170, R01 AI049494] NR 47 TC 127 Z9 130 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2005 VL 174 IS 2 BP 953 EP 961 PG 9 WC Immunology SC Immunology GA 888FV UT WOS:000226360500046 PM 15634918 ER PT J AU Doerre, S Mesires, KP Daley, KM McCarty, T Knoetig, S Corley, RB AF Doerre, S Mesires, KP Daley, KM McCarty, T Knoetig, S Corley, RB TI Reductions in I kappa B epsilon and changes in NF-kappa B activity during B lymphocyte differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED IMMUNODEFICIENCY SYNDROME; RECEPTOR-MEDIATED APOPTOSIS; CD40 LIGAND RESCUE; TRANSCRIPTION FACTORS; CELL DIFFERENTIATION; T-CELLS; SIGNAL-TRANSDUCTION; SUBUNIT COMPOSITION; IMMUNE-RESPONSES; REL PROTEINS AB The levels and stability of IkappaBis an element of have been examined in unstimulated and stimulated splenic B cells and compared with that of IkappaBalpha and IkappaBbeta. Primary murine splenic B cells but not T cells were found to contain high levels of IkappaBis an element of protein. equivalent to levels of the abundant IkappaBalpha. Most agents that activate IkappaBalpha and IkappaBbeta degradation do not induce rapid degradation of IkappaBis an element of. Interestingly, however, the levels of IkappaBis an element of, but not of IkappaBalpha or IkappaBbeta, are dramatically reduced upon the stimulation of B cells both in vivo and in vitro. Since IkappaBis an element of exhibits substrate specificity for NF-kappaB Rel homodimers. this suggested the possibility, that changes in NF-kappaB-responsive genes might also occur during this transition. Consistent with this hypothesis, we found that a NF-kappaB reporter construct sensitive to p65/RelA homodimers is activated at the time that IkappaBis an element of levels dectine following B cell stimulation. In IgG(+) B cell lines, which contain low levels of IkappaBis an element of, this same reporter construct was inactive, suggesting that the increases in Rel homodimer activity that accompany B cell stimulation are transient. However, there are. differences in the level of expresssion of NF-kappaB-responsive genes in these IgG(+) B cell lines compared with their IgM(+) counterparts. From these data, we conclude that there are transient changes in NF-kappaB activity due to reductions in IkappaBis an element of. which might contribute to long-term, persistent changes that accompany B cell differentiation. We propose an important role for IkappaBis an element of in the differential regulation of nuclear NF-kappaB activity in stimulated B cells. C1 Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Corley, RB (reprint author), Boston Univ, Sch Med, Dept Microbiol, 715 Albany St,L504, Boston, MA 02118 USA. EM rbcorley@bu.edu FU NCI NIH HHS [CA36642, R01 CA036642-19]; NIAID NIH HHS [R01 AI031209-13, AI31209] NR 62 TC 7 Z9 8 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2005 VL 174 IS 2 BP 983 EP 991 PG 9 WC Immunology SC Immunology GA 888FV UT WOS:000226360500050 PM 15634922 ER PT J AU Mukundan, L Bishop, GA Head, KZ Zhang, LH Wahl, LM Suttles, J AF Mukundan, L Bishop, GA Head, KZ Zhang, LH Wahl, LM Suttles, J TI TNF receptor-associated factor 6 is an essential mediator of CD40-activated proinflammatory pathways in monocytes and macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; HUMAN DENDRITIC CELLS; CD40-CD40 LIGAND; MOLECULAR-MECHANISMS; SIGNAL-TRANSDUCTION; ENDOTHELIAL-CELLS; FACTORS TRAFS; CD40 LIGAND; INTERLEUKIN-1 AB The interaction between CD40 and its ligand, CD154, has been shown to play a role in the onset and maintenance of inflammatory disease. Contributing to this process is the ability of CD40 to signal monocyte and rnacrophage inflammatory cytokine production. We have shown that this event is dependent on Src family tyrosine kinase activity and the subsequent activation of ERK1/2. To address the role of TNFR-associated factor (TRAF) family members in facilitating this signaling pathway, we transfected a CD40-deficient macrophage cell line with wild-type human CD40, or with CD40 containing disrupted TRAY binding sites. Ligation of either wild-type CD40, or a CD40 mutant unable to bind TRAF2/3/5, resulted in the stimulation of inflammatory cytokine production. However, ligation of a CD40 mutant lacking a functional TRAF6 binding site did not initiate inflammatory cytokine production, and this mutant was found to be defective in CD40-mediated activation of ERK1/2, as well as IkappaB kinase (IKK) and NF-kappaB. Likewise, introduction of a dominant-negative TRAF6 into a wild-type (CD40(+)) macrophage cell line resulted in abrogation of CD40-mediated induction of inflammatory cytokine synthesis. Finally, treatment of monocytes with a cell-permeable peptide corresponding to the TRAF6-binding motif of CD40 inhibited CD40 activation of ERK1/2, IKK, and inflammatory cytokine production. These data demonstrate that TRAF6 acts as a critical adapter of both the Src/ERK1/2 and IKK/NF-kappaB proinflammatory signaling pathways in monocytes and macrophages. C1 Univ Louisville, Sch Med, Dept Microbiol & Immunol, Louisville, KY 40292 USA. Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. Vet Affairs Med Ctr, Iowa City, IA 52242 USA. Natl Inst Dental & Craniofacial Res, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. RP Suttles, J (reprint author), Univ Louisville, Sch Med, Dept Microbiol & Immunol, 319 Abraham Flexner Way, Louisville, KY 40292 USA. EM jill.suttles@louisville.edu FU NCI NIH HHS [CA099997]; NIAID NIH HHS [AI28847, AI49993] NR 55 TC 68 Z9 70 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 JAN 15 PY 2005 VL 174 IS 2 BP 1081 EP 1090 PG 10 WC Immunology SC Immunology GA 888FV UT WOS:000226360500061 PM 15634933 ER PT J AU Yao, YF Sturdevant, DE Otto, M AF Yao, YF Sturdevant, DE Otto, M TI Genomewide analysis of gene expression in Staphylococcus epidermidis biofilms: Insights into the pathophysiology of S-epidermidis biofilms and the role of phenol-soluble modulins in formation of biofilms SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID COAGULASE-NEGATIVE STAPHYLOCOCCI; PSEUDOMONAS-AERUGINOSA BIOFILMS; INTERCELLULAR ADHESIN; ANTIBIOTIC-RESISTANCE; AUREUS; INFECTIONS; ACCUMULATION; PEPTIDES; PROTEIN; MODEL AB Many bacterial pathogens form cellular agglomerations known as biofilms, which considerably limit the success of both antibiotic treatment and the human immune defense. To gain insight into the pathophysiology of the leading nosocomial pathogen, Staphylococcus epidermidis, we analyzed the genome of biofilm-forming S. epidermidis, constructed a microarray representing its entire transcriptome, and performed expression profiling of an S. epidermidis biofilm. Gene-regulated processes in the biofilm led to a nonaggressive and protected form of bacterial growth with low metabolic activity, which is optimally suited to guarantee long-term survival during chronic infection. A class of peptides known as phenol-soluble modulins, which combine proinflammatory activity with a putative role in detachment of biofilms, evolved as potential key determinants controlling the switch between aggressive and quiescent modes of infection. Our data suggest that S. epidermidis adjusts its lifestyle to varying requirements during colonization and infection by means of an expansive change of gene expression. The observed physiological characteristics of the biofilm mode of growth-in particular, the contribution of surfactant-like peptides-might serve as a model for a variety of biofilm-forming pathogens. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Otto, M (reprint author), 903 S 4th St, Hamilton, MT 59840 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 NR 42 TC 137 Z9 146 U1 2 U2 14 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 JAN 15 PY 2005 VL 191 IS 2 BP 289 EP 298 DI 10.1086/426945 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 881SK UT WOS:000225889500019 PM 15609240 ER PT J AU Spouge, JL AF Spouge, JL TI Finite-size corrections to Poisson approximations in general renewal-success processes SO JOURNAL OF MATHEMATICAL ANALYSIS AND APPLICATIONS LA English DT Article DE renewal-success process; finite-size correction; regenerative process with a rare event ID ALIGNMENT; SEQUENCE AB Consider a renewal process, and let K greater than or equal to 0 denote the random duration of a typical renewal cycle. Assume that on any renewal cycle, a rare event called "success" can occur. Such successes lend themselves naturally to approximation by Poisson point processes. If each success occurs after a random delay, however, Poisson convergence can be relatively slow, because each success corresponds to a time interval, not a point. If K is an arithmetic variable, a "finite-size correction" (FSC) is known to speed Poisson convergence by providing a second, subdominant term in the appropriate asymptotic expansion. This paper generalizes the FSC from arithmetic K to general K. Genomics applications require this generalization, because they have already heuristically applied the FSC to p-values involving absolutely continuous distributions. The FSC also sharpens certain results in queuing theory, insurance risk, traffic flow, and reliability theory. (C) 2004 Elsevier Inc. All rights reserved. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Spouge, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM spouge@ncbi.nlm.nih.gov NR 20 TC 2 Z9 2 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 0022-247X J9 J MATH ANAL APPL JI J. Math. Anal. Appl. PD JAN 15 PY 2005 VL 301 IS 2 BP 401 EP 418 DI 10.1016/j.jmaa.2004.07.035 PG 18 WC Mathematics, Applied; Mathematics SC Mathematics GA 879SL UT WOS:000225739100013 ER PT J AU Wu, T Hallett, M AF Wu, T Hallett, M TI The influence of normal human ageing on automatic movements SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; AGE-RELATED-CHANGES; SEQUENTIAL FINGER MOVEMENTS; WORKING-MEMORY; FRONTAL-CORTEX; FUNCTIONAL MRI; BRAIN ACTIVATION; MOTOR SEQUENCE; BASAL GANGLIA AB There is evidence that aged normal subjects have more difficulty in achieving automaticity than young subjects. The underlying central neural mechanism for this phenomenon is unclear. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the effect of normal ageing on automaticity. Aged healthy subjects were asked to practice self-initiated, self-paced, memorized sequential finger movements with different complexity until they could perform the tasks automatically. Automaticity was evaluated by having subjects perform a secondary task simultaneously with the sequential movements. Although it took more time, most aged subjects eventually performed the tasks automatically at the same level as the young subjects. Functional MRI results showed that, for both groups, sequential movements activated similar brain regions before and after automaticity was achieved. No additional activity was observed in the automatic condition. While performing automatic movements, aged subjects had greater activity in the bilateral anterior lobe of cerebellum, premotor area, parietal cortex, left prefrontal cortex, anterior cingulate, caudate nucleus and thalamus, and recruited more areas, including the pre-supplementary motor area and the bilateral posterior lobe of cerebellum, compared to young subjects. These results indicate that most healthy aged subjects can perform some complex motor tasks automatically. However, aged subjects appear to require more brain activity to perform automatically at the same level as young subjects. This appears to be the main reason why aged subjects have more difficulty in achieving automaticity. C1 NINCDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD USA. RP Hallett, M (reprint author), Bldg 10,Room 5 N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov NR 50 TC 88 Z9 88 U1 0 U2 10 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 15 PY 2005 VL 562 IS 2 BP 605 EP 615 DI 10.1113/j.physiol.2004.076042 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 890RH UT WOS:000226528000022 PM 15513939 ER PT J AU Brogden, KA Guthmiller, JM Taylor, CE AF Brogden, KA Guthmiller, JM Taylor, CE TI Human polymicrobial infections SO LANCET LA English DT Review ID RESPIRATORY SYNCYTIAL VIRUS; STAPHYLOCOCCUS-AUREUS; HUMAN METAPNEUMOVIRUS; STREPTOCOCCUS-PNEUMONIAE; HTLV-II; COLONIZATION; ASSOCIATION; BIOFILMS; CHILDREN; PATHOGENS AB Context Polymicrobial diseases, caused by combinations of viruses, bacteria, fungi, and parasites, are being recognised with increasing frequency. In these infections, the presence of one micro-organism generates a niche for other pathogenic micro-organisms to colonise, one micro-organism predisposes the host to colonisation by other micro-organisms, or two or more non-pathogenic micro-organisms together cause disease. Starting point Recently, Gill Regev-Yochay (JAMA 2004; 292: 716-20) and Debby Bogaert (Lancet 2004; 363: 1871-72), and their colleagues, suggested another interaction: microbial interference-the ability of Streptococcus pneumoniae carriage to protect against Staphylococcus aureus carriage, and the inverse effect of pneumococcal conjugate vaccination on the increased carriage of Staph aureus and Staph-aureus-related disease. Strep pneumoniae carriage protected against Staph aureus carriage, and the bacterial interference could be disrupted by vaccinating children with pneumococcal conjugate vaccines that reduced nasopharyngeal carriage of vaccine-type Strep pneumoniae. Where next The medical community is recognising the significance of polymicrobial diseases and the major types of microbial community interactions associated with human health and disease. Many traditional therapies are just starting to take into account the polymicrobial cause of diseases and the repercussions of treatment and prevention. C1 Univ Iowa, Coll Dent, Dept Periodont, Iowa City, IA 52242 USA. Univ Iowa, Coll Dent, Dows Inst Dent Res, Iowa City, IA 52242 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Brogden, KA (reprint author), Univ Iowa, Coll Dent, Dept Periodont, Iowa City, IA 52242 USA. EM kim-brogden@uiowa.edu FU NIDCR NIH HHS [R13 DE015562-01] NR 34 TC 133 Z9 140 U1 4 U2 34 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 15 PY 2005 VL 365 IS 9455 BP 253 EP 255 DI 10.1016/S0140-6736(05)70155-0 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 887MG UT WOS:000226309600031 PM 15652608 ER PT J AU Rettmann, ME Tosun, D Tao, XD Resnick, SM Prince, JL AF Rettmann, ME Tosun, D Tao, XD Resnick, SM Prince, JL TI Program for assisted labeling of sulcal regions (PALS): description and reliability SO NEUROIMAGE LA English DT Article DE human brain cortex; watershed; fast marching; cortical features; sulci; sulcus ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; HUMAN BRAIN CORTEX; GRAY-MATTER LOSS; ALZHEIMERS-DISEASE; CORTICAL SURFACE; IN-VIVO; STATISTICAL-ANALYSIS; OLDER-ADULTS; MRI AB With the improvements in techniques for generating surface models from magnetic resonance (MR) images, it has recently become feasible to study the morphological characteristics of the human brain cortex in vivo. Studies of the entire surface are important for measuring global features, but analysis of specific cortical regions of interest provides a more detailed understanding of structure. We have previously developed a method for automatically segmenting regions of interest from the cortical surface using a watershed transform. Each segmented region corresponds to a cortical sulcus and is thus termed a "sulcal region." In this work, we describe two important augmentations of this methodology. First, we describe a user interface that allows for the efficient labeling of the segmented sulcal regions called the Program for Assisted Labeling of Sulcal Regions (PALS). An additional augmentation allows for even finer divisions on the cortex with a methodology that employs the fast marching technique to track a curve on the cortical surface that is then used to separate segmented regions. After regions of interest have been identified, we compute both the cortical surface area and gray matter volume. Reliability experiments are performed to assess both the long-term stability and short-term repeatability of the proposed techniques. These experiments indicate the proposed methodology gives both highly stable and repeatable results. (C) 2004 Elsevier Inc. All rights reserved. C1 NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. RP Rettmann, ME (reprint author), NIA, Lab Personal & Cognit, NIH, 5600 Nathan Shcok Dr, Baltimore, MD 21224 USA. EM maryam.rettmann@nih.gov; dtosun@jhu.edu; xtao2@jhu.edu; susan.resnick@nih.gov; prince@jhu.edu RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 NR 76 TC 9 Z9 9 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2005 VL 24 IS 2 BP 398 EP 416 DI 10.1016/j.neuroimage.2004.08.014 PG 19 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 889PI UT WOS:000226454500013 PM 15627582 ER PT J AU DelParigi, A Chen, KW Salbe, AD Reiman, EM Tataranni, PA AF DelParigi, A Chen, KW Salbe, AD Reiman, EM Tataranni, PA TI Sensory experience of food and obesity: a positron emission tomography study of the brain regions affected by tasting a liquid meal after a prolonged fast SO NEUROIMAGE LA English DT Article DE hyperphagia; homeostasis; tomography ID HUMAN ORBITOFRONTAL CORTEX; HUMAN OLFACTORY CORTEX; INSULAR CORTEX; ENERGY-BALANCE; HUMAN AMYGDALA; ACTIVATION; PREFERENCES; SATIATION; HUMANS; REPRESENTATION AB The sensory experience of food is a primary reinforcer of eating and overeating plays a major role in the development of human obesity . However, whether the sensory experience of a forthcoming meal and the associated physiological phenomena (cephalic phase response, expectation of reward), which prepare the organism for the ingestion of food play a role in the regulation of energy intake and contribute to the development of obesity remains largely unresolved. We used positron emission tomography (PET) and O-15-water to measure changes in regional cerebral blood flow (rCBF) and to assess the brain's response to the oral administration of 2 ml of a liquid meal (Ensure Plus, 1.5 kcal/ml) after a 36-h fast and shortly before consuming the same meal. Twenty-one obese (BMI > 35 kg/m(2), 10M/11F, age 28 +/- 6 years, body fat 40 +/- 6%) and 20 lean individuals (BMI < 25 kg/m(2), 10M/10F age 33 +/- 9 years, body fat 21 +/- 7%) were studied. Compared to lean individuals, obese individuals had higher fasting plasma glucose (83.3 +/- 6.2 vs. 75.5 +/- 9.6 mg/dl; P = 0.0003) and insulin concentrations (6.1 +/- 3.5 vs. 2.5 +/- 1.7 muU/ml; P < 0.0001) and were characterized by a higher score of dietary disinhibition (i.e., the susceptibility of eating behavior to emotional factors and sensory cues, 5.7 +/- 3.6 vs. 3.5 +/- 2.7; P = 0.01) assessed by the Three Factor Eating Questionnaire. In response to the sensory experience of food, differences in rCBF were observed in several regions of the brain, including greater increases in the middle-dorsal insula and midbrain, and greater decreases in the posterior cingulate, temporal, and orbitofrontal cortices in obese compared to lean individuals (P < 0.05, after small volume correction). In a multiple regression model, percentage of body fat (P = 0.04), glycemia (P = 0.01), and disinhibition (P = 0.07) were independent correlates of the neural response to the sensory experience of the meal in the middle-dorsal insular cortex (R-2 = 0.45). We conclude that obesity is associated with an abnormal brain response to the sensory aspects of a liquid meal after a prolonged fast especially in areas of the primary gustatory cortex. This is only partially explained by the elevated glycemia and high level of disinhibition which characterize individuals with increased adiposity. These results provide a new perspective on the understanding of the neuroanatomical correlates of abnormal eating behavior and their relationship with obesity in humans. Published by Elsevier Inc. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Obes Diabet & Energy Metab Unit, Phoenix, AZ 85016 USA. Banner Good Samaritan Med Ctr, Positron Emiss Tomography Ctr, Phoenix, AZ USA. Univ Arizona, Dept Psychiat, Phoenix, AZ USA. Translat Genom Res Inst, Neurogenom Program, Phoenix, AZ USA. RP DelParigi, A (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, Obes Diabet & Energy Metab Unit, 4212 N 16Th St, Phoenix, AZ 85016 USA. EM adelpari@mail.nih.gov RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 NR 68 TC 85 Z9 89 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2005 VL 24 IS 2 BP 436 EP 443 DI 10.1016/j.neuroimage.2004.08.035 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 889PI UT WOS:000226454500016 PM 15627585 ER PT J AU Buchsbaum, BR Olsen, RK Koch, PF Kohn, P Kippenhan, JS Berman, KF AF Buchsbaum, BR Olsen, RK Koch, PF Kohn, P Kippenhan, JS Berman, KF TI Reading, hearing, and the planum temporale SO NEUROIMAGE LA English DT Article DE planum temporale; fMRI; Sylvian-parietal-temporal ID POSITRON-EMISSION-TOMOGRAPHY; VERBAL WORKING-MEMORY; HUMAN AUDITORY-CORTEX; FUNCTIONAL NEUROANATOMY; CONDUCTION APHASIA; HEMISPHERIC-SPECIALIZATION; SPEECH-PERCEPTION; PREMOTOR CORTEX; PARIETAL CORTEX; HUMAN-BRAIN AB Many neuroimaging studies of single-word reading have been carried out over the last 15 years, and a consensus as to the brain regions relevant to this task has emerged. Surprisingly, the planum temporale (PT) does not appear among the catalog of consistently active regions in these investigations. Recently, however, several studies have offered evidence suggesting that the left posteromedial PT plays a role in both speech production and speech perception. It is not clear, then, why so many neuroimaging studies of single-word reading - a task requiring speech production - have tended not to rind evidence of PT involvement. In the present work, we employed a high-powered rapid event-related fMRI paradigm involving both single pseudoword reading and single pseudoword listening to assess activity related to reading and speech perception in the PT as a function of the degree of spatial smoothing applied to the functional images. We show that the speech area of the PT [Sylvian-parietal-temporal (Spt)] is best identified when only a moderate (5 mm) amount of spatial smoothing is applied to the data before statistical analysis. Moreover, increasing the smoothing window to 10 turn obliterates activation in the PT, suggesting that failure to find PT activation in past studies may relate to this factor. (C) 2004 Elsevier Inc. All rights reserved. C1 NIMH, NIH, Dept Hlth & Human Serv, Unit Integrat Neuroimaging,Clin Brain Disorders B, Bethesda, MD 20892 USA. RP Buchsbaum, BR (reprint author), NIMH, NIH, Dept Hlth & Human Serv, Unit Integrat Neuroimaging,Clin Brain Disorders B, IRP,9000 Rockville Pike,Bldg 10,Room 4C-101, Bethesda, MD 20892 USA. EM brad.buchsbaum@nih.gov OI Olsen, Rosanna/0000-0002-2918-4152 NR 61 TC 55 Z9 55 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2005 VL 24 IS 2 BP 444 EP 454 DI 10.1016/j.neuroimage.2004.08.025 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 889PI UT WOS:000226454500017 PM 15627586 ER PT J AU Baiardi, G Macova, M Armando, I Ando, H Tyurmin, D Saavedra, JM AF Baiardi, G Macova, M Armando, I Ando, H Tyurmin, D Saavedra, JM TI Estrogen upregulates renal angiotensin II AT(1) and AT(2) receptors in the rat SO REGULATORY PEPTIDES LA English DT Article DE renin-angiotensin system; ovarian hormones; kidney function; prostaglandins ID TISSUE-SPECIFIC EXPRESSION; IN-SITU HYBRIDIZATION; TYPE-2 RECEPTOR; MESANGIAL CELLS; PROSTAGLANDIN E(2); MESSENGER-RNA; QUANTITATIVE AUTORADIOGRAPHY; MEDULLARY CIRCULATION; POSTMENOPAUSAL WOMEN; PASTE STANDARDS AB We studied renal AT(1) and AT(2) receptors in male, female, ovariectomized and ovariectomized-estrogen-treated Wistar-Hanover and Wistar-Kyoto rats. AT(1) receptors and AT(1A) receptor mRNA predominated, with no significant differences between males and females. AT(2) receptor expression was restricted in female rats to the capsule, the transition zone between outer and inner medulla, the endothelium lining the papilla, and arcuate arteries and veins. There were no AT(2) receptors in male rats, while male mice express substantial numbers of estrogen-dependent AT(2) receptors. Arcuate arteries and veins expressed AT(1B) mRNA in males and females, and AT(2) mRNA in females only. AT(1) receptor and AT(2) receptor expression were estrogen-dependent, with increases in AT(1) and AT(2) receptor expression after estrogen treatment in ovariectomized rats. Estrogen treatment increased prostaglandin E-2 (PGE(2)) and cGMP concentrations in the renal medulla, and eNOS expression in cortical arteries. In rodents, expression of renal Angiotensin II receptor types is estrogen-dependent, with significant species, strain and area differences. Our results Support an important role for AT(2) receptors in the regulation of renal function and in the protective effects of estrogen in the kidney. (C) 2004 Published by Elsevier B.V. C1 NIMH, Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, NIH, 10 Ctr Dr,MSC 1514,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA. EM saaverdrj@intra.nimh.nih.gov NR 62 TC 58 Z9 59 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD JAN 15 PY 2005 VL 124 IS 1-3 BP 7 EP 17 DI 10.1016/regpep.2004.06.021 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 878HU UT WOS:000225638300002 PM 15544836 ER PT J AU Liu, AY Schisterman, EF Zhu, Y AF Liu, AY Schisterman, EF Zhu, Y TI On linear combinations of biomarkers to improve diagnostic accuracy SO STATISTICS IN MEDICINE LA English DT Article DE sensitivity and specificity; receiver operating characteristic (ROC) curve; dominance of an ROC curve; maximizing sensitivity ID MARKERS AB We consider combining multiple biomarkers to improve diagnostic accuracy. Su and Liu derived the linear combinations that maximize the area under the receiver operating characteristic (ROC) curves. These linear combinations, however, may have unsatisfactory low sensitivity over a certain range of desired specificity. In this paper, we consider maximizing sensitivity over a range of specificity. We first present a simpler proof for Su and Liu's main theorem and further investigate some other optimal properties of their linear combinations. We then derive alternative linear combinations that have higher sensitivity over a range of high (or low) specificity. The methods are illustrated using data from a study evaluating biomarkers for coronary heart disease. Copyright 2004 John Wiley Sons, Ltd. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Liu, AY (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, 6100 Execut Blvd, Rockville, MD 20852 USA. EM Liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X NR 13 TC 38 Z9 39 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 15 PY 2005 VL 24 IS 1 BP 37 EP 47 DI 10.1002/sim.1922 PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 884RG UT WOS:000226103000004 PM 15515132 ER PT J AU Xu, XD Yang, DM Ding, JH Wang, W Chu, PH Dalton, ND Wang, HY Bermingham, JR Ye, Z Liu, F Rosenfeld, MG Manley, JL Ross, J Chen, J Xiao, RP Cheng, HP Fu, XD AF Xu, XD Yang, DM Ding, JH Wang, W Chu, PH Dalton, ND Wang, HY Bermingham, JR Ye, Z Liu, F Rosenfeld, MG Manley, JL Ross, J Chen, J Xiao, RP Cheng, HP Fu, XD TI ASF/SF2-Regulated CaMKII delta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle SO CELL LA English DT Article ID PROTEIN-KINASE-II; MESSENGER-RNA EXPORT; DILATED CARDIOMYOPATHY; VENTRICULAR MYOCYTES; HEART-FAILURE; SR PROTEINS; ISOFORM; ASF/SF2; GENE; SC35 AB The transition from juvenile to adult life is accompanied by programmed remodeling in many tissues and organs, which is key for organisms to adapt to the demand of the environment. Here we report a novel regulated alternative splicing program that is crucial for postnatnal heart remodeling in the mouse. We identify the essential splicing factor ASF/SF2 as a key component of the program, regulating a restricted set of tissue-specific alternative splicing events during heart remodeling. Cardiomyocytes deficient in ASF/SF2 display an unexpected hypercontraction phenotype due to a defect in postnatal splicing switch of the Ca2+/calmodulin-dependent kinase IIdelta (CaMKIIdelta) transcript. This failure results in mistargeting of the kinase to sarcolemmal membranes, causing severe excitation-contraction coupling defects. Our results validate ASF/SF2 as a fundamental splicing regulator in the reprogramming pathway and reveal the central contribution of ASF/SF2-regulated CaMKIIdelta alternative splicing to functional remodeling in developing heart. C1 Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Inst Mol Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. RP Fu, XD (reprint author), Univ Calif San Diego, Dept Cellular & Mol Med, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM xdfu@ucsd.edu RI Chen, Ju/E-5579-2011; Chu, Pao-Hsien/G-3685-2010; OI Xu, Xiangdong/0000-0003-2220-0890; Wang, Wang/0000-0001-9093-412X FU NHLBI NIH HHS [R01 HL66100, R01 HL066100]; NIGMS NIH HHS [R01 GM49369, R37 GM48259] NR 54 TC 191 Z9 200 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JAN 14 PY 2005 VL 120 IS 1 BP 59 EP 72 DI 10.1016/j.cell.2004.11.036 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 888HS UT WOS:000226365400011 PM 15652482 ER PT J AU Ueda, T Brenner, S Malech, HL Langemeijer, SM Perl, S Kirby, M Phang, OA Krouse, AE Donahue, RE Kang, EM Tisdale, JF AF Ueda, T Brenner, S Malech, HL Langemeijer, SM Perl, S Kirby, M Phang, OA Krouse, AE Donahue, RE Kang, EM Tisdale, JF TI Cloning and functional analysis of the rhesus macaque ABCG2 gene - Forced expression confers an SP phenotype among hematopoietic stem cell progeny in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CANCER RESISTANCE PROTEIN; BONE-MARROW-CELLS; CHRONIC GRANULOMATOUS-DISEASE; MULTIDRUG-RESISTANCE; EX-VIVO; REPOPULATING CELLS; FUMITREMORGIN C; CARCINOMA-CELLS; P-GLYCOPROTEIN; CD34(+) CELLS AB Hematopoietic cells can be highly enriched for repopulating ability based upon the efflux of the fluorescent Hoechst 33342 dye by sorting for SP ( side population) cells, a phenotype attributed to expression of ABCG2, a member of the ABC transporter superfamily. Intriguingly, murine studies suggest that forced ABCG2 expression prevents hematopoietic differentiation. We cloned the full-length rhesus ABCG2 and introduced it into a retroviral vector. ABCG2-transduced human peripheral blood progenitor cells (PBPCs) acquired the SP phenotype but showed significantly reduced growth compared with control. Two rhesus macaques received autologous PBPCs split for transduction with the ABCG2 or control vectors. Marking levels were similar between fractions with no discrepancy between bone marrow and peripheral blood marking. Analysis for the SP phenotype among bone marrow and mature blood populations confirmed ABCG2 expression at levels predicted by vector copy number long term, demonstrating no block to differentiation in the large animal. In vitro studies showed selective protection against mitoxantrone among ABCG2-transduced rhesus PBPCs. Our results confirm the existence of rhesus ABCG2, establish its importance in conferring the SP phenotype, suggest no detrimental effect of its overexpression upon differentiation in vivo, and imply a potential role for its overexpression as an in vivo selection strategy for gene therapy applications. C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NHLBI, Res Court, NIH, Bethesda, MD 20892 USA. Univ Klinikum Carl Gustav Carus, Klin Kinder & Jugend Med, D-01307 Dresden, Germany. RP Tisdale, JF (reprint author), NIDDK, Mol & Clin Hematol Branch, NIH, Bldg 10,Rm 9N116,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Brenner, Sebastian/D-7456-2013; OI Malech, Harry/0000-0001-5874-5775 NR 42 TC 13 Z9 15 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 14 PY 2005 VL 280 IS 2 BP 991 EP 998 DI 10.1074/jbc.M409796200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 885ZF UT WOS:000226195200018 PM 15516692 ER PT J AU Kamaraju, SK Roberts, AB AF Kamaraju, SK Roberts, AB TI Role of Rho/ROCK and p38 MAP kinase pathways in transforming growth factor-beta-mediated Smad-dependent growth inhibition of human breast carcinoma cells in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; TGF-BETA; MESENCHYMAL TRANSDIFFERENTIATION; SIGNALING PATHWAY; DIRECT BINDING; CANCER CELLS; TUMOR-CELLS; C-MYC; EXPRESSION; RAS AB TGF-beta is a multifunctional cytokine known to exert its biological effects through a variety of signaling pathways of which Smad signaling is considered to be the main mediator. At present, the Smad-independent pathways, their interactions with each other, and their roles in TGF-beta-mediated growth inhibitory effects are not well understood. To address these questions, we have utilized a human breast cancer cell line MCF10CA1h and demonstrate that p38 MAP kinase and Rho/ROCK pathways together with Smad2 and Smad3 are necessary for TGF-beta-mediated growth inhibition of this cell line. We show that Smad2/3 are indispensable for TGF-beta- mediated growth inhibition, and that both p38 and Rho/ROCK pathways affect the linker region phosphorylation of Smad2/3. Further, by using Smad3 mutated at the putative phosphorylation sites in the linker region, we demonstrate that phosphorylation at Ser(203) and Ser(207) residues is required for the full transactivation potential of Smad3, and that these residues are targets of the p38 and Rho/ROCK pathways. We demonstrate that activation of the p38 MAP kinase pathway is necessary for the full transcriptional activation potential of Smad2/Smad3 by TGF-beta, whereas activity of Rho/ROCK is necessary for both down-regulation of c-Myc protein and up-regulation of p21(waf1) protein, directly interfering with p21(waf1) transcription. Our results not only implicate Rho/ROCK and p38 MAPK pathways as necessary for TGF-beta-\mediated growth inhibition, but also demonstrate their individual contributions and the basis for their cooperation with each other. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bldg 41,Rm C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. EM robertsa@dce41.nci.nih.gov NR 63 TC 13 Z9 13 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 14 PY 2005 VL 280 IS 2 BP 1024 EP 1036 DI 10.1074/jbc.M403960200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 885ZF UT WOS:000226195200022 ER PT J AU Kusaba, H Ghosh, P Derin, R Buchholz, M Sasaki, C Madara, K Longo, DL AF Kusaba, H Ghosh, P Derin, R Buchholz, M Sasaki, C Madara, K Longo, DL TI Interleukin-12-induced interferon-gamma production by human peripheral blood T cells is regulated by mammalian target of rapamycin (mTOR) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IFN-GAMMA; SERINE PHOSPHORYLATION; NATURAL-KILLER; TRANSCRIPTIONAL ACTIVITY; MOLECULAR-MECHANISMS; PROMOTER ACTIVATION; MAXIMAL ACTIVATION; STIMULATORY FACTOR; GENE-EXPRESSION; CYCLOSPORINE-A AB Depending on the type of external signals, T cells can initiate multiple intracellular signaling pathways that can be broadly classified into two groups based on their sensitivity to the immunosuppressive drug cyclosporin A (CsA). Interleukin (IL)-12-mediated interferon (IFN)-gamma production by activated T cells has been shown to be CsA-insensitive. In this report, we demonstrate that the IL-12-induced CsA-resistant pathway of IFN-gamma production is sensitive to rapamycin. Rapamycin treatment resulted in the aberrant recruitment of Stat3, Stat4, and phospho-c-Jun to the genomic promoter region resulting in decreased IFN-gamma transcription. IL-12-induced phosphorylation of Stat3 on Ser-727 was affected by rapamycin, which may be due to the effect of rapamycin on the IL-12-induced interaction between mammalian target of rapamycin ( mTOR) and Stat3. In accordance with this, reduction in the mTOR protein level by small interfering RNA resulted in suppression of Stat3 phosphorylation and decreased production of IFN-gamma after IL-12 stimulation. These results suggest that mTOR may play a major role in IL-12-induced IFN-gamma production by activated T cells. C1 NIA, Lymphocyte Cell Biol Unit, Immunol Lab, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Ghosh, P (reprint author), NIA, Lymphocyte Cell Biol Unit, Immunol Lab, Gerontol Res Ctr,NIH, 5600 Nathan Schock Dr, Baltimore, MD 21224 USA. EM ghoshp@grc.nia.nih.gov NR 37 TC 27 Z9 28 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 14 PY 2005 VL 280 IS 2 BP 1037 EP 1043 DI 10.1074/jbc.M405204200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 885ZF UT WOS:000226195200023 PM 15522880 ER PT J AU Narayanan, A Nogueira, ML Ruyechan, WT Kristie, TM AF Narayanan, A Nogueira, ML Ruyechan, WT Kristie, TM TI Combinatorial transcription of herpes simplex virus and varicella zoster virus immediate early genes is strictly determined by the cellular coactivator HCF-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EARLY PROTEIN IE62; MAMMALIAN-CELLS; HOMEO DOMAIN; FACTOR SP1; C1 FACTOR; VP16; ACTIVATION; RECOGNITION; EXPRESSION; SEQUENCES AB The mammalian transcriptional coactivator host cell factor-1 (HCF-1) functions in concert with Oct-1 and VP16 to assemble the herpes simplex virus (HSV) immediate early (IE) transcription enhancer core complexes that mediate the high level transcription of these genes upon infection. Although this transcriptional model has been well characterized in vitro, the requirements and significance of the components have not been addressed. Oct-1 was previously determined to be critical but not essential for HSV IE gene expression. In contrast, RNA interference-mediated depletion of HCF-1 resulted in abrogation of HSV IE gene expression. The HSV IE gene enhancer domain is a model of combinatorial transcription and consists of the core enhancer and multiple binding sites for factors such as Sp1 and GA-binding protein. It was striking that HCF-1 was strictly required for VP16-mediated transcriptional induction via the core enhancer as well as for basal level transcription mediated by GA-binding protein and Sp1. HCF-1 was also found to be essential for the induction of varicella zoster virus IE gene expression by ORF10, the VZV ortholog of the HSV IE transactivator VP16, and the autostimulatory IE62 protein. The critical dependence upon HCF-1 demonstrates that this cellular component is a key factor for control of HSV and VZV IE gene expression by functioning as the common element for distinct factors cooperating at the IE gene enhancers. The requirements for this protein supports the model whereby the regulated transport of HCF-1 from the cytoplasm to the nucleus in sensory neurons may control IE gene expression and reactivation of these viruses from the latent state. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Dept Microbiol & Immunol, Buffalo, NY 14214 USA. RP Kristie, TM (reprint author), Bldg 4,Rm 131,4 Ctr Dr, Bethesda, MD 20892 USA. EM thomas_kristie@nih.gov RI Nogueira, Mauricio/B-7599-2012 OI Nogueira, Mauricio/0000-0003-1102-2419 FU NIAID NIH HHS [AI18449] NR 42 TC 35 Z9 38 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 14 PY 2005 VL 280 IS 2 BP 1369 EP 1375 DI 10.1074/jbc.M410178200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 885ZF UT WOS:000226195200063 PM 15522876 ER PT J AU Salameh, W Choucair, M Guo, TB Zahed, L Wu, SM Leung, MYK Rennert, OM Chan, WY AF Salameh, W Choucair, M Guo, TB Zahed, L Wu, SM Leung, MYK Rennert, OM Chan, WY TI Leydig cell hypoplasia due to inactivation of luteinizing hormone receptor by a novel homozygous nonsense truncation mutation in the seventh transmembrane domain SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE LH receptor; male pseudohermaphroditism; Leydig cell hypoplasia ID CHORIONIC-GONADOTROPIN RECEPTOR; MALE PSEUDOHERMAPHRODITISM; OVARIAN RESISTANCE; SEXUAL DEVELOPMENT; GENE; CHORIOGONADOTROPIN; POLYMORPHISMS; EXPRESSION; PHYSIOLOGY AB Inactivating mutations in the LH receptor are the predominant cause for male pseudohermaphroditism in subjects with Leydig cell hypoplasia (LCH). The severity of the mutations, correlates with residual receptor activities. Here.. we detail the clinical presentation of one subject with complete male pseudohermaphroditism and LCH. We identify within the proband and her similarly afflicted sibling a homozygous T to G transversion at nucleotide 1836 in exon 11 of the LH/CGR gene. This causes conversion of a tyrosine codon into a stop codon at codon 612 in the seventh transmembrane domain, resulting in a truncated receptor that lacks a cytoplasmic (ail. In vitro. in contrast to cells expressing a normal LHR, cells transfected with the mutant cDNA exhibit neither surface binding of radiolabeled hCG nor cAMP generation. In vitro expression under the control of the LHR signal peptide of either a wild type or mutant LHR-GFP fusion protein shows no differences in receptor cellular localization. In conclusion, the in vitro studies suggest that residues in the seventh transmembrane domain and cytoplasmic tail are important for receptor binding and activation without playing a major role in receptor cellular trafficking. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Div Endocrinol & Metab, Torrance, CA 90502 USA. Res & Educ Inst, Torrance, CA 90502 USA. NICHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. Amer Univ Beirut, Med Ctr, Beirut, Lebanon. RP Salameh, W (reprint author), Harbor UCLA Med Ctr, Div Endocrinol, Box 446,1000 W Carson St, Torrance, CA 90509 USA. EM wsalameh@labiomed.org; ms00@aub.edu.lb FU NCRR NIH HHS [M01 RR00425] NR 28 TC 9 Z9 12 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JAN 14 PY 2005 VL 229 IS 1-2 BP 57 EP 64 DI 10.1016/j.mce.2004.09.005 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 891QU UT WOS:000226596400008 PM 15607529 ER PT J AU O'Shea, JJ Kanno, Y Chen, XM Levy, DE AF O'Shea, JJ Kanno, Y Chen, XM Levy, DE TI Stat acetylation - A key facet of cytokine signaling? SO SCIENCE LA English DT Editorial Material ID NF-KAPPA-B; DEACETYLASE ACTIVITY; GENE-EXPRESSION; TRANSACTIVATION; TRANSCRIPTION C1 NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA. RP O'Shea, JJ (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. RI Kanno, Yuka/B-5802-2013; OI Kanno, Yuka/0000-0001-5668-9319 NR 14 TC 34 Z9 36 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 14 PY 2005 VL 307 IS 5707 BP 217 EP 218 DI 10.1126/science.1108164 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 888GJ UT WOS:000226361900030 PM 15653493 ER PT J AU Petkova, AT Leapman, RD Guo, ZH Yau, WM Mattson, MP Tycko, R AF Petkova, AT Leapman, RD Guo, ZH Yau, WM Mattson, MP Tycko, R TI Self-propagating, molecular-level polymorphism in Alzheimer's beta-amyloid fibrils SO SCIENCE LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; STRUCTURAL MODEL; COMMON MECHANISM; PRION PROTEIN; PEPTIDE; STATE; PROTOFIBRILS; CONSTRAINTS; MICROSCOPY; NANOWIRES AB Amyloid fibrils commonly exhibit multiple distinct morphologies in electron microscope and atomic force microscope images, often within a single image field. By using electron microscopy and solid-state nuclear magnetic resonance measurements on fibrils formed by the 40-residue beta-amyloid peptide of Alzheimer's disease (Abeta(1-40)), we show that different fibril morphologies have different underlying molecular structures, that the predominant structure can be controlled by subtle variations in fibril growth conditions, and that both morphology and molecular structure are self-propagating when fibrils grow from preformed seeds. Different Abeta(1-40) fibril morphologies also have significantly different toxicities in neuronal cell cultures. These results have implications for the mechanism of amyloid formation, the phenomenon of strains in prion diseases, the role of amyloid fibrils in amyloid diseases, and the development of amyloid-based nanomaterials. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM rt46d@nih.gov RI Mattson, Mark/F-6038-2012 NR 30 TC 986 Z9 1003 U1 27 U2 229 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 14 PY 2005 VL 307 IS 5707 BP 262 EP 265 DI 10.1126/science.1105850 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 888GJ UT WOS:000226361900045 PM 15653506 ER PT J AU Zhu, ZZ Cong, WM Liu, SF Dong, H Zhu, GS Wu, MC AF Zhu, Zhong-Zheng Cong, Wen-Ming Liu, Shu-Fang Dong, Hui Zhu, Guan-Shan Wu, Meng-Chao TI Homozygosity for Pro of p53 Arg72Pro as a potential risk factor for hepatocellular carcinoma in Chinese population SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Hepatocellular carcinoma; p53 gene; Arg72Pro ID CHRONIC LIVER-DISEASE; HEPATITIS-B CARRIERS; CODON-72 POLYMORPHISM; LUNG-CANCER; GENETIC POLYMORPHISMS; AFLATOXIN EXPOSURE; SUSCEPTIBILITY; HAPLOTYPES; SELECTION; JAPANESE AB AIM: Codon 72 exon 4 polymorphism (Arg72Pro) of the p53 gene has been implicated in cancer risk. Our objective was to investigate the possible association between p53 Arg72Pro polymorphism and susceptibility to hepatocellular carcinoma (HCC) among Chinese population. METHODS: The p53 Arg72Pro genotypes were determined by PCR-based restriction fragment length polymorphism (RFLP) analysis in 507 HCC cases and 541 controls. Odds ratios (ORs) for HCC and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks. Potential risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotype and HCC. RESULTS: The frequencies for Pro and Arg alleles were 44.5%, 55.5% in HCC cases, and 40.3% and 59.7% in controls, respectively. The Pro allele was significantly associated with the presence of HCC (P = 0.05) and had a higher risk for HCC (OR = 1.19, 95% CI 1.00-1.41) as compared with the Arg allele. After adjusted for potential risk factors, Arg/Pro heterozygotes had an 1.21-fold increased risk (95% CI 0.82-1.78, P = 0.34) of HCC compared with Arg homozygotes, whereas the risk for Pro homozygotes was 1.79 (95% CI 1.06-3.01, P = 0.03) times higher than that for Arg homozygotes. Pro-allele carriers had a higher relative risk of HCC than the Arg-only carriers (adjusted OR = 1.33, 95% CI 0.92-1.92, P = 0.13), although the difference was not statistically significant. CONCLUSION: Homozygosity for Pro of p53 Arg72Pro is potentially one of the genetic risk factors for HCC in Chinese population. The p53 Arg72Pro polymorphism may be used as a stratification marker in screening individuals at a high risk of HCC. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved. C1 [Zhu, Zhong-Zheng; Cong, Wen-Ming; Dong, Hui; Wu, Meng-Chao] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Pathol, Shanghai 200438, Peoples R China. [Liu, Shu-Fang] HealthDigit Co Ltd, Shanghai 200233, Peoples R China. [Zhu, Guan-Shan] Second Mil Med Univ, Changhai Hosp, Dept Infect Dis, Shanghai 200433, Peoples R China. [Zhu, Guan-Shan] NIAAA, NIH, Rockville, MD 20852 USA. RP Cong, WM (reprint author), Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Pathol, Shanghai 200438, Peoples R China. EM wmcong@smmu.edu.cn FU National Natural Science Foundation of China [30370645]; Hundred Leading Scientists Program of the Public Health Sector of Shanghai [98BR007] FX Supported by the National Natural Science Foundation of China, No. 30370645, and by the Hundred Leading Scientists Program of the Public Health Sector of Shanghai, No. 98BR007 NR 39 TC 29 Z9 30 U1 0 U2 0 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD JAN 14 PY 2005 VL 11 IS 2 BP 289 EP 292 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19UY UT WOS:000208098500027 PM 15633234 ER PT J AU Dayam, R Sanchez, T Clement, O Shoemaker, R Sei, S Neamati, N AF Dayam, R Sanchez, T Clement, O Shoemaker, R Sei, S Neamati, N TI beta-Diketo acid pharmacophore hypotesis. 1. Discovery of a novel class of HIV-1 integrase inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DRUG DESIGN; CONFORMATIONAL COVERAGE; 4-POINT PHARMACOPHORE; ACTIVE-SITE; IDENTIFICATION; PERMEABILITY; DERIVATIVES; BINDING; REPLICATION; VALIDATION AB HIV-1 Integrase (IN) is an essential enzyme for viral replication. The discovery of beta-diketo acids was crucial in the validation of IN as a legitimate target in drug discovery against HIV infection. In this study, we discovered a novel class of IN inhibitors using a 3D pharmacophore guided database search. We used S-1360 (1), the first IN inhibitor to undergo clinical trials, and three other analogues to develop a common feature pharmacophore hypothesis. Testing this four-featured pharmacophore against a multiconformational database of 150 000 structurally diverse small molecules yielded 1700 compounds that satisfied the 3D query. Subsequently, all 1700 compounds were docked into the active site of IN. On the basis of docking scores, Lipinski's rule-of-five, and structural novelty, 110 compounds were selected for biological screening. We found that compounds that contain both salicylic acid and a 2-thioxo-4-thiazolidinone (rhodanine) group (e.g. 5-13) showed significant inhibitory potency against, IN, while the presence of either salicylic acid or a rhodanine group alone did not. Although some of the compounds containing only a salicylic acid showed inhibitory potency against IN, none of the compounds containing only rhodanine exhibited considerable potency. Of the 52 compounds reported in this study, 11 compounds (5, 6, 8, 10-13, 32-33, 51, and 53) inhibited T-processing or strand transfer activities of IN with IC50 less than or equal to 25 muM. This is the first reported use of S-1360 and its analogues as leads in developing a pharmacophore hypothesis for IN inhibition and for identification of new compounds with potent inhibition of this enzyme. C1 Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, Los Angeles, CA 90089 USA. Accelrys Inc, San Diego, CA 92121 USA. SAIC Frederick, Lab Antiviral Drug Mech, Ft Detrick, MD 21702 USA. NCI, Screening Technol Branch, DTP, DCTD, Ft Detrick, MD 21702 USA. RP Neamati, N (reprint author), Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, 1985 Zonal Ave, Los Angeles, CA 90089 USA. EM neamati@usc.edu NR 49 TC 75 Z9 80 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 13 PY 2005 VL 48 IS 1 BP 111 EP 120 DI 10.1021/jm0496077 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 886FS UT WOS:000226212900011 PM 15634005 ER EF